СПОСОБЫ ЛЕЧЕНИЯ ПОЛИПОЗА НОСА ПУТЕМ ВВЕДЕНИЯ АНТАГОНИСТА IL-4R

Группа изобретений относится к медицине, а именно к оториноларингологии, и может быть использована для лечения полипоза носа. Способы по изобретению включают введение субъекту, нуждающемуся в этом, фармацевтической композиции, включающей антитело против IL-4R или его антигенсвязывающий фрагмент, которые специфично связывают рецепторы интерлейкина-4 (IL-4R). Использование изобретений позволяет лечить назальный полипоз за счет снижения биомаркеров, связанного с Т-хелперами-2 воспаления. 3 н. и 20 з.п. ф-лы, 16 табл., 1 ил., 4 пр.

ФАРМАЦЕВТИЧЕСКИЕ КОМБИНАЦИИ ИНГИБИТОРА CDK4/6 И ИНГИБИТОРА В-Raf

Фармацевтическая комбинация, содержащая (а) ингибитор CDK4/6, (b) ингибитор B-Raf и необязательно (c) ингибитор MEK 1/2; их комбинированные композиции и фармацевтические композиции; применение такой комбинации в лечении пролиферативных заболеваний; способы лечения субъектов, страдающих от пролиферативных заболеваний, включая введение терапевтически эффективного количества такой комбинации. 5 н. и 5 з.п. ф-лы, 4 пр., 1 ил.

ФАРМАЦЕВТИЧЕСКАЯ КОМБИНАЦИЯ ДЛЯ ЛЕЧЕНИЯ И/ИЛИ ХЕМОСЕНСИБИЛИЗАЦИИ ОПУХОЛЕЙ, УСТОЙЧИВЫХ К ПРОТИВОРАКОВЫМ СРЕДСТВАМ

Изобретение относится к медицине, в частности к молекулярной и экспериментальной онкологии, и представляет собой фармацевтическую комбинацию для одновременного, раздельного или последовательного введения, которая содержит ингибитор сайта фосфорилирования на субстратах СК2, который включает пептид Р15 (CWMSPRHLGTC) вместе с цитостатическим веществом, фармацевтически приемлемо смешанным с соответствующими переносчиками. Изобретение обеспечивает повышение терапевтического индекса текущих цитотоксических веществ, при помощи уменьшения эффективной дозы и естественной токсичности, проявляемой этим видом лекарственных средств, а также обход химической устойчивости опухоли по отношению к традиционным цитотоксическим веществам, 4 н. и 8 з.п. ф-лы, 4 табл., 2 ил.

ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ 4-АМИНОЦИКЛОГЕКСАНА

Изобретение относится к новым соединениям общей формулы (1), которые обладают сродством к µ-опиоидному рецептору и ORL1-рецептору, к лекарственным средствам, содержащим эти соединения, и к применению этих соединений для получения лекарственных средств, пригодных для лечения боли, страха, стресса и других заболеваний или состояний. В общей формуле (1)Y, Y′, Y, Y′, Y, Y′, Yи Y′ означают -H; Rи Rнезависимо друг от друга означают -H или -CH; при условии что Rи Rоба одновременно не означают -H; Q означает: -C-арил, незамещенный или моно- или многократно замещенный -F, -Cl, -Br или -I; или-гетероарил; Rозначает: -C-алкил, незамещенный или моно- или многократно замещенный -OR, где Rозначает незамещенный -C-алкил; незамещенный -C-циклоалкил-C-алкил; незамещенный -C-алкил-C-циклоалкил; -C-арил, незамещенный или моно- или многократно замещенный -F, -Cl, -Br, -I, -CN, -Rили -OR, где Rозначает незамещенный -C-алкил; или -гетероарил; n означает 0; X означает -NR-; Rозначает -H или -R; где Rозначает ...

ЛИПОСОМАЛЬНЫЙ ФАРМАЦЕВТИЧЕСКИЙ ПРЕПАРАТ И СПОСОБ ЕГО ИЗГОТОВЛЕНИЯ

Группа изобретений относится к медицине и касается липосомного лекарственного препарата, содержащего мультивалентный ионный лекарственный препарат в качестве активного вещества с двумя или несколькими диссоциирующимися группами с константой диссоциации 4,5-9,5, где липосома имеет размер около 30-80 мм и фосфолипидный бислой имеет фосфолипид с температурой фазового перехода выше температуры тела, так что температура фазового перехода липосомы выше температуры тела; способа лечения опухоли у пациента, включающего введение указанного липосомного лекарственного препарата. Группа изобретений обеспечивает повышение эффективности терапевтического индекса липосомного препарата, особенно повышение эффективности контролирования выведения липосомального лекарственного средства после нацеливания на пораженную опухолью область, снижение потери лекарственного средства во время циркуляции липосомального лекарственного средства в крови и повышение эффективности высвобождения лекарства в целевые ткани.

ПРИМЕНЕНИЕ ЛИПОСОМ С ГИДРОХЛОРИДОМ МИТОКСАНТРОНА И ЦИКЛОФОСФАМИДА, ВИНКРИСТИНА И ПРЕДНИЗОНА

Применение липосомы с гидрохлоридом митоксантрона и циклофосфамида, винкристина и преднизона для получения лекарства для лечения периферической Т-клеточной лимфомы (PTCL), которую ранее не лечили. Другие препараты первого и второго ряда для лечения PTCL также могут быть дополнительно использованы на основании вышеизложенного. Способ лечения PTCL включает введение пациенту терапевтически эффективного количества липосомы с гидрохлоридом митоксантрона и циклофосфамида, винкристина и преднизона. Комбинированное введение лекарств является безопасным и переносимым, имеет низкую токсичность и мало побочных эффектов и может обеспечить более высокую общую частоту объективной ремиссии (ORR) у пациентов с PTCL, ранее не получавших лечения. 3 н. и 8 з.п. ф-лы, 1 табл., 1 пр.

Способ лечения мочеполового туберкулеза

Изобретение относится к медицине, а именно к фтизиоурологии, и может быть использовано для лечения мочеполового туберкуклеза. Для этого вводят изониазид в дозе 600 мг и ПАСК в дозе 8000 мг внутривенно капельно два раза в неделю, рифампицин в дозе 600 мг вводят ректально в составе лечебного коктейля: новокаин 0,5% - 20 мл + димексид 2 мл + галидор 2 мл + пиридоксин 2 мл ежедневно. Дополнительно проводят иммунорепараторную терапию дезоксирибонуклеатом натрия (деринат), который вводят через две недели после начала противотуберкулезной терапии внутримышечно в дозе 75 мг каждые 48 часов, 15 инъекций на курс. Способ позволяет преодолеть предел эффективности противотуберкулезной полихимиотерапии, быстро устранить дизурию и купировать боль при повышении качества жизни пациента. 1 табл., 1 пр.

Способ восстановления репродуктивной функции у пациенток с маточной формой бесплодия, обусловленной хроническим эндометритом

Изобретение относится к медицине, в частности к гинекологии, и может применяться для восстановления репродуктивной функции у пациенток с маточной формой бесплодия, обусловленной хроническим эндометритом. Проводится два курса лечения. Первый курс: с первого дня менструального цикла принимают внутрь антибиотик – таблетки диспергируемые доксициклина моногидрат по 100 мг 2 раза в день в течение 10 дней; с 5-9-го дня применяют иммуномодулирующую терапию, которая проводится комплексом экзогенных природных противомикробных пептидов и цитокинов Суперлимф, суппозитории по 25 ЕД 1 раз в день ректально вечером ежедневно в течение 20 дней. В этом же менструальном цикле с 5-9-го дня проводят орошение полости матки кавитированным раствором хлоргексидина 0,05% в количестве 200–300 мл на процедуру, продолжительность воздействия 3-5 мин, 5 процедур, ежедневно, 1 раз в сутки. Второй курс: в следующем менструальном цикле с 5-9-го дня применяют иммуномодулирующую терапию, которая проводится комплексом экзогенных ...

СОДЕРЖАЩЕЕ 3-(3-ДИМЕТИЛАМИНО-1-ЭТИЛ-2-МЕТИЛПРОПИЛ)ФЕНОЛ ЛЕКАРСТВЕННОЕ СРЕДСТВО С ЗАМЕДЛЕННЫМ ВЫСВОБОЖДЕНИЕМ ДЕЙСТВУЮЩЕГО ВЕЩЕСТВА

... 1. Фармацевтическая композиция с замедленным высвобождением действующего вещества, которая содержит 3-(3-диметиламино-1-этил-2-метилпропил)фенол или одну из его фармацевтически приемлемых солей в матрице, которая обеспечивает замедленное высвобождение действующего вещества и содержит от 1 до 80 мас.% одного либо нескольких гидрофильных или гидрофобных полимеров в качестве фармацевтически приемлемых матрицеобразователей и которая характеризуется следующей скоростью высвобождения действующего вещества in vitro, измеренной рекомендуемым согласно Европейской Фармакопее методом с использованием мешалки при частоте ее вращения 75 об/мин в буферном растворе (также согласно Европейской Фармакопее) при значении рН 6,8 и при температуре 37°С и обнаружении с помощью УФ-спектроскопии 3-35 мас.% 3-(3-диметиламино-1-этил-2-метилпропил)фенола (в пересчете на 100 мас.% действующего вещества) высвобождаются по истечении 0,5 ч, 5-50 мас.% 3-(3-диметиламино-1-этил-2-метилпропил)фенола высвобождаются по истечении ...

Способ получения смеси биологически активных веществ: биогенных аминов гистамина, триптамина, тирамина, кинуренина, а также производного кинуренина - кинуреновой кислоты

Изобретение относится к области химико-фармацевтической промышленности, а именно к способу получения смеси биологически активных веществ – биогенных аминов гистамина, триптамина, тирамина, кинуренина и кинуреновой кислоты. Способ получения смеси биологически активных веществ: биогенных аминов гистамина, триптамина, тирамина, кинуренина и производного кинуренина - кинуреновой кислоты, включающий измельчение биомассы моховидного растения Vesicularia dubyana, экстрагирование из измельченной растительной биомассы смеси биологически активных веществ в присутствии растворителя - метилового 100% либо этилового спирта 96% - в соотношении измельченная биомасса растения : растворитель, равном 1 к 10, в условиях перемешивания на протяжении 1 часа, затем центрифугирование при скорости 4 тыс. об/мин на протяжении 10 минут, далее охлаждение в термостате при температуре 6°С на протяжении 8 часов, после чего повторное центрифугирование при 13,5 тыс. об/мин и далее отфильтровывание полученного экстракта ...

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ДЛЯ ПРОФИЛАКТИКИ И/ИЛИ ЛЕЧЕНИЯ РАКОВЫХ ЗАБОЛЕВАНИЙ, ДЛЯ УВЕЛИЧЕНИЯ АКТИВНОСТИ ПРОТИВОРАКОВЫХ ЛЕКАРСТВ И СНИЖЕНИЯ ПОБОЧНЫХ ЭФФЕКТОВ ПРОТИВОРАКОВЫХ ЛЕКАРСТВ

... 1. Фармацевтическая композиция, отличающаяся тем, что она содержит наночастицы, обладающие высоким сродством к вырожденным клеткам, по меньшей мере, одно терапевтическое средство, выбираемое из группы, включающей актиномицин D, аминоглутетимид, антрациклины, амсакрин, анастрозол, анатагонисты пуриновых и пиримидиновых оснований, антрациклины, ингибиторы ароматазы, аспарагиназу, антиэстрогены, бексаротен, блеомицин, бузерелин, бусульфан, производные камптотецина, капецитабин, карбоплатин, кармустин, хлорамбуцил, цисплатин, кладрибин, циклофосфамид, цитарабин, цитозина арабинозид, алкилирующие цитостатики, дакарбазин, дактиномицин, даунорубицин, доцетаксел, доксорубицин (адриамицин), доксорубицин липо, эпирубицин, эстрамустин, этопозид, экземестан, флударабин, фторурацил, антагонисты фолиевой кислоты, форместан, гемцитабин, глюкокортикоиды, гозерелин, гормоны и гормональные антагонисты, гикамтин, гидроксимочевина, идарубицин, ифосфамид, иматиниб, иринотекан, милтефозин, митомицины, ингибиторы ...

НОВЫЕ ЛЕКАРСТВЕННЫЕ СРЕДСТВА ДЛЯ МЕСТНОГО ПРИМЕНЕНИЯ НА ОСНОВЕ СУЛЬФАТИРОВАННОЙ ГИАЛУРОНОВОЙ КИСЛОТЫ В КАЧЕСТВЕ СТИМУЛЯТОРОВ ИЛИ ИНГИБИТОРОВ ЦИТОКИНОВОЙ АКТИВНОСТИ

... 1. Сульфатированная гиалуроновая кислота для местного применения для профилактики и/или лечения воспалительных/вызывающих раздражение заболеваний кожи, выбранных из дерматита, атопического дерматита, фотодерматита, сыпи, витилиго, экземы, псориаза, всех раздражений кожи, связанных с активацией провоспалительных цитокинов, таких как IL-1, IL-2, IL-6, IL-7, IL-8, IL-12 и TNF, причем указанная сульфатированная гиалуроновая кислота (HA) имеет молекулярную массу в диапазоне от 10000 до 50000 Да, от 150000 до 250000 Да или от 500000 до 750000 Да и степень сульфатации, равную 1 или 3.2. Сульфатированная гиалуроновая кислота для местного применения в качестве гидратирующего агента для лечения патологических состояний кожи, характеризуемых сухостью, лихенификацией, раздражением, зудом и гиперемией, воспалением и шелушением, причем указанная сульфатированная гиалуроновая кислота (HA) имеет молекулярную массу в диапазоне от 10000 до 50000 Да, от 150000 до 250000 Да или от 500000 до 750000 Да и степень ...

ПРИМЕНЕНИЕ ЛЕВОЦИТИРИЗИНА И МОНТЕЛУКАСТА ПРИ ЛЕЧЕНИИ АУТОИММУНЫХ РАССТРОЙСТВ

ФАРМАЦЕВТИЧЕСКАЯ КОМБИНАЦИЯ ДЛЯ ЛЕЧЕНИЯ ОТ БОЛИ

... 1. Комбинация, включающая в качестве компонента(ов):(a) как минимум один 3-(3-диметиламино-1-этил-2-метил-пропил)-фенол формулы (I),необязательно в форме одного из его стереоизомеров, в частности, энантиомера или диастереомера, рацемата или в форме смеси его стереоизомеров, в частности, энантиомеров и/или диастереомеров в любом соотношении смешивания, или любой его соответствующей кислотной аддитивной соли, и(b) как минимум один антагонист NMDA.2. Комбинация по п.1, отличающаяся тем, что соединение формулы (I) выбирают из группы, к которой относятся(1R,2R)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенол,(1S,2S)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенол,(1R,2S)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенол,(1S,2R)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенол, и любая их смесь.3. Комбинация по п.2, отличающаяся тем, что соединение формулы (I) выбирают из группы; к которой относятся(1R,2R)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенол,(1S,2S)-3-(3-диметиламино-1-этил-2-метил-пропил ...

НОВЫЕ ЛЕКАРСТВЕННЫЕ СРЕДСТВА ДЛЯ МЕСТНОГО ПРИМЕНЕНИЯ НА ОСНОВЕ СУЛЬФАТИРОВАННОЙ ГИАЛУРОНОВОЙ КИСЛОТЫ В КАЧЕСТВЕ СТИМУЛЯТОРОВ ИЛИ ИНГИБИТОРОВ ЦИТОКИНОВОЙ АКТИВНОСТИ

... 1. Сульфатированная гиалуроновая кислота для местного применения для профилактики и/или лечения простого герпеса губ и половых органов, вируса везикулярного стоматита и цитомегаловируса, причем указанная сульфатированная гиалуроновая кислота (HA) имеет молекулярную массу в диапазоне от 10000 до 50000 Да, от 150000 до 250000 Да или от 500000 до 750000 Да и степень сульфатации, равную 1 или 3.2. Фармацевтическая композиция для местного применения, содержащая сульфатированную гиалуроновую кислоту по п. 1, возможно, совместно с фармакологически и/или биологически активными средствами.3. Фармацевтическая композиция по п. 2, содержащая стероиды, гормоны, белки, трофические факторы, витамины, нестероидные противовоспалительные лекарственные средства, химиотерапевтические лекарственные средства для местного применения, антибиотики, противовирусные средства, местные анестетики, антикоагулянты и/или фибринолитические средства, ферменты и/или другие протеазы.4. Фармацевтическая композиция по п. 3, ...

СОСТАВ ДЛЯ ЛЕЧЕНИЯ ГЕМОРРОЕВ

... 1. Состав для лечения геморроев, содержащий некоторое количество смазывающего вещества и некоторое количество метилрозанилина, смешанного с указанным количеством смазывающего вещества, для получения композиционной смеси. 2. Состав по п.1, отличающийся тем, что указанное смазывающее вещество содержит вазелин. 3. Состав по п.1, отличающийся тем, что указанный метилрозанилин и указанное смазывающее вещество присутствуют в указанной композиционной смеси в отношении по меньшей мере примерно от 0,2 до 0,3 мл указанного метилрозанилина на чайную ложку указанного смазывающего вещества. 4. Состав по п.3, отличающийся тем, что указанное смазывающее вещество содержит вазелин. 5. Состав для лечения геморроев, полученный путем смешивания некоторого количества метилрозанилина с некоторым количеством смазочного вещества, образующим композиционную смесь. 6. Состав по п.5, отличающийся тем, что указанное смазывающее вещество содержит вазелин. 7. Состав по п.5, отличающийся тем, что указанный метилрозанилин ...

Способ лечения начального пульпита с биоактивным заменителем дентина

Изобретение относится к стоматологии и может быть использовано при консервативном лечении начального пульпита. Осуществляют удаление мягкого зубного налета абразивной пастой с RDA150-200. Препарируют кариозную полость алмазными и твердосплавными борами, установленными в наконечнике с воздушно-водяным охлаждением. Твердые ткани обрабатывают кинетической воздушно-абразивным бластером Rondoflex и порошком с частицами оксида алюминия размером 27 мкм. Осуществляют установку коффердама и проводят, при показателях ЭОД от 19-25 мкА, аппликации антисептическим 2% водным раствором хлоргексидина биглюконата с последующей аппликацией трикальцийсиликатного цемента, где порошок цемента замешивают на дистиллированной воде до получения однородной массы, которую распределяют лайнерно или точечно по всей поверхности дна твердых тканей кариозной полости, а после твердения массы кариозную полость обрабатывают адгезивной системой, содержащей 10 - метакрилоилоксидецилдигидроген фосфат с супер адаптационной поддержкой ...

VERFAHREN ZUR BEHANDLUNG VON CHRONISCHEM SCHMERZ DURCH VERABREICHUNG VON EINEM MEK HEMMER

POLYHYDROXYLIERTE AROMATISCHEN VERBINDUNGEN FÜR DIE BEHANDLUNG VON AMYLOIDOSIS UND ALPHA-SYNUCLEIN FIBRIL KRANKHEITEN

POLYCYCLISCHE DIANTHRACHINONE ALS ANTIKREBSMITTEL UND ANTIANGIOGENESEMITTEL

VERWENDUNG VON MEMANTIN (NAMENDA) ZUR BEHANDLUNG VON AUTISMUS, ZWANGSVERHALTEN UND IMPULSIVITÄT

Cancer treatment

Pharmaceutical compositions comprising a proton pump inhibitor and a prokinetic agent

Method for obtaining aqueous formulations of oxidation sensitive active principles.

The invention concerns the field of organic chemistry and more particularly that of therapeutic chemistry. More precisely, it concerns a method for obtaining aqueous formulations of easily oxidizable active principles, in particular phenols, stable over a prolonged period, which consists in advanced bubbling deoxygenation with an inert gas and/or vacuumizing them, while protecting them against possible oxygen uptake by maintaining them under inert gas atmosphere, by filling under inert gas into bottles previously made air-free by inert gas blowing, then in subjecting them when they are being closed to a vacuum so as to obtain in the bottle a pressure of not more than 65.000 Pa, thereby obtaining solutes having a residual oxygen concentration in the solution, less than 2 ppm, and preferably of the order of 1 ppm and even 0.5 ppm. The invention is useful in particular for preparing injection preparations having an oxygen content in the solution, less than 2 ppm.

Method for obtaining aqueous formulation of oxidation sensitive active principles

Pharmaceutical compositions comprising a proton pump inhibitor and a prokinetic agent

Inhibitors of metazoan parasite proteases

Method for obtaining aqueous formulation of oxidation sensitive active principles

Method for obtaining aqueous formulation of oxidation sensitive active principles

Pharmaceutical compositions comprising a proton pump inhibitor and a prokinetic agent

FUNKTIONALISIERTE HIGHER ONE DIAMANTOIDE

CONNECTION OF A B3-REZEPTOR-AGONISTEN WITH MONOAMIN WIEDERAUFNAHMEHEMMERN, PHARMACEUTICAL COMPOSITION THEREBY AND THERAPEUTIC USE FOR IT

MANUFACTURING METHOD OF A STENTS WITH ANTI-ANGIOGENIC COMPOSITION

PRAY-PRAYING A2 ADRENERGIC AGONISTEN FOR THE TREATMENT OF CHRONIC NEUROPATI ALLODYNIE

CANCER CELL TARGETING WITH NANO-PARTICLES

HEMMER FOR THE PRODUCTION AND RELEASE OF INFLAMMATORY ONES ZYTOKINE

TOPI DAPSON FOR THE TREATMENT OF ACNE

ANTI-ANGIOGENIC MEANS AND PROCEDURES FOR THEIR USE

USE OF MEMANTIN (NAMENDA) FOR THE TREATMENT OF AUTISMUS, OBLIGATION BEHAVIOR AND IMPULSIVIT�T

DRUG CONTAINING A EFFEKTOR OF THE GLUTATHIONMETABOLISMUS (AMBROXOL) TOGETHER WITH ALPHA LIPONSÄURE ONES IN THE CONTEXT OF THE TREATMENT THE DIABETES MELLITUS

ANTI-ARRHYTHMIC COMPOSITIONS AND TREATMENT PROCEDURES

SOLUTIONS FROM ANTHRACHINONEN TO THE PARENTERAL APPLICATION

CONNECTIONS, WHICH ARE TO OF A NEW PLACE ON RECEPTOR-STIMULATED CALCIUM CHANNELS EFFECTIVE, USABLE FOR THE TREATMENT OF NEUROLOGICAL DISEASES

INHIBITORS THAT METAZOENPARASITEN PROTEASEN

CONNECTIONS, WHICH TO A NEW PLACE ON RECEPTOR - FUNCTIONING ARE CALCIUM CHANNEL EFFECTIVE, TO THE TREATMENT OF NEUROLOGICAL ILLNESSES

MEANS FOR THE FIGHT AGAINST NEOSPORA SPEC, THE ACTIVE SUBSTANCES, MIKROTUBULINSYTEM AGAINST PLANZEN RESTRAINING, CONTAINING

Bacterial ghosts for the treatment of cancer

The present invention relates to a composition comprising Bacterial Ghosts, optionally an active agent, and a pharmaceutically acceptable carrier and/or excipient for use in the treatment of cancer.

Topical dapsone and dapsone/adapalene compositions and methods for use thereof

Dapsone and dapsone/adapalene compositions can be useful for treating a variety of dermatological conditions. The compositions of this disclosure include dapsone and/or adapalene in a polymeric viscosity builder. Subject compositions can be adjusted to optimize the dermal delivery profile of dapsone to effectively treat dermatological conditions and improve the efficiency of pharmaceutical products applied to the skin. Use of the polymeric viscosity builder provides compositions with increased concentrations of diethylene glycol monoethyl ether relative to compositions without the polymeric viscosity builder.

Muscarinic acetylcholine M1 receptor antagonists

Provided herein are compounds which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

Trk-inhibiting compound

T RK-INHIBIT ING COMPOUND The present invention provides a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy for Trk-related diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I): Aj A3 0 A, 0 ip (R2)q N N 5Y 6 N'JN CY 6 (143)r HH wherein all symbols represent the same meanings as described in the specification, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

Amantadine compositions, preparations thereof, and methods of use

Provided herein are oral pharmaceutical compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, and which have a low level of organic solvent. Provided are also methods of orally administrating a composition comprising amantadine, or a pharmaceutically acceptable salt thereof, to a subject, which has reduced gastrointestinal side effects or sleep disturbances. Further provided are extended release oral compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, that are suitable for once daily administration.

Pharmaceutical composition of S-ketamine hydrochloride

OF THE INVENTION The present invention is directed to an aqueous formulation of S-ketamine hydrochloride, preferably for nasal administration, wherein the formulation does not contain an antimicrobial preservative.

Functionalized magnetic nanoparticles and use in imaging amyloid deposits and neurofibrillary tangles

OF THE DIsCLOSURE The present disclosure provides functionalized magnetic nanoparticles (MNPs) comprising a functional group that binds to p-amyloid deposits and/or neurofibrillary tangles. The present disclosure provides compositions comprising the functionalized MNPs, and methods of using the functionalized MNPs in imaging -amyloid deposits and neurofibrillary tangles.

Using selective antagonists of persistent sodium current to treat neurological disorders and pain

Tri-aryl compounds and compositions comprising the same

Enhanced production of clotting factors by cryoprecipitation

Methods of treatment using combination therapy

Provided herein are methods of treating a proliferative disease in a subject, comprising administering to the subject a therapeutically effective amount of AC220 and a nucleoside analog, a topoisomerase inhibitor or an anthracycline, or a combination thereof.

Modulators of ATP-Binding Cassette Transporters

The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Combinations comprising alpha-2-delta ligands and serotonin / noradrenaline re-uptake inhibitors

Method for obtaining aqueous formulations of oxidation-sensitive active principles

Percutaneous delivery system

Treatment of dyskinesia

Compositions and methods for reversal of drug resistance

METHOD OF TREATMENT OF HYPERTENSION USING SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS (SSRIs)

TETRAFLUOROBENZYL DERIVATIVES AND PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING ACUTE AND CHRONIC NEURODEGENERATIVE DISEASES IN CENTRAL NERVOUS SYSTEM CONTAINING THE SAME

Targeted polymerized nanoparticles for cancer treatment

The invention relates to a novel drug delivery vehicle. Various embodiments of the invention provide a hybrid polymerized liposomal nanoparticle comprising both polymerizable lipids and non-polymerizable lipids. Therapeutic agents can be loaded into the polymerized liposomal nanoparticle and targeting agents can be conjugated to the surface of the polymerized liposomal nanoparticle. Also described in the invention are methods, compositions and kits that utilize the hybrid polymerized liposomal nanoparticle to treat disease conditions such as various cancers.

Inhibitors of notch signalling pathway and use thereof in treatment of cancers

The present invention relates to use of inhibitors of Notch signalling pathway selected from the group consisting of 6-(4-Tert-Butylphenoxy)Pyridin-3-Amine (I3), its derivatives, in treating and/or preventing cancers.

Non-platimun-based anti-cancer compounds for use in targeted chemotherapy

Disclosed herein are non-platinum-based (NPB) anti-cancer compounds useful for targeted chemotherapy, e.g., to generate anti-cancer effects for the treatment of cancer and other disorders while having no or minimal toxicity. The compounds have the general formula I: (I) wherein A represents an aromatic core; at least one of R ...

Combination therapy for treating malignancies

Provided are methods and compositions for treating AML in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and an AML induction and consolidation therapy.

Aromatic compounds derived from imine, their preparation and their use in human and veterinary medicine and in cosmetics

Anti-angiogenic compositions and methods of use

Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-l. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

Dermal anesthetic agents

Local delivery of therapeutic agents

Polyhydroxylated aromatic compounds for the treatment of amyloidosis and alpha-synuclein fibril diseases

As-needed administration of tricyclic and other non-sri antidepressant drugs to treat premature ejaculation

Polycyclic dianthraquinones as anti-cancer and anti-angiogenic agents

Sulfonyl fluorides for the treatment of alzheimer's disease

COMBINATION OF DAPSONE WITH ADAPALENE

A composition suitable for topical application that contains at least two active ingredients, one of these being dapsone and one selected from the group consisting of adapalene, tazarotene and treinion for the effective treatment of acne and other dermatological conditions.

CANCER CELL TARGETING USING NANOPARTICLES

The present invention generally relates to polymers and macromolecules, in particular, to polymers useful in particles such as nanoparticles. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. In some cases, the nanoparticle may contain a drug. Other aspects of the invention are directed to methods using nanoparticle libraries.

TRIARYLMETHANE ANALOGS AND THEIR USE IN TREATING CANCERS

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are triphenyl methane analogs. The compounds and compositions can be used to treat and/or prevent a wide variety of cancers, including drug resistant cancers, inflammatory, degenerative and vascular diseases, including various ocular diseases, and parasitic infections. Representative triphenyl methane analogs include triphenyl methane analogues of various dyes, hormones, sugars, peptides, oligonucleotides, amino acids, nucleotides, nucleosides, and polyols. The compounds are believed to function by inhibiting tNOX expression, the effects of ROS, and/or the production of HIF2. Thus, the compounds are novel therapeutic agents for a variety of cancers and other diseases.

TOPICAL DAPSONE FOR THE TREATMENT OF ACNE

The present invention relates to a method of treating acne by topically applying a dermatological composition comprising dapsone. In addition to inflammatory lesions, the compositions also treats non-inflammatory acne. The composition is formulated to include dapsone in a both a dissolved and microparticulate state.

METHODS OF TREATMENT USING COMBINATION THERAPY

Provided herein are methods of treating a proliferative disease in a subject, comprising administering to the subject a therapeutically effective amount of AC220 and a nucleoside analog, a topoisomerase inhibitor or an anthracycline, or a combination thereof.

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

AMBROXOL FOR TREATING TINNITUS

The invention concerns the use of ambroxol and its pharmaceutically acceptable salts for producing a medicine for treating tinnitus and other otologic disorders.

USE OF CALORIC RESTRICTION MIMETICS FOR POTENTIATING CHEMO-IMMUNOTHERAPY FOR THE TREATMENT OF CANCERS

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-l. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

TOPICAL ANESTHETIC COMPOSITION

A topical anesthetic composition comprising benzocaine, pharmaceutically acceptable salt thereof, amide thereof and/or ester thereof; tetracaine and/or pharmaceutically acceptable salt thereof; ethanol; polyethylene glycol; propylene glycol; water; and benzyl alcohol is provided. Also provided is method for dispensing the above topical anesthetic composition to a desired site such by spraying the topical anesthetic from a pump actuated metered dose spray device. The topical anesthetic composition can also be administered subgingivally with a syringe and applicator tip. A product comprising the above topical anesthetic spray composition contained in a pump actuated metered dose spray device.

COMBINATION THERAPY FOR TREATING MALIGNANCIES

Provided are methods and compositions for treating AML in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and an AML induction and consolidation therapy.

PHARMACEUTICAL COMPOSITIONS AND METHODS FOR COUNTERING CHEMOTHERAPY INDUCED CARDIOTOXICITY

This disclosure provides methods and pharmaceutical compositions for reducing or eliminating cardiotoxicity, particularly cardiotoxicity induced by a cancer treatment or other therapy. In some cases, the methods and compositions prevent or reduce cardiotoxicity caused by anthracycline treatment. The methods provided herein often comprise administering a protective agent such as myricetin, tricetin, robinetin, ficetin, vitexin, quercetin, dihydrorobinetin, kaempferol, 7,3',4',5'-tetrahydroxyflavone, and myricitrin in conjunction with the administration of a cancer drug or other treatment. They may comprise administering a protective agent in combination with dexrazoxane. The compositions provided herein include co-formulations of a protective agent with a different protective agent or with a cancer treatment (e.g., anthracycline drug).

AGENTS FOR INCREASING THE SECRETION OF ANTI-INFLAMMATORY CYTOKINES

The authors of the present invention have found a method for enhancing the endogenous production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), in mammalian cells or tissues, comprising administering to a subject, preferably a human subject, in need thereof an effective amount of a LRH-1 agonist according to the invention or a pharmaceutically acceptable salt thereof. This method is shown in the present specification as particularly suitable for treating diseases wherein immunomodulation by an increase in the secretion of anti-inflammatory cytokines, such as IL-10, is desirable, for instance for the treatment of cancer and anti-inflammatory diseases such as type I diabetes, in particular early stage type I diabetes, type II diabetes and autoimmune hepatitis.

CK2 INHIBITORS, COMPOSITIONS AND METHODS THEREOF

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. (formula I) For Formula (I) compounds R1, R2, R3, Ar and Z are as defined in the specification. The inventive Formula (I) compounds are inhibitors of CK2 and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer, inflammation and immunological disorders.

COMPOSITION FOR TREATING JOINT DISEASES AND KIT INCLUDING SAME

The present invention pertains to a composition for treating joint diseases and a kit including the same, and the purpose of the present invention is to provide a composition for treating joint diseases which can be used in patients with joint diseases, and a kit which includes the same. Specifically provided is a composition for treating joint diseases that obtains higher efficacy than prior preparations by means of a composition for treating joint diseases which includes a modified hyaluronic acid having a group derived from an anti-inflammatory compound or a pharmaceutically acceptable salt of the modified hyaluronic acid, and which is targeted at patients with human joint diseases who have a BMI of 25 kg/m2 or higher.

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ACUTE DISORDERS

COMBINATION THERAPY FOR TREATING CANCER

The present invention relates to compositions comprising inhibitors of human histone methyltransferase DOTIL and one or more therapeutic agents, particularly anticancer agents, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

METHOD OF TREATING CANCER USING SELECTIVE ESTROGEN RECEPTOR MODULATORS

Disclosed herein are methods of treating subjects suffering from estrogen receptor positive cancer of the brain by administering a selective estrogen receptor degrader (SERM). Also disclosed are methods of treating a cancer that is resistant to an estrogen receptor modulator by administering a SERM.

COMPARATIVE EFFICACY AND TOLERABILITY OF DAPSONE 5% IN ADULT VERSUS ADOLESCENT FEMALES WITH ACNE VULGARIS

The present invention provides a method of treating facial acne vulgaris in an adult female (=18 years of age) in need of such treatment, comprising topically administering dapsone 5% gel twice daily to the face of the adult female.

PHARMACEUTICAL CONTAINING 3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYL-PROPYL)PHENOL AND PROVIDING DELAYED RELEASE OF THE ACTIVE INGREDIENT

The invention relates to a pharmaceutical formulation which is characterised by delayed release of the active ingredient. Said formulation contains 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or one of its pharmaceutically acceptable salts in a matrix with delayed release of the active ingredient. Said matrix contains between 1 and 80 wt.% of at least one hydrophilic or hydrophobic polymer as a pharmaceutically acceptable matrix forming agent and exhibits, in vitro, the following dissolution speed: between 3 and 35 wt.% (in relation to 100 wt.% of active ingredient) of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol is released after half an hour, between 5 and 50 wt.% of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol is released after one hour, between 10 and 75 wt.% of 3-(3-dimethylamino-1-ethyl- 2- methyl-propyl)phenol is released after two hours, between 15 and 82 wt.% of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol is released after three hours, between 30 and 97 wt ...

COMPLEMENT ANTAGONISTS AND USES THEREOF

Disclosed are antagonists designed to inhibit or block expression of a mammalian complement such as complement component 6 (C6). The invention has a wide range of uses including use in the preparation of a medicament for the enhancement of nerve regeneration following acute or chronic nerve damage in a mammal.Additional applications include use in the treatment of multiple sclerosis either alone or in combination with another drug.

SMALL MOLECULE INHIBITORS OF USP1 DEUBIQUITINATING ENZYME ACTIVITY

Provided are small molecule inhibitors of ubiquitin specific protease 1 (USP1) activity and methods for their use in treating and characterizing cancers. The small molecule USP1 inhibitors of the invention are particularly useful in the treatment of cancers that are resistant to DNA cross-linking agents.

Compositions and methods relating to proliferative diseases

Anti-cancer compositions and methods are described herein. In particular, compositions including one or more of leelamine, a leelamine derivative, abietylamine, an abietylamine derivative, and an abietic acid derivative are described. Methods for treatment of pathological conditions particularly cancer, in a subject using one or more of leelamine, a leelamine derivative, abietylamine, an abietylamine derivative, and an abietic acid derivative are described herein.

Polymer Formulations for Delivery of Bioactive Materials

PLGA, PLA and PGA polymers which have crystallinity resulting from the presence of long chain alkyl groups in terminal units. The polymers are particularly useful for drug delivery.

Combination therapy for cancer comprising a platinum-based antineoplastic agent and a biocompatible electron donor

The combination of a biocompatible electron donor and a platinum-based antineoplastic agent exhibits improved efficacy in treating cancer This improved activity appears to be the result of electron transfer from the aforementioned donor compound to the platinum-based antineoplastic agent As the electron donor alone has no chemotherapeutic utility in treating cancer, the resulting combinations appear to be synergistic in nature In select preferred embodiments, the biocompatible electron donor is an amine (such as N,N,N′,N′-tetramethyl-p-phenylene diamine or indocyanine green), a phenolic compound (such as a flavanol or catechin), or a quinone (such as an aromatic quinone), while the antineoplastic is cisplatin.

Soluble pharmaceutical formulations of n,n-diaminodiphenyl sulfone for optimal use in the treatment of various diseases

The present invention aims to demonstrate that a soluble pharmaceutical formulation can be prepared of N,N′-Diamino-diphenyl sulfone which is useful in the development of an ideal drug for use against cerebral infarction, epilepsy, traumatic spinal cord injury, cranio-encephalic trauma, leprosy, Pneumocystis carinii infections and any condition which requires rapid and complete absorption of the compound. As a representative example of this application, the dissolution of N,N′-Diamino-diphenyl sulfone was evaluated as a neuroprotector in a model of acute cerebral infarction in rats. In this study, N,N′-Diamino-diphenyl sulfone showed significant prevention of brain damage, without presenting adverse effects in animals. It is also shown that the soluble pharmaceutical formulations prepared in this manner produce peak blood levels 30 minutes from oral administration and immediately via the intravenous route.

Substituted 4-aminocyclohexane derivatives

The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain and other conditions.

Extended-release formulation for reducing the frequency of urination and method of use thereof

Methods and compositions for reducing the frequency of urination are disclosed. One method comprises administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising an analgesic agent formulated in an extended-release formulation. Another method comprises administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising multiple active ingredients formulated for extended-release. Yet another method comprises administering to a subject in need thereof an effective amount of a diuretic followed with another administration of a pharmaceutical composition comprising an analgesic agent formulated for extended-release.

Small molecules that covalently modify transthyretin

A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

Compositions and methods for treating alzheimers disease

Pharmaceutical compositions for treating Alzheimer's disease are disclosed. The pharmaceutical compositions include a compound having the general formula: and a pharmaceutically acceptable carrier. Methods for treating Alzheimer's disease, inhibiting ATase I and/or ATase 2, reducing the activity of BACE1, reducing the level of amyloid β-peptide (Aβ), and/or reducing the level of APP intracellular domain peptide (AICD) by administering such compositions are also disclosed.

Antiviral Compounds and Methods of Use Thereof

Inhibitors of retroviral propagation, methods of treatment and prevention of retroviral infections using the inhibitors, and pharmaceutical compositions including the inhibitors, are disclosed. 1. (canceled)34-. (canceled)6. (canceled)7. The composition of claim 5 , wherein at least one of R4 claim 5 , R5 claim 5 , R6 claim 5 , R7 claim 5 , R15 claim 5 , R16 claim 5 , and R17 is other than H.8. (canceled)9. The composition of claim 1 , further comprising an additional antiviral agent.10. The composition of claim 9 , wherein the additional antiviral agent is an entry inhibitor claim 9 , integrase inhibitor claim 9 , reverse transcriptase inhibitor claim 9 , protease inhibitor claim 9 , or an immune-based therapeutic agent.11. A method of treating a retroviral infection claim 1 , comprising administering a composition of .12. The method of claim 11 , wherein the inhibitor inhibits retroviral reverse transcription.13. The method of claim 11 , wherein the inhibitor inhibits viral recruitment of the retroviral primer used in translation claim 11 , human tRNA.14. The method of claim 11 , wherein the inhibitor inhibits the final packaging and assembly of new virions.15. The method of claim 11 , wherein the inhibitor inhibits the binding of a host cell tRNA to a target nucleic acid molecule.16. The method of claim 11 , further comprising the co-administration of a second antiretroviral compound.17. The method of claim 16 , wherein the second antiretroviral agent is selected from the group consisting of NRTIs claim 16 , NNRTIs claim 16 , VAP anti-idiotypic antibodies claim 16 , CD4 and CCR5 receptor inhibitors claim 16 , entry inhibitors claim 16 , antisense oligonucleotides claim 16 , ribozymes claim 16 , protease inhibitors claim 16 , neuraminidase inhibitors claim 16 , tyrosine kinase inhibitors claim 16 , PI-3 kinase inhibitors claim 16 , and Interferons.18. The method of any of claim 11 , wherein the retrovirus is selected from the group consisting of Feline ...

Kinase protein binding inhibitors

The invention relates to phosphorylation inhibitor compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating cell proliferative disorders, especially cancer.

CHEMICAL AGENTS FOR THE PREVENTION OF INHIBITION OR TUMOR METASTASIS

The present invention provides methods of preventing or inhibiting tumor metastasis in a subject by administering a therapeutically effective amount of (1) a compound from a group of enumerated compounds, or a pharmaceutically acceptable salt thereof; (2) an agent that covalently modifies at least one cysteine residue of S100A4 protein; or (3) an agent that inhibits the interaction between S100A4 and myosin-IIA. 2. The method of claim 1 , wherein the compound is the compound of formula (I).5. The method of claim 1 , wherein the compound is the compound of formula (III).8. The method of claim 1 , wherein the compound comprises 2 claim 1 ,3-dihydrobenzo[g][1 claim 1 ,4]benzodithiine-5 claim 1 ,10-dione claim 1 , 2 claim 1 ,3-bis(2-hydroxyethylsulfanyl)naphthalene-1 claim 1 ,4-dione claim 1 , 2-(2-hydroxyethylsulfanyl)naphthalene-1 claim 1 ,4-dione claim 1 , 3-(1 claim 1 ,4-dioxonaphthalen-2-yl)sulfanylpropanoic acid claim 1 , 2-ethylsulfanylnaphthalene-1 claim 1 ,4-dione claim 1 , 4 claim 1 ,11-diaminonaphtho[2 claim 1 ,3-f]isoindole-1 claim 1 ,3 claim 1 ,5 claim 1 ,10-tetrone claim 1 , 2-(3-methyl-1 claim 1 ,4-dioxonaphthalen-2-yl)sulfanylacetic acid claim 1 , 2-butylsulfanylnaphthalene-1 claim 1 ,4-dione claim 1 , 2-ethylsulfanyl-3-methylnaphthalene-1 claim 1 ,4-dione claim 1 , 2-(2-hydroxyethylsulfanyl)-3-methylnaphthalene-1 claim 1 ,4-dione claim 1 , 2-methyl-3-methylsulfanylnaphthalene-1 claim 1 ,4-dione claim 1 , (1 claim 1 ,4-dioxonaphthalen-2-yl) 4-methylbenzoate claim 1 , N-[3-(4-chlorophenyl)sulfanyl-1 claim 1 ,4-dioxonaphthalen-2-yl]acetamide claim 1 , 2-benzylsulfanyl-3-methylnaphthalene-1 claim 1 ,4-dione claim 1 , N-(3-chloro-1 claim 1 ,4-dioxonaphthalen-2-yl)-N-(4-fluorophenyl)acetamide claim 1 , 2-methylquinoline-5 claim 1 ,8-dione claim 1 , N-(7-chloro-5 claim 1 ,8-dioxoquinolin-6-yl)acetamide claim 1 , 6-amino-7-chloroquinoline-5 claim 1 ,8-dione claim 1 , 7-amino-6-methoxyquinoline-5 claim 1 ,8-dione claim 1 , 6 claim 1 ,7-dichloroquinoline-5 claim ...

METHODS OF TREATMENT USING COMBINATION THERAPY

Provided herein are methods of treating a proliferative disease in a subject, comprising administering to the subject a therapeutically effective amount of AC220 and a nucleoside analog, a topoisomerase inhibitor or an anthracycline, or a combination thereof. 6. The method of further comprising administering:{'sup': '2', '45 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '50 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '45-60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '70 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '12 mg/m/day of idarubicin for 3 days,'}{'sup': '2', '8 mg/m/day of idarubicin for 2 days, or'}{'sup': '2', '12 mg/m/day of mitoxantrone for 3 days.'}7. The method of further comprising administering:{'sup': '2', '45 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '50 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '45-60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '70 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '12 mg/m/day of idarubicin for 3 days,'}{'sup': '2', '8 mg/m/day of idarubicin for 2 days, or'}{'sup': '2', '12 mg/m/day of mitoxantrone for 3 days.'}8. The method of claim 1 , wherein the proliferative disease is leukemia.9. The method of claim 8 , wherein the leukemia is acute myeloid leukemia.10. The method of claim 8 , wherein the leukemia is positive for the FLT3-ITD mutation.11. The method of claim 8 , wherein the mammal is a patient of 65 years or younger with newly diagnosed acute myeloid leukemia.12. The method of claim 2 , wherein the proliferative disease is leukemia.13. The method of claim 12 , wherein the leukemia is acute myeloid leukemia.14. The method of claim 12 , wherein the leukemia is positive for the FLT3-ITD mutation.15. The method of claim 12 , wherein the mammal is a patient of 65 years or younger with newly diagnosed acute myeloid leukemia.16. The method of claim 3 , ...

Use of FAAH Inhibitors for Treating Parkinson's Disease and Restless Legs Syndrome

The present disclosure relates to methods of using fatty acid amide hydrolase (FAAH) inhibitors to treat aspects of Parkinson's disease (PD), restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), the use of FAAH inhibitors for the manufacture of medicaments for use in the treatment of PD, RLS and PLMD, as well as pharmaceutically acceptable compositions comprising FAAH inhibitors for use in the treatment of PD, RLS and PLMD. 182-. (canceled)83. A method of treating or preventing an impulse control disorder (ICD) , dopamine dysregulation syndrome (DDS) or sleep disorder arising from the treatment of a patient suffering from Parkinson's disease (PD) , restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) or combination thereof with a dopaminergic agent , comprising administering a therapeutically effective amount of a FAAH inhibitor , or a therapeutically effective amount of a dopaminergic agent and a therapeutically effective amount of a FAAH inhibitor to said patient.84. The method according to claim 83 , wherein the dopaminergic agent is a dopamine replacement agent claim 83 , a dopamine agonist claim 83 , a dopamine uptake inhibitor or a monoamine oxidase inhibitor.85. The method according to claim 84 , wherein the dopamine replacement agent comprises melevodopa or L-3 claim 84 ,4-dihydroxyphenylalanine (levodopa claim 84 , L-DOPA) claim 84 , or an AADC enzyme inhibitor or both an AADC enzyme inhibitor and a COMT inhibitor.86. The method according to claim 85 , wherein the AADC enzyme inhibitor is carbidopa or benserazide and the COMT inhibitor claim 85 , if present claim 85 , is entacapone or tolcapone.87. The method according to claim 84 , wherein the dopamine agonist is bromocriptine (Parlodel®) claim 84 , pergolide (Permax®) claim 84 , pramipexole (Mirapex®) claim 84 , ropinirole (Requip®) claim 84 , rotigotine (Neupro®) claim 84 , cabergoline (Dostinex®) claim 84 , apomorphine (Apokyn®) claim 84 , lisuride (Dopergine®) or ...

Neutralization of flt3 ligand as a leukemia therapy

Disclosed herein are methods and compositions for treating leukemia and preventing leukemia relapse related to the administration of agents that inhibit the binding of FLT3 ligand to FLT3.

Methods for inhibition of cell proliferation, synergistic transcription modules and uses thereof

The invention provides for methods for treating nervous system cancers in a subject. The invention further provides methods for treating nervous system tumor cell invasion, migration, proliferation, and angiogenesis associated with nervous system tumors.

SUBSTITUTED CIS- AND TRANS-STILBENES AS THERAPEUTIC AGENTS

The present invention relates to method(s) of treating a subject afflicted with cancer or a precancerous condition, an inflammatory disease or condition, and/or stroke or other ischemic disease or condition, the method comprising administering to the subject or patient in need a composition comprising a therapeutically effective amount of a substituted cis or trans-stilbene. A method of treating or reducing the likelihood of Alzheimer's disease in a patient is an additional embodiment of the present invention. 135-. (canceled)40. The method according to wherein said compound is coadministered with resveratrol.41. The method according to wherein said compound is coadministered with resveratrol.42. The method according to wherein said mixture of compounds is coadministered with resveratrol.47. The method according to wherein said compound is coadministered with resveratrol.48. The method according to wherein said compound is coadministered with resveratrol.49. The method according to wherein said mixture of compounds is coadministered with resveratrol.54. The method according to wherein said compound is coadministered with resveratrol.55. The method according to wherein said compound is coadministered with resveratrol.56. The method according to wherein said mixture of compounds is coadministered with resveratrol.57. The method according to wherein said compound is administered orally to said patient.59. The composition according to further including an effective amount of reservatrol.62. A composition according to which is adapted for oral administration. This application is a continuation-in-part application of U.S. patent application Ser. No. 11/789,583, filed Apr. 26, 2007, which claims the benefit of priority of provisional application No. 60/794,765, filed Apr. 25, 2006. The previously filed applications are incorporated by reference in their entirety herein.The present invention relates to method(s) of treating a subject afflicted with cancer or a precancerous ...

Compositions and Methods for Combinations of Oligoamines with 2-Difluoromethylornithine (DFMO)

The present invention is based on the seminal discovery of a synergistic effect for combinations of oligoamines with 2-difluoromethylornithine (DFMO) for treatment of cancer. The invention provides combinations of at least one inhibitor of a histone demethylase enzyme and at least one inhibitor of ornithine decarboxylase (ODC). The invention also provides methods for treatment of cancer using such combinations and methods for altering methylation in a cell using such combinations. The invention provides that certain silenced genes can be re-expressed using combinations disclosed herein.

Cancer cell targeting using nanoparticles

The present invention generally relates to polymers and macromolecules, in particular, to polymers useful in particles such as nanoparticles. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. In some cases, the nanoparticle may contain a drug. Other aspects of the invention are directed to methods using nanoparticle libraries.

SMALL MOLECULE INHIBITORS OF USP1 DEUBIQUITINATING ENZYME ACTIVITY

Provided are small molecule inhibitors of ubiquitin specific protease 1 (USP1) activity and methods for their use in treating and characterizing cancers. The small molecule USP1 inhibitors of the invention are particularly useful in the treatment of cancers that are resistant to DNA cross-linking agents. 3. The pharmaceutical composition of claim 1 , further comprising a DNA cross-linking agent.4. The pharmaceutical composition of claim 1 , further comprising a poly(adenosine diphosphate (ADP)-ribose)polymerase (PARP) inhibitor7. The pharmaceutical composition of claim 5 , further comprising a DNA cross-linking agent.8. The pharmaceutical composition of claim 5 , further comprising a poly(adenosine diphosphate (ADP)-ribose)polymerase (PARP) inhibitor.10. The pharmaceutical composition of claim 9 , further comprising a poly(adenosine diphosphate (ADP)-ribose)polymerase (PARP) inhibitor.11. (canceled)13. (canceled)15. (canceled)1821-. (canceled)2326-. (canceled)2830-. (canceled)32. (canceled)34. (canceled)36. A method to identify a cancer that is responsive to ubiquitin specific protease 1 (USP1) inhibition claim 9 , comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting cancer cells from a cancer with a small molecule inhibitor of USP1 according to Formula I of'}or a pharmaceutically acceptable salt thereof; andmeasuring USP1 activity in the cancer cells contacted with the small molecule inhibitor of USP1,wherein reduced USP1 activity in the cancer cells contacted with the small molecule inhibitor of USP1 relative to control USP1 activity in the cancer cells not contacted with the small molecule inhibitor of USP1 identifies the cancer as a cancer that that is responsive to USP1 inhibition.37. (canceled)38. A method to identify a cancer that is responsive to ubiquitin specific protease 1 (USP1) inhibition claim 9 , comprising{'claim-ref': {'@idref': 'CLM-00005', 'claim 5'}, 'contacting cancer cells from a cancer with a small molecule inhibitor of USP1 ...

PHARMACEUTICAL FORMULATION HAVING NEUROPROTECTIVE ACTIVITY

[Problem] The purpose of the present invention is to provide a neuroprotective agent which is capable of effectively protecting intraocular cells including optic nerves and is effective as a composition for ophthalmic membrane staining in cases where removal of an ophthalmic membrane is carried out. 1. A neuroprotective agent comprising , as an active ingredient:Brilliant Blue G, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof; andtriamcinolone acetonide, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.2. The neuroprotective agent according to claim 1 , being a protective agent of an optic nerve.3. The neuroprotective agent according to claim 1 , further being used as a staining composition for staining an ophthalmic membrane when the ophthalmic membrane removal is performed.4. The neuroprotective agent according to claim 1 , further being used as a staining composition for staining vitreous.5. The neuroprotective agent according to claim 1 , further being used as an anti-inflammatory agent. The present invention relates to a neuroprotective agent having a neuroprotective effect. In more detail, the present invention relates to a neuroprotective agent containing Brilliant Blue G, and triamcinolone acetonide.In the specification of U.S. Pat. No. 7731941 (Patent Literature 1), there is a disclosure that Brilliant Blue G (BBG) is effective as an ophthalmic membrane staining when the ophthalmic membrane removal is performed.In U.S. Application Publication No. 2010-74884 (Patent Literature 2), there is a disclosure that BBG is an antagonist of a P2X receptor and inhibits or blocks the pathological action of ATP. Further, in the same Patent Literature, there is a disclosure that BBG has a neuroprotective effect.On the other hand, in U.S. Application Publication No. 2004-65137 (Patent Literature 3), there is a disclosure of a preparation for injection containing steroid triamcinolone ...

Treatments for cellular proliferative disorders and identification thereof

This invention concerns methods of identifying treatments for treating various disorders and related computer products and systems. Also disclosed are methods for treating cellular proliferative disorders and use of compounds identified for such treatment.

Formulations for the prevention and treatment of Wolbachia-related disease

The invention encompasses pharmaceutical formulations for the prevention and treatment of -related disease wherein the formulations comprise a compound previously unknown and unused for such a purpose, the compound being one or more of: Pararosaniline Pamoate, Pyrvinium Pamoate, Clofoctol, and Isoreserpine, derivatives, metabolites, precursors, pro-drugs and variants thereof. 1WolbachiaWolbachia. A pharmaceutical formulation for the prevention and treatment of -related disease , the pharmaceutical formulation containing a drug that kills in vitro and in vivo , wherein the drug is selected from the group consisting of one or more of Pararosaniline Pamoate , Pyrvinium Pamoate , Clofoctol , and Isoreserpine , either singly or in combination.2. The pharmaceutical formulation of wherein the drug consists of Pararosaniline Pamoate.3. The pharmaceutical formulation of wherein the drug consists of Pyrvinium Pamoate.4. The pharmaceutical formulation of wherein the drug consists of Clofoctol.5. The pharmaceutical formulation of wherein the drug consists of Pararosaniline Pamoate claim 1 , Pyrvinium Pamoate claim 1 , Clofoctol claim 1 , and Isoreserpine6. The pharmaceutical formulation of that additionally comprises one or more additives claim 1 , for example pharmaceutically acceptable excipients claim 1 , carriers claim 1 , penetration enhancers claim 1 , stabilizers claim 1 , buffers or other materials.79-. (canceled)10WolbachiaWolbachiaWolbachiaWolbachiaWolbachia. A method for treating of preventing -related disease comprising the following steps: (1) providing an anti-formulation wherein the formulation comprises at least one compound selected from the group consisting of Pararosaniline Pamoate claim 1 , Pyrvinium Pamoate claim 1 , Clofoctol claim 1 , and Isoreserpine; (2) providing a subject in need of treatment or prevention of a -related disease; (3) providing to the subject a therapeutically effective amount of the anti-formulation by various means including (but not ...

Small molecule modulators of the cold and menthol receptor trpm8

The present invention relates to the use of compounds which are capable of producing a cooling sensation when they are brought into contact with the human body. In particular, the present invention relates to the use of compounds modulating TRPM8, and optionally to the use of compounds selectively exhibiting agonist activity at the TRPM8 channel. Such compounds have applications in many fields, particularly in oral and personal hygiene products and foodstuffs, but also in pharmaceutical composition products, cosmetics, textile products and packaging products. The present invention further relates to products containing such compounds and to the medical use of such compounds.

Combination therapy of an afucosylated cd20 antibody with fludarabine and/or mitoxantrone

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with fludarabine and/or mitoxantrone for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody with fludarabine and/or mitoxantrone.

DRUG COMBINATIONS CONTAINING PDE4 INHIBITORS AND NSAIDS

Drug combinations which contain a PDE4-inhibitor and a non-steroidal anti-inflammatory drug (NSAID), processes for preparing them, and their use in treating in particular respiratory complaints such as COPD, chronic sinusitis, and asthma. The PDE4 inhibitors of the drug combinations include compounds of general formula 1 2. The method according to claim 1 , wherein for the PDE4 inhibitor of formula 1:X is SO;{'sup': '1', 'Ris H;'}{'sup': 2', '2', '2.1', '2.2', '2.3', '2.1', '2.1', '2.1', '2.2', '2.3', '2.2', '2.3', '2', '2.1', '2.2', '2.3', '2', '2.3, 'sub': 1-6', '3', '2', '2', '2', '3-7', '2', '3', '2', '2', '1-2', '2, 'Ris H or C-alkyl optionally substituted by one or more groups selected from F, CF, CHF, or CHF or optionally substituted by one or more groups selected from ORCOOR, CONRR, SR, SO—R, SO—R, phenyl, het, hetaryl, a monocyclic C-cycloalkyl, CH—NRR, and NRR, each of which in turn is optionally substituted by one or more groups selected from OH, F, Cl, Br, CF, CHF, CHF, ORoxo, methyl, ethyl, propyl, isopropyl, C-alkanol, phenyl, COOR, CH—NRR, and NRR,'}{'sup': 2', '2.1', '2.1', '2.1', '2.2', '2.3', '2.2', '2.3', '2.1', '2.2', '2.3, 'sub': 3-7', '1-2', '1-3', '1-3', '2', '1-2', '1-2', '3-7', '3', '2', '2, 'Ris a monocyclic Ccycloalkyl, which may optionally be substituted by a group selected from branched or unbranched C-alkanol, C-fluoroalkyl, C-alkylene-OR, OR, COOR, SO—NRR, het, methyl, ethyl, propyl, isopropyl, phenyl, phenyl-C-alkylene, hetaryl-C-alkylene, monocyclic Ccycloalkyl, and NRR, which may optionally be substituted by one or more groups selected from OH, OR, oxo, halogen, CF, CHF, CHF, methyl, ethyl, propyl, isopropyl, phenyl, and NRR, or'}{'sup': 2', '2.1', '2.1', '2.2', '2.3', '2.2', '2.3', '2.2', '2.3', '2.1', '2.2', '2.3, 'sub': 2', '3-7', '3', '2', '2', '1-2', '1-2', '1-2', '2', '3', '2', '2', '3', '2', '3', '2', '2, 'Ris a phenyl, which may optionally be substituted by OH, SH, F, Cl or Br or by one or more groups selected from OR, COOR, ...

Modulators of atp-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Combination Therapy with Leukotoxin

The invention relates to pharmaceutical compositions comprising leukotoxin, a chemotherapeutic agent and a pharmaceutically acceptable carrier, including methods to treat cancer, and methods to induce apoptosis. 1. A pharmaceutical composition comprising leukotoxin , at least one other chemotherapeutic agent , and a pharmaceutically acceptable carrier.2. The composition of wherein the other chemotherapeutic agent is selected from the group consisting of a topoisomerase II inhibitor claim 1 , a DNA alkylating agent claim 1 , and a BCR-ABL inhibitor.3. The composition of wherein the topoisomerase II inhibitor is selected from the group consisting of etoposide claim 2 , mitoxantrone claim 2 , daunorubicin and pharmaceutically acceptable salts thereof.4. The composition of wherein the DNA alkylating agent is busulfan.5. The composition of wherein the BCR-ABL inhibitor is imatinib or imatinib mesylate.6. A method for inducing apoptosis of a cancer cell comprising contacting the cell with leukotoxin and at least one other chemotherapeutic agent in amounts effective to induce apoptosis.7. The method of wherein the other chemotherapeutic agent is selected from the group consisting of a topoisomerase II inhibitor claim 6 , a DNA alkylating agent claim 6 , and a BCR-ABL inhibitor.8. The method of wherein the topoisomerase II inhibitor is selected from the group consisting of etoposide claim 7 , mitoxantrone claim 7 , daunorubicin and pharmaceutically acceptable salts thereof.9. The method of wherein the DNA alkylating agent is busulfan.10. The method of wherein the BCR-ABL inhibitor is imatinib or imatinib mesylate.11. The method of wherein the leukotoxin and the other chemotherapeutic agent are contacted with the cell simultaneously or sequentially.12. The method of wherein the cancer cell expresses leukocyte function antigen (LFA-1).13. The method of wherein the cancer cell is a hematological cancer cell.14. The method of wherein the hematological cancer cell is selected ...

INHIBITION AND TREATMENT OF BIOFILMS

Treatment of a fungal biofilm on implants is via a combination of drugs and/or via the implant pre-treatment with one drug or via the combination of drugs. 127.-. (canceled)28. A medical implant device , comprising:a solid structural element;a first porous element, which is attached to or bonded with said solid element, said first porous element having a pore size in the range of 50 nm to 1000 μm; anda second porous material, being an amorphous silica material, having a pore size in the range of 1 to 30 nm and embedded in said first porous element or surrounding said first porous element, wherein said first porous element is in ceramic materials, in metals or in metal alloys.29. The medical implant device of further comprising an injection port incorporated in said solid structural element claim 28 , wherein said injection port allows delivery of a bioactive agent into the porous part of the medical implant device.30. The medical implant device of further comprising a cavity able to contain a fluid comprising a bioactive agent claim 29 , wherein said cavity is connected with both the injection port and the porous element.31. The medical implant device of claim 30 , wherein the cavity is located in the solid element of the implant or extends into the first porous element and/or the second porous material.32. The medical implant device of claim 28 , wherein the first porous element is in titanium or in titanium derivatives.33. The medical implant device of claim 28 , wherein the first porous element has a pore size in the range of 200 nm to 1000 nm.34. The medical implant device of claim 30 , wherein the first porous element has a pore size in the range of 200 nm to 1000 nm.35. The medical implant device of claim 28 , wherein the second porous material has a pore size in the range of 2 nm to 25 nm.36. The medical implant device of claim 30 , wherein the second porous material has a pore size in the range of 2 nm to 25 nm.37. The medical implant device of claim 28 , ...

Cardiac glycosides are potent inhibitors of interferon-beta gene expression

The invention provides for a method of inhibiting interferon-beta gene expression and/or reducing the level of interferon-beta in a cell by contacting the cell with a Na + , Ca 2+ , or K + ion-channel modulator. The invention also provides for a method of treating a disease or disorder characterized by elevated interferon beta levels or elevated levels of interferon-beta gene expression. Additionally, the invention provides a method for treating pathogenic or non-pathogenic infections.

SULFUR (VI) FLUORIDE COMPOUNDS AND METHODS FOR THE PREPARATION THEREOF

This application describes modified amino acids and polypeptides comprising a SOF or CHCHSOF group bound to the side chain of an amono acid or amino acid residue of a polypeptide in place of a hydrogen of a hydroxyl or amino substituent thereof. Methods of covalently binding the polypeptides to receptot sites of receptor proteins are also described herein. 1. A modified amino acid comprising an amino acid core group bound to a SOF or CHCHSOF group; wherein the amino acid core group has a side chain comprising a hydroxyl or amino substituent , and the SOF or CHCHSOF group is bound to the side chain in place of a hydrogen of the hydroxyl or amino substituent thereof.2. The modified amino acid of claim 1 , wherein the amino acid core group is tyrosine.3. The modified amino acid of claim 1 , wherein the amino acid core group is 2 claim 1 ,6-dimethyltyrosine.4. The modified amino acid of claim 1 , wherein the amino acid core group is histidine.5. The modified amino acid of claim 1 , wherein the amino acid core group is lysine.6. The modified amino acid of claim 1 , wherein the amino acid core group is arginine.7. A polypeptide comprising a modified amino acid residue bearing a SOF or CHCHSOF group; wherein the a modified amino acid residue comprises an amino acid residue core group having a side chain comprising a hydroxyl or amino substituent claim 1 , and the SOF or CHCHSOF group is bound to the side chain in place of a hydrogen of the hydroxyl or amino substituent thereof.8. The polypeptide of claim 7 , wherein the amino acid residue core group is a tyrosine residue.9. The polypeptide of claim 7 , wherein the amino acid residue core group is a 2 claim 7 ,6-dimethyltyrosine residue.10. The polypeptide of claim 7 , wherein the amino acid residue core group is a histidine residue.11. The polypeptide of claim 7 , wherein the amino acid residue core group is a lysine residue.12. The polypeptide of claim 7 , wherein the amino acid residue core group is an arginine residue. ...

CYCLOPROPYLAMINE INHIBITORS OF OXIDASES

The invention relates to cyclopropylamine compounds, in particular the compounds of Formula (I) as described and defined herein, and their use in therapy, including, e.g., the treatment or prevention of cancer. 127-. (canceled)29. The method of claim 28 , wherein said cancer is chosen from breast cancer claim 28 , lung cancer claim 28 , prostate cancer claim 28 , colorectal cancer claim 28 , brain cancer claim 28 , skin cancer claim 28 , blood cancer claim 28 , leukemia and lymphoma.3031-. (canceled)32. The method of claim 28 , wherein said neurological disease or condition is chosen from depression claim 28 , Alzheimer's disease claim 28 , Huntington disease claim 28 , Parkinson's disease claim 28 , and or Dementia with Lewy Bodies.33. (canceled)35. The method of claim 34 , wherein histone-3 lysine-4 methylation levels are modulated.36. The method of claim 34 , wherein histone-3 lysine-9 methylation levels are modulated.3846-. (canceled)47. The method of claim 28 , wherein said subject is a human.48. The method of claim 28 , wherein L1 is —NH—.49. The method of claim 28 , wherein L1 is —NH—CH—.50. The method of claim 28 , wherein G is aryl or heterocyclyl.51. The method of claim 28 , wherein G is aryl or heteroaryl.52. The method of claim 28 , wherein G is heterocyclyl.53. The method of claim 28 , wherein E is —X═X—.54. The method of claim 53 , wherein one of X claim 53 , X claim 53 , X claim 53 , and Xis N or C(R2) and the other ones of X claim 53 , X claim 53 , X claim 53 , and Xare each independently C(R2).55. The method of claim 53 , wherein one of X claim 53 , X claim 53 , Xand Xis N and the other ones of X claim 53 , X claim 53 , Xand Xare each independently C(R2).56. The method of claim 28 , wherein each R1 is independently chosen from lower alkyl claim 28 , lower alkynyl claim 28 , amido claim 28 , halo claim 28 , lower haloalkyl claim 28 , cyano claim 28 , hydroxyl claim 28 , and alkoxy.57. The method of claim 28 , wherein each R2 is —H.58. The method of ...

SOLID-FORMING LOCAL ANESTHETIC FORMULATIONS FOR PAIN CONTROL

Solid-forming local anesthetic formulations for pain control can include a lidocaine base and tetracaine base, polyvinyl alcohol, water, and an emulsifier. The formulation can be prepared to be in a semi-solid state prior to application to a skin surface, can form a soft solidified layer after application, and can provide pain relief when applied to a skin surface proximate a pain site. 1. A solid forming local anesthetic formulation , comprising:lidocaine,tetracaine,from about 10 wt % to about 18 wt % polyvinyl alcohol,from about 30 wt % to about 50 wt % water, andan emulsifying agent,wherein the water to polyvinyl alcohol weight ratio (w/w) is greater than 2.4.2. The formulation of claim 1 , wherein the lidocaine and tetracaine are collectively present in the formulation from about 8 wt % to about 20 wt %.3. The formulation of claim 2 , wherein the lidocaine is present in the formulation from about 4 wt % to about 10 wt % and the tetracaine is present in the formulation from about 4 wt % to about 10 wt %.4. The formulation of claim 1 , wherein the lidocaine and tetracaine are each in their base form.5. The formulation of claim 4 , wherein the lidocaine and tetracaine are in the form of a eutectic mixture.6. The formulation of claim 1 , wherein the polyvinyl alcohol has an average mass from about 30 claim 1 ,000 Daltons to about 80 claim 1 ,000 Daltons.7. The formulation of claim 1 , wherein the emulsifying agent comprises sorbitan monopalminate or sorbitan monostearate.8. The formulation of claim 1 , wherein the emulsifying agent is sorbitan monostearate.9. The formulation of claim 1 , further comprising petrolatum.10. The formulation of claim 1 , wherein the water to polyvinyl alcohol ratio is greater than 2.5.11. The formulation of claim 1 , wherein the lidocaine and tetracaine is present as a eutectic mixture at a 2:1 to 1:2 weight ratio.12. The formulation of claim 1 , wherein the lidocaine and tetracaine is present as a eutectic mixture at about a 1:1 weight ...

CANCER TREATMENT METHOD USING Trk INHIBITOR AND KINASE INHIBITOR IN COMBINATION

An object of the present invention is to provide a combination therapy in which an antitumor effect is enhanced as compared to when a Trk inhibitor or any of various kinase inhibitors is administered alone. A Trk inhibitor, particularly, a compound represented by General Formula (I): 4. The method according to claim 1 , wherein the compound represented by Formula (I) claim 1 , a salt thereof claim 1 , an N-oxide thereof claim 1 , a solvate thereof claim 1 , or a prodrug thereof is1-(2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl)-3-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)urea,1-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-(4-methyl-1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)phenyl)urea,1-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(5-(trifluoromethyl)-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)urea,1-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-chloro-5-(trifluoromethyl)phenyl)urea,1-(2-(1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl-3-(6-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyridin-3-yl)urea,1-(2-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)phenyl-3-(6-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyridin-3-yl)urea,1-(6-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyridin-3-yl)-3-(2-(pyridin-3-yl)-5-(trifluoromethyl)phenyl)urea,1-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)phenyl)urea,1-(2-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)phenyl)-3-(2-(4-(2-amino-5-fluoropyridin-3-yl)phenoxy)pyrimidin-5-yl)urea,1-(2-(4-(2-amino-5-fluoropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-(pyridin-3-yl)-5-(trifluoromethyl)phenyl)urea,1-(2-(1H-pyrazol-1-yl)-4-(trifluoromethyl)phenyl)-3-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)urea,1-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-fluoro-4-(trifluoromethyl)phenyl)urea,1-(2-(4-(2-amino-5-chloropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-chloro-4-(trifluoromethyl)phenyl) ...

METHOD OF TREATING MAJOR DEPRESSIVE DISORDER

The present invention provides a method for safe and efficacious administration of esketamine. 1. A method of treating major depressive disorder (MDD) in a human patient in need thereof comprising the administration to said patient of esketamine over a treatment regimen of at least 28 days wherein{'sub': 'max', 'a. the esketamine Cof said administration is 30 ng/ml or less, or'}{'sub': '0-t', 'b. the esketamine AUCof said administration is 60 ng*h/ml or less, or'}{'sub': max', '0-t, 'c. the esketamine Cof said administration is 30 ng/ml or less and the AUCof said administration is 60 ng*h/ml or less.'}2. The method of claim 1 , wherein the treatment regimen is between 28 days and about 730 days.3. The method of claim 1 , wherein the treatment regimen is between 28 days and about 365 days.4. The method of claim 1 , wherein the administration is daily.5. The method of claim 1 , wherein the administration is intermittent over a period of once every second day to once a month.6. The administration of claim 5 , wherein the administration is twice a week.7. The administration of claim 5 , wherein the administration is once a week.8. The administration of claim 5 , wherein the administration is once a month.9. The administration of claim 5 , wherein the frequency of the intermittent administration varies over the treatment regimen.10. The method of claim 1 , wherein the administration is oral.11. The method of claim 1 , wherein the administration is parenteral.12. The method of claim 11 , wherein the administration is intravenous.13. The method of claim 11 , wherein the administration is intranasal.14. The method of claim 11 , wherein the administration is rectal.15. The method of claim 11 , wherein the administration is sublingual.16. The method of claim 11 , wherein the administration is buccal.17. The method of claim 1 , further comprising the administration of a second medication other than (R)-ketamine.18. The method of claim 17 , wherein the second medication is an ...

Regulators of the endoplasmic reticulum proteostasis network

The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.

METHOD OF TREATING CANCER USING SELECTIVE ESTROGEN RECEPTOR MODULATORS

Disclosed herein are methods of treating subjects suffering from estrogen receptor positive cancer of the brain by administering a selective estrogen receptor degrader (SERM). Also disclosed are methods of treating a cancer that is resistant to an estrogen receptor modulator by administering a SERM. 2. The method of claim 1 , wherein the cancer is Breast cancer brain metastases claim 1 , Astrocytoma claim 1 , Atypical Teratoid Rhabdoid Tumor (ATRT) claim 1 , Chondrosarcoma claim 1 , Choroid Plexus Carcinoma claim 1 , Craniopharyngioma claim 1 , Ependymoma claim 1 , Germ Cell Tumor claim 1 , Glioblastoma claim 1 , Glioma claim 1 , Hemangioma claim 1 , Juvenile Pilocytic Astrocytoma claim 1 , Medulloblastoma claim 1 , Meningioma claim 1 , Neurofibroma claim 1 , Neuronal and Mixed Neuronal-Glial Tumors claim 1 , Oligoastrocytoma claim 1 , Oligodendroglioma claim 1 , Pineal Tumor claim 1 , Pituitary Tumor claim 1 , PNET—(primitive neuroectodermal tumor) claim 1 , Schwannoma claim 1 , and Leptomeningeal metastases.5. The method of claim 4 , wherein the cancer is de novo resistant to the estrogen receptor modulator.6. The method of claim 4 , wherein the resistance to the estrogen receptor modulator is acquired.7. The method of claim 4 , wherein the estrogen receptor modulator is a selective estrogen receptor modulator (SERM).8. The method of claim 7 , wherein the SERM is tamoxifen claim 7 , idoxifene claim 7 , raloxifene or ICI 182 claim 7 ,780.9. The method of any one of - claim 7 , wherein the cancer is breast claim 7 , endometrial or ovarian cancer.10. The method of any one of - claim 7 , wherein the cancer is breast cancer.11. The method of any one of - claim 7 , wherein Rand Rindependently represent a hydrogen atom claim 7 , a methyl group claim 7 , an ethyl group claim 7 , a n-propyl group claim 7 , an iso-propyl group claim 7 , a n-butyl group claim 7 , an iso-butyl group claim 7 , or a tert-butyl group.12. The method of any one of - claim 7 , wherein -T-Z— ...

NON-PLATINUM-BASED ANTI-CANCER COMPOUNDS FOR USE IN TARGETED CHEMOTHERAPY

Disclosed herein are non-platinum-based (NPB) anti-cancer compounds useful for targeted chemotherapy, e.g., to generate anti-cancer effects for the treatment of cancer and other disorders while having no or minimal toxicity. The compounds have the general formula I: (I) wherein A represents an aromatic core; at least one of Rand Ris an electron transfer promoter as defined herein, e.g., NH; and at least one of Ris a leaving group as defined herein, e.g., halogen; and the remainder of the molecule is as defined herein. Pharmaceutical compositions, methods, uses, kits and commercial packages comprising the anti-cancer compounds are also disclosed. 166-. (canceled)68. (canceled)69: The commercial package or kit of claim 67 , wherein X and Y are C—R.70: The commercial package or kit of claim 67 , wherein X is C—Rand Y is N.71: The commercial package or kit of claim 67 , wherein Y is C—Rand X is N.72: The commercial package or kit of claim 69 , wherein Ris H.73: The commercial package or kit of claim 70 , wherein Ris H.74: The commercial package or kit of claim 71 , wherein Ris H.75: The commercial package or kit of claim 67 , wherein X and Y are each N.78: The commercial package or kit of claim 67 , wherein the kit further comprises one or more additional chemotherapeutic agents or cancer therapies.79: The commercial package or kit of claim 76 , wherein the kit further comprises one or more additional chemotherapeutic agents or cancer therapies.80: The commercial package or kit of claim 67 , wherein the cancer is selected from the group consisting of: ovarian cancer claim 67 , cervical cancer claim 67 , breast cancer claim 67 , lung cancer claim 67 , head and neck cancer claim 67 , and pancreatic cancer.81: The commercial package or kit of claim 76 , wherein the cancer is selected from the group consisting of: ovarian cancer claim 76 , cervical cancer claim 76 , breast cancer claim 76 , lung cancer claim 76 , head and neck cancer claim 76 , and pancreatic cancer.84: The ...

Substitute diphenylamine compounds use thereof as antitumor agents

The invention relates to substituted diphenylamine compounds using as antitumor agents. The structure of the compounds is represented as the general formula (I): The groups are as defined as specification. The compound represented by formula (I) showed potent antitumor activity, especially to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The preferred cancers are: colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx cancer or stomach cancer.

MEDICINES FOR TOPIC USE BASED ON SULFATED HYALURONIC ACID AS ACTIVATING OR INHIBITING AGENT OF THE CYTOKINE ACTIVITY

The object of the present invention relates to the new and surprising use of sulfated hyaluronic acid (HAS) as regulator agent of the cytokine activity (pro- and anti-inflammatory) and consequently the use of HAS for the preparation of a new medicine for topic use in the prevention and treatment of pathologies associated with the activation and/or deficiency of cytokines of a pro- and anti-inflammatory nature. The Applicant has in fact discovered the exclusive capacity of HAS in modulating the activity of these particular proteins, it has studied the action mechanism and demonstrated the substantial difference between the different sulfated types known in the state of the art, but above all it has demonstrated an unexpectedly high activity of HAS vs different types and strains of Herpes virus, Cytomegalovirus and the virus of vesicular stomatitis. Finally, a further object of the present invention is the use of HAS as a skin absorption promoter of drugs of an anti-inflammatory nature. 1. A method for treating skin pathologies characterized by dryness , lichenification , irritation , pruritus and redness , inflammation and desquamation , said method comprising topically applying to a patient in need thereof a sulphated hyaluronic acid (HA) , said sulphated hyaluronic acid being prepared starting from a hyaluronic acid having a molecular weight ranging from 10 ,000 to 50 ,000 Da , 150 ,000 to 250 ,000 Da and 500 ,000 to 750 ,000 Da and a sulphation degree equal to 1 or 3.2. A method for preventing and/or treating HIV , Herpes Simplex Labialis and Herpes Genitalis , the virus of Vesicular Stomatitis and Cytomegalovirus , said method comprising topically applying to a patient in need thereof a sulphated hyaluronic acid (HA) , said sulphated hyaluronic acid being prepared starting from a hyaluronic acid having a molecular weight ranging from 10 ,000 to 50 ,000 Da , 150 ,000 to 250 ,000 Da and 500 ,000 to 750 ,000 Da and a sulphation degree equal to 1 or 3.3. The method ...

METHODS FOR TREATING NASAL POLYPOSIS BY ADMINISTERING AN IL-4R ANTAGONIST

The present invention provides methods for treating nasal polyposis. The methods include administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody or antigen binding fragment thereof. 1. A method for treating nasal polyposis , the method comprising administering to a subject in need thereof a pharmaceutical composition comprising an antibody or antigen binding fragment thereof that specifically binds an interleukin-4 receptor (IL-4R) , wherein the antibody or antigen binding fragment thereof comprises heavy chain and light chain CDR sequences from the heavy chain variably region (HCVR) and light chain variable region (LCVR) sequence pair of SEQ ID NOs:1 and 2.2. The method of claim 1 , wherein the antibody or antigen binding fragment thereof comprises light chain CDR sequences of SEQ ID NOs:6 claim 1 , 7 claim 1 , and 8 claim 1 , and heavy chain CDR sequences of SEQ ID NOs:3 claim 1 , 4 and 5.3. The method of claim 1 , wherein the subject has one or more of sinusitis claim 1 , rhinitis claim 1 , asthma claim 1 , aspirin hypersensitivity claim 1 , non-steroidal anti-inflammatory drug (NSAID) hypersensitivity claim 1 , or has undergone surgery for nasal polyps or chronic rhinosinusitis.4. (canceled)5. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is administered at a dose selected from the group consisting of: 0.1 mg to 600 mg claim 1 , 100 mg to 400 mg claim 1 , or 300 mg.67-. (canceled)8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR having the amino acid sequence of SEQ ID NO:1 and an LCVR having the amino acid sequence of SEQ ID NO:2.9. (canceled)10. The method of claim 1 , wherein one or more of the following conditions are met:a) the pharmaceutical composition is administered to the subject systemically;b) the pharmaceutical composition is administered to the subject locally;c) ...

Treatment of demyelinating disorders

This invention discloses methods and compositions for the treatment of demyelinating disorders. Specifically, the invention relates to the use guanabenz or guanabenz derivative for treating demyelinating disorders.

TISSUE RESIDENT MEMORY CELL PROFILES, AND USES THEREOF

This disclosure provides methods of treating cancer or eliciting an anti-tumor response in a subject by administering an effective amount of a population of T-cells that exhibits higher or lower than baseline expression of one or more genes. In other aspects, methods are provided to diagnose cancer and determine prognosis of cancer patients. Also provided are methods to identify the antigens or antigen receptors associated with the isolated and/or purified cell populations that elicit a more positive prognosis. 1. A method of treating cancer and/or eliciting an anti-tumor response in a subject comprising administering to the subject an effective amount of a population of T-cells that exhibit higher than or lower than baseline expression of one or more genes set forth in Table 1 , Table 2 , Table 3 , Table 4 , Table 5 and/or Table 7 , or that express a T-cell receptor comprising at least one of the amino acid sequences set forth in Table 6 , thereby treating cancer and/or eliciting an anti-tumor response in the subject.2. A method of treating cancer and/or eliciting an anti-tumor response in a subject comprising administering to the subject an effective amount of an agent that induces higher than or lower than baseline expression of one or more genes set forth in Table 1 , Table 2 , Table 3 , Table 4 , Table 5 and/or Table 7 in T-cells , or a T-cell receptor comprising at least one of the amino acid sequences set forth in Table 6 , thereby treating cancer and/or eliciting an anti-tumor response in the subject.3. A method of treating cancer and/or eliciting an anti-tumor response in a subject or sample comprising administering an effective amount of one or more an agent that induces or inhibits in T-cells activity of one or more proteins encoded by genes set forth in Table 1 , Table 2 , Table 3 , Table 4 , Table 5 and/or Table 7 to the subject , thereby treating cancer and/or eliciting an anti-tumor response in the subject.4. The method of any one of to , wherein the ...

IMPLANTABLE DRUG DELIVERY COMPOSITIONS COMPRISING NON-POLYMERIC SORPTION ENHANCERS AND METHODS OF TREATMENT THEREOF

A drug delivery composition comprises a drug elution rate-controlling excipient comprising an elastomeric polymer defining a reservoir. The reservoir contains at least one discrete solid dosage form comprising at least one active pharmaceutical ingredient (API) and one or more non-polymeric sorption enhancers (e.g., one or more non-polymeric acids, bases, or salts). The drug delivery composition is in an implantable dosage form. A method of treating or preventing one or more diseases or conditions in a subject comprises implanting the drug delivery composition into a subject to systemically deliver a therapeutically effective amount of the API to the subject for a period of time of at least one month at a pseudo-zero order elution rate. 1) A drug delivery composition comprising:a drug elution rate-controlling excipient comprising an elastomeric polymer defining a reservoir,wherein the reservoir contains at least one discrete solid dosage form comprising at least one active pharmaceutical ingredient (API) and one or more non-polymeric sorption enhancers,wherein the drug delivery composition is in an implantable dosage form.2) The drug delivery composition according to claim 1 , wherein the one or more non-polymeric sorption enhancers are selected from the group consisting of acids claim 1 , bases claim 1 , salts claim 1 , and combinations thereof.3) The drug delivery composition according to claim 1 , wherein the one or more non-polymeric sorption enhancers are selected from the group consisting of amino acids and salts thereof; citric acid and salts thereof; salts of tartaric acid claim 1 , gluconic acid claim 1 , acetic acid claim 1 , ascorbic acid claim 1 , and boric acid; polyamino carboxylic acids and salts thereof; and combinations thereof.4) The drug delivery composition according to claim 1 , wherein the one or more non-polymeric sorption enhancers are selected from the group consisting of glutamic acid monosodium salt claim 1 , sodium gluconate claim 1 , ...

TREATMENT OF NEURODEGENERATIVE DISEASES, CAUSATION OF MEMORY ENHANCEMENT, AND ASSAY FOR SCREENING COMPOUNDS FOR SUCH

Methods for enhancing memory and/or learning and prevent neurodegeneration by administration of certain heterocyclic and aromatic compounds are described. The methods are particularly useful for treating patients suffering from a neurodegenerative disease such as (without limitation) Alzheimer's, Parkinsons's, and Lou Gehrig's (ALS) disease or memory or learning impairment. A neuronal human cell-based assay that assess NF-kB gene up-regulation using a luciferase reporter is also provided that screens for compounds useful in methods for enhancing memory or learning. 1. (canceled)3. The method of claim 2 , wherein in formula (2) Y is S.4. The method of claim 2 , wherein in formula (2) Ris H.5. The method of claim 2 , wherein in formula (2) Ris H.6. The method of claim 2 , wherein in formula (2) Ris selected from the group consisting of H claim 2 , substituted or unsubstituted alkyl claim 2 , and substituted or unsubstituted aryl claim 2 , or R claim 2 , Rcombine with the N atom to which both groups are covalently linked as to form the morpholin-1-yl group.8. The method of claim 2 , wherein in formula (12) at least one occurrence of Ris selected from the group consisting of H claim 2 , halogen and alkoxy claim 2 , or two adjacent Rgroups on the phenyl ring combine as to form the —CHOCH— group.9. The method of claim 2 , wherein Ris H.10. The method of claim 2 , wherein Ris substituted or unsubstituted aryl.11. The method of claim 2 , wherein the carbon labeled as β is not further substituted with a methyl group.12. The method of claim 2 , wherein the carbon labeled as β is further substituted with a methyl group.14. The method of claim 2 , wherein the neurodegenerative disease is at least one selected from the group consisting of Alzheimer's Disease claim 2 , Parkinson's Disease claim 2 , amyotrophic lateral sclerosis claim 2 , spinal muscular atrophy claim 2 , brain traumatic injury and associated neurodegeneration claim 2 , vascular dementia claim 2 , Huntington's ...

ANTIVIRAL COMPOUNDS AND METHODS OF USE THEREOF

Inhibitors of retroviral propagation, methods of treatment and prevention of retroviral infections using the inhibitors, and pharmaceutical compositions including the inhibitors, are disclosed. 4. The composition of claim 1 , further comprising an additional antiviral agent.5. The composition of claim 4 , wherein the additional antiviral agent is an entry inhibitor claim 4 , integrase inhibitor claim 4 , reverse transcriptase inhibitor claim 4 , protease inhibitor claim 4 , or an immune-based therapeutic agent.6. A method of treating or preventing a retroviral infection claim 1 , comprising administering a composition of .7. The method of claim 6 , further comprising the co-administration of a second antiretroviral compound.8. The method of claim 7 , wherein the second antiretroviral agent is selected from the group consisting of NRTIs claim 7 , NNRTIs claim 7 , VAP anti-idiotypic antibodies claim 7 , CD4 and CCR5 receptor inhibitors claim 7 , entry inhibitors claim 7 , antisense oligonucleotides claim 7 , ribozymes claim 7 , protease inhibitors claim 7 , neuraminidase inhibitors claim 7 , tyrosine kinase inhibitors claim 7 , PI-3 kinase inhibitors claim 7 , and Interferons.9. The method of any of claim 6 , wherein the retrovirus is selected from the group consisting of Feline Immunodeficiency Virus (FIV) claim 6 , Simian Immunodeficiency Virus (SIV) claim 6 , Avian Leucosis Virus claim 6 , Feline Leukemia Virus claim 6 , Walleye Dermal Sarcoma Virus claim 6 , Human T-Lymphotropic Virus claim 6 , and Human Immunodeficiency Viruses (HIV).10. The method of any of claim 6 , wherein the retrovirus is HIV.11. The method of claim 10 , wherein the HIV is selected from the group consisting of HIV-I claim 10 , HIV-II claim 10 , HIV-III (also known as HTLV-II claim 10 , LAV-I claim 10 , LAV-2) claim 10 , and mutated versions thereof. This Application is a divisional application claiming priority to U.S. Ser. No. 13/634,464, filed on Sep. 12, 2012, which in turn is the ...

Clenbuterol for use in treatment of autism

Clenbuterol or its salt for use in the treatment of autism, in particular pediatric autism. Improved contact with surroundings, better concentration, improved ability to plan a specific task, improved understanding, calming, and reduced psychomotor anxiety were observed.

FORMATION OF SEMI-PERMEABLE POROUS ARTIFICIAL SCAB

Porous semi-permeable artificial self-attaching scab designed to protect the eroded or injured surfaces. It can be applied on any living being (including plants). The polymerized mesh of the scab is formed when applied on the injured area by a process in which the lysed cells release enzymes that catalyze the reaction. Under this protective surface, the growth of new normal cells that can breathe freely without drying up is promoted. As a result, loss of water, proteins and electrolytes can be avoided; infections can be prevented; and the use of dressing and gauze bandage can be eliminated since they harm the new skin removed. The aqueous thixotropic red-colored fluid applied by brushing or spraying was obtained as a result of the reaction occurred in the container by the combination of the following substances: azosulfamide 1% to 5%+gentian violet 0.004% to 0.007%+dexamethasone 0.001% to 0.003′%+pantothenyl alcohol 0.5% to 2%+gentamicin 0.03% to 0.06%. 1. A fluid that forms an artificial scab , comprising:1-5 weight % of azosulfamide;0.004-0.007 weight % of gentian violet;0.001-0.003 weight % of dexamethasone;0.5-2 weight % of panthenol; and0.03-0.06 weight % of gentamycin, wherein the azosulfamide, gentian violet, dexamethasone, panthenol, and gentamycin are mixed together to form an aqueous thixotropic fluid and the aqueous fluid forms an artificial scab when applied to damaged human tissue.2. The fluid that forms an artificial scab of claim 1 , further comprising a three dimensional web formed by a reaction after the application of the aqueous fluid to the damaged human tissue.3. The fluid that forms an artificial scab of claim 1 , wherein the web comprises a plurality of ionic and covalent bonds generated by the reaction after the application of the aqueous fluid to the damaged human tissue.4. The fluid that forms an artificial scab of claim 1 , wherein the artificial scab is three dimensional.5. The fluid that forms an artificial scab of claim 1 , the ...

REDUCTION OF GASTROINTESTINAL TRACT COLONISATION BY CAMPYLOBACTER

are the commonest reported bacterial causes of gastroenteritis in the UK and industrialized worlds. This invention relates to a method of preventing or reducing the colonisation of the gastrointestinal tract of an animal with . Accordingly, the present invention provides a method for disinfection of an animal comprising administering to said animal at least one compound that binds to MOMP or FlaA of in an effective amount to reduce the number of present in the gastrointestinal tract of said animal. The present invention also provides a method of preventing or reducing transmission of from one animal to another. 1CampylobacterCampylobacterCampylobacter. A method for treating or preventing colonization in an animal or meat product comprising administering at least one compound that binds to Major Outer Membrane Protein (MOMP) or the flagella (FlaA) of in an effective amount to reduce the number of present in the gastrointestinal tract of the animal or meat product.2CampylobacterCampylobacter jejuniCampylobacter Coli.. The method of claim 1 , wherein the is or3. The method of claim 1 , wherein the at least one compound is a compound that blocks the interaction of MOMP or FlaA with the cells of gastrointestinal tract.4. The method of claim 1 , wherein the compound specifically binds to at least one of amino acid residues Arg claim 1 , Thr claim 1 , Lys claim 1 , Lys claim 1 , Asn claim 1 , Leu claim 1 , Tyr claim 1 , Phe claim 1 , Ile claim 1 , Arg claim 1 , Asp claim 1 , and Serof MOMP (SEQ ID No. 1).5. The method of claim 1 , wherein the compound specifically binds to at least amino acid residue Throf MOMP (SEQ ID NO. 1)6. The method of claim 1 , wherein the compound is a human histo blood group antigen or a synthetic human histo blood group antigen.8. The method of claim 1 , wherein the compound is administered orally.9. The method of claim 1 , wherein the compound is administered in the animal's feed or drinking water.10. The method of claim 1 , wherein the compound ...

Selective inhibitors of undifferentiated cells

Uses of a compound of any of Formulas I-VI as a cytotoxic inhibitor of undifferentiated cells are disclosed herein, as well as pharmaceutical compositions comprising a compound of any of Formulas I-VI, and methods for identifying a lead candidate for inhibiting undifferentiated cells. Further disclosed are uses of an SCD-1 inhibitor as a cytotoxic inhibitor of undifferentiated cells.

TAU AGGREGATION INHIBITOR

A tau aggregation inhibitor can sufficiently inhibit a tau protein from aggregating in cells. The inhibitor includes a 4-substituted catechol structure compound, having, at position 4 of its catechol ring, an electron-donating substituent R other than a hydrocarbon group, or a salt thereof. The 4-substituted catechol structure compound is preferably 4-aminocatechol or 1,2,4-benzenetriol. Examples of tauopathies to which this inhibitor is applicable include AD, Down's syndrome, frontotemporal dementia, cotricobasal degeneration (CBD) and progressive supranuclear palsy (PSP). 1. A tau aggregation inhibitor for use to alleviate occurrence of and/or treat a tauopathy , the inhibitor comprising:a 4-substituted catechol structure compound having, at position 4 of its catechol ring, substituent R which is any one of an amino group, a hydroxyl group, an alkoxy group and a thiol group; ora 3-substituted catechol structure compound having, at position 3 of its catechol ring, substituent R which is any one of an amino group, an alkoxy group or a thiol group; ora salt of any of these compounds.2. (canceled)3. The tau aggregation inhibitor of claim 1 , wherein the 4-substituted catechol structure compound is 4-aminocatechol.4. The tau aggregation inhibitor of claim 1 , wherein the 4-substituted catechol structure compound is 1 claim 1 ,2 claim 1 ,4-benzenetriol.5. The tau aggregation inhibitor of claim 1 , wherein the 4-substituted catechol structure compound is either 4-(isopentylamino)catechol or 4-methoxycatechol.6. The tau aggregation inhibitor of claim 1 , wherein the 4-substituted catechol structure compound is 4-(diisopentylamino)catechol.7. (canceled)8. The tau aggregation inhibitor of claim 1 , wherein the 3-substituted catechol structure compound is a 3-methoxycatechol.9. (canceled)10. The tau aggregation inhibitor of claim 1 , wherein the 3-substituted catechol structure compound is 3-aminocatechol.11. A tau aggregation inhibitor for use to prevent alleviate ...

Liposome having inner water phase containing sulfobutyl ether cyclodextrin salt

A liposome comprising bilayer and inner water phase is disclosed. Said inner water phase may contain sulfobutyl ether cyclodextrin and an active compound. 1. A liposome comprising bilayer , inner water phase and metal cation ionophore , wherein the inner water phase comprises a salt of sulfobutyl ether cyclodextrin and an active compound.2. The liposome according to claim 1 , wherein the metal cation ionophore is selected from the group consisting of nikkomycin claim 1 , A23187 and ionomycin.3. The liposome according to claim 1 , wherein the sulfobutyl ether cyclodextrin is sulfobutyl ether-α-cyclodextrin claim 1 , sulfobutyl ether-β-cyclodextrin or sulfobutyl ether-γ-cyclodextrin.4. The liposome according to claim 1 , wherein the sulfobutyl ether cyclodextrin has about 6.5 sulfo groups at average per molecule.5. The liposome according to claim 1 , wherein the salt of sulfobutyl ether cyclodextrin is formed by sulfobutyl ether cyclodextrin with one or more of sodium ion claim 1 , potassium ion and calcium ion.6. The liposome according to claim 1 , wherein the active compound is a weak alkalescent compound.7. The liposome according to claim 1 , wherein the active compound is one or more of vinorelbine claim 1 , vincristine claim 1 , topotecan and irinotecan.8. The liposome according to claim 1 , wherein the bilayer comprises phospholipid claim 1 , cholesterol and hydrophilic polymer-modified lipid.9. A liposome comprising bilayer and inner water phase claim 1 , wherein the inner water phase comprises a salt of sulfobutyl ether cyclodextrin and an active compound claim 1 , and wherein the salt of sulfobutyl ether cyclodextrin is formed by sulfobutyl ether cyclodextrin with one or more of ammonium hydroxide claim 1 , triethylamine and triethanolamine.10. The liposome according to claim 9 , wherein the sulfobutyl ether cyclodextrin is sulfobutyl ether-α-cyclodextrin claim 9 , sulfobutyl ether-β-cyclodextrin or sulfobutyl ether-γ-cyclodextrin.11. The liposome according ...

PARTICLES COMPRISING LUMINESCENT LANTHANIDE COMPLEXES

The present invention relates to particles, useful for drug release detection, comprising: 2. The particle according to claim 1 , wherein the lanthanide is selected from the group consisting of Ce claim 1 , Pr claim 1 , Nd claim 1 , Sm claim 1 , Eu claim 1 , Gd claim 1 , Tb claim 1 , Dy claim 1 , Ho claim 1 , Er claim 1 , Tm and Yb.3. The particle according to claim 1 , wherein the ligand is a polyaminocarboxylate ligand.4. The particle according to claim 1 , wherein the ligand further comprises a lipophilic unit.6. The particle according to claim 5 , wherein A is a nitrogen-containing aromatic heterocycle ring in C-C.9. The particle according to claim 8 , wherein A′ is a cyclen ring.11. The particle according to claim 1 , wherein the drug is an anticancer agent.12. The particle according to claim 11 , wherein the anticancer agent is chosen selected from the group consisting of doxorubicin claim 11 , mitoxantrone and irinotecan.13. The particle according to claim 1 , wherein the particle is selected from the group consisting of a core/shell particle claim 1 , a liposome claim 1 , a lipoparticle claim 1 , a coated solid particle claim 1 , a particle obtained via polymerization claim 1 , a gelified particle claim 1 , a hollow particle claim 1 , and a particle resulting from sonication.14. The particle according to claim 13 , wherein the particle is a liposome comprising an aqueous core surrounded by a phospholipid bilayer.15. (canceled)16. (canceled)19. The method according to claim 18 , wherein the liposomes are formed by hydrating said film and sonicating the resulting mixture.20. The method according to claim 18 , wherein the drug is loaded into said liposomes by incubating the liposomes in a solution comprising said drug. The present invention relates to particles useful for drug delivery, particularly to luminescent particles.Particles, notably nanoparticles such as liposomes and natural or synthetic lipoproteins, have been widely explored for drug delivery and ...

Combination therapy for copd

Aerosol formulations comprising glycopyrronium bromide, formoterol or a salt thereof, and beclometasone dipropionate are useful for the prevention or treatment of moderate/severe chronic obstructive pulmonary disease.

Modulators of atp-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

SULFUR(VI) FLUORIDE COMPOUNDS AND METHODS FOR THE PREPARATION THEREOF

This application describes a compound represented by Formula (I): 1. A compound represented by Formula (I):{'br': None, 'sup': 1', '2, 'sub': m', 'n, 'Y\ue8a0Z\ue8a0X—S(O)(X)F)]\u2003\u2003(I)'}wherein:Y is a biologically active organic core group comprising one or more unsubstituted or substituted moiety selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, a nonaromatic heterocyclic group, to which each Z independently is covalently bonded;n is 1, 2, 3, 4 or 5;each Z independently is O, NR, or N;{'sup': '1', 'when Z is O, m is 1, Xis a covalent bond, and the Z is covalently bonded to an aryl or heteroaryl moiety of Y;'}{'sup': '1', 'sub': 2', '2, 'when Z is NR, m is 1, Xis a covalent bond or CHCH, and the Z is covalently bonded to a nonaromatic hydrocarbyl, a nonaromatic heterocyclic, an aryl, or heteroaryl moiety of Y;'}{'sup': 1', '1, 'sub': 2', '2', '2', '2, 'when Z is N, either (a) m is 2, Xis CHCHand the Z is covalently bonded to a nonaromatic hydrocarbyl, a nonaromatic heterocyclic, an aryl, or a heteroaryl moiety of Y; or (b) m is 1, Xis a covalent bond or CHCH, and the Z is a nitrogen in an aromatic or non-aromatic heterocyclic ring portion of core group Y;'}{'sup': '2', 'each Xindependently is O or NR; and'}each R independently comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group.2. The compound of claim 1 , wherein each Xis O claim 1 , each Z independently is O claim 1 , NR claim 1 , or N; and at least one Z is O.3. The compound of claim 1 , wherein claim 1 , each Xis O claim 1 , each Z independently is O claim 1 , NR claim 1 , or N; and at least one Z is NR.4. The compound of claim 1 , wherein claim 1 , each Xis O claim 1 , each Z independently is O claim 1 , NR claim 1 , or N; and at least one Z is N.5. The compound of claim 1 , wherein claim 1 , each Xis O claim 1 , each Xis a covalent bond claim 1 ...

PREDICTING RESPONSE TO ALVOCIDIB BY MITOCHONDRIAL PROFILING

The present disclosure provides diagnostic methods useful for predicting a patient's response to alvocidib and guiding a physician decision to administer alvocidib to the patient. 131-. (canceled)32. A method of treating a mammal with acute myeloid leukemia (AML) whose disease is dependent on MCL-1 comprisingadministering alvocidib, cytarabine, and mitoxantrone to the mammal with bone marrow cells having MCL-1 priming of at least 40%.33. A method of treating a mammal with acute myeloid leukemia (AML) whose disease is dependent on MCL-1 comprising:determining a MCL-1 priming of a plurality of the mammal's bone marrow cells; andadministering alvocidib, cytarabine, and mitoxantrone to the mammal if the bone marrow cells have the MCL-1 priming of at least 40%.34. A method of treating a mammal with acute myeloid leukemia (AML) whose disease is dependent on MCL-1 comprising:acquiring a plurality of bone marrow cells from the mammal;determining an MCL-1 priming of the bone marrow cells; andadministering alvocidib, cytarabine, and mitoxantrone to the mammal if the bone marrow cells have the MCL-1 priming of at least 40%.35. The method of wherein the determination of MCL-1 priming includes permeabilizing the bone marrow cells.36. The method of wherein the determination of MCL-1 priming includes permeabilizing the bone marrow cells.37. The method of wherein the determination of MCL-1 priming includes permeabilizing the bone marrow cells.38. The method of wherein the AML is refractory.39. The method of wherein the AML is refractory.40. The method of wherein the AML is refractory.41. The method of wherein the AML is relapsed or refractory.42. The method of wherein the AML is relapsed or refractory.43. The method of wherein the AML is relapsed or refractory. The present disclosure is generally directed to methods for treating cancer by administration of an alvocidib-containing regimen to a patient having a high likelihood of response to the alvocidib-containing regimen. In some ...

Bacterial ghosts for the treatment of cancer

The present invention relates to a composition comprising Bacterial Ghosts, optionally an active agent, and a pharmaceutically acceptable carrier and/or excipient for use in the treatment of cancer.

COMBINATION THERAPY FOR TREATING CANCER

The disclosure relates to combinations comprising inhibitors of human histone methyltransferase DOT1L and one or more therapeutic agents, particularly anticancer agents, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer. 1. A combination comprising a compound selected from Compound A2 , Compound D16 , and pharmaceutically acceptable salts thereof , and one or more therapeutic agents.211-. (canceled)12. A pharmaceutical composition comprising a therapeutically effective amount of the combination of and a pharmaceutically acceptable carrier.13. A method of treating or alleviating a symptom of a disease comprising administering to a subject in need thereof a therapeutically effective amount of a combination comprising a compound selected from Compound A2 claim 1 , Compound D16 claim 1 , and pharmaceutically acceptable salts thereof claim 1 , and one or more therapeutic agents claim 1 , wherein the compound and the one or more therapeutic agents are administered simultaneously or sequentially.14. The method of claim 13 , wherein the disease is cancer or a precancerous condition.15. The method of claim 13 , wherein the disease can be influenced by modulating the methylation status of histones or other proteins.16. The method of claim 15 , wherein the methylation status is mediated at least in part by the activity of DOT1L.17. The method of claim 13 , wherein the compound and the one or more therapeutic agents are administered simultaneously.18. (canceled)19. The method of claim 13 , further comprising administering to the subject in need thereof a therapeutically effective dose of a compound selected from Compound A2 claim 13 , Compound D16 claim 13 , and pharmaceutically acceptable salts thereof claim 13 , prior to administering the therapeutically effective dose of the combination comprising the compound selected from Compound A2 claim 13 , Compound D16 claim 13 , and pharmaceutically acceptable salts thereof ...

Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-1. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

Novel Tumor Microenvironment-Related Target TAK1 and Application Thereof in Inhibition of Tumor

Disclosed are a novel tumor microenvironment-related target TAK1 and an application thereof in inhibition of a tumor. TAK1, as a research target for SASP regulation, can be used as a marker in tumor diagnosis and prognosis, and can also be used as a tumor microenvironment specific target to develop tumor inhibitory drugs.

BILIRUBIN DERIVATIVE-BASED DIAGNOSTIC AND THERAPEUTIC ULTRASOUND CONTRAST AGENT

Provided is a bilirubin derivative-based ultrasound contrast agent for diagnosis and treatment. The fine particles including the bilirubin derivative are sensitive to reactive oxygen species (ROS), bind with hydrophobic drugs, and can effectively chelate metals such as iron oxide nanoparticles. Therefore, the fine particle of the present invention can be used as an ultrasound contrast agent for diagnosis, as a magnetic resonance imaging contrast agent, or as a carrier for hydrophobic drugs or platinum-based drugs. 1. A fine particle , comprising:a core containing a gas; anda shell comprising a bilirubin derivative and surrounding the core.2. The fine particle of claim 1 ,{'sub': 6', '1', '10, 'wherein the gas is selected from the group consisting of air, nitrogen, helium, argon, carbon dioxide, sulfur hexafluoride (SF), and Cto Cperfluorocarbons.'}3. The fine particle of claim 1 ,wherein the bilirubin derivative is a bilirubin conjugated with a hydrophilic molecule.4. The fine particle of claim 3 ,wherein the hydrophilic molecule is selected from the group consisting of dextran, carbodextran, polysaccharide, cyclodextran, pluronic, cellulose, starch, glycogen, carbohydrate, monosaccharide, disaccharide and oligosaccharide, polypeptide, polyphosphazene, polyethylene glycol, PEG, Methoxy polyethylene glycol (methoxy polyethylene glycol, mPEG), polypropylene glycol, polyethylenimine, poly-L-lysine, polyglycolide, polymethyl methacrylate, Polyvinylpyrrolidone, poly(acrylate), poly(acrylamide), poly(vinylester), poly(vinyl alcohol) (poly[vinyl alcohol]), polystyrene, polyoxide, polyelectrolyte, poly(N-vinylpyrrolidone), poly(N-vinyl pyrrolidone), polyvinylamine, poly(beta-hydroxyethyl methacrylate), polyethylene oxide, poly(ethylene oxide-b-propylene oxide), and polylysine.5. The fine particle of claim 1 , further comprising:a metal ion or a metal compound selected from the group consisting of Cu, Ga, Rb, Zr, Y, Tc, In, Ti, Gd, Mn, Fe, Au, Pt, Zn, Na, K, Mg, Ca, Sr, and ...

Method for the Treatment of a Solid Tumour

The present invention relates generally to a method of treating a neoplastic condition and to agents useful for same. More particularly, the present invention is directed to a method of facilitating the treatment of a solid tumor in a localised manner via the co-administration of particulate material and a cellular toxin. The method of the present invention is useful in a range of therapeutic treatments including the treatment of primary and metastatic tumors. 1. A method of treating a solid tumour in a subject , said method comprising co-administering to said subject an effective amount of particulate material and a cellular toxin for a time and under conditions sufficient to facilitate distribution of said particulate material and toxin to said tumour wherein:(i) said particulate material is administered in the form of a dispersion in a liquid carrier, the particulate material being maintained in the dispersed state by a stabiliser; and(ii) said stabiliser comprising an anchoring portion that (a) anchors the stabiliser to the particulate material, and (b) is different from the remainder of the stabiliser;and wherein said particulate material and toxin penetrate said solid tumour.2. Use of particulate material and a cellular toxin in the manufacture of a medicament for the treatment of a solid tumour wherein:(i) said particulate material is in the form of a dispersion in a liquid carrier, the particulate material being maintained in the dispersed state by a stabiliser; and(ii) said stabiliser comprising an anchoring portion that (a) anchors the stabiliser to the particulate material, and (b) is different from the remainder of the stabiliser;and wherein said particulate material and toxin penetrate said solid tumour.3. The method according to claim 1 , wherein the stabiliser is a steric stabiliser comprising a steric stabilising polymeric segment and an anchoring portion claim 1 , wherein the steric stabilising polymeric segment is different from the anchoring ...

Novel Scaffolds for Intracellular Compound Delivery for the Detection of Cancer Cells

Disclosed are folic acid or pteroic acid conjugates and methods for using such conjugates. The conjugates described herein comprise a chemotherapeutic drug or imaging agent covalently bound thereto through a bond or via a linker that is intracellularly disrupted by, e.g., endogenous enzymes such as esterases, lipases and the like so as to provide for the chemotherapeutic drug free of the folic or pteroic acid. 1. A conjugate that comprises:a targeting agent that targets the conjugate to cancer cells and where the conjugate is subsequently absorbed by said cancer cells wherein said conjugate targets said cancer cells at a rate of at least 2:1 greater than it targets non-cancerous cells; anda masked fluorescent imaging agent wherein the masking group is covalently attached to the imaging agent provided that the imaging agent is not a fluorescent-fluorescent quencher pair and wherein the targeting agent is covalently bound to a masked fluorescent imaging agent via a bond or a linker; andfurther wherein, upon absorption of the conjugate by the cancer cell, the masked fluorescent imaging agent is unmasked to permit the imaging agent to be capable of producing a detectible fluorescent signal.2. The conjugate of wherein the linker is a oxyalkylene linker comprising from 1 to oxyalkylene units.4. The conjugate of claim 3 , wherein Y is >NR.5. The conjugate of claim 4 , wherein L is a linker of the formula —NH—R—NH— where R is selected from the group consisting -(oxyalkylene)- (where n is 1 to 10) claim 4 , alkylene claim 4 , alkarylene claim 4 , arylalkylene claim 4 , arylene claim 4 , heteroarylene claim 4 , heterocycloalkylene claim 4 , alkenylene claim 4 , alkynylene claim 4 , and cycloalkylene claim 4 , each optionally substituted with 1 to 5 substituents selected from the group consisting of alkoxy claim 4 , substituted alkoxy claim 4 , amino claim 4 , substituted amino claim 4 , acyl claim 4 , carboxyl claim 4 , carboxyl esters claim 4 , cyano claim 4 , halo claim 4 , ...

TRANSDERMAL COMPOSITION

A formulation include a cannabinoid extract that is pharmaceutically effective via topical application. A unit dose having a cannabinoid component in the range of from I milligram to 100 milligram is included within an oil or other solution sourced from the same plant or same type of plant from which the cannabinoid component is sourced, another cannabinoid-producing plant, and/or one or more suitable oils known in the art. One version contains the cannabinoid extract provided in a unit dose within the range by volume of a pharmaceutically-active composition of from less than 0.3 milliliter to 3.0 milliliter that contains a cannabinoid component preferably in the range of from 1 milligram to 100 milligram. The unit dose may include Jojoba oil, dimethyl sulfoxide, bromelain, olive oil, fulvic acid, and/or seed oil. 124.-. (canceled)25. A transdermal pharmaceutical composition for delivery of at least one cannabinoid into the systemic circulation of a subject comprising:{'i': 'Vaccinium corymbosum', '#text': '(a) a mixture of seed oil, bromelain, and fulvic acid; and'}(b) a volume of at least one cannabinoid.26. The transdermal pharmaceutical composition of claim 25 , wherein the at least one cannabinoid comprises cannabidiol (CBD) and/or tetrahydrocannabinol (THC).27. The transdermal pharmaceutical composition of claim 25 , wherein the cannabinoid(s) is/are present in a range of 1 mg to 100 mg.28. The transdermal pharmaceutical composition of claim 25 , further comprising a volume of hydrogenated soybean phosphatidylcholine.29Arnica montana. The transdermal pharmaceutical composition of claim 25 , further comprising a volume of powder or extract.30. The transdermal pharmaceutical composition of claim 25 , further comprising a volume of Vitamin E.31Hamamelis virginiana. The transdermal pharmaceutical composition of further comprising a volume of (witch hazel).32Vitis vinifera. The transdermal pharmaceutical composition of claim 25 , further comprising a volume of DMSO ...

Bone Morphogenetic Protein Pathway Activation, Compositions for Ossification, and Methods Related Thereto

The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair and methods related thereto. In certain embodiments, the disclosure relates to compositions comprising one or more compound(s) disclosed herein, such as clotrimazole, honokiol, magnolol, tacrolimus, pimecrolimus, sirolimus, everolimus, temsirolimus, spironolactone, fluticasone, fluticasone propionate, fluticasone furoate, linezolid, telmisartan, chlorambucil, retinol, isotretinoin, acitretin, etretinate, retinoic acid (tretinoin), teniposide, mitomycin C, cytarabine, decitabine, vinblastine, vincristine, vindesine, vinorelbine, valrubicin, doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxantrone, pixantrone, plicamycin, pazopanib, topotecan, camptothecin, irinotecan, sunitinib, derivatives, or salt thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement. 1. A method of forming bone in vivo comprising implanting a graft composition comprising a collagen matrix and tacrolimus in a subject such that bone forms in the graft.2. The method of claim 1 , wherein more than 0.7 mg of tacrolimus is present per 150 mmof bone graft volume.3. A method of forming bone in vivo comprising implanting a graft composition comprising a hydrogel matrix and tacrolimus in a subject such that bone forms in the graft.4. The method of claim 3 , wherein more than 0.7 mg of tacrolimus is present per 150 mmof bone graft volume.5. A method of forming bone in vivo comprising implanting a graft composition comprising calcium phosphates and tacrolimus in a subject such that bone forms in the graft.6. The method of claim 5 , wherein more than 0.7 mg of tacrolimus is present per 150 mmof bone graft volume.7. The method of claim 5 , wherein said calcium phosphates are hydroxyapatite and tricalcium phosphate.8. A method of performing ...

PROLONGED RELEASE PHARMACEUTICAL COMPOSITION CONTAINING 3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYL-PROPYL)PHENOL

A pharmaceutical formulation for prolonged release of the active ingredient 3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol or a pharmaceutically acceptable salt thereof in a matrix containing between 1 and 80 wt. % of at least one pharmaceutically acceptable hydrophilic or hydrophobic polymer as a matrix forming agent and exhibiting in vivo the following release rate: 3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours; 5 to 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 1 hour; 10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours; 15 to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours; 30 to 97% by weight 3-(3-dimethylaminol-1-ethyl-2-methyl-propyl)phenol released after 6 hours; more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours; more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours. 1. A slow-release pharmaceutical formulation containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof as active ingredient in a matrix , wherein the matrix contains 1 to 80% by weight of one or more pharmaceutically acceptable hydrophilic or hydrophobic polymers as matrix forming agents and has the following release rate in vitro , measured by the Ph. Eur. Paddle Method at 75 rpm in a buffer (to Ph. Eur.) at a pH of 6.8 at 37° C. and detected using a UV spectrometer:3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours,5 to 50% by weight 3-(3-dimethylaminol-ethyl-2-methyl-propyl)phenol released after 1 hour,10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl) ...

Formulations, methods, kit, and dosage forms for treating bacterial infection

Pharmaceutical formulations for treating bacterial or fungal infections comprising iclaprim or its enantiomers and a sulfonamide antibiotic, and treatment and manufacturing methods, kits and dosage forms thereof, are provided.

METHODS FOR TREATING NASAL POLYPOSIS BY ADMINISTERING AN IL-4R ANTAGONIST

The present invention provides methods for treating nasal polyposis. The methods include administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody or antigen binding fragment thereof. 1. A method for treating nasal polyposis , the method comprising administering to a subject in need thereof a pharmaceutical composition comprising an antibody or antigen binding fragment thereof that specifically binds an interleukin-4 receptor (IL-4R) , wherein the antibody or antigen binding fragment thereof comprises heavy chain and light chain CDR sequences from the heavy chain variably region (HCVR) and light chain variable region (LCVR) sequence pair of SEQ ID NOs:1 and 2.2. The method of claim 1 , wherein the antibody or antigen binding fragment thereof comprises light chain CDR sequences of SEQ ID NOs:6 claim 1 , 7 claim 1 , and 8 claim 1 , and heavy chain CDR sequences of SEQ ID NOs:3 claim 1 , 4 and 5.3. The method of claim 1 , wherein the subject has one or more of sinusitis claim 1 , rhinitis claim 1 , asthma claim 1 , aspirin hypersensitivity claim 1 , non-steroidal anti-inflammatory drug (NSAID) hypersensitivity claim 1 , has undergone surgery for nasal polyps claim 1 , or has chronic rhinosinusitis.4. (canceled)5. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is administered at a dose of 0.1 mg to 600 mg claim 1 , 100 mg to 400 mg claim 1 , or 300 mg.6. (canceled)7. (canceled)8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR having the amino acid sequence of SEQ ID NO:1 and an LCVR having the amino acid sequence of SEQ ID NO:2 claim 1 , orwherein the antibody is dupilumab or an antigen binding fragment thereof.9. (canceled)10. The method of claim 1 , wherein the pharmaceutical composition is administered to the subject systemically or locally claim 1 , orwherein the pharmaceutical ...

COMBINATION THERAPY FOR TREATING CANCER

The present invention relates to compositions comprising inhibitors of human histone methyltransferase DOT1L and one or more therapeutic agents, particularly anticancer agents, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer. 3. A composition comprising any one of the compounds listed in Tables 1-4 or pharmaceutically acceptable salts thereof and one or more therapeutic agents.4. A composition comprising Compound A2 , or pharmaceutically acceptable salts thereof , and one or more therapeutic agents.5. A composition comprising Compound D16 , or pharmaceutically acceptable salts thereof , and one or more therapeutic agents.65. The composition of any one of - claims 1 , wherein the one or more therapeutic agents are anti-cancer agents.75. The composition of any one of - claims 1 , wherein the one or more therapeutic agents are selected from Ara-C claims 1 , Daunorubicin claims 1 , Decitabine claims 1 , Vidaza claims 1 , Mitoxantrone claims 1 , JQ1 claims 1 , IBET151 claims 1 , Panobinostat claims 1 , Vorinostat claims 1 , Quizartinib claims 1 , Midostaurin claims 1 , Tranylcypromine claims 1 , LSD1 inhibitor II claims 1 , Navitoclax claims 1 , and analogs claims 1 , derivatives claims 1 , or combinations thereof.85. The composition of any one of - claims 1 , wherein the therapeutic agent is Ara-C claims 1 , Daunorubicin claims 1 , Vidaza or an analog or derivative thereof.98. A pharmaceutical composition comprising a therapeutically effective amount of composition of any one of - and a pharmaceutically acceptable carrier.10. A method of treating or alleviating a symptom of a disease comprising administering to a subject in need thereof a therapeutically effective amount of a composition of .11. The method of claim 10 , wherein the disease is cancer or a precancerous condition.12. The method of claim 10 , wherein the disease can be influenced by modulating the methylation status of histones or other proteins. ...

Treatment of Fibrosis

The present invention relates an aldehyde dehydrogenase inhibitor for use in the treatment or prevention of fibrosis. 1. An aldehyde dehydrogenase inhibitor for use in the treatment or prevention of fibrosis in the eye.2. The aldehyde dehydrogenase inhibitor for use according to claim 1 , wherein the aldehyde dehydrogenase inhibitor is tetraethylthioperoxydicarbonic diamide (disulfiram).3. The aldehyde dehydrogenase inhibitor for use according to claim 1 , wherein the aldehyde dehydrogenase inhibitor is 4-(diethylamino)benzaldehyde (DEAB).4. The aldehyde dehydrogenase inhibitor for use according to any one of the preceding claims claim 1 , wherein the fibrosis is ocular mucous membrane pemphigoid (OcMMP).5. The aldehyde dehydrogenase inhibitor for use according to any one of to claim 1 , wherein the fibrosis is scarring in response to an injury.6. The aldehyde dehydrogenase inhibitor for use according to any one of the preceding claims claim 1 , wherein the aldehyde dehydrogenase inhibitor is administered topically to the eye.7. Use of an aldehyde dehydrogenase inhibitor as defined in any one of to claim 1 , in the manufacture of a medicament for treating or preventing fibrosis in the eye claim 1 , wherein said fibrosis is as defined in any one of claim 1 , and .8. A method for treating or preventing fibrosis in the eye in a patient in need thereof claim 1 , the method comprising administering to said patient an aldehyde dehydrogenase inhibitor as defined in any one of to claim 1 , wherein said fibrosis is as defined in any one of claim 1 , and .9. A cosmetic method for treating scarring in the eye in response to an injury in a subject claim 1 , the method comprising administering an aldehyde dehydrogenase inhibitor as defined in any one of to to the subject. The present invention relates to the treatment and/or prevention of fibrosis.Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in response to an injury and/or inflammation. ...

THERAPEUTIC AGENTS FOR USE IN THE PROPYLAXIS AND/OR TREATMENT OF HYPERKINETIC MOVEMENT DISORDERS

(RS)-[2-(3,4-dimethoxyphenyl)ethyl][2-hydroxy-3-(3-methylphenoxy)propyl]amine having the formula (IA), or a pharmaceutically acceptable salt thereof for the formulation of a pharmaceutical composition is useful for the prophylaxis and/or the treatment of hyperkinetic movement disorders associated with Huntington's disease, Wilson's disease, Tourette syndrome, restless leg syndrome, and tardive dyskinesia. 2. (canceled)4. The method of claim 1 , wherein said prophylaxis or treatment comprises administering as a unique active ingredient the compound of formula (IA).6. The method of claim 5 , wherein the combination therapy comprises administering to a subject simultaneously claim 5 , sequentially or separately the compound of formula (IA) and the additional therapeutic agent.7. The method of claim 5 , wherein the additional therapeutic agent is selected from the group consisting of a compound of formula (IB) claim 5 , a compound of formula (IC) claim 5 , amantadine claim 5 , riluzole claim 5 , tetrabenazine claim 5 , reserpine claim 5 , and donepezil.9. The method of claim 1 , further comprising combining an additional therapeutic agent.10. The method of claim 1 , wherein the hyperkinetic movement disorder is selected from the group consisting of abdominal dyskinesias claim 1 , akathisic movements claim 1 , asynergia claim 1 , ataxia claim 1 , athetosis claim 1 , ballism claim 1 , chorea claim 1 , dysmetria claim 1 , dystonia claim 1 , hemifacial spasm claim 1 , hyperekplexia claim 1 , hypnogenic dyskinesias claim 1 , jumpy stumps claim 1 , moving toes and/or fingers claim 1 , myoclonus claim 1 , myokymia claim 1 , myorhythmia claim 1 , paroxysmal dyskinesias claim 1 , tics claim 1 , and tremors.11. The method of claim 1 , wherein the hyperkinetic movement disorder is chorea associated to Huntington's disease claim 1 , Tourette syndrome claim 1 , and tardive dyskinesia.12. The method of claim 1 , wherein the hyperkinetic movement disorder is chorea associated to ...

Methods and compositions for treatment of epileptic disorders

Use of allosteric modulators and/or gaboxadol for the treatment of epileptic disorders in a subject in need thereof.

NON-PEPTIDE BDNF NEUROTROPHIN MIMETICS

Methods and compounds for treating neurological and other disorders are provided. Included is the administering to a subject in need thereof an effective amount of a compound having binding and/or modulation specificity for a TrkB receptor molecule, optionally optionally in combination with a TrkA and/or TrkC receptor molecule. 2. The compound of wherein{'sup': 4', '5', 'C', 'D, 'each of Rand Ris independently —F, —Cl, —NRR, optionally substituted morpholinyl, optionally substituted thiomorpholinyl, optionally substituted piperazinyl, optionally substituted piperidinyl, optionally substituted pyrrolidinyl, optionally substituted cyclohexadienyl, or optionally substituted phenyl;'}{'sub': 1', '6, 'A is —H, C-Calkyl, optionally substituted phenyl, or optionally substituted bicyclic heteroaryl;'}E is —H or —Cl; and{'sup': C', 'D, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'each of Rand Ris independently —H, C-Calkylene-O—C-Calkyl, C-Calkyl, C-Caminoalkyl, or C-Chydroxyalkyl.'}3. The compound of claim 1 , wherein{'sup': 4', '5', 'C', 'D, 'each of Rand Ris independently —F, —Cl, —NRR, optionally substituted N-bound morpholinyl, optionally substituted N-bound piperidinyl, or optionally substituted cyclohexa-1,4-dienyl;'}{'sub': 3', '6, 'A is —H, C-Calkyl, optionally substituted phenyl, optionally substituted quinolinyl, or optionally substituted tetrahydroquinolinyl;'}E is —H; and{'sup': C', 'D, 'sub': 2', '2', '3', '2', '4', '2', '4, 'each of Rand Ris independently —H, methyl, ethyl, —(CH)OCH, C-Caminoalkylene, or C-Chydroxyalkylene.'}4. The compound of any of to claim 1 , wherein each of A is not —H.5. The compound of any of to claim 1 , wherein A is C-Calkyl and E is —H.6. The compound of any of to claim 1 , wherein A is C-Calkyl and E is —H.7. The compound of or claim 1 , wherein Rand Rare —NRR claim 1 , wherein each of Rand Ris C-Calkylene-O—C-Calkyl claim 1 , or C-Chydroxyalkylene.8. The compound of claim 7 , wherein each of Rand Ris —CHCH—OCH.9. The ...

METHODS FOR TREATING DISEASE AND REDUCING DRUG-INDUCED LIVER INJURY IN PATIENT POPULATIONS

The present disclosure provides methods of reducing the risk of developing, and/or severity of, an adverse drug reaction such as drug-induced liver injury (DILI). The methods include identifying patients at risk for developing DILI by determining the presence or absence of one or more HLA alleles in the patients. 1. A method for reducing the risk of drug-induced liver injury (DILI) in a subject , comprising first determining that the subject has an HLA profile that does not include an HLA-B*39:01 allele , then administering to the subject a therapeutically effective amount of a therapeutic agent , wherein the therapeutic agent is a protein that comprises an amino acid sequence according to SEQ ID NO: 1 , SEQ ID NO: 2 , SEQ ID NO: 3 , SEQ ID NO: 4 , SEQ ID NO: 5 , SEQ ID NO: 6 , SEQ ID NO: 7 , SEQ ID NO: 8 , SEQ ID NO: 9 , SEQ ID NO: 10 , SEQ ID NO: 11 , or any combination thereof.2. A method of reducing the risk of DILI in a subject , comprising:(i) identifying the subject as not having a genetic variation comprising the HLA-B*39:01 allele; and(ii) administering a therapeutically effective amount of a therapeutic agent to the subject, wherein the therapeutic agent is a protein that comprises an amino acid sequence according to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or any combination thereof;whereby the subject has a decreased risk of DILI compared to an otherwise identical subject having the genetic variation.3. A method for reducing the risk of DILI in a subject comprising treating the subject with a therapeutic agent , wherein the therapeutic agent is a protein that comprises an amino acid sequence according to SEQ ID NO: 1 , SEQ ID NO: 2 , SEQ ID NO: 3 , SEQ ID NO: 4 , SEQ ID NO: 5 , SEQ ID NO: 6 , SEQ ID NO: 7 , SEQ ID NO: 8 , SEQ ID NO: 9 , SEQ ID NO: 10 , SEQ ID NO: 11 , or any combination thereof , the method comprising the steps of:(i) ...

Targeted Delivery of Hydrophilic Drugs

A method of designing a pharmaceutical composition for providing the liver of a person or animal, as a therapeutic target, with a predetermined concentration of a sulfate or sulfonate of a pharmacologically active agent, during a predetermined period, includes determining the correlation between the solubility of a sulfate and/or sulfonate of a pharmacologically active agent of the formula D(RSO)or D(ROSO)for various carbon chain lengths X, Y in an aqueous solvent and the expected concentration of the pharmaceutically active agent D in the therapeutic target upon administration of the pharmacologically active agent D to the person or animal, defining a target solubility of the sulfate or sulfonate based on a desired concentration of said pharmaceutically active substance D in the therapeutic target, and determining the carbon chain length(s) X, Y corresponding to the target solubility. 1. A method of designing a pharmaceutical composition for providing , during a predetermined period , as a therapeutic target , the liver of a person or animal , with a predetermined concentration of a sulfate or sulfonate of a pharmacologically active agent comprising from 1 to 4 amino groups represented by formula (1) or (2) , or a mixture of these agents:{'br': None, 'sup': n+', '1', '−, 'sub': 3', 'n, 'D(RSO)\u2003\u2003(1)'}{'br': None, 'sup': n+', '2', '−, 'sub': 3', 'n, 'D(ROSO)\u2003\u2003(2)'}{'sup': 1', '2, 'sub': 6', '30', '6', '30, 'wherein Ris straight chain C-Calkyl; Ris straight chain C-Calkyl; n is an integer from 1 to 4; wherein the method comprises{'sup': n+', '1', '−', 'n+', '2', '−, 'sub': 3', 'n', '3', 'n, 'i) determining the solubility of D(RSO)or D(ROSO)for various carbon chain lengths X, Y in an aqueous solvent;'}ii) determining the correlation between the solubility of said sulfate or sulfonate of said pharmacologically active agent and the expected concentration of said pharmaceutically active agent D in the therapeutic target upon administration of said ...

PREDICTING RESPONSE TO ALVOCIDIB BY MITOCHONDRIAL PROFILING

The present disclosure provides diagnostic methods useful for predicting a patient's response to alvocidib and guiding a physician decision to administer alvocidib to the patient. 1. A method for treatment of cancer in a patient in need thereof , the method comprising:a) requesting BH3 profiling data for a cancer cell specimen obtained from the bone marrow of the patient; andb) administering a treatment regimen comprising an MCL1 inhibiting therapy to the patient if NOXA priming in the cancer cell specimen is at least 15%.2: The method of wherein the MCL1 therapy comprises administering a treatment comprising administering at least one pro-apoptotic agent to the patient.3: The method of wherein the therapy is a pro-apoptotic agent is at least one selected from the group consisting of ABT-263 (Navitoclax) claim 1 , obatoclax claim 1 , WEP claim 1 , bortezomib claim 1 , and carfilzomib.4: A method of treatment of cancer in a patient in need thereof claim 1 , the method comprising:a) requesting Bad profiling data for a cancer cell specimen obtained from the bone marrow of the patient; andb) administering a treatment regimen comprising at least substance selected from the group consisting of kinesin spindle protein inhibitors, cyclin-dependent kinase therapy inhibitor, Arsenic Trioxide (TRISENOX), MEK inhibitors, pomolidomide, azacytidjne, decitibine, vorinostat, entinostat, dinaciclib, gemtuzumab, BTK inhibitors, PB kinase delta inhibitors, lenolidimide, anthracyclines, cytarabine, melphalam, Akt inhibitors, and mTOR inhibitors to the patient if the Bad profiling indicates the patient's cancer is not MCL1 primed.5: The method of wherein the cancer is selected from the group consisting of acute lymphoblastic leukemia (ALL) claim 1 , acute myeloid leukemia (AML) claim 1 , adrenocortical carcinoma claim 1 , AIDS-related cancers claim 1 , anal cancer claim 1 , appendix cancer claim 1 , astrocytoma (e.g. childhood cerebellar or cerebral) claim 1 , basal-cell carcinoma claim ...

FOCAL ADHESION KINASE INHIBITOR AS A THERAPEUTIC AGENT IN DIABETES

It is disclosed herein that a FAK inhibitor induces conversion of acinar cells into beta cells. Methods are provided for increasing beta cell proliferation by administering an effective amount of a FAK inhibitor to a subject in need thereof. Methods are also provided for treating a subject with diabetes or at risk of developing diabetes, comprising administering to the subject a therapeutically effective amount of a FAK inhibitor. 1. A method for treating a subject with diabetes , pre-diabetes , or a predisposition for diabetes , comprising:administering to the subject a therapeutically effective amount of a focal adhesion kinase (FAK) inhibitor, thereby treating the diabetes, pre-diabetes, or predisposition for diabetes.2. The method of claim 1 , further comprising selecting the subject with diabetes claim 1 , pre-diabetes claim 1 , or the predisposition for diabetes for treatment with the FAK inhibitor.3. The method of claim 1 , wherein the FAK inhibitor is an inhibitor of FAK kinase activity.4. The method of claim 3 , wherein the FAK inhibitor is PF-562271 claim 3 , GSK2256098 claim 3 , NVP-TAC544 claim 3 , PF-573228 claim 3 , TAE226 claim 3 , VS-4718 claim 3 , PF-04554878 claim 3 , Y11 claim 3 , or Y15.5. The method of claim 1 , wherein the FAK inhibitor is administered in a dose of 75 mg claim 1 , 100 mg claim 1 , or 125 mg claim 1 , given once or twice daily.6. The method of claim 1 , further comprising measuring a beta cell function of the subject.7. The method of claim 1 , further comprising measuring glucose tolerance claim 1 , insulin resistance claim 1 , plasma glucose levels claim 1 , plasma insulin levels claim 1 , serum triglycerides claim 1 , free fatty acids claim 1 , and/or HbA1c levels in a sample from the subject.8. The method of claim 1 , wherein administering the therapeutically effective amount of the FAK inhibitor increases a number of beta cells in the subject.9. The method of claim 1 , wherein administering the therapeutically effective ...

COMBINATION THERAPY OF ANTI-MIF ANTIBODIES AND CHEMOTHERAPEUTICS

The present invention pertains to anti-MIF antibodies, in particular their use in combination with cancer therapeutics, i.e. chemotherapeutics, in the treatment of cancer. 1. An anti-MIF antibody in combination with a chemotherapeutic agent for use in the treatment of cancer , wherein said anti-MIF antibody is selected from the group consisting of: a) a light chain comprising SEQ ID NO:12, and', 'b) a heavy chain comprising SEQ ID NO:11;, 'i. a RAM9 antibody, wherein said RAM9 antibody comprises a) a light chain comprising SEQ ID NO:10, and', 'b) a heavy chain comprising SEQ ID NO:9; and, 'ii. a RAM0 antibody, wherein said RAM0 antibody comprises a) a light chain comprising SEQ ID NO:14, and', 'b) a heavy chain comprising SEQ ID NO:13., 'iii. a RAM4 antibody, wherein said RAM4 antibody comprises2. The anti-MIF antibody in combination with a chemotherapeutic agent according to for use in the treatment of cancer claim 1 , wherein the cancer is selected from the group consisting of pancreatic cancer claim 1 , ovarian cancer claim 1 , prostate cancer claim 1 , breast cancer claim 1 , lung cancer and colon cancer claim 1 , more preferred pancreatic cancer claim 1 , prostate cancer claim 1 , and ovarian cancer.3. The anti-MIF antibody in combination with a chemotherapeutic agent according to wherein the anti-MIF antibody is wherein said RAM9 antibody comprises:a) a light chain comprising SEQ ID NO:12, andb) a heavy chain comprising SEQ ID NO:11.4. The anti-MIF antibody in combination with a chemotherapeutic agent according to claim 1 , wherein the chemotherapeutic is selected from the group consisting of mitoxantrone claim 1 , doxorucibin claim 1 , and cisplatin.5. The anti-MIF antibody in combination with a chemotherapeutic agent according to claim 1 , wherein the anti-MIF antibody is RAM9 claim 1 , the chemotherapeutic is doxorubicin claim 1 , and the cancer is ovarian cancer.6. The anti-MIF antibody in combination with a chemotherapeutic agent according to claim 1 , ...

Compositions and methods for treating ocular diseases

The compositions and methods disclosed herein provide for treatments of ocular disorders of the eye, such as ocular surface diseases as well as those associated with inflammation of internal cells and cell layers of the eye. The methods disclosed herein describe methods for treating ocular disorders, particularly dry eye disorders, comprising topically administering to an ocular region of a subject a composition comprising a pharmaceutically effective amount of at least one aldosterone antagonist or salt thereof and a pharmaceutically acceptable carrier. Included is a method for treating dry eye comprising topically administering to an ocular region of a subject a composition comprising spironolactone and hydroxypropyl methylcellulose; and reducing or preventing one or more symptoms or causes of dry eye.

Modulators of atp-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

MULTI DRUG COMPOSITE, METHODS AND USES THEREOF

The invention provides mesoporous nanoparticles loaded within its pores with at least one loaded pharmaceutically active agent and at least one capping pharmaceutically active agent chemically coordinated with at least one ligand being boronic acid or derivative thereof on the surface of said pores; compositions comprising such mesoporous nanoparticles and uses thereof. 122.-. (canceled)23. Mesoporous nanoparticle (MP-NP) loaded within its pores with at least one loaded pharmaceutically active agent; comprising at least one ligand baring boronic acid or derivative thereof on the surface of said pores chemically coordinated with at least one capping pharmaceutically active agent.24. The MP-NP of claim 23 , being selected from silica claim 23 , alumina claim 23 , zirconia claim 23 , titania claim 23 , carbon nanoparticle claim 23 , and any combinations thereof.25. The MP-NP of claim 23 , wherein said at least one loaded pharmaceutically active agent is selected an anti-cancer agent.26. The MP-NP of claim 23 , wherein said at least one loaded pharmaceutically active agent is selected mitoxantrone.27. The MP-NP of claim 23 , wherein said at least one capping pharmaceutically active agent is an anti-cancer agent.28. The MP-NP of claim 23 , wherein said at least one capping pharmaceutically active agent is gossypol.29. The MP-NP of claim 23 , wherein said at least one capping pharmaceutically active agent is cyclodextrin.30. The MP-NP of claim 23 , further comprising at least one ligand on the surface of said nanoparticle chemically coordinated with at least one further active agent.31. The MP-NP of claim 23 , capable of triggered simultaneous release of said at least one loaded pharmaceutically active agent and said at least one capping pharmaceutically active agent.32. The MP-NP of claim 23 , capable of triggered simultaneous controlled release of said at least one loaded pharmaceutically active agent and said at least one capping pharmaceutically active agent.33. A ...

METHODS OF TREATING AUTOPHAGY-ASSOCIATED DISORDERS AND RELATED PHARMACEUTICAL COMPOSITIONS, DIAGNOSTICS, SCREENING TECHNIQUES AND KITS

The invention provides methods of treating autophagy mediated diseases and disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits. In one embodiment, the invention provides a method of determining whether a subject suffers from, or is at risk of developing, and autophagy mediated disease state and/or condition by evaluating LC3 levels. 1. A method of determining whether a patient or subject suffers from , or is at risk of developing an autophagy mediate disease state or condition , the method comprising determining LG3 levels on white blood cells or in plasma obtained from the subject and comparing the determined LC3 level to a control LC3 level , wherein an increase or decrease in LC3 levels compared to a control LC3 level indicates an increased likelihood that the subject suffers from or is at risk of developing an autophagy-mediated disease state or condition.246-. (canceled)47. A pharmaceutical composition comprising:(a) an autophagy modulator (autostatin) in an effective amount; and optionally(b) a pharmaceutically-acceptable carrier, additive and/or excipient, and further optionally(c) at least one additional bioactive agent.48. The composition according to wherein said autophagy modulator is selected from the group consisting of flubendazole claim 47 , hexachlorophene claim 47 , propidium iodide claim 47 , bepridil claim 47 , clomiphene citrate (Z claim 47 ,E) claim 47 , GBR 12909 claim 47 , propafenone claim 47 , metixene claim 47 , dipivefrin claim 47 , fluvoxamine claim 47 , dicyclomine claim 47 , dimethisoquin claim 47 , ticlopidine claim 47 , memantine claim 47 , bromhexine claim 47 , norcyclobenzaprine claim 47 , diperodon claim 47 , nortriptyline claim 47 , tetrachlorisophthalonitrile and phenylmercuric acetate claim 47 , pharmaceutically acceptable salts thereof and mixtures thereof.49. The composition according to wherein said autophagy modulator is selected from the group consisting of flubendazole claim 47 , ...

Functionalized Magnetic Nanoparticles and Use in Imaging Amyloid Deposits and Neurofibrillary Tangles

The present disclosure provides functionalized magnetic nanoparticles (MNPs) comprising a functional group that binds to β-amyloid deposits and/or neurofibrillary tangles. The present disclosure provides compositions comprising the functionalized MNPs, and methods of using the functionalized MNPs in imaging β-amyloid deposits and neurofibrillary tangles. 1. A pharmaceutical composition comprising:a) a functionalized magnetic nanoparticle (MNP) comprising a magnetic core and a functional group that binds aggregated β-amyloid protein and/or neurofibrillary tangles, wherein said functional group is coupled via a linker to the magnetic core, wherein said functionalized magnetic nanoparticle is capable, when introduced into the bloodstream of a mammalian subject, of crossing the blood-brain barrier of a mammalian subject; andb) a pharmaceutically acceptable carrier.2. The pharmaceutical composition of claim 1 , wherein the functional group is 2-(1-{6-[(2-hydroxyethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (HODDNP) claim 1 , or a derivative or analog thereof.3. The pharmaceutical composition of claim 1 , wherein the functional group is (4′-aminophenyl)-6-hydroxybenzothiazole (PIB-2) claim 1 , or a derivative or analog thereof.13. The pharmaceutical composition of claim 1 , wherein the functionalized magnetic nanoparticle (MNP) of the formula:M-S-(L)-Z, wherein M is a magnetic core, S is a polymer, L is an optional linker, and Z is the functional group.14. The pharmaceutical composition of claim 13 , wherein the functional group is attached to the polymer directly or via a linker.15. The pharmaceutical composition of claim 1 , wherein the functional group is coupled to the magnetic core via an epoxy group.16. The pharmaceutical composition of claim 2 , wherein the HODDNP functional group is coupled to the magnetic core via the hydroxyl group of HODDNP.17. The pharmaceutical composition of claim 3 , wherein the PIB-2 functional group is coupled to the magnetic ...

TREATING AND PREVENTING DISEASES BY MODULATING CELL MECHANICS

Described are methods of treating or preventing a disease in a subject treatable by modulating cell mechanics. The method includes administering to a subject having or at risk for such a disease a pharmaceutical composition. comprising an agent selected from the group comprising a salt, solvate, or stereoisomer of compound (VIII) or its derivatives or a mixture of their constituents, where the compound has the formula: 2. The method of wherein myosin II is activated in the subject compared to a reference subject that has not been administered the effective amount of compound (V).3. The method of claim 1 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 1 , parenteral claim 1 , intranasal claim 1 , sublingual claim 1 , rectal claim 1 , and transdermal administration.4. The method of claim 1 , further comprising the step of administering a bioactive agent.6. The method of claim 4 , wherein the bioactive agent is a chemotherapy agent.7. The method of wherein the subject has a disease that is treated or prevented by modulating the cell mechanics of the subject.8. The method of wherein the disease is cancer.9. The method of wherein the cancer is pancreas or kidney cancer.12. The method of wherein myosin II is activated in the subject compared to a reference subject that has not been administered the effective amount of compound (VIII).13. The method of claim 11 , wherein the method of administering is systemic delivery selected from the group consisting of oral claim 11 , parenteral claim 11 , intranasal claim 11 , sublingual claim 11 , rectal claim 11 , and transdermal administration.14. The method of claim 11 , further comprising the step of administering a bioactive agent.16. The method of claim 14 , wherein the bioactive agent is a chemotherapy agent.17. The method of wherein the subject has a disease that is treated or prevented by modulating the cell mechanics of the subject.18. The method of wherein the ...

ANTI-AGING COMPOUNDS

Anti-aging compounds identified using the lead compounds violuric acid and 1-naphthoquinone-2-monoxime are described. The compounds are redox catalysts that appear to improve the function of hematopoietic stem cells. The compounds can be used to decrease the rate of aging in a subject, or to treat or decrease the risk of developing an age-related disease or disorder. 2. (canceled)3. The anti-aging compound of claim 1 , wherein the compound is according to formula II.4. The anti-aging compound of claim 1 , wherein the compound is according to formula III.5. (canceled)6. (canceled)7. The anti-aging compound of claim 1 , further comprising a pharmaceutically acceptable carrier.9. (canceled)10. (canceled)11. The anti-aging compound of claim 8 , further comprising a pharmaceutically acceptable carrier.12. A method of decreasing the rate of aging of a subject claim 1 , comprising administering a therapeutically effective amount of a compound according to to the subject.13. The method of claim 12 , wherein the subject is an adult subject.14. A method of decreasing the rate of aging of a subject claim 8 , comprising administering a therapeutically effective amount of a compound according to to the subject.15. The method of claim 14 , wherein the subject is an adult subject.16. A method of treating or decreasing the risk of developing an age-related disease or disorder in a subject claim 1 , comprising administering a therapeutically effective amount of a compound according to to the subject.17. The method of claim 16 , wherein the age-related disease or disorder is associated with mitochondrial function loss claim 16 , telomere dysfunction claim 16 , senescence deterioration and age-dependent cell loss claim 16 , mitochondrial deterioration claim 16 , and/or cell cycle-arrested state in post-mitotic cells.18. A method of treating or decreasing the risk of developing an age-related disease or disorder in a subject claim 8 , comprising administering a therapeutically ...

METHOD FOR CARRYING THERAPEUTIC SUBSTANCES INTO CELLS

The present invention relates to compositions containing nanoparticies and uses of said composition for transferring therapeutically active substances into cells by means of specifically coated nanoparticles. The chemical design of the particles is such that a large amount thereof is absorbed into the cells. No direct bond between nanoparticle and the therapeutically active substance is required for the transfer into the cells. Thanks to said transfer, an increased efficacy of the substance and simultaneously reduced systemic toxicity is achieved, i.e. an increase in the efficacy while the side effects are reduced. 114-. (canceled)15. A method for increasing the activity of an anti-cancer drug comprising the steps of administering to a patient in need thereof a pharmaceutical composition comprising magnetic nanoparticles having an affinity to degenerated cells , at least one anti-cancer drug and at least one pharmaceutically acceptable carrier , excipient and/or solvent , wherein the magnetic nanoparticles have a positive surface charge , wherein the magnetic nanoparticles and the at least one anti-cancer drug are administered separately , and wherein the magnetic particles carry the anti-cancer drug into the degenerated cells.16. The method for increasing the activity of an anti-cancer drug according to for complementing conventional methods for the treatment of cancer.17. The method for increasing the activity of an anti-cancer drug according to claim 15 , wherein the pharmaceutical composition is adopted in hypothermia claim 15 , magnetic fluid hyperthermia claim 15 , thermotherapy with magnetic fluids claim 15 , radiation therapy and/or chemotherapy.18. The method for increasing the activity of an anti-cancer drug according to claim 15 , wherein the nanoparticles and the anti-cancer drug are present at the same time in the patient.19. The method according to claim 15 , wherein the magnetic nanoparticles comprise a coating comprising substances which can be ...

COMBINATION THERAPY OF ANTI-MIF ANTIBODIES AND CHEMOTHERAPEUTICS

The present invention pertains to anti-MIF antibodies, in particular their use in combination with therapeutics, i.e. chemotherapeutics, in the treatment of cancer. 1. An anti-MIF antibody in combination with a chemotherapeutic agent for use in the treatment of cancer , wherein the chemotherapeutic agent is preferably gemcitabine , cisplatin and/or doxorubicin.2. The anti-MIF antibody in combination with chemotherapeutic agent according to for use in the treatment of cancer claim 1 , wherein the cancer is selected from the following group: pancreatic cancer claim 1 , ovarian cancer claim 1 , prostate cancer claim 1 , breast cancer claim 1 , lung cancer and colon cancer claim 1 , more preferred pancreatic cancer claim 1 , prostate cancer and ovarian cancer.3. The combination according to or wherein the anti-MIF antibody is selected from the following group: anti-MIF antibody RAM9 claim 1 , RAM0 and/or RAM4.4. The combination therapy according to any of to wherein the chemotherapeutic is gemcitabine.5. The combination therapy according to any of to claim 1 , the anti-MIF antibody is RAM9 claim 1 , the chemotherapeutic is doxorubicin claim 1 , optionally in combination with cisplatin and the cancer is ovarian cancer.6. The combination therapy according to any of to claim 1 , the anti-MIF antibody is RAM9 claim 1 , the chemotherapeutic is gemcitabine and the cancer is pancreas carcinoma.7. The combination therapy according to any of to claim 1 , the anti-MIF antibody is RAM0 claim 1 , the chemotherapeutic is doxorubicin claim 1 , optionally in combination with cisplatin and the cancer is ovarian cancer.8. The combination therapy according to any of to claim 1 , the anti-MIF antibody is RAM0 claim 1 , the chemotherapeutic is gemcitabine and the cancer is pancreas carcinoma.9. The combination therapy according to any of to claim 1 , the anti-MIF antibody is RAM4 claim 1 , the chemotherapeutic is doxorubicin claim 1 , optionally in combination with cisplatin and the cancer ...

CHEMICALLY MODIFIED CURCUMINS AS INHIBITORS OF ANTHRAX LETHAL FACTOR

The present invention provides a method of inhibiting the binding of anthrax lethal factor with protective antigen comprising contacting the anthrax lethal factor with a compound having the structure: 2. The method of claim 1 , wherein the compound inhibits anthrax lethal factor or anthrax lethal factor protease activity.3. The method of claim 1 , wherein the compound is a non-competitive inhibitor or uncompetitive inhibitor of anthrax lethal factor.4. (canceled)6Bacillus anthracis.. The method of claim 5 , wherein the compound inhibits anthrax lethal factor or anthrax lethal factor protease activity in the subject infected with7Bacillus anthracis.. The method of claim 5 , wherein the compound inhibits the binding of anthrax lethal factor with protective antigen in the subject infected with8Bacillus anthracis.. The method of claim 5 , wherein the compound inhibits the binding of anthrax edema factor with protective antigen in the subject infected with9Bacillus anthracis.. The method of claim 7 , wherein the compound inhibits the formation of anthrax lethal toxin in the subject infected with10Bacillus anthracis.. The method of claim 8 , wherein the compound inhibits the formation of anthrax edema toxin in the subject infected with11Bacillus anthracis.. The method of claim 5 , further comprising administering an antibiotic to the subject infected with13. The method of claim 12 , wherein at least one of R claim 12 , R claim 12 , R claim 12 , R claim 12 , and Rand at least one of R claim 12 , R claim 12 , R claim 12 , R claim 12 , and R claim 12 , are each claim 12 , independently claim 12 , —OR.14. The method of claim 12 ,wherein{'sub': 14', '15', '16', '17, 'Ris methoxy, —ORor —NRR;'}{'sub': 15', '3-10', '2-10', '2-10, 'Ris H, Calkyl, Calkenyl, or Calkynyl;'}{'sub': 16', '17', '1-10', '2-10', '2-10, 'Rand Rare each, independently, H, Calkyl, Calkenyl, Calkynyl, aryl, heteroaryl, or heterocyclyl;'}or a salt thereof.1518-. (canceled)21. (canceled)22. (canceled)24. The ...

Methods and compositions for treating resistant and recurrent forms of cancer

A method for treating prostate cancer in a subject involves selecting a subject having prostate cancer and cytochrome c-deficiency, and administering, to the selected subject, a therapeutically effective amount of one or more agents capable of restoring cytochrome-c activity. Also presented is a method of inducing apoptosis in drug resistant cancer cells involving selecting drug resistant cancer cells having cytochrome-c deficiency, and administering to the selected cells, one or more agents that restore cytochrome-c activity in an amount effective to sensitize said cancer cells to drug induced apoptosis. A combination therapeutic comprising one or more agents increases cytochrome-c activity and efficacy of a chemotherapeutic agent. Another method involves selecting a subject having cancer, and obtaining a cell sample including tumor tissues/biopsy and blood samples from said subject, and further involves measuring cytochrome-c expression levels and Drp1 phosphorylation levels in said sample.

COMPOSITIONS AND METHODS FOR IMMUNE-MEDIATED CANCER THERAPY

Disclosed herein are methods and compositions for enhancing an immune response to a solid tumor in a subject. In some embodiments, a method comprises: (a) administering to the subject a hypoxia-activated bioreductive agent (HABA); (b) inducing hypoxia by (i) administering a hypoxia-inducing agent to the subject or (ii) embolizing one or more blood vessels supplying the solid tumor; and (c) administering an immune checkpoint inhibitor prior to, simultaneously with, or subsequent to step (b) in an amount effective to enhance an immune response to the solid tumor, as compared to an immune response in the absence of the immune checkpoint inhibitor. Kits for use in the disclosed methods are also provided. 1. A method of enhancing an immune response to a solid tumor in a subject , the method comprising:(a) administering to the subject a hypoxia-activated bioreductive agent (HABA);(b) inducing hypoxia by (i) administering a hypoxia-inducing agent to the subject or (ii) embolizing one or more blood vessels supplying the solid tumor; and(c) administering an immune checkpoint inhibitor prior to, simultaneously with, or subsequent to step (b) in an amount effective to enhance an immune response to the solid tumor, as compared to an immune response in the absence of the immune checkpoint inhibitor.2. The method of claim 1 , wherein the hypoxia-activated bioreductive agent is tirapazamine.3. The method of claim 1 , wherein step (b) comprises administering a hypoxia-inducing agent that is a vascular disrupting agent.4. The method of claim 3 , wherein the vascular disrupting agent is DMXAA claim 3 , a stilbene claim 3 , or a stilbene derivative.5. The method of claim 4 , wherein the stilbene derivative is selected from the group consisting of: combretastatin claim 4 , combretastatin derivatives claim 4 , cis-3 claim 4 ,4′ claim 4 ,5-trimethoxy-3′-aminostilbene (stilbene 5c) claim 4 , cis-3 claim 4 ,4′ claim 4 ,5-trimethoxy-3′-hydroxystilbene (stilbene 6c) claim 4 , and a prodrug ...

NOVEL INHIBITORS FOR ERG ONCOGENE POSITIVE CANCERS

Alterations to the ERG gene are some of the most prominent genomic changes associated with many cancers including prostate cancer. Such cancer specific alterations result in the overexpression of wild type ERG protein or an altered ERG protein. The present invention provides selective inhibitors of wild type or an altered ERG protein expression. The ERG inhibitors of the invention, therefore, are therapeutic agents for treating ERG positive cancers. 1. A method for treating or preventing an ERG positive cancer related to overexpression of wild type ERG protein , an altered ERG protein , increased ERG gene transcription , or ERG mRNA translation in a patient suffering therefrom , comprising the step of administering to the patient a therapeutically-effective amount of an inhibitor of ERG expression.2. The method according to claim 1 , wherein the inhibitor selectively inhibits the altered ERG protein.3. The method according to claim 1 , wherein the inhibitor selectively inhibits ERG gene transcription or ERG mRNA translation.4. The method according to claim 1 , wherein the inhibitor further inhibits the growth of ERG positive cancer cells.7. The method according to claim 1 , wherein the ERG positive cancer is selected from the group consisting of prostate cancer claim 1 , colorectal cancer claim 1 , Ewing sarcoma claim 1 , a vascular tumor and leukemia.8. The method according to claim 1 , wherein the ERG positive cancer is prostate cancer.9. The method according to claim 1 , further comprising co-administration of an anti-cancer therapeutic.1011-. (canceled)12. A method for treating or preventing a cancer related to overexpression of wild type ERG protein claim 1 , an altered ERG protein claim 1 , increased ERG gene transcription claim 1 , or increased ERG mRNA translation in a patient suffering therefrom claim 1 , comprising the step of administering to the patient a therapeutically-effective amount of an inhibitor of ERG expression.13. The method according to claim ...

Pharmaceutical Composition Of S-Ketamine Hydrochloride

The present invention is directed to an aqueous formulation of S-ketamine hydrochloride, preferably for nasal administration, wherein the formulation does not contain an antimicrobial preservative. 1. A pharmaceutical composition comprising:(S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride and water;wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 120 mg/mL to about eq. 250 mg/mL, based on the total volume of the pharmaceutical composition.2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for nasal administration.3. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition exhibits a shelf life of at least three months under accelerated storage conditions comprising 40° C. and 75% relative humidity.4. The pharmaceutical composition of claim 1 , wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 120 mg/mL to about eq. 175 mg/mL claim 1 , based on the total volume of the pharmaceutical composition.5. The pharmaceutical composition of claim 1 , wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 125 mg/mL to about eq. 180 mg/mL claim 1 , based on the total volume of the pharmaceutical composition.6. The pharmaceutical composition of claim 1 , wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 125 mg/mL to about eq. 150 mg/mL claim 1 , based on the total volume of the pharmaceutical composition.7. The pharmaceutical composition of claim 1 , wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 140 mg/mL to about eq. 160 mg/mL claim 1 , based on the ...

AMANTADINE COMPOSITIONS, PREPARATIONS THEREOF, AND METHODS OF USE

Provided herein are oral pharmaceutical compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, and which have a low level of organic solvent. Provided are also methods of orally administrating a composition comprising amantadine, or a pharmaceutically acceptable salt thereof, to a subject, which has reduced gastrointestinal side effects or sleep disturbances. Further provided are extended release oral compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, that are suitable for once daily administration. 1. An oral pharmaceutical composition , comprising:a drug, wherein the drug is amantadine or a pharmaceutically acceptable salt thereof, and wherein said oral pharmaceutical composition comprises from 50 mg to 500 mg of the amantadine or an equivalent amount of the pharmaceutically acceptable salt thereof; andat least one excipient that modifies the release of at least a portion of said drug; (i) 0% to 10% in 2 hours,', '(ii) 3% to 14% in 4 hours,', '(iii) 23% to 40% in 6 hours,', '(iv) 50% to 70% in 8 hours, and', '(v) not less than 80% in 12 hours;', 'wherein the dissolution profile is determined with a USP Type 2 apparatus (paddles) at 50 rpm at 37.0±0.5° C. with 500 ml water as the dissolution medium; and, 'wherein said oral pharmaceutical composition has a dissolution profile of said drug which shows at least four of{'sub': '0-inf', 'wherein said oral pharmaceutical composition provides (i) a Tmax for amantadine of 11 to 19 hours, and (ii) an AUCfor amantadine of 44 to 72 ng*hr/ml per mg of said drug, when said oral pharmaceutical composition is dosed in healthy subjects of a single dose, human pharmacokinetic study, wherein the subjects are dosed in the morning after an overnight fast.'}2. The oral pharmaceutical composition of claim 1 , wherein said dissolution profile is (i) 0% to 9% in 2 hours claim 1 , (ii) 3% to 14% in 4 hours claim 1 , (iii) 24% to 40% in ...

MARKERS FOR PERSONALIZED CANCER TREATMENT WITH LSD1 INHIBITORS

Provided herein are methods of treating cancers characterized by a high expression of GFIIB, comprising administering a therapeutically effective amount of a KDMIA inhibitor. 1. A method of treating a subject with a cancer characterized by a high expression level of GFI1B , comprising administering to the subject a therapeutically effective amount of a KDM1A inhibitor , wherein high expression level of GFI1B is characterized by an expression value falling within the top quartile of measured values from a collection of tissue samples obtained from the same cancer type in a population of subjects.2. The method of claim 1 , wherein prior to treatment claim 1 , the cancer was determined to have a high expression level of GFI1B.3. The method of claim 1 , comprising the step of performing a biopsy of the subject's cancer prior to treatment and determining if the cancer exhibits a high expression level of GFI1B.4. A method of treating a subject with a cancer comprising determining the expression level of GFI1B; and administering to the subject a therapeutically effective amount of an KDM1A inhibitor claim 1 , if the subject's cancer exhibits a high expression level of GFI1B.5. (canceled)6. (canceled)7. The method of claim 4 , further comprising administering to the subject a therapeutically effective amount of a cancer therapy other than the administration of a KDM1A inhibitor claim 4 , if the expression level of GFI1B is not high.8. The method of claim 1 , wherein high expression level of GFI1B is characterized by an expression value falling within the top quartile of measured values from a collection of tissue samples obtained from the same cancer type in a population of subjects.9. The method of claim 1 , wherein the collections of tissue samples are taken from tumors.10. The method of claim 1 , wherein the population of subjects is at least 25 subjects having the same cancer.11. The method of claim 1 , wherein the population of subjects is at least 50 subjects having ...

Inhibitors of indoleamine 2,3-dioxygenase and methods of their use

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the disclosure.

COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH FLUDARABINE AND/OR MITOXANTRONE

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with fludarabine and/or mitoxantrone for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody with fludarabine and/or mitoxantrone. 1. Use of an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 , for the manufacture of a medicament for the treatment of cancer in combination with fludarabine and/or mitoxantrone.2. Use according to any one of to characterized in that said cancer is a B-Cell Non-Hodgkin's lymphoma (NHL).3. Use according to claim 1 , characterized in that said antibody is a humanized B-Ly1 antibody.4. Use according to claim 3 , characterized in that the treatment of cancer is in combination with fludarabine.5. Use according to characterized in that the humanized B-Ly1 antibody is administered in a dosage of 800 to 1600 mg on day 1 of up to six or seven 3- to 4-week-dosage-cycles claim 4 , and fludarabine is administered in a dosage of 20 mg/mto 30 mg/mon day 1 claim 4 , 2 and 3 of up to six or seven 4-week-dosage-cycles.6. Use according to claim 3 , characterized in that the treatment of cancer is in combination with fludarabine and cyclophosphamide.7. Use according to any one of characterized in that the humanized B-Ly1 antibody is administered in a dosage of 800 to 1600 mg on day 1 of up to six or seven 3- to 4-week-dosage-cycles claims 6 , fludarabine is administered in a dosage of 20 mg/mto 30 mg/mon day 1 claims 6 , 2 and 3 of up to six or seven 4-week-dosage-cycles claims 6 , and cyclophosphamide is administered in a dosage of 200 mg/mto 300 mg/mon day 1 claims 6 , 2 and 3 of up to six or seven 4-week-dosage-cycles.8. Use according to any one of to claims 6 , characterized in that the treatment of cancer is in combination with mitoxantrone.9. Use according to any one of to claims 6 , ...

FIXED DOSE COMBINATION THERAPY OF PARKINSON'S DISEASE

A pharmaceutical composition for use in treatment of Parkinson's disease is provided comprising a pharmaceutically acceptable carrier and a fixed dose combination of pramipexole and rasagiline, wherein the fixed dose combination contains a subtherapeutic dose of pramipexole and a subtherapeutic dose of rasagiline, and the dose of pramipexole is lower than or equal to the dose of rasagiline. 1. A pharmaceutical composition for use in treatment of Parkinson's disease comprising a pharmaceutically acceptable carrier and a fixed dose combination of pramipexole and rasagiline , wherein the fixed dose combination contains a subtherapeutic dose of pramipexole and a subtherapeutic dose of rasagiline , and the dose of pramipexole is lower than the dose of rasagiline.2. The pharmaceutical composition of claim 1 , wherein the molar ratio of pramipexole to rasagiline is selected from a range of 1:1.1 to 1:20 claim 1 , 1:1.1 to 1:10 claim 1 , 1:1.1 to 1:5 claim 1 , 1:1.1 to 1:3 or 1:1.1 to 1:2.3. The pharmaceutical composition of claim 1 , wherein said fixed dose combination contains from 0.05 mg to 1.0 mg of pramipexole and from 0.05 mg to 1.0 mg of rasagiline.4. The pharmaceutical composition of claim 1 , wherein said pramipexole and rasagiline are formulated for extended release.5. The pharmaceutical composition of claim 4 , in the form of a monolithic matrix; a tablet claim 4 , preferably a bi- or multi-layered tablet claim 4 , matrix tablet claim 4 , disintegrating tablet claim 4 , dissolving tablet claim 4 , or chewable tablet; a capsule or sachet claim 4 , preferably filled with granules claim 4 , grains claim 4 , beads claim 4 , or pellets; or a depot system based on a biodegradable polymer such as poly(D claim 4 ,L-lactide) (PLA) claim 4 , polyglycolide (PGA) claim 4 , and poly(D claim 4 ,L-lactide-co-glycolide) (PLGA).6. The pharmaceutical composition of claim 1 , formulated for oral administration.7. The pharmaceutical composition of comprising extended-release ...

Preventives/remedies for stress urinary incontinence and method of screening the same

An agent for the prophylaxis or treatment of stress urinary incontinence, which contains a substance that activates a serotonin 5-HT 2C receptor, an agent for the prophylaxis or treatment of stress urinary incontinence, which contains a substance that stimulates an androgen binding site, and a method of screening for a drug for the prophylaxis or treatment of abdominal pressure incontinence, which includes electrostimulating the abdominal muscles or a nerve controlling them of an animal to increase the abdominal pressure, and measuring the leak point pressure at that time.

Modulators of atp-binding cassette transporters

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Combination therapy for copd

Aerosol formulations comprising glycopyrronium chloride in combination with formoterol may be administered by means of a pressurized metered dose inhaler (pMDI) for the prevention or treatment of chronic obstructive pulmonary disease. The formulation further comprises a HFA propellant, a co-solvent, and an amount of inorganic acid sufficient to stabilize both the glycopyrronium chloride and the formoterol components. Optionally, the formulation may further comprise beclometasone dipropionate.