ЛЕКАРСТВЕННЫЕ СОСТАВЫ С КОНТРОЛИРУЕМЫМ ВЫСВОБОЖДЕНИЕМ, ОСНОВАННЫЕ НА БЛОК-СОПОЛИМЕРАХ

Изобретение раскрывает фармацевтическую композицию для контролируемого высвобождения относительно токсичных активных соединений, в особенности биоактивных протеинов из класса интерферонов. Композиция содержит биоразлагаемый блок-сополимер, состоящий из поли(этиленгликоль)терефталата (ПЭГТ) в количестве от 50 до 95% вес. и поли(бутилентерефталата) (ПБТ). Композиция может быть представлена в виде инъекционных микрочастиц, инъекционной жидкости, обладающей способностью самостоятельного гелеобразования или твердого имплантата. Кроме того, изобретение предлагает фармацевтический набор, включающий упомянутую композицию, способы приготовления композиции и фармацевтические варианты ее применения. Изобретение обеспечивает первоначальное высвобождение в течение 4 часов не более приблизительно 10% включенного количества одного или более альфа-интерферонов и, по меньшей мере, 80% одного или более альфа-интерферонов высвобождается в мономерной неагрегированной форме. 30 з.п. ф-лы, 2 ил.

ЛЕКАРСТВЕННЫЕ СРЕДСТВА С КОНТРОЛИРУЕМЫМ ВЫСВОБОЖДЕНИЕМ, СОДЕРЖАЩИЕ ПЕПТИДЫ

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СИСТЕМА ИНТРАВЕНТРИКУЛЯРНОЙ ДОСТАВКИ ЛЕКАРСТВЕННОГО СРЕДСТВА ДЛЯ УЛУЧШЕНИЯ ИСХОДА ПОСЛЕ ПОВРЕЖДЕНИЯ ГОЛОВНОГО МОЗГА, НАРУШАЮЩЕГО МОЗГОВОЕ КРОВООБРАЩЕНИЕ

Группа изобретений относится к медицине, а именно к неврологии, нейрохирургии и фармакологии, и может быть использована для терапевтического лечения отсроченного осложнения состояния, при котором кровь попадает в субарахноидальное пространство. Предложено применение микродисперсной композиции для изготовления лекарственного средства для терапевтического лечения таких состояний. Композиция содержит порошковую суспензию микрочастиц, содержащих терапевтическое количество средства, выбранного из группы, состоящей из антагониста кальциевых каналов, антагониста эндотелина (ЕТ) и антагониста каналов с транзиторным рецепторным потенциалом (TRP), импрегнированного в матрицу или на матрицу из биополимера, и фармацевтический носитель, который придает композиции вязкость. Микрочастицы имеют однородное распределение размера микрочастиц. Средний размер частиц составляет 66 μм. В каждую микрочастицу включено по меньшей мере 40% по весу терапевтического средства. Предложен также способ лечения, предполагающий ...

ПРЕПАРАТИВНАЯ ФОРМА С ЗАМЕДЛЕННЫМ ВЫСВОБОЖДЕНИЕМ, СОДЕРЖАЩАЯ ОКТРЕОТИД И ТРИ ЛИНЕЙНЫХ ПОЛИМЕРА ПОЛИ(ЛАКТИД-СО-ГЛИКОЛИДА)

В заявке описаны препаративные формы с замедленным высвобождением, содержащие в качестве действующего вещества октреотид или его фармацевтически приемлемую соль и три различных линейных полимера поли(лактид-со-гликолида) (PLGA). Первый PLGA имеет соотношение лактид:гликолид 65:35, второй PLGA имеет соотношение лактид:гликолид 75:25, третий PLGA имеет соотношение лактид:гликолид 85:15. Композиция октреотида, содержащая три различных линейных полимера PLGA, характеризуется концентрацией октреотида в плазме с низкой вариабельностью за период времени, составляющий более чем три месяца. Композиция предназначена для пролонгированной поддерживающей терапии страдающих акромегалией пациентов и для лечения диареи и приливов крови, ассоциированных со злокачественными карциноидными опухолями и опухолями, продуцирующими вазоактивные кишечные пептиды (опухоли типа випом). 5 н. и 13 з.п. ф-лы, 4 табл., 5 пр.

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Изобретение относится к получению биоразлагаемых микрочастиц, образованных из полилактидно-полигликолидных сополимеров (PLGA), и к обеспечению сигмоидального высвобождения рисперидона из этих микрочастиц. Описаны варианты способа получения биоразлагаемых микрочастиц из сополимера D,L-лактида и гликолида (PLGA), характеризующихся сигмоидальным профилем высвобождения рисперидона, который содержится в микрочастицах, включающий следующие стадии: a) получение внутренней масляной фазы путем растворения полимера PLGA и рисперидона в органическом растворителе, при этом концентрация полимера во внутренней масляной фазе находится в диапазоне 5-8% по весу; b) получение внешней водной фазы, состоящей из воды, поливинилового спирта (PVA), необязательно водного буферного раствора для доведения рН до значения, при котором рисперидон характеризуется более низкой растворимостью, и такого же органического растворителя, что и используемый в масляной фазе, при этом количество органического растворителя, добавленного ...

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Изобретение относится к области клинической фармакологии. Сущность заключается в том, что создана фармацевтическая композиция для пролонгированного высвобождения пептида, обладающего терапевтическим действием, или его соли, где указанный пептид представлен следующей последовательностью: pyroGlu-His-Trp-Ser-Xaa1-Gly-Xaa2-Xaa3-Pro-Gly-NH2, где Хаа1 представляет собой His или Tyr, Хаа2 представляет собой Trp или Leu и Хаа3 представляет собой Tyr или Arg, при условии, что в том случае, когда Хаа1 представляет собой Tyr и Хаа2 представляет собой Leu, Хаа3 не означает Arg, причем композиция дополнительно содержит фармацевтически приемлемый биоразлагаемый полимер. Технический результат - расширение арсенала композиций, используемых для лечения заболеваний, связанных с нарушением костей и простаты. 4 н. и 9 з.п. ф-лы, 1 ил., 2 табл.

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Изобретение относится к медицине, в частности к композиции микросфер гозерелина ацетата с пролонгированным высвобождением, а также к их применению для получения лекарственного средства для лечения рака предстательной железы, преждевременного полового созревания, аденомиоза, женского бесплодия или гистеромиомы. Микросферы включают гозерелин, по меньшей мере один поли(лактидгликолид) и полоксамер или ПЭГ. Осуществление изобретения позволяет получить микросферы с пролонгированным высвобождением, которые имеют сравнительно высокую биодоступность, которая способствует полному проявлению действия лекарственного средства, и имеют эффективность захвата свыше 90%. 2 н. и 11 з.п. ф-лы, 4 ил., 6 табл., 24 пр.

СПОСОБ И УСТРОЙСТВО ДЛЯ ПОЛУЧЕНИЯ ТВЕРДОЙ ДИСПЕРСИИ

Изобретение относится к области фармацевтики и может быть использовано для получения твердой дисперсии никардипина. Способ экструзии из расплава для получения твердой дисперсии, содержащей фармацевтически активный ингредиент, полимерное связующее и необязательно одно или более вспомогательных средств, включает: а) помещение порционным образом определенного количества полимерного связующего, активного ингредиента и необязательно вспомогательного средства (средств) в сосуд для расплава; плавление полимерного связующего в сосуде для расплава при встряхивании для диспергирования активного ингредиента в полимерном связующем с получением расплавленной предисперсии; b) подачу предисперсии в экструдер для гомогенизации предисперсии и высвобождение расплава через головку; и c) предоставление расплаву возможности затвердеть. При этом активный ингредиент выбран из никардипина, его фармацевтически приемлемой соли, гидрата или сольвата, а полимерное связующее содержит (i) поли(сополимер лактида и гликолида ...

СИСТЕМА ДОСТАВКИ ДЛЯ АКТИВНЫХ СРЕДСТВ

Группа изобретений относится к медицине. Описана система доставки, содержащая активное средство в полимерном материале, образованном из термопластичной композиции. Посредством избирательной регуляции относительно определенной природы термопластичной композиции, а также способа, с помощью которого она образована, образована поровая сеть, которая содержит множество микропор и нанопор. Возможность достижения такого многомодального распределения пор по размеру может обеспечить варьирование скорости доставки активного средства для определенного применения. 4 н. и 14 з.п. ф-лы, 10 ил., 11 пр.

СОДЕЖАЩИЙ ОКТРЕОТИД СОСТАВ С ЗАМЕДЛЕННЫМ ВЫСВОБОЖДЕНИЕМ СО СТАБИЛЬНО ВЫСОКИМ УРОВНЕМ ВОЗДЕЙСТВИЯ

Группа изобретений относится к области фармацевтики и медицины и касается фармацевтического состава с замедленным высвобождением, содержащего в качестве активного ингредиента октреотид или его фармацевтически приемлемую соль и два различных линейных сополимера полилактида и гликолида (СПЛГ), характеризующихся молярным соотношением лактид/гликолид 75:25 и различными значениями вязкости, для продолжительного поддерживающего лечения пациентов с акромегалией и для лечения тяжелых форм диареи и гиперемии, связанных со злокачественными карциноидными опухолями и опухолями, клетки которых вырабатывают вазоактивный интестинальный пептид. Группа изобретений обеспечивает стабильно высокий уровень и быстрое достижение необходимого уровня воздействия активного вещества. 2 н. и 8 з.п. ф-лы, 5 пр., 3 табл., 1 ил.

СИСТЕМЫ С РЕГУЛИРУЕМЫМ ВЫСВОБОЖДЕНИЕМ И НИЗКИМИ ДОЗАМИ АНДРОГЕНОВ, СПОСОБ ИХ ПОЛУЧЕНИЯ И СПОСОБ ЛЕЧЕНИЯ С ПОМОЩЬЮ ЭТИХ СИСТЕМ

Изобретение относится к медицине. Раскрываются частицы пролонгированного высвобождения, включающие андрогенный стероид, диспергированный в биологически разлагаемом полимерном связующем вещества при их массовом соотношении от 1:4 до 7:3 соответственно. Андрогенным стероидом является медроксипрогестерона ацетат или мегестрола ацетат. Биологическое разложение полимерного связующего вещества способствует высвобождению указанного андрогенного стероида со скоростью и продолжительностью, которые обеспечивают его концентрацию в сыворотке крови от 1,0 до 50,0 нМ/л за период от 48 часов до 28 дней после введения. Также рассмотрены способ активации рецепторов андрогена, способ ингибирования роста клеток рака молочной железы и способы контрацепции, предусматривающие введение терапевтически эффективных количеств части пролонгированного высвобождения. Новые инъецируемые системы доставки с пролонгированным высвобождением медроксипрогестерона ацетата и мегестрола ацетата позволяют поддерживать низкие концентрации ...

КОМПОЗИЦИЯ БИОРАЗЛАГАЮЩИХСЯ МИКРОСФЕР, ПРИГОДНАЯ ДЛЯ КОНТРОЛИРУЕМОГО ВЫСВОБОЖДЕНИЯ КОНТРОЛИРУЮЩЕГО УРОВЕНЬ ГЛЮКОЗЫ ПЕПТИДА, И ЕЕ СОСТАВ

Изобретение относится к фармакологии и касается способа получения микросфер из биоразлагающегося полимера, включающего: добавление органического растворителя к полимеру с получением раствора полимера (стадия 1); диспергирование регулирующего уровень глюкозы пептида в растворе полимера стадии 1 с получением дисперсии лекарственного средства и смешивание спирта или смеси спирта и органической кислоты с дисперсией лекарственного средства с получением раствора с диспергированным в нем лекарственным средством (стадия 2); и получение микросферы из раствора с диспергированным в нем лекарственным средством стадии 2 (стадия 3), где регулирующий уровень глюкозы пептид представляет собой эксендин-4 и где биоразлагающийся полимер выбран из группы, состоящей из поли-L-молочной кислоты, сополимера D-молочной кислоты и гликолевой кислоты, сополимера L-молочной кислоты и гликолевой кислоты и сополимера D,L-молочной кислоты и гликолевой кислоты. Изобретение обеспечивает получение микросфер, которые не демонстрируют ...

ЛЕКАРСТВЕННАЯ ФОРМА ДЛИТЕЛЬНОГО ДЕЙСТВИЯ, СОДЕРЖАЩАЯ РИВАСТИГМИН, И СПОСОБ ЕЕ ИЗГОТОВЛЕНИЯ

Настоящее изобретение относится к микросфере с замедленным высвобождением для инъекционных лекарственных форм длительного действия, содержащей одно или несколько действующих активных веществ, выбранных из группы, состоящей из ривастигмина и его фармацевтически приемлемых плохо растворимых солей и биоразлагаемого полимера, и к содержащей ее инъекционной лекарственной форме длительного действия для профилактики или лечения болезни Альцгеймера, а также к способу изготовления микросферы; а также оно может уменьшить побочные эффекты со стороны желудочно-кишечного тракта пациента, которые часто наблюдаются у обычных препаратов для перорального введения, и повысить адаптируемость к приему лекарства, тем самым максимально увеличивая терапевтический эффект, путем обеспечения инъекционной лекарственной формы длительного действия, содержащей микросферу с ривастигмином с замедленным высвобождением, которая имеет высокое содержание, с одновременным эффективным регулированием начального взрывного высвобождения ...

КОМПОЗИЦИИ И СПОСОБЫ ЛЕЧЕНИЯ ИЛИ ПРЕДУПРЕЖДЕНИЯ ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ

... 1. Способ лечения или предупреждения рассеянного склероза, включающий введение пациенту терапевтически эффективного количества антимикротрубочкового агента таким образом, что рассеянный склероз лечится или предупреждается. 2. Способ по п.1, в котором вышеуказанный антимикротрубочковый агент выбран из группы, состоящей из эпотилона А или В, дискодермолида, оксида дейтерия (D2 O), гексиленгликоля, туберцидина, LY290181, фторида алюминия, бис(сукцинимидилсукцината)этиленгликоля, этилового эфира глицина, а также их аналогов или производных. 3. Способ по п.1, в котором вышеуказанный антимикротрубочковый агент является паклитакселом или его аналогом или производным. 4. Способ лечения или предупреждения псориаза, включающий введение пациенту терапевтически эффективного количества антимикротрубочкового агента таким образом, что псориаз лечится или предупреждается. 5. Способ по п.4, в котором вышеуказанный антимикротрубочковый агент выбран из группы, состоящей из эпотилона А или В, дискодермолида ...

КОМПОЗИЦИИ ОПИОИДНОГО АГОНИСТА, СОДЕРЖАЩИЕ ВЫСВОБОЖДАЕМЫЙ И ИЗОЛИРОВАННЫЙ АНТАГОНИСТ

... 1. Пероральная лекарственная форма, включающая (i) терапевтически эффективное количество опиоидного агониста; (ii) опиоидный антагонист в высвобождаемой форме; и (iii) изолированный от контакта опиоидный антагонист, который не высвобождается при введении интактной лекарственной формы. 2. Пероральная лекарственная форма, включающая (i) первый компонент, содержащий терапевтически эффективное количество опиоидного агониста; (ii) второй компонент, содержащий опиоидный антагонист в высвобождаемой форме; и (iii) третий компонент, содержащий изолированный опиоидный антагонист, который не высвобождается при введении интактной лекарственной формы. 3. Пероральная лекарственная форма, включающая (i) первый компонент, содержащий терапевтически эффективное количество опиоидного агониста; (ii) второй компонент, содержащий опиоидный антагонист в высвобождаемой форме и изолированный от контакта опиоидный антагонист, который не высвобождается при введении интактной лекарственной формы. 4. Пероральная лекарственная ...

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ ОКТРЕОТИДНЫЕ МИКРОЧАСТИЦЫ

... 1. Фармацевтическая композиция, включающая микрочастицы октреотидацетата, изготовленные из линейного сополимера лактида с гликолидом, в которой полимер содержит менее 1% силиконового масла или гептана, предпочтительно, не содержащего силиконового масла или гептана. 2. Фармацевтическая композиция, включающая микрочастицы октреотидацетата, изготовленные из линейного сополимера лактида с гликолидом, в смеси или в ассоциации с разбавителем, включающим неионогенное поверхностно-активное вещество. 3. Фармацевтическая композиция по п.1 или 2, дополнительно включающая вещество, препятствующее агломерации. 4. Способ получения микрочастиц октреотидацетата, включающий стадии а) растворения или диспергирования октреотидацетата в метиленхлориде, содержащем растворенный линейный сополимер лактида с гликолидом, с получением дисперсии; б) объединения указанной дисперсии с эффективным количеством сплошной рабочей среды с получением эмульсии, которая содержит указанную сплошную рабочую среду и микрокапельки ...

СУСПЕНЗИЯ ДЛЯ ВИЗУАЛИЗАЦИИ ПРОЗРАЧНОЙ ТКАНИ В ГЛАЗУ

... 1. Суспензия для визуализации прозрачной ткани глаза, содержащая тонкодисперсные частицы биоразлагаемого макромолекулярного соединения и, по меньшей мере, одну соль, выбранную из группы, состоящей из солей двухвалентных металлов и солей трехвалентных металлов в водной среде, при этом композиция предназначена для вливания в глаз для приведения в контакт с прозрачными тканями глаза с целью улучшения их различимости. ! 2. Суспензия для визуализации прозрачной ткани глаза по п.1, в которой один грамм тонкодисперсных частиц биоразлагаемого макромолекулярного соединения невозможно полностью растворить в менее чем 30 мл воды в течение 30 мин при 20°C. ! 3. Суспензия для визуализации прозрачной ткани глаза по п.1 или 2, в которой биоразлагаемое макромолекулярное соединение выбрано из группы, состоящей из полимолочной кислоты, полигликолевой кислоты и сополимера молочной кислоты/гликолевой кислоты. ! 4. Суспензия для визуализации прозрачной ткани глаза по п.1, в которой концентрация соли трехвалентного ...

КОМПОЗИЦИЯ С РЕГУЛИРУЕМЫМ ВЫСВОБОЖДЕНИЕМ И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

... 1. Композиция с регулируемым высвобождением, включающая (1) физиологически активное соединение или его соль в количестве примерно от 14 до примерно 24% от общей массы всей композиции,(2) оксинафтойную кислоту, выбранную из группы, состоящей из 3-окси-2-нафтойной кислоты и 1- окси-2-нафтойной кислоты или ее соли, и (3) полимер молочной кислоты или ее соли, имеющий среднемассовую молекулярную массу от 15000 до 50000, в котором содержание полимеров с молекулярной массой от 5000 или ниже составляет 5% по массе или ниже, причем молярное соотношение оксинафтойной кислоты или ее соли к физиологически активному соединению или его соли равняется от 3:4 до 4:3. 2. Композиция с регулируемым высвобождением по п.1, где полимер молочной кислоты имеет среднемассовую молекулярную массу от 15000 до 30000. 3. Композиция с регулируемым высвобождением по п.1, где физиологически активное соединение представляет производное LH-RH. 4. Композиция с регулируемым высвобождением по п.3, где производное LH-RH представляет ...

СПОСОБ ЛЕЧЕНИЯ АТРОФИЧЕСКОЙ ВОЗРАСТНОЙ МАКУЛЯРНОЙ ДЕГЕНЕРАЦИИ

Группа изобретений относится к медицине, а именно к офтальмологии, и может быть использована для лечения сухой возрастной дегенерации желтого пятна (сухой ВДЖП). Для этого готовят биосовместимую систему доставки лекарственного средства с замедленным высвобождением, содержащую от 5 мкг до 20 мкг бевацизумаба, и носитель из полимерной гиалуроновой кислоты, ассоциированной с бевацизумабом, которую вводят в стекловидную полость при помощи 25-30-мерного шприца. В среднем в течение 24 ч высвобождается от 14 до 120 нг бевацизумаба в период от трех до шести месяцев. При этом система доставки имеет вязкость от 130000 сПз до 300000 сПз при скорости сдвига 0,1/секунду при 25°С. Использование данных изобретений позволяет лечить сухую ВДЖП при предотвращении или замедлении ее развития во влажную ВДЖП. 2 н. и 3 з.п. ф-лы, 1 ил., 3 пр.

КОМПОЗИЦИИ И СПОСОБЫ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ НОГТЕЙ

... 1. Способ лечения заболевания ногтевой субъединицы, включающий в себя локальное введение в пределах пальца, имеющего дистальную часть, среднюю часть и проксимальную часть, композиции, включающей в себя более чем 30% по массе активного агента. 2. Способ по п.1, в котором заболевание ногтевой субъединицы представляет собой грибковую инфекцию. 3. Способ по п.2, в котором грибковая инфекция представляет собой онихомикоз. 4. Способ по п.1, в котором композицию вводят в дистальную часть пальца. 5. Способ по п.1, в котором дистальная часть пальца включает в себя ногтевую субъединицу, имеющую ногтевую пластину, ногтевое ложе, ногтевой валик и матрикс. 6. Способ по п.5, в котором композицию вводят в матрикс. 7. Способ по п.5, в котором композицию вводят в ногтевой валик. 8. Способ по п.1, в котором композицию вводят в среднюю часть пальца. 9. Способ по п.1, в котором композицию вводят в проксимальную часть пальца. 10. Способ по п.1, в котором палец представляет собой палец руки. 11. Способ по п.1 ...

ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ МИКРОСФЕР ГОЗЕРЕЛИНА С ПРОЛОНГИРОВАННЫМ ВЫСВОБОЖДЕНИЕМ

КОМПОЗИЦИИ ПРОЛОНГИРОВАННОГО ДЕЙСТВИЯ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ

... 1. Композиция с замедленным высвобождением, включающая фармакологически активное вещество или его соль, гидроксинафтойную кислоту или ее соль и сополимер молочной кислоты-гликолевой кислоты или его соль, в котором произведение среднемассовой молекулярной массы указанного сополимера молочной кислоты-гликолевой кислоты на количество (мкмоль) концевых карбоксильных групп на единицу массы (г) указанного сополимера молочной кислоты-гликолевой кислоты составляет от 1200000 до 3000000 (включительно). 2. Композиция с замедленным высвобождением по п.1, где фармакологически активное вещество является физиологически активным пептидом. 3. Композиция с замедленным высвобождением по п.1, где фармакологически активное вещество является производным LH-RH. 4. Композиция с замедленным высвобождением по п.1, где гидроксинафтойная кислота является 1-гидрокси-2-нафтойной кислотой или 3-гидрокси-2-нафтойной кислотой. 5. Композиция с замедленным высвобождением по п.1, где гидроксинафтойная кислота является 1- ...

ЭКСТРАКЦИЯ РАСТВОРИТЕЛЯ ИЗ БИОРАЗЛАГАЕМЫХ МИКРОЧАСТИЦ

СПОСОБ ПОЛУЧЕНИЯ ПОРОШКА, СОДЕРЖАЩЕГО БЕЛОК, ПРЕДСТАВЛЯЮЩИЙ СОБОЙ ФАКТОР СВЕРТЫВАНИЯ КРОВИ ЧЕЛОВЕКА, И ПОЛИМЕР НА ОСНОВЕ МОЛОЧНОЙ КИСЛОТЫ

КОМПОЗИЦИИ РОТИГОТИНА, ИХ ПРОИЗВОДНЫХ ИЛИ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫХ СОЛЕЙ РОТИГОТИНА ИЛИ ИХ ПРОИЗВОДНЫХ

... 1. Композиция на основе ротиготина или его фармацевтически приемлемой соли, характеризующаяся тем, что содержит, по крайней мере, один полилактид-гликолид (ПЛГлА); и по крайней мере, одну жирную кислоту, причем, по крайней мере, одна жирная кислота составляет порядка 1-15 вес.% от общей массы состава.2. Композиция по п.1, характеризующаяся тем, что он находится в форме микросфер.3. Композиция по п.2, характеризующаяся тем, что ротиготин или его фармацевтически приемлемая соль составляют 20-40 вес.% от общей массы состава.4. Композиция по п.3, характеризующаяся тем, что, по крайней мере, один ПЛГлА составляет порядка 45-79 вес.% от общей массы состава.5. Композиция по п.4, характеризующаяся тем, что фармацевтически приемлемая соль образована с неорганической или органической кислотой.6. Композиция по п.5, характеризующаяся тем, что неорганическая кислота выбрана из списка: соляная кислота, серная кислота, фосфорная кислота и азотная кислота.7. Композиция по п.5, характеризующаяся тем, что ...

НЕЙРОТРОФИНЫ ДЛЯ ПРИМЕНЕНИЯ В ЛЕЧЕНИИ ТУГОУХОСТИ

Способы сушки для регулировки свойств микрочастиц

КОМПОЗИЦИИ И СПОСОБЫ ДЛИТЕЛЬНОГО ВЫСВОБОЖДЕНИЯ АНТАГОНИСТОВ ГОНАДОТРОПИН-ВЫСВОБОЖДАЮЩЕГО ГОРМОНА (GnRH)

ЛЕЧЕНИЕ ЛЕГОЧНОЙ ГИПЕРТЕНЗИИ ПУТЕМ ИНГАЛЯЦИИ ИЛОПРОСТАТА С ПРЕПАРАТОМ МИКРОЧАСТИЦ

... 1. Композиция, содержащая систему доставки твердой дозы, включающей в себя наполнитель и эффективное количество илопроста, в которой наполнитель содержит гидрофобный модифицированный углевод (HDC). 2. Композиция по п.1, которая дополнительно содержит по меньшей мере одно физиологически приемлемое стекло, выбранное из группы, состоящей из карбоксилата, нитрата, сульфата и бисульфата. 3. Композиция по п.1, где HDC имеет углеводный остов и содержит больше одной гидроксильной группы, замещенной ее менее гидрофильным производным. 4. Композиция по п.3, где производное представляет собой сложный эфир или простой эфир с углеродной цепью любой длины или типа, или любые его функциональные модификации, при этом функциональные модификации выбраны из группы, состоящей из замены атома кислорода гетероатомом. 5. Композиция по п.4, где HDC выбран из группы, состоящей из 6:6′-бис(β-тетраацетил-глюкуронил)гексаацетилтрегалозы, гексаацетата сорбита, пентаацетата α-глюкозы, пентаацетата β-глюкозы, тетраацетата ...

МАГНИТНЫЕ НАНОЧАСТИЦЫ ДЛЯ ПРИМЕНЕНИЯ ПРИ ГИПЕРТЕРМИИ, ИХ ПРИГОТОВЛЕНИЕ И ПРИМЕНЕНИЕ В КОНСТРУКТАХ ДЛЯ ФАРМАКОЛОГИЧЕСКОГО ИСПОЛЬЗОВАНИЯ

... 1. Конструкты, включающие магнитную нанометровую частицу, функционализированную бифункциональными соединениями, полимер, возможно содержащий фармакологически активную молекулу, и, когда указанный полимер является нерастворимым в воде, внешний защитный слой поверхностных агентов. ! 2. Конструкты по п.1, в которых указанная фармакологически активная молекула, если она присутствует, соединена с полимером или диспергирована в нем. ! 3. Конструкты по п.1, в которых указанные магнитные нанометровые частицы являются шпинелями и оксидами MIIMIII 2O4 типа, где MII=Fe, Co, Ni, Zn, Mn; MIII=Fe, Cr в нанометровой форме. ! 4. Конструкты по п.3, в которых указанные магнитные нанометровые частицы выбраны из: феррита кобальта, магнетита и маггемита. ! 5. Конструкты по п.1, в которых указанные бифункциональные соединения выбраны из: тиолов, карбоновых кислот, гидроксамовых кислот, фосфорных кислот, их эфиров и солей, имеющих алифатическую цепь, несущую вторую функциональную группу в концевом положении ( ...

HERSTELLUNG BIOLOGISCH ABBAUBARER, EINEN BIOLOGISCH AKTIVEN STOFF ENTHALTENDER, MIKROPARTIKEL

WASSERUNLOESLICHE POLYPEPTIDE

MIKROKAPSELN MIT GESTEUERTER FREIGABE SOWIE DEREN VERWENDUNG ZUR STIMULIERUNG DES NERVENFASERWACHSTUMS

VERFAHREN ZUR HERSTELLUNG WIRKSTOFFHALTIGER MIKROPARTIKEL AUS HYDROLYTISCH ABBAUBAREN POLYMEREN.

HEMMUNG DER POSTOPERATIVEN ADHAESIONSBILDUNG DURCH TOPISCHE VERABREICHUNG EINES ENTZUENDUNGSHEMMENDEN NICHTSTEROIDEN WIRKSTOFFS.

Künstliche Sauerstoffträger und ihre Verwendung

Die Erfindung betrifft Dispersionen von künstlichen Sauerstoffträgern, wobei die Dispersionen Kapseln mit reversibler Sauerstoffspeicherfähigkeit enthalten, wobei die Kapseln ein sauerstoffpermeables Kapselmaterial umfassen, welches fluorierte, insbesondere perfluorierte Kohlenwasserstoffe, vorzugsweise Perfluorcarbone, enthält und/oder einschließt. Die Dispersionen eignen sich insbesondere als Blutersatzstoff, vorzugsweise zu Zwecken der Transfusion, z.B. bei Zuständen nach Blutverlusten des menschlichen oder tierischen Körpers, insbesondere nach operativen Eingriffen, Unfällen, Verletzungen etc., oder zur prophylaktischen und/oder therapeutischen Behandlung von ischämischen Zuständen oder von Zuständen nach Reperfusion.

MODIFIZIERTE MRNA ZUSAMMENSETZUNGEN

Verfahren zum Herstellen eines Polypeptids von Interesse in einer Säugerzelle oder einem Säugergewebe, wobei das Verfahren ein Inkontaktbringen der Säugerzelle oder des Säugergewebes mit einer Formulierung umfasst, die eine modifizierte mRNA umfasst, die für das Polypeptid von Interesse codiert, wobei die Formulierung aus der Gruppe bestehend aus Nanopartikeln, Poly(milchsäure-co-glykolsäure)(PLGA)-Mikrosphären, Lipidoid, Lipoplex, Liposom, Polymeren, Kohlenhydraten (einschließlich einfacher Zucker), kationischen Lipiden, Fibringel, Fibrinhydrogel, Fibrinkleber, Fibrindichtmittel, Fibrinogen, Thrombin, schnell eliminierten Lipidnanopartikeln (reLNPs) und Kombinationen davon ausgewählt ist.

Wirkstoffdepotsystem sowie Kit zur in situ Polymerisation des Wirkstoffdepotsystems

Ein Wirkstoffdepotsystem für subkutane, subkonjunktivale und intramuskuläre Anwendungen, umfassend Mikropartikel eines Vinylester-basierten Elektrolyt-Hydrogels, einen Wirkstoff, welcher an die Mikropartikel nicht-kovalent gebunden ist und eine biodegradierbare Polyharnstoffmatrix, welche die Mikropartikel einbettet.Sowie ein entsprechendes Kit zur in situ Polymerisation des Wirkstoffdepotsystems, umfassend die Komponenten:a) Mikropartikel eines Vinylester-basierten Elektrolyt-Hydrogels mit nicht-kovalent gebundenem Wirkstoff; undb) ein Oligoester mit endständigen Isocyanatgruppen zur Bildung einer biodegradierbaren Polyharnstoffmatrix, welche die Mikropartikel einbettet.

VERFAHREN ZUR HERSTELLUNG VON MIKROPARTIKELN MIT EINEM AUSGEWÄHLTEN POLYMERMOLEKULARGEWICHT

Herstellung von Microspheren

POLYHYDROXYALKANOATZUSAMMENSETZUNGEN MIT KONTROLLIERTEN ABBAUGESCHWINDIGKEITEN

MISSBRAUCHSICHERE TRANSDERMALE ABGABEVORRICHTUNG FÜR OPIOIDE, ENTHALTEND OPIOIDANTAGONIST IN FORM VON MIKROKÜGELCHEN

Preparation method of biodegradable micro-particles containing drugs

Intraventricular drug delivery system for improving outcome after a brain injury affecting cerebral blood flow

Process for removing organic phase solvent from plga microspheres containing a lipophilic drug

Pharmaceutical formulations comprising microcapsules

MICRO-ENCAPSULATION OF MEDICAMENTS

LHRH analogues

The process is aimed at providing a composition designed for the sustained and controlled release of medicamentous peptide substances, obtained in the form of microspheres of a biodegradable polymeric material incorporating said medicamentous substance. It consists in converting first a water-soluble peptide or peptide salt into a water-insoluble peptide, respectively peptide salt. The following steps include preparing an organic-aqueous emulsion and then extracting the organic solvent in an excess of aqueous medium.

PHARMACEUTICAL DEPOT FORMS CONTAINING BROMOCRIPTINE

Pharmaceutical composition

Ophthalmic delivery device

Process for preparing microparticles

A process for preparing microparticles comprising a biologically active material and a polymer and having a mean particle size expressed as the volume mean diameter (VMD) of from 10 to 500 m, wherein the biologically active material is substantially insoluble in the polymer, which process comprises: a. contacting a mixture of the biologically active material or a precursor thereof, the polymer or a precursor thereof and a processing aid with a supercritical fluid which is capable of swelling the polymer under temperature and pressure conditions necessary to maintain the fluid in a supercritical state; b. allowing the supercritical fluid to penetrate and liquefy the polymer, whilst maintaining the temperature and pressure conditions so that the fluid is maintained in a supercritical state; c. releasing the pressure to precipitate microparticles comprising the biologically active agent and the polymer.

Process

CO-OLIGO-LACTIDE-GLYCOLIDES

A product of an oligomer derived from glycolic acid and/or lactic acid, the oligomer having a molecular weight of from 500 to 10,000, the free carboxylic acid group of the oligomer being at least partially in the form of an amide with an amino acid or an ester with a sterol may be used as a matrix material for depot forms, containing pharmacologically active agents.

Organic compounds

Ophthalmic delivery device

OLIGOMERIC HYDROXYCARBOXYLIC ACID DERIVATIVES

SUSTAINED RELEASE FORMULATIONS OF WATER SOLUBLE PEPTIDES

Apparatus for a mass production of monodisperse biodegradable polymer-based microspheres and a multi-channel forming device incorporatable therein

Production of microparticles

Apparatus for a mass production of monodisperse biodegradable polymer-based microspheres and a multi-channel forming device incorporatable therein

Apparatus for a mass production of monodisperse biodegradable polymer-based microspheres and a multi-channel forming device incorporatable therein

Microparticle liquid stream

Ophthalmic delivery device and ophthalmic drug compositions

Biodegradable polymer encapsulated serotonin receptor antagonist and method for preparing the same

Biodegradable polymer encapsulated serotonin receptor antagonist and method for preparing the same.

The present invention discloses and claims a method for the production of a pharmaceutical composition comprising the steps of: a) mixing a suitable amount of pharmaceutically active compound of Formula I: or a pharmaceutically acceptable salt thereof with a suitable amount of biodegradable polymer for a sufficient period of time and at suitable temperature and pressure conditions to form a dry mixture of said pharmaceutically active compound and said polymer, wherein said biodegradable polymer has a glass transition temperature (Tg) of less than 60 °C; b) subjecting said dry mixture to a suitable shear mixing using a single screw extruder under suitable temperature and pressure conditions for a sufficient period of time such that said polymer softens to form a fluidized medium and said pharmaceutically active compound is sufficiently dissolved to form a solid solution having substantially homogeneously dispersed mixture of said pharmaceutically active compound and said polymer, and said ...

Tamper-resistant oral opioid agonist formulations.

Disclosed is an oral dosage form comprising (i) an opioid agonists in releasable form and (ii) a sequestered opioid antagonist which is substantially not released when the dosage form is administered intact, such that the ratio of the amount of antagonist released from said dosage form after tampering to the amount of said antagonist released from said intact dosage form is about 4:1 or greater, based on the in-vitro dissolution at 1 hour of said dosage form in 900ml of Simulated Gastric Fluid using a USP Type II (paddle) apparatus at 75 rpm at 37 degrees C wherein said agonist and antagonist are interdispersed and are not isolated from each other in two distinct layers.

Novel "burst free" sustained release poly-(lactide/glycolide microspheres).

Novel burst-free, sustained release biocompatible and biodegradable microcapsules which can be programmed to release their active core for variable durations ranging from 1-100 days in an aqueous physiological environment. The microcapsules are comprised of a core of polypeptide or other biologically active agent encapsulated in a matrix of poly(lactide/glycolide)copolymer as a blend of uncapped (free carboxyl end group)and end-capped forms ranging in rations from 100/0 to 1/99.

Novel-burst free sustained release poly-(lactide/glycolide) microspheres

Biodegradable polymer encapsulated serotonin receptor antagonist and method for preparing the same

Tamper-resistant oral opioid agonist formulation

Slow release pharmaceutical composition made of microparticles

Slow release pharmaceutical composition made of microparticles

Pharmaceutical dosage form

PHARMACEUTICAL DOSAGE FORM

Sustained release compositions, method of its production and use thereof.

Tamper-resistant oral opioid agonist formulations.

Microsphere of two anti-tubercular drugs and a biodegradable polymer administered by inhalation alone or combined with oral route, and process thereof.

“Carried out of preparation of compositions prolonged release and compositions thus obtained”.

Process for the preparation of particles prepared dry dry prepared particles thus obtained and pharmaceutical compositions containing of such

Biodegradable polymer encapsulated serotonin receptor antagonist and method for preparing the same.

Pharmaceutical dosage form

Novel-burst free sustained release poly-(lactide/glycolide) microspheres

Slow release pharmaceutical composition made of microparticles

Tamper-resistant oral opioid agonist formulation

Pharmaceutical dosage form

Biodegradable polymer encapsulated serotonin receptor antagonist and method for preparing the same

Slow release pharmaceutical composition made of microparticles

Tamper-resistant oral opioid agonist formulation

VERFAHREN ZUR HERSTELLUNG VON ZUSAMMENSETZUNGEN, DIE STOFFE ANHALTEND ABGEBEN UND SO ERHALTENE ZUSAMMENSETZUNGEN

BIOLOGICALLY DEGRADABLE ONE INTRAOKULARE IMPLANTS WITH PROSTAMIDEN

BIOCOMPATIBLE CONNECTIONS FOR PHARMACEUTICAL SYSTEMS TO THE DRUG DELIVERY

IMPROVED FORMULATIONS OF POWDER FOR INHALATION

CHEMICAL IGF I COMPOSITION FOR THE TREATMENT AND PREVENTION OF NEURODEGENERATIVE ILLNESSES

PROCEDURE COMPREHENSIVE AN INDUCED PHASE TRANSITION FOR THE PRODUCTION OF HYDROPHOBE ACTIVE SUBSTANCES ABSTENTIONS MICRO PARTICLES

MICRO PARTICLE FOR THE ADMINISTRATION OF NUCLEIC ACIDS

BIOABSORB-CASH PHARMACEUTICAL COMPOSITION CONTAINING A PLGA COPOLYMER

CARRIER IN PARTIKELFORM FOR THE IMPROVEMENT OF THE ORAL ABSORPTION OF WIKSTOFFEN

Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use

Methods of preventing adhesion between issues are provided that utilizes in situ crosslinked biomaterials. The biomaterial contains at least the crosslinked product of two biocompatible, non-immunogenic components having reactive groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Exemplary uses for the crosslinked compositions include preventing adhesions following surgery or injury, and preventing scar tissue formation.

Methods for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor

Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

Emulsion Method For Preparing Low Residual Solvent Microparticles

The method disclosed herein comprises using a non-polar alkane in the continuous phase of an emulsion process to aid in the removal of dispersed phase solvent from the microparticles. The microparticles can further be subjected to a post-production treatment process, involving a non-polar alkane suspension and a rinse, to further reduce residual dispersed phase solvent levels.

In vivo transfer methods for wound healing

The present invention relates to an in vivo method for specific targeting and transfer of DNA into mammalian repair cells. The transferred DNA may include any DNA encoding a therapeutic protein of interest. The invention is based on the discovery that mammalian repair cells proliferate and migrate into a wound site where they actively take up and express DNA. The invention further relates to pharmaceutical compositions that may be used in the practice of the invention to transfer the DNA of interest. Such compositions include any suitable matrix in combination with the DNA of interest.

Biodegradable immunomodulatory formulations and methods for use thereof

The invention provides new compositions and methods for immunomodulation of individuals. Immunomodulation is accomplished by administration of immunomodulatory polynucleotide/microcarrier (IMP/MC) complexes. The IMP/MC complexes may be covalently or non-covalently bound, and feature a polynucleotide comprising at least one immunostimulatory sequence bound to a biodegradable microcarrier or nanocarrier.

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.

Depot systems comprising glatiramer or pharmacologically acceptable salt thereof

The present invention provides long acting parenteral pharmaceutical compositions comprising a therapeutically effective amount of glatiramer. In particular, the present invention provides a long acting pharmaceutical composition comprising a therapeutically effective amount of glatiramer acetate in depot form suitable for administering at a medically acceptable location in a subject in need thereof. The depot form is suitable for subcutaneous or intramuscular implantation or injection.

Pharmaceutical Dosage Forms for the Release of Active Compounds

Pharmaceutical form containing at least an active compound and a polymeric matrix, wherein said polymeric matrix comprises at least one polymer of cationic nature and at least one biodegradable polymer, process for the preparation thereof, pharmaceutical formulations comprising said pharmaceutical form, and their uses. The pharmaceutical form provides enhanced absorption of active compounds across the mucosa.

Drug Delivery Systems and Use Thereof

The invention provides a microsphere formulation for the sustained delivery of an aptamer, for example, an anti-Vascular Endothelial Growth Factor aptamer, to a preselected locus in a mammal, such as the eye. In addition, the invention provides methods for making such formulations, and methods of using such formulations to deliver an aptamer to a preselected locus in a mammal. In particular, the invention provides a method for delivering the aptamer to an eye for the treatment of an ocular disorder, for example, age-related macular degeneration.

Drug delivery from rapid gelling polymer composition

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Ophthalmic Depot Formulations for Periocular or Suconjunctival Administration

The present invention relates to ophthalmic depot formulations comprising an active agent, e.g. embedded in a pharmacologically acceptable biocompatible polymer or a lipid encapsulating agent, e.g. for periocular or subconjunctival administration.

Drug Loaded Polymeric Nanoparticles and Methods of Making and Using Same

The present disclosure generally relates to nanoparticles having about 0.2 to about 35 weight percent of a therapeutic agent; and about 10 to about 99 weight percent of biocompatible polymer such as a diblock poly(lactic) acid-poly(ethylene)glycol. Other aspects of the invention include methods of making such nanoparticles.

Corticosteroids for the Treatment of Joint Pain

Corticosteroid microparticle formulations are provided for use for treating pain, including pain caused by inflammatory diseases such as osteoarthritis or rheumatoid arthritis, and for slowing, arresting or reversing structural damage to tissues caused by an inflammatory disease, for example damage to articular and/or peri-articular tissues caused by osteoarthritis or rheumatoid arthritis. Corticosteroid microparticle formulations are administered locally as a sustained release dosage form (with or without an immediate release component) that results in efficacy accompanied by clinically insignificant or no measurable effect on endogenous cortisol production.

Sustained-release composition and process for producing the same

Present invention is to provide a sustained-release composition which contains a physiologically active substance in high content even when gelatin is not included, and suppresses its initial excessive release and, thus, can achieve a stable release rate over about one month. A sustained-release composition containing a lactic acid-glycolic acid polymer having a ratio or weight average molecular weight and number average molecular weight of about 1.90 or lower, or a salt thereof, and a physiologically active substance.

Methods for treating retinopathy with extended therapeutic effect

Methods for treating and preventing retinopathic conditions by administering a glucocorticoid to the vitreous chamber of a patient at risk of, or suffering from, the retinopathy.

Drug-containing implants and methods of use thereof

The present invention provides implants comprising a therapeutic drug and a polymer containing polylactic acid (PLA) and optionally polyglycolic acid (PGA). The present invention also provides methods of maintaining a therapeutic level of a drug in a subject, releasing a therapeutic drug at a substantially linear rate, and treating schizophrenia and other diseases and disorders, utilizing implants of the present invention.

Biodegradable ocular implant

The present invention relates to a biodegradable ocular implant for sustained drug delivery, comprising a first layer comprising a first biodegradable polymer, wherein the first layer contains a drug dispersed or dissolved therein. A multi-layered biodegradable ocular implant is also disclosed.

Particles and contrast agent including the same for optical imaging

A particle includes a copolymer of lactic acid and glycolic acid, and at least one compound selected from silicon naphthalocyanine and derivatives of silicon naphthalocyanine, in which the particle has a particle size of 10 nm or more and less than 1000 nm.

Formulation and delivery of plga microspheres

The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

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.

Nanoparticles based on poly (lactic glycolic) acid for cosmetic applications

On one hand, the present invention relates to cosmetic compositions comprising poly(lactic glycolic)acid (PLGA) nanoparticles for applications to the skin. On the other hand, it also concerns polymeric nanoparticles having on its surface a plurality of cosmetically active agents, each of said agents being associated to said nanoparticle via oleylcysteineamide, delivery systems for topical application based on said particles and cosmetic formulations comprising said particles.

Method for Reducing or Preventing Transplant Rejection in the Eye and Intraocular Implants for Use Therefor

Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

Sustained release drug delivery systems comprising a water soluble therapeutic agent and a release modifier

A biocompatible, sustained release intraocular drug delivery system comprising a protein or polynucleotide therapeutic agent, a polymeric carrier for the therapeutic agent and a long chain fatty alcohol release modifier. The biocompatible, sustained release intraocular drug delivery system can be used to treat an ocular condition.

Ocular implant made by a double extrusion proces

The invention provides biodegradable implants sized for implantation in an ocular region and methods for treating medical conditions of the eye. The implants are formed from a mixture of hydrophilic end and hydrophobic end PLGA, and deliver active agents into an ocular region without a high burst release.

Drug Loaded Polymeric Nanoparticles and Methods of Making and Using Same

The present disclosure generally relates to nanoparticles having about 0.2 to about 35 weight percent of a therapeutic agent; and about 10 to about 99 weight percent of biocompatible polymer such as a diblock poly(lactic) acid-poly(ethylene)glycol. Other aspects of the invention include methods of making such nanoparticles.

Novel sustained release polymer

A polymer and a method for its preparation are provided. The polymer comprises poly(lactide), poly(lactide/glycolide) or poly(lactic acid/glycolic acid) segments bonded by ester linkages to both ends of an alkanediol core unit. The polymer is for use in a controlled release formulation for a medicament, preferably leuprolide acetate. The controlled release formulation is administered to a patient as a subcutaneous depot of a flowable composition comprising the polymer, a biocompatible solvent, and the medicament. Controlled release formulations comprising the polymer release leuprolide for treatment of prostate cancer patients over periods of 3-6 months.

Use of cytokine-releasing, biodegradable particles in hyaluronic acid for the treatment of cartilage defects, in particular of osteoarthrosis

The present invention relates to a composition comprising, or consisting of 2-50 mg/ml hyaluronic acid, 0.1-500 mg/ml of biodegradable particles with an average mean particle diameter of 1 nm-500 μm, 1 pg/ml-10 μg/ml cytokines, where the concentrations specified are based in each case on the total volume (w/v) of the composition and where the cytokines are enclosed in the biodegradable particles, and to their use in the treatment of cartilage defects, for example traumatic cartilage defects or osteoarthrosis.

Method for preparing microparticles with reduced initial burst and microparticles prepared thereby

A method for preparing polymer microparticles with a reduced initial burst, and the polymer microparticles prepared thereby, the method including: contacting polymer microparticles with an alcohol aqueous solution, the polymer microparticles prepared thereby, and use for drug delivery of the polymer microparticles.

Peptide Conjugated Particles

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance). 191-. (canceled)92. A composition comprising surface functionalized biodegradable particles comprising one or more encapsulated antigens or antigenic epitopes thereof , wherein the particles have a negative zeta potential of about −100 mV to about −30 mV , and wherein the antigen is associated with type-1 diabetes (T1D).93. The composition of claim 92 , wherein the particles are poly (lactic acid) (PLA) claim 92 , poly (glycolic acid) (PGA) claim 92 , or poly (lactic co-glycolic acid) (PLGA) particles.94. The composition of claim 92 , wherein the antigens are selected from the group consisting pancreatic beta-cell antigen claim 92 , insulin claim 92 , proinsulin claim 92 , islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) claim 92 , glutamic acid decarboxylase (GAD) claim 92 , zinc transporter 8 isoform a claim 92 , and protein tyrosine phosphatase receptor type N.95. The composition of claim 92 , wherein the antigens or antigenic epitopes are selected from the group consisting of SEQ ID: 1798 claim 92 , SEQ ID: 1987 claim 92 , SEQ ID: 4981 claim 92 , SEQ ID: 1971 claim 92 , SEQ ID: 2065 claim 92 , SEQ ID: 2240 claim 92 , SEQ ID: 2266 claim 92 , SEQ ID: 1839 claim 92 , SEQ ID: 1832 claim 92 , SEQ ID: 1841 claim 92 , SEQ ID: 1871 claim 92 , SEQ ID: 1994 claim 92 , SEQ ID: 2012 claim 92 , SEQ ID: 2070 claim 92 , SEQ ID: 2114 claim 92 , SEQ ID: 2249 claim 92 , SEQ ID: 1925 claim 92 , SEQ ID: 1961 claim 92 , SEQ ID: 2110 claim 92 , SEQ ID: 2421 claim 92 , SEQ ID NO: 2028 claim 92 , and SEQ ID NO: 2074.96. The composition of claim 95 , wherein the negative zeta potential of the particles is achieved by surface ...

TOPICAL FORMULATION OF HYPERBRANCHED POLYGLYCEROL-COATED PARTICLES THEREOF

Core-shell particles have a hydrophobic core and a shell formed of or containing hyperbranched polyglycerol (HPG). The HPG can be covalently bound to the one or more materials that form the core or coated thereon. The HPG coating can be modified to adjust the properties of the particles. For example, unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption. Alternatively, the hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups on tissue or otherwise interact with tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins. Such functional groups include, but not limited to, aldehydes, amines, and O-substituted oximes. Topical formulation for application to the skin contain these HPG coated nanoparticles. In some embodiments, the particles include therapeutic, diagnostic, nutraceutical, and/or prophylactic agents such as those used as sunblock compositions. 114-. (canceled)15. A method of adhering particles to a tissue , the method comprising administering particles a comprising:a hydrophobic polymer core and a shell comprising hyperbranched polyglycerol covalently bound to the hydrophobic polymer of the hydrophobic polymer core;wherein the hyperbranched polyglycerol is functionalized with one or more reactive functional groups, or functional groups having tissue targeting moieties bound thereto, or a combination thereof, whereinthe one or more reactive functional groups and the functional groups having tissue targeting moieties bound thereto adhere to tissue, cells, or proteins; andone or more agents selected from agents protecting the skin from ultraviolet light, therapeutic agents, diagnostic agents, prophylactic agents, and combinations thereof;wherein the one or more agents are encapsulated within the particles, associated with the surface of the particles, or a combination thereof.16. The method of ...

Polymer particles for neutrophil injury

Provided herein are methods of treatment, compositions, systems and kits using polymer particles as restraints of neutrophil function. Such methods include, but are not limited to, methods of preventing, treating, and/or ameliorating inflammatory diseases, infections, autoimmune diseases, malignant diseases, and other diseases or conditions in which neutrophils may be implicated. In some embodiments, polymer particles are useful for diagnosing neutrophil related diseases or conditions.

SINGLE-INJECTION METHODS AND FORMULATIONS TO INDUCE AND CONTROL MULTIPLE OVARIAN FOLLICLES IN BOVINE, CAPRINE, OVINE, CAMELID AND OTHER FEMALE ANIMALS

Methods and formulations for a simplified, single-injection method to induce and control the synchronous growth (superstimulation), and ovulation (superovulation) of multiple ovarian follicles in bovine, ovine, caprine, camelid and other female animals enabling the subsequent collection of (a) multiple oocytes when conducting in-vitro fertilization, or (b) multiple embryos when conducting multiple ovulation embryo transfer. 1. A method of inducing superovulation in bovine , ovine , camelid and other female animals , the method comprising the steps of:administering a protein microsphere matrix having a diameter ranging from 50-70 microns to a bovine animal, the protein microsphere matrix including a controlled release agent,wherein the step of administering the protein microsphere matrix to the bovine animal is performed via a single administration, andwherein the protein microsphere matrix induces dominant follicle removal, superovulation and timed ovulation of matured follicle cohort in the bovine animal.2. The method of claim 1 , wherein the protein microsphere matrix comprises at least one polymer.3. The method of claim 1 , wherein the protein microsphere matrix comprises poly(lactic acid) (PLA) or poly(lactide-co-glycolide) (PGLA).4. The method of claim 1 , wherein the protein microsphere matrix comprises an organic polymer.5. The method of claim 1 , wherein superovulation in the bovine animal involves stimulating at least two primordial follicles in the bovine animal to mature simultaneously.6. The method of claim 1 , wherein the controlled release agent includes a single dose of follicle stimulating hormone (FSH) and zero to two doses of luteinizing hormone (LH).7. The method of claim 6 , wherein the controlled release agent causes regression of the dominant follicle in the bovine animal via LH.8. The method of claim 7 , wherein the regression of the dominant follicle begins immediately post administration of the controlled release agent.9. The method of claim ...

Compositions, methods and devices for forming implants from injected liquids

A method of forming an implant in the tissue can include: providing an injectable composition having a neat liquid carrier, wherein the neat liquid carrier is substantially liquid at room temperature and/or about body temperature; and injecting the neat liquid solution into the tissue at the rate of 10-12000 injections per minute and/or at an amount of 1.0E-02 ml to 1.0E-16 ml per needle per injection. The neat liquid carrier can be polymeric or non-polymeric. The neat liquid carrier can be biodegradable. The neat liquid carrier can include a viscosity-modifying agent. The injecting can form an implant with area greater than or equal to 5 mm 2 . The neat liquid carrier can be injected at a depth of 10 microns to 5 mm. The neat liquid solution can include a drug or other agent.

Aggregating microparticles for medical therapy

The present invention is a surface treated drug-loaded solid (e.g., non-porous) microparticle that aggregates in vivo to form a consolidated larger particle for medical therapy. In one embodiment, the particles are used for ocular therapy. Processes for producing the surface treated microparticle and injectable formulations which include the surface treated microparticle are also provided. When used in the eye, long-term consistent intraocular delivery can be achieved without disrupting vision and minimizing undesirable inflammatory responses.

HYPERBRANCHED POLYGLYCEROL-COATED PARTICLES AND METHODS OF MAKING AND USING THEREOF

Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins. 1. Particles comprising(a) a core comprising one or more hydrophobic materials; and(b) a shell comprising hyperbranched polyglycerol modified to be either bioadhesive or non-bioadhesive through modification of groups on the hyperbranched polyglycerol.2. The particles of claim 1 , wherein the one or more hydrophobic materials is a polymer.3. The particle of claim 2 , wherein the polymer is biodegradable.4. The particles of claim 3 , wherein the biodegradable polymer is an aliphatic polyester.5. The particles of claim 4 , wherein the aliphatic polyester is selected from the group consisting of poly(lactic acid) claim 4 , poly(glycolic acid) claim 4 , and copolymers thereof.6. The particles of claim 5 , wherein the aliphatic polyester is polylactic acid.7. The particles of claim 1 , wherein the hyperbranched polyglycerol is covalently bound to the one or more hydrophobic materials.8. The particles of claim 1 , wherein the hyperbranched polyglycerol is functionalized with one or more reactive functional groups that adhere to tissue claim 1 , cells claim 1 , and/or proteins.9. The particles of claim 8 , wherein the one or more reactive functional groups are selected from the group consisting of aldehydes claim 8 , amines claim 8 , O-substituted oximes claim 8 , and combinations thereof.10. ...

Peptide Conjugated Particles

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance). 124-. (canceled)25. A composition comprising particles having a negative surface charge and comprising one or more antigens or allergens conjugated to the surface of the particles or encapsulated within the particle , wherein the particles comprise polylactide-co-glycolide (PLGA) and a polyamino acid having a carboxyl group on the side chain , wherein the particles have a negative zeta potential ranging from about −100 mV to about −30 mV.26. The composition of claim 25 , wherein the polyamino acid having a carboxyl group on the side chain is poly(aspartic acid) or poly(glutamic acid).27. The composition of claim 26 , wherein the polyamino acid having a carboxyl group on the side chain is poly(gamma-glutamic acid) claim 26 , poly(L-glutamic acid) claim 26 , poly(D-glutamic acid) claim 26 , or poly(D claim 26 ,L-glutamic acid).28. The composition of claim 25 , wherein the particles are microparticles or nanoparticles.29. The composition of claim 25 , wherein the particles have a zeta potential ranging from about −80 mV to −30 mV claim 25 , or about −75 mV to −30 mV claim 25 , or about −50 mV to −30 mV claim 25 , or about −100 mV to −50 mV claim 25 , or about −75 mV to −50 mV claim 25 , or about −75 mV to −25 mV.30. The composition of claim 25 , wherein the particles have a zeta potential ranging from about −80 mV to −30 mV31. The composition of claim 25 , wherein the PLGA has a molecular weight of 1 claim 25 ,000 Da to 100 claim 25 ,000 Da.32. The composition of claim 31 , wherein the PLGA has a molecular weight of 12 claim 31 ,000 Da to 98 claim 31 ,000 Da.33. The composition of claim 32 , wherein the PLGA has a molecular weight of 12 claim 32 , ...

Pharmaceutical Dosage Form

This invention relates to pharmaceutical dosage forms, particularly to pH dependent pharmaceutical dosage forms with enhanced and/or prolonged distribution of a pharmaceutical compound at a target site. More specifically, this invention relates to a controlled release intravaginal pharmaceutical dosage form and, more particularly, to a pharmaceutical dosage form which comprises microspheres encapsulated and/or embedded within a bioerodible polymeric matrix, together the microspheres and the matrix are formed into a caplet and/or tablet. 1. A pharmaceutical dosage form for releasing , at a target site in the vagina of a human , in a controlled and rate modulated manner , a pharmaceutical compound , said pharmaceutical dosage form comprising:at least one microsphere, which microsphere comprises a pectin (PEC) framework providing rigidity to the microsphere, porcine gastric mucin (MUC) substantially encapsulated and/or embedded in the pectin (PEC) framework and polyethylene glycol (PEG), such that in use, the pharmaceutical dosage form is inserted into the vagina and the polyethylene glycol (PEG) provides a neutral charge facilitating passage of the microspheres across vaginal mucus lining the target site, the target site located on the vaginal wall, and the pectin (PEC) and porcine gastric mucin (MUC) modulate release of the pharmaceutical compound at the target site in a pH dependent manner, wherein an increase in pH facilitates an increase in the release rate of the pharmaceutical compound from the microsphere and wherein a decrease in pH facilitates a decrease in the release rate of the pharmaceutical compound from the microsphere.2. (canceled)3. The pharmaceutical dosage form according to claim 1 , wherein the polyethylene glycol (PEG) is in the form of a hydrophilic coating around the microsphere to form a PEC-MUC-PEG microsphere.4. The pharmaceutical dosage form according to claim 1 , wherein the polyethylene glycol (PEG) is blended with the microsphere to form ...

SLOW RELEASE OXYSTEROLS AND METHODS OF USE

Provided is a slow release composition to promote bone growth, the slow release composition comprising: an oxysterol encapsulated in a biodegradable polymer to control the release of the oxysterol. Methods of making and use are further provided. 1. A slow release composition to promote bone growth , the slow release composition comprising: an oxysterol encapsulated in a biodegradable polymer to control the release of the oxysterol.2. A slow release composition according to claim 1 , wherein the oxysterol comprises (3S claim 1 ,5S claim 1 ,6S claim 1 ,8R claim 1 ,9S claim 1 ,10R claim 1 , 13S claim 1 , 14S claim 1 ,17S) 17-((S)-2-hydroxyoctan-2-yl)-10 claim 1 , 13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3 claim 1 ,6-diol (Oxy133) claim 1 , Oxy153 or hydrates claim 1 , solvates claim 1 , amorphous forms claim 1 , or pharmaceutically acceptable salts thereof.3. A slow release composition according to claim 1 , wherein the biodegradable polymer is in the form of microspheres.4. A slow release composition according to claim 1 , wherein the oxysterol is in an amount of about 0.1 wt % to about 50 wt % of the composition.5. A slow release composition according to claim 3 , wherein the microspheres release the oxysterol over a period of about 1 to about 30 days.6. A slow release composition according to claim 3 , wherein (i) the microspheres are from about 1 to about 750 μm in size; (ii) the microspheres are porous and comprise pores having a size from about 1 μm to about 100 μm; and (iii) the oxysterol is administered at a dose from 1.0 g/day to about 15.0 g/day.7. A slow release composition according to claim 1 , wherein the biodegradable polymer comprises at least one poly(lactide-co-glycolide) (PLGA) claim 1 , polylactide (PLA) claim 1 , polyglycolide (PGA) claim 1 , D-lactide claim 1 , D claim 1 ,L-lactide claim 1 , L-lactide claim 1 , D claim 1 ,L-lactide-co-ε-caprolactone claim 1 , L-lactide-co-ε-caprolactone claim 1 , D claim 1 ,L-lactide-co-glycolide-co ...

BUPRENORPHINE NANOPARTICLE COMPOSITION AND METHODS THEREOF

Stable nanoparticle compositions comprising buprenorphine and at least one biodegradable polymer. The disclosure also provides methods of controlling pain in an animal and methods of treating addiction in a human utilizing the stable nanoparticle compositions, as well as pharmaceutical formulations comprising the stable nanoparticle compositions. The stable nanoparticle compositions are capable of releasing buprenorphine over several days, weeks, or months following administration. The stable nanoparticle compositions of buprenorphine utilize biodegradable polymers capable of degrading into non-toxic components in the body of an animal and may be excreted in the urine of the animal following their metabolism in the body. The stable nanoparticle compositions can advantageously provide sustained release of buprenorphine in the body after a single administration without the need for surgical removal of implanted matrices subsequent to depletion of the drug. 1. A stable nanoparticle composition comprising buprenorphine and at least one biodegradable polymer.2. The stable nanoparticle composition of claim 1 , wherein the biodegradable polymer is selected from the group consisting of polycaprolactone (PCL) claim 1 , polyglycolic acid (PGA) claim 1 , poly(DL)-lactide (PLA) claim 1 , poly(DL)-lactide-co-glycolide (PLGA) claim 1 , or mixtures thereof.3. The stable nanoparticle composition of claim 1 , wherein the biodegradable polymer is PLA.4. The stable nanoparticle composition of claim 1 , wherein the biodegradable polymer is PLGA.5. The stable nanoparticle composition of claim 1 , wherein the stable nanoparticle composition has a release profile of buprenorphine of at least 7 days.6. The stable nanoparticle composition of claim 1 , wherein the stable nanoparticle composition has a release profile of buprenorphine of at least 14 days.7. The stable nanoparticle composition of claim 1 , wherein the release profile of the stable nanoparticle composition is a linear release ...

COMPOSITIONS FOR STABILIZING AND DELIVERING PROTEINS

Compositions for stabilizing and delivering proteins and/or other bioactive agents are disclosed. The bioactive agents are embedded or encapsulated in a crystalline matrix. Typically the bioactive agents are in the form of micro- or nanoparticles. The crystalline matrix confers enhanced stability to the agents embedded therein relative to other microparticulate or nanoparticulate bioactive agents. The carriers are especially useful for stabilizing bioactive macromolecules, such as proteins. 123.-. (canceled)24. A method of making a composition comprising a semi-crystalline matrix comprising (i) microparticles , nanoparticles , or a combination thereof , comprising a protein or peptide and at least one biocompatible polymer , wherein the microparticles , nanoparticles , or a combination thereof is entrapped in the matrix , and (ii) at least one semi-crystalline water soluble polymer , wherein the total amount of the semi-crystalline water soluble polymer in the matrix is at least 65% by weight of the total mass of the matrix , wherein the matrix is characterized by a melting point of at least 40° C. ,the method comprising:(a) dissolving the semi-crystalline water soluble polymer in an effective amount of a solvent,(b) dissolving or dispersing microparticles, nanoparticles, or a combination thereof, comprising the protein or peptide and at least one biocompatible polymer, in the effective amount of the solvent of step (a), wherein the semi-crystalline water soluble polymer, the microparticles, nanoparticles, or a combination thereof, and the solvent form a mixture having a continuous phase and wherein the solvent is the continuous phase, and 1) introducing the product of step (b) into an effective amount of a non-solvent,', '2) spray drying the product of step (b),', '3) film casting the product of step (b),', '4) pan coating the product of step (b) in a fluidized bed reactor, or', '5) lyophilizing the product of step (b)., '(c) performing at least one of the ...

MICROPARTICLE FORMULATIONS OF ADENOSINE RECEPTOR ANTAGONISTS FOR TREATING CANCER

The invention provides compositions comprising microparticles wherein the microparticles comprise at least one adenosine 2a receptor antagonist (A2ARA), at least one pharmaceutically acceptable polymer and at least one pharmaceutically acceptable negatively charged agent wherein the microparticles optionally have a highly negative zeta potential of less than about −40 mV. The invention also provides pharmaceutical compositions of the microparticles of the invention and methods of using the compositions of the invention to enhance an immune response in a patient in need thereof and as anti-cancer immunotherapy. 1. A composition comprising microparticles wherein the microparticles comprise at least one adenosine 2a receptor antagonist (A2ARA) , at least one pharmaceutically acceptable polymer and optionally at least one pharmaceutically acceptable negatively charged agent wherein the microparticles have a negatively charged surface.2. The composition of claim 1 , wherein the at least one pharmaceutically acceptable polymer is PLGA.3. The composition of sing at least one pharmaceutically acceptable negatively charged agent.4. A method of treating cancer in a subject in need thereof comprising administering an effective amount of the microparticle composition of .5. A method of enhancing an immune response in a patient in need thereof claim 1 , said method comprising administering a therapeutically effective amount of an A2ARA microparticle composition of to a patient.6. The method of claim 4 , wherein the patient is in need of immunotherapy for the treatment of cancer.7. The method of claim 1 , wherein the zeta potential of the microparticles is about −25 mV or lower.8. The method of claim 1 , wherein the zeta potential of the microparticles is about −35 mV or lower.9. The method of claim 4 , further comprising administering a checkpoint inhibitor claim 4 , chemotherapy claim 4 , radiation claim 4 , or any combination thereof10. A method of treating a cancerous tumor ...

WOUND HEALING

The invention relates to methods and compositions for improving wound healing and in particular for preventing scar formation and thus loss of function that can occur in injured tissues during the natural wound healing process. Particularly, although by no means exclusively, the invention relates to the healing of chronic wounds such as diabetic ulcers. 1. A therapeutic composition comprising isolated or purified choroid plexus (CP) secreted proteins , wherein the CP secreted proteins are isolated or purified from CP conditioned media.2. The therapeutic composition as claimed in claim 1 , wherein the CP secreted proteins comprise a mixture of at least 2 of the following factors VEGF claim 1 , CTGF claim 1 , PDGF claim 1 , BMP-7 claim 1 , FGF-2 claim 1 , TGFβ claim 1 , TGF-α claim 1 , IL-6 claim 1 , IL-8/CXC chemokines claim 1 , IGF-1 claim 1 , Cystatin claim 1 , α-2microglobulin claim 1 , Pleiotrophic factor β claim 1 , NGF claim 1 , NT claim 1 , transthyretin claim 1 , retinoic acid claim 1 , PTHLH claim 1 , haptocorrin claim 1 , tropomodulin 3 claim 1 , PEDF claim 1 , β-2-microglobulin claim 1 , somatostatin claim 1 , fibronectin claim 1 , laminin β1 and secreted extracellular matrix factors.3. The therapeutic composition as claimed in further comprising one or more immunostimulatory compounds selected from the group consisting of glucocorticosteroids claim 1 , non-steroidal anti-inflammatory drugs (NSAIDS) claim 1 , PDGF claim 1 , EGF claim 1 , IGF and TNF-α antagonists.4. The therapeutic composition as claimed in claim 1 , formulated for systemic or local administration.5. A therapeutic composition as claimed in claim 4 , formulated for oral claim 4 , intravenous claim 4 , cutaneous claim 4 , intradermal claim 4 , topical claim 4 , nasal claim 4 , intramuscular or intraperitoneal administration.6. The cosmetic composition comprising isolated or purified CP secreted proteins as claimed in .7. The cosmetic composition as claimed in claim 6 , formulated for topical ...

SUSTAINED-RELEASE INJECTION COMPRISING DESLORELIN, AND PREPARATION METHOD THEREFOR

The present disclosure relates to a sustained-release injection formulation comprising biodegradable polymer microspheres containing deslorelin as an active ingredient, and a preparation method therefor. The sustained-release microsphere injection containing deslorelin, according to the present disclosure, has good administrability and enables, with a single administration, a deslorelin drug to be maintained at an effective concentration for 6 months without rapid temporary release into the blood of an animal. 1. A sustained-release microsphere containing deslorelin , comprising 5 to 25% by weight of deslorelin based on the total weight of the microsphere , and two or more polymers selected from the group consisting of poly(lactide-co-glycolide) and polylactide polymers.2. The sustained-release microsphere containing deslorelin according to claim 1 , wherein two or more polymers selected from the group consisting of poly(lactide-co-glycolide) and polylactide polymers of the sustained-release microsphere containing deslorelin are contained in one type of microsphere or each independently contained in two or more types of microspheres.3. The sustained-release microsphere containing deslorelin according to claim 1 , wherein when the sustained-release microsphere containing deslorelin is administered to an animal via a subcutaneous or intramuscular route claim 1 , more than 85% of deslorelin in the microsphere is released for 6 months.4. The sustained-release microsphere containing deslorelin according to claim 1 , wherein an intrinsic viscosity of the poly(lactide-co-glycolide) or polylactide is 0.16 to 1.2 dL/g.5. The sustained-release microsphere containing deslorelin according to claim 1 , wherein an average particle size of the microsphere is 10 μm to 100 μm.6. The sustained-release microsphere containing deslorelin according to claim 1 , wherein a span value of the microsphere is 1.2 or less.7. The sustained-release microsphere containing deslorelin according to ...

ORGANIC COMPOUNDS

A pharmaceutical composition comprises octreotide acetate microparticles of linear poly (lactide-co-glycolide) polymer wherein the polymer contains less than 1% silicone oil or heptane. 1. A process for the production of octreotide acetate microparticles , comprising the steps of:a) forming a solution or dispersion by combining a first mixture which comprises octreotide acetate dissolved in a polar organic solvent that is miscible with methylene dichloride, with a second mixture which comprises a linear poly (lactide-co-glycolide) free from silicone oil or heptane dissolved in methylene chloride;b) combining said solution or dispersion with an effective amount of an aqueous process medium to form an emulsion that contains said process medium and microdroplets which are free from silicone oil or heptane comprising said octreotide acetate, said methylene dichloride and said linear poly (lactide-co-glycolide); andc) forming said microparticles by combining said emulsion with an effective amount of an extraction medium.2. A process of wherein said polar organic solvent that is miscible with methylene dichloride is methanol.3. A process of wherein said second mixture contains from about 1% to about 40% of linear poly (lactide-co-glycolide).4. A process of wherein said second mixture contains from 2% to 2.5% of linear poly (lactide-co-glycolide).5. A process of wherein said first mixture contains from about 1% to about 20% of octreotide acetate.6. A process of wherein said first mixture contains from 4% to 10% of octreotide acetate.7. A process of wherein said polar organic solvent that is miscible with methylene dichloride is methanol.8. A process of wherein said aqueous process medium is water saturated with methylene dichloride.9. A process of wherein said aqueous process medium comprises a stabilizing agent.10. A process of wherein said stabilizing agent is selected from the group consisting of polyvinyl pyrolidone claim 9 , carboxymethyl cellulose sodium claim 9 , ...

Hypotensive lipid-containing biodegradable intraocular implants and related implants

Biocompatible intraocular implants include a prostamide component and a biodegradable polymer that is effective in facilitating release of the prostamide component into an eye for an extended period of time. The prostamide component may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The implants may be placed in an eye to treat or reduce a at least one symptom of an ocular condition, such as glaucoma. 148.-. (canceled)49. A method of treating elevated intraocular pressure , the method comprising placing a biodegradable intraocular implant into the anterior chamber of an eye of a patient in need thereof , the implant comprising bimatoprost or a pharmaceutically acceptable salt thereof and a biodegradable polymer matrix that releases an amount of the bimatoprost or a pharmaceutically acceptable salt thereof from the implant effective to reduce at least one symptom of glaucoma , wherein the amount of the bimatoprost or a pharmaceutically acceptable salt thereof is released into the eye for a period of time greater than about one week after the implant is placed into the anterior chamber of the eye.50. The method of claim 49 , wherein the symptom is increased intraocular pressure in the eye.51. The method of claim 49 , wherein the biodegradable polymer matrix comprises a polylactic acid polymer.52. The method of claim 51 , wherein the biodegradable polymer matrix further comprises a polylactic acid polyglycolic acid copolymer.53. The method of claim 52 , wherein the method is effective in maintaining the intraocular pressure in the eye at a reduced level.54. The method of claim 50 , wherein the implant is injected into the anterior chamber of the patient with a needle.55. The method of claim 53 , wherein the implant is injected into the anterior chamber of the patient with a needle. The present invention generally relates to devices and methods to treat an eye of a patient, and more specifically to intraocular ...

FLUTICASONE EXTENDED-RELEASE FORMULATIONS AND METHODS OF USE THEREOF

This disclosure relates to extended-release fluticasone propionate (FP) formulations that include small microparticles and/or nanoparticles and methods of using these extended-release FP formulations for treating pain and/or inflammation in a subject. 1. An extended-release formulation comprising nanoparticles , small microparticles , or a combination thereof , wherein the small microparticles and/or nanoparticles comprise fluticasone propionate (FP) or a commercially available chemical analogue or a pharmaceutically-acceptable salt thereof and a polymer matrix.2. The extended-release formulation of claim 1 , wherein the polymer matrix comprises a poly(lactic-co-glycolic) acid copolymer (PLGA) copolymer matrix.3. The extended-release formulation of claim 1 , wherein the polymer matrix comprises a polylactic acid (PLA) polymer matrix.4. The extended-release formulation of claim 1 , wherein the small microparticles have a mean diameter of between 1 μm to 10 μm.5. The extended-release formulation of claim 1 , wherein the nanoparticles have a mean diameter of between 100 nm to 1000 nm.6. The extended-release formulation of claim 1 , wherein the FP is released for at least greater than 14 days.7. The extended-release formulation of claim 1 , wherein the FP is released for between 14 days and 90 days.8. The extended-release formulation of claim 1 , wherein the FP is released for between 14 days and 180 days.9. The extended-release formulation of claim 1 , wherein the extended release formulation is a controlled- or sustained-release formulation.10. A method of treating pain or inflammation in a patient comprising administering to said patient a therapeutically effective amount of the extended-release formulation of .11. The method of claim 10 , further comprising the step of maintaining a local concentration of the FP at or near the site of administration in the range of about 0.95 ng/ml to about 157.58 ng/ml.12. The method of claim 11 , wherein the local concentration of ...

ENHANCED THERAPEUTIC USAGE OF A PURINE NUCLEOSIDE PHOSPHORYLASE OR NUCELOSIDE HYDROLASE PRODRUG

The use of a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression of one of these enzymes is detailed along with the use of a prodrug cleaved by the purine nucleoside phosphorylase or nucleoside hydrolase for the preparation of a direct injection inhibition of replicating or non-replicating targeted cells. The targeted cells do not normally express the introduced purine nucleoside phosphorylase or nucleoside hydrolase. The enzyme and prodrug are amenable to intermixing and injection as a single dose or as separate injection or administration to the targeted cells. The substance and prodrug efficacy are enhanced through exposure of the targeted cells to X-ray radiation. Administration of a prodrug regardless of administration route to the targeted cells is effective in combination with X-ray radiation therapy to kill or inhibit function of the targeted cells. 1. A process to sequentially destroy large regions of a solid tumor comprising:delivering a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression thereof directly into the solid tumor; andinjecting intratumorally a prodrug cleaved by said purine nucleoside phosphorylase or nucleoside hydrolase directly into the solid tumor to release a purine base cytotoxic into a portion of the solid tumor to sequentially destroy large regions of the solid tumor.2. The process of wherein said purine nucleoside phosphorylase or nucleoside hydrolase is delivered with a viral vector containing a nucleic acid encoding said purine nucleoside phosphorylase.3. The process of wherein said viral vector is an adenoviral vector.4E. coli.. The process of wherein said purine nucleoside phosphorylase is present and is a mutant of5. The process of wherein said purine nucleoside phosphorylase is present and is a tailed mutant.6. The process of further comprising exposing the targeted cells to X-ray radiation.7. The process of wherein said purine nucleoside phosphorylase is ...

OIL-IN-WATER METHOD FOR MAKING POLYMERIC IMPLANTS CONTAINING A HYPOTENSIVE LIPID

Biocompatible microparticles include an ophthalmically active cyclic lipid component and a biodegradable polymer that is effective, when placed into the subconjunctival space, in facilitating release of the cyclic lipid component into the anterior and posterior segments of an eye for an extended period of time. The cyclic lipid component can be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the cyclic lipid component can be encapsulated by the polymeric component. The present microparticles include oil-in-water emulsified microparticles. The subconjunctivally administered microparticles can be used to treat or to reduce at least one symptom of an ocular condition, such as glaucoma or age related macular degeneration.

HYPERCOMPRESSED PHARMACEUTICAL FORMULATIONS

A pharmaceutical dosage form which comprises a lactide, glycolide or lactide-glycolide polymer, a block polymer of polyglycolide, trimethylene carbonate, poly-caprolactone, and polyethylene oxide that is combined with a peptide or protein therapeutic agent in the form of microparticles which are compressed using a pressure of 50,000 to 350,000 psi. 1. A pharmaceutical dosage form which comprises a lactide , glycolide or lactide-glycolide polymer , a block polymer of polyglycolide and trimethylene carbonate or a block polymer of poly-caprolactone and trimethylene carbonate or polyethylene oxide that is combined with a peptide or protein therapeutic agent in the form of microparticles which are compressed using a pressure of 50 ,000 to 350 ,000 psi.2. A pharmaceutical dosage form as defined in where the therapeutic agent is selected from the group consisting of recombinant proteins claim 1 , antibodies for therapy claim 1 , immunotoxins claim 1 , cytokines and ECM proteins.3. A pharmaceutical dosage form as defined in where the polymer is selected from the group consisting of poly(dl-lactide) claim 1 , polyglycolide claim 1 , poly(glycolide-co-lactide) claim 1 , poly(glycolide-co-dl-lactide) or a mixture of any of the foregoing.4. A pharmaceutical dosage form as defined in where the lactide claim 1 , glycolide or lactide-glycolide claim 1 , or poly-caprolactone polymer is acid capped.5. A pharmaceutical dosage form as defined in where the lactide claim 1 , glycolide or lactide-glycolide claim 1 , or poly-caprolactone polymer is ester capped.6. A pharmaceutical dosage form as defined in where the microparticles have been compressed by the application of 50K psi to 170K psi.7. A pharmaceutical dosage form as defined in where the microparticles have been compressed by the application of 100 Kpsi to 300 Kpsi.8. A pharmaceutical dosage form as defined in where the microparticles have been compressed by the application of 60 Kpsi to 170 Kpsi.9. A pharmaceutical dosage form ...

RADIATION STERILIZATION OF HYPERCOMPRESSED POLYMER DOSAGE FORMS

A sterile pharmaceutical dosage form which comprises an ester capped lactide polymer, glycolide polymer or a lactide-glycolide copolymer hypercompressed with an active pharmaceutical ingredient wherein said sterile pharmaceutical dosage form has been sterilized with an electron beam and a method of preparing said sterile pharmaceutical dosage form. 1. A sterile pharmaceutical dosage form which comprises an ester capped lactide polymer , glycolide polymer or a lactide-glycolide copolymer hypercompressed with an active pharmaceutical ingredient wherein said sterile pharmaceutical dosage form has been sterilized with an electron beam.2. A sterile pharmaceutical dosage form as defined in where the active pharmaceutical pharmaceutical ingredient is selected from the group consisting of steroids claim 1 , non-steroidal anti-inflammatory drugs claim 1 , antihistamines claim 1 , antibiotics claim 1 , mydriatics claim 1 , beta-adrenergic antagonists anesthetics claim 1 ,alpha-2-beta adrenergic agonists claim 1 , mast cell stabilizers claim 1 , prostaglandin analogues claim 1 , sympathomimetics claim 1 , parasympathomimetics claim 1 , antiproliferative agents claim 1 , agents to reduce ocular angiogenesis and neovascularization claim 1 , vasoconstrictors claim 1 , anti-neoplastic agents claim 1 , a polynucleotide claim 1 , or a recombinant protein analog an angiogenic inhibitors and combinations thereof.3. A sterile pharmaceutical dosage form as defined in where the polymer is selected from the group consisting of poly(dl-lactide) claim 1 , polyglycolide claim 1 , poly(glycolide-co-lactide) claim 1 , poly(glycolide-co-dl-lactide) claim 1 , a block polymer of polyglycolide claim 1 , trimethylene carbonate and polyethylene oxide claim 1 , or a mixture of any of the foregoing.4. A sterile pharmaceutical dosage form as defined in where the microcapsule has been compressed by the application of 50 Kpsi to 350 Kpsi.5. A sterile pharmaceutical dosage form as defined in where the ...

OCULAR IMPLANT MADE BY A DOUBLE EXTRUSION PROCES

The invention provides biodegradable implants sized for implantation in an ocular region and methods for treating medical conditions of the eye. The implants are formed from a mixture of hydrophilic end and hydrophobic end PLGA, and deliver active agents into an ocular region without a high burst release. 1. A method for treating uveitis or macular edema in the eye of a patient , the method comprising implanting into an ocular region of an eye of a patient in need thereof a bioerodible implant comprising particles of an active agent dispersed within a biodegradable polymer matrix , whereinat least 75% of the particles of the active agent have a diameter of less than 20 μm,the biodegradable polymer comprises poly(lactic-co-glycolic)acid (PLGA) copolymer,the ratio of lactic to glycolic acid monomers in the PLGA copolymer is 50/50 weight percentage, andthe bioerodible implant is prepared by milling the biodegradable polymer and subjecting the active agent and the biodegradable polymer to a double extrusion process.2. The method of claim 1 , wherein at least 99% of the particles of the active agent have a diameter of less than 20 μm.3. The method of claim 1 , wherein the active agent is selected from the group consisting of ace-inhibitors claim 1 , endogenous cytokines claim 1 , agents that influence basement membrane claim 1 , agents that influence the growth of endothelial cells claim 1 , adrenergic agonists or blockers claim 1 , cholinergic agonists or blockers claim 1 , aldose reductase inhibitors claim 1 , analgesics claim 1 , anesthetics claim 1 , antiallergics claim 1 , anti-inflammatory agents claim 1 , steroids claim 1 , antihypertensives claim 1 , pressors claim 1 , antibacterials claim 1 , antivirals claim 1 , antifungals claim 1 , antiprotozoals claim 1 , anti-infective agents claim 1 , antitumor agents claim 1 , antimetabolites and antiangiogenic agents.4. The method of claim 1 , wherein the active agent comprises an anti-inflammatory agent or any ...

THERMORESPONSIVE HYDROGEL CONTAINING POLYMER MICROPARTICLES FOR CONTROLLED DRUG DELIVERY TO THE EAR

Methods for treating an ear condition in a subject, comprising topically administering to the ear of the subject in need thereof a composition comprising: (i) an anti-infective agent-loaded biodegradable polymer microspheres; and (ii) a thermoresponsive hydrogel. 1. A method for treating an ear condition in a subject , comprising topically administering to the ear of the subject in need thereof a composition comprising: (i) anti-infective agent-loaded biodegradable polymer microparticles; and (ii) a thermoresponsive hydrogel.2. The method of claim 1 , wherein the anti-infective agent is selected from an antiviral agent claim 1 , an antibiotic agent claim 1 , an antifungal agent or a combination thereof.3. The method of wherein the anti-infective agent is selected from ofloxacin claim 1 , ciprofloxacin claim 1 , finafloxacin claim 1 , neomycin claim 1 , gentamicin claim 1 , tobramycin claim 1 , tolnaftate claim 1 , nystatin claim 1 , clotrimazole claim 1 , miconazole claim 1 , or a combination thereof.4. The method of claim 1 , wherein the ear condition is otitis media.5. The method of claim 4 , wherein the ear condition is acute otitis media.6. The method of claim 4 , wherein the ear condition is chronic otitis media.7. The method of claim 1 , wherein the ear condition is acute or chronic otitis externa claim 1 , tympanic membrane perforation claim 1 , otomycosis claim 1 , stenosis claim 1 , herpes zoster claim 1 , or myringitis.8. The method of claim 1 , wherein only a single drop of the composition is administered for the duration of treatment.9. The method of claim 1 , wherein the method provides for a sustained linear release rate of the anti-infective agent.10. (canceled)11. The method of claim 1 , wherein the anti-infective agent is released for up to 14 days after administration.12. The method of claim 1 , wherein the hydrogel also includes an anesthetic claim 1 , an anti-inflammatory claim 1 , an antiseptic claim 1 , or a combination thereof.13. The method ...

DRUG LOADED MICROSPHERES FOR POST-OPERATIVE CHRONIC PAIN

A microsphere is disclosed. The microsphere includes at least one biodegradable polymer and at least one local anesthetic, wherein about 75% of the at least one local anesthetic is released by about 72 hours and from about 80% to about 90% of the at least one local anesthetic is released by about 120 hours, thereby relieving chronic pain for at least 28 days. 118.-. (canceled)19. A method for treating chronic pain comprising:implanting at least one microsphere at a treatment site, the microsphere including poly(lactic-co-glycolic acid) and a plurality of active pharmaceutical ingredients;wherein about 75% of the plurality of active pharmaceutical ingredients is released by about 72 hours and from about 80% to about 90% of the plurality of active pharmaceutical ingredients is released by about 120 hours; andrelieving chronic pain for at least 28 days.20. The method for treating chronic pain according to claim 19 , wherein the poly(lactic-co-glycolic acid) includes polylactic acid and glycolic acid at a ratio of about 75:25.21. The method for treating chronic pain according to claim 19 , wherein the poly(lactic-co-glycolic acid) includes polylactic acid and glycolic acid at a ratio of about 65:35.22. The method for treating chronic pain according to claim 19 , wherein the poly(lactic-co-glycolic acid) includes polylactic acid and glycolic acid at a ratio of about 50:50.23. The method for treating chronic pain according to claim 19 , wherein the plurality of active pharmaceutical ingredients is released in a substantially linear manner.24. The method for treating chronic pain according to claim 19 , wherein the at least one microsphere is from about 0.001 micrometers to about 1 claim 19 ,000 micrometers.25. The method for treating chronic pain according to claim 19 , wherein the at least one microsphere is from about 0.01 micrometers to about 500 micrometers.26. The method for treating chronic pain according to claim 19 , wherein at least one active pharmaceutical ...

Novel pharmaceutical formulations containing indirubin and derivatives thereof and methods of making and using the same

The invention described herein provides various indirubin compositions for treating diseases.

Oil-in-Oil emulsified polymeric implants containing a hypotensive lipid and related methods

Biocompatible intraocular implants, such as microparticles, include a prostamide component and a biodegradable polymer that is effective in facilitating release of the prostamide component into an eye for an extended period of time. The prostamide component may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the prostamide component may be encapsulated by the polymeric component. The present implants include oil-in-oil emulsified implants or microparticles. Methods of producing the present implants are also described. The implants may be placed in an eye to treat or reduce a at least one symptom of an ocular condition, such as glaucoma. 1. An intraocular implant comprising therapeutic polymeric microparticles , the microparticles made by the steps of:encapsulating a prostaglandin analog with a polymeric component to form a population of prostaglandin analog encapsulated microparticles by an oil-in-oil emulsion process, wherein the prostaglandin analog-encapsulated microparticles have an effective average particle size of less than about 3000 nanometers.2. The implant of claim 1 , wherein the oil-in-oil emulsion process comprises forming an oil-in-oil emulsion containing the prostaglandin analog and the polymeric component; drying the emulsion to form a dried emulsion product; contacting the dried emulsion product with a solvent to form a solvent-containing composition; and removing the solvent from the solvent-containing composition to form the population of microparticles comprising the prostaglandin analog and the polymeric component.38.-. (canceled)9. The implant of claim 1 , wherein the prostaglandin analog of the microparticles so produced is encapsulated by the polymeric component to preserve therapeutic activity of the prostaglandin analog after a terminal sterilization procedure.10. The implant of claim 1 , wherein the polymeric component comprises a biodegradable polymer or biodegradable copolymer.11. ...

Pharmaceutical composition for parenteral administration, containing donepezil

The present invention relates to a composition for parenteral administration, containing donepezil as an active ingredient, and a preparation method therefor. Donepezil, which has been conventionally used for oral or transdermal administration, is prepared as microparticles comprising a biodegradable and biocompatible polymer and a release controller so as to be provided as a pharmaceutical composition for sustained release parenteral administration, thereby enabling in vivo sustained release continuously for 2-12 weeks or more. Therefore, it is possible to reduce the frequency of administration to a patient and maintain an effective concentration in the blood for a long time.

PHARMACEUTICAL COMPOSITIONS OF GOSERELIN SUSTAINED RELEASE MICROSPHERES

A composition of goserelin sustained release microspheres is provided. The microspheres comprise goserelin, at least one poly(lactide-co-glycolide) and poloxamer or PEG. The sustained release microspheres have comparatively high bioavailability, which promotes the drug taking its full effect and have entrapment efficiency over 90%. 1. A pharmaceutical composition of sustained release goserelin microspheres , comprising (a) goserelin or a salt thereof , (b) poly(lactide-co-glycolide) , and (c) poloxamer or polyethylene glycol (PEG).2. The pharmaceutical composition according to claim 1 , wherein the poloxamer is poloxamer 188 or poloxamer 407.3. The pharmaceutical composition according to claim 1 , wherein the PEG is PEG 2000 claim 1 , PEG 4000 or PEG 6000.4. The pharmaceutical composition according to claim 2 , wherein the content by weight of poloxamer or PEG is within a range from 1% to 10%.5. The pharmaceutical composition according to claim 1 , wherein the content by weight of the goserelin or a salt thereof is within a range from 1% to 10%.6. The pharmaceutical composition according to claim 1 , wherein the molar ratio of lactide to glycolide in the poly(lactide-co-glycolide) is within a range from 90:10 to 10:90.7. The pharmaceutical composition according to claim 1 , wherein the poly(lactide-co-glycolide) has an intrinsic viscosity of 0.10-0.40 dl/g.8. The pharmaceutical composition according to claim 1 , wherein the weight average molecular weight of the poly(lactide-co-glycolide) is 4 claim 1 ,000-45 claim 1 ,000 Dalton.9. The pharmaceutical composition according to claim 1 , wherein the weight content of the poly(lactide-co-glycolide) is 80-98%.10. The pharmaceutical composition according to claim 1 , further comprising (d) acetic acid.11. The pharmaceutical composition according to claim 10 , wherein the weight content of the acetic acid is less than 0.1%.12. The pharmaceutical composition according to claim 11 , wherein the weight content of the acetic ...

Contraceptive and related device

An intravaginal ring for the controlled release of at least one bioactive agent may further contain at least one of a non-bioabsorbable microparticulate ion-exchanging polymer, a fully bioabsorbable polymeric matrix, a biostable hydrophilic elastomeric polymeric matrix, a biostable amphiphilic elastomeric polymeric matrix, a biostable elastomeric polymeric matrix containing an inorganic microparticulate, and a biostable elastomeric porous polymeric matrix, each to aid in the release and/or modulate the release of the bioactive agent.

Adjuvant and antigen particle formulation

A composition as disclosed is comprised of a plurality of particles and a pharmaceutically acceptable carrier. The particles are comprised of (1) an adjuvant; (2) a biocompatible polymer which maybe a co-polymer such as PLGA, and (3) a peptide of a sequence of interest, e.g. a sequence which corresponds to a sequence presented on a surface of a cell infected with a virus. The carrier includes an adjuvant such as a monophosphoryl lipid A (MPL) different from the adjuvant in the particles. The particles may be sized such that they are sufficiently large so as to prevent more than the contents of a single particle from being presented to a single immune system cell.

Pharmaceutical formulation containing opioid agonist, opioid antagonist and gelling agent

Disclosed in certain embodiments is an oral dosage form comprising a therapeutically effective amount of an opioid analgesic, an opioid antagonist and one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid.

Hypotensive lipid-containing biodegradable intraocular implants and related implants

Biocompatible intraocular implants include a prostamide component and a biodegradable polymer that is effective in facilitating release of the prostamide component into an eye for an extended period of time. The prostamide component may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The Implants may be placed in an eye to treat or reduce a at least one symptom of an ocular condition, such as glaucoma. 148.-. (canceled)49. A method of treating glaucoma , the method comprising placing a biodegradable intraocular implant into the anterior chamber of an eye of a patient in need thereof , the implant comprising bimatoprost or a pharmaceutically acceptable salt thereof and a biodegradable polymer matrix that releases an amount of the bimatoprost or a pharmaceutically acceptable salt thereof from the implant effective to reduce at least one symptom of glaucoma , wherein the amount of the bimatoprost or a pharmaceutically acceptable salt thereof is released into the eye for a period of time greater than about one week after the implant is placed into the anterior chamber of the eye.50. The method of claim 49 , wherein the symptom is increased intraocular pressure in the eye.51. The method of claim 49 , wherein the biodegradable polymer matrix comprises a polylactic acid polymer.52. The method of claim 51 , wherein the biodegradable polymer matrix further comprises a polylactic acid polyglycolic acid copolymer.53. The method of claim 52 , wherein the method is effective in maintaining the intraocular pressure in the eye at a reduced level.54. The method of claim 52 , wherein the method is effective in reducing intraocular pressure in the eye.55. The method of claim 50 , wherein the implant is injected into the anterior chamber of the patient with a needle.56. The method of claim 54 , wherein the implant is injected into the anterior chamber of the patient with a needle. The present invention generally relates to devices ...

Adipose tissue-derived stem cells for veterinary use

The invention provides for compositions and methods for making and using adipose-derived stem cells for treating non-human mammals for various medical conditions.

Targeted conjugates encapsulated in particles and formulations thereof

Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

COMPOSITIONS, METHODS AND DEVICES FOR FORMING IMPLANTS FROM INJECTED LIQUIDS

A method of forming a gel implant in tissue can include: providing an injectable composition configured for thermoreversible gel formation at about 37° C.; injecting the injectable composition into the tissue at the rate of about 10-12000 injections per minute; and forming a thermoreversible gel at about 37° C. from the injected injectable composition so as to form the gel implant. The injecting can be at an amount of 1.0E-02 ml to 1.0E-16 ml per needle per injection. The injecting can form an implant with area greater than or equal to 5 mm. The injecting can be at a depth of 10 microns to 5 mm. The injectable composition can include a visualization agent, drug or other agent. 1. A method of forming a gel implant in a tissue , the method comprising:providing an injectable composition configured for thermoreversible gel formation at about 37° C.;injecting the injectable composition into the tissue at the rate of about 10-12000 injections per minute; andforming a thermoreversible gel at about 37° C. from the injected injectable composition so as to form the gel implant.2. The method according to claim 1 , wherein injectable composition comprises a biostable or biodegradable polymer dissolved in an aqueous solution.3. The method according to claim 2 , wherein the biostable or biodegradable polymer shows a thermoreversible property in the aqueous solution and is selected from a group consisting of polymers or copolymers of: pluronics; poly ethyleneoxides; polypropylene oxides; reverse pluronics; polyacrylamides; gelatins; cellulose derivatives; polylactones claim 2 , polylactic acids; polyglycolic acids; polylactice-co-glycolides; polyhydroxy acids; and combinations thereof.4. The method according to claim 2 , wherein a concentration of the biostable or biodegradable polymer in the aqueous solution ranges from about 2% to about 45%.5. The method according to claim 1 , comprising forming a shape of the gel implant to be a straight line claim 1 , crossed line claim 1 , ...

EFFICIENT AQUEOUS ENCAPSULATION AND CONTROLLED RELEASE OF BIOACTIVE AGENTS

A drug delivery system comprises a porous, self-healing biodegradable polymer matrix having a ionic, charged, biopolymer and a pH modifying species disposed within the pores. An ionic macromolecule having the opposite charge binds the biopolymer and forms a nonsoluble polyelectrolyte complex. The molecular weight of the biopolymer, the self healing polymer matrix, the concentration of pore forming agent and the concentration of the pH modifying species are selected for optimal binding and release of the macromolecule. 120.-. (canceled)21. A porous self-healing biodegradable polymer matrix suitable for encapsulation of an active macromolecule , wherein the matrix comprises a biodegradable polymer and has pores and wherein:a biopolymer is disposed within the pores; anda pH modifying species is disposed within the pores;wherein the biopolymer is present at a level of greater than 0.5% and below 10% by weight based on the weight of the biodegradable polymer, and{'sub': 3', '2', '3, 'wherein the pH modifying species is selected from the group consisting of MgCO, Mg(OH), and ZnCO.'}22. The porous self-healing biodegradable polymer matrix of wherein the biodegradable polymer is selected from poly(lactides) claim 21 , poly(glycolides) claim 21 , poly(lactide-co-glycolides) claim 21 , poly(lactic-acid)s claim 21 , poly(glycolic acid)s claim 21 , poly(lactic acid-co-glycolic acid)s claim 21 , poly(hydroxymethyl glycolide-co-lactide) claim 21 , polycaprolactone claim 21 , polycarbonates claim 21 , polyesteramides claim 21 , polyanhydrides claim 21 , poly(amino acids) claim 21 , polyorthoesters claim 21 , polycyanoacrylates claim 21 , poly(p-dioxanone) claim 21 , poly(alkylene oxalate)s claim 21 , biodegradable polyurethanes claim 21 , homopolymers claim 21 , copolymers claim 21 , and blended polymers.23. The porous self-healing biodegradable polymer matrix of wherein the self-healing biodegradable polymer comprises poly(lactic-co-glycolic acid).24. The porous self-healing ...

Dosage Regimen for a Controlled-Release PTH Compound

The present invention relates to a pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH, pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH, wherein said pharmaceutical composition is administered no more frequent than once every 24 hours with a dosage of the controlled-release PTH compound that corresponds to no more than 70% of the molar equivalent dose of PTH 1-84 administered every 24 hours required to maintain serum calcium within normal levels over said 24 hour period in humans. 115-. (canceled)16. A method of treating , controlling , delaying or preventing in a mammalian patient one or more conditions that can be treated , controlled , delayed or prevented with PTH , comprising the step of administering a pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt , hydrate or solvate thereof no more frequent than once every 24 hours with a dosage of the controlled-release PTH compound that corresponds to no more than 70% of the molar equivalent dose of PTH 1-84 administered at the same dosing frequency required to maintain serum calcium within normal levels over a 24 hour period.17. The method of claim 16 , wherein the pharmaceutical composition is administered once every 24 hours.18. The method of claim 16 , wherein the pharmaceutical composition is administered once every week.19. The method of any one of claims 16 , wherein the pharmaceutical composition is administered by injection.20. The method of any one of claims 16 , wherein the ...

SUSTAINED RELEASE TREPOSTINIL-COMPOUND MICROPARTICLE COMPOSITIONS

Provided herein are new compositions comprising novel microparticles that are configured to provide a long acting release of one or more treprostinil compounds when administered to mammalian subjects. The microparticles of the invention are biocompatible and typically injectable through a needle or other injection system. The invention also provides methods of using such compositions, such as in the treatment of pulmonary arterial hypertension. 1. A pharmaceutically acceptable composition comprising an effective amount of biocompatible , injectable , sustained-release treprostinil compound particles , at least about 90% of the particles having a maximum diameter of between about 10 μm and about 200 μm; at least 65% of the particles having a maximum particle diameter within 35% of the average particle diameter of the particles; and the particles releasing an effective amount of treprostinil over a treatment period of at least one day when administered to patients.2. The composition of claim 1 , wherein less than about 10% of particles of the composition have a maximum diameter that is more than 50% greater than the average diameter of particles in the composition.3. The composition of claim 2 , wherein the treprostinil compound is selected from the group comprising a) treprostinil; b) an analog or derivative of treprostinil; c) a prodrug claim 2 , hydrate claim 2 , solvate claim 2 , polymorph claim 2 , or salt of either of a) or b); or d) a mixture of any or all of (a) claim 2 , (b) claim 2 , or (c).4. The composition of claim 3 , wherein the composition does not comprise a carrier.5. The composition of claim 3 , wherein the particles of the composition comprise a carrier claim 3 , and the drug load of the particles is between 1-80%.6. The composition of claim 5 , wherein the carrier is a non-resorbable carrier.7. The composition of claim 5 , wherein the carrier is a resorbable carrier.8. The composition of claim 7 , wherein the particles comprise a resorbable ...

SPHERICAL MICROPARTICLES

The present invention relates to a composition of spherical microparticles composed of a wall material and at least one cavity that comprises a gas and/or a liquid, which have pores on the surface thereof, wherein the spherical microparticles have a mean particle diameter of 10-600 μm and wherein at least 80% of those microparticles, the particle diameter of which does not deviate from the mean particle diameter of the microparticles of the composition by more than 20%, each have on average at least 10 pores, the diameter of which is in the range from 1/5000 to 1/5 of the mean particle diameter, and, furthermore, the diameter of each of these pores is at least 20 nm, wherein the wall material consists of a composition comprising at least one aliphatic-aromatic polyester and at least one additional polymer, wherein the additional polymer is selected from the group consisting of polyhydroxy fatty acids, poly(p-dioxanones), polyanhydrides, polyesteramides, polysaccharides and proteins, to a method for the preparation thereof and use thereof. 116.-. (canceled)17. A composition of spherical microparticles composed of a wall material and at least one cavity that comprises a gas and/or a liquid , which have pores on the surface thereof , wherein the spherical microparticles have a mean particle diameter of 10-600 μm and wherein at least 80% of those microparticles , the particle diameter of which does not deviate from the mean particle diameter of the microparticles of the composition by more than 20% , each have on average at least 10 pores , the diameter of which is in the range from 1/5000 to 1/5 of the mean particle diameter , and , furthermore , the diameter of each of these pores is at least 20 nm , wherein the wall material consists of a composition comprising at least one aliphatic-aromatic polyester and at least one additional polymer , wherein the additional polymer is selected from the group consisting of polyhydroxy fatty acids , poly(p-dioxanones) , ...

SUSTAINED RELEASE MICROSPHERES AND METHOD OF PRODUCING SAME

A method of making a sustained release microsphere formulation, wherein the release rate of a bioactive ingredient is manipulated by controlling the crystallinity of said bioactive ingredient, includes the steps of combining the active ingredient and an encapsulating polymer in at least one solvent, or mixtures thereof, to form a dispersed phase and processing the dispersed phase without filtering, filtering the combined dispersed phase with a hydrophobic or a hydrophilic filter, or filtering the active ingredient and encapsulating polymer individually with a hydrophobic or hydrophilic filter before combining them to form the dispersed phase. The dispersed phase is then combined with a continuous phase to form the microsphere formulation. 1. A method of making a sustained release microsphere formulation , wherein the release rate of a bioactive ingredient is manipulated by controlling the crystallinity of said bioactive ingredient , comprising the steps of:(a) sterilizing an active ingredient to form a sterilized active ingredient;(b) dissolving an encapsulating polymer in a solvent or mixtures thereof;(c) filtering the result of step (b); wherein said filtering is accomplished with a hydrophobic or hydrophilic filter;(d) combining (a) and step (c) to form a dispersed phase,(e) combining the dispersed phase with a continuous phase to form the microsphere formulation.2. The method of claim 1 , wherein the encapsulating polymer is selected from a polylactide or polylactide-co-glycolide.3. The method of claim 1 , wherein the active ingredient is betamethasone.4. The method of claim 1 , wherein the sterilized active ingredient is dissolved in a solvent or solvent mixture before it is combined with the result of step (c) claim 1 , but not sterile filtered.5. The method of claim 1 , wherein the continuous phase comprises polyvinyl alcohol.6. The method of claim 1 , wherein the at least one solvent comprises dichloromethane claim 1 , benzyl alcohol claim 1 , or mixtures ...

Pharmaceutical depot for n-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl)-3-fluoro-4-(pyridin-2-ylmethoxy)benzamide

A pharmaceutical depot comprising (i) N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-fluoro-4-(pyridin-2-ylmethoxy)benzamide, or a pharmaceutically-acceptable salt thereof, as a pharmaceutical agent (PA) and (ii) a polymer which degrades to create an acidic microclimate, wherein the PA is released from the polymer upon polymer degradation.

Angiogenic Factors

The disclosure relates to methods for obtaining angiogenic factors, as well as to methods of treating cardiovascular disease and methods for stimulating angiogenesis. 1. (canceled)2. A method for obtaining an angiogenic factor from one or more cells comprising:i) ;ii) attaching one or more cells which produce an angiogenic factor to a structure obtained by thermally induced phase separation;iii) culturing the one or more attached cells in appropriate conditions for the cells to produce the angiogenic factor; andiv) isolating the angiogenic factor produced by the cells.3. The method of wherein the structure is a coating on a substrate.4. The method of wherein the substrate is a cell culture plate or flask.5. The method of wherein the cells are Human Adipose Derived Stem Cells (ADMSCs).6. The method of wherein the angiogenic factor is Vascular Endothelial Growth Factor (VEGF).7. The method of wherein the isolating is by collection of the liquid in which the cells are cultured.8. The method of wherein the thermally induced phase separation comprises:i) coating the substrate with a polymer and a solvent;ii) quenching the substrate having the polymer and solvent coating in a quenching fluid; andiii) freeze-drying the coating to obtain the substrate coated with the structure.9. The method of wherein the polymer is PLGA.10. The method of wherein the solvent is dimethyl carbonate.11. The method of wherein the quenching fluid is liquid nitrogen.122. The method of wherein the method is performed in vitro.13. (canceled)14. A method for obtaining Vascular Endothelial Growth Factor (VEGF) from one or more Adipose Derived Stem Cells (ADMSCs) comprising:i) attaching one or more ADMSCs to a coating on a tissue culture plate or flask formed by thermally induced phase separation;ii) culturing the ADMSCs in appropriate conditions for the cells to produce VEGF; andiii) isolating the VEGF produced by the cells.15. A method of treating cardiovascular disease comprising:administering to a ...

SYNTHETIC INNATE IMMUNE RECEPTOR LIGANDS AND USES THEREOF

An adjuvant formulation includes a monophosphoryl Lipid A (MPLA) analogue, a Pam3CSK4 analogue, or a muramyldipeptide (MDP) analogue, or combinations thereof. The adjuvant may be formulated in soluble form or in a nanoparticle, such as polylactic glycolic acid nanoparticles. A vaccine formulation comprises the adjuvant formulation and an immunogen. Methods of vaccinating an animal include delivering the vaccine formulation to the animal. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. The adjuvant of claim 1 , wherein the peptide comprises one peptide or two peptides separated by a linker.7. The adjuvant of claim 6 , wherein the peptide comprises two peptides separated by a linker comprising an alkylene (CH) claim 6 , where n is an integer 1≤n≤20.8. The adjuvant of claim 7 , wherein 2≤n≤10.9. The adjuvant of claim 6 , wherein the peptide comprises two peptides separated by a linker and a first peptide comprises 4 to 7 amino acids.10. The adjuvant of claim 9 , where the first peptide comprises Ser claim 9 , Lys claim 9 , Asp claim 9 , Ala claim 9 , Gln and Lys claim 9 , or any combination thereof claim 9 , in any sequence including multiple repeats of any single amino acid.11. The adjuvant of claim 9 , wherein the first amino acid of the first peptide is Ser.12. The adjuvant of claim 9 , wherein the last amino acid of the first peptide is Lys.13. The adjuvant of claim 6 , wherein a second peptide comprises a chemotactic peptide.14. The adjuvant of claim 13 , wherein the chemotactic peptide is a tripeptide comprising Phe claim 13 , Leu and formyl Met.17. The adjuvant of claim 16 , wherein X is substituted or unsubstituted alkylene linker comprising between 6 to 20 carbon atoms.18. (canceled)19. (canceled)20. (canceled)21. The adjuvant of wherein R is a tripeptide comprising Ala claim 16 , IsoGln and Ser.23. (canceled)24. (canceled)25. (canceled)26. (canceled)27. (canceled)28. (canceled)29. An adjuvant formulation comprising a combination of at least two ...

PROCESS FOR THE PREPARATION OF DRUG LOADED MICROPARTICLES

Provided is a process for the production of nano- and/or microparticles containing a therapeutically active agent embedded in a polymer matrix or encapsulated by a polymer shell, and nano- and/or microparticles obtainable by the process, said process comprising the steps of: a) providing a solution of a polymer selected from polylactide, polyglycolide, and polyester copolymers comprising copolymerized units of lactic acid and/or glycolic acid in an organic solvent SI having limited water solubility: b) providing a solution or dispersion of a therapeutically active agent in as solvent or mixture of organic solvents S2 comprising at least 50 vol. % benzyl alcohol, c) combining the solution or the solution and suspension provided in step a) and step b) to provide an organic phase which comprises dissolved polymer and dissolved therapeutically active agent in a mixture of the organic solvents S I and S2; d) agitating the organic phase provided in step c) in a vessel and adding an aqueous surfactant solution to the agitated organic phase in a volume ratio of at least 2:1 in terms of the total volume of the aqueous surfactant solution to the total volume of the organic phase as provided in step c), thus causing the formation of a dispersion containing a continuous aqueous phase and a discontinuous organic phase; and e) allowing the spontaneous formation of the nano- and/or microparticles via transfer of organic solvent from the discontinuous organic phase into the continuous aqueous phase directly after the dispersion has been formed. 1. A process for the production of nano- and/or microparticles containing a therapeutically active agent embedded in a polymer matrix or encapsulated by a polymer shell , said process comprising the steps of:a) providing a solution of a polymer selected from polylactide, polyglycolide, and polyester copolymers comprising copolymerized units of lactic acid and/or glycolic acid in an organic solvent S1 having limited water solubility;b) ...

HYPERBRANCHED POLYGLYCEROL-COATED PARTICLES AND METHODS OF MAKING AND USING THEREOF

Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins. 124.-. (canceled)25. Particles comprising a core comprising a hydrophobic polymer covalently bound to hyperbranched polyglycerol forming a shell , wherein the particles comprise:one or more chemotherapeutic agents, andone or more tumor targeting agents.26. The particles of claim 25 , wherein at least one of the one or more chemotherapeutic agents is encapsulated within the particles claim 25 , associated with the surface of the particles claim 25 , or a combination thereof.27. The particles of claim 26 , wherein at least one of the one or more chemotherapeutic agents is encapsulated within the particles.28. The particles of claim 25 , wherein the one or more chemotherapeutic agents are topoisomerase inhibitors.29. The particles of claim 28 , wherein the one or more topoisomerase inhibitors are camptothecins.30. The particles of claim 29 , wherein the camptothecins are selected from the group consisting of camptothecin claim 29 , irinotecan claim 29 , topotecan claim 29 , and a combination thereof.31. The particles of claim 25 , comprising one or more targeting.32. The particles of claim 25 , wherein the hydrophobic polymer is an aliphatic polyester.33. The particles of claim 33 , wherein the aliphatic polyester is selected from the group consisting of poly(lactic acid) claim 33 , poly( ...

Multiparticulate solid dosage form having an elastic texture

The present invention relates to a multiparticulate solid dosage form ( 1 ) which has an elastic texture and which contains a plurality of microcapsules ( 2 ) having a core ( 2 a ) and a shell ( 2 b ) that are embedded in an edible matrix ( 3 ). Microcapsules ( 2 ) contain an active ingredient which may be a pharmaceutical drug and/or a micronutrient. The multiparticulate solid dosage form of the invention is obtainable by a method wherein a mixture comprising water, microcapsules and starch particles is casted. The starch particles swell or dissolve only after casting.

PROSTAMIDE-CONTAINING INTRAOCULAR IMPLANTS AND METHODS OF USE THEREOF

Prostamide-containing intraocular implants that biodegrade in the eye and that are effective for reducing intraocular pressure in an eye for a sustained period. The implants generally contain a prostamide, such as bimatoprost, and at least three distinct biodegradable polymers selected from polylactide and poly(lactide-co-glycolide) polymers and are optimized for placement in and compatibility with the anterior chamber of the eye, particularly the anterior chamber angle. Methods for making and using the implants to reduce ocular hypertension and intraocular pressure in a patient are described. 118.-. (canceled)19. A method for reducing ocular pressure in an eye of a patient , the method comprising:injecting a biodegradable intraocular implant into an eye of a patient in need thereof, the biodegradable intraocular implant comprising a biodegradable polymer matrix, polyethylene glycol 3350, and bimatoprost, wherein the bimatoprost and polyethylene glycol 3350 are associated with the biodegradable polymer matrix; andtreating the eye after injecting of the biodegradable intraocular implant into the eye, wherein the biodegradable intraocular implant swells during the treating, and wherein the biodegradable intraocular implant reaches a maximum swell size by about 2 months and contracts in size after the about 2 months.20. The method of claim 19 , wherein the biodegradable polymer matrix comprises:a) an ester end poly(D,L-lactide) having an inherent viscosity of 0.25-0.35 dl/g,b) an acid end poly(D,L-lactide) having an inherent viscosity of 0.16-0.24 dl/g, andc) an ester end poly(D,L-lactide-co-glycolide) having an inherent viscosity of 0.16-0.24 dl/g and a D,L-lactide to glycolide molar ratio of about 75:25;wherein the bimatoprost comprises 18 to 22% of the biodegradable intraocular implant by weight, the ester end poly(D,L-lactide) comprises 18 to 22% of the biodegradable intraocular implant by weight, the acid end poly(D,L-lactide) comprises 13.5 to 16.5% of the ...

MICROSPHERE SKIN TREATMENT

This application provides a microsphere suitable for tissue engineering that comprises connective tissue growth factor (CTGF). Also provided is a matrix, material or scaffold suitable for tissue engineering that comprises connective tissue growth factor (CTGF) and basic fibroblast growth factor (bFGF). Additionally, methods of treating skin of a human are provided. The methods comprise administering to the skin microspheres comprising a growth factor that increases fibroblast proliferation or collagen, elastin, or glycosaminoglycan synthesis. Further provided are the use of the above microspheres for the treatment of the skin of a human. Additionally, this application proves the use of the above microsphere for the manufacture of a medicament for the treatment of the skin of a human. 1. A method of treating skin of a subject comprising:administering to skin of a subject (i) a first microsphere comprising connective tissue growth factor (CTGF) and basic fibroblast growth factor (bFGF) or (ii) a second microsphere comprising CTGF and a third microsphere comprising bFGF;wherein the CTGF and the bFGF in combination increases fibroblast proliferation; collagen synthesis; elastin synthesis; or glycosaminoglycan synthesis.2. The method of claim 1 , comprising administering the second microsphere comprising CTGF.3. The method of claim 1 , comprising administering the third microsphere comprising bFGF.4. The method of claim 1 , comprising administering the first microsphere comprising CTGF and bFGF.5. The method of claim 1 , wherein administering to skin of a subject comprises:administering the third microsphere comprising basic fibroblast growth factor (bFGF); andadministering the second microsphere comprising connective tissue growth factor (CTGF).6. The method of claim 1 , wherein the microsphere comprises:(i) between about 0.0001 and about 10,000,000 ng CTGF/ml microspheres and between about 0.0001 and about 10,000,000 ng bFGF/ml microspheres;(ii) between about 0.001 and ...

Controlled Release Microparticles

Formulations for controlled, sustained release of biologically active agents for the treatment of ocular disorders have been developed. These formulations are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. The microparticles are characterized by low burst levels and efficient drug loading and sustained release.

NANOPARTICLE FABRICATION METHODS, SYSTEMS, AND MATERIALS

Nano-particles are molded in nano-scale molds fabricated from non-wetting, low surface energy polymeric materials. The nano-particles can include pharmaceutical compositions, taggants, contrast agents, biologic drugs, drug compositions, organic materials, and the like. The molds can be virtually any shape and less than 10 micron in cross-sectional diameter. 1223.-. (canceled)224. A pharmaceutical composition , comprising: a pharmaceutically or therapeutically active agent, wherein said agent is present throughout the particle;', 'wherein each particle of the plurality has a substantially uniform three-dimensional engineered shape having parallel lateral surfaces and parallel top and bottom surfaces in cross-section, wherein;', 'the size of each particle of the plurality is less than about 100 micrometers in a broadest dimension; and', 'further comprising a predetermined negative zeta potential in solution., 'a plurality of particles in a liquid solution wherein each particle of the plurality comprises225. The pharmaceutical composition of claim 224 , further comprising a biocompatible material selected from the group consisting of a poly(ethylene glycol) claim 224 , a poly(lactic acid) claim 224 , a poly(lactic acid-co-glycolic acid) claim 224 , a lactose claim 224 , a phosphatidylcholine claim 224 , a polylactide claim 224 , a polyglycolide claim 224 , a hydroxypropylcellulose claim 224 , a wax claim 224 , a polyester claim 224 , a polyanhydride claim 224 , a polyamide claim 224 , a phosphorous-based polymer claim 224 , a poly(cyanoacrylate) claim 224 , a polyurethane claim 224 , a polyorthoester claim 224 , a polydihydropyran claim 224 , a polyacetal claim 224 , a biodegradable polymer claim 224 , a polypeptide claim 224 , a hydrogel claim 224 , a carbohydrate claim 224 , and combinations thereof.226. The pharmaceutical composition of claim 224 , wherein each of said particles further comprises a diagnostic agent claim 224 , or a linker.227. The pharmaceutical ...

COMPOSITION AND METHODS FOR THE TREATMENT OF PERIPHERAL NERVE INJURY

Provided herein are methods of treating a peripheral nerve injury in a subject. The methods include administering to the subject at or near the site of the peripheral nerve injury an effective amount of a composition comprising an agent that promotes remyelination of the peripheral nerve. Also provided are methods of determining whether a peripheral nerve injury has a capacity for recovery. The methods include selecting a subject with a peripheral nerve injury, administering to the subject a first dose of a composition comprising and agent that promote remyelination and detecting after the first dose one or more characteristics of peripheral nerve recovery, the presence of one or more characteristics of peripheral nerve recovery indicating a peripheral nerve injury has a capacity for recovery and the absence of characteristics of peripheral nerve recovery indicating a peripheral nerve injury without a capacity for recovery. 1. A biocompatible composition comprising 4-aminopyridine (4-AP) or analog thereof , wherein the composition provides sustained release of the 4-AP or analog thereof to at least one portion of the peripheral nervous system of a mammal.2. The composition of claim 1 , wherein the 4-AP or analog thereof is at least partially encapsulated in a polymer or hydrogel.3. The composition of claim 2 , wherein the polymer comprises poly(lactic-co-glycolic acid) (PLGA).4. The composition of claim 1 , wherein the mammal is human.5. The composition of claim 1 , wherein the composition provides a local concentration of 4-AP or analog thereof of at least one ng/kg/day in the at least one portion of the peripheral nervous system of the mammal.6. A method of treating claim 1 , ameliorating claim 1 , or preventing chronic or acute peripheral nerve injury in a mammal in need thereof claim 1 , the method comprising administering to the mammal a therapeutically effective amount of a biocompatible composition comprising 4-aminopyridine (4-AP) or an analog thereof claim ...

IMMUNOGENIC COMPOSITION

A process of producing an immunogenic particle includes mixing an aqueous solvent A wherein an antigen(s) is/are dissolved and a water-immiscible organic solvent B wherein an amphiphilic polymer(s) whose hydrophobic segment(s) is/are poly(hydroxy acid) is/are dissolved, to form a reversed-phase emulsion; and removing the solvent from the reversed-phase emulsion to obtain an antigen-adjuvant microparticle complex, wherein the aqueous solvent A and/or the water-immiscible organic solvent B contains a surfactant. 1. A process of producing an immunogenic particle comprising:mixing an aqueous solvent A wherein an antigen(s) is/are dissolved and a water-immiscible organic solvent B wherein an amphiphilic polymer(s) whose hydrophobic segment(s) is/are poly(hydroxy acid) is/are dissolved, to form a reversed-phase emulsion; andremoving the solvent from said reversed-phase emulsion to obtain an antigen-adjuvant microparticle complex,wherein said aqueous solvent A and/or said water-immiscible organic solvent B contains a surfactant.2. A process of producing an immunogenic particle comprising:mixing an aqueous solvent A wherein an antigen(s) is/are dissolved and a water-immiscible organic solvent B wherein an amphiphilic polymer(s) whose hydrophobic segment(s) is/are poly(hydroxy acid) is/are dissolved, to form a reversed-phase emulsion;removing the solvent from said reversed-phase emulsion to obtain an antigen-adjuvant microparticle complex; andintroducing an antigen-adjuvant microparticle complex dispersion C to a liquid phase D wherein a surface modifier is dissolved, followed by removing the dispersion medium,wherein said aqueous solvent A, said water-immiscible organic solvent B and/or said dispersion C contains a surfactant.3. The process according to claim 1 , wherein said surfactant comprises a fatty acid ester structure.4. The process according to claim 1 , wherein said hydrophilic segment of said amphiphilic polymer is a polysaccharide.5. The process according to ...

THERAPEUTIC POLYMERIC NANOPARTICLES COMPRISING CORTICOSTEROIDS AND METHODS OF MAKING AND USING SAME

The present disclosure generally relates to therapeutic nanoparticles. Exemplary nanoparticles disclosed herein may include about 0.1 to about 50 weight percent of a corticosteroid; and about 50 to about 99 weight percent biocompatible polymer. 1. A therapeutic nanoparticle comprising:about 0.1 to about 50 weight percent of a corticosteroid; and a) a diblock poly(lactic) acid-poly(ethylene)glycol copolymer;', 'b) a diblock poly(lactic)-co-(glycolic) acid-poly(ethylene)glycol copolymer;', 'c) a combination of a) and a poly (lactic) acid homopolymer or poly(lactic)-co-(glycolic) acid;', 'd) a combination of b) and a poly (lactic) acid homopolymer or poly(lactic)-co-(glycolic) acid;', 'e) 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene)glycol copolymer; and', 'f) a combination of e) and a poly (lactic) acid homopolymer or poly(lactic)-co-(glycolic) acid., 'about 50 to about 99 weight percent biocompatible polymer, wherein the biocompatible polymer is selected from the group consisting of'}2. The therapeutic nanoparticle of wherein said corticosteroid is selected from budesonide claim 1 , fluocinonide claim 1 , triamcinolone claim 1 , mometasone claim 1 , amcinonide claim 1 , halcinonide claim 1 , ciclesonide claim 1 , beclomethasone claim 1 , or a pharmaceutically acceptable salt thereof.3. The therapeutic nanoparticle of claim 1 , wherein the diameter of the therapeutic nanoparticle is about 60 to about 230 nm.4. The therapeutic nanoparticle of claim 1 , comprising about 1 to about 9 weight percent of the corticosteroid.5. The therapeutic nanoparticle of claim 1 , wherein said diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprises poly(lactic acid) having a number average molecular weight of about 15 to 60 kDa and poly(ethylene)glycol having a number average molecular weight of about 4 to about 12 kDa.6. The therapeutic nanoparticle of claim 1 , wherein said diblock poly(lactic)-co-glycolic acid-poly(ethylene)glycol copolymer comprises poly( ...

NOVEL CONTROLLED RELEASE COMPOSITION

The present disclosure provides a controlled release composition comprising a plurality of microparticles and a matrix, wherein: the plurality of microparticles comprises a first material; the matrix comprises a second material; and the melting temperature of the first material is higher than the melting temperature of the second material. Also provided are methods of making and using the same. 1. A controlled release implantable pharmaceutical composition comprising a plurality of microparticles distributed or embedded in a matrix , wherein:the plurality of microparticles comprises poly(L-lactide acid) and a first active agent;the matrix comprises poly(lactide-co-glycolide acid);the plurality of microparticles have a diameter ranging from about 120 μm to about 1000 μm.2. The controlled release implantable pharmaceutical composition of claim 1 , wherein the plurality of microparticles further comprises a material selected from the group consisting of:dextran, poly(ethylene glycol oxalate), poly(p-dioxanone-co-ε-caprolactone), poly(ethylcyanoacrylate), poly(butylcyanoacrylate), poly (β-hydroxybutyrate), poly(3-hydroxybutyrate-co-4-hydroxyvalerate), poly(1,3-bis(carboxyphenoxy)propane-co-sebacic acid), cholesterol, cellulose acetate, hydroxypropyl methyl cellulose phthalate, zein and a combination thereof.3. The controlled release implantable pharmaceutical composition of claim 1 , wherein the matrix further comprises a material selected from the group consisting of:poly(ε-caprolacton), poly(1,4-dioxan-2-one), poly(sebacic anhydride), poly(dodecanoic anhydride), poly(ethylene glycol), polyoxyethylene, stearic acid, stearyl alcohol; ethylene glycol palmitostearate, cetyl esters wax, poly(1,3-bis(carboxyphenoxy)propane-co-sebacic acid), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and a combination thereof.4. The controlled release implantable pharmaceutical composition of claim 1 , wherein the first active agent is selected from the group consisting of: local ...

EXENATIDE-CONTAINING COMPOSITION AND PREPARATION METHOD THEREFOR

An exenatide-containing composition is in the form of microspheres, which are prepared by using exenatide acetate and polylactic-co-glycolic acid (PLGA) as raw materials, and the content of acetic acid in the prepared composition is lower than 0.01%. A method for preparing the exenatide-containing microspheres includes selecting a cleaning fluid of a proper external water Phase and a proper amount to clean microspheres, and selecting a proper re-drying temperature to cure the after the microspheres are freeze dried. 1. An exenatide-containing composition , wherein the composition is in a form of microspheres and is prepared with exenatide acetate or a salt or an analogue thereof and a copolymer of lactide and glycolide (PLGA) as raw materials , wherein a content of acetic acid in the exenatide-containing composition is lower than 0.01%.2. The composition according to claim 1 , wherein a content of exenatide is 2-10% by weight.3. The composition according to claim 2 , wherein a content of the copolymer of lactide and glycolide (PLGA) is 90-98% by weight.4. The composition according to claim 3 , wherein a weight average molecular weight of the PLGA is 6 claim 3 ,000-45 claim 3 ,000 Dalton.5. The composition according to claim 3 , wherein a molar ratio of lactide to glycolide in the PLGA is from 90:10 to 10:90.6. The composition according to claim 4 , wherein the PLGA has an intrinsic viscosity of 0.10-0.40 dl/g.7. The composition according to claim 1 , wherein the microspheres are prepared by emulsion-solvent evaporation technique claim 1 , which includes adding the PLGA into an organic solvent to obtain an organic solution claim 1 , then adding exenatide acetate into the prepared organic solution to obtain a primary emulsion claim 1 , then adding the primary emulsion into an outer aqueous phase to form an emulsion claim 1 , then solidifying and volatilizing the emulsion to remove the organic solvent; and then washing the residue claim 1 , followed by freeze-drying ...

OCTREOTIDE DEPOT FORMULATION WITH CONSTANTLY HIGH EXPOSURE LEVELS

The present invention relates to sustained release formulations comprising as active ingredient octreotide or a pharmaceutically-acceptable salt thereof and two different linear polylactide-co-glycolide polymers (PLGAs). 1. A depot formulation in form of microparticles comprising as active ingredient octreotide , or a pharmaceutically acceptable salt thereof , incorporated into a biodegradable polymer matrix consisting of a blend and of two different linear polylactide-co-glycolide polymers (PLGAs) each having a molar lactide:glycolide (L:G) ratio of 75:25 and wherein said two polymers have different viscosities , wherein one of the PLGAs has an ester and the other an acid end group , wherein said polymers have inherent viscosities between 0.1 dl/g and 0.8 dl/g in CHClat 25° C. at a concentration of 0.1% , where the active ingredient which is used to prepare the depot formulation is in the form of an amorphous powder.2. The depot pharmaceutical formulation of claim 1 , wherein the amorphous powder of the active ingredient has a has a particle size of 0.1 microns to 15 microns (99%>0.1 microns claim 1 , 99%<15 microns).3. The depot pharmaceutical formulation of claim 1 , wherein said polymers have inherent viscosities between 0.1 dl/g and 0.5 dl/g in CHCl.4. The depot pharmaceutical formulation according to wherein the active ingredient is octreotide pamoate.5. The depot pharmaceutical formulation composition according to wherein the microparticles have a diameter between 10 μm and 90 μm.6. The depot pharmaceutical formulation according to wherein the microparticles are covered or coated with an anti-agglomerating agent.7. The depot pharmaceutical formulation according to in the form of microparticles comprising octreotide pamoate and blend of 30% linear polymer PLGA 75:25 acid 0.2 dL/g (%) and 70% linear polymer PLGA 75:25 ester 0.4 dL/g (%) claim 1 , with a drug load of 20% claim 1 , with a PLGA concentration of 20% and a Xparticle size of 60 micrometers. The ...

PHARMACEUTICAL COMPOSITIONS OF GOSERELIN SUSTAINED RELEASE MICROSPHERES

A composition of goserelin sustained release microspheres is provided. The microspheres comprise goserelin, at least one poly (lactide-co-glycolide) and poloxamer or PEG. The sustained release microspheres have comparatively high bioavailability, which promotes the drug taking its full effect and have entrapment efficiency over 90%. 1. A pharmaceutical composition of sustained release goserelin microspheres , comprising (a) goserelin or a salt thereof , (b) poly(lactide-co-glycolide) , and (c) poloxamer or polyethylene glycol (PEG).2. The pharmaceutical composition according to claim 1 , wherein the poloxamer is poloxamer 188 or poloxamer 407.3. The pharmaceutical composition according to claim 1 , wherein the PEG is PEG 2000 claim 1 , PEG 4000 or PEG 6000.4. The pharmaceutical composition according to claim 2 , wherein the content by weight of poloxamer or PEG is within a range from 1% to 10%.5. The pharmaceutical composition according to claim 1 , wherein the content by weight of the goserelin or a salt thereof is within a range from 1% to 10%.6. The pharmaceutical composition according to claim 1 , wherein the molar ratio of lactide to glycolide in the poly(lactide-co-glycolide) is within a range from 90:10 to 10:90.7. The pharmaceutical composition according to claim 1 , wherein the poly(lactide-co-glycolide) has an intrinsic viscosity of 0.10-0.40 dl/g.8. The pharmaceutical composition according to claim 1 , wherein the weight average molecular weight of the poly (lactide-co-glycolide) is 4 claim 1 ,000-45 claim 1 ,000 Dalton.9. The pharmaceutical composition according to claim 1 , wherein the weight content of the poly(lactide-co-glycolide) is 80-98%.10. The pharmaceutical composition according to claim 1 , further comprising (d) acetic acid.11. The pharmaceutical composition according to claim 10 , wherein the weight content of the acetic acid is less than 0.1%.12. The pharmaceutical composition according to claim 11 , wherein the weight content of the acetic ...

Microsphere formulations comprising ketamine and methods for making and using the same

Extended-release, injectable microsphere formulations comprising ketamine are provided. Methods for making and using the microsphere formulations are also provided.

PLGA/PEI PARTICLES AND METHODS OF MAKING AND USING THE SAME

Poly(lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) particles and methods directed to the preparation of PLGA/PEI particles are provided. Methods of using PLGA/PEI particles for the proliferation of stem cells and/or delivery of stem cells are also provided. For example, methods of treating a subject having, or at risk of developing, a cardiovascular disorder can include administering a therapeutically effective amount of stem cell-loaded PLGA/PEI particles to the subject. 1. A method of treating a subject having , or at risk of developing , a cardiovascular disorder , comprising:administering to the subject a therapeutically effective amount of stem cell-loaded poly(lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) particles to reduce a pathological effect or symptom associated with the cardiovascular disorder, or to reduce a risk of developing the cardiovascular disorder.2. The method of claim 1 , wherein the stem cells comprise mesenchymal stem cells.3. The method of or claim 1 , wherein the particles are selected from at least one of microparticles claim 1 , microbeads claim 1 , or microspheres.4. The method of any one of - claim 1 , wherein the stem cell-loaded PLGA/PEI particles form scaffolds.5. The method of any one of - claim 1 , wherein the PEI comprises a low molecular weight PEI.6. The method of claim 5 , wherein the PEI comprises PEI.7. The method of claim 6 , wherein the PLGA/PEIparticles are porous.8. The method of any one of - claim 6 , wherein the PLGA/PEI particles are porous.9. The method of any one of - claim 6 , wherein the pathological effect or symptom is selected from at least one of cardiac tissue damage; cardiomyocyte necrosis; contractile dysfunction; cardiac extracellular matrix remodeling; cardiomyocyte loss; apoptosis; necrosis; cardiac fibrosis; angiogenesis; hemodynamic and cardiac geometric deterioration in the heart claim 6 , coronary artery claim 6 , or vascular system; or systolic/diastolic dysfunction.10. The method of ...

ORGANIC COMPOUND

The invention relates to a particular substituted heterocycle fused gamma-carboline, in free, or pharmaceutically acceptable salt, and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HTreceptor, the serotonin transporter (SERT), and/or pathways involving the dopamine Dand Dreceptor signaling system. 3. The composition according to claim 2 , wherein the composition is formulated for sustained or delayed release claim 2 , optionally as an injectable depot.4. The composition according to claim 3 , wherein the composition further comprises a polymeric matrix.5. The composition according to claim 4 , wherein the polymeric matrix is a biodegradable poly(d claim 4 ,l-lactide-co-glycolide) microsphere.6. A method for the treatment or prophylaxis of a central nervous system disorder claim 1 , comprising administering to a patient in need thereof a compound according to .7. The method according to claim 6 , wherein the central nervous system disorder is a disorder involving serotonin 5-HTA claim 6 , dopamine D2 and/or D1 receptor system and/or the serotonin reuptake transporter (SERT) pathways.8. The method according to claim 6 , wherein the central nervous system disorder is a disorder selected from the group consisting of obesity claim 6 , anxiety claim 6 , depression (for example refractory depression and MDD (major depressive disorder)) claim 6 , psychosis (including psychosis associated with dementia claim 6 , such as hallucinations in advanced Parkinson's disease or paranoid delusions) claim 6 , schizophrenia claim 6 , sleep disorders (particularly sleep disorders associated with schizophrenia and other psychiatric and neurological diseases) claim 6 , sexual disorders claim 6 , migraine claim 6 , conditions associated with cephalic pain claim 6 , social phobias claim 6 , agitation in dementia (e.g. claim 6 , agitation in Alzheimer's disease) claim 6 , agitation in autism ...

NANOPARTICLES FOR DELIVERY OF CHEMOPREVENTIVE AGENTS

Disclosed herein are nanoparticle compositions and methods of use such as for chemoprevention of cancer, for example oral squamous cell carcinoma (OSCC). The nanoparticle composition comprises a Janus particle comprising at least two chemopreventive agents, wherein at least one of the chemopreventive agents is selected from freeze-dried black raspberries (BRB), a synthetic vitamin A analogue, N-acetylcysteine (NAC), and an anti-interleukin 6 agent. Methods for improving oral health comprising administering to a subject the nanoparticle compositions are also disclosed. 1. A nanoparticle composition comprising: a Janus particle comprising at least two chemopreventive agents , wherein at least one of the chemopreventive agents is selected from the group consisting of freeze-dried black raspberries (BRB) , a synthetic vitamin A analogue , N-acetylcysteine (NAC) , and an anti-interleukin 6 agent.2. The nanoparticle composition of claim 1 , wherein the at least two chemopreventive agents selected are BRB and fenretinide (4-HPR).3. The nanoparticle composition of claim 1 , wherein the at least two chemopreventive agents selected are 4-HPR and NAC.4. The nanoparticle composition of claim 1 , wherein the at least two chemopreventive agents selected are 4-HPR and tocilizumab.5. The nanoparticle composition of claim 1 , wherein the at least two chemopreventive agents selected are NAC and tocilizumab.6. The nanoparticle composition of claim 1 , wherein the Janus particle comprises poly(lactic-co-glycolic acid).7. The nanoparticle composition of claim 2 , wherein the concentration ratio of BRB and 4-HPR is between 1:1 and 1 claim 2 ,000:1.8. The nanoparticle composition of claim 1 , further comprising a mucoadhesive.9. The nanoparticle composition of claim 8 , wherein the mucoadhesive comprises lectin.10. The nanoparticle composition of claim 1 , further comprising a mucous penetration enhancer.11. The nanoparticle composition of claim 10 , wherein the mucous penetration ...

COMPOSITION FOR MANAGEMENT OF PERIODONTAL DISEASE

The composition for management of periodontal diseases includes a gel matrix having a polymer system and a plurality of microspheres dispersed in the polymer system. The polymer system contains about one-half a dose of medicament, while the microspheres contain the remainder. Upon administration of the composition into the periodontal cavity, the medicament in the polymer system provides an initial therapeutic benefit, while the remainder of the medication is released over time via degradation of the microspheres. This biphasic pattern of medicament delivery provides increased efficacy of the medicament through sustained delivery of the same. 1. A delivery system for management of periodontal diseases , comprising:a polymer system forming a gel matrix adapted for carrying about one-half of a dose of a medicament for treating periodontal disease, the gel matrix providing rapid release of the medicament to achieve therapeutic levels, the gel matrix including about 0.5% to about 1.5% by weight chitosan and about 20% to about 30% by weight poloxamer members; anda plurality of microspheres suspended and dispersed in the gel matrix, the microspheres containing the remainder of the dose, the microspheres providing gradual time release of the medicament to maintain the therapeutic levels of medicament for a sustained period of time.2. The delivery system according to claim 1 , wherein the poloxamer members include poloxamer 407 and poloxamer 188.3. The delivery system according to claim 2 , wherein said gel matrix comprises about 15% to about 20% by weight poloxamer 407 and about 5% to about 15% by weight poloxamer 188.4. The delivery system according to claim 2 , wherein said polymer system comprises about 18% by weight poloxamer 407 and about 10% by weight poloxamer 188.5. The delivery system according to claim 2 , wherein said polymer system comprises about 18% by weight poloxamer 407 and about 5% by weight poloxamer 188.6. The delivery system according to claim 2 , ...

Sustained Release Olanzapine Formulations

The disclosure is directed to methods of treating schizophrenia or bipolar disorder by subcutaneously administering a sustained-release dosage form of olanzapine, or a pharmaceutically acceptable salt thereof. Methods of subcutaneously administering olanzapine, or a pharmaceutically acceptable salt thereof, are also described. 1. A sustained-release pharmaceutical dosage form comprising between 150 mg and 900 mg of olanzapine , or a pharmaceutically acceptable salt thereof ,{'sub': 'max, avg', 'wherein the dosage form comprises microparticles comprising olanzapine, or a pharmaceutically acceptable salt thereof, wherein said dosage form provides a therapeutically effective dose of olanzapine for a period of at least 21 days, wherein the upper limit of a 95% Confidence Interval for the Cis ≤100 ng/ml; for use in treating schizophrenia or bipolar disorder in a patient, wherein said treatment comprises subcutaneously administering said dosage form to the patient, with a frequency of no more than once per 21 days, and wherein said treatment is performed without monitoring for post-injection delirium/sedation syndrome (PDSS).'}2. The pharmaceutical dosage form according to claim 1 , comprising between about 300 mg and about 600 mg of olanzapine or a pharmaceutically acceptable salt thereof that is equivalent to between about 300 mg and about 600 mg of olanzapine.3. The pharmaceutical dosage form according to claim 2 , comprising about 300 mg of olanzapine or a pharmaceutically acceptable salt thereof that is equivalent to about 300 mg of olanzapine.4. The pharmaceutical dosage form according to claim 2 , comprising about 405 mg olanzapine or a pharmaceutically acceptable salt thereof that is equivalent to about 405 mg of olanzapine.5. The pharmaceutical dosage form according to claim 2 , comprising claim 2 , or about 600 mg olanzapine or a pharmaceutically acceptable salt thereof that is equivalent to about 600 mg of olanzapine.6. The pharmaceutical dosage form according ...

COMPOSITIONS FOR INHIBITING INFLAMMATION IN A SUBJECT WITH A SPINAL CORD INJURY AND METHODS OF USING THE SAME

Provided herein are compositions for inhibiting inflammation in a subject with a spinal cord injury comprising one or more agents capable of specifically reducing TNF-α signaling and a biodegradable carrier. Further provided herein are compositions for inhibiting inflammation in a subject with a spinal cord injury comprising one or more agents capable of modulating MCP-1 signaling and a biodegradable carrier. Methods of treating inflammation in a subject having a spinal cord injury and kits for producing the compositions are also disclosed. 1. A composition for inhibiting inflammation in a subject with a spinal cord injury comprising:one or more agents capable of specifically reducing TNF-α signaling; anda biodegradable carrier.2. The composition of claim 1 , wherein the one or more agents comprise a TNF-α inhibitor claim 1 , a protein that specifically binds TNF-α claim 1 , an anti-inflammatory cytokine claim 1 , or any combination thereof.3. The composition of claim 2 , wherein the protein that specifically binds TNF-α is etanercept claim 2 , infliximab claim 2 , adalimumab claim 2 , certolizumab pegol claim 2 , or any combination thereof.4. The composition of claim 2 , wherein the protein that specifically binds is an antibody.5. The composition of claim 2 , wherein the TNF-α inhibitor is pentoxifylline claim 2 , methotrexate claim 2 , pirfenidone claim 2 , bupropion claim 2 , or any combination thereof.6. The composition of claim 2 , wherein the anti-inflammatory cytokine is IL-10 claim 2 , IL-4 claim 2 , or any combination thereof.7. The composition of claim 1 , wherein the one or more agents are exposed on the surface of the biodegradable carrier claim 1 , incorporated within the biodegradable carrier claim 1 , or both.8. The composition of claim 1 , wherein the one or more agents are exposed on the surface of the biodegradable carrier.9. The composition of claim 8 , wherein the one or more agents comprise a protein that specifically binds TNF-α.10. The ...

NANOPARTICLES COMPRISING DOCETAXEL FOR TREATING CANCERS HAVING A K-RAS MUTATION

The present disclosure relates in part to methods of treating cancers having a mutation in a Ras gene in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a nanoparticle composition, wherein the nanoparticle composition comprises nanoparticles. 1. A method of treating cancer having a K-Ras mutation in a patient in need thereof , comprising administering to the patient a therapeutically effective amount of a nanoparticle composition , wherein the nanoparticle composition comprises nanoparticles comprising:about 10 to about 99.8 weight percent poly(lactic) acid-poly(ethylene)glycol copolymer or a diblock poly(lactic acid-co-glycolic acid)-poly(ethylene)glycol copolymer; andabout 0.2 to about 35 weight percent docetaxel.2. The method of claim 1 , wherein the therapeutically effective amount of the nanoparticle composition is about 50 to about 75 mg/mof docetaxel.3. The method of claim 1 , wherein the therapeutically effective amount of the nanoparticle composition is about 60 to about 75 mg/mof docetaxel.4. The method of claim 3 , wherein the therapeutically effective amount of the nanoparticle composition is about 60 mg/mof docetaxel.5. The method of any one of - claim 3 , further comprising administering the nanoparticle composition about every three weeks to said patient.6. The method of any one of - claim 3 , wherein the nanoparticle composition is administered by intravenous infusion over about 1 hour.7. The method of any one of - claim 3 , wherein the cancer was not stabilized by administration to the patient of free therapeutic agent.8. The method of any one of - claim 3 , wherein the hydrodynamic diameter of the nanoparticles is about 60 to about 150 nm.9. The method of any one of - claim 3 , wherein the hydrodynamic diameter of the nanoparticles is about 90 to about 140 nm.10. The method of any one of - claim 3 , wherein the hydrodynamic diameter of the nanoparticles is about 90 to about 120 nm.11. The ...

PARTICULATE POLY(LACTIC-CO-GLYCOLIC) ACID, METHOD FOR MANUFACTURING PARTICULATE POLY(LACTIC-CO-GLYCOLIC) ACID, AND PARTICULATE POLY(LACTIC-CO-GLYCOLIC) ACID MANUFACTURING APPARATUS

A particulate poly(lactic-co-glycolic) acid (PLGA) is provided. The particulate PLGA comprises a poly(lactic-co-glycolic) acid (PLGA), and has an average volume-based particle diameter of 80 nm or less and a relative span factor (R.S.F.) satisfying the following formula (1):

Microparticle formulations of adenosine receptor antagonists for treating cancer

The invention provides compositions comprising microparticles wherein the microparticles comprise at least one adenosine 2a receptor antagonist (A2ARA), at least one pharmaceutically acceptable polymer and at least one pharmaceutically acceptable negatively charged agent wherein the microparticles optionally have a highly negative zeta potential of less than about −40 mV. The invention also provides pharmaceutical compositions of the microparticles of the invention and methods of using the compositions of the invention to enhance an immune response in a patient in need thereof and as anti-cancer immunotherapy.

METHODS, COMPOSITIONS, AND DEVICES FOR DRUG / LIVE CELL MICROARRAYS

Methods and compositions are for preparing microimplant arrays for sustained drug delivery or live cell based therapy. The “array in array” (AIA) device enables formation of microimplant arrays without having tissue piercing elements to the microimplant. The methods and compositions are for solid state delivery of drugs, especially biologics drugs without forming a drug solution prior to injection. New methods and compositions are for preparing in situ arrays for sustained drug delivery or live cell based therapy. Tissue surface is first treated with laser drilling, microneedle array, mechanical drilling or other methods to create artificial micro-porosity of various sizes, shapes and patterns. The artificial pores created are then infused with sustained drug delivery compositions or live cell suspensions. The compositions are converted into solid or semisolid state by physical or chemical reaction/s to entrap drug or live cells. The entrapped drug or live cells provide local or systemic therapeutic benefit. 1. A method of forming an implant in a tissue , the method comprising:providing an injectable composition including live mammalian cells suspended in an aqueous solution; andinjecting the injectable composition into the tissue at the rate of about 10-12000 injections per minute.2. The method of claim 1 , comprising injecting the injectable composition into the tissue at a depth of about 10 microns to about 5 mm.3. The method of claim 1 , wherein the aqueous composition comprises a visualization agent.4. The method of claim 3 , wherein the visualization agent is a colored compound claim 3 , a fluorescent compound claim 3 , an x-ray imaging agent claim 3 , or a MRI agent.5. The method of claim 4 , wherein the colored compound is a dye or pigment or microparticle that is biocompatible.6. The method of claim 4 , wherein the colored compound is selected from methylene blue; Eosin Y; fluorescein sodium; ferric ammonium citrate; D&C Blue No. 9; D&C Green No. 5; FD&C ...

PHARMACEUTICAL FORMULATION CONTAINING IRRITANT

Disclosed in certain embodiments is an oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse; and an effective amount of an irritant to impart an irritating sensation to an abuser upon administration of said dosage form after tampering. 128-. (canceled)29. An abuse-deterrent oral controlled release dosage form comprising particles comprising a homogeneous mixture comprising:a therapeutically effective amount of a CNS stimulant,an aversive agent, anda material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, oils and mixtures of any of the foregoing,the aversive agent and the material are in the amounts that spoil or hinder the pleasure of obtaining a high from the CNS stimulant when the dosage form is tampered with by crushing, shearing, grinding, chewing, dissolution in a solvent, heating, or any combination thereof, and administered orally, whereinthe aversive agent comprises an irritant, andthe particles are from about 0.1 mm to about 2.5 mm in diameter.30. The dosage form of claim 29 , wherein the irritant is selected from the group consisting of capsaicin claim 29 , a capsaicin analog and mixtures thereof.31. The dosage form of claim 30 , wherein the irritant is a capsaicin analog selected from the group consisting of resiniferatoxin claim 30 , tinyatoxin claim 30 , heptanoylisobutylamide claim 30 , heptanoyl guaiacylamide claim 30 , other isobutylamides or guaiacylamides claim 30 , dihydrocapsaicin claim 30 , homovanillyl octylester claim 30 , nonanoyl vanillylamide claim 30 , and mixtures thereof.32. The dosage form of claim 29 , wherein the aversive agent and the material are in the amounts that hinder the pleasure of obtaining a rapid high from the CNS stimulant when the dosage form is tampered with by crushing claim 29 , shearing claim 29 , grinding claim 29 , chewing claim 29 , dissolution in a solvent claim 29 , heating claim 29 , or any combination thereof claim 29 , ...

Sustained release small molecule drug formulation

An injectable depot formulation includes a biocompatible polymer, an organic solvent combined with the biocompatible polymer to form a viscous gel, and a small molecule drug incorporated in the viscous gel such that the formulation exhibits an in vivo release profile having a C max to C min ratio of less than 200 and a lag time less than 0.2.

Sustained release formulations using non-aqueous carriers

The disclosure provides one-component, injectable, sustained release formulations which comprise microspheres containing active pharmaceutical ingredients (e.g., exenatide), wherein the microspheres are suspended in a non-aqueous carrier. The non-aqueous carrier can be an oil, a fractionated oil, triglycerides, diglycerides, monoglycerides, propylene glycol fatty acid diesters, and the like. The formulations offer distinct advantages of long shelf life for the stability and potency of the formulation and sustained release of active pharmaceutical ingredients to reduce the frequency of medication dosing and to increase patient compliance.