ВОДНЫЙ ИНЪЕКЦИОННЫЙ РАСТВОР АНТАГОНИСТА LHRH И СПОСОБ ЕГО ПОЛУЧЕНИЯ

Настоящее изобретение относится к медицине и описывает водный инъекционный раствор антагониста рилизинг-гормона лютеинизирующего гормона (LHRH), содержащий глюконовую кислоту, наполнитель и, необязательно, поверхностно-активное вещество, отличающийся тем, что антагонист LHRH выбран из группы веществ: цетрореликс, тевереликс, D-63153 (Ac-D-Nal-pCl-D-Phe-3-D-Pal-Ser-N-Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2), ганиреликс, абареликс, антид или азалин В; глюконовая кислота в форме дельта-лактона в количестве больше эквимолярного по отношению к количеству антагониста LHRH, а наполнителем является маннит. Антагонист LHRH имеет в значительной мере улучшенную растворимость и может быть приготовлен в более высоких концентрациях и с повышенной биодоступностью. Тенденция антагониста LHRH к агрегации значительно снижена. 2 н. и 5 з.п. ф-лы, 1 табл.

ОФТАЛЬМИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ АСКОМИЦИН

Настоящее изобретение относится к применению местной офтальмической композиции, включающей аскомицин и носитель. Носитель включает триглицерид жирной кислоты со средней цепью, представляет основу для мази, а также может включать воду и эмульсификатор, консервант. Изобретение обеспечивает применение композиции для приготовления лекарственного средства для лечения себорейного, аллергического и стафилоккокового блефарита. 11 з.п. ф-лы.

ТРАНСДЕРМАЛЬНАЯ ТЕРАПЕВТИЧЕСКАЯ СИСТЕМА, СОДЕРЖАЩАЯ АЗЕНАПИН

Группа изобретений относится к области медицины, а именно к трансдермальной терапевтической системе для трансдермального введения азенапина, включающей в себя структуру самоклеящегося слоя, содержащую терапевтически эффективное количество азенапина, при этом указанная структура самоклеящегося слоя содержит: A) подложку; B) азенапинсодержащий матричный слой, состоящий из композиции матричного слоя, которая содержит: 1) азенапин, включенный в форме свободного основания; 2) полимер, выбранный из акриловых полимеров, причем полимер представляет собой сополимер на основе винилацетата, 2-этилгексилакрилата, 2-гидроксиэтилакрилата и глицидилметакрилата или сополимер на основе винилацетата, 2-этилгексилакрилата и 2-гидроксиэтилакрилата; 3) дополнительный полимер, выбранный из поливинилпирролидонов; и 4) α-токоферол в количестве от 0,01 до 2 масс. % композиции матричного слоя и аскорбилпальмитат в количестве, составляющем по меньшей мере 0,01 масс. % композиции матричного слоя, в качестве стабилизаторов ...

СРЕДСТВО, ПОТЕНЦИРУЮЩЕЕ ПРОТИВООПУХОЛЕВЫЙ ЭФФЕКТ,И ПРОТИВООПУХОЛЕВОЕ СРЕДСТВО

Противоопухолевое средство включает в качестве активных ингредиентов тегафур в терапевтически эффективном количестве, гимерацил в количестве, эффективном для усиления противоопухолевого эффекта, отерацил калия в количестве, эффективном для ингибирования побочного эффекта, и по меньшей мере один элемент, выбранный из группы, состоящей из фолиновой кислоты и ее фармакологически приемлемых солей, в количестве, эффективном для усиления противоопухолевого эффекта. Молярное соотношение тегафур:гимерацил:отерацил калия: по меньшей мере один элемент, выбранный из группы, состоящей из фолиновой кислоты и ее фармакологически приемлемых солей, составляет 1:0,4:1: от 0,01 до 10. Использование комбинированного лекарственного средства тегафур/гимерацил/отерацил калия в комбинации с фолинатом кальция значительно усиливает противоопухолевую активность без усугубления токсичности. Усиленный противоопухолевый эффект является значительно большим, чем при использовании комбинированного лекарственного средства ...

КОНСЕРВИРУЮЩАЯ КОМПОЗИЦИЯ ДЛЯ ОФТАЛЬМОЛОГИЧЕСКОГО ПРИМЕНЕНИЯ

Изобретение относится к области медицины, в частности к офтальмологии. Жидкий препарат для офтальмологического применения, содержит консервирующую композицию для офтальмологического применения включающую хлорит и по меньшей мере один стабилизатор, выбранный из группы: 1) креатинин, 2) гераниол, 3) глюкоза, 4) токоферола ацетат, 5) оксихинолина сульфат, 6) сахароспирт и 7) полиоксиэтиленовый эфир сорбита и жирной кислоты. Изобретение обеспечивает предотвращение образования диоксида хлора в жидком препарате для офтальмологического применения, содержащем хлорит, и проявляет продолжительный консервирующий эффект на длительный период времени. 3 н. и 3 з.п. ф-лы, 5 табл.

КОМПОЗИЦИЯ И ЛЕКАРСТВЕННАЯ ФОРМА, СОДЕРЖАЩИЕ ТВЕРДУЮ ИЛИ ПОЛУТВЕРДУЮ МАТРИЦУ

Композиция для медицинских целей содержит твердую или полутвердую матрицу, по меньшей мере, один равномерно диспергированный в ней активный ингредиент. Матрица содержит, по меньшей мере, один фармацевтически приемлемый образующий матрицу агент и соединение 1,3-бис(лактамил)бутана, особенно 1,3-бис(пирролидон-1-ил)бутан. Активный ингредиент имеет растворимость в воде при 25°С менее 1 г/100 мл. Активный ингредиент, предпочтительно, диспергирован в матрице в состоянии твердого раствора. Образующий матрицу агент выбран из группы сахарных спиртов, производных сахарных спиртов, фармацевтически приемлемых полимеров и их смесей. Композиция предназначена для получения фармацевтических лекарственных форм для орального введения активного ингредиента. Композиция по изобретению обеспечивает повышенную биодоступность плохорастворимого в воде активного ингредиента за счет его присутствия в композиции в некристаллическом состоянии. 4 н. и 15 з.п. ф-лы.

ГИПЕРТОНИЧЕСКИЙ РАСТВОР И СПОСОБ ОЧИЩЕНИЯ ТОЛСТОЙ КИШКИ МЛЕКОПИТАЮЩЕГО

Группа изобретений относится к медицине и предназначена для очищения толстой кишки. Описан гипертонический раствор, содержащий на литр водного раствора от 30 до 350 г полиэтиленгликоля, от 3 до 20 г компонента аскорбиновой кислоты, выбранного из группы, состоящей из аскорбиновой кислоты, соли аскорбиновой кислоты или их смеси, сульфата щелочного металла или щелочноземельного металла, предпочтительно в количестве от 1 до 15 г, и (необязательно) одного или более электролитов, выбранных из хлорида натрия, хлорида калия и гидрокарбоната натрия, а также предпочтительно содержащая вкусовые добавки. Также описано применение гипертонического раствора для очищения толстой кишки. Группа изобретений позволяет обеспечить эффективное очищение кишечника, соблюдение режима пациентом и эффективное использование амбулаторными больными. 3 н. и 20 з.п. ф-лы, 6 пр., 29 табл.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ТАКСОИДОВ

Настоящее изобретение относится к стабильной пероральной фармацевтической композиции таксоида для введения млекопитающим, содержащей: таксоид, выбранный из паклитаксела или доцетаксела или их фармацевтически приемлемых солей; солюбилизатор, выбранный из диэтиленгликоля моноэтилового эфира (Transcutol HP) и гликофурола; стабилизирующий агент, выбранный из пиперина, привитого сополимера поливинилкапролактам - поливинилацетат - полиэтиленгликоля (Soluplus), поливинилпирролидона и гидроксипропилметилцеллюлозы; поверхностно-активное вещество, выбранное из каприл/капроил макрогол глицеридов, альфа-токоферил-полиэтиленгликоль 1000 сукцината, полисорбата и ПЭГ гидрогенизированного касторового масла и их комбинаций; растворитель, выбранный из пропиленгликоля и этилового спирта и их комбинаций; и масло, выбранное из 1) триглицеридов жирных кислот со средней длиной цепи, таких как фракционированное кокосовое масло, триглицериды каприловой/каприновой кислот, 2) сложных эфиров жирных кислот и моновалентных ...

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ПЕМБРОЛИЗУМАБА И ЕЕ ПРИМЕНЕНИЕ

Группа изобретений относится к области фармацевтики и медицины. 1 и 2 объекты представляют собой фармацевтическую композицию пембролизумаба для лечения злокачественного новообразования или инфекционного заболевания, содержащую: 5-50 мг/мл пембролизумаба; 0,087-0,432 мг/мл гистидина; 0,464-0,931 мг/мл гистидина гидрохлорида моногидрата; 1-2 мг/мл глицина; 70-130 мг/мл трегалозы и 0,8-1,2 мг/мл полоксамера 188 или 20-34 мг/мл пролина; и воду для инъекций до 1 мл, а также полученную лиофилизацией указанной композиции. 3 и 4 объекты – применение фармацевтической композиции пембролизумаба для лечения злокачественного новообразования или инфекционного заболевания и для получения лекарственного средства. Технический результат заключается в стабильности фармацевтической композиции пембролизумаба и сохранении активности белковой молекулы в составе. 4 н. и 22 з.п. ф-лы, 6 ил., 34 табл., 7 пр.

КОНЪЮГАТ ХРИЗОФАНОЛА, СПОСОБ ЕГО ПОЛУЧЕНИЯ, ПРИМЕНЕНИЕ ЕГО В КАЧЕСТВЕ ЛЕКАРСТВЕННОГО СРЕДСТВА ДЛЯ ЛЕЧЕНИЯ ДИАБЕТИЧЕСКОЙ НЕФРОПАТИИ, СПАЕК КИШОК, ОСТЕОАРТРИТА

Изобретение относится к конъюгату хризофанола или его производного, характеризующемуся общей формулой (I), в которой R1-R8 представляют собой группу, выбранную из групп -Н, -ОН, -ОСН3, -СН3, при условии, что не менее двух групп из R1-R8 означают -Н и при условии, что одна или две группы R2, R3, R6, R7 является группой -СООН, М представляет собой азотное органическое основание, выбранное из группы, состоящей из хитозамина, глюкозамина, или основную аминокислоту, выбранную из группы, состоящей из аргинина, лизина, карнитина, и группа М связана с хризофаноловой частью в конъюгат. Изобретение также относится к способу получения этого конъюгата, к применению конъюгата в качестве лекарственного средства для профилактики или лечения диабетической нефропатии, остеоартрита, ревматического или ревматоидного артрита, спаек кишок, восстановление перистальтики кишечника, и к лекарственному средству на его основе. ! ! 4 н. и 4 з.п. ф-лы, 4 ил., 19 табл.

НОВАЯ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ НЕИОННЫЕ СУРФАКТАНТЫ

Группа изобретений относится к области медицины, а именно к фармацевтической композиции для лечения или профилактики злокачественного новообразования, где злокачественное новообразование представляет собой немелкоклеточный рак легкого, содержащей а) 9-этил-6,6-диметил-8-(4-морфолин-4-ил-пиперидин-1-ил)-11-оксо-6,11-дигидро-5H-бензо[b]карбазол-3-карбонитрил или его фармацевтически приемлемую соль, б) неионное поверхностно-активное вещество А, при комнатной температуре находящееся в твердом состоянии, где поверхностно-активное вещество А представляет собой производное токоферола или лауроил полиоксилглицерид, и в) неионное поверхностно-активное вещество В, при комнатной температуре находящееся в жидком состоянии, где поверхностно-активное вещество В представляет собой полиоксиэтиленовый эфир сорбита и жирной кислоты или пропиленгликоля монолаурат, где значение гидрофильно-липофильного баланса (ГЛБ) поверхностно-активных веществ А и В независимо является равным или превышает 8 и где действующие ...

ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ ПРОТИВОТУБЕРКУЛЕЗНЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВ И СПОСОБ ИХ ИЗГОТОВЛЕНИЯ

Предложено: фармацевтические композиции противотуберкулезных лекарственных средств и способ их изготовления. Фармацевтическая композиция отличается тем, что выполнена в виде двухслойной таблетки, включающей сердцевинную таблетку с энтеросолюбильным покрытием, содержащую изониазид и наполнители, и наружную таблетку, содержащую рифампицин и наполнители, причем наружная таблетка имеет пленочное покрытие, обеспечивающее немедленное высвобождение рифампицина. Изобретение обеспечивает повышение биодоступности рифампицина за счет отсроченного во времени высвобождения с изониазидом и расширяет арсенал средств и способов указанного назначения. 2 н. и 1 з.п. ф-лы.

ЖИДКОТЕКУЧИЕ КОМПОЗИЦИИ ДЛЯ ИНЪЕКЦИЙ, ВКЛЮЧАЮЩИЕ БУПРЕНОРФИН

Группа изобретений относится к медицине. Описана жидкотекучая композиция для подкожных инъекций, включающая бупренорфин в форме свободного основания или фармацевтически приемлемой соли, биоразрушаемый термопластичный поли(DL-лактид-со-гликолид) и N-метил-2-пирролидон в качестве биосовместимой полярной апротонной жидкости. Система доставки бупренорфина с продолжительным высвобождением включает жидкотекучую композицию и твердый имплантат для продолжительного высвобождения бупренорфина. Имплантат образуется из жидкотекучей композиции. Система доставки бупренорфина с продолжительным высвобождением обеспечивает in situ 1-месячный и 3-месячный профили высвобождения, характеризуемые исключительно высокой биодоступностью, минимальным риском устойчивого повреждения тканей и, как правило, отсутствием опасности некроза мышц. 5 н. и 14 з.п. ф-лы, 5 ил., 6 табл., 5 пр.

СУСПЕНЗИЯ, СОДЕРЖАЩАЯ ОКСКАРБАЗЕПИН

Фармацевтическая композиция используется в качестве антиконвульсивного средства для предупреждения и лечения эпилептических припадков. Приготавливается в форме суспензии, содержащей окскарбазепин. Суспензия после встряхивания харатеризуется вязкостью от 5 до 52 мПа·с. В предпочтительном варианте тиксотропная пероральная суспензия содержит 6% (г/мл) окскарбазепина. В следующем варианте суспензия окскарбазепина содержит смесь карбоксиметилцеллюлозы и микрокристаллической целлюлозы, составляющую от 1,25 до 1,95% (г/мл) в пересчете на общий объем композиции. В следующем варианте суспензия содержит окскарбазепин и менее 0,5% (г/мл) гидроксиэтилцеллюлозы. Новая пероральная суспензия окскарбазепина может долго храниться без образования комков, имеет удовлетворительные характеристики текучести, сохраняет стабильность и хорошо переносится при пероральном введении. 5 н. и 8 з.п. ф-лы.

НАЗАЛЬНАЯ КОМПОЗИЦИЯ И СПОСОБ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ПРОСТУДЫ И ГРИППА ВИРУСНОГО ПРОИСХОЖДЕНИЯ

Назальная композиция включает пироглутаминовую кислоту в концентрации от 0,01 до 20% от массы композиции и другую органическую кислоту в количестве от 0,01 до 10% от массы композиции. Органическая кислота обладает значением константы диссоциации (рКа) от 3,0 до 5,0. Комбинация указанных пироглутаминовой и органической кислот обеспечивает на поверхности ткани носовой полости значение рН от 3,5 до 5,5. Композиция является эффективной для предотвращения появления симптомов простуды и гриппа вирусного происхождения или их значительного смягчения, если субъект уже страдает от таких симптомов. 2 с. и 4 з.п. ф-лы.

ДОБАВКА И МЕДИЦИНСКИЙ КОНТЕЙНЕР ДЛЯ ОБОГАЩЕННОЙ ЭРИТРОЦИТАМИ ЖИДКОСТИ

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ПРОЗРАЧНЫЕ СТАБИЛЬНЫЕ КОМПОЗИЦИИ ПРОПОФОЛА

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Группа изобретений относится к химико-фармацевтической промышленности и коллоидной химии, и касается использования для получения кровезаменителей с газотранспортной функцией полиэтиленгликолевого эфира токоферола. Сущность изобретений заключается в том, что полиэтиленгликолевый эфир токоферола применяют в качестве поверхностно-активного вещества при получении эмульсии перфторорганических соединений с газотранспортными свойствами. Указанная эмульсия содержит смесь перфторорганических соединений, при этом смесь перфторорганических соединений представляет собой смесь перфтордекалина и перфтор-n-метилциклогексилпиперидина в соотношении 2:1 при общей концентрации смеси 20 об.%, и поверхностно-активное вещество, в качестве которого используется полиэтиленгликолевый эфир токоферола или его смесь с проксанолом. Способ получения указанной эмульсии заключается в том, что смесь перфтордекалина и перфтор-n-метилциклогексилпиперидина стабилизируют поверхностно-активным веществом, в качестве которого ...

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Изобретение относится к композициям для поддержания сердечно-сосудистой системы и/или сосудов в здоровом состоянии, содержащим эффективное количество мономера и/или олигомера процианидина какао и эффективное количество холестеринснижающего реагента на основе стерина и/или станола, и к способам поддержания сосудистой системы в здоровом состоянии, включая лечение и профилактику атеросклероза и сердечно-сосудистого заболевания. Технический результат: усиленное воздействие на состояние сосудистой системы млекопитающего, в частности человека, по сравнению с ранее известными композициями при лечении и профилактике атеросклероза и сердечно-сосудистого заболевания. 12 н. и 26 з.п. ф-лы, 7 табл., 8 ил.

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Изобретение относится к области ветеринарии. Описана жидкая гомогенная фаза для трансдермальных фармацевтических композиций, которая обеспечивает абсорбцию физиологически активных веществ через кожные покровы животного при отсутствии раздражающего эффекта, обладает свойствами, препятствующими слизыванию животными, и имеет значение pH в пределах от 4 до 6. Фаза состоит из низковязкой смеси эфирного и амидного растворителя и высоковязкой смеси пенетрантов. Фаза может быть использована при доставке в организм млекопитающего местных и системных физиологически активных агентов, удобна в хранении и использовании в условиях производства. 4 з.п. ф-лы, 6 табл., 38 пр.

СПОСОБ ПОДАВЛЕНИЯ ВЫЦВЕТАНИЯ СО ВРЕМЕНЕМ АДГЕЗИВНОЙ КОМПОЗИЦИИ, СОДЕРЖАЩЕЙ ДОНЕПЕЗИЛ

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Изобретение относится к области биофармацевтических и терапевтических средств. Предложены ионизируемые соединения, а также фармацевтическая композиция на основе ионизируемых соединений. Технический результат – получение ионизируемых соединений, которые используются для доставки и распределения действующих агентов или лекарственных средств. 12 н. и 16 з.п. ф-лы, 32 ил., 10 табл., 40 пр.

СРЕДСТВА БОРЬБЫ С ПАРАЗИТАМИ ЖИВОТНЫХ И ИХ ПРИМЕНЕНИЕ ДЛЯ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННОГО СРЕДСТВА

Изобретение относится к средствам борьбы с паразитами животных. Средство содержит N-арилпиразол общей формулы: ! ! где R1 и R2 независимо друг от друга означают галоген, ! R2 означает галогеналкил с 1-3 атомами углерода, ! R4 означает цианогруппу или -C(=S)NH2. Средство дополнительно содержит алифатический циклический карбонат, алифатический ациклический простой полиэфир, являющийся производным диолов, имеющих до 8 атомов углерода и фармацевтически приемлемые вспомогательные или дополнительные вещества. Его применяют для производства лекарственного средства. Изобретение позволяет повысить эффективность и безопасность средства. 2 н. и 4 з.п. ф-лы, 3 табл., 5 пр.

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Изобретение относится к фармацевтической пероральной твердой форме, включающей обработанную в расплаве смесь по меньшей мере одного активного ингредиента, который представляет собой твердую дисперсию по меньшей мере одного фармацевтически приемлемого полимера и солюбилизирующей композиции, включающей по меньшей мере одно токоферилсодержащее соединение и по меньшей мере один пропиленгликолевый моноэфир жирной кислоты или смесь пропиленгликолевых моно- и диэфиров жирной кислоты. Активным ингредиентом (ингредиентами) может быть ингибитор протеазы ВИЧ. Солюбилизирующая композиция увеличивает биологическую доступность активного ингредиента после перорального введения. Изобретение также относится к способу получения вышеуказанной фармацевтической формы, который заключается в получении однородного расплава указанного активного ингредиента, указанного фармацевтически приемлемого полимера, и указанной солюбилизирующей композиции, и предоставление расплаву возможности затвердеть с образованием твердого ...

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Изобретение относится к кристаллической микрочастице для доставки активных агентов, которая содержит дикетопиперазин и полисорбат 80. Изобретение также относится к способу получения указанной микрочастицы. Способ включает стадии получения раствора дикетопиперазина с ограниченной растворимостью при низком значении рН, добавления полисорбата 80 к раствору и осаждения микрочастиц дикетопиперазина на стадии добавления кислоты к раствору. Изобретение также относится к способу нанесения покрытия на предварительно сформированную указанную микрочастицу. Способ включает получение суспензии, содержащей предварительно сформированную кристаллическую микрочастицу, активный агент и растворитель, изменение свойств суспензии для регулирования энергетического взаимодействия между указанным активным агентом и предварительно сформированной кристаллической микрочастицей и адсорбирование активного агента на поверхности микрочастицы для обеспечения нанесения покрытия. При этом стадия изменения свойств и стадия ...

НИКОТИНСОДЕРЖАЩАЯ ТАБЛЕТКА И СПОСОБ ЛЕЧЕНИЯ ОТ КУРЕНИЯ

Изобретение относится к области медицины, а именно к наркологии. Таблетка содержит никотин в количестве 0,5 - 5,0 мг, адсорбирующий наполнитель, непитательный подсластитель и целевые добавки. Таблетку вводят буккально и осуществляют контроль содержания никотина в крови на уровне 5 - 50 нг/мл. Способ позволяет повысить эффективность лечения. 2 с. и 21 з.п. ф-лы, 2 табл., 2 ил.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ ИБУПРОФЕН, ФАРМАЦЕВТИЧЕСКИЙ ПРЕПАРАТ НА ЕЕ ОСНОВЕ И СПОСОБ ЕГО ПОЛУЧЕНИЯ

Настоящее изобретение относится к новой фармацевтической композиции, предназначенной для приготовления порошков или шипучих таблеток, включающих ибупрофен или одну из его фармацевтически приемлемых солей в качестве активного ингредиента. Эта композиция содержит эффективное количество ибупрофена или одной из его фармацевтически приемлемых солей, фармацевтически приемлемую газирующую систему, включающую по крайней мере один щелочной карбонат и по крайней мере одну органическую кислоту, предпочтительно в количестве, достаточном для получения рН ниже примерно 8, по крайней мере один фармацевтически приемлемый антиоксидант в количестве, достаточном для стабилизации ибупрофена. Композиция обладает стабильностью как в виде порошка, так и в виде таблеток. 3 с. и 13 з.п. ф-лы, 4 табл.

КОМБИНИРОВАННАЯ ВАКЦИНА ДЛЯ СВИНЕЙ

Группа изобретений относится к области медицины, а именно к ветеринарии, иммунологии и вирусологии, и предназначена для вакцинирования свиней против заболевания, ассоциированного с инфекцией цирковируса свиней типа 2 (PCV2) и вируса репродуктивного и респираторного синдрома свиней (PRRSV). Комбинированная вакцина содержит неспособный к воспроизведению антиген из PCV2 и живой PRRSV. Вакцина представляет собой эмульсию масло-в-воде, содержащую сквалан и ацетат витамина E. Также, представлены способы получения указанной комбинированной вакцины. В другом воплощении представлена эмульсия масло-в-воде, содержащая сквалан и ацетат витамина E, неспособный к воспроизведению антиген из PCV2 и живой PRRSV. В другом воплощении представлено применение неспособного к воспроизведению антигена из PCV2 и живого PRRSV для изготовления комбинированной вакцины. Кроме того, представлен способ вакцинации свиней против PCV2 и PRRSV посредством введения указанной комбинированной вакцины. Использование группы изобретений ...

Обезболивающая жидкая фармацевтическая композиция

Изобретение относится к области химико-фармацевтической промышленности и касается жидкой фармацевтической композиции, обладающей обезболивающим эффектом. Композиция включает метамизол натрия, цитратный буфер, сахаринат натрия, натрия цикламат, экстракт боярышника и воду очищенную при определенном количественном соотношении компонентов для получения композиции (в мас.%): метамизола натрия - от 250000 до 750000, лимонная кислота безводная - от 0,0045 до 0,0133, натрия цитрат дигидрат - от 1,8312 до 5,4935, сахаринат натрия - от 0,1500 до 0,4500, натрия цикламат - от 1,2500 до 3,7500, сухой экстракт боярышника - от 0,1500 до 0,4500, вода очищенная - до 100 мл. Фармацевтическая композиция по изобретению обладает приятным вкусом и улучшенной биодоступностью по сравнению с лекарственным средством по прототипу. 4 табл., 1 ил., 5 пр.

БИОМАТЕРИАЛ И СРЕДСТВО С БИОМАТЕРИАЛОМ, СТИМУЛИРУЮЩИЕ ПРОТИВООПУХОЛЕВУЮ АКТИВНОСТЬ

Изобретение относится к области медицины, а именно к онкологии, и может быть использовано для биологической терапии опухолей. Описан биоматериал, стимулирующий противоопухолевую активность, который содержит лиофилизат постнатальных индуцированных лимфатических узлов (ПНИЛУ) больного раком. Описано средство, стимулирующее противоопухолевую активность, которое содержит в качестве действующего вещества лиофилизат ПНИЛУ больного раком, а в качестве растворителя воду для инъекций, кремофор RH-40, эмульгатор Т-2, масло персиковое, глицерин, коллидон CL-M и бензиловый спирт при определенном соотношении компонентов. Использование изобретения обеспечивает получение нового средства отечественного производства, содержащего биоматериал, стимулирующий противоопухолевую активность, обладающего выраженным пролонгированным действием, удобного в применении. 2 н. и 1 з.п. ф-лы, 5 ил., 3 пр.

ЛЕКАРСТВЕННОЕ СРЕДСТВО ДЛЯ ПАРЕНТЕРАЛЬНОГО ВВЕДЕНИЯ

Изобретение относится к области медицины и касается лекарственного средства для парентерального введения. Технический результат заключается в устранении побочных явлений. Сущность изобретения заключается в том, что предложенное средство содержит систему растворителей: α -тетрагидрофурфурил-w-гидроксиполиоксиэтилен, полиэтиленгликоль со средней мол. м. 200 - 600, воду, активное вещество, содержащее минимум одно производное триазола, формулы: где R1 означает фенильный радикал, имеющий в случае необходимости 1 - 3 заместителя, выбранных из группы, включающей F, Cl, Br, J, CF3, алкил C1-C4 и алкокси C1-C4 , или 5-хлор-пирид-2-ил; X означает OH, F, Cl или Br, R2 представляет собой H, CH3 или F, R3 - H или F при определенном соотношении компонентов.

Средство седативного действия для детей

Изобретение относится к химико-фармацевтической промышленности, а именно к средству седативного действия для детей. Средство седативного действия для детей, содержащее натрия бромид, магния сульфат, настойку пустырника, настойку валерианы, раствор цитраля спиртовой 1%, фруктозу, желатин, кислоту аскорбиновую, воду очищенную при следующем соотношении ингредиентов на 1 пастилку: натрия бромид 0,005 г, магния сульфат 0,01 г, настойка валерианы 0,01 мл, настойка пустырника 0,01 мл, раствор цитраля спиртовой 1% 0,01 мл, фруктоза 0,1 г, желатин 0,2 г, аскорбиновая кислота 0,05 г, вода очищенная до 1,0 г. Вышеуказанное изобретение позволяет расширить арсенал средств седативного действия для детей.

САМОКЛЕЯЩАЯСЯ ЧРЕСКОЖНАЯ МАТРИЧНАЯ СИСТЕМА И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Изобретение относится к медицине, а именно к чрескожной матричной системе для чрескожного введения гормона, при этом матричная система имеет подложку и самоклеящуюся матрицу, которая включает матрицу, содержащую 20 - 42 мас. ч. трехблочного сополимера поли (стирол-изопрен-стирола), 35 - 55 мас.ч. смолы, повышающей клейкость, 5 - 25 мас.ч. пластификатора, выбранного из группы, состоящей из олеинового спирта, пегликоль-5-олеата, пропиленгликольлаурата или полипропоксилового эфира цетилового спирта, 5 - 15 мас.ч. по крайней мере одного соединения, выбранного из группы, состоящей из кротаматона и N-замещенных 2-пирролидонов формулы I где R представляет (C1 - C15)-алкильную, циклогексильную или 2-гидроксиэтильную группу, 0,01 - 1 мас.ч. стабилизатора и 0,1 - 5 мас.ч. гормона, выбранного из группы, состоящей из эстрогеновых компонентов, прогестогеновых компонентов и их смесей. Способ получения упомянутой системы включает смешение компонентов, затем гомогенизацию полученной смеси, с последующим ...

ЭМУЛЬСИЯ ПЕРФТОРОРГАНИЧЕСКИХ СОЕДИНЕНИЙ С ГАЗОТРАНСПОРТНЫМИ СВОЙСТВАМИ

Изобретение относится к медицине и коллоидной химии и может быть использовано для получения кровезаменителей с газотранспортной функцией на основе эмульсий перфторорганических соединений (ПФС). Цель - изобретения уменьшение токсичности и увеличение стабильности при хранении эмульсий ПФС. Эмульсия ПФС с газотранспортными свойствами содержит в качестве носителя газов быстровыводящийся перфторуглерод, объемная концентрация которого в эмульсии составляет от 40 до 50 об.%, высокомолекулярную перфорированную добавку, концентрация которой составляет от 1 до 10 об.%, и фосфолипиды в концентрации от 2 до 6 мас.%. В качестве высокомолекулярной перфорированной добавки может использоваться перфтор-n-метил-циклогексилпиперидин. 2 з. п. ф-лы, 2 ил., 4 табл.

ЖИДКАЯ АНТИБАКТЕРИАЛЬНАЯ КОМПОЗИЦИЯ

Изобретение относится к области ветеринарии, а именно к антибактериальным препаратам. Композиция содержит, мас.%: 10-50 флорфеникола; 10-65 N-метил-2-пирролидона, 5-40 полиэтиленгликоля и 5-15 пропиленгликоля или этанола. 4 табл.

ЛЕКАРСТВЕННОЕ СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ И СПОСОБ ЕГО ПОЛУЧЕНИЯ

Использование: в медицине для лечения шизофрении. Сущность изобретения: средство содержит клозапин и рецептор радикалов при их массовом соотношении 1: 30-40. Акцептор радикалов - L-аскорбиновая кислота и/или ее Na-соль. Средство может представлять собой дозовую форму для однократного введения, форму для орального введения, таблетки. Оно может содержать указанную смесь в количестве 25 мг или 100 мг, может содержать целевые добавки. Средство получают смешением компонентов. 2 с. и 6 з.п. ф-лы, 4 табл.

МИКРОЧАСТИЦЫ ДИКЕТОПИПЕРАЗИНА С ОПРЕДЕЛЕННЫМ СОДЕРЖАНИЕМ ИЗОМЕРОВ

Описаны составы и микрочастицы фумарил дикетопиперазина (FDKP) с содержанием определенного транс-изомера, составляющим от приблизительно 45% до приблизительно 65%. Микрочастицы FDKP могут содержать лекарственное средство, такое как эндокринный гормон, включая пептид, включая инсулин, глюкагон, паратиреоидный гормон, и могут применяться для получения порошкового состава для легочной доставки лекарственного средства. Микрочастицы фумарил дикетопиперазина (FDKP) с указанным содержанием транс-изомера демонстрируют улучшенные аэродинамические характеристики. 7 н. и 20 з.п. ф-лы, 6 ил., 6 табл., 3 пр.

СПОСОБ ОЧИЩЕНИЯ КИШЕЧНИКА И НАБОР ДЛЯ ЕГО ОСУЩЕСТВЛЕНИЯ

Группа изобретений относится к медицине и предназначена для очищения кишечника. Раскрыт набор для получения слабительного лекарственного препарата, состоящего из трех частей в виде сухих форм для смешивания с водой. Первая часть содержит полиэтиленгликоль 75,0-125,0 г, сульфат натрия 7,0-11,0 г, хлорид натрия 1,5-2,5 г и хлорид калия 0,5-1,5 г; вторая часть содержит полиэтиленгликоль 30,0-50,0 г, хлорид натрия 3,0-3,5 г, хлорид калия 1,0-1,5 г, и бикарбонат натрия 16,0-25,0 г; и третья часть содержит L-аскорбиновую кислоту 40,0-60,0 г. В способе очищения кишечника указанные части после смешивания с водой вводят в виде раствора перорально в два этапа, на первом этапе вводят раствор, полученный смешиванием с водой части 1 слабительного лекарственного препарата, а на втором этапе вводят раствор, полученный смешиванием с водой частей 2 и 3 слабительного лекарственного препарата. Группа изобретений обеспечивает улучшение вкусовых свойств препарата и небольшой объем принимаемой жидкости. 2 н.

Ранозаживляющий гель с липосомами и способ его получения

Изобретение относится к процессам ранозаживления и регенерации тканей, а именно к ранозаживляющему гелю. Ранозаживляющий гель с липосомами включает метронидазол (метрогил), лидокаин, желатин, гиалуроновую кислоту, карбомер 940 и липосомы. В состав липосом входят лецитин, образующий бислой липосом, α-токоферол и оротат калия. Также изобретение относится к способу получения ранозаживляющего геля. Предложенный гель обладает противомикробным, противопаразитным, анестезирующим и улучшающим регенерацию тканей действием. 2 н.п. ф-лы, 4 ил.

КОМПОЗИЦИИ И СПОСОБ ДЛЯ ЛЕЧЕНИЯ МИКРОБНЫХ И ПАРАЗИТАРНЫХ ИНФЕКЦИЙ У КРУПНОГО РОГАТОГО СКОТА И ДРУГИХ ЖИВОТНЫХ

... 1. Композиция для лечения микробной и паразитарной инфекции у животного, включающая а) соединение, выбранное из группы, состоящей из соединения формулы I где R представляет собой фрагмент, выбранный из группы, содержащей метил или этил или их галогенированное производное, дигалогендейтерометил, 1-галоген-1-дейтероэтил, 1, 2-дигалоген-1-дейтероэтил, азидометил и метилсульфонилметил; каждый из Х и X' представляет собой фрагмент, независимо выбранный из группы, включающей: NO2, SO2R1, SOR1, SR1, SONH2, SO2NH2, SONHR1, SO2NHR1, COR1, OR1, R1, CN, галоген, водород, фенил и фенил, замещенный галогеном, NO2, R1, PO2R1, CONHR1, NHR1, NR1R2, CONR1R2, OCOR1 или OR1, где каждый из R1 и R2представляет собой фрагмент, независимо выбранный из группы, содержащей метил, этил, н-пропил, изопропил, бутил, трет-бутил, изобутил и фенил; и Z представляет собой водород или ацильную группу углеводород-карбоновой кислоты, содержащей до 16 атомов углерода, или ацильную группу аминоуглеводород-карбоновой кислоты ...

СПОСОБ СНИЖЕНИЯ ТОКСИЧНОСТИ ЛЕКАРСТВЕННЫХ СРЕДСТВ, МЕТАЛЛОВ, ОРГАНИЧЕСКИХ И НЕОРГАНИЧЕСКИХ СОЕДИНЕНИЙ И ДРУГИХ ТОКСИНОВ

... 1. Способ снижения токсичности лекарственных средств, металлов, органических и неорганических соединений и других токсинов путем применения химических соединений, отличающийся тем, что в качестве химических соединений применяют 1-гидроксигерматран (германтранол, 1-гидрокси-1-герма-2,8,9-триокса-5- азабицикло[3.3.3.]ундекан) и его производные общей формулы I где R1 - водород или органический радикал или элементоорганический радикал, в том числе, производное лекарственных препаратов; R1 - R12 - водород или органический радикал; X - кислород или сера; и/или производные 1-герма-2,8-диокса-5- азациклооктана (II) где R1 - R2 - водород или органический радикал или элементоорганический радикал в том числе производное лекарственных препаратов; R3 - R11 - водород или органический радикал; X - кислород или сера; радикалы R1 и R2 могут быть химически связаны друг с другом, которые вводят перорально в виде инъекций или местно из расчета 0,001 - 0,1 г в день. 2. Способ по п.1, отличающийся тем, что в ...

ПАРЕНТЕРАЛЬНЫЕ КОМПОЗИЦИИ, СОДЕРЖАЩИЕ ГИДРОКСИЭФИРЫ РАПАМИЦИНА

... 1. Концентрат сорастворителя и CCI-779, который включает CCI-779, растворитель, приемлемый для парентерального применения, и антиоксидантный компонент. 2. Концентрат сорастворителя по п. 1, где растворителем, приемлемым для парентерального применения, является диметилацетамид. 3. Концентрат сорастворителя по п. 1, где растворителем, приемлемым для парентерального применения, является спиртовой растворитель. 4. Концентрат сорастворителя по п. 3, где спиртовой растворитель включает этанол, пропиленгликоль, полиэтиленгликоль 300, полиэтиленгликоль 400, полиэтиленгликоль 600 или полиэтиленгликоль 1000. 5. Концентрат сорастворителя по любому из пп. 1-4, где антиоксидантный компонент включает лимонную кислоту, глицин, d,1--токоферол, BHA, BHT, монотиоглицерин, аскорбиновую кислоту или пропилгаллат. 6. Концентрат сорастворителя и CCI-779 по п.1, который включает CCI-779, лимонную кислоту и дегидратированный этанол. 7. Концентрат сорастворителя и CCI-779 по п.1, который включает CCI-779, дегидратированный ...

ИНЪЕЦИРУЕМЫЕ КОМПОЗИЦИИ ДЛЯ КОНТРОЛИРУЕМОЕЙ ДОСТАВКИ ФАРМАКОЛОГИЧЕСКИ АКТИВНОГО СОЕДИНЕНИЯ

... 1. Композиция для введения млекопитающему фармакологически активного соединения, включающая соль фармакологически активного соединения с липофильным противоионом; и фармацевтически приемлемый растворитель; объединенные вместе с образованием инъецируемой композиции, которая выпадает в осадок при инъекции в воду; и где при инъекции млекопитающему композиция высвобождает активное соединение во времени. 2. Композиция по п.1, где фармацевтически приемлемый растворитель является смешивающимся с водой растворителем. 3. Композиция по п.1, где фармакологически активное соединение является антибиотиком. 4. Композиция по п.1, где фармакологически активное соединение является тилмикозином, окситетрациклином, доксициклином, флуоксетином, рокситромицином, тербинафином или метопрололом. 5. Композиция по п.1, где фармакологически активное соединение выбрано из группы, состоящей из триметоприма, неомицина, стрептомицина, гентамицина, дибукаина, бупивакаина, бензокаина, тетракаина, ацепромазина, итраконазола ...

КОМПОЗИЦИИ НАЛТРЕКСОНА ГИДРОХЛОРИДА

... 1. Фармацевтическая композиция, содержащая налтрексон гидрохлорид в количестве 20 мг или менее и стабилизатор, который ингибирует образование, по меньшей мере, одного продукта разложения налтрексона гидрохлорида. 2. Фармацевтическая композиция по п.1, отличающаяся тем, что указанный стабилизатор ингибирует образование продукта разложения, выбранного из группы, состоящей из 10-гидроксиналтрексона; 10-кетоналтрексона; 2,2’-бисналтрексона(псевдоналтрексона); оксидов 2,2’-бисналтрексона; диоксидов 2,2’-бисналтрексона, продукта альдольной конденсации ("альдольного аддукта") налтрексона и 10-гидроксиналтрексона; продукта альдольной конденсации налтрексона и 10-кетоналтрексона; налтрексон-N-оксида; 10-гидроксиналтрексон-N-оксида; 10-кетоналтрексон-N-оксида; семихинонов налтрексона; свободнорадикальных пероксидов налтрексона; продукта альдольной конденсации налтрексона; продуктов альдольной конденсации налтрексона, конденсированных по положению (связи) 7,6; продуктов альдольной конденсации налтрексона ...

СОДЕРЖАЩИЕ ДЕЙСТВУЮЩЕЕ ВЕЩЕСТВО ПЛЕНОЧНЫЕ ПРЕПАРАТЫ С ПОВЫШЕННОЙ ХИМИЧЕСКОЙ СТОЙКОСТЬЮ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

... 1. Содержащие действующее вещество пленочные препараты для применения в ротовой полости или через слизистую оболочку, отличающиеся тем, что их переписное число максимально равно 40. 2. Препарат по п.1, отличающийся тем, что его перекисное число максимально равно 15, предпочтительно максимально 5. 3. Препарат по п.1 или п.2, отличающийся тем, что он преимущественно не содержит активный кислород, означающий молекулярный кислород, а также содержащие кислород соединения, в которых окислительное состояние кислорода превышает-2, в особенности, пероксиды с общей структурой R-O-O-R', в которой R и R' означают атомы водорода, либо R означает алкильный остаток, а R' означает атом водорода, либо R и R' означают алкильные остатки, при этом R и R' могут быть идентичны или отличаться друг от друга. 4. Препарат по п.1, отличающийся тем, что он содержит по меньшей мере один антиокислитель, предпочтительно выбранный из группы, включающей аскорбиновую кислоту, аскорбилпальмитат, сульфит натрия, дисульфит ...

КОМПОЗИЦИИ КОНТРОЛИРУЕМОГО ВЫСВОБОЖДЕНИЯ, СОДЕРЖАЩИЕ НИМЕСУЛИД

... 1. Фармацевтическая композиция контролируемого высвобождения нимесулида, которая включает в себя в качестве активного лекарственного средства нимесулид в количестве до 99 мас.%/мас. композиции, одно или более веществ, контролирующих высвобождение, в количестве 0,1-99 мас.%/мас. композиции и фармацевтические наполнители в количестве от 0 до 90 мас.%/мас. композиции. 2. Фармацевтическая композиция контролируемого высвобождения нимесулида по п.1, которая включает в себя в качестве активного лекарственного средства нимесулид в количестве от 20 до 70 мас.%/мас. композиции, одно или более веществ, обеспечивающих контролируемое высвобождение, в количестве от 5 до 65 мас.%/мас. композиции и фармацевтические наполнители в количестве от 10 до 70 мас.%/мас. композиции. 3. Фармацевтическая композиция контролируемого высвобождения нимесулида по пп.1 и 2, где нет потери биодоступности по сравнению с композицией немедленного высвобождения. 4. Фармацевтическая композиция контролируемого высвобождения нимесулида ...

СОСТАВ, СОДЕРЖАЩИЙ АНТИТЕЛО

ВОДНЫЕ КОМПОЗИЦИИ, СОДЕРЖАЩИЕ МЕТРОНИДАЗОЛ

Способ получения водного раствора, содержащего бета-циклодекстрин в концентрации более 0,5% мас./мас., включающий комбинирование в водной жидкости бета-циклодекстрина и ниацинамида или ниацина, где количество ниацинамида или ниацина, которое комбинируют в водной жидкости, достаточно для того, чтобы обеспечить концентрацию растворенного бета-циклодекстрина более 0,5% мас./мас. при температуре 5°С.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ СЛИТОГО БЕЛКА РЕЦЕПТОРА ТРАНСФОРМИРУЮЩЕГО ФАКТОРА РОСТА БЕТА И ЕЕ ПРИМЕНЕНИЕ

ЭНДОПАРАЗИТИЦИДНОЕ СРЕДСТВО

... 1. Эндопаразитицидное средство, содержащее в качестве действующих веществ эмодепсид, а также празиквантел или эпсипрантел, и в качестве растворителя 1,2-изопропилиденглицерин, причем содержание воды в средстве составляет не более 1 вес.%. ! 2. Эндопаразитицидное средство по п.1, отличающееся тем, что в качестве действующих веществ оно содержит эмодепсид и празиквантел. ! 3. Эндопаразитицидное средство по п.1, отличающееся тем, что используемый растворитель содержит, по меньшей мере, 60 об.% 1,2-изопропилиденглицерина. ! 4. Эндопаразитицидное средство по пп.1-3, отличающееся тем, что оно содержит 1,2-изопропилиденглицерин в качестве единственного растворителя. ! 5. Метод получения эндопаразитицидного средства по пп.1-4, отличающийся тем, что действующие вещества смешивают с растворителями и при необходимости с дополнительными добавками. ! 6. Использование эмодепсида и празиквантела или эпсипрантела для получения эндопаразитицидного средства, которое содержит 1,2-изопропилиденглицерин в качестве ...

Составы фармацевтической жевательной резинки

... 1. Способ доставки лекарственного средства субъекту, включающий стадии обеспечения жевательной резинки, в состав которой входит лекарственное средство, жевание указанной жевательной резинки с целью вызвать высвобождение из ее состава лекарственного средства в ротовую полость субъекта, а также продолжение процесса жевания, что создает давление, заставляющее указанное лекарственное средство через слизистую рта субъекта поступать в системы его организма. 2. Способ по п.1, отличающийся тем, что указанную жевательную резинку жуют в течение по крайней мере 2 мин. 3. Способ по 1, отличающийся тем, что указанная жевательная резинка создает в слюне концентрацию лекарственного средства от приблизительно 1700×10-6 до приблизительно 4400× 10-6. 4. Способ по п.1, отличающийся тем, что указанное лекарственное средство выбирают из группы, включающей анальгетики, мышечные релаксанты, антибиотики, противовирусные средства, антигистаминные средства, противовоспалительные средства, противоотечные средства ...

КОМПОЗИЦИИ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ПРОСТУДНЫХ И ГРИППОПОДОБНЫХ СИМПТОМОВ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

... 1. Слабораздражающая назальная композиция для профилактики и лечения от вирусов простуды и гриппа, включающая пироглутаминовую кислоту, альтернативно, пироглутаминовую кислоту в концентрации примерно от 0,01 до 20% от композиции, и органическую кислоту, обладающую значением константы диссоциации (рКа) от 3,0 до 5,0, альтернативно, от 0,01 до 10% органической кислоты, где комбинация указанных пироглутаминовой и органической кислот обеспечивает значение рН поверхности ткани носовой полости от рН 3,5 до 5,5. 2. Композиция по п.1, где органическая кислота выбрана из группы, состоящей из аскорбиновой кислоты, моно-, ли-, трикарбоновых кислот и их смесей, альтернативно, органическая кислота выбрана из группы, состоящей из салициловой, фумаровой, бензойной, глутаровой, молочной, лимонной, малоновой, уксусной, гликолевой, яблочной, адипиновой, янтарной, аспарагиновой, фталевой, винной, глутаминовой, глюконовой кислот, и их смесей. 3. Слабораздражающая назальная композиция для профилактики и лечения ...

ДОБАВКА И МЕДИЦИНСКИЙ КОНТЕЙНЕР ДЛЯ ОБОГАЩЕННОЙ ЭРИТРОЦИТАМИ ЖИДКОСТИ

... 1. Добавка для обогащенной эритроцитами жидкости, полученная путем добавления ингибитора гемолиза и поверхностно-активного вещества в раствор для хранения крови, в которойзначение гидрофильно-липофильного баланса (HLB) поверхностно-активного вещества составляет не менее 13; ачисло оксиэтиленовых групп в гидрофильном сегменте молекулярной структуры поверхностно-активного вещества - не менее 20.2. Добавка для обогащенной эритроцитами жидкости по п.1, отличающаяся тем, чтогидрофильный сегмент молекулярной структуры поверхностно-активного вещества состоит из полиоксиэтиленсорбитана;а раствор для хранения эритроцитов представляет собой смешанный раствор, содержащий маннитол, глюкозу, аденин, фосфатную соль, цитратную соль и хлорид натрия.3. Добавка для обогащенной эритроцитами жидкости по п.1, отличающаяся тем, чтогидрофильный сегмент в молекулярной структуре поверхностно-активного вещества состоит из полиоксиэтиленсорбитана;а раствор для хранения эритроцитов представляет собой смешанный раствор ...

ФАРМАЦЕВТИЧЕСКИЕ И ВЕТЕРИНАРНЫЕ ПАСТООБРАЗНЫЕ КОМПОЗИЦИИ

... 1. Фармацевтическая или ветеринарная пастообразная композиция, содержащая (a) эффективное количество терапевтически активного средства; (b) коллоидный диоксид кремния; (c) модификатор вязкости, содержащий две или более функциональные группы для образования водородных связей на поверхности коллоидного диоксида кремния; (d) носитель, причем пастообразная композиция не требует нагревания или охлаждения при получении и обнаруживает низкую чувствительность к сдвигу или не обнаруживает ее вовсе, и проявляет низкую чувствительность к действию температуры или не проявляет ее вовсе. 2. Пастообразная композиция по п.1, содержащая (a) терапевтически активное средство, выбираемое из группы, состоящей из инсектицидов, акарицидов, паразитицидов, антибиотиков, стимуляторов роста или маслорастворимых NSAID; (b) коллоидный диоксид кремния; (c) модификатор вязкости; (d)абсорбент; (e) краситель; (f) носитель, которым является триацетин, моноглицерид, диглицерид или триглицерид. 3. Пастообразная композиция ...

Водорастворимые композиции с биологически активными липофильными соединени ми

... 1. Водорастворимая композиция, содержащая биологически активное липофильное соединение и солюбилизирующий агент общей формулы где Х - остаток гидрофобной части молекулы, выбранной из группы, состоящей из стеринов, токоферолов и их производных, Y - остаток гидрофильной части молекулы, выбранной из группы, состоящей из полимерных спиртов, полиэфиров и их производных, р = 1 или 2, m = 0 или 1, и n - целое число в интервале: 0≤n≤18, при условии, что если р и m равны 1, а гидрофобная часть молекулы является α-(+)-токоферолом, то n не равно 2. 2. Композиция по п.1, отличающаяся тем, что биологически активное липофильное соединение выбрано из группы, состоящей из убихинонов, убихинолей, витаминов, провитаминов, полиеновых макролидных антибиотиков и их смесей, при условии, что если биологически активное липофильное соединение - убихинон, а гидрофобная часть молекулы - холестерин, то n не равно 8. 3. Композиция по п.1, отличающаяся тем, что гидрофобная часть молекулы выбрана из группы, состоящей ...

КОМПОЗИЦИИ ДЛЯ ИНКАПСУЛИРОВАНИЯ И РЕГУЛИРУЕМОГО ВЫСВОБОЖДЕНИЯ

... 1. Композиция, содержащая: матрицу, содержащую молекулы, которые нековалентно сшиты между собой многовалентными катионами, причем молекулы, имеющие нековалентные сшивки, не являются полимерными, имеют более чем одну карбоксильную функциональную группу, и имеют, по меньшей мере, частично ароматическую или гетероароматическую структуру. 2. Композиция для инкапсулирования и контролируемого высвобождения, содержащая композицию по п.1, отличающуюся тем, что молекулы, имеющие нековалентные сшивки, - это молекулы хозяина и композиция характеризуется тем, что гостевая молекула может быть инкапсулирована в матрице и впоследствии высвобождена из нее. 3. Композиция для инкапсулирования и контролируемого высвобождения по п.2, отличающаяся тем, что молекула-хозяин является цвиттер-ионной. 4. Композиция для инкапсулирования и контролируемого высвобождения по п.2, отличающаяся тем, что содержит дополнительно гостевую молекулу. 5. Композиция для инкапсулирования и контролируемого высвобождения по п.4, ...

СПОСОБ УСИЛЕНИЯ ЛЕЧЕБНОГО ЭФФЕКТА ЛЕКАРСТВЕННЫХ СРЕДСТВ

... 1. Способ усиления лечебного эффекта лекарственных средств путем применения лекарственного средства вместе с химическими соединениями, отличающийся тем, что в качестве химических соединений применяют 1-гидроксигерматран (герматранол, 1-гидрокси-1- герма-2,8,9-триокса- 5-азабицикло[3.3.3.] ундекан) и его производные общей формулы I где R1 - водород или органический радикал или элементоорганический радикал, в том числе производное лекарственных препаратов; R1 - R12 - водород или органический радикал; X - кислород или сера; и/или производные 1-герма-2,8- диокса-5- азациклооктана II где R1 - R2 - водород или органический радикал или элементоорганический радикал в том числе производное лекарственных препаратов; R3 - R11 - водород или органический радикал; X - кислород или сера; радикалы R1 и R2 могут быть химически связаны друг с другом, перед применением добавляют в лекарственное средство и которые вводят перорально в виде инъекций или местно, из расчета 0,001 - 0,1 г в день. 2. Способ по п ...

ПОЛУЧЕНИЕ И ХРАНЕНИЕ ЛИПОСОМНЫХ ПРЕПАРАТОВ РНК, ПРИГОДНЫХ ДЛЯ ТЕРАПИИ

СПОСОБ ПОЛУЧЕНИЯ ПЕРОРАЛЬНОЙ ФОРМЫ СУБСТАНЦИИ, СОДЕРЖАЩЕЙ ИНСУЛИН

ПЕРОРАЛЬНАЯ ДОЗИРОВАННАЯ ФОРМА СУЛЬФОНАМИДНОГО ПРОЛЕКАРСТВА

... 1. Способ лечения или профилактики опосредуемого COX-2 заболевания у субъекта, где данный способ включает (а) предоставление фармацевтической композиции, которая является по существу безводной и содержит, по меньшей мере, одну дозировочную единицу, содержащую терапевтически эффективное количество соединения Х-SO2-NHR1 или его фармацевтически приемлемой соли, где Х является группой, выбранной так, что соединение Х-SO2-NH2 является селективным ингибирующим COX-2 лекарственным средством, причем соединение Х-SO2-NHR1 или его соль легко разлагаются ex vivo до лекарственного средства Х-SO2 -NH2; и где R1 является группой, имеющей не более 8 атомов углерода, выбранной из алкильной, гидроксиалкильной, алкоксиалкильной, карбоксиалкильной, ацильной, алкилкарбонильной, алкоксикарбонильной, гидроксиалкилкарбонильной, алкоксиалкилкарбонильной, карбоксиалкилкарбонильной, аминоалкилкарбонильной, фенилкарбонильной, бензилкарбонильной, фенил(гидрокси)метилкарбонильной, алкоксикарбонилкарбонильной, алкоксикарбонилалкилкарбонильной ...

Гормональное средство для регуляции половой охоты у мелких домашних животных

Группа изобретений относится к области ветеринарии, а именно к средствам для регуляции половой охоты у мелких домашних животных. Средство для регуляции половой охоты у мелких домашних животных в форме раствора для перорального применения содержит диеногест 0,01-1 мас.% и вспомогательные вещества: эфирное масло кошачьей мяты – 0,1 мас.%, бутилгидроксианизол – 0,2 мас.%, бутилгидрокситолуол – 0,1 мас.%, N – Метилпирролидон – 5 мас.%, альфа-токоферол ацетат – 0,1 мас. %, масло соевое – до 99,99 мас. %. Средство для регуляции половой охоты у мелких домашних животных в таблетированной форме для перорального применения содержит диеногест – 0,01-1 мас.% и вспомогательные вещества:, кроскармеллоза натрия – 5,0 мас.%, стеарат кальция – 1,0 мас.%, желатин – 1,0 мас.%, аэросил – 1 мас. % и краситель Понсо Е 124 – 0,05 мас.%, лактоза – до 99,99 мас.%. Средство для регуляции половой охоты у мелких домашних животных в форме раствора для топикального нанесения содержит диеногест 0,01-1 мас.% и вспомогательные ...

КОМБИНИРОВАННАЯ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ЛЕКАРСТВЕННОЕ СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ КОРОНАВИРУСНОЙ ИНФЕКЦИИ

Изобретение относится к области медицины и химико-фармацевтической промышленности и может быть использовано для лечения и/или профилактики вирусных заболеваний путем блокирования активности 3C-подобных вирусных протеаз. Фармацевтическая композиция для лечения и/или профилактики вирусных заболеваний путем блокирования активности 3C-подобных вирусных протеаз содержит ритонавир или его фармацевтически приемлемую соль или сольват в количестве от 5,0 до 50,0 мас.% от массы фармацевтической композиции и нирматрелвир или его фармацевтически приемлемую соль или сольват в количестве от 10,0 до 60,0 мас.% от массы фармацевтической композиции, наполнители, представляющие собой лактозу или ее моногидрат и целлюлозу микрокристаллическую в количестве от 12,0 до 32,0 мас.% от массы фармацевтической композиции, по меньшей мере один разрыхлитель, представляющий собой кроскармеллозу натрия в количестве от 5,0 до 7,0 мас.% от массы фармацевтической композиции, по меньшей мере одно связующее, выбранное из ...

CПOCOБ ПOЛУЧEHИЯ CPEДCTBA C TPAHCДEPMAЛЬHЫM ПPOHИKHOBEHИEM

CПOCOБ ПPИГOTOBЛEHИЯ AHTИKOKЦИДИЙHOГO COCTABA

Способ получения средства с трансдермальным проникновением

Изобретение относится к химико-фармацевтической промышленности и касается способа получения средства с трансдер- мальным проникновением. Цель изобретения - повышение биодоступности. Сущность изобретения заключается в том, что смешивают активное вещество или про- лекарство, выбранное из группы, включающей метилсалицилат, силициловую кислоту, ибупрофен, амлодипин, глипизид, доксадо- зин, индометацин, пропрамолол, пирекси- кам, пролекарственную форму пироксинама с водно-этанольным растворителем усилителем проникновения,такого как олеиновая кислота (цис-9-OKi адекановая кислота), цис- 11-октадеценовая кислота и 1-додецилаза- цикло-гептан-2-он (азан), полученный гель нагревают и охлаждают. 13 табл.

Makromolekulare Mikropartikel und Verfahren zur ihrer Herstellung

Antimykotische Zusammensetzung zur äusserlichen Anwendung, die im Stratum Corneum retentiv ist

CYCLOPEPTIDE ALS RESORPTIONSFOERDERER BEI APPLIKATION AUF DIE SCHLEIMHAEUTE.

The use of adjuvants or their physilogically tolerable salts for the prodn. of a pharmaceutical preparation contg. a pharmacologically active amount of the adjuvant in a pharmaceutically innocuouscarrier for promoting the absorption or peptides and proteins on application to the mucous membranes is new. Pref. absorption-promoting adjuvant are cyclic peptide cpds. of formula (I). in (I), B = basic amino acid; A/B = acidic or basic amino acid; X = neutral and hydrophilic amino acid; L = lipophitic neutral amino acid; R = H or acyl.

PLASMA- UND REKOMBINATIONSPROTEINFORMULIERUNGEN IN EINEM MILIEU HOHER IONENSTAERKE.

MITTEL ZUR VERBESSERUNG DER PERKUTANEN ABSORPTION, DIESE ENTHALTENDE ARZNEIMITTEL UND METHODE ZU IHRER VERWENDUNG.

Verfahren zur beschleunigten Aufnahme vom Carotinoiden in Serum und Gewebe

The invention relates to a method for accelerated administration of carotenoid mixtures in serum and tissues, characterized in that carotenoid and tocopherol mixtures are administered to the human organism by topical application or orally. The mixtures are particularly suitable for use in the production of sun protection agents.

Stabilisierte pharmazeutische Formulierung, umfassend Wachstumshormon und Histidin

Rutin solubility and dissolution rate improvement - by conversion into solid dispersions in hydroxyalkyl-theophylline or -theobromine derivs. e.g. hydroxyethyl-theophylline

Process for increasing the solubility and dissolution rate of rutin, with the objective of improving absorption from the gastrointestinal tract, comprises the prodn. of solid dispersions (solid solns.) from (a) rutin and (b) readily water-soluble hydroxyalkyl derivs. of theophy-line (1,3-dimethylxanthine) and the obromine (3,7-dimethyl(xanthine). The solid dispersions or solns. have better water solubility and dissolution rate than rutin or its physical mixtures with water-soluble hydroxyalkyl theophylline or theobromine derivs. Pref. hydroxyalkyl-theophlline and theobromine derivs are hydroxyethyltheophylline, duhydroxypropyltheophylline, hydroxypropyltheophylline, hydroxyethyltheobromine, dihydroxypropyltheobromine, hydroxypropyltheobromine, and their mixtures.

GESCHMACKSMASKIERTE ORALE ZUBEREITUNG VON TELITHROMYCIN

PARENTERALE FORMULIERUNGEN MIT EINEM RAPAMYCIN HYDROXYESTER

IL-7 ALS WIRKSTOFF, IL-7-HALTIGE ZUSAMMENSETZUNG, HERSTELLUNGSVERFAHREN UND VERWENDUNGEN

Bukkale Anästhetika.

ARZNEISTOFFHALTIGER KAUGUMMI, DESSEN HERSTELLUNGSVERFAHREN UND SO ERHALTENE TABLETTE

MITTEL ZUR ERHOEHUNG DER TRANSDERMALEN PERMEATION.

Trandermales Therapeutisches System (TTS) mit dem Wirkstoff-Fentanyl

The invention relates to transdermal therapeutic systems with fentanyl or an analogous fentanyl derivative as active ingredient. In order to prevent inadvertent overdosage by uncontrolled release of active ingredient as a result of damage, the active ingerdient is contained in fluid-filled micro-reservoirs in the layer containing the active ingredient. The layer containing the active ingredient can optionally be provided with a membrane.

TOPISCHE HORMONHALTIGE ZUSAMMENSETZUNG MIT SYSTEMISCHER WIRKUNG

Verfahren zur Herstellung therapeutisch wertvoller Saponinzubereitungen

t-PA pro STABILISIERUNG.

TRICYCLIC OXYGENATED COMPOUNDS DERIVED FROM NORBORNANE, AND THEIR USE AS PERFUMING INGREDIENTS

KOSMETISCHE UND DERMATOLOGISCHE ZUBEREITUNGEN, ENTHALTEND ERHÖHTE ELEKTROLYTKONZENTRATIONEN

ANTIBIOTISCHE AZALID-ZUSAMMENSETZUNGEN

PARTIKEL ZUR ORALEN VERABREICHUNG VON PEPTIDEN UND PROTEINEN

ZUSAMMENSETZUNG ZUR IN-VITRO BEFRUCHTUNG

ZUSAMMENSEZTUNGEN UND VERFAHREN ZUR BEHANDLUNG VON HAARAUSFALL UNTER VERWENDUNG VON C16-C20 AROMATISCHEN TETRAHYDRO-PROSTAGLANDINEN

POLYMERE VERABREICHUNGSFORM VON LEUPROLID MIT VERBESSERTER WIRKSAMKEIT

Verfahren zur Stabilisierung von kolloides Wismut enthaltenden Injektionsfluessigkeiten

BENZAMIDFORMULIERUNG MIT HISTON-DEACETYLASE-INHIBITORAKTIVITÄT

Compounds and Compositions for Nucleic Acid Formulation and Delivery

The invention relates to compositions containing compounds of formula I: 2. A lipid nanoparticle composition of comprising a compound of formula I claim 1 , wherein R is linoleyl claim 1 , Ris chloromethyl; Rand Rare methyl; and n is 2.3. A lipid nanoparticle composition of comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) a compound of formula I in ;'} 1,2-dipalmitoyl-sn-glycero-3-phosphocholine,', '1,2-distearoyl-sn-glycero-3-phosphocholine, and', '1,2-dioleoyl-sn-glycero-3-phosphocholine;, 'b) a phospholipid selected from the group consisting ofc) cholesterol; [{'sub': '2000', 'R-3-[(ω-methoxy-poly(ethyleneglycol))carbamoyl]-1,2-dimyristyloxy-propyl-3-amine; and'}, '1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; and, 'd) a pegylated lipid compound selected from the group consisting ofe) a polynucleotide.4. A lipid nanoparticle composition of comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'claim-text': N-(chloromethyl)-2-(2,2-di((9Z,12Z)-octadeca-9,12-dienyl)-1,3-dioxolan-4-yl)-N,N-dimethylethanamonium chloride;', '2-(2,2-di((9Z,12Z)-octadeca-9,12-dienyl)-1,3-dioxolan-4-yl)-N,N,N-trimethyl-ethanamonium iodide; and', '2-(2,2-di((9Z,12Z)-octadeca-9,12-dienyl)-1,3-dioxolan-4-yl)-N-ethyl-N,N-dimethyl-ethanamonium iodide;, 'a) a compound of formula I in selected from the group consisting of'} 1,2-dipalmitoyl-sn-glycero-3-phosphocholine,', '1,2-distearoyl-sn-glycero-3-phosphocholine, and', '1,2-dioleoyl-sn-glycero-3-phosphocholine;, 'b) a phospholipid selected from the group consisting ofc) cholesterol; [{'sub': '2000', 'R-3-[(ω-methoxy-poly(ethyleneglycol))carbamoyl]-1,2-dimyristyloxy-propyl-3-amine; and'}, '1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N4methoxy(polyethylene glycol)-2000]; and, 'd) a pegylated lipid compound selected from the group consisting ofe) a polynucleotide.5. A lipid nanoparticle composition of further comprising claim 4 ,2-(2,2-di((9Z,12Z)-octadeca-9,12-dienyl)-1,3- ...

Use of neoflavonoids for flavor modification

The present invention relates primarily to the use of one or a plurality of neoflavonoids of formula (I) and/or one or a plurality of physiologically acceptable salts of one or a plurality of neoflavonoids of formula (I) for flavor modification, in particular for altering or masking a bitter, astringent and/or metallic flavor impression of a bitter, astringent and/or metallic tasting substance and a corresponding method of flavor modification. The present invention further relates to certain mixtures and certain preparations fit for consumption containing one or a plurality of neoflavonoids of formula (I) and/or one or a plurality of physiologically acceptable salts of one or a plurality of neoflavonoids of formula (I). 2. The use as claimed in claim 1 , wherein one claim 1 , two claim 1 , a plurality of or all of the compounds used in each case are selected from the group consisting of the compounds of formula (I) and physiologically acceptable salts thereof claim 1 , whereinE each denote OH or both E together denote oxygen,R1, in each case independently of the other residue R1, denotes hydrogen or hydroxyl,{'sup': b', 'b, 'R2, independently of the other residues R2, denotes hydrogen, hydroxyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, tert-butoxy or OR, wherein Ris C5 alkenyl,'}{'sub': '2', 'wherein optionally two directly adjacent residues R2 together represent a group OCHO,'}wherein preferably one or a plurality of the residues R1 or R2 denote a hydroxyl group.5. The use of one claim 1 , two or a plurality of different salts of one claim 1 , two or a plurality of different compounds of formula (I) as defined in any one of the preceding claims orof a mixture of one, two or a plurality of different compounds of formula (I) as defined in any one of the preceding claims with one, two or a plurality of different physiologically acceptable salts of one, two or a plurality of different compounds of formula (I) as defined in any one of the preceding ...

Compositions for Delivery of Insoluble Agents

Compositions and methods of making the same for in vivo delivery of lixivaptan to a subject in need thereof are described. The composition includes a substantially water-insoluble pharmacologically active agent (e.g., lixivaptan) and a substantially water-insoluble matrix forming material (e.g., a Vitamin E semi-ester), wherein the pharmacologically active agent is dispersed in said matrix forming material, and wherein the composition delivers said substantially water-insoluble pharmacologically active agent upon exposure to physiological medium. 1. A pharmaceutical composition comprising a single oral dosage form including an oil-free and substantially water-free solid dispersion , the dispersion including a therapeutically effective amount of lixivaptan and 50% or more by weight of a vitamin E semi-ester.2. The composition of claim 1 , wherein the dispersion further includes a surfactant.3. The composition of claim 2 , wherein the surfactant is an alkyl sulfate salt.4. The composition of claim 3 , wherein the alkyl sulfate salt is sodium lauryl sulfate.5. The composition of claim 1 , wherein the dispersion is substantially free of crystalline lixivaptan.6. The composition of claim 1 , wherein the dispersion includes 60% or more by weight of vitamin E semi-ester.7. (canceled)8. (canceled)9. The composition of further including a disintegrant.10. The composition of claim 9 , wherein the disintegrant is a crosslinked poly(vinylpyrrolidone).11. The composition of claim 1 , wherein the dispersion further includes a water soluble polymer.12. The composition of claim 1 , the dispersion further includes a plant protein.13. The composition of claim 12 , wherein the plant protein is zein.14. The composition of further including a surfactant.15. The composition of claim 14 , wherein the surfactant is an alkyl sulfate salt.16. The composition of claim 15 , wherein the alkyl sulfate salt is sodium lauryl sulfate.17. The composition of claim 1 , wherein the vitamin E semi-ester ...

Pharmaceutical Compositions Comprising Paracetamol and Process for Preparing The Same

Disclosed herein are injectable compositions containing high concentration of paracetamol or its pharmaceutically acceptable salts wherein the concentration of paracetamol or its pharmaceutically acceptable salt is >150 mg/ml in a judiciously tailored solvent system comprising glycofurol, ethanol, water or a solvent system comprising glycofurol, ethanol, polyethylene glycol, water. The viscosity of the said injectables is <28 cps. Further disclosed is the process for preparing the said injectables. The injectables can be administered by intramuscular route, intravenous route or as intravenous infusion after diluting in one of the routinely used intravenous fluids, infusion solutions of antibacterial, antifungal and amoebicidal drugs and along with anxiolytics (Midazolam injection) or narcotic analgesics (Fentanyl Citrate injection etc) as they remain stable, clear and transparent at least for 6 hours after dilution. 1. High concentration parenteral compositions of paracetamol or its pharmaceutically acceptable salts delivering full therapeutic dose of 500 mg paracetamol in 2-3 ml in a solvent system wherein the concentration of paracetamol or its pharmaceutically acceptable salts is >150mg/ml and viscosity <28 cps2. High concentration parenteral compositions of paracetamol or its pharmaceutically acceptable salts as claimed in wherein the concentration of paracetamol is 166 mg to 250 mg/ ml.3. High concentration parenteral compositions of paracetamol or its pharmaceutically acceptable salts as claimed in any of the claim 1 , wherein the solvent system comprises glycofurol claim 1 , ethanol and water.4. High concentration parenteral compositions of paracetamol or its pharmaceutically acceptable salts as claimed in any of the claim 1 , wherein the solvent system comprises glycofurol claim 1 , ethanol polyethylene glycol and water.54. High concentration parenteral compositions of paracetamol or its pharmaceutically acceptable salts as claimed in - wherein the viscosity ...

CATIONIC LIPID

The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) 2. The cationic lipid according to claim 1 , wherein Land Lare —O— or —O—CO— claim 1 , and Rand Rare dodecyl claim 1 , tetradecyl claim 1 , hexadecyl claim 1 , octadecyl claim 1 , icosyl claim 1 , docosyl claim 1 , tetracosyl claim 1 , (Z)-tetradec-9-enyl claim 1 , (Z)-hexadec-9-enyl claim 1 , (Z)-octadec-6-enyl claim 1 , (Z)-octadec-9-enyl claim 1 , (E)-octadec-9-enyl claim 1 , (Z)-octadec-11-enyl claim 1 , (9Z claim 1 ,12Z)-octadec-9 claim 1 ,12-dienyl claim 1 , (9Z claim 1 ,12Z claim 1 ,15Z)-octadec-9 claim 1 ,12 claim 1 ,15-trienyl claim 1 , (Z)-icos-11-enyl claim 1 , (11Z claim 1 ,14Z)-icos-11 claim 1 ,14-dienyl claim 1 , 3 claim 1 ,7 claim 1 ,11-trimethyldodeca-2 claim 1 ,6 claim 1 ,10-trienyl or 3 claim 1 ,7 claim 1 ,11 claim 1 ,15-tetramethylhexadec-2-enyl.3. The cationic lipid according to claim 1 , wherein Land Lare —CO—O— claim 1 , and Rand Rare tridecyl claim 1 , pentadecyl claim 1 , heptadecyl claim 1 , nonadecyl claim 1 , heneicosyl claim 1 , tricosyl claim 1 , (Z)-tridec-8-enyl claim 1 , (Z)-pentadec-8-enyl claim 1 , (Z)-heptadec-5-enyl claim 1 , (Z)-heptadec-8-enyl claim 1 , (E)-heptadec-8-enyl claim 1 , (Z)-heptadec-10-enyl claim 1 , (8Z claim 1 ,11Z)-heptadec-8 claim 1 ,11-dienyl claim 1 , (8Z claim 1 ,11Z claim 1 ,14Z)-octadec-8 claim 1 ,11 claim 1 ,14-trienyl claim 1 , (Z)-nonadec-10-enyl claim 1 , (10Z claim 1 ,13Z)-nonadec-10 claim 1 ,13-dienyl claim 1 , (11Z claim 1 ,14Z)-icos-11 claim 1 ,14-dienyl claim 1 , 2 claim 1 ,6 claim 1 ,10-trimethylundec-1 claim 1 ,5 claim 1 ,9-trienyl or 2 claim 1 ,6 claim 1 ,10 claim 1 ,14-tetramethylpentadec-1-enyl.43. The cationic lipid according to any one of to claims 1 , wherein a and b are both 0 or 1.5. The cationic lipid according to any one of or claims 1 , wherein Lis a single bond claims 1 , Ris a hydrogen atom claims 1 , methyl claims 1 , pyrrolidin-3-yl claims 1 , ...

PHARMACEUTICAL FORMULATIONS

A stable pharmaceutical formulation is provided that comprises a biologically active protein and an excipient selected from carnitine, creatine or creatinine. 120-. (canceled)21. A liquid pharmaceutical formulation comprising in acetate buffer a therapeutic protein at a concentration of at least 70 mg/ml and an excipient consisting of creatine , creatinine , carnitine or mixtures thereof.22. The liquid pharmaceutical formulation of wherein the excipient is creatine claim 21 , creatinine or a mixture thereof.23. A liquid pharmaceutical formulation comprising a therapeutic protein at a concentration of at least 70 mg/ml and an excipient consisting of creatine claim 21 , creatinine or mixtures thereof.24. The liquid pharmaceutical formulation of claim 21 , or wherein the concentration of creatine/creatinine is from about 0.002 mM to about 750 mM.25. The liquid pharmaceutical formulation of wherein the concentration of creatine/creatinine is from about 0.01 mM to about 50 mM.26. The liquid pharmaceutical formulation of wherein the excipient is carnitine.27. The liquid pharmaceutical formulation of wherein the concentration of carnitine is between about 1 mM and about 3 M.28. The liquid pharmaceutical formulation of wherein the concentration of carnitine is between about 5 mM and about 300 mM.29. The liquid pharmaceutical formulation of claim 27 , or claim 27 , wherein the pH of the formulation is about 4.0 to about 6.0.30. The liquid pharmaceutical formulation of wherein the pH is about 5.0 to about 5.5.31. The liquid pharmaceutical formulation of claim 29 , or wherein the therapeutic protein is an antibody.32. The liquid pharmaceutical formulation of wherein the therapeutic protein is an antibody. This application claims the benefit of prior U.S. provisional application No. 60/975,780 filed Sep. 27, 2007, hereby incorporated by reference in its entirety.The invention relates to pharmaceutical formulations of proteins that contain creatine/creatinine or carnitine. ...

TARGETED DELIVERY USING TISSUE-SPECIFIC PEPTIDOMIMETIC LIGANDS

Compositions and methods for tissue-specific targeted delivery of therapeutic agents through the use of tissue-specific peptidomimetic ligands are disclosed herein. The ligand comprises a composition of formula A-scaffold-A′ and one or more hydrophobic anchors covalently linked to the scaffold. The A and A′ compounds linked to the scaffold comprise monovalent peptidomimetic compounds wherein each monovalent peptidomimetic compound is selected from the group consisting of fragments IKs, GKs, IDs, GSs, GTs, VSs, TKs, KTs, ARs, KIs, KEs, AEs, GRs, YSs, IRs, and morpholino. 2. The targeted ligand of claim 1 , wherein A and A′ are the same.3. The targeted ligand of claim 1 , wherein the scaffold comprises a reactive dichlorotriazine group.4. The targeted ligand of claim 1 , wherein one or more of the hydrophobic anchors comprise a hydrocarbon moiety.5. The targeted ligand of claim 4 , wherein one or more of the hydrophobic moieties comprise an octadecyl group.6. The targeted ligand of claim 1 , further comprising one or more linkers functionally interposed between the scaffold and the hydrophobic anchors.7. The targeted ligand of claim 6 , wherein one or more of the linkers are specifically cleavable.8. The targeted ligand of claim 1 , wherein the tissue is a cancerous cell claim 1 , tissue or endothelium selected from pancreatic cancer claim 1 , breast cancer claim 1 , non-small cell lung carcinoma (NSCLC) claim 1 , pancreatic cancer vascular endothelium or NSCLC cancer vascular endothelium.10. The method of claim 9 , wherein the selected monovalent peptidomimetic compounds are identical.11. The method of claim 9 , wherein the scaffold comprises a reactive dichlorotriazine group.12. The method of claim 9 , wherein one or more of the hydrophobic anchors comprise a hydrocarbon moiety.13. The method of claim 12 , wherein one or more of the hydrophobic moieties comprise an octadecyl group.14. The method of claim 9 , comprising the additional step of functionally interposing ...

COMPOSITION, METHOD, AND KIT FOR ALPHA-1 PROTEINASE INHIBITOR

The present invention provides compositions comprising API and at least one amino acid, in particular a liquid API formulation comprising amino acids, and methods and kits related thereto. These amino acids when incorporated into the API composition afford stability to the API formulation. 1. A composition comprising:(a) an alpha 1-proteinase inhibitor (API); and(b) at least one amino acid.2. The composition of claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount sufficient such that the API retains at least 50% of its activity when the composition is exposed to a temperature for a period of time.3. The composition of claim 2 , wherein the temperature is about 5° C. to about 40° C.4. The composition of claim 2 , wherein the time is at least about 6 months.5. The composition of claim 1 , wherein the at least one amino acid is a neutral or a hydrophilic amino acid.6. The composition of claim 1 , wherein the at least one amino acid is selected from the group consisting of alanine claim 1 , threonine claim 1 , serine claim 1 , hydroxyproline claim 1 , glycine claim 1 , proline claim 1 , leucine claim 1 , and histidine.7. The composition of claim 1 , wherein the amino acid is alanine.8. The composition of claim 1 , wherein the at least one amino acid is present in the composition in a total amino acid amount of about 0.01 M to about 3 M.9. The composition of further comprising one or more excipients.10. The composition of claim 1 , wherein the one or more excipients is selected from the group consisting of: sucrose claim 1 , mannitol claim 1 , glycerol claim 1 , sorbitol claim 1 , dextran claim 1 , trehalose claim 1 , hydroxyethyl starch (HES) claim 1 , and 1 claim 1 ,2-propanediol.11. The composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.12. The composition of claim 1 , wherein the composition is suitable for intravenous administration to a subject.13. The ...

COMPOSITIONS AND METHODS FOR IMPROVED ORGAN TRANSPLANT PRESERVATION AND ACCEPTANCE

The invention provides a novel aqueous composition for the storage and preservation of transplants, such as organ or tissue allografts. The composition comprises the compound N-octanoyl dopamine in solubilised form. The composition may also be administered as a pre-treatment of transplant donors. Moreover, it may be used in transplant recipients, optionally in combination with immunosuppressants. 1. A pharmaceutical composition comprising:(a) an effective amount of N-octanoyl dopamine;(b) a physiologically acceptable aqueous solvent; and(c) a physiologically acceptable amphiphilic excipient;wherein the N-octanoyl dopamine is present in a molecularly or colloidally dispersed state.2. The composition of in the form of a micellar solution or microemulsion.3. The composition of claim 2 , wherein the amphiphilic excipient is a nonionic surfactant.4. The composition of claim 3 , wherein the nonionic surfactant is a polysorbate.5. The composition of in the form of a liposomal dispersion.6. The composition of claim 5 , wherein the amphiphilic excipient is a vesicle-forming phospholipid.7. The composition of claim 1 , having a pH of not higher than about 7.8. The composition of claim 1 , further comprising an acid and/or an antioxidant.9. Use of the composition of as a medicine or as a preparation for organ or tissue preservation.10. The use according to claim 9 , wherein the composition is administered to an organ or tissue donor.11. The use according to claim 9 , wherein the composition is administered to an organ or tissue transplant recipient.12. The use according to claim 11 , wherein the composition is administered parenterally.13. A non-aqueous pharmaceutical composition comprising an effective amount of N-octanoyl dopamine and a physiologically acceptable amphiphilic excipient claim 1 , being adapted to yield a composition according to upon mixing with a physiologically acceptable aqueous solvent.14. Use of N-octanoyl dopamine in the prevention of organ or tissue ...

Pharmaceutical Formulations Containing Lipoic Acid Derivatives

Pharmaceutical formulations containing lipoic acid derivatives and ion pairs thereof are described. The pharmaceutical formulations are useful in the treatment of medical disorders, such as cancer. 152-. (canceled)54. The method of claim 53 , wherein the at least one ion pairing agent is a tertiary amine.55. The method of claim 53 , wherein the at least one ion pairing agent is selected from the group consisting of triethanolamine claim 53 , polyethyleneimine claim 53 , diethanolamine claim 53 , monoethanolamine claim 53 , mefenamic acid claim 53 , tromethamine claim 53 , and combinations thereof.56. The method of claim 53 , wherein the at least one ion pairing agent is triethanolamine.57. The method of claim 53 , wherein the at least one ion pairing agent and the at least one compound of Formula I is present in a ratio ranging from 20:1 to 1:20.58. The method of claim 56 , wherein the at least one ion pairing agent and the at least one compound of Formula I is present in a ratio ranging from 20:1 to 1:20.59. The method of claim 53 , wherein the at least one ion pairing agent and the at least one compound of Formula I is present in a ratio ranging from 10:1 to 1:10.60. The method of claim 56 , wherein the at least one ion pairing agent and the at least one compound of Formula I is present in a ratio ranging from 10:1 to 1:10.61. The method of claim 56 , wherein the at least one ion pairing agent and the at least one compound of Formula I is present in a ratio of about 8:1.62. The method of claim 53 , wherein the ion pair is present in the pharmaceutical formulation in an amount to provide from about 0.001 mg/mto about 10 g/mof the compound of Formula I upon administration of the pharmaceutical formulation to the patient.63. The method of claim 53 , wherein the diluent is selected from the group consisting of saline claim 53 , a sugar solution claim 53 , an alcohol claim 53 , dimethylformamide claim 53 , dimethylsulfoxide claim 53 , dimethylacetamide claim 53 , and ...

Stabilized Formulations Containing Anti-PCSK9 Antibodies

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human proprotein convertase subtilisin/kexin type 9 (PCSK9). The formulations may contain, in addition to an anti-PCSK9 antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months. 1. A liquid pharmaceutical formulation comprising:(a) an antibody, which comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO:2, an HCDR2 of SEQ ID NO:3, an HCDR3 of SEQ ID NO:4, a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 6, an LCDR2 of SEQ ID NO:7, and an LCDR3 of SEQ ID NO:8, and which binds specifically to human proprotein convertase subtilisin/kexin type 9 (human PCSK9);(b) histidine;(c) polysorbate 20; and(d) sucrose, at pH of 6.0±0.32. The pharmaceutical formulation of claim 1 , wherein the antibody comprises a heavy chain variable domain (HCVD) of SEQ ID NO:1 and a light chain variable domain (LCVD) of SEQ ID NO:5.3. The pharmaceutical formulation of claim 1 , wherein(a) over 90% of the antibodies have a molecular weight of 155 kDa±1 kDa;(b) over 50% of the antibodies have an isoelectric point of about 8.5; and(c) from 75% to 90% of the antibodies are fucosylated.4. The pharmaceutical formulation of claim 1 , wherein the antibody concentration is from 50 mg/mL±7.5 mg/mL to 175 mg/mL±26.25 mg/mL.5. The pharmaceutical formulation of claim 1 , wherein the histidine concentration is 10 mM±1.5 mM.6. The pharmaceutical formulation of claim 1 , wherein the polysorbate 20 concentration is from 0.01% w/v±0.0015% to 0.2% w/v±0.03%.7. The pharmaceutical formulation of claim 1 , wherein the sucrose concentration is from 5%±0.75% to 12%±1.8%.8. The pharmaceutical formulation of claim 2 , wherein the antibody concentration is 175 mg/mL±26.25 mg/mL claim 2 , ...

New Particles of Tetracyclines and Protecting Agent

Particles containing a tetracycline or one of its pharmaceutically acceptable salts and an antioxidant, formulations containing the same and their use in the treatment of infectious diseases are described. Methods of encapsulation of a tetracycline or one of its pharmaceutically acceptable salts and an antioxidant are also disclosed. 1. A particle comprising a tetracycline and an antioxidant characterized in that the tetracycline and the antioxidant are encapsulated in a polymeric material , wherein , in use , the tetracycline and the antioxidant are delivered simultaneously in precise and fixed proportions.2. A particle according to characterized in that the tetracycline is doxycycline claim 1 , minocycline claim 1 , tigecycline or tetracycline or one of their pharmaceutically acceptable salts.3. A particle according to wherein the tetracycline is doxycycline or minocycline or a pharmaceutically acceptable salt thereof.4. A particle according to claim 1 , characterized in that the antioxidant is ascorbic acid (vitamin C); a tocopherol or a tocotrienol such as vitamin E; a carotene; a flavonoid such as quercetin or a mixture of one or more of the above.5. A particle according to claim 1 , wherein the antioxidant is ascorbic acid (vitamin C) or quercetin.6. A particle according to claim 1 , characterized in that the polymer is a polysaccharide such as a starch claim 1 , a maltodextrine or gum arabic claim 1 , a lipid such as stearic acid or a mono or diglyceride claim 1 , a protein such as gelatin claim 1 , casein or soy claim 1 , a polymer such hydroxypropylmethyl cellulose or its derivatives claim 1 , polymethacrylate or its derivatives claim 1 , polyvinylpyrrolidone or its derivatives claim 1 , polyethyleneglycol or its derivatives; or a mixture of one or more of the above.7. A particle according to wherein the polymer is a hydropropylmethyl cellulose derivative such as hydropropylmethyl cellulose acetate succinate.8. A particle according to claim 1 , ...

Surgical Adjuvant Composition and Associated Methods of Use

Disclosed herein are surgical adjuvant compositions for ameliorating tissue and cellular necrosis and/or apoptosis. In addition, surgical methods are described which include the use of the adjuvant of the composition to reduce tissue and cellular necrosis and/or apoptosis. 1. A method for ameliorating tissue or cellular damage in a patient due to an invasive procedure comprising administering to the patient an effective amount of an adjuvant comprising isotonic phosphate buffered saline a high molecular weight dextran , ascorbate , transferrin , and poloxamer surfactant P188 before , during , and/or after a surgical procedure , wherein the composition ameliorates tissue or cellular damage.2. The method of claim 1 , wherein the adjuvant further comprises an anesthetic.3. The method of claim 1 , wherein the adjuvant further comprises epinephrine.4. The method of claim 1 , wherein the procedure is an arthroscopic surgical procedure.5. The method of claim 1 , wherein the procedure is a minimally invasive endoscopic surgical procedure.6. The method of claim 1 , wherein the composition is administered prior to the procedure.7. The method of claim 1 , wherein the composition is administered during the procedure.8. The method of claim 1 , wherein the composition is administered after the procedure.9. The method of claim 1 , wherein the composition is administered at multiple times selected from the group consisting of before the procedure claim 1 , during the procedure claim 1 , after the procedure claim 1 , and combinations thereof.10. The method of claim 1 , wherein the composition is administered continuously during a portion of or throughout the entire procedure.11. The method of claim 10 , wherein the continuously for at least one time interval selected from the group consisting of: a time point prior to the procedure until the procedure is complete claim 10 , a time point during the procedure until a time point after the procedure or claim 10 , a time point prior to ...

COMPOSITIONS AND METHODS THEREOF FOR ORAL ADMINISTRATION OF DRUGS

The present invention provides therapeutic compositions including a therapeutic agent in a non-aqueous matrix having an absorption enhancer and therapeutic agent, as well as methods for administering such compositions and providing enhanced oral bioavailability. 1. A composition for delivery of a therapeutic agent , the composition comprising:a) a non-aqueous matrix comprising an alkylsaccharide absorption enhancer; andb) at least one therapeutic agent soluble in the non-aqueous matrix.2. The composition of claim 1 , wherein the alkylsaccharide has an alkyl chain including between 10 to 16 carbons.3. The composition of claim 1 , wherein the alkylsaccharide is linked by glycosidic linkage to a maltose.4. The composition of claim 1 , wherein the alkylsaccharide is selected from the group consisting of: dodecyl maltoside claim 1 , tridecyl maltoside claim 1 , tetradecyl maltoside claim 1 , sucrose dodecanoate claim 1 , or sucrose cocoate.5. The composition of claim 1 , wherein the alkylsaccharide is a β-anomer.6. The composition of claim 5 , wherein the alkylsaccharide is tetradecyl-β-D-maltoside or dodecyl-β-D-maltoside.7. The composition of claim 1 , wherein the alkylsaccharide is present at a concentration between about 0.01% and 20% (w/v).8. The composition of claim 7 , wherein the alkylsaccharide is present at a concentration between about 0.01% and 10% (w/v) claim 7 , about 0.05% and 20% (w/v) claim 7 , about 0.1% and 10% (w/v) claim 7 , or about 0.1% and 5% (w/v).9. The composition of claim 1 , wherein the non-aqueous matrix comprises a non-aqueous solvent.10. The composition of claim 9 , wherein the non-aqueous matrix comprises a tocopherol claim 9 , a tocotrienol claim 9 , vitamin E claim 9 , vitamin E TPGS claim 9 , pharmaceutically acceptable oil claim 9 , an alcohol claim 9 , a glycol claim 9 , or combination thereof.11. The composition of claim 10 , wherein the alcohol is ethanol claim 10 , propyl alcohol claim 10 , butyl alcohol claim 10 , pentanol claim ...

COMPOSITION FOR TREATING CANCER BY THE CONTROLLED RELEASE OF AN ACTIVE SUBSTANCE

The invention relates to a novel composition for treating cancer, which allows the active substance to be released in the direct presence of the cells which are to be treated with the active substance. Said composition comprises an active substance carrier which is in the form of a liposome comprising a disulfide group, a cytostatic agent being contained in the active substance carrier. The invention also relates to a method for the locally defined release of a cytostatic agent. 110.-. (canceled)12. The composition as claimed in claim 11 , characterized in that the chemical group X comprises at least eight carbon atoms.13. The composition as claimed in claim 11 , characterized in that the chemical group X additionally comprises at least one carboxylic acid ester group.14. The composition as claimed in claim 11 , characterized in that the at least one amine group or ammonium group of the chemical group X of the substances according to formula (I) in the active ingredient carrier is a quaternary ammonium group.17. The composition as claimed in claim 11 , characterized in that it comprises claim 11 , in the active ingredient carrier claim 11 , also phospholipids.18. The composition as claimed in claim 11 , characterized in that the cytostatic agent is selected from the group consisting of doxorubicin claim 11 , pemetrexed claim 11 , melphalan claim 11 , amsacrin claim 11 , asparaginase claim 11 , bevacizumab claim 11 , bleomycin claim 11 , busulfan claim 11 , irinotecan claim 11 , carmustine claim 11 , daunorubicin claim 11 , cisplatin claim 11 , dactinomycin claim 11 , gancyclovir claim 11 , cytarabine claim 11 , dacarbazine claim 11 , cytarabine claim 11 , vindesine claim 11 , oxaliplatin claim 11 , cyclophosphamide claim 11 , cetuximab claim 11 , etoposide claim 11 , epirubicin claim 11 , fludarabine claim 11 , 5-fluorouracil claim 11 , gemcitabine claim 11 , trastuzumab claim 11 , ifosfamide claim 11 , topotecan claim 11 , cladribine claim 11 , alemtuzumab claim 11 ...

NOVEL LIPID DIPEPTIDE AND GEL

There is provided a gelator that is capable of forming a gel by an extremely small amount of addition in a wide pH range from acidic to alkaline regions, and a gel having high environmental compatibility, biocompatibility, and biodegradability. A gelator comprising: a lipid peptide of Formula (1) wherein Ris a Caliphatic group, Ris a hydrogen atom or a Calkyl group optionally having a Cbranched chain, Ris a —(CH)—X group, n is a number from 1 to 4, and X is an amino group, a guanidino group, a —CONHgroup, or a 5-membered ring optionally having 1 to 3 nitrogen atoms, a 6-membered ring optionally having 1 to 3 nitrogen atoms, or a fused heterocycle including a 5-membered ring and a 6-membered ring that optionally has 1 to 3 nitrogen atoms); or a pharmaceutically usable salt of the lipid peptide. 2. A gel comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the lipid peptide or the pharmaceutically usable salt of the lipid peptide as claimed in ; and a solvent.'}3. The gel according to claim 2 , wherein the solvent is water claim 2 , an alcohol claim 2 , an aqueous solution claim 2 , an alcoholic solution claim 2 , a hydrophilic organic solution claim 2 , a higher alcohol claim 2 , a fatty acid claim 2 , higher fatty acid esters claim 2 , a glyceride claim 2 , a hydrophobic organic solution claim 2 , or a miscible mixed solvent thereof.4. The gel according to claim 3 , wherein the solvent is water claim 3 , an alcohol claim 3 , an aqueous solution claim 3 , an alcoholic solution claim 3 , a hydrophilic organic solution claim 3 , a higher alcohol claim 3 , a hydrophobic organic solution claim 3 , or a miscible mixed solvent thereof.5. The gel according to claim 3 , wherein the alcoholic solution is a mixed solution of at least one alcohol selected from a group consisting of methanol claim 3 , ethanol claim 3 , 2-propanol claim 3 , and i-butanol and water.6. The gel according to claim 3 , wherein the hydrophilic organic solution is a mixed solution of at least ...

Preparation Comprising Insulin, Nicotinamide and an Amino Acid

Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid. 1. An insulin preparation comprising:an insulin compound;a nicotinic compound;arginine; anda buffer.2. The insulin preparation of claim 1 , wherein the buffer is a phosphate buffer.3. The insulin preparation of claim 2 , wherein the insulin compound comprises B28Asp human insulin.4. The insulin preparation of claim 1 , wherein the insulin compound is selected from the group consisting of B28Asp human insulin claim 1 , B28LysB29Pro human insulin claim 1 , and B3LysB29Glu human insulin.5. The insulin preparation of claim 4 , wherein the buffer is a phosphate buffer.6. An insulin preparation comprising:B28Asp human insulin;nicotinamide;zinc;arginine; anda phosphate buffer.7. The insulin preparation of claim 6 , wherein the nicotinamide is present at a concentration ranging from about 1 mM to about 300 mM.8. The insulin preparation of claim 7 , wherein less than about 4 zinc ions are present per six B28Asp human insulin molecules.9. The insulin preparation of claim 8 , wherein the arginine is present in a concentration from about 10 mM to about 60 mM.10. The insulin preparation of claim 9 , wherein the arginine is present in a concentration ranging from about 10 mM to about 40 mM.11. The insulin preparation of claim 10 , wherein the preparation has a pH of about 7.4 or less.12. The insulin preparation of claim 11 , wherein the preparation has a pH of about 7.1.13. The insulin preparation of wherein the nicotinamide is present at a concentration ranging from about 80 mM to about 260 mM.14. The insulin preparation of claim 13 , wherein the arginine is present in a concentration ranging from about 10 mM to about 40 mM.15. The insulin preparation of claim 14 , wherein the preparation has a pH of about 7.4 or less.16. The insulin preparation of claim 15 , wherein less than about 4 zinc ions are present per six B28Asp human insulin ...

PHARMACEUTICAL COMPOSITION

A pharmaceutical composition comprising: (A) an androgen; (B) a cyclic enhancer of the type used in the compositions and methods claimed by U.S. Pat. No. 5,023,252 to Hsieh; and (C) a thickening agent; including, for example, a composition in which the cyclic enhancer is a macrocyclic ester or a macrocyclic ketone; the use of the composition to treat a condition, for example, male hypogonadism, in a patient by applying the composition to the membrane of the patient; and a method for making the composition. 2. The method of further comprising a crystallization inhibitor that is capable of inhibiting crystallization of testosterone.3. The method of wherein the lower alkanol ranges from about 50 wt. % to about 75 wt. %.4. The method of wherein the lower alkanol ranges from about 60 wt. % to about 75 wt. %.5. The method of wherein the lower alkanol comprises ethanol.6. The method of wherein the lower alkanol comprises isopropanol.7. The method of further comprising propylene glycol.8. The method of further comprising glycerin.9. The method of wherein the enhancer is selected from the group of consisting of 3-methylcyclopentadecanone claim 1 , 9-cycloheptadecen-1-one claim 1 , cyclohexadecanone claim 1 , cyclopentadecanone claim 1 , oxacyclohexadecan-2-one and mixtures thereof.10. The method of wherein the macrocyclic enhancer is 3-methylcyclopentadecanone.11. The method of wherein the macrocyclic enhancer is 9-cycloheptadecen-1-one.12. The method of wherein the macrocyclic enhancer is cyclohexadecanone.13. The method of wherein the macrocyclic enhancer is cyclopentadecanone.14. The method of wherein the macrocyclic enhancer is oxacyclohexadecan-2-one.15. The method of wherein said composition is maintained on said skin for a period of time sufficient for delivery of the testosterone to the body of the male and is applied to the skin in the form of a unit dose which contains about 1 to about 300 mg of testosterone and such that claim 1 , following a single application of ...

Controlled Delivery System

The present invention relates to novel anesthetic compositions containing a non-polymeric carrier material and an anesthetic, where the compositions are suitable for providing a sustained local anesthesia without an initial burst and having a duration for about 24 hours or longer. Certain compositions are also provided that include a first anesthetic and a second anesthetic. In such compositions, the second anesthetic is a solvent for the first anesthetic and provides an initial anesthetic effect upon administration to a subject. The non-polymeric carrier may optionally be a high viscosity liquid carrier material such as a suitable sugar ester. The compositions can further include one or more additional ingredients including active and inactive materials. Methods of using the compositions of the invention to produce a sustained anesthetic effect at a site in a subject are also provided. 1. A composition comprising an anesthetic and a pharmaceutically acceptable non-polymeric carrier , wherein the non-polymeric carrier controls release of the anesthetic to provide an anesthetic effect characterized by sustained local anesthesia after administration to a subject without an initial burst and having a duration of at least about 24 hours after administration.2. The composition of claim 1 , wherein the non-polymeric carrier is sufficient to provide either a first order controlled-release profile of the anesthetic claim 1 , or a pseudo-zero order release profile of said anesthetic.3. The composition of claim 1 , wherein the anesthetic provides sustained local anesthesia for at least about 36 to 48 hours after administration to a subject.4. The composition of claim 3 , wherein the anesthetic provides sustained local anesthesia for at least about 48 to 72 hours after administration to a subject.5. The composition of claim 1 , wherein the anesthetic is a local anesthetic.6. The composition of claim 5 , wherein the anesthetic is an amide- or ester-type local anesthetic.7. The ...

SELF MICRO-EMULSIFYING DRUG DELIVERY SYSTEM WITH INCREASED BIOAVAILABILITY

The invention provides a formulation comprising (a) a drug that is poorly water-soluble, (b) at least one surfactant, and (c) at least one polar lipid, wherein the formulation is substantially free of a polar solvent, as well as methods of preparing the formulation and methods of increasing the bioavailability of a drug using the formulation. 2. The formulation of claim 1 , wherein the at least one surfactant is selected from the group consisting of nonionic claim 1 , cationic claim 1 , and anionic surfactants.3. The formulation of claim 1 , wherein the at least one polar lipid is selected from the group consisting of mono- and di-glycerides claim 1 , esters of fatty acids claim 1 , and polysilane esthers.4. The formulation of claim 1 , wherein formulation contains 10-90% surfactants.5. The formulation of claim 1 , wherein the formulation contains 10-90% polar lipids.6. The formulation of claim 5 , wherein the formulation contains two polar lipids.7. The formulation of claim 6 , wherein the at least one surfactant is a polysorbate and the two polar lipids are propylene glycol monocaprylate and propylene glycol dicaprate.8. The formulation of comprising 10-30% (w/w) propylene glycol monocaprylate claim 7 , 20-60% (w/w) propylene glycol dicaprate claim 7 , and 10-30% (w/w) polysorbate.9. The formulation of comprising 15-20% (w/w) propylene glycol monocaprylate claim 7 , 35-50% (w/w) propylene glycol dicaprate claim 7 , and 15-20% (w/w) polysorbate.10. The formulation of comprising 15-17% (w/w) propylene glycol monocaprylate claim 7 , 38-42% (w/w) propylene glycol dicaprate claim 7 , and 15-17% (w/w) polysorbate.11. The formulation of claim 7 , wherein the polysorbate is selected from the group consisting of polysorbate 20 claim 7 , polysorbate 40 claim 7 , polysorbate 60 claim 7 , polysorbate 65 claim 7 , polysorbate 80 claim 7 , and mixtures thereof.12. The formulation of claim 8 , wherein the polysorbate is selected from the group consisting of polysorbate 20 claim ...

CAROTENOID-CONTAINING COMPOSITION AND METHOD FOR PRODUCING THE SAME

Provided are a carotenoid-containing composition containing at least one carotenoid; at least one selected from the group consisting of ascorbic acid, derivatives thereof and salts of the acid and the derivatives; and an emulsifier, the at least one selected from the group consisting of ascorbic acid, derivatives thereof and salts of the acid and the derivatives being contained in an amount, in terms of a number of moles of ascorbic acid, in a range of from 30 times to 190 times a total number of moles of the at least one carotenoid, and the composition having a pH in the range of from 6.5 to 9.0; and a method for preparing the composition. 1. A carotenoid-containing composition comprising:at least one carotenoid;at least one selected from the group consisting of ascorbic acid, derivatives thereof and salts of the acid and the derivatives; andan emulsifier,the at least one selected from the group consisting of ascorbic acid, derivatives thereof and salts of the acid and the derivatives being contained in an amount, in terms of a number of moles of ascorbic acid, in a range of from 30 times to 190 times a total number of moles of the at least one carotenoid, and the composition having a pH in the range of from 6.5 to 9.0.2. The carotenoid-containing composition according to claim 1 , wherein the at least one carotenoid are at least one selected from lycopene or fucoxanthin.3. The carotenoid-containing composition according to claim 1 , wherein the at least one selected from ascorbic acid claim 1 , derivatives thereof and salts of the acid and the derivatives claim 1 , is at least one selected from L-ascorbic acid claim 1 , sodium L-ascorbate claim 1 , or calcium L-ascorbate.4. The carotenoid-containing composition according to claim 1 , further comprising at least one selected from the group consisting of tocopherols and aromatic carboxylic acids claim 1 , cinnamic acids and ellagic acids as phenolic antioxidizing agents.5. The carotenoid-containing composition ...

CURED OIL-HYDROGEL BIOMATERIAL COMPOSITIONS FOR CONTROLLED DRUG DELIVERY

The present invention is generally directed to materials, gels, coatings and films prepared using a biomaterial (e.g., a fatty acid-based material comprising a network of cross-linked fatty acids) and a fixating material, layer or film (e.g., a fixating material comprising Na—CMC). The materials, gels, coatings and films disclosed herein can be used to facilitate the delivery of one or more therapeutic agents to a targeted tissue and a desired rate of release. 1. A coating material for a medical device , comprising:a biomaterial, wherein the biomaterial comprises fatty acids cross-linked to each other; anda fixating material, wherein the fixating material is disposed on an outer surface of the biomaterial relative to the medical device;wherein at least one of the biomaterial and the fixating material comprises one or more therapeutic agents;wherein the coating material effects controlled delivery in a patient of the one or more therapeutic agents from the coating material; andwherein the controlled delivery is at least partially characterized by total and relative amounts of the biomaterial and the fixating material in the coating material.2. The coating material of claim 1 , wherein the biomaterial comprises the one or more therapeutic agents and wherein the rate of release of the one or more therapeutic agents from the fixating material is controlled at least in part by the degree of protonation of the fixating material caused by a relative amount of fatty acids in the biomaterial.3. The coating material of claim 1 , wherein the biomaterial comprises a first therapeutic agent claim 1 , wherein the fixating material comprises a second therapeutic agent claim 1 , wherein the biomaterial releases the first therapeutic agent at a first rate claim 1 , and wherein the fixating material releases the second therapeutic agent at a second rate.4. The coating material of claim 3 , wherein the second rate is influenced by a composition of the biomaterial.5. The coating ...

PARTICULATE CONSTRUCTS FOR RELEASE OF ACTIVE AGENTS

Particulate constructs stabilized by amphiphilic copolymers and comprising at least one active coupled to a hydrophobic moiety provide sustained release of the active in both in vitro and in vivo environments. 1. A composition comprising particles which would result from forming said particle from a mixture ofa) an amphiphilic stabilizer, {'br': None, 'sub': 'n', '(active-linker)-hydrophobic moiety\u2003\u2003(1)'}, 'b) a conjugate of the formula'}wherein n is an integer of 1-100; andwherein “active” refers to at least a first therapeutic agent;“linker” is a covalent bond, a divalent residue of an organic molecule or a chelator which comprises a bond that is selectively cleavable to control release of said active; and“hydrophobic moiety” refers to the residue of an organic molecule that is insoluble in aqueous solution; andc) a second therapeutic agent different from the first therapeutic agent.2. The composition of claim 1 , wherein n is an integer of 2-100.3. The composition of claim 1 , wherein the hydrophobic moiety is vitamin E claim 1 , vitamin A or vitamin K claim 1 , or a retinol; orwherein the hydrophobic moiety is polycaprolactone, polylactic acid, polystyrene, polybutadiene, polycaproic acid, polymethylbenzylate, poly(D,L-lactide), poly(D,L-lactide-co-glycolide), poly(glycolide), poly(hydroxybutyrate), poly(alkylcarbonate) poly(orthoesters), polyesters, poly(hydroxyvaleric acid), or copolymers thereof.4. The composition of claim 1 , wherein the amphiphilic stabilizer is methoxypolyethylene glycol (mPEG)-polycaprolactone (PCL) claim 1 , mPEG-polystyrene claim 1 , mPEG-polybutadiene claim 1 , mPEG-polylactate claim 1 , block copolymers of polyethylene oxide claim 1 , and polypropylene oxide claim 1 , or block copolymers of polyethylene oxide and polybutylene oxide.5. The composition of claim 1 , wherein the linker is the residue of a divalent organic molecule claim 1 , and said residue of a divalent organic molecule comprises a site for hydrolytic cleavage ...

DRY POWDER INHALER AND SYSTEM FOR DRUG DELIVERY

A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable. 1. Fumaryl diketopiperazine (FDKP) microparticles comprising a trans-FDKP isomer content of about 45% to about 63%.2. The FDKP microparticles of having a trans-FDKP isomer content of about 53% to about 63%.3. The FDKP microparticles of having a trans-FDKP isomer content of about 50% to about 56%.4. The FDKP microparticles of having a trans-FDKP isomer content of about 54% to about 56%.5. The FDKP microparticles of wherein the FDKP microparticles comprise a drug.6. The FDKP microparticles of having a trans-FDKP isomer content of about 50% to about 56%.7. The FDKP microparticles of wherein the drug is insulin.8. The microparticles of wherein the insulin content is about 3 to about 4 U/mg.9. A dry powder comprising the microparticles of .10. The dry powder of claim 9 , wherein the microparticles have a trans-FDKP isomer content of about 53% to about 63%.11. A method of treating an insulin-related disorder comprising administering the microparticles of to a person in need thereof.12. FDKP microparticles having improved aerodynamic performance that have been prepared by a process comprising:determining the trans-FDKP isomer content;wherein the ...

COMPOSITIONS FOR NUCLEIC ACID DELIVERY

A method for delivering a nucleic acid to a cell can include exposing sample cells to a composition which includes charged lipids. 5. The compound of claim 4 , wherein E is O(CO) claim 4 , (CO)O claim 4 , OC(O)N(R′) claim 4 , or N(R′)C(O)O.7. A method for delivering a nucleic acid to a cell comprising contacting cells with a compound according to .8. The method of claim 7 , wherein the composition further comprises a lipid capable of reducing aggregation.9. The method of claim 7 , wherein the composition further comprises a nucleic acid.10. The method of claim 7 , wherein the cell is in suspension.11. The method of claim 10 , wherein the volume of the suspension is at least 0.050 L.12. The method of claim 10 , wherein the volume of the suspension is at least 3 L.13. The method of claim 10 , wherein the volume of the suspension is at least 25 L.14. The method of claim 10 , wherein the volume of the suspension is at least 40 L.15. The method of claim 9 , wherein the nucleic acid includes a chemically modified nucleic acid.16. The method of claim 9 , wherein the nucleic acid is 10 to 50 nucleotides long.17. The method of claim 9 , wherein the nucleic acid is an oligonucleotide.18. The method of claim 17 , wherein the oligonucleotide is 10 to 50 nucleotides long.19. The method of claim 18 , wherein the oligonucleotide is double stranded.20. The method of claim 18 , wherein the oligonucleotide is single stranded.21. The method of claim 9 , wherein the nucleic acid is siRNA.22. The method of claim 9 , wherein the nucleic acid is mRNA.23. The method of claim 9 , wherein the nucleic acid is an antisense nucleic acid claim 9 , a microRNA claim 9 , an antimicro RNA claim 9 , an antagomir claim 9 , a microRNA inhibitor claim 9 , or an immune stimulatory nucleic acid.24. A storage-stable composition comprisinga cryoprotectant selected from sucrose, trehalose, glucose, 2-hydroxypropyl-α-cyclodextrin, and sorbitol, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound ...

Off-Note Masking

A method of masking an off-note in an orally-receivable or -ingestible composition, including the addition thereto of an off-note masking quantity of 1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propane-1-one or a salt thereof. The effect may be further enhanced by the addition of Compound 2 and/or 2-[(3-ethyl-4,8-dimethyl-2-oxo-2H-chromen-7-yl)oxy]propanoic acid, or salts thereof. 1. A method of masking an off-note in an orally-receivable or -ingestible composition , comprising the addition thereto of an off-note masking quantity of 1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propane-1-one or a salt thereof.2. The method according to claim 1 , in which there is additionally added to the composition a compound selected from the group consisting of 4-[2 claim 1 ,2 claim 1 ,3-trimethyl-cyclopentyl]-butanoic acid claim 1 , 2-[(3-ethyl-4 claim 1 ,8-dimethyl-2-oxo-2H-chromen-7-yl)oxy]propanoic acid claim 1 , and salts thereof.3. An off-note-masked orally-receivable or -ingestible composition comprising an off-note masking quantity of 1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propane-1-one or a salt thereof.4. An off-note-masked orally-receivable or -ingestible composition comprising an off-note masking quantity of a masking composition comprising 1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propane-1-one and at least one of 4-[2 claim 1 ,2 claim 1 ,3-trimethyl-cyclopentyl]-butanoic acid or 2-[(3-ethyl-4 claim 1 ,8-dimethyl-2-oxo-2H-chromen-7-yl)oxy]propanoic acid or salts thereof.5. An off-note-masking composition consisting of 1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propane-1-one and at least one of 4-[2 claim 1 ,2 claim 1 ,3-trimethyl-cyclopentyl]-butanoic acid or 2-[(3-ethyl-4 claim 1 ,8-dimethyl-2-oxo-2H-chromen-7-yl)oxy]propanoic acid or salts thereof.6. The off-note-masking composition according to claim 5 , consisting of 1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propane-1-one and 4-[2 claim 5 ,2 claim 5 ,3-trimethyl-cyclopentyl]-butanoic acid claim 5 , or salts thereof.7. The off-note-masking composition ...

DRY POWDER INHALER AND SYSTEM FOR DRUG DELIVERY

A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable. 1. Fumaryl diketopiperazine (FDKP) microparticles comprising a trans-FDKP isomer content of about 45% to about 63%.2. The FDKP microparticles of having a trans-FDKP isomer content of about 53% to about 63%.3. The FDKP microparticles of having a trans-FDKP isomer content of about 50% to about 56%.4. The FDKP microparticles of having a trans-FDKP isomer content of about 54% to about 56%.5. The FDKP microparticles of wherein the FDKP microparticles comprise a drug.6. The FDKP microparticles of having a trans-FDKP isomer content of about 50% to about 56%.7. The FDKP microparticles of wherein the drug is insulin.8. The microparticles of wherein the insulin content is about 3 to about 4 U/mg.9. A dry powder comprising the microparticles of .10. The dry powder of claim 9 , wherein the microparticles have a trans-FDKP isomer content of about 53% to about 63%.11. A method of treating an insulin-related disorder comprising administering the microparticles of to a person in need thereof.12. FDKP microparticles having improved aerodynamic performance that have been prepared by a process comprising:determining the trans-FDKP isomer content;wherein the ...

FORMULATIONS WITH REDUCED VISCOSITY

The present invention is directed to a method for reducing the viscosity of a formulation containing acetate and a therapeutic protein and formulations made using the claimed method. 1. A method for reducing the viscosity of a formulation containing acetate and a therapeutic polypeptide , the method comprising; (a) providing a formulation comprising acetate; and (b) adding glycine and/or arginine to the formulation to a concentration of about 1.0% w/v , wherein the viscosity of the formulation with the glycine and/or arginine is reduced compared to the viscosity of the same formulation without glycine and/or arginine.2. (canceled)3. The method of claim 1 , wherein the viscosity of the formulation with glycine and/or arginine is less than about 25 cP or less than about 20 cP.4. A method for reducing the viscosity of a formulation containing acetate and a therapeutic polypeptide claim 1 , the method comprising; (a) providing a formulation comprising acetate; and (b) adding methionine to the formulation to a concentration of about 0.04% w/v claim 1 , wherein the viscosity of the formulation with the methionine is reduced compared to the viscosity of the same formulation without methionine.5. (canceled)6. The method of claim 4 , wherein the viscosity of the formulation with methionine is less than about 25 cP or less than about 20 cP.7. A method for reducing the viscosity of a formulation containing acetate and a therapeutic polypeptide claim 4 , the method comprising; (a) providing a formulation comprising acetate; and (b) adding phenylalanine to the formulation to a concentration of about 0.8% w/v claim 4 , wherein the viscosity of the formulation with the phenylalanine is reduced compared to the viscosity of the same formulation without phenylalanine8. (canceled)9. The method of claim 7 , wherein the viscosity of the formulation with phenylalanine is less than about 20 cP or less than about 15 cP.10. A method for reducing the viscosity of a formulation containing ...

RNAi PHARMACEUTICAL COMPOSITION FOR SUPPRESSING EXPRESSION OF KRAS GENE

The present invention provides a composition for suppressing the expression of a KRAS gene, comprising a lipid particle containing, as a drug, a double-stranded nucleic acid having an antisense strand having a sequence of bases complementary to the sequence of at least 19 continuous bases of any one KRAS gene's mRNA of sequence Nos. 1 to 3; and 3. The composition according to claim 2 , wherein Rand Rare identically dodecyl claim 2 , tridecyl claim 2 , tetradecyl claim 2 , 2 claim 2 ,6 claim 2 ,10-trimethylundecyl claim 2 , pentadecyl claim 2 , 3 claim 2 ,7 claim 2 ,11-trimethyldodecyl claim 2 , hexadecyl claim 2 , heptadecyl claim 2 , octadecyl claim 2 , 6 claim 2 ,10 claim 2 ,14-trimethylpentadecan-2-yl claim 2 , nonadecyl claim 2 , 2 claim 2 ,6 claim 2 ,10 claim 2 ,14-tetramethylpentadecyl claim 2 , icosyl claim 2 , 3 claim 2 ,7 claim 2 ,11 claim 2 ,15-tetramethylhexadecyl claim 2 , henicosyl claim 2 , docosyl claim 2 , tricosyl claim 2 , tetracosyl claim 2 , (Z)-tetradec-9-enyl claim 2 , (Z)-hexadec-9-enyl claim 2 , (Z)-octadec-6-enyl claim 2 , (Z)-octadec-9-enyl claim 2 , (E)-octadec-9-enyl claim 2 , (Z)-octadec-11-enyl claim 2 , (9Z claim 2 ,12Z)-octadeca-9 claim 2 ,12-dienyl claim 2 , (9Z claim 2 ,12Z claim 2 ,15Z)-octadeca-9 claim 2 ,12 claim 2 ,15-trienyl claim 2 , (Z)-icos-11-enyl claim 2 , (11Z claim 2 ,14Z)-icosa-11 claim 2 ,14-dienyl claim 2 , 3 claim 2 ,7 claim 2 ,11-trimethyldodeca-2 claim 2 ,6 claim 2 ,10-trienyl claim 2 , or 3 claim 2 ,7 claim 2 ,11 claim 2 ,15-tetramethylhexadec-2-enyl.4. The composition according to claim 2 , wherein Rand Rare identically tetradecyl claim 2 , hexadecyl claim 2 , (Z)-hexadec-9-enyl claim 2 , (Z)-octadec-6-enyl claim 2 , (Z)-octadec-9-enyl claim 2 , (9Z claim 2 ,12Z)-octadeca-9 claim 2 ,12-dienyl claim 2 , (Z)-icos-11-enyl claim 2 , or (11Z claim 2 ,14Z)-icosa-11 claim 2 ,14-dienyl.5. The composition according to claim 3 , wherein Ris a hydrogen atom claim 3 , methyl claim 3 , pyrrolidin-3-yl claim 3 , piperidin-3-yl ...

Solid Oral Formulations of a Pyridopyrimidinone

A solid oral dosage pharmaceutical formulation of (R)-2-Amino-7-[4-fluoro-2-(6-methoxy-pyridin-2-yl)-phenyl]-4-methyl-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one or its salt; and a surfactant or an acid. 2. The pharmaceutical formulation of claim 1 , wherein the surfactant is vitamin E TPGS claim 1 , polysorbate 80 claim 1 , polysorbate 20 claim 1 , sodium lauryl sulfate claim 1 , an alkyl sulfate anionic surfactant claim 1 , sodium claim 1 , potassium n-dodecyl sulfate magnesium n-dodecyl sulfate claim 1 , n-tetradecyl sulfate claim 1 , n-hexadecyl sulfate claim 1 , n-octadecyl sulfate claim 1 , an alkyl other sulfate claim 1 , sodium n-dodecyloxyethyl sulfate claim 1 , potassium n-dodecyloxyethyl sulfate claim 1 , magnesium n-dodecyloxyethyl sulfate claim 1 , n-tetradecyloxyethyl sulfate claim 1 , n-hexadecyloxyethyl sulfate claim 1 , n-octadecyloxyethyl sulfate claim 1 , an alkanesulfonate claim 1 , sodium n-dodecanesulfonate claim 1 , potassium n-dodecanesulfonate claim 1 , magnesium n-dodecanesulfonate claim 1 , n-tetradecanesulfonate claim 1 , n-hexadecanesulfonate claim 1 , n-octadecanesulfonate claim 1 , a non-ionic fatty acid polyhydroxy alcohol ester surfactant claim 1 , sorbitan monolaurate claim 1 , sorbitan trioleate claim 1 , a polyoxyethylene fatty acid claim 1 , a polyhydroxy alcohol ester claim 1 , polyoxyethylene sorbitan monolaurate claim 1 , polyoxyethylene sorbitan monooleate claim 1 , polyoxyethylene sorbitan monostearate claim 1 , polyoxyethylene sorbitan monopalmitate claim 1 , polyoxyethylene sorbitan tristearate claim 1 , polyoxyethylene sorbitan trioleate claim 1 , a polyethylene glycol fatty acid ester claim 1 , polyoxyethyl stearate claim 1 , polyethylene glycol 400 stearate claim 1 , polyethylene glycol 2000 stearate claim 1 , an ethylene oxide block polymer claim 1 , or a propylene oxide block polymer.3. The pharmaceutical formulation of claim 2 , wherein the surfactant is vitamin E TPGS claim 2 , polysorbate λor sodium lauryl sulfate. ...

LIPID NANO PARTICLES COMPRISING COMBINATION OF CATIONIC LIPID

The present invention provides a lipid nano-particles, which allow nucleic acids to be easily introduced into cells, comprising a cationic lipid represented by formula (I) 2. The lipid nano particles according to claim 1 , wherein Rand Rare dodecyl claim 1 , tetradecyl claim 1 , (Z)-dodec-7-enyl claim 1 , (Z)-tetradec-7-enyl claim 1 , (Z)-hexadec-4-enyl claim 1 , (Z)-hexadec-7-enyl claim 1 , (E)-hexadec-7-enyl claim 1 , (Z)-hexadec-9-enyl claim 1 , (7Z claim 1 ,10Z)-hexadec-7 claim 1 ,10-dienyl claim 1 , (7Z claim 1 ,10Z claim 1 ,13Z)-hexadec-7 claim 1 ,10 claim 1 ,13-trienyl claim 1 , (Z)-octadec-9-enyl or (9Z claim 1 ,12Z)-octadec-9 claim 1 ,12-dienyl.3. The lipid nano particles according to claim 1 , wherein Rand Rare identically tetradecyl claim 1 , hexadecyl claim 1 , (Z)-tetradec-9-enyl claim 1 , (Z)-hexadec-9-enyl claim 1 , (Z)-octadec-6-enyl claim 1 , (Z)-octadec-9-enyl claim 1 , (E)-octadec-9-enyl claim 1 , (Z)-octadec-11-enyl claim 1 , (9Z claim 1 ,12Z)-octadeca-9 claim 1 ,12-dienyl claim 1 , (9Z claim 1 ,12Z claim 1 ,15Z)-octadeca-9 claim 1 ,12 claim 1 ,15-trienyl claim 1 , (Z)-icos-11-enyl or (11Z claim 1 ,14Z)-icosa-11 claim 1 ,14-dienyl.4. The lipid nano particles according to claim 1 , wherein Lis a single bond claim 1 , Ris a hydrogen atom claim 1 , methyl claim 1 , pyrrolidin-3-yl claim 1 , piperidin-3-yl claim 1 , piperidin-4-yl claim 1 , or alkyl having a carbon number of from 1 to 6 or alkenyl having a carbon number of from 3 to 6 claim 1 , each substituted with 1 to 3 substituent(s) claim 1 , which is(are) claim 1 , the same or different claim 1 , amino claim 1 , monoalkylamino claim 1 , dialkylamino claim 1 , trialkylammonio claim 1 , hydroxy claim 1 , alkoxy claim 1 , carbamoyl claim 1 , monoalkylcarbamoyl claim 1 , dialkylcarbamoyl claim 1 , pyrrolidinyl claim 1 , piperidyl or morpholinyl.5. The lipid nano particles according to claim 1 , wherein Lis —CO— or —CO—O— claim 1 , Ris pyrrolidin-3-yl claim 1 , piperidin-3-yl claim 1 , piperidin-4- ...

PHARMACEUTICAL COMPOSITION AND METHODS FOR PEPTIDE TREATMENT

Disclosed are compositions and methods for treating a patient with a pharmaceutically active agent other than insulin selected from the group consisting of peptides, peptidomimetics, and proteins, wherein the pharmaceutical composition is in the form of an emulsified nasal spray comprising: a macrocyclic permeation enhancer, a liquid carrier comprising water, and a therapeutically effective amount of a pharmaceutically active agent other than insulin selected from the group consisting of peptides, peptidomimetics, and proteins; wherein the macrocyclic permeation enhancer is a Hsieh enhancer emulsified in the liquid carrier. 2. The pharmaceutical composition of claim 1 , wherein said Hsieh enhancer is selected from the group consisting of 3-methylcyclopentadecanone claim 1 , 9-cycloheptadecen-1-one claim 1 , cyclohexadecanone claim 1 , cyclopentadecanone claim 1 , oxacyclohexadecan-2-one and mixtures thereof.3. The pharmaceutical composition of claim 2 , wherein said Hsieh enhancer is oxacyclohexadecan-2-one.4. The pharmaceutical composition of claim 1 , further comprising a crystallization inhibitor.5. The pharmaceutical composition of claim 1 , further comprising an enzyme inhibitor.6. The pharmaceutical composition of claim 1 , wherein the emulsifying agent consists of a surfactant.7. The pharmaceutical composition of claim 1 , wherein the surfactant is a non-ionic surfactant or combination of non-ionic surfactants.8. The pharmaceutical composition of claim 7 , wherein said non-ionic surfactant or combination of non-ionic surfactants has an HLB of from about 7 to about 14.9. The pharmaceutical composition of claim 1 , wherein the surfactant is selected from the group consisting of an anionic surfactant and a cationic surfactant.11. The method of claim 10 , wherein said Hsieh enhancer is selected from the group consisting of 3-methylcyclopentadecanone claim 10 , 9-cycloheptadecen-1-one claim 10 , cyclohexadecanone claim 10 , cyclopentadecanone claim 10 , ...

PHARMACETUICAL COMPOSITION COMPRISING DROTAVERINE

The present invention relates to a pharmaceutical composition of drotaverine hydrochloride in a solvent system suitable as a liquid fill composition. 1. A pharmaceutical composition for oral administration comprising:5 to 30% (w/w) of drotaverine hydrochloride; andat least 60% (w/w) of a liquid mixture of at least one non-ionic hydrophilic surfactant and at least one non-ionic hydrophobic surfactant.2. The pharmaceutical composition according to claim 1 , wherein the total amount of the liquid mixture of surfactant ranges from 75 to 90%.3. The pharmaceutical composition according to claim 1 , wherein the non-ionic hydrophobic surfactant has an HLB value from 4 to 6.4. The pharmaceutical composition according to claim 1 , wherein the non-ionic hydrophobic surfactant is propylene glycol monocaprylate.5. The pharmaceutical composition according to claim 1 , wherein the hydrophobic surfactant is present in amounts ranging from 75% to 90% by weight of the composition.6. The pharmaceutical composition according to claim 1 , wherein the non-ionic hydrophilic surfactant has an HLB value from 11 to 16.7. The pharmaceutical composition according to claim 1 , wherein the non-ionic hydrophilic surfactant is polysorbate 80.8. The pharmaceutical composition according to claim 1 , wherein the non-ionic hydrophilic surfactant is present in amounts ranging from 3% to 7% by weight of the composition.9. The pharmaceutical composition according to claim 1 , wherein the non-ionic hydrophobic surfactant is propylene glycol monocaprylate and the non-ionic hydrophilic surfactant is polysorbate 80.10. The pharmaceutical composition according to claim 1 , wherein the weight ratio of drotaverine hydrochloride to the liquid mixture of surfactant is from 1:3 to 1:7.11. The pharmaceutical composition according to claim 1 , wherein the final pH value of the composition is between 4 and 6.12. The pharmaceutical composition according to claim 1 , in the form of a soft capsule.13. A method for ...

FORMULATION OF HUMAN ANTIBODIES FOR TREATING TNF-ALPHA ASSOCIATED DISORDERS

A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability. 1. A stable liquid aqueous pharmaceutical formulation comprising(a) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, or an antigen-binding portion thereof, at a concentration of 20 to 150 mg/ml,(b) a polyol,(c) a surfactant, and(d) a buffer system having a pH of 4 to 8,wherein the antibody comprises a light chain variable region comprising the light chain complementarity determining region (CDR) 1, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the heavy chain CDR1, CDR2, and CDR3 of D2E7.2. The formulation of claim 1 , wherein the concentration of the antibody or antigen-binding portion is 45 to 105 mg/ml.3. The formulation of claim 2 , wherein the concentration of the antibody or antigen-binding portion is 50 mg/ml.4. The formulation of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 2.5. The formulation of claim 1 , wherein the antibody comprises the light and heavy chain variable regions of D2E7.6. The formulation of claim 5 , wherein the antibody is D2E7.7. The formulation of claim 1 , wherein the polyol is a sugar alcohol.8. The formulation of claim 7 , wherein the sugar alcohol is mannitol.9. The formulation of claim 1 , wherein the polyol is a sugar.10. The formulation of claim 9 , wherein the sugar is trehalose.11. (canceled)12. The formulation of claim 1 , wherein the surfactant is a polysorbate.13. The formulation of claim 12 , wherein the polysorbate is polysorbate 80.14. The formulation of claim 13 , wherein the polysorbate 80 concentration is from 0.1 to 10 mg/ml.15. The formulation of claim 13 , wherein the polysorbate 80 concentration is 1 mg/ml.16. The formulation of claim 1 , wherein the pH is from 4.5 to 7.0.17. The ...

FORMULATION OF HUMAN ANTIBODIES FOR TREATING TNF-ALPHA ASSOCIATED DISORDERS

A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability. 1. A stable liquid aqueous pharmaceutical formulation comprising(a) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, or an antigen-binding portion thereof, at a concentration of 20 to 150 mg/ml,(b) a polyol,(c) a surfactant, and(d) a buffer system comprising acetate and having a pH of 4 to 8,wherein the antibody comprises a light chain variable region comprising the light chain complementarity determining region (CDR) 1, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the heavy chain CDR1, CDR2, and CDR3 of D2E7.2. The formulation of claim 1 , wherein the concentration of the antibody or antigen-binding portion is 45 to 105 mg/ml.3. The formulation of claim 2 , wherein the concentration of the antibody or antigen-binding portion is 50 mg/ml.4. The formulation of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 2.5. The formulation of claim 1 , wherein the antibody comprises the light and heavy chain variable regions of D2E7.6. The formulation of claim 5 , wherein the antibody is D2E7.7. The formulation of claim 1 , wherein the polyol is a sugar alcohol.8. The formulation of claim 7 , wherein the sugar alcohol is mannitol.9. The formulation of claim 1 , wherein the the polyol is a sugar.10. The formulation of claim 9 , wherein the sugar is a nonreducing sugar.11. The formulation of claim 10 , wherein the nonreducing sugar is trehalose.12. The formulation of claim 1 , wherein the surfactant is a polysorbate.13. The formulation of claim 12 , wherein the polysorbate is polysorbate 80.14. The formulation of claim 13 , wherein the polysorbate 80 concentration is from 0.1 to 10 mg/ml.15. The formulation of claim 13 , wherein the polysorbate 80 ...

FORMULATION OF HUMAN ANTIBODIES FOR TREATING TNF-ALPHA ASSOCIATED DISORDERS

A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability. 1. A stable liquid aqueous pharmaceutical formulation comprising(a) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, or an antigen-binding portion thereof, at a concentration of 20 to 150 mg/ml,(b) a polyol,(c) a surfactant, and(d) a buffer system comprising histidine and having a pH of 4 to 8,wherein the antibody comprises a light chain variable region comprising the light chain complementarity determining region (CDR) 1, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the heavy chain CDR1, CDR2, and CDR3 of D2E7.2. The formulation of claim 1 , wherein the concentration of the antibody or antigen-binding portion is 45 to 105 mg/ml.3. The formulation of claim 2 , wherein the concentration of the antibody or antigen-binding portion is 50 mg/ml.4. The formulation of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 2.5. The formulation of claim 1 , wherein the antibody comprises the light and heavy chain variable regions of D2E7.6. The formulation of claim 5 , wherein the antibody is D2E7.7. The formulation of claim 1 , wherein the polyol is a sugar alcohol.8. The formulation of claim 7 , wherein the sugar alcohol is mannitol.9. The formulation of claim 1 , wherein the polyol is a sugar.10. The formulation of claim 9 , wherein the sugar is trehalose.11. (canceled)12. The formulation of claim 1 , wherein the surfactant is a polysorbate.13. The formulation of claim 12 , wherein the polysorbate is polysorbate 80.14. The formulation of claim 13 , wherein the polysorbate 80 concentration is from 0.1 to 10 mg/ml.15. The formulation of claim 13 , wherein the polysorbate 80 concentration is 1 mg/ml.16. The formulation of claim 1 , wherein the pH is ...

Storage-Stable Dust-Free Homogeneous Particulate Formulation Comprising At Least One Water-Soluble Vitamin E-Derivative And At Least One Hydrophilic Polymer

A storage-stable dust-free homogeneous particulate formulation comprising at least one water-soluble Vitamin E-derivative and at least one hydrophilic polymer. In one embodiment the storage-stable dust-free homogeneous particle formulation, consists of 1. A storage-stable dust-free homogeneous particulate formulation , consisting of(e) at least one water-soluble Vitamin E-derivative,(f) at least one hydrophilic polymer,(g) optionally additional surface-active substances, and(h) optionally additional pharmaceutical additives,(i) with the proviso, that the sum of (a), (b), (c) and (d) equals 100% by weight of the formulation, and wherein the fines fraction with particle diameters of less than 100 μm is less than 10% by weight,wherein the particle formulation is produced by a spray granulation process.2. The formulation according to having an average particle size D of from 300 to 800 μm.3. The formulation according to claim 1 , wherein component (a) is a tocopheryl polyethyleneglycol succinate.4. The formulation according to claim 1 , wherein component (b) is selected from the group consisting of homo- or copolymers of an N-vinyl lactam claim 1 , cellulose derivatives claim 1 , polyacrylic polymers claim 1 , polyalkylene oxides claim 1 , polyvinyl alcohols and oligo- and polysaccharides.5. The formulation according to claim 4 , wherein component (b) is a homo- or copolymer of an N-vinyl lactam.6. The formulation according to claim 5 , wherein component (b) is a homo- or copolymer of N-vinyl pyrrolidone.7. The formulation according to claim 6 , wherein component (b) is a copolymer of N-vinyl pyrrolidone and vinyl acetate.8. The formulation according to claim 4 , wherein component (b) is a copolymer of N-vinyl caprolactam claim 4 , vinyl acetate and polyethylene glycol.9. The formulation according to claim 4 , wherein component (b) is a cellulose derivative.10. The formulation according to claim 1 , wherein component (c) is selected from the group consisting of ...

ANTIBODY FORMULATION

The invention provides a stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody, optionally, not subjected to prior lyophilization, a buffer maintaining the pH in the range from about 4.0 to about 6.0, and an optional surfactant, methods for making such a formulation, and methods of using such a formulation. 1. A stable aqueous pharmaceutical formulation , the formulation comprising a therapeutically effective amount of an antibody in an arginine buffer , pH 4.0 to 6.0.2. The formulation of claim 1 , wherein the buffer is an arginine acetate buffer claim 1 , pH 4.5 to 5.5.3. The formulation of claim 1 , wherein the buffer is an arginine acetate buffer claim 1 , pH 4.8 to 5.4.4. The formulation of claim 1 , wherein the buffer is an arginine acetate buffer claim 1 , pH 5.2.54. The formulation of claim 1 , claim 1 , or wherein the arginine actetate concentration in the buffer is from about 25 mM to about 250 mM.64. The formulation of claim 1 , claim 1 , or wherein the arginine actetate concentration in the buffer is from about 50 mM to about 250 mM.74. The formulation of claim 1 , claim 1 , or wherein the arginine actetate concentration in the buffer is from about 75 mM to about 250 mM.84. The formulation of claim 1 , claim 1 , or wherein the arginine actetate concentration in the buffer is from about 100 mM to about 250 mM.94. The formulation of claim 1 , claim 1 , or claim 1 , wherein the arginine acetate concentration in the buffer is from about 120 mM to about 240 mM.104. The formulation of claim 1 , claim 1 , or claim 1 , wherein arginine acetate concentration in the buffer is from about 150 mM to about 225 mM.114. The formulation of claim 1 , claim 1 , or claim 1 , wherein the arginine acetate concentration in the buffer is about 200 mM.12. The formulation of claim 1 , further comprising a surfactant.13. The formulation of claim 12 , wherein the surfactant is polysorbate.14. The formulation of claim 13 , wherein the ...

COMPOSITIONS AND METHODS TO IMPROVE ADOPTIVE CELL THERAPIES

Compositions and methods of enhancing the potency and efficacy of adoptive cell therapy using integrin-ligand stabilizers, wherein the integrin is selected from the group consisting of α4β1, α5β1, α4β7, αvβ3 and αLβ2, and contacting the effector cells ex vivo with agonists or stabilizers having the general Formula (I); methods of treating integrin-expressing cells with such stabilizers to enhance tumor infiltration; and therapeutic methods comprising administering stabilizer or agonist-treated cells to a mammal requiring treatment of solid tumors, hematologic cancers. 1. A composition comprising:an effector cell, andan effective amount of one or a plurality of association enhancing compounds,where the association enhancing compounds are capable of enhancing integrin-mediated binding of integrins of the effector cells to their respective ligands.2. The composition of claim 1 , wherein the integrins include α4β1 claim 1 , αβ7 claim 1 , α5β1 claim 1 , αLβ2 and/or αVβ3.3. The composition of claim 1 , wherein the ligands include VCAM-1 claim 1 , fibronectin claim 1 , MAdCAM-1 claim 1 , ICAM-1 claim 1 , ICAM-2 claim 1 , and/or vitronectin.4. The composition of claim 1 , wherein the association enhancing compounds are given by the general Formula (I):{'br': None, 'sup': 1', '1', '2', '2', '3', '4', '5', '6', '3, 'R-M-N(R)-M-M-M-M-M-R\u2003\u2003(I)'} [{'sup': '1', 'Ris selected from the group consisting of aryl and aralkyl,'}, {'sup': '2', 'Ris alkyl, aryl, or aralkyl,'}, {'sup': '1', 'sub': '2', 'Mis CH,'}, {'sup': '2', 'Mis CO,'}, {'sup': 3', '6', '6, 'Mis O, S, or NR, where Rwhen present is hydrogen or lower alkyl,'}, {'sup': '4', 'sub': '2', 'Mis absent or CH,'}, {'sup': 5', '11', '12, 'Mis (CRR),'}, {'sup': 11', '12', '21', '22', '23', '21', '24', '21', '24', '21', '24', '24', '24', '24', '24', '21', '22', '23', '3', '6', '4', '12', '22', '23', '23', '24, 'sub': 2', '2', '2', 's, 'Ris hydrogen, Ris selected from the group consisting of hydrogen, NRCONRR, NRCOR, NSOR, ...

Stabilized Formulations Containing Anti-Interleukin-6 Receptor (IL-6R) Antibodies

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R). The formulations may contain, in addition to an anti-hIL-6R antibody, at least one amino acid, at least one sugar, and/or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months. 131-. (canceled)32. A stable pharmaceutical formulation comprising:(i) a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R), wherein the antibody is at a concentration of from about 25 mg/ml to about 200 mg/ml and comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO:18 and a light chain variable region having the amino acid sequence of SEQ ID NO:26;(ii) histidine at a concentration of from about 10 mM to about 25 mM;(iii) arginine at a concentration of from about 25 mM to about 50 mM;(iv) sucrose in an amount of from about 5% to about 10% w/v; and(v) polysorbate in an amount of from about 0.1% to about 0.2% w/v, wherein the formulation has a pH of about 5.8, about 6.0, or about 6.2, and at least 90% of the native form of the antibody is recovered after 1 month of storage at 45° C., as determined by size exclusion chromatography.33. The pharmaceutical formulation of claim 32 , wherein the histidine is at a concentration of 21 mM.34. The pharmaceutical formulation of claim 33 , wherein the arginine is present at a concentration of 45 mM.35. The pharmaceutical formulation of claim 34 , wherein the sucrose is present in an amount of 5% w/v.36. The pharmaceutical formulation of claim 35 , wherein the polysorbate is present at a concentration of 0.2% w/v.37. The pharmaceutical formulation of that has a pH of 6.38. The pharmaceutical formulation of claim 32 , comprising from 50 mg/mL to 180 mg/mL of the human antibody that specifically binds to hIL-6R.39. The ...

STABLE LIQUID COMPOSITION COMPRISING PROTEIN

Disclosed is a stable liquid formulation of a protein. Provided is a liquid protein composition comprising a protein, and being free of a buffer and/or comprising histidine, and a preparation method thereof. 1. A liquid composition , which comprises an anti-RANKL antibody , has a pH of 5 to 7 and is free of an acetate.2. The liquid composition of claim 1 , which is free of a succinate claim 1 , or free of a glutamate claim 1 , or free of both of a succinate and a glutamate.3. The liquid composition of comprising histidine.4. The liquid composition of claim 2 , comprising histidine.56.-. (canceled)7. The liquid composition of claim 1 ,(1) wherein as measured following storage at 40° C. for four weeks, the liquid composition has variation in high molecular weight (Δ% HMW) of 5.0% or less; or has variation in high molecular weight (Δ% HMW) lower by at least 0.05% than that of the same composition with an exception of comprising at least one selected from the group consisting of an acetate, a succinate, and a glutamate, and/or being free of histidine;(2) as measured following storage at 40° C. for four weeks, the liquid composition has variation in acidic variant amount (Δ% Acidic) of 25.0% or less; or has variation in acidic variant amount (Δ% Acidic) lower by at least 0.05% than that of the same composition with an exception of comprising at least one selected from the group consisting of an acetate, a succinate, and a glutamate and/or being free of histidine; or(3) both of (1) and (2).8. The liquid composition of claim 2 , wherein(1) as measured following storage at 40° C. for four weeks, the liquid composition has variation in high molecular weight (Δ% HMW) of 5.0% or less; or has variation in high molecular weight (Δ% HMW) lower by at least 0.05% than that of the same composition with an exception of comprising at least one selected from the group consisting of an acetate, a succinate, and a glutamate, and/or being free of histidine;(2) as measured following ...

LIQUID FORMULATIONS OF BENDAMUSTINE

Stable liquid formulations of bendamustine, and pharmaceutically acceptable salts thereof, and polar aprotic solvents, are described. 1. A liquid formulation comprising bendamustine and 1-methyl-2-pyrrolidone (NMP). This application is a continuation of U.S. application Ser. No. 16/601,293, filed Oct. 14, 2019, which is a continuation of U.S. application Ser. No. 16/433,510, filed Jun. 6, 2019, which is continuation of U.S. application Ser. No. 16/245,672, filed Jan. 11, 2019, now abandoned, which is a continuation of U.S. application Ser. No. 15/688,182, filed Aug. 28, 2017, which is a continuation of U.S. application Ser. No. 14/814,570, filed Jul. 31, 2015, now abandoned, which is a continuation of U.S. application Ser. No. 14/221,422, filed Mar. 21, 2014, now abandoned, which is a continuation of U.S. application Ser. No. 14/151,242, filed Jan. 9, 2014, now abandoned, which is a continuation of U.S. application Ser. No. 13/655,498, filed Oct. 19, 2012, now abandoned, which is a continuation of U.S. application Ser. No. 13/362,430, filed Jan. 31, 2012, now U.S. Pat. No. 8,344,006, which is a continuation of U.S. application Ser. No. 13/048,325, filed Mar. 15, 2011, now abandoned, which is a continuation of International Application No. PCT/US2009/58023, filed Sep. 23, 2009, which claims the benefit of U.S. Provisional Application No. 61/100,074, filed Sep. 25, 2008, the entireties of which are incorporated by reference herein.The present invention relates to liquid formulations of bendamustine, and the pharmaceutical salts thereof.is an atypical structure with a benzimidazole ring, which structure includes an active nitrogen mustard. Bendamustine was initially synthesized in 1963 in the German Democratic Republic and was available from 1971 to 1992 in that location under the name Cytostasan®. Since that time, it has been marketed in Germany under the tradename Ribomustin®. It is currently available for use in the United States under the tradename Treanda® ( ...

Novel Insulin Derivatives and the Medical Uses Hereof

The present invention is in the therapeutic fields of drugs for medical conditions relating to diabetes. More specifically the invention relates to novel acylated derivatives of human insulin analogues. The invention also provides pharmaceutical compositions comprising such insulin derivatives, and relates to the use of such derivatives for the treatment or prevention of medical conditions relating to diabetes. 1. An insulin derivative , which insulin derivative is an acylated analogue of human insulin , which analogue is{'br': None, '[A22K,desB27,B29R,desB30] relative to human insulin;'} {'br': None, '[Acyl]-[Linker]-'}, 'and which insulin analogue is derivatized by acylation of the epsilon amino group of the lysine residue at the A22 position with a group of Formula II'}wherein the Linker group is an amino acid chain composed of from 1 to 10 amino acid residues selected from -gGlu- and -OEG-; whereingGlu represents a gamma glutamic acid residue;{'sub': 2', '2', '2', '2', '2, 'OEG represents the residue of 8-amino-3,6-dioxaoctanoic acid (i.e. a group of the formula —NH—(CH)—O—(CH)—O—CH—CO—);'}which amino acid residues may be present in any order; andwhich amino acid chain comprises at least one gGlu residue; and 1,14-tetradecanedioic acid;', '1,15-pentadecanedioic acid; and', '1,16-hexadecanedioic acid;, 'wherein the Acyl group is a residue of an α,ω-di-carboxylic acid selected from'}which acylated analogue, may additionally comprise the A14E, and/or B3E or B3Q substitutions.2. The insulin derivative according to claim 1 , which analogue is [A14E claim 1 , A22K claim 1 , B3E claim 1 , desB27 claim 1 , B29R claim 1 , desB30]; [A14E claim 1 , A22K claim 1 , desB27 claim 1 , B29R claim 1 , desB30]; [A22K claim 1 , B3E claim 1 , desB27 claim 1 , B29R claim 1 , desB30]; [A22K claim 1 , B3Q claim 1 , desB27 claim 1 , B29R claim 1 , desB30]; or [A22K claim 1 , desB27 claim 1 , B29R claim 1 , desB30]; relative to human insulin; and which insulin analogue is acylated at the ...

TOPICAL LOCALIZED ISOXAZOLINE FORMULATION COMPRISING GLYCOFUROL

This invention provides topical localized formulations comprising an isoxazoline compound and a pharmaceutically or veterinary acceptable liquid carrier vehicle comprising glycofurol and an improved method for controlling, and preventing parasite infestation in animals. 3. The topical localized formulation according to claim 1 , wherein Ris H and Ris CH—C(O)—NH—CH—CF claim 1 , CH—C(O)—NH—CH—CH claim 1 , CH—CH—CFor CH—CF.4. The topical localized formulation according to claim 1 , wherein the formulation comprises 4-[5-(3 claim 1 ,5-Dichlorophenyl)-5-trifluoromethyl-4 claim 1 ,5-dihydroisoxazol-3-yl]-2-methyl-N-[(2 claim 1 ,2 claim 1 ,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide.5. The topical localized formulation according to wherein the liquid carrier vehicle comprises glycofurol as solvent and a co-solvent selected from the group consisting of acetone claim 1 , acetonitrile claim 1 , benzyl alcohol claim 1 , butyl diglycol claim 1 , dimethylacetamide claim 1 , dimethylsulfoxide claim 1 , dimethylformamide claim 1 , N claim 1 ,N-diethyl-3-methylbenzamide claim 1 , dipropylene glycol n-butyl ether claim 1 , ethyl alcohol claim 1 , isopropanol claim 1 , methanol claim 1 , phenylethyl alcohol claim 1 , isopropanol claim 1 , ethylene glycol monoethyl ether claim 1 , ethylene glycol monomethyl ether claim 1 , monomethylaceamide claim 1 , dipropylene glycol monomethyl ether claim 1 , liquid polyoxyethylene glycols claim 1 , propylene glycol claim 1 , N-methylpyrrolidone claim 1 , 2-pyrrolidone claim 1 , limonene claim 1 , eucalyptol claim 1 , diethylene glycol monoethyl ether claim 1 , ethylene glycol claim 1 , diethyl phthalate claim 1 , polyethoxylated castor oil claim 1 , methyl ethyl ketone claim 1 , ethyl-L-lactate claim 1 , and a mixture of at least two of these co-solvents.6. The topical localized formulation according to claim 1 , wherein the liquid carrier vehicle comprises glycofurol as solvent and a co-solvent selected from the group consisting of dimethyl ...

HIGH CONCENTRATION LOCAL ANESTHETIC FORMULATIONS

A transdermal topical anesthetic formulation, which can be used to ameliorate or inhibit pain, has been developed. In the preferred embodiment, the topical anesthetic is a local anesthetic such as lidocaine, most preferably lidocaine free-base in a gel, and the dosage of the local anesthetic is effective in the painful area or immediately adjacent areas, to ameliorate or eliminate the pain. High concentration of local anesthetic in solution in the carrier is used to drive rapid release and uptake of the drug. Relief is typically obtained for a period of several hours. 119-. (canceled)20. A topical anesthetic formulation in the form of a non-aqueous gel , comprising(a) about 40% by weight of a free base caine alkaloid local anesthetic, wherein the free base caine alkaloid local anesthetic is lidocaine free base; and(b) a pharmaceutically acceptable carrier for topical application, wherein the carrier comprises an alkylene glycol and an alcohol;wherein the formulation is a non-aqueous gel, and the formulation can provide pain relief for 3 hours when applied topically to a site at or adjacent a painful region without systemic toxicity.21. The formulation of claim 20 , wherein the alkylene glycol is propylene glycol.22. The formulation of claim 20 , further comprising diglycol monoethyl ether.23. The formulation of claim 21 , further comprising diglycol monoethyl ether.24. The formulation of claim 20 , further comprising hydroxypropyl cellulose.25. The formulation of claim 21 , further comprising hydroxypropyl cellulose.26. The formulation of claim 22 , further comprising hydroxypropyl cellulose.27. The formulation of claim 23 , further comprising hydroxypropyl cellulose.28. The formulation of claim 21 , wherein the alcohol is ethanol.29. The formulation of claim 22 , wherein the alcohol is ethanol.30. The formulation of claim 23 , wherein the alcohol is ethanol.31. The formulation of claim 25 , wherein the alcohol is ethanol.32. The formulation of claim 27 , wherein ...

ANTI-CONNEXIN ANTIBODY FORMULATIONS

The present disclosure relates to pharmaceutical compositions and methods for treating a disease or condition associated with opening of Cx43 hemichannels in astrocytes or osteocytes, preferably for treating an inflammatory disease or condition or a neurodegenerative disease such as spinal cord injury. 1. A pharmaceutical formulation comprising:an anti-Cx43 antibody or antigen binding fragment thereof;a buffer;a surfactant; anda stabilizer;wherein the pharmaceutical formulation has a pH of between about 5 and about 6; a first, second and third heavy chain complementarity determining region (CDR) sequence having the amino acid sequence of SEQ ID NOs: 1, 2, and 3, respectively; and', 'a first, second and third light chain CDR sequence having the amino acid sequence of SEQ ID NOs: 4, 5, and 6, respectively., 'wherein the anti-Cx43 antibody or antigen binding fragment thereof comprises2. The pharmaceutical formulation of claim 1 , wherein the anti-Cx43 antibody or antigen binding fragment thereof comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 7 claim 1 , and a light chain variable domain having the amino acid sequence of SEQ ID NO: 8.3. The pharmaceutical formulation of claim 2 , wherein the anti-Cx43 antibody or antigen binding fragment thereof comprises a heavy chain having an amino acid sequence selected from the group consisting of SEQ ID NOs: 9-17 claim 2 , and a light chain having the amino acid sequence of SEQ ID NO: 18.4. The pharmaceutical formulation of claim 1 , wherein the anti-Cx43 antibody or antigen binding fragment thereof binds to an epitope located within the amino acid sequence of FLSRPTEKTI (SEQ ID NO: 19).5. The pharmaceutical formulation of claim 4 , wherein the epitope comprises one or more amino acids selected from the group consisting of R4 claim 4 , P5 claim 4 , E7 claim 4 , K8 and I10 of SEQ ID NO: 19.6. The pharmaceutical formulation of claim 4 , wherein the epitope consists of R4 claim 4 , P5 claim 4 , ...

DELIVERY AND FORMULATION OF ENGINEERED NUCLEIC ACIDS

Provided are formulations, compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the delivery of biological moieties, and are useful for production of proteins. 1. A method of producing a polypeptide of interest in a cell in a subject in need thereof , comprising administering to the subject a pharmaceutical composition comprising a modified messenger RNA (mmRNA) such that the mmRNA is introduced into the cell , wherein the mmRNA comprises a translatable region encoding the polypeptide of interest and comprises the modified nucleoside 1-methyl-pseudouridine , and wherein the pharmaceutical composition comprises an effective amount of the mmRNA providing for increased polypeptide production and substantially reduced innate immune response in the cell , as compared to a composition comprising a corresponding unmodified mRNA.2. The method of claim 1 , wherein the mmRNA comprises the modified nucleoside 1-methyl-pseudouridine in combination with 5-methyl-cytidine.3. The method of claim 2 , wherein the mmRNA comprises at least about 80% claim 2 , at least about 85% claim 2 , at least about 90% claim 2 , at least about 95% claim 2 , or about 100% 1-methyl-pseudouridine in place of uracils and at least about 80% claim 2 , at least about 85% claim 2 , at least about 90% claim 2 , at least about 95% claim 2 , or about 100% 5-methyl-cytidine in place of cytosines.4. The method of claim 3 , wherein the mmRNA comprises at least about 95% 1-methyl-pseudouridine in place of uracils and at least about 95% 5-methyl-cytidine in place of cytosines.5. The method of claim 3 , wherein the mmRNA comprises about 100% 1-methyl-pseudouridine in place of uracils and about 100% 5-methyl-cytidine in place of cytosines.6. The method of claim 1 , wherein the innate immune response is reduced by 80% claim 1 , 90% claim 1 , 95% claim 1 , 99% claim 1 , 99.9% claim 1 , or greater ...

PHARMACEUTICAL COMPOSITION COMPRISING RAPAMYCIN OR DERIVATIVE THEREOF

It is an object of the present invention to provide a pharmaceutical composition, which can suppress a reduction in the content of an active ingredient caused by oxidation or decomposition of rapamycin or a derivative thereof, can ensure long-term stability, and has high safety. In the present invention, the inventors have found that a tocopherol derivative and an ascorbic acid fatty acid ester are used in combination in a pharmaceutical formulation comprising rapamycin or a derivative thereof, so that oxidation or decomposition of the rapamycin or a derivative thereof can be suppressed, thereby completing the present invention. The rapamycin or a derivative thereof, and the tocopherol derivative and the ascorbic acid fatty acid ester are preferably in the form of a solid mixture produced by preparing a solution containing these components and then removing the solvent from the solution. 1. A pharmaceutical composition comprising (A) rapamycin or a derivative thereof , and (B) a tocopherol derivative and (C) an ascorbic acid fatty acid ester.2. The pharmaceutical composition according to claim 1 , which is produced by preparing a solution containing (A) rapamycin or a derivative thereof claim 1 , and (B) a tocopherol derivative and (C) an ascorbic acid fatty acid ester claim 1 , and then removing the solvent from the solution.3. The pharmaceutical composition according to claim 1 , which comprises 0.0001 to 5.0 parts by mass of (B) the tocopherol derivative and 0.001 to 10.0 parts by mass of (C) the ascorbic acid fatty acid ester claim 1 , based on 1 part by mass of (A) the rapamycin or a derivative thereof claim 1 , and the mixing ratio between the components (B) and (C) claim 1 , (B):(C) claim 1 , is 1:0.1 to 100.4. The pharmaceutical composition according to claim 1 , which further comprises an antioxidant other than (B) the tocopherol derivative and (C) the ascorbic acid fatty acid ester.5. The pharmaceutical composition according to claim 1 , which comprises a ...

COMPOSITION AND METHODS FOR STABILIZING LIQUID PROTEIN FORMULATIONS

The present disclosure provides liquid formulations comprising polypeptides and surfactants. In particular, it discloses a liquid formulation comprising a polypeptide and a surfactant, wherein at least about 70% (wt %) of the surfactant are isosorbide polyoxyethylene (POE) fatty acid esters. The invention also provides methods for making such liquid formulations, articles of manufacture comprising such liquid formulations and methods of treating a patient with such liquid formulations. 1. A liquid formulation comprising a polypeptide and a surfactant , wherein at least about 70% (wt %) of the surfactant are isosorbide polyoxyethylene (POE) fatty acid esters.2. The liquid formulation of claim 1 , wherein the isosorbide POE fatty acid esters comprise about 5-30 POE units.3. The liquid formulation of claim 1 , wherein the isosorbide POE fatty acid esters comprise about 20 POE units.4. The liquid formulation of claim 1 , wherein the isosorbide POE fatty acid esters comprise fatty acid chains selected from the group consisting of an optionally substituted Calkyl and an optionally substituted Calkenyl.5. The liquid formulation of claim 1 , wherein the isosorbide POE fatty acid esters are monoesters.6. The liquid formulation of claim 5 , wherein the monoesters are selected from the group consisting of isosorbide POE monolaurate claim 5 , isorsobide POE monomyristate claim 5 , isosorbide POE monopalmitate claim 5 , isosorbide POE monostearate and isosorbide POE monooelate.7. The liquid formulation of claim 1 , wherein the isosorbide POE fatty acid esters are monoesters claim 1 , diesters claim 1 , or a mixture of the foregoing.9. The liquid formulation of claim 8 , wherein the sum of a and b is 9.10. The liquid formulation of claim 8 , wherein Ris H and Ris —C(O)R″.11. The liquid formulation of claim 8 , wherein Ris —C(O)R″ and Ris H.12. The liquid formulation of claim 8 , wherein both Rand Rare —C(O)R″.13. The liquid formulation of claim 8 , wherein R″ is an unsubstituted ...

LIPID NANOPARTICLES FOR IN-VIVO DRUG DELIVERY, AND USES THEREOF

The present invention relates to lipid nanoparticles for in vivo drug delivery and uses thereof, and the lipid nanoparticle are liver tissue-specific, have excellent biocompatibility and can deliver a gene therapeutic agent with high efficiency, and thus it can be usefully used in related technical fields such as lipid nanoparticle mediated gene therapy. 1. A lipid nanoparticle comprising an ionizable lipid in which a 6-membered heterocyclic amine and an alkyl-epoxide are bonded; a phospholipid; cholesterol; and a lipid-PEG (polyethyleneglycol) conjugate.2. The lipid nanoparticle according to claim 1 , wherein the 6-membered heterocyclic amine is a chain or non-chain amine comprising a tertiary amine.4. The lipid nanoparticle according to claim 1 , wherein the alkyl-epoxide is 1 claim 1 ,2-epoxydodecane.5. The lipid nanoparticle according to claim 1 , wherein the phospholipid is one or more kinds selected from the group consisting of DOPE claim 1 , DSPC claim 1 , POPC claim 1 , EPC claim 1 , DOPC claim 1 , DPPC claim 1 , DOPG claim 1 , DPPG claim 1 , DSPE claim 1 , Phosphatidylethanolamine claim 1 , dipalmitoylphosphatidylethanolamine claim 1 , 1 claim 1 ,2-dioleoyl-sn-glycero-3-phosphoethanolamine claim 1 , POPE claim 1 , POPC claim 1 , DOPS claim 1 , and 1 claim 1 ,2-dioleoyl-sn-glycero-3-[phospho-L-serine].6. The lipid nanoparticle according to claim 1 , wherein the lipid in the lipid-PEG conjugate is one or more kinds selected from the group consisting of ceramide claim 1 , dimyristoylglycerol (DMG) claim 1 , succinoyl-diacylglycerol (s-DAG) claim 1 , distearoylphosphatidylcholine (DSPC) claim 1 , distearoylphosphatidylethanolamine (DSPE) claim 1 , and cholesterol.7. The lipid nanoparticle according to claim 1 , wherein the lipid-PEG conjugate is comprised in 0.25 to 10 mol %.8. The lipid nanoparticle according to claim 1 , wherein the lipid nanoparticle comprises the ionizable lipid:phospholipid:cholesterol:lipid-PEG conjugate at a molar ratio of 20 to 50:10 to ...

Oral Solution Formulations of Aripiprazole

Oral solution formulations of aripiprazole, methods of manufacture of these formulations, methods of administration, and kits containing same. 1. A pharmaceutical formulation suitable for oral administration comprising aripiprazole , glycerin , propylene glycol , a buffer , a sweetener , and a flavoring agent , wherein said pharmaceutical formulation does not comprise a sugar , and wherein said pharmaceutical formulation has a pH of 4.3 or greater.2. The pharmaceutical formulation of claim 1 , wherein said pharmaceutical formulation does not comprise a preservative.3. The pharmaceutical formulation of claim 1 , wherein said sweetener is saccharin.4. The pharmaceutical formulation of claim 1 , wherein said buffer comprises citric acid and sodium citrate.5. The pharmaceutical formulation of claim 1 , wherein the pH is about 4.5.6. The pharmaceutical formulation of claim 1 , wherein said aripiprazole is present at a concentration of about 0.5 mg/ml to about 1.5 mg/ml.7. The pharmaceutical formulation of claim 6 , wherein said concentration is about 1.0 mg/ml.8. The pharmaceutical formulation of claim 1 , wherein said glycerin is present at a concentration of about 30% to about 70%.9. The pharmaceutical formulation of claim 1 , wherein said propylene glycol is present at a concentration of about 15% to about 30%.10. A preservative-free pharmaceutical formulation suitable for oral administration comprising aripiprazole at a concentration of about 0.5 mg/ml to about 1.5 mg/ml claim 1 , glycerin at a concentration of about 30% to about 70% claim 1 , propylene glycol at a concentration of about 15% to about 30% claim 1 , citric acid claim 1 , sodium citrate claim 1 , saccharin claim 1 , and a flavoring agent claim 1 , wherein said pharmaceutical formulation does not comprise a sugar claim 1 , and wherein said pharmaceutical formulation has a pH of about 4.3 or greater.11. A preservative-free pharmaceutical formulation suitable for oral administration comprising aripiprazole ...

PHARMACEUTICAL COMPOSITION COMPRISING RAPAMYCIN OR DERIVATIVE THEREOF

It is an object of the present invention to provide a pharmaceutical composition, which can suppress a reduction in the content of an active ingredient caused by oxidation or decomposition of rapamycin or a derivative thereof, can ensure long-term stability, and has high safety. In the present invention, the inventors have found that (B) a salt of an ascorbic acid or a derivative thereof and/or a salt of chelating agent is used in a pharmaceutical formulation comprising rapamycin or a derivative thereof, so that oxidation or decomposition of the rapamycin or a derivative thereof can be suppressed, thereby completing the present invention. The rapamycin or a derivative thereof, and (B) the salt of an ascorbic acid or a derivative thereof and/or the salt of chelating agent are preferably in the form of a solid mixture produced by preparing a solution containing these components and then removing the solvent from the solution. 1. A pharmaceutical composition comprising (A) rapamycin or a derivative thereof , and (B) a salt of an ascorbic acid or a derivative thereof and/or a salt of chelating agent.2. The pharmaceutical composition according to claim 1 , which is produced by preparing a solution containing (A) rapamycin or a derivative thereof claim 1 , and (B) a salt of an ascorbic acid or a derivative thereof and/or a salt of chelating agent claim 1 , and then removing the solvent from the solution.3. The pharmaceutical composition according to claim 1 , wherein (B) the salt of an ascorbic acid or the derivative thereof and/or a salt of chelating agent has a pH of 4 to 11 in 5 mg/mL 50% (v/v) ethanol aqueous solution.4. The pharmaceutical composition according to claim 1 , which comprises 0.0001 to 20.0 parts by mass of (B) a salt of an ascorbic acid or a derivative thereof and/or a salt of chelating agent based on 1 part by mass of (A) the rapamycin or a derivative thereof.5. The pharmaceutical composition according to claim 1 , which comprises a cellulose ...

NOVEL CATIONIC LIPID EXHIBITING IMPROVED INTRACELLULAR DYNAMICS

The invention provides a cationic lipid, a lipid membrane structure containing same, and use thereof. The cationic lipid is represented by the formula (1) 3. The cationic lipid according to claim 2 , wherein s is 0.4. The cationic lipid according to claim 1 , wherein Xand Xare each independently a cyclic alkylene tertiary amino group having 2-5 carbon atoms and 1-2 tertiary amino groups.5. The cationic lipid according to claim 1 , wherein Rand Rare each independently a residue derived from a reaction product of a liposoluble vitamin having a hydroxyl group claim 1 , and succinic anhydride or glutaric anhydride claim 1 , or an aliphatic hydrocarbon group having 12-22 carbon atoms.6. The cationic lipid according to claim 5 , wherein Rand Rare each independently a residue derived from a reaction product of a liposoluble vitamin having a hydroxyl group claim 5 , and succinic anhydride or glutaric anhydride.7. The cationic lipid according to claim 5 , wherein Rand Rare each independently an aliphatic hydrocarbon group having 12-22 carbon atoms.8. A lipid membrane structure comprising the cationic lipid according to as a constituent lipid of the membrane.9. A nucleic acid-introducing agent claim 1 , comprising the cationic lipid according to claim 1 , or the lipid membrane structure according to .10. A method for introducing a nucleic acid into a cell in vitro claim 9 , comprising bringing the nucleic acid-introducing agent according to encapsulating the nucleic acid into contact with the cell.11. A method for introducing a nucleic acid into a target cell claim 9 , comprising administering the nucleic acid-introducing agent according to encapsulating the nucleic acid to a living organism to allow for delivery of the nucleic acid to the cell.12. The cationic lipid according to claim 3 , wherein Xand Xare each independently a cyclic alkylene tertiary amino group having 2-5 carbon atoms and 1-2 tertiary amino groups.13. The cationic lipid according to claim 12 , wherein Rand ...

STABLE AQUEOUS ANTI-TAU ANTIBODY FORMULATIONS

The present disclosure provides stable, aqueous, buffered compositions comprising a high concentration of ABBV-8E12, such as a stable, aqueous buffered composition including ABBV-8E12 at a concentration of about 100 mg/ml, at least one buffer, an excipient, a surfactant, and optionally an antioxidant. 1. A stable aqueous , buffered composition comprising:an antibody at a concentration of about 100 mg/ml, wherein the antibody comprises a variable heavy chain that comprises a CDR1 sequence of SEQ ID NO: 6, a CDR2 sequence of SEQ ID NO:7, and a CDR3 sequence of SEQ ID NO: 8; and a variable light chain that comprises a CDR1 sequence of SEQ ID NO:2, a CDR2 sequence of SEQ ID NO: 3, and a CDR3 sequence of SEQ ID NO: 4;at least one buffer;an excipient;a surfactant; andoptionally an anti-oxidant.2. The composition according to claim 1 , wherein the antibody comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 9 and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO: 10.3. The composition according to any of the preceding claims claim 1 , wherein the buffer is selected from the group consisting of histidine claim 1 , phosphate claim 1 , and succinate buffer.4. The composition according to claim 3 , wherein the buffer is histidine.5. The composition according to any of the preceding claims claim 3 , wherein the surfactant is a polysorbate.6. The composition according to claim 5 , wherein the surfactant is Polysorbate 80.7. The composition according to any of the preceding claims claim 5 , wherein the composition comprises an excipient selected from the group consisting of a salt claim 5 , a sugar claim 5 , and a polyol.8. The composition according to claim 7 , wherein the excipient is sodium chloride.9. The composition according to claim 7 , wherein the excipient is a polyol selected from the group consisting of mannitol claim 7 , sorbitol claim 7 , and trehalose.10. The composition according to claim 7 , wherein the ...

RECOMBINANT FACTOR VIII FORMULATIONS

Provided are liquid and lyophilized recombinant Factor VIII formulations, including formulations for polymer-conjugated FVIII such as PEGylated Factor VIII. 1. A rFVIII formulation comprising:(a) a range of from about 1 mM to about 5 mM divalent cation;(b) a range of from about 150 mM to about 250 mM sodium chloride or potassium chloride;(c) a range of from about 50 ppm to about 200 ppm of a non-ionic surfactant; and(d) a range of from about 100 IU/ml to about 5000 IU/ml of a rFVIII, wherein the rFVIII comprises an amino acid sequence that has one or more non-cysteine residues in the amino acid sequence of SEQ ID NO: 3 replaced with cysteine residues such that at least one pair of cysteine residues creates a disulfide bond not found in wild type FVIII;wherein the rFVIII formulation has a pH in a range of from about pH 6.0 to about pH 7.5.2. The rFVIII formulation of further comprising:(a) a range of from about 10 mM to about 50 mM histidine;(b) a range of from about 10 mM to about 100 mM of a sugar or sugar alcohol; and(c) a range of from about 150 mM to about 400 mM glycine.3. A rFVIII formulation comprising:(a) a range of from 10 mM to 100 mM MOPS;(b) a range of from 0.5% to 10% by weight of a sugar or a sugar alcohol;(c) a range of from 0.5 mM to 20 mM of a divalent cation;(d) a range of from 10 mM to 100 mM sodium chloride or potassium chloride;(e) a range of from 50 to 150 ppm of a non-ionic surfactant; and(f) a range of from about 1000 IU/ml to about 1500 IU/ml of rFVIII;wherein the rFVIII formulation contains less than 5.0% by weight of components other than rFVIII having primary or secondary amine groups.4. The rFVIII formulation of that is essentially free of histidine and glycine.5. A method for the covalent conjugation of rFVIII to a biocompatible polymer comprising:{'claim-ref': {'@idref': 'CLM-00003', 'claim 3'}, '(a) obtaining the rFVIII formulation of ;'}(b) adding a functionalized polymer to create a reaction mixture, wherein the polymer is ...

PHARMACEUTICAL COMPOSITION 271

The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament; and to processes for the preparation of said compositions. 1. A pharmaceutical composition comprising a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide , and a carrier matrix , wherein the carrier matrix consists essentially of one or more pharmaceutically acceptable carriers selected from the following groups:(a) d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS); and(b) polyglycolised glycerides; andwherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the carrier matrix; andwherein the pharmaceutical composition is for oral administration.2. A pharmaceutical composition according to claim 1 , wherein the polyglycolised glycerides are Lauroyl Macrogol-32 Glycerides.3. A pharmaceutical composition according to claim 2 , wherein the carrier matrix is a mixture of d-alpha-tocopheryl polyethylene glycol 1000 succinate and Lauroyl Macrogol-32 Glycerides and wherein the Lauroyl Macrogol-32 Glycerides are present in an amount to make up approximately 30-55% by weight of the carrier matrix component of the composition.4. A pharmaceutical composition according to claim 1 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate.5. A pharmaceutical composition according to claim 4 , wherein the d-alpha-tocopheryl polyethylene glycol 1000 succinate is present in an amount to make up approximately 65 to 95% by weight of the composition.6. A pharmaceutical composition according claim 1 , wherein greater than 90% by weight ...

Stable, concentrated radionuclide complex solutions

The present invention relates to radionuclide complex solutions of high concentration and of high chemical stability, that allows their use as drug product for diagnostic and/or therapeutic purposes. The stability of the drug product is achieved by at least one stabilizer against radiolytic degradation. The use of two stabilizers introduced during the manufacturing process at different stages was found to be of particular advantage. 1. A pharmaceutical aqueous solution comprising: [{'sup': '177', '(ai) the radionuclide Lu (Lutetium-177), and'}, '(aii) a somatostatin receptor binding peptide linked to the chelating agent DOTA; and, '(a) a complex formed by'}(b) at least two different stabilizers against radiolytic degradation; said radionuclide is present in a concentration that it provides a volumetric radioactivity of from 250 to 500 MBq/mL; and', 'said stabilizers are present in a total concentration of from 0.2 to 20.0 mg/mL., 'wherein'}2. The pharmaceutical aqueous solution according to claim 1 , (bi) gentisic acid or a salt thereof; and', '(bii) ascorbic acid or a salt thereof., 'wherein said component (b) comprises the stabilizers3. The pharmaceutical aqueous solution according to claim 2 , (bi) gentisic acid is present in a concentration of from 0.5 to 2 mg/mL, preferably from 0.5 to 1 mg/mL; and', '(bii) ascorbic acid is present in a concentration of from 2.0 to 5.0 mg/mL., 'wherein'}4. The pharmaceutical aqueous solution according to claim 3 , further comprising:(c) diethylentriaminepentaacetic acid (DTPA) or a salt thereof in a concentration of from 0.01 to 0.10 mg/mL.5. The pharmaceutical aqueous solution according to or claim 3 , further comprising:(d) an acetate buffer composed of:(di) acetic acid in a concentration of from 0.3 to 0.7 mg/mL; and(dii) sodium acetate in a concentration from 0.4 to 0.9 mg/mL;preferably said acetate buffer provides for a pH of from 4.5 to 6.0, preferably from 5.0 to 5.5.6. The pharmaceutical aqueous solution according to ...

Stable, concentrated radionuclide complex solutions

The present invention relates to radionuclide complex solutions of high concentration and of high chemical stability, that allows their use as drug product for diagnostic and/or therapeutic purposes. The stability of the drug product is achieved by at least one stabilizer against radiolytic degradation. The use of two stabilizers introduced during the manufacturing process at different stages was found to be of particular advantage. 1. A pharmaceutical aqueous solution comprising: [{'sup': '177', '(ai) the radionuclide Lu (Lutetium-177), and'}, '(aii) a somatostatin receptor binding peptide linked to the chelating agent DOTA; and, '(a) a complex formed by'} (bi) gentisic acid or a salt thereof; and', '(bii) ascorbic acid or a salt thereof;, '(b) at least two different stabilizers against radiolytic degradation comprising'} said radionuclide is present in a concentration that it provides a volumetric radioactivity of from 250 to 500 MBq/mL;', 'said stabilizers are present in a total concentration of from 1.0 to 5.0 mg/mL; and', 'the pharmaceutical aqueous solution is substantially free of ethanol, and the radiochemical purity (determined by HPLC) of the solution is maintained at ≥95% for at least 72 h when stored at 25° C., 'wherein'}2. A pharmaceutical aqueous solution comprising: [{'sup': '177', '(ai) the radionuclide Lu (Lutetium-177), and'}, '(aii) a somatostatin receptor binding peptide linked to the chelating agent DOTA; and, '(a) a complex formed by'} (bi) gentisic acid or a salt thereof as a first stabilizer; and', '(bii) ascorbic acid or a salt thereof as a second stabilizer;, '(b) stabilizers against radiolytic degradation consisting essentially of two stabilizers said radionuclide is present in a concentration that it provides a volumetric radioactivity of from 250 to 500 MBq/mL; and', 'said stabilizers are present in a total concentration of from 1.0 to 5.0 mg/mL., 'wherein'}3. The pharmaceutical aqueous solution according to claim 1 , '(bi) gentisic acid ...

FORMULATION OF ANTIBODY BASED DRUGS FOR TREATING LUNG CANCER BY INHALATION

The present invention relates to formulations and method of drug administration useful for treating lung cancer (in particular, non-small lung cancer) by administering a therapeutic antibody drug with a soft mist inhaler or by nebulization. 1. A liquid , propellant-free pharmaceutical preparation comprising: (a) an active substance; (b) a solvent; and (c) a pharmacologically acceptable excipient.2. The pharmaceutical preparation according to claim 1 , wherein the active substance is selected from the group consisting of Atezolizumab claim 1 , Nivolumab claim 1 , Pembrolizumab claim 1 , Durvalumab claim 1 , Avastin claim 1 , and any combination thereof.3. The pharmaceutical preparation according to claim 1 , wherein active substances is present in an amount of from about 1 mg/ml to about 100 mg/ml.4. The pharmaceutical preparation according to claim 1 , wherein the pharmacologically acceptable excipient is selected from the group consisting of L-Histidine claim 1 , L-Histidine hydrochloride monohydrate claim 1 , sodium citrate dihydrate claim 1 , polysorbate 80 claim 1 , polysorbate 20 claim 1 , sodium chloride claim 1 , sodium phosphate claim 1 , mannitol claim 1 , pentetic acid claim 1 , α claim 1 , α-trehalose dehydrate claim 1 , sucrose claim 1 , and any combination thereof.5. The pharmaceutical preparation according to claim 1 , comprising about 1 mg/ml to about 25 mg/ml Pembrolizumab claim 1 , about 1 mM to about 10 mM of L-histidine claim 1 , about 50 mM to about 200 mM sucrose claim 1 , and about 0.05 mM to about 0.15 mM polysorbate 80 claim 1 , wherein the pharmaceutical preparation has a pH of about 5.5 to about 5.7 claim 1 , and the pharmaceutical preparation is stable for at least 12 months when stored under refrigerated conditions at 2° C. to 8° C.6. The pharmaceutical preparation according to claim 1 , comprising about 10 mg/ml to about 65 mg/ml of Atezolizumab claim 1 , about 50 mM to about 450 mM of L-histidine claim 1 , about 500 mM to about 2450 mM ...

NANOPARTICLES FOR IMAGING AND TREATING CHLAMYDIAL INFECTION

Compositions of nanoparticles and targeting moieties for imaging and treating Chlamydial infection are provided, including nanoparticles conjugated to folic acid and comprising at least one antibiotic effective against 15-. (canceled)6ChlamydiaChlamydia. A composition comprising nanoparticles conjugated with folic acid , wherein said particles comprise a first antibiotic in a form and in a dosage suitable for treatment of a persistent intracellular infection wherein of said infection lack ftsK transcription or lack ftsK and ftsW transcription at the time the composition is administered.7Chlamydia. The composition of comprising nanoparticles conjugated with folic acid claim 6 , wherein said particles further comprise one or more other antibiotic(s) active against persistent intracellular infection.8. The composition of claim 6 , wherein said first antibiotic is selected from the group consisting of azithromycin claim 6 , amoxicillin claim 6 , rifampicin claim 6 , erythromycin claim 6 , erythromycin ethylsuccinate claim 6 , ofloxacin claim 6 , levofloxacin doxycycline claim 6 , and tetracycline.9. The composition of claim 7 , wherein said one or more other antibiotics is selected from the group consisting of azithromycin claim 7 , amoxicillin claim 7 , rifampicin claim 7 , erythromycin claim 7 , erythromycin ethylsuccinate claim 7 , ofloxacin claim 7 , levofloxacin doxycycline claim 7 , and tetracycline claim 7 , and said one or more other antibiotics is different from said first antibiotic.1012-. (canceled)13ChlamydiaChlamydia. A composition for imaging persistent intracellular infection in a cell claim 7 , comprising nanoparticles conjugated with folic acid claim 7 , wherein said nanoparticles further comprise at least one detectably labeled moiety and wherein of said infection lack ftsK transcription or lack ftsK and ftsW transcription at the time of imaging.14. The composition of claim 13 , wherein said nanoparticles are fluorescently labeled. This application is ...

Pharmaceutical Composition Of A Potent HCV Inhibitor For Oral Administration

A pharmaceutical composition of the following Compound (1), a potent hepatitis C viral (HCV) inhibitor, or a pharmaceutically acceptable salt thereof, for oral administration. 2. A pharmaceutical composition in accordance with claim 1 , wherein the surfactant has a hydrophilic/lipophilic balance of greater than 10.3. A pharmaceutical composition in accordance with claim 1 , wherein the surfactant is Vitamin E TPGS claim 1 , a polyethoxylated castor oil claim 1 , a polyoxyl hydrogenated castor oil claim 1 , a polyoxyethylene sorbitan fatty ester claim 1 , a caprylocaproyl macrogolglyceride or a mixture thereof.4. A pharmaceutical composition in accordance with claim 1 , wherein the pharmaceutically acceptable solvent is propylene glycol claim 1 , polypropylene glycol claim 1 , polyethylene glycol claim 1 , glycerol claim 1 , ethanol claim 1 , triacetin claim 1 , dimethyl isosorbide claim 1 , glycofurol claim 1 , propylene carbonate claim 1 , water claim 1 , dimethyl acetamide or mixtures thereof.5. A pharmaceutical composition in accordance with claim 1 , wherein the solvent is a mixture of water claim 1 , polyethylene glycol having a mean molecular weight of greater than 300 but lower than 600 and propylene glycol.6. A pharmaceutical composition in accordance with claim 1 , wherein the pharmaceutical composition does not contain any lipid.7. A pharmaceutical composition in accordance with claim 1 , wherein the pharmaceutical composition is substantially free of propylene glycol.8. A pharmaceutical composition in accordance with claim 1 , wherein the pharmaceutical composition is substantially free of an amine.9. A pharmaceutical composition in accordance with wherein the Compound (1) or pharmaceutically acceptable salt thereof comprises from 1% to 40% by weight of the total composition.10. A pharmaceutical composition in accordance with wherein the surfactant comprises 2 to 50% by weight of the total composition.11. A pharmaceutical composition in accordance with ...

LONG ACTING COMPOSITIONS

The present invention relates to a long-acting composition for the treatment of an animal in need thereof wherein the composition includes a therapeutically effective amount of a bioactive agent, characterised in that the composition includes a non-aqueous carrier and a solvent system comprising castor oil and at least one cyclic amide. 1. A long-acting veterinary pharmaceutical composition comprising a therapeutically effective amount of a bioactive agent , a non-aqueous carrier , and a solvent system comprising castor oil and at least one cyclic amide.2. The composition as claimed in wherein the cyclic amide is a pyrrolidone.3. The composition as claimed in wherein the cyclic amide is N-Methylpyrrolidone (NMP).4. The composition as claimed in wherein the cyclic amide is present in an amount between 1-50% w/v.5. The composition as claimed in wherein the castor oil is present in an amount between 1-20% w/v.6. The composition as claimed in wherein the composition is an injectable composition.7. The composition as claimed in wherein the bioactive agent is an anthelmintic compound.8. The composition as claimed in wherein the anthelmintic is selected from the group consisting of avermectin claim 7 , moxidectin claim 7 , milbemycin claim 7 , ivermectin claim 7 , abamectin claim 7 , doramectin claim 7 , epinomectin and selamectin.9. The composition as claimed in wherein the anthelmintic compound is present in an amount between 0.005 to 5% w/v.10. The composition as claimed in wherein the anthelmintic compound is moxidectin.11. The composition as claimed in wherein the non-aqueous carrier comprises an oil selected from the group consisting of canola oil claim 1 , corn oil claim 1 , cottonseed oil claim 1 , olive oil claim 1 , peanut oil claim 1 , sesame oil claim 1 , soyabean oil claim 1 , safflower oil claim 1 , coconut oil claim 1 , sunflower oil claim 1 , palm oil claim 1 , monoglyceride claim 1 , diglyceride and triglyceride medium chain succinic acid triglyceride.12. ...

CONCENTRATED, INHALABLE CIPROFLOXACIN FORMULATION

A concentrated inhalable formulation of an antibiotic drug such as ciprofloxacin is disclosed. The antibiotic is formulated with sodium acetate and liposome which incorporate antibiotic. The formulation is aerosolized and inhaled for treatment of respiratory tract infections and other medical conditions. 127.-. (canceled)28. A formulation , comprising:free unencapsulated ciprofloxacin;a pharmaceutically acceptable excipient; andliposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar, have an average particle size of 1 nanometer to 10 microns, and comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC);wherein the formulation is formulated for aerosolized delivery such that the liposomes maintain integrity when aerosolized, and provide a ciprofloxacin release rate of 0.5% to 20% per hour.29. The formulation of claim 28 , wherein the liposomes have a diameter in a range from 20 nanometers to 1 micron.30. The formulation of claim 29 , wherein the free ciprofloxacin comprises between about 1 and about 75% of the total free and liposome-encapsulated ciprofloxacin.31. The formulation of claim 28 , wherein the liposomes provide a ciprofloxacin release rate of 2% to 10% per hour.32. The formulation of claim 28 , further comprising:an isotonic histidine buffer.33. The formulation of claim 28 , wherein the formulation pH is 6.0.34. The formulation of claim 28 , wherein the formulation osmolarity is 300 mOsm/kg.35. The formulation of claim 28 , wherein the formulation is in an isotonic histidine buffer at pH 6.0 claim 28 , and an osmolarity of 300 mOsm/kg.36. A formulation for aerosolized delivery claim 28 , comprising:free unencapsulated ciprofloxacin;a pharmaceutically acceptable excipient; andliposome-encapsulated ciprofloxacin wherein the liposomes comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC), are unilamellar and wherein the liposomes are comprised of cholesterol and hydrogenated soy phosphatidyl-choline (HSPC), and ...

LYOPHILIZED FORMULATION OF TAT-NR2B9C

The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. Such formulations are stable at room temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital. 1. A prelyophilized formulation comprising TAT-NR2B9c (SEQ ID NO:6) , histidine and trehalose at a pH of 6-7.2. The prelyophilized formulation of claim 1 , wherein the TAT-NR2B9c is at a concentration of 70-120 mg/ml claim 1 , the histidine is at a concentration of 15-100 mM claim 1 , and the trehalose is at a concentration of 80-160 mM.3. The prelyophilized formulation of claim 1 , wherein the TAT-NR2B9c is at a concentration of 70-120 mg/ml claim 1 , the histidine is at a concentration of 20-100 mM claim 1 , and the trehalose is at a concentration of 100-140 mM.4. The prelyophilized formulation of claim 1 , wherein the Tat-NR2B9c is at a concentration of 70-120 mg/ml claim 1 , the concentration of histidine 20-50 mM claim 1 , and the concentration of trehalose is 100-140 mM.5. The prelyophilized formulation of claim 1 , wherein the concentration of histidine is 20 mM and the concentration of trehalose is 100-200 mM claim 1 , preferably 120 mM and the concentration of TAT-NR2B9c is 90 mg/ml.6. A lyophilized formulation prepared by lyophilizing the prelyophilized formulation of any of -.7. A reconstituted formulation prepared by combining the lyophilized formulation of with an aqueous solution.8. The reconstituted formulation of claim 7 , wherein the aqueous solution is water or normal saline.9. The reconstituted formulation of claim 7 , wherein the volume of the reconstituted formulation is 3-6 times the volume of the prelyophilized formulation.10. A reconstituted formulation comprising TAT-NR2B9c at concentration of 15-25 ...

AMPHIPHILIC DERIVATIVES OF TRIAZAMACROCYCLIC COMPOUNDS, PRODUCTS AND COMPOSITIONS INCLUDING SAME, AND SYNTHESIS METHODS AND USES THEREOF

The invention relates to amphiphilic derivatives of a triazamacrocyclic compound, as well as to said derivatives as active molecule transporters. The invention also relates to a nanodrug including at least one amphiphilic derivative of a triazamacrocyclic compound and at least one active molecule of a protein such as an antibody, in particular for the treatment of autoimmune diseases or for the treatment of cancer. 3. The nanodrug according to wherein the compound is selected from the group consisting of:1,4-didodecyl-N(7′-carboxymethyl-1′,4′,7′-triazacyclononane)-L-aspartate;1,5-didodecyl-N(7′-carboxymethyl-1′,4′,7-triazacyclononane)-L-glutamate;1,4-ditetradecyl-N(7′-carboxymethyl-1′,4′,7′-tri-azacyclononane)-L-aspartate;1,5-ditetradecyl-(7′-carboxymethyl-1′,4′,7′-tri-azacyclononane)-L-glutamate;1,4-dihexadecyl-N(7′-carboxymethyl-1′,4′,7′-tri-azacyclononane)-L-aspartate;1,5-dihexadecyl-N(7′-carboxymethyl-1′,4′,7′-tri-azacyclononane)-L-glutamate;1,4-dioctadecyl-N(7′-carboxymethyl-1′,4′,7′-tri-azacyclononane)-L-aspartate;1,5-dioctadecyl-N(7′-carboxymethyl-1′,4′,7′-tri-azacyclononane)-L-glutamate;1,4-dioleyl-N(7′-carboxymethyl-1′,4′,7′-triaza-cyclononane)-L-aspartate;1,5-dioleyl-N(7′-carboxymethyl-1′,4′,7′-triaza-cyclononane)-L-glutamate;1,4-dioleyl-N(1′,4′-dibetainyl-7′-carboxymethyl-1′,4′,7′-triaza-cyclononane)-L-aspartate;1,5-dioleyl-N(1′,4′-dibetainyl-7′-carboxymethyl-1′,4′,7′-triaza-cyclononane)-L-glutamate;1,4-dioctadecyl-7-ornithyl-1,4,7-triazacyclononane;1,4-dioleyl-7-ornithyl-1,4,7-triazacyclononane;1,4-dioctadecyl-7-arginyl-1,4,7-triazacyclononane;1,4-dioleyl-7-arginyl-1,4,7-triazacyclononane;1,4-dioctadecyl-7-lysyl-1,4,7-triazacyclononane;1,4-dioleyl-7-lysyl-1,4,7-triazacyclononane;1,4-dioleyl-N(1′,4′-ornithyl-1′,4′,7′-triaza-cyclononane-7′-carboxymethyl)-L-aspartate;1,5-dioleyl-N(1′,4′-ornithyl-1′,4′,7′-triaza-cyclononane-7′-carboxymethyl)-L-glutamate;1,4-dioleyl-N(1′,4′-arginyl-1′,4′,7′-triaza-cyclononane-7′-carboxymethyl)-L-aspartate; and1,5-dioleyl-N(1 ...

DEHYDRATED HYDROGEL INCLUSION COMPLEX

The invention provides a controlled release biodegradable polymer formulation adapted for administering bioactive agents, such as therapeutic proteins, to a patient through implantation of a bolus that forms a depot within the patient's body tissues. The formulation includes a dehydrated inclusion complex of the bioactive agent within a hydrogel. A method of forming the inventive formulation is also provided, as well as a method for using the formulation in the treatment of a malcondition in a patient in need thereof. 1. A formulation comprising (i) a dehydrated inclusion complex comprising a bioactive agent within a hydrogel; (ii) a biodegradable polymer; and (iii) an organic solvent.2. A method of treating a malcondition in a patient in need thereof claim 1 , the mehtod comprising administering a therapeutically effective amount of the formulation of to the patient to treat the malcondition.3. The method of claim 2 , wherein the bioactive agent is a protein or a compound having a molecular weight of about 1 claim 2 ,000 Daltons or less.4. The method of claim 2 , wherein the biodegradable polymer comprises a poly(lactide-glycolide) copolymer; and wherein the organic solvent comprises N-methylpyrrolidone claim 2 , dimethylacetamide claim 2 , dimethylformamide claim 2 , dimethyl sulfoxide claim 2 , a polyethyleneglycol claim 2 , or a combination of two or more thereof.5. The method of claim 2 , wherein the hydrogel comprises a polyalkyleneglycol diacrylate.6. A kit comprising:a first container comprising a biodegradable polymer and an organic solvent;(ii) a second container comprising a dehydrated inclusion complex which comprises a bioactive agent within a hydrogel; and(iii) instructions for use.7. The kit of claim 6 , wherein the first container is a syringe; and wherein the second container is syringe.8. The kit of claim 6 , wherein the bioactive agent is a protein or a compound having a molecular weight of about 1 claim 6 ,000 Daltons or less.9. The kit of claim ...

COMPOSITION COMPRISING DUTASTERIDE

A composition of the present invention relates to a composition comprising dutasteride, wherein said composition may maintain a constant concentration of dutasteride in blood and continuously release a drug thereof for a long period of time while not precipitating dutasteride in a solid form when being administered into the human body, and also has an excellent safety without causing local irritations in an administration site. 1. A composition comprising dutasteride , optical isomers thereof or pharmaceutically acceptable salts thereof , lipid and an organic solvent.2camellia. The composition according to claim 1 , wherein lipid is selected from the group consisting of tocopherol claim 1 , tocopherol acetate claim 1 , castor oil claim 1 , safflower oil claim 1 , sesame oil claim 1 , olive oil claim 1 , almond oil claim 1 , oil claim 1 , corn oil claim 1 , cottonseed oil claim 1 , soybean oil claim 1 , medium chain triglyceride (MCT) claim 1 , pharmaceutically acceptable salts thereof and mixtures thereof.3. The composition according to claim 1 , wherein lipid is selected from the group consisting of tocopherol claim 1 , tocopherol acetate claim 1 , pharmaceutically acceptable salts thereof and mixtures thereof.4. The composition according to claim 1 , wherein the organic solvent is selected from the group consisting of N-methyl-2-pyrrolidone claim 1 , dimethyl sulfoxide claim 1 , benzyl benzoate claim 1 , benzyl alcohol claim 1 , dimethylacetamide claim 1 , ethanol and mixtures thereof.5. The composition according to claim 1 , wherein the organic solvent is selected from the group consisting of N-methyl-2-pyrrolidone claim 1 , dimethyl sulfoxide claim 1 , benzyl benzoate and mixtures thereof.6. The composition according to claim 1 , wherein said composition is for treating benign prostatic hyperplasia or androgenetic alopecia.7. The composition according to claim 1 , wherein said composition is administered through an injection.8. The composition according to claim ...

PHARMACOTHERAPY FOR PREVENTING OR TREATING GLAUCOMA

A pharmacotherapy is provided for preventing glaucoma or preventing or treating ocular hypertension, the pharmacotherapy providing potent intraocular pressure-lowering action with fast-acting properties and prolonged duration. A combination of (S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or a salt thereof, or a solvate of (S)−)-1-(4-fluoro-S-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or the salt thereof and an αagonist for preventing or treating glaucoma. 1. A composition , comprising:(S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or a salt thereof, or a solvate of (S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or the salt; and{'sub': '2', 'an αagonist, which is brimonidine or a salt thereof, or a solvate of brimonidine or the salt.'}23-. (canceled)4. A kit comprising:a first agent comprising (S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or a salt thereof, or a solvate of (S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or the salt;{'sub': '2', 'a second agent comprising an αagonist, which is brimonidine or a salt thereof, or a solvate of brimonidine or the salt; and'}instructions for administering the first and second agents together.59-. (canceled)10. A method for treating glaucoma , the method comprising:{'sub': '2', 'administering to a subject in need thereof (S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or a salt thereof, or a solvate of (S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine or the salt thereof in combination with and an αagonist, which is brimonidine or a salt thereof, or a solvate of brimonidine or the salt, simultaneously or separately at an interval of less than 30 minutes.'}11. A method for treating ocular hypertension , the method comprising:{'sub': '2', 'administering to a subject in need thereof (S)-(−)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4- ...

MICROPARTICLES

The invention provides a blood substitute product comprising haemoglobin and a self-assembled microparticle having an acid having two or more acid groups and an organic base in a solvent. The particle is of micron scale. The microparticle may be obtained by contacting a bis-acid and organic base in a hydrophilic solvent, wherein the acid is insoluble or sparingly soluble in the hydrophilic solvent and the organic base is soluble in a hydrophilic solvent. 1. A blood substitute product comprising mammalian haemoglobin and a self-assembled microparticle.2. A blood substitute product according to in which the microparticle comprises an acid having two or more acid groups and an organic base which is soluble in a hydrophilic solvent.3. A blood substitute product according to or in which the blood substitute product comprises a stable polymerized haemoglobin solution claim 1 , comprising mammalian haemoglobin cross-linked with a self-assembled microparticle.4. A blood substitute product according to any one of the preceding claims in which the microparticle has a particle size of 0.5 to 10 microns claim 1 , preferably 1 to 5 microns.5. A blood substitute product according to any one of the preceding claims in which the molar ratio of acid groups to basic groups in the acid and base is from 0.6 to 1.4:1.6. A blood substitute product according to any one of the preceding claims in which the molar ratio of acid groups to basic groups is from 0.7 to 1.3:1.7. A blood substitute product according to any one of the preceding claims in which the microparticle comprises an acid having two or more acid groups and an organic base obtainable by a process comprising contacting the bis-acid and organic base in a hydrophilic solvent claim 1 , wherein the acid is insoluble or sparingly soluble in the hydrophilic solvent and the organic base is soluble in a hydrophilic solvent.8. A blood substitute product according to in which the solvent comprises an aqueous solution.9. A blood ...

DRY POWDER INHALER AND SYSTEM FOR DRUG DELIVERY

A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and/or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable. 1. A fumaryl diketopiperazine (FDKP) composition comprising a trans isomer content of about 45% to about 59%.2. The FDKP composition according to claim 1 , wherein said trans isomer content is from about 49% to about 58%.3. The FDKP composition according to claim 1 , wherein said trans isomer content is from about 53% to about 56%.4. Microparticles comprising the FDKP composition of .5. The FDKP microparticles of wherein the FDKP microparticles comprise an active agent.6. The FDKP microparticles of wherein the active agent comprises at least one of a naturally occurring claim 5 , recombinant or synthetic protein claim 5 , polypeptide claim 5 , or peptide; a nucleic acid; an organic macromolecule; a synthetic organic compound; a polysaccharide or other sugar; a fatty acid; a lipids; or an antibody or fragment thereof.7. The FDKP microparticles of claim 6 , wherein the active agent comprises a protein claim 6 , polypeptide claim 6 , or peptide.8. The FDKP microparticles of claim 6 , wherein the active agent comprises an antibody or fragment thereof.9. The FDKP microparticles of wherein the active agent comprises at least one of a vasoactive ...

NANOPARTICLES OF A METAL AND A NUCLEOBASE

A process for making nanoparticles of biocompatible materials is described, wherein an aqueous reaction mixture comprising a metal ion, a nucleobase, an oxidant, and water, is provided along with temperature conditions to directly form within the reaction mixture, a stable dispersion of nanoparticles. Biocompatible nanoparticles comprised of cerium or iron as the metal ion, and a purine and/or a pyrimidine as the nucleobase, are described. 1. A process of making nanoparticles , comprising:(a) forming a reaction mixture comprising a metal ion, a nucleobase, an oxidant, and water; and(b) forming in the reaction mixture a dispersion of nanoparticles.2. The process according to claim 1 , further comprising the step of heating or cooling said reaction mixture to a temperature in the range of about 0° C. to about 100° C.3. The process according to claim 1 , wherein said metal ion comprises cerium or iron.4. The process according to claim 1 , wherein said nanoparticles comprise a metal oxide phase.5. The process according to claim 4 , wherein said metal oxide phase comprises a cerium oxide phase or an iron oxide phase.6. The process according to claim 1 , wherein said nucleobase is a purine.7. The process according to claim 6 , wherein said purine is adenine or caffeine.8. The process according to claim 1 , wherein said nucleobase is a pyrimidine.9. The process according to claim 8 , wherein said pyrimidine is cytosine claim 8 , thymine or uracil.10. The process according to claim 1 , wherein said nucleobase is a mixture of a purine and a pyrimidine.11. The process according to claim 10 , wherein said mixture comprises adenine and thymine.12. The process according to claim 1 , wherein said oxidant is hydrogen peroxide.13. A nanoparticle comprising a metal and a nucleobase.14. The nanoparticle of claim 13 , wherein said metal comprises cerium or iron.15. The nanoparticle of claim 13 , wherein said metal comprises a metal oxide.16. The nanoparticle of claim 15 , wherein said ...

TAMPER RESISTANT FORMULATION OF EPHEDRINE AND ITS DERIVATIVES

A pharmaceutical dosage form having a breaking strength of at least 300 N and comprising an ephedrine component selected from the group consisting of ephedrine, pseudoephedrine and the physiologically acceptable salts thereof, wherein the weight content of the ephedrine component is within the range of from 0.1 to 60 wt.-%, relative to the total weight of the pharmaceutical dosage form. 1. A pharmaceutical dosage form having a breaking strength of at least 300 N and comprising an ephedrine component selected from the group consisting of ephedrine , pseudoephedrine and the physiologically acceptable salts thereof , wherein the weight content of the ephedrine component is within the range of from 0.1 to 60 wt.-% , relative to the total weight of the pharmaceutical dosage form.2. The pharmaceutical dosage form according to claim 1 , wherein the ephedrine component comprises pseudoephedrine hydrochloride or pseudoephedrine sulfate.3. The pharmaceutical dosage form according to claim 1 , wherein the weight content of the ephedrine component is within the range of from 10 to 50 wt.-% claim 1 , relative to the total weight of the pharmaceutical dosage form.4. (canceled)5. The pharmaceutical dosage form according to claim 1 , which comprises a polyalkylene oxide.6. (canceled)7. The pharmaceutical dosage form according to claim 5 , wherein the polyalkylene oxide has a weight average molecular weight of at least 200 claim 5 ,000 g/mol.8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. The pharmaceutical dosage form according to claim 1 , which comprises an antioxidant.17. The pharmaceutical dosage form according to claim 16 , wherein the antioxidant is selected from the group consisting of ascorbic acid claim 16 , salts of ascorbic acid claim 16 , butylhydroxyanisole claim 16 , butylhydroxytoluene claim 16 , monothioglycerol claim 16 , phosphorous acid claim 16 , α-tocopherol claim 16 , α-tocopheryl acetate claim ...

DEEP SEA WATER EXTRACT AND USE THEREOF

The present invention provides a deep sea water extract and a method for inhibiting the proliferation of strains using the deep sea water extract, wherein the deep sea water extract has an organic component with a molecular weight of to to and to . The deep sea water extract of the present invention can be applied in the prevention and treatment of infection. 1Helicobacter pylori. A method of inhibiting infection , comprising administering an effective amount of a deep sea water extract to a subject in need thereof , wherein the deep sea water extract is obtained from a deep sea water by a manufacturing method , the manufacturing method is a combination of reverse osmosis (RO) and electrodialysis (ED) , or a nanofiler method; andwherein the deep sea water extract is characterized to contain an organic component, and the organic component is selected from the group consisting of a molecular weight of 685 to 690, 733 to 738 and 1,070 to 1,075.2. The method according to claim 1 , wherein the manufacturing method further comprises a method selected from the group consisting of gel filtration claim 1 , dichloromethane (DCM) extraction claim 1 , acetone extraction and chloroform extraction.3. The method according to claim 1 , wherein the organic component has a preferable molecular weight of 1 claim 1 ,070 to 1 claim 1 ,075.4. The method according to claim 1 , wherein the deep sea water is obtained at a depth greater than 200 m under the surface of the sea.5. The method according to claim 1 , wherein the deep sea water extract further comprises an antioxidant to delay the degradation of the organic component claim 1 , and the antioxidant is quercetin claim 1 , (−)-epigallocatechin-3-gallate (EGCG) or H.6. The method according to claim 1 , wherein the hardness of the deep sea water extract is 2 claim 1 ,400 ppm to 4 claim 1 ,800 ppm.7. The method according to claim 1 , wherein the deep sea water extract is obtained from pasteurization or sterile filtration.8Helicobacter ...

PHENYL C-GLUCOSIDE DERIVATIVE CONTAINING DEOXYGLUCOSE STRUCTURE, PREPARATION METHOD AND USE THEREOF

The present invention provides a phenyl C-glucoside derivative containing a deoxyglucose structure as represented by formula I, preparation method thereof, a pharmaceutical composition comprising the same, and uses thereof in the preparation of medicaments for treating diabetes, wherein substituents R-Rare as defined in the specification. The present invention also provides a method for synthesizing the phenyl C-glucoside derivative containing a deoxyglucose structure and an intermediate product. The method has advantages of being simple to manage and of low cost, which is suitable for large-scale industrial production. The present invention further provides a cocrystal of (1S)-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-1,6-dideoxy-D-glucose and L-proline, and preparation method and uses thereof. 112-. (canceled)14. The method according to claim 13 , wherein removing the iodine in step (1) is performed under the conditions selected from the group consisting of: (a) n-BuSnH/AIBN claim 13 , wherein AIBN is azodiisobutyronitrile; (b) TMSSiH/AIBN; (c) LiAlH; and (d) catalytic hydrogenation claim 13 , wherein the catalyst is selected from Pd/C or Pd(OH) claim 13 , the hydrogen source is selected from hydrogen gas claim 13 , formic acid claim 13 , ammonium formate claim 13 , or cyclohexene.1517-. (canceled)2122-. (canceled)23. A cocrystal of (1S)-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-1 claim 13 ,6-dideoxy-D-glucose and L-proline claim 13 , characterized in that claim 13 , the Powder X-ray Diffraction represented by 2θ angle has diffraction peaks near 4.74 claim 13 , 7.32 claim 13 , 9.74 claim 13 , 14.28 claim 13 , 16.46 claim 13 , 17.60 claim 13 , 18.70 claim 13 , 19.52 claim 13 , 20.62 claim 13 , 21.58 claim 13 , 23.02 claim 13 , 23.50 claim 13 , 26.30 claim 13 , and 27.90.24. The cocrystal according to claim 23 , wherein claim 23 , the Powder X-ray Diffraction of the cocrystal has diffraction peaks near the positions where the interplanar spacing d values are 18.63 claim 23 ...

Stabilized Formulations Containing Anti-PCSK9 Antibodies

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human proprotein convertase subtilisin/kexin type 9 (PCSK9). The formulations may contain, in addition to an anti-PCSK9 antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months. 113.-. (canceled)14. A liquid pharmaceutical formulation consisting of:(a) 50±7.5 mg/mL to 250±37.5 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;(b) 5±0.75 mM to 10±1.5 mM histidine, pH 6.0±0.3;(c) 0.01±0.0015% w/v polysorbate 20; and(d) 10±1.5% w/v sucrose.15. The liquid pharmaceutical formulation of claim 14 , wherein the formulation comprises 50 mg/mL of the antibody or antigen-binding fragment thereof.16. The liquid pharmaceutical formulation of claim 14 , wherein the formulation comprises 75 mg/mL of the antibody or antigen-binding fragment thereof.17. The liquid pharmaceutical formulation of claim 14 , wherein the formulation comprises 100 mg/mL of the antibody or antigen-binding fragment thereof.18. The liquid pharmaceutical formulation of claim 14 , wherein the formulation comprises 150 mg/mL of the antibody or antigen-binding fragment thereof.19. The liquid pharmaceutical formulation of claim 14 , wherein the formulation comprises 175 mg/mL of the antibody or antigen-binding fragment thereof.20. A liquid pharmaceutical formulation consisting of:(a) 75 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding ...

NUCLEIC ACID-CONTAINING LIPID PARTICLES AND RELATED METHODS

Lipid particles containing a nucleic acid, devices and methods for making the lipid particles, and methods for using the lipid particles. 1. A method for making lipid particles with encapsulated nucleic acid , comprising:(a) introducing a first stream comprising a nucleic acid in a first solvent into a microfluidic device; wherein the device has a first region adapted for flowing one or more streams introduced into the device and a second region for mixing the contents of the one or more streams with a microfluidic mixer;(b) introducing a second stream comprising lipid particle-forming materials in a second solvent into the device to provide first and second streams flowing under laminar flow conditions, wherein the lipid particle-forming materials comprise a cationic lipid, and wherein the first and second solvents are not the same;(c) flowing the one or more first streams and the one or more second streams from the first region of the device into the second region of the device; and(d) mixing the one or more first streams and the one or more second streams in the second region of the device to provide a third stream comprising lipid particles with encapsulated nucleic acid,wherein the lipid particles with encapsulated nucleic acid comprise:(i) a substantially solid core consisting of nucleic acid, cationic lipid, and optionally second lipids; and(ii) PEG-lipid surrounding the core,wherein the lipid particle has a core and a periphery, the core has an area-averaged electron density that is not less than 20% of the maximum density of the periphery as measured by cryo transmission electron microscopy, and{'sup': '31', 'wherein the P nuclear magnetic resonance spectrum of the lipid particle measured in solution after treatment with 150 mM ammonium acetate does not exhibit a resonance due to the nucleic acid.'}2. The method of claim 1 , wherein the nucleic acid is encapsulated in the lipid particle with an efficiency of from 90 to 100%.3. The method of claim 1 , ...

PHARMACEUTICAL FORMULATIONS

A stable pharmaceutical formulation is provided that comprises a biologically active protein and an excipient selected from carnitine, creatine or creatinine. 1. A method for reducing the viscosity of a liquid pharmaceutical formulation comprising a therapeutic protein at a concentration of at least 70 mg/ml , comprising the step of combining the therapeutic protein with a viscosity-reducing concentration of an excipient selected from the group consisting of creatine , creatinine , carnitine and mixtures thereof.211-. (canceled)12. A method of preparing a lyophilized powder comprising the step of lyophilizing a pharmaceutical formulation of any of .13. A lyophilized powder comprising a therapeutic protein and an excipient selected from the group consisting of creatine claim 1 , creatinine claim 1 , carnitine and mixtures thereof claim 1 , wherein the excipient is present at a weight:weight concentration effective to reduce viscosity upon reconstitution with a diluent.14. A lyophilized powder of wherein the excipient is creatine claim 13 , creatinine or a mixture thereof claim 13 , present at a concentration of creatine/creatinine between about 4 ng per mg therapeutic protein to about 1.25 mg per mg therapeutic protein.15. A lyophilized powder of wherein the excipient is carnitine at a concentration between 2 μg to about 7 mg per mg therapeutic protein.16. A method for reconstituting a lyophilized powder of claim 13 , comprising the step of adding a sterile aqueous diluent.17. The method of wherein the therapeutic protein is an antibody.18. (canceled)19. The lyophilized powder of wherein the therapeutic protein is an antibody.20. The lyophilized powder of wherein the therapeutic protein is an antibody.21. The lyophilized powder of wherein the therapeutic protein is an antibody.22. A method for reconstituting the lyophilized powder of claim 14 , comprising the step of adding a sterile aqueous diluent.23. A method for reconstituting the lyophilized powder of claim 15 , ...

STABILIZED FORMULATIONS CONTAINING ANTI-PCSK9 ANTIBODIES

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human proprotein convertase subtilisin/kexin type 9 (PCSK9). The formulations may contain, in addition to an anti-PCSK9 antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months. 152-. (canceled)53. A pre-filled pen delivery device comprising a liquid pharmaceutical formulation , wherein the liquid pharmaceutical formulation consists of:(a) 50±7.5 mg/mL to 250±37.5 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;(b) 5±0.75 mM to 10±1.5 mM histidine, pH 6.0±0.3;(c) 0.01±0.0015% w/v polysorbate 20; and(d) 10±1.5% w/v sucrose.54. The pre-filled pen delivery device of claim 53 , wherein the pen delivery device is used to subcutaneously deliver the liquid pharmaceutical formulation.55. The pre-filled pen delivery device of claim 53 , wherein the pen delivery device is reusable.56. The pre-filled pen delivery device of claim 53 , wherein the pen delivery device is disposable.57. A pre-filled pen delivery device comprising a liquid pharmaceutical formulation claim 53 , wherein the liquid pharmaceutical formulation consists of:(a) 75 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;(b) 8±1.2 mM histidine, pH 6.0±0.3;(c) 0.01±0.0015% w/v polysorbate 20; ...

EXCIPIENT DRUG COMPOSITION

A excipient drug composition is disclosed. The excipient drug composition may include a vegetable cellulose or a fruit cellulose, an active ingredient and a genetically modified organism free starch. The vegetable cellulose or fruit cellulose may be derived from wood free vegetable pulp and the fruit cellulose is a wood pulp free cellulose. The genetically modified organism free starch may be selected from the group consisting of a genetically modified organism free rice starch, a genetically modified organism free potato starch or a genetically modified organism free pea starch. 1. An excipient drug composition , comprising:a vegetable cellulose or a fruit cellulose; andan active ingredient.2. The excipient drug composition according to claim 1 , wherein the vegetable cellulose is derived from wood free vegetable pulp.3. The excipient drug composition according to claim 1 , wherein the fruit cellulose is a wood pulp free cellulose.4. The excipient drug composition according to claim 1 , further comprising a genetically modified organism free starch.5. The excipient drug composition according to claim 1 , further comprising a vitamin E preservative or a vitamin C preservative.6. The excipient drug composition according to claim 1 , wherein the active ingredient is ibuprofen.7. The excipient drug composition according to claim 1 , wherein the active ingredient is acetaminophen.8. The excipient drug composition according to claim 1 , wherein the active ingredient is selected from the group consisting of acetaminophen and ibuprofen.9. The excipient drug composition according to claim 1 , wherein the active ingredient is selected from the group consisting of acetaminophen claim 1 , ibuprofen and phenylephrine.10. The excipient drug composition according to claim 1 , wherein the active ingredient is selected from the group consisting of acetaminophen claim 1 , ibuprofen and pseudoephedrine.11. The excipient drug composition according to claim 1 , wherein the active ...

SWEET FLAVOR MODIFIER

The present invention includes compounds having structural formula (I), or pharmaceutically acceptable salts, solvate, and/or ester thereof. These compounds are useful as sweet flavor modifiers. The present invention also includes compositions comprising the present compounds and methods of enhancing the sweet taste of ingestible compositions. Furthermore, the present invention provides methods for preparing the compounds. 2. The compound of claim 1 , wherein the Formula (I) is subject to the following provisos:{'sub': '2', 'sup': 7', '7', '1', '2', '1', '2', '1', '2, '(a) when D is substituted phenyl; B is hydrogen; C is —COR; Ris hydrogen or alkyl; A is —NRR; and one of Rand Ris hydrogen; then the other of Rand Ris not substituted arylalkyl; and'}{'sub': 2', '2, 'sup': 7', '7', '1', '2', '1', '2', '4', '4, '(b) when D is phenyl or substituted phenyl; C is —COR; Ris alkyl; A is —NRR; and Rand Rare both hydrogen; then B is not —COR; wherein Ris alkyl.'}3. The compound of claim 1 , wherein the Formula (I) does not include the following compounds:8-Bromo-4-(4-methoxybenzyl)amino-5-methoxyquinoline-3-carboxylic acid ethyl ester;4-(4-Methoxybenzyl)amino-5-methoxyquinoline-3-carboxylic acid ethyl ester;4-(4-Methoxybenzyl)amino-5-methoxyquinoline-3-carboxylic acid;4-(4-Methoxybenzyl)amino-8-methoxyquinoline-3-carboxylic acid ethyl ester;4-(4-Methoxybenzyl)amino-8-methoxyquinoline-3-carboxylic acid;4-Amino-3-ethoxycarbonyl-2-ethoxycarbonylmethylquinoline; and4-Amino-3-ethoxycarbonyl-2-ethoxycarbonylmethyl-5-methoxyquinoline.4. The compound of claim 1 , wherein Rand Rare independently hydrogen claim 1 , alkyl claim 1 , substituted alkyl claim 1 , aryl claim 1 , substituted aryl claim 1 , arylalkyl claim 1 , acyl claim 1 , substituted acyl claim 1 , heteroalkyl claim 1 , substituted heteroalkyl claim 1 , heteroaryl claim 1 , substituted heteroaryl claim 1 , heteroarylalkyl or substituted heteroarylalkyl; or alternatively claim 1 , Rand R claim 1 , Rand R claim 1 , Rand R ...

CARBETOCIN DRUG PRODUCT AND PROCESS FOR PREPARING SAME

The present disclosure includes a method of making an improved carbetocin drug product. The disclosed method for making an improved carbetocin drug product comprises agitating a carbetocin preparation containing an aqueous solution of carbetocin and one or more excipients for a period of time to initiate the formation of aggregate-forming solids and filtering off the aggregates that form before further processing the remaining carbetocin into a final drug product. The present disclosure also relates to an improved carbetocin drug product, wherein the drug product is substantially free of aggregate-forming solids. The disclosed carbetocin drug product can be used for the treatment of a neurodevelopmental disorder, such as Präder-Willi syndrome. Additionally, the disclosed carbetocin drug product shows content uniformity of carbetocin over long periods of time before and after one or more freeze/thaw cycles, provides enhanced convenience and patient compliance, and/or are highly concentrated. 117-. (canceled)18. A carbetocin drug product comprising carbetocin or a pharmaceutically acceptable salt thereof with increased resistance to aggregation , wherein the concentration of carbetocin is about 10 mg/mL to about 70 mg/mL and the carbetocin drug product is substantially free of the aggregate-forming solids , prepared by a process comprising:(a) dissolving carbetocin or a pharmaceutically acceptable salt thereof and one or more excipients chosen from a surface active agent, solubilizer, tonicity enhancer, an agent to adjust the pH, and combinations thereof to form an aqueous solution;(b) agitating the aqueous solution from step (a) for a time period of hours to form aggregate-forming solids;(c) removing the formed aggregate-forming solids from the agitated solution to form a post-agitation solution; and(d) adding the post-agitation solution to a container to form a final drug product; wherein the carbetocin drug product has increased resistance to aggregation when ...

METHOD OF TREATMENT OF NEUROENDOCRINE TUMORS

The present invention relates to methods of treating cancers that overexpress somatostatin receptors, e.g. neuroendocrine tumors (NET). In particular, the invention provides novel therapies based on the combination of a peptide receptor radionuclide therapeutic (PRRT) agent and immuno-oncology (I-O) therapeutic agents, wherein said I-O therapeutic agents are selected from the group consisting of LAG-3 inhibitors, TIM-3 inhibitors, GITR angonists, TGF-β inhibitors, IL15/IL-15RA complex, and selected PD-1 inhibitors. 1. (canceled)2. A method of treating a somatostatin receptor over-expressing cancer in a subject , comprising administering to the subject a combination of a peptide receptor radionuclide therapeutic (PRRT) agent and one or two immuno-oncology (I-O) therapeutic agent(s) , wherein said I-O therapeutic agent(s) is(are) selected from the group consisting of an LAG-3 inhibitor , a TIM-3 inhibitor , a GITR angonists , a TGF-β inhibitor , an IL15/IL-15RA complex , and a PD-1 inhibitor , wherein said PD-1 inhibitor is selected from the group consisting of Spartalizumab , Pembrolizumab , Pidilizumab , Durvalomab , Atezolizumab , Avelumab , MEDI0680 , REGN2810 , TSR-042 , PF-06801591 , BGB-A317 , BGB-108 , INCSHR1210 , and AMP-224.3. The method of claim 2 , wherein the PRRT agent comprises the radionuclide Lutetium-177 (177Lu) and a somatostatin receptor binding molecule linked to a chelating agent.4. The method of claim 3 , wherein the somatostatin receptor binding molecule is selected from the group consisting of octreotide claim 3 , octreotate claim 3 , lanreotide claim 3 , vapreotide claim 3 , pasireotide claim 3 , and satoreotide.5. The method of claim 4 , wherein the chelating agent is 1 claim 4 ,4 claim 4 ,7 claim 4 ,10-Tetraazacyclododecane-1 claim 4 ,4 claim 4 ,7 claim 4 ,10-tetraacetic acid (DOTA).6. The method of claim 3 , wherein the somatostatin receptor binding molecule linked to the chelating agent is selected from the group consisting of DOTA-OC: [ ...

LOW VISCOSITY CONCENTRATED PROTEIN DISPERSIONS

Disclosed herein are, inter alia, low viscosity dispersions comprising proteins and viscosity lowering agents; pharmaceutical compositions comprising low viscosity dispersions; and methods of making and using the pharmaceutical compositions and low viscosity dispersions. 1. A low viscosity dispersion comprising a protein and a viscosity lowering agent selected from the group consisting of proline , histidine , lysine , arginine , glutamic acid , betaine , glutamine , asparagine , imidazole , and a combination of two or more thereof; whereinthe viscosity lowering agent is present at a concentration from about 10 mg/mL to about 400 mg/mL;the protein is present at a concentration greater than 200 mg/mL and within a plurality of protein nanoclusters; andthe viscosity is about 1 cP to about 125 cP.2. The dispersion of claim 1 , wherein the protein is present at a concentration greater than 200 mg/mL to about 500 mg/mL; or from about 225 mg/mL to about 300 mg/mL.3. The dispersion of claim 1 , wherein the protein is an antibody.4. The dispersion of claim 1 , wherein the viscosity is about 1 cP to about 100 cP; or from about 1 cP to about 50 cP; or from about 5 cP to about 25 cP.5. The dispersion of claim 1 , wherein the viscosity is with a shear rate of about 5 secto about 200 claim 1 ,000 sec; or a shear rate of about 5 secto about 150 claim 1 ,000 sec; or a shear rate of about 100 secto about 10 claim 1 ,000 sec; or a shear rate of about 1 claim 1 ,000 secto about 5 claim 1 ,000 sec; or a shear rate of about 2 claim 1 ,000 secto about 4 claim 1 ,000 sec.6. The dispersion of having a pH from about 4.0 to about 10.0; or from about 5 to about 9; or from about 5 to about 7; or from about 5 to about 6; or from about 5.5 to about 6.5; or about 5.5.7. The dispersion of further comprising a saccharide.8. The dispersion of claim 7 , wherein the saccharide is trehalose claim 7 , sucrose claim 7 , or a combination thereof.9. The dispersion of claim 7 , wherein the saccharide is ...

Growth Hormone Compound Formulation

The present inventions relates to compositions of growth hormone compounds, including pharmaceutical formulations. The compositions are able to provide initial and long term stability of the growth hormone compounds, rendering such compositions suited for use as a pharmaceutical formulation. 1. A pharmaceutical composition comprising 2-20 mg/mL growth hormone albumin-binder conjugate (GH-AB) , a buffer , a preservative and 0.5-5.0 mg/mL surfactant.2. The composition according to claim 1 , wherein the composition comprises 1 mg/mL poloxamer 188 as surfactant.3. The composition according to claim 1 , wherein the composition comprises histidine buffer.4. The composition according to claim 1 , wherein the composition does not comprise glycine.5. The composition according to claim 1 , wherein pH of the composition is 6.5-7.0 claim 1 , preferably 6.8.6. The composition according to claim 1 , wherein the composition comprises 2.0-4.0 mg/mL phenol or 3.0-4.0 mg/mL phenol.7. The composition according to claim 1 , wherein the composition comprises an isotonic agent.8. The composition according to claim 1 , wherein AB- is attached to GH via a cys residue in GH.9. (canceled)10. (canceled)11. (canceled)12. A method for treatment of growth hormone deficiency (GHD) or growth hormone deficiency in adults (AGHD) claim 1 , comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition according to .13. The method according to claim 12 , wherein the composition is administered once weekly.14. The method according to claim 12 , wherein the composition is administered to an adult patient suffering from growth hormone deficiency once weekly.15. The method according to claim 12 , wherein the composition is administered to a patient suffering from growth hormone deficiency wherein 0.01-0.08 mg/kg of the growth hormone albumin binder conjugate is administered per dosage.16. The method according to claim 13 , wherein the composition ...

PHARMACEUTICAL COMPOSITION

The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament; and to processes for the preparation of said compositions. 1. A pharmaceutical composition comprising a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide , and a carrier matrix , wherein the carrier matrix consists essentially of one or more pharmaceutically acceptable carriers selected from the following groups:(a) d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS); and(b) polyglycolised glycerides; andwherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the carrier matrix; andwherein the pharmaceutical composition is for oral administration.2. A pharmaceutical composition according to claim 1 , wherein the polyglycolised glycerides are Lauroyl Macrogol-32 Glycerides.3. A pharmaceutical composition according to claim 2 , wherein the carrier matrix is a mixture of d-alpha-tocopheryl polyethylene glycol 1000 succinate and Lauroyl Macrogol-32 Glycerides and wherein the Lauroyl Macrogol-32 Glycerides are present in an amount to make up approximately 30-55% by weight of the carrier matrix component of the composition.4. A pharmaceutical composition according to claim 1 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate.5. A pharmaceutical composition according to claim 4 , wherein the d-alpha-tocopheryl polyethylene glycol 1000 succinate is present in an amount to make up approximately 65 to 95% by weight of the composition.6. A pharmaceutical composition according claim 1 , wherein greater than 90% by weight ...

High Concentration Alpha-Glucosidase Compositions For The Treatment Of Pompe Disease

The present application provides for compositions comprising high concentrations of acid α-glucosidase in combination with an active site-specific chaperone for the acid α-glucosidase, and methods for treating Pompe disease in a subject in need thereof, that includes a method of administering to the subject such compositions. The present application also provides methods for increasing the in vitro and in vivo stability of an acid α-glucosidase enzyme formulation. 1. A composition comprising acid α-glucosidase and an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyldeoxynojirimycin , wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and 500 mg/mL , and the active site-specific chaperone is present in an amount between about 20 mg/mL and about 200 mg/mL.2. The composition of claim 1 , wherein the composition has less than about 5% aggregate protein.3. The composition of claim 2 , wherein the composition has less than about 1% aggregate protein.4. The composition of claim 1 , wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and 250 mg/mL.5. The composition of claim 4 , wherein the acid α-glucosidase is present in an amount between about 10 mg/mL and 200 mg/mL.6. The composition of claim 1 , wherein the acid α-glucosidase is present in an amount of about 25 mg/mL.7. The composition of claim 1 , wherein the composition is a liquid formulation.8. The composition of claim 7 , wherein the composition has a pH ranging from about 7.0-7.5.9. The composition of claim 7 , wherein the composition is in a frozen state.10. The composition of claim 1 , further comprising an excipient.1110. The composition claim 1 , wherein the excipient is selected from the group consisting of polyethylene glycol 400 claim 1 , arginine claim 1 , glutamic acid claim 1 , proline claim 1 , gammacyclodextrin and combinations thereof.12. The composition of claim 1 , further comprising a buffer ...

METHOD FOR SOLUBILIZING 5-AMINO-2,3-DIHYDRO-1,4-PHTHALAZINEDIONE

The present invention relates to a method for solubilizing 5-amino-2,3-dihydro-1,4-phthalazinedione or salts thereof, to the solubilisate produced by this method and respective uses in pharmaceutical dosage forms. A phosphatidylcholine-based solubilization method is disclosed. 1. A method for solubilizing 5-amino-2 ,3-dihydro-1 ,4-phthalazinedione , comprising the following steps:a) Providing 5-amino-2,3-dihydro-1,4-phthalazinedione in the overall range of 0.1% to 25% per weight at room temperature and a pressure of 0.2 bar to 1 bar; at least one medium-chained triglyceride in the overall range of 10% to 70% per weight,', 'at least one lysophosphatidylcholine in the overall range of 1% to 15% per weight,', {'sub': 2', '4', '14', '20, 'at least one Cto Calcohol in the overall range of 1% to 20% per weight, and at least one of glyceryl stearate and/or a saturated or unsaturated Cto Cfatty acid in the overall range of 0.5% to 10% per weight, respectively,'}, 'wherein the relative weight percentages of all ingredients add up to 100% and all solubilization agents are independently from one another a food additive and/or a pharmaceutically acceptable excipient;, 'b) Adding in any sequence the solubilization agents of at least one phosphatidylcholine in the overall range of 20% to 80% per weight,'}c) Cautiously heating the resulting mixture by continuously increasing the temperature with a continuous temperature increment of 0.5° C./min-3° C./min over a period of 20-60 minutes;d) Stopping the temperature increase in a temperature range of 30° C. to 125° C. as soon as a clear solution is reached; ande) Letting the resulting solubilisate cool down to room temperature.3. The method according to claim 1 , wherein said at least one saturated or unsaturated Cto Cfatty acid is oleic acid.4. The method according to claim 1 , wherein said at least one Cto Calcohol is ethanol.5. The method according to claim 1 , wherein additionally in step b) at least one antioxidant in the overall ...

METHOD FOR ENHANCING ANTI-TUMOR EFFECT OF A MICROTUBULE-TARGETING DRUG, AND A METHOD FOR TREATMENT OF TUMOR

A method for treating a tumor by combining a piperidine compound of formula (I) or salt thereof and a microtubule-targeting drug, in which the microtubule-targeting drug is administered once per 7 days or more one cycle, and the piperidine compound is administered once or more per day for 4 days or more: 2. The method according to claim 1 , whereinthe microtubule-targeting drug is administered on day 1 in 7 days as one cycle, andadministration of the piperidine compound or a salt thereof is initiated on day 1 or day 2, wherein a period of consecutive daily administration is performed for 4 or 5 days.3. The method according to claim 1 , whereinthe microtubule-targeting drug is administered on day 1 in 21 days as one cycle, andadministration of the piperidine compound or a salt thereof is initiated on day 1 or day 2, wherein a period of consecutive daily administration is performed for 4 to 12 days.4. The method according to claim 1 , wherein the piperidine compound or a salt thereof is 1-(2 claim 1 ,3-dichlorobenzoyl)-4-((5-fluoro-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid or a salt thereof.5. (canceled)6. The method according to claim 1 , wherein the taxane antitumor agent is paclitaxel claim 1 , docetaxel claim 1 , cabazitaxel claim 1 , albumin-binding paclitaxel claim 1 , albumin-binding docetaxel claim 1 , docosahexaenoic acid binding paclitaxel claim 1 , polyglutamated paclitaxel or peptide-binding paclitaxel.8. The method according to claim 7 , whereinthe microtubule-targeting drug is administered on day 1 in 7 days as one cycle, andadministration of the piperidine compound or a salt thereof is initiated on day 1 or day 2, wherein a period of consecutive daily administration is performed for 4 or 5 days.9. The method according to claim 7 , whereinthe microtubule-targeting drug is administered on day 1 in 21 days as one cycle, andadministration of the piperidine compound or a salt thereof is initiated on day 1 or day 2, ...

OIL/SURFACTANT MIXTURES FOR SELF-EMULSIFICATION

Methods of manufacturing squalene and alpha-tocopherol-containing oil-in-water emulsions having small oil droplet particle sizes. Such emulsions being of use as vaccine adjuvants. 1. A composition comprising squalene , a tocopherol and a biocompatible metabolisable surfactant , wherein the squalene is 40% v/v or more of the composition , the tocopherol is 25% v/v or less of the composition , the surfactant is 60% v/v or less of the composition , which when mixed with an excess volume of substantially surfactant-free aqueous material , forms an adjuvant having an average oil particle diameter of 200 nm or less.24-. (canceled)5. A composition comprising squalene , a tocopherol and a biocompatible metabolisable surfactant , wherein the squalene is 50 to 70% v/v of the composition , the tocopherol is 10 to 20% v/v of the composition and the surfactant is 10 to 40% v/v of the composition.6. The composition according to claim 5 , wherein the squalene is 55 to 65% v/v of the composition claim 5 , the tocopherol is 10 to 20% v/v of the composition and the surfactant is 20 to 30% v/v of the composition.78-. (canceled)9. A method for preparing an oil-in-water emulsion adjuvant comprising squalene claim 1 , a tocopherol claim 1 , a biocompatible metabolisable surfactant and an aqueous component claim 1 , said method comprising mixing a composition according to with an excess volume of an aqueous component.10. The method of claim 9 , wherein the aqueous component comprises an antigen or antigenic component.11. The method of claim 10 , further comprising a step of drying the oil-in-water emulsion claim 10 , such as by lyophilisation.12. (canceled)13. A dried composition obtainable by the method of .14. An oil-in-water emulsion adjuvant composition comprising squalene claim 11 , a tocopherol claim 11 , a biocompatible metabolisable surfactant and an excess volume of an aqueous component claim 11 , wherein the squalene is 40% v/v or more of the total amount of squalene claim 11 , ...

VIRULENCE FACTORS OF STREPTOCOCCUS PNUEMONIAE

The present invention provides proteins/genes, which are essential for survival, and consequently, for virulence of in vivo, and thus are ideal vaccine candidates for a vaccine preparation against pneumococcal infection. Further, also antibodies against said protein(s) are included in the invention. 114-. (canceled)15. A method for prophylactic or therapeutic treatment of a pneumococcal infection in a subject in need thereof , comprising:administering to the subject a therapeutically effective amount of a vaccine formulation comprising at least 20 μg of an isolated protein encoded by the gene SP1690 or an immunogenic part thereof with at least one of a pharmaceutically acceptable diluent, carrier, excipient or adjuvant therefore.16. The method of claim 15 , wherein the vaccine formulation comprises at least 20 μg and up to 275 μg of the isolated protein encoded by the gene SP1690.17. The method of claim 15 , wherein the vaccine formulation comprises an oil in water adjuvant system.18. The method of claim 17 , wherein an oil phase of the vaccine formulation comprises an oil selected from the group consisting of mineral oil claim 17 , a non-mineral oil claim 17 , and combinations of any thereof.19. The method of claim 17 , wherein the vaccine formulation comprises 40-75% water phase and 25-60% oil phase.20. The method of claim 18 , wherein the vaccine formulation comprises 50% water phase and 50% oil phase.21. The method of claim 15 , where the vaccine formulation comprises vitamin E.22Streptococcus pneumoniae.. The method of claim 15 , wherein the pneumococcal infection is an infection by23. The method of claim 15 , wherein the subject is a mammal selected from the group consisting of a human claim 15 , ape claim 15 , monkey claim 15 , horse claim 15 , cow claim 15 , pig claim 15 , goat claim 15 , dog claim 15 , cat claim 15 , rat claim 15 , mouse claim 15 , and sheep.24. The method of claim 23 , wherein the subject is a human.25. The method of claim 15 , wherein the ...

ANTIBODY FORMULATION

The present invention provides high concentration liquid formulations of antibodies or fragments thereof that specifically bind to a human interferon alpha polypeptide. 1102-. (canceled)103. A sterile , stable aqueous formulation comprising a 13H5 anti-human interferon alpha antibody , and further comprising histidine , sodium chloride , sucrose , trehalose or polysorbate 80.104. The composition of claim 103 , wherein said composition comprises a 13H5 anti-human interferon alpha antibody claim 103 , histidine claim 103 , trehalose and polysorbate 80.105. The composition of claim 104 , wherein said composition comprises between about 50 mg/ml and about 150 mg/ml of a 13H5 anti-human interferon alpha antibody claim 104 , between about 1 mM and about 100 mM histidine claim 104 , between about 1% and about 40% trehalose and between about 0.001% and about 5% polysorbate 80 and wherein the pH of said composition is between about 5 and about 7.106. The composition of claim 104 , wherein said composition comprises between about 80 mg/ml and about 120 mg/ml of a 13H5 anti-human interferon alpha antibody claim 104 , between about 10 mM and about 50 mM histidine claim 104 , between about 4% and about 20% trehalose and between about 0.005% and about 1% polysorbate 80 and wherein the pH of said composition is between about 5.5 and about 6.5.107. The composition of claim 104 , wherein said composition comprises about 100 mg/ml of a 13H5 anti-human interferon alpha antibody claim 104 , about 25 mM histidine claim 104 , about 8% trehalose and about 0.02% polysorbate 80 and wherein the pH of said composition is about 6.108. The composition of claim 103 , wherein said composition comprises a 13H5 anti-human interferon alpha antibody claim 103 , histidine claim 103 , sucrose and polysorbate 80.109. The composition of claim 108 , wherein said composition comprises about 100 mg/ml of a 13H5 anti-human interferon alpha antibody claim 108 , about 25 mM histidine claim 108 , about 5% ...

STABLE ANTIBODY COMPOSITIONS AND METHODS OF STABILIZING SAME

The invention provides compositions and methods for inhibiting fractionation of immunoglobulins comprising a lambda light chain based on the observation that iron, in the presence of histidine, results in increased fragmentation of a recombinant fully human IgG molecule containing a lambda light chain due to cleavage in the hinge region. The invention further provides an aqueous pharmaceutical formulation comprising an antibody, or antigen-binding portion thereof, that binds the p40 subunit of IL-12/IL-23 and a buffer system comprising histidine, wherein the formulation has enhanced stability, including enhanced resistance to fragmentation. 1144.-. (canceled)145. A pharmaceutical formulation comprising:(a) 45 mg of antibody C340,(b) 1-10% sucrose,(c) 0.001-0.1% polysorbate 80, and(d) a buffer system comprising 1-50 mM histidine and having a pH of 5.7 to 6.3.146. A pharmaceutical formulation comprising:(a) 90 mg/mL of antibody C340,(b) 1-10% sucrose,(c) 0.001-0.1% polysorbate 80, and(d) a buffer system comprising 1-50 mM histidine and having a pH of 5.7 to 6.3.147. The formulation of claim 145 , wherein the formulation has a pH of about 6.148. The formulation of claim 145 , wherein the histidine comprises L-histidine.149. The formulation of claim 145 , wherein the formulation has a shelf life of at least 18 months.150. The formulation of claim 146 , wherein the formulation has a pH of about 6.151. The formulation of claim 146 , wherein the histidine comprises L-histidine.152. The formulation of claim 146 , wherein the formulation has a shelf life of at least 18 months.153. A method of treating a subject having a disorder in which the activity of the p40 subunit of IL-12 and/or IL-23 is detrimental claim 145 , the method comprising administering the formulation of to the subject claim 145 , thereby treating the subject.154. The method of claim 153 , wherein the disorder is psoriasis.155. The method of claim 153 , wherein the disorder is psoriatic arthritis.156. The ...

DELIVERY MOLECULES FOR THERAPEUTICS

Activity-generating delivery molecules comprising the structure R—(C═O)-Xaa-NH—Rwherein Xaa is any D- or L-amino acid residue with a non-hydrogen, substituted or unsubstituted side chain, R—(C═O)— and —NH—Rare independently a long chain group, each long chain group containing one or more carbon-carbon double bonds, and salts, compositions and methods of use thereof. The activity-generating delivery compounds and compositions are useful for generating activity of an active agent in a cell, tissue, or subject. 1. A compound comprising an amino acid having a long chain alkenoyl group at the N-terminus and a long chain alkenylamino group at the C-terminus , wherein each long chain group has from 12 to 24 carbon atoms and one or more carbon-carbon double bonds.2. The compound of claim 1 , wherein at least one long chain group has two or more carbon-carbon double bonds.4. The compound of claim 3 , wherein R—(C═O)— is independently a substituted or unsubstituted C(12-24)alkenoyl and —NH—Ris independently a substituted or unsubstituted C(12-24)alkenylamino.5. The compound of claim 3 , wherein R claim 3 ,Rare each independently C12alkenyl claim 3 , C13alkenyl claim 3 , C14alkenyl claim 3 , C15alkenyl claim 3 , C16alkenyl claim 3 , C17alkenyl claim 3 , C18alkenyl claim 3 , C19alkenyl claim 3 , C20alkenyl claim 3 , C21alkenyl claim 3 , C22alkenyl claim 3 , C23alkenyl claim 3 , or C24alkenyl.6. The compound of claim 3 , wherein:{'sup': '3', 'R—(C═O)— is independently C12alkenoyl, C13 alkenoyl, C14alkenoyl, C15 alkenoyl, C16alkenoyl, C17alkenoyl, C18alkenoyl, C19alkenoyl, C20alkenoyl, C21alkenoyl, C22alkenoyl, C23alkenoyl, or C24alkenoyl; and'}{'sup': '4', '—NH—Ris independently C12alkenylamino, C13alkenylamino, C14alkenylamino, C15alkenylamino, C16alkenylamino, C17alkenylamino, C18alkenylamino, C19alkenylamino, C20alkenylamino, C21alkenylamino, C22alkenylamino, C23alkenylamino, or C24alkenylamino.'}7. The compound of claim 3 , wherein:{'sup': '3', 'R—(C═O)— is independently C( ...

SUSTAINED RELEASE BIODEGRADABLE INTRACANALICULAR INSERTS COMPRISING A HYDROGEL AND CYCLOSPORINE

Provided herein are sustained release biodegradable intracanalicular insert comprising a hydrogel and cyclosporine, methods of treating or preventing an ocular disease in a subject in need thereof by administering such inserts as well as methods of manufacturing such inserts. 1. A sustained release biodegradable intracanalicular insert comprising a hydrogel and cyclosporine , wherein the cyclosporine is in the form of particles and wherein the cyclosporine particles are dispersed within the hydrogel.2. The sustained release biodegradable intracanalicular insert of claim 1 , wherein the cyclosporine particles have a d50 value of less than about 50 μm.3. The sustained release biodegradable intracanalicular insert of claim 2 , wherein the cyclosporine particles have a d50 value ranging from 3 to 17 μm.4. The sustained release biodegradable intracanalicular insert of claim 1 , wherein the hydrogel comprises a polymer network comprising crosslinked polymer units that are identical or different claim 1 , and the crosslinked polymer units are polyethylene glycol units.5. The sustained release biodegradable intracanalicular insert of claim 4 , wherein the polymer network comprises polyethylene glycol units having an average molecular weight in the range from about 2 claim 4 ,000 to about 100 claim 4 ,000 Daltons.6. The sustained release biodegradable intracanalicular insert of claim 4 , wherein the polymer network comprises one or more crosslinked multi-arm polymer units comprising one or more 2- to 10-arm polyethylene glycol units.7. The sustained release biodegradable intracanalicular insert of claim 6 , wherein the four arms of the 4-arm polyethylene glycol units are connected to a core molecule of pentaerythritol.8. The sustained release biodegradable intracanalicular insert of claim 6 , wherein the polymer network is formed by reacting an electrophilic group-containing multi-arm-polymer precursor with a nucleophilic group-containing cross-linking agent.9. The sustained ...

TRANSDERMAL ABSORPTION-TYPE PATCH PREPARATION COMPRISING ZONISAMIDE

To provide to a transdermal absorption-type patch preparation containing zonisamide, that is a transdermal absorption-type patch preparation containing zonisamide or an alkali metal salt thereof, being capable of maintaining a high concentration of a drug in a dissolved state in the preparation and exhibiting sufficient and sustained drug efficacy. A transdermal absorption-type patch preparation containing an adhesive layer, the adhesive layer containing zonisamide or an alkali metal salt thereof, an adhesive agent containing a (meth)acrylic copolymer having a pyrrolidone group, and a transdermal absorption promoter containing N-alkylpyrrolidone. 1. A transdermal absorption-type patch preparation comprising an adhesive layer , the adhesive layer comprisingzonisamide or an alkali metal salt thereof,an adhesive agent comprising a (meth)acrylic copolymer having a pyrrolidone group, anda transdermal absorption promoter comprising N-alkylpyrrolidone.2. The transdermal absorption-type patch preparation according to claim 1 , wherein the N-alkylpyrrolidone is N-laurylpyrrolidone claim 1 , N-octylpyrrolidone claim 1 , N-heptylpyrrolidone claim 1 , N-hexylpyrrolidone claim 1 , N-nonylpyrrolidone claim 1 , N-decylpyrrolidone claim 1 , N-undecylpyrrolidone claim 1 , N-tridecylpyrrolidone claim 1 , N-tetradecylpyrrolidone claim 1 , N-pentadecylpyrrolidone claim 1 , N-hexadecylpyrrolidone claim 1 , N-heptadecylpyrrolidone claim 1 , or N-octadecylpyrrolidone.3. The transdermal absorption-type patch preparation according to claim 2 , wherein the N-alkylpyrrolidone is N-laurylpyrrolidone or N-octylpyrrolidone.4. The transdermal absorption-type patch preparation according to claim 3 , wherein the N-alkylpyrrolidone is N-laurylpyrrolidone.5. The transdermal absorption-type patch preparation according to claim 1 , wherein the adhesive agent comprises a (meth)acrylic copolymer having a pyrrolidone group and a (meth)acrylic copolymer having a carboxyl group.6. The transdermal absorption ...

PARENTERAL COMPOSITIONS OF CARMUSTINE

Described herein are parenteral compositions of carmustine. More particularly, described herein are ready to use parenteral compositions of carmustine in the form of solutions. 1. A ready to use liquid parenteral composition comprising:(i) carmustine or a pharmaceutically acceptable salt thereof, and(ii) one or more solvents selected from propylene glycol, dimethylacetamide, N-methyl pyrrolidone, polyethylene glycol, monothioglycerol, dehydrated alcohol, and mixtures thereof.2. The ready to use parenteral composition according to claim 1 , wherein the composition is in the form of a solution.3. The ready to use parenteral composition according to claim 1 , comprising about 25 mg/ml to about 100 mg/ml of carmustine.4. The ready to use parenteral composition according to claim 1 , wherein the composition further comprises one or more pharmaceutically acceptable excipients selected from a bulking agent claim 1 , a solubilizer claim 1 , a buffer claim 1 , a pH adjustment aid claim 1 , a chelating agent claim 1 , an antioxidant claim 1 , an antibacterial preservative claim 1 , and combinations thereof.5. A parenteral composition comprising 25 mg/mL or 100 mg/mL of carmustine; one or more solvents selected from propylene glycol claim 1 , dimethylacetamide claim 1 , N-methyl pyrrolidone claim 1 , polyethylene glycol claim 1 , monothioglycerol claim 1 , dehydrated alcohol claim 1 , and mixtures thereof; the composition having not more than 1% of Impurity A.6. A method of making a ready to use parenteral solution composition according to claim 1 , comprising:(a) adding a weighed quantity of carmustine to one or more solvents selected from N-methyl pyrrolidone, N, N dimethylacetamide, propyleneglycol, polyethylene glycol, monothioglycerol, dehydrated alcohol, and mixtures thereof and stirring continuously until complete dissolution of the carmustine,(b) filtering the solution and filling the filtered solution into vials, and(c) stoppering and sealing the vials.7. A method of ...

TRI-MODAL NUCLEIC ACID DELIVERY SYSTEMS

Provided herein are nucleic acid delivery compositions, surfactants, kits comprising said materials, methods and uses thereof, and methods for the preparation thereof. In particular, nucleic acid delivery compositions described herein may include tri-modal nucleic acid delivery compositions which may comprise at least one peptide enhancer, at least one surfactant, and at least one helper lipid. By way of example, certain of the tri-modal nucleic acid delivery compositions described herein include a peptide enhancer; a surfactant which is a functionalized cationic gemini surfactant; and a helper lipid which is a neutral lipid such as DOPE. 1. A tri-modal nucleic acid delivery composition comprising:at least one peptide enhancer;at least one surfactant; andat least one helper lipid.2. The tri-modal nucleic acid delivery composition according to claim 1 , wherein the peptide enhancer is zwitterionic claim 1 , cationic claim 1 , and/or comprises at least one histidine claim 1 , lysine claim 1 , or arginine residue.3. The tri-modal nucleic acid delivery composition according to claim 1 , wherein the peptide enhancer comprises an RGD sequence motif.4. The tri-modal nucleic acid delivery composition according to claim 1 , wherein the peptide enhancer comprises an amino acid sequence of P(GRGDSPG; SEQ ID NO: 1) claim 1 , P(H(R)H(R)HG; SEQ ID NO: 2) claim 1 , P(GRGDSPGH(R)H(R)HG; SEQ ID NO: 3) claim 1 , P((H); SEQ ID NO: 4) claim 1 , P(GRGDSPG(H); SEQ ID NO: 5) claim 1 , P((H)R(H)R(H)G; SEQ ID NO: 6) claim 1 , P(GRGDSPG(H)R(H)R(H)G; SEQ ID NO: 7) claim 1 , or GRGDSP (SEQ ID NO: 16).5. (canceled)6. The tri-modal nucleic acid delivery composition according to claim 1 , wherein the surfactant comprises a cationic gemini surfactant713.-. (canceled)14. The tri-modal nucleic acid delivery composition of claim 1 , wherein the surfactant is functionalized with a functional moiety which comprises an imidazole-containing functional group claim 1 , a thiol-containing functional group ...

NOVEL FORMULATIONS FOR THE TREATMENT OF VAGINAL DISORDERS

The present disclosure provides novel formulations suitable for the intravaginal delivery of tinidazole, as well as methods of using the same. 1. A formulation suitable for the intravaginal delivery of tinidazole to a subject in need thereof , the formulation comprising water , tinidazole , a thermoreversible gelling agent , one or more pharmaceutically acceptable C-Calcohols , a solubility enhancer , and , optionally , one or more preservatives.2. The formulation of claim 1 , wherein the thermoreversible gelling agent is triblock copolymer having a central hydrophobic block flanked on each side with a hydrophilic block.3. The formulation of claim 2 , wherein the hydrophobic block is polypropylene oxide).4. The formulation of claim 3 , wherein the hydrophilic block is poly(ethylene oxide).54. The formulation of any one of - claims 1 , wherein the thermoreversible gelling agent is poloxamer 407.65. The formulation of any one of - claims 1 , wherein the one or more pharmaceutically acceptable C-Calcohols comprise a first pharmaceutically acceptable C-Calcohol and a second pharmaceutically acceptable C-Calcohol.7. The formulation of claim 6 , wherein the first and second pharmaceutically acceptable C-Calcohols are independently selected from the group consisting of methanol claim 6 , ethanol claim 6 , isopropanol claim 6 , propylene glycol claim 6 , 2-(2-ethoxyethoxy)ethanol claim 6 , benzyl alcohol claim 6 , and combinations thereof.8. The formulation of any one of or claim 6 , wherein the first pharmaceutically acceptable C-Calcohol is benzyl alcohol.98. The formulation of - claims 6 , wherein the second pharmaceutically acceptable C-Calcohol is isopropanol.10. The formulation of or claims 6 , wherein the isopropanol is a 60% (w/w) solution in water.1110. The formulation of any one of - claims 1 , wherein the solubility enhancer is selected from the group consisting of mono- and di-alkyl ethers of isosorbide.12. The formulation of claim 11 , wherein the mono- or di- ...

HIGH CAPACITY DIKETOPIPERAZINE MICROPARTICLES AND METHODS

Disclosed herein are diketopiperazine microparticles having high capacity for adsorbing a drug or active agent. In particular, the diketopiperazine microparticle are formed using fumaryl diketopiperazine and can comprise a drug in large doses for the treatment of disease or disorders by pulmonary delivery via oral inhalation. 1. A method of delivering a drug or an active agent to a patient in need thereof comprising administering to the patient in need thereof an inhalable composition comprising a drug or active agent and diketopiperazine microparticles , each of the diketopiperazine microparticles comprising a plurality of structural domains , each of the plurality of structural domains comprising a nucleus surrounded by layers of a porous crystalline material , and each of the diketopiperazine microparticles have a mass-weighted average particle size of about 33 ,000 to about 216 ,000 voxels measured by X-ray tomography for particle sizes measuring from about 0.5 μm to about 4 μm in geometric diameter.2. The method of claim 1 , wherein said diketopiperazine is fumaryl diketopiperazine or 3 claim 1 ,6-bis(N-fumaryl-4-aminobutyl)-2 claim 1 ,5-diketopiperazine; or salt thereof.3. The method of claim 1 , wherein the diketopiperazine microparticles comprise structural domains ranging in number-weighted size from about 250 voxels to about 1 claim 1 ,400 voxels.4. The method of claim 1 , wherein the diketopiperazine microparticles comprise structural domains ranging in voxel-weighted size from about 500 voxels to about 2 claim 1 ,000 voxels.5. The method of claim 1 , wherein the diketopiperazine microparticles have a specific surface area greater than 70 m/g.6. The method according to claim 1 , further comprising a surfactant.7. The method according to claim 6 , wherein said surfactant is polysorbate 80.8. The method of claim 1 , wherein said drug or active agent is a small organic molecule claim 1 , peptide or protein claim 1 , a lipid claim 1 , or a nucleic acid ...

PHARMACEUTICAL PREPARATIONS

Pharmaceutical preparations are proposed, comprising bitter-masking acting substances for reducing and/or inhibiting gastric acid secretion induced by food constituents. 1. A pharmaceutical preparation , comprising bitter-masking acting substances for reducing and/or inhibiting gastric acid secretion induced by food constituents.2. The preparation as claimed in claim 1 , wherein the bitter-masking acting substances (component a) are selected from the group consisting of hydroxyflavanones claim 1 , hydroxybenzamides claim 1 , hydroxyphenylalkanediols claim 1 , γ-aminobutyric acid claim 1 , 4-hydroxyhydrochalcones claim 1 , vanillyl lignans claim 1 , enterolactone and mixtures thereof.3. The preparation as claimed in claim 2 , wherein the substances comprising the component (a) are selected from the group consisting of eriodictyol claim 2 , homoeriodictyol and salts thereof claim 2 , matairesinol claim 2 , lariciresinol or enterolactone and mixtures thereof.4. The preparation as claimed in claim 1 , wherein the food constituents inducing gastric acid secretion (component b) are selected from the group consisting of xanthine claim 1 , fruit acids claim 1 , phenolic glycosides claim 1 , flavone glycosides claim 1 , dihydrochalcone glycosides claim 1 , hydrolyzable and non-hydrolyzable tannins and oligomers thereof claim 1 , terpenoid or iridoid bitter substances and triterpene glycosides and mixtures thereof.5. The preparation as claimed in claim 4 , wherein the substances comprising the component (b) are selected from the group consisting of caffeine claim 4 , theobromine claim 4 , theophylline claim 4 , tartaric acid claim 4 , racemic acid claim 4 , malic acid claim 4 , succinic acid claim 4 , salicin claim 4 , arbutin claim 4 , neohesperidin claim 4 , eriocitrin claim 4 , neoeriocitrin claim 4 , narirutin claim 4 , naringin claim 4 , phloridzin claim 4 , trilobatin claim 4 , gallic and ellagic esters of carbohydrates claim 4 , galloylated catechins and epicatechins ...