CN102008428A - 用于眼周或结膜下施用的眼长效制剂 - Google Patents
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Abstract
本发明涉及包含活性剂的眼长效制剂,例如用于眼周或结膜下施用,其中所述活性剂例如包埋在可药用的生物相容聚合物或脂类胶囊剂中。
Description
本申请是申请日为2002年9月13日、发明名称为“用于眼周或结膜下施用的眼长效制剂”的中国专利申请02815574.2的分案申请。
本发明涉及治疗眼病的眼长效制剂,尤其涉及视网膜和脉络膜疾病的治疗。
眼病难以治疗,因为将活性剂导入眼并维持其治疗有效浓度是困难的。
口服施用活性剂或肠胃外施用活性剂至除眼外的部位,活性剂可在全身分布。为达到有效的眼内浓度,全身施用需要施与往往是不可接受的高水平活性剂。
将包含活性剂的组合物注射入眼可能是无效的,由于活性剂可被冲洗掉,或从眼中进入全身循环而消耗掉,导致需要重复施用,例如如US 5,632,984所述每天注射3次,注射3到42天。
通过注射或外科方法如激光切除、光致凝固法、冷冻疗法、热凝固法等将缓释组合物即植入物导入眼,例如如US 4,853,224所述导入眼前节或眼后节,例如如US 5,164,188所述导入眼的脉络膜周隙或睫状体平坦部,或例如如US 5,824,072所述导入眼的非玻璃体部位,包括脉络膜周隙、无血管区或手术导入的无血管区,对患者是极疼的并使患者紧张。当治疗结束或不再有效时,植入物可能不得不取出。
本申请人发现可眼周或结膜下施用包含活性剂的眼长效制剂,其中所述眼周施用例如眼球后或眼球囊下施用。
因此一方面,本发明提供了包含活性剂的眼长效制剂,例如用于眼周施用,诸如眼球后或眼球囊下施用,或结膜下施用。
发现包含例如包埋在生物相容的可药用聚合物如在包囊聚合物基质中、或包埋在脂类胶囊剂中的活性剂的眼长效制剂诸如微粒或纳粒(下文中称微粒)制剂尤其合适。眼长效制剂也可包含基本上为纯活性剂的微粒,例如由活性剂组成的微粒。
这些微粒有高的接触面。
一方面,本发明提供了包含基本上为纯活性剂的微粒的眼长效制剂。
基本上为纯活性剂的微粒,例如由活性剂组成的微粒,可为无定形或结晶形式,例如具有的颗粒大小为1至200微米。
另一方面,本发明提供了包含例如包埋在生物相容的可药用聚合物或脂类胶囊剂中的活性剂的眼长效制剂如微粒。
本发明的长效制剂,例如特别是微粒制剂,适合长时间例如几个星期到6个月,释放所有的或基本上所有的活性物质。如果存在基质,例如聚合物或脂类基质,适合在释放所有的或基本上所有的活性剂后1至6个月内,充分降解以便从施用部位运输走。
聚合物微粒的聚合物基质可为合成的或天然的聚合物。聚合物可为可生物降解的或不可生物降解的或为可生物降解和不可生物降解聚合物的组合,优选地为可生物降解的。
合适的聚合物包括
(a)线性聚酯或自多羟基部分例如葡萄糖发出直链的支化聚酯,
(b)聚酯诸如D-、L-或外消旋的聚乳酸、聚乙醇酸(polyglycolic acid)、聚羟基丁酸、聚己酸内酯、聚亚烷基草酸酯、克雷伯氏(三羧酸)循环例如柠檬酸循环中酸类的聚亚烷基二醇酯等以及它们的组合,
(c)有机醚、酐、酰胺和原酸酯的聚合物
(d)有机酯、醚、酐、酰胺和原酸酯它们自身的共聚物或与其它单体的组合,
(e)聚乙烯醇。
聚合物可为交联或非交联的,通常不超过5%,一般少于1%。
降解聚合物所需的速率和活性剂所需的释放曲线根据使用单体的类型、是否为同聚物或共聚物、或是否为聚合物的混合物而不同。
本发明优选的聚合物为线性聚酯和支链聚酯。线性聚酯可从α-羟基羧酸,例如乳酸和乙醇酸,通过缩合内酯二聚体而制备,参见例如US 3,773,919。
优选使用的线性聚丙交酯-共-乙交酯(PLG)适宜地具有在25,000和100,000之间的分子量且多分散性Mw/Mn例如在1.2和2之间。
根据本发明优选使用的支化聚酯可用多羟基化合物例如多元醇类如葡萄糖或甘露醇作为起始物而制备。多羟基化合物的这些酯是公知的,并在GB 2,145,422B中进行了描述。多羟基化合物包含至少3个羟基,并具有的分子量达20,000,多羟基化合物的羟基中至少有1个,优选地至少2个,例如平均3个以酯基形式存在,其包含聚-丙交酯或共-聚-丙交酯链。一般用0.2%葡萄糖起始聚合反应。支化聚酯(Glu-PLG)具有带线性聚丙交酯链分支的中心葡萄糖部分,例如它们有星形结构。根据本发明优选使用的线性和星形聚合化合物中优选的聚酯链为α-羧酸部分、乳酸和乙醇酸的共聚物、或为内酯二聚体的共聚物。丙交酯∶乙交酯的摩尔比从约75∶25至25∶75,例如60∶40至40∶60,其中从55∶45至45∶55,例如55∶45至50∶50是最优选的。
具有带线性聚丙交酯链分支的中心葡萄糖部分的支化聚酯(Glu-PLG)可通过将多羟基化合物与丙交酯且也优选地与乙交酯在有催化剂存在时于高温下反应而制备,其中所述催化剂使开环聚合反应可行。
具有带线性聚丙交酯链分支的中心葡萄糖部分的支化聚酯(Glu-PLG)优选地具有的平均分子量Mn介于约10,000至200,000之间,优选25,000至100,000,尤其35,000至60,000且多分散性例如从1.7至3.0,例如2.0至2.5。Mn 35,000和Mn 60,000的星形聚合物在氯仿中的特性粘数分别为0.36和0.51dl/g。Mn 52,000的星形聚合物在氯仿中的粘度为0.475dl/g。
脂类微粒的合适脂类胶囊剂包括磷脂酰化合物诸如磷脂酰胆碱(PC)、磷脂酰丝氨酸(PS)和磷脂酰乙醇胺(PE)、鞘脂类、脑苷脂类、神经节苷脂类、类固醇类例如胆固醇等。
在本发明中,认为术语微球、微胶囊和微粒可互换,表示聚合物将活性剂封入胶内,优选活性剂遍及分布在作为活性剂基质的聚合物中。在这种情况下优选使用的术语为微球或更通常用微粒。
微粒,例如微球或微胶囊,其直径可从几亚微米至几毫米,例如从约0.01微米至约2mm,例如从约0.1微米至约500微米。对于药用微粒,其直径争取至多约250微米,例如10至200微米,优选10至130微米,更优选10至90微米,甚至更优选10至60微米,例如为了利于通过注射针头。
一般地,活性剂占聚合物微粒重量的约1至80,更通常为10至75%,占脂类微粒重量的1至20%。
另一方面,本发明提供了液体制剂,其包含可药用聚合物和溶解或分散的活性剂。注射后,聚合物在注射部位形成储库,例如通过凝胶化或沉淀形成。
本发明的长效制剂尤其是微粒制剂适于掺入多种水溶性或疏水性活性剂。
特定目的的活性剂包括
i)抗青光眼药物,诸如β-阻断剂,例如马来酸噻吗心安、倍他洛尔、卡替洛尔和美替洛尔;肾上腺素和前体药物;诸如地匹福林;碳酸酐酶抑制剂;诸如杜塞酰胺(dorzolamide)、布吲佐胺(brinzolamide)、乙酰唑胺、二氯磺胺和甲醋唑胺;多巴胺能、前列腺素、docosanoids、α2激动剂;血管紧张肽II拮抗剂;α1拮抗剂;大麻酯(cannabinoid);内皮素拮抗剂;
ii)缩瞳药,例如匹鲁卡因、氯化乙酰胆碱、异氟磷、地美溴铵、碘乙膦硫胆碱、碘化二乙氧磷酰硫胆碱、卡巴胆碱和毒扁豆碱;
iii)治疗黄斑变性的药物,诸如干扰素,尤其是α-干扰素;转化生长因子(TGF),例如TGF-β;
iv)抗白内障和抗增生型糖尿病性视网膜病变(PDR)的药物,诸如醛糖还原酶抑制剂:例如特力他,或血管紧张肽-转化酶抑制剂,例如赖诺普利、依那普利;
v)治疗年龄相关的渗出性黄斑变性(AMD)的药物,例如,治疗眼新生血管性疾病的药物,诸如星形孢菌素、2,3-二氮杂萘衍生物;
vi)抗凝剂,诸如组织纤维蛋白溶酶原激活剂、尿激酶和链激酶;
vii)治疗眼炎性疾病的药物,诸如皮质类固醇;例如氢化泼尼松、氟羟氢化泼尼松、地塞米松、氟轻松、可的松、氢化泼尼松、氟米龙等,非类固醇抗炎药物,诸如氨丁三醇、双氯芬酸钠、消炎痛、苯氟布洛芬钠和舒洛芬;
viii)抗生素,诸如头孢噻啶(先锋霉素II)、氯霉素、氯林可霉素、丁胺卡那霉素、庆大霉素、托普霉素、甲氧苯青霉素、林可霉素、苯唑青霉素、青霉素、两性霉素B、多粘菌素B、头孢菌素类、氨苄西林、杆菌肽、羧苄青霉素、头孢噻酚、粘菌素、红霉素、链霉素、新霉素、磺胺醋酰、 万古霉素、硝酸银、磺胺异唑二乙醇胺盐、喹诺酮和四环素;
ix)抗真菌或抗病毒药,诸如咪康唑、酮康唑、疱疹净、三氟哩啶、阿糖腺苷(腺嘌呤阿糖苷)、阿昔洛韦(无环鸟苷)、更昔洛韦、膦甲酸钠、西多福韦、伐昔洛韦、泛昔洛韦、三磺嘧啶-2、制霉菌素、氟胞嘧啶、游霉素、芳族二脒如二羟基二脒替(dihydroxystilbamidine)和哌嗪衍生物,例如乙胺嗪;
x)睫状肌麻痹剂和散瞳剂,诸如阿托品、环喷托酯(cyclopentolate)、东莨菪碱、后马托品、托吡卡胺(tropicamide)和苯肾上腺素;
xi)治疗视神经变性性疾病的药物,诸如异丙基乌诺前列酮、谷氨酸受体拮抗剂如美金刚胺、天冬氨酸特异性半胱氨酸蛋白酶抑制剂、钙拮抗剂、钠通道封阻剂、NOS-2抑制剂或神经营养因子,例如胶质细胞源性神经营养因子(GDNF)或睫状神经营养因子(CNTF);
xii)肽药物诸如降钙素、赖氨酸加压素或促生长素抑制素或它们的类似物,
xiii)抗-VEGF药物;
xiv)磷酸二酯酶抑制剂;
xv)反义药物诸如福米韦生钠(fomivirsen sodium);
xvi)免疫抑制剂;诸如硫唑嘌呤、环孢菌素A、氨甲喋呤、秋水仙碱;
xvii)治疗眼血管发生的药物诸如血管静态类固醇(angiostaticsteroids)、PKC抑制剂、VEGF拮抗剂、COX2抑制剂、ACE抑制剂或血管紧张肽II拮抗剂;
xviii)自由基清除剂,例如α生育酚、类胡萝卜素、含巯基化合物。
优选地,活性剂是用于治疗眼眶区和眼附属器的药物,以及用于治疗视网膜和脉络膜疾病的药物,其中所述疾病包括但不限于年龄相关的黄斑变性、糖尿病性视网膜病变、青光眼、炎症例如眼内炎及细菌、真菌或病毒感染。甚至更优选地,活性剂为式(I)的星形孢菌素、式(II)的2,3-二氮杂萘或它们的可眼科用盐。甚至更优选地为式(I)中R为苯甲酰基的星形孢菌素(下文称化合物A),和式(II)中Z为4-pyrididyl、X为亚氨基、n为0且Y为4-氯苯基的2,3-二氮杂萘(下文称化合物B)。
其中 其中
R为烃基Ro或酰基Ac n为0至2,
R为H或低碳烷基;
X为亚氨基、氧杂或硫杂;
Y为芳基;以及
Z为未取代的或取代的吡啶基,或为该化
合物的N-氧化物,其中一个或多个N原子
带有氧原子。
另一方面,本发明提供了这样的长效制剂和微粒,其包含例如包埋在生物相容的可药用聚合物中的式(I)的星形孢菌素、式(II)的2,3-二氮杂萘或它们的可眼科用盐,例如用于眼周如眼球后或眼球囊下施用或用于结膜下施用。
本发明的微粒可通过任何常规技术制备,例如溶剂蒸发、有机相分离、喷雾干燥、低温溶剂萃取或乳化法如三重乳化法。用相分离或乳化技术时,聚合物与药物共同沉淀,随后为所得产物的硬化。
另一方面,本发明提供了用于产生微粒的方法,其包括下列步骤:
a)用有机溶剂例如二氯甲烷溶解聚合物或脂类胶囊剂和活性剂,
b)将a)的溶液与聚乙烯醇水溶液(例如0.5%)混合,例如用静态混合器混合,
c)收集产生的微粒,例如通过沉淀、过滤或用旋风分离器收集,
d)任选地例如在缓冲液如pH为3.0至8.0的缓冲液中或蒸馏水中洗涤微粒,以及
e)在真空下干燥,例如温度为20℃至40℃。
本发明也涉及通过该方法制备的微粒。
本发明的微粒和长效制剂用于治疗已知的眼适应症,所述微粒和长效制剂中掺入了特定的活性剂。本发明所述制剂的效用可从标准动物试验和临床试验观察到。
在更进一步的方面,本发明提供了治疗眼病的方法,其包括:
i)提供了包含例如包埋在生物相容的可药用聚合物或脂类胶囊剂中的活性剂的长效制剂,例如微粒制剂,和
ii)眼周如眼球后或眼球囊下施用或结膜下施用所述长效制剂,例如微粒制剂。
本方法允许所述活性剂从所述长效制剂例如微粒制剂扩散到所述眼病部位,例如脉络膜、视神经、视网膜或玻璃体。优选地,活性剂对所述眼病在所述眼病部位长时间例如几周至6个月维持有效剂量。
长效制剂,例如微粒制剂,可通过多种方式包括注射、套针等眼周如眼球后或眼球囊下施用,或结膜下施用。优选地,活性剂颗粒或微粒悬浮在合适的液体载体中。
待施用的包埋在聚合物中的活性剂的精确数量,即长效制剂如微粒制剂的精确数量,取决于诸多因素,例如所治疗的疾病、治疗所需持续时间、活性剂释放速率和聚合物基质的降解性。需要的活性剂的量可在公知的体外或体内技术的基础上决定。当聚合物基质已充分降解时,可反复施用本发明的长效制剂。
大量活性剂,例如达300mg的活性剂,如以悬液形式存在时,可在单次施用中施与,例如通过一次注射。施用剂量的次数依病症的严重性而不同。对严重病例可每月给一次药。当疾病状况改善时,给药次数减少。此时,给药次数可减少至每4或5个月一次。
可在长效制剂灭菌前或灭菌后进行装填。本发明的制剂和初步包装的灭菌可通过例如γ射线照射而进行,例如能量为25kGy,同时不会降解活性剂和/或微粒。
以下仅以实施例的方式描述本发明的长效制剂。
实施例1至3:微粒的制备
化合物A和聚合物Glu-PLG溶于二氯甲烷。用静态混合器将得到的溶液与1.5%的聚乙烯醇水溶液一起泵入聚乙烯醇水溶液(0.5%)的搅拌液中。得到的悬液搅拌下在60分钟内加热至42-48℃并再维持在此温度30分钟,然后在50分钟内,将混合物冷却至约22℃。悬液沉淀约10分钟。聚乙烯水溶液在真空下还原。微粒用水洗涤约5分钟。沉淀10分钟后,去除溶液,并将微粒用Ultipor滤器过滤,用水洗涤,真空干燥。
Claims (10)
1.用于眼周或结膜下施用的眼科制剂,其中所述眼科制剂包含包埋于用于所述施用的生物相容可药用聚合物中的活性剂,且其中所述聚合物为多羟基化合物的聚丙交酯-共-乙交酯,且其中所述多羟基化合物含有至少3个羟基且分子量不超过20000。
2.权利要求1的眼科制剂,其中聚合物为所述多羟基化合物的40/60至60/40的聚丙交酯-共-乙交酯。
3.权利要求1的眼科制剂,其中所述多羟基化合物是葡萄糖或甘露糖醇。
4.权利要求1的眼科制剂,其中所述制剂包含纯活性剂的微粒。
5.权利要求4的眼科制剂,其中微粒的外表面不含活性剂。
6.权利要求1的眼科制剂,其中活性剂是溶解或分散的。
7.权利要求1的眼科制剂,其中所述制剂通过眼球后、眼球囊下或结膜下施用。
8.权利要求1的眼科制剂,其中所述制剂是液体且在眼注射部位形成凝胶或沉淀。
9.权利要求1的眼科制剂,其中活性剂为式(I)的星形孢菌素、式(II)的2,3-二氮杂萘或它们的可眼科用盐,其中式(I)和式(II)如下所定义:
其中R为苯甲酰基, 其中:
n为0至2,
R为H或低级烷基;
X为亚氨基、氧杂或硫杂;
Y为芳基;以及
Z为未取代的或取代的吡啶基,或为
该化合物的N-氧化物,其中一个或多
个N原子带有氧原子。
10.权利要求1至9任一项的眼科制剂在制备用于眼周或结膜下施用的长效药剂中的用途。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018036523A1 (zh) * | 2016-08-24 | 2018-03-01 | 上海毕傲图生物科技有限公司 | 唑类化合物眼用制剂 |
Families Citing this family (83)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8202979B2 (en) | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
US20060177416A1 (en) | 2003-10-14 | 2006-08-10 | Medivas, Llc | Polymer particle delivery compositions and methods of use |
US9994853B2 (en) | 2001-05-18 | 2018-06-12 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
US20030119812A1 (en) * | 2001-11-08 | 2003-06-26 | Brazzell Romulus Kimbro | Method for decreasing capillary permeability in the retina |
US9657294B2 (en) | 2002-02-20 | 2017-05-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US9181551B2 (en) | 2002-02-20 | 2015-11-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
ES2428354T3 (es) | 2002-09-18 | 2013-11-07 | Trustees Of The University Of Pennsylvania | Rapamicina para usar en la inhibición o prevención de la neovascularización coroidea |
US9216106B2 (en) | 2003-04-09 | 2015-12-22 | Directcontact Llc | Device and method for the delivery of drugs for the treatment of posterior segment disease |
US20050009910A1 (en) * | 2003-07-10 | 2005-01-13 | Allergan, Inc. | Delivery of an active drug to the posterior part of the eye via subconjunctival or periocular delivery of a prodrug |
US20060286173A1 (en) * | 2003-08-20 | 2006-12-21 | Kazuhito Yamada | Drug delivery system for sub-tenon s capsule adminstration of fine grains |
BRPI0506983A (pt) * | 2004-01-20 | 2007-07-03 | Allergan Inc | composições para terapia localizada dos olhos, compreendendo preferencialmente acetonida de triancinolona e ácido hialurÈnico |
US20050244458A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular neuropathies |
US8673341B2 (en) * | 2004-04-30 | 2014-03-18 | Allergan, Inc. | Intraocular pressure reduction with intracameral bimatoprost implants |
US7993634B2 (en) | 2004-04-30 | 2011-08-09 | Allergan, Inc. | Oil-in-oil emulsified polymeric implants containing a hypotensive lipid and related methods |
US7771742B2 (en) | 2004-04-30 | 2010-08-10 | Allergan, Inc. | Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods |
US8722097B2 (en) | 2004-04-30 | 2014-05-13 | Allergan, Inc. | Oil-in-water method for making polymeric implants containing a hypotensive lipid |
US7799336B2 (en) | 2004-04-30 | 2010-09-21 | Allergan, Inc. | Hypotensive lipid-containing biodegradable intraocular implants and related methods |
AU2011213904B2 (en) * | 2004-04-30 | 2014-06-05 | Allergan, Inc. | Sustained release intraocular implants comprising a beta adrenergic receptor antagonist and methods for treating ocular neuropathies |
US20060182781A1 (en) * | 2004-04-30 | 2006-08-17 | Allergan, Inc. | Methods for treating ocular conditions with cyclic lipid contraining microparticles |
US9498457B2 (en) | 2004-04-30 | 2016-11-22 | Allergan, Inc. | Hypotensive prostamide-containing biodegradable intraocular implants and related implants |
US10508277B2 (en) | 2004-05-24 | 2019-12-17 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
WO2006086750A1 (en) | 2005-02-09 | 2006-08-17 | Macusight, Inc. | Liquid formulations for treatment of diseases or conditions |
US8663639B2 (en) | 2005-02-09 | 2014-03-04 | Santen Pharmaceutical Co., Ltd. | Formulations for treating ocular diseases and conditions |
JP2006257080A (ja) * | 2005-02-18 | 2006-09-28 | Santen Pharmaceut Co Ltd | ステロイド化合物の副作用軽減または回避方法 |
US8440217B1 (en) * | 2005-06-15 | 2013-05-14 | Mawaheb M. EL-Naggar | Method and system with contact lens product for treating and preventing adverse eye conditions |
US9877921B2 (en) | 2005-09-09 | 2018-01-30 | Nova Southeastern University | Epinephrine nanoparticles, methods of fabrication thereof, and methods for use thereof for treatment of conditions responsive to epinephrine |
US20160045457A1 (en) | 2005-09-09 | 2016-02-18 | Ousama Rachid | Epinephrine fine particles and methods for use thereof for treatment of conditions responsive to epinephrine |
WO2013059629A1 (en) | 2011-10-21 | 2013-04-25 | Nova Southeastern University | Epinephrine nanoparticles, methods of fabrication thereof, and methods for use thereof for treatment of conditions responsive to epinephrine |
WO2007038246A2 (en) | 2005-09-22 | 2007-04-05 | Medivas, Llc | Solid polymer delivery compositions and methods for use thereof |
JP5192384B2 (ja) | 2005-09-22 | 2013-05-08 | メディバス エルエルシー | ビス−(α−アミノ)−ジオール−ジエステル含有ポリ(エステルアミド)およびポリ(エステルウレタン)組成物および使用の方法 |
JP5528708B2 (ja) | 2006-02-09 | 2014-06-25 | 参天製薬株式会社 | 安定な製剤ならびにそれらを調製および使用する方法 |
US8222271B2 (en) | 2006-03-23 | 2012-07-17 | Santen Pharmaceutical Co., Ltd. | Formulations and methods for vascular permeability-related diseases or conditions |
JP5445130B2 (ja) * | 2006-05-02 | 2014-03-19 | メディバス エルエルシー | 眼の外部または内部への眼科用薬剤の送達法 |
US8969415B2 (en) | 2006-12-01 | 2015-03-03 | Allergan, Inc. | Intraocular drug delivery systems |
WO2008157614A2 (en) * | 2007-06-21 | 2008-12-24 | Yale University | Sustained intraocular delivery of drugs from biodegradable polymeric microparticles |
US20110206773A1 (en) * | 2008-05-20 | 2011-08-25 | Yale University | Sustained delivery of drugs from biodegradable polymeric microparticles |
AU2011207281B2 (en) | 2010-01-22 | 2016-10-20 | Allergan, Inc. | Intracameral sustained release therapeutic agent implants |
WO2011106702A2 (en) | 2010-02-25 | 2011-09-01 | The Johns Hopkins University | Sustained delivery of therapeutic agents to an eye compartment |
US20120322884A1 (en) | 2010-03-01 | 2012-12-20 | University Of Manitoba | Epinephrine nanoparticles, methods of fabrication thereof, and methods for use thereof for treatment of conditions responsive to epinephrine |
US10307372B2 (en) | 2010-09-10 | 2019-06-04 | The Johns Hopkins University | Rapid diffusion of large polymeric nanoparticles in the mammalian brain |
EP3327125B1 (en) | 2010-10-29 | 2020-08-05 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
US9327037B2 (en) | 2011-02-08 | 2016-05-03 | The Johns Hopkins University | Mucus penetrating gene carriers |
RU2456979C1 (ru) * | 2011-04-11 | 2012-07-27 | Общество с ограниченной ответственностью "ЭкоБиоФармДубна" | Индометацин на основе фосфолипидных наночастиц для применения в офтальмологии |
CN103748139B (zh) | 2011-06-23 | 2016-08-17 | 帝斯曼知识产权资产管理有限公司 | 用于递送生物活性剂的包含生物可降解的聚酯酰胺共聚物的微米颗粒或纳米颗粒 |
US9873765B2 (en) | 2011-06-23 | 2018-01-23 | Dsm Ip Assets, B.V. | Biodegradable polyesteramide copolymers for drug delivery |
AU2013209452B2 (en) | 2012-01-19 | 2015-11-05 | The Johns Hopkins University | Nanoparticle formulations with enhanced mucosal penetration |
KR20230104761A (ko) * | 2012-01-23 | 2023-07-10 | 알러간, 인코포레이티드 | 고화 디포-형성 주사가능 약물 제형에 현탁된 서방형생분해성 또는 생체흡수성 미소구체 또는 미립자 |
JP6138904B2 (ja) | 2012-03-16 | 2017-05-31 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 活性剤の送達のための非線状マルチブロックコポリマー薬物コンジュゲート |
CA2867381C (en) | 2012-03-16 | 2016-09-20 | The Johns Hopkins University | Controlled release formulations for the delivery of hif-1 inhibitors |
CA2871778C (en) | 2012-05-03 | 2022-09-13 | Kala Pharmaceuticals, Inc. | Pharmaceutical nanoparticles showing improved mucosal transport |
US11596599B2 (en) | 2012-05-03 | 2023-03-07 | The Johns Hopkins University | Compositions and methods for ophthalmic and/or other applications |
US9827191B2 (en) | 2012-05-03 | 2017-11-28 | The Johns Hopkins University | Compositions and methods for ophthalmic and/or other applications |
EP2844227B1 (en) | 2012-05-03 | 2020-11-18 | Kala Pharmaceuticals, Inc. | Pharmaceutical nanoparticles showing improved mucosal transport |
WO2013166498A1 (en) | 2012-05-04 | 2013-11-07 | The Johns Hopkins University | Lipid-based drug carriers for rapid penetration through mucus linings |
EP2861224A4 (en) | 2012-06-15 | 2015-11-18 | Univ Nova Southeastern | EPINHEPHRINE NANOPARTICLES, PROCESS FOR THEIR MANUFACTURE AND METHODS OF USE THEREOF FOR THE TREATMENT OF EPINEPHRINE-RESPONSIBLE DISORDERS |
WO2014124006A1 (en) | 2013-02-05 | 2014-08-14 | The Johns Hopkins University | Nanoparticles for magnetic resonance imaging tracking and methods of making and using thereof |
HUE055773T2 (hu) | 2013-03-22 | 2021-12-28 | Univ Nova Southeastern | Epinefrin finom részecskék és módszerek azok alkalmazására az epinefrinre reagáló állapotok kezelésében |
KR20150139899A (ko) | 2013-04-01 | 2015-12-14 | 알러간, 인코포레이티드 | 지속적인 안구내 방출을 위한 마이크로스피어 약물 전달 시스템 |
BR112016009575B1 (pt) | 2013-10-31 | 2022-12-13 | Allergan, Inc | Implante intraocular biodegradável, uso do mesmo, aparelho para liberar um implante intraocular biodegradável e método para preparar um implante intraocular biodegradável |
WO2015127389A1 (en) | 2014-02-23 | 2015-08-27 | The Johns Hopkins University | Hypotonic enema formulations and methods of use |
MX2017000855A (es) | 2014-07-18 | 2017-05-01 | Allergan Inc | Composiciones en suspension de ciclosporina a para inyecciones subconjuntivales y perioculares. |
RU2616258C2 (ru) * | 2014-11-10 | 2017-04-13 | федеральное государственное автономное образовательное учреждение высшего образования "Московский физико-технический институт (государственный университет)" | Способ получения полимерных наночастиц низкосиалированного эритропоэтина с высокой степенью сорбции для лечения неврологических заболеваний |
WO2016100392A1 (en) | 2014-12-15 | 2016-06-23 | The Johns Hopkins University | Sunitinib formulations and methods for use thereof in treatment of ocular disorders |
EP3233067B1 (en) | 2014-12-18 | 2019-11-06 | DSM IP Assets B.V. | Drug delivery system for delivery of acid sensitive drugs |
JP6846351B2 (ja) | 2015-01-27 | 2021-03-24 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 粘膜表面における活性薬剤の増強された輸送のための低張ヒドロゲル製剤 |
EP3340982B1 (en) | 2015-08-26 | 2021-12-15 | Achillion Pharmaceuticals, Inc. | Compounds for treatment of immune and inflammatory disorders |
AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
MX2018005932A (es) | 2015-11-12 | 2019-05-20 | Graybug Vision Inc | Microparticulas aglomerantes para terapia medica. |
CN109641874A (zh) | 2016-05-10 | 2019-04-16 | C4医药公司 | 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体 |
WO2017197055A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
WO2017197036A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
US11395853B2 (en) * | 2016-06-23 | 2022-07-26 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Biomimetic drug delivery of an immunomodulatory agent for the treatment of ocular conditions |
CA3029262A1 (en) | 2016-06-27 | 2018-01-04 | Achillion Pharmaceuticals, Inc. | Quinazoline and indole compounds to treat medical disorders |
RU2019102647A (ru) | 2016-07-01 | 2020-08-03 | Г1 Терапьютикс, Инк. | Антипролиферационные средства на основе пиримидина |
BR112019019452A2 (pt) | 2017-03-23 | 2020-04-14 | Graybug Vision Inc | composto, e, uso de um composto |
RU2019139817A (ru) | 2017-05-10 | 2021-06-10 | Грейбуг Вижн, Инк. | Микрочастицы с замедленным высвобождением и их суспензии для лекарственной терапии |
JP2021519337A (ja) | 2018-03-26 | 2021-08-10 | シー4 セラピューティクス, インコーポレイテッド | Ikarosの分解のためのセレブロン結合剤 |
CA3104468A1 (en) * | 2018-06-19 | 2019-12-26 | Cella Therapeutics, Llc | Sustained-release drug delivery systems comprising an intraocular pressure lowering agent, a c-type natriuretic peptide compound, an natriuretic peptide receptor-b compound, a tie-2 agonist, or neurotrophic agent for use for treating glaucoma or ocular hypertension |
US20230022157A1 (en) | 2018-08-20 | 2023-01-26 | Achillion Pharmaceuticals, Inc. | Pharmaceutical compounds for the treatment of complement factor d medical disorders |
EP3866773A4 (en) | 2018-10-16 | 2022-10-26 | Georgia State University Research Foundation, Inc. | CARBON MONOXIDE PRODRUGS FOR THE TREATMENT OF MEDICAL CONDITIONS |
MX2022005063A (es) | 2019-10-30 | 2022-08-04 | Perfuse Therapeutics Inc | Tratamiento de enfermedades oculares con antagonistas de receptor de endotelina. |
CA3168810A1 (en) | 2020-02-06 | 2021-08-12 | Perfuse Therapeutics, Inc. | Compositions for treatment of ocular diseases |
CA3218251A1 (en) | 2021-04-30 | 2022-11-03 | Perfuse Therapeutics, Inc. | Pharmaceutical compositions and intravitreal drug delivery systems for the treatment of ocular diseases |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) * | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
BE788575A (fr) * | 1971-09-09 | 1973-01-02 | Alza Corp | Dispositif oculaire pour l'administration d'un |
US3960150A (en) * | 1971-09-09 | 1976-06-01 | Alza Corporation | Bioerodible ocular device |
US4177256A (en) * | 1973-04-25 | 1979-12-04 | Alza Corporation | Osmotic bursting drug delivery device |
GB1425550A (en) * | 1973-04-25 | 1976-02-18 | Alza Corp | Device for releasing active agent and process for producing the same |
US3914402A (en) * | 1973-06-14 | 1975-10-21 | Alza Corp | Ophthalmic dosage form, for releasing medication over time |
CH656884A5 (de) * | 1983-08-26 | 1986-07-31 | Sandoz Ag | Polyolester, deren herstellung und verwendung. |
DE3722837A1 (de) * | 1987-07-10 | 1989-01-19 | Ruetgerswerke Ag | Ophthalmisches depotpraeparat |
US4853224A (en) * | 1987-12-22 | 1989-08-01 | Visionex | Biodegradable ocular implants |
US4997652A (en) * | 1987-12-22 | 1991-03-05 | Visionex | Biodegradable ocular implants |
US4865846A (en) * | 1988-06-03 | 1989-09-12 | Kaufman Herbert E | Drug delivery system |
PH30995A (en) * | 1989-07-07 | 1997-12-23 | Novartis Inc | Sustained release formulations of water soluble peptides. |
US5538739A (en) * | 1989-07-07 | 1996-07-23 | Sandoz Ltd. | Sustained release formulations of water soluble peptides |
US5164188A (en) * | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
JPH05507683A (ja) * | 1990-04-27 | 1993-11-04 | アラーガン、インコーポレイテッド | ポリマードラッグデリバリーシステム |
WO1995003009A1 (en) * | 1993-07-22 | 1995-02-02 | Oculex Pharmaceuticals, Inc. | Method of treatment of macular degeneration |
US5443505A (en) * | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
US5801146A (en) * | 1996-05-03 | 1998-09-01 | Abbott Laboratories | Compound and method for inhibiting angiogenesis |
ES2158611T3 (es) * | 1996-12-20 | 2001-09-01 | Alza Corp | Composicion en gel inyectable con efecto retard y procedimiento para la preparacion de dicha composicion. |
ATE371453T1 (de) * | 1998-08-13 | 2007-09-15 | Novartis Pharma Gmbh | Verfahren zur behandlung von okularen neovaskularen erkrankungen |
BR9915569A (pt) * | 1998-11-23 | 2001-08-14 | Novartis Ag | Método para o tratamento de doenças neovasculares oculares |
UA75350C2 (en) * | 2000-03-24 | 2006-04-17 | Novartis Ag | Method for photodynamic treatment of undesirable subfoveal choroidal neovascularization using antiangiogenic agent |
AU2001296770A1 (en) * | 2000-10-06 | 2002-04-15 | Durect Corporation | Devices and methods for management of inflammation |
US6673802B2 (en) * | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
US8425929B2 (en) * | 2004-04-30 | 2013-04-23 | Allergan, Inc. | Sustained release intraocular implants and methods for preventing retinal dysfunction |
-
2001
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2002
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- 2002-09-13 KR KR10-2004-7001255A patent/KR20040030869A/ko active Search and Examination
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- 2002-09-13 CN CN2010105534172A patent/CN102008428A/zh active Pending
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- 2010-10-01 JP JP2010224231A patent/JP2011026338A/ja not_active Withdrawn
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2012
- 2012-06-14 US US13/523,537 patent/US20120269894A1/en not_active Abandoned
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2018036523A1 (zh) * | 2016-08-24 | 2018-03-01 | 上海毕傲图生物科技有限公司 | 唑类化合物眼用制剂 |
CN109689049A (zh) * | 2016-08-24 | 2019-04-26 | 上海毕傲图生物科技有限公司 | 唑类化合物眼用制剂 |
CN109689049B (zh) * | 2016-08-24 | 2021-04-27 | 上海毕傲图生物科技有限公司 | 唑类化合物眼用制剂 |
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