СОЕДИНЕНИЕ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описываются соединения формулы (I) или их фармацевтически приемлемые соли, в которой R1 и R2 являются одинаковыми или разными и независимо выбраны из группы, включающей арил и гетероарил, каждый из которых необязательно содержит в качестве заместителя от одной до шести групп, выбранных из группы, включающей: а) галоген; b) -OCF3 или -OCHF2; с) -CF3; d) -CN; е) алкил; f) R18-гетероалкил; k) гидроксил; l) алкоксил, включающий циклопропилметоксил; и s) трифторалкоксил; R3 означает Н; R4, R5, R7 и R8 являются одинаковыми или разными и независимо выбраны из группы, включающей H, -ОН, алкил, гетероалкил и , при условии, что, если Z и/или Х означает N, то все R4, R5, R7 и R8 не означают -ОН; R6 означает -C(O)R15; R9 и R10 означают Н; R11 выбран из группы, включающей Н и алкил; R12 выбран из группы, включающей Н и алкил; R13 выбран из группы, включающей алкил и алкоксил; R14 означает Н; R15 выбран из группы, включающей -NR16R17, -OR16 и алкил; R16 и R17 являются одинаковыми или разными и независимо ...

ПРОИЗВОДНЫЕ БЕНЗОФУРАЗАНА ИЛИ БЕНЗО-2,1,3-ТИАДИАЗОЛА И СПОСОБ ЛЕЧЕНИЯ

Изобретение относится к производным бензофуразана или бензо-2,1,3-тиадиазола формулы I, в которой R1 представляет кислород или серу, R2 и R3 независимо выбирают из группы, состоящей из -СR=, М представляет =СR4-, где R4 независимо представляет R, R8 представляет водород, R5 выбирают из группы, состоящей из -СR=CR1-, -CR=CX-, -(СRR1)n-, R7 выбирают из группы, состоящей из -(CRR1)n-, -C(O)-, -CRX-, -CXX1-, R6 выбирают из группы, состоящей из -(CRR1)m-, -C(O)-, -CRX -, -CXX1-, -S- и -O-. Соединения обладают усиливающими АМРА рецепторы свойствами. Эти соединения можно использовать для таких терапевтических целей, как облегчение обучению поведению, и для лечения состояний, таких, как нарушения памяти из-за уменьшения количества или эффективности АМРА рецепторов или синапсов, использующих эти рецепторы. Описан также способ лечения с помощью заявленных соединений. 2 с. и 28 з.п. ф-лы, 3 ил., 1 табл.

ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, ВКЛЮЧАЮЩИЕ КОЛЛОИДНУЮ ДВУОКИСЬ КРЕМНИЯ

Изобретение относится к медицине и описывает фармацевтическую композицию, включающую твердую дисперсию рапамицина или производного рапамицина, выбранного из группы, состоящей из 16-O-замещенных производных рапамицина, 40-O-замещенных производных рапамицина, 32-O-дигидро или замещенных производных рапамицина, 32-дезоксорапамицина и 16-пент-2-инилокси-32(S)-дигидрорапамицина, дезинтегрирующее средство и коллоидную двуокись кремния, где композиция содержит от 1 до 5% по массе коллоидной двуокиси кремния. Данная композиция обладает высокой стабильностью и физической сохранностью, будучи запрессованной в таблетку, композиция обладает улучшенными механическими свойствами в сочетании с быстрым диспергированием в водных растворах. 3 н. и 4 з.п. ф-лы.

ПРИМЕНЕНИЕ СОЕДИНЕНИЙ, КОТОРЫЕ ЯВЛЯЮТСЯ ЭФФЕКТИВНЫМИ КАК СЕЛЕКТИВНЫЕ МОДУЛЯТОРЫ ОПИАТНОГО РЕЦЕПТОРА

Предложено применение асимадолина или его фармацевтически приемлемых солей для изготовления фармацевтических препаратов для лечения расстройств пищеварения, в частности гастропареза, гастроатонии, гастропаралича и стеноза желудочно-кишечного тракта. Препарат эффективен для модулирования тонуса желудочно-кишечного тракта, сытости. Показано, что асимадолин (N-метил-N-[(1S)-1-фенил-2-((3S)-3-гидроксипирролидин-1-ил)этил]-2,2-дифенилацетамид (EMD 61753), селективный модулятор опиатного каппа-рецептора) дозозависимо регулирует аппетит, способствует увеличению объема поглощенной пищи без возникновения послеобеденных симптомов: вздутия, тошноты, боли, следующей за приемом пищи. 7 з.п. ф-лы, 5 ил., 4 табл.

АНТАГОНИСТ РЕЦЕПТОРА S1P3

Изобретение относится к новым соединениям, - ариламидразоновым производным формулы (I), где R1 представляет собой С2-С8алкильную группу или С2-С8алкокси группу, которые могут быть замещены галогеном или С1-С8алкокси группой; 5-7-членный ароматический гетероцикл, содержащий 1 или 2 атома кислорода, азота или серы, или фенил, которые могут быть замещены галогеном, С1-С8алкильной группой, галоС1-С8алкильной группой или C1-C8алкокси группой; или -NR4R5; R2 и R3 одинаковые или отличные друг от друга, и каждый представляет собой атом водорода, атом галогена, галогенС1-С8алкильную группу, С1-С8алкильную группу, С2-С6алкинильную группу, C1-C8алкокси группу, цианогруппу, С2-С6алканоильную группу или C1-С8алкилсульфонильную группу; А представляет собой бензольное, пиридиновое, хинолиновое или изохинолиновое кольцо; D представляет собой простую связь или метилен; m имеет значение от 1 до 3, и n представляет от 1 до 5, обладающим антагонистическим действием в отношении S1P3 рецепторов, а так же к лекарственным ...

НОВЫЕ СОЕДИНЕНИЯ, ОБЛАДАЮЩИЕ АНТИБАКТЕРИАЛЬНОЙ АКТИВНОСТЬЮ

Изобретение относится к новым антибактериальным соединениям формулы (I) Соединения формулы (I) ! ! где Q означает группу следующей структуры R1 означает водород, галоген, гидрокси, амино, меркапто, алкил, гетероалкил, алкилокси, гетероалкилокси, циклоалкил, гетероциклоалкил, алкилциклоалкил, гетероалкилциклоалкил, циклоалкилокси, алкилциклоалкилокси, гетероциклоалкилокси или гетероадкилциклоалкилокси, X1, X2, X3, X4, X5 и X6 каждый независимо друг от друга означает атом азота или группу формулы CR2, R2 означает водород, галоген или гидрокси, амино, алкильную, алкенильную, алкинильную или гетероалкильную группу, R3 выбран из следующих групп R5 означает группу формулы -B-Y, где В означает алкилен, алкенилен, алкинилен, -NH- или гетероалкилен, a Y означает арил, гетероарил, аралкил, гетероаралкил, циклоалкил, гетероциклоалкил, алкилциклоалкил или гетероалкилциклоалкил, или их фармацевтически приемлемую соль, сольват, гидрат или фармацевтически приемлемую композицию, а также к фармацевтической ...

ГЕТЕРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ ПЕРВИЧНЫХ АМИНДИАЗЕНИУМДИОЛАТОВ

Изобретение относится к соединениям формулы I или их фармацевтически приемлемым солям, которые обладают антигипертензивным действием. В формуле I X представляет собой О или NR; группаприсоединена к любому атому углерода кольца, отличному от атома углерода, к которому присоединены Rи R; Rпредставляет собой водород или вместе с Rобразует =O; Rпредставляет собой водород или вместе с Rобразует =O; Rпредставляет собой -Салкил; Rи R, которые присоединены к любому доступному атому углерода кольца, независимо представляют собой водород или Rи Rв тех случаях, когда они присоединены к одному и тому же атому углерода, вместе образуют =O; Rпредставляет собой -Салкил, -С(О)O-Cалкил, -С(О)O-Cалкилен-CRRR, -С(О)Салкил, -С(О)ОСкарбоцикл, -С(О)арил, -С(О)гетероарил, где гетероарил представляет собой ненасыщенное 5- или 6-членное кольцо, содержащее 1-4 гетероатома, выбранных из N, -С(О)NHCалкил, -С(О)NH-адамантил, -SOCалкил, арил или ненасыщенное 5- или 6-членное гетероарильное кольцо, содержащее 1-4 гетероатома ...

НОВАЯ ЛЕКАРСТВЕННАЯ ФОРМА

Группа изобретений относится к лекарственным средствам и касается способа изготовления фармацевтической композиции в виде таблетки. Для этого активный фармацевтический ингредиент формулы I ! ! являющийся антагонистом рецептора NK1, или его фармацевтически приемлемые соли присоединения кислоты, и водорастворимый полоксамер вместе обрабатывают экструзией из горячего расплава перед смешиванием с другими ингредиентами. Экструзия из горячего расплава, единственными компонентами которого являются активный ингредиент формулы I и водорастворимый полоксамер, приводит к получению микрокристаллической твердой дисперсии, при объединении которой с другими ингредиентами получают таблетку, обладающую характеристиками растворимости, необходимыми для биодоступности лекарственного средства. 2 н. и 12 з.п.ф-лы, 1 табл.

СПОСОБ ИНГИБИРОВАНИЯ МЕЖКЛЕТОЧНОЙ АДГЕЗИИ И СПОСОБ ИНГИБИРОВАНИЯ ВОСПАЛИТЕЛЬНОГО ПРОЦЕССА

Изобретение относится к медицине. Предложены способ ингибирования межклеточной адгезии и способ ингибирования воспалительного процесса с использованием ралоксиорена. Изобретение позволяет снизить экспрессию адгезивных молекул в клетках эндотелия. 2 с. и 2 з.п. ф-лы, 4 табл.

СПОСОБ КРИСТАЛЛИЗАЦИИ ГИДРОХЛОРИДА 1-[2-(2-НАФТИЛ)ЭТИЛ]-4-(3-ТРИФТОРМЕТИЛФЕНИЛ)-1,2,3,6-ТЕТРАГИДРОПИРИДИНА, ПОЛУЧЕННЫЕ КРИСТАЛЛИЧЕСКИЕ ФОРМЫ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описывается способ кристаллизации гидрохлорида 1-[2-(2-нафтил)этил]-4-(3-трифторметилфенил)-1,2,3,6-тетрагидропиридина (SR 57746A), заключающийся в том, что а) указанное соединение растворяют при нагревании в растворителе, выбранном из алканолов, имеющих 1 - 2 атомов углерода, ацетона, диметилсульфоксида и этилацетата, причем указанный растворитель необязательно содержит 5 - 30% воды или водной хлористоводородной кислоты, б) полученный раствор охлаждают до температуры 0 - 10oС со скоростью 3 - 100oС/ч при перемешивании со скоростью 0 - 600 об/мин, с) полученный продукт выделяют и необязательно микронизируют. Описываются полученные три формы (SR 57746A): форма I, форма II, форма III и смесь формы I и III, а также фармацевтическая композиция для лечения нейродегенерации, содержащая соединение SR 57746A в необязательно микронизированной кристаллической форме, выбранной из формы I, формы II, формы III и смеси формы I/формы III. Технический результат - повышение активности активного ингредиента ...

ПРОИЗВОДНЫЕ ПИПЕРИДИНА И ФАРМАЦЕВТИЧЕСКИЙ ПРЕПАРАТ НА ИХ ОСНОВЕ

Изобретение относится к новым производным пиперидина формулы I, где R1 означает бензотиенил, бензофуранил, нафтил, которые могут быть замещены галогеном, С1-С6-алкилом, С1-С6-алкоксигруппой, замещенный тиенил или замещенный фуранил, которые замещены галогеном, С1-С6-алкилом, С3-С6-циклоалкилом или С1-С6-алкенилом, R2 означает галоген и R3 означает С1-С6-алкил или С3-С6-циклоалкилметил, или их фармацевтически приемлемым солям, или сольватам. Соединения формулы I обладают антипсихотической активностью и могут найти применение в медицине. 2 с. и 6 з.п.ф-лы, 2 табл.

КОМБИНИРОВАННЫЙ ПРЕПАРАТ ДЛЯ ЛЕЧЕНИЯ СЛАБОУМИЯ

Изобретение относится к медицине, конкретно к средствам терапии слабоумия. Сущность изобретения заключается в создании комбинированного препарата на основе активных компонентов, содержащего соединение, обладающее эффектом торможения ацетилхолинэстеразы или обнаруживающее мускаринергическое действие, и соединение, которое повышает эндогенный внеклеточный уровень аденозина. Технический результат заключается в повышении эффективности препарата за счет эффекта потенцирования. 2 с. и 4 з.п. ф-лы, 4 табл., 3 ил.

СПОСОБЫ ПРИМЕНЕНИЯ ПРОИЗВОДНЫХ ЦИКЛИЧЕСКОГО АМИДА ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ

Группа изобретений относится к медицине, а именно к психиатрии, и касается лечения шизофрении. Для этого вводят эффективное количество соединенияили его фармацевтически приемлемой соли. Это обеспечивает эффективное лечение симптомов шизофрении и коррекцию расстройств сна. 6 н. и 17 з.п. ф-лы, 3 пр.

СОЕДИНЕНИЯ ПИПЕРАЗИНА И ПИПЕРИДИНА

Изобретение относится к производным пиперазина и пиперидина формулы (I), где ---Z представляет =C или -N и Q является бензилом или 2-, 3- или 4-пиридилметилом, которые могут быть замещены одним или более заместителями, выбранными из группы, содержащей галоген, циано, С1-С3-алкоксигруппу, CF3, OCF3, SCF3, С1-С4-алкил, С1-С3-алкилсульфонил, и их солям, а также к способу их получения.Было обнаружено, что данные соединения обладают интересными фармакологическими свойствами благодаря сочетанию (частичного) агонизма по отношению к членам D2-подтипа допаминовых рецепторов и аффинности (сродства) по отношению к соответствующим серотониновым и/или норадренергическим рецепторам и могут быть пригодны в получении композиций для лечения страха и/или депрессии или болезни Паркинсона. 2 н. и 5 з. п. ф-лы, 1 табл.

ПРОИЗВОДНЫЕ КАРБОНОВЫХ КИСЛОТ (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ СЕЛЕКТИВНОГО ИНГИБИРОВАНИЯ СВЯЗЫВАНИЯ α4β1 ИНТЕГРИНА У МЛЕКОПИТАЮЩЕГО

Изобретение относится к новым производным карбоновых кислот, имеющих структуру где Y в каждом случае независимо выбирают из группы, содержащей С(O), N, CR1, C(R2)(R3), NR5, CH; q означает целое число от 3 до 10; А выбирают из группы, содержащей NR6; Е выбирают из группы, содержащей NR7; J выбирают из группы, содержащей О; Т выбирают из группы, содержащей (СН2)b, где b означает 0; М выбирают из группы, содержащей C(R9)(R10), (CH2)u, где u означает целое число от 0 до 3; L выбирают из группы, содержащей NR11 и (СН2 )n, где n означает 0; Х выбирают из группы, содержащей СО2Н, тетразолил; W выбирают из группы, содержащей С, CR15 и N; R1, R2, R3, R15 независимо выбирают из группы, содержащей водород, галоген, гидроксил, алкил, алкокси, -CF3, амино, -NHC(O)N(C1-С3алкил)С(O)NH(С1-С3алкил), -NHC(O)NH(C1-C6алкил), алкиламино, алкоксиалкокси, циклоалкил, арил, арилокси, ариламино, гетероциклил, гетероциклилалкил, гетероциклиламино, где гетероатом выбирают из N или О, -NHSO2(C1-С3алкил), арилоксиалкил ...

ПРОИЗВОДНЫЕ СПИРО(2H-1-БЕНЗОПИРАН-2,4`-ПИПЕРИДИНА) КАК ИНГИБИТОРЫ ТРАНСПОРТА ГЛИЦИНА

Настоящее изобретение относится к новым производным спиро[2Н-1-бензопиран-2,4’-пиперидина], имеющим общую формулу (I) где пунктирная линия обозначает необязательную связь; Y обозначает 1-4 заместителя, независимо выбираемые из водорода, галогена, (С1-6)алкила (необязательно замещенного одним или более галогенами), (C1-6)алкилокси (необязательно замещенного одним или более галогенами или (С3-6)циклоалкилом), (С2-6)алкенилокси, (С2-6 )алкинилокси, (С3-6)циклоалкилокси, (С6-12)арилокси, арилалкилокси, пиридилметокси, SR3, NR3R4, OSO2R5 и NR3 SO2R4; 2 заместителя Y могут вместе образовывать O-(СН2)n-O или O-(CF2)n-O, где n принимает значение 1 или 2; или Y обозначает конденсированную (С5-6)арильную группу; X обозначает 1-3 заместителя, независимо выбираемые из водорода, галогена, гидрокси, (C1-6)алкилокси, и (С1-4)алкила; r1 обозначает водород, (С1-4)алкил или (C6-12)арил; r2, r3 и R4 обозначают независимо водород или (C1-4)алкил; R5 обозначает (С6-12)арил; или его фармацевтически приемлемой ...

42-ОКСИМЫ И ГИДРОКСИЛАМИНЫ РАПАМИЦИНА, СПОСОБ ПОЛУЧЕНИЯ, ПРОМЕЖУТОЧНЫЙ ПРОДУКТ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ

Описываются новые соединения формулы I, где Х-Y является С=NОR1 или СНNНОR2, в которых R1 обозначает водород, алкил с 1 - 6 атомами углерода, алкенил с 2 - 7 атомами углерода, алкинил с 2 - 7 атомами углерода, группа формулы -(СН2)mAr, в которой Ar представляет фенил или пиридинил и m = 1 - 6; R2 представляет водород или радикал формулы -(СН2)mAr, в которой Ar представляет пиридинил, или их фармацевтически приемлемые соли. Описывается также способ их получения, промежуточный продукт, фармацевтическая композиция и способ лечения заболевания. Новые соединения полезны в качестве иммунодепрессивных, противовоспалительных, противогрибковых, антипролиферативных и противоопухолевых средств. 5 с. и 13 з.п.ф-лы.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ ГИДРОХЛОРИД ТИАГАБИНА, И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Изобретение относится к области медицины, к новой стабильной фармацевтической композиции, содержащей в качестве активного ингредиента гидрохлорид тиагабина и антиоксидант, выбранный из α-токоферола и аскорбилпальмитата. Композиция обладает повышенной стабильностью. 2 с. и 5 з.п. ф-лы, 10 табл.

АНЕСТЕТИЧЕСКИЕ КОМПОЗИЦИИ С ЗАМЕДЛЕННЫМ ВЫСВОБОЖДЕНИЕМ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Группа изобретений относится к способу получения анестетической композиции с замедленным высвобождением и к композиции для местного введения анестетика субъекту, нуждающемуся в этом, полученной указанным способом. Способ получения анестетической композиции с замедленным высвобождением предусматривает: растворение липидной смеси и по меньшей мере одного анестетика амидного типа в системе растворителя с получением жидкой структуры; удаление системы растворителя из жидкой структуры, где система растворителя содержит трет-бутанол или трет-бутанол/воду в качестве сорастворителя, для получения липидной структуры с высокой степенью захвата (HELS); гидратацию HELS с применением водного буферного раствора при pH от 5,5 до 8,0. Причем в результате гидратации HELS образуются многослойные везикулы (MLV) с захваченным анестетиком амидного типа; причем медианный диаметр везикул MLV с захваченным анестетиком амидного типа составляет по меньшей мере 1 мкм; и молярное соотношение анестетика амидного типа ...

СОЕДИНЕНИЯ И СПОСОБЫ ИНГИБИРОВАНИЯ ВЗАИМОДЕЙСТВИЯ БЕЛКОВ BCL С КОМПОНЕНТАМИ СВЯЗЫВАНИЯ

Настоящее изобретение относится к гетероциклическим соединениям формулы I ! ! где Y означает -(С=O)-, Х означает -N(R10)-, А означает -C(A1)(A2)-, В означает О, S, -(С=O)- или характеризуется формулой ! ! где D означает N или СR10 и где значения остальных заместителей раскрыты в формуле изобретения. Соединения формулы 1, а также композиции на его основе обладают способностью ингибировать белки семейства bcl-2, что обуславливает возможность применения таких соединений и композиций при лечении или модулировании нарушений, ассоциированных с гиперпролиферацией, таких как рак. 7 н. и 13 з.п. ф-лы.

НОВЫЕ ФОСФОРСОДЕРЖАЩИЕ ТИРОМИМЕТИКИ

Настоящее изобретение относится к соединениям формулы VIII, пригодным в медицине качестве Т3 миметиков: ! ! где G - О, -S(=O)2- или -CH2-; R2 - галоген, алкил, -CF3, -OCF3, алкокси или циано; R3 и R4 - Н, галоген, алкил или -(CRa 2)mарил; Т выбран из -(CRa 2)k-, -CRb=CRb-(CRa 2)n-, -(CRa 2)n-CRb=CRb, -(CRa 2)-CRb=CRb-(CRa 2)-, -O(CRa 2)(CRa 2)n-, -S(CRa 2)(CRa 2)n-, -N(Rc)(CRb 2)(CRa 2)n-, -N(Rb)C(O)(CRa 2)n-, -(CRa 2)nCH(NRbRc)-, -C(O)(CRa 2)m -, -(CRa 2)mC(O)-, -(CRa 2)C(O)(CRa 2)n-, -(CRa 2)nC(O)(CRa 2)- и -C(O)NH(CRb 2)(CRa 2)p-; Ra, Rb, Rc, R1, R6, R7, R8 и R9 - Н, галоген или алкил; или R6 и Т с атомом С образуют 5-6-членное кольцо с 0-2 группами -NRi-, -О- или -S-; Ri - Н, -С(O)алкил, алкил или арил; R5 - ОН, алкокси, -OC(O)Re, -OC(O)ORh, -F, -NHC(O)Re, -NHS(=O)Re, -NHS(=O)2Re, -NHC(S)NH(Rh) или -NHC(O)NH(Rh); Re - алкил, -(CRa 2)n-арил, -(CRa 2)n-циклоалкил или -(CRa 2)n- гетероциклоалкил; Rh - Н или алкил; Х -Р(O)YR11Y'R11; Y и Y' - О или -NRv-; R11 - Н, алкил, -С(Rz)2-ОС(O)Ry, ...

БИЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ, СПОСОБ ПОДАВЛЕНИЯ СЛИПАНИЯ ТРОМБОЦИТОВ И КОМПОЗИЦИЯ ДЛЯ ЕГО ОСУЩЕСТВЛЕНИЯ

Описываются новые бициклические соединения, имеющие ядро, сформированное из двух конденсированных шестичленных колец, А и В, представленное формулой I, либо фармацевтически приемлемая соль, сольват или пролекарственная производная этого соединения, в котором бициклическое ядро из колец А и В выбирается из группы, состоящей из формул (17)-(21), R3 является кислотной группой, содержащей кислотный радикал, выбранный из формул группы (С), n = 0-6; R0 является одинаковым или разным и выбирается независимо из водорода, алкила, связующая группа -(L)- является связью или выбирается из формул -C(=O)-N(H)- и -С(Н2)-O-, Q является основной группой и выбирается из амидиногруппы и пиперидина. Новые бициклические соединения полезны в качестве препаратов, нейтрализующих действие гликопротеина IIв/IIIа, для предотвращения тромбоза. Описывается также способ подавления слипания тромбоцитов и композиция для его осуществления. 13 с. и 12 з.п. ф-лы, 1 табл.

НОВЫЕ ПРОИЗВОДНЫЕ ГИДРОКСАМОВОЙ КИСЛОТЫ, ПОЛЕЗНЫЕ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С ДЕГЕНЕРАЦИЕЙ СОЕДИНИТЕЛЬНОЙ ТКАНИ

Изобретение относится к производным гидроксамовой кислоты формулы I, где X означает -CH2-, -NR5-, -C(O); Y означает -CH2-, -NR5, при условии, что если X является -NR5-, то Y означает -CH2-; R1 означает H, C1-C20 алкил, -(CH2)j арил, -(CH2)j циклоалкил и др.; R2 означает H, C1-C20-алкил, -(CH2)j -R8, -(CH2)j -NR6R7, -(CH2)j -NR5-; -C(O)R5 и др.; R3 означает H, C1-C6алкил, -(CH2)j-арил, -(CH2)j - C3-6-циклоалкил и др., R5 означает H, C1-C6алкил, возможно замещенный 1 - 3 галогенами и др.; R6 и R7, одинаковые или различные, и означают H, C1-C6алкил и др., R8 означает -S-R8 и др., R9-галоген, C1 -C6 алкил и др., R10 - H; арил - фенил, возможно замещенный, Het - пиридинил, тиенил и др., i - 1 - 6, j - 0 - 4. Соединения I ингибируют избыток матрицы металлопротеиназы, что позволяет использовать их в фармацевтической композиции. 2 с. и 12 з.п.ф-лы, 1 табл.

ПРОИЗВОДНЫЕ ОКСАЗОЛИДИНОНА, СПОСОБЫ ИХ ПОЛУЧЕНИЯ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Описываются новые производные окcазолидинона формулы (I), где R1 обозначает амидинофенил, R3 обозначает Н, А, C1 - C10-алканоил, C1 - C8-алкоксикарбонил, бензоил, нафтоил, C1 - C6 -алкилсульфонил, бензилсульфонил или незамещенный или монозамещенный C1 - C6-алкилом фенилсульфонил, R3 обозначает водород или C1 - C6-алкил, А обозначает алкил с 1 - 16 С-атомами, а а также их физиологически приемлемые соли. Соединения оказывают тормозящее воздействие на привязывание фибриногена к соответствующему рецептору и могут использоваться для лечения тромбозов, остеопорозов, раковых заболеваний, артериосклероза и остеолитических заболеваний. Описываются также способы их получения, содержащая их фармацевтическая композиция и способ ее получения. 5 с. и 2 з.п.ф-лы, 1 табл.

ПРОИЗВОДНЫЕ 4-ГИДРОКСИПИПЕРИДИНА

Изобретение относится к новым производным 4-гидроксипиперидина общей формулы (I), где Х обозначает -О-, -NH-, -CH2-, -СН= , -СО2-, -СОN(низший алкил)- или -CONH-, R1 - R4, независимо друг от друга, - водород, гидрокси, нитрогруппа, низший алкилсульфонамид, 1- или 2-имидазолил, 1-(1,2,4-триазолил), R5 и R6, независимо друг от друга, - водород, низший алкил, гидрокси- или оксогруппа, R7 - R10, независимо друг от друга, - водород, низший алкил, галоген, трифторметил или низшая алкоксигруппа, n = 0 или 1, или к их фармацевтически приемлемым кислотно-аддитивным солям. Изобретение может быть использовано как лекарственное средство в качестве селективного блокатора подтипа NMDA-рецептора. Также раскрыто лекарственное средство на основе 4-гидроксипиперидина. 2 с. и 10 з. п. ф-лы, 3 табл.

КАРБОКСАМИДНЫЕ ПРОИЗВОДНЫЕ ПИРРОЛИДИНА ИЛИ ПИПЕРИДИНА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ИНГИБИРОВАНИЯ АГРЕГАЦИИ ТРОМБОЦИТОВ

Изобретение относится к новым производным пирролидина или пиперидина ф-лы (I), их энантиомерам и фармацевтически приемлемым солям где R10 - Н или C(O)N(R1)YZ, R1 - Н, Y - (СН2)р, (CH2)qCH(R3) или CH(R3)(CH2)q, R3 - арил, аралкил или гетероарил, q = 1-3, р = 2 или 3, Z - CO2H, СО2-алкил или 5-тетразол, Х-С(O), М-(СН2)n, или пиперидин-1-ил, m = 2, n = 2, R5 - Н, А выбирают из пиперидин-2-ила, пиперидин-3-ила, пиперидин-4-ила или N-замещенного пиперидина. Соединения ф-лы (I) ингибируют агрегацию тромбоцитов и могут найти применение в медицине. 3 с. и 2 з.п. ф-лы, 6 табл.

СПОСОБ ЛЕЧЕНИЯ ИHCД АГОНИСТАМИ RXR

Изобретение относится к медицине, в частности к эндокринологии, и касается лечения инсулиннезависимого сахарного диабета (ИНСД). Способ заключается во введении агониста ретиноид-Х-рецептора (RXR) отдельно или в сочетании с агонистом пероксисом-пролиферативно-активирующим рецептором (PPARγ). К последним относят тиазолидиндионовые производные. Для этого предлагается использовать также и фармацевтические композиции, содержащие указанные компоненты. Изобретение обеспечивает повышение потребления глюкозы тканями, уменьшая содержание глюкозы, триглицеридов, холестерина в крови. 3 с. и 29 з.п. ф-лы, 2 табл., 8 ил.

ТРАНСДЕРМАЛЬНАЯ ДОСТАВКА ЛАЗОФОКСИФЕНА

Настоящее изобретение относится к медицине и описывает трансдермальный препарат, содержащий резервуар для лекарственного средства; эффективное количество лазофоксифена и его фармацевтически приемлемых солей; эффективное количество усилителя проницаемости для лекарственного средства, где усилитель проницаемости для лекарственного средства содержит эффективное количество низшего алканола и эффективное количество моноолеата глицерина. Также описаны устройства введения активного средства. Такие устройства могут находиться в виде матричных пластырей (лекарственное средство в адгезиве) или резервуарных пластырей (лекарственное средство в жидком или полимерном резервуаре с расположенным по периметру в виде полосок или в виде расположенного поверх слоя самоприклеивающимся адгезивом). Кроме того, настоящее изобретение относится к способам лечения или профилактики расстройства, связанного с дефицитом эстрогена. Данное изобретение обеспечивает удобство, непрерывный режим лечения, высокую степень контроля ...

КОМБИНИРОВАННАЯ ТЕРАПИЯ С ИСПОЛЬЗОВАНИЕМ АНТАГОНИСТОВ C-C ХЕМОКИНОВОГО РЕЦЕПТОРА 4 (CCR4) И ОДНОГО ИЛИ БОЛЕЕ ИНГИБИТОРОВ КОНТРОЛЬНЫХ ТОЧЕК

Группа изобретений относится к фармацевтической промышленности, а именно к способу лечения злокачественного новообразования у млекопитающего, включающему введение эффективного количества антагониста C-C хемокинового рецептора 4 (CCR4 антагонист) и антитела к цитотоксическому T-лимфоцит-ассоциированному белку 4 (анти-CTLA-4 антитело); а также к применению комбинации CCR4 антагониста и анти-CTLA-4 антитела в качестве терапевтических средств в указанном способе лечения. При этом в предложенных способе и применении CCR4 антагонист представляет собой соединение 1 Группа изобретений обеспечивает повышение эффективности лечения злокачественных новообразований по сравнению с одним или более ингибиторами контрольных точек, используемыми отдельно. 2 н. и 9 з.п. ф-лы, 26 ил., 2 табл., 4 пр.

ЛЕКАРСТВЕННЫЕ ФОРМЫ В ВИДЕ КАПСУЛ

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СОЕДИНЕНИЕ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Раскрыты соединения формулы (I) или их приемлемые с фармацевтической точки зрения соли, в которой: пунктирная линия означает необязательную двойную связь; Х1 означает необязательно замещенную (С1-С12)-алкильную, (С3-С12)-циклоалкильную, фенильную, фуранильную, тиенильную, пиридильную, тиазолильную, 1H-индолильную группу; Х2 означает –CHO, -CN, -(CH2)vOR13, -(CH2)vNR21R22или -(CH2)vNHC(O)R21, v равно 0 или 1 или Х1означает необязательно замещенную сконденсированную с бензольным кольцом гетероциклическую группу и X2 означает водород; или X1 и X2 совместно образуют необязательную сконденсированную с бензольным кольцом спирогетероциклическую группу; R1, R2, R3 и R4 независимо означают Н и (С1-С6)-алкильную группу, или (R2 и R4) совместно могут образовать алкиленовый мостик из 1 - 3 атомов углерода; Z1 означает замещенный фенил, Z2 означает замещенный фенил, Z3 означает водород; или Z1, Z2 и Z3 вместе с атомом углерода, к которому они присоединены, образуют бициклические насыщенные кольца; фармацевтическая ...

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Изобретение относится к новым производным сульфонамидов формулы (I) или их фармацевтически приемлемым солям: , где R1 означает -ОН или -NHOH; R2 означает водород; R3 означает алкил, алкоксиалкил, арилалкил, пиридилалкил или морфолинилалкил; А означает пиперидил или тетрагидрофуранил; n равно 0; Е означает ковалентную связь; С1-С4-алкилен, -С(=O)-, -С(=O)O- или -SO2-; Х означает водород, алкил, арил, арилалкил, алкоксиалкил, морфолинил или тетрагидропиранил; каждый из G и G’ означает -C(R5)=C(R5), где R5 и R5 означают водород, М означает группу -CH-; z означает группу -(CR7R7’)a-L-R8, где а равно 0; каждый из R7 и R7означает водород; L означает ковалентную связь; и R8 означает галоген или алкокси. Соединения формулы (I) являются ингибиторами металлопротеаз и могут найти применение для лечения артрит, раковых опухолей и других заболеваний. 2 н. и 13 з.п. ф-лы, 7 табл.

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Изобретение относится к новым нафтилпроизводным ф-лы (I), где R1 и R2 - Н, -ОН или -O(С1-С4-алкил); R3 - 1-пиперидинил, 1-пирролидинил, метил-1-пирролидинил, диметил-1-пирролидинил, 4-морфолинил, диалкиламино- или 1-гексаметилен-иминогруппа; n = 2 или 3, или их фармацевтически приемлемым солям. Соединения ф-лы (I) ингибируют проявление симптомов постклимактерического синдрома и могут найти применение в качестве средства для облегчения симптомов постклимактерического синдрома, представляющих собой остеопороз, сердечно-сосудистые заболевания, гиперлипидемию или гормонально зависимое раковое заболевание. Описываются также промежуточные соединения ф-лы (II), где R1a - Н или OR5, R2a - Н или OR6, R5 и R6 - гидроксизащитная группа, R4 - -ОН или - СНО. 4 с. и 9 з.п. ф-лы, 6 табл.

ПРОИЗВОДНЫЕ 5-ФЕНИЛ-3-(ПИПЕРИДИН-4-ИЛ)-1,3,4-ОКСАДИАЗОЛ-2(3Н)-ОНА, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И ЛЕКАРСТВЕННОЕ СРЕДСТВО

Изобретение относится к производным 5-фенил-3-(пиперидин-4-ил)-1,3, 4-оксадиазол-2(ЗН)-она общей формулы I, в которой R1 представляет собой группу (С1-С4)алкил или группу (С3-С7)циклоалкилметил; X1 - атом водорода или галогена или группа (С1-С4 )алкокси или OR1 и X1 вместе - группа формулы -ОСН2O-, -O(СН2)2-; -O(СН2)2O- или -O(СН2)3О-; Х2 - атом водорода или аминогруппа; Х3 - атом водорода или галогена; R2 - атом водорода, либо возможно замещенная группа (С1-С6)алкил, или группа фенил(С1-С4)алкил, которая возможно замещена по фенильному кольцу, либо группа фенил(С2-С3 )алкенил, или группа фенокси(С2-С4)алкил, или группа цикло(C3-С7)алкилметил, либо группа 2,3-дигидро-1Н-инден-1-ил или 2,3-дигидро-1Н-инден-2-ил, либо группуа общей формулы -(СН2)nСО-Z, в которой n = 1 - 6, a Z - группа пиперидин-1-ил или 4-(диметиламино)пиперидин-1-ил. Указанные соединения можно использовать для лечения и предупреждения расстройств, в которые вовлечены рецепторы 5-НT4 и/или Н3, особенно в центральной нервной ...

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Изобретение относится к новым 4-арил-1-фенилалкил-1,2,3,6-тетрагидропиридинам ф-лы (I), где Y-CH или -N-; R1-H, галоген, CF3; R2-H, галоген, (C3 - C4)алкил или (C1 - C4)алкокси; R3 и R4 - H или (C1 - C3)алкил; X представляет собой: a) (C3 - C6 )алкил, (C3 - C6)алкокси или (C1 - C4)алкоксикарбонил(C3 - C6)алкокси, b) (C3 - C7)циклоалкил или c) заместитель, выбираемый из группы, включающей фенил, феноксибензил, их солям, сольватам или четвертичным аммониевым солям. Соединения ф-лы (I) обладают нейротропной и нейрозащитной активностью и могут быть использованы в медицине для лечения заболеваний центральной нервной системы. изобретение относится также к промежуточным соединения ф-лы (II'), где R'1-галоген или CF3, и ф-лы (i), где R1 - R4 и Y имеют указанные значения для соединений ф-лы (I), и W обозначает метиленовую или карбонильную группу. 6 с. и 5 з.п. ф-лы, 1 табл.

СПОСОБ ДЛЯ ЛЕЧЕНИЯ И ПРЕДУПРЕЖДЕНИЯ РАЗРЕЖЕНИЯ КОСТИ И ОСТЕОПОРОЗА И СОЕДИНЕНИЯ ДЛЯ НЕГО

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Изобретение относится к новым производным мочевины общей формулы (I) и их фармацевтически приемлемым солям, где А представляет собой -СН- или атом азота, R1 представляет собой С3-10 алкил, С3-10циклоалкил, С3-10циклоалкил-С1-10алкил, 6-членный азотсодержащий гетероциклил, 6-членный азотсодержащий гетероциклил-С1-10 алкил, фенил, фенил-С1-10алкил, 5-10-членный гетероарил или 5-10-членный гетероарил-С1-10алкил и др.; R2 представляет собой водород, С1-6алкил, С0-2 алкил-С3-10циклоалкил, С0-2алкил-фенил, С3-10циклоалкил-С0-2алкил или фенил-С0-2алкил; R5 представляет собой C1-6алкил, С3 -10циклоалкил, 6-членный азотсодержащий гетероциклил и др.; L1 представляет собой -S-, -S(О)-, -S(O)2, -С(O)-, -N(Rc)-, -CH2- и др.; L2 представляет собой ковалентную связь, -О-, -С(O)-, -ОС(O)-, -N(Rc)- и др.; W представляет собой О или S; Z представляет собой -C(O)ORd; Rc, Rd и Re представляют собой водород или алкил; Rb представляет собой -ORe, -NO2, галоген, -CN, -CF3, C1-6алкил; р представляет собой целое ...

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Изобретение относится к медицине, а именно к способам и фармацевтическим композициям для стимуляции роста невритов в нервных клетках, содержащим нейротрофическое количество соединения, которое связывается с FK-506-связывающим белком (FKBP), и нейротрофический фактор, такой как фактор роста нервов. Композиции ускоряют заживление нейронного повреждения, вызванного болезнью или физической травмой. 20 с. и 21 з.п. ф-лы, 8 табл., 2 ил.

ПРОИЗВОДНЫЕ ЗАМЕЩЕННОЙ МОЧЕВИНЫ, ФАРМАЦЕВТИЧЕСКАЯКОМПОЗИЦИЯ И ЛЕКАРСТВЕННОЕ СРЕДСТВО НА ИХ ОСНОВЕ,ОБЛАДАЮЩИЕ РЕТИНОИДНОЙ АКТИВНОСТЬЮ

Изобретение относится к новым производным замещенной мочевины формулы (I) или их фармацевтически приемлемым солям, обладающим ретиноидной активностью, а также к фармацевтической композиции и лекарственному средству на их основе. В формуле (I) n обозначает целое число от 0 до 2; Х обозначает О; A-Y обозначает ; R1 и R3 независимо друг от друга обозначают водород, C1-6алкил, С1-4алкиленС1-4алкокси, С1-4алкиленфенил, необязательно замещенный в кольце атомом галогена, С1-4алкоксигруппой, C1-4алкиленбензилокси, С1-4алкиленгидрокси, С1-4алкилен(моноциклический гетероарил, содержащий 5 кольцевых атомов и один или два гетероатома, выбранных из N, O или S), необязательно замещенный в кольце С1-6алкилом; R2 обозначает водород, при условии, что R1 не обозначает водород или C1-6алкил, если R3 обозначает водород. 3 н. и 9 з.п. ф-лы, 10 табл.

ПРОИЗВОДНЫЕ N-[ГЕТЕРОАРИЛ(ПИПЕРИДИН-2-ИЛ)МЕТИЛ]БЕНЗАМИДА И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ

Изобретение относится к новым соединениям общей формулы (I): ! ! в которой: R1 представляет собой либо прямой или разветвленный (С1-С7)алкил, либо (С2-С4)алкенил; R2 представляет собой пиридинил, тиенил, тиазолил; R3 представляет собой один или несколько заместителей, выбранных из атомов галогена и следующих групп: трифторметил, прямой или разветвленный (С1-С6)алкил; в форме свободного основания или аддитивной соли с кислотой. ! Изобретение также относится к лекарственному средству, к фармацевтической композиции, а также к применению. ! Технический результат - получение новых биологически активных соединений, обладающих активностью в отношении специфических ингибиторов переносчиков глицина glyt 1 и/или glyt 2. 5 н. и 1 з.п. ф-лы, 1 табл.

ПРОИЗВОДНЫЕ БЕНЗАМИДА, СПОСОБ ИХ ПОЛУЧЕНИЯ И ИХ ПРИМЕНЕНИЕ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ОБЕСПЕЧЕНИЯ ИНГИБИРУЮЩЕГО ДЕЙСТВИЯ ПО ОТНОШЕНИЮ К HDAC

Изобретение относится к соединению формулы (I), ! ! (значения радикалов изложены в формуле изобретения) или его фармацевтически приемлемым солям, к способам его получения, фармацевтической композиции, которая его содержит. Соединения обладают ингибирующей активностью в отношении HDAC. Описывается применение соединения для изготовления лекарственного средства, предназначенного для обеспечения ингибирующего действия по отношению к HDAC у теплокровного животного, при изготовлении средства, используемого для лечения злокачественного новообразования. Описывается также способ обеспечения ингибирующего действия у теплокровного животного. 10 н. и 5 з.п. ф-лы, 17 табл.

АМИДИНОВЫЕ СОЕДИНЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ ФАКТОР ХА ИНГИБИРУЮЩИМ ДЕЙСТВИЕМ

Описываются новые соединения амидина формулы (I), где R представляет группу формулы а), б) или с), R4 - атом водорода или атом галогена, R5 - атом водорода, циано-, карбокси- или низшая алкоксикарбонильная группа, R6 - атом водорода гидрокси-, карбокси-, низшая алкоксикарбонильная группа, фенильная группа, которая необязательно замещенная амидиногруппой; пиридил, необязательно замещенный 1-3 заместителями, выбранными из низшей алкильной группы, бензоиламиногруппы, хинолил, пиримидил, X2 - атом кислорода, атом серы, X3 - (СН2)m, где m равно 0, целому числу от 1 до 3, X4 - -C(=NH)-, -SO2NH-, пиридинил, или прямую связь; X5 - алкиленовая группа, содержащая 1-6 атомов углерода, алкениленовая группа, содержащая 2-6 атомов углерода, или прямая связь; R7 - атом водорода или группа где R9 - NH, NR11, где R11 - низшая алкильная группа, бензильная группа, R10 - низшая алкильная группа или аминогруппа, R8 - циклоалкильная группа, необязательно замещенная карбоксигруппой; фенильная группа, бензильная ...

2-(АРИЛФЕНИЛ)АМИНОИМИДАЗОЛИНОВЫЕ ПРОИЗВОДНЫЕ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к производным 2-(арилфенил)аминоимидазолина формулы I, где R1 обозначает группу формулы (А), (В) или (С), a R2, R3, R4, R5, R6 и Х такие, как определено в формуле изобретения. Также описана фармацевтическая композиция на основе этих соединений. Технический результат: получены новые соединения, обладающие ценными биологическими свойствами. Изобретение может быть использовано в области медицины в качестве лекарственного средства. 2 с. и 18 з.п.ф-лы, 2 ил., 4 табл.

ОПТИЧЕСКИ АКТИВНЫЕ ПРОИЗВОДНЫЕ БЕНЗОПИРАНА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ ЧУВСТВИТЕЛЬНЫХ К ЭСТРОГЕНАМ ЗАБОЛЕВАНИЙ

Изобретение относится к новым оптически активным производньм бензопирана формулы где R и R независимо выбраны из группы, состоящей из гидроксила и радикала, который может преобразовываться in vivo в гидроксил, такой как ацилокси, -OR4, -OC(O)R7 или -OC(O)OR4 (где R4 представляет собой алкил, алкенил, алкинил или арил; и R7 представляет собой амино, алкиламино, аминоалкил и алкилсульфанил); и R3 представляет собой -СН2- или -СН2СН2-; или его фармацевтически приемлемая соль, где указанное соединение или соль являются оптически активными, поскольку содержат более 50% (по массе относительно всех стереоизомеров) 2S стереоизомеров. Эти соединения обладают ингибирующей активностью в отношении полового стероида и могут использоваться при лечении чувствительных к эстрогенам заболеваний, таких как рак молочной железы и рак эндометрия. Изобретение относится также к фармацевтической композиции на основе этих соединений и способу лечения чувствительных к эстрогенам заболеваний. Технический результат ...

СПОСОБ ПОЛУЧЕНИЯ ПЛЕВРОМУТИЛИНОВ

Настоящее изобретение относится к способу получения 14-O-[(N-(3-метил-2-аминобутирилпиперидинил)сульфанил)ацетил]мутилинов формулы (I), заключающемуся в снятии защиты с N-защищенного пиперидинил-сульфанил-ацетил-мутилина формулы (II), выделением полученного соединения формулы (III) и его ацилированием с получением соединения формулы (IV) и последующим снятием защиты и выделением соединения формулы (I). Также изобретение относится к соединению формулы (IV), метансульфонатной соли соединения формулы (III), кристаллическому гидрохлориду 14-O-[(N-3-метил-2-(R)-аминобутирилпиперидин-3(S)-ил)сульфанил-ацетил]мутилина, способу его получения и фармацевтической композиции на его основе. Технический результат: разработан новый способ получения соединения формулы (I), отличающийся пониженными затратами времени, ресурсов и труда. 6 н. и 12 з.п. ф-лы, 2 пр.

ПРИМЕНЕНИЕ ПРОИЗВОДНЫХ N-ПИПЕРИДИНА ДЛЯ ЛЕЧЕНИЯ НЕЙРОДЕГЕНЕРАТИВНЫХ ПАТОЛОГИЙ

Настоящее изобретение относится к области фармацевтики и медицины и касается применения производных N-пиперидина для изготовления лекарственного средства для лечения нейродегенеративных патологий. Средство обеспечивает высокую эффективность лечения. 2 н. и 5 з.п. ф-лы, 2 ил., 2 табл.

ТРАНСДЕРМАЛЬНАЯ СИСТЕМА ДОСТАВКИ ДОНЕПЕЗИЛА

Изобретение относится к трансдермальной системе доставки для системной доставки донепезила. Предложенная система содержит: контактирующий с кожей адгезивный слой для приклеивания системы на кожу потребителя и резервуар лекарственного средства, содержащий (i) акрилатный сополимер, (ii) глицерин и (iii) основание донепезила, образующееся реакцией донепезила HCl и щелочной соли, где щелочная соль представляет собой бикарбонат натрия или бикарбонат калия. Также предложен способ доставки донепезила. Система предусматривается для лечения болезни Альцгеймера и достигает трансдермальной доставки терапевтического средства, которая биоэквивалентна пероральному введению терапевтического средства, а также обеспечивает стабильное и эффективное высвобождение средства в течение периода введения и имеет подходящую адгезию для длительного введения. 2 н. и 21 з.п. ф-лы, 10 ил., 5 табл., 5 пр.

ПРОИЗВОДНЫЕ ПИРИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ ДИПЕПТИДИЛПЕПТИДАЗЫ IV

Изобретение описывает новое соединение, представленное формулой I, ! где R1 и R2 являются одинаковыми или различными и каждый представляет собой: (1) С1-10алкильную группу, необязательно замещенную 1-3 заместителями, выбранными из С3-10циклоалкильной группы, C1-6алкоксикарбонильной группы b C1-6алкоксигруппы; (2) С6-14арильную группу, необязательно замещенную 1-3 заместителями, выбранными из атома галогена, карбоксильной группы, C1-6алкоксикарбонильной группы b карбамоильной группы; или (3) С7-13аралкильную группу; R3 представляет собой С6-14арильную группу, необязательно замещенную 1-3 заместителями, выбранными из C1-6алкильной группы, необязательно замещенной 1-3 атомами галогена, атома галогена, C1-6алкоксикарбонильной группы, карбоксильной группы, гидроксигруппы, Ci-балкоксигруппы, необязательно замещенной 1-3 атомами галогена; R4 представляет собой аминогруппу; L представляет собой С1-10алкиленовую группу; Q представляет собой связь, С1-10алкиленовую группу или С2-10алкениленовую группу ...

НОВОЕ ПРИМЕНЕНИЕ

Изобретение относится к области медицины и ветеринарии и касается применения 4-трифторметилбензилового эфира ! (S)-3-[3-(1-карбокси-1-метилэтокси)фенил]пиперидин-1-карбоновой кислоты в производстве лекарственного средства для паллиативной, профилактической или лекарственной терапии отрицательного энергетического баланса у жвачных животных, где данное заболевание выбрано из синдрома жировой инфильтрации печени, дистоции, иммунного нарушения, ослабленной иммунной функции, токсификации, первичных и вторичных кетозов, синдрома падающей коровы, расстройства пищеварения, утраты аппетита, задержки отделения плаценты, смещения сычуга, мастита, (эндо-)-метрита, бесплодия, низкой фертильности и хромоты. Изобретение обеспечивает высокую эффективность лечения. 2 н. и 4 з.п. ф-лы, 4 ил., 8 табл.

КОМБИНАЦИИ АКТИВАТОРОВ КАЛИЕВЫХ КАНАЛОВ И БЛОКАТОРОВ НАТРИЕВЫХ КАНАЛОВ ИЛИ АКТИВНЫХ ВЕЩЕСТВ, ВОЗДЕЙСТВУЮЩИХ НА НАТРИЕВЫЕ КАНАЛЫ, ДЛЯ ЛЕЧЕНИЯ БОЛЕВЫХ СОСТОЯНИЙ

Изобретение относится к медицине и биохимии и касается лекарственного средства из комбинации флупиртина или его фармацевтически применимых солей с толперизоном или его аналогами, эперизоном или силперизоном, или их терапевтически приемлемыми солями для лечения болевых состояний, которые сопряжены с повышенным мышечным тонусом. Изобретение обеспечивает синергический эффект в отношении снятия боли и расслабления мышц. 2 н. и 6 з.п. ф-лы, 6 табл.

АМИНОБЕНЗОФЕНОНЫ

Изобретение относится к новым производным аминобензофенонов общей формулы I, обладающих свойствами ингибитора интерлейкина-1β(IL-1β) и фактора некроза опухоли(ТМР-α). Соединения могут найти применение для получения лекарственного средства для лечения и профилактики заболеваний, связанных с регулирующей системой цитокинов, таких как воспалительные заболевания. Изобретение также относится к фармацевтическим композициям и применению. В общей формуле I ! ! Х является кислородом; R1 является (C1-C3)алкилом, R2 является одним или более, одинаковыми или разными заместителями, выбранными из группы, включающей водород и галоген; R3 является одним или более, одинаковыми или разными заместителями, выбранными из группы, включающей водород и галоген, R4 является водородом, R5 является водородом, R6 является (C1-C10)алкил-гетероциклилом, (C1-C10)алкилом, (C2-C10)олефиновой группой, гетероциклилом, Y1R21, Y2R22 или Y4R24; где (C1-C10)алкил, (C2-C10)олефиновая группа замещены одним или более одинаковыми ...

ИНГИБИТОРЫ ПРОТЕАЗ, РАСЩЕПЛЯЮЩИХ ЗА ПРОЛИНОМ

Изобретение относится к соединениям формулы 1 и их фармацевтически приемлемым солям в качестве ингибиторов пост-пролиновых аминопептидаз, а также к фармацевтической композиции на их основе и применение для изготовления такой композиции, и способу ингибирования с их использованием. Соединения могут найти применение для лечения заболеваний, опосредованных активностью пост-пролиновых аминопептидаз, таких как диабет типа II и нарушеной толерантности к глюкозе. В общей формуле 1 либо G1 представляет собой -CH2-Х2-(CH2)а-G3, и G2 представляет собой Н, либо G2представляет собой -CH2-(CH2)a-G3, и G1 представляет собой Н; G3 выбран из группы согласно общей формуле 2, группы согласно общей формуле 3 и группы согласно общей формуле 4; а равно 0, 1 или 2; b равно 1 или 2; X1 выбран из СН2, S, CF2, CHF и О; X2выбран из CH2; X3, X4 и X5 выбраны из N; X6 выбран из NH; X7 выбран из NH; R1 выбран из Н и CN; R2 представляет собой Н; R3 выбран из Н, Cl, ОН, NH2, NH-C1-С10алкила и N(С1-С10алкил)2; R4, R5, ...

ПРОИЗВОДНОЕ ЦИКЛИЧЕСКОГО АМИНА, СОДЕРЖАЩЕЕ ГЕТЕРОАРИЛЬНЫЙ ЦИКЛ

Настоящее изобретение относится к соединениям, проявляющим активность в ингибировании агрегации тромбоцитов, их фармакологически приемлемым солям. Конкретно к соединениям, имеющим общую формулу (I) (где R1 представляет собой С1-С6 алкил и т.д., R2 представляет собой водород, С2-С7 алканоил, С7-С11 арилкарбонил, группу формулы R4-(CH2)1- и т.д., R3 представляет собой С6-С10 арил и т.д., X1, X2, X3, X4 и X5независимо представляют собой каждый водород, галоген и т.д. и n представляет собой целое число от 0 до 2), его фармакологически приемлемые соли. В соответствии с настоящим изобретением предлагаются фармацевтические композиции, ингибирующие активацию тромбоцитов и содержащие в качестве активного начала заявляемые соединения. Указанные соединения пригодны в качестве средств для профилактики и лечения заболеваний, связанных с тромбо- или эмболообразованием. 3 н. и 23 з.п. ф-лы, 8 табл.

НАПРАВЛЕННАЯ РЕГЕНЕРАЦИЯ ПЕРЕЛОМАННОЙ КОСТИ ПОСРЕДСТВОМ СТИМУЛЯЦИИ РЕЦЕПТОРА ПАРАТИРЕОИДНОГО ГОРМОНА

Изобретение относится к соединению, имеющему структуру: X-Y-Z; где: X представляет собой полипептид, имеющий по меньшей мере на 80% идентичность последовательности с SEQ ID NO: 3; Z представляет собой молекулу, осуществляющую доставку в кости, содержащую 4 или более кислых аминокислотных остатка, полифосфат, аминоадипиновую кислоту, алендронат и/или бисфосфонат; и Y представляет собой линкер, содержащий полипептид, имеющий по меньшей мере на 80% идентичность последовательности с аминокислотными остатками 35-46 полноразмерного родственного паратиреоидному гормону пептида; или его фармацевтически приемлемой соли, а также к способу лечения перелома кости. Технический результат: разработана система доставки лекарственного средства, которая корректирует некоторые побочные эффекты, вызываемые свободным анаболическим лекарственным средством, такие как высокая концентрация кальция в крови. 3 н. и 12 з.п. ф-лы, 27 ил., 1 табл., 4 пр.

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ПИПЕРИДИНА И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описываются новые замещенные производные пиперидина общей формулы I, где R1 - бензотиенил или тиенил, замещенный С1-6-алкилом; R2 - фенил, замещенный галогеном; R3 - -(СН2)mХСОNR4R5 или -(СН2)mNR6COR7, где R4 и R5 вместе с атомом N, к которому они присоединены, образуют 4-, 5- или 6-членную гетероциклическую группу; Х - связь или фенил; R6 - водород или С1-6-алкил; R7 - С3-6-циклоалкил или фенил, возможно замещенный С1-6-алкилом; m - целое число 1, 2, 3 или 4, их фармацевтически приемлемые соли или сольваты и фармацевтическая композиция, их содержащая. Описываемые соединения обладают нейролептическим действием и могут применяться при лечении психотических расстройств. 2 с. и 2 з.п. ф-лы, 2 табл.

СИНЕРГИЧНЫЙ ФАРМАЦЕВТИЧЕСКИЙ СОСТАВ ДЛЯ ПРОФИЛАКТИКИ ИЛИ ЛЕЧЕНИЯ ДИАБЕТА

Изобретение относится к лекарственным средствам и касается синергичного фармацевтического состава, включающего: (а) первую фармацевтическую композицию, содержащую противодиабетический активный агент, выбранный из группы, состоящей из инсулина, метформина и глибурида, или антигиперлипидемический активный агент, выбранный из группы, состоящей из ловастатина и симвастатина, и один или более стандартных носителей, и (b) вторую фармацевтическую композицию, содержащую O-(3-пиперидино-2-гидрокси-1-пропил)-никотинамидоксим или его фармацевтически приемлемую соль и один или более стандартных носителей. Фармацевтический состав пригоден для профилактики или лечения инсулинорезистентности, метаболического Х-синдрома или сахарного диабета типа 2. Состав по изобретения обладает высокой эффективностью при более низких дозах, что приводит к снижению токсичности лечения. 2 н. и 1 з.п. ф-лы, 5 табл.

3- ИЛИ 4-ЗАМЕЩЕННЫЕ ПИПЕРИДИНОВЫЕ СОЕДИНЕНИЯ

Описываются рацемически или энантиомерно обогащенные соединения 3-замещенного пиперидина общей формулы (I)или их фармацевтически приемлемые соли, где A означает фенил, нафтил, возможно замещенные, или бензотиофенил; B - азол, выбранный из группы, состоящей из триазола, бензотриазола, 5-метил- или 5-фенилтетразола;Y - CHи X - N-R, где R - водород или Cалкил, фармацевтические композиции, содержащие данные соединения, и способы лечения депрессии, тревожности и болевого расстройства у млекопитающего. 7 н. и 4 з.п. ф-лы, 4 табл., 126 прим.

БИЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ ВЗАИМОДЕЙСТВИЯ/АКТИВАЦИИ PD1/PD-L1

Изобретение относится к соединениям формулы I, их стереоизомерам и фармацевтически приемлемым солям, которые являются ингибиторами активации PD-1/PD-L1. В формуле (I) X1 выбирают из -CH2O-; R4 выбирают из водорода; X выбирают из CR3 или N; R1, R2, R3, R6 и R7 независимо выбирают из водорода, галогена, C1-6 алкила, (4-10-членный гетероциклоалкил)-C1-4 алкила-, ORa или C(O)ORa, где C1-6 алкил и (4-10-членный гетероциклоалкил)-C1-4 алкил- независимо необязательно замещены 1, 2 или 3 Rb заместителями, и 4-10-членный гетероциклоалкил имеет 1-3 гетероатома, выбранных из азота и кислорода, и является моно- или бициклическим; Ra выбирают из C1-6 алкила, C1-4 галоалкила, C6-10 арил-C1-4 алкила-, C3-10 циклоалкил-C1-4 алкила-, (5-10-членный гетероарил)-C1-4 алкила- или (4-10-членный гетероциклоалкил)-C1-4 алкила-, где C1-6 алкил, C6-10 арил-C1-4 алкил-, C3-10 циклоалкил-C1-4 алкил-, (5-10-членный гетероарил)-C1-4 алкил- и (4-10-членный гетероциклоалкил)-C1-4 алкил- независимо необязательно замещены ...

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ БЕНЗОЛА ИЛИ ИХ СОЛИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Описывается производное бензола формулы (I) или его соль где X1 обозначает -C(=O)-NR5-, -NR5-С(=O)-; X2 обозначает -NR6-C(=O)-, -NR6-СН2-; R1 - атом галогена, низший алкил или низшая алкоксигруппа; R2 и R3 - атом водорода или галогена; R4 - атом водорода, -SO3Н- или остаток сахара; кольцо А - кольцо бензола или пиридина; кольцо В - кольцо пиперидина, а также фармацевтическая композиция на его основе. Предложенные соединения обладают антикоагулирующим действием, основанным на ингибировании актированного фактора Х коагуляции крови, и полезны в качестве антикоагулянтов или профилактических агентов против болезней, вызываемых тромбозом или эмболией. 2 н. и 3 з.п. ф-лы, 9 табл.

Способы применения производных циклического амида для лечения опосредуемых сигма-рецепторами расстройств

Настоящая группа изобретений относится к медицине, а именно к неврологии и психиатрии, и касается применения циклического амида для лечения опосредуемых сигма-рецепторами расстройств. Для этого вводят эффективное количество соединения формулы. Это обеспечивает эффективное лечение депрессии за счет селективного связывания данного соединения с сигма-2-рецепторами. 2 н. и 15 з.п. ф-лы, 2 пр.

СПОСОБ ПОДАВЛЕНИЯ ВЫЦВЕТАНИЯ СО ВРЕМЕНЕМ АДГЕЗИВНОЙ КОМПОЗИЦИИ, СОДЕРЖАЩЕЙ ДОНЕПЕЗИЛ

Изобретение относится к медицине. Описана донепезил адгезивная композиция, содержащая донепезил. По меньшей мере один вид стабилизатора, выбранного из группы, состоящей из аскорбиновой кислоты, металлической соли или сложного эфира таковой, изоаскорбиновой кислоты или металлической соли таковой, этилендиаминтетрауксусной кислоты или металлической соли таковой, 2-меркаптобензимидазола, 3(2)-трет-бутил-4-гидроксианизола, 2,6-ди-трет-бутил-4-метилфенола, тетракис[3-(3′,5′-ди-трет-бутил-4′-гидроксифенил)]пропионата пентаэритрита, (±)-α-токоферола, (±)-α-токоферолацетата, рутина, гипофосфорной кислоты, метабисульфитной соли металла и металлической соли гидроксиметансульфиновой кислоты, примешивают в слой приклеивающегося при надавливании клеевого средства, который содержит отверждаемое под давлением клеевое средство и донепезил. Содержащая донепезил адгезивная композиция подавляет выцветание с течением времени. 2 з.п. ф-лы, 3 табл.

ЦИКЛИЧЕСКОЕ ПРОИЗВОДНОЕ АМИНА, СОДЕРЖАЩЕЕ ЗАМЕЩЕННУЮ АЛКИЛЬНУЮ ГРУППУ

Изобретение относится к новым соединениям, имеющим общую формулу (I), представленную ниже, ! ! где R1 представляет собой атом водорода, С1-С6 алкильную группу, С3-С6 циклоалкильную группу или С1-С6 алкоксигруппу; R2 представляет собой атом водорода или С1-С6 алкильную группу; R3 представляет собой замещенную С1-С6 алкильную группу {указанный заместитель представляет собой гетероциклильную группу или гетероциклильную группу, замещенную от 1 до 5 заместителями, выбранными из <группы заместителей α> (указанные гетероциклильные группы могут быть замещены от 1 до 4 оксогруппами); гетероарильную группу или гетероарильную группу, замещенную от 1 до 5 заместителями, выбранными из <группы заместителей α>; или заместитель, выбранный из <группы заместителей β>}, или гетероциклильную группу или гетероциклильную группу, замещенную от 1 до 5 заместителями, выбранными из <группы заместителей α> (указанные гетероциклильные группы могут быть замещены от 1 до 4 оксогруппами); где гетероарильная группа представляет ...

ПРОИЗВОДНЫЕ НАФТАЛИНА, ПРИГОДНЫЕ В КАЧЕСТВЕ ЛИГАНДОВ РЕЦЕПТОРОВ 3 ГИСТАМИНА

Изобретение относится к новым производным нафталина формулы I , а также к их фармацевтически приемлемым солям, которые могут найти применение для лечения и/или профилактики заболеваний, связанных с модулированием Н-3 рецепторов. В формуле I R1 выбран из водорода, низшего алкила, фенила, фенила-низшего алкила и низшего алкоксиалкила; R2 выбран из водорода, низшего алкила, С3-С7-циклоалкила, низшего алкоксиалкила или низшего алкилсульфанилалкила (все значения R1 и R2 приведены в формуле изобретения); или R1 и R2 вместе с атомом азота, к которому они присоединены, образуют 4-7-членное насыщенное или частично ненасыщенное гетероциклическое кольцо, которое может содержать еще один гетероатом, выбранный из атомов азота, кислорода и серы, где указанное гетероциклическое кольцо может быть незамещенным или замещенным 1-2 группами, либо оно может быть конденсировано с незамещенным фенильным кольцом; ! А выбран из ! или ! (значения R3-R7, R9, R10, X, m, n, t, p, q и s приведены в формуле изобретения ...

КОМБИНАЦИЯ ЧАСТИЧНОГО АГОНИСТА НИКОТИНОВЫХ РЕЦЕПТОРОВ И ИНГИБИТОРА АЦЕТИЛХОЛИНЕСТЕРАЗЫ, СОДЕРЖАЩАЯ ЕЕ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ЕЕ ПРИМЕНЕНИЕ В ЛЕЧЕНИИ КОГНИТИВНЫХ РАССТРОЙСТВ

Изобретение относится к комбинации частичного агониста никотиновых рецепторов типа альфа 7 и ингибитора ацетилхолинестеразы, предназначенной для лечения когнитивных расстройств, отличающейся тем, что частичный агонист никотиновых рецепторов типа альфа 7 является (2Е)-бут-2-ендиоатом 4-бромфенил-1,4-диазабицикло[3.2.2]нонан-4-карбоксилатом и ингибитор ацетилхолинестеразы выбран из ривастигмина и донепезила, к фармацевтической композиции, к набору, содержащим комбинацию по изобретению, и к ее применению в лечении когнитивных расстройств. Показан лучший эффект комбинации по шкале про-когнитивных фармакологических эффектов по сравнению с эффектом, который дают оба активные вещества, взятые отдельно. 4 н. и 3 з.п. ф-лы, 5 ил., 3 табл.

КОМБИНАЦИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ ПАЦИЕНТОВ, СТРАДАЮЩИХ ДЕПРЕССИЕЙ

Изобретение может быть использовано в медицине для лечения пациентов, страдающих депрессией. Предложена комбинация, включающая миртазапин или его фармацевтически приемлемую соль и один или несколько селективных ингибиторов обратного захвата серотонина или их фармацевтически приемлемые соли. Фармацевтическая композиция включает комбинацию указанных компонентов и один или более фармацевтически приемлемых носителей. Способ лечения пациентов от депрессии осуществляется введением терапевтически эффективного количества комбинации или композиции. 3 с. и 4 з.п. ф-лы.

ПРОЛЕКАРСТВА МНОГОФУНКЦИОНАЛЬНЫХ ПРОИЗВОДНЫХ НИТРОКСИДА И ИХ ПРИМЕНЕНИЕ

Изобретение относится к пролекарствам соединений, содержащим донор оксида азота и катализатор разложения активных форм кислорода (АФК), в частности 1-пирролидинилокси-, 1-пиперидинилокси- и 1-азепанилоксипроизводные, и содержащим их фармацевтические композиции. Указанные соединения и фармацевтические композиции являются подходящими для предотвращения, лечения или контролирования заболеваний, расстройств или состояний, связанных с окислительным стрессом или эндотелиальной дисфункцией. 4 н. и 13 з.п. ф-лы, 7 ил., 11 табл., 17 пр.

ПРОИЗВОДНЫЕ 1-[М-КАРБОКСАМИДО(ГЕТЕРО)АРИЛ-МЕТИЛ]-ГЕТЕРОЦИКЛИЛ-КАРБОКСАМИДА

Изобретение относится к соединениям 1-[m-карбоксамидо(гетеро)арил-метил]-гетероциклил-карбоксамида формулы (I)в которой Arпредставляет собой группу фенилена или 5- или 6-членную группу гетероарилена, которая означает 5-6-членное моноциклическое или бициклическое ароматическое кольцо, содержащее от одного до максимально четырех гетероатомов, каждый из которых независимо выбран из кислорода, азота и серы; при этом группа -CHR- и группа -NH-CO-X-Rв Формуле (I) присоединены в мета-расположении к кольцевым атомам углерода Ar; при этом указанный фенилен или 5- или 6-членный гетероарилен независимо является незамещенным или монозамещенным, где заместитель выбран из группы, которая включает (С)алкил, (С)алкокси, галоген, (С)фторалкил и (С)фторалкокси; X представляет собой • прямую связь; • -(С)алкилен- который необязательно является монозамещенным, где заместитель представляет собой гидрокси; • -(С)циклоалкилен-; • -СН-О-, при этом кислород связан с группой R; или • -СН=СН-; Rпредставляет собой ...

КОМБИНАЦИЯ АНТАГОНИСТА 5-HT6-РЕЦЕПТОРА И ИНГИБИТОРА АЦЕТИЛХОЛИНЭСТЕРАЗЫ ДЛЯ ПРИМЕНЕНИЯ ПРИ ЛЕЧЕНИИ БОЛЕЗНИ АЛЬЦГЕЙМЕРА У СУБПОПУЛЯЦИИ ПАЦИЕНТОВ, КОТОРЫЕ ЯВЛЯЮТСЯ НОСИТЕЛЯМИ АЛЛЕЛЕЙ APOE4

Группа изобретений относится к области медицины и фармацевтики. Первое изобретение – применение комбинации антагониста 5-НТ6-рецептора, представляющего собой N-(2-(6-фтор-1Н-индол-3-ил)-этил)-3-(2,2,3,3-тетрафторпропокси)-бензиламин или его фармацевтически приемлемую соль, и ингибитора ацетилхолинэстеразы, представляющего собой донепезил или его фармацевтически приемлемую соль, для лечения болезни Альцгеймера, где пациент является носителем одного или двух аллелей ApoE4. Второе изобретение – применение фармацевтической композиции, содержащей указанную комбинацию, для лечения болезни Альцгеймера, где пациент является носителем одного или двух аллелей ApoE4. Третье изобретение – способ лечения болезни Альцгеймера, при котором пациент является носителем одного или двух аллелей ApoE4 и подвергается лечению ингибитором ацетилхолинэстеразы, представляющим собой донепезил или его фармацевтически приемлемую соль, при этом способ включает дополнительное введение антагониста 5-HT6-рецептора, представляющего ...

КОМПОЗИЦИИ ДЛЯ ЛЕЧЕНИЯ И ПРОФИЛАКТИКИ ВАЗОМОТОРНЫХ СИМПТОМОВ

Изобретение относится к способу лечения или профилактики вазомоторных симптомов у женщин, таких как приливы и потливость, включающему введение 50 мг в день антагониста меластатина-8 с транзиторным рецепторным потенциалом (TRPM8), представляющего собой 4-({(4-циклопропилизохинолин-3-ил)[4-(трифторметокси)бензил]амино}сульфонил)бензойную кислоту, а также применению антагониста TRPM8, представляющего собой 4-({(4-циклопропилизохинолин-3-ил)[4-(трифторметокси)бензил]амино}сульфонил)бензойную кислоту, для лечения или предотвращения вазомоторных симптомов. Технический результат: лечение вазомоторных симптомов у женщин путем введения 4-({(4-циклопропилизохинолин-3-ил)[4-(трифторметокси)бензил]амино}сульфонил)бензойной кислоты в дозе 50 мг в день. 2 н. и 11 з.п. ф-лы, 4 ил., 1 табл., 2 пр.

ИНГИБИТОРЫ ФУКОЗИДАЗЫ

Изобретение относится к соединению формулы I, обладающему свойствами ингибиторов ферментов фукозидаз, и его применению для лечения опухоли или ракового заболевания, представляющего собой рак печени. В общей формуле I X1, X2 и X3 представляют собой OH; R представляет собой C1-3алкил; R1 представляет собой H; R2 выбран из группы, состоящей из -NRbC(O)Ra, и -C(O)NRbRa; Ra обозначает ; и Rb представляет собой H. 3 н. и 5 з.п. ф-лы, 3 ил., 9 табл., 10 пр. (I) ...

КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ СРЕДСТВО ПРОТИВ ДЕМЕНЦИИ

Изобретение относится к области медицины. Предложено лекарственное средство против деменции, содержащее донепезил или его фармацевтически приемлемую соль и мемантин или его фармацевтически приемлемую соль. Лекарственное средство содержит часть с длительным высвобождением, содержащую независимое от рН полимерное вещество и зависимое от рН полимерное вещество. Содержание зависимых от рН полимерных веществ в пересчете на 1 часть по массе независимых от рН полимерных веществ в каждой части с длительным высвобождением составляет в целом от 0,1 до 10 частей по массе. Изобретение обеспечивает композицию, содержащую 2 вида средств против деменции, в которой высвобождение средств является контролируемым, посредством чего достигается комбинированный эффект при лечении деменции. 8 з.п. ф-лы, 5 ил., 9 пр.

ЗАМЕЩЕННЫЕ 1,2,3,4,5,6-ГЕКСАГИДРО-2,6-МЕТАНО-3-БЕНЗАЗОЦИН-10-ОЛЫ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к производным бензазоцинола общей формулы (I), где X, R1, R2, R3, R4, R5, R6 и R7 такие, как определено в формуле изобретения. Также описана фармацевтическая композиция для блокирования зависимого от напряжения натриевого канала на основе этих соединений. Технический результат: получены новые соединения, обладающие ценными биологическими свойствами. Изобретение может быть использовано в медицине в качестве лекарственного средства. 2 с. и 8 з.п.ф-лы, 1 табл.

ГЕТЕРОАРИЛ-1-ПИПЕРИДИНЫ И ПИПЕРАЗИНЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ, СПОСОБ ЛЕЧЕНИЯ ПСИХОЗОВ И ОСЛАБЛЕНИЯ БОЛИ

Описываются гетероарил-1-пиперидины и пиперазины общей формулы (I), где Х представляет собой О, S, NH или М(R2), R2 выбран из группы: бензоил, (С2-С18)алканоил и алкоксикарбонил, р = 1, Y - водород, хлор, фтор, Q - пиперидинил или пиперазинил, замещенный в 1 положении Y2, Y2 выбирают из 21 группы. Описываются также фармацевтическая композиция на основе этих соединений, способ ослабления боли и лечения психозов с использованием соединений, а также 1-[4-(3-хлорпропокси)-3-метоксифенил]-2-гидроксиэтанон, являющийся исходным соединением в синтезе соединений формулы (I). Технический результат - антипсихотические и анальгетические свойства соединений позволяют использовать их для ослабления боли и лечения психозов. 13 с. и 112 з. п. ф-лы, 2 табл.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Изобретение относится к медицине. Фармацевтические композиции, включают в себя усилитель чувствительности к инсулину в сочетании с другими антидиабетическими препаратами, отличными от указанного усилителя по механизму действия, которые могут применяться для профилактики и лечения диабета. Предложенные композиции оказывают более сильное подавляющее действие в отношении гипергликемии. 2 с. и 31 з.п. ф-лы, 2 табл.

ПОЛИЦИКЛИЧЕСКОЕ СОЕДИНЕНИЕ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ СВОЙСТВАМИ АНТАГОНИСТА РЕЦЕПТОРА H3, И СПОСОБ ЛЕЧЕНИЯ С ЕГО ПРИМЕНЕНИЕМ

Изобретение относится к новым полициклическим соединениям формулы (I), в которой радикалы и символы имеют значения, определенные в формуле изобретения. Соединения формулы (I) обладают свойствами антагониста рецептора Н3. Объектами изобретения также являются фармацевтическая композиция, содержащая соединения формулы (I), и способ лечения болезни из группы, включающей заложенность носа, ожирение, сонливость, нарколепсию, дефицит внимания с гиперактивностью, болезнь Альцгеймера и шизофрению, с использованием соединений формулы (I) необязательно в комбинации с антагонистом рецептора H1. 3 н. и 36 з.п. ф-лы, 3 табл.

4-ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ПИПЕРИДИНА И СПОСОБ ИХ ПОЛУЧЕНИЯ

Изобретение относится к новым 4-замещенным производным пиперидина, относящимся к непептидным антагонистам нейрокинина 2 (НК2), которые могут быть использованы, например, при лечении таких заболеваний, как астма, и способу их получения. 4-Замещенные производные пиперидина соответствуют общей формуле I, где значения m, D, G, J, L, М, Δ имеют значения, указанные в формуле изобретения. Способ получения соединений формулы I заключается в том, что соединение формулы I подвергают конденсации с диактивированным карбонильным или тиокарбонильным производным, соответственно, с последующим при необходимости окислением полученного пиперидинового производного для получения N-оксида, или алкилированием соединения, где R12 - алкил. 2 с. и 7 з.п. ф-лы, 3 ил., 1 табл.

ТАБЛЕТКА ПАРАЦЕТАМОЛА И ДОМПЕРИДОНА С ПЛЕНОЧНЫМ ПОКРЫТИЕМ

Таблетка содержит ядро и пленочное покрытие. Ядро включает парацетамол и домперидон в качестве активных ингредиентов и фармацевтически приемлемый носитель. При изготовлении таблетки осуществляют влажное гранулирование активных ингредиентов с фармацевтически приемлемым носителем, сухое перемешивание полученного гранулята, прессование смеси в таблетки и покрытие таблеток пленочной оболочкой. При лечении пациента, страдающего мигренью, ему вводят терапевтически эффективное количество лекарственного средства, содержащего гранулированную смесь парацетамола и домперидона. Совместное введение домперидона и парацетамола в виде одной таблетки обеспечивает удобство для пациента при приеме лекарства для лечения мигрени. Таблетка имеет наименьший возможный размер и при этом содержит требуемую дозу около 500 мг парацетамола и около 10 мг домперидона на дозированную единицу. 4 с. и 9 з. п. ф-лы, 2 табл.

ПРОИЗВОДНЫЕ ПИПЕРИДИНА ИЛИ ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ

Производные пиперидина общей формулы I, где R2, R3 каждый представляет водород или R2 - Н и R3 - ОН; R4 - фенил, фурил, пиридил, 1,3,4-оксадиазол-2-ил или 2-имидазолил, возможно замещенные галогеном, гидрокси, алкилом, алкоксилом, СООRk, Rk - алкил, -СОNR1Rm, R1, Rm - H, алкил, S(O)nRN, RN - алкил; n = 0, 1 или 2, или R2 и R4 вместе с бирадикалом X1 и атомом углерода, к которому они присоединены, могут образовывать спироциклическое кольцо - спиро(изобензофуран-1/3Н/-4'-пиперирин) или оксоспиро(изобензофуран-1/3Н/-4'-пиперирин), R3 - Н, или их фармацевтически приемлемые соли проявляют свойства антагониста NКА. 6 с. и 10 з.п.ф-лы, 3 ил.,1 табл.

ЗАМЕЩЕННЫЕ АМИНОАЛКИЛАМИНОПИРИДИНЫ И ЛЕКАРСТВЕННОЕ СРЕДСТВО НА ИХ ОСНОВЕ

Замещенные аминоалкиламинопиридины формулы I, где R1, R2 - H; R3 - галоген или алкил; A, R4- С1-7алкил; n - 0 или 1; Х обозначает N или СН; R5 - С1-7 алкил или Аr-С1-4 алкил; Аr - фенил, нафтил, фурил или замещенный на R7, R8 и R9 фенил, или R5 и R6 вместе с атомом азота, с которым они связаны, образуют возможно замещенный 5-, 6- или 7-членный гетероцикл (другие обозначения см. в п.1 формулы изобретения). Соединения формулы I эффективны против бактерий Helicobacter, что позволяет применять их в качестве действующих веществ при лечении заболеваний, вызываемых этим видом бактерий. 2 с. и 4 з. п. ф-лы, 1 ил., 1 табл.

СУЛЬФОНАМИДНЫЕ ИНГИБИТОРЫ HIY - АСПАРТИЛ-ПРОТЕАЗЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ЛЕЧЕНИЯ, СПОСОБ ИДЕНТИФИКАЦИИ ИНГИБИТОРА

Изобретение относится к новому классу сульфонамидов, которые являются ингибиторами аспартил-протеазы формулы I. Изобретение относится к новому классу H1У аспартил-протеазных ингибиторов, отличающемуся специфическими структурными и физико-химическими характеристиками. Изобретение относится также к фармацевтическим композициям, содержащим эти соединения. Соединения и фармацевтические композиции изобретения особенно подходят для ингибирования Н1У-1 и Н1У-2 протеазной активности, и, соответственно, их можно с выгодой использовать в качестве вирусных агентов против Н1У-1 и Н1У-2 вирусов. Изобретение относится также к способам ингибирования активности Н1У аспартил-протеазы, за счет использования соединений настоящего изобретения, и способам скринирования соединений по их анти-HIУ активности. 5 с. и 21 з.п. ф-лы, 3 ил., 8 табл.

ПРОИЗВОДНЫЕ ТЕТРАГИДРОПИРАНА И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Изобретение относится к новым соединениям формулы (I), в которой R1 представляет собой группу формулы (Iа) или (Iв), в которых либо R7 представляет собой необязательно защищенную гидроксигруппу, ацилоксигруппу, галоген, -OR10, где R10 представляет собой низший алкил, необязательно защищенный -O(СН2)mOН, где m = 2 - 4, или -ОСОNН2, и R7a - водород, либо R7 и R7a вместе представляют собой оксогруппу, R8 представляет собой гидрокси- или метоксигруппу и R9 - гидрокси- или ацилоксигрупа; R2 - водород, ацилоксигруппа или необязательно защищенная гидроксигруппа, и между двумя атомами углерода, соединенными пунктирной линией, существует простая или двойная связь; R3 - метил, этил, н-пропил или аллил; либо R4 представляет собой водород или гидроксигруппу, а R4a - водород, либо R4 и R4a вместе представляют собой оксогруппу; либо R5 представляет собой гидроксигруппу, а R5a - водород, либо R5 и R5a вместе представляют собой оксогруппу; и А представляет собой группу формулы -СН(OR6)-СН2-(СН2)n или-СН ...

ПРОИЗВОДНЫЕ ПИПЕРИДИНА И ПИПЕРАЗИНА, СПОСОБ ИХ ПОЛУЧЕНИЯ, СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И СПОСОБ ИХ ПОЛУЧЕНИЯ

Производные пиперидина и пиперазина формулы I, где Ind - индол-3-ильный остаток, однократно замещенный ОН, ОА, CN или COR2; R1 - бензофуран, 2,3-дигидрофуран-5-ил, хроман-6-ил, возможно однократно замещенный СН2ОН или COR2; Q - СmН2m; Z - N или CR3; А - C1-6-алкил; R2 - ОН, ОА, NH2; m = 2, 3, 4, а также их физиологически приемлемые соли оказывают воздействие на центральную нервную систему, прежде всего 5-НТ1A-агонистические и 5-HT-Reupt ake-подавляющие действия. 4 c. и 1 з. п. ф-лы, 1 табл.

ПРОИЗВОДНЫЕ АМИНА И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Производные амина формулы I где R - галоид, гидроксил, C1-3-алкил, C1-3 -алкоксил; Q - остаток формулы (IIа), (IIб) V - метилен или этилен, Х - C0-2-алкиленовая цепь, X' - C1-4-алкиленовая цепь, Т-фенил, пиридил, пиразинил, бензо[b]фуранил, 1,4-бензодиоксанил, хиназолинил, возможно замещенные галоидом, метоксилом или трифторметилом, m = 0 или 1, и их фармацевтически приемлемые соли, обладают высоким сродством в отношении рецепторов 5-HT1 и D2. 2 с. и 4 з.п. ф-лы, 1 табл.

Кристаллическая β-модификация 3-(4-амино-1-оксо-1,3-дигидро-2Н-изоиндол-2-ил)-пиперидин-2,6-диона, способ её получения и фармацевтическая композиция на её основе

Изобретение касается новой кристаллической модификации 3-(4-амино-1-оксо-1,3-дигидро-2Н-изоиндол-2-ил)-пиперидин-2,6-диона (леналидомид - международное непатентованное название), названной β-модификацией, характеризующейся следующим набором межплоскостных расстояний (d, Å) и соответствующих им интенсивностей (I, %): 12,358 - 8,39%; 11,893 - 29,79%; 11,551 - 100,00%; 8,606 - 8,39%; 7,641 - 4,62%; 7,024 - 8,05%; 5,927 - 8,05%; 5,811 - 19,86%; 5,262 - 28,42%; 5,117 - 9,42%; 4,850 - 5,99%; 4,595 - 5,99%; 4,215 - 10,45%; 4,011 - 6,68%; 3,948 - 11,47%; 3,877 - 51,88%; 3,843 - 39,73%; 3,698 - 16,44%; 3,426 - 6,51%; 3,316 - 4,97%; 3,201 - 5,14%; 3,103 - 4,45%; 3,025 - 3,42%; 2,989 - 2,91%; 2,905 - 9,93%; 2,846 - 5,99%; 2,826 - 5,65%; 2,702 - 10,27%; 2,640 - 7,88%; 2,555 - 10,27%; 2,478 - 7,19%; 2,339 - 6,51%; 2,647 - 23,12%; 2,282 - 11,82%; 2,243 - 9,93%; 2,168 - 5,82%; 2,107 - 9,08%; 2,081 - 7,36%; 2,066 - 10,96%; 2,027 - 9,76%; 1,943 - 5,65%; 1,912 - 24,83%; 1,795 - 4,45%; 1,719 - 4,62%; 1,694 ...

СРЕДСТВО ДЛЯ ИНГИБИРОВАНИЯ НЕЙРОТОКСИЧНОСТИ, ВЫЗЫВАЕМОЙ БЕТА-АМИЛОИДНЫМИ ПЕПТИДАМИ

Изобретение относится к медицине, конкретно к фармакологии. Предложено средство для ингибирования нейротоксичности, вызываемой β-амилоидными пептидами. В качестве такого средства предложено соединение общей формулы (I), ранее известное как антиэстроген где R1 и R2 независимо друг от друга представляют собой водород; где Ar - необязательно эамещенный фенил; R2 выбирается из группы, состоящей из пирролидино и пиперидино, или его фармацевтически приемлемой соли или сольвата. Изобретение расширяет арсенал средств указанного назначения. 1 з.п.ф-лы.

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ АЗОЛОНА, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Для получения лекарственных средств, предназначенных для лечения связанных с Helicobacter заболеваний, применяют соединения формулы (I), их фармацевтически приемлемые соли с кислотами или их стереохимические изомеры, где Х и У каждый независимо представляет СH или N; R1; R2 и R3 каждый независимо представляет водород или С1-С4-алкил; R4 и R5 каждый независимо представляет водород, галоген, С1-С4-алкил, С1-С4 -алкилоксигруппу, гидроксигруппу, трифторметил, трифторметилоксигруппу или дифторметилоксигруппу; Z - представляет С=О или СНОН и Ar представляет фенил, возможно замещенный вплоть до трех заместителями выбранными из гидроксигруппы, С1-С4-алкила, С1-С4-алкилоксигруппы, галогена, трифторметила, три(С1-С4 -алкил)силилоксигруппы, или пиридинил, замещенный гидроксигруппой и С1-С4-алкилоксигруппой, и (А) представляет радикал формул (а-1), (а-2), (а-3), (а-4), (а-5). Описывается способ их получения, а также фармацевтический препарат, содержащий в качестве активного компонента замещенные производные ...

СПОСОБЫ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ ТРАНС-6-[2-ЗАМЕЩЕННЫЙ-ПИРРОЛ-1-ИЛ)АЛКИЛ]-ПИРАН-2-ОНА, ИХ ДИГИДРОКСИСОДЕРЖАЩИХ КИСЛОТ И СОЛЕЙ, ГИДРОКСИ- ИЛИ 1,3-ДИОКСАН ИЛИ ПИРРОЛСОДЕРЖАЩИЕ КАРБОНОВЫЕ КИСЛОТЫ В КАЧЕСТВЕ ПРОМЕЖУТОЧНЫХ ПРОДУКТОВ ДЛЯ ПОЛУЧЕНИЯ УКАЗАННЫХ ПРОИЗВОДНЫХ ПИРАН-2-ОНА

Производные транс-6-[2-(замещенный-пиррол-1-ил)алкил]-пиран-2-она формулы I, где R1 - фенил, возможно замещенный F, Cl или Br, R2, R3 - Н, алкил, фенил или -CONR5R6; R5, R6 - Н, алкил, фенил, возможно замещенный F, С1 или Br; R4 - С1-C6-алкил, получают взаимодействием соединения II с соединением формулы III с последующим взаимодействием полученного промежуточного продукта формулы IV с R102ВОСН3 или R103B с последующим взаимодействием с бораном в среде растворителя. Полученное соединение NC-CH2CH (ОН)-СН2СН(ОН)-СН2-СO-NR8R9 подвергают реакции с реагентом R11R12C(OCH3)2 или R11R12CO в присутствии кислоты. Полученный кеталь формулы V гидрируют и вводят в реакцию с соединением R1 COCHR2CHR3COR4. Полученное промежуточное соединение формулы VI обрабатывают кислотой в среде растворителя, а затем подвергают гидролизу основанием с последующей нейтрализацией кислотой и растворением и/или в среде растворителя при одновременном удалении воды с получением целевого соединения I с более высоким выходом ...

ПРОИЗВОДНЫЕ 3-(5-ТЕТРАЗОЛИЛБЕНЗИЛ)АМИНОПИПЕРИДИНА, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Производные 3-(5-тетразолилбензил)аминопиперидина формулы I, где R1 - С1-4алкокси; R2 - остаток формулы (a); R3 - Н или галоген; R4, R5 - Н, галоген, С1-4алкил, С1-4алкокси, CF3; R6 - Н, C1-4алкил, (СН2)mциклопропил, -S(O)n С1-4алкил, фенил, NR7R8, СН2С(O)СF3 или СF3; R7, R8 - Н, С1-4алкил или ацил; х = 0 или 1; n = 0, 1 или 2; m = 0 или 1, или их фармацевтически приемлемые соли, или сольваты являются сильными и специфическими антагонистами тахикининов, включая вещество Р и другие нейрокинины. 5 с. и 17 з. п. ф-лы, 1 ил.

СУЛЬФОНАМИДОКАРБОКСАМИДЫ, ИХ ГИДРАТЫ И ФИЗИОЛОГИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Описываются новые сульфонамидокарбоксамиды общей формулы (I), где значения А, У, Х указаны в п.1 формулы изобретения, обладающие антиагрегантной и антикоагулянтной активностью. Описываются их гидраты и физиологически приемлемые соли, обладающие свойством подавлять амидолитическую активность тромбина, а также фармацевтическая композиция на основе соединений формулы (I), обладающая вышеуказанными свойствами. 2 с. и 15 з.п. ф-лы, 2 табл.

ПРОИЗВОДНЫЕ ОКСАЗОЛИДИН-2-ОНА И ЛЕКАРСТВЕННОЕ СРЕДСТВО НА ИХ ОСНОВЕ

Описываются новые производные оксазолидин-2-она общей формулы I, где R обозначает низший алкил; Х обозначает циклоалкенил; бицикло (2,2,1)гепт-2-ил, необязательно замещенный фенил-2-оксо-5-метоксиметилоксазолидинилом; бицикло (2,2,1)гепт-5-ен-2-ил; адамантил или циклоалкил либо пиперидин, необязательно одно- или многократно замещенный галогеном, амино, низшим алкилом, нитрилом, оксогруппой, гидроксиимино, этилендиоксигруппой или OR1, где R1 обозначает -СН(С6Н5)2, -(CН2)nС6Н5, низший алкил, водород, -(СН2)nNНСОСН3-(СН2)nNH2, -(CH2)nSOCH3, -(CH2 )n СN, -(CH2)nSCH3, -(CH2)nSO2CH3-СО-низший алкил, -СОС6Н5, необязательно замещенный оксазолидиниловой группой, или замещенный =CR2R3, где R2 обозначает водород или низший алкил; R3 обозначает водород, нитрил, низший алкил, фенил или СОО-низший алкил, или замещенный -(СН2)nR4, где R4 обозначает нитрил, амино, -NНСОСН3-, -СОС6Н4гал, фенил или гидроксильную группу; или замещенный -COR5, где R5 обозначает низший алкил, -СН=СН-С6Н5, -С6Н5СF3, -О-С/СН3 ...

СОЕДИНЕНИЯ 3-ЗАМЕЩЕННОГО 1-АРИЛИНДОЛА И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ

Соединения 3-замещенного 1-арилиндола формулы I, где Аr - фенил, возможно замещенный галогеном; Х - ОСН2, СН2 или СН2СН2; пунктирная линия обозначает необязательную связь; R1-R4 - водород, галоген, низший алкил, низший алкокси, гидрокси, нитро, низший алкилтио, низший алкилсульфонил, низший алкил- или диалкиламино, циано, трифторметил, трифторметилсульфонилокси и трифторметилтио; R5 - водород, гидрокси, низший алкокси, галоген, трифторметил, низший алкил, необязательно замещенный гидроксигруппой, или низший алкенил, необязательно замещенный гидроксилом; R6-R8 - водород; R8 - низший алкил, низший алкенил (другие обозначения см. п.1 формулы изобретения), обладают основной антисеротонергической активностью и некоторые из них дополнительно антидопаминергической активностью. Соединения формулы I могут использоваться для лечения тревоги, агрессии, депрессии, нарушения сна, мигрени, негативных симптомов шизофрении путем связывания 5НТ2-рецепторов и Д2-рецепторов. 2 с. и 10 з.п. ф-лы, 1 табл.

КОМБИНАЦИЯ ИНГИБИТОРА ВИЧ-ПРОТЕАЗЫ С ДРУГИМИ АНТИВИРУСНЫМИ СОЕДИНЕНИЯМИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ПОЛУЧЕНИЯ ФАРМАЦЕВТИЧЕСКОЙ КОМПОЗИЦИИ

Изобретение относится к медицине. Комбинация соединений включает N-(2(R)-гидрокси-1(S)-инданил-2(R)-фенилметил-4(S)-гидрокси-5-(1-(4-(3-пиридилметил)-2(S)-N'(трет-бутилкарбамоил) пиперазинил)пентанамид или его фармацевтически приемлемую соль и любое из соединений, выбранных из 3'-азидо-3'-деокситимидина, 2',3'-дидеоксиинозина и 2',3'-дидеоксицитидина. Указанная комбинация соединений может быть использована как таковая либо в виде фармацевтической композиции в сочетании с фармацевтически приемлемым носителем для ингибирования ВИЧ-протеазы. Технический результат заключается в реализации указанного назначения. 3 с. и 2 з.п.ф-лы, 6 табл.

ПРОИЗВОДНЫЕ 3-(ПИПЕРИДИНИЛ-1)-ХРОМАН-4,7-ДИОЛА И 1-(4-ГИДРОКСИФЕНИЛ)-2-(ПИПЕРИДИНИЛ-1)-АЛКАНОЛА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ СВЯЗЫВАНИЯ NMDA РЕЦЕПТОРА

Изобретение относится к производным 3-(пиперидинил-1)-хромана-5,7-диола и 1-(4-гидроксифенил)-2-(пиперидинил-1)алканола общей формулы I или их фармацевтически приемлемым солям присоединения кислот, в которой (a) R2 и R5 взяты в отдельности и R1, R2, R3 и R4 независимо представляют собой водород, (C1-C6)-алкил, галоген, ОН или OR7, а R5 представляет собой метил; или (b) R2 и R5, взятые вместе, образуют кольцо хроман-4-ола, a R1, R3 и R4 каждый независимо представляют собой водород, (C1 -C6)-алкил, галоген, OН или OR7; R7 представляет собой метил; а R6 представляет собой замещенный пиперидинил или 8-азабицикло[3,2,1]октанильное производное; при условии, что (a) если R2 и R5 взяты в отдельности, то по крайней мере один из R1, R2, R3 и R4 не является водородом; и (b) если R2 и R5 взяты вместе, то по крайней мере один из R1, R3 и R4 не является водородом, обладающие свойством NMDA антагониста. Предложены также фармацевтическая композиция на их основе и способ связывания NMDA рецептора. 8 с.

ХЛОРГИДРАТ О-БЕНЗОИЛОКСИМА 1,2,5-ТРИМЕТИЛПИПЕРИДОНА-4, ОБЛАДАЮЩИЙ АНТАГОНИСТИЧЕСКОЙ АКТИВНОСТЬЮ ПО ОТНОШЕНИЮ К МОРФИНУ, ПРОМЕДОЛУ И ЭТАНОЛУ

COMPOSITIONS AND METHODS FOR TREATMENT OF NEUROPSYCHOLOGICAL DEFICITS

Pharmaceutical compositions and methods for the treatment of neuropsychological impairment in human patients comprising a central nervous system (CNS) stimulant in a daily low-dosage amount, and a micronutrient composition containing acetyl L-carnitine, L-tyrosine, N-acetyl cysteine, and alpha-lipoic acid. The CNS stimulant and micronutrient components may be in admixture for convenient daily oral administration of a low dosage CNS stimulant and micronutrients in the range of bout 60-250 mg acetyl L-carnitine, 50-200 mg L-tyrosine, 60-250 mg N-acetyl cystein, and 25-100 mg alpha-lipoic acid per day. 1. An oral dosage composition for the treatment of neuropsychological impairment , comprising:a central nervous system stimulant in up to a low-dosage amount;60 to 250 mg acetyl L-carnitine;50 to 200 mg L-tyrosine;60 to 250 mg N-acetyl cysteine;25 to 100 mg alpha-lipoic acid.2. The composition of claim 1 , wherein acetyl L-carnitine is present in a range of 90 to 190 mg.3. The composition of claim 1 , wherein acetyl L-carnitine is present in a range of 100 to 150 mg.4. The composition of claim 1 , wherein L-tyrosine is present in a range of 70 to 150 mg.5. The composition of claim 1 , wherein L-tyrosine is present in a range of 80 to 100 mg.6. The composition of claim 1 , wherein N-acetyl cysteine is present in a range of 90 to 190 mg.7. The composition of claim 1 , wherein N-acetyl cysteine is present in a range of 100 to 150 mg.8. The composition of claim 1 , wherein alpha-lipoic acid is present in a range of 35 to 75 mg.9. The composition of claim 1 , wherein alpha-lipoic acid is present in a range of 40 to 60 mg.10. The composition of claim 1 , further comprising about 25 to 100 mg L-taurine.11. The composition of claim 10 , wherein L-taurine is present in a range of 35 to 75 mg.12. The composition of claim 1 , wherein the central nervous system stimulant is atomoxetine HCl in an amount of about 2 mg to 20 mg.13. The composition of claim 1 , wherein the central ...

Methods Of Diminishing Co-Abuse Potential

Methods of diminishing or eliminating the co-abuse of a methylphenidate drug comprising identifying a patient or patient group suspected or likely to abuse said methylphenidate drug in combination with a substance known or suspected to give rise to l-ethylphenidate or psychotropic effect when ingested in the combination and making available to said patent or patient group said methylphenidate drug substantially free of l-threo methylphenidate. 1. A method of reducing co-abuse of a methylphenidate drug and ethyl alcohol comprising:identifying a patient or patient group abusing the methylphenidate drug and ethyl alcohol; andproviding to the patient or patient group a methylphenidate drug substantially free of 1-threo methylphenidate.2. The method of wherein said methylphenidate drug is made available orally claim 1 , intravenously claim 1 , parenterally claim 1 , via an aerosol or gaseous suspension claim 1 , or transdermally.3. The method of comprising up to 10 mg of methylphenidate drug.4. The method of comprising up to 5 mg of methylphenidate drug.5. The method of comprising up to 3 mg of methylphenidate drug.6. The method of comprising from about 0.1 mg to about 100 mg of methylphenidate drug.7. The method of wherein said patient has or is suspected of having ADD or ADHD. This application is continuation of U.S. application Ser. No. 13/370,663, filed Feb. 10, 2012, which is a continuation of U.S. application Ser. No. 12/269,471, filed Nov. 12, 2008, now abandoned, which is a continuation of U.S. application Ser. No. 10/832,210, filed Apr. 26, 2004, now abandoned, the entireties of which are incorporated herein.This invention relates to methods of reducing or eliminating the co-abuse of methylphenidate drugs with abusable substances such as alcohol, cocaine, opioids or nicotine. Also disclosed are methods to reduce adverse effects associated with co-administration of phenidate drugs and substances such as alcohol or other central nervous system active agents in ...

METHODS AND DEVICES FOR PROVIDING PROLONGED DRUG THERAPY

Methods and devices for maintaining a desired therapeutic drug effect over a prolonged therapy period are provided. In particular, oral dosage forms that release drug within the gastrointestinal tract at an ascending release rate over an extended time period are provided. The dosage forms may additionally comprise an immediate-release dose of drug. 1. A method that comprises administering a pharmaceutically acceptable composition comprising methylphenidate or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a patient in a manner that achieves an ascending release rate of said methylphenidate beginning with a first periodic interval that begins at time t=0 and continuing through about 5.5 hours following said administration.2. A method for effectively treating Attention Deficit Disorder or Attention Deficit Hyperactivity Disorder in a subject comprising orally administering a dosage form to said subject , wherein said dosage form comprisesan immediate release coating comprising methylphenidate hydrochloride; anda sustained release portion comprising methylphenidate hydrochloride and a pharmaceutically acceptable carrier,wherein:said dosage form provides release of said methylphenidate hydrochloride over a period comprising first, second, third, and fourth sequential, one-hour time intervals; andsaid sustained release portion releases more of said methylphenidate hydrochloride during said second interval than during said first interval, more of said methylphenidate hydrochloride during said third interval than during said second interval, and more of said methylphenidate hydrochloride during said fourth interval than during said third interval.3. The method according to wherein said dosage form is administered one time per day for multiple days.4. The method according to wherein said dosage form is administered to a non-adult subject.5. The method according to wherein said dosage form is a non-osmotic dosage form.6. The method ...

TREATMENT OF HEART FAILURE

The invention relates to perhexiline, or a pharmaceutically acceptable salt thereof, for use in the treatment of heart failure, as well as to a method for treating heart failure, which comprises administering to an animal in need thereof an effective amount of perhexiline, or a pharmaceutically acceptable salt thereof, to treat said heart failure. The invention further relates to a treatment programme for treating heart failure, which involves the co-use or co-administration of perhexiline with one or more other compounds that are advantageous in treating heart failure or the symptoms thereof. 1. A method for treating heart failure in a mammal having a left ventricular ejection fraction of at least 50% or a symptomatic component/feature/condition thereof , comprising:administering to said mammal in need thereof a therapeutically-effective amount of perhexiline.2. The method of claim 1 , wherein the therapeutically-effective amount of perhexiline is sufficient to reduce or ameliorate the heart failure or a symptomatic component/feature/condition thereof in the mammal.3. The method of claim 1 , wherein the perhexiline is in the form of a pharmaceutically acceptable salt.4. The method of claim 2 , wherein the perhexiline is in the form of a maleate salt.5. The method of claim 1 , wherein the mammal is a human.6. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound.7. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound advantageous in treating heart failure in a mammal having a left ventricular ejection fraction of at least 50% or a symptomatic component/feature/condition thereof.8. The method of claim 6 , wherein the therapeutic compound is selected from a member of the group consisting of Alpha Blockers claim 6 , Beta Blockers claim 6 , Calcium Channel Blockers claim 6 , Diuretics claim 6 , Ace (Angiotensin-Converting Enzyme) Inhibitors claim 6 , Arb ( ...

TREATMENT OF HEART FAILURE

The invention relates to perhexiline, or a pharmaceutically acceptable salt thereof, for use in the treatment of heart failure, as well as to a method for treating heart failure, which comprises administering to an animal in need thereof an effective amount of perhexiline, or a pharmaceutically acceptable salt thereof, to treat said heart failure. The invention further relates to a treatment programme for treating heart failure, which involves the co-use or co-administration of perhexiline with one or more other compounds that are advantageous in treating heart failure or the symptoms thereof. 1. A method for treating hypertrophic cardiomyopathy or a symptomatic component/feature/condition thereof in a mammal , comprising:diagnosing the mammal as having hypertrophic cardiomyopathy or a symptomatic component/feature/condition thereof; andadministering to said mammal a therapeutically-effective amount of perhexiline.2. The method of claim 1 , wherein the therapeutically-effective amount of perhexiline is sufficient to reduce or ameliorate the hypertrophic cardiomyopathy or a symptomatic component/feature/condition thereof in the mammal.3. The method of claim 1 , wherein the perhexiline is in the form of a pharmaceutically acceptable salt.4. The method of claim 2 , wherein the perhexiline is in the form of a maleate salt.5. The method of claim 1 , wherein the mammal is a human.6. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound.7. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound advantageous in treating hypertrophic cardiomyopathy or a symptomatic component/feature/condition thereof.8. The method of claim 6 , wherein the therapeutic compound is selected from a member of the group consisting of Alpha Blockers claim 6 , Beta Blockers claim 6 , Calcium Channel Blockers claim 6 , Diuretics claim 6 , Ace (Angiotensin-Converting Enzyme) Inhibitors claim 6 , ...

ORALLY EFFECTIVE METHYLPHENIDATE EXTENDED RELEASE POWDER AND AQUEOUS SUSPENSION PRODUCT

An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile. 1. A methylphenidate aqueous extended release oral suspension comprising an immediate release methylphenidate component , a sustained release methylphenidate component , and water , said suspension having a pH of about 3.5 to about 5 ,wherein said suspension provides a single mean average plasma concentration peak and a therapeutically effective plasma profile of about 12 hours for methylphenidate, and{'sub': 0-∞', 'max', 'max', '1/2, 'wherein the suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for d-methylphenidate has an area under the curve (AUC)of about 114 ng-hr/mL to about 180 ng-hr/mL, Cof about 11 ng/mL to about 17 ng/mL, Tof about 4 hours to about 5.25 hours and Tof about 5 hours to about 7 hours following a single oral administration of an aqueous liquid suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults.'}2. The methylphenidate aqueous extended release oral suspension according to claim 1 , wherein said suspension has a pH in the range of about 4 to about 4.5.3. The methylphenidate aqueous extended release oral suspension according to wherein the ...

Oral Drug Delivery System

Dosage forms and drug delivery devices suitable for administration of pharmaceutical compounds and compositions, including the oral drug administration of compounds. 179.-. (canceled)80. A composition comprising:a drug;sucrose acetate isobutyrate (SAIB);a cellulose acetate butyrate (CAB) having at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%; anda solvent.81. The composition of claim 80 , wherein the drug is present in an amount ranging from about 2 mg to about 250 mg.82. The composition of claim 80 , wherein the drug comprises an opioid claim 80 , a central nervous system (CNS) depressant claim 80 , or a stimulant.83. The composition of claim 80 , wherein the drug comprises hydrocodone claim 80 , hydromorphone claim 80 , morphine claim 80 , oxymorphone claim 80 , or oxycodone.84. The composition of claim 80 , wherein the drug comprises a stimulant selected from dextroamphetamine and methylphenidate.85. The composition of claim 80 , wherein the drug comprises methylphenidate.86. The composition of claim 80 , wherein the composition comprises from about 20 weight percent to about 90 weight percent of the SAIB.87. The composition of claim 80 , wherein the CAB has a butyryl content ranging from about 17% to about 38%.88. The composition of claim 80 , wherein the CAB has an acetyl content ranging from about 13% to about 30%.89. The composition of claim 80 , wherein the CAB has a butyryl content ranging from about 17% to about 38% and an acetyl content ranging from about 13% to about 30%.90. The composition of claim 80 , wherein the composition comprises from about 1 weight percent to about 8.6 weight percent of the CAB.91. The composition of claim 80 , wherein the composition comprises from about 20 weight percent to about 50 weight percent of the solvent.92. The composition of claim 80 , wherein the solvent ...

METHODS AND COMPOSITIONS TO PREVENT ADDICTION

Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject comprising, administering a therapeutic amount of the neurological stimulant and administering an antagonist of the kappa opioid receptor, to thereby reduce or prevent the development of aversion to the CNS stimulant in the subject. Also disclosed is a method of reducing or preventing the development of addiction to a CNS stimulant in a subject, comprising, administering the CNS stimulant and administering a mu opioid receptor antagonist to thereby reduce or prevent the development of addiction to the CNS stimulant in the subject. Also disclosed are pharmaceutical compositions comprising a central nervous system stimulant and an opioid receptor antagonist. Examples of central nervous system stimulants (such as methylphenidate) and opioid receptor antagonists (such as naltrexone) are provided. 1. A method of reducing or preventing the development of aversion to a CNS stimulant in a subject comprising , administering a therapeutic amount of the neurological stimulant and administering an antagonist of the kappa opioid receptor , to thereby reduce or prevent the development of aversion to the CNS stimulant in the subject.2. The method of claim 1 , further comprising selecting a subject at risk for the development of aversion to the CNS stimulant claim 1 , prior to the administering.3. The method of claim 1 , wherein the subject is diagnosed with attention deficit hyperactivity disorder (ADHD) claim 1 , narcolepsy claim 1 , chronic fatigue syndrome claim 1 , or depression.4. A method to decrease the dysphoria associated with the use of therapeutic doses of a CNS nervous system stimulant comprising administering a therapeutic amount of the CNS stimulant and administering a kappa opioid receptor antagonist claim 1 , to thereby decrease the dysphoria.5. The method of claim 4 , further comprising claim 4 , selecting a subject at risk for the development of ...

REVERSAL OF GENERAL ANESTHESIA BY ADMINISTRATION OF METHYLPHENIDATE, AMPHETAMINE, MODAFINIL, AMANTADINE, AND/OR CAFFEINE

The present invention generally relates to compositions comprising anesthesia-reversing agents which facilitate or increase the time of awakening or reverse the effects of general anesthesia-induced unconsciousness. In some embodiments, the anesthesia reversing agent can be selected from any or a combination of methylphenidate (MPH), amphetamine, modafinil, amantadine, caffeine, or analogues or derivatives thereof. In some embodiments, compositions comprising at least one or more anesthesia-reversing agents can be used to facilitate awakening from anesthesia without or decreasing occurrence of delirium, and can be used in methods to treat or prevent the symptoms associated with emergence delirium, as well as treat a subject oversedated with general an esthesia. The invention also relates to methods for administering these compositions comprising anesthesia-reversing agents to subjects and for use. 1. A method of facilitating emergence from general anesthesia in a subject treated with a general anesthetic agent comprising administering to the subject an effective amount of a composition comprising at least one anesthesia-reversing agent , wherein the anesthesia-reversing agent facilitates emergence of the subject from the general anesthesia.2. The method of claim 1 , wherein the anesthesia-reversing agent is selected from any or a combination of methylphenidate (MPH) claim 1 , amphetamine claim 1 , modafinil claim 1 , amantadine claim 1 , or caffeine.3. The method of claim 2 , wherein the methylphenidate is dextro-methylphenidate (D-MPH) or levo-methylphenidate (L-MPH) or a combination thereof claim 2 , or an analogue or derivative thereof.4. The method of claim 2 , wherein the methylphenidate is racemic methylphenidate.5. The method of claim 2 , wherein the amphetamine is L-amphetamine.6. The method of claim 1 , wherein emergence of the subject from general anesthesia comprises restoration of mobility or consciousness in the subject.7. The method of claim 1 , ...

COMPOSITIONS AND METHOD FOR TREATMENT OF ATTENTION DEFICIT DISORDER AND ATTENTION DEFICIT/HYPERACTIVITY DISORDER WITH METHYLPHENIDATE

The invention relates to a method of treating Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) and compositions for topical application of methylphenidate comprising methylphenidate in a flexible, finite system wherein the methylphenidate is present in an amount sufficient to achieve substantially zero order kinetics for delivery to the skin or mucosa of a patient in need thereof over a period of time at least 10 hours. 1. A composition for topical application of methylphenidate comprising methylphenidate and a pharmaceutically acceptable adhesive carrier in a flexible , finite system ,wherein the methylphenidate is present in an amount sufficient to achieve substantially zero order kinetics for delivery to the skin or mucosa of a patient in need thereof over a period of time at least 10 hours,wherein the proportion of methylphenidate : silicone adhesive : acrylic adhesive (wt % dry) is about 5-30:0-70:0-90, respectively, andwherein the composition is substantially free of ritalinic acid at the time of manufacture.2. A composition for topical application of methylphenidate comprising methylphenidate and a pharmaceutically acceptable adhesive carrier in a flexible , finite system ,wherein the methylphenidate is present in an amount sufficient to achieve substantially zero order kinetics for delivery to the skin or mucosa of a patient in need thereof over a period of time at least 10 hours,wherein the proportion of methylphenidate:silicone adhesive:acrylic adhesive (wt % dry) is about 5-30:0-70:0-80, respectively, andwherein the composition is substantially free of ritalinic acid at the time of manufacture.3. A composition for topical application of methylphenidate comprising methylphenidate in a flexible , finite system ,wherein the methylphenidate is present in an amount sufficient to permit a delivery rate from about 0.5 mg/24 hours to about 100 mg/24 hours in order to achieve a therapeutically effective dose in a patient,wherein ...

PERHEXILINE FOR TREATING CHRONIC HEART FAILURE

Disclosed are methods for the treatment of chronic heart failure, comprising administering to an animal in need thereof an effective amount of perhexiline, or a pharmaceutically acceptable salt thereof, to treat said chronic heart failure. The chronic heart failure maybe non-ischaemic or ischaemic. Also disclosed is the use of perhexiline in the manufacture of a medicament to treat chronic heart failure, including chronic heart failure of a non-ischaemic origin and chronic heart failure of an ischaemic origin. 1. A method for treating a mammal having chronic heart failure or a symptomatic component/feature/condition thereof due to or associated with a member of the group consisting of: ischaemia , coronary artery disease , cardiomyopathy , hypertension , diabetes , and valvular disease , the method comprising:diagnosing the mammal as having chronic heart failure or a symptomatic component/feature/condition thereof; andadministering to said mammal a therapeutically-effective amount of perhexiline.2. The method of claim 1 , wherein the therapeutically-effective amount of perhexiline is sufficient to reduce or ameliorate the chronic heart failure or a symptomatic component/feature/condition thereof in the mammal.3. The method of claim 1 , wherein the perhexiline is in the form of a pharmaceutically acceptable salt.4. The method of claim 2 , wherein the perhexiline is in the form of a maleate salt.5. The method of claim 1 , wherein the mammal is a human.6. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound.7. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound advantageous in treating chronic heart failure or a symptomatic component/feature/condition thereof.8. The method of claim 6 , wherein the therapeutic compound is selected from a member of the group consisting of Alpha Blockers claim 6 , Beta Blockers claim 6 , Calcium Channel Blockers claim 6 , ...

Oral Pharmaceutical Dosage Forms

Controlled release oral dosage forms suitable for administration of methylphenidate are provided. Abuse-resistant controlled release oral dosage forms suitable for administration of methylphenidate are also provided. Methods of treating ADD and ADHD using the oral dosage forms are also provided. 2. The controlled release oral dosage form of claim 1 , wherein the initial increasing-rate phase is sufficient to provide an onset of action within about 1 hour post administration.3. (canceled)4. The controlled release oral dosage form of claim 1 , wherein the subsequent non-ascending phase is sufficient to provide a therapeutically effective amount of methylphenidate through at least 14 hours post administration58.-. (canceled)9. The controlled release oral dosage form of claim 1 , wherein the dosage form is abuse-resistant.10. The abuse-resistant controlled release oral dosage form of claim 9 , wherein the formulation provides a decreased risk of misuse or abuse.11. The abuse-resistant controlled release oral dosage form of claim 10 , wherein said decreased risk of misuse or abuse is characterized by a low in vitro solvent extractability value of the methylphenidate from the dosage form claim 10 , wherein less than 45% of the methylphenidate is extracted after 60 min of extraction in 40% ethanol at 25° C.12. The abuse-resistant controlled release oral dosage form of claim 10 , wherein said decreased risk of misuse or abuse is characterized by the absence of any significant effect on absorption of the methylphenidate from the dosage form upon co-ingestion of the dosage form and alcohol by a subject wherein both the Cratio and the AUC ratio of absorption of the methylphenidate from the dosage form when taken with water or with 40% ethanol is within a range of about 0.8 to 1.2.13. The abuse-resistant controlled release oral dosage form of claim 10 , wherein said decreased risk of misuse or abuse is characterized by a low injectability potential claim 10 , wherein the force ...

Dosage forms for oral administration and methods of treatment using the same

The invention relates to dosage forms that provide prolonged therapy. In particular, the invention relates to dosage forms including various pluralities of drug-containing resin particles. The invention also relates to methods of making these dosage forms and methods of treating using these dosage forms.

DOSAGE FORMS FOR ORAL ADMINISTRATION AND METHODS OF TREATMENT USING THE SAME

The invention relates to dosage forms that provide prolonged therapy. In particular, the invention relates to dosage forms including various pluralities of drug-containing resin particles. The invention also relates to methods of making these dosage forms and methods of treating using these dosage forms. 1. A pharmaceutical composition comprising an ADHD effective agent complexed with ion-exchange resin particles to form drug-resin particles , wherein said ADHD effective agent is methylphenidate , and wherein said composition comprises a first plurality of drug-resin particles that are uncoated and a second plurality of drug-resin particles that are coated with a delayed release coating.2. The composition of claim 1 , wherein the second plurality of drug-resin particles comprises a triggered-release coating triggered by a pH change.3. The composition of claim 2 , wherein the triggered-release coating is cellulose acetate phthalate claim 2 , cellulose acetate trimellitate claim 2 , hydroxypropyl methylcellulose phthalate claim 2 , polyvinyl acetate phthalate claim 2 , carboxymethylethylcellulose claim 2 , co-polymerized methacrylic acid/methacrylic acid methyl esters claim 2 , co-polymerized methacrylic acid/acrylic acid ethyl esters claim 2 , or mixtures thereof.4. The composition of claim 3 , wherein the composition additionally contains polistirex claim 3 , polacrilex claim 3 , cholestyramine claim 3 , polacrilin or mixtures thereof.5. The composition of claim 2 , wherein said drug-resin particles coated with a triggered-release coating further comprise a diffusion barrier coating.6. The composition of claim 5 , wherein the diffusion barrier coating contains polyvinylpyrrolidone claim 5 , polyvinylacetate claim 5 , polyvinylalcohol or mixtures thereof.7. The composition of claim 4 , wherein the diffusion barrier coating is a water insoluble claim 4 , water permeable membrane.8. The composition of claim 5 , wherein the water insoluble claim 5 , water permeable ...

TREATMENT FOR CEREBRAL PALSY IMPAIRED SPEECH IN CHILDREN

Cerebral palsy impaired speech in children and adolescents are effectively treated by administration of a psychostimulant. Low doses of the psychostimulant significantly increases the percentage of correctly pronounced intelligible syllables or words and the ability to more intelligibly communicate. The improvement in speech persists after cessation of or prior to continued psychostimulant treatment. 1. A method for treating a speech impairment secondary to cerebral palsy in a subject in need of such treatment , said method comprises:(a) providing a psychostimulant;(b) administering the psychostimulant in a therapeutically effective dose to the subject;whereby the speech impairment is diminished.2. The method of claim 1 , wherein the subject has a chronological age is greater than the speech-language age equivalence prior to step (a) and the difference between the chronological age and speech language age equivalence is diminished after step (b).3. The method of claim 1 , wherein there is a diminished difference in chronological age to speech-language age equivalence that persists after the psychostimulant is no longer efficaciously active in the subject.4. The method of claim 1 , wherein the subject is unable to pronounce one or more of the bilabial consonants prior to step (a) and is able to pronounce the one or more bilabial consonants after step (b).5. The method of claim 1 , wherein steps (a) and (b) are repeated periodically over a period of time and wherein the diminishment in the impaired speech continues over the period of time.6. The method of claim 1 , wherein further comprising prior to step (a) determining the cognitive functional age of the subject through non-verbal means claim 1 , and wherein the cognitive functional age is at least about two years.7. The method of claim 1 , wherein the diminished speech impairment comprises a percentage increase in correctly pronounced syllables and words of from at least about 20% to several hundred percent.8. The ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF KRABBE AND OTHER NEURODEGENERATIVE DISEASES

Provided are compositions and methods for the treatment of Krabbe and other neurodegenerative diseases associated with psychosine (and/or other storage material)—mediated axonal degeneration. Compositions and methods employ one or more inhibitor(s) of (1) a phosphotransferase activity of one or more kinase(s) such as CDK5, P38, jnk, src, CK2, PKC, GSK3α and β; (2) a phosphotransferase activity of one or more phosphatase(s) such as PP1 and PP2; (3) a caspase/calpain activity of one or more caspases such as caspase 3 and calpains such as calpain 1 and 2; and/or (4) a sodium/calcium exchange protein such as NCX1. Inhibitors include small molecules (e.g., the GSK3β inhibitor L803 and the NCX1 inhibitor flecainide) and siRNA molecules that downmodulate cellular levels of one or more mRNA, such as PP1 mRNA. Inhibitors disclosed can cross the blood-brain barrier and, thus, are available to the CNS and effective in reducing psychosine-mediated axonal degeneration. 136.-. (canceled)37. A method for the treatment of a neurodegenerative disease in a patient suffering from a psychosine-mediated neurological disorder , storage disease , and/or aging-related neuropathy , said method comprising the step of:(a) administering to said patient a composition comprising an inhibitor of an effector of psychosine-mediated axonal degeneration, wherein the inhibitor is selected from the group consisting of a small-molecule antagonist of said effector, a peptide antagonist of said effector, or a siRNA molecule(s) that is targeted against, and leads to the downregulation of, a mRNA that encodes said effector.38. The method of wherein said inhibitor is the siRNA molecule(s) claim 37 , and wherein the siRNA molecule(s) is administered to said patient between 0 days and 60 days following the birth of said patient.39. (canceled)40. The method of wherein said inhibitor is the siRNA molecule(s) claim 37 , and wherein the siRNA molecule(s) is targeted against an mRNA that encodes CDK5 (SEQ ID NO: 16 ...

DOSAGE FORMS FOR ORAL ADMINISTRATION AND METHODS OF TREATMENT USING THE SAME

The invention relates to dosage forms that provide prolonged therapy. In particular, the invention relates to dosage forms including various pluralities of drug-containing resin particles. The invention also relates to methods of making these dosage forms and methods of treating using these dosage forms. 1. A method for treating Attention-Deficit Disorder or Attention-Deficit Hyperactivity Disorder comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising an ADHD effective agent complexed with ion-exchange resin particles to form drug-resin particles , wherein said ADHD effective agent is methylphenidate , and wherein said composition comprises a first plurality of drug-resin particles that provide for an immediate release of methylphenidate and a second plurality of drug-resin particles that provide for a delayed release of methylphenidate.2. The method of claim 1 , wherein the second plurality of drug-resin particles comprises a triggered-release coating triggered by a pH change.3. The method of claim 2 , wherein the triggered-release coating is cellulose acetate phthalate claim 2 , cellulose acetate trimellitate claim 2 , hydroxypropyl methylcellulose phthalate claim 2 , polyvinyl acetate phthalate claim 2 , carboxymethylethylcellulose claim 2 , co-polymerized methacrylic acid/methacrylic acid methyl esters claim 2 , co-polymerized methacrylic acid/acrylic acid ethyl esters claim 2 , or mixtures thereof.4. The method of claim 2 , wherein said drug-resin particles coated with a triggered-release coating further comprise a diffusion barrier coating.5. The method of claim 4 , wherein the diffusion barrier coating is a water insoluble claim 4 , water permeable membrane.6. The method of claim 5 , wherein the diffusion barrier coating contains polyvinylpyrrolidone claim 5 , polyvinylacetate claim 5 , polyvinylalcohol or mixtures thereof.7. The method of claim 5 , wherein the water insoluble claim 5 , water ...

CONTROLLED RELEASE FORMULATIONS HAVING RAPID ONSET AND RAPID DECLINE OF EFFECTIVE PLASMA DRUG CONCENTRATIONS

The invention is directed to oral modified/controlled release drug formulations which provide a rapid initial onset of effect and a prolonged duration of effect. Preferably, the peak concentration is lower than that provided by the reference standard for immediate release formulations of the drug, and the duration of effect falls rapidly at the end of the dosing interval. 120-. (canceled)22. The formulation of claim 21 , wherein the formulation provides a time to maximum plasma concentration at about 0.5 to about 2 hours after oral administration.23. The formulation of claim 21 , wherein about 40% of the dose of methylphenidate is in the outer immediate release layers of the beads and about 60% of the dose of methylphenidate is in the immediate release cores of the beads.24. The formulation of claim 21 , wherein about 30% of the dose of methylphenidate is in the outer immediate release layers of the beads and about 70% of the dose of methylphenidate is in the immediate release cores of the beads.25. The formulation of claim 21 , wherein the plurality of the multi-layer release beads is incorporated into a hard gelatin capsule.26. The formulation of claim 21 , wherein the immediate release core further comprises a spheroid or a bead.27. The formulation of claim 21 , wherein the spheroid or the bead is sprayed with the further portion of the dose of the methylphenidate.28. The formulation of claim 21 , wherein each bead comprises a coat of a barrier agent between the immediate release core and the controlled release layer.29. The formulation of claim 28 , wherein the barrier agent is hydroxypropylmethylcellulose.30. The formulation of claim 21 , wherein the dose is 20 mg.32. The formulation of claim 31 , wherein the immediate release core further comprises a spheroid or a bead.33. The formulation of claim 32 , wherein the spheroid or the bead is sprayed with the further portion of the dose of the methylphenidate.34. The formulation of claim 32 , wherein each bead ...

METHOD OF TREATING APRAXIA OF SPEECH IN CHILDREN

A therapeutic method for treating apraxia of speech in children. The child can also be diagnosed with autism, mental retardation, dyslexia. Verbal development stages and nonverbal development stages are tested and observed. If a child demonstrates at least 18 to 24 month development stage of either the verbal development or the non-verbal development, a therapeutic dosage of dopamine agonistic medicine is administered to the child in addition to speech therapy and language training. 1. A method of treating a child with a mental development disease , comprising the steps of:testing and observing a nonverbal development stage and a verbal development stage of said child;determining said verbal development stage and said non-verbal development stage of said child; andadministering a therapeutic dosage of a dopamine agonistic medicine to said child upon said child being determined to demonstrate an equivalent 18 to 24 month development level with either said verbal development stage or said non-verbal development stage.2. The method of claim 1 , wherein said dopamine agonistic medicine is Methylphenidate or Dextroamphetamine.3. The method of claim 1 , wherein said dopamine agonistic medicine is an analog of Methylphenidate or an analog of Dextroamphetamine.4. The method of claim 1 , wherein said mental development disease is one of a group of mental development diseases including: a clinically diagnosed autism claim 1 , a mental retardation claim 1 , a dyslexia claim 1 , an apraxia claim 1 , and a clinically diagnosed speech and communication disorder claim 1 , according to the standard of the medical field at this patent application time.5. The method of claim 1 , wherein said child is of age between 2 to 12 years old.6. The method of claim 1 , wherein said dopamine agonistic medicine is administered at a dosage of 0.5 to 5 mg per day.7. The method of claim 1 , wherein said 18 to 24 months nonverbal development is determined by being capable of gestures and motions of ...

Therapeutic Treatment

This invention discloses a treatment for a patient receiving medication to treat an attention deficit disorder such as ADHD wherein the treatment results in a loss of appetite and impairment of the patient's attentiveness. The treatment combines a treatment for an attention deficit disorder with an appetite stimulant, wherein the appetite stimulant increases the caloric intake of a patient, which can increase the patient's attentiveness. The combination treatment can be given for an indefinite, including, without limitation, life-long, to allow a patient to maintain normal caloric intake during treatment for an attention deficit disorder.

METHOD FOR DETERMINING FORMULATION ORIENTATION OF ASYMMETRIC MULTI-LAYERED OSMOTIC TABLETS

The present invention relates to a method for preparing asymmetric multi-layered osmotic tablets using rapid and accurate determination of the orientation of tablets with respect to different internal formulation layers proximate to the opposite curved surfaces. In particular, the invention relates to detect degree of curvature using an image recognition system and drill the desired surface using a laser beam. 1. A method of preparing a multi-layered osmotic tablet having a push end and a dispensing end for laser drilling of a delivery port in the dispensing end , the method comprising the steps of:detecting an orientation of the tablet by detecting an angle of the curved surface on a side of the tablet corresponding to one or another formulation layer depending on the formulation orientation of the tablet, wherein both the ends have different degrees of curvature;conveying signal to a laser gun regarding orientation of the dispensing end;passing the tablet through a conveyor belt; anddrilling the desired surface using a laser beam.2. The method according to claim 1 , wherein the laser gun is present on the both sides of the conveyor belt.3. The method according to claim 1 , wherein the angle of the curved surface is detected by an image recognition system.4. The method according to claim 1 , wherein the multi-layered osmotic tablet comprises methylphenidate or a salt thereof.5. The method according to claim 1 , wherein the multi-layered osmotic tablet comprises paliperidone or a salt thereof.6. The method according to claim 1 , wherein the dispensing end has higher degree of curvature.7. The method according to claim 1 , wherein the tablet comprising an angle formed by the outer curved surface of the drug containing layer and the lateral surface is in between 120° to 180°.8. The method according to claim 1 , wherein the tablet comprising an angle formed by the outer curved surface of the push layer and the lateral surface is in between 95° to 150°.9. The method ...

Pharmaceutical Formulation Containing Gelling Agent

Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient. 140-. (canceled)41. A controlled release oral solid dosage form comprising:(i) particles comprising methylphenidate or a pharmaceutically acceptable salt thereof and(ii) particles comprising polyethylene oxide,the dosage form providing a therapeutic effect for about 12 hours to about 24 hours when orally administered to a human patient, and when dissolved in from about 0.5 ml to about 10 ml of an aqueous liquid, forming a viscous gel,wherein the particles comprising polyethylene oxide are free from said methylphenidate or pharmaceutically acceptable salt thereof.42. The controlled release oral solid dosage form of claim 41 , wherein the viscous gel is unsuitable for injection.43. The controlled release oral solid dosage form of claim 41 , wherein the particles comprising polyethylene oxide comprise a hydrophobic material.44. The controlled release oral solid dosage form of claim 43 , wherein the hydrophobic material is an ammonio methacrylate copolymer.45. The controlled release oral solid dosage form of claim 41 , wherein the viscous gel cannot be injected through an insulin syringe.46. The controlled release oral solid dosage form of claim 41 , wherein the particles comprising polyethylene oxide comprise polyvinylpyrrolidone.47. The controlled release oral solid dosage form of claim 44 , wherein the particles ...

Methods and Compositions Particularly for Treatment of Attention Deficit Disorder

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described. 1. A method of treating attention deficit hyperactivity disorder (ADHD) in a subject in need thereof , the method comprising orally administering to the subject a dosage form providing 25 , 30 , 35 , 45 , 55 , 75 , 85 , or 100 mg methylphenidate hydrochloride and means for providing an in vivo methylphenidate Tof about 3 hours and Tof about 13.5 hours in the fed state.2. The method of claim 1 , wherein the in vivo methylphenidate Tof about 3 hours and Tof about 13.5 hours are achieved after a single oral administration of the dosage form.3. The method of claim 1 , wherein the dosage form releases a first portion of the methylphenidate hydrochloride immediately upon oral administration.4. The method of claim 3 , wherein the dosage form releases a second portion of the methylphenidate hydrochloride in a controlled and delayed release manner after oral administration.5. The method of claim 4 , wherein about 20% by weight of the methylphenidate hydrochloride in the dosage form is released as the first portion.6. The method of claim 5 , wherein about 80% by weight of the ...

TRANSDERMAL DELIVERY SYSTEM CONTAINING METHYLPHENIDATE OR ITS SALTS AND METHODS THEREOF

Disclosed herein is a transdermal delivery system comprising methylphenidate or its salt as an active ingredient. Also provided are methods of delivering a therapeutically effective amount of methylphenidate to a subject for the treatment of a disease condition. The disease condition includes a neurological condition such as Attention Deficit Disorder (ADD) and/or Attention Deficit/Hyperactivity Disorder (ADHD). Kits including the transdermal delivery system and methods of making and using the transdermal delivery system are also provided. 1. A transdermal delivery system comprising:(i) a silicone adhesive layer; and{'sup': 2', '2, '(ii) a drug-containing matrix layer comprising: (a) methylphenidate or its pharmaceutically acceptable salt; and (b) a rubber-based polymer that comprises a hydrogenated synthetic hydrocarbon tackifier, wherein the transdermal delivery system has a flux rate ranging from about 6 μg/cm/hr-100 μg/cm/hr between 2-18 hours after treatment is initiated.'}2. The transdermal delivery system of claim 1 , wherein the rubber-based polymer is styrene-butadiene block copolymer rubber.3. The transdermal delivery system of consisting essentially of a backing layer claim 1 , the silicon adhesive layer claim 1 , the drug-containing matrix layer claim 1 , and a release liner.4. The transdermal delivery system of claim 1 , wherein the methylphenidate or its pharmaceutically acceptable salt is about 10 to about 20% by weight based on the total weight of the drug-containing matrix layer.5. The transdermal delivery system of claim 1 , wherein the methylphenidate or its pharmaceutically acceptable salt is about 12 claim 1 , about 15 or about 17% by weight based on the total weight of the drug-containing matrix layer.6. The transdermal delivery system of claim 1 , wherein the hydrogenated synthetic hydrocarbon tackifier is about 10-80% by weight based on the total weight of the drug-containing matrix layer.7. The transdermal delivery system of wherein the ...

COMPOSITIONS AND METHODS FOR TREATING PSYCHIATRIC DISORDERS

Methods of treating psychiatric disorders are provided which include administration of one or more anti-epileptic agents and, optionally, one or more a psychostimulants. Also provided are pharmaceutical compositions comprising, in combination, one or more anti-epileptic agents and one or more psychostimulants. Psychiatric disorders include those associated with impaired cognitive processing, degenerative disorders such as Mild Cognitive Impairment, Parkinson's disease, dementia, non-compliance with therapeutic regimes and eating disorders, although without limitation thereto. 128-. (canceled)29. A method of treating a psychiatric disorder which is selected from Mild Cognitive Impairment (MCI) , Alzheimer's Disease and dementia in a subject in need thereof , including the step of administering to the subject one or more anti-epileptic agents , or a pharmaceutically acceptable salt thereof , and optionally one or more psychostimulants , or pharmaceutically acceptable salt thereof , to thereby treat the psychiatric disorder , wherein the amount of anti-epileptic agent is less than 30% of the daily dose of anti-epileptic agent minimally therapeutic in mood stabilization or treatment of epilepsy or epileptic symptoms.30. The method of claim 29 , wherein a single anti-epileptic agent is administered.31. The method of claim 29 , wherein two or more anti-epileptic agents are administered.32. The method of claim 29 , wherein the amount of anti-epileptic agent is less than 20% of the daily dose of anti-epileptic agent minimally therapeutic in mood stabilization or treating epilepsy or epileptic symptoms.33. The method of claim 29 , wherein the anti-epileptic agent is selected from: AMPA antagonists claim 29 , Benzodiazepines claim 29 , Barbiturates claim 29 , Valproates claim 29 , GABA analogs claim 29 , Iminostilbenes claim 29 , Hydantoins claim 29 , NMDA antagonists claim 29 , Sodium channel blockers claim 29 , Carboxylic acids claim 29 , oxazolidinediones claim 29 , ...

ORAL PHARMACEUTICAL DOSAGE FORMS

Controlled release oral dosage forms suitable for administration of methylphenidate are provided. Abuse-resistant controlled release oral dosage forms suitable for administration of methylphenidate are also provided. Methods of treating ADD and ADHD using the oral dosage forms are also provided. 157.-. (canceled)58. A formulation comprising:methylphenidate;sucrose acetate isobutyrate (SAIB);a rheology modifier;a network former;a solvent;a viscosity enhancing agent; anda saturated polyglycolized glyceride,wherein the formulation does not include hydroxyethylcellulose (HEC).59. The formulation of claim 58 , wherein the methylphenidate is present in the formulation at about 5 wt % to about 30 wt % relative to the total weight of the formulation.60. The formulation of claim 58 , wherein the SAIB is present in the formulation at about 30 wt % to about 45 wt % relative to the total weight of the formulation.61. The formulation of claim 58 , wherein the rheology modifier comprises isopropyl myristate (IPM).62. The formulation of claim 61 , wherein the IPM is present in the formulation at about 2 wt % to about 15 wt % relative to the total weight of the formulation.63. The formulation of claim 58 , wherein the network former comprises cellulose acetate butyrate (CAB).64. The formulation of claim 63 , wherein the CAB is present in the formulation at about 2 wt % to about 10 wt % relative to the total weight of the formulation.65. The formulation of claim 58 , wherein the solvent comprises triacetin.66. The formulation of claim 65 , wherein the triacetin is present in the formulation at about 15 wt % to about 40 wt % relative to the total weight of the formulation.67. The formulation of claim 58 , wherein the viscosity enhancing agent comprises a stiffening agent.68. The formulation of claim 58 , wherein the viscosity enhancing agent comprises silicon dioxide (SiO).69. The formulation of claim 68 , wherein the SiOis present in the formulation at about 0.1 wt % to about 2 wt % ...

CONTROLLED RELEASE FORMULATIONS

The invention is directed to oral modified/controlled release drug formulations which provide a rapid initial onset of effect and a prolonged duration of effect. Preferably, the peak concentration is lower than that provided by the reference standard for immediate release formulations of the drug, and the duration of effect falls rapidly at the end of the dosing interval. 120.-. (canceled)21. An oral controlled release formulation , comprisinga plurality of substrates comprising a portion of an effective dose of methylphenidate or a pharmaceutically acceptable salt thereof in immediate release form,a hydrophobic material comprising an acrylic polymer coated onto the surface of said substrates in an amount sufficient to retard the release of said portion of the methylphenidate or a pharmaceutically acceptable salt thereof,an enteric coating applied over said hydrophobic coating to obtain enteric coated substrates, wherein said enteric coating is in an amount sufficient to substantially delay the release of said methylphenidate or a pharmaceutically acceptable salt thereof from said substrates until after said formulation passes through the stomach, wherein said enteric coating is derived from an aqueous dispersion comprising an acrylic/methacrylic copolymer, a plasticizer and a glidant,the formulation further comprising the remaining portion of the effective dose of the methylphenidate or pharmaceutically acceptable salt thereof in immediate release form, andwherein the formulation provides a maximum plasma concentration of methylphenidate at about 0.5 to about 2 hours after oral administration,and the duration of effect provided by the methylphenidate or pharmaceutically acceptable salt thereof contained in the formulation falls below effective plasma concentrations at about 10 to about 12 hours after the oral administration.22. The oral controlled release formulation of claim 21 , wherein said formulation comprises methylphenidate hydrochloride.23. The oral ...

Use of Flecainide as an Anti-Connexin Agent and Method for Potentiating the Effects of a Psychotropic Drug

The present invention relates to the use of flecainide as an anti-connexin agent. This anti-connexin agent is advantageously used to potentiate the therapeutic effect of various psychotropic drugs. More specifically, the invention provides a combination product containing flecainide and modafinil. 114.-. (canceled)15. A method for potentiating the effects of a psychotropic drug in a patient in need thereof , said method comprising administration of an anti-connexin agent flecainide in said patient.16. The method of claim 15 , wherein said psychotropic drug is selected from the group consisting of GABAergic claim 15 , dopaminergic claim 15 , norepinephrinergic claim 15 , serotoninergic claim 15 , histaminergic claim 15 , and glutamatergic effectors claim 15 , and those having an effect on the hypocretin/orexin system.17. The method of claim 15 , wherein said psychotropic drug is selected from the group consisting of caffeine claim 15 , mazindol claim 15 , sodium oxybate claim 15 , pitolisant claim 15 , amphetamine claim 15 , methylphenidate claim 15 , (R)-(beta-amino-benzenepropyl) carbamate mono-hydrochloride claim 15 , and armodafinil.18. The method of claim 15 , for potentiating the effects of a psychotropic drug selected in the group consisting of caffeine claim 15 , mazindol claim 15 , sodium oxybate claim 15 , pitolisant claim 15 , amphetamine claim 15 , methylphenidate claim 15 , (R)-(beta-amino-benzenepropyl) carbamate mono-hydrochloride claim 15 , and armodafinil.19. The method of claim 15 , wherein said anti-connexin agent Flecainide potentiates a promnesiant effect and/or an awakening effect of a psychotropic drug selected from the group consisting of caffeine claim 15 , mazindol claim 15 , sodium oxybate claim 15 , pitolisant claim 15 , amphetamine claim 15 , methylphenidate claim 15 , (R)-(beta-amino-benzenepropyl) carbamate mono-hydrochloride claim 15 , and armodafinil.20. The method of claim 15 , for increasing the efficacy and/or safety and/or the ...

COMPOSITIONS COMPRISING METHYLPHENIDATE-PRODRUGS, PROCESSES OF MAKING AND USING THE SAME

The present technology is directed to d-threo-methylphenidate conjugates and a composition comprising d-threomethylphenidate conjugated to nicotinoyl-L-serine, or salt thereof. The present technology also relates to a composition comprising at least one conjugate of d-methylphenidate having at least two or more chiral centers. The composition is optically active. The present technology additionally relates to oral formulations and pharmaceutical kits comprising at least one d-threo-methylphenidate conjugate. 2. The method of wherein the disorder is cocaine dependence or stimulant dependence.3. The method of claim 1 , wherein the compound is a prodrug.4. The method of claim 1 , wherein the salt of the compound is at least one pharmaceutically or therapeutically acceptable salt form or salt mixture thereof.5. The method of claim 4 , wherein the at least one pharmaceutically or therapeutically acceptable salt form is independently selected from the group consisting of acetate claim 4 , l-aspartate claim 4 , besylate claim 4 , bicarbonate claim 4 , carbonate claim 4 , d-camsylate claim 4 , l-camsylate claim 4 , citrate claim 4 , edisylate claim 4 , formate claim 4 , fumarate claim 4 , gluconate claim 4 , hydrobromide/bromide claim 4 , hydrochloride/chloride claim 4 , d-lactate claim 4 , l-lactate claim 4 , d claim 4 ,l-lactate claim 4 , d claim 4 ,l-malate claim 4 , l-malate claim 4 , mesylate claim 4 , pamoate claim 4 , phosphate claim 4 , succinate claim 4 , sulfate claim 4 , bisulfate claim 4 , d-tartrate claim 4 , martrate claim 4 , d claim 4 ,l-tartrate claim 4 , meso-tartrate claim 4 , benzoate claim 4 , gluceptate claim 4 , d-glucuronate claim 4 , hybenzate claim 4 , isethionate claim 4 , malonate claim 4 , methylsulfate claim 4 , 2-napsylate claim 4 , nicotinate claim 4 , nitrate claim 4 , orotate claim 4 , stearate claim 4 , tosylate claim 4 , thiocyanate claim 4 , acefyllinate claim 4 , aceturate claim 4 , aminosalicylate claim 4 , ascorbate claim 4 , borate ...

COMPOSITIONS COMPRISING METHYLPHENIDATE-PRODRUGS, PROCESSES OF MAKING AND USING THE SAME

The present technology is directed to d-threo-methylphenidate conjugates and a composition comprising d-threomethylphenidate conjugated to nicotinoyl-L-serine, or salt thereof. The present technology also relates to a composition comprising at least one conjugate of d-methylphenidate having at least two or more chiral centers. The composition is optically active. The present technology additionally relates to oral formulations and pharmaceutical kits comprising at least one d-threo-methylphenidate conjugate. 2. The method of wherein the disorder is selected from the group consisting of attention-deficit hyperactivity disorder (ADHD) claim 1 , attention deficit disorder (ADD) claim 1 , autistic spectrum disorder claim 1 , autism claim 1 , Asperger's disorder claim 1 , or pervasive developmental disorder.3. The method of wherein the disorder is selected from the group consisting of sleep disorder claim 1 , obesity claim 1 , depression claim 1 , bipolar disorder claim 1 , eating disorder claim 1 , binge eating disorder claim 1 , chronic fatigue syndrome claim 1 , schizophrenia claim 1 , major depressive disorder claim 1 , narcolepsy claim 1 , excessive daytime sleepiness (EDS) claim 1 , cocaine dependence claim 1 , stimulant dependence claim 1 , or autistic spectrum disorder.4. The method of claim 1 , wherein the compound is a prodrug.5. The method of claim 1 , wherein the salt of the compound is at least one pharmaceutically or therapeutically acceptable salt form or salt mixture thereof.6. The method of claim 5 , wherein the at least one pharmaceutically or therapeutically acceptable salt form is independently selected from the group consisting of acetate claim 5 , l-aspartate claim 5 , besylate claim 5 , bicarbonate claim 5 , carbonate claim 5 , d-camsylate claim 5 , l-camsylate claim 5 , citrate claim 5 , edisylate claim 5 , formate claim 5 , fumarate claim 5 , gluconate claim 5 , hydrobromide/bromide claim 5 , hydrochloride/chloride claim 5 , d-lactate claim 5 , l ...

METHYLPHENIDATE EXTENDED RELEASE CHEWABLE TABLET

An oral methylphenidate extended release tablet is described, which can be scored and still retain its extended release profile. The tablet contains a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and an uncomplexed methylphenidate active component. Following administration of a single dose of the extended release methylphenidate chewable tablet, a therapeutically effective amount of methylphenidate is reached in less than about 20 minutes and the composition provides a twelve-hour extended release profile. 1. An extended release racemic methylphenidate chewable tablet , wherein said chewable tablet is a uniform solid dispersion comprising:(a) a sustained release racemic methylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate-ion exchange resin complex in a polymeric matrix, wherein said barrier coating which provides a sustained release profile to the racemic methylphenidate is over the racemic methylphenidate-ion exchange resin complex-matrix;(b) a first immediate release component which comprises an immediate release uncoated racemic methylphenidate-ion exchange resin complex;(c) a second immediate release racemic methylphenidate component which comprises an uncomplexed racemic methylphenidate acceptable salt thereof;wherein said first immediate release component (b) has a slower onset of release than (c);wherein about 50% w/w to about 90% w/w of the racemic methylphenidate active component is provided by the sustained release component based on the total amount of racemic methylphenidate in the tablet, and{'sub': 0-∞', 'max, 'wherein said chewable tablet is capable of being divided and providing tablet portions which retain a therapeutically effective extended release profile, and a pharmacokinetic profile in which the methylphenidate has at least one of: a geometric mean for area under the curve ( ...

METHODS AND COMPOSITIONS FOR TREATMENT OF METASTATIC AND REFRACTORY CANCERS AND TUMORS

A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided. 1. A method of treating a mammalian subject with cancer comprising:(a) administering to said subject having a cancer or tumor a small molecule inhibitor of a target signaling molecule within the MEK/MAPK pathway, which inhibitor impairs T cell activation; and(b) administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor;wherein the combination of (a) and (b) reduces the proliferation of said cancer and tumor cells in vivo.2. The method according to claim 1 , wherein said target signaling molecule is Ras claim 1 , Raf claim 1 , MEK claim 1 , or ERK.3. The method according to claim 2 , wherein the target is MEK.4. The method according to claim 3 , wherein the inhibitor is trametinib claim 3 , AZD6244 claim 3 , GDC0973 claim 3 , GDC0623 claim 3 , MK1833 claim 3 , rafametinib claim 3 , binimetinib claim 3 , or U0126.5. The method according to claim 1 , wherein the T cell proliferation molecule is a proliferative cytokine or an agonist of a proliferative cytokine claim 1 , wherein said cytokine is IL-15 claim 1 , or IL-2 or IL-7.6. The method according to claim 5 , wherein the molecule is an IL-15 agonist.7. The method according to claim 6 , wherein the agonist comprises:(a) the partial or whole sequence of soluble IL-15R;(b) an IL-15:IL-15Rα-Fc complex,(c) a hyperagonist IL-15-sIL-15Rα-sushi ...

COMPOSITIONS AND METHODS FOR THE TRANSDERMAL DELIVERY OF METHYLPHENIDATE

Compositions for the transdermal delivery of methylphenidate in a flexible, finite form are described. The compositions comprise a polymer matrix that includes methylphenidate or a pharmaceutically acceptable salt and at least one acrylic polymer that is non-reactive with methylphenidate. Methods using the compositions to achieve transdermal delivery of methylphenidate or for treating Attention Deficit Disorder (ADD) and/or Attention Deficit/Hyperactivity Disorder (ADHD), postural orthostatic tachycardia syndrome, or narcolepsy also are described. 1. A composition for the transdermal delivery of methylphenidate in the form of a flexible finite system for topical application , comprising a polymer matrix consisting essentially of:(a) methylphenidate or a pharmaceutically acceptable salt thereof; and(b) at least one non-reactive acrylic polymer.2. The composition as claimed in claim 1 , wherein the polymer matrix consists essentially of a first non-reactive acrylic polymer and said methylphenidate or pharmaceutically acceptable salt thereof.3. The composition as claimed in claim 1 , wherein the polymer matrix consists essentially of a first non-reactive acrylic polymer claim 1 , a second non-reactive acrylic polymer claim 1 , and claim 1 , optionally claim 1 , additional non-reactive acrylic polymers claim 1 , and said methylphenidate or pharmaceutically acceptable salt thereof.4. The composition as claimed in claim 1 , wherein the non-reactive acrylic polymer(s) include one or more monomers selected from the group consisting of methyl acrylate claim 1 , methyl methacrylate claim 1 , butyl acrylate claim 1 , butyl methacrylate claim 1 , hexyl acrylate claim 1 , hexyl methacrylate claim 1 , 2-ethylbutyl acrylate claim 1 , 2-ethylbutyl methacrylate claim 1 , isooctyl acrylate claim 1 , isooctyl methacrylate claim 1 , 2-ethylhexyl acrylate claim 1 , 2-ethylhexyl methacrylate claim 1 , decyl acrylate claim 1 , decyl methacrylate claim 1 , dodecyl acrylate claim 1 , ...

Delayed Release Methylphenidate Compositions

The present disclosure provides programmable osmotic-controlled oral compositions providing delayed extended release of a therapeutically acceptable amount of methylphenidate hydrochloride. The programmable osmotic-controlled compositions of the disclosure provide a lag time that is independent of the presence or absence of food, type of food, pH, gastric emptying, and volume of gastric fluid. The compositions of the disclosure can be programmed to provide a desired and precise lag time, and release drug, after the lag time, at a rhythm that matches the circadian rhythm of an individual being treated to optimize therapeutic outcome and minimize side effects. 1. An osmotic-controlled oral pharmaceutical composition providing delayed release of methylphenidate or a pharmaceutically acceptable salt thereof , the composition comprising:a) a multilayer core comprising a placebo layer, an active layer, and a push layer, wherein:(i) the placebo layer comprises at least one polyethylene oxide polymer having an average molecular weight of from about 400,000 Da to about 900,000 Da,(ii) the active layer comprises methylphenidate or a pharmaceutically acceptable salt thereof, and at least one polyethylene oxide polymer having an average molecular weight of from about 100,000 Da to about 300,000 Da,(iii) the push layer comprises at least one polyethylene oxide polymer having an average molecular weight of greater than or equal to 1000,000 Da;b) a semipermeable membrane, containing at least one orifice and surrounding the core,wherein the layers in the multilayer core are placed in the following order:the placebo layer in fluid communication with the orifice in the semipermeable membrane; the active layer; and the push layer facing away from the orifice.2. The composition of claim 1 , wherein the composition provides a lag time of at least about 4 hours claim 1 , during which the composition releases no more than 10 wt % of the methylphenidate or a pharmaceutically acceptable ...

TREATMENT FOR CEREBRAL PALSY GAIT IMPAIRMENT

A methylphenidate, particularly including dextro-threo-methylphenidate, is administered to a child to treat a gait impairment secondary to cerebral palsy, or a gait impairment resultant side effect from anti-cancer and anti-seizure drugs. The administered methylphenidate simultaneously treats speech and gait or limb impairments secondary to a disease or disorder. 1. A pharmaceutical intervention for treating a gait impairment secondary to cerebral palsy in a child in need of such treatment , said pharmaceutical intervention comprises:a methylphenidate;whereby the gait impairment is diminished.2. The pharmaceutical intervention of claim 1 , wherein the methylphenidate comprises dextro-threo-methylphenidate.3. The pharmaceutical intervention of claim 1 , wherein the methylphenidate comprises an analog of a methylphenidate.4. The pharmaceutical intervention of claim 3 , wherein the methylphenidate analog comprises a nonlinear lower alkyl phenidate.5. The pharmaceutical intervention of claim 4 , wherein the nonlinear lower alkyl phenidate comprises isopropylphenidate.6. The pharmaceutical intervention of claim 1 , wherein the GMFCS level number after administration of the pharmaceutical intervention is at least one level number less than before the intervention.7. The pharmaceutical intervention of claim 1 , when the gait impairment diminishment persists wherein the methylphenidate is no longer efficaciously present in the child.8. The pharmaceutical intervention of claim 7 , wherein the child has a speech impairment secondary to cerebral palsy claim 7 , and the speech impairment is diminished and the speech impairment diminishment persists when the methylphenidate is no longer efficaciously present in the body.9. The pharmaceutical intervention of claim 1 , wherein the methylphenidate consists essentially of dextro-threo-methylphenidate.10. The pharmaceutical intervention of claim 6 , wherein the methylphenidate consists essentially of dextro-threo-methylphenidate.11. ...

DOSAGE FORMS FOR ORAL ADMINISTRATION AND METHODS OF TREATMENT USING THE SAME

The invention relates to dosage forms that provide prolonged therapy. In particular, the invention relates to dosage forms including various pluralities of drug-containing resin particles. The invention also relates to methods of making these dosage forms and methods of treating using these dosage forms. 1. A pharmaceutical composition comprising an ADHD effective agent complexed with ion-exchange resin particles to form drug-resin particles , wherein said ADHD effective agent is methylphenidate , and wherein said composition comprises a first plurality of drug-resin particles that are uncoated and a second plurality of drug-resin particles that are coated with a delayed release coating.2. The composition of claim 1 , wherein the second plurality of drug-resin particles comprises a triggered-release coating triggered by a pH change.3. The composition of claim 2 , wherein the triggered-release coating is cellulose acetate phthalate claim 2 , cellulose acetate trimellitate claim 2 , hydroxypropyl methylcellulose phthalate claim 2 , polyvinyl acetate phthalate claim 2 , carboxymethylethylcellulose claim 2 , co-polymerized methacrylic acid/methacrylic acid methyl esters claim 2 , co-polymerized methacrylic acid/acrylic acid ethyl esters claim 2 , or mixtures thereof.4. The composition of claim 3 , wherein the composition additionally contains polistirex claim 3 , polacrilex claim 3 , cholestyramine claim 3 , polacrilin or mixtures thereof.5. The composition of claim 2 , wherein said drug-resin particles coated with a triggered-release coating further comprise a diffusion barrier coating.6. The composition of claim 5 , wherein the diffusion barrier coating contains polyvinylpyrrolidone claim 5 , polyvinylacetate claim 5 , polyvinylalcohol or mixtures thereof.7. The composition of claim 4 , wherein the diffusion barrier coating is a water insoluble claim 4 , water permeable membrane.8. The composition of claim 5 , wherein the water insoluble claim 5 , water permeable ...

Use of Flecainide as an Anti-Connexin Agent and Method for Potentiating the Effects of a Psychotropic Drug

The present invention relates to the use of flecainide as an anti-connexin agent. This anti-connexin agent is advantageously used to potentiate the therapeutic effect of various psychotropic drugs. More specifically, the invention provides a combination product containing flecainide and modafinil. 114.-. (canceled)15. A method for potentiating the effects of a psychotropic drug in a patient in need thereof , said method comprising administration of an anti-connexin agent flecainide in said patient.16. The method of claim 15 , wherein said psychotropic drug is selected from the group consisting of: GABAergic claim 15 , dopaminergic claim 15 , norepinephrinergic claim 15 , serotoninergic claim 15 , histaminergic claim 15 , and glutamatergic effectors claim 15 , and those having an effect on the hypocretin/orexin system.17. The method of claim 15 , wherein said psychotropic drug is selected from the group consisting of: caffeine claim 15 , mazindol claim 15 , sodium oxybate claim 15 , pitolisant claim 15 , amphetamine claim 15 , methylphenidate claim 15 , (R)-(beta-amino-benzenepropyl) carbamate mono-hydrochloride claim 15 , and armodafinil.18. The method of claim 15 , for potentiating the effects of a psychotropic drug selected from the group consisting of: caffeine claim 15 , mazindol claim 15 , sodium oxybate claim 15 , pitolisant claim 15 , amphetamine claim 15 , methylphenidate claim 15 , (R)-(beta-amino-benzenepropyl) carbamate mono-hydrochloride claim 15 , and armodafinil.19. The method of claim 15 , wherein said anti-connexin agent Flecainide potentiates a promnesiant effect and/or an awakening effect of a psychotropic drug selected from the group consisting of: caffeine claim 15 , mazindol claim 15 , sodium oxybate claim 15 , pitolisant claim 15 , amphetamine claim 15 , methylphenidate claim 15 , (R)-(beta-amino-benzenepropyl) carbamate mono-hydrochloride claim 15 , and armodafinil.20. The method of claim 15 , for increasing the efficacy and/or safety and/or ...

Methylphenidate Extended Release Chewable Tablet

An oral methylphenidate extended release tablet is described, which can be scored and still retain its extended release profile. The tablet contains a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and an uncomplexed methylphenidate active component. Following administration of a single dose of the extended release methylphenidate chewable tablet, a therapeutically effective amount of methylphenidate is reached in less than about 20 minutes and the composition provides a twelve-hour extended release profile. 1(a) a sustained release methylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, methylphenidate-ion exchange resin complex in a polymeric matrix, wherein said barrier coating is over the methylphenidate-ion exchange resin complex-matrix;(b) a first immediate release component which comprises an immediate release uncoated methylphenidate-ion exchange resin complex;(c) a second immediate release methylphenidate component which comprises an uncomplexed methylphenidate;wherein said first immediate release component (b) has a slower onset of release than (c);wherein about 50% w/w to about 90% w/w of the methylphenidate active component is provided by the sustained release component based on the total amount of methylphenidate in the tablet, andwherein said chewable tablet is capable of being divided and providing tablet portions which retain a therapeutically effective immediate release and 12 hour extended release profile.. A methylphenidate extended release chewable tablet having a therapeutically effective immediate release and a 12-hour extended release profile, wherein said chewable tablet is a uniform solid dispersion comprising: Methylphenidate hydrochloride (HCl) and dexmethylphenidate hydrochloride both have the empirical formula CHNO.HCl. Methylphenidate HCl is a racemic mixture of d,1-threo-methyl α-phenyl-2- ...

NOVEL ANTIARRHYTHMIC FORMULATION

Pharmaceutical compositions comprising an antiarrhythmic agent for treatment of a heart condition via inhalation. Methods of treating a heart condition include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. Nebulized drug product and kits are also disclosed. 1. A kit , comprising: (a) a salt of flecainide,', '(b) a cyclodextrin, and', '(c) an acid;, '(1) a pharmaceutical composition that comprises(2) a receptacle containing said pharmaceutical composition; and(3) instructions for use of a nebulizer to inhalationally administer a dose of said pharmaceutical composition in aerosol to a subject, wherein said dose contains from about 50 mg to about 250 mg of said salt of flecainide, and said aerosol of said pharmaceutical composition has droplets that have a mass median aerodynamic diameter of less than 10 μm; andwherein said pharmaceutical composition is in the form of a liquid solution that has:(i) said salt of flecainide at a concentration of from about 65 mg/mL to about 95 mg/mL;(ii) said cyclodextrin at a concentration of from about 10% (w/v) to about 30% (w/v) of said solution; and(iii) a pH of from about 5.5 to about 6.5 when said pH is measured at room temperature.2. The kit of claim 1 , wherein said concentration of said salt of flecainide is from about 70 mg/mL to about 80 mg/mL.3. The kit of claim 1 , wherein said concentration of said salt of flecainide is about 75 mg/mL.4. The kit of claim 1 , wherein said salt of flecainide is selected from the group consisting of:flecainide acetate, flecainide hydrochloride, flecainide citrate, flecainide phosphate, and flecainide nitrate.5. The kit of claim 1 , wherein said salt of flecainide comprises flecainide acetate.6. The kit of claim 1 , wherein said acid is selected from the group consisting of: acetic acid claim 1 , citric acid claim 1 , nitric acid claim 1 , hydrochloric acid claim 1 , ascorbic acid claim 1 , lactic acid claim 1 ...

ANTIARRHYTHMIC FORMULATION

Pharmaceutical compositions comprising an antiarrhythmic agent for treatment of a heart condition via inhalation. Methods of treating a heart condition include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. Nebulized drug product and kits are also disclosed. 1. A pharmaceutical composition , comprising: a therapeutically effective amount of a salt of flecainide , a cyclodextrin , and an acid , wherein said pharmaceutical composition is in the form of a liquid solution that has said salt of flecainide at a concentration above 60 mg/mL , said cyclodextrin at a concentration of from about 5% (w/v) to about 50% (w/v) of said solution , and a pH above 5.5 when measured at room temperature.2. The pharmaceutical composition of claim 1 , wherein said concentration of said cyclodextrin is from about 15% (w/v) to about 25% (w/v) of said solution.3. The pharmaceutical composition of claim 1 , wherein said concentration of said cyclodextrin is about 20% (w/v) of said solution.4. The pharmaceutical composition of claim 1 , wherein said cyclodextrin is selected from the group consisting of: α-cyclodextrin claim 1 , β-cyclodextrin claim 1 , γ-cyclodextrin claim 1 , hydroxypropyl-β-cyclodextrin claim 1 , hydroxyethyl-β-cyclodextrin claim 1 , hydroxypropyl-γ-cyclodextrin claim 1 , hydroxyethyl-γ-cyclodextrin claim 1 , dihydroxypropyl-β-cyclodextrin claim 1 , glucosyl-α-cyclodextrin claim 1 , glucosyl-β-cyclodextrin claim 1 , diglucosyl-β-cyclodextrin claim 1 , maltosyl-α-cyclodextrin claim 1 , maltosyl-β-cyclodextrin claim 1 , maltosyl-γ-cyclodextrin claim 1 , maltotriosyl-β-cyclodextrin claim 1 , maltotriosyl-γ-cyclodextrin dimaltosyl-β-cyclodextrin claim 1 , succinyl-β-cyclodextrin claim 1 , 6A-amino-6A-deoxy-N-(3-hydroxypropyl)-β-cyclodextrin claim 1 , sulfobutylether-β-cyclodextrin claim 1 , sulfobutylether-γ-cyclodextrin claim 1 , sulfoalkylether-β-cyclodextrins claim 1 , and sulfoalkylether-γ- ...

COMPOSITIONS AND METHODS FOR SUSTAINED RELEASE OF FLECAINIDE

The invention relates generally to sustained release compositions. Specifically, the invention relates to biphasic and triphasic compositions and methods for controlling the release of a medication to treat a heart disease. 1. A method for treating a heart disease , the method comprising administering to a subject in need thereof a composition comprising flecainide combined with a binding agent , wherein said binding agent is capable of facilitating a slow release of said flecainide over a predetermined time period for once daily dosing , and wherein said heart disease is supraventricular tachycardia , atrial fibrillation , atrial flutter , or a combination thereof.2. The method according to claim 1 , wherein said predetermined time period is 6-24 hours.3. A composition for preventing AV nodal conduction time increase during treatment of atrial fibrillation claim 1 , comprising:an IC class anti-arrhythmic drug; anda rate control agent.4. The composition according to claim 3 , wherein said IC class anti-arrhythmic drug is selected from a group consisting of:flecainide acetate; andflecainide tartrate.5. The composition according to claim 3 , wherein said rate control agent is selected from a group consisting of:a beta blocker;a calcium channel blocker; andmetoprolol.6. A biphasic delayed release capsule claim 3 , comprising:a first compartment, containing a first medication;a second compartment, containing a second medication;a first coating, surrounding said first compartment; anda second coating, surrounding said second compartment and separating said first compartment from said second compartment,wherein said first coating dissolves immediately, thereby immediately releasing said first medication; andwherein said second coating is time released according to a predetermined time period, thereby providing a sustained release of said second medication.7. The biphasic delayed release capsule according to claim 6 , wherein said first medication is a rate control agent ...

PHACETOPERANE FOR THE TREATMENT OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER

The invention relates to the treatment of an attention deficit hyperactivity disorder (ADHD) with alpha-phenyl(piperidin-2-yl)methanol, or the pharmaceutically acceptable salts and esters thereof, in particular the acetate derivative, more particularly dextrophacetoperane. The invention additionally provides a method of synthesis of the (S,S) enantiomer of alpha-phenyl(piperidin-2-yl)methanol as well as a method of synthesis of dextrophacetoperane. 1. A method for treating an attention deficit hyperactivity disorder (ADHD) in a patient , which method comprises administering alpha-phenyl(piperidin-2-yl)methanol , or the pharmaceutically acceptable salts and esters thereof.2. The method according to claim 1 , comprising administering the patient with alpha-phenyl(piperidin-2-yl)methyl acetate in the threo form (phacetoperane) or a pharmaceutically acceptable salt thereof.3. The method of claim 2 , wherein said phacetoperane is in its dextrorotatory form.4. The method of claim 2 , wherein said phacetoperane is in its laevorotatory form.5. The method of claim 1 , wherein the patient is an adults.6. The method of claim 1 , wherein alpha-phenyl(piperidin-2-yl)methanol claim 1 , or a pharmaceutically acceptable salt and ester thereof claim 1 , is administered by the oral route.7. The method of claim 6 , wherein alpha-phenyl(piperidin-2-yl)methanol claim 6 , or the pharmaceutically acceptable salt and ester thereof claim 6 , is in a form suitable for prolonged release.8. The method of claim 6 , wherein alpha-phenyl(piperidin-2-yl)methanol claim 6 , or a pharmaceutically acceptable salt and ester thereof claim 6 , is in the form of a combination or of a mixture of microgranules for immediate release claim 6 , and of microgranules for prolonged release.10. A method of preparing the (S claim 6 ,S) enantiomer of alpha-phenyl(piperidin-2-yl)methyl acetate(dextrophacetoperane) or a pharmaceutically acceptable salt thereof claim 6 , said method comprising the following steps:{' ...

METHODS OF TREATING BEHAVIORAL SYNDROMES USING PIPRADROL

Methods of treating behavioral syndromes by administering a pharmaceutical composition of pipradrol or a pharmaceutically acceptable salt thereof are provided. The methods may be used to treat Attention-Deficit Disorder (ADD) and Attention-Deficit Hyperactivity Disorder (ADHD). 1. A method of treating a behavioral syndrome selected from Attention-Deficit Disorder (ADD) or Attention-Deficit Hyperactivity Disorder (ADHD) comprising administering to a patient in need thereof a pharmaceutical composition comprising pipradrol or a pharmaceutically acceptable salt thereof.2. The method of wherein the composition provides reduction in hyperactivity claim 1 , impulsiveness claim 1 , inattentiveness claim 1 , or a combination of symptoms in a patient diagnosed with a behavioral syndrome.3. The method of wherein the pipradrol or a pharmaceutically acceptable salt thereof is administered to the patient a daily dosage in the range of about 0.1 mg to about 50 mg.4. The method of further comprising administering a compound selected from the group consisting of gaboxadol claim 1 , acetazolamide claim 1 , carbamazepine claim 1 , clobazam claim 1 , clonazepam claim 1 , eslicarbazepine acetate claim 1 , ethosuximide claim 1 , gabapentin claim 1 , lacosamide claim 1 , lamotrigine claim 1 , leviteracetam claim 1 , nitrazepam claim 1 , oxcarbazepine claim 1 , perampanel claim 1 , piracetam claim 1 , phenobarbital claim 1 , phenytoin claim 1 , pregabalin claim 1 , primidone claim 1 , retigabine claim 1 , rufinamide claim 1 , sodium valproate claim 1 , stiripentol claim 1 , tiagabine claim 1 , topiramate claim 1 , vigabatrin claim 1 , and zonisamide. This application is a continuation of U.S. patent application Ser. No. 15/604,776, filed May 25, 2017, which claims the benefit of and priority to U.S. Provisional Application Ser. No. 62/341,855, filed on May 26, 2016, the entire contents of which are herein incorporated by reference.Methods of using a composition including pipradrol, a ...

PHACETOPERANE FOR TREATING OF ATTENTION DEFICIT HYPERACTIVITY DISORDER

The invention relates to the treatment of an attention deficit hyperactivity disorder (ADHD) with alpha-phenyl(piperidin-2-yl)methanol, or the pharmaceutically acceptable salts and esters thereof, in particular the acetate derivative, more particularly dextrophacetoperane. The invention additionally provides a method of synthesis of the (S,S) enantiomer of alpha-phenyl(piperidin-2-yl)methanol as well as a method of synthesis of dextrophacetoperane. 110-. (canceled)11. A pharmaceutical composition comprising a therapeutically effective amount of levophacetoperane , or a pharmaceutically acceptable salt thereof , for the treatment of attention deficit hyperactivity disorder (ADHD) and a pharmaceutical acceptable excipient.12. The pharmaceutical composition of claim 11 , wherein the therapeutically effective amount for the treatment of ADHD ranges from about 5 mg to about 20 mg.13. The pharmaceutical composition of claim 12 , wherein the therapeutically effective amount for the treatment of ADHD ranges from about 5 mg to about 10 mg.14. A tablet comprising the pharmaceutical composition of . The invention relates to the treatment of attention deficit hyperactivity disorder.Attention deficit hyperactivity disorder (ADHD) is a combination of behavioural hyperactivity, inattentiveness, and impulsiveness. Diagnosis is based on clinical criteria defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV TR). ADHD is first and foremost the exaggerated, permanent and continual expression of behavioural manifestations that are not due to educational, pedagogical or socio-economic deprivation.This disorder is a frequent reason for consultation in child psychopathology. According to studies, its prevalence in the general child population is from 2 to 5%. The signs of inattentiveness may persist beyond childhood and are responsible for social, relational and affective difficulties. Up to 60% of children with ADHD continue to present characteristic symptoms at ...

TOPICAL REGIONAL NEURO-AFFECTIVE THERAPY

A method of treating a disease state or condition in humans via topical brainstem afferent stimulation therapy via the administration of a drug to the back of the neck of a human patient at the hairline in close proximity to and under or on the area of skin above the brain stem to provide regional neuro-affective therapy is disclosed. 1. A method of treating ADD/ADHD in a human patient , comprising administering a drug for the treatment of ADD/ADHD in a therapeutically effective amount to treat the disease state or condition , to the back of the neck at the hairline in close proximity to and under or on the area of skin above the brain stem to provide regional neuro-affective therapy to the human patient.2. The method of claim 1 , wherein the drug is an amphetamine derivative.3. (canceled)4. The method of claim 2 , wherein the drug is selected from the group consisting of lisdexamfetamine claim 2 , d-amphetamine claim 2 , l-amphetamine claim 2 , methylphenidate claim 2 , dextroamphetamine claim 2 , dexmethylphenidate hydrochloride claim 2 , atomoxetine claim 2 , phentermine claim 2 , fenfluramine claim 2 , dexfenfluramine and mixtures thereof.5. The method of claim 2 , diseases wherein the drug comprises phentermine.6. The method of claim 1 , wherein the drug is selected from the group consisting of lisdexamfetamine claim 1 , d-amphetamine claim 1 , l-amphetamine claim 1 , methylphenidate claim 1 , dextroamphetamine claim 1 , dexmethylphenidate hydrochloride claim 1 , atomoxetine claim 1 , and mixtures of any of the foregoing.7. The method of claim 2 , wherein the drug consists of phentermine.824-. (canceled)25. The method of claim 1 , wherein the drug is formulated in a pharmaceutically acceptable immediate release topical carrier.26. The method of claim 25 , wherein the carrier is aqueous-based.27. The method of claim 1 , further comprising formulating the drug for the treatment of ADD/ADHD in a pharmaceutically acceptable immediate release aqueous-based carrier ...

Methods of treating attention deficit hyperactivity disorder

The invention is directed to oral modified/controlled release drug formulations which provide a rapid initial onset of effect and a prolonged duration of effect. Preferably, the peak concentration is lower than that provided by the reference standard for immediate release formulations of the drug, and the duration of effect falls rapidly at the end of the dosing interval. 120-. (canceled)21. A method of treating Attention Deficit Hyperactivity Disorder in a subject identified in need thereof , comprising:administering an oral controlled release formulation to the subject, wherein the oral controlled release formulation comprises:a plurality of substrates comprising a portion of an effective dose of methylphenidate or a pharmaceutically acceptable salt thereof in immediate release form,a hydrophobic material comprising an acrylic polymer coated onto the surface of said substrates in an amount sufficient to retard the release of said portion of the methylphenidate or a pharmaceutically acceptable salt thereof,an enteric coating applied over said hydrophobic coating to obtain enteric coated substrates, wherein said enteric coating is in an amount sufficient to substantially delay the release of said methylphenidate or a pharmaceutically acceptable salt thereof from said substrates until after said formulation passes through the stomach, wherein said enteric coating is derived from an aqueous dispersion comprising an acrylic/methacrylic copolymer, a plasticizer and a glidant,the formulation further comprising the remaining portion of the effective dose of the methylphenidate or pharmaceutically acceptable salt thereof in immediate release form, andwherein the formulation provides a maximum plasma concentration of methylphenidate at about 0.5 to about 2 hours after oral administration,and the duration of effect provided by the methylphenidate or pharmaceutically acceptable salt thereof contained in the formulation falls below effective plasma concentrations at about 10 ...

ORALLY EFFECTIVE METHYLPHENIDATE EXTENDED RELEASE POWDER AND AQUEOUS SUSPENSION PRODUCT

An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile. 1. A methylphenidate aqueous oral suspension , wherein said suspension has a pH of about 4.2;(i) an immediate release methylphenidate component;(ii) a sustained release methylphenidate component comprising a water-insoluble, water-permeable, sustained release barrier coated methylphenidate-ion exchange resin complex-optional matrix, and(iii) water;{'sub': '0-∞', 'wherein the aqueous oral suspension provides a pharmacokinetic profile in which d-methylphenidate has an area under the curve (AUC) of about 114 ng-hr/mL to about 180 ng-hr/mL following a single oral administration of the aqueous oral suspension to adult subjects under fasted conditions at a dose equivalent to 60 mg racemic methylphenidate HCl.'}2. The methylphenidate aqueous oral suspension according to claim 1 , wherein said suspension comprises at least about 80% w/w water based on the total weight of the suspension.3. The methylphenidate aqueous oral suspension according to claim 1 , wherein the immediate release methylphenidate component and the sustained release methylphenidate component in said suspension provides a dose equivalent to about 25 mg racemic methylphenidate HCl ...

Orally Effective Methylphenidate Extended Release Powder and Aqueous Suspension Product

An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate—ion exchange resin complex, a barrier coated methylphenidate—ion exchange resin complex—matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile. 1. A methylphenidate aqueous oral suspension , wherein said suspension has a pH of about 4.2;(i) an immediate release methylphenidate component;(ii) a sustained release methylphenidate component comprising a water-insoluble, water-permeable, sustained release barrier coated methylphenidate—ion exchange resin complex—optional matrix, and(iii) water;{'sub': '0-∞', 'wherein the aqueous oral suspension provides a pharmacokinetic profile in which d-methylphenidate has an area under the curve (AUC) of about 114 ng-hr/mL to about 180 ng-hr/mL following a single oral administration of the aqueous oral suspension to adult subjects under fasted conditions at a dose equivalent to 60 mg racemic methylphenidate HCl.'}2. The methylphenidate aqueous oral suspension according to claim 1 , wherein said suspension comprises at least about 80% w/w water based on the total weight of the suspension.3. The methylphenidate aqueous oral suspension according to claim 1 , wherein the immediate release methylphenidate component and the sustained release methylphenidate component in said suspension provides a dose equivalent to about 25 mg racemic methylphenidate HCl ...

Methods and Compositions Particularly for Treatment of Attention Deficit Disorder

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described. 2. The composition of claim 1 , wherein the oral solid pharmaceutical composition is in the form of a capsule comprising the plurality of coated beads.3. The composition of claim 1 , wherein the inner controlled release coating is selected from the group consisting of an ethylcellulose polymer claim 1 , a cellulose ether claim 1 , a polyethylene oxide claim 1 , a polyvinyl alcohol derivate claim 1 , a methacrylic acid copolymer claim 1 , polyethylene glycol claim 1 , a polyglycolic acid claim 1 , a polylactic acid claim 1 , a polycaprolactone claim 1 , a poly(n-hydroxybutyrate) claim 1 , a polyamino acid claim 1 , a poly(amide-enamine) claim 1 , a polyester claim 1 , an ethylene-vinyl acetate (EVA) claim 1 , a polyvinyl pyrrolidone (PVP) claim 1 , a poly (acrylic acid) (PAA) claim 1 , a poly (methacrylic acid) (PMAA) claim 1 , and mixtures thereof.4. The composition of claim 1 , wherein the inner controlled release coating comprises ammonio methacrylate copolymer claim 1 , Type B USP/NF.5. The composition of claim 1 , wherein the inner controlled release coating is ...

Methylphenidate-Prodrugs, Processes of Making and Using the Same

The present technology is directed to prodrugs and compositions for the treatment of various diseases and/or disorders comprising methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof. In some embodiments, the conjugates further include at least one linker. The present technology also relates to the synthesis of methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof or combinations thereof. 191.-. (canceled)93. The composition of claim 92 , wherein when Gis present claim 92 , Gis attached to Gat ortho claim 92 , meta claim 92 , or para positions.94. The composition of claim 92 , wherein Gand Gare each independently an amino acid claim 92 , wherein the amino acid comprises standard amino acids claim 92 , non-standard amino acids or synthetic amino acids.95. The composition of claim 92 , wherein the oxygen protecting group is tert-butyl group.96. The composition of claim 94 , wherein the amino acid is selected from the group consisting of alanine claim 94 , arginine claim 94 , asparagine claim 94 , aspartic acid claim 94 , cysteine claim 94 , glutamic acid claim 94 , glutamine claim 94 , glycine claim 94 , histidine claim 94 , isoleucine claim 94 , leucine claim 94 , lysine claim 94 , methionine claim 94 , phenylalanine claim 94 , proline claim 94 , pyrrolysine claim 94 , selenocysteine claim 94 , serine claim 94 , threonine claim 94 , tryptophan claim 94 , tyrosine and valine.97. The composition of claim 94 , wherein the conjugate is a pharmaceutically acceptable anionic claim 94 , amphoteric claim 94 , zwitterionic or cationic salt form or salt mixtures thereof.98. The composition of claim 97 , wherein the anionic salt form is selected from the group consisting of acetate claim 97 , l-aspartate claim 97 , besylate claim 97 , bicarbonate claim 97 , carbonate claim 97 , d-camsylate claim 97 , l-camsylate claim 97 , ...

Oral Pharmaceutical Dosage Forms

Controlled release oral dosage forms suitable for administration of methylphenidate are provided. Abuse-resistant controlled release oral dosage forms suitable for administration of methylphenidate are also provided. Methods of treating ADD and ADHD using the oral dosage forms are also provided. 1. An oral controlled release dosage form comprising methylphenidate and a controlled release carrier system , wherein said dosage form is characterized by providing:(i) an initial increasing in vivo rate of release of methylphenidate from the controlled release system suitable to provide an initial increasing-rate phase of less than or equal to about 2 hours, and sufficient to provide a therapeutically effective amount of methylphenidate for a rapid onset of action;(ii) a second, non-ascending in vivo rate of release of methylphenidate from the controlled release system that provides a subsequent non-ascending phase sufficient to provide a therapeutically effective amount of methylphenidate through at least about 11 to 12 hours post administration; and{'sub': 'max', '(iii) a single Tof about 5.5 to 7.5 hours post administration.'}2. The controlled release oral dosage form of claim 1 , wherein the initial increasing-rate phase is sufficient to provide an onset of action within about 1 to 1.5 hours post administration.3. The controlled release oral dosage form of claim 1 , wherein the single Toccurs at about 6 to 7 hours post administration.4. The controlled release oral dosage form of claim 1 , wherein the subsequent non-ascending phase is sufficient to provide a therapeutically effective amount of methylphenidate through at least about 12 to 14 hours post administration5. The controlled release oral dosage form of claim 1 , wherein the dosage form is further characterized by having a food effect.6. The controlled release oral dosage form of claim 5 , wherein the oral bioavailability of the methylphenidate from the dosage form is increased upon co-administration with food.7. ...

TRANSMUCOSAL DRUG DELIVERY SYSTEM

Disclosed are preparations and formulations of high thermodynamic activity lipophilic associations (LA), in which there is pairing between an ionizable pharmaceutical agent and a lipophilic species having ionic characteristics opposite to that of the pharmaceutical agent. Such lipophilic associations manifest high thermodynamic activity, as evidenced by their being predominantly in a liquid phase at room temperature or solvated in a lower-than-water dielectric solvent. Further the pharmaceutical agent being solubilized means that dissolution is not rate limiting to transmucosal absorption. This LA or LA-solvate is formulated into a low dielectric dosage form, from whence, upon the dosage form's hydration, the pharmaceutical agent is driven through the mucosal tissue and into systemic circulation. The invention therefore provides an enhanced transmucosal drug delivery system for ionizable pharmaceutical agents at or near physiological pH. 1. A pharmaceutical composition , comprising: a rapid-release solid tablet further comprising: an adsorbent , and a liquid solution comprising methylphenidate and a fatty acid.2. The pharmaceutical composition of claim 1 , wherein the adsorbent is silica.3. The pharmaceutical composition of claim 1 , wherein the fatty acid is selected from the group consisting of caproic acid claim 1 , caprylic acid claim 1 , capric acid claim 1 , lauric acid claim 1 , myristic acid claim 1 , palmitic acid claim 1 , stearic acid claim 1 , arachidic acid claim 1 , behenic acid claim 1 , lignoceric acid claim 1 , myristoleic acid claim 1 , palmitoleic acid claim 1 , oleic acid claim 1 , gadoleic acid claim 1 , erucic acid claim 1 , ricinoleic acid claim 1 , linoleic acid claim 1 , linolenic acid claim 1 , licanic acid claim 1 , arachidonic acid and clupanadonic acid.4. The pharmaceutical composition of claim 1 , further including a co-solvent.5. The pharmaceutical composition of claim 4 , wherein the co-solvent comprises polyethylene glycol (PEG) ...

ATTENTION EVALUATION AND METHODS FOR MEDICATING

Provided are methods for diagnosing or selecting a mammal in need of a stimulant ADHD drug, conducting a non-specific electro-dermal responses (EDAs) analysis and/or an auditory sustained attention (ASAT) analysis on the mammal and administering or adjusting the dose of a stimulant ADHD drug to be administered to the mammal. 1. A method comprising the steps of:(i) diagnosing or selecting a subject in need of a stimulant ADHD drug;(ii) conducting a non-specific electro-dermal responses (EDAs) analysis on said subject;(iii) administering said stimulant ADHD drug to said subject having higher value of said EDAs compared to a control value.2. The method of claim 1 , wherein said method confirms or predicts responsiveness of said subject to said stimulant ADHD drug.3. The method of claim 1 , wherein said subject having higher value of said EDAs compared to a control value is responsive to said stimulant ADHD drug.4. The method of claim 1 , wherein said stimulant ADHD drug is selected from: a short-acting stimulant drug claim 1 , a long-acting stimulant drug claim 1 , an intermediate-acting stimulant drug claim 1 , or any combination thereof.5. The method of claim 1 , wherein said stimulant ADHD drug comprises methylphenidate or any derivative thereof.6. The method of claim 1 , further comprising the step of: conducting an auditory sustained attention (ASAT) analysis on said subject following step (ii) claim 1 , and administering said stimulant ADHD drug to said subject having both: lower baseline ASAT performance compared to a control value and higher value of said EDAs compared to a control value.7. A method for adjusting a dose of a stimulant ADHD drug in a subject claim 1 , the method comprising the steps of:(i) selecting a subject treated with an initial dosage or dose of said stimulant ADHD drug;(ii) conducting a non-specific electro-dermal responses (EDAs) analysis on said subject;(iii) increasing said initial dose of said stimulant ADHD drug to said subject having ...

TOPICAL REGIONAL NEURO-AFFECTIVE THERAPY

A method of treating a disease state or condition in humans via topical brainstem afferent stimulation therapy via the administration of a drug to the back of the neck of a human patient at the hairline in close proximity to and under or on the area of skin above the brain stem to provide regional neuro-affective therapy is disclosed. 1. A method of treating ADD/ ADHD in a human patient , comprising administering a drug for the treatment of ADD/ ADHD which is an amphetamine derivative in a therapeutically effective amount to treat the disease state or condition , to the back of the neck to provide regional neuro-affective therapy to the human patient.2. (canceled)3. (canceled)4. The method of claim 1 , wherein the drug is selected from the group consisting of lisdexamfetamine claim 1 , d-amphetamine claim 1 , l-amphetamine claim 1 , methylphenidate claim 1 , dextroamphetamine claim 1 , dexmethylphenidate hydrochloride claim 1 , atomoxetine claim 1 , phentermine claim 1 , fenfluramine claim 1 , dexfenfluramine and mixtures thereof.5. The method of claim 1 , wherein the drug comprises phentermine.6. (canceled)7. The method of claim 1 , wherein the drug consists of phentermine.824.-. (canceled)25. The method of claim 1 , wherein the drug is formulated in a pharmaceutically acceptable immediate release topical carrier.26. The method of claim 25 , wherein the carrier is aqueous-based.27. The method of claim 1 , further comprising formulating the drug for the treatment of ADD/ADHD in a pharmaceutically acceptable immediate release aqueous-based carrier claim 1 , and applying a sufficient amount to the back of the neck at the hairline (“BONATH”) of the human patient such that the onset of clinical effect occurs in less than about 30 minutes.28. (canceled)29. The method of claim 25 , wherein the carrier is a gel or cream.30. The method of claim 29 , further comprising adding at least one adjuvant selected from the group consisting of a penetration enhancer claim 29 , ...

UNIT DOSES, AEROSOLS, KITS, AND METHODS FOR TREATING HEART CONDITIONS BY PULMONARY ADMINISTRATION

Methods of treating atrial arrhyththmia include administering an effective amount of at least one antiarrthythmic pharmaceutical agent to a patient in need thereof, such that the at least one antiarrhythmic pharmaceutical agent first enters the heart through the pulmonary vein to the left atrium. Other methods of treating atrial arrhythmia include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. An amount of the at least one antiarrhythmic pharmaceutical agent may peak in the coronary sinus of the heat at a time ranging from 10 seconds to 30 minutes from initiation of the administering. Unit does, aerosols, and kits are also contemplated. 1. A kit comprising an aerosolization device and a unit dose comprising a pharmaceutical composition that comprises a therapeutically effective amount of an antiarrhythmic agent for cardioversion of atrial arrhythmia in a subject in need thereof when said pharmaceutical composition is inhaled by said subject via aerosolization , wherein said antiarrhythmic agent is selected from the group consisting of: class Ia , Ib , Ic , III , and IV antiarrhythmics , a salt , and a solvate thereof , and any combination thereof2. The kit of claim 1 , wherein said aerosolization device comprises a jet nebulizer.3. The kit of claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent in said unit dose is less than an amount of said antiarrhythmic agent in an intravenous dose that is effective for cardioversion.4. The kit of claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent in said unit dose is between 1 mg and 100 mg.5. The kit of claim 1 , wherein said pharmaceutical composition comprises a liquid solution of said antiarrhythmic agent.6. The kit of claim 5 , wherein a volume of said unit dose is about 1 mL to about 10 mL.7. The kit of claim 5 , wherein a volume of said unit dose is about 2 mL to about 6 mL. ...

Methods of Treatment of Attention Deficit Hyperactivity Disorder

Therapeutic compositions and methods for treatment of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) include dosage forms that deliver a therapeutic amount of active drug in a delayed and controlled release formulation. The dosage form can be administered at night and drug release is delayed for from 5 to 7 hours or longer, followed by an ascending release rate. When administered at night the composition provides early morning improvement in symptoms of ADHD and sustained improvement over a period of at least 12 hours. 1. A method of treating a subject with a disorder or condition responsive to the administration of a methylphenidate , comprising:orally administering an effective amount of a methylphenidate or a pharmaceutical salt thereof in a formulation comprising one or more water soluble capsules containing a unit dose of methylphenidate or a pharmaceutical salt thereof in a solid dosage form that comprises a plurality of beads,wherein said beads comprise a sustained release formulation comprising the methylphenidate or a pharmaceutical salt thereof enclosed in a delayed release coating that is insoluble in an aqueous medium at pH below 5.5,wherein the sustained release formulation comprises a drug-containing core enclosed in a sustained release coating comprising ethyl cellulose and hydroxypropyl cellulose in a ratio of about 1:3 to 1:5, dibutyl sebacate and from 25% to 50% magnesium stearate, andwherein the method comprises administering the unit dose form 5-8 hours prior to the desired treatment period.2. The method of claim 1 , wherein the delayed release coating comprises methacrylic acid copolymer type-B claim 1 , mono- and di-glycerides and polysorbate 80.3. The method of claim 1 , wherein administration of the formulation is timed to administer the drug prior to a subject's bed time and to allow the subject to sleep during a period of absorption of less than 5% of the total therapeutic dose and to have absorbed a ...

PHACETOPERANE FOR TREATING OF ATTENTION DEFICIT HYPERACTIVITY DISORDER

The invention relates to the treatment of an attention deficit hyperactivity disorder (ADHD) with alpha-phenyl(piperidin-2-yl)methanol, or the pharmaceutically acceptable salts and esters thereof, in particular the acetate derivative, more particularly dextrophacetoperane. The invention additionally provides a method of synthesis of the (S,S) enantiomer of alpha-phenyl(piperidin-2-yl)methanol as well as a method of synthesis of dextrophacetoperane. 1. Alpha-phenyl(piperidin-2-yl)methanol , or the pharmaceutically acceptable salts and esters thereof , for use in the treatment of an attention deficit hyperactivity disorder (ADHD).210-. (canceled) The invention relates to the treatment of attention deficit hyperactivity disorder.Attention deficit hyperactivity disorder (ADHD) is a combination of behavioural hyperactivity, inattentiveness, and impulsiveness. Diagnosis is based on clinical criteria defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV TR). ADHD is first and foremost the exaggerated, permanent and continual expression of behavioural manifestations that are not due to educational, pedagogical or socio-economic deprivation.This disorder is a frequent reason for consultation in child psychopathology. According to studies, its prevalence in the general child population is from 2 to 5%. The signs of inattentiveness may persist beyond childhood and are responsible for social, relational and affective difficulties. Up to 60% of children with ADHD continue to present characteristic symptoms at adult age, although the typical presentation corresponds to completely different criteria (work, relationships, parenthood, etc.). Studies have shown that the disorder is clinically significant at adult age, with dysfunction in professional, familial and affective respects. Moreover, comorbidity is high, and can complicate diagnosis and treatment.Ritalin® (methylphenidate hydrochloride) is currently the drug most prescribed for treating ADHD, but it ...

METHYLPHENIDATE-PRODRUGS, PROCESSES OF MAKING AND USING THE SAME

The present technology is directed to compositions comprising d-threo-methylphenidate conjugates and unconjugated methylphenidate. The present technology also relates to compositions and oral formulations comprising d-threo-methylphenidate conjugated to nicotinoyl-L-serine, and/or a pharmaceutically acceptable salt thereof, and unconjugated methylphenidate and/or a pharmaceutically acceptable salt thereof. The present technology additionally relates to a pharmaceutical kit containing the composition comprising d-threo-methylphenidate conjugated to nicotinoyl-L-serine, and/or a pharmaceutically acceptable salt thereof, and unconjugated methylphenidate and/or a pharmaceutically acceptable salt thereof. 1105-. (canceled)107. The pharmaceutical kit of claim 106 , wherein the pharmaceutically acceptable salts of the unconjugated methylphenidate and/or compound is independently selected from the group consisting of acetate claim 106 , l-aspartate claim 106 , besylate claim 106 , bicarbonate claim 106 , carbonate claim 106 , d-camsylate claim 106 , l-camsylate claim 106 , citrate claim 106 , edisylate claim 106 , formate claim 106 , fumarate claim 106 , gluconate claim 106 , hydrobromide/bromide claim 106 , hydrochloride/chloride claim 106 , d-lactate claim 106 , l-lactate claim 106 , d claim 106 ,l-lactate claim 106 , d claim 106 ,l-malate claim 106 , l-malate claim 106 , mesylate claim 106 , pamoate claim 106 , phosphate claim 106 , succinate claim 106 , sulfate claim 106 , bisulfate claim 106 , d-tartrate claim 106 , martrate claim 106 , d claim 106 ,l-tartrate claim 106 , meso-tartrate claim 106 , benzoate claim 106 , gluceptate claim 106 , d-glucuronate claim 106 , hybenzate claim 106 , isethionate claim 106 , malonate claim 106 , methylsulfate claim 106 , 2-napsylate claim 106 , nicotinate claim 106 , nitrate claim 106 , orotate claim 106 , stearate claim 106 , tosylate claim 106 , thiocyanate claim 106 , acefyllinate claim 106 , aceturate claim 106 , aminosalicylate ...

DEVICE FOR TRANSDERMAL ADMINISTRATION OF DRUGS INCLUDING ACRYLIC BASED POLYMERS

A transdermal delivery system is provided where the drug delivery rates, onset and profiles of at least one active agent are controlled by selectively manipulating the monomeric make up of an acrylic-based polymer in the transdermal drug delivery system. The drug carrier composition may be comprised of (a) one or more acrylic-based polymers having one or more different monomers selected from the group consisting of hard and soft monomers; (b) one or more silicone-based polymers; and (c) one or more active agents where the device provides a desired solubility for the active agent and controls drug delivery rates, onset and profiles of at least one active agent. 119-. (canceled)20. A method for transdermally delivering a drug to a user in need thereof , comprising administering to the user a transdermal drug delivery system comprising a polymer composition comprising a blend of:{'sub': g', 'g, '(a) at least one acrylic-based polymer which acrylic-based polymer is polymerized with monomers that include: (i) a soft acrylic monomer having a glass transition temperature (T) from about −70° C. to about −10° C. in an amount of from about 20 to about 70% by weight of the acrylic-based polymer; and (ii) a hard acrylic monomer having a glass transition temperature (T) from about −5° C. to about 120° C. in an amount of from about 30 to about 80% by weight of the acrylic-based polymer; and'}(b) about 0.3% to about 30% by weight of the composition of one or more drugs,wherein said acrylic based polymers are not polymerized with methacrylic acid monomers.21. The method according to claim 20 , wherein the one or more drugs comprises methylphenidate.22. The method according to claim 20 , wherein the composition comprises from about 0.5% to about 15% by weight of the one or more drugs.23. The method according to claim 20 , wherein the composition comprises from about 1% to about 10% by weight of the one or more drugs.24. The method according to claim 20 , wherein the composition ...

METHODS OF TREATING DEVELOPMENTAL DISORDERS USING PIPRADROL

Methods of treating developmental disorders by administering a pharmaceutical composition of pipradrol or a pharmaceutically acceptable salt thereof are provided. The methods may be used to treat conditions such as epilepsy, Landau-Kleffner Syndrome, Lennox-Gastaut syndrome (LGS) and Dravet syndrome. 17-. (canceled)8. A method of treating a seizure disorder comprising administering to a patient in need thereof pipradrol or a pharmaceutically acceptable salt thereof.9. The method of wherein the seizure disorder is selected from the group consisting of epilepsy claim 8 , Landau-Kleffner syndrome claim 8 , benign rolandic epilepsy (BRE) claim 8 , intractable childhoof epilepsy (ICE) claim 8 , childhood absence epilepsy (CAE) claim 8 , juvenile myoclonic epilepsy (JME) claim 8 , infantile spasms (or West syndrome) claim 8 , a sodium channel protein type 1 subunit alpha (Scn1A)-related disorder claim 8 , and Lennox-Gastaut syndrome (LGS).10. The method of wherein the seizure disorder is a childhood epilepsy syndrome selected from the group consisting of benign rolandic epilepsy (BRE) claim 8 , childhood absence epilepsy (CAE) claim 8 , juvenile myoclonic epilepsy (JME) claim 8 , infantile spasms (or West syndrome) claim 8 , and Lennox-Gastaut syndrome (LGS).11. The method of wherein the seizure disorder is epilepsy.12. The method of wherein the seizure disorder is Lennox-Gastaut syndrome (LGS).13. The method of wherein the seizure disorder is Landau-Kleffner syndrome.14. The method of wherein the patient is administered a daily dosage in the range of about 0.1 mg to about 50 mg pipradrol or a pharmaceutically acceptable salt thereof15. The method of wherein the patient is administered pharmaceutical composition comprising about 0.1 mg to about 50 mg pipradrol or a pharmaceutically acceptable salt thereof.16. The method of wherein the composition provides reduction in the frequency of seizures claim 8 , the severity of seizures claim 8 , or a combination thereof in a ...

Compositions for Treatment of Attention Deficit Hyperactivity Disorder

Therapeutic compositions deliver a therapeutic amount of methylphenidate in a delayed and extended release formulation. The dosage form exhibits a lag time prior to release of from 6 to 8 hours or longer, followed by a sustained release period. 1. A solid , oral pharmaceutical composition comprising coated particles:said particles comprising:(a) a core comprising methylphenidate or a pharmaceutical salt thereof;(b) a sustained release layer enclosing the core, wherein the sustained release layer comprises a water-insoluble and water-permeable polymer, a water soluble polymer, a hydrophobic plasticizer, and a hydrophobic binder; and(c) a pH dependent polymer or copolymer that is insoluble in aqueous medium at pH lower than 5.5; wherein the formulation provides at least an 8 hour lag time during which the formulation releases no more than 10% of the total methylphenidate or a pharmaceutical salt thereof followed by a sustained release period of 10-12 hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl pH 1.1, for up to 2 hours followed by 4 hours in sodium phosphate buffer at pH 6.0; followed by 14 hours in sodium phosphate buffer, pH 7.2 at 37° C.+−0.0.5° C., as measured by the USP Apparatus I.2. The composition of claim 1 , wherein the core comprises methylphenidate hydrochloride.3. The composition of claim 1 , wherein the sustained release layer comprises ethyl cellulose claim 1 , hydroxypropyl cellulose claim 1 , dibutyl sebacate and a metal stearate.4. The composition of claim 1 , wherein the sustained release layer comprises ethyl cellulose claim 1 , hydroxypropyl cellulose claim 1 , dibutyl sebacate and magnesium stearate.5. The composition of claim 1 , wherein the pH dependent copolymer is methacrylic acid copolymer Type B.6. The composition of claim 1 , further comprising mono- and diglycerides claim 1 , dibutyl sebacate and polysorbate 80.7. The composition of claim 1 , contained in a single dosage form containing 1 mg to 150 mg of ...

METHODS OF TREATING ATTENTION DEFICIT HYPERACTIVITY DISORDER

The invention is directed to oral modified/controlled release drug formulations which provide a rapid initial onset of effect and a prolonged duration of effect. Preferably, the peak concentration is lower than that provided by the reference standard for immediate release formulations of the drug, and the duration of effect falls rapidly at the end of the dosing interval. 1: An oral controlled release formulation comprisinga plurality of substrates comprising a portion of an effective dose of a drug in an immediate release form,a hydrophobic material coated onto the surface of said substrates in an amount sufficient to retard the release of said drug,an enteric coating applied over said hydrophobic coating in an amount sufficient to substantially delay the release of said drug from said substrate until after said formulation passes through the stomach,the formulation further comprising the remaining portion of said drug in an immediate release form.213-. (canceled)14: A method for preparing an oral controlled release formulation comprisingpreparing immediate release drug-coated inert beads by spraying a solution of a drug onto inert beads;applying a controlled release coating to said immediate release drug-coated inert beads to convert the same into controlled release beads;applying an enteric coating onto said controlled release coating; andapplying an immediate release overcoat of said drug onto the surface of said enteric coated beads.1520-. (canceled)21: A method of treating Attention Deficit Hyperactivity Disorder in a child comprising:administering an oral dose of a controlled release methylphenidate hydrochloride formulation to the child once in the morning to produce a clinical effect that is at least equivalent to two doses of immediate-release methylphenidate given at breakfast and lunchtime, with a duration of action that may reduce the need for a third dose of immediate release methylphenidate later in the day, the formulation having a rapid onset ...

Methods and Compositions Particularly for Treatment of Attention Deficit Disorder

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described. 129.-. (canceled)37. The method of claim 30 , wherein the pharmaceutical composition is efficacious for at least 13 hours.38. A method of treating ADHD in a pediatric subject aged at least 6 years old to 17 years of age claim 30 , the method comprising administering to the pediatric subject in need thereof an oral solid pharmaceutical composition comprising 25 mg of methylphenidate hydrochloride once daily with or without food in the morning and optionally titrating to 35 mg claim 30 , 45 mg claim 30 , 55 mg claim 30 , 70 mg claim 30 , or 85 mg methylphenidate hydrochloride using an oral solid pharmaceutical composition comprising 35 mg claim 30 , 45 mg claim 30 , 55 mg claim 30 , 70 mg claim 30 , or 85 mg methylphenidate hydrochloride claim 30 , in intervals of no less than five days. The present invention relates to methods and compositions, particularly for treatment of attention deficit disorder.Sustained release dosage forms are important in the search for improved therapy, both through improved patient compliance and decreased incidences of adverse drug reactions. ...

Methods and Compositions Particularly for Treatment of Attention Deficit Disorder

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described.

ABUSE AND MISUSE DETERRENT TRANSDERMAL SYSTEMS

An abuse deterrent and misuse deterrent transdermal patch comprising aversive agents incorporated in the backing layer of the patch. The aversive agents can exhibit biphasic or sustained kinetics of release with an immediate portion released rapidly and an extended portion released in a prolonged manner when exposed to a dissolution medium. The prolonged aversive agent release provides deterrence against extraction of drug from fresh and used patches and serves to prevent accidental misuse of used patches by children. The abuse deterrent and misuse deterrent patch systems can be used for transdermal delivery of therapeutically active agents and particularly those drugs that are highly prone to abuse such as opiate and opioid analgesics and stimulants. 1. An abuse deterrent or misuse deterrent transdermal patch system comprising a patch backing layer , wherein said backing layer comprises a distal side and a proximal side , wherein one or more aversive agents is incorporated into or irreversibly adhered onto the distal side of the backing layer , and wherein the one or more aversive agents exhibits a biphasic or sustained release profile when immersed in a dissolution medium.2. The system of claim 1 , wherein the system further comprises an adhesive layer adhered to the proximal side of the backing layer.3. The system of claim 2 , wherein the transdermal patch system and the adhesive layer is free or essentially free of any drug.4. The system of claim 2 , wherein the adhesive layer is an adhesive drug-containing layer.5. The system of claim 4 , wherein the therapeutically active agent is selected from the group consisting of sex steroid hormones claim 4 , non-steroidal anti-inflammatory agents claim 4 , glucocorticoids claim 4 , opioids claim 4 , opiate analgesics claim 4 , and stimulants.6. The system of claim 5 , wherein the therapeutically active agent is selected from the group consisting of an opioid claim 5 , an opiate analgesic and a stimulant.7. The system of ...

METHODS OF TREATING BEHAVIORAL SYNDROMES USING PIPRADROL

Methods of treating behavioral syndromes by administering a pharmaceutical composition of pipradrol or a pharmaceutically acceptable salt thereof are provided. The methods may be used to treat Attention-Deficit Disorder (ADD) and Attention-Deficit Hyperactivity Disorder (ADHD). 1. A method of treating a behavioral syndrome selected from Attention-Deficit Disorder (ADD) or Attention-Deficit Hyperactivity Disorder (ADHD) comprising administering to a patient in need thereof a pharmaceutical composition comprising pipradrol or a pharmaceutically acceptable salt thereof.2. The method of wherein the composition provides reduction in hyperactivity claim 1 , impulsiveness claim 1 , inattentiveness claim 1 , or a combination of symptoms in a patient diagnosed with a behavioral syndrome.3. The method of wherein the pipradrol or a pharmaceutically acceptable salt thereof is administered to the patient a daily dosage in the range of about 0.1 mg to about 50 mg.4. The method of further comprising administering a compound selected from the group consisting of gaboxadol claim 1 , acetazolamide claim 1 , carbamazepine claim 1 , clobazam claim 1 , clonazepam claim 1 , eslicarbazepine acetate claim 1 , ethosuximide claim 1 , gabapentin claim 1 , lacosamide claim 1 , lamotrigine claim 1 , leviteracetam claim 1 , nitrazepam claim 1 , oxcarbazepine claim 1 , perampanel claim 1 , piracetam claim 1 , phenobarbital claim 1 , phenytoin claim 1 , pregabalin claim 1 , primidone claim 1 , retigabine claim 1 , rufinamide claim 1 , sodium valproate claim 1 , stiripentol claim 1 , tiagabine claim 1 , topiramate claim 1 , vigabatrin claim 1 , and zonisamide. This application is a continuation of U.S. patent application Ser. No. 15/788,168, filed Oct. 19, 2017, which is a continuation of U.S. patent application Ser. No. 15/604,776, filed May 25, 2017, now U.S. Pat. No. 9,827,233, issued Nov. 28, 2017, which claims the benefit of and priority to U.S. Provisional Application Ser. No. 62/341,855, ...

METHODS OF PREPARING ORAL CONTROLLED RELEASE FORMULATIONS

The invention is directed to oral modified/controlled release drug formulations which provide a rapid initial onset of effect and a prolonged duration of effect. Preferably, the peak concentration is lower than that provided by the reference standard for immediate release formulations of the drug, and the duration of effect falls rapidly at the end of the dosing interval. 1: An oral controlled release formulation comprisinga plurality of substrates comprising a portion of an effective dose of a a drug in an immediate release form,a hydrophobic material coated onto the surface of said substrates in an amount sufficient to retard the release of said drug,an enteric coating applied over said hydrophobic coating in an amount sufficient to substantially delay the release of said drug from said substrate until after said formulation passes through the stomach,the formulation further comprising the remaining portion of said drug in an immediate release form.220-. (canceled)21: A method of preparing an oral controlled release once-a-day formulation comprising:coating a controlled release substrate comprising a first portion of methylphenidate hydrochloride with an enteric coating, andovercoating the enteric coating with an immediate release coating comprising a second portion of methylphenidate hydrochloride,wherein the enteric coating is of a type and in an amount that would delay release of the first portion of methylphenidate from the controlled release substrate until the plasma concentration of methylphenidate provided by the second portion of methylphenidate falls from its peak.22: The method of claim 21 , wherein the controlled release substrate comprises a copolymer of acrylic and methacrylic esters having a molar ratio of ammonium groups to the remaining neutral (meth)acrylic esters of 1:20.23: The method of claim 22 , wherein the enteric coating comprises a methacrylic acid copolymer which does not swell at about pH<5.7 and is soluble at about pH>6.24: The method ...

Orally Effective Methylphenidate Extended Release Powder and Aqueous Suspension Product

An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile. 1. A powder which is reconstitutable into an aqueous oral suspension comprising (i) an immediate release methylphenidate component , (ii) a sustained release water-insoluble , water-permeable , pH-independent , barrier coated methylphenidate-ion exchange resin complex , and (iii) a buffering agent which adjusts the pH of the reconstituted oral aqueous suspension to a pH of about 4.2 ,{'sub': 0-∞', 'max, 'wherein the reconstituted oral aqueous suspension has a pharmacokinetic profile in which the d-methylphenidate has an area under the curve (AUC) of about 114 ng-hr/mL to about 180 ng-hr/mL and a Cof about 11 ng/mL to about 17 ng/mL following a single oral administration of the reconstituted oral aqueous suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults under fasted conditions.'}2. The powder which is reconstitutable into an aqueous oral suspension according to claim 1 , wherein the powder is reconstitutable into a suspension which comprises at least about 80% of water based on the total weight of the suspension.3. The powder which is reconstitutable into an aqueous oral suspension according to claim 2 , wherein ...

TREATMENT FOR CEREBRAL PALSY IMPAIRED SPEECH IN CHILDREN

Cerebral palsy impaired speech in children and adolescents are effectively treated by administration of a psychostimulant. Low doses of the psychostimulant significantly (p=0.0025) increases the percentage of correctly pronounced intelligible syllables or words and the ability to more intelligibly communicate (p=0.0309). The improvement in speech persists after cessation of or prior to continued psychostimulant treatment. 1. A method for treating speech impairment secondary to cerebral palsy in a subject in need of such treatment , said method comprises:(a) providing a psychostimulant;(b) administering the psychostimulant in a therapeutically effective dose to the subject;whereby the speech impairment is improved.2. The method of claim 1 , wherein the subject has a chronological age greater than the speech-language age equivalence prior to step (a) and the difference between the chronological age and speech language age equivalence is diminished after step (b).3. The method of claim 1 , wherein there is a diminished difference in chronological age to speech-language age equivalence that persists after the psychostimulant is no longer efficaciously active in the subject.4. The method of claim 1 , wherein the subject is unable to pronounce one or more of the bilabial consonants prior to step (a) and is able to pronounce the one or more bilabial consonants after step (b).5. The method of claim 1 , wherein steps (a) and (b) are repeated periodically over a period of time and wherein the diminishment in the impaired speech continues over the period of time.6. The method of claim 1 , wherein further comprising prior to step (a) determining the cognitive functional age of the subject through non-verbal means claim 1 , and wherein the cognitive functional age is at least about two years.7. The method of claim 1 , wherein the improved speech impairment comprises a percentage increase in correctly pronounced syllables and words of from at least about 1.2 fold to upwards of 5 ...

Methods for preparing d-threo-methylphenidate using diazomethane, and compositions thereof

Novel methods and systems for producing a substantially pure d-threo stereoisomer of methylphenidate or a salt thereof are provided. In particular, methods and systems for producing d-threo-methylphenidate hydrochloride in pure stereoisomeric form from d-threo-ritalinic acid hydrochloride using diazomethane are described. The described methods can be performed on a large scale, and thus provide d-threo methylphenidate or a salt thereof, and particularly the hydrochloride salt of d-threo-methylphenidate, in stereoisomerically pure form and in large quantities from a single batch reaction. Also described are novel compositions of d-threo methylphenidate hydrochloride.

Methylphenidate Extended Release Chewable Tablet

An oral methylphenidate extended release tablet is described, which can be scored and still retain its extended release profile. The tablet contains a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and an uncomplexed methylphenidate active component. Following administration of a single dose of the extended release methylphenidate chewable tablet, a therapeutically effective amount of methylphenidate is reached in less than about 20 minutes and the composition provides a twelve-hour extended release profile. 1. (canceled)2. An extended release racemic methylphenidate tablet , wherein the tablet is a solid dispersion comprising: (i) a racemic methylphenidate-cation exchange resin complex comprising racemic methylphenidate and a pharmaceutically acceptable cation ion exchange resin, wherein the racemic methylphenidate is bound to the pharmaceutically acceptable cation exchange resin;', '(ii) a water-insoluble, water-permeable, pH-independent, barrier coating comprising a water-insoluble polymer and a plasticizer over the racemic methylphenidate-cation exchange resin complex of (a)(i), wherein the barrier coating modifies the release of the racemic methylphenidate in the complex; and', 'wherein about 50% w/w to about 90% w/w of total racemic methylphenidate in the tablet is provided by the racemic methylphenidate component of (a); and, '(a) a racemic methylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate-cation exchange resin complex which comprises(b) at least one immediate release methylphenidate component which provides a release of the racemic methylphenidate in less than about 30 minutes as determined in an in vitro dissolution assay;{'sub': 0-∞', 'max', 'max, 'wherein the tablet is capable of being swallowed intact or following being divided or chewed and the tablet provides a pharmacokinetic profile ...

DEVICE FOR TRANSDERMAL ADMINISTRATION OF DRUGS INCLUDING ACRYLIC BASED POLYMERS

A transdermal delivery system is provided where the drug delivery rates, onset and profiles of at least one active agent are controlled by selectively manipulating the monomeric make up of an acrylic-based polymer in the transdermal drug delivery system. The drug carrier composition may be comprised of (a) one or more acrylic-based polymers having one or more different monomers selected from the group consisting of hard and soft monomers; (b) one or more silicone-based polymers; and (c) one or more active agents where the device provides a desired solubility for the active agent and controls drug delivery rates, onset and profiles of at least one active agent. 119-. (canceled)20. A method of making a transdermal drug delivery system comprising , forming a carrier composition comprising a blend of(a) a polymer composition comprising at least one acrylic-based polymer polymerized from monomers that consist of: (i) soft acrylic monomers selected from the group consisting of 2-ethyl hexyl acrylate, isobutyl acrylate, ethyl acrylate, butyl acrylate, dodecyl methacrylate, 2-ethylhexyl methacrylate, 2-ethoxyethyl acrylate, isopropyl acrylate, and 2-methoxyethyl acrylate, in an amount of 20% by weight of the acrylic-based polymer; and (ii) hard acrylic monomers selected from the group consisting of methacrylate, N-butyl acrylate, acrylic acid, butyl methacrylate, ethyl methacrylate, methyl methacrylate, hexyl methacrylate, and methyl acrylate, in an amount of 80% by weight of the acrylic-based polymer; and(b) a drug in an amount of from 0.1% to 50% by weight of the carrier composition, wherein all acrylic-based polymers present in said polymer composition of the transdermal drug delivery system are polymerized from monomers that consist of monomers selected from the group consisting of said soft and hard acrylic monomers (i) and (ii).21. The method according to claim 20 , wherein the drug is methylphenidate.22. The method according to claim 20 , wherein the drug is ...

METHOD FOR FORMULATING LARGE DIAMETER SYNTHETIC MEMBRANE VESICLES

The present invention generally relates to the field of pharmaceutical sciences. More specifically, the present invention includes apparatus and devices for the preparation of pharmaceutical formulations containing large diameter synthetic membrane vesicles, such as multivesicular liposomes, methods for preparing such formulations, and the use of specific formulations for therapeutic treatment of subjects in need thereof. Formation and use of the pharmaceutical formulations containing large diameter synthetic membrane vesicles produced by using the apparatus and devices for therapeutic treatment of subjects in need thereof is also contemplated. 1104-. (canceled)105. A composition comprising a suspension of multivesicular liposomes in a suspending medium , said multivesicular liposomes having a structure including multiple non-concentric chambers and comprising at least one amphipathic lipid , at least one neutral lipid and a therapeutic agent , a solvent removal vessel having a top, a bottom and a circular wall;', 'a rinse nozzle mounted to and extending through the top of the solvent removal vessel;', 'a carrier gas entrance orifice;', 'a solvent removal gas exit orifice centrally connected to the top and further comprising a gas outlet tube extending into the solvent removal vessel, wherein the gas outlet tube is fitted with a narrowing cone and the narrowing cone includes a tip through which gas residing in the solvent removal vessel enters the narrowing cone;', 'a product exit orifice connected to the bottom of the vessel; and', 'a product outlet pipe connected to the product exit orifice;', 'a first fluid conduit and a second fluid conduit each having at least one entrance orifice and at least one exit orifice; a fluid contacting chamber having a top comprising at least one entrance orifice and having a bottom comprising at least one exit orifice and said at least one entrance orifice connecting to the at least one exit orifice of the first fluid conduit and ...

TREATMENT FOR CEREBRAL PALSY GAIT IMPAIRMENT

A methylphenidate, particularly including dextro-threo-methylphenidate, is administered to a child to treat a gait impairment and a speech impairment secondary to a non degenerative disease or disorder acquired in utero, at birth or in infancy, but later manifested. 1. A pharmaceutical intervention for a gait or limb impairment secondary to a non degenerative disease or disorder acquired in utero , during birth or in infancy , in a subject in need of the intervention , wherein the limb or gait impairment is manifested later in the life of the subject , said pharmaceutical intervention comprises:a psychostimulant having mood-elevating or anti-depressant activity;whereby the gait or limb impairment is diminished.2. The pharmaceutical intervention of claim 1 , wherein the psychostimulant comprises a methylphenidate.3. The pharmaceutical intervention of claim 2 , wherein the methylphenidate comprises dextro-threo-methylphenidate.4. The pharmaceutical intervention of claim 2 , wherein the methylphenidate comprises an analog of methylphenidate.5. The pharmaceutical intervention of claim 1 , said psychostimulant comprises a non linear lower alkyl phenidate.6. The pharmaceutical intervention of claim 1 , wherein said subject had a speech impairment comprising dysarthric speech prior to the pharmaceutical intervention claim 1 , and the dysarthric speech impairment is diminished after the pharmaceutical intervention.7. The pharmaceutical intervention of claim 1 , wherein the gait impairment comprises toe-to-heel gait.8. The pharmaceutical intervention of claim 7 , wherein the heel-to-toe gait is greater than toe-to-heel gait after the pharmaceutical intervention.9. The pharmaceutical intervention of claim 8 , wherein the improved heel-to-toe gait persists when the pharmaceutical intervention is no longer efficaciously present.10. The pharmaceutical intervention of claim 1 , wherein the disease or disorder is genetically related.11. A pharmaceutical intervention for treating a ...

COMPOSITIONS AND METHOD FOR TREATMENT OF ATTENTION DEFICIT DISORDER AND ATTENTION DEFICIT/HYPERACTIVITY DISORDER WITH METHYLPHENIDATE

The invention relates to a method of treating Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) and compositions for topical application of methylphenidate comprising methylphenidate in a flexible, finite system wherein the methylphenidate is present in an amount sufficient to achieve substantially zero order kinetics for delivery to the skin or mucosa of a patient in need thereof over a period of time at least 10 hours. 1. A composition for topical application of methylphenidate comprising methylphenidate in an adhesive carrier of a flexible , finite system , where the adhesive carrier consists of:methylphenidate in an amount of 5 to 35 wt % methylphenidate, based on the total weight of the adhesive composition, effective to achieve substantially zero order kinetics for delivery to the skin or mucosa of a patient in need thereof over a period of at least 10 hours, andone or more non-functional or minimally functional acrylic polymers having no more than about 5 wt % of acid functional monomers, based on the weight of the acrylic polymer, and having no vinyl acetate monomers, andoptionally, one or more excipients, tackifiers, plasticizers, and crosslinking agents.2. The composition according to claim 1 , wherein the methylphenidate comprises methylphenidate base.3. The composition according to claim 1 , wherein the methylphenidate consists essentially of d-threo-methylphenidate.4. The composition according to claim 1 , wherein the one or more acrylic polymers has no more than about 1 wt % of acid functional monomers claim 1 , based on the weight of the acrylic polymer.5. The composition according to claim 1 , wherein the one or more acrylic polymers is a non-functional acrylic polymer.6. A composition for topical application of methylphenidate comprising methylphenidate in an adhesive carrier of a flexible claim 1 , finite system claim 1 , where the adhesive carrier comprises:methylphenidate in an amount of 5 to 35 wt % ...

ABUSE-DETERRENT PHARMACEUTICAL COMPOSITIONS OF OPIOIDS AND OTHER DRUGS

An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. In a preferred embodiment, a drug is modified to increase its lipophilicity. In some embodiments the modified drug is homogeneously dispersed within spherical microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and/or organic solvent insoluble. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract. 1. An orally administrable abuse-deterrent pharmaceutical composition comprising a therapeutically effective amount of microparticles comprising(a) a lipophilic drug prone to abuse or lipophilic derivative of a drug prone to abuse, and(b) one or more carrier materials selected from the group consisting of fats, fatty substances, waxes, wax-like substances and mixtures thereof,wherein the drug is dispersed within the one or more carrier materials, and the release of a portion of incorporated drug is retarded when the physical integrity of the composition is compromised and the compromised composition is exposed to water.2. An orally administrable abuse-deterrent pharmaceutical composition comprising a therapeutically effective amount of microparticles comprising(a) a lipophilic derivative of a drug prone to abuse(b) one or more carrier materials which either dissolve slowly in water or are insoluble in water, andwherein the lipophilic derivative of the drug is dispersed within the one or ...

Compositions for Treatment of Attention Deficit Hyperactivity Disorder

Therapeutic compositions deliver a therapeutic amount of methylphenidate in a delayed and extended release formulation. The dosage form exhibits a lag time prior to release of from 6 to 8 hours or longer, followed by a sustained release period. 19-. (canceled)10. A solid , oral pharmaceutical composition comprising: a core comprising methylphenidate hydrochloride;', 'a sustained release layer enclosing the core; and', 'a delayed release layer enclosing the sustained release layer;, 'coated particles comprisingwherein the coated particles further comprise microcrystalline cellulose, dibutyl sebacate, diglycerides, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, methacrylic acid copolymer Type B, monoglycerides, polysorbate 80 and talc; and{'sub': 'max', 'wherein the composition provides at least a 6 hour lag time during which the composition releases no more than 5% of the total methylphenidate hydrochloride followed by a sustained release period with a median Tof about 12-16 hours when administered to healthy adults.'}11. The composition of claim 10 , wherein the composition provides at least an 8 hour lag time during which the composition releases no more than about 5% of the total methylphenidate hydrochloride.12. The composition of claim 10 , wherein the composition provides at least a 10 hour lag time during which the composition releases no more than 10% of the total methylphenidate hydrochloride.13. The solid claim 10 , oral pharmaceutical composition of claim 10 , wherein the composition is contained in a capsule comprising hydroxypropyl methylcellulose.14. The solid claim 10 , oral pharmaceutical composition of claim 10 , wherein the composition provides pediatric or adolescent subjects having Attention Deficit Hyperactivity Disorder (ADHD) with a significant improvement compared to a placebo in Swanson claim 10 , Kotkin claim 10 , Agler claim 10 , M-Flynn claim 10 , and Pelham Scale (SKAMP) combined scores for a ...

CNS STIMULANT AND OPIOID RECEPTOR ANTAGONIST COMBINATION AS A NON-ADDICTIVE, NON-AVERSIVE AND SYNERGISTIC ANTI-OBESITY TREATMENT

Combinations comprise a therapeutically effective amount of one or more stimulants and and/or pharmaceutically acceptable analogs, salts, or hydrates of the one or more stimulants, and one or more non-selective opioid receptor antagonists, and/or pharmaceutically acceptable analogs, salts or hydrates of the one or more non-selective opioid receptor antagonists. These combinations may be used for treating obesity via administration to a subject having a need thereof. 1. A method for treating obesity comprising administering to a subject having a need thereof a combination comprising two or more compounds , wherein the two or more compounds comprise:a therapeutically effective amount of naltrexone and/or pharmaceutically acceptable analogs, salts, or hydrates of naltrexone; anda therapeutically effective amount of methylphenidate and/or pharmaceutically acceptable analogs, salts, or hydrates of methylphenidate.2. The method of claim 1 , wherein methylphenidate and/or pharmaceutically acceptable analogs claim 1 , salts or hydrates of methylphenidate are administered to a human subject at a daily dose from about 0.75 mg/kg to about 2 mg/kg of subject body weight.3. The method of claim 1 , wherein naltrexone and/or pharmaceutically acceptable analogs claim 1 , salts or hydrates of naltrexone are administered to a human subject at a daily dose from about 0.5 mg/kg to about 1.5 mg/kg of subject body weight.4. The method of claim 1 , wherein the two or more compounds in the combination are simultaneously administered to the subject.5. The method of claim 1 , wherein the two or more compounds in the combination are administered to the subject sequentially; and wherein the naltrexone and/or pharmaceutically acceptable analogs claim 1 , salts claim 1 , or hydrates of naltrexone are administered to the subject prior to an administration of methylphenidate and/or pharmaceutically acceptable analogs claim 1 , salts claim 1 , or hydrates of methylphenidate.6. The method of claim 1 ...

METHODS FOR TREATMENT OF ATTENTION DEFICIT HYPERACTIVITY DISORDER

Therapeutic compositions and methods for treatment of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) include dosage forms that deliver a therapeutic amount of active drug in a delayed and controlled release formulation. The dosage form can be administered at night and drug release is delayed for from 4 to 6 hours or longer, followed by an ascending release rate. 1. A method of treating a condition in a subject with a disorder or condition responsive to the administration of a methylphenidate , comprising orally administering an effective amount of methylphenidate or a pharmaceutical salt thereof in a formulation comprising a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient; a sustained release layer enclosing the core and a delayed release layer enclosing the sustained release layer , wherein when the formulation provides an 8 hour lag time during which the formulation releases no more than 10% of the total methylphenidate or a pharmaceutical salt thereof followed by a sustained release period of 10-12 hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl pH 1.1 , for up to 2 hours followed by 2-6 hours in sodium phosphate buffer at pH 6.0; followed by 6-20 hours in sodium phosphate buffer , pH 7.2 at 37° C.±0.5° C. , measured by the USP Apparatus I.2. The method of claim 1 , wherein the formulation releases between about 0% and about 5% of the drug after 8 hours claim 1 , between about 5% and about 30% after 10 hours claim 1 , between about 20% and about 65% after 12 hours and between about 45% and about 95% after 15 hours claim 1 , and wherein the rate of release between about 8 and 12 hours is lower than the rate of release from about 12 to about 16 hours.3. The method of claim 1 , wherein the formulation comprises a unit dose of methylphenidate or a pharmaceutical salt thereof in a solid dosage form that comprises a sustained release ...

COMPOSITIONS FOR REDUCTION OF SIDE EFFECTS

The present invention provides drug therapy formulations. In some embodiments, the present invention provides combinations of pharmaceutical agents (e.g., stimulant and non-stimulant), pharmaceutical formulations (e.g., nanoparticualte, non-nanoparticualte, etc.), and release profiles (e.g., immediate release, delayed release, sustained release, etc.) to provide therapeutic benefit with reduced side effects. 188-. (canceled)89. A method of treating a subject with ADHD , the method comprising:administering to the subject a once daily dose of a pharmaceutical composition comprising:a) nanoparticulate formulated stimulant for rapid release and rapid onset of therapeutic action; andb) a non-stimulant;wherein the pharmaceutical composition is formulated for sequential release of the stimulant followed by the non-stimulant.90. The method of claim 89 , wherein said stimulant is an amphetamine.91. The method of claim 89 , wherein said stimulant is a methylphenidate.92. The method of claim 89 , wherein said stimulant or non-stimulant is provided as a prodrug.93. The method of claim 92 , wherein said stimulant is lisdexamfetamine.94. The method of claim 89 , wherein said non-stimulant is guanfacine.95. The method of claim 89 , wherein the pharmaceutical composition is formulated for sequential release of the stimulant between 0.15 hours or less and 2 hours and non-stimulant between 3 and 12 hours.96. The method of claim 89 , wherein the non-stimulant is coated for enteric release.97. The method of claim 89 , wherein the pharmaceutical composition comprises 10 mg or less of said stimulant.98. The method of claim 89 , wherein said pharmaceutical composition is formulated to provide a peak blood concentration of said stimulant in less than 15 minutes after administration.99. The method of claim 89 , wherein said pharmaceutical composition further comprises an agent to deter abuse of said pharmaceutical composition.100. The method of claim 89 , wherein the subject is a human ...

PHARMACEUTICAL INTERVENTION AND METHOD FOR TREATING AN APRAXIA OF SPEECH IN CHILDREN

A pharmaceutical intervention and therapeutic method for treating an apraxia of speech in children. The child can also be diagnosed with gait abnormalities or impairment autism, mental retardation and dyslexia. If the child demonstrates at least an 18 to 24 month development stage of either verbal development or non-verbal development, a therapeutic dose of a dopamine agonistic, particularly a nonlinear lower alkyl phenidate or dextro-threo-methylphenidate is administered to the child. 12.-. (canceled)3. A method for treating an apraxia of speech in a child in need of such treatment , said method comprises:(a) administering a therapeutically effective dose of a nonlinear lower alkyl phenidate to the child;whereby the apraxia of speech impairment is diminished.4. The method of claim 3 , wherein the nonlinear lower alkyl phenidate comprises an isopropylphenidate.5. The method of claim 3 , wherein the nonlinear lower alkyl comprises Cor C.6. The method of claim 5 , wherein the nonlinear lower alkyl comprises isobutyl claim 5 , sec-butyl or t-butyl.7. (canceled)8. A pharmaceutical intervention for treating an apraxia of speech in a child in need of such treatment claim 5 , said pharmaceutical intervention comprises:a nonlinear lower alky phenidate;whereby the apraxia of speech is diminished.9. The pharmaceutical intervention of claim 8 , said nonlinear lower alkyl comprises isopropyl.10. (canceled)11. A pharmaceutical intervention for treating an apraxia of speech in a child in need of such treatment claim 8 , said pharmaceutical intervention comprises a daily regimen of a therapeutically effective dose of a nonlinear lower alkyl phenidate.12. The pharmaceutical intervention of claim 11 , said nonlinear lower alkyl phenidate comprises isopropylphenidate.13. (canceled) This application is a divisional patent application of continuation-in-part patent application Ser. No. 14/736,406, filed Jun. 11, 2015, now U.S. Pat. No. 9,220,712. Application Ser. No. 14/736,406 is a ...

ANIMAL TRAINING USING COGNITIVE ENHANCEMENT

Methods are disclosed to enhance the training potential of a domestic animal during training, thereby shortening the training period and/or increasing the effectiveness of the training. The method involves first administering to the domestic animal a pharmaceutical composition comprising a cognitive enhancing agent in an amount effective to improve cognitive function. The enhanced cognition allows the domestic animal to learn to perform a task and/or to change its existing behavior more effectively and on an accelerated basis. Therefore, while the animal's cognitive function is enhanced, the method then involves conditioning the domestic animal to perform a task or change an existing behavior. 1. A method for enhancing training of a canine subject , comprising(a) administering to the canine subject a pharmaceutical composition comprising a cognitive enhancing agent in an amount effective to improve cognitive function; and(b) conditioning the canine subject to perform a task or change an existing behavior.2. The method of claim 1 , wherein the cognitive enhancing agent comprises a psychostimulant drug.3. The method of claim 2 , wherein the psychostimulant drug comprises a substituted phenethylamine.4. The method of claim 3 , wherein the substituted phenethylamine is selected from the group consisting of amphetamine claim 3 , methylphenidate claim 3 , dexmethylphenidate claim 3 , dextroamphetamine claim 3 , mixed amphetamine salts claim 3 , dextromethamphetamine claim 3 , and lisdexamfetamine.5. The method of claim 4 , wherein the psychostimulant drug comprises dextroamphetamine salts and levoamphetamine salts.6. The method of claim 2 , wherein the psychostimulant drug comprises a γ-aminobutyric acid (GABA) antagoinist.7. The method of claim 4 , wherein the GABA antagonist comprises metrazole.8. The method of claim 2 , wherein the psychostimulant drug comprises a selective serotonin reuptake inhibitor (SSRI).9. The method of claim 8 , wherein the SSRI is selected from ...

PERHEXILINE FOR USE IN THE TREATMENT OF HYPERTROPHIC CARDIOMYOPATHY (HCM)

The invention relates to perhexiline, or a pharmaceutically acceptable salt or enantiomer thereof, for use in the treatment of hypertrophic cardiomyopathy, as well as to a method of treating HCM, which comprises administering to an animal in need thereof an effective amount of perhexiline, or a pharmaceutically acceptable salt or enantiomer thereof, to treat said HCM. The invention further relates to a treatment programme for treating HCM, which involves the co-use or co-administration of perhexiline with one or more other compounds that are advantageous in treating HCM or the symptoms thereof. 1. A method for treating hypertrophic cardiomyopathy in a mammal in need thereof , comprising:diagnosing the mammal as having hypertrophic cardiomyopathy or at least one of a symptomatic component, feature or condition thereof; andadministering to said mammal a therapeutically-effective amount of (−)-perhexiline.2. The method of claim 1 , wherein the therapeutically-effective amount of (−)-perhexiline is sufficient to reduce or ameliorate the hypertrophic cardiomyopathy or at least one of a symptomatic component claim 1 , feature or condition thereof in the mammal.3. The method of claim 1 , wherein the (−)-perhexiline is in the form of a pharmaceutically acceptable salt.4. The method of claim 2 , wherein the (−)-perhexiline is in the form of a maleate salt.5. The method of claim 1 , wherein the mammal is a human.6. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound.7. The method of claim 1 , further comprising co-administering to said mammal at least one therapeutic compound advantageous in treating hypertrophic cardiomyopathy or at least one of a symptomatic component claim 1 , feature or condition thereof.8. The method of claim 6 , wherein the therapeutic compound is selected from a member of the group consisting of Alpha Blockers claim 6 , Beta Blockers claim 6 , Calcium Channel Blockers claim 6 , Diuretics claim 6 ...

CONTROLLED RELEASE DELIVERY DEVICE COMPRISING AN ORGANOSOL COAT

A controlled release delivery device for controlled release of an active ingredient comprising: (i) a core particle comprising the active ingredient homogenously dispersed or dissolved therein; and (ii) an organosol polymeric coat comprising a homogenous mixture of, (a) a water soluble gel forming polymer and a water insoluble organosoluble polymer in a dry weight ratio of from about 20:80 to about 50:50, (b) an organosolvent, and (c) an anti-tacking agent; the organosol polymeric coat being applied directly to and substantially enveloping the core particle. 1. A method for providing site specific , timed , pulsed , chronotherapeutic , or extended delivery of an active ingredient , said method comprising:controlling release of said active ingredient by a controlled release delivery device for controlled release of said active ingredient comprising:(i) a core particle comprising the active ingredient homogenously dispersed or dissolved therein; and (a) a water soluble gel forming polymer and a water insoluble organosoluble polymer in a dry weight ratio of from about 20:80 to about 50:50,', '(b) an organosolvent, and', '(c) an anti-tacking agent;, '(ii) an organosol polymeric coat comprising a homogenous mixture of,'}the organosol polymeric coat being applied directly to and substantially enveloping the core particle.5. A method of treating a patient with a therapeutically effective amount of the controlled release delivery device according to wherein the suitable vehicle is water claim 4 , paste claim 4 , gel claim 4 , suspension or an emulsion.6. A method of treating a patient with a therapeutically effective amount of the controlled release delivery device according to claim 4 , wherein the controlled release delivery device and the suitable vehicle are in a different housing and admixed prior to use. The present application is a Divisional application of U.S. patent application Ser. No. 12/225,954, filed on Apr. 6, 2009, which is a Continuation-in-Part of U.S. ...

METHODS AND COMPOSITIONS PARTICULARLY FOR TREATMENT OF ATTENTION DEFICIT DISORDER

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described. 1. A coated bead comprising:(a) a granule;(b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and(c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and(d) a third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein.2. The coated bead defined in claim 1 , wherein the second layer comprises an inner controlled release coating and an outer delayed release coating.3. The coated bead defined in claim 2 , wherein the inner controlled release coating is selected from the group consisting of an ethylcellulose ...

STIMULANT ABUSE-DETERRENT COMPOSITIONS

The present invention provides an abuse deterrent oral fixed-dose composition, comprising a stimulant or opioid and an abuse deterrent active, wherein the abuse deterrent active is configured to be bioavailable only when the composition is crushed, ground or dissolved. 1. An abuse deterrent oral fixed-dose composition , comprising a stimulant or opioid and an abuse deterrent active , wherein the abuse deterrent active is configured to be bioavailable only when the composition is crushed , ground , or dissolved.2. The composition of claim 1 , wherein the abuse deterrent active is a dopamine receptor agonist which activates the dopamine receptor claim 1 , inducing nausea claim 1 , vomiting claim 1 , or nausea and vomiting claim 1 , and diminishing the dopamine-induced reward feeling via activation of a positive feedback mechanism claim 1 , resulting in reduction of dopamine at extracellular level.3. The composition of claim 1 , wherein the abuse deterrent active exhibits emetic effect claim 1 , hyperactivity blocking effect claim 1 , or emetic and hyperactivity blocking effects.4. A method of treatment of a patient in need thereof claim 1 , comprising the administration to the patient of the composition of claim 1 , wherein less than 10% of the abuse deterrent active is bioavailable within the first 24 hrs post administration.5. (canceled)6. (canceled)7. The composition of claim 1 , wherein the stimulant is selected from the group consisting of metamphetamine claim 1 , methylphenidate claim 1 , dexmethylphenidate claim 1 , methylphenidate derivatives amphetamine claim 1 , modafinil claim 1 , and combinations thereof.8. The composition of claim 1 , wherein the opioid is selected from the group consisting of: morphine claim 1 , ethylmorphine claim 1 , hydromorphone claim 1 , dihydromorphine claim 1 , codeine claim 1 , hydrocodone claim 1 , oxycodone claim 1 , butorphanol claim 1 , buprenorphine claim 1 , levorphanol claim 1 , meperidine claim 1 , alfentanil claim 1 , ...

METHODS AND DEVICES FOR PROVIDING PROLONGED DRUG THERAPY

Methods and devices for maintaining a desired therapeutic drug effect over a prolonged therapy period are provided. In particular, oral dosage forms that release drug within the gastrointestinal tract at an ascending release rate over an extended time period are provided. The dosage forms may additionally comprise an immediate-release dose of drug. 1. A method that comprises administering a pharmaceutically acceptable composition comprising methylphenidate or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a patient in a manner that achieves an ascending release rate of said methylphenidate beginning with a first periodic interval that begins at time t=0 and continuing through about 5.5 hours following said administration.2. A method for effectively treating Attention Deficit Disorder or Attention Deficit Hyperactivity Disorder in a subject comprising orally administering a dosage form to said subject , wherein said dosage form comprisesan immediate release coating comprising methylphenidate hydrochloride; anda sustained release portion comprising methylphenidate hydrochloride and a pharmaceutically acceptable carrier,wherein:said dosage form provides release of said methylphenidate hydrochloride over a period comprising first, second, third, and fourth sequential, one-hour time intervals; andsaid sustained release portion releases more of said methylphenidate hydrochloride during said second interval than during said first interval, more of said methylphenidate hydrochloride during said third interval than during said second interval, and more of said methylphenidate hydrochloride during said fourth interval than during said third interval.3. The method according to wherein said dosage form is administered one time per day for multiple days.4. The method according to wherein said dosage form is administered to a non-adult subject.5. The method according to wherein said dosage form is a non-osmotic dosage form.6. The method ...

COMPOSITIONS FOR TREATMENT OF ATTENTION DEFICIT HYPERACTIVITY DISORDER

Therapeutic compositions and methods for treatment of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) include dosage forms that deliver a therapeutic amount of active drug in a delayed and controlled release formulation. The dosage form can be administered at night and drug release is delayed for from 4 to 6 hours or longer, followed by an ascending release rate. 1. A solid , oral pharmaceutical composition comprising:a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient;a sustained release layer enclosing the core; anda delayed release layer enclosing the sustained release layer,wherein the formulation provides an 8 hour lag time during which the formulation releases no more than 10% of the total methylphenidate or a pharmaceutical salt thereof followed by a sustained release period of 10-12 hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl pH 1.1, for up to 2 hours followed by 2-6 hours in sodium phosphate buffer at pH 6.0; followed by 6-20 hours in sodium phosphate buffer, pH 7.2 at 37° C.±0.5° C., as measured by the USP Apparatus I.2. The solid claim 1 , oral pharmaceutical composition of claim 1 , wherein the formulation releases between 0 and about 5% of the drug after 8 hours claim 1 , between about 5% and about 30% after 10 hours claim 1 , between about 20% and about 65% after 12 hours and between 45% and 95% after 15 hours claim 1 , and wherein the rate of release between about 8 and about 12 hours is lower than the rate of release from about 12 to about 16 hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl pH 1.1 claim 1 , for 2 hours followed by hours 2-6 in sodium phosphate buffer at pH 6.0; followed by hours 6-20 in sodium phosphate buffer claim 1 , pH 7.2 at 37° C.±0.5° C. claim 1 , as measured by the USP Apparatus I.3. The solid claim 1 , oral pharmaceutical composition of claim 1 , wherein the core ...

Abuse and Misuse Deterrent Transdermal Systems

An abuse deterrent and misuse deterrent transdermal patch comprising aversive agents incorporated in the backing layer of the patch. The aversive agents can exhibit biphasic or sustained kinetics of release with an immediate portion released rapidly and an extended portion released in a prolonged manner when exposed to a dissolution medium. The prolonged aversive agent release provides deterrence against extraction of drug from fresh and used patches and serves to prevent accidental misuse of used patches by children. The abuse deterrent and misuse deterrent patch systems can be used for transdermal delivery of therapeutically active agents and particularly those drugs that are highly prone to abuse such as opiate and opioid analgesics and stimulants. 1. An abuse deterrent or misuse deterrent transdermal patch system comprisinga patch backing layer comprising a distal side and a proximal side;one or more aversive agents incorporated into or irreversibly adhered onto the distal side of the backing layer; andan adhesive layer adhered to the proximal side of the backing layer, the adhesive layer utilized to adhere the transdermal patch system to skin,wherein the one or more aversive agents exhibits a biphasic release profile comprising an immediate release phase followed by an extended release phase when the transdermal patch system is immersed in a dissolution medium, andwherein the backing layer is impermeable to the one or more aversive agents to prevent the one or more aversive agents from contacting the proximal side of the backing layer and the skin.2. The system of claim 1 , wherein the transdermal patch system and the adhesive layer is free or essentially free of any drug.3. The system of claim 1 , wherein the adhesive layer is a therapeutically active agent-containing adhesive layer.4. The system of claim 3 , wherein the therapeutically active agent is selected from the group consisting of sex steroid hormones claim 3 , non-steroidal anti-inflammatory agents ...

ATRIAL FIBRILLATION THERAPY

Provided is a method of facilitating the determination of treatment of a subject displaying atrial fibrillation, the method comprising determining a level of pitx2c expression in a sample from the subject and selecting a treatment based upon the level of pitx2c expression. Treatment with a sodium channel blocker may be selected if the level of pitx2c expression is determined to be reduced or below a predetermined threshold. Also provided are an assay system and a kit for use in the methods of the invention. 1. A method of facilitating the determination of treatment of a subject displaying atrial fibrillation , the method comprising determining a level of pitx2c expression in a sample from the subject and selecting a treatment based upon the level of pitx2c expression.2. The method of claim 1 , wherein selecting a treatment comprises selecting treatment with a sodium channel blocker if the level of pitx2c expression is determined to be reduced or below a predetermined threshold.3. The method of claim 1 , wherein the sample comprises at least one of urine claim 1 , saliva claim 1 , blood claim 1 , sputum claim 1 , semen claim 1 , faeces claim 1 , a nasal swab claim 1 , tears claim 1 , a vaginal swab claim 1 , a rectal swab claim 1 , a cervical smear claim 1 , a tissue biopsy claim 1 , and a urethral swab.4. The method of claim 3 , wherein the sample is blood.5. The method of claim 1 , wherein the level of pitx2c expression is determined directly by determining the pitx2c protein level or mRNA level.6. The method of claim 1 , wherein the level of pitx2c expression is determined indirectly by determining the level of a biomarker which is indicative of the level of pitx2c expression.7. The method of claim 6 , wherein the biomarker is ccl21.8. (canceled)9. The method of claim 2 , wherein the sodium channel blocker type 1 antiarrhythmic drug.10. The method of claim 2 , the sodium channel blocker is flecainide or propafenone.11. The method of claim 1 , wherein determining a ...

Methods for Treatment of Attention Deficit Hyperactivity Disorder

Therapeutic compositions and methods for treatment of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) include dosage forms that deliver a therapeutic amount of active drug in a delayed and controlled release formulation. The dosage form can be administered at night and drug release is delayed for from 4 to 6 hours or longer, followed by an ascending release rate. 1. A method of treating a condition in a subject with a disorder or condition responsive to the administration of a methylphenidate , comprising orally administering an effective amount of methylphenidate or a pharmaceutical salt thereof in a formulation that provides a lag period of at least 5 hours during which the plasma concentration of methylphenidate or a pharmaceutical salt thereof is less than 10% of the maximum concentration (Cmax) and wherein the time to Cmax (Tmax) is between 12 and 19 hours after administration.2. The method of claim 1 , wherein the plasma area under the curve at 6 hours (AUC) after administration is less than about 5% of the AUC.3. The method of claim 1 , wherein the plasma area under the curve at 6 hours (AUC) after administration is less than about 3% of the AUC.4. The method of claim 1 , wherein the plasma area under the curve at 10 hours (AUC) after administration is less than about 7% of AUC.5. The method of claim 1 , wherein the disorder or condition is attention deficit disorder claim 1 , attention deficit hyperactivity disorder claim 1 , excessive daytime sleepiness claim 1 , major depressive disorder claim 1 , bipolar depression claim 1 , negative symptoms in schizophrenia claim 1 , chronic fatigue claim 1 , fatigue associated with chemotherapy or binge eating disorder.6. The method of claim 1 , wherein the disorder or condition is attention deficit disorder or attention deficit hyperactivity disorder.7. The method of claim 1 , wherein the disorder is binge eating disorder.8. The method of claim 1 , wherein administration of the ...

Compositions for Treatment of Attention Deficit Hyperactivity Disorder

Therapeutic compositions and methods for treatment of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) include dosage forms that deliver a therapeutic amount of active drug in a delayed and controlled release formulation. The dosage form can be administered at night and drug release is delayed for from 4 to 6 hours or longer, followed by an ascending release rate. 1. A solid , oral pharmaceutical composition comprising a plurality of particles , each comprising:a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient;a sustained release layer enclosing the core; anda delayed release layer enclosing the sustained release layer,wherein when the composition is orally administered to a human subject, there is a lag period of at least 5 hours during which the plasma concentration of methylphenidate or a pharmaceutical salt thereof is less than 10% of the maximum concentration (Cmax) and wherein the time to Cmax (Tmax) is between 12 and 19 hours after administration.2. The solid claim 1 , oral pharmaceutical composition of claim 1 , wherein the core comprises a substantially spherical bead.3. The solid claim 1 , oral pharmaceutical composition of claim 1 , wherein the core comprises methylphenidate hydrochloride.4. The solid claim 1 , oral pharmaceutical composition of claim 1 , wherein the core comprises one or more excipients selected from polyvinyl pyrollidone claim 1 , hydroxypropylmethyl cellulose claim 1 , lactose claim 1 , sucrose claim 1 , microcrystalline cellulose and combinations of any thereof.5. The solid claim 1 , oral pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is microcrystalline cellulose.6. The solid claim 1 , oral pharmaceutical composition of claim 1 , wherein the core comprises a non-pareil bead coated with a layer comprising the methylphenidate or a pharmaceutical salt thereof and at least one ...

Compositions for Treatment of Attention Deficit Hyperactivity Disorder

Therapeutic compositions deliver a therapeutic amount of methylphenidate in a delayed and extended release formulation. The dosage form exhibits a lag time prior to release of from 6 to 8 hours or longer, followed by a sustained release period. 19-. (canceled)11. The method of claim 10 , wherein the core comprises methylphenidate hydrochloride.12. The method of claim 10 , wherein the sustained release layer comprises ethyl cellulose claim 10 , hydroxypropyl cellulose claim 10 , dibutyl sebacate and a metal stearate.13. The composition of claim 10 , wherein the sustained release layer comprises ethyl cellulose claim 10 , hydroxypropyl cellulose claim 10 , dibutyl sebacate and magnesium stearate.14. The method of claim 10 , wherein the pH dependent copolymer is methacrylic acid copolymer Type B.15. The method of claim 10 , wherein the composition further comprise mono- and diglycerides claim 10 , dibutyl sebacate and polysorbate 80.16. The method of claim 10 , wherein the composition is contained in a single dosage form containing 1 mg to 150 mg of methylphenidate or a pharmaceutical salt thereof.17. The method of claim 10 , wherein the composition is contained in a single dosage form containing 1 mg to 80 mg of methylphenidate or a pharmaceutical salt thereof.18. The method of claim 10 , wherein the sustained release layer comprises ethyl cellulose and hydroxypropyl cellulose in a ratio of about 1:3 to 1:5 claim 10 , dibutyl sebacate and from 25% to 50% by weight magnesium stearate. This application is a continuation of co-pending U.S. application Ser. No. 15/069,734, filed Mar. 14, 2016, which is a continuation of U.S. application Ser. No. 14/704,836, filed May 5, 2015, now U.S. Pat. No. 9,283,214, which is a continuation-in-part of U.S. application Ser. No. 14/589,839, filed Jan. 5, 2015, now U.S. Pat. No. 9,023,389, which is a continuation of U.S. application Ser. No. 14/230,053, filed Mar. 31, 2014 and issued as U.S. Pat. No. 8,927,010, which is a continuation-in ...

THE USE OF A H3R INVERSE AGONIST FOR THE TREATMENT OF SHIFT WORK DISORDER

The invention relates to the use of a H3R inverse agonist for the treatment of shift work disorder. 1. Use of 1-(1-methyl-6-oxo-1 ,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate , or pharmaceutically acceptable salt thereof , in the manufacture of a medicament for the treatment of shift work disorder.2. Use of 1-(1-methyl-6-oxo-1 ,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate , or pharmaceutically acceptable salt thereof , in the manufacture of a medicament being an agent modulating circadian rhythm dysfunctions due to shift work.3. Use of 1-(1-methyl-6-oxo-1 ,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate , or pharmaceutically acceptable salt thereof , in the manufacture of a medicament for the treatment of excessive sleepiness associated with shift work disorder.4. Use of 1-(1-methyl-6-oxo-1 ,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate , or pharmaceutically acceptable salt thereof , in the manufacture of a medicament for promoting wakefulness in a shift work disorder patient.5. Use of 1-(1-methyl-6-oxo-1 ,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate , or pharmaceutically acceptable salt thereof , in the manufacture of a medicament for the treatment of cognitive function impairment associated with shift work disorder; such as learning impairment , psychomotor function impairment , attention impairment , sustained attention impairment , working memory impairment , episodic memory impairment , executive function impairment , auditory information processing speed impairment , auditory information processing flexibility impairment , and calculation ability impairment , which are each associated with shift work disorder.6. Use of 1-(1-methyl-6-oxo-1 claim 1 ,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate claim 1 , or pharmaceutically acceptable salt thereof claim 1 , in the manufacture of a ...

FLECAINIDE COMBINATION AND CONTROLLED-RELEASE FORMULATIONS FOR TREATING HEART DISEASES

The invention relates to flecainide formulations and to methods of their administration. Specifically, the invention relates to combination formulations of a flecainide and a rate control agent for treating various heart diseases, and to controlled-release flecainide formulations, including such formulations in combination with rate control agents. 1. A pharmaceutical formulation comprising a flecainide in combination with a rate control agent , wherein the rate control agent comprises a β blocker , and wherein the β blocker is metoprolol.211.-. (canceled)12. The pharmaceutical formulation of claim 1 , wherein the flecainide comprises a flecainide acetate.13. The pharmaceutical formulation of claim 1 , configured in a dosage form selected from once daily claim 1 , twice daily claim 1 , once every two days claim 1 , once every three days claim 1 , once every four days claim 1 , once every five days claim 1 , once every six days claim 1 , and once weekly.14. The pharmaceutical formulation of claim 1 , wherein the flecainide is present in an amount of about 50 to about 500 mg.15. The pharmaceutical formulation of claim 1 , wherein the rate control agent is present in an amount of about 50 to about 500 mg.16. The pharmaceutical formulation of claim 1 , wherein the formulation further comprises an effective amount of one or more additional therapeutic agents.17. A method of treating atrial fibrillation claim 1 , atrial flutter claim 1 , and/or supraventricular tachycardia (SVT) in a subject claim 1 , the method comprising administering the pharmaceutical formulation of to a subject in need thereof.1835.-. (canceled)36. A controlled-release pharmaceutical formulation comprising a flecainide and a controlled-release excipient.37. The controlled-release pharmaceutical formulation of wherein the controlled-release formulation comprises a once daily sustained-release formulation.38. The controlled-release pharmaceutical formulation of claim 36 , wherein the controlled-release ...

CONTROLLED RELEASE FORMULATIONS HAVING RAPID ONSET AND RAPID DECLINE OF EFFECTIVE PLASMA DRUG CONCENTRATIONS

The invention is directed to oral modified/controlled release drug formulations which provide a rapid initial onset of effect and a prolonged duration of effect. Preferably, the peak concentration is lower than that provided by the reference standard for immediate release formulations of the drug, and the duration of effect falls rapidly at the end of the dosing interval. 1. An oral controlled release formulation comprisinga plurality of substrates comprising a portion of an effective dose of a drug in an immediate release form,a hydrophobic material coated onto the surface of said substrates in an amount sufficient to retard the release of said drug,an enteric coating applied over said hydrophobic coating in an amount sufficient to substantially delay the release of said drug from said substrate until after said formulation passes through the stomach,the formulation further comprising the remaining portion of the effective dose in an immediate release form.213-. (canceled)14. A method for preparing an oral controlled release formulation comprisingpreparing immediate release drug-coated inert beads by spraying a solution of a drug onto said inert beads;applying a controlled release coating to said immediate release drug-coated inert beads to convert the same into controlled release beads;applying an enteric coating onto said controlled release coating; andapplying an immediate release overcoat of said drug onto the surface of said enteric coated beads.1520.-. (canceled)21. A method of treating ADHD in a child: comprising administering encapsulated multi-layer release beads comprising an effective dose of methylphenidate hydrochloride to the child.22. The oral controlled release formulation of claim 1 , wherein the drug is methylphenidate hydrochloride claim 1 , and the formulation comprises a plurality of encapsulated multi-layered release beads comprising an effective dose of methylphenidate hydrochloride claim 1 , each bead comprisinga core,a coating of a ...

Methylphenidate Extended Release Chewable Tablet

An oral methylphenidate extended release tablet is described, which can be scored and still retain its extended release profile. The tablet contains a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and an uncomplexed methylphenidate active component. Following administration of a single dose of the extended release methylphenidate chewable tablet, a therapeutically effective amount of methylphenidate is reached in less than about 20 minutes and the composition provides a twelve-hour extended release profile.

METHYLPHENIDATE EXTENDED RELEASE CHEWABLE TABLET

An oral dexmethylphenidate extended release tablet is described, which can be scored and still retain its extended release profile. The tablet contains a combination of an uncoated dexmethylphenidate-ion exchange resin complex, a barrier coated dexmethylphenidate-ion exchange resin complex-matrix, and an uncomplexed dexmethylphenidate active component. Following administration of a single dose of the extended release dexmethylphenidate chewable tablet, a therapeutically effective amount of dexmethylphenidate is reached in less than about 20 minutes and the composition provides a twelve-hour extended release profile. 1. An extended release dexmethylphenidate chewable tablet , wherein said chewable tablet is a uniform solid dispersion comprising:(a) a sustained release dexmethylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, dexmethylphenidate-ion exchange resin complex in a polymeric matrix, wherein said barrier coating which provides a sustained release profile to the dexmethylphenidate-is over the dexmethylphenidate-ion exchange resin complex-matrix;(b) a first immediate release component which comprises an immediate release uncoated dexmethylphenidate-ion exchange resin complex;(c) a second immediate release dexmethylphenidate component which comprises an uncomplexed dexmethylphenidate acceptable salt thereof;wherein said first immediate release component (b) has a slower onset of release than (c);wherein about 50% w/w to about 90% w/w of the dexmethylphenidate active component is provided by the sustained release component based on the total amount of dexmethylphenidate in the tablet, and{'sub': 0-∞', 'max, 'wherein said chewable tablet is capable of being divided and providing tablet portions which retain a therapeutically effective extended release profile, and a pharmacokinetic profile in which the dexmethylphenidate has at least one of: a geometric mean for area under the curve (AUC)of about 110 ng-hr/mL to ...

Cooperative Medication Combination Systems

This invention aims to capture and teach the high-level concept of combining doses of medications in unconventionally substandard amounts, for the treatment of medical pathologies. By combining multiple medications, each of which is aimed at treating the same disease process and each in a given substandard dosage, it should allow for greater comprehensive efficacy while simultaneously bypassing conventional side-effects, clinically significant medication interactions, and other potentially unforeseen deleterious effects, all because the dosage is small enough and collaborative chemical diversity manifests favorable kinetic dynamics, thereby mitigating unwanted drug effects while enhancing the targeted indication. 1. A method for lowering clinically significant individual doses , the method comprising of the steps: determining a first set of low doses for each of at least three prescription medications to achieve an original goal; and determining a second set of substandard doses for each of the at least three prescription medications to achieve a coordinated goal by cooperatively combining at least three prescription medications using the second set of doses;wherein the coordinated goal is equivalent to or better than the original goal;wherein the second set of doses is proportionally lower than the first set of doses; andwherein each mechanism of the at least three prescription medications differs from one another.2. The method of claim 1 , wherein a component selected from the group consisting of vitamins claim 1 , minerals claim 1 , supplements claim 1 , non-legend medications claim 1 , herbs and nutraceuticals is added to at least three prescription medications.3. The method of claim 1 , wherein hypertension is treated by at least three prescription medications (EXAMPLE of carvedolol 6.25 mg claim 1 , lisinopril 10 mg claim 1 , chlorthalidone 25 mg claim 1 , amlodipine 2.5 mg claim 1 , clonidine 0.2 mg claim 1 , and hydralazine 40 mg in a 24 hour dose using the ...

METHYLPHENIDATE EXTENDED RELEASE CHEWABLE TABLET

An oral methylphenidate extended release tablet is described, which can be scored and still retain its extended release profile. The tablet contains a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and an uncomplexed methylphenidate active component. Following administration of a single dose of the extended release methylphenidate chewable tablet, a therapeutically effective amount of methylphenidate is reached in less than about 20 minutes and the composition provides a twelve-hour extended release profile. 1. An extended release chewable tablet having a therapeutically effective immediate release and an extended release profile , wherein said chewable tablet is a uniform solid dispersion comprising:(a) a sustained release dexmethylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, dexmethylphenidate-ion exchange resin complex in a polymeric matrix, wherein said barrier coating is over the dexmethylphenidate-ion exchange resin complex-matrix;(b) a first immediate release component which comprises an immediate release uncoated dexmethylphenidate-ion exchange resin complex;(c) a second immediate release dexmethylphenidate component which comprises an uncomplexed dexmethylphenidate;wherein said first immediate release component (b) has a slower onset of release than (c);wherein about 50% w/w to about 90% w/w of the dexmethylphenidate active component is provided by the sustained release component based on the total amount of dexmethylphenidate in the tablet, and{'sub': 0-∞', 'max, 'wherein said chewable tablet is capable of being divided and providing tablet portions which retain a therapeutically effective immediate release and an extended release profile, and a pharmacokinetic profile in which the dexmethylphenidate has an area under the curve (AUC) of about 110 ng-hr/mL to about 140 ng-hr/mL and a Cof about 10 ng/mL to about 15 ...