АПТАМЕР К ХИМАЗЕ И ЕГО ПРИМЕНЕНИЕ

Группа изобретений относится к обоасти биохимии и биотехнологии. Представлены аптамер, связывающийся с химазой и ингибирующий активность химазы, содержащий нуклеотидную последовательность, представленную как XGAUAGANNUAAX, где Xи Xидентичны или не идентичны друг другу и каждый означает A или G, а Nи Nидентичны или не идентичны друг другу и каждый означает A, G, C, U или T; комплекс, включающий аптамер и функциональное вещество, например вещество, обладающее сродством, вещество для мечения, фермент, средство доставки лекарственного средства, лекарственное средство; лекарственное средство или реагент, содержащее аптамер или комплекс; способы детекции и очистки химазы с использованием аптамера или комплекса. 9 н. и 7 з.п. ф-лы, 8 ил., 9 табл., 9 пр.

ПРИМЕНЕНИЕ ЭКСТРАКТА IRIDACEAE, КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ ЕГО И СПОСОБ КОСМЕТИЧЕСКОГО ЛЕЧЕНИЯ

Применение экстракта клеток по меньшей мере одного растения из семейства Iridaceae в фармацевтической композиции в качестве антагониста CGRP и/или вещества Р. Косметические или фармацевтические композиции, содержащие экстракт клеток по меньшей мере одного растения из семейства Iridaceae и продукт с раздражающим действием или соединение, снижающее синтез или активность медиатора воспаления. Способ косметологического лечения, включающий использование одной из композиций. Изобретение позволяет получать и применять стандартизированный материал для терапевтического и косметологического лечения кожи, волос и слизистых оболочек. 7 с. и 46 з.п. ф-лы.

НОВЫЕ НЕСТЕРОИДНЫЕ ПРОТИВОВОСПАЛИТЕЛЬНЫЕ ВЕЩЕСТВА, СОСТАВЫ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Настоящее изобретение относится к новым нестероидным противовоспалительным соединениям, представленным формулой I: где М представляет собой макролидную субъединицу формулы D представляет собой нестероидную субъединицу, полученную из нестероидного противовоспалительного средства, L представляет собой соединительную группу с формулой X1-(CH2)m-Q-(CH2)n-X2, или их фармацевтически допустимым солям или отдельным диастереоизомерам. Кроме того, настоящее изобретение относится к способу получения соединений формулы I (варианты), к фармацевтическому составу на основе соединений формулы I или их фармацевтически допустимых солей, а также к применению соединений формулы I или их фармацевтически допустимых солей для получения медикамента (варианты). Значение заместителей R1-R6, А, В, Е, U, Y, Z, W, S1, М, D, X1, X2, Q, m, n указаны в формуле изобретения. 7 н. и 4 з.п. ф-лы, 1 табл., 7 схем.

СПОСОБЫ ВЫЯВЛЕНИЯ ИНДУКТОРОВ И ИНГИБИТОРОВ ПРОТЕОЛИТИЧЕСКИХ АНТИТЕЛ, КОМПОЗИЦИИ НА ИХ ОСНОВЕ И ИХ ПРИМЕНЕНИЕ

Изобретение относится к области молекулярной биологии и касается способов выявления индукторов и ингибиторов протеолитических антител, композиций на их основе и их применения. Изобретение включает ковалентно-реактивный антигенный аналог (КРАА) структурной формулы X1-Y-E-X2, где X1 и Х2 - пептидные последовательности из 3-10 аминокислот эпитопа пептида, связанного с болезнью; Y - положительно заряженный остаток аминокислоты и Е -электрофильный реакционный центр, способ стимуляции выработки антител с каталитической активностью, каталитическое антитело, способ пассивной иммунизации пациента, способ активной иммунизации пациента в отношении микробной инфекции, фармацевтическую композицию для лечения патологического состояния. Преимущество изобретения заключается в создании композиций и способов стимуляции выработки каталитических антител. 10 с. и 12 з.п. ф-лы, 19 ил.

СПОСОБ КОРРЕКЦИИ НЕДИФФЕРЕНЦИРОВАННОЙ ДИСПЛАЗИИ СОЕДИНИТЕЛЬНОЙ ТКАНИ

Изобретение относится к медицине, в частности к терапии, и касается лечения недифференцированной дисплазии соединительной ткани. Для этого в дополнении к витамину В6 и магнию вводят витамины А, Е, С, D, B1, В2, В12, пантотеновую кислоту, фолиевую кислоту в комплексе с кальцием, причем введение всех витаминов и микроэлементов осуществляют в дозах, не превышающих суточной потребности организма, в течение двух-четырех недель, курс лечения повторяют не менее 2 раз в год. Такое выполнение способа обеспечивает эффективное лечение при отсутствии побочных эффектов за счет коррекции метаболизма коллагена - снижения скорости его образования и деградации. 2 табл.

ЛЕКАРСТВЕННАЯ КОМПОЗИЦИЯ ДЛЯ ЛОКАЛЬНОГО ЛЕЧЕНИЯ ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ СУСТАВОВ И МЫШЦ

Изобретение относится к созданию средства для лечения и профилактики воспалительных заболеваний опорно-двигательного аппарата (миозиты, артриты, тендовагиниты и т.п.). Лекарственная композиция для локального лечения воспалительных заболеваний суставов и мышц включает (мас.%): эфирное масло пихты (1,0-2,0), камфару (4,0-5,0), масляный экстракт красного стручкового перца (0,06-0,08), биологически активный компонент, выделенный из медицинской пиявки или ее частей (0, 01-6,5), ибупрофен (60,0-65,0), этоксидигликоль (3,0-5,0), эмульгин В2 (0,4-0,6), карбомер (0,5-0,8), триэтаноламин (0,6-0,8), метилпарабен (0,2-0,3), пропилпарабен (0,02-0,03), бутилоксианизол (0, 08-0,1), бронопол (0,04-0,05), воду (остальное). Композиция активизирует обменные процессы в коже и подкожно-жировом пласте, нормализует кровоснабжение, ликвидирует застойные явления, ускоряет проникновение активных лечебных веществ в мембраны биологических клеток, которое приводит к быстрому достижению стойкого лечебного эффекта в ...

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ВКЛЮЧАЮЩАЯ ФЕРМЕНТ, РАЗРУШАЮЩИЙ ГЛИКОЗАМИНОГЛИКАНЫ, И ПРИМЕНЕНИЕ УКАЗАННОГО ФЕРМЕНТА ДЛЯ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННОГО ПРЕПАРАТА ДЛЯ ТЕРАПИИ ГРЫЖИ МЕЖПОЗВОНОЧНОГО ДИСКА

Изобретение может быть использовано в медицине, а именно для терапии грыжи межпозвоночного диска. Фармацевтическая композиция для введения в вертебральное эпидуральное пространство включает фермент, разрушающий гликозаминогликаны, и фармацевтический носитель. Также изобретение относится к применению фермента, разрушающего гликозаминогликаны, в качестве лекарственного препарата для терапии грыжи межпозвоночного диска, который характеризуется наличием в эпидуральном пространстве студенистого ядра, где указанный препарат вводится в вертебральное эпидуральное пространство. Изобретение повышает эффективность терапии грыжи межпозвоночного диска. 2 с. и 11 з.п.ф-лы, 1 табл., 1 ил.

СПИРОЦИКЛИЧЕСКИЕ ИНГИБИТОРЫ МЕТАЛЛОПРОТЕАЗ

Изобретение относится к новым спирокеталям формулы I где Ar - фенил, замещенный фенил, где заместители представляют: алкокси, алкил, алкоксиалкил, фенокси, галоген, пиридилокси, алкоксиалкокси, галогенфенокси; R1 - H; R2 - H, С1-С4алкил; W представляет О или один или несколько С1-С4 алкильных фрагментов; Y - независимо один или несколько членов группы, состоящей из H2, SR3, алкокси; R3 - H, алкил; Z - карбоциклический или гетероциклический спиро-фрагмент с 3-7 членами кольцевой системы, где гетероциклический фрагмент включает 2 атома кислорода или серы, или один атом азота, причем спироцикл может быть незамещенным или замещен гидрокси, С1-С4алкилом, бензилокси; n=1-3; оптические изомеры, диастереомеры или энантиомеры или их фармацевтически приемлемые соли. Соединение I ингибируют металлопротеазу, что позволяет использовать их в фармацевтической композиции для лечения или предупреждения заболевания, связанного с повышенной активностью металлопротеаз. 2 с. и 8 з.п. ф-лы, 5 табл.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ДЛЯ ЛЕЧЕНИЯ ТЕРМИЧЕСКИХ ТРАВМ И РАН В СОЧЕТАНИИ С ПОВРЕЖДЕНИЕМ КОСТИ

Настоящее изобретение относится к фармацевтической композиции для лечения ран, осложненных повреждением кости. Фармацевтическая композиция для лечения ран, осложненных повреждением кости, которая состоит из от 4% вес. до 12% вес. пчелиного воска и от 88% вес. до 96% вес. экстракта, полученного с помощью кунжутного масла, из исходных ингредиентов, включающих Radix Scutellariae, Coptis Chinensis, Cortex Phellodendri, Pericarpium Papaveris и Lumbricus, на основе общего веса указанной композиции, причем индивидуальное содержание каждого из Radix Scutellariae, Coptis Chinensis, Cortex Phellodendri, Pericarpium Papaveris и Lumbricus на основе их сухого веса составляет от 1% до 6% от общего веса кунжутного масла соответственно. Применение фармацевтической композиции для получения лекарственного средства для лечения термической травмы, осложненной повреждением кости. Фармацевтическая композиция для лечения термической травмы, осложненной повреждением кости. Способ лечения открытых травм, осложненных ...

ЭКСТРАКТ БРОМЕЛАИНА С ПРОТЕОЛИТИЧЕСКОЙ АКТИВНОСТЬЮ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ СОЕДИНИТЕЛЬНЫХ ТКАНЕЙ

Изобретение относится к медицине и может быть использовано для лечения заболеваний соединительной ткани. Для этого применяют фармацевтическую композицию, содержащую протеолитический экстракт, полученный из бромелаина. При этом бромелаин получен из стебля ананаса. Протеолитический экстракт содержит бромелаин стебля, ананаин и джакалин-подобный лектин. Заболевание соединительной ткани связано с избыточным отложением коллагена, такое как болезнь Дюпюитрена и болезнь Пейрони. Изобретение обеспечивает эффективность и селективность действия в отношении деградации коллагена типа III в тяжах Дюпюитрена и не повреждает здоровую соединительную ткань. 15 з.п. ф-лы, 13 ил., 2 пр.

СТАБИЛЬНЫЕ ВОДНЫЕ КОМПОЗИЦИИ БЕЛКА MIA/CD-RAP

Настоящее изобретение относится к биохимии, в частности к стабильной водной композиции, содержащей примерно от 5 до 30 мг/мл белка CD-RAP и заряженную аминокислоту, имеющую суммарный заряд при рН приблизительно от 6 до 8, и набору для восстановления хряща, содержащему указанную композицию и инструкции для применения. Настоящее изобретение позволяет получать стабильные водные композиции белка CD-RAP, содержащие указанный белок в высокой концентрации, в которых при этом снижена агрегация полипептидов CD-RAP на протяжении длительного периода времени и при повторных циклах замораживания-оттаивания. Композиция по настоящему изобретению предназначена для применения в лечении воспалительных расстройств, предпочтительно остеоартрита. 2 н. и 8 з.п. ф-лы, 11 ил., 5 табл., 8 пр.

ЧЕТВЕРТИЧНЫЕ АММОНИЕВЫЕ СОЛИ ОМЕГА-АМИНОАЛКИЛАМИДОВ R-2- АРИЛПРОПИОНОВЫХ КИСЛОТ И СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ СОСТАВЫ

... 1. Соединения (R)-2-арилпропионамида формулы (I) где Ar означает замещенную или незамещенную арильную группу; R означает водород, C1-C4-алкил, C2-C4-алкенил, C2-C4-алкинил, необязательно замещенный группой CO2R4, где R4 означает водород или линейную или разветвленную C1-C6-алкильную группу или линейную или разветвленную C2-C6-алкенильную группу; Х означает линейный или разветвленный C1-C6-алкилен, C4-C6-алкенилен, C4-C6-алкинилен, необязательно замещенный группой CO2R4 или группой CONHR5, где R5 означает водород, линейный или разветвленный C2-C6-алкил или группу OR4, где R4 определен выше; фенил или группу фенилметилена формулы группу (CH2)m-B-(CH2)n, необязательно замещенную группой CO2R4 или CONHR5, как определено выше, где В означает атом кислорода или серы, m означает ноль или целое число от 2 до 3 и n означает целое число от 2 до 3; или В означает группу СО, SO или CONH, m означает целое число от 1 до 3 и n означает целое число от 2 до 3; или Х вместе с атомом азота, к которому он ...

ПРОИЗВОДНЫЕ НИКОТИНАМИДА, ПОЛЕЗНЫЕ В КАЧЕСТВЕ Р38-ИНГИБИТОРОВ

... 1. Соединение формулы (I) где R1 выбран из водорода, С1-6алкила, возможно замещенного группами в количестве до трех включительно, выбранными из С1-6алкокси, галогена и гидрокси, С2-6алкенила, С3-7 циклоалкила, возможно замещенного одной или более чем одной С1-6алкильной группой, фенила, возможно замещенного группами в количестве до трех включительно, выбранными из R5 и R6, и гетероарила, возможно замещенного группами в количестве до трех включительно, выбранными из R5 и R6; R2 выбран из водорода, С1-6алкила и -(CH2)q-C3-7циклоалкил, возможно замещенного одной или более чем одной С1-6алкильной группой, или (СН2)mR1 и R2 совместно с атомом азота, к которому они присоединены, образуют (четырех-шести)членное гетероциклическое кольцо, возможно замещенное С1-6алкильными группами в количестве до трех включительно; R3 представляет собой хлоро или метил; R4 представляет собой группу -NH-CO-R7 или -CO-NH-(CH2)q -R8; R5 выбран из С1-6алкила, С1-6алкокси, -{СН2)q-С3-7циклоалкил, возможно замещенного ...

КОМПОЗИЦИИ ЛЕГОЧНОГО СУРФАКТАНТА С РЕЖИМОМ ДИНАМИЧЕСКОГО НАБУХАНИЯ

... 1. Композиция легочного сурфактанта, содержащая легочный сурфактант, который при диспергировании в виде порошка или частиц в 0,9% мас./мас. хлористом натрии при концентрации 10% мас./мас. при температуре окружающей среды способен образовывать в процессе набухания сеть или трубочки с двойным лучепреломлением на поверхности раздела воздух-жидкость-твердое вещество в пределах периода времени от приблизительно 0,5 до приблизительно 120 мин при наблюдении с помощью поляризационной микроскопии. 2. Композиция легочного сурфактанта по п.1, в которой легочный сурфактант включает фосфолипиды. 3. Композиция легочного сурфактанта по п.2, в которой фосфолипиды находятся в форме смеси насыщенных и ненасыщенных фосфолипидов. 4. Композиция легочного сурфактанта по п.2 или 3, в которой концентрация фосфолипидов составляет от приблизительно 80 до приблизительно 99,5% мас./мас., как, например, от приблизительно 85 до приблизительно 98% мас./мас. или от приблизительно 90 до приблизительно 98% мас./мас. композиции ...

Антагонисты рецептора брадикинина

... 1. Соединение формулы IA где R5А обозначает -XA-R6A или –N(R7A)R8A, где XA обозначает пиперидинилен или пиперазинилен, R6A обозначает Н, С1-С4алкил, С3-С4алкенил, С3-С4алкинил, С1-С4(алкоксиалкил), С1-С4 (карбоксиалкил), С5-С7гетероциклическую группу или фенилС1-С4алкил; R7A обозначает аминоС1-С4алкил или моно- или ди(С1-С5алкил)амино-С2-С5алкил и R8A обозначает Н, Сl-С4алкил или имеет значения, указанные для R7A; X1 обозначает двухвалентную группу формулы IA’ где n = 0 или 1; X3 обозначает СН или N; (а) X4 обозначает прямую связь, R3A и R4A вместе обозначают этилен и m = 2; или (б) X4 обозначает прямую связь, R3A обозначает Н, С1-С4алкил, С3-С6циклоалкил, С3-С6алкенил, С3-С6 алкинил, С7-С10аралкил или С6-C9 гетероаралкил, R4A обозначает Н и m = 1 или 2 или 3; или (в) X4 обозначает -CH(R12 )-, R3A обозначает Н и R4A и R12 вместе обозначают пропилен и m = 1, или этилен и m = 2; X2 обозначает двухвалентную группу формулы IA’’ где X3 обозначает СН или N; R11 обозначает С1-С4алкил, С3-С6циклоалкил ...

МОЛЕКУЛЫ АНТИТЕЛ ЧЕЛОВЕКА К IL-13

... 1. Способ получения антигенсвязывающего домена антитела, специфичного в отношении IL-13 человека, при этом способ включает в себя получение посредством присоединения, делеции, замены или инсерции одной или нескольких аминокислот в аминокислотной последовательности исходного домена VH, содержащего HCDR 1, HCDR2 и HCDR3, где HCDR1, HCDR2 и HCDR3 исходного домена VH представляют собой набор HCDR BAK167A11, в котором, согласно определению, HCDR1 имеет аминокислотную последовательность SEQ ID NO: 55, HCDR2 имеет аминокислотную последовательность SEQ ID NO: 56, HCDR3 имеет аминокислотную последовательность SEQ ID NO: 57, набор HCDR BAK615E3, в котором, согласно определению, HCDR1 имеет аминокислотную последовательность SEQ ID NO: 153, HCDR2 имеет аминокислотную последовательность SEQ ID NO: 154, HCDR3 имеет аминокислотную последовательность SEQ ID NO: 155, набор HCDR BAK582F7, в котором, согласно определению, HCDR1 имеет аминокислотную последовательность SEQ ID NO: 141, HCDR2 имеет аминокислотную ...

BMP-12, BMP-13 UND DIESE ENTHALTENDE SEHNE-INDUZIERENDE ZUSAMMENSETZUNGEN

VERFAHREN ZUR IDENTIFIZIERUNG VON INDUKTOREN UND INHIBITOREN PROTEOLYTISCHER ANTIKÖRPER, ZUSAMMENSETZUNGEN SOWIE DEREN VERWENDUNGEN

AZABICYCLOVERBINDUNG, MATRIXMETALLPROTEASEINHIBITOR UND ZUBEREITUNG FÜR HAUT

ANSAMYCINE MIT VERBESSERTEN PHARMAKOLOGISCHEN UND BIOLOGISCHEN EIGENSCHAFTEN

1-(PYRROLIDIN-1-YLMETHYL)-3-(PYRROL-2-YLMETHYLIDEN)-2-INDOLINON DERIVATE UND DEREN VERWENDUNG ALS PROTEIN KINASE INHIBITOREN

ESTROGEN-17-SULPHAMATE ZUR HEMMUNG VON STEROID SULFATASE

SYNERGISTISCHE KOMBINATIONEN MIT EINEM RENIN-INHIBITOR FÜR KARDIOVASKULÄRE ERKRANKUNGEN

MONO-UND DISULFOSUBSTITUIERTE ANTHRACHINONE UND DEREN VERWENDUNG ZUR BEHANDLUNG VON KNOCHENMATRIXERKRANKUNGEN

IL-13 binding molecules

There are described recombinant VH and VL domains of human antibodies that bind IL-13. A series of proteins characterised by three CDR in each VH/VL are described. Preferably the molecules are single chain Fv or antibody molecules. Nucleic acids expressing the VH and VL domains are selected from phage display libraries. Neutralization potency of the resulting scFv's was tested in TF proliferation assays. The fragments and antibodies showed efficacy for IL-13 binding in murine models of pulmonary inflammation, the primate (cynomolgus) model of dermal allergy, IgE release from B cells and histamine potentiation in Ca2+ signalling in smooth muscle. Mice transgenic for human IL-13 antibodies and epitope mapping studies are also described. It is envisaged that the anti I1-13 reagents may be used to treat asthma, atopic dermatitis, allergic rhinitis, fibrosis, IBS, or Hodgkin's lymphoma.

Methods of inhibiting fibrogenesis and treating fibrotic disease

The present invention relates to the discovery of an epigenetic relay pathway that controls hepatic stellate cell activation and the wound-healing response in fibrogenesis, including fibrogenesis of the injured liver. Methods of inhibiting fibrogenesis, including liver fibrogenesis and secondary disease states and conditions thereof, and in treating liver damage, including cirrhosis of the liver (which may be caused by viruses or chemicals, including alcohol), are aspects of the present invention. The methods utilize certain nucleoside compounds and/or antibodies which are optionally conjugated. Pharmaceutical compositions represent additional aspects of the invention.

Methods of inhibiting fibrogenesis and treating fibrotic disease

Therapy

Tissue repair

Vitamin A for use in the treatment of tissue damage in a human subject following a neurological injury, wherein the vitamin A is administered systemically by oral or intravenous administration in a dose of >10,000 IU to 100,000 IU vitamin A per day is provided. The neurological injury may comprise a spinal cord injury (SCI), a brain injury or a peripheral nerve injury. The vitamin A may be the form of a retinyl ester, retinol, a carotenoid (beta-carotene, alpha-carotene, beta-cryptoxanthin), retinal or retinoic acid. The vitamin A may inhibit glial scar tissue formation. A multi-dose formulation for use in the treatment of tissue damage in a human subject following a neurological injury wherein the formulation comprises a plurality of unit doses comprising >10,000 IU to 100,000 IU of vitamin A is provided. Vitamin A for use in treating soft tissue injuries wherein the soft tissue comprises ligaments and tendons is described. The combination of vitamin A and one or more regenerative cells ...

Calcilytic compounds

Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors

Calcilytic compounds.

Pyrimidine-2, 4,6-trine metalloproteinaise inhibitors

Purine derivatives

Metalloprotease inhibitors

Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors

Combination of gaba agonists and aldose reductase inhibitors

Piperazine and piperidine derivatives.

The present invention relates to piperazine and piperidine derivatives, which are especially useful for treating or preventing neuronal damage, particularly damage asssociated with neurological diseases. These compounds are also useful for stimulating nerve growth. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage or for stimulating nerve growth.

Ox (ADI) azolyl-hydroxamic acids useful as procollagen C- proteinase inhibitors.

Compounds of formula (I) and their salts, solvates, prodrugs, etc., wherein the substituents have the values mentioned herein, are Procollagen C-Proteinase (PCP) inhibitors and have utility in conditions mediated by PCP.

Purine derivatives.

The present invetion relates to compounds of the formula and pharmaceutically acceptable salts and solvates thereof, to processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as adenosine a2a receptor agonists.

Compounds for the treatment of ischemia.

Nhe-1 inhibitors, methods of using such nhe-1 inhibitors and pharmaceutical compositions containing such nhe-1 inhibitors. The nhe-1 inhibitors are useful for the reduction of tissue damage resulting from tissue ischemia ...

Calcilytic compounds.

Novel calcilytic compounds are provided.

Metalloprotease inhibitors.

Compounds of formula (i)and pharmaceutically-acceptable derivatives thereof, are matrix metalloprotease inhibitors, useful in treatment of conditions mediated by matrix metalloproteases, such as chronic dermal ulcers.

Pyrimidine-2,4,6-trione metalloproteinase inhibitors.

The present inventin relates to pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein x, y, a, b and r1 are as defined in the specification, and to pharmaceutical compositions and methods of treating infalammation, cancer and other disorders.

COMBINATION OF GABA AGONISTS AND ALDOSE REDUCTASE INHIBITORS.

This invention relates to pharmaceutical compositions comprising combinations of a GABA agonist, a prodrug thereof or a pharmaceutically acceptable salt of said GABA agonist or said prodrug and an ARI, a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug, kits containing such combinations and methods of using such combinations to treat mammals, including humans, suffering from diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers.

Intraorally disintergrating valdecoxib compositions prepared by spray drying process

Orally disintergrating valdecoxib fast-melt tablets and processes for preparing such dosage forms are provided. The compositions are useful in treatment or prophylaxis of cycloosygenase-2 mediated conditions and disorders.

3-(imidazolyl)-2-alkoxypropanoic acids as tafia inhibitors

Compounds according to formula (I) wherein n is 0-3, R1 is optionally substituted C1-6 alky], C2-6 alkenyl, or C2-6alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R2, R3, R4, R5, R6, R7, R8 and R9 are each ind pendently selected from hydrogen and optionally substituted C1-6 alky, or R5 t R8 are an alkylene chain, are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition.

Spiro-pyrimidine-2,4,6-Trione Metalloproteinase inhibitors

The present invention relates to 5-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein said "A" is a 5-7 membered heterocyclic ring as defined in the specification and to pharmaceutical compositions and methods of treating inflamation, cancer and other disorders.

CARBOXAMIDE DERIVATIVES

Metalloprotease inhibitors

Pyrimidine-2, 4,6-trine metalloproteinaise inhibitors

Purine derivatives

Metalloprotease inhibitors.

N-Ä(substituted five-membered di-or triaza diunsaturated ring)carbonylÜ guanidine derivatives for the treatment of ischemia.

Intraorally disintegrating valdecoxib compositionsprepared by spray drying process.

Ox(adi)azolyl-hydroxamic acids useful as procollagen C-proteinase inhibitors.

Combination of GABA agonists and aldose reductase inhibitors.

Indole or benzimidazole derivatives for modulatingIKB-kinase.

Pyrimidine-2,4,6-trione metalloproteinase inhibitors.

Methods of tissue induction using a combination ofbone morphogenetic protein and parathyroid hormon e-related peptide

3-(Imidazolyl)-2-alkoxypropanoic acids as tafia inhibitors.

Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors.

Bmp-12 bmp-13 and tendon-inducing compositions th ereof

Ox (adi) azolyl-hydroxamic acids useful as procollaen c-proteinase inhibitors

3-(imidazolyl)-2-alkoxypropanoic acids as tafia inhibitors

Compounds for the treatment of ischemia

Intraorally disintergrating valdecoxib compositions prepared by spray drying process.

Ox (adi) azolyl-hydroxamic acids useful as procollaen c-proteinase inhibitors

CARBOXAMIDE DERIVATIVES

Calcilytic compounds

Combination of gaba agonists and aldose reductase inhibitors

CARBOXAMIDE DERIVATIVES

Intraorally disintergrating valdecoxib compositions prepared by spray drying process.

3-(imidazolyl)-2-alkoxypropanoic acids as tafia inhibitors

PROCEDURE FOR THE TREATMENT BY ACUTE ONE AND BY EXCESSIVE DEMAND CAUSED OF PULLING AND VERSE DIPPING WITH HYALURONSÄURE

TREATMENT OF FIBROSEN

MEANS AND PROCEDURE FOR THE PROTECTION, FOR THE TREATMENT AND TO THE REPAIR OF CONNECTIVE TISSUE

A DIOXINO (2,3-G) CHINOLIN-9-CARBONSÄURE DERIVATIVE AS NK3 RECEPTOR ANTAGONIST

1-AMIDO-4-PHENYL-4-BENZYLOXYMETHYL-PIPERIDIN of DERIVATIVES AND RELATED CONNECTIONS AS NEUROKININ-1 (NK-1) ANTAGONSISTEN FOR the TREATMENT OF VOMITING, DEPRESSIONS, FEAR CONDITIONS AND COUGHS

HUMAN CYR61

ORALLY GIVING PREPARATIONS FROM FOOD ADDITIVES TO THE HEALING OF JOINT CARTILAGES

TETRAHYDROPYRIDYL ALKYL HETEROZYKLE ONE, PROCEDURE FOR YOUR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS IT CONTAINING

HETERO-CYCLIC CONDENSED PYRAZOLDERIVATE AS KINASEINHIBITOREN

NUCLEIC ACIDS AND POLYPEPTIDE, ITSELF ON B7 REFERRING AND YOUR USES TO the IMMUNE MODULATING

DEVICE TO THE DELIVERY OF THERAPEUTIC ACTIVE SUBSTANCES

ANSAMYCINE WITH IMPROVED PHARMAKOLOGI AND BIOLOGICAL CHARACTERISTICS

USE OF TRUNKS OF THE PARAPOXVIRUS OVIS AGAINST ORGANFIBROSEN

INSTRUMENTS FOR THE AUTOLOGE TRANSPLANT

HETEROLOGES POLYPEPTID OF THE TNF FAMILY

NAPHTHALINDERIVATE

PROTEIN C FOR THE CICATRISATION

IDENTIFICATION AND ISOLATION OF SOMATIC MAIN CELLS AND USES OF IT

METHODS AND COMPOSITIONS FOR HEALING AND REPAIR OF JOINT CARTILAGES

BLOCKING PEPTID FOR THE SECRETION OF INFLAMMATION CELLS

NF-KAPPAB-INHIBITORS

CONDENSED CYCLIC MODULATORS OF THE FUNCTION OF NUCLEAR HORMONE RECEPTORS

CONNECTIONS TO THE ADJUSTMENT OF THE HEDGEHOG OF SIGNAL PATH, COMPOSITIONS AND USES OF IT

PHARMACEUTICAL CONNECTIONS

CARBOCYCLI HYDRAZINO HEMMER OF CUPREOUS AMINOXIDASEN

INDOLDERIVATE AND THEIR USE AS LIGAND THAT RECEPTOREN CB2

Methods and uses of hypoxic compartment cells

The disclosure relates to methods of maintaining and/or expanding an in vitro population of hypoxia compartment cells comprising culturing said population of cells optionally in an oxygen controlled environment, wherein the population of hypoxia compartment cells is exposed to an oxygen concentration of between about 1.5% and about 10%, preferably between about 2% and about 5%, and uses of cells expanded according to these methods.

Il-17 homologous polypeptides and therapeutic uses thereof

The present invention is directed to novel polypeptides having sequence identity with IL-17, IL-17 receptors and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.

CD86 Antagonist Multi-Target Binding Proteins

This disclosure provides a multi-specific fusion protein composed of a CD86 antagonist binding domain and another binding domain that is an IL-10 agonist, an HLA-G agonist, an HGF agonist, an IL-35 agonist, a PD-1 agonist, a BTLA agonist, a LIGHT antagonist, a GITRL antagonist or a CD40 antagonist. The multi-specific fusion protein may also include an intervening domain that separates the other domains. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.

Olfactory stem cells and uses thereof

Some aspects of this invention are based, at least in part, on the discoveries (i) pluripotent stem cell populations can be obtained from olfactory mucosa, (ii) that various regions of the olfactory mucosa contain pluripotent stem cells, (iii) that cells from these olfactory mucosa derived stem cell populations can be maintained in cultures containing EGF and/or bFGF, (iv) that cells from these olfactory mucosa derived stem cell populations are able to form neurospheres, and/or (v) that cells from these olfactory mucosa derived stem cell populations can differentiate into various lineages, including mesenchymal and neuronal lineages.

Integrin heterodimer and an alpha subunit thereof

A recombinant or isolated integrin heterodimer comprising a novel subunit α11 in association with a subunit β is described. The integrin or the subunit α11 can be used as marker or target of all types of cells. The integrin or subunit α11 thereof can be used as marker or target in different physiological or therapeutic methods. They can also be used as active ingredients in pharmaceutical compositions and vaccines.

Modified hyaluronic acid polymer compositions and related methods

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses.

Composition including an unsaponifiable fraction

The present invention relates to a composition, notably cosmetic, nutraceutical, dermatological, pharmaceutical or dietary, including at least one unsaponif iable extract, a drug including one such composition, the use of one such composition, a treatment method consisting in administering one such composition and a method comprising the administration of one such composition.

Implantable material and a method for the preparation thereof

A method for the preparation of a regenerated silk fibroin solution comprises the steps of: treating silk or silk cocoons with an ionic reagent comprising an aqueous solution of monovalent cations and monovalent anions, the cations and anions having ionic radii of at least 1.05 Angstroms and a Jones-Dole B coefficient of between −0.001 and −0.05 at 25° C.; and subsequently degumming the treated silk or silk cocoons; or alternatively, degumming silk or silk cocoons; and subsequently treating the degummed silk or silk cocoons with an ionic reagent comprising an aqueous solution of monovalent cations and monovalent anions, the cations and anions having ionic radii of at least 1.05 Angstroms and a Jones-Dole B coefficient of between −0.001 and −0.05 at 25° C. The invention also extends to fibroin solution, a fibroin material and an implant useful for cartilage repair.

Soluble lymphotoxin-beta receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological diseases

Compositions and methods comprising “lymphotoxin-β receptor blocking agents” which block lymphotoxin-β receptor signalling and are useful for altering immunological diseases, and particularly antibody mediated immune responses.

Novel Formulations of Volatile Anesthetics and Methods of Use for Reducing Inflammation

The present invention provides methods for treating inflammation or a wound in a subject in need of such wound treatment or inflammation treatment by delivering a volatile anesthetic to the wound or the inflammation site.

Immunoneutral silk-fiber-based medical devices

Silk is purified to eliminate immunogenic components (particularly sericin) and is used to form fabric that is used to form tissue-supporting prosthetic devices for implantation. The fabrics can carry functional groups, drugs, and other biological reagents. Applications include hernia repair, tissue wall reconstruction, and organ support, such as bladder slings. The silk fibers are arranged in parallel and, optionally, intertwined (e.g., twisted) to form a construct; sericin may be extracted at any point during the formation of the fabric, leaving a construct of silk fibroin fibers having excellent tensile strength and other mechanical properties.

Freeze-dried fibrin matrices and methods for preparation thereof

Methods for treating diseased or injured tissue by implanting into the tissue at a site of the disease or injury a porous freeze-dried fibrin matrix formed from plasma proteins. The proteins include fibrinogen cleaved by the action of thrombin at varying concentrations sufficient to cleave the fibrinogen and Factor XIII. The matrix has less than 10% residual moisture and is devoid of exogenous anti-fibrinolytic agents, plasminogen and of organic chelating agents. Alternatively, the plasma proteins comprise partially purified plasma proteins that are devoid of plasminogen.

Tissue transplant compositions and methods for use

Provided are transplants and methods for augmenting formation and restoration of organ and tissue, for example, bone formation, by administering autologous or allogeneic human embryonic-like adult stem cells (ELA cells). Also provided is a method for augmenting formation of tissues and organs by administering a transplant having ELA stem cells or combination of ELA stem cells.

Transdermal Delivery of Medicinal Cetylated Fatty Esters using Phonophoresis or Iontophoresis

The use of phonophoresis or iontophoresis to enhance transdermal delivery of medicinal Cetylated fatty esters when applied in cream or gel compositions is disclosed. These compositions provide hydrophilic salt forms and penetration-enhancing vehicles that work in conjunction with phonophoresis or iontophoresis to increase the efficacy of the medicinal actives.

Gene delivery

The present invention relates to a method of delivery of a therapeutic agent to a target cell, the method comprising targeting particles comprising the therapeutic agent to the cell using magnetic means to apply a magnetic force to said particles so as to tend to move said particles towards said magnetic means and at the same time moving said magnetic means.

Humanized anti-il 10 antibodies for the treatment of systemic lupus erythematosus (sle)

Provided is a humanized or chimeric antibody or fragment thereof capable of binding to interleukin-10 (Th-10), wherein said antibody or fragment thereof is capable of being administered to a subject in the absence of an intolerable increase in the level of pro-inflammatory cytokines. Further provided are methods of treatment involving the use of the antibody or fragment thereof.

Methods of identifying obm modulators

Novel proteins and polypeptides binding to osteoclastogenesis inhibitory factor (OCIF) (OCIF-binding molecules, OBMs) and nucleic acids encoding these proteins and polypeptides are provided. Processes for producing these proteins, polypeptides, and nucleic acid molecules by genetic engineering are provided. Medicinal compounds are provided which comprise proteins and nucleic acids according to the invention, as well as proteins which bind to OBM, including anti-OBM antibodies. These compounds may be used for the treatment of bone disease.

Dihydropteridinones, method for production and use thereof

The present invention relates to new dihydropteridinones of general formula (12) wherein the groups R 1 to R 5 and L, n, and m have the meanings given in the claims and specification, the isomers thereof, processes for preparing these dihydropteridinones and the use thereof as pharmaceutical compositions.

Antagonist anti-il-7 receptor antibodies and methods

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus.

Sap variants and their use

Polypeptides are susceptible to denaturation or enzymatic degradation in the blood, liver or kidney. Due to the low stability of some polypeptides, it has been required to administer polypeptide drugs in a sustained frequency to a subject in order to maintain an effective plasma concentration of the active substance. Furthermore, pharmaceutical compositions of therapeutic peptides preferably have a shelf-life of several years in order to be suitable for common use. However, peptide compositions are inherently unstable due to sensitivity towards chemical and physical degradation. In part, the invention provides SAP variant proteins, compositions, pharmaceutical preparations and formulations having a prolonged in vivo half-life, prolonged shelf-life, or rather increased in vitro stability, or increased manufacturing efficiency compared to human SAP. Advantages of increased plasma half-life include, but are not limited to, reducing the amount and/or frequency of dosing.

Fatty acid cox inhibitor derivatives and their uses

The invention relates to fatty acid COX inhibitor derivatives; compositions comprising an effective amount of a fatty acid COX inhibitor derivative; and methods for treating or preventing a metabolic, autoimmune, inflammatory, or neurodegenerative disorder comprising the administration of an effective amount of a fatty acid COX inhibitor derivative.

B cell activating factor antagonist and preparation method and use thereof

The present invention relates to the field of genetic engineering drugs, particularly to a novel B cell activating factor (BAFF) antagonist and use thereof. The technical problem to be solved by the invention is to find a new and effective selection for the prevention and treatment of autoimmune diseases. The B cell activating factor receptor antagonist is mainly obtained by the fusion of the domain 2 binding BAFF in TACI receptor and the domain binding BAFF in Br3 receptor, and it also can be fused with a Fc segment of IgG1 to obtain a new fusion protein molecule. Experiments indicate that said new fusion protein molecule has the function of BAFF antagonist, which can treat the autoimmune diseases, and supply a new and effective selection for the prevention and treatment of the autoimmune diseases.

Joint Repair Using Mesenchymal Stem Cells

A method of repairing and/or stabilizing a joint by administering mesenchymal stem cells to the joint. Such a method provides for the regeneration of cartilaginous tissue in the joint, including meniscal tissue.

BMP Mutants with Decreased Susceptibility to Noggin

The present invention provides modified, highly potent bone morphogenetic proteins. In particular, the present invention relates to the observation that BMP-6 and BMP-9 are less susceptible to inhibition by Noggin that are other members of the BMP subfamily of proteins. The present invention features chimeric bone morphogenetic proteins in which the middle portion of BMP-6 or BMP-9 replaces the middle portion of another BMP subfamily protein to cause resistance to inhibition by Noggin or other Noggin-like antagonists. Other embodiments of modified BMPs, compositions and methods of use are also included.

Polynucleotides encoding recombinant lubricin molecules and uses thereof

Recombinant lubricin molecules and uses thereof. Novel recombinant lubricin molecules and their uses as lubricants, anti-adhesive agents and/or intra-articular supplements for, e.g., synovial joints, meniscus, tendon, peritoneum, pericardium and pleura, are provided.

Injectable Cross-Linked Polymeric Preparations and Uses Thereof

A therapeutic composition for treatment of a body tissue which includes an aqueous solution of a cross-linked polymer being capable of: (i) maintaining a liquid state in storage at room temperature for at least 24 hours; and (ii) assuming a gel state following deposition within the body tissue. The therapeutic composition can be effectively administered into a damaged body tissue via injection or catheterization, thereby treating the damaged body tissue.

Treatment and Composition for Wound Healing

A method and medicament for promoting wound healing in a subject is disclosed. The medicament comprises an effective amount of an agent comprising one or more of; (i) an activated protein C (APC), (ii) a functional fragment of an APC, (iii) an APC mimetic compound, and (iv) protein C. Delivery systems including gels, sponges, gauzes and meshes incorporating the agent for topical administration are also described.

Use of selective estrogen receptor modulator for joint fusion and other repair or healing of connective tissue

Methods for facilitating joint immobilization or fusion using selective estrogen receptor modulator (SERM) such as raloxifene are disclosed. The SERM may be administered systemically or locally. In conjunction with SERM, other therapeutic agents such as calcium, vitamin D, bone morphogenetic protein may be administered simultaneously. The method can similarly be applied to facilitate bone repair, bone healing, and connective tissue healing processes in a patient.

Cd89 activation in therapy

The invention relates to the use of CD89 activating molecules, in particular Fc alpha comprising molecules, and more particularly, IgA, for inducing apoptosis in neutrophils. Anti-CD89 antibodies can alternatively be used. The CD89 activation is beneficial in the treatment of various disorders associated with increases in neutrophils, such as autoimmune disorders, inflammatory disorders, NETosis, or cystic fibrosis.

Textured bone block implants

Implantable pliable bone blocks comprising a solid block of cortical bone characterized by a length, width and thickness, having a first and a second face on opposite sides of the block. The first and second faces have a plurality slot features. The angle of incidence of the slot features of the first face and the x-axis and the angle of incidence of the slot features of the second face and the x-axis (a 2 ) are such that the slots would intersect if they were in the same plane. Methods are provided for making implantable pliable bone blocks.

Tendon Stem Cells

The invention relates to tendon stem cells useful for treating a variety of diseases and condition, including tendon repair and attachment of tendon to bone. The invention is also directed to treatment and/or inhibition of bone formation by use of biglycan and/or fibromodulin.

Prognostic tests for development of dermal stretch marks and implications for the preventative treatment thereof

Various methods of assessing the regenerative potential of dermal tissue in a patient may be determined and methods to determine the potential development of stretch marks in a patient are provided. Through the analysis of a series of dermal tissue samples, a method of monitoring the aging process of the dermal tissue of a patient is possible. Damaged or stretched marked skin may also be used in the development of various diagnostic therapies relating to the inducement of the extracellular matrix components of the skin due to the loss of elastic fibers generally found in stretch marked skin.

Connective tissue monitoring, compositions for connective tissue treatment and methods for treating connective tissue

Methods and computer instruction code for monitoring, screening and classifying the response to load of a connective tissue or part thereof are disclosed. The method includes the steps of obtaining or receiving an ultrasound scan of a connective tissue or part thereof and analysing the ultrasound scan to detect one or more region of differential structural disorganisation in the connective tissue or part thereof. The connective tissue or part thereof is then classified according to the detected one or more region of differential structural organisation to thereby monitor the response to load of the connective tissue or part thereof. Also disclosed are compositions and methods of treatment for a connective tissue disease or condition.

Liquid Crystalline Collagen Materials and Use in Connective Tissue Repair

Compositions and methods are provided to accelerate and improve wound repair and reconstruction of connective tissue structures, including tendons, by assembly of collagen using liquid crystalline collagen. The compositions and methods can be used to treat various forms of connective tissue injury or to prevent or slow degeneration to vulnerable tendons that are generally refractory to repair. 1. A non-naturally occurring , stable , liquid crystal collagen composition , wherein the composition comprises type I , II , III , V , and/or XI collagen organized into fibril-like structures 50-200 nm in diameter , wherein the fibril-like structures are locally aligned along their longitudinal axis and have D-periodic banding structure larger than about 67 nm , and wherein the composition has a density of at least about 500 mg/mL.2. The collagen composition of claim 1 , wherein the fibril-like structures shed monomeric collagen at a rate less than 1% per day at 37° C.3. The collagen composition of claim 1 , wherein the composition has a density of about 800 mg/mL.4. A non-naturally occurring claim 1 , metastable claim 1 , liquid crystal collagen composition claim 1 , wherein the composition comprises type I claim 1 , II claim 1 , III claim 1 , V claim 1 , and/or XI collagen organized into fibril-like structures 50-100 nm in diameter claim 1 , wherein the fibrils are locally aligned along their longitudinal axis and substantially lack native D-periodic banding structure claim 1 , and wherein the composition has a density in the range from about 100 to about 500 mg/mL.5. A bi-stable liquid crystal collagen composition comprising the composition of and the composition of .6. The bi-stable liquid crystal collagen composition of claim 1 , wherein the relative amounts of the composition of and the composition of are selected to provide a desired collagen delivery rate in a collagen assembly process.7. The composition of any one of - configured as a plurality of particles claim 1 , ...

CD146 AND USES THEREOF AS A BIOMARKER AND AS A THERAPEUTIC TARGET IN THE DIAGNOSIS AND TREATMENT OF FIBROSIS

The present invention relates to the field of medicine and in particular to the diagnostic and treatment of fibrosis. More particularly, the invention relates to CD146 and uses thereof as a biomarker in the diagnosis of fibrosis and as a therapeutic target in the treatment of fibrosis. The invention also relates to compositions and methods of detecting predisposition to, of diagnosing, prognosing and/or monitoring fibrosis in a subject. It further relates to CD146 inhibitors, and to compositions comprising a CD146 inhibitor, for use in prevention or treatment of fibrosis in a subject, as well as to compositions, kits and uses thereof in a diagnostic or therapeutic context. 119-. (canceled)20. An in vitro or ex vivo method of:a) detecting predisposition to or of diagnosing and/or prognosing cardiac or renal fibrosis in a subject, the method comprising a step of determining the soluble CD146 protein level of expression in a biological sample of the subject, wherein the soluble CD146 protein is selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7; orb) detecting predisposition to or of diagnosing and/or prognosing fibrosis in a subject, the method comprising a step of determining the level of expression of the I5-13 soluble CD146 protein of SEQ ID NO:8 or the I10 soluble CD146 protein of SEQ ID NO:9 in a biological sample of the subject.21. The method according to claim 20 , wherein the method of detecting predisposition to or of diagnosing and/or prognosing cardiac or renal fibrosis comprises the steps of i) determining the soluble CD146 protein expression level in a biological sample of the subject claim 20 , said soluble CD146 protein being selected from SEQ ID NO:1 claim 20 , SEQ ID NO:2 claim 20 , SEQ ID NO:3 claim 20 , SEQ ID NO:4 claim 20 , SEQ ID NO:5 claim 20 , SEQ ID NO:6 and SEQ ID NO:7 claim 20 , ii) comparing the expression level determined at step i) with a reference value and iii) concluding that the ...

CARTILAGE-HOMING PEPTIDES

Peptides that home, target, migrate to, are directed to, are retained by, or accumulate in and/or binds to the cartilage of a subject are disclosed. Pharmaceutical compositions and uses for peptides or peptide-active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of a drug to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver peptide or peptide-active agent complexes to target regions, tissues, structures or cells targeted by the peptide. 1118.-. (canceled)119. A knotted peptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 325.120. The knotted peptide of claim 119 , wherein the knotted peptide 4 or more cysteine residues and a plurality of disulfide bridges formed between cysteine residues.121. The knotted peptide of claim 119 , wherein the knotted peptide homes claim 119 , targets claim 119 , migrates to claim 119 , accumulates in claim 119 , binds to claim 119 , is retained by claim 119 , or is directed to a cartilage.122. The knotted peptide of claim 119 , wherein the knotted peptide has a sequence of SEQ ID NO: 325.123. The knotted peptide of claim 119 , wherein the knotted peptide is linked to an active agent.124. The knotted peptide of claim 123 , wherein the active agent comprises a therapeutic agent claim 123 , a detectable agent claim 123 , or a combination thereof.125. The knotted peptide of claim 124 , wherein the therapeutic agent comprises a therapeutic small molecule.126. The knotted peptide of claim 124 , wherein the therapeutic agent comprises an antibiotic claim 124 , an anti-viral agent claim 124 , an anti-fungal agent claim 124 , an anti-inflammatory agent claim 124 , a protease inhibitor claim 124 , an immune modulator claim 124 , an anti-cytokine agent claim 124 , a tyrosine kinase inhibitor claim 124 , a growth factor claim 124 , a cytotoxic T-lymphocyte-associated protein 4 (CTLA4) ...

Ionic Self-Assembling Peptides

Provided herein are ionic self-assembling peptides, pharmaceutical compositions comprising the peptides, and methods of using and making the same. 2. The pharmaceutical composition of claim 1 , wherein the self-assembling peptide comprises an amino acid sequence as set forth in Formula I.3. The pharmaceutical composition of claim 1 , wherein the self-assembling peptide comprises an amino acid sequence as set forth in Formula II.4. The pharmaceutical composition of claim 1 , wherein the self-assembling peptide comprises an amino acid sequence as set forth in Formula III.5. The pharmaceutical composition of claim 1 , wherein the self-assembling peptide comprises an amino acid sequence as set forth in Formula IV.6. The pharmaceutical composition of claim 1 , wherein each (X) is a basic amino acid selected from the group consisting of arginine claim 1 , lysine claim 1 , histidine claim 1 , and ornithine.7. The peptide of claim 1 , wherein each (X) is an acidic amino acid claim 1 , selected from the group consisting of aspartic acid and glutamic acid.8. The pharmaceutical composition of claim 1 , wherein each (Y) is selected from the group consisting of alanine claim 1 , valine claim 1 , leucine claim 1 , isoleucine claim 1 , methionine claim 1 , phenylalanine claim 1 , tryptophan claim 1 , and glycine.9. The pharmaceutical composition of claim 1 , wherein each (Z) is selected from the group consisting of the group consisting of serine claim 1 , threonine claim 1 , tyrosine claim 1 , cysteine claim 1 , glutamine claim 1 , asparagine claim 1 , and methionine.10. The pharmaceutical composition of claim 1 , wherein each of i claim 1 , j claim 1 , k claim 1 , and l is 1.11. The pharmaceutical composition of claim 1 , wherein m is an integer of 2 claim 1 , 3 claim 1 , or 4.12. The pharmaceutical composition of claim 1 , wherein the self-assembling peptide comprises an amino acid sequence as set forth in SEQ ID NOs: 1-20 claim 1 , and 94-96.13. The pharmaceutical composition ...

METHOD FOR REPAIRING DAMAGED TISSUE

In order to provide (i) a repair agent for damaged tissue and (ii) a method for producing the repair agent, the present invention uses mesenchymal stem cells cultured in a serum-free medium. 1. A method for repairing damaged tissue , comprising administering to the damaged tissue a repair agent comprising mesenchymal stem cells cultured in a serum-free medium , wherein the damaged tissue is tissue damage that accompanies chronic renal failure , a chronic kidney disease , cirrhosis , viral hepatitis , alcoholic hepatitis , or non-alcoholic steatohepatitis.2. The method of claim 1 , wherein the repair agent is intended to suppress fibrosis of a living tissue.3. The method of claim 1 , wherein the repair agent is intended to suppress infiltration of an inflammatory cell.4. The method of claim 1 , wherein the repair agent is intended to control activity of a macrophage.5. The method of claim 1 , wherein the serum-free medium contains an FGF claim 1 , a PDGF claim 1 , an EGF claim 1 , at least one phospholipid claim 1 , and at least one fatty acid.6. The method of claim 1 , wherein the mesenchymal stem cells are mesenchymal stem cells which have been selected by screening and are non-tumorigenic.7. The method of claim 1 , wherein the mesenchymal stem cells have been subcultured at least once.8. The method of claim 7 , wherein the mesenchymal stem cells which are being subcultured are detached with use of a cell detaching agent containing neither a mammal-derived component nor a microorganism-derived component.9. The method of claim 1 , wherein the mesenchymal stem cells are cultured with use of a culture vessel suitable for culture of the mesenchymal stem cells. This application is a continuation of U.S. patent application Ser. No. 16/473,987, filed Jun. 26, 2019, which is a 371 National Entry of PCT/JP2017/046427, filed Dec. 25, 2017, which claims priority to Japanese Patent Application No. 2017-187074, filed Sep. 27, 2017, and Japanese Patent Application No. 2016- ...

Compositions and Methods for Cartilage Repair

Autologous compositions and methods are provided for cartilage repair in patients in need thereof. Some aspects include combinations of platelet-based materials with chondrogenesis inducing agents in the presence or absence of cell-based therapies.

Substituted pyrido[3,4-b]indoles for the treatment of cartilage disorders

The present invention relates to 8-aryl-substituted and 8-heteroaryl-substituted 9H-pyrido[3,4-b]indoles of the formula (I), in which A, E, G, R 1 to R 6 and R 10 are as defined in the claims, which stimulate chondrogenesis and cartilage matrix synthesis and can be used in the treatment of cartilage disorders and conditions in which a regeneration of damaged cartilage is desired, for example joint diseases such as osteoarthritis. The invention furthermore relates to processes for the synthesis of the compounds of the formula (I), their use as pharmaceuticals, and pharmaceutical compositions comprising them.

Compositions and methods for treating and preventing skeletal muscle deficiencies

The present invention relates to compositions and methods for treating and preventing skeletal muscle deficiencies. In particular, the present invention provides compositions comprising poloxamers (e.g., poloxamer 188-P188) and methods of using the same for treating and preventing skeletal muscle deficiencies and injuries (e.g., dystrophin-deficient skeletal muscle; skeletal muscle having a contraction force deficit; skeletal muscle having a Ca 2+ imbalance; skeletal muscle having microtears).

Methods and compositions for treating peripheral vascular disease

The invention features a method of treating a peripheral vascular disease or a condition associated with a peripheral vascular disease by administering to a subject an effective amount of at least one phosphodiesterase type 5 inhibitor and at least one nitric oxide donor. The invention also features compositions formulated for topical or oral administration including at least one phosphodiesterase type 5 inhibitor, at least one nitric oxide donor, and a pharmaceutically acceptable carrier, as well as kits including these compositions. These methods, compositions, and kits can optionally include other therapeutic agents.

Andrographolide derivatives and method of using the same for treatment or prevention of fibrosis

A method of treatment or prevention of fibrosis of human tissue or organ. The method includes administering a patient in need thereof a compound of formula (I).

INHIBITOR AND ACTIVATOR OF DISCOIDIN DOMAIN RECEPTOR 1 AND THEIR USE

The present invention relates to a use of Discoidin Domain Receptor 1 (DDR1) inhibitor in preparing a medicament for preventing or treating a joint disease. The present invention further relates to a use of DDR1 activator in preparing a medicament for preventing or treating abnormalities of endochondral ossification-related conditions. 110-. (canceled)11. A method for treating or alleviating a joint symptom in a subject , comprising:identifying the subject having the degenerative arthritis; andadministering to the subject an effective amount of a composition including a Discoidin Domain Receptor 1 (DDR1) inhibitor.12. The method as claimed in claim 11 , wherein the DDR1 inhibitor includes a DDR1 inhibitory antibody claim 11 , a small interfering ribonucleic acid (siRNA) or an antisense nucleic acid.13. The method as claimed in claim 11 , wherein the joint symptom is a joint disease.14. The method as claimed in claim 13 , wherein the joint disease is a degenerative joint disease.15. The method as claimed in claim 14 , wherein the degenerative joint disease is osteoarthritis.16. The method as claimed in claim 14 , wherein the degenerative joint disease is caused by a joint injury claim 14 , an anterior cruciate ligament injury claim 14 , or aging.17. The method as claimed in claim 16 , wherein the joint injury is at least one of a traumatic injury and a post-operative injury.18. The method as claimed in claim 11 , wherein the subject is a human subject.21. The method as claimed in claim 11 , wherein the subject has a condition associated with increased levels of mammalian target of rapamycin (mTOR) and collagen type X.22. The method as claimed in claim 21 , wherein the condition associated with the increased levels of mTOR and collagen type X increases a potential development of at least one of a cartilage degradation and a chondrocyte death in the subject claim 21 , and the administration of the composition inhibits claim 21 , mitigates or alleviates the condition.23 ...

COMPOSITION FOR TREATING FIBROCARTILAGE TISSUE DAMAGE

The present invention has an objective of providing a novel composition for treating a fibrocartilaginous tissue injury. The present invention provides a composition for treating a fibrocartilaginous tissue injury, which is to be applied to an injured fibrocartilaginous tissue part of a target and which comprises a monovalent metal salt of alginic acid, more preferably a low endotoxin monovalent metal salt of alginic acid. 1. A composition for treating a fibrocartilaginous tissue injury , which is to be applied to an injured fibrocartilaginous tissue part of a target , which has fluidity or is flaky or powdery when applied to the injured fibrocartilaginous tissue part , and which comprises a monovalent metal salt of alginic acid.2. The composition according to claim 1 , wherein the monovalent metal salt of alginic acid is a low endotoxin monovalent metal salt of alginic acid.3. The composition according to either one of and claim 1 , wherein the timing of applying the composition to the injured fibrocartilaginous tissue part is the timing of bringing the composition into contact with the injured fibrocartilaginous tissue part.4. The composition according to any one of - claim 1 , wherein the composition having fluidity is used so as to be at least partially cured after the application to the injured fibrocartilaginous tissue part.5. The composition according to any one of - claim 1 , wherein the composition having fluidity is cured by bringing a crosslinking agent into contact with at least a part of the surface of the composition.6. The composition according to any one of - claim 1 , wherein the apparent viscosity of the composition having fluidity is 100 mPa·s-30000 mPa·s as measured with a cone-plate viscometer under a condition of 20° C.7. The composition according to any one of - claim 1 , wherein the weight-average molecular weight (absolute molecular weight) of the monovalent metal salt of alginic acid is 30 claim 1 ,000 or more as measured by a GPC-MALS ...

COMPOSITIONS COMPRISING THE PROPEPTIDE OF LYSYL OXIDASE AND USES THEREOF

A method of treating fibrosis in a subject in need thereof is provided. The method comprising administering to the subject a polypeptide comprising a propeptide of lysyl oxidase (LOX), the polypeptide being devoid of LOX catalytic activity, thereby treating the fibrosis in the subject, wherein the method does not comprise administration of D-penicillamine. Also provided are polypeptide compositions for use in therapy. 1. A synthetic polypeptide comprising a propeptide of human lysyl oxidase (LOX) , said polypeptide being devoid of LOX catalytic activity , said synthetic polypeptide comprising a modification which imparts said polypeptide with enhanced stability under physiological conditions as compared to a native form of said polypeptide not comprising said modification , wherein said modification comprises a proteinaceous modification and said polypeptide is a chimeric polypeptide.2. The polypeptide of claim 1 , wherein said proteinaceous modification is selected from the group consisting of immunoglobulin claim 1 , human serum albumin claim 1 , and transferrin.3. The polypeptide of claim 2 , wherein said immunoglobulin comprises an Fc domain.4. A method of treating fibrosis in a subject in need thereof claim 2 , the method comprising administering to the subject a polypeptide comprising a propeptide of lysyl oxidase (LOX) claim 2 , said polypeptide being devoid of LOX catalytic activity claim 2 , wherein the method does not comprise administration of D-penicillamine claim 2 , thereby treating fibrosis in the subject.5. A method of treating DMD in a subject in need thereof claim 2 , the method comprising administering to the subject a propeptide of lysyl oxidase (LOX) claim 2 , said polypeptide being devoid of LOX catalytic activity claim 2 , thereby treating DMD in a subject in need thereof.6. The polypeptide of claim 1 , wherein said polypeptide is:glycosylated on at least one or two or all of N81, N97 and N144 of SEQ ID NO: 1;not glycosylated on N81, N97 and ...

Cartilage Mosaic Compositions and Methods

Compositions comprising a cartilage sheet comprising a plurality of interconnected cartilage tiles and a biocompatible carrier are provided. Methods of manufacturing cartilage compositions comprising a cartilage sheet comprising a plurality of interconnected cartilage tiles are also provided.

Stable mia/cd-rap formulation

The present invention relates to stable aqueous formulations comprising at least 5 mg/mL CD-RAP and a charged amino acid, said amino acid preferably having a net charge at a pH between about 6 and 8. The ingredients of the formulation preferably provide stability over repeated freeze-thaw cycles. In a preferred aspect, the formulation is for use in therapy, preferably for use in the treatment of inflammatory disorders, preferably osteoarthritis. Furthermore, a kit comprising the formulation of the invention is provided

Treatment of fibrosis

This invention is in the field of treatment of fibrosis. In particular, it relates to the treatment of IPF using N-Cadherin antibodies. The antibody may be any antagonising or neutralizing N-Cadherin antibody suitable for therapeutic use.

REGULATION OF A FOREIGN BODY RESPONSE

IL-17-producing γδ T cells and CD4T17 cells were identified in fibrotic tissue surrounding human breast implants. In both murine and human tissue samples, senescent cells developed around the implants, which was linked to the IL-17 response. Activation of the T17 pathway in the foreign body response/reaction (FBR) defines an adaptive immune response to synthetic materials, providing multiple new targets for therapeutic inhibition. 1. A method of inhibiting a foreign body response (FBR) in a subject , comprising:administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an agent which inhibits interleukin-17 (IL-17) activity or function, thereby, inhibiting the foreign body response.2. The method of claim 1 , wherein the agent inhibiting IL-17 inhibits IL-17-producing γδ T cells and CD4 T17 cells in tissue surrounding the foreign body.3. The method of claim 1 , wherein administration of the agent inhibiting IL-17 results in reduction of expression of p16 claim 1 , p21 claim 1 , IL-17 claim 1 , type I collagen claim 1 , S100a4 or combinations thereof.4. The method of any one of through claim 1 , further comprising administering a senolytic agent claim 1 , a senomorphic agent claim 1 , an inhibitor of interleukin-6 (IL-6) claim 1 , an inhibitor of interleukin 1β (IL-1β) claim 1 , an inhibitor of tumor necrosis factor α (TNFα) claim 1 , an inhibitor of interleukin-23 (IL-23) or combinations thereof.5. The method of claim 4 , wherein the senolytic agent comprises: dasatinib claim 4 , quercetin claim 4 , ABT-263 (navitoclax) claim 4 , ABT-737 claim 4 , piperlongumine (PL) claim 4 , fisetin claim 4 , HSP90 inhibitors claim 4 , A1331852 claim 4 , A1155463 claim 4 , ATTAC claim 4 , BCL-Xinhibitor claim 4 , analogues or combinations thereof.6. The method of any one of through claim 4 , wherein the senolytic agent or the agent inhibiting IL-17 comprise: antibodies claim 4 , antibody fragments claim 4 , oligonucleotides claim 4 , ...

TREATMENT OF INTERVERTEBRAL DISC DEGENERATION

The present application discloses a method for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site, which includes injecting a mammalian connective tissue cell into the intervertebral disc defect site. 16.-. (canceled)7. A method for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site of a mammal comprising:a) inserting a gene encoding a protein having intervertebral disc regenerating function into a mammalian cell, andb) transplanting the mammalian cell into the intervertebral disc defect site, wherein the mammalian cells are human embryonic kidney cells or epithelial cells.8. The method according to claim 7 , wherein said gene belongs to TGF-β superfamily.9. The method according to claim 8 , wherein said gene encodes TGF-β1.10. The method according to claim 7 , wherein the mammalian cell is allogeneic relative to the mammal.11. (canceled)12. The method according to claim 7 , wherein the mammal is human.13. A method for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site of a mammal comprising:a) inserting a gene encoding a protein having intervertebral disc regenerating function into a first mammalian cell, andb) transplanting a mixture of the mammalian cell of a) and unmodified second mammalian connective tissue cell into the intervertebral disc defect site, wherein said first mammalian cell is human embryonic kidney cells or epithelial cells; and second mammalian connective tissue cell is chondrocyte.14. The method according to claim 13 , wherein said gene belongs to TGF-β superfamily.15. (canceled)16. The method according to claim 15 , wherein the chondrocyte is non-disc chondrocyte or juvenile chondrocyte.17. The method according to claim 13 , wherein the chondrocyte for the second mammalian connective tissue is primed chondrocyte.18. The method according to claim 13 , wherein the first or second cell is allogeneic relative ...

Orally administrable compositions comprising avocado/soybean unsaponifiables and lipoic acid and methods of administration

An orally administrable composition for treating or reducing damage to connective tissue or for treating or reducing inflammatory symptoms associated with damage to connective tissue includes a synergistic combination of: (i) avocado/soybean unsaponifiables; and (ii) lipoic acid, or a salt or derivative thereof. Methods for treating or reducing damage to connective tissue, for treating or reducing inflammatory symptoms associated with damage to connective tissue, or for reducing levels of one or more inflammatory mediators in connective tissue include administering the orally administrable composition to an avian or mammalian subject.

Compositions and Methods for Managing or Improving Bone Disorders, Cartilage Disorders, or Both

The present disclosure provides mixtures of prenylated flavonoids, stilbenes, or both with flavans or curcuminoids or both capable of useful for promoting, managing or improving bone health, cartilage health or both, or for preventing or treating a bone disorder, cartilage disorder or both. Such a mixture of prenylated flavonoids, stilbenes, or both with flavans or curcuminoids or both can optionally be used in combination with other bone and cartilage management agents, such as calcium, magnesium, zinc, boron, vitamin D, vitamin K, glucosamine and/or chondroitin compounds, non-steroidal anti-inflammatory agents/analgesics, COX/LOX inhibiting agents, neuropathic pain relief agents, or the like.

ADENO-ASSOCIATED VIRUS VECTOR DELIVERY OF MICRORNA-29 AND MICRO-DYSTROPHIN TO TREAT MUSCULAR DYSTROPHY

The invention provides for recombinant AAV vectors comprising a polynucleotide sequence comprising the guide strand of miR-29c and methods of using the recombinant vectors to reduce or prevent fibrosis in subjects suffering from dystrophinopathy or muscular dystrophy. The invention also provides for combination therapies comprising expressing both miR-29 and micro-dystrophin to reduce and prevent fibrosis in patients suffering from dystrophinopathy or muscular dystrophy. 1. A method of treating muscular dystrophy or dystrophinopathy comprising administering i) a therapeutically effective amount of recombinant AAV vector expressing miR-29c and ii) a therapeutically effective amount of recombinant AAV vector expressing micro-dystrophin.2. A method of reducing or preventing fibrosis in a subject suffering from muscular dystrophy or dystrophinopathy comprising administering i) a therapeutically effective amount of recombinant AAV vector expressing miR-29c and ii) a therapeutically effective amount of recombinant AAV vector expressing micro-dystrophin.3. A method of increasing muscular force or muscle mass in a subject suffering from muscular dystrophy or dystrophinopathy comprising administering i) a therapeutically effective amount of recombinant AAV vector expressing miR-29c and ii) a therapeutically effective amount of recombinant AAV vector expressing micro-dystrophin.4. A method of any one of - wherein the muscular dystrophy is Duchenne muscular dystrophy or Becker muscular dystrophy.5. The method of any one of - wherein the recombinant AAV vector expressing miR-29c comprisesa) the nucleotide sequences of SEQ ID NO: 3 and SEQ ID NO: 4,b) the nucleotide sequence of SEQ ID NO: 2,c) the nucleotide sequence of SEQ ID NO: 1 ord) the nucleotide sequence of SEQ ID NO: 12.6. The method of any one of - wherein the recombinant AAV vector expressing micro-dystrophin comprisesa) a nucleotide sequence having at least 85% identity to the nucleotide sequence SEQ ID NO: 7 and ...

PHARMACEUTICAL COMPOSITION USING ENDOGENOUS CELLS FOR PREVENTING OR TREATING MUSCULOSKELETAL DISORDERS

The present disclosure relates to a pharmaceutical composition for preventing or treating musculoskeletal disease, which has the effect of proliferating endogenous cells in bone marrow. More specifically, the pharmaceutical composition of the present disclosure can be used for the treatment of musculoskeletal disease since it proliferates endogenous cells in bone marrow and enhances the functions thereof. 1. A pharmaceutical composition for preventing or treating a musculoskeletal disease , comprising platelet-rich plasma (PRP) , batroxobin , calcium and tranexamic acid as active ingredients.2. The pharmaceutical composition for preventing or treating a musculoskeletal disease according to claim 1 , wherein a mixing weight ratio of the platelet-rich plasma (PRP) claim 1 , the batroxobin claim 1 , the calcium and the tranexamic acid is 10-20:1-4:1:1-3.3. The pharmaceutical composition for preventing or treating a musculoskeletal disease according to claim 1 , wherein the platelet-rich plasma (PRP) is autologous or allogeneic.4. The pharmaceutical composition for preventing or treating a musculoskeletal disease according to claim 1 , wherein the concentration of the platelet-rich plasma (PRP) is 200-5 claim 1 ,000×10platelets/microL.5. The pharmaceutical composition for preventing or treating a musculoskeletal disease according to claim 1 , wherein the pharmaceutical composition is a gel-type injection injected to an affected part.6. The pharmaceutical composition for preventing or treating a musculoskeletal disease according to claim 5 , wherein the affected part is a bone-tendon junction or a bone-ligament junction.7. The pharmaceutical composition for preventing or treating a musculoskeletal disease according to claim 5 , wherein the affected part is an intraosseous passage formed through multiple channeling.8. The pharmaceutical composition for preventing or treating a musculoskeletal disease according to claim 1 , wherein the musculoskeletal disease is one or ...

Solid forms for tissue repair

This invention provides aragonite- and calcite-based scaffolds for the repair, regeneration, enhancement of formation or a combination thereof of cartilage and/or bone, which scaffolds comprise at least two phases, wherein each phase differs in terms of its chemical content, or structure, kits comprising the same, processes for producing solid aragonite or calcite scaffolds and methods of use thereof.

Proteolytic extract from bromelain for the treatment of connective tissue disorders

The present invention relates to a proteolytic extract obtained from bromelain for the treatment of connective tissue diseases. In particular, the present invention relates to a pharmaceutical composition that includes proteolytic extract obtained from bromelain for the treatment of diseases such as Dupuytren's disease and Peyronie's disease.

Differentiation of stem cells with nanoparticles

This invention relates to stimulation of stem cells and other progenitors of differentiated cells using nanoparticles and electromagnetic stimulation. The invention provides a method for differentiating mesenchymal stem cells (MSCs) towards osteoblasts and other connective tissue. The invention provides osteoinductive materials useful for bone regeneration and reconstruction in treatment of bone trauma and bone related diseases, and to correct birth defects. The invention also provides for reduced adipogenesis.

Method for monomerizing matrix metalloproteinase 7 (mmp-7) aggregate

A method for monomerization of MMP-7 aggregates is provided. A method for monomerization of MMP-7 aggregates which comprises treating MMP-7 aggregates with a buffer solution comprising a monovalent cation chloride (sodium chloride, potassium chloride, etc.) at a low concentration or with a buffer solution not comprising a monovalent cation chloride, a process for preparing MMP-7 which involves said method for monomerization, and a (pharmaceutical) composition comprising MMP-7 in the aforementioned buffer solution. In case that a (pharmaceutical) composition comprising MMP-7 at a low concentration is prepared, the aforementioned buffer solution comprising sugar alcohols or sugars is used.

Compositions and methods directed to treating liver fibrosis

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the COL1A1, TGF-β, and SMAD2/3 genes, and methods of using such dsRNA compositions to inhibit expression of COL1A1, TGF-β, and SMAD2/3.

Platelet-Derived Growth Factor Compositions and Methods for the Treatment of Tendinopathies

Provided herein are compositions and methods for the treatment of tendinopathies, such as tenosynovitis, tendinosis or tendinitis, including Achilles tendinopathy, patellar tendinopathy, lateral epicondylitis or “tennis elbow,” medial epicondylitis or “golfer's elbow,” plantar fasciitis, and rotator cuff tendinopathy, and in particular to methods for the treatment of tendinopathies by administering compositions comprising platelet-derived growth factor (PDGF).

TREATMENTS UTILIZING A POLYMER-PROTEIN CONJUGATE

A composition for use in treating a condition associated with degeneration of articular cartilage and/or with subchondral bone loss is disclosed herein. The composition comprises a conjugate which comprises a polypeptide having attached thereto at least two polymeric moieties, at least one of the polymeric moieties exhibiting a reverse thermal gelation. Further disclosed is a composition comprising the aforementioned conjugate along with a hyaluronic acid, an anti-inflammatory agent, an analgesic, a growth factor, a blood fraction, a nucleic acid, and/or a cell, the composition being an aqueous composition which forms a hydrogel at a temperature in a range of from 32° C. to 37° C., as well as a method utilizing such a composition comprising a nucleic acid for effecting gene delivery. 1. A method of treating a condition associated with degeneration of articular cartilage and/or with subchondral bone loss in a subject in need thereof , the method comprising administering to the subject a composition comprising a conjugate which comprises a polypeptide having attached thereto at least two polymeric moieties , at least one of said polymeric moieties exhibiting a reverse thermal gelation , thereby treating the condition.2. The method of claim 1 , comprising intra-articular administration of the composition.3. (canceled)4. The method of claim 1 , wherein said degeneration is associated with friction at a surface of said articular cartilage.5. (canceled)6. The method of claim 1 , wherein said degeneration of articular cartilage and/or said subchondral bone loss is associated with an inflammation.7. The method of claim 1 , wherein said condition is associated with a subchondral bone cyst.8. (canceled)9. The method of claim 1 , wherein the composition is characterized by water uptake of less than 20 weight percents upon incubation with an aqueous liquid for 48 hours at a temperature of 37° C.10. The method of claim 1 , wherein the composition comprises an aqueous solution of ...

Use of adipose tissue-derived stromal cells for chondrocyte differentiation and cartilage repair

Methods and compositions for directing adipose-derived stromal cells cultivated in vitro to differentiate into cells of the chondrocyte lineage are disclosed. The invention further provides a variety of chondroinductive agents which can be used singly or in combination with other nutrient components to induce chondrogenesis in adipose-derived stromal cells either in cultivating monolayers or in a biocompatible lattice or matrix in a three-dimensional configuration. Use of the differentiated chondrocytes for the therapeutic treatment of a number of human conditions and diseases including repair of cartilage in vivo is disclosed.

TREATMENT OF FIBROSIS WITH GENETICALLY-ENGINEERED MACROPHAGES

Provided herein are macrophages engineered for treating fibrosis and ameliorating the effects of fibrotic lesions in various organs and tissues. Certain embodiments are directed to genetically-engineered macrophages capable of treating fibrosis or reducing fibrotic lesions. In certain aspects macrophages can be genetically-engineered to (1) target extracelluar matrix (ECM) or components thereof, (2) enhance degradation of ECM, or (3) target ECM and enhance degradation of ECM. Further provided is a cellular therapy product comprising a genetically-engineered macrophage comprising at least one of a recombinant targeting protein and a recombinant catalytic enzyme. Further provided is a method of treating an individual for fibrosis comprising administering the cellular therapy product. 1. A genetically-engineered macrophage , comprising:a recombinant extracellular matrix (ECM) targeting protein; and/ora recombinant protease.2. The genetically-engineered macrophage of claim 1 , wherein the recombinant targeting protein is a collagen receptor or a subunit thereof.3. The genetically-engineered macrophage of claim 2 , wherein the collagen receptor or a subunit thereof comprises one or more of an integrin claim 2 , a discoidin domain receptor claim 2 , a mannose family receptor claim 2 , and an immunoglobulin-like receptor.4. The genetically-engineered macrophage of claim 3 , wherein the integrin is an α1β1 claim 3 , α2β1 claim 3 , α10β1 claim 3 , and/or α11β1 integrin.5. The genetically-engineered macrophage of claim 3 , wherein the discoidin domain receptor is DDR1 and/or DDR2.6. The genetically-engineered macrophage of claim 3 , wherein the mannose family receptor is M-phospholipase A2 receptor and/or Endo180.7. The genetically-engineered macrophage of claim 3 , wherein the immunoglobulin-like receptor is glycoprotein VI.8. The genetically-engineered macrophage of claim 1 , wherein the recombinant targeting protein is ITGA-1.9. The genetically-engineered macrophage of ...

Methods and compositions for the treatment, prevention, and alleviation of bone and cartilage diseases or injuries and hair loss

The present invention provides pharmaceutical compositions, and methods of preparation and use for the treatment, prevention or alleviation of bone and cartilage diseases or injuries and hair loss. The present invention discloses a method and a pharmaceutical composition comprising mesenchymal stem cells, platelets, activating factors and scaffolding materials for the treatment, prevention, or alleviation of bone diseases, bone injuries or hair loss, and a method and a pharmaceutical composition further comprising dexamethasone for the treatment, prevention, or alleviation of cartilage diseases or injuries.

INHIBITORS OF ENPP1 AND METHODS OF USING SAME

Disclosed herein are methods for inhibiting ectopic calcification in soft tissues, such as heart tissue. Also provided herein are ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) inhibitors. 1. A method of treating or preventing ectopic calcification in a subject , comprising administering an ENPP1 inhibitor.2. The method of claim 1 , wherein the ENPP1 inhibitor is selected from rosmarinic acid claim 1 , ARL67156 claim 1 , and etidronic acid claim 1 , or a pharmaceutically acceptable salt and/or prodrug thereof.3. The method of claim 1 , wherein the ENPP1 inhibitor is rosmarinic acid or a pharmaceutically acceptable salt and/or prodrug thereof.4. The method of claim 1 , wherein the ENPP1 inhibitor is ARL67156 or a pharmaceutically acceptable salt and/or prodrug thereof.5. The method of claim 1 , wherein the ENPP1 inhibitor is etidronic acid or a pharmaceutically acceptable salt and/or prodrug thereof.6. The method of claim 1 , wherein the subject has diabetes claim 1 , kidney disease claim 1 , heart disease and/or myocardial injury claim 1 , or vascular disease.7. The method of claim 6 , wherein the subject has heart disease.8. The method of claim 7 , wherein the ectopic calcification is in heart tissue.9. The method of claim 8 , wherein the heart issue is a heart valve.10. The method of claim 6 , wherein the subject has myocardial injury.11. The method of claim 1 , further comprising inhibiting the level of cardiac fibroblast calcification activity.12. The method of claim 1 , wherein the subject has a soft tissue injury or organ injury.13. The method of claim 1 , wherein the subject has pseudoxanthoma elasticum.14. The method of claim 1 , further comprising reducing cellular levels of pyrophosphate.15. The method of claim 1 , wherein rosmarinic acid and ARL67156 are conjointly administered to the subject.16. The method of claim 1 , wherein rosmarinic acid and etidronic acid are conjointly administered to the subject.17. The method of claim 1 , wherein ...

Anti-kit antibodies and uses thereof

Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-associated disorder or disease and methods of diagnosing a KIT-associated disorder or disease using the antibodies described herein.

Surface binding of nanoparticle based drug delivery to tissue

Microparticles and nanoparticles and compositions thereof are provided. The microparticles and nanoparticles and compositions may be used for the treatment of musculoskeletal disease, such as osteoarthritis and injury.

USE OF CELIPROLOL FOR TREATING VASCULAR EHLERS-DANLOS SYNDROME IN WOMEN DURING PREGNANCY AND PERIPARTUM PERIOD

The present disclosure relates to the use of celiprolol or a pharmaceutically acceptable salt thereof for treating vascular Ehlers-Danlos syndrome in women during pregnancy and peripartum period. 1. A method for treating vascular Ehlers-Danlos syndrome in a woman during pregnancy , during delivery , or during the peripartum period , the method comprising administering celiprolol , or a pharmaceutically acceptable salt thereof , to the woman during pregnancy , during delivery , or during the peripartum period , thereby treating vascular Ehlers-Danlos syndrome in the woman.2. The method of claim 1 , wherein celiprolol claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is administered to the woman a dosage of at least 100 mg per day.3. The method of claim 1 , wherein celiprolol claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is administered to the woman at a dosage ranging from about 200 mg to about 600 mg per day.4. The method of claim 1 , wherein celiprolol claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is administered to the woman at a daily dosage of about 200 mg to about 400 mg.5. The method of claim 1 , wherein celiprolol claim 1 , or the pharmaceutically acceptable salt thereof claim 1 , is administered twice daily.6. The method of claim 1 , wherein the method prevents or reduces the risk of cardiovascular and/or digestive and/or obstetrical events.7. The method of claim 1 , wherein the method prevents or reduces the risk of arterial dissection and rupture.8. The method of claim 1 , wherein the method prevents or reduces the risk of obstetrical accidents.9. The method of claim 1 , wherein the method prevents or reduces the risk of uterine rupture.10. The method of claim 1 , wherein the method reduces the risk of pregnancy-related death.11. The method of claim 1 , wherein the method reduces the risk of death of the woman during the first year following termination of pregnancy.12. The method of claim 1 , wherein ...

METHODS AND COMPOSITIONS FOR THE TREATMENT OF INTERVERTEBRAL DISC HERNIATION

The invention relates to methods and compositions for use in the treatment or prophylaxis of intervertebral disc herniation in a mammal. The composition according to the invention comprises an inhibitor of T-cell activation, said inhibitor being capable of inhibiting CD28-mediated co-stimulation of T-cells. The said inhibitor of T-cell activation is preferably a protein comprising either an exact or a modified version of the extracellular domain of CTLA-4, such as abatacept, belatacept, XPro9523 and/or ASP2408. 118-. (canceled)19. A method for the treatment or prophylaxis of intervertebral disc herniation , comprising administering to a mammal in need thereof a therapeutically effective dose of an inhibitor of CD28-mediated co-stimulation of T-cells , which inhibitor is a protein comprising at least one extracellular domain of CTLA-4; wherein the treatment or prophylaxis comprises (a) reduction or prevention of disc hernia formation; (b) reduction of disc hernia size , or both.20. The method according to wherein the inhibitor of CD28-mediated co-stimulation of T-cells is a protein which is capable of binding to CD80/CD86.21. (canceled)22. The method according to wherein the protein is a fusion protein comprising the Fc region of immunoglobulin G (IgG) fused to the at least one extracellular domain of CTLA-4.23. The method according to wherein the extracellular domain of CTLA-4 is chosen from:(a) a polypeptide having an amino acid sequence comprising the sequence shown as SEQ ID NO: 3 or SEQ ID NO: 4;(b) a polypeptide having an amino acid sequence which is at least 90% identical with the sequence shown as SEQ ID NO: 3 or SEQ ID NO: 4;(c) a polypeptide having an amino acid sequence consisting essentially of the sequence shown as SEQ ID NO: 3 or SEQ ID NO: 4; or(d) a polypeptide having an amino acid sequence consisting of SEQ ID NO: 3 or SEQ ID NO: 4.24. The method according to wherein the fusion protein is a dimer comprising two monomers chosen from:(a) a polypeptide ...

Resorbable biodegradable medical and cosmetic composition comprising poly(1,3-trimethylene carbonate)

The present invention relates to the field of resorbing biodegradable medical and cosmetic compositions.

A METHOD OF IN VITRO CHONDROCYTE AND CARTILAGE CULTURE TO OBTAIN MATERIAL FOR THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS

The present invention relates to a new method for treating human or animal tissue such as cartilage, particularly damaged tissue. More specifically, the invention relates to a method to obtain material for treating the damaged tissue, for example any cartilage damage, in particular as a result of traumatic or degenerative cartilage damage. 1. A method for producing a cartilage tissue implant in vitro , characterized by the following features:i) providing at least a first and a second fragment of cartilage tissue, which each have at least one edge;ii) placing the fragments in a culture medium in such that at least one edge of the first fragment is spaced <1 cm or less apart from at least one edge of the second fragment;iii) adding a suspension of chondrocytes to the fragments; andiv) cultivating the fragments and chondrocytes under cell culture conditions.2. The method according to claim 1 , wherein the edges of the fragments are in contact with each other along a tangential section.3. The method according to claim 1 , wherein the culture medium comprises a medium containing one or more salts claim 1 , amino acids claim 1 , further components such as galactose claim 1 , dextransulfate claim 1 , spemidine claim 1 , beta-glycerolphosphat and adenine; and a buffer.4. The method according to claim 1 , wherein the medium further comprises growth factors claim 1 , comprised for example in human and/or calf serum claim 1 , preferably FBS claim 1 , preferably the medium is free of serum.5. The method according to claim 1 , wherein the culture medium comprises IGF and/or TGF.6. The method according to claim 1 , wherein the fragments are cultured in the culture medium for at least 14 days after step (ii) before adding the suspension of chondrocytes in step (iii).7. The method according to claim 1 , wherein the chondrocytes are added to the culture medium in step (iii) to a final concentration of at least 4 claim 1 ,000.8. The method according to claim 1 , wherein the ...

CARTILAGE-HOMING PEPTIDES

Peptides that home, target, migrate to, are directed to, are retained by, or accumulate in amd/or binds to the cartilage of a subject are disclosed. Pharmaceutical compositions and uses for peptides or peptide-active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of a drug to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver peptide or peptide-active agent complexes to target regions, tissues, structures or cells targeted by the peptide. 13-. (canceled)4. A composition comprising a peptide , the peptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 111 or a functional fragment thereof.511-. (canceled)12. The composition of claim 4 , wherein the peptide comprises a knotted peptide.13. The composition of claim 4 , wherein the peptide comprises:(a) 4 or more cysteine residues(b) a plurality of disulfide bridges formed between cysteine residues; or(c) at least 30 residues.1449-. (canceled)50. The composition of claim 4 , wherein the peptide is linked to an active agent.5163-. (canceled)64. The composition of claim 50 , wherein the active agent is: a peptide claim 50 , an oligopeptide claim 50 , a polypeptide claim 50 , a polynucleotide claim 50 , a polyribonucleotide claim 50 , a DNA claim 50 , a cDNA claim 50 , a ssDNA claim 50 , a RNA claim 50 , a dsRNA claim 50 , a microRNA claim 50 , an oligonucleotide claim 50 , an antibody claim 50 , an antibody fragment claim 50 , an aptamer claim 50 , a cytokine claim 50 , an enzyme claim 50 , a growth factor claim 50 , a chemokine claim 50 , a neurotransmitter claim 50 , a chemical agent claim 50 , a fluorophore claim 50 , a metal claim 50 , a metal chelate claim 50 , an X-ray contrast agent claim 50 , a PET agent claim 50 , a radioisotope claim 50 , a photosensitizer claim 50 , a radiosensitizer claim 50 , a radionuclide chelator claim 50 , a therapeutic small ...

VEGF GENE THERAPY FOR TENDON AND LIGAMENT INJURIES

Provided are compositions comprising a viral vector and a VEGF gene or a fragment thereof, and methods of using the compositions for the treatment of an injury of a fibrous connective tissue. 1. A method of treating an injury of a fibrous connective tissue in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a polynucleotide comprising a sequence encoding vascular endothelial growth factor (VEGF) or a fragment thereof.2. The method of claim 1 , wherein said polynucleotide further comprises a sequence encoding a gene product for kanamycin resistance.3. The method of claim 1 , wherein said sequence encoding a gene product for kanamycin resistance comprises the sequence of SEQ ID NO: 10.4. The method of claim 3 , wherein said polyncleotide comprises the sequence of SEQ ID NO: 11.5. The method of claim 1 , wherein said VEGF comprises a nucleic acid sequence of any one of SEQ ID Nos: 1-9.6. The method of claim 1 , wherein said VEGF comprises the nucleic acid sequence of SEQ ID NO: 9.7. The method of claim 1 , wherein said fibrous connective tissue is a ligament claim 1 , a tendon claim 1 , a fascia or any combination thereof.8. The method of claim 1 , wherein said polynucleotide is within a viral vector.9. The method of claim 8 , wherein said viral vector is an adeno-associated viral type-2 (AAV2) vector.10. The method of claim 1 , wherein said polynucleotide is administered directly into or onto said fibrous connective tissue.11. The method of claim 1 , wherein said polynucleotide is administered via an injection.12. The method of claim 1 , wherein said polynucleotide is formulated as a solution claim 1 , a gel claim 1 , a paste claim 1 , a powder claim 1 , or a suspension.13. A composition comprising a viral vector and a VEGF gene or a fragment thereof.14. The composition of claim 13 , wherein said VEGF gene comprises the nucleic acid sequence of any one of SEQ ID Nos: 1-9.15. The composition of claim 13 , wherein ...

DOPAMINE RECEPTOR D1 AGONISTS AND METHODS OF USE

Described herein are small molecule agonists of dopamine receptor D1 that inhibit YAP/TAZ, compositions, and methods of using these compounds and compositions. The methods of using such compounds in the treatment of conditions, diseases, or disorders associated with fibrotic disease are described herein. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': 1', '2', 'a, 'sub': 1', '6, 'each Rand Ris independently hydrogen, halogen, —OH, —OR, or C-Calkyl.'}3. The compound of or claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': 1', '2', 'a, 'each Rand Ris independently —OH or —OR.'}4. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': 1', '2, 'each Rand Ris —OH.'}5. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': 1', '2', '8, 'Rand Rwith the intervening atoms to which they are attached form a fused 5-membered or 6-membered ring that is a fused cycloalkyl, fused heterocycloalkyl, fused phenyl, or fused heteroaryl; wherein the fused ring is unsubstituted or substituted with one or two R.'}6. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': 2', '5, 'Xis CR;'}{'sup': 3', '6, 'Xis CR; and'}{'sup': 4', '7, 'Xis CR.'}7. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': 5', '6', '7', 'a', '8, 'sub': 1', '6', '2', '6', '2', '6', '1', '6', '1', '6, 'each R, R, and Ris independently hydrogen, halogen, —CN, —OH, —OR, C-Calkyl, C-Calkenyl, C-Calkynyl, or C-Cheteroalkyl; wherein alkyl, alkenyl, alkynyl and C-Cheteroalkyl is unsubstituted or substituted with one, two, or three R.'}8. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein:{'sup': '5', ' ...

Compositions and Methods for Treating Defects in Avascular Cartilaginous Tissue by Directly Administering One or More Metabolites of Simvastatin

Controlled release hydrogel formulations of one or more simvastatin metabolites 3′-hydroxy simvastatin (hSV), 6′-exomethylene simvastatin (eSV), 3′,5′-dihydrodiol simvastatin, 3′,5′-dihydrodiol simvastatin (dSV), simvastatin-beta-hydroxy acid (SVA), and methods for the treatment of patients suffering from injured or degenerating substantially avascular cartilaginous tissue. 1. A method of repairing or retarding damage to injured substantially avascular cartilaginous tissue , the method comprising administering to a subject in need thereof a composition comprising at least one oxidative metabolite of simvastatin (SV) directly to the site of the avascular tissue.2. The method according to claim 1 , wherein the step of administering comprises administering a controlled release formulation of the at least one oxidative metabolite simvastatin (SV) claim 1 , wherein said composition is released in said avascular cartilaginous tissue at a rate and an amount effective to permit repairing or retarding damage.3. The method according to claim 1 , wherein the at least one oxidative metabolite of SV is selected from the group consisting of 3′-hydroxy simvastatin (hSV) claim 1 , 6′-exomethylene simvastatin (eSV) claim 1 , 3′ claim 1 ,5′-dihydrodiol simvastatin claim 1 , 3′ claim 1 ,5′-dihydrodiol simvastatin (dSV) claim 1 , simvastatin-beta-hydroxy acid (SVA) claim 1 , and combinations thereof.4. The method according to wherein the at least one oxidative metabolite of SV comprises SVA.5. The method according to claim 1 , further comprising administering S in conjunction with the at least one metabolite claim 1 , wherein “in conjunction” includes simultaneous administration claim 1 , tandem administration claim 1 , or administration within a therapeutic time frame.6. The method according to claim 1 , wherein the cartilaginous tissue is in a spinal disc.7. The method according to claim 1 , wherein the cartilaginous tissue is in a joint.8. The method according to claim 7 , wherein ...

CONNECTIVE TISSUE MONITORING, COMPOSITIONS FOR CONNECTIVE TISSUE TREATMENT AND METHODS FOR TREATING CONNECTIVE TISSUE

A method for treating a non-hemorrhoidal tendon injury in a performance animal in need thereof includes administering to the animal a composition comprising a pro-inflammatory cytokine inhibitor, an antioxidant or catechin, and an anti-inflammatory to thereby treat the non-hemorrhoidal tendon injury in the performance animal. 1. A method for treating a non-hemorrhoidal tendon injury in a performance animal in need thereof , the method comprising:administering to the animal a composition comprising a pro-inflammatory cytokine inhibitor, an antioxidant or catechin, and an anti-inflammatory to thereby treat the non-hemorrhoidal tendon injury in the performance animal.2. The method of claim 1 , wherein the anti-inflammatory comprises a Non-Steroidal Anti-Inflammatory Drug (NSAID) and/or an inhibitor of cell activity.3. The method of claim 1 , wherein the composition further comprises an inhibitor of cell activity.4. The method of claim 3 , wherein the inhibitor of cell activity comprises a compound that damps down cell activity claim 3 , inhibits cell proliferation claim 3 , settles down or stabilizes an overactive state of a cell claim 3 , inhibits protein production from the cell claim 3 , inhibits production of one or more cytokines claim 3 , comprises an antimitotic or inhibits proteoglycan production.5. The method of claim 3 , wherein the inhibitor of cell activity comprises a steroid or a glucocorticoid steroid.6. The method of claim 3 , wherein the composition comprises copper ibuprofenate claim 3 , doxcycyline claim 3 , EGCG and dexamethasone.7. The method of claim 1 , wherein the pro-inflammatory cytokine inhibitor comprises doxycycline claim 1 , the antioxidant or catechin comprises a green tea extract or epigallocatechin gallate (EGCG) and the anti-inflammatory comprises ibuprofen or copper ibuprofenate.8. The method of claim 7 , wherein the pro-inflammatory cytokine inhibitor claim 7 , the antioxidant or catechin and the anti-inflammatory are present at ...

Compounds And Methods For Treating Fibrotic Pathologies

The present application provides methods for treating or preventing diseases and conditions associated with tissue fibrosis. 3. (canceled)4. The compound of claim 1 , wherein Ris 5-6-membered heteroaryl ring comprising 1 or 2 heteroatoms selected from N claim 1 , O claim 1 , and S claim 1 , which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from R.5. The compound of claim 1 , wherein Ris selected from pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , diazinyl claim 1 , triazinyl claim 1 , tetrazinyl claim 1 , and pentazinyl claim 1 , each of which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from R.6. (canceled)7. The compound of claim 1 , wherein Ris pyridinyl claim 1 ,{'sup': '2', 'optionally substituted with 1, 2, or 3 substituents independently selected from R.'}10. (canceled)11. The compound of claim 1 , wherein Ris 3-7-membered heterocycloalkyl ring comprising 1 or 2 heteroatoms selected from N claim 1 , O claim 1 , and S claim 1 , which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from R.12. The compound of claim 11 , wherein Ris selected from tetrahydropyranyl claim 11 , piperidinyl claim 11 , tetrahydrofuranyl claim 11 , pyrrolidinyl claim 11 , pyranyl claim 11 , morpholinyl claim 11 , oxazinyl claim 11 , dioxanyl claim 11 , dioxinyl claim 11 , diazinanyl claim 11 , triazinanyl claim 11 , trioxanyl claim 11 , azepanyl claim 11 , azepinyl claim 11 , oxepanyl claim 11 , oxepinyl claim 11 , diazepanyl claim 11 , diazepinyl claim 11 , azocanyl claim 11 , azocinyl claim 11 , oxocanyl claim 11 , oxocinyl claim 11 , azonanyl claim 11 , azoninyl claim 11 , oxonanyl claim 11 , and oxoninyl claim 11 , each of which is optionally substituted with 1 claim 11 , 2 claim 11 , or 3 substituents independently selected from R.13. (canceled)14. The compound of claim 11 , wherein Ris tetrahydropyranyl claim 11 , ...

Hydroxytyrosol compositions for treatment of cartilage injuries in joints

The invention relates to the use of hydroxytyrosol for inducing or enhancing cartilage repair or cartilage regeneration. Furthermore, the invention relates to nutraceutical and pharmaceutical compositions comprising hydroxytyrosol for regeneration and repair of cartilage injuries in joints, in particular of traumatic cartilage injuries.

INHIBITORS OF RHO ASSOCIATED COILED-COIL CONTAINING PROTEIN KINASE

The invention relates to inhibitors of ROCK1 and/or ROCK2. Also provided are methods of inhibiting ROCK1 and/or ROCK2 that are useful for the treatment of disease. 10. A method of treating a fibrotic disorder in a subject comprising administering to the subject a therapeutically effective amount of a compound according to .11. The method of claim 10 , wherein fibrotic disorder is selected from the group consisting of pulmonary fibrosis including cystic and idiopathic pulmonary fibrosis claim 10 , radiation induced lung injury claim 10 , liver fibrosis including cirrhosis claim 10 , cardiac fibrosis including arterial fibrosis claim 10 , endomyocardial fibrosis claim 10 , old myocardial infraction claim 10 , arterial stiffness claim 10 , atherosclerosis claim 10 , restenosis claim 10 , arthrofibrosis claim 10 , Crohn's disease claim 10 , myelofibrosis claim 10 , Peyronie's diseases claim 10 , nephrogenic systemic fibrosis claim 10 , progressive massive fibrosis claim 10 , retroperitoneal cavity fibrosis claim 10 , schleroderma/systemic sclerosis claim 10 , mediastinal fibrosis claim 10 , Keloids and hypertrophic scars claim 10 , glial scaring claim 10 , or renal fibrosis.12. A method of treating a central nervous system disorder in a subject comprising administering to the subject a therapeutically effective amount of a compound according to .13. The method of claim 12 , wherein the central nervous system disorder is selected from the group consisting of Huntington's disease claim 12 , Parkinson's Disease claim 12 , Alzheimer's claim 12 , Amyotrophic lateral sclerosis (ALS) claim 12 , Batten disease claim 12 , dementia claim 12 , spinal muscular atrophy claim 12 , motor neurone diseases claim 12 , spinocerebellar ataxia claim 12 , acute or chronic pain claim 12 , dementia claim 12 , neuronal degeneration claim 12 , spinal cord injury claim 12 , cerebral vasospasm or multiple sclerosis.14. A method of treating glaucoma in a subject comprising administering to the ...

Degradable Microparticles for Protein and Small Molecule Delivery

The invention relates to a microparticle platform and pharmaceutical compositions capable of recruiting pro-regenerative cells to and/or reducing inflammation at the site of muscle, joint, tendon, and/or ligament damage. The invention further relates to methods of treating muscle, joint, tendon, and/or ligament damage comprising administering the microparticles or pharmaceutical compositions comprising the microparticles. 1. A degradable microparticle comprising a GAG-based body and an active agent selected from a protein and a small molecule , wherein the active agent is positively charged.2. The degradable microparticle of claim 1 , wherein the GAG-based body is an N-desulfated heparin-based body.3. The degradable microparticle of claim 1 , wherein the degradable microparticle further comprises DTT or a poly (ethylene glycol)-based linker.4. The degradable microparticle of claim 3 , wherein the poly (ethylene glycol)-based linker is a PEGDA-based linker.5. The degradable microparticle of claim 1 , wherein the active agent is a protein.6. The degradable microparticle of claim 5 , wherein the active agent is SDF-1α or TSG-6.7. The degradable microparticle of claim 1 , wherein the active agent is a small molecule.8. The degradable microparticle of claim 1 , wherein the degradable microparticle is between about 30 and about 80 micrometers in diameter.9. The degradable microparticle of claim 1 , wherein the GAG-based body is an N-desulfated heparin-based body claim 1 , the degradable microparticle further comprises DTT and a PEGDA-based linker claim 1 , the active agent is selected from SDF-1α claim 1 , TSG-6 claim 1 , FTY720 and combinations thereof claim 1 , and wherein the degradable microparticle is between about 30 and about 80 micrometers in diameter.10. A pharmaceutical composition comprising a plurality of the degradable microparticles of and a pharmaceutically acceptable carrier claim 1 , additive claim 1 , or excipient claim 1 , wherein the pharmaceutical ...

HUMAN TISSUE DERIVED COMPOSITIONS AND USES THEREOF

Disclosed are compositions comprising a non-homogenized chorionic matrix, a homogenized amniotic matrix and a homogenized UC (UC) matrix, wherein the non-homogenized chorionic matrix comprises viable cells. Disclosed are methods of making the compositions disclosed herein comprising preparing a non-homogenized chorionic matrix, preparing a homogenized amniotic matrix, preparing a homogenized UC matrix, and combining the non-homogenized chorionic matrix, the non-homogenized chorionic matrix, and the homogenized UC matrix. Disclosed are methods of treating a tissue injury or chronic pain comprising administering any of the disclosed compositions to an area of a subject comprising a tissue injury. 146-. (canceled)47. A composition comprising a non-homogenized chorionic matrix , a homogenized amniotic matrix , a homogenized UC matrix and a viscous modifier , wherein the non-homogenized chorionic matrix comprises viable cells.48. A composition comprising a minced chorionic matrix , a homogenized amniotic matrix and a devitalized homogenized umbilical cord (UC) matrix , wherein the minced chorionic matrix comprises viable cells , wherein the composition does not comprise trophoblasts.49. A composition comprising an isolated chorionic cells , a homogenized amniotic matrix and a devitalized homogenized umbilical cord (UC) matrix , wherein the composition does not comprise trophoblasts.50. A composition comprising a minced chorionic matrix and a devitalized homogenized umbilical cord (UC) matrix , wherein the minced chorionic matrix comprises viable cells , wherein the composition does not comprise trophoblasts or an amniotic matrix.51. A composition comprising an isolated chorionic cells and a devitalized homogenized umbilical cord (UC) matrix , wherein the composition does not comprise trophoblasts or an amniotic matrix.52. The composition of claim 47 , wherein the viscous modifier is hyaluronic acid claim 47 , methylcellulose claim 47 , carboxymethylcellulose claim 47 , ...

DELIVERY OF AUTOLOGOUS CELLS COMPRISING MATRIX METALLOPROTEINASE FOR TREATMENT OF SCLERODERMA

The present invention relates to a method for the treatment of scleroderma through the delivery of matrix metalloproteinase (MMP) to a patient in need thereof, preferably under the control of a gene switch. In this manner, the use of a ligand activator to activate or deactivate the expression of MMP controls the gene switch. In another embodiment, the invention is directed to the delivery of autologous genetically modified cells transfected/transduced with a polynucleotide encoding MMP under the control of a gene switch activatable through the use of an activator ligand for the treatment or scleroderma. 1. A method of treating a sclerotic condition comprising administration of an expression vector , or cells comprising an expression vector , wherein said vector or cells comprise a polynucleotide encoding a fusion protein comprising a non-matrix metalloproteinase (non-MMP) signal peptide and a matrix metalloproteinase (MMP) polypeptide , or an enzymatically active collagen-degrading fragment thereof.2. The method of claim 1 , wherein the cells are first isolated from a patient suffering from scleroderma.3. The method of claim 2 , wherein the isolated cells are cultured ex vivo.4. The method of claim 3 , wherein the cells are fibroblasts.5. The method of claim 1 , wherein the polynucleotide encoding MMP or a collagen-degrading fragment thereof is further operably linked to a gene switch expression system.6. The method of claim 5 , wherein the gene expression switch system is activated to express MMP in the presence of an activator ligand and deactivated to reduce expression of MMP in the absence of the activator ligand.7. The method of claim 1 , wherein MMP is matrix metalloproteinase-1 (MMP-1).8. The method of claim 7 , wherein MMP-1 is human MMP-1.9. The method of claim 1 , wherein the expression vector is a viral vector.10. The method of claim 8 , wherein the viral vector is derived from a virus selected from lentivirus claim 8 , adenovirus claim 8 , and adeno- ...

TRUNCATED CARTILAGE-HOMING PEPTIDES AND PEPTIDE COMPLEXES AND METHODS OF USE THEREOF

Truncated, variant, or mutated peptides that home, target, migrate to, are directed to, are retained by, or accumulate in and/or bind to the cartilage or kidney of a subject are disclosed. Pharmaceutical compositions and uses for truncated or mutated peptides or truncated or mutated peptide-active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of an active agent to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver truncated or mutated peptide or truncated, variant, or mutated peptides or peptide-active agent complexes to target regions, tissues, structures or cells targeted by the peptide. 1. A peptide comprising:a) any one of SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 219, SEQ ID NO: 223, SEQ ID NO: 225, or a functional fragment thereof, or [{'sup': 1', '2', '3', '4', '5', '6', '7', '8, 'i) for SEQ ID NO: 89, wherein Xis selected from N, S, or G, wherein Xis selected from L or Y, wherein Xis selected from D or E, wherein Xis selected from M or T, wherein Xis selected from N, Q, A, S, T, or L, wherein Xis selected from S, G, or R, wherein Xis selected from H or Y, and wherein Xis selected from T or Y;'}, {'sup': 1', '2', '3', '4', '5', '6', '7, 'ii) for SEQ ID NO: 106, wherein Xis selected from L or Y, wherein Xis selected from D or E, wherein Xis selected from M or T, wherein Xis selected from N, Q, A, S, T, or L, wherein Xis selected from S, G, or R, wherein Xis selected from H or Y, and wherein Xis selected from T or Y;'}, {'sub': 1-13', '1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'iii) for SEQ ID NO: 221, wherein each X and Xare individually any amino acid or no amino acid and at least one of the following residues at the denoted position, more than one of the following residues at the denoted position, or all of the following residues at the denoted position is included in ...

Pyridine compounds

The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity. The present invention provides a compound represented by the formula (I): wherein R 1 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R 2 and R 3 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R 4 and R 5 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R 6 represents a hydrogen atom or the like, each R 7 may be the same or different and may each represent an optionally substituted C1-6 alkoxy group or the like, X represents —CH═, —C(—R 7 )═, or —N═, and m represents 1 to 4, or a pharmacologically acceptable salt thereof.

1,8-CINEOL COATED IMPLANTS

Apparatuses, devices, compositions, and methods to ameliorate undesired side effects or outcomes, such as fibrosis due to surgical implants, wounds, or other bodily injury. In particular, described are apparatuses, devices, and compositions containing inhibitors of Wnt11 as well as methods of making and using them. These apparatuses, devices, compositions, and methods may be especially useful for preventing, reducing or treating unwanted fibrosis, such as that resulting from a biomedical implant implanted in an individual. 1. A biomedical device comprising an effective amount of a composition containing a Wnt11 inhibitor for preventing , inhibiting or treating capsular fibrosis.2. A biomedical device comprising an effective amount of a composition containing a monoterpenoid for preventing , inhibiting or treating capsular fibrosis.3. A biomedical device comprising an effective amount of a composition containing 1 ,8-cineol for preventing , inhibiting or treating capsular fibrosis.4. The biomedical device of wherein the biomedical device is an implant configured to prevent claim 1 , inhibit claim 1 , or treat capsular fibrosis when the biomedical device is implanted into a body of an individual having or at risk of having capsular fibrosis.5. The biomedical device of wherein the implant is configured to stay in the body at least 2 weeks claim 4 , at least 4 weeks claim 4 , at least 8 weeks claim 4 , at least 3 months claim 4 , at least 6 months claim 4 , or at least one year.6. The biomedical device of wherein the biomedical device is an insert configured to prevent claim 1 , inhibit claim 1 , or treat capsular fibrosis when the biomedical device is inserted into a body of an individual having or at risk of having capsular fibrosis.7. The biomedical device of wherein the biomedical device is an interface configured to prevent claim 1 , inhibit claim 1 , or treat capsular fibrosis when placed on a body of an individual having or at risk of having capsular fibrosis.8. ...

COMPOSITIONS AND METHODS OF USE OF BETA-HYDROXY-BETA-METHYLBUTYRATE (HMB) FOR ENHANCING RECOVERY FROM SOFT TISSUE TRAUMA

The present invention provides a composition comprising HMB. Methods of administering HMB to an animal are also described. HMB is administered to enhance recovery from soft tissue trauma, including both acute and non-acute soft tissue trauma. Enhanced recovery includes reduced recovery time and enhanced soft tissue healing. Soft tissue trauma includes administration of a Botulinum toxin, such as Botox. Administration of HMB in association with administration of a Botulinum toxin increases muscle strength and/or function in muscle, including adjacent and/or contralateral muscles and prevents or lessens loss of contractile material. 1. A method of increasing strength in muscle following administration of Botulinum toxin , comprising administering to a human in need thereof a composition comprising from about 0.5 to about 30 grams of β-hydroxy-β-methylbutyric acid (HMB) , wherein the HMB further comprises HMB in its free acid form , its salt , its ester or its lactone.2. The method of claim 1 , wherein strength is increased in the injected muscle.3. The method of claim 1 , wherein strength is increased in adjacent muscle.4. The method of claim 1 , wherein strength is increased in at least one contralateral muscle.5. The method of claim 1 , wherein the Botulinum toxin further comprises Botox claim 1 , Xeomin claim 1 , Myobloc claim 1 , Dysport claim 1 , or Jeuveau.6. A method of lessening or preventing the loss of contractile material in muscle following administration of Botulinum toxin claim 1 , comprising administering to a human in need thereof a composition comprising from about 0.5 to about 30 grams of β-hydroxy-β-methylbutyric acid (HMB) claim 1 , wherein the HMB further comprises HMB in its free acid form claim 1 , its salt claim 1 , its ester or its lactone.7. The method of claim 6 , wherein the lessening or preventing of the loss of contractile material is in an adjacent muscle.8. The method of claim 6 , wherein the lessening or preventing of the loss of ...

BISAMIDE DERIVATIVE OF DICARBOXYLIC ACID AS AN AGENT FOR STIMULATING TISSUE REGENERATION AND RECOVERY OF DIMINISHED TISSUE FUNCTION

The invention relates to the field of medicine and concerns an agent that stimulates tissue regeneration and the recovery of diminished tissue and organ function. A medicinal agent for the treatment and/or prophylaxis of a pathological condition selected from the group including metabolic syndrome, impaired glucose tolerance, hepatitis, particularly chronic hepatitis and toxic hepatitis, idiopathic pulmonary fibrosis (IPF), emphysema of the lungs, chronic obstructive pulmonary disease (COPD) and cachexia, particularly as a result of impaired glucose tolerance, pulmonary fibrosis, chronic obstructive pulmonary disease, cancer and other diseases, is proposed in the form of an agent based on Treamide. The latter is a bisamide derivative of dicarboxylic acid of formula (I) or a pharmaceutically acceptable salt thereof. 24-. (canceled)6. The method of claim 5 , wherein the tissue is selected from the group consisting of a pancreatic tissue claim 5 , a liver tissue claim 5 , a lung tissue claim 5 , a muscular tissue claim 5 , a spermatogenic tissue claim 5 , a testicular tissue claim 5 , and a prostate tissue.78and . (canceled)10. The method of claim 9 , wherein the tissue is selected from the group consisting of a pancreatic tissue claim 9 , a liver tissue claim 9 , a lung tissue claim 9 , a muscular tissue claim 9 , a spermatogenic tissue claim 9 , a testicular tissue claim 9 , and a prostate tissue.11. The method of claim 10 , wherein the pathological condition is selected from the group consisting of metabolic syndrome claim 10 , glucose tolerance failure claim 10 , hepatitis claim 10 , idiopathic pulmonary fibrosis claim 10 , pulmonary emphysema claim 10 , chronic obstructive pulmonary disease claim 10 , cachexia claim 10 , hypogonadism claim 10 , prostatitis claim 10 , benign prostatic hyperplasia claim 10 , correlative testicular failure claim 10 , and autoimmune orchitis.12. The method of claim 11 , wherein the prostatitis is chronic prostatitis claim 11 , in ...

Methods to prevent or treat periodontitis or peri-implantitis

Compositions and methods to prevent, inhibit or treat aveolar or periodontal bone loss, enhance bone regeneration, prevent, inhibit or treat peri-implantitis or periodontitis, e.g., periodontitis or peri-implantitis associated with bone loss, or to prevent, inhibit or treat osteoarthritis are provided.

Method for monomerizing matrix metalloproteinase 7 (mmp-7) aggregate

A method for monomerization of MMP-7 aggregates is provided. A method for monomerization of MMP-7 aggregates which comprises treating MMP-7 aggregates with a buffer solution comprising a monovalent cation chloride (sodium chloride, potassium chloride, etc.) at a low concentration or with a buffer solution not comprising a monovalent cation chloride, a process for preparing MMP-7 which involves said method for monomerization, and a (pharmaceutical) composition comprising MMP-7 in the aforementioned buffer solution. In case that a (pharmaceutical) composition comprising MMP-7 at a low concentration is prepared, the aforementioned buffer solution comprising sugar alcohols or sugars is used.

Method of treating tendinopathy using interleukin-17 (il-17)

The present disclosure relates to methods for treating tendinopathy, e.g., rotator cuff tendinopathy, using IL-17 antagonists, e.g., secukinumab. Also disclosed herein are uses of IL-17 antagonists, e.g., IL-17 antibodies, such as secukinumab, for treating tendinopathy patients, as well as medicaments, dosing regimens, pharmaceutical formulations, dosage forms, and kits for use in the disclosed uses and methods.

Improved Compound for Treatment of Heart Failure

The present invention refers to an oligonucleotide which is an effective inhibitor of microRNA miR-132 and its use in medicine, particularly in the prevention or treatment of cardiac and/or fibrotic disorders. 2. The oligonucleotide of claim 1 , wherein +G and +T are locked nucleotide (LNA) building blocks having a 2′-O—CH2-4′ bridge.3. The oligonucleotide of having a length of 16 building blocks.4. The oligonucleotide of comprising at least one modified internucleosidic linkage claim 1 , including at least one phosphorothioate or phosphorodiamidate internucleosidic linkage.5. The oligonucleotide of claim 1 , wherein all internucleosidic linkages are phosphorothioate linkages.7. The oligonucleotide of conjugated to a heterologous moiety.8. A pharmaceutical composition comprising an oligonucleotide of and a pharmaceutically acceptable carrier.9. The oligonucleotide of claim 1 , in particular for use in human medicine.10. The oligonucleotide of for use in the prevention or treatment of a disorder associated with claim 1 , accompanied by and/or caused by pathological expression of miR-132.11. The oligonucleotide of for use in the prevention or treatment of cardiac disorders claim 1 , or cardiac hypertrophy-associated disorders.12. The oligonucleotide of for use in the prevention or treatment of contractile dysfunction claim 1 , cardiac decompensation or heart failure.13. The oligonucleotide of for use in the prevention of treatment of cardiac disorders wherein the compound is administered to patients selected from:(i) patients having an increased risk for developing heart failure,(ii) patients suffering from (congestive) heart failure, including patients having an increased risk of heart failure progression;(iii) post-myocardial infarction patients, and/or(iv) patients with congenital heart diseases associated to cardiac hypertrophy, pulmonal vein stenosis, atrial or ventricular septum defects.14. The oligonucleotide of for use in the treatment or prevention of cardiac ...

Messenger RNA Therapy for Treatment of Articular Disease

The present invention provides, among other things, a method of intra-articular delivery of messenger RNA (mRNA), comprising administering into a joint of a subject in need of delivery a composition comprising an mRNA encoding a protein, such that the administering of the composition results in expression of the protein encoded by the mRNA in the joint.

Compositions for the mobilization, homing, expansion and differentiation of stem cells and methods of using the same

The invention provides compositions that increase the mobilization, homing, expansion, and/or differentiation of stem cells and methods of using the same for the treatment of mammals.

Compositions for treatment of osteochondral disorders

The application provides biocompatible carriers comprising bone forming and/or cartilage forming cells and methods for making them. The application further provides pharmaceutical compositions comprising said ATMPs and method of treatments using said ATMPs. The application further relates to said ATMPS for use in the treatment of bone disorders, cartilage disorders and joint disorders. The current invention further relates to method of treatments of bone disorders, cartilage disorders and joint disorders.

Combination of unsaponifiable lipids combined with polyphenols and/or catechins for the protection, treatment and repair of cartilage in joints of humans and animals

The present invention relates to a composition for the protection, treatment and repair of cartilage in humans and animal joints. The composition contains a combination of unsaponifiable lipids together with one or more of polyphenols and/or catechins. The composition or kit may contain avocado:soybean unsaponifiables (ASU) and green tea.

Method for preparing zonal layered chondrocyte sheets and treating method thereof

A method for preparing zonal layered chondrocyte sheets, comprising the steps: (a) providing a cartilage sample from a subject; (b) isolating chondrocytes from the cartilage sample and then isolating superficial zone chondrocytes, middle zone chondrocytes and deep zone chondrocytes from the chondrocytes; (c) culturing the deep zone chondrocytes until reaching 100% cell confluence to form a deep zone chondrocyte sheet; (d) seeding the middle zone chondrocytes on the top of the cultured deep zone chondrocyte sheet from the step (c) and culturing the middle zone chondrocytes until reaching 100% cell confluence to form a middle zone chondrocyte sheet; and (e) seeding the superficial zone chondrocytes on the top of the cultured middle zone chondrocyte sheet from the step (d) and culturing the superficial zone chondrocytes until reaching 100% cell confluence to form a superficial zone chondrocyte sheet to obtain the zonal layered chondrocyte sheets.

ALK4:ACTRIIB HETEROMULTIMERS AND USES THEREOF

In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of an ALK4 receptor and an extracellular domain of ActRIIB. In certain aspects, such soluble ALK4:ActRIIB complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, and/or cancerous cells. In certain aspects, such ALK4:ActRIIB complexes are can be used to improve muscle formation, bone formation, metabolic parameters, and disorders associated with these tissues, cellular networks, kidney, and endocrine systems. 1. A recombinant ALK4:ActRIIB heteromultimer comprising at least one ALK4-Fc fusion protein and at least one ActRIIB-Fc fusion protein , wherein the ALK4-Fc fusion protein comprises one or more amino acid modifications that alter the isoelectric point (pI) of the ALK4-Fc fusion protein and/or wherein the ActRIIB-Fc fusion protein comprises one or more amino acid modifications that alter the pI of the ActRIIB-Fc fusion protein.297-. (canceled)98. A recombinant ALK4:ActRIIB heteromultimer comprising at least one ALK4-Fc fusion protein and at least one ActRIIB-Fc fusion protein , wherein:a) the ALK4-Fc fusion protein comprises an IgG1 Fc domain comprising a cysteine at the position corresponding to S132 of SEQ ID NO: 31 (S132C), a tryptophan at the position corresponding to T144 of SEQ ID NO: 31 (T144W), and an acidic amino acid at the position corresponding to H213 of SEQ ID NO: 31; andb) the ActRIIB-Fc fusion protein comprises an IgG1 Fc domain comprising a cysteine at the position corresponding to Y127 of SEQ ID NO: 31 (Y127C), a serine at the position corresponding to T144 of SEQ ID NO: 31 (T144S), an alanine at the position corresponding to L146 of SEQ ID NO: 31 (L146A), and a valine at the position corresponding to Y185 of SEQ ID NO: 31 (Y185V).99. (canceled)100. A recombinant ALK4:ActRIIB heteromultimer comprising at least one ALK4-Fc ...

COMPOSITIONS DERIVED FROM HUMAN AMNION CELLS & RELATED METHODS

A method for making an acellular human amnion-derived composition configured for therapeutic use is disclosed and generally includes the steps: obtaining amniotic membrane tissue; testing the amniotic membrane tissue for pathogens; washing the amniotic membrane tissue; manually removing blood-containing chorion tissue from the amniotic membrane tissue decellularizing the amniotic membrane tissue with xeno-free enzymes; collecting amniotic cells from the decellularized amniotic membrane tissue; seeding the amniotic cells for culture into xeno-free media formulated for mesenchymal stem cells; growing the amniotic cells to a specified confluency; collecting conditioned media; and freezing the collected conditioned media; wherein the method further includes irradiating the conditioned media. 1. An acellular human amnion-derived composition , comprising:one or more tissue-remodeling biomolecules selected from the group consisting of: cystatin B (CSTB); cystatin C (CST3); plasminogen activator inhibitor-1 (PAI-1); matrix metallopeptidase 1 (MMP1); nidogen-1 (NID1); cathepsin L (CTSL); clusterin (CLU); extracellular matrix metalloproteinase inducer (EMMPRIN); TIMP metallopeptidase inhibitor 1 (TIMP1); TIMP metallopeptidase inhibitor 2 (TIMP2); decorin (DCN); tumor necrosis factor superfamily member 11A (TNFRS11A); transforming growth factor beta-induced protein ig-h3 (BIGH3); or a combination thereof,one or more proliferation biomolecules selected from the group consisting of: dipeptidyl peptidase 4 (DPP4); macrophage-colony stimulating factor (MCSF); or a combination thereof,one or more angiogenic biomolecules selected from the group consisting of: pentraxin 3 (PTX3); angiogenin (ANG); fms related tyrosine kinase 1 (FLT1); thrombospondin 1 (THBS1); transforming growth factor beta induced (TGFBI); angiopoietin 1 (ANG1); or a combination thereof,one or more migration biomolecules selected from the group consisting of: syndecan 4 (SDC4); dickkopf WNT signaling pathway ...

Compositions and methods for wound healing and tissue repair

Provided are peptides that can inhibit collagen synthesis, processing and/or secretion from scar forming cells or fibroblasts. Also provided are methods for using the peptides to produce an anti-fibrotic, anti-scarring, anti-inflammatory, and/or pro-regenerative effect, e.g., on an injured or diseased tissue.