ГИАЛУРОНИДАЗА И СПОСОБ ЕЕ ПРИМЕНЕНИЯ

Изобретение относится к биотехнологии и медицине и представляет собой фармацевтический состав для расщепления гиалуроновой кислоты in vivo, содержащий эффективное количество выделенного белка гиалуронидазы, который имеет молекулярный вес 44±1 кДа и содержит аминокислотную последовательность, по меньшей мере на 90% идентичную последовательности SEQ ID NO: 1, SEQ ID NO: 2 и SEQ ID NO: 4, и фармацевтически приемлемый эксципиент, носитель, разбавитель или вспомогательный агент. Изобретение относится также к способу минимизации проявления рубца, включающему местное применение такого фармацевтического состава, а также к способу повышения терапевтической эффективности лекарственного средства, включающему введение пациенту лекарственного средства совместно с фармацевтическим составом. Изобретение позволяет расширить ассортимент средств для улучшения проникновения одновременно вводимого активного вещества через кожу. 7 н. и 35 з.п. ф-лы, 16 ил., 23 табл., 12 пр.

СПОСОБЫ ИНГИБИРОВАНИЯ УМЕНЬШЕНИЯ ТРАНСДЕРМАЛЬНОГО ДВИЖЕНИЯ ЛЕКАРСТВЕННОГО СРЕДСТВА ПОСРЕДСТВОМ ИНГИБИРОВАНИЯ ЗАКРЫТИЯ ПУТЕЙ

Изобретение относится к медицине и касается способа ингибирования уменьшения трансдермального движения агента, который доставляется через кожу или образец которого отбирается через кожу, в течение длительного времени, при котором доставка агента или отбор его образцов сопровождается нарушением целостности по меньшей мере слоя кожи stratum corneum с формированием путей, через которые проходит агент. Осуществление способа достигается посредством использования при доставке или отборе агента (первого агента) определенного количества по меньшей мере одного агента, препятствующего заживлению. Используют такое количество агента, препятствующего заживлению, которое эффективно в отношении ингибирования уменьшения трансдермального движения первого агента, по сравнению с движением первого агента при практически идентичных условиях, за исключением отсутствия указанного по меньшей мере одного агента, препятствующего заживлению. Предлагаются также устройство для осуществления способа и набор для наложения ...

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ДЛЯ ПАРЕНТЕРАЛЬНОГО ВВЕДЕНИЯ В ФОРМЕ СУСПЕНЗИИ С ДЛИТЕЛЬНЫМ ВЫСВОБОЖДЕНИЕМ В НИЗКОЙ И ОЧЕНЬ НИЗКОЙ ДОЗЕ ПРИ ГОРМОНАЛЬНОЙ ТЕРАПИИ КЛИМАКТЕРИЧЕСКОГО СИНДРОМА

Изобретение относится к медицине и представляет собой фармацевтическую композицию с замедленным высвобождением для парентерального введения один раз в месяц. Композиция предназначена для заместительной гормональной терапии у млекопитающих женского пола и содержит эстрадиол в количестве от 0,25 мг до 1,0 мг в форме микрочастиц, где микрочастицы включают эстрадиол и холестерин; прогестерон в количестве 15 мг или от 20 мг до 75 мг в форме микрочастиц; поверхностно-активный агент; изоосмотический агент; агент, увеличивающий вязкость; консервант и водный наполнитель. рН композиции составляет от 4 до 7. Микрочастицы имеют размер от 1 до 100 микрометров, и при их получении действующие вещества расплавляют, распыляют, замораживают и кристаллизуют с получением стабильных форм действующих веществ. Изобретение заключается также в применении композиции для лечения симптомов и дискомфорта, связанных с климактерическим синдромом у женщин с маткой. 4 н. и 12 з.п. ф-лы, 5 пр., 9 табл., 3 ил.

ГЛЮКОЗОЧУВСТВИТЕЛЬНАЯ СИСТЕМА ДОСТАВКИ ИНСУЛИНА С ИСПОЛЬЗОВАНИЕМ ЧУВСТВИТЕЛЬНЫХ К ГИПОКСИИ НАНОКОМПОЗИТОВ

Изобретение относится к композиция для глюкозочувствительной доставки средства для лечения диабета нуждающемуся в этом субъекту. Композиция содержит: амфифильный полимерный материал, причем амфифильный полимерный материал содержит гидрофильный полимер, конъюгированный с чувствительной к гипоксии гидрофобной группой, причем указанная чувствительная к гипоксии гидрофобная группа содержит чувствительный к гипоксии фрагмент, который может восстанавливаться в присутствии гипоксического окружения с образованием гидрофильного фрагмента, причем гидрофильный полимер выбран из группы, состоящей из полиаминокислоты, синтетического блок-сополимера и полисахарида, и причем чувствительная к гипоксии гидрофобная группа представляет собой нитроимидазол; средство для лечения диабета; и окисляющее глюкозу средство. Также предложены наночастица, везикула, микроигольчатая матрица, система доставки инсулина замкнутого контура, способ доставки средства для лечения диабета, способ получения микроигольчатой матрицы ...

ГИАЛУРОНИДАЗА И СПОСОБ ЕЕ ПРИМЕНЕНИЯ

Изобретение относится к области биохимии. Представлены выделенный белок гиалуронидазы, который имеет молекулярный вес приблизительно 44±1 кДа, содержащий аминокислотную последовательность, по меньшей мере, на 90% идентичную последовательности, которая содержит SEQ ID NO: I, SEQ ID NO: 2 и SEQ ID NO: 4, приведенные в описании, а также кодирующая его ДНК. Описан фармацевтический лекарственный состав для повышения проницаемости ткани или уменьшения вязкости соединительной ткани, содержащий эффективное количество выделенной указанной гиалуронидазы и фармацевтически приемлемый эксципиент, носитель, разбавитель или вспомогательный агент. Предложены способы: 1) предотвращения или минимизации образования рубца, включающий местное введение указанного фармацевтического состава; 2) сокращения проявления морщин посредством уменьшения вязкости соединительной ткани, включающие местное введение указанного фармацевтического состава; 3) облегчения дискомфорта или боли, вызванной ревматическим артритом, ...

ТРАНСДЕРМАЛЬНАЯ ДОСТАВКА ВЫСОКОВЯЗКИХ БИОАКТИВНЫХ АГЕНТОВ

Группа изобретений относится к медицине и касается устройства и способа трансдермальной доставки высоковязкой композиции. Устройство содержит микроиглу и множество изготовленных на ее поверхности наноструктур. Они скомпонованны в заданный паттерн, обеспечивающий нанотопографию, которая, взаимодействуя с окружающими тканями, способствует транспортировке высоковязкой композиции через дермальный барьер. Устройство содержит также сообщающуюся по текучей среде с микроиглой композицию, содержащую биоактивный агент и имеющую вязкость свыше примерно 5 сантипуаз. Способ доставки биоактивного агента включает обеспечение проникновения через роговой слой субъекта микроиглой заявленного устройства и создание условий транспортирования композиции через микроиглу со скоростью свыше примерно 0,4 мг/час/смв зависимости от площади поверхности микроиглы. Изобретения обеспечивают доставку через дермальный барьер высоковязкой лечебной композиции. 2 н. и 10 з.п. ф-лы, 3 пр., 3 табл. 34 ил.

СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ СТАРЕНИЯ КОЖИ И РУБЦОВ

Группа изобретений относится к медицине, а именно к косметологии, и может быть использована для лечения старения кожи. Для чего используют средство, содержащее основной фактор роста фибробластов (bFGF) как единственный активный ингредиент, которое вводится внутрикожно или подкожно в место рубца, или в окружающую его часть, например келоида, гипертрофического рубца и рубцовой контрактуры; кроме того, средство также предназначено для лечения одного или более видов старения кожи, выбранных из следующего перечня: морщины на коже, обвисшая кожа, грубая кожа, истончение кожи и снижение упругоэластичности кожи из-за разрыва дермальных тканей или снижения функций фибробластовых клеток. При этом старение кожи является фотостарением, а величина дозы основного фактора роста фибробластов (bFGF) составляет от 0,1 мкг до 1 мг на 1 смкожи, являющейся целью лечения. Изобретения обеспечивают достоверное уменьшение морщин, улучшение структуры кожи, в том числе за счет повышения ее тургора и увеличения объема ...

ORNITHODOROS MOUBATA ИГИБИТОР КОМПЛЕМЕНТА, ПРЕДНАЗНАЧЕННЫЙ ДЛЯ ЛЕЧЕНИЯ ОПОСРЕДОВАННЫХ КОМПЛЕМЕНТОМ ЗАБОЛЕВАНИЙ ПАЦИЕНТА С ПОЛИМОРФИЗМОМ С5 КОМПЛЕМЕНТА

Группа изобретений относится к медицине и касается способа лечения или профилактики опосредованного комплементом заболевания и/или расстройства, включающего введение субъекту, который имеет полиморфизм C5 комплемента и нуждающемуся в таком введении, терапевтически или профилактически эффективного количества средства, которое ингибирует классический путь комплемента, альтернативный путь комплемента и лектиновый путь комплемента, где средство представляет собой: (a) белок, содержащий или состоящий из аминокислот 19-168 аминокислотной последовательности SEQ ID NO: 2, или является функциональным эквивалентом такого белка; (b) белок, содержащий или состоящий из аминокислот 1-168 аминокислотной последовательности SEQ ID NO: 2, или является функциональным эквивалентом такого белка; или (c) молекулу нуклеиновой кислоты, кодирующую белок, указанный в (a) или (b); и где полиморфизм C5 комплемента снижает эффективность экулизумаба. Группа изобретений также касается применения средства, которое ингибирует ...

МАССИВ ПОЛЫХ МИКРОИГЛ И СПОСОБ ЕГО ИСПОЛЬЗОВАНИЯ

Изобретение относится к медицине и может быть использовано при необходимости интрадермального введения препаратов. Для этого предложен способ, включающий этапы накладывания на кожу пациента массива микроигл, содержащего от 10 до 30 полых микроигл длиной более 100 мкм. Глубина проникновения микроигл менее 1 мм. Среднее расстояние между соседними микроиглами в массиве составляет в среднем не менее 1,5 мм. Через полые микроиглы вводят более чем 200 мкл лекарственного средства со скоростью, превышающей 20 мкл/мин. Способ обеспечивает эффективную трансдермальную доставку лекарственных препаратов при одновременном снижении уровня боли за счет использования определенных параметров микроигл в массиве. 11 з.п. ф-лы, 6 табл., 11 ил., 3 пр.

СПОСОБ ОБЕСЦВЕЧИВАНИЯ КОЖИ В ОБЛАСТИ КРОВОПОДТЕКА

Изобретение относится к медицине, в частности к дерматологии, косметологии, врачебной косметике и клинической фармакологии, и представляет собой способ обесцвечивания кожи в области кровоподтека, включающий определение локализации и размера участка повреждения, обкалывание его по общим правилам раствором лекарственного средства с определенной температурой посредством последовательных инъекций первоначально по периферии поврежденного участка вплоть до создания полного замкнутого инфильтрационного кольца, а затем внутренней части, отличающийся тем, что освещают избранный участок тела потоком белого рассеянного света, определяют на глаз локализацию и размер кровоподтека в коже, лекарственное средство вводят в кожу путем внутрикожных инъекций, в качестве средства используют изотонический раствор 0,9% натрия хлорида при температуре 37-42°C, кожу внутренней части кровоподтека обкалывают вплоть до создания полного инфильтрационного поля и слияния его с инфильтрационным кольцом с формированием ...

ПОЛИПЕПТИДЫ, ОБРАБОТАННЫЕ HAS, ОСОБЕННО ЭРИТРОПОЭТИН, ОБРАБОТАННЫЙ HAS

... 1. Конъюгат гидроксиалкилкрахмала (HAS)-эритропоэтина (EPO) (HAS-EPO), содержащий одну или несколько молекул HAS, где каждый HAS конъюгирован с EPO через углеводный фрагмент. 2. HAS-EPO по п.1, отличающийся тем, что указанный EPO имеет аминокислотную последовательность человеческого EPO. 3. HAS-EPO по п.1, отличающийся тем, что указанный EPO содержит одну или несколько углеводных боковых цепей, присоединенных к EPO посредством N- и/или O-гликозилирования, где предпочтительно указанные углеводные боковые цепи присоединены к EPO в процессе продукции в клетках млекопитающего, особенно человека, насекомого или дрожжей. 4. HAS-EPO по любому из пп.1-3, отличающийся тем, что указанный HAS конъюгирован с EPO через линкерную молекулу. 5. HAS-EPO по любому из пп.1-3, отличающийся тем, что указанный HAS конъюгирован с EPO по его восстанавливающему концу, предпочтительно, исключительно по его восстанавливающему концу. 6. HAS-EPO по любому из пп.1-3, отличающийся тем, что указанный HAS конъюгирован ...

КОНЪЮГИРОВАННЫЙ ФАКТОР СВЕРТЫВАНИЯ КРОВИ VIIa

... 1. Конъюгат фактор FVIIa-полиэтиленгликоль, в котором одна или несколько групп полиэтиленгликоля конъюгированы с FVIIa посредством линкерной группы, связывающей атомы серы двух остатков цистеина, которые формировали дисульфидную связь в FVIIa,при этом указанный конъюгат имеет структуругде заместитель Rпредставляет собой непосредственную связь, алкиленовую группу (предпочтительно Cалкилен), или возможно замещенную арильную или гетероарильную группу; причем арильные группы включают фенил, бензоил и нафтил группы; при этом подходящие гетероарильные группы включают пиридин, пиррол, фуран, пиран, имидазол, пиразол, оксазол, пиридазин, пиримидин и пурин; при этом связь с полимером является гидролитически лабильной или нелабильной связью.2. Конъюгат фактор FVIIa-полиэтиленгликоль по п.1, отличающийся тем, что полиэтиленгликоль имеет молекулярный вес около 5-100 кДа.3. Фармацевтическая композиция, содержащая конъюгат фактор FVIIa-полиэтиленгликоль по любому из предыдущих пунктов.4. Фармацевтическая ...

СПОСОБЫ ДИАГНОСТИКИ И ЛЕЧЕНИЯ ЭОЗИНОФИЛЬНЫХ ЗАБОЛЕВАНИЙ

СОСТАВЫ НА ОСНОВЕ АНТИТЕЛА

АНТИ-IgE АНТИТЕЛА

КОМПОЗИЦИИ И СПОСОБЫ ЛЕЧЕНИЯ ВНУТРИМОЗГОВОГО КРОВОИЗЛИЯНИЯ

ИНГИБИТОР КОНТРОЛЬНЫХ ТОЧЕК И ЦЕЛЬНОКЛЕТОЧНАЯ МИКРОБАКТЕРИЯ ДЛЯ ИСПОЛЬЗОВАНИЯ ПРИ ЛЕЧЕНИИ ОНКОЛОГИЧЕСКОГО ЗАБОЛЕВАНИЯ

КОМПОЗИЦИИ, СОДЕРЖАЩИЕ ГЛЮКОЦЕРЕБРОЗИДАЗУ И ИЗОФАГОМИН

МИКРОСТРУКТУРА, ВКЛЮЧАЮЩАЯ ПОПЕРЕЧНО-СШИТЫЙ ГИДРОГЕЛЬ ГИАЛУРОНОВОЙ КИСЛОТЫ, И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

ДИАРИЛГИДАНТОИНЫ

Способы применения интерлейкина-10 для лечения заболеваний и расстройств

КОМПОЗИЦИЯ СО СШИТОЙ ГИАЛУРОНОВОЙ КИСЛОТОЙ ДЛЯ НАРАЩИВАНИЯ ТКАНЕЙ

... 1. Композиция гиалуроновой кислоты (НА), содержащая частицы геля сшитой не растворимой в воде гидратированной НА, где НА включает связки, представленные следующей структурной формулой: HA'-U-R2-U-HA', в которой каждая группа НА' означает ту же или другую молекулу сшитой НА; каждая U независимо означает необязательно замещенную O-ацилизомочевину или N-ацилмочевину; и R2 представляет собой необязательно замещенный алкил, алкенил, алкинил, алкокси, циклоалкил, циклоалкенил, циклоалкинил, арил, гетероарил, гетероциклический радикал, циклоалифатический алкил, аралкил, гетероаралкил или гетероциклолалкил, и в которой НА частицы имеют распределение среднего диаметра, выбранное из группы, состоящей из гидратированных частиц со средним диаметром от 20 до 1000 мкм и средним диаметром дегидратированных частиц от 10 до 500 мкм. 2. Композиция НА по п.1, в которой частицы включают, по меньшей мере, один биоактивный агент, выбранный из группы, состоящей из клеток, генов, белков, антител, пептидов и фармацевтических ...

Use of telomerase inhibitors for the treatment of myeloproliferative disorders and myeloprolifarative neoplasms

Conjugated blood coagulation factor VIIA

Conjugated blood coagulation factor VIII

Formulation of drugs and vaccines in the form of percutaneous injectable needles.

Formulation of drugs and vaccines in the form of percutaneous injectable needles.

Formulation of drugs and vaccines in the form of percutaneous injectable needles.

USE OF LIPOSOMEN WITH SAPONINEN AND STEROLEN IN THE PRODUCTION OF INTRADERMALEN VACCINES

DEVICE FOR TRANSDERMALEN THE ADMINISTRATION OF ACTIVE SUBSTANCES

PHARMACEUTICAL COMPOSITION FROM MICRO BALLS TO THE PREVENTION OF A AMPUTATION OF A DIABETI FOOT

DIARYLHYDANTOIN CONNECTION

IMPROVED LIPOLYTIKUM FORMULATION WITH DELAYING ACTIVE SUBSTANCE RELEASE FOR THE AREA TREATMENT OF FATTY TISSUE

LIQUID DELIVERY DEVICE REGULARLY BY A ANALYTEN AND A MONITORING OF THE ANALYTEN

HYDROXYLIERTE METABOLITES AND DERIVATIVES OF DOXAZOSIN AGAINST ATHEROSKLEROSE

APPLIKATOR ALSO ON SCHLEIFFENDE SURFACE COVERED SUBSTANCE FOR LAYING ON SKIN

SYSTEM AND PROCEDURE FOR THE TRANSPLANT OF CELLS

MODIFIED NUCLEOSIDES, NUCLEOTIDES, AND NUCLEIC ACIDS, AND USES THEREOF

Abstract The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them. W:\NRPortbl\GHMatters\MICHELES66656_1.docx9/08/17 Figure 10 80 eFNa w 60 B C$ c -TNra S40~ 20K' 100% 75%S 5A% 25% CAI -20w %Modified Nucleotdes ...

Modified RNA encoding VEGF-A polypeptides, formulations, and uses relating thereto

The disclosure relates to modified RNA molecules encoding VEGF-A polypeptides and formulations comprising the modified RNA. Aspects of the disclosure further relate to preparations and uses of formulations comprising the modified RNA in treating subjects suffering from diseases responsive to VEGF-A therapy.

Subcutaneous administration of a P2Y12 receptor antagonist

The present invention relates to a P2Y ...

Fused ring compounds

Provided are fused ring compounds of Formula (I), Formula (II), or Formula (III), as further detailed herein, which are used for the inhibition of Ras proteins, as well as compositions comprising these compounds and methods treatment by their administration.

Plasminogen activator inhibitor 1 (PAI-1) inhibitors and uses therefor

The present disclosures provides new technologies for treatment and/or prevention of certain dermatological conditions, specifically including graying hair. Among other things, the present disclosure provides an insight that plasminogen activator inhibitor -1 (PAI-1) inhibitors may be useful in the treatment and/or prevention of certain dermatological conditions, and in particular in treatment and/or prevention of graying hair.

Three-dimensional microfluidics devices for the delivery of actives

A dermal delivery device includes a film having first and second outwardly facing major surfaces; at least one liquid reservoir contained within the film; at least one microfluidic channel having a transverse dimension between about 100 nm and 0.5 mm disposed within the film and in fluid communication with the at least one liquid reservoir; and at least one outlet port operatively connected to the first outwardly facing major surface of the film in fluid communication with the at least one microfluidic channel.

Subcutaneous biodegradable reservoir device

A reservoir device comprising an active agent formulation contained within a reservoir is described. The reservoir is defined by a biodegradable, permeable polymer membrane having a thickness of at least 45 µm. The membrane allows for diffusion of an active agent of the formulation there through when positioned subcutaneously in a body of a subject.

Conjugates for use in methods of treating cancer

Disclosed are methods of treating cancer in a subject, comprising subcutaneously administering to the subject an effective amount of a dendrimer of formula (I): (I) and pharmaceutically acceptable salts thereof.

Shared antigens

Disclosed herein are compositions that include antigen-encoding nucleic acid sequences and/or antigen peptides. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines.

Applicator system containing a microneedle array which comprises an active ingredient for wound healing

The invention relates to an applicator system containing a microneedle array and the use thereof for intradermal application of active ingredients, in particular drugs, said microneedle array being suitable for the penetration of human or animal skin and comprising at least one active ingredient for wound healing.

Microneedle array assembly and fluid delivery apparatus having such an assembly

A microneedle array assembly includes a microneedle array that has a plurality of microneedles. A distribution manifold includes a fluid supply channel that is coupled in flow communication to a plurality of resistance channels. Each of the resistance channels are coupled in flow communication to a respective one of the microneedles of the microneedle array. The resistance channels have a resistance value to a fluid flow through each resistance channel that is in the range between about 5 times greater to about 100 times greater than a resistance to the fluid flow through the supply channel.

Modulated immunodominance therapy

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating ...

METHODS AND DEVICES FOR DETECTION AND ACQUISITION OF BIOMARKERS

The present invention provides devices and methods for detecting and capturing molecular biomarkers from a subject in situ. Specifically, the devices contain an array of microneedles to which are attached probes specific for one or more biomarkers of interest. The devices can be used directly on a subject (e.g., via skin piercing) in detecting the biomarkers in the body of the subject (e.g., tissues, blood stream).

Therapeutic peptide formulations for coating microneedles with improved stabitity containing at least one counterion

Medicament microdevice delivery system with a cartridge

Improved intra-dermal delivery of biologically active agents

Microprojection array application with sculptured microprojections for high drug loading

Transdermal drug delivery systems, devices, and methods employing opioid agonist and/or opioid antagonist

Methods of device-assisted drug delivery

Methods for the inhibition of scarring

Preparation for application to body surface and preparation holding sheet for application to body surface

It is intended to provide a microneedle and a microneedle array comprising an auto-soluble base and capable of realizing higher absorptivity and pharmacological effect. A preparation for application to the body surface 1 has two portions divided in an insertion direction, i.e., a fore-end portion 5 and a rear-end portion 6. The fore-end portion 5 includes a body surface insertion end 2 and holds a base-soluble target substance. The rear-end portion 6 includes a pressing end 3 and is mainly constituted by only a base and does not hold a target substance. When the preparation for application to the body surface 1 is inserted into the body surface such as the skin, even if a portion of the rear end side is not inserted into the body surface and remains outside, an actual given dose of the target substance is not less than a desired amount because the target substance is contained in the fore-end portion 5, and a high absorptivity and pharmacological effect can be realized.

Methods and devices for desmopressin drug delivery

Disclosed are devices for urine voiding postponement, and methods for treating conditions such as central diabetes insipidus, enuresis, nocturia, urinary frequency or incontinence. The devices deliver a desmopressin flux through the skin of a patient in a low dose amount just necessary to achieve a desired anti-diuretic effect without undesirable side effects such as hyponatremia. The devices are designed to permit a state of normal urinary production to return quickly after the desmopressin flux is terminated.

Treatment of diseases

Vaccines

Tricyclic compounds and methds of making and using same

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

Nanopatterned medical device with enhanced cellular interaction

Disclosed are nanotopography-based methods and devices for interacting with a component of the dermal connective tissue. Devices include structures fabricated on a surface to form a nanotopography. A random or non-random pattern of structures may be fabricated such as a complex pattern including structures of differing sizes and/or shapes. Microneedles may be beneficially utilized for delivery of an agent to a cell or tissue. Devices may be utilized to directly or indirectly alter cell behavior through the interaction of a fabricated nanotopography with the plasma membrane of a cell and/or with an extracellular matrix component.

Solid solution perforator containing drug particle and/or drug-adsorbed particles

A solid drug solution perforator (40Q) containing drug particles (402) and/or drug adsorbed or loaded particles with an associated drug reservoir (SSPP system) are provided for delivering therapeutic, prophylactic and/or cosmetic compounds, diagnostics, and for nutrient delivery and drug targeting For drug delivery, the SSPP system includes an active drug ingredient in particulate form (402) or drug adsorbed on the particle surface in a matrix material (41 1) that dissolves upon contact with a patient's body (1 1). In a preferred method of transdermal drug delivery, an SSPP system containing a drug-adsorbed microparticle (402) penetrates into the epidermis (15) or dermis (17), and the drug (402) is released from the (dissolving) SSPP system perforator (400) and desorbed from the particles. An additional drug is optionally delivered from a patch reservoir (601) through skin pores created by insertion of the perforator (602). Formulation and fabrication procedures for the SSPP and associated ...

Apparatus and method for transdermal delivery of influenza vaccine

Treatment of androgen - deprivation induced osteoporosis

Apparatus and method for transdermal delivery of multiple vaccines

Methods for inhibiting decrease in transdermal drug flux by inhibition of pathway closure

IMPROVED ANTHRAX VACCINES AND DELIVERY METHODS

Vaccine

Dissolvable microneedles for skin treatment

A skin treatment device is provided including bioerodible polymeric microneedles which are designed to more effectively deliver beneficial agents to the skin. The device includes a flexible substrate and an arrangement, for example, an array, of microneedles projecting from the substrate.

Treatment and prevention of Alzheimer's Disease (AD)

The invention discloses aluminium oxyhydroxide for use in the treatment and prevention of AD.

Rapid action insulin formulations and pharmaceutical delivery systems

The present invention provides rapid-acting insulin and insulin analogue formulations. The invention further provides delivery devices, particularly infusion sets, which allow for the rapid absorption of insulin and insulin analogues, as well as other active agents. Methods of using the insulin and insulin analogue formulations as well as the insulin delivery devices for treating subjects with diabetes mellitus are also provided.

Microstructure array for delivery of active agents

Provided herein is a microstructure array comprising a plurality of dissolving microstructures such as microprojections attached to a base. The plurality of microstructures comprise an active agent in a biocompatible and water-soluble matrix, where the water-soluble matrix preferably comprises a polysaccharide polymer and a sugar alcohol, and the base typically comprises a non-water soluble matrix. The plurality of microstructures, upon penetration of the subject's skin, undergo dissolution to deliver the active agent. Also provided are related microstructure formulations, in dried and liquid form, methods for preparing the above-described microstructure arrays, and methods for administering an active agent by application of a microstructure array as provided herein to a subject's skin, among other features.

Use of telomerase inhibitors for the treatment of myeloproliferative disorders and myeloprolifarative neoplasms

Modulated immunodominance therapy

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating ...

Methods and devices for detection and acquisition of biomarkers

The present invention provides devices and methods for detecting and capturing molecular biomarkers from a subject in situ. Specifically, the devices contain an array of microneedles to which are attached probes specific for one or more biomarkers of interest. The devices can be used directly on a subject (e.g., via skin piercing) in detecting the biomarkers in the body of the subject (e.g., tissues, blood stream).

Microneedle patch for delivering an active ingredient to skin

The present invention relates to a microneedle patch composition comprising one or more microneedles each comprising: (a) a tapered tip portion containing a therapeutically active ingredient dispersed in a matrix of a biodegradable polymer capable of providing sustained release of the therapeutically active ingredient over a period of at least two days after insertion of the microneedle or microneedles into the skin, and (b) a fast dissolving microneedle backing layer portion containing a water-soluble polymer overlayering the tip portion, said microneedle or microneedles being attached to and extending from an adhesive surface of a removable substrate.

Method of producing hydroxyalkyl starch derivatives

Novel formulations for treatment of migraine

Systems and methods are described for treating un-met medical needs in migraine and related conditions such as cluster headache. Included are treatments that are both rapid onset and long acting, which include sustained release formulations, and combination products. Also included are treatments for multiple symptoms of migraine, especially headache and nausea and vomiting. Systems that are self contained, portable, prefilled, and simple to self administer at the onset of a migraine attack are disclosed, and preferably include a needle-free injector and a high viscosity formulation, to eliminate such issues as fear of self administration with needles, and needle stick and cross contamination.

Methods for better delivery of active agents to tumors

Novel RIG-I ligands and methods for producing them

The present invention relates to new triphosphate-modified oligonucleotides which may act as RIG-I ligands as well as a new method allowing the synthesis and purification in high yield and purity suitable for pharmaceutical applications.

Therapeutic and/or preventive agent comprising 1-indansulfamide derivative for pain

A medicine comprising a 1-indansulfamide compound such as N-[(1s)-2,2,5,7-tetrafluoro-2,3-dihydro-1H-indene-1-yl]sulfamide, or N-[(1s)-2,2-difluoro-7-methyl-2,3-dihydro-1H-indene-1-yl]sulfamide, or a pharmaceutically acceptable salt thereof has an analgesic effect in the mouse hot-plate test and rat constriction nerve injury model and thus holds promise as a therapeutic agent for acute pain and chronic pain.

Methods of using interleukin-10 for treating diseases and disorders

Methods of treating subjects having diseases, disorders, or conditions, including cancer and immune- and inflammatory-related disorders, via the administration of IL-10 in combination with one or more additional agents, and methods and models associated therewith, are provided.

Methods of reducing doses of erythropoietin stimulating agents in hyporesponsive patients

The invention provides for methods of treating a dialysis patient that is hyporesponsive to erythropoietin stimulating agents (ESA) comprising administering soluble ferric triphosphate (SFP) composition and administering a dose of ESA that is significantly reduced compared to the dose of ESA required by a dialysis patient that is hyporesponsive to ESA that has not received SFP.

Methods of treating acute myeloid leukemia

A method of treating acute myeloid leukemia (AML), including the steps of (i) measuring a density of blast cells in the peripheral blood and the bone marrow of a subject with AML; (ii) administering to the subject a CXCR4 antagonist; and (iii) administering to the subject a therapeutically effective amount of the CXCR4 antagonist and a therapeutically effective amount of a chemotherapeutic agent, if the blast cell density in the peripheral blood is less than 10 % of the total peripheral white blood cells, or at least five-fold lower than the blast cell density in the bone marrow, or at least two-fold higher one day or more following step (ii).

Solid formulation

A solid dosage form for injection and a method of making said dosage form wherein the dosage form has a moisture content of 5% (w/w) or less. The solid dosage form comprises a dried matrix including a first excipient and 0.01 to 50 % (w/w) or more than50% and up to80%(w/w) of a therapeutic peptide; and one or more additional excipients and at least 5 % (w/w) of CMC, based on the total weight of the solid dosage form, wherein the dosage form has a width of 0.5mm to 2mm.

Compositions and methods for treating metabolic diseases

Provided herein are compositions and methods of treating a metabolic disease, such as diabetes and hyperlipidemia, in a subject, by administering to the subject a therapeutically effective amount of a polypeptide derived from hepatitis B virus or a pharmaceutical composition comprising the polypeptide.

Transdermal delivery of particulate vaccine compositions

Methods of measuring the concentration of an analyte in a subject

VACCINATION BY TRANSCUTANEOUS TARGETING

The present invention relates to a method of vaccination via hair follicles that makes it possible to target vaccine components to the antigen-presenting cells in order to induce a protective and effective immune response against pathogens.

METHOD AND APPARATUS FOR REDUCING THE INCIDENCE OF TOBACCO USE

TRANSDERMAL DRUG DELIVERY DEVICES HAVING COATED MICROPROTRUSIONS

A device (12) and method are provided for percutaneous transdermal delivery of a potent pharmacologically active agent. The agent is dissolved in water to form an aqueous coating solution having an appropriate viscosity for coating extremely tiny skin piercing elements (10). The coating solution is applied to the skin piercing elements (10) using known coating techniques and then dried. The device (12) is applied to the skin of a living animal (e.g., a human), causing the microprotrusions (10) to pierce the stratum corneum and deliver a therapeutically effect dose of the agent to the animal.

APPARATUS AND METHOD FOR TRANSDERMAL DELIVERY OF INFLUENZA VACCINE

An apparatus and method for transdermally delivering an immunologically active agent comprising a delivery system having a microprojection member (or system) that includes a plurality of micrpojections (or array thereof) that are adapted to pierce through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers, the micrprojection member having a biocompatible coating disposed thereon that includes the immunologically active agent. Preferably, the biocompatible coating is formed from a vaccine coating formulation.

METHODS OF DEVICE-ASSISTED DRUG DELIVERY

This invention describes the simultaneous or sequential administration of therapeutic or diagnostic agents using different devices in combination with a chemical formulation that incorporates or uses vasomodulatory chemical agents as part of the drug delivery vehicle. Methods include the addition of various vasodilatory and vasoconstructive agents to enhance the systemic or localized tissue delivery of therapeutic or diagnostic agents delivered into a body through the use of an apparatus or device.

Compositions and methods for biological remodeling with frozen particle compositions

Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Block Copolymer For Intraperitoneal Administration Containing Anti-Cancer Agent, Micelle Preparation Thereof, And Cancer Therapeutic Agent Comprising The Micelle Preparation As Active Ingredient

To provide a therapeutic method using a water soluble, high molecular weight block polymer to enable that an intraperitoneally administered anti-cancer agent may maintain for a long-term retention in the abdominal cavity to enoughly exert the effect of the anti-cancer agent and reduce adverse side-effects thereof. A therapeutic agent as a micelle preparation, comprising a copolymer having a hydrophilic polymeric moiety and a polycarboxylic acid derivative moiety; and an anti-cancer agent bonding to or encapsulated in the copolymer, wherein the micelle preparation may exhibit sustained drug release capability, and enables an extension of a retention time period of the anti-cancer agent in an abdominal cavity, is provided. A superior life-prolonging effect was found in an intraperitoneal administration mouse model compared with a case in which only an encapsulated drug is administered, and thus the present invention was completed accordingly.

Drug delivery devices and methods with collimated gas stream and release-activatable tape

Drug delivery devices and methods are provided for delivering a substance into a human or animal tissue. The device includes a gas source comprising a gas or capable of selectively producing a gas. The device also includes a drug source positioned and configured to release a drug into the gas. The drug source includes a release-activatable tape having the drug disposed thereon. The device also includes a first collimator fluidly connected with the gas source. The first collimator, which has an inlet end and an outlet end, is adapted to form a collimated gas stream comprising the drug in the gas.

Pharmaceutical compositions comprising attenuated plasmodium sporozoites and glycolipid adjuvants

Disclosed herein are pharmaceutical compositions comprising Plasmodium sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range Plasmodium and analogues of α-galactosylceramide (α-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided.

Device having array provided with fine protrusions

An array 1 provided with microprotrusions comprises a base 2 and tapered microprotrusions 3 each disposed on the base 2 and tapering down toward the tip from the bottom. Letting a distance from the tip to the bottom on an arbitrary side of each microprotrusion 3 as a and letting the length of a second line segment prepared by projecting a first line segment representing the distance a onto the base 2 as b, a relationship of 1.0<(a/b)≦7.5 holds.

Tricyclic Compounds and Methods of Making and Using Same

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

AQUEOUS FORMULATIONS FOR COATING MICRONEEDLE ARRAYS

Aqueous formulations that include at least one active pharmaceutical ingredient; and at least one excipient, wherein the aqueous formulation has a viscosity of from 500 to 30,000 centipoise when measured at a shear rate of 100 sand a temperature of 25° C.; a surface tension that is not greater than 60 dynes/cm when measured under ambient conditions; or a contact angle on a medical grade polymeric material of 50° or greater when measured under ambient conditions. Methods of coating and coated microneedle arrays using the aqueous formulations are also disclosed herein. 1. A method of forming a coated microneedle array comprisingproviding a microneedle array comprising a microneedle substrate and a plurality of microneedles;providing a coating substrate;{'sup': '−1', 'providing an aqueous formulation comprising at least one active pharmaceutical ingredient and at least one excipient, wherein the aqueous formulation has a viscosity of from 500 to 30,000 centipoise when measured at a shear rate of 100 sand a temperature of 25° C.;'}applying the aqueous formulation to the coating substrate;bringing the aqueous formulation and the microneedles of the microneedle array into contact with one another;removing the microneedles from the aqueous formulation; andallowing at least a portion of the aqueous formulation to evaporate.2. The method according to claim 1 , wherein the viscosity is from 500 to 10 claim 1 ,000 centipoise when measured at a shear rate of 100 sand a temperature of 25° C.3. The method according to claim 1 , wherein the viscosity is from 500 to 8 claim 1 ,000 centipoise when measured at a shear rate of 100 sand a temperature of 25° C.4. The method according to claim 1 , wherein the aqueous formulation has a contact angle on a medical grade polymeric material of 50° or greater when measured under ambient conditions.5. The method according to claim 1 , wherein the aqueous formulation has a contact angle on a medical grade polymeric material of 65° or greater ...

Micro-needle coating method

Since all methods of applying a drug liquid to a tip portion of a microneedle are application of the drug liquid in an open system, evaporation of the solvent from the drug liquid is unavoidable, such that the concentration of the drug liquid changes easily, and a large amount of the drug liquid is necessary. The invention provides a method of applying a drug to a pin-frog-shaped microneedle by using a small amount of the solution and without variation of the concentration of the drug liquid. A member having plural grooves is produced, and one end thereof is immersed in a drug liquid tank to fill the grooves with the drug liquid. The drug can be uniformly applied to a tip portion of the microneedle by setting the pin-frog-shaped microneedle to pass through the drug liquid in the grooves.

Methods for Treating Skin Aging and Scars

It is to provide a method for treating skin aging, or a method for treating skin scar that can exert a sufficient effect. A composition for treating skin aging comprising bFGF for treating aging of the skin that is administered intradermally or subcutaneously, or a composition for treating skin scar comprising bFGF for treating scar of skin that is administered intradermally or subcutaneously is utilized. Preferred examples of aging of skin include skin wrinkle, pigmented spot, sagging skin, rough skin, skin thinning, decrease of skin viscoelasticity, etc., and preferred examples of scar include keloid, hypertrophic scar, scar contracture, etc. 1. A method for treating a skin scar comprising administering bFGF intradermally or subcutaneously to a site of the scar that is a target of treatment or a surrounding part thereof.2. The method according to claim 1 , wherein the scar is one or more selected from the group consisting of keloid claim 1 , hypertrophic scar claim 1 , scar contracture claim 1 , depressed scar and atrophic scar.3. The method according to claim 1 , wherein the scar is caused by external injuries.4. The method according to claim 1 , wherein the scar is caused by surgical procedures.5. The method according to claim 1 , wherein the dosage amount of bFGF is 0.1 μg to 1 mg per 1 cmof skin that is a target of treatment.6. The method according to claim 1 , wherein the intradermal or subcutaneous administration is conducted once or plural times.7. The method according to claim 1 , wherein the intradermal or subcutaneous administration is administration by injection. This application is a Divisional of U.S. patent application Ser. No. 13/233,315, filed Sep. 15, 2011, which is a Continuation of U.S. patent application Ser. No. 12/934,299 filed Sep. 24, 2010, now abandoned, which is a National Stage Entry of PCT/JP2009/001303 filed Mar. 24, 2009. This application also claims priority to JP2008-085952 filed Mar. 28, 2008. The entire contents of these ...

Percutaneous application system

The invention relates to an application system for the transepidermal surface administration of medications, said system comprising a container ( 1 ) accommodating a sprayable, active agent-containing composition, a propellant gas source ( 3 ) for pressurized gas consisting of at least 25% v/v of oxygen, and a spraying device ( 2 ), wherein container ( 1 ), propellant gas source ( 3 ), and spraying device ( 2 ) are flow-connected with each other in such a manner that the propellant gas atomizes the sprayable composition and, when the spraying device ( 2 ) is actuated, forces it out of the spraying device ( 2 ), with the composition being forced out of the spraying device ( 2 ) in the form of a conical spray jet at an exit velocity of ≧100 m/s. With the help of the inventive application system active agents can be effectively administered via the skin without causing injury to the skin. As a result of the high exit velocity the penetration rate is especially favorable even when larger molecules are introduced.

Method Of Drug Delivery For PTH, PTHrP And Related Peptides

The present invention provides compositions, devices, methods and processes related to the intradermal delivery of PTHrP and PTHrP analogues, particularly [Glu, Leu, Aib, Lys]hPTHrP(1-34)NH. 190-. (canceled)91. A method of treating post-menopausal osteoporosis comprising administering [Glu , Leu , Aib , Lys]hPTHrP(1-34)NHto a woman in need thereof said administering comprising contacting the skin of said woman with a microprojection arraywherein said microprojection array comprises a backing material with a plurality of attached microprojections and a coating on at least a part of one of said microprojections,{'sup': 22,25', '23,28,31', '29', '26,30, 'sub': '2', 'wherein said coating comprises [Glu, Leu, Aib, Lys]hPTHrP(1-34)NH, and'}{'sub': max', '2, 'sup': 22,25', '23,28,31', '29', '26,30, 'wherein said contacting occurs with sufficient force to cause penetration of one or more of said microprojection members into the skin of said woman and wherein said administration results in Cplasma levels of [Glu, Leu, Aib, Lys]hPTHrP(1-34)NHof greater than 200 pg/mL.'}92. The method of wherein said administering results in Cplasma levels of [Glu claim 91 , Leu claim 91 , Aib claim 91 , Lys]hPTHrP(1-34)NHof greater than 300 pg/mL.93. The method of wherein said administering results in Cplasma levels of [Glu claim 91 , Leu claim 91 , Aib claim 91 , Lys]hPTHrP(1-34)NHof greater than 400 pg/mL.94. The method of wherein said administering results in Cplasma levels of [Glu claim 91 , Leu claim 91 , Aib claim 91 , Lys]hPTHrP(1-34)NHof greater than 500 pg/mL.95. The method of wherein the plasma Toccurs at less than one hour post-administration time.96. The method of wherein the plasma Toccurs at less than ½ hour post administration time.97144-. (canceled)145. The method of wherein said microprojection array comprises from about 85 μg to about 230 μg of [Glu claim 91 , Leu claim 91 , Aib claim 91 , Lys]hPTHrP(1-34)NH.146. The method of wherein said microprojection array comprises ...

Method Of Drug Delivery For PTH, PTHrP And Related Peptides

The present invention provides compositions, devices, methods and processes related to the intradermal delivery of PTHrP and PTHrP analogues, particularly [Glu, Leu, Aib, Lys]hPTHrP(1-34)NH. 1144-. (canceled)145. A method of a method of stimulating bone formation in a subject in need thereof comprising administering [Glu , Leu , Aib , Lys]hPTHrP(1-34)NHby contacting the skin of said subject with a microprojection array ,wherein said microprojection array comprises a backing material with a plurality of attached microprojections and a coating on at least a part of one of said microprojections,{'sup': 22,25', '23,28,31', '29', '26,30, 'sub': '2', 'wherein said coating comprises [Glu, Leu, Aib, Lys]hPTHrP(1-34)NH, and'}wherein said contacting occurs with sufficient force to cause penetration of one or more of said microprojections into the skin of said subject.146. The method of wherein said subject has osteopenia.147. The method of wherein said subject is characterized as having bone mineral density at one or more skeletal sites of more than 1 standard deviations below the norm.148. The method of wherein said subject is characterized as having bone mineral density at one or more skeletal sites of more than 2 standard deviations below the norm.149. The method of wherein said subject has osteoarthritis.150. The method of wherein said subject has a bone fracture.151. A method of wherein said bone fracture is selected from vertebral fracture claim 150 , femoral fracture claim 150 , and radial fracture.152. A method of wherein said bone fracture is a traumatic bone fracture.153. A method of wherein said bone fracture is a non-traumatic bone fracture.154. The method of wherein said administering is a once-daily administration.155. The method of wherein said microprojection array is left in place with one or more of said microprojections embedded in the skin after said contacting for a period of from about 3 seconds to about 10 minutes.156. The method of wherein said ...

Highly Concentrated Stable Meloxicam Solutions for Needleless Injection

A method for treating pain, inflammation, fever and respiratory complaints in mammals comprising administering by needleless injection to a mammal in need of such treatment an aqueous cyclodextrin-free solution of meloxicam containing a pharmacologically acceptable meloxicam salt of an organic or inorganic base. 1. A method for treating pain , inflammation , fever and respiratory complaints in mammals comprising administering by needleless injection to a mammal in need of such treatment a composition comprising:40 to 80 mg/ml meloxicam;a pharmacologically acceptable organic or inorganic base capable of forming a salt with the meloxicam and selected from the group consisting of meglumine, sodium, potassium and ammonium; anddisodium EDTA;wherein the solution is free of cyclodextrin.2. The method of claim 1 , wherein the administration of the composition is to a large farm animal in need of such treatment.3. The method of claim 1 , wherein the administration of the composition is to a mammal that is at least 50 kg and up to 750 kg.4. The method of claim 3 , wherein the solution is administered in a dosage range of from 0.2 to 1.0 mg of meloxicam/kg of bodyweight of the mammal.5. The method of claim 3 , wherein the mammal is suffering from at least one of acute mastitis claim 3 , diarrhea claim 3 , lameness claim 3 , and oncological indications.6. The method of claim 1 , wherein the solution has a pH of between 8.5 and 9.7. The method of claim 1 , wherein the solution comprises disodium EDTA in an amount such that the weight ratio of meloxicam to disodium EDTA is between 100:1 and 35:1.8. The method of claim 1 , wherein the solution further comprises:a polyethylene glycol;a polyoxyethylene-polypropylene copolymer; andethanol;wherein the solution is free of cyclodextrin, the solution has a pH of between 8.5 and 9, and the solution has a shelf-life after opening of 28 days or more.9. The method according to claim 1 , wherein the pharmacologically acceptable organic or ...

MICRONEEDLE DEVICES AND METHODS

A medical device, comprising: an array of microneedles, and a coating disposed on the microneedles, wherein the coating comprises: a local anesthetic selected from the group consisting of lidocaine, prilocalne, and a combination thereof; and a local anesthetic dose-extending component selected from the group consisting of alpha 1 adrenergic agonists, alpha 2 adrenergic agonists, and a combination thereof; wherein the local anesthetic is present in an amount of at least 1 wt-% based upon total weight of solids in the coating, and wherein the dose-extending component/local anesthetic weight ratio is at least 0.0001; a medical device, comprising an array of dissolvable microneedles, the microneedles comprising: a dissolvable matrix material; at least 1 wt-% of a local anesthetic selected from the group consisting of lidocaine, prilocalne, and a combination thereof; and a local anesthetic dose-extending component selected from the group consisting of alpha 1 adrenergic agonists, alpha 2 adrenergic agonists, and a combination thereof; wherein the dose-extending component/local anesthetic weight ratio is at least 0.0001, and wherein wt-% is based upon total weight of solids in all portions of the dissolvable microneedles which contain the local anesthetic; a method of extending a topically delivered local anesthetic dose in mammalian tissue using the devices; and methods of making the devices are provided. 1. A medical device , comprising:an array of microneedles, anda coating disposed on the microneedles, a local anesthetic selected from the group consisting of lidocaine, prilocalne, and a combination thereof; and', 'a local anesthetic dose-extending component selected from the group consisting of alpha 1 adrenergic agonists, alpha 2 adrenergic agonists, and a combination thereof;', 'wherein the local anesthetic is present in an amount of at least 1 wt-% based upon total weight of solids in the coating, and', 'wherein the dose-extending component/local anesthetic weight ...

MICRONEEDLE DEVICES AND METHODS

A medical device, comprising: an array of microneedles, and a coating disposed on the microneedles, wherein the coating comprises: a local anesthetic selected from the group consisting of lidocaine, prilocaine, and a combination thereof; and a local anesthetic dose-extending component selected from the group consisting of tetracaine, ropivacaine, bupivacaine, procaine and a combination thereof; wherein the local anesthetic is present in an amount of at least 1 wt-% based upon total weight of solids in the coating, and wherein the local anesthetic and dose-extending component are in a non-eutectic weight ratio; a medical device, comprising an array of dissolvable microneedles, the microneedles comprising: a dissolvable matrix material; at least 1 wt-% of a local anesthetic selected from the group consisting of lidocaine, prilocaine, and a combination thereof; and a local anesthetic dose-extending component selected from the group consisting of tetracaine, ropivacaine, bupivacaine, procaine and a combination thereof; wherein the local anesthetic and dose-extending component are in a non-eutectic weight ratio, and wherein wt-% is based upon total weight of solids in all portions of the dissolvable microneedles which contain the local anesthetic; a method of extending a topically delivered local anesthetic dose in mammalian tissue using the devices; and methods of making the devices are provided. 1. A medical device , comprising:an array of microneedles, anda coating disposed on the microneedles, a local anesthetic selected from the group consisting of lidocaine, prilocaine, and a combination thereof; and', 'a local anesthetic dose-extending component selected from the group consisting of tetracaine, ropivacaine, bupivacaine, procaine and a combination thereof;', 'wherein the local anesthetic is present in an amount of at least 1 wt-% based upon total weight of solids in the coating, and', 'wherein the local anesthetic and dose-extending component are in a non-eutectic ...

Block Copolymer For Intraperitoneal Administration Containing Anti-Cancer Agent, Micelle Preparation Thereof, And Cancer Therapeutic Agent Comprising The Micelle Preparation As Active Ingredient

To provide a therapeutic method using a water soluble, high molecular weight block polymer to enable that an intraperitoneally administered anti-cancer agent may maintain for a long-term retention in the abdominal cavity to enoughly exert the effect of the anti-cancer agent and reduce adverse side-effects thereof. A therapeutic agent as a micelle preparation, comprising a copolymer having a hydrophilic polymeric moiety and a polycarboxylic acid derivative moiety; and an anti-cancer agent bonding to or encapsulated in the copolymer, wherein the micelle preparation may exhibit sustained drug release capability, and enables an extension of a retention time period of the anti-cancer agent in an abdominal cavity, is provided. A superior life-prolonging effect was found in an intraperitoneal administration mouse model compared with a case in which only an encapsulated drug is administered, and thus the present invention was completed accordingly.

Transdermal pharmaceutical formulations for the treatment of multiple sclerosis

The present disclosure relates to the to the transdermal administration of THC and/or CBD and derivatives of these compounds, for the treatment and/or prevention and/or control of multiple sclerosis, multiple sclerosis-related muscle spasms, and pain and/or spasticity in multiple sclerosis.

INTRADERMAL JET INJECTION ELECTROPORATION DEVICE

An jet injection and electroporation device for use with an agent cartridge defining a volume containing a pre-measured dose of agent therein, the electroporation device including a housing having an axis extend therethrough, a nozzle at least partially positioned within the housing, and a cavity sized to receive at least a portion of the agent cartridge therein. The device also includes an array having a plurality of electrodes extending therefrom, a propulsion cartridge configured to operatively engage the cartridge when the agent cartridge is positioned within the cavity; and a power supply in electrical communication with the array. 1) An electroporation device for use with an agent cartridge defining a volume containing a pre-measured dose of agent therein , the electroporation device comprising:a housing having an axis extend therethrough;a nozzle at least partially positioned within the housing;a cavity sized to receive at least a portion of the agent cartridge therein, and wherein the nozzle is in fluid communication with the volume of the agent cartridge when the agent cartridge is positioned within the cavity;an array having a plurality of electrodes extending therefrom;a propulsion cartridge configured to operatively engage the agent cartridge when the agent cartridge is positioned within the cavity; anda power supply in electrical communication with the array.2) The electroporation device of claim 1 , wherein the propulsion cartridge is adjustable between an armed configuration and a deployed configuration claim 1 , and wherein the propulsion cartridge is biased toward the deployed configuration.3) The electroporation device of claim 2 , wherein adjusting the propulsion cartridge from the armed configuration to the deployed configuration mechanically expels a portion of the pre-measured dose of agent through the nozzle.4) The electroporation device of claim 2 , further comprising a trigger claim 2 , and wherein the trigger is adjustable between a first ...

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.

Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines and cluster headaches

Compositions, devices and methods employing therapeutic concentrations of a triptan for treatment of migraine are described.

In vivo efficacy of ny-eso-1 plus adjuvant

The invention relates to the discovery that administration of NY-ESO-1 protein, in combination with a saponin based adjuvant leads to an unexpectedly strong immune response against NY-ESO-1 expressing cells. Preferably, the combination is administered intramuscularly.

MICRONEEDLE COATING COMPOSITION AND MICRONEEDLE DEVICE

Disclosed is a microneedle coating composition comprising a Japanese encephalitis vaccine antigen, a basic amino acid, and an acid, wherein the mole number of the acid for one mole of the basic amino acid is larger than 1/(N+1) and less than 2, where N represents the valence of the acid. 1. A microneedle coating composition comprising:a Japanese encephalitis vaccine antigen;a basic amino acid; andan acid, whereina mole number of the acid for one mole of the basic amino acid is larger than 1/(N+1) and less than 2, where N represents a valence of the acid.2. The microneedle coating composition according to claim 1 , wherein the acid has a melting point of 40° C. or more.3. The microneedle coating composition according to claim 1 , wherein the acid is at least one acid selected from the group consisting of phosphoric acid claim 1 , lactic acid claim 1 , benzoic acid claim 1 , maleic acid claim 1 , citric acid claim 1 , tartaric acid claim 1 , succinic acid claim 1 , ascorbic acid claim 1 , and aspartic acid.4. The microneedle coating composition according to claim 1 , wherein the basic amino acid is arginine.5. The microneedle coating composition according to claim 1 , comprising lysine or lysine hydrochloride.6. A microneedle device comprising:a microneedle; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a coating layer formed from the microneedle coating composition according to on the microneedle.'}7. The microneedle device according to claim 6 , whereinthe coating layer is formed on a tip portion of the microneedle.8. The microneedle coating composition according to claim 3 , wherein the basic amino acid is arginine.9. The microneedle coating composition according to claim 8 , comprising lysine or lysine hydrochloride.10. A microneedle device comprising:a microneedle; and{'claim-ref': {'@idref': 'CLM-00008', 'claim 8'}, 'a coating layer formed from the microneedle coating composition according to on the microneedle.'}11. A microneedle device comprising:a ...

Microneedle-mediated delivery of tolerogenic immunotherapeutics

Methods, compositions and kits are provided that include microneedles coated with or formed of antigens to which immune tolerance is desired. Use of the microneedles is demonstrated using glatiramer acetate and animal models of multiple sclerosis. Dose sparing and beneficial polarization of immune responses are demonstrated.

MODULATORS OF COMPLEMENT ACTIVITY

The present disclosure provides methods of treating paroxysmal nocturnal hemoglobinuria (PNH) in subjects with varying exposure to eculizumab by administering R5000. The methods include methods of switching subjects from treatment with eculizumab to R5000. 1. A method of treating paroxysmal nocturnal hemoglobinuria (PNH) in a subject , wherein the subject has not been previously treated with eculizumab , the method comprising daily self-administration of R5000 by the subject by subcutaneous injection for a period of at least 12 weeks.2. The method of claim 1 , wherein R5000 is administered using a pre-loaded syringe.3. The method of claim 1 , wherein R5000 is administered at a dose of from about 0.1 mg/kg to about 0.3 mg/kg.4. The method of claim 1 , wherein an initial loading dose of R5000 is administered claim 1 , the initial loading dose comprising about 0.3 mg/kg of R5000.5. The method of claim 1 , wherein R5000 is administered at an initial treatment dose of about 0.1 mg/kg for about 2 weeks and a modified treatment dose of about 0.3 mg/kg thereafter claim 1 , wherein subject lactate dehydrogenase (LDH) levels are greater than or equal to 1.5 times the upper limit normal (ULN) level during the first two weeks of R5000 administration.6. The method of claim 1 , wherein R5000 is administered for at least 24 weeks.7. The method of claim 1 , wherein R5000 is administered for at least 48 weeks.8. The method of claim 1 , wherein percent hemolysis levels in subject samples are reduced by about 90% or more after 1 week of R5000 administration.9. The method of claim 1 , wherein subject LDH levels are less than four times the ULN level for greater than 50% of the R5000 administration period.10. The method of claim 1 , wherein risk of breakthrough hemolysis is reduced.11. The method of claim 1 , wherein the subject is converted from a transfusion-dependent subject to a transfusion-independent subject during the R5000 administration period.12. The method of claim 1 , ...

Photodynamically active organosilica nanoparticles and medical uses thereof

The present application provides an organosilica nanoparticle comprising: (a) a photosensitizer for photodynamic therapy covalently incorporated therein; and (b) optionally, at least one agent encapsulated therein, as well as a pharmaceutical composition comprising said organosilica nanoparticle. Also provided herein are said organosilica nanoparticle or pharmaceutical composition for use as a medicament or in the treatment of a disease, disorder, or condition. More specifically, provided is a method for treating a disease, disorder, or condition in a subject using said aid organosilica nanoparticle or pharmaceutical composition.

HYALURONIC ACID-BASED GELS INCLUDING LIDOCAINE

Disclosed herein are cohesive soft tissue fillers, for example, dermal and subdermal fillers, based on hyaluronic acids and pharmaceutically acceptable salts thereof. In one aspect, hyaluronic acid-based compositions described herein include a therapeutically effective amount of at least one anesthetic agent, for example, lidocaine. The present hyaluronic acid-based compositions including lidocaine have an enhanced stability and cohesivity, relative to conventional compositions including lidocaine, for example when subjected to sterilization techniques or when stored for long periods of time. Methods and processes of preparing such hyaluronic acid-based compositions are also provided. 1. A device for restoring fat loss-related tissue volume loss in the face , the device comprising:a syringe;a sterile viscoelastic gel contained in the syringe, the gel comprising hyaluronic acid crosslinked with 1,4-butanediol diglycidyl ether (BDDE), and including an amount of lidocaine.2. The device of wherein the syringe has an internal volume of about 0.4 mL to about 3 mL.3. The device of wherein the syringe has an internal volume between about 0.5 mL and about 1.5 mL.4. The device of wherein the syringe has an internal volume between about 0.8 mL and about 2.5 mL.5. The device of wherein the amount of lidocaine present in the gel is 0.3%.6. A device for restoring fat loss-related tissue volume loss in the face claim 2 , the device comprising:a syringe having an internal volume between about 0.8 mL and about 2.5 mL;a sterile viscoelastic gel contained in the syringe, the gel comprising hyaluronic acid crosslinked with 1,4-butanediol diglycidyl ether (BDDE), and including 0.3% lidocaine. This application is a continuation of U.S. patent application Ser. No. 14/754,504, filed on Jun. 29, 2015, which is a continuation of U.S. patent application Ser. No. 14/242,752, filed on Apr. 1, 2014, which is a continuation of U.S. patent application Ser. No. 13/419,079, filed Mar. 13, 2012, now ...

MODIFIED THERAPEUTIC AGENTS AND COMPOSITIONS THEREOF

Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof. 1. A modified therapeutic agent (mTA) comprising a therapeutic agent , a first half-life extending molecule , and a first staple , wherein the therapeutic agent is a modified or unmodified therapeutic peptide that is covalently attached to the first staple via two amino acid residues on the modified or unmodified therapeutic peptide; each of the two amino acid residues has an amine-containing sidechain for attachment to the first staple through the formation of an amide; the first half-life extending molecule is covalently attached to the first staple; and the half-life of the mTA is longer than the half-life of the unmodified therapeutic peptide alone.2. The mTA of claim 1 , wherein the first half-life extending molecule comprises a lipid claim 1 , a polyglycol region claim 1 , or a combination thereof.3. The mTA of claim 2 , wherein the first half-life extending molecule comprises a lipid.4. The mTA of claim 2 , wherein the first half-life extending molecule comprises a lipid and a polyglycol region.5. The mTA of claim 2 , wherein the first half-life extending molecule comprises a polyglycol region.6. The mTA of any one of - claim 2 , wherein the lipid is selected from a group consisting of sterols claim 2 , sterol derivatives claim 2 , bile acids claim 2 , vitamin E derivatives claim 2 , fatty di-acids claim 2 , fatty acids claim 2 , fatty amides claim 2 , fatty amines claim 2 , and fatty alcohols claim 2 , and derivatives thereof.7. The mTA of any one of claim 2 , claim 2 , and claim 2 , wherein the polyglycol region comprises one or more polyethylene glycol units claim 2 , polypropylene glycol units claim 2 , or polybutylene glycol units claim 2 , or a ...

MICRONEEDLE ARRAYS FOR ACTIVE AGENT DELIVERY

The present invention provides for microneedle arrays and related systems and methods. Particularly, microneedle arrays that are configured to deliver active agents, including nucleic acids and vaccines, are provided. Additional related methods of vaccinating and minimizing the amount of vaccine necessary for effective inoculation are also provided. 1. A method of providing visual verification of microneedle placement in a skin surface , comprising ,providing a microneedle array having a plurality of microneedles attached thereto, said microneedles including an indicatorapplying the microneedle array to a skin surface of a subject such that the microneedles are embedded into the skin surface,verifying successful application of the microneedles through observation of the indicator's presence in the skin.2. The method of claim 1 , wherein the indicator is a dye.3. The method of claim 1 , wherein the indicator forms an image on the skin of the subject.4. The method of claim 1 , wherein the indicator is visible when light is shown onto the microneedles.5. The method of claim 1 , wherein the indicator is a fluorophore.6. The method of claim 5 , wherein the flourophore includes fluorescein.7. A system for delivering siRNA to a subject claim 5 , comprising:an amount of a self-delivering siRNA a base, and', 'a plurality of microneedles attached to the base, said microneedles comprising a bioabsorbable/biodegradable material and being and configured to be detached from the base after being embedded in a skin surface., 'a microneedle array, said microneedle array comprising'}8. The system of claim 7 , wherein the microneedles include a plurality of longitudinal channels.9. The system of claim 8 , wherein the self-delivering siRNA are present in the longitudinal channels.10. The system of claim 7 , wherein the bioabsorbable/biodegradable material is selected from the group consisting of polyvinyl alcohol claim 7 , polyvinylpyrrolidone claim 7 , chitin claim 7 , carboxymethyl ...

PROPHYLACTIC NORMALIZATION OF CUTANEOUS WOUND REPAIR

The present invention relates to methods of inhibiting scar formation in a skin wound as well as methods of promoting tissue regeneration in a skin wound in a subject in need thereof comprising administering in or near said wound an effective amount of one or more neurotoxins. 1. A method of decreasing scar formation in a skin wound in a subject in need thereof comprising administering to said subject in or near said wound an effective amount of one or more neurotoxins , wherein said amount is sufficient to decrease formation of scar tissue and insufficient to produce muscular paralysis in said wound.2. A method of promoting tissue regeneration in a skin wound in a subject in need thereof comprising administering to said subject in or near said wound an effective amount of one or more neurotoxins , wherein said amount is sufficient to promote regeneration of skin morphology in said wound characteristic of dermis in uninjured skin.3. The method of or wherein said neurotoxin is botulinum neurotoxin or a derivative thereof.4. The method of wherein the botulinum neurotoxin is selected from the group consisting of botulinum neurotoxin A claim 3 , B claim 3 , C claim 3 , D claim 3 , E claim 3 , F claim 3 , and G.5. The method of claim 4 , wherein said botulinum neurotoxin is botulinum neurotoxin A or a derivative thereof.6. The method of wherein the botulinum neurotoxin A is selected from the group consisting of incobotulinumtoxinA claim 5 , onabotulinumtoxinA claim 5 , and abobotulinumtoxinA or a derivative thereof.7. The method of claim 4 , wherein said botulinum neurotoxin is botulinum neurotoxin B or a derivative thereof.8. The method of wherein the botulinum neurotoxin B is rimabotulinumtoxinB or a derivative thereof.9. The method of or wherein said method further comprises administering one or more agents in addition to the neurotoxin in or near said wound.10. The method of wherein said agent is administered prior to administration of said neurotoxin claim 9 , after ...

SKIN MICROENVIRONMENT TARGETED DELIVERY FOR PROMOTING IMMUNE AND OTHER RESPONSES

Methods are provided for promoting, reducing, or desensitizing various immune responses by delivery of sub-immunogenic doses of an allergen, alone or with other agents, or by delivery of antigens and adjuvants to a cutaneous microenvironment of a subject. Microneedle arrays can be used in connection with this delivery. 1. A method for reducing or desensitizing an immune response of a subject in need thereof , the method comprising:administering one or more sub-immunogenic or non-immunogenic doses of an allergen/antigen to a cutaneous microenvironment of the subject, and thereby reducing or desensitizing the immune response of the subject.2. The method of claim 1 , wherein administering the one or more sub-immunogenic or non-immunogenic doses of the allergen comprises the use of one or more microneedle arrays containing the allergen/antigen therein.3. The method of claim 1 , further comprising:administering one or more immune suppressants and/or tolerizing agents to the cutaneous microenvironment.4. The method of claim 3 , wherein administering the one or more sub-immunogenic or non-immunogenic doses of the allergen/antigen and the one or more immune suppressants and/or tolerizing agents comprises the use of one or more microneedle arrays containing the allergen/antigen and the one or more immune suppressants and/or tolerizing agents therein.5. The method of claim 3 , wherein the one or more immune suppressants and/or tolerizing agents comprises at least one selected from the group of NKR antagonists claim 3 , Foxo3 inhibitors claim 3 , and Anti-TNF Ab.6. The method of claim 3 , wherein at least two immune suppressants and/or tolerizing agents are administered.7. The method of claim 1 , wherein the subject is at risk of acquiring or having at least one of the following conditions or disorders: contact dermatitis claim 1 , atopic dermatitis claim 1 , psoriasis claim 1 , immunobullous diseases claim 1 , inflammatory skin disorders claim 1 , Type I-V hypersensitivity ...

THREE-DIMENSIONAL MICROFLUIDICS DEVICES FOR THE DELIVERY OF ACTIVES

A transdermal delivery device includes a film having first and second outwardly facing major surfaces; at least one liquid reservoir contained within the film; at least one microfluidic channel having a transverse dimension between about 100 nm and 0.5 mm disposed within the film and in fluid communication with the at least one liquid reservoir; and at least one outlet port associated with at least one microneedle operatively connected to the first outwardly facing major surface of the film in fluid communication with the at least one microfluidic channel. 1. A transdermal delivery device comprising:(a) film having first and second outwardly facing major surfaces;(b) at least one liquid reservoir disposed within the film;(c) at least one microfluidic channel (having a major transverse dimension between about 100 nm and 0.5 mm) disposed within the film and in fluid communication with the at least one liquid reservoir;(d) at least one outlet port operatively connected to the first outwardly facing major surface of the film in fluid communication with the at least one microfluidic channel;(e) at least one microneedle in fluid communication with the at least one outlet port.2. The transdermal delivery device of further comprising a sensor.3. The transdermal delivery device of wherein the sensor detects an amount of a liquid delivered over time.4. The transdermal delivery device of wherein the at least one liquid reservoir disposed within the film contains Cetirizine HCl or a pharmaceutically equivalent Cetirizine compound in a pharmaceutically acceptable solvent.5. The transdermal delivery device of comprising a total amount of Cetirizine HCl or a pharmaceutically equivalent Cetirizine compound of between about 70 mg and about 100 mg.6. The transdermal delivery device of wherein the at least one liquid reservoir disposed within the film contains an analgesic compound in a pharmaceutically acceptable solvent.7. The transdermal delivery device of wherein the analgesic is ...

TRANSDERMAL DELIVERY OF HIGH VISCOSITY BIOACTIVE AGENTS

A device and method for delivery of a bioactive agent across a dermal barrier of a subject. The device including a microneedle with a channel and a plurality of nanostructures and microstructures located on the microneedle. The nanostructures and microstructures are arranged in a fractal-like pattern. A reservoir is in fluid communication with the channel and contains a composition having a viscosity of greater than about 5 centipoise and comprising a bioactive agent. The method includes penetrating a stratum corneum of the subject with the microneedle and transporting a composition through the microneedle at a rate of greater than about 0.4 mg/hr/cm2 based upon the surface area of the microneedle. 1. A device for delivery of a bioactive agent across a dermal barrier , the device comprising:a microneedle and a plurality of nanostructures and microstructures located on the microneedle, the nanostructures and microstructures being arranged in a fractal-like pattern, wherein the microneedle further contains a channel; anda reservoir that is in fluid communication with the channel of the microneedle and that contains a composition having a viscosity of greater than about 5 centipoise and comprising a bioactive agent.2. The device according to claim 1 , wherein the composition includes the bioactive agent in a concentration of greater than about 5 mg/mL.3. The device according to claim 2 , wherein the composition includes the bioactive agent in a concentration of from about 35 mg/mL to about 500 mg/mL.4. The device according to claim 1 , wherein the bioactive agent has a molecular weight of greater than about 100 kDa.5. The device according to claim 1 , wherein the bioactive agent is a protein therapeutic.6. The device according to claim 1 , the composition further comprising one or more pharmaceutically acceptable excipients.7. The device according to claim 6 , wherein the pharmaceutically acceptable excipient comprises a solvent claim 6 , a penetration enhancer claim 6 ...

Fgf-21 conjugate formulations

The present application provides pharmaceutical formulations comprising PEGylated FGF-21, e.g., a FGF-21 conjugate, and one or more stabilizers such as the chelator DPTA. The formulations can be can further stabilized by including a surfactant such as polysorbate 80 and/or adjusting the pH to about 7.1. Also provided are methods of manufacture, methods of treatment, and kits.

ALUM-CONTAINING COATING FORMULATIONS FOR MICRONEEDLE VACCINE PATCHES

Compositions for coating microneedles with aluminum-adjuvanted vaccines are provided comprising an aluminum-containing wet gel suspension selected from aluminum hydroxide wet gel suspension and aluminum phosphate wet gel suspension; a vaccine in an amount effective to stimulate an immune response in a mammal; a sugar, sugar alcohol, or combinations thereof; and a thickener. Some embodiments of the compositions have a viscosity of 500 to 30,000 cps when measured at 100 sand temperature of 25 C. Microneedle devices coated with the compositions, as well as methods of forming the compositions and coating the microneedles, and methods of maximizing the aluminum content of vaccine-coated microneedle arrays are also provided. 1. A composition comprising:an aluminum-containing wet gel suspension selected from aluminum hydroxide wet gel suspension and aluminum phosphate wet gel suspension;a vaccine in an amount effective to stimulate an immune response in a mammal;a sugar, sugar alcohol, or combinations thereof; anda thickener;{'sup': '−1', 'wherein the composition has a viscosity of 500 to 30,000 cps when measured at 100 sand temperature of 25° C.'}2. The composition of claim 1 , comprising a sugar claim 1 , wherein the sugar is selected from raffinose claim 1 , stachyose claim 1 , sucrose claim 1 , trehalose claim 1 , apiose claim 1 , arabinose claim 1 , digitoxose claim 1 , fucose claim 1 , fructose claim 1 , galactose claim 1 , glucose claim 1 , gulose claim 1 , hamamelose claim 1 , idose claim 1 , lyxose claim 1 , mannose claim 1 , ribose claim 1 , tagatose claim 1 , xylose claim 1 , cellobiose claim 1 , gentiobiose claim 1 , lactose claim 1 , lactulose claim 1 , maltose claim 1 , melibiose claim 1 , primeverose claim 1 , rutinose claim 1 , scillabiose claim 1 , sophorose claim 1 , turanose claim 1 , and vicianose.3. The composition of claim 2 , wherein the sugar is a non-reducing sugar.4. (canceled)5. The composition of claim 1 , comprising a sugar alcohol claim 1 , ...

IMMUNOTHERAPEUTIC CONSTRUCTS AND METHODS OF THEIR USE

Disclosed herein are immunotherapeutic constructs comprising a delivery particle, at least one adjuvant, and one or more therapeutic agents/compounds that cause antigen release and/or modulate immunosuppressive tumor microenvironment. These immunotherapeutic constructs create adaptive immunity or anti-cancer immune response(s) that can be used, for instance, to prevent and treat broad types of cancer. Further disclosed are uses of the immunotherapeutic constructs, including to prevent and treat cancer in humans and animals. 1. An immunotherapeutic construct comprising:a delivery system comprising a mesoporous silica nanoparticle;an siRNA that inhibits expression or an activity of STAT3; andan adjuvant comprising a CpG oligonucleotide, wherein the immunotherapeutic construct does not comprise a tumor-specific antigen or ovalbumin.2. The immunotherapeutic construct of claim 1 , wherein the mesoporous silica nanoparticle is coated with cross-linked polyethyleneimine and polyethylene glycol.3. The immunotherapeutic construct of claim 1 , wherein the CpG oligonucleotide is CpG ODN 7909.4. The immunotherapeutic construct of claim 1 , wherein the mesoporous silica nanoparticle has a size of about 30-80 nm.5. The immunotherapeutic construct of claim 1 , having a hydrodynamic size of about 80 nm to 200 nm.6. The immunotherapeutic construct of claim 1 , wherein the siRNA is 0.5 to 10% by weight of the immunotherapeutic construct.7. The immunotherapeutic construct of claim 1 , wherein the adjuvant is 0.5 to 20% by weight of the immunotherapeutic construct.8. A composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the immunotherapeutic construct of ; and'}at least one pharmaceutically acceptable carrier, excipient, diluent, or mixture thereof.9. A method of treating a subject diagnosed as having a hyperproliferative disease or condition or having a high-risk of developing such disease or condition claim 8 , comprising administering to the subject an ...

Microneedle Immunotherapeutic Multi-Component System and a Method for Vaccination

A dissoluble microneedle drug delivery system includes a fixation component having an opening window area, and at least two replaceable and/or dissoluble inner matrices fitting into the window area one after another. The fixation component comprises an array of microneedles attached on its base, at least part of the microneedles being configured to fix the delivery system onto skin. The first inner matrix comprises a multitude of microneedles attached on its base, at least part of the microneedles configured to prepare the skin to vaccination by the subsequent second inner matrix. The second inner matrix is a vaccine/immunization matrix configured to replace the first inner matrix and comprising an array of microneedles attached on its base, at least part of the microneedles configured to deliver a vaccination. The system may include a microchannel network within at least one inner matrices for delivery of components regulating dissolution of the microneedles. 1. A dissoluble microneedle drug delivery system , comprising:an outer microneedle matrix, and the outer microneedle matrix optionally mounted on a fixation frame and having an opening window in its center, and having a microneedle array affixed on its base, the microneedle array comprising microneedles of different lengths such that the longest microneedles are located on outer edges of the outer microneedle matrix, and the shorter microneedles are located around the opening window area, the longest microneedles configured to be used for fixation of the matrix onto the skin and additionally for delivery of an adjuvant, and the shorter microneedles being configured to be used for adjuvant preparation of the skin;', 'the first inner matrix fitting into the opening window area and having a microneedle array affixed onto its base, the microneedle array comprising a multitude of dissoluble microneedles containing skin preparation components and being configured to prepare skin underneath the matrix for vaccination ...

Microneedle sheet

The microneedle sheet according to an embodiment comprises a plurality of microneedles formed on a sheet generally along a main surface of the sheet; a bending resistance of the sheet as measured in accordance with a 45° cantilever method defined by JIS L 1096:2010 is 4.2 cm to 12.5 cm; and a material of the sheet is a biodegradable polymer. The microneedles rise from the main surface when the sheet is bent, and the raised microneedles pierce the skin.

MICRONEEDLES AND COMPOSITIONS FOR SKIN AUGMENTATION

The present invention provides microneedles for administration of biocompatible materials effective in augmentation of skin or other skin treatments, and applicators comprising such microneedles. In particular, the microneedles and applicators of the present invention are aimed at filling the undesired lines, wrinkles, depressed scars and folds of a subject's facial and neck skin and restoring youthful fullness to the skin. 2. The microneedle of claim 1 , wherein the shape of the cross-section area of the rod section claim 1 , the tip section and the base section is selected from: rectangular claim 1 , triangular claim 1 , circular claim 1 , oval claim 1 , polygonal claim 1 , and any combination thereof.3. The microneedle of claim 1 , wherein the at least one cavity comprises the biocompatible medical composition claim 1 , and wherein the biocompatible medical composition or at least part of the biocompatible medical composition is solid and/or semi-solid at room temperature and is configured to be released from the cavity/ies to the dermis and/or hypodermis upon contact with liquid in the dermis layer and/or hypodermis layer.4. The microneedle of claim 3 , wherein at least one of the following holds true:the biocompatible medical composition is configured to at least partially separate from the cavity and the microneedle, when in dermis and/or hypodermis environment;biocompatible medical composition comprises at least one of: skin augmentation material, botulinum composition, medical pigment composition, steroids and any combination thereof; at least one of: skin augmenting material, botulinum material, medical pigment material, steroids, and any combination thereof;', 'at least one dispersant material, configured to disperse the at least one of: skin augmenting material, botulinum material, medical pigment material, steroids upon contact with the dermis layer and/or the hypodermis layer and any combination thereof; and', 'at least one dispersant material, ...

CATIONIC LIPIDS AND TRANSFECTION METHODS

The present invention relates in part to novel cationic lipids and their use, e.g., in delivering nucleic acids to cells. 2. The compound of claim 1 , wherein n is 2-15.3. The compound of claim 1 , wherein n is 2-12.12. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier or excipient.13. A lipid aggregate comprising the compound of .14. The lipid aggregate of claim 13 , wherein the lipid aggregate does not comprise one or more additional lipids or polymers.15. The lipid aggregate of claim 13 , further comprising a nucleic acid claim 13 , selected from a DNA or RNA molecule. The present application claims priority to U.S. patent application Ser. No. 16/746,279, filed on Jan. 17, 2020, U.S. Provisional Application No. 62/870,245, filed on Jul. 3, 2019, U.S. Provisional Application No. 62/880,435, filed on Jul. 30, 2019, and U.S. Provisional Application No. 63/023,654, filed on May 12, 2020, the contents of which are herein incorporated by reference in their entireties.The present invention relates, in part, to various novel lipids, including methods, compositions, and products for delivering nucleic acids to cells.The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jul. 3, 2020, is named FAB-012US_ST25.txt and is 1,441,638 bytes in size.Lipid-based materials, such as liposomes, are used as biological carriers for pharmaceutical and other biological applications, e.g., to introduce agents into cultured cell lines. Lipids are commonly used to deliver nucleic acids to cells in vitro under low-serum or serum-free conditions, for instance in transfection. However, serum components inhibit the activity of many lipids, limiting their use in the presence of serum, both in vitro and in vivo. Improved lipid delivery systems, e.g., to achieve higher levels of transfection both in vitro and ...

Method and Device for Manufacturing Dissolving Microneedle

A method and a device for manufacturing dissolving microneedle, wherein the method comprises manufacturing a mold with a plurality of microporous cavities, and manufacturing a polymer solution to be sprayed into the microporous cavity by a high pressure spraying device to enable the sprayed solution to fill in each microporous cavity. After the dryness of the solution, a microneedle is extracted from the mold. The process for manufacturing the microneedle is without vacuum pumping or any load of centrifugal force, and the process is simple and the excellent rate is high. 1. A method for manufacturing dissolving microneedle , comprising manufacturing a microneedle mold , said microneedle mold has a plurality of microporous cavities , wherein a polymer solution is sprayed into the microporous cavity by a high pressure spraying device to enable the polymer solution to fill into each of the microporous cavities; and the solidified microneedle are extracted from the microneedle mold after the dryness of polymer solution.2. The method for manufacturing dissolving microneedle according to claim 1 , wherein said polymer solution sprayed into the microporous cavity by the high pressure spray device comprises the atomized polymer solution sprayed into the microporous cavity by a high pressure atomizing device.3. The method for manufacturing dissolving microneedle according to claim 2 , wherein the particle size of said atomized polymer solution sprayed by the high pressure atomizing device ranges from 0.1 to 100 micrometers.4. The method for manufacturing dissolving microneedle according to claim 1 , wherein said polymer solution sprayed into the microporous cavity by the high pressure spray device comprises the droplets of the polymer solution sprayed to the microporous cavity by the high pressure spotting device.5. The method for manufacturing dissolving microneedle according to claim 4 , wherein the particle size of said droplets of the polymer solution sprayed by the high ...

INACTIVATED WHOLE VIRION VACCINE-CONTAINING MICRONEEDLE ARRAY PREPARATION AND METHOD FOR ADMINISTERING THE SAME

Provided is a microneedle. The microneedle array includes a needle portion, which contains an inactivated whole virion influenza vaccine, and a sheet portion. Also provided is an administration method in which the microneedle array is administered and then administered secondly after an interval of equal to or greater than 24 hours and less than 2 months. 1. A microneedle array comprising:a needle portion containing an inactivated whole virion influenza vaccine; anda sheet portion.2. The microneedle array according to claim 1 ,wherein the needle portion contains a water-soluble polymer and dissolves after being inserted into a body.3. The microneedle array according to claim 2 ,wherein the water-soluble polymer is at least one kind of polymer selected from the group consisting of hydroxyethyl starch, dextran, sodium chondroitin sulfate, sodium hyaluronate, carboxymethyl cellulose, polyvinyl pyrrolidone, polyoxyethylene polyoxypropylene glycol, and polyethylene glycol.4. The microneedle array according to claim 1 ,wherein the influenza vaccine is at least one kind of virus selected from the group consisting of an A/H1N1 type, an A/H3N2 type, an A/H5N1 type, and a B type.5. The microneedle array according to claim 2 ,wherein the influenza vaccine is at least one kind of virus selected from the group consisting of an A/H1N1 type, an A/H3N2 type, an A/H5N1 type, and a B type.6. The microneedle array according to claim 1 ,wherein 90% by mass or more of the inactivated whole virion influenza vaccine with respect to a total mass of the vaccine is contained in a region that accounts for not more than 80% of a height of the needle portion from a tip of the needle portion, and/or in a region that extends not longer than 500 μm from a tip of the needle portion.7. The microneedle array according to claim 2 ,wherein 90% by mass or more of the inactivated whole virion influenza vaccine with respect to a total mass of the vaccine is contained in a region that accounts for not more ...

MICRONEEDLE WITH POROUS COATING LAYER, MANUFACTURING METHOD THEREOF AND MICRONEEDLE PATCH WITH THE SAME

The present invention relates to a microneedle coated with a porous coating layer, a manufacturing method thereof and a microneedle patch with the same, which can secure a channel to deliver medicine in a surface of a needle body and improve an efficiency of collecting and delivering the medicine based on merits of a material. 1. A microneedle coated with a porous coating layer , comprising:a needle body hard enough to penetrate an outer skin layer; anda coating layer coated to surround the needle body,wherein the needle body is made of metal,wherein the coating layer comprises a plurality of communicating holes recessed or penetrated to be filled with medicine,wherein the plurality of communicating holes communicate with one another to form a moving path of the medicine,wherein the coating layer is made of a soft material comprising at least one of biocompatible polymer and biocompatible hydrogel; and water-soluble porogen different in state from the soft material,wherein the communicating holes are recessed or penetrated as the porogent is removed from the coating layer,wherein the porogen comprises at least one of phosphate buffer saline (PBS), water-soluble hydrogel, and salt,wherein the needle body is shaped like a horn or a column, a tip of which is formed by its material characteristic.2. The microneedle coated with the porous coating layer according to claim 1 , whereinthe biocompatible polymer comprises at least one of poly lactic-co-glycolic acid (PLGA) and poly lactic acid (PLA), andthe biocompatible hydrogel comprises at least one of poly ethylene glycol (PEG), poly ethylene glycol diacrylate (PEGDA), and poly ethylene glycol methyl ether acrylate (PEGMEA).3. A method of manufacturing a microneedle of which a needle body is coated with a coating layer claim 1 ,the method comprising:an emulsion producing operation of dissolving a soft material as a raw material of the coating layer in a solvent and mixing porogen with the dissolved soft material to ...

Systems and methods to facilitate delivery of a therapeutic agent into the skin of a subject

The present disclosure is directed to systems and methods that facilitate delivery of a therapeutic agent into the skin of a subject. A first mechanism can create a first angled channel through a first location on a surface of a subject's skin at a first angle relative to the surface of the subject's skin. A second mechanism, associated with the first mechanism, can create a second angled channel through a second location on the surface of the subject's skin at a second angle relative to the surface of the subject's skin. The first angled channel and the second angled channel intersect to form a connected channel under the surface of the subject's skin.

A microneedle patch

The present invention provides a microneedle patch which can solve the problem that microneedle production is difficult and requires high accuracy, the problem that time and mental burdens on a health professional and a patient are large, and the problem caused by compounding a plurality of drugs. The microneedle patch comprises a large number of drug-carrying microprojections 4 erected on one support sheet, each microprojection 4 having a drug layer 5 soluble in vivo at its top part and having an intermediate layer 6 under the drug layer 5, the intermediate layer 6 containing a polymeric substance for adhesion of the drug layer 5 to the support sheet, the drug layer 5 at the top part of the microprojection 4 containing a single drug, the microprojections 4 holding difference types of drugs being arranged together on the support sheet 2.

GLUCOSE RESPONSIVE INSULIN DELIVERY COMPOSITIONS AND METHODS

Disclosed herein is a glucose-responsive insulin delivery system based on the interaction between the glucose-modified insulin and glucose transporters (GLUTs) on erythrocytes (or red blood cells, RBCs). After being conjugated with glucose, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of blood glucose (BG) level in vivo. In some embodiments, the delivery vehicle can include: 1) intravenously injectable polymeric nanoparticles (˜100 nm in diameter) coated with RBC membrane and loaded with glucose-modified insulin and/or 2) painless microneedle (MN) patches loaded with the complex of GLUT and glucose-modified insulin. 1. A composition comprising;a glucose-modified insulin molecule comprising an insulin moiety conjugated to at least one glucose moiety by at least one linker molecule, andwherein the glucose-modified insulin molecule is configured to reversibly bind a glucose binding structure,wherein the glucose-binding structure releases a portion of the glucose-modified insulin in high glucose conditions.2. The composition of claim 1 , further comprising the glucose binding structure claim 1 , wherein the glucose binding structure is bound to the glucose-modified insulin molecule.3. The composition of or claim 1 , wherein the glucose-modified insulin molecule comprises two or more glucose moieties claim 1 , wherein each glucose moiety is conjugated to the insulin moiety by a distinct linker molecule.4. The composition of claim 3 , wherein the glucose-modified insulin molecule comprises two glucose moieties.5. The composition of any one of - claim 3 , wherein the linker molecule is synthetic.6. The composition of any one of - claim 3 , wherein the linker molecule comprises a maleimide group.7. The composition of any one of - claim 3 , wherein the linker molecule comprises a polyethylene glycol (PEG) group.8. The composition of any one of - claim 3 , ...

MICRONEEDLE TATTOO PATCHES AND USE THEREOF

Microneedle patches have been developed that can be used to deliver therapeutic, prophylactic, diagnostic agents and/or dyes to the skin. The microneedles encapsulate the agent(s) to be delivered. These are formed of a biodegradable polymer that dissolves upon insertion into skin or tissue, so that the microneedles break off from the substrate forming the patch, remaining in the skin/tissue at the site of insertion. The patches are used to create a tattoo or to deliver therapeutic, prophylactic or diagnostic agent in combination with a tattoo. In one embodiment, the microneedle patch contains both vaccine and dye pigments to administer vaccine and record such administration in one application of the microneedle patch. 1. A microneedle array structure comprisinga flexible base element anda plurality of biodegradable microneedles each having a first end and a second sharpened end for penetration of skin,the microneedles extending outwardly from the base element at the first end of the microneedles,The microneedles comprising therapeutic, prophylactic and/or diagnostic agent and/or dye,wherein the microneedles are released from the base element within 15 minutes of administration into the skin.2. The microneedle array structure of wherein the therapeutic claim 1 , prophylactic or diagnostic agent and/or dye is microencapsulated prior to incorporation into the microneedles.3. The microneedle array structure of wherein the microneedles are formed of biodegradable polymer or a sugar composition.4. The microneedle array structure of wherein the dye is selected from the group consisting of inorganic nanocrystals claim 1 , lanthanide-based dyes claim 1 , other fluorophores claim 1 , and non-fluorescent imaging agents.5. The microneedle array structure of wherein the dye is carbon or a tattoo ink claim 1 , or a cosmetic ink.6. The microneedle array structure of any of wherein the dye is a near infrared imaging agent with an excitation wavelength and an emission wavelength in ...

MICRONEEDLE PARTICLES, COMPOSITIONS, AND METHODS OF TREATMENT AND DELIVERING A SUBSTANCE OF INTEREST

Provided herein are microneedle particles, compositions that include microneedle particles, methods of treating skin, and methods of delivering a substance of interest. The microneedle particles may include one or more microneedles, and the microneedle particles may be configured to prevent the entire microneedle particle from penetrating the biological tissue. The microneedle particles may be dispersed in a liquid medium to form a composition. A biological tissue may be contacted with the microneedle particles to pre-treat the biological tissue, and a substance of interest may be applied to the pre-treated biological tissue. 1. A microneedle particle comprising:a core structure; andone or more microneedles extending from the core structure, the one or more microneedles being structured to penetrate a biological tissue;wherein at least one of (i) the core structure, (ii) the one or more microneedles, and (iii) a spatial relationship between/among two or more of the microneedles is configured to prevent the entire microneedle particle from penetrating the biological tissue.2. The microneedle particle of claim 1 , wherein the microneedle particle comprises three microneedles claim 1 , four microneedles claim 1 , five microneedles claim 1 , six microneedles claim 1 , seven microneedles claim 1 , eight microneedles claim 1 , or ten microneedles extending from the core structure.3. The microneedle particle of claim 1 , wherein the one or more microneedles are planar microneedles.4. The microneedle particle of claim 1 , wherein the microneedle particle comprises three or more microneedles claim 1 , and at least one of the three or more microneedles is a non-planar microneedle.5. The microneedle particle of claim 1 , wherein each of the one or more microneedles independently has a length of about 10 μm to about 2 claim 1 ,000 μm.6. The microneedle particle of claim 1 , wherein each of the one or more microneedles independently has a length of about 100 μm to about 1 claim ...

APPLICATION DEVICE FOR A FLUID DELIVERY APPARATUS AND METHOD OF USE

An application device for a fluid delivery includes a housing having a bore extending from a bottom of the housing. The bore is sized and shaped for receiving at least a portion of the fluid delivery apparatus. The application device also includes an impact component for impacting the fluid delivery apparatus and moving at least a portion of the fluid delivery apparatus towards a user's skin. The application device includes a safety arm that is positionable relative to the impact component between a locked configuration in which the impact component is secured in a safety position, and a released configuration in which the impact component is free to move within the housing for impacting the fluid delivery apparatus. 1. An application device for a fluid delivery apparatus , the application device comprising:a housing having a bore extending from a bottom of the housing, the bore being sized and shaped for receiving at least a portion of the fluid delivery apparatus therein;an impact component for impacting the fluid delivery apparatus and moving at least a portion of the fluid delivery apparatus towards a users skin; anda safety arm positionable relative to the impact component between a locked configuration in which the impact component is secured in a safety position, and a released configuration in which the impact component is free to move within the housing for impacting the fluid delivery apparatus,wherein the housing further comprises a retention member for securing the impact component in the safety position, the retention member being a body that extends radially inward from the bore.2. The application device in accordance with further comprising a safety arm biasing device configured to bias the safety arm in the locked configuration.3. The application device in accordance with further comprising an impact component biasing device configured to bias the impact component relative to the housing.4. The application device in accordance with claim 3 , wherein ...

Oral dissolving films containing microencapsulated vaccines and methods of making same

An oral dissolving film containing nano- or micro-encapsulated bioactive material and methods of forming the film. The film may be prepared by dispensing a mixture of a film-forming agent, a crosslinking agent, a solution of nano- or micro-encapsulated bioactive material, and a photoinitiator into a plurality of wells in a tray using a 3D printer. The dispensed material is exposed to radiation in order to crosslink the material and form a film.

COMPOSITION FOR ENHANCED ABSORPTION OF SUPPLEMENTS

A composition that includes at least one target supplement and at least one rehydration formulation is described. When the at least one target supplement is ingested as part of the composition, the bioavailability of at least one target supplement is enhanced as compared to when it is ingested separate from the composition. The at least one target supplement is absorbed more quickly and in a greater amount when it is ingested as part of the composition than when it is ingested separate from the composition. The composition also hydrates a subject more quickly. 1. A composition comprising:at least one target supplement having a first absorption rate when ingested separately from the composition; andat least one rehydration formulation, wherein, when the at least one target supplement is ingested as part of the composition, the at least one target supplement has a second absorption rate measured after ingestion that is greater than the first absorption rate.2. The composition of claim 1 , wherein the at least one hydration formulation comprises sodium claim 1 , chloride claim 1 , glucose-containing saccharide claim 1 , potassium claim 1 , and citrate.3. The composition of claim 2 , wherein the glucose osmolarity is greater than the sodium osmolarity in the composition4. The composition of claim 2 , wherein the osmolarity of sodium in the composition is at least 50 mmol/L claim 2 , and wherein the osmolarity of the glucose is at least 50 mmol/L.5. The composition of claim 1 , wherein the at least one target supplement comprises at least one of melatonin claim 1 , L-theanine claim 1 , valerian root claim 1 , 5-hydroxytryptophan claim 1 , or passionflower.6. The composition of claim 1 , wherein the at least one rehydration formulation includes at least:about 9.0 to about 12.6 grams of glucose per liter solvent;about 12.9 to about 14.8 grams of sucrose per liter solvent;about 2.0 to about 2.3 grams of sodium chloride per liter solvent;about 0.98 to about 1.5 grams of ...

COMPOSITIONS AND METHODS INVOLVING POLYMER, SOLVENT, AND HIGH VISCOSITY LIQUID CARRIER MATERIAL

Compositions may include a pharmaceutical active agent, a high viscosity liquid carrier material (HVLCM), a lactic acid-based polymer, and an organic solvent. Related compositions and methods are also disclosed. For instance, a carrier formulation for controlled release of injectable drugs is disclosed. The formulation may include a non-water soluble high viscosity liquid which may be sucrose acetate isobutyrate, a lactic- acid based polymer which may be a poly(lactic acid)(glycolic acid), and an organic solvent which maintains the composition in a monophasic form at 25° C. in one atmosphere. Drug in the formulation may be released upon administration such that less than 10% (e.g. 2-8%) of drug is released in the first 5 hours; 10% to 80% of the drug is released during a period of 5 hours to 7 days after administration; and 10% to 40% of the drug is released gradually over a period of 7 days to 28 days from initial administration. The drug may be an anti-schizophrenia agent delivered by injection. 123.-. (canceled)24. A composition comprising:0.5 wt % to 50 wt %, based on total weight of the composition, of particles comprising a pharmaceutical active agent, the particles having a median particle size, as measured by laser diffraction, ranging from 0.1 micrometer to 100 micrometers;10 wt % to 60 wt %, based on total weight of the composition, of sucrose acetate isobutyrate;1 wt % to 30 wt %, based on total weight of the composition, of a lactic acid-based polymer comprising an alkoxy end group having 8 to 24 carbons, the lactic acid-based polymer having a lactic acid to glycolic acid molar ratio ranging from 100:0 to 40:60, the lactic acid-based polymer having a weight average molecular weight ranging from 4000 Daltons to 30,000 Daltons; and10 wt % to 50 wt %, based on total weight of the composition, of an organic solvent comprising at least one member selected from N-methyl-pyrrolidone, dimethylsulfoxide, propylene carbonate, and benzyl benzoate.25. The ...

SUBSTANCE DELIVERY DEVICE AND SUBSTANCE DELIVERY METHOD USING THE SAME

A substance delivery device comprises a substrate, a plurality of dissolvable supporting structures and a plurality of carriers. The substrate attaches to a tissue. The dissolvable supporting structures are disposed on the substrate. The carriers are disposed on the dissolvable supporting structures and encapsulating substances. The present invention further provides a substance delivery method. The substance delivery device and the substance delivery method of present invention is advantageous for providing sustained release effect and rising the applicability of transdermal or transmucosal delivery techniques. 1. A substance delivery device comprises:a substrate attaching to a tissue;a plurality of dissolvable supporting structures disposed on the substrate; anda plurality of carriers disposed on the dissolvable supporting structures and encapsulating the substances.2. The substance delivery device according to claim 1 , wherein the dissolvable supporting structures can be dissolved in the tissue.3. The substance delivery device according to claim 1 , wherein the dissolvable supporting structures include polyvinylpyrrolidone claim 1 , polyvinyl alcohol claim 1 , γ-poly-glutamic acid claim 1 , hyaluronic acid claim 1 , starch claim 1 , gelatin claim 1 , or their combinations.4. The substance delivery device according to claim 1 , wherein substances are encapsulated in the dissolvable supporting structures claim 1 , and the substances are the same as the substances encapsulated in the carriers.5. The substance delivery device according to claim 1 , wherein substances are encapsulated in the dissolvable supporting structures claim 1 , and the substances are different from the substances encapsulated in the carriers.6. The substance delivery device according to claim 1 , wherein the carriers include a material capable of melting after exposure to a radiation.7. The substance delivery device according to claim 1 , wherein the components of the carriers include chitosan ...

MICRONEEDLE ARRAY WITH COMPOSITE FORMULATION, AND METHOD FOR MANUFACTURING SAME

The present invention relates to a microneedle array and a method for manufacturing the same, the microneedle array comprising: a support; and a plurality of microneedles loaded with a solid-phase formulation which protrude from the upper portion of the support, wherein a liquid-phase formulation is applied or added dropwise onto an area of the upper portion of the support in which the microneedles are not formed, or in a case where one or more holes are formed in the support, the liquid-phase formulation is released, through the holes, onto the area of the upper portion of the support in which the microneedles are not formed. 1. A microneedle array , comprising:a support; anda plurality microneedles loaded with a solid-phase formulation material which protrude from the upper portion of the support,wherein a liquid-phase formulation material is applied or added dropwise onto an area of the upper portion of the support in which the microneedle is not formed, or in a case where one or more holes are formed in the support, the liquid-phase formulation material is released, through the holes, onto the area of the upper portion of the support in which the microneedle is not formed.2. The microneedle array according to claim 1 ,wherein the microneedle is loaded with two or more solid-phase forming materials to form a multi-layer structure.3. The microneedle array according to claim 1 ,wherein a type of the liquid-phase formulation material is the same as or different from that of the solid-phase formulation material.4. The microneedle array according to claim 3 ,wherein in a case where the type of the liquid-phase formulation material is different from that of the solid-phase formulation material, the liquid-phase formulation material contains a fat-soluble material including one or more selected from the group consisting of horse oil, vitamin A and a derivative thereof, vitamin D and a derivative thereof, vitamin E and a derivative thereof, vitamin K and a derivative ...

Composition for treating il-6-related diseases

The present invention provides a pharmaceutical composition for treating IL-6-related diseases containing an IL-6 inhibitor as an active ingredient, wherein the pharmaceutical composition is routinely administered after a short-interval dosing period where the same dose as the routine dose is administered at a shorter interval than the routine dosing interval.

MEDICATION DISPENSING SYSTEM

A method for treating cancer is disclosed by boiling blended material with oil and collecting oil infused with ; targeting cancerous cells in a body; and injecting the oil infused with into the body portion with cancerous cells. 1cannabis. A method for infusing with plant or vegetable oil , comprising:{'i': 'cannabis', 'mixing a mixture with a ratio of about 230 grams of , about ½ pound plant or vegetable oil, about 5-7 cups of water, sugar leaf and bud plant parts;'}boiling the mixture in a magnetic pot and decarboxylating the mixture;straining the decarboxylated mixture and after pressing the decarboxylated mixture dry to form a dry mixture, providing boiling water to the dry mixture to form an aqueous mixture in a second pot and boiling the aqueous mixture;cooling the aqueous mixture and removing a top oily layer floating to the top of the cooled aqueous mixture;placing the top oily layer in a cup; and{'i': 'cannabis.', 'placing the cup surrounded by a different oil and then boiling the cup in the different oil until water evaporates leaving oil infused'}2. A method for delivering a substance , comprising:contacting a set of hyaluronic acid (HA) microneedle or a set of synthetic hydrogel microneedle on a backing structure;providing medication to be dispensed through the microneedle; andapplying the microneedles to penetrate skin in a solid state, wherein the microneedles swell upon encountering bodily fluid for dispensing medication.3. The method of claim 2 , wherein the synthetic hydrogel comprises polyvinyl alcohol (8%) gel and water (92%) claim 2 , cross-linked by freezing/thawing cycles.4cannabiscannabis;. A method for treating cancer comprising boiling blended material with oil and collecting oil infused withtargeting cancerous cells in a body; and{'i': 'cannabis', 'injecting the oil infused with into the body portion with cancerous cells.'}5. The method of claim 4 , wherein the body comprises a breast. This invention relates to medical dispensers.is a ...

MEDICATION DISPENSING SYSTEM

A method for treating cancer is disclosed by boiling blended cannabis material with oil and collecting oil infused with cannabis; targeting cancerous cells in a body; and injecting the oil infused with cannabis into the body portion with cancerous cells. 1. A method for infusing cannabis with plant or vegetable oil , comprising:mixing a mixture with a ratio of about 230 grams of cannabis, about ½ pound plant or vegetable oil, about 5-7 cups of water, sugar leaf and bud plant parts;boiling the mixture in a magnetic pot and decarboxylating the mixture;straining the decarboxylated mixture and after pressing the decarboxylated mixture dry to form a dry mixture, providing boiling water to the dry mixture to form an aqueous mixture in a second pot and boiling the aqueous mixture;cooling the aqueous mixture and removing a top oily layer floating to the top of the cooled aqueous mixture;placing the top oily layer in a cup; andplacing the cup surrounded by a different oil and then boiling the cup in the different oil until water evaporates leaving oil infused cannabis.2. A method for delivering a substance , comprising:contacting a set of hyaluronic acid (HA) microneedle or a set of synthetic hydrogel microneedle on a backing structure;providing medication to be dispensed through the microneedle; andapplying the microneedles to penetrate skin in a solid state, wherein the microneedles swell upon encountering bodily fluid for dispensing medication.3. The method of claim 2 , wherein the synthetic hydrogel comprises polyvinyl alcohol (8%) gel and water (92%) claim 2 , cross-linked by freezing/thawing cycles.4. A method for treating cancer comprisingboiling blended cannabis material with oil and collecting oil infused with cannabis;targeting cancerous cells in a body; andinjecting the oil infused with cannabis into the body portion with cancerous cells.5. The method of claim 4 , wherein the body comprises a breast. This invention relates to medical dispensers.is a substance ...

MEDICATION DISPENSING SYSTEM

A method for treating cancer is disclosed by boiling blended material with oil and collecting oil infused with ; targeting cancerous cells in a body; and injecting the oil infused with into the body portion with cancerous cells. 1cannabis. A method for infusing with plant or vegetable oil , comprising:{'i': 'cannabis', 'mixing a mixture with a ratio of about 230 grams of , about ½ pound plant or vegetable oil, about 5-7 cups of water, sugar leaf and bud plant parts;'}boiling the mixture in a magnetic pot and decarboxylating the mixture;straining the decarboxylated mixture and after pressing the decarboxylated mixture dry to form a dry mixture, providing boiling water to the dry mixture to form an aqueous mixture in a second pot and boiling the aqueous mixture;cooling the aqueous mixture and removing a top oily layer floating to the top of the cooled aqueous mixture;placing the top oily layer in a cup; and{'i': 'cannabis.', 'placing the cup surrounded by a different oil and then boiling the cup in the different oil until water evaporates leaving oil infused'}2. A method for delivering a substance , comprising:contacting a set of hyaluronic acid (HA) microneedle or a set of synthetic hydrogel microneedle on a backing structure;providing medication to be dispensed through the microneedle; andapplying the microneedles to penetrate skin in a solid state, wherein the microneedles swell upon encountering bodily fluid for dispensing medication.3. The method of claim 2 , wherein the synthetic hydrogel comprises polyvinyl alcohol (8%) gel and water (92%) claim 2 , cross-linked by freezing/thawing cycles.4cannabiscannabis;. A method for treating cancer comprising boiling blended material with oil and collecting oil infused withtargeting cancerous cells in a body; and{'i': 'cannabis', 'injecting the oil infused with into the body portion with cancerous cells.'}5. The method of claim 4 , wherein the body comprises a breast. This invention relates to medical dispensers.is a ...

MEDICATION DISPENSING SYSTEM

A method for treating cancer is disclosed by boiling blended material with oil and collecting oil infused with ; targeting cancerous cells in a body; and injecting the oil infused with into the body portion with cancerous cells. 1cannabis. A method for infusing with plant or vegetable oil , comprising:{'i': 'cannabis', 'mixing a mixture with a ratio of about 230 grams of , about ½ pound plant or vegetable oil, about 5-7 cups of water, sugar leaf and bud plant parts;'}boiling the mixture in a magnetic pot and decarboxylating the mixture;straining the decarboxylated mixture and after pressing the decarboxylated mixture dry to form a dry mixture, providing boiling water to the dry mixture to form an aqueous mixture in a second pot and boiling the aqueous mixture;cooling the aqueous mixture and removing a top oily layer floating to the top of the cooled aqueous mixture;placing the top oily layer in a cup; and{'i': 'cannabis.', 'placing the cup surrounded by a different oil and then boiling the cup in the different oil until water evaporates leaving oil infused'}2. A method for delivering a substance , comprising:contacting a set of hyaluronic acid (HA) microneedle or a set of synthetic hydrogel microneedle on a backing structure;providing medication to be dispensed through the microneedle; andapplying the microneedles to penetrate skin in a solid state, wherein the microneedles swell upon encountering bodily fluid for dispensing medication.3. The method of claim 2 , wherein the synthetic hydrogel comprises polyvinyl alcohol (8%) gel and water (92%) claim 2 , cross-linked by freezing/thawing cycles.4. A method for treating cancer comprising{'i': cannabis', 'cannabis;, 'boiling blended material with oil and collecting oil infused with'}targeting cancerous cells in a body; and{'i': 'cannabis', 'injecting the oil infused with into the body portion with cancerous cells.'}5. The method of claim 4 , wherein the body comprises a breast. This invention relates to medical ...

METHODS AND PRODUCTS FOR NUCLEIC ACID PRODUCTION AND DELIVERY

The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices. Methods and products for altering the DNA sequence of a cell are described, as are methods and products for inducing cells to express proteins using synthetic RNA molecules, including cells present in vivo. Therapeutics comprising nucleic acids encoding gene-editing proteins are also described. 1202.-. (canceled)203. An in vivo method for treating epidermolysis bullosa , comprisingdelivering a synthetic RNA encoding a gene-editing protein that targets a COL7 gene to a patient in need thereof andinducing a double-strand break in the COL7 gene of the patient's keratinocytes, ["the synthetic RNA is delivered to the patient's keratinocytes by injection to the epidermis and", 'the gene-editing protein comprises a DNA-binding domain and a nuclease domain., 'thereby eliminating a mutation that is at least partially responsible for a disease phenotype, wherein204. The method of claim 203 , wherein the gene-editing protein is capable of targeting a nucleic acid sequence that encodes the amino acid sequence of SEQ ID NO: 78.205. The method of claim 203 , wherein the gene-editing protein is selected from the group consisting of a nuclease claim 203 , a transcription activator-like effector nuclease (TALEN) claim 203 , a zinc-finger nuclease claim 203 , a meganuclease claim 203 , a nickase claim 203 , and a clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein.206. The method of claim 203 , wherein the synthetic RNA further comprises one or both of a 5′-cap structure and a 3′- ...

MICROSTRUCTURE USING CROSS-LINKED HYALURONIC ACID HYDROGEL, AND METHOD FOR PRODUCING SAME

The present invention provides microstructures using crosslinked hyaluronic acid hydrogels and the method for preparing the same. The present invention for preparing microstructures using crosslinked hyaluronic acid hydrogels allows the preparation of microstructures with a uniform shape and minimum deformation. Furthermore, the microstructures made using crosslinked hyaluronic acid hydrogels in the present invention can improve skin aging, e.g. wrinkles, replenish moisture, easily absorb body fluids due to its outstanding swelling performance, provide a longer duration in the body due to its resistance against a hyaluronic acid hydrolyzing enzyme, enabling the safe delivery of effective components in the body. 1. A microstructure comprising crosslinked hyaluronic acid hydrogels and non-crosslinked hyaluronic acid.2. The microstructure of claim 1 , wherein the crosslinked hyaluronic acid hydrogel has the crosslinking rate of 1-50%.3. (canceled)4. The microstructure of claim 1 , wherein the solid content of crosslinked hyaluronic acid hydrogel is equal to or below 15% (w/v).5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. The microstructure of claim 12 , wherein the ratio of non-crosslinked hyaluronic acid and crosslinked hyaluronic acid is characterized by 5˜2000 to 100 (w/w).14. (canceled)15. A method for preparing microstructures comprising the following steps:(a) supplying a mixture of crosslinked hyaluronic acid hydrogel and non-crosslinked hyaluronic acid into a micro-mold;(b) injecting the mixture into the micro-mold cavities; and(c) separating the micro-mold and the mixture to form a microstructure.16. The method of claim 15 , wherein the crosslinked hyaluronic acid hydrogel is characterized by having a crosslinking density of 1-50%.17. The method of claim 15 , wherein the injection is characterized by being carried out by applying an external force to the mixture18. The method of claim 17 , ...

MEDICATION DISPENSING SYSTEM

A method for delivering therapeutics includes infusing a hydrogel with cannabis; and contacting the hydrogel infused with cannabis into a human which causes the controlled timed releasing of the cannabis with hydrophobic molecules to permeate through a lipid pathway. 1. A method for delivering therapeutics , comprising:infusing a hydrogel with cannabis; andcontacting the hydrogel infused with cannabis into a human which causes the controlled timed releasing of the cannabis with hydrophobic molecules to permeate through a lipid pathway.2. The method of claim 1 , comprising providing botox with cannabis.3. The method of claim 1 , comprising providing medication with cannabis.4. The method of claim 1 , comprising providing cancer medication with cannabis.5. The method of claim 1 , comprising providing cosmetics or skin care solution.6. The method of claim 1 , comprising providing a slow release compound claim 1 , a fast release compound claim 1 , or a mixture thereof7. The method of claim 1 , comprising applying arthritis medication.8. The method of claim 1 , comprising providing a hormone with cannabis.9. A method for delivering therapeutics claim 1 , consisting essentially of:infusing polyvinyl alcohol with cannabis; andcontacting the cannabis and polyvinyl alcohol into a human which causes the controlled timed releasing of the cannabis with hydrophobic molecules to permeate through a lipid pathway.10. The method of claim 9 , comprising providing botox with cannabis.11. The method of claim 9 , comprising providing medication with cannabis.12. The method of claim 9 , comprising providing cancer medication with cannabis.13. The method of claim 9 , comprising providing cosmetics or skin care solution.14. The method of claim 9 , comprising providing a slow release compound claim 9 , a fast release compound claim 9 , or a mixture thereof15. The method of claim 9 , comprising applying arthritis medication.16. The method of claim 9 , comprising providing a hormone with ...

MICRODEVICE AND METHOD FOR TRANSDERMAL DELIVERY AND SAMPLING OF ACTIVE SUBSTANCES

A system and method of using a high-aspect ratio microdevice for treating, preventing or ameliorating a medical condition is provided. 1. A method of delivering an agent , or a combination of agents , for a medical condition to a mammal , comprisingapplying an applicator comprising a microdevice to cause the microdevice to contact an area of skin of the mammal to generate a prepared area of skin comprising a plurality of nanopores or nanochannels through the stratum corneum of the prepared area of skin and removing the applicator and microdevice from the skin immediately after the microdevice has penetrated the skin,applying a wet formulation comprising the agent to the area of skin being prepared either before or after the microdevice has generated the plurality of nanopores or nanochannels in the prepared area of skin,subsequently applying an occlusive layer over the agent and directly on the prepared area of skin such that the occlusive layer prevents air from coming into contact with the prepared area of skin following the removal of the applicator and microdevice from the skin, andcausing an effective amount of agent to deliver to the patient through the nanopores or nanochannels in the stratum corneum at a rate percent penetration that is higher than the rate of percent penetration if no nanopores or nanochannels are present.2. The method of claim 1 , wherein causing an effective amount of the agent to deliver to the patient comprises:allowing the agent to diffuse into the patient from the formulation, ordriving the agent into the patient by applying a driving force to the formulation.3. The method of claim 1 , wherein agent is encapsulated within elastic liposomes.4. The method of claim 1 , wherein the wet formulation does not comprise elastic liposomes.5. The method of claim 3 , wherein the elastic liposome comprises liposome nanoparticles.6. The method of claim 2 , wherein the driving force is selected from iontophoresis claim 2 , sonophoresis claim 2 , ...

NANOPATTERNED MEDICAL DEVICE WITH ENHANCED CELLULAR INTERACTION

A medical device for delivering a drug compound through a includes a support having an aperture, an array of microneedles extending outwardly from the support, a plurality of nanostructures associated with each microneedle, and a reservoir wherein the drug compound is retained. At least one microneedle contains a shaft extending from the support. The shaft includes a tip configured to penetrate the . The shaft defines a channel extending from the support to the tip. The channel is in at least partial alignment with the aperture. At least some of the microneedles of the array of microneedles each have a cross-sectional dimension of from about 1 micrometer to about 1 millimeter. At least some of the nanostructures have a cross-sectional dimension less than about 500 nanometers and greater than about 5 nanometers and an aspect ratio of from about 0.2 to about 5. 1Stratum corneum. A medical device for delivering a drug compound through a and to a subdermal location , the medical device comprising:a support having an aperture;{'i': 'Stratum corneum', 'an array of microneedles that extend outwardly from the support, wherein at least one microneedle contains a shaft extending from the support, the shaft including a tip configured to penetrate the , the shaft defining a channel extending from the support to the tip, the channel being in at least partial alignment with the aperture of the support, wherein at least some of the microneedles of the array of microneedles each have a cross-sectional dimension of from about 1 micrometer to about 1 millimeter;'}a plurality of nanostructures associated with each microneedle of the array of microneedles, wherein the plurality of nanostructures are arranged in a pattern that comprises a fractal and/or fractal-like geometry; anda reservoir wherein the drug compound is retained, the reservoir being in fluid communication with the aperture of the support and the channel of the microneedle for delivery of the drug compound to the ...

COMPOSITIONS AND METHODS FOR REDUCING BODY FAT

The present invention relates to compositions, such as bimatoprost, latanoprost and travoprost, and methods to reduce fat in the body of an individual, for example, by topical administration, injection, and/or implantation of such compositions. 2. The method of claim 1 , wherein the individual has a cosmetic condition that comprises excess body fat.3. The method of claim 1 , wherein the individual has obesity.4. The method of claim 1 , wherein the excess deposit of body fat comprises obesity.5. The method of claim 1 , wherein the excess deposit of body fat is diffuse.6. The method of claim 1 , wherein the excess deposit of body fat is local.7. The method of claim 1 , wherein the excess deposit of body fat is on an area of the body selected from the group consisting of face claim 1 , chin claim 1 , neck claim 1 , arms claim 1 , chest claim 1 , abdomen claim 1 , buttocks claim 1 , hips claim 1 , thighs claim 1 , and legs.8. The method of claim 1 , wherein the reducing occurs at a localized area selected from the group consisting of face claim 1 , chin claim 1 , neck claim 1 , arms claim 1 , chest claim 1 , abdomen claim 1 , buttocks claim 1 , hips claim 1 , thighs claim 1 , and legs.9. The method of claim 1 , wherein the administering is to a localized area selected from the group consisting of face claim 1 , chin claim 1 , neck claim 1 , arms claim 1 , chest claim 1 , abdomen claim 1 , buttocks claim 1 , hips claim 1 , thighs claim 1 , and legs.10. The method of claim 1 , wherein the route of administration is local.11. The method of claim 1 , wherein the composition is selected from the group consisting of a solution claim 1 , a cream claim 1 , an ointment claim 1 , a gel claim 1 , a lotion claim 1 , a foam claim 1 , a spray claim 1 , a patch claim 1 , and an implantable depot.12. The method of claim 1 , wherein the composition comprises a sustained-release formulation.13. The method of claim 1 , wherein the route of administration is selected from the group ...

Tissue expansion method

The invention provides a method for skin expansion utilizing at least one polymer.

Dermal patch for transdermal administration of ghrelin pathway blocker

Embodiments of the innovation relate to a dermal patch, comprising a substrate; a set of projections coupled to the substrate and configured to be at least partially insertable into skin, at least a portion of each projection of the set of projections comprising a biodegradable material; and a ghrelin blocker material encapsulated in the plurality of projections. The set of projections are coupled to the substrate via an adhesive that is configured to be dissolved within the skin after the patch is applied to the skin for a predetermined time, thus resulting in separation of the set of projections from the substrate. Once embedded in the skin, the protrusions can degrade and release the anti-ghrelin antibody encapsulated therein. The released anti-ghrelin antibody can find its way into the subject's circulatory system.

THROMBIN-RESPONSIVE HYDROGELS AND DEVICES FOR AUTO-ANTICOAGULANT REGULATION

The present disclosure relates to a thrombin-responsive closed-loop patch for prolonged heparin delivery in a feedback-controlled manner. The microneedle-based patch can sense the activated thrombin and subsequently release heparin to prevent coagulation in the blood flow. The patch can be transcutaneously inserted into skin without drug leaking and can sustainably regulate blood coagulation in response to thrombin. 16.-. (canceled)7. A device for transport of a material across a biological barrier of a subject comprising:a plurality of microneedles each having a base end and a tip;a substrate to which the base ends of the microneedles are attached or integrated; and a non-peptidic polymer, wherein the non-peptidic polymer is selected from hyaluronic acid, poly(ethylene glycol), poly(propylene glycol), ethylene glycol-propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, polysaccharide, dextran, polyvinyl ethyl ether, poly(lactic glycolic acid), lipid polymer, chitin, alginate, a combination thereof, or a derivative thereof;', 'a thrombin-cleavable peptide, wherein the thrombin-cleavable peptide is selected from: GGLVPRGSGGC (SEQ ID NO:1), PRSFL (SEQ ID NO: 2), DPRSFL (SEQ ID NO: 3), or LVPRGS (SEQ ID NO: 4); and', 'heparin;', 'wherein the heparin is linked to the non-peptidic polymer by the thrombin-cleavable peptide., 'a hydrogel, wherein the hydrogel comprises8. The device of claim 7 , wherein the non-peptidic polymer is hyaluronic acid.9. The device of claim 7 , wherein the non-peptidic polymer is methacrylated hyaluronic acid.10. The device of claim 7 , wherein the thrombin-cleavable peptide is about 5 to about 30 amino acids in length.11. The device of claim 7 , wherein the thrombin-cleavable peptide comprises a sequence of GGLVPRGSGGC (SEQ ID NO:1).12. The device of claim 7 , wherein the heparin is unfractionated heparin.13. A method for treating or preventing thrombosis in a subject in need thereof claim 7 , comprising:{'claim-ref': {'@ ...

METHOD FOR RELIEVING CHRONIC PAIN

The method is for use in a part of a mammal having one or more tender points and comprises a dministering a fluid, by a needleless, pressure-based injector, to substantially all of the tender points in the part. The volume of the fluid that is administered to each of the tender points can be about 0.5 cc. The operating pressure of the injector can be about 150 psig. The fluid can be a local anesthetic such as ropivacaine. 1. A method of relieving chronic non-malignant pain in a part of a mammal having one or more tender points , the method comprising:administering a fluid, by a needleless, pressure-based injector, to substantially all of the tender points in the part.2. The method of claim 1 , wherein the fluid is an inert fluid safe for mammalian injection.3. The method of claim 2 , wherein a volume of the fluid that is administered to each of the tender points is about 0.5 cc.4. The method of claim 1 , wherein an operating pressure of the injector is about 150 psig relative to atmospheric pressure.5. The method of claim 1 , wherein the operating pressure of the injector is such that welts form in the skin at the injection sites.6. The method of claim 1 , wherein the fluid is a local anesthetic.7. The method of claim 6 , wherein the local anesthetic is ropivacaine.8. The method of claim 7 , wherein a volume of the fluid that is administered to each of the tender points is about 0.5 cc and the concentration of the ropivacaine that is administered to each of the tender points is about 5 mg/ml. This application claims priority to U.S. Provisional Patent Application Ser. No. 62/030,795 filed Jul. 30, 2014, which is herein incorporated by reference.1. Field of the InventionThe present invention relates to the field of pain treatment.2. Prior Art.Many people suffer from chronic non-malignant pain due to various diseases, such as fibromyalgia, osteoarthritis, carpal tunnel syndrome, migraines, irritable bowel syndrome, spastic bladder syndrome, stroke, multiple sclerosis ...

POLYMER MICRO-NEEDLE ARRAY CHIP, PREPARATION PROCESS AND USE THEREOF

The invention discloses a polymer micro-needle array chip, comprising a substrate and a micro-needle array standing thereon; the material for preparing the micro-needle array is a polyacrylamides polymer, with the molecular weight of 1.0×10-2.0×10, the Vickers hardness of 150-600 HV, and the impact strength of 5-30 J/m. The polymer micro-needle array chip has a high mechanical strength and a sharp needle tip, and it can easily dissolve or swell on contact with a water-containing environment, which helps the drug to be released slowly in the skin. 1. A polymer micro-needle array chip , comprising a substrate and a micro-needle array standing thereon , whereinthe material for preparing the micro-needle array is a polyacrylamides polymer;{'sup': 4', '5, 'the molecular weight of the polyacrylamides polymer is in range of 1.0×10-2.0×10;'}the Vickers hardness of the polyacrylamides polymer is in range of 150-600 HV;the impact strength of the polyacrylamides polymer is in range of 5-30 J/m.2. The polymer micro-needle array chip according to claim 1 , wherein a square sheet prepared by the polyacrylamides polymer and having a thickness of 2 mm and sides of length 1 cm claim 1 , dissolves at least 50 vol % after immersing in a still physiological saline for about 6 hours.3. The polymer micro-needle array chip according to claim 1 , wherein the polyacrylamides polymer is polymerized from acrylamide monomer; the amount of residual acrylamide monomer in the polyacrylamides polymer is not more than 0.5 ppm.4. The polymer micro-needle array chip according to claim 1 , wherein the polyacrylamides polymer is mixed with bioactive substances or drugs claim 1 , the bioactive substances or drugs being present in the mixture in amount of 0.1-50 mass %; preferably claim 1 , 10-20 mass %.5. The polymer micro-needle array chip according to claim 4 , wherein the bioactive substances or drugs is one or more selected from the group consisting of vaccines claim 4 , polypeptides claim 4 , ...

TREATMENT VACCINE FOR PROSTATE CANCER

A method of treating prostate cancer by intradermally injecting a person with a composition comprising (a) a recall antigen and (b) prostate specific antigen (PSA) or peptides that are fragments of PSA is provided. The recall antigen may be extract, Trichophyton antigens, or mumps antigen, or other recall antigen. 1. A composition comprising:(a) a recall antigen, and(b) one or more purified polypeptides or peptides comprising antigens specific for prostate tissue or prostate cancer; and(c) a pharmaceutically acceptable diluent;wherein the composition is sterile.2. The composition of wherein the component (b) is a purified polypeptide comprising prostate specific antigen (SEQ ID NO:1) or is one or more purified antigenic peptide fragments of SEQ ID NO:1.3. The composition of wherein the component (b) is one or more purified antigenic peptide fragments of SEQ ID NO:1 claim 2 , wherein the peptide fragments are 10-80 amino acid residues in length.4. The composition of wherein the one or more purified antigenic peptide fragments are selected from peptides consisting of residues 1-40 claim 3 , residues 41-80 claim 3 , 81-120 claim 3 , residues 161-200 claim 3 , residues 201-240 claim 3 , and residues 241-261 of SEQ ID NO:1.5. The composition of wherein component (b) is a plurality of antigenic peptide fragments of SEQ ID NO:1 claim 3 , wherein the peptide fragments are each 15-50 amino acid residues in length and collectively comprise residues 1-120 and 161-261 of SEQ ID NO:1.6. The composition of wherein the plurality of antigenic peptide fragments of SEQ ID NO:1 do not collectively comprise residues 121-160 of SEQ ID NO:1.7. The composition of wherein component (b) consists of peptide fragments of SEQ ID NO:1 consisting of residues 1-40 claim 5 , 41-80 claim 5 , 81-120 claim 5 , 201-240 claim 5 , and 241-261 of SEQ ID NO:1.8. The composition of wherein the peptides are acetylated on their N-terminus or amidated on their C-terminus claim 1 , or both acetylated on their ...

METHOD OF PRODUCING TRANSDERMAL ABSORPTION SHEET

The method of producing a transdermal absorption sheet includes: preparing a mold having needle-like recessed portions and an angle of an inlet portion of 120° to 160°, and a liquid feeder including an opening portion and a lip land portion; filling the needle-like recessed portions with a solution by feeding the solution to the mold and moving the liquid feeder while bringing a rear end of a lip land portion on the secondary side of the liquid feeder into contact with the mold; and forming needle portions and a sheet portion using a polymer solution. In the filling of the solution, when the rear end of the lip land portion on the secondary side matches with a secondary side inlet of the needle-like recessed portion, the shortest distance from a primary side inlet of the needle-like recessed portion to a secondary side block is 220 μm or less. 1. A method of producing a transdermal absorption sheet comprising:an apparatus preparing step of preparing a mold having needle-like recessed portions and having an angle of 120° or more and 160° or less inside the mold, the angle being formed between a flat portion of a surface and an inlet portion of the needle-like recessed portion, and a liquid feeding apparatus including a slit-shaped opening portion formed at a nozzle tip end portion and a lip land portion;a filling step of filling the needle-like recessed portions with a solution by feeding the solution to the mold from the liquid feeding apparatus and moving the liquid feeding apparatus while, when a travelling direction of the liquid feeding apparatus is set to a primary side and a direction opposite to the travelling direction is set to a secondary side, bringing at least a rear end of the lip land portion on the secondary side into contact with the mold; anda sheet portion forming step of forming needle portions and a sheet portion using a polymer solution,wherein in the filling step, when the rear end of the lip land portion on the secondary side of the liquid ...

TRANSDERMAL PHARMACEUTICAL FORMULATIONS OF NABILONE ALONE AND IN COMBINATION WITH CANNABINOIDS

The present disclosure relates to the to the transdermal administration of nabilone and cannabinoids and derivatives of these compounds, for the treatment and/or prevention and/or control of medical conditions. 1. A pharmaceutical composition comprising an active agent selected from the group consisting of tetrahydrocannabinol (THC) , cannabidiol (CBD) , nabilone , the free base thereof , salts thereof , isomers thereof , amorphous forms thereof , crystalline forms thereof , co-crystalline forms thereof , prodrugs thereof , analogs thereof , derivatives thereof , synthetic forms thereof , biosynthetic forms thereof , active metabolites thereof , polymorphs thereof , ion-pairs thereof , stereoisomers thereof , racemic forms thereof , and combinations thereof , in a dosage form for transdermal delivery.2. The pharmaceutical composition of which comprises at least about 0.1% to about 80% (w/w) of active agent.3. The pharmaceutical composition of which comprises at least about 0.5-30% of active agent.4. The pharmaceutical composition of which comprises active agent at a concentration of claim 1 , independently claim 1 , about 0.1% claim 1 , about 0.2% claim 1 , about 0.3% claim 1 , about 0.4% claim 1 , about 0.5% claim 1 , about 0.6% claim 1 , about 0.7% claim 1 , about 0.8% claim 1 , about 0.9% claim 1 , about 1% claim 1 , about 2% claim 1 , about 3% claim 1 , about 4% claim 1 , about 5% claim 1 , about 6% claim 1 , about 7% claim 1 , about 8% claim 1 , about 9% claim 1 , about 10% claim 1 , about 11% claim 1 , about 12% claim 1 , about 13% claim 1 , about 14% claim 1 , about 15% claim 1 , about 16% claim 1 , about 17% claim 1 , about 18% claim 1 , about 19% claim 1 , about 20% claim 1 , about 21% claim 1 , about 22% claim 1 , about 23% claim 1 , about 24% claim 1 , about 25% claim 1 , about 26% claim 1 , about 27% claim 1 , about 28% claim 1 , about 29% claim 1 , about 30% claim 1 , about 35% claim 1 , about 40% claim 1 , about 45% claim 1 , about 50% claim 1 , about ...

MICRONEEDLE ARRAY FOR ADMINISTERING VARIOUS TYPES OF DRUGS, MICRONEEDLE STRUCTURE INCLUDING MICRONEEDLE ARRAY, METHOD OF FABRICATING MICRONEEDLE ARRAY, AND METHOD OF FABRICATING MICRONEEDLE STRUCTURE

The present disclosure provides a microneedle array for administering various drugs, a microneedle structure including the microneedle array, a method of fabricating the microneedle array, and a method of fabricating the microneedle structure. The microneedle array of the present disclosure includes a plurality of microneedles, the surfaces of which are coated with a liquid drug and a base for supporting the microneedles. According to the present disclosure, the microneedles are divided into two or more areas, and the surfaces of microneedles disposed in each of the divided areas are coated with different liquid drugs. In this case, the ingredient of a liquid drug coated on microneedles disposed in one of the divided areas is different from the ingredients of liquid drugs coated on microneedles disposed in the remainder of the divided areas. 1. A microneedle array , comprising:a plurality of microneedles, surfaces of which are coated with a liquid drug; anda base for supporting the microneedles,wherein the microneedles are divided into two or more areas, and surfaces of microneedles disposed in each of the divided areas are coated with different liquid drugs, wherein an ingredient of a liquid drug coated on microneedles disposed in one of the divided areas is different from ingredients of liquid drugs coated on microneedles disposed in a remainder of the divided areas.2. The microneedle array according to claim 1 , wherein the microneedles and the base are integrally formed.3. The microneedle array according to claim 1 , wherein the areas that divide microneedles are spaced apart from each other by a predetermined interval.4. The microneedle array according to claim 3 , wherein an interval between the areas is formed wider than an interval between the microneedles.5. The microneedle array according to claim 1 , wherein one or more microneedles disposed in one of the areas are coated with a liquid drug of an identical ingredient.6. The microneedle array according to ...

Composition and method for reducing chemotherapy-induced neutropenia via the administration of plinabulin and a g-csf agent

Plinabulin and one or more G-CSF drugs are used for treating a chemotherapy induced neutropenia, stimulating neutrophil survival, reducing bone pain induced by the G-CSF drug and alleviating immune suppression effect induced by the G-CSF drug. For example, docetaxel-induced neutropenia can be reduced by-co-administering plinabulin and one or more G-CSF compounds.

TREATMENT OF POST-BARIATRIC HYPOGLYCEMIA USING MINI-DOSE STABLE GLUCAGON

Post-bariatric hypoglycemia (PBH) is an increasingly-recognized complication of gastric bypass surgery. Current therapeutic options have suboptimal efficacy. Small doses of stable liquid glucagon can be used to treat or prevent post-bariatric hypoglycemia. 135-. (canceled)36. A method of preventing or treating hypoglycemia in a post-bariatric surgery subject comprising:(a) determining whether or not the post-bariatric surgery subject is at risk of developing post-bariatric hypoglycemia (PBH); and(b) administering a therapeutic formulation comprising a glucagon peptide, a glucagon analog, or salts thereof to the subject if the subject is determined to be at risk of developing PBH.37. The method of claim 36 , further comprising monitoring the subject's blood glucose levels.38. The method of claim 36 , wherein the hypoglycemia is a post-prandial hypoglycemia episode.39. The method of claim 36 , wherein the hypoglycemia is a severe hypoglycemia episode.40. The method of claim 38 , wherein the subject's post-prandial blood glucose levels are decreasing and are below 100 claim 38 , 90 claim 38 , 80 claim 38 , 70 claim 38 , 60 claim 38 , or 50 mg/dL.41. The method of claim 40 , wherein the subject's blood glucose falls below 100 claim 40 , 90 claim 40 , 80 claim 40 , 70 claim 40 , 60 claim 40 , or 50 mg/dL within 90 claim 40 , 80 claim 40 , 70 claim 40 , 60 claim 40 , 50 claim 40 , 40 claim 40 , 30 claim 40 , 25 claim 40 , 20 claim 40 , 15 claim 40 , 10 claim 40 , 9 claim 40 , 8 claim 40 , 7 claim 40 , 6 claim 40 , 5 claim 40 , 4 claim 40 , 3 claim 40 , 2 claim 40 , or 1 minutes after a meal.42. The method of claim 36 , wherein the therapeutic formulation is administered 10 to 90 minutes after a meal.43. The method of claim 37 , wherein the therapeutic formulation is administered when the subject's blood glucose decreases by 0.5 to 10 mg/dL/min 90 claim 37 , 80 claim 37 , 70 claim 37 , 60 claim 37 , 50 claim 37 , 40 claim 37 , 30 claim 37 , 25 claim 37 , 20 claim 37 , 15 ...

ZIKA VIRUS VACCINES

Disclosed is an immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, optionally a signal peptide, and a multimerization domain. The signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain. Nucleic acids, vectors, and microneedle arrays including these compositions are disclosed. Methods of producing an immune response to ZIKV are also disclosed. 1. An immunogen comprising a fusion protein , wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein , optionally a signal peptide , and a multimerization domain , wherein:the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, andthe multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.2. The immunogen of claim 1 , wherein the ZIKV envelope protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6 or SEQ ID NO: 7.3. The immunogen of claim 2 , wherein the ZIKV envelope protein comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.4. The immunogen of claim 1 , comprising the human secretory signal peptide hidden Markov model claim 1 , wherein the human secretory signal peptide hidden Markov model comprises an amino acid sequence at least 95% identical to SEQ ID NO: 2.5. The immunogen of claim 6 , wherein the human secretory signal peptide hidden Markov model comprises the amino acid sequence of SEQ ID NO: 2.6. The immunogen of claim 1 , comprising the IgG signal peptide claim 1 , whereina) the IgG signal peptide is a mouse IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO: 3; orb) the ...

PHARMACEUTICAL COMPOSITIONS COMPRISING ATTENUATED PLASMODIUM SPOROZOITES AND GLYCOLIPID ADJUVANTS

Disclosed herein are pharmaceutical compositions comprising sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range and analogues of α-galactosylceramide (α-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided. 2. The pharmaceutical composition of wherein R═(CH)Ph(p-F).3P. falciparum, P. vivax, P. ovale, P. knowlesi, P. malariaeP. yoelii.. The pharmaceutical composition of wherein said species are selected from the group consisting of: claim 1 , and4P. falciparum.. The pharmaceutical composition of wherein said species comprises5. The pharmaceutical composition of wherein said sporozoite-stage parasites are attenuated.7. The method of wherein R═(CH)Ph(p-F).8. The method of wherein said host is a mammalian host.9. The method of wherein said host is a human host.10. The method of wherein said one or more doses comprise no more than 150 claim 6 ,000 sporozoites.11. The method of wherein said one or more doses comprise no more than 50 claim 10 ,000 sporozoites.12. The method of wherein said one or more doses comprise no more than 25 claim 11 ,000 sporozoites.13. The method of wherein the number of doses is no more than 3.14. The method of wherein the number of doses is no more than 2.15. The method of wherein the number of doses is no more than 1.16PlasmodiumP. falciparum, P. vivax, P. ovale, P. knowlesiP. malariae.. The method of wherein said species of said pharmaceutical composition are selected from the group consisting of claim 6 , and17PlasmodiumP. falciparum.. The method of wherein said species of said pharmaceutical composition comprises18. The method of wherein said pharmaceutical composition is administered by a parenteral route chosen from the group consisting of intravenous claim 6 , intramuscular claim 6 , intradermal claim 6 , and ...

Long-acting polymeric delivery systems

Compositions comprised of a delivery vehicle or delivery system and an active agent dispersed within the delivery vehicle or system, wherein the delivery vehicle or system contains a polyorthoester polymer and a polar aprotic solvent. Also disclosed are low viscosity delivery systems for administration of active agents. The low viscosity delivery systems have a polyorthoester polymer, a polar aprotic solvent and a solvent containing a triglyceride viscosity reducing agent. Compositions described include an amide- or anilide-type local anesthetic of the “caine” classification, and a non-steroidal anti-inflammatory drug (NSAID), along with related methods, e.g., for treatment of post-operative pain or for prophylactic treatment of pain. The compositions are suitable for delivery via, e.g., direct application and instillation, intradermal injection, subcutaneous injection, and nerve block (perineural).

Compositions and Methods Involving Polymer, Solvent, and High Viscosity Liquid Carrier Material

Compositions may include a pharmaceutical active agent, a high viscosity liquid carrier material (HVLCM), a lactic acid-based polymer, and an organic solvent. Related compositions and methods are also disclosed. For instance, a carrier formulation for controlled release of injectable drugs is disclosed. The formulation may include a non-water soluble high viscosity liquid which may be sucrose acetate isobutyrate, a lactic-acid based polymer which may be a poly(lactic acid)(glycolic acid), and an organic solvent which maintains the composition in a monophasic form at 25° C. in one atmosphere. Drug in the formulation may be released upon administration such that less than 10% (e.g. 2-8%) of drug is released in the first 5 hours; 10% to 80% of the drug is released during a period of 5 hours to 7 days after administration; and 10% to 40% of the drug is released gradually over a period of 7 days to 28 days from initial administration. The drug may be an anti-schizophrenia agent delivered by injection. 1. A composition comprising:a pharmaceutical active agent;25 wt % to 80 wt %, based on total weight of the composition, of a non-polymeric, non-water soluble high viscosity liquid carrier material (HVLCM) having a viscosity of at least 5000 cP at 37° C. that does not crystallize neat at 25° C. and 1 atmosphere;a lactic acid-based polymer comprising an alkoxy end group; andan organic solvent.2. The composition of claim 1 , wherein the lactic-acid based polymer has a weight average molecular weight ranging from 1000 Daltons to 30 claim 1 ,000 Daltons.3. The composition of claim 1 , wherein the pharmaceutical active agent comprises at least one member selected from peptide claim 1 , protein claim 1 , and small molecule.4. The composition of claim 1 , wherein the pharmaceutical active agent comprises risperidone or pharmaceutically acceptable salt thereof.5. The composition of claim 1 , wherein the pharmaceutical active agent comprises particles having a median particle size ...

VACCINE GENERATION

An apparatus for vaccine generation includes a syringe with a cavity that includes a solution with photosensitizers. Microbial particles are added to the solution. A light source is capable of emitting one or more wavebands of light that are effectively absorbed by the one photosensitizers to generate singlet oxygen in the solution and other radical species that rapidly react with and damage lipids, proteins, DNA, and RNA of the microbial particles. This damage produces immunogens that can be applied as a vaccine to viruses and other infectious microbial particles. A plunger that fits within a proximal opening in the syringe is used for forcing the solution including the immunogens through the filter and out of the syringe while the photosensitizers, debris and unwanted microbial particles are trapped within the filter. 1. An apparatus for vaccine generation , comprising:a syringe defining a cavity for containing a solution that includes one or more photosensitizers;one or more light sources capable of emitting light at one or more wavebands that activate the one or more photosensitizers to generate singlet oxygen in the solution, wherein a plurality of immunogens are created in the solution by interaction of the singlet oxygen with a plurality of microbial particles that are added to the solution;a plunger that fits within an opening at a proximal end of the syringe, wherein advancement of the plunger from the proximal end to another position at the distal end of the syringe causes evacuation of the solution with the plurality of immunogens through the other opening at the distal end; andone or more filters capable of trapping one or more of debris and the plurality of microbial particles during evacuation of the solution.2. The apparatus of claim 1 , wherein the one or more photosensitizers includes one or more of erythrosine claim 1 , riboflavin claim 1 , or methylene blue.3. The apparatus of claim 1 , wherein the solution includes one or more aqueous solutions.4 ...

Continuous Delivery of Lenalidomide and Other Immunomodulatory Agents

Provided are systems and methods for continuously administering to a subject in need of treatment a formulation comprising an immunomodulatory imide compound. In some embodiments, the method are for use in treating multiple myeloma, transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes, mantle cell lymphoma, hematologic cancers, or solid tumor cancers.

NANOPARTICLES, CONTROLLED-RELEASE DOSAGE FORMS, AND METHODS FOR DELIVERING AN IMMUNOTHERAPEUTIC AGENT

The present disclosure relates to nanoparticles, controlled-release dosage forms, and methods for the administration of an immunotherapeutic agent. 110.-. (canceled)11. A method of chemoprevention comprising: administering to a host a controlled-release pharmaceutical dosage form in an amount sufficient to prevent the recurrence of a cancer; wherein the controlled-release pharmaceutical dosage form comprises a CpG oligodeoxynucleotide nano-cocoon , wherein the nano-cocoon is loaded with a therapeutic agent and is attached to inflammation-responsive nanoparticles , wherein the nanoparticles encapsulate a restriction enzyme.12. The method of claim 11 , wherein the therapeutic agent is selected from an anti-PD1 antibody claim 11 , an anti-PDL1 antibody claim 11 , an anti-CTLA4 antibody claim 11 , or a combination thereof.13. The method of claim 12 , wherein the therapeutic agent is an anti-PD1 antibody.14. The method of claim 13 , wherein the anti-PD1 antibody is nivolumab.15. The method of claim 13 , wherein the anti-PD1 antibody is pembrolizumab.16. The dosage form of claim 12 , wherein the therapeutic agent is an anti-CTLA4 antibody.17. The method of claim 16 , wherein the anti-CTLA4 antibody is ipilimumab.18. The method of claim 12 , wherein the therapeutic agent is an anti-PD1 antibody in combination with an anti-CTLA4 antibody.19. The method of claim 11 , wherein the inflammation-responsive nanoparticles comprise triglycerol monostearate (TGMS).20. The method of claim 11 , wherein the restriction enzyme is HhaI.21. The method of claim 11 , wherein the cancer is a solid tumor.22. The method of claim 11 , wherein the cancer is melanoma.2339.-. (canceled)40. The method of claim 11 , wherein the therapeutic agent is selected from a small-molecule drug claim 11 , a small interfering RNA (siRNA) claim 11 , an immunostimulatory oligonucleotide CpG claim 11 , a photosensitizer claim 11 , or a protein.41. The method of claim 11 , wherein the therapeutic agent is an ...

COATING LIQUID FOR MICRONEEDLES, MICRONEEDLE-COATING SUBSTANCE, AND MICRONEEDLE ARRAY

To provide a composition of a coating liquid for microneedle which is optimal for coating a microneedle with a medicinal ingredient. 1. A coating liquid for microneedle comprising an aqueous solution containing , as essential components of a base , a water-soluble polysaccharide , monosaccharide and/or disaccharide , and a surfactant.2. The coating liquid for microneedle according to claim 1 , wherein hardness of a coating material after being dried is 10 N or more.3. The coating liquid for microneedle according to claim 1 , further containing a water-soluble polyalcohol as the base.4. The coating liquid for microneedle according to claim 1 , wherein in the base claim 1 , the water-soluble polysaccharide is 2 to 60 mass % claim 1 , the monosaccharide and/or the disaccharide is 30 to 95 mass % claim 1 , the surfactant is 0.05 to 5 mass % claim 1 , and the water-soluble polyalcohol is 10 mass % or less.5. The coating liquid for microneedle according to claim 1 , wherein the water-soluble polysaccharide is at least one kind of compound selected from a group consisting of hydroxypropyl cellulose claim 1 , hyaluronic acid claim 1 , chondroitin sulfate claim 1 , dextran claim 1 , and carboxymethyl cellulose.6. The coating liquid for microneedle according to claim 1 , wherein the monosaccharide is glucose claim 1 , and the disaccharide is sucrose or trehalose.7. The coating liquid for microneedle according to claim 1 , wherein the surfactant is at least one kind of compound selected from a group consisting a polysorbate 80 claim 1 , polysorbate 20 claim 1 , and polyoxyethylene polyoxypropylene glycol.8. The coating liquid for microneedle according to claim 3 , wherein the water-soluble polyalcohol is at least one kind of compound selected from a group consisting of glycerin claim 3 , ethylene glycol claim 3 , propylene glycol claim 3 , butylene glycol claim 3 , and polyethylene glycol with a molecular weight of 500 or less.9. The coating liquid for microneedle according to ...

NANOSPHERES ENCAPSULATING BIOACTIVE MATERIAL AND METHOD FOR FORMULATION OF NANOSPHERES

A method of transdermal delivery of a vaccine, comprising preparing microparticles of encapsulated vaccine by spray drying a mixture of the vaccine and at least one polymer, and injecting the microparticles transdermally using a microneedle delivery apparatus. 1preparing microparticles of encapsulated vaccine by spray drying a mixture of the vaccine and at least one polymer;providing a microneedle delivery apparatus;introducing the microparticles into the microneedle delivery apparatus; and,injecting the microparticles transdermally using the microneedle delivery apparatus.. A method of transdermal delivery of a vaccine, comprising: This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 12/569,867, filed Sep. 29, 2009, entitled NANOSPHERES ENCAPSULATING BIOACTIVE MATERIAL AND METHOD FOR FORMULATION OF NANOSPHERES, which claims priority to U.S. Provisional Patent Application No. 61/100,886, filed Sep. 29, 2008, commonly assigned to the assignee of the present application, the disclosures of which are incorporated by reference in their entirety herein.The present disclosure relates to, among other aspects:1) Buccal and transdermal delivery of microparticulate-based vaccines againsta) Cancer (examples include: melanoma, breast, ovarian cancer vaccines)b) Infectious diseases (examples include: influenza, HPV, measles, meningitis, gonorrhea, RSV)2) Potentiation of vaccine efficacy using probiotic Microparticles, and 3) Encapsulation of pancreatic beta cells for treatment of insulin dependent Diabetes MellitusThe skin provides a unique site for the vaccination purposes as it is easily accessible and houses various immune cells for an efficient immune response against a range of antigens. Skin serves as a barrier against various pathogens and is equipped with the skin associated lymphoid tissues (SALT) to combat any insult from invading pathogens. Various skin cells assist in generation of effective immune response. Keratinocytes are the ...

Combinations of gabaa alpha 5 agonists and sv2a inhibitors and methods of using in the treatment of cognitive impairment

This disclosure relates to methods, uses, combinations, pharmaceutical compositions, combinations for use, and pharmaceutical compositions for use useful for treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of inhibitors of synaptic vesicle glycoprotein 2A (SV2A), in combination with GABA A α5 receptor agonists, in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, mild cognitive impairment (MCI), amnestic MCI (aMCI), age-associated memory impairment (AAMI), age related cognitive decline (ARCD), dementia, Alzheimer's disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease, autism, compulsive behavior, and substance addiction. Further, the disclosure relates to methods, uses, combinations, pharmaceutical compositions, combinations for use, and pharmaceutical compositions for use useful for treating cognitive impairment associated with brain cancer or for treating brain cancer itself in a subject in need thereof. Additionally, the disclosure relates to methods, uses, combinations, pharmaceutical compositions, combinations for use, and pharmaceutical compositions for use useful for treating Parkinson's disease psychosis in a subject in need thereof.

Injectable Botulinum Toxin Formulations And Methods Of Use Thereof Having Long Duration Of Therapeutic Or Cosmetic Effect

This invention provides novel injectable compositions comprising toxin that may be administered to a subject for various therapeutic, aesthetic and/or cosmetic purposes. The injectable compositions embraced by the invention exhibit one or more advantages over conventional toxin formulations, including reduced antigenicity, a reduced tendency to undergo unwanted localized diffusion following injection, increased duration of clinical efficacy or enhanced potency relative, faster onset of clinical efficacy, and/or improved stability. According to the invention, single treatment of the compositions by injection affords significant clinical responses and at least a 6-month duration of effect in a subject undergoing treatment, as provided by the described treatment methods.

METHOD TO PRINT MICRONEEDLE PATCHES RAPIDLY

This invention teaches a method to achieve rapid 3D printing of microneedle patches. The 3D printing method comprises a printing nozzle of multiple micro-holes and cold plate/platform on which the microneedle-supporting sheet (membrane) is placed. The solution or aqueous solution of microneedle-forming materials is printed onto the cold microneedle-supporting sheet with programed rate of injection from the nozzle and velocity of the nozzle lifting. The relationship between the injection rate and the lifting velocity determines the shape of the microneedle tips. The freshly printed microneedles on the cold sheet are dried in two ways, drying at a temperature close to the ice point of water or drying after a freeze-thaw treatment of the microneedles. 1. A method for producing microneedle patches characterized by printing , injecting , cumulating , or piling up an aqueous solution of microneedle forming materials on a frozen or cold supporting sheet or plate on which the formed frozen microneedles stand.2. The method of claim 1 , wherein an injection or injecting pump is used to print claim 1 , inject claim 1 , cumulate claim 1 , or pile up claim 1 , i.e. 3D print claim 1 , the solution of microneedle-forming materials.3. The method of claim 2 , wherein the injection or injecting pump is equipped with a nozzle head which has single or multiple micro-holes aligned to an array.4. The method of claim 1 , wherein the frozen supporting sheet or plate for microneedles to stand on is made of the same or similar materials of the microneedle forming materials claim 1 , or made of the materials on which the microneedles may stand.5. The method of claim 1 , wherein the supporting sheet or plate is loaded on a holder made of metal or other suitable heat-conducting materials which is laid on a cold platform for freezing the sheet or plate.6. The method of claim 1 , wherein the microneedle printing claim 1 , injecting claim 1 , cumulating claim 1 , or piling up is followed by ...

Stable Glucagon Peptide Formulations

There is provided glucagon formulations suitable for preparing coatings on microneedle patches for the transdermal delivery of glucagon. The coated patches may be used for the treatment of low blood sugar in diabetic patients. Also provided are glucagon loaded patches, methods for their preparation, and methods of their use. 1. A liquid pharmaceutical formulation comprising glucagon and lyso-myristoyl phosphatidylcholine (LMPC) , wherein the amount of LMPC is between 2 and 8 fold less than the amount of glucagon and further comprises 50 mg/mL trehalose , 50 mg/mL tartaric acid , 50 mg/mL glycine and Sodium Carboxymethyl Cellulose (NaCMC) , wherein the concentration of NaCMC is greater than 0.1 mg/ml and less than 1 mg/ml , and wherein the pH of said liquid pharmaceutical formulation is between 2.8 and 3.2.2. The liquid pharmaceutical formulation of claim 1 , wherein glucagon is at a concentration of 200 mg/mL claim 1 , and wherein LMPC is at a concentration of 100 mg/mL.3. The liquid pharmaceutical formulation of or claim 1 , wherein NaCMC is at a concentration of 0.5 mg/mL.4. A solid pharmaceutical formulation comprising glucagon and lyso-myristoyl phosphatidylcholine (LMPC) claim 1 , wherein the amount of LMPC is between 2 and 8 fold less than the amount of glucagon and further comprises 11.1% w/w trehalose claim 1 , 11.1% w/w tartaric acid and 11.1% w/w glycine.5. The solid pharmaceutical formulation of claim 4 , comprising 44.5% w/w glucagon claim 4 , 22.2% w/w LMPC claim 4 , 11.1% w/w trehalose claim 4 , 11.1% w/w tartaric acid and 11.1% w/w glycine.6. A medical device for the delivery of a pharmaceutical agent through the skin claim 1 , the device comprising an array of microneedles having coated thereon a liquid composition according to .7. The medical device of carrying a therapeutic dose of glucagon ranging from of 0.5 mg to 1.0 mg.8. A medical device for the delivery of a pharmaceutical agent through the skin claim 4 , the device comprising an array of ...

METHOD OF DRUG DELIVERY FOR PTH, PTHrP AND RELATED PEPTIDES

The present invention provides compositions, devices, methods and processes related to the intradermal delivery of PTHrP and PTHrP analogues, particularly [Glu, Leu, Aib, Lys]hPTHrP(1-34)NH. 1. An aqueous formulation comprising [Glu , Leu , Aib , Lys]hPTHrP(1-34)NH(SEQ ID NO: 2) , wherein said formulation is suitable for coating a microprojection array and wherein said formulation comprises at least 5% by weight of [Glu , Leu , Aib , Lys]hPTHrP(1-34)NH(SEQ ID NO: 2).2144.-. (canceled) This application is a continuation of U.S. patent application Ser. No. 16/279,770, filed Feb. 19, 2019, which is a continuation of U.S. patent application Ser. No. 15/351,317, filed Nov. 14, 2016, which is a continuation of U.S. patent application Ser. No. 13/791,360, filed Mar. 8, 2013. U.S. patent application Ser. No. 15/351,317 is also a continuation of U.S. Ser. No. 13/791,170, filed Mar. 8, 2013. U.S. patent application Ser. No. 13/791,360, filed Mar. 8, 2013 and U.S. patent application Ser. No. 13/791,170, filed Mar. 8, 2013 are continuation applications of U.S. patent application Ser. No. 13/452,412, filed Apr. 20, 2012 which claims the benefit of U.S. Provisional Application No. 61/578,120, filed Dec. 20, 2011 and U.S. Provisional Application No. 61/478,466, filed Apr. 20, 2011. The entire contents of the above applications are incorporated herein by reference.The instant application contains a Sequence Listing which has been submitted electronically in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created Aug. 31, 2020 is named R105231 1050 USCS SL.TXT and is 1,463 bytes in size.Parathyroid hormone-related protein (“PTHrP”) is a 139 to 173 amino acid-protein. PTHrP, especially the C-terminal 1-36 secretory product and certain analogs, are known to be useful for the treatment of osteoporosis and related disorders by stimulating bone formation to improve bone mineral density (BMD). PTHrP analogues having excellent ...

GLUCOSE RESPONSIVE COMPOSITE GEL COMPOSITION, METHOD FOR PRODUCING SAME, INSULIN DELIVERY MICRONEEDLE INCLUDING SAID GLUCOSE RESPONSIVE COMPOSITE GEL COMPOSITION, AND PRODUCTION METHOD THEREOF

A gel composition which can be used suitably for a microneedle that can release insulin according to the glucose concentration in a self-regulated manner and a microneedle using the same. An insulin delivery microneedle comprises a base part fabricated with silk fibroin, at least one needle part integrally provided on the base part, and an insulin reservoir. At least a tip portion of the needle part comprises a composite gel composition comprising a copolymer comprising a phenylboronic acid-based monomer unit and silk fibroin. 1. A glucose-responsive composite gel composition comprising: a copolymer comprising a phenylboronic acid-based monomer unit; and silk fibroin.2. The glucose-responsive composite gel composition according to claim 1 , wherein a proportion of the silk fibroin in a solid content of the composite gel composition is 10 to 90% by weight.3. The glucose-responsive composite gel composition according to claim 1 , wherein the phenylboronic acid-based monomer unit comprises a phenylboronic acid-based monomer claim 1 , a gelling agent claim 1 , and a crosslinking agent.4. A method for producing a glucose-responsive composite gel composition claim 1 , comprising:providing a monomer mixture comprising a phenylboronic acid-based monomer; andcopolymerizing the monomer mixture in a presence of silk fibroin.5. The method for producing a glucose-responsive composite gel composition according to claim 4 , wherein a proportion of the silk fibroin in a total solid content is 10 to 90% by weight in the step of copolymerizing.6. The method for producing a glucose-responsive composite gel composition according to claim 4 , wherein the copolymerizing is performed at normal temperature.7. The method for producing a glucose-responsive composite gel composition according to claim 4 , wherein the monomer mixture comprises the phenylboronic acid-based monomer claim 4 , a gelling agent claim 4 , a crosslinking agent claim 4 , and a solvent.8. The method for producing a ...

METHODS FOR BETTER DELIVERY OF ACTIVE AGENTS TO TUMORS

The present invention concerns delivery of agents through the skin. Methods for delivering agents such as bioactive agents are contemplated by the present invention. Specifically, methods for the targeted delivery of agents to one or more areas of the epidermis and thereby, to one or more cancer tumors are described. 1. A method of treating a subject with a disease comprising one or more tumors by administering one or more bioactive agents to the one or more tumors comprising:(a) applying one or more delivery devices having between 2 and 50,000 delivery structures to one or more sites of a skin of a subject comprising blood vasculature and lymphatic vasculature, wherein the delivery device contacts one or more layers of epidermis with one or more reversible permeability enhancers that induces a reversible increase in the permeability of one or more barrier cells of the epidermis to at least the one or more bioactive agents;(b) administering a total liquid dosage in between 2 and 50,000 sub-doses of the one or more bioactive agents at a controlled administration flow rate through the delivery device;wherein each sub-dose of the one or more bioactive agents is independently administered, in an administering step, to a plurality of independent depths within the epidermis prior to any subsequent diffusion or movement of the one or more bioactive agents within the epidermis; andwherein following the administering step, the one or more bioactive agents moves or diffuses deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis to achieve an uptake of a portion of the one or more bioactive agents by one or more susceptible blood capillary plexus or lymphatic capillary plexus;wherein after administration and uptake, the one or more bioactive agents circulates through the blood vasculature or lymphatic vasculature to one or more tumors; andwherein a greater concentration of the one or more bioactive agents is ...

THERAPEUTIC METHOD USING TOLEROGENIC PEPTIDES

The present invention relates to a therapeutic method using a tolerogenic peptide. In particular, the invention relates to a dosage regimen fora tolerogenic peptide. The therapeutic method can be used to treat or prevent conditions associated with aberrant, hypersensitivityor pathological immune responses to endogenous or exogenous proteins that results in a loss of immune tolerance. 1. A method of treating or preventing in a subject a condition associated with aberrant immune tolerance (autoimmune disease) , comprising administering to the patient a tolerogenic peptide via a dose escalation protocol in the following doses:Day 1: a first dose of about 15 to about 40 μg;Day 14±7 days: a second dose of about 35-65 μg;Day 28±7 days: a third dose of about 80-120 μg;Day 42±7 days: a fourth dose of about 300-500 μg;Day 56±7 days: a fifth dose of about 600-1500 μg;Day 70±7 days: a sixth dose of about 600-1500 μg;Day 84±7 days: a seventh dose of about 600-1500 μg;Day 98±7 days: an eighth dose of about 600-1500 μg;Day 112±7 days: a ninth dose of about 600-1500 μg; andDay 126±7 days: a tenth dose of about 600-1500 μg.2. The method of wherein the first dose is about 25 μg.3. The method of wherein the second dose is about 50 μg.4. The method of claim 1 , wherein the third dose is about 100 μg.5. The method of claim 1 , wherein the fourth dose is about 400 μg.6. The method of claim 1 , wherein an eleventh dose of about 600-1500 μis administered on day 140±7 days.7. The method of claim 6 , wherein a twelfth dose of about 600-1500 μg is administered on day 154±7 days.8. The method of claim 7 , wherein a thirteenth dose of about 600-1500 μg is administered on day 168±7 days.9. The method of claim 1 , wherein the fifth claim 1 , sixth claim 1 , seventh claim 1 , eighth claim 1 , ninth and tenth claim 1 , and optionally an eleventh claim 1 , optionally a twelfth claim 1 , and optionally a thirteenth claim 1 , doses are each about 800 μg.10. The method of claim 1 , wherein ...

Methods and products for nucleic acid production and delivery

The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices. Methods and products for altering the DNA sequence of a cell are described, as are methods and products for inducing cells to express proteins using synthetic RNA molecules, including cells present in vivo. Therapeutics comprising nucleic acids encoding gene-editing proteins are also described.

SYSTEMS AND METHODS FOR DELIVERY OF A THERAPEUTIC AGENT

Methods and apparatus are provided for applying an fragment of a neurotoxin such as the active light chain (LC) of the botulinum toxin (BoNT), such as one of the serotype A, B, C, D, E, F or G botulinum toxins, via permeabilization of targeted cell membranes to enable translocation of the botulinum neurotoxin light chain (BoNT-LC) molecule across the targeted cell membrane to the cell cytosol where a therapeutic response is produced in a mammalian system. The methods and apparatus include use of catheter based delivery systems, non-invasive delivery systems, and transdermal delivery systems. 1. A method of treating a nasal condition of a patient comprising:positioning a distal portion of a treatment device proximate to target tissue in a nasopharyngeal passage of a patient; andadministering therapy to the target tissue with the treatment device so as to disrupt neural activity such that mucus secretion is reduced in the nasopharyngeal passage;wherein administering therapy comprises at least one of delivering energy to the target tissue and changing the temperature of the target tissue.2. The method of claim 1 , wherein administering therapy comprises delivering energy from at least one energy delivery element on the treatment device.3. The method of claim 2 , wherein the energy comprises RF energy.4. The method of claim 2 , wherein the energy comprises ultrasound energy.5. The method of claim 2 , wherein the energy comprises microwave energy.6. The method of claim 2 , wherein the energy comprises AC or DC current.7. The method of claim 1 , wherein changing the temperature comprises transferring thermal energy between the treatment device and the target tissue.8. The method of claim 1 , wherein the energy is delivered or the temperature is changed so as to electroporate cells in the target tissue.9. The method of claim 1 , wherein administering therapy comprises contacting target tissue with a delivery portion of the treatment device.10. The method of claim 9 , ...

TREATMENT FOR MULTIPLE MYELOMA (MM)

The present disclosure relates to the treatment of multiple myeloma. Monoclonal antibody MOR202 is efficacious when administered to patient at certain dosage regimens. 1. An antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1) or SYYMN (SEQ ID NO: 2) , an HCDR2 region of sequence GISGDPSNTYYADSVKG (SEQ ID NO: 3) , an HCDR3 of sequence DLPLVYTGFAY (SEQ ID NO: 4) , an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 5) , an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 6) , and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 7) for use in the treatment of multiple myeloma , wherein said antibody is administered at a dose of 8 mg/kg or more.2. The antibody according to claim 1 , wherein said antibody is administered at a dose of 16 mg/kg or more.3. The antibody according to claim 1 , wherein said antibody is administered once every two weeks (q2w) over at least eight weeks.4. The antibody according to claim 1 , wherein said antibody is administered once weekly (q1w) over at least eight weeks.5. The antibody according to claim 1 , wherein said antibody is administered intravenously.6. The antibody according to claim 1 , wherein said antibody is administered intravenously over a period of two hours.7. The antibody according to claim 1 , wherein said antibody comprises a variable heavy chain of the sequence QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYYMNWVRQAPGKGLEWVSGISGDPSNTYYADSV KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLPLVYTGFAYWGQGTLVTVSS (SEQ ID NO: 8) and a variable light chain of the sequence DIELTQPPSVSVAPGQTARISCSGDNLRHYYVYWYQQKPGQAPVLVIYGDSKRPSGIPERFSGS NSGNTATLTISGTQAEDEADYYCQTYTGGASLVFGGGTKLTVLGQ (SEQ ID NO: 9).8. The antibody according to claim 1 , wherein said antibody comprises an IgG1 Fc region.9. The antibody according to claim 1 , wherein said antibody is administered in combination with dexamethasone.10. The antibody according to claim 9 , wherein said antibody is administered in combination with dexamethasone claim 9 , wherein ...

MICRONEEDLE SHEET

A microneedle sheet according to an embodiment includes a plurality of microneedles formed on a sheet generally along a principal surface of the sheet. The material of the microneedles is selected from among hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, and a graft copolymer of polyvinyl alcohol and polyethylene glycol. The microneedles are raised from the principal surface by bending the sheet, and the raised microneedles pierce skin. 1. A microneedle sheet comprising a plurality of microneedles formed on a sheet generally along a principal surface of the sheet , whereinthe microneedles are formed of a material selected from among hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, and a graft copolymer of polyvinyl alcohol and polyethylene glycol, andthe microneedles are raised from the principal surface by bending the sheet, and the raised microneedles pierce skin.2. The microneedle sheet according to claim 1 , wherein the sheet has a thickness of 10 to 300 μm.3. The microneedle sheet according to claim 1 , wherein an insertion angle of the raised microneedle to the skin is 34 degrees or greater and less than 180 degrees.4. The microneedle sheet according to claim 1 , wherein a maximum angle between the microneedle raised from the principal surface and an imaginary line extending from center of curvature of the sheet to a base of the microneedle is greater than 90 degrees.5. The microneedle sheet according to claim 4 , wherein the maximum angle is 95 to 130 degrees. An aspect of the present invention relates to a microneedle sheet used for assisting in administration of an active component by microneedles.Microneedles for administrating active components through skin and devices including the microneedles are conventionally known. For example, a rotatable microstructure apparatus disclosed in Patent Literature 1 below includes a curved substrate and a roller structure including a plurality of microelements ...

A TRANSDERMAL DRUG ADMINISTRATION DEVICE

A transdermal drug administration device comprising a drug delivery element attached to a solvent-swellable and/or solvent-soluble substrate, wherein the drug delivery element defines a contact surface for location, in use, against a patient's skin. The drug delivery element comprises an active pharmaceutical ingredient and a porous solid material. 1. A transdermal drug administration device comprising a drug delivery element attached to a water-swellable substrate comprising one or more organic polymers , wherein the drug delivery element defines a contact surface for location , in use , against a patient's skin , further wherein the drug delivery element comprises an active pharmaceutical ingredient and a porous solid material , wherein the porous solid material is based on one or more ceramic materials or one or more geopolymeric materials.2. A transdermal drug administration device according to wherein the porous solid material is formed from a self-setting ceramic.3. A transdermal drug administration device according to claim 1 , wherein the porous solid material is based on a calcium sulfate claim 1 , a calcium phosphate claim 1 , a calcium silicate claim 1 , a calcium carbonate or a magnesium carbonate.4. A transdermal drug administration device according to claim 3 , wherein the porous solid material is calcium sulfate hemihydrate or acidic calcium phosphate.5. A transdermal drug administration device according to claim 1 , wherein the active pharmaceutical ingredient is predominantly located within the pores of the porous solid.6. A transdermal drug administration device according to claim 1 , wherein the active pharmaceutical ingredient is predominantly located on the outer surface of the porous solid.7. A transdermal drug administration device according to claim 1 , wherein the drug delivery element is an array of microscopic protrusions.8. A transdermal drug administration device according to claim 1 , wherein the contact surface of the drug delivery ...

Stable Glucagon Peptide Formulations

There is provided glucagon formulations suitable for preparing coatings on microneedle patches for the transdermal delivery of glucagon. The coated patches may be used for the treatment of low blood sugar in diabetic patients. Also provided are glucagon loaded patches, methods for their preparation, and methods of their use. 1. A liquid pharmaceutical formulation comprisinga. 15-20% (w/w) of glucagon;b. 7.5-10% (w/w) of a stabilizing agent selected from either a cationic or neutral surfactant;c. 3.75-5% (w/w) of an amino acid;d. 3.75-5% (w/w) of an organic acid; ande. a pharmaceutically acceptable diluent; andwherein the formulation has a pH between 2 and 3.2. The pharmaceutical formulation according to claim 1 , wherein the surfactant is a phospholipid.3. The pharmaceutical formulation according to claim 2 , wherein the phospholipid is lyso-myristoyl phosphatidylcholine.4. The pharmaceutical formulation according to claim 1 , wherein the surfactant is decanoyl sucrose.5. The pharmaceutical formulation according to claim 1 , wherein the amino acid is selected from the group consisting of glutamine and glycine.6. The pharmaceutical formulation according to has a viscosity in the range of 20-200 cP.7. The pharmaceutical formulation according to claim 1 , wherein the organic acid is selected from the group consisting of methanoic acid claim 1 , ethanoic acid claim 1 , tartaric acid claim 1 , malonic acid claim 1 , glycolic acid claim 1 , malic acid claim 1 , gluconic acid claim 1 , citric acid claim 1 , caproic acid claim 1 , benzoic acid claim 1 , lactic acid claim 1 , propionic acid claim 1 , and sorbic acid.8. The pharmaceutical formulation according to claim 1 , wherein the surfactant is decanoyl sucrose claim 1 , the amino acid is glutamine and the organic acid is tartaric acid.9. The pharmaceutical formulation according to claim 1 , wherein the surfactant is decanoyl sucrose claim 1 , the amino acid is glycine and the organic acid is tartaric acid.10. The ...

Therapeutic constructs for co-delivery of mitotic kinase inhibitor and immune checkpoint inhibitor

Disclosed herein are therapeutic constructs including a delivery particle, at least one mitotic kinase inhibitor, and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.

MODIFIED THERAPEUTIC AGENTS AND COMPOSITIONS THEREOF

Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof. 141-. (canceled)43. The mTA of claim 42 , wherein the TA comprises an amino acid sequence that is at least 97% homologous to an amino acid sequence selected from SEQ ID NOS: 7-30.44. The mTA of claim 42 , wherein the TA comprises any one of SEQ ID NOS: 7-30.45.45. The mTA of claim 42 , wherein each of the two amino acid residues is lysine.46. The mTA of claim 42 , further comprising a second staple and a second half-life extending molecule claim 42 , wherein the second half-life molecule is covalently attached to the second staple.47. The mTA of claim 42 , wherein the half-life of the mTA is longer than the half-life of the unmodified TA alone.48. The mTA of claim 42 , wherein the half-life of the mTA is at least 5-fold longer than the half-life of the unmodified TA alone.49. A pharmaceutical composition comprising the mTA of and a pharmaceutically acceptable excipient.50. A method for treating a disease or condition in a subject in need thereof claim 42 , the method comprising administering to the subject a composition comprising a therapeutically effective amount of the mTA of .51. The method of claim 50 , wherein the disease or condition is diabetes or obesity claim 50 , or a medical condition associated with diabetes claim 50 , obesity claim 50 , non-alcoholic fatty liver disease (NAFLD) claim 50 , nonalcoholic steatohepatitis (NASH) claim 50 , cardiovascular disease claim 50 , short bowel syndrome (SBS) claim 50 , inflammatory bowel disease (IBD) claim 50 , inflammatory bowel syndrome (IBS) claim 50 , psoriasis claim 50 , Crohn's disease claim 50 , ulcerative colitis claim 50 , Alzheimer's disease claim 50 , Parkinson's disease claim 50 , Huntington's disease.52. ...