CN105748407A - 用于治疗眼后节的组合物及方法 - Google Patents
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Abstract
提供了用以注射至人或动物眼后节的组合物,及使用所述组合物的方法。所述组合物包括治疗有效量的含皮质类固醇成分的颗粒、粘性诱发成分及水性载体成分。组合物在0.1/秒切速下的粘度为至少约10cps或约100cps。一个优选实施方案中,其粘度为约140,000cps至约300,000cps。组合物有利地使颗粒长时间悬浮。
Description
本申请是2004年11月8日提交的申请号为PCT/US2004/037436、发明名称为“用于治疗眼后节的组合物及方法”的国际申请的分案申请,所述国际申请于2006年5月11日进入中国国家阶段,其申请号为200480033259.0。
本发明涉及用于治疗人或动物眼后节的组合物及方法。更具体而言,本发明涉及可有效注射至所述眼后节的包括皮质类固醇成分的组合物,还涉及使用所述组合物以提供所需治疗效果的方法。
现有的惯常用于治疗眼后节病症的疗法之一,是在玻璃体内注射皮质类固醇,例如曲安奈德(TA),所述眼后节病症例如葡萄膜炎、黄斑变性、黄斑水肿等。参见,例如Billson等人的美国专利US5,770,589,所述专利的公开内容在此通过援引的方式完整纳入。
一种常用于以上眼科疗法的药物是40。每毫升(ml)40组合物包含40毫克(mg)TA、氯化钠作为张力调节剂(tonicityagent)、10mg苯甲醇作为防腐剂、以及7.5mg羧甲基纤维素和0.4mg聚山梨醇酯80作为再悬浮助剂。尽管该市售制剂被眼科医生广泛采用,但其仍具有许多重要的局限性。
例如,苯甲醇防腐剂及聚山梨醇酯80表面活性剂的存在易在敏感的眼组织内引起不必要的和/或过度的细胞损害或其他毒性。即使某些临床医生依常规用盐水“清洗”TA沉淀物数次,以降低上述不良物质的浓度,这种清洗也是既不方便又耗时的,最重要的是,这种清洗会增加微生物或内毒素污染的可能,从而导致眼内感染及炎症。
此外,40中的TA还易从组合物残余物中快速分离并沉淀出来。例如,该组合物如果静置1至2小时,会造成TA沉淀物从组合物残余物中大量分离。因此,如果该组合物注射至眼内,就必须将其剧烈摇晃并在摇晃后立即使用,以在眼内提供大体均匀的悬浮液。另外,再悬浮处理还需要使用上述再悬浮助剂,而至少一种所述助剂并不是敏感的眼组织所完全需要的。
需要用以注射至人或动物眼后节的新组合物,以及在人或动物眼后节提供所需治疗效果的方法。
发明内容
现已发现用于治疗人或动物眼后节的新组合物及方法。本发明的组合物非常适于玻璃体内给药于眼后节,既无需任何“清洗步骤”,同时还能在眼内使用时提供降低的眼内损伤,例如视网膜损伤。有利的是,本发明的组合物基本未添加防腐剂成分,例如不含苯甲醇防腐剂。另外有利的是,本发明的组合物亦不需要再悬浮助剂。总而言之,本发明的组合物可简便有效地注射至人或动物眼后节,还可无需再悬浮处理,例如无需摇晃或搅动组合物以获得大体的悬浮均匀性,而长时间维持大体均匀的悬浮状态,例如维持至少约一周或更久。简言之,本发明的组合物和方法,例如相对于现有技术40组合物及使用所述现有组合物的方法而言,在人或动物眼后节内提供了显著的改进和优势。
本发明的一个较宽泛的方面,提供了用以注射至人或动物眼后节的组合物。所述组合物包括皮质类固醇成分、粘性诱发成分(viscosityinducingcomponent)及水性载体成分。皮质类固醇成分为治疗有效量。皮质类固醇成分在组合物中以大量颗粒的形式存在。
本发明的组合物可包括最多达组合物的约25%(w/v)或更多的皮质类固醇成分。在一个非常有益的实施方案中,皮质类固醇成分的量为至少约80mg/ml组合物。优选皮质类固醇成分的量为组合物的约1%至约10%或约20%(w/v)。
在一个非常有益的实施方案中,皮质类固醇成分包括曲安奈德。
粘性诱发成分的量为有效提高组合物粘度的量。
任何适合的粘性诱发成分,优选可眼用的粘性诱发成分,均可依据本发明而使用。多数所述粘性诱发成分已被建议用在眼上或眼内用眼科组合物中,和/或已经用在上述眼科组合物中。有利的是,粘性诱发成分的量为组合物的约0.5%至约20%(w/v)。在一个特别有益的实施方案中,粘性诱发成分为透明质酸聚合物成分,例如透明质酸钠。
在一个实施方案中,本发明的组合物在0.1/秒切速下的粘度为至少约10cps或至少约100cps,优选至少约1,000cps,更优选至少约10,000cps,进一步更优选至少约70,000cps,例如最高达约250,000cps,或约300,000cps。本发明的组合物被改造成一定构造或具有一定结构(arestructuredorhavemake-ups),以有效地例如以手动的方式优选通过27号针管、更优选通过29号或30号针管注射至人或动物眼后节。
在并非希望将本发明限制于任何具体作用理论的前提下,认为如本申请所述使用相对高粘度的组合物,提供了有效的、优选大体均匀的类固醇成分颗粒悬浮液,同时还能通过常用针管或比常用针管小的针管注射至眼后节。
在本发明的一个实施方案中,皮质类固醇成分以大量颗粒的形式存在,所述颗粒大体均匀地悬浮于组合物中,并且在组合物中维持大体均匀的悬浮状态至少约1周,优选至少约2周或至少约1个月,并进一步更优选至少约6个月或至少约1年或至少约2年,同时无需再悬浮处理,即无需摇晃或搅动以使皮质类固醇成分颗粒在组合物中维持大体均匀的悬浮状态。
具有大体均匀悬浮的所述皮质类固醇成分颗粒的组合物,提供了相对现有技术而言的显著优势。特别是,本发明的组合物可制造、运输及储存很长时间,皮质类固醇成分颗粒也不会从组合物的残余物中沉淀出来。在组合物中具有大体均匀悬浮的皮质类固醇成分颗粒,使组合物能够快速有效地用以提供对人或动物眼后节的治疗,又不必考虑使所述颗粒再悬浮。
水性载体成分有利地是可眼用的,并可包括一种或多种用于眼科组合物的常规赋形剂。
例如,载体成分可包括有效量的防腐剂成分、张力调节剂成分及缓冲剂成分中的至少一种。
在一个有利的实施方案中,本发明的组合物未添加防腐剂成分。这一特征降低了可由防腐剂成分存在所引起的或与其相关的眼内不良反应,或将所述不良反应最小化,或者甚至基本消除了所述不良反应。
尽管再悬浮成分可依据本发明而使用,但由于本发明的组合物无需再悬浮处理即能长时间维持大体均匀的悬浮状态,因此多数情况下组合物有利地未添加再悬浮成分。
还公开了治疗人或动物眼后节的方法,所述方法包括于本发明的范围内。一般而言,所述方法包括将含有皮质类固醇成分的组合物,例如本发明的组合物给药于,例如注射至人或动物的眼后节。所述给药能有效地提供所需治疗效果。给药步骤有利地包括至少一种以下方式:玻璃体内注射、结膜下注射、眼球筋膜下(sub-tenon)注射、眼球后注射、脉络膜上注射等。
本申请中所述的每一个特征,及两个或更多个所述特征的每一种结合,均包括在本发明的范围内,只要包括于所述结合中的特征不是彼此矛盾的。
本发明的上述及其他的方面和优势在以下具体实施方式、实施例及权利要求中显而易见。
具体实施方式
本发明涉及用以放置于,优选通过注射的方式放置于人或动物眼后节的组合物。所述眼后节内的组合物,例如玻璃体内的组合物,对一种或多种眼后节病症和/或疾病、和/或一种或多种所述眼后节病症和/或疾病的症状而言,是治疗有效的。
一般而言,本发明的组合物包括皮质类固醇成分;粘性诱发成分;及水性载体成分。所述组合物有利地是可眼用的。
本发明组合物的一个重要优势在于,相对早前建议的用以玻璃体内注射至眼后节的组合物而言,例如相对商标为的市售组合物而言,本发明组合物对眼后节中的组织,如视网膜的相容性更好或更友好。特别是,本发明的组合物有利地基本未添加防腐剂成分,或包括如下有效防腐剂成分,所述有效防腐剂成分相对包括于组合物中的苯甲醇防腐剂而言,其眼后节(如视网膜)的相容性更好或更友好。
另外,本发明的组合物优选不添加再悬浮成分,或优选包括以下再悬浮成分,所述再悬浮成分相对包括于组合物中的聚山梨醇酯80而言,其眼后节(如视网膜)的相容性更好或更友好。本申请另述的本发明的许多其他特征,也使本发明的组合物相对现有技术组合物而言,例如相对而言,对放置其的眼后节的相容性更好或更友好。
如上所述,本发明的组合物包括皮质类固醇成分。所述皮质类固醇成分在组合物中为治疗有效量,即在放置有组合物的眼内有效提供所需治疗效果的量。皮质类固醇成分在组合物中以大量颗粒的形式存在。
任何适合的皮质类固醇成分均可依据本发明而使用。所述皮质类固醇成分有利地在例如25EC水中具有有限的溶解度。例如,皮质类固醇成分优选在25EC水中的溶解度小于10mg/ml。皮质类固醇成分自然应是可眼用的,即应基本不对眼结构或眼组织产生显著或过度的有害影响。本发明的有益皮质类固醇成分的一个特别有益的特征在于,所述成分能够在放置有该组合物的眼后节中减轻由一种或多种眼后节疾病和/或病症所引起的炎症。
有益皮质类固醇成分的实例包括但不限于:可的松、泼尼松龙、去炎松、曲安奈德、氟氢缩松、地塞米松、甲羟松、氯替泼诺、其衍生物及其混合物。如本申请所使用,术语“衍生物”是指与被确认为衍生物的物质相比,结构足够相似,从而在代替所述物质进行使用时功能或活性基本相似的任何物质,所述功能或活性例如治疗有效性。
在一个非常有益的实施方案中,皮质类固醇成分包括曲安奈德。
皮质类固醇成分的量有利地为至少约10mg每ml组合物。本发明的一个重要优势在于,本发明的组合物能够有效地包括相对较多量或较高浓度的皮质类固醇。因此,皮质类固醇在本发明组合物中的量可为,组合物的约1%或更低至约5%或约10%或约20%或约30%或更高(w/v)。本发明的组合物中提供相对较高浓度或较多量的皮质类固醇成分,有益于降低所需放置于或注射至眼后节的组合物的量,从而相对包括有低于4%(w/v)皮质类固醇成分的组合物而言,例如相对而言,能够在眼后节内提供相同量或更多的皮质类固醇成分。因此,在一个非常有益的实施方案中,本发明的组合物包括大于约4%(w/v)、例如至少约5%(w/v)、至约10%(w/v)或约20%(w/v)或约30%(w/v)的皮质类固醇成分。
粘性诱发成分的量为有效提高组合物粘度的量,有利地为有效地显著提高组合物粘度的量。在并非希望将本发明限制于任何具体作用理论的前提下,认为组合物粘度提高至高于水的粘度时,例如0.1/秒切速下至少约100cps时,得到的组合物能够非常有效地放置于,例如注射至人或动物眼后节内。本发明组合物的相对较高粘度,除了能使本发明的组合物有利地放置于或注射至后节之外,还认为其能够提高本发明组合物的以下能力,即无需再悬浮处理而使皮质类固醇成分颗粒在组合物中长时间维持大体均匀悬浮状态的能力,例如维持至少约一周。本发明组合物的相对较高粘度的另一个益处在于,至少有助于组合物在,例如使所述皮质类固醇成分长时间维持大体均匀悬浮状态的同时,还能具有更多量或更高浓度的皮质类固醇成分,如本申请另述。
有利的是,本发明组合物在0.1/秒切速下的粘度为至少约10cps或至少约100cps或至少约1000cps,更优选至少约10,000cps,并进一步更优选至少约70,000cps或更高,例如最高达约200,000cps或约250,000cps,或约300,000cps或更高。本发明的组合物不仅具有上述相对较高的粘度,还能有效地放置于,或者被改造成一定构造或结构后有效地放置于,例如注射至人或动物眼后节内,优选通过27号针管、或甚至30号针管。
本发明的有益粘性诱发成分优选为剪切稀化成分(shearthinningcomponent),这是由于,当含有所述剪切稀化粘性诱发成分的本发明的组合物通过狭窄的空间,例如通过27号针管传递至或注射至眼后节时,组合物的粘度在所述传递过程中在高剪切条件下显著降低。经过上述传递后,组合物基本恢复至其注射前的粘度,以使皮质类固醇成分颗粒在眼内维持悬浮状态。
任何适合的粘性诱发成分,例如可眼用的粘性诱发成分,均可依据本发明而使用。多数所述粘性诱发成分已被建议用在眼上或眼内用眼科组合物中,和/或已经用在上述眼科组合物中。粘性诱发成分的量为向组合物有效提供所需粘度的量。有利的是,粘性诱发成分的量为组合物的约0.5%或约1.0%至约5%或约10%或约20%(w/v)。粘性诱发成分的精确用量取决于诸多因素,包括,例如但不限于,所使用的具体的粘性诱发成分、所使用的粘性诱发成分的分子量、所制备的和/或所使用的本发明组合物的所需粘性、等等。对粘性诱发成分进行选择,以使本发明的组合物在以下方面具有至少一个优势,优选多个优势,例如:可注射至眼后节,粘度,无需再悬浮处理而使皮质类固醇颗粒长时间维持悬浮状态、例如维持大体均匀的悬浮状态,对放置有组合物的眼后节组织的相容性等等。所选定的粘性诱发成分更优选可有效提供上述两种或更多种益处,并进一步更优选提供上述所有益处。
粘性诱发成分优选包括聚合物成分和/或至少一种粘弹剂(viscoelasticagent),例如用于眼外科方法的物质。
有益粘性诱发成分的实例包括但不限于:透明质酸、卡波姆、聚丙烯酸、纤维素衍生物、聚丙烯酸树脂、聚乙烯吡咯烷酮、明胶、糊精、多糖、聚丙烯酰胺、聚乙烯醇、聚乙酸乙烯酯、其衍生物及其混合物。
本发明的有益粘性诱发成分的分子量可为,约10,000道尔顿或更低至约2,000,000道尔顿或更高。在一个特别有益的实施方案中,粘性诱发成分的分子量为,约100,000道尔顿或约200,000道尔顿至约1,000,000道尔顿或约1,500,000道尔顿。另外,本发明使用的粘性诱发成分的分子量可依据以下因素在相当宽的范围内变化:所使用的粘性诱发成分的种类、所述本发明组合物的所需最终粘度、以及一个或多个其他可能因素。
在一个非常有益的实施方案中,粘性诱发成分为聚合透明质酸盐成分,例如透明质酸金属盐成分,优选选自透明质酸碱金属盐、透明质酸碱土金属盐及其混合物,并进一步更优选选自透明质酸钠及其混合物。所述透明质酸盐成分的分子量优选为,约50,000道尔顿或约100,000道尔顿至约1,300,000道尔顿或约2,000,000道尔顿。在一个实施方案中,本发明的组合物包括约0.05%至约0.5%(w/v)的聚合透明质酸盐成分。在另一个有益的实施方案中,透明质酸盐成分的量为组合物的约1%至约4%(w/v)。在后一种情形下,极高的聚合物粘度能够形成使颗粒沉降速率降低至以下程度的凝胶,即在预期的组合物保存期内,例如在至少约2年内不必进行再悬浮处理。由于凝胶不易用针管和注射器从散装容器(bulkcontainer)中转移,因此所述组合物可预装在注射器内出售。
水性载体成分有利地是可眼用的,并可包括一种或多种用于眼科组合物的常规赋形剂。
本发明的组合物优选包括大量的液态水。本发明的组合物例如在用于眼内之前可以是无菌的,并且优选是无菌的。
本发明的组合物优选包括至少一种有效控制组合物pH的量的缓冲剂成分,和/或包括至少一种有效控制组合物张力或渗透压的量的张力调节剂成分。更优选的,本发明的组合物既包括缓冲剂成分也包括张力调节剂成分。
缓冲剂成分及张力调节剂成分可从眼科领域常规且已知的相应成分中选取。
所述缓冲剂成分的实例包括但不限于:乙酸盐缓冲剂、柠檬酸盐缓冲剂、磷酸盐缓冲剂、硼酸盐缓冲剂等及其混合物。特别有益的是磷酸盐缓冲剂。有益的张力调节剂成分包括但不限于:盐,特别是氯化钠、氯化钾,任何合适的其他可眼用张力调节剂成分及其混合物。
缓冲剂成分的用量优选足以使组合物的pH在约6至约8范围,更优选约7至约7.5范围。张力调节剂成分的用量优选足以使本发明组合物的渗透压分别在约200至约400mOsmol/kg范围,更优选约250至约350mOsmol/kg范围。有利的是,本发明的组合物基本是等渗的。
本发明的组合物可包括一种或多种其他成分,所述其他成分的量为有效向本发明组合物提供一种或多种有益性能和/或益处的量。例如,尽管本发明的组合物可基本不添加防腐剂成分,但在其他实施方案中,本发明的组合物还是包括了有效量的防腐剂成分,所述防腐剂成分对放置有组合物的眼后节中的组织而言,优选比苯甲醇更相容或更友好。所述防腐剂成分的实例包括但不限于:苯扎氯铵,氯己定,PHMB(聚六亚甲基双胍),尼泊金甲酯及尼泊金乙酯,海克西定,亚氯酸盐成分,例如稳定态二氧化氯、亚氯酸金属盐等,其他可眼用的防腐剂等及其混合物。本发明组合物中防腐剂成分的浓度,如果有的话,为使组合物有效防腐的浓度,通常为组合物的约0.00001%至约0.05%或约0.1%(w/v)。
此外,本发明的组合物还可包括有效量的再悬浮成分,所述再悬浮成分可有效促进皮质类固醇成分颗粒悬浮或再悬浮于本发明的组合物中。如上所述,在某些实施方案中,本发明的组合物未添加再悬浮成分。本发明组合物的其他实施方案则使用了有效量的再悬浮成分,例如以更加确保皮质类固醇成分颗粒按需处于悬浮状态,和/或更加确保皮质类固醇成分颗粒可相对容易地再悬浮于本发明的组合物中,其中所述再悬浮状态是所需要的。有利的是,本发明所使用的再悬浮成分,如果有的话,对其进行选择,以使其对放置有组合物的眼后节中的组织而言,比聚山梨醇酯80更相容或更友好。
任何适合的再悬浮成分均可依据本发明而使用。所述再悬浮成分的实例包括但不限于:表面活性剂,例如泊洛沙姆(poloxane),例如商标名为的市售泊洛沙姆;四丁酚醛;肌氨酸盐;聚氧乙烯化蓖麻油,其他表面活性剂等及其混合物。
一类非常有益的再悬浮成分选自维生素衍生物。尽管上述物质早前已被建议在眼科组合物中用作表面活性剂,但已经发现其可在本发明组合物中有效用作再悬浮成分。有益维生素衍生物的实例包括但不限于:维生素E生育酚聚乙二醇丁二酸酯,例如维生素E生育酚聚乙二醇1000丁二酸酯(维生素ETPGS)。其他有益的维生素衍生物包括但不限于:维生素E生育酚聚乙二醇丁二酰胺(polyethyleneglycolsuccinamide),例如维生素E生育酚聚乙二醇1000丁二酰胺(维生素ETPGSA),其中聚乙二醇与丁二酸之间的酯键被酰胺基取代。
本发明的有益再悬浮成分在本发明组合物中的量,如果有的话,为例如在组合物制备过程中或其后有效促进颗粒悬浮于本发明组合物中的量。再悬浮成分的精确用量可依据,例如以下因素在较宽的范围内变化:所使用的具体的再悬浮成分、其中使用再悬浮成分的具体组合物、等等。再悬浮成分在本发明组合物中的适合浓度,如果有的话,通常为组合物的约0.01%至约5%,例如约0.02%或约0.05%至约1.0%(w/v)。
对于微溶于眼内组织的皮质类固醇成分,例如曲安奈德而言,其溶解速率可能会限制该物质的可用性。溶解较慢对患者既有利也有害。一方面,单独玻璃体内注射本发明的组合物之后,在玻璃体未切除(nonvitrectonize)的患者中有利的是,曲安奈德的平均消除半衰期相当长,例如约19天,并且可测药物水平在最长约3个月内均可检测到。另一方面,由于皮质类固醇成分颗粒的溶解速率慢,因此眼玻璃体腔可能在约1至约3天内无法达到治疗药物水平。
本发明的一个实施方案中,在组合物中提供了有效量的加溶成分(solubilizingcomponent),以使少量的皮质类固醇成分溶解,即低于50%,例如1%或约5%至约10%或约20%的皮质类固醇成分溶解。例如,包括约0.5至约5.0%(w/v)的环糊精成分,例如β-环糊精、磺丁醚β-环糊精(SBE)、其他环糊精等及其混合物,可使约1至约10%初始剂量的曲安奈德溶解。预先溶解的这一部分提供了易于生物利用的负荷剂量(loadingdose),从而避免了治疗有效性的延期发生。
所述加溶成分的使用,有利于皮质类固醇成分快速释放至眼内以获得治疗有效性。所述加溶成分自然应是可眼用的,或至少对放置有组合物的眼后节具有足够的相容性,以避免对所述眼后节组织造成过度的损伤。
玻璃体内给药皮质类固醇成分(例如曲安奈德)的药代动力学既可涉及药物的溶解速率,也可涉及药物经眼前节途径(anteriorroute)流出的速率。例如,单独玻璃体内注射含有4%(w/v)曲安奈德的组合物之后,TA浓度在数天后达到最高值(房水中监测),即每mL数千毫微克。该最高值(Cmax)之后,是持续约200小时的快速下降,最后是半衰期约19天的较慢的消除阶段。患者通常需要反复给药,例如约每三个月一次。
在本发明的一个实施方案中,组合物还包含有效降低局部扩散速率和/或皮质类固醇颗粒溶解速率的量的缓释成分,例如聚合物,例如聚(D,L-丙交酯)或聚(D,L-丙交酯-乙交酯共聚物)。其结果是得到Cmax更低的更平直(flatter)的消除速率曲线和更长的治疗窗带,以此延长多数患者需要注射的时间间隔。
任何适合的缓释成分,优选条件性接受(conditionallyacceptable)的缓释成分,均可采用。有益的实例如上所述。缓释成分优选是眼内可生物降解的,或是眼内可生物吸收的,以实现长时间内无残余物残留。所包括的缓释成分的量可依据例如以下因素在相对较宽的范围内变化:所使用的具体的缓释成分、所需的具体的释放曲线、等等。包括于本发明组合物中的缓释成分的通常用量,如果有的话,为组合物的约0.05%至0.1%至约0.5%或约1%(w/v)或更高。
本发明的组合物可通过适合的混合/加工技术或技术制备,例如通过一种或多种常规混合技术。应对加工制备方法进行选择以使本发明组合物成为可放置于或注射至人或动物眼后节的形式。在一个有益的实施方案中,使皮质类固醇成分与水结合,制备了浓的皮质类固醇成分分散液,其中赋形剂(取代粘性诱发成分)包括于最终组合物中。上述组分混合,使皮质类固醇成分分散,然后高压灭菌。或者,类固醇粉末在加至无菌载体前也可由γ-激发。粘性诱发成分既可购买市售无菌产品,也可通过常规方法灭菌,例如使稀溶液过滤,然后低压升华干燥得到无菌粉末。使无菌的粘性诱发成分与水结合,制得水性浓液。无菌条件下,混合浓的皮质类固醇成分分散液,并以浆液的形式加至粘性诱发成分浓液中。加入足量(适量)水,以提供所需组合物,然后使组合物混合至均匀。
还提供了使用本发明组合物的方法,所述方法包括于本发明的范围内。一般而言,所述方法包括将本发明的组合物给药于人或动物眼后节,以此获得所需的治疗效果。给药步骤有利地包括至少一种以下方式:玻璃体内注射、结膜下注射、眼球筋膜下注射、眼球后注射、脉络膜上注射等。包括适当尺寸针管(例如27号针管或30号针管)的注射器械,可有效地用以将组合物注射至人或动物眼后节。
可依据本发明治疗或处理的疾病/病症包括但不限于:
黄斑病变/视网膜变性:非渗出性年龄相关性黄斑变性(ARMD)、渗出性年龄相关性黄斑变性(ARMD)、脉络膜新生血管形成、糖尿病性视网膜病变、急性黄斑视神经视网膜病变、中心性浆液性脉络膜视网膜病变、囊样黄斑水肿、糖尿病性黄斑水肿;
葡萄膜炎/视网膜炎/脉络膜炎:急性多灶性鳞状色素上皮病变、贝切特氏病(Behcet′sDisease)、鸟枪弹样视网膜脉络膜病变、传染性疾病(梅毒、莱姆病(Lyme)、结核病、弓形体病)、中间葡萄膜炎((睫状体平坦部炎)、多灶性脉络膜炎、多发性一过性白点综合征(MultipleEvanescentWhiteDotSyndrome,MEWDS)、眼结节病(OcularSarcoidosis)、后巩膜炎、匐行性脉络膜炎(serpiginouschoroiditis)、视网膜下纤维化及葡萄膜炎综合征、伏格特-小柳-原田综合征;
血管疾病/渗出性疾病:视网膜动脉阻塞疾病、视网膜中央静脉阻塞、弥散性血管内凝血病、视网膜静脉分枝阻塞、高血压性眼底改变、眼缺血综合征、视网膜动脉微动脉瘤、慢性渗出性视网膜病(Coat′sDisease)、旁中心凹毛细管扩张、视网膜半侧静脉阻塞(Hemi-RetinalVeinOcclusion)、视乳头静脉炎(Papillophlebitis)、视网膜中央动脉阻塞、视网膜动脉分枝阻塞、颈动脉疾病(CAD)、霜样树枝状脉管炎(FrostedBranchAngitis)、镰状细胞性视网膜病变及其他血红蛋白病变(Hemoglobinopathy)、血管样条纹症、家族性渗出性玻璃体视网膜病变、伊耳斯氏病(EalesDisease);
外伤性/手术性:交感性眼炎、葡萄膜炎视网膜病、视网膜脱离、外伤、激光、PDT、光凝固、手术中血流灌注不足、辐射性视网膜病变、骨髓移植视网膜病变;
增生性病症:增生性玻璃体视网膜病变及视网膜前膜(EpiretinalMembrane)、增生性糖尿病性视网膜病变;
传染性病症:眼组织胞浆菌病、眼弓蛔虫病、拟眼组织胞浆菌病综合征(POHS)、眼内炎、弓形体病、与HIV感染相关的视网膜疾病、与HIV感染相关的脉络膜疾病、与HIV感染相关的葡萄膜疾病、病毒性视网膜炎、急性视网膜坏死、进行性视网膜外层坏死(ProgressiveOuterRetinalNecrosis)、真菌性视网膜疾病、眼梅毒、眼结核病、弥漫性单侧性亚急性视神经视网膜炎、蝇蛆病;
遗传性病症:视网膜色素变性、与视网膜营养不良相关的全身性病症、先天性静止性夜盲、锥体营养不良、斯塔加特氏病(Stargardt′sDisease)及眼底黄色斑点症、贝斯特氏病(Best′sDisease)、视网膜色素上皮的图形营养不良(patterndystrophy)、X伴性(X-linked)视网膜劈裂症、索斯比氏眼底营养不良(Sorsby′sFundusDystrophy)、良性同心性黄斑病变(BenignConcentricMaculopathy)、比埃特氏结晶样营养障碍(Bietti′sCrystallineDystrophy)、弹性假黄瘤;
视网膜裂孔/裂洞:视网膜脱离、黄斑裂洞、巨大视网膜裂孔;
肿瘤:与肿瘤相关的视网膜疾病、RPE先天性肥大、后葡萄膜黑色素瘤(PosteriorUvealMelanoma)、脉络膜血管瘤、脉络膜骨瘤、脉络膜转移、视网膜及视网膜色素上皮混合性错构瘤、视网膜母细胞瘤、眼底血管增生性肿瘤、视网膜星形细胞瘤、眼内淋巴瘤;
其他:点状内脉络膜病变、急性后极部多灶性鳞状色素上皮病变、近视性视网膜变性、急性视网膜色素上皮炎等。
本发明的方法可包括单独注射至眼后节,也可包括一定时间内的反复注射,例如约一周或约1个月或约3个月至约6个月或约1年或更长时间内反复注射。
以下非限制性实施例阐述了本发明的某些方面。
实施例1至4
四种组合物如下:
上述各组合物制备如下。
使曲安奈德与水结合,如果有的话还与维生素E-TPGS及8-环糊精结合,以制备浓的曲安奈德分散液。上述组分混合,使曲安奈德分散,然后高压灭菌。透明质酸钠既可购买市售无菌粉末,也可通过以下方法灭菌:使稀溶液过滤,然后低压升华干燥得到无菌粉末。使无菌透明质酸钠溶于水中,制得水性浓液。使浓的曲安奈德分散液混合,并以浆液的形式加至透明质酸钠浓液中。加入适量水,使混合物混合至均匀。
上述各组合物使得曲安奈德的团聚(floctuation)松散,从而易于通过适度倒置即可再悬浮。上述组合物可装入小容量药用级玻璃瓶中出售,已发现上述组合物在玻璃体内注射至人眼内时,对黄斑水肿治疗有效。
实施例5至7
三种组合物如下:
组分 | 实施例5 | 实施例6 | 实施例7 |
曲安奈德 | 2.0%(w/v) | 4.0%(w/v) | 8.0%(w/v) |
透明质酸钠 | 3.0%(w/v) | 2.5%(w/v) | 2.0%(w/v) |
磷酸钠 | 0.4%(w/v) | 0.4%(w/v) | 0.4%(w/v) |
注射用水 | 适量 | 适量 | 适量 |
0.1/秒切速下粘度 | 180,000cps | 120,000cps | 80,000cps |
上述组合物以与实施例1所述基本相似的方式制备。
组合物的较高粘度使颗粒的沉降速率显著降低至以下程度,即在预期的组合物保存期内,例如约2年内不必或不需要进行再悬浮处理。由于所述组合物不易用针管和注射器从容器中转移,因此可预装在注射器内出售。然而,预装在注射器内的组合物,仍可通过27号或30号针管有效注射至人眼后节,以在人眼内提供所需治疗效果。
实施例5至7的组合物采用或包括了浓度足够高的高分子量透明质酸钠,以在玻璃体内注射至人眼时形成胶状栓(gelatinousplug)或药物贮库(drugdepot)。与例如使用其粘度与水相似的组合物,如40相比,曲安奈德颗粒有效地捕集于或保存于上述粘稠的栓中,从而避免了有害的“卷流(pluming)”的发生,亦显著降低了药物颗粒不利地直接沉积于视网膜组织上的风险。由于透明质酸钠溶液受到极强的剪切稀化作用,因此上述制剂易于通过27号针管或甚至30号针管注射。
实施例8和9
两种组合物如下:
组分 | 实施例8 | 实施例9 |
曲安奈德 | 2.0%(w/v) | 8.0%(w/v) |
透明质酸钠 | 2.5%(w/v) | 2.3%(w/v) |
氯化钠 | 0.63%(w/v) | 0.6%(w/v) |
磷酸氢二钠,七水合物 | 0.30%(w/v) | 0.30%(w/v) |
磷酸二氢钠,一水合物 | 0.04%(w/v) | 0.04%(w/v) |
注射用水 | 适量 | 适量 |
0.1/秒切速下粘度 | 170,000±25%cps | 200,000±25%cps |
上述组合物以与实施例1所述基本相似的方式制备。
组合物的较高粘度使颗粒的沉降速率显著降低至以下程度,即在预期的组合物保存期内,例如约2年内不必或不需要进行再悬浮处理。由于所述组合物不易用针管和注射器从容器中转移,因此可预装在注射器内出售。然而,预装在注射器内的组合物,仍可通过27号或30号针管有效注射至人眼后节,以在人眼内提供所需治疗效果。
上述组合物中(以及本申请实施例确定的其他组合物中)所使用的透明质酸钠粉末的含水量为约4重量%至约20重量%,优选约4重量%至约8重量%。粉末的含水量,特别是粉末与粉末间含水量的不同,可导致两种或更多种“名义上”化学组成相同的本发明组合物具有不同的粘度。因此,本申请所指的粘度应理解为目标粘度,而组合物在其实际粘度高于或低于(±)目标粘度的约25%或约30%或约35%时均可使用。
由于实施例所述各组合物的密度均为约1mg/ml,因此本申请中所述基于重量对体积(w/v)的百分比也可被认为是基于重量对重量(w/w)的百分比。
实施例8和9的组合物采用或包括了浓度足够高的高分子量透明质酸钠,以在玻璃体内注射至人眼时形成胶状栓或药物贮库。与例如使用其粘度与水相似的组合物,如40相比,曲安奈德颗粒有效地捕集于或保存于上述粘稠的栓中,从而避免了有害的“卷流”的发生,亦显著降低了药物颗粒不利地直接沉积于视网膜组织上的风险。由于透明质酸钠溶液受到极强的剪切稀化作用,因此上述制剂易于通过27号针管或甚至30号针管注射。
尽管就不同的具体实施例和实施方式对本发明进行了叙述,仍应理解为本发明并非限制于此,本发明可在以下权利要求的范围内以不同方式实施。
Claims (15)
1.一种用以注射至人或动物眼后节的组合物,所述组合物包括:
2%至8%w/v的去炎松;
2.3%至2.5%w/v的透明质酸钠;
0.6%至0.63%w/v的氯化钠;
0.3%w/v的磷酸氢二钠;
0.04%w/v的磷酸二氢钠;
水;和
不添加防腐剂。
2.权利要求1的组合物,其中所述去炎松为曲安奈德。
3.权利要求1的组合物,其中所述去炎松以大量颗粒的形式存在,所述颗粒无需再悬浮处理而大体均匀地悬浮于组合物中至少1年。
4.权利要求1的组合物,其中所述组合物包含8%w/v的去炎松。
5.一种药物组合物,其由以下组成:
8%w/v的去炎松;
2.3%w/v的透明质酸钠;
0.6%w/v的氯化钠;
0.3%w/v的磷酸氢二钠;
0.04%w/v的磷酸二氢钠;
水;和
不添加防腐剂。
6.权利要求5的药物组合物,其中所述药物组合物在0.1/秒切速下的粘度为200,000cps。
7.权利要求5的药物组合物,其中所述去炎松以大量颗粒的形式存在,所述颗粒无需再悬浮处理而大体均匀地悬浮于组合物中至少1年。
8.权利要求5的药物组合物,其中所述药物组合物在给药后提供至少19天的去炎松半衰期。
9.权利要求1-4中任一项的组合物或权利要求5-8中任一项的药物组合物在制备用于通过给药至人或动物眼后节而治疗眼后节疾病的药剂中的用途。
10.权利要求9的用途,其中所述药剂通过玻璃体内注射给药。
11.权利要求9的用途,其中所述药剂通过结膜下注射给药。
12.权利要求9的用途,其中所述药剂通过眼球筋膜下注射给药。
13.权利要求9的用途,其中所述药剂通过眼球后注射给药。
14.权利要求9的用途,其中所述药剂通过脉络膜上注射给药。
15.组合物在制备用于通过给药至人或动物眼后节而治疗眼后节疾病的药剂中的用途,其中所述组合物由以下组成:
2%至8%w/v的去炎松;
2.3%至2.5%w/v的透明质酸钠;
不添加防腐剂,和
可眼用的赋形剂,其包含0.6%至0.63%w/v的氯化钠、0.3%w/v的磷酸氢二钠、0.04%w/v的磷酸二氢钠,和水。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024099419A1 (zh) * | 2022-11-11 | 2024-05-16 | 北京华视诺维医疗科技有限公司 | 一种曲安奈德组合物及其制备方法 |
Families Citing this family (94)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060280774A1 (en) * | 1995-06-02 | 2006-12-14 | Allergan, Inc. | Compositions and methods for treating glaucoma |
US5869079A (en) * | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
US6726918B1 (en) | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
US6699493B2 (en) | 2000-11-29 | 2004-03-02 | Oculex Pharmaceuticals, Inc. | Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor |
US20050048099A1 (en) | 2003-01-09 | 2005-03-03 | Allergan, Inc. | Ocular implant made by a double extrusion process |
FR2861734B1 (fr) | 2003-04-10 | 2006-04-14 | Corneal Ind | Reticulation de polysaccharides de faible et forte masse moleculaire; preparation d'hydrogels monophasiques injectables; polysaccharides et hydrogels obtenus |
US20060141049A1 (en) * | 2003-11-12 | 2006-06-29 | Allergan, Inc. | Triamcinolone compositions for intravitreal administration to treat ocular conditions |
US20070224278A1 (en) * | 2003-11-12 | 2007-09-27 | Lyons Robert T | Low immunogenicity corticosteroid compositions |
US20050250737A1 (en) * | 2003-11-12 | 2005-11-10 | Allergan, Inc. | Therapeutic ophthalmic compositions containing retinal friendly excipients and related methods |
US20090148527A1 (en) * | 2007-12-07 | 2009-06-11 | Robinson Michael R | Intraocular formulation |
US20050101582A1 (en) * | 2003-11-12 | 2005-05-12 | Allergan, Inc. | Compositions and methods for treating a posterior segment of an eye |
BRPI0506983A (pt) | 2004-01-20 | 2007-07-03 | Allergan Inc | composições para terapia localizada dos olhos, compreendendo preferencialmente acetonida de triancinolona e ácido hialurÈnico |
US20050244469A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Extended therapeutic effect ocular implant treatments |
US8147865B2 (en) | 2004-04-30 | 2012-04-03 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
US8119154B2 (en) | 2004-04-30 | 2012-02-21 | Allergan, Inc. | Sustained release intraocular implants and related methods |
EP2216026B1 (en) * | 2004-07-12 | 2016-04-20 | Allergan, Inc. | Ophthalmic compositions and uses for treating ophthalmic conditions |
US20060073184A1 (en) * | 2004-09-29 | 2006-04-06 | Bausch & Lomb Inc. | Viscoelastic composition, methods of use and packaging device with anti-oxidant |
US20080008762A1 (en) * | 2004-11-17 | 2008-01-10 | Government Of The Us, As Represented By The Secretary, Department Of Health And Human Services | Steroid Formulation And Methods Of Treatment Using Same |
AT501376B1 (de) * | 2005-01-17 | 2010-11-15 | Pregenzer Bruno | Glucokortikoid-hältiges arzneimittel |
PL1845780T3 (pl) * | 2005-01-20 | 2011-12-30 | Ampio Pharmaceuticals Inc | Zastosowanie pochodnych metylofenidatu |
KR101318806B1 (ko) | 2005-01-20 | 2013-10-16 | 인스티튜트 포 몰리큘러 메디신, 인코포레이티드 | 메틸페니데이트 유도체 및 그 용도 |
WO2007009087A2 (en) | 2005-07-12 | 2007-01-18 | Dmi Biosciences, Inc. | Methods and products for treatment of diseases |
AU2006304416B2 (en) * | 2005-10-18 | 2013-03-28 | Allergan, Inc. | Ocular therapy using Glucocorticoid Derivatives selectively penetrating posterior segment tissues |
US20090082321A1 (en) * | 2007-09-21 | 2009-03-26 | Allergan, Inc. | Steroid containing drug delivery systems |
US20070178138A1 (en) * | 2006-02-01 | 2007-08-02 | Allergan, Inc. | Biodegradable non-opthalmic implants and related methods |
US20070202186A1 (en) | 2006-02-22 | 2007-08-30 | Iscience Interventional Corporation | Apparatus and formulations for suprachoroidal drug delivery |
US8197435B2 (en) | 2006-05-02 | 2012-06-12 | Emory University | Methods and devices for drug delivery to ocular tissue using microneedle |
US20070260203A1 (en) * | 2006-05-04 | 2007-11-08 | Allergan, Inc. | Vasoactive agent intraocular implant |
US20070275030A1 (en) * | 2006-05-25 | 2007-11-29 | The General Hospital Corporation Dba Massachusetts General Hospital | Anti-cross-linking agents and methods for inhibiting cross-linking of injectable hydrogel formulations |
US8802128B2 (en) | 2006-06-23 | 2014-08-12 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
US8969415B2 (en) * | 2006-12-01 | 2015-03-03 | Allergan, Inc. | Intraocular drug delivery systems |
US11078262B2 (en) * | 2007-04-30 | 2021-08-03 | Allergan, Inc. | High viscosity macromolecular compositions for treating ocular conditions |
WO2008147867A2 (en) * | 2007-05-23 | 2008-12-04 | Allergan, Inc. | Cross-linked collagen and uses thereof |
US8318695B2 (en) * | 2007-07-30 | 2012-11-27 | Allergan, Inc. | Tunably crosslinked polysaccharide compositions |
US8697044B2 (en) | 2007-10-09 | 2014-04-15 | Allergan, Inc. | Crossed-linked hyaluronic acid and collagen and uses thereof |
HUE042931T2 (hu) | 2007-11-16 | 2019-07-29 | Aclaris Therapeutics Inc | Kompozíciók és eljárások purpura kezelésére |
US8394784B2 (en) * | 2007-11-30 | 2013-03-12 | Allergan, Inc. | Polysaccharide gel formulation having multi-stage bioactive agent delivery |
US20090143348A1 (en) * | 2007-11-30 | 2009-06-04 | Ahmet Tezel | Polysaccharide gel compositions and methods for sustained delivery of drugs |
US8394782B2 (en) | 2007-11-30 | 2013-03-12 | Allergan, Inc. | Polysaccharide gel formulation having increased longevity |
US9044477B2 (en) | 2007-12-12 | 2015-06-02 | Allergan, Inc. | Botulinum toxin formulation |
US9161970B2 (en) * | 2007-12-12 | 2015-10-20 | Allergan, Inc. | Dermal filler |
US8128960B2 (en) | 2008-03-11 | 2012-03-06 | Alcon Research, Ltd. | Low viscosity, highly flocculated triamcinolone acetonide suspensions for intravitreal injection |
EP2300011A4 (en) | 2008-05-27 | 2012-06-20 | Dmi Life Sciences Inc | METHODS AND THERAPEUTIC COMPOUNDS |
US8821870B2 (en) * | 2008-07-18 | 2014-09-02 | Allergan, Inc. | Method for treating atrophic age related macular degeneration |
US8450475B2 (en) | 2008-08-04 | 2013-05-28 | Allergan, Inc. | Hyaluronic acid-based gels including lidocaine |
ES2829971T3 (es) | 2008-09-02 | 2021-06-02 | Tautona Group Lp | Hilos de ácido hialurónico y/o derivados de los mismos, métodos para fabricar los mismos y usos de los mismos |
US20100098772A1 (en) * | 2008-10-21 | 2010-04-22 | Allergan, Inc. | Drug delivery systems and methods for treating neovascularization |
US20100104654A1 (en) | 2008-10-27 | 2010-04-29 | Allergan, Inc. | Prostaglandin and prostamide drug delivery systems and intraocular therapeutic uses thereof |
GB0904423D0 (en) * | 2009-03-14 | 2009-04-29 | Univ Strathclyde | Improving the solubility of chemicals |
US20100278897A1 (en) * | 2009-05-01 | 2010-11-04 | Allergan, Inc. | Intraocular bioactive agent delivery system with molecular partitioning system |
EA027524B1 (ru) | 2009-06-22 | 2017-08-31 | Ампио Фармасьютикалс, Инк. | Способ ингибирования гиперпроницаемости сосудов при отеке маклы |
EP2512389B1 (en) | 2009-12-16 | 2015-09-02 | Allergan, Inc. | Intracameral devices for sustained delivery |
US20110171286A1 (en) * | 2010-01-13 | 2011-07-14 | Allergan, Inc. | Hyaluronic acid compositions for dermatological use |
US20110172180A1 (en) | 2010-01-13 | 2011-07-14 | Allergan Industrie. Sas | Heat stable hyaluronic acid compositions for dermatological use |
US9114188B2 (en) | 2010-01-13 | 2015-08-25 | Allergan, Industrie, S.A.S. | Stable hydrogel compositions including additives |
US20110171311A1 (en) * | 2010-01-13 | 2011-07-14 | Allergan Industrie, Sas | Stable hydrogel compositions including additives |
DK2525776T3 (en) | 2010-01-22 | 2016-02-08 | Allergan Inc | Intracameral implants WITH depot preparation |
CA2792729C (en) | 2010-03-12 | 2016-06-28 | Allergan Industrie, Sas | Fluid compositions for improving skin conditions |
DK2550027T4 (da) | 2010-03-22 | 2019-05-13 | Allergan Inc | Tværbundne polysaccharid- og protein-polysaccharid-hydrogeler til blødvævsforøgelse |
EP2555750A2 (en) * | 2010-04-07 | 2013-02-13 | Allergan, Inc. | Combinations of preservative compositions for ophthalmic formulations |
US9005605B2 (en) | 2010-08-19 | 2015-04-14 | Allergan, Inc. | Compositions and soft tissue replacement methods |
US8889123B2 (en) | 2010-08-19 | 2014-11-18 | Allergan, Inc. | Compositions and soft tissue replacement methods |
US8697057B2 (en) | 2010-08-19 | 2014-04-15 | Allergan, Inc. | Compositions and soft tissue replacement methods |
US8883139B2 (en) | 2010-08-19 | 2014-11-11 | Allergan Inc. | Compositions and soft tissue replacement methods |
US8507496B2 (en) | 2010-09-07 | 2013-08-13 | Dmi Acquisition Corp. | Treatment of diseases |
EP3520749A1 (en) | 2010-10-15 | 2019-08-07 | Clearside Biomedical, Inc. | Device for ocular access |
US11957753B2 (en) | 2010-11-22 | 2024-04-16 | Bausch Health Ireland Limited | Pharmaceutical formulations containing corticosteroids for topical administration |
US8809307B2 (en) * | 2010-11-22 | 2014-08-19 | Dow Pharmaceutical Sciences, Inc. | Pharmaceutical formulations containing corticosteroids for topical administration |
US9393263B2 (en) | 2011-06-03 | 2016-07-19 | Allergan, Inc. | Dermal filler compositions including antioxidants |
EP3536307B1 (en) | 2011-06-03 | 2021-10-20 | ALLERGAN Industrie, SAS | Dermal filler compositions including antioxidants |
US9408797B2 (en) | 2011-06-03 | 2016-08-09 | Allergan, Inc. | Dermal filler compositions for fine line treatment |
US20130096081A1 (en) | 2011-06-03 | 2013-04-18 | Allergan, Inc. | Dermal filler compositions |
US9662422B2 (en) | 2011-09-06 | 2017-05-30 | Allergan, Inc. | Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation |
US20130244943A1 (en) | 2011-09-06 | 2013-09-19 | Allergan, Inc. | Hyaluronic acid-collagen matrices for dermal filling and volumizing applications |
US9241829B2 (en) | 2011-12-20 | 2016-01-26 | Abbott Medical Optics Inc. | Implantable intraocular drug delivery apparatus, system and method |
US9694050B2 (en) | 2012-10-21 | 2017-07-04 | University Of Rochester | THY1 (CD90) as a novel therapy to control adipose tissue accumulation |
US20150258120A1 (en) | 2012-11-08 | 2015-09-17 | Clearside Biomedical, Inc. | Methods and devices for the treatment of ocular diseases in human subjects |
CN104968350A (zh) | 2012-12-19 | 2015-10-07 | 安皮奥制药股份有限公司 | 疾病的治疗方法 |
AU2014205213B2 (en) * | 2013-01-11 | 2017-09-21 | Carbylan Therapeutics, Inc. | Stabilized compositions comprising hyaluronic acid |
WO2014116876A1 (en) * | 2013-01-23 | 2014-07-31 | Semnur Pharmaceuticals, Inc. | Pharmaceutical formulation comprising an insoluble corticosteroid and a soluble corticosteroid |
JP6379183B2 (ja) | 2013-05-03 | 2018-08-22 | クリアサイド バイオメディカル,インコーポレイテッド | 眼球注射の装置および方法 |
WO2014197317A1 (en) | 2013-06-03 | 2014-12-11 | Clearside Biomedical, Inc. | Apparatus and methods for drug delivery using multiple reservoirs |
WO2015142853A1 (en) * | 2014-03-17 | 2015-09-24 | Encompass Development, Inc. | Ocular formulations |
WO2015195842A1 (en) * | 2014-06-17 | 2015-12-23 | Clearside Biomedical, Inc. | Methods and devices for treating posterior ocular disorders |
RU2710491C2 (ru) | 2014-06-20 | 2019-12-26 | Клиасайд Байомедикал, Инк. | Устройство для инъекции лекарственного средства в глазную ткань и способ инъекции лекарственного средства в глазную ткань |
ES2761558T3 (es) | 2014-09-30 | 2020-05-20 | Allergan Ind Sas | Composiciones de hidrogel estables que incluyen aditivos |
WO2016128783A1 (en) | 2015-02-09 | 2016-08-18 | Allergan Industrie Sas | Compositions and methods for improving skin appearance |
US10390901B2 (en) | 2016-02-10 | 2019-08-27 | Clearside Biomedical, Inc. | Ocular injection kit, packaging, and methods of use |
JP2019514581A (ja) | 2016-05-02 | 2019-06-06 | クリアサイド バイオメディカル,インコーポレイテッド | 眼の薬物送達のためのシステムおよび方法 |
CN110177527B (zh) | 2016-08-12 | 2022-02-01 | 科尼尔赛德生物医学公司 | 用于调节药剂递送用针的插入深度的装置和方法 |
US11273072B2 (en) | 2017-01-13 | 2022-03-15 | Gyroscope Therapeutics Limited | Suprachoroidal injection device |
WO2019136512A1 (en) * | 2018-01-10 | 2019-07-18 | Eye Co Pty Ltd | Medical device and pharmaceutical composition for treatment of an eye disease or condition |
WO2020171889A1 (en) | 2019-02-19 | 2020-08-27 | University Of Rochester | Blocking lipid accumulation or inflammation in thyroid eye disease |
US20220387554A1 (en) * | 2021-06-04 | 2022-12-08 | Mark H. Nelson | Treatments for exudative maculopathies |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1140988A (zh) * | 1994-02-18 | 1997-01-22 | 希巴-盖古股份公司 | 液体眼科缓释投药系统 |
CN1215589A (zh) * | 1997-10-27 | 1999-05-05 | Ss制药株式会社 | 用于治疗关节病的关节内制剂 |
WO2002100437A2 (en) * | 2001-06-08 | 2002-12-19 | Novartis Ag | Ophthalmic compositions comprising hyaluronic acid |
CN1411814A (zh) * | 2002-08-21 | 2003-04-23 | 王晓伟 | 洗眼液 |
Family Cites Families (204)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT252264B (de) * | 1965-03-17 | 1967-02-10 | Etapharm Chem Pharm Lab Ges M | Verfahren zur Herstellung eines reinen hochviskosen Hyaluronsäurepräparates |
US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
SE390255B (sv) * | 1974-02-18 | 1976-12-13 | N G Y Torphammar | Upprullningsanordning foretredesvis for ett sekerhetsbelte i ett fordon |
GB1478759A (en) * | 1974-11-18 | 1977-07-06 | Alza Corp | Process for forming outlet passageways in pills using a laser |
US3966749A (en) * | 1975-02-10 | 1976-06-29 | Interx Research Corporation | Novel synthesis of optically active m-acyloxy-α-[(methylamino)methyl]benzyl alcohols, the pharmaceutically acceptable acid addition salts thereof and intermediate useful in the preparation thereof |
US4014335A (en) * | 1975-04-21 | 1977-03-29 | Alza Corporation | Ocular drug delivery device |
US4144317A (en) * | 1975-05-30 | 1979-03-13 | Alza Corporation | Device consisting of copolymer having acetoxy groups for delivering drugs |
US4052505A (en) | 1975-05-30 | 1977-10-04 | Alza Corporation | Ocular therapeutic system manufactured from copolymer |
US4057619A (en) | 1975-06-30 | 1977-11-08 | Alza Corporation | Ocular therapeutic system with selected membranes for administering ophthalmic drug |
US4063064A (en) | 1976-02-23 | 1977-12-13 | Coherent Radiation | Apparatus for tracking moving workpiece by a laser beam |
US4186184A (en) * | 1977-12-27 | 1980-01-29 | Alza Corporation | Selective administration of drug with ocular therapeutic system |
US4190642A (en) * | 1978-04-17 | 1980-02-26 | Alza Corporation | Ocular therapeutic system for dispensing a medication formulation |
US4200098A (en) * | 1978-10-23 | 1980-04-29 | Alza Corporation | Osmotic system with distribution zone for dispensing beneficial agent |
US4285987A (en) | 1978-10-23 | 1981-08-25 | Alza Corporation | Process for manufacturing device with dispersion zone |
US4303637A (en) | 1980-04-04 | 1981-12-01 | Alza Corporation | Medication indicated for ocular hypertension |
US4281654A (en) | 1980-04-07 | 1981-08-04 | Alza Corporation | Drug delivery system for controlled ocular therapy |
US4396625A (en) | 1980-05-13 | 1983-08-02 | Sumitomo Chemical Company, Limited | Treatment of glaucoma or ocular hypertension and ophthalmic composition |
US4425346A (en) * | 1980-08-01 | 1984-01-10 | Smith And Nephew Associated Companies Limited | Pharmaceutical compositions |
US4304765A (en) | 1980-10-14 | 1981-12-08 | Alza Corporation | Ocular insert housing steroid in two different therapeutic forms |
US4327725A (en) * | 1980-11-25 | 1982-05-04 | Alza Corporation | Osmotic device with hydrogel driving member |
US4383992A (en) * | 1982-02-08 | 1983-05-17 | Lipari John M | Water-soluble steroid compounds |
JPS58126435U (ja) | 1982-02-19 | 1983-08-27 | オリンパス光学工業株式会社 | Ttlオ−トストロボ用絞り制御回路 |
US4599353A (en) * | 1982-05-03 | 1986-07-08 | The Trustees Of Columbia University In The City Of New York | Use of eicosanoids and their derivatives for treatment of ocular hypertension and glaucoma |
DE3220156C2 (de) * | 1982-05-28 | 1990-01-25 | Heida Houston Tex. Thurlow | Mit Metallgriffen, insbesondere Edelstahlgriffen, versehenes Koch- und Bratgeschirr mit Deckel |
US4649151A (en) * | 1982-09-27 | 1987-03-10 | Health Research, Inc. | Drugs comprising porphyrins |
US5166331A (en) * | 1983-10-10 | 1992-11-24 | Fidia, S.P.A. | Hyaluronics acid fractions, methods for the preparation thereof, and pharmaceutical compositions containing same |
IT1229075B (it) | 1985-04-05 | 1991-07-17 | Fidia Farmaceutici | Medicamenti per uso topico, ottenuti tramite l'impiego dell'acido ialuronico |
US4521210A (en) * | 1982-12-27 | 1985-06-04 | Wong Vernon G | Eye implant for relieving glaucoma, and device and method for use therewith |
US4478818A (en) | 1982-12-27 | 1984-10-23 | Alza Corporation | Ocular preparation housing steroid in two different therapeutic forms |
US4727064A (en) * | 1984-04-25 | 1988-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Pharmaceutical preparations containing cyclodextrin derivatives |
US4693885A (en) | 1984-07-18 | 1987-09-15 | Nippon Petrochemicals Co., Ltd. | Tetrapyrrole therapeutic agents |
US4675338A (en) * | 1984-07-18 | 1987-06-23 | Nippon Petrochemicals Co., Ltd. | Tetrapyrrole therapeutic agents |
US5128326A (en) | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
FR2577509B1 (fr) | 1985-02-21 | 1987-05-07 | Nirvana Espar Systems Sa | Mat de bateau a voile |
US4656186A (en) * | 1985-04-30 | 1987-04-07 | Nippon Petrochemicals Co., Ltd. | Tetrapyrrole therapeutic agents |
US6407079B1 (en) * | 1985-07-03 | 2002-06-18 | Janssen Pharmaceutica N.V. | Pharmaceutical compositions containing drugs which are instable or sparingly soluble in water and methods for their preparation |
US4668506A (en) * | 1985-08-16 | 1987-05-26 | Bausch & Lomb Incorporated | Sustained-release formulation containing and amino acid polymer |
US4713446A (en) * | 1985-09-06 | 1987-12-15 | Minnesota Mining And Manufacturing Company | Viscoelastic collagen solution for ophthalmic use and method of preparation |
DE3684887D1 (de) * | 1985-11-29 | 1992-05-21 | Biomatrix Inc | Arzneistoffabgabesysteme auf basis von hyaluronan, dessen derivaten und salzen sowie verfahren zu deren herstellung. |
FR2594438B1 (fr) * | 1986-02-14 | 1990-01-26 | Labaz Sanofi Nv | Derives d'indolizine, leur procede de preparation ainsi que les compositions en contenant |
EP0244178A3 (en) * | 1986-04-28 | 1989-02-08 | Iolab, Inc | Intraocular dosage compositions and method of use |
US4959217A (en) | 1986-05-22 | 1990-09-25 | Syntex (U.S.A.) Inc. | Delayed/sustained release of macromolecules |
IL80298A (en) * | 1986-10-14 | 1993-01-31 | Res & Dev Co Ltd | Eye drops |
US4863457A (en) | 1986-11-24 | 1989-09-05 | Lee David A | Drug delivery device |
US5089509A (en) * | 1988-09-15 | 1992-02-18 | Allergan, Inc. | Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity |
US4981871A (en) * | 1987-05-15 | 1991-01-01 | Abelson Mark B | Treatment of ocular hypertension with class I calcium channel blocking agents |
DE3802158A1 (de) * | 1987-08-11 | 1989-02-23 | Hoechst Ag | Vorrichtung zur applikation von implantaten |
NZ226171A (en) | 1987-09-18 | 1990-06-26 | Ethicon Inc | Gel formulation containing polypeptide growth factor |
DE3734223A1 (de) | 1987-10-09 | 1989-04-20 | Boehringer Ingelheim Kg | Implantierbares, biologisch abbaubares wirkstofffreigabesystem |
US4853224A (en) * | 1987-12-22 | 1989-08-01 | Visionex | Biodegradable ocular implants |
US4997652A (en) * | 1987-12-22 | 1991-03-05 | Visionex | Biodegradable ocular implants |
US4920104A (en) * | 1988-05-16 | 1990-04-24 | Medchem Products, Inc. | Sodium hyaluronate composition |
US4865846A (en) | 1988-06-03 | 1989-09-12 | Kaufman Herbert E | Drug delivery system |
US5190966A (en) * | 1988-07-06 | 1993-03-02 | Health Research, Inc. | Purified hematoporphyrin dimers and trimers useful in photodynamic therapy |
US4968715A (en) | 1988-07-06 | 1990-11-06 | Health Research, Inc. | Use of purified hematoporphyrin trimers in photodynamic therapy |
US5093349A (en) * | 1988-07-20 | 1992-03-03 | Health Research Inc. | Photosensitizing agents |
US5198460A (en) * | 1988-07-20 | 1993-03-30 | Health Research Inc. | Pyropheophorbides and their use in photodynamic therapy |
US5002962A (en) * | 1988-07-20 | 1991-03-26 | Health Research, Inc. | Photosensitizing agents |
ES2213504T1 (es) | 1988-09-06 | 2004-09-01 | Pfizer Health Ab | Derivados de prostaglandina para el tratamiento del glaucoma o hipertension ocular. |
US5702716A (en) | 1988-10-03 | 1997-12-30 | Atrix Laboratories, Inc. | Polymeric compositions useful as controlled release implants |
US4935498A (en) * | 1989-03-06 | 1990-06-19 | Board Of Regents, The University Of Texas System | Expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles |
US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
US5098443A (en) * | 1989-03-23 | 1992-03-24 | University Of Miami | Method of implanting intraocular and intraorbital implantable devices for the controlled release of pharmacological agents |
US5173504A (en) | 1989-04-21 | 1992-12-22 | Health Research, Inc. | Bacteriochlorophyll-a derivatives useful in photodynamic therapy |
US5171741A (en) | 1989-04-21 | 1992-12-15 | Health Research, Inc. | Bacteriochlorophyll-a derivatives useful in photodynamic therapy |
US5019400A (en) * | 1989-05-01 | 1991-05-28 | Enzytech, Inc. | Very low temperature casting of controlled release microspheres |
US5324519A (en) * | 1989-07-24 | 1994-06-28 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
US5487897A (en) * | 1989-07-24 | 1996-01-30 | Atrix Laboratories, Inc. | Biodegradable implant precursor |
US6271216B1 (en) * | 1989-07-24 | 2001-08-07 | Allergan | Stable solution of hyaluronate in a balanced salt medium |
US5077049A (en) | 1989-07-24 | 1991-12-31 | Vipont Pharmaceutical, Inc. | Biodegradable system for regenerating the periodontium |
US5034413A (en) * | 1989-07-27 | 1991-07-23 | Allergan, Inc. | Intraocular pressure reducing 9,11-diacyl prostaglandins |
US5268178A (en) | 1989-09-25 | 1993-12-07 | The Board Of Regents, The University Of Texas System | Biodegradable antibiotic implants and methods of their use in treating and preventing infections |
US5503721A (en) * | 1991-07-18 | 1996-04-02 | Hri Research, Inc. | Method for photoactivation |
US5164188A (en) | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
US5025621A (en) * | 1990-03-16 | 1991-06-25 | Demarco Vito A | Combination garden implement |
US5075115A (en) | 1990-04-02 | 1991-12-24 | Fmc Corporation | Process for polymerizing poly(lactic acid) |
US5232844A (en) | 1990-05-15 | 1993-08-03 | New York Blood Center | Photodynamic inactivation of viruses in cell-containing compositions |
US5209926A (en) * | 1990-06-12 | 1993-05-11 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
US5124154A (en) | 1990-06-12 | 1992-06-23 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
US5256408A (en) * | 1990-06-12 | 1993-10-26 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
US5100431A (en) * | 1990-09-27 | 1992-03-31 | Allergan, Inc. | Single stitch suture needle and method |
US5492936A (en) * | 1990-11-30 | 1996-02-20 | Allergan, Inc. | Bimodal molecular weight hyaluronate formulations and methods for using same |
KR0185215B1 (ko) * | 1990-11-30 | 1999-05-01 | 요시다 쇼오지 | 서방성 안구삽입용 약제 |
US5552160A (en) | 1991-01-25 | 1996-09-03 | Nanosystems L.L.C. | Surface modified NSAID nanoparticles |
US5378475A (en) * | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
ATE142460T1 (de) * | 1991-06-21 | 1996-09-15 | Genetics Inst | Osteogene proteine enthaltende arzneimittel |
US5356629A (en) | 1991-07-12 | 1994-10-18 | United States Surgical Corporation | Composition for effecting bone repair |
US5169638A (en) | 1991-10-23 | 1992-12-08 | E. R. Squibb & Sons, Inc. | Buoyant controlled release powder formulation |
US5543154A (en) * | 1991-12-27 | 1996-08-06 | Merck & Co., Inc. | Controlled release nifedipine delivery device |
US5656297A (en) | 1992-03-12 | 1997-08-12 | Alkermes Controlled Therapeutics, Incorporated | Modulated release from biocompatible polymers |
IT1263116B (it) | 1992-04-09 | 1996-07-30 | Rotta Research Lab | Derivati basici dell'acido glutammico ed acido aspartico, procedimento per la loro preparazione e loro uso farmaceutico |
US5655832A (en) | 1992-04-16 | 1997-08-12 | Tir Technologies, Inc. | Multiple wavelength light processor |
US5244914A (en) | 1992-04-27 | 1993-09-14 | American Cyanamid Company | Stable porfimer sodium compositions and methods for their manufacture |
US5178635A (en) * | 1992-05-04 | 1993-01-12 | Allergan, Inc. | Method for determining amount of medication in an implantable device |
US6217869B1 (en) * | 1992-06-09 | 2001-04-17 | Neorx Corporation | Pretargeting methods and compounds |
US5324718A (en) * | 1992-07-14 | 1994-06-28 | Thorsteinn Loftsson | Cyclodextrin/drug complexation |
US5472954A (en) | 1992-07-14 | 1995-12-05 | Cyclops H.F. | Cyclodextrin complexation |
US5688819A (en) | 1992-09-21 | 1997-11-18 | Allergan | Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
US5972991A (en) * | 1992-09-21 | 1999-10-26 | Allergan | Cyclopentane heptan(ene) oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents |
US5922773A (en) * | 1992-12-04 | 1999-07-13 | The Children's Medical Center Corp. | Glaucoma treatment |
US5494901A (en) * | 1993-01-05 | 1996-02-27 | Javitt; Jonathan C. | Topical compositions for the eye comprising a β-cyclodextrin derivative and a therapeutic agent |
US5707643A (en) * | 1993-02-26 | 1998-01-13 | Santen Pharmaceutical Co., Ltd. | Biodegradable scleral plug |
US5770589A (en) * | 1993-07-27 | 1998-06-23 | The University Of Sydney | Treatment of macular degeneration |
US5504074A (en) * | 1993-08-06 | 1996-04-02 | Children's Medical Center Corporation | Estrogenic compounds as anti-angiogenic agents |
US5385887A (en) * | 1993-09-10 | 1995-01-31 | Genetics Institute, Inc. | Formulations for delivery of osteogenic proteins |
US5540930A (en) * | 1993-10-25 | 1996-07-30 | Pharmos Corporation | Suspension of loteprednol etabonate for ear, eye, or nose treatment |
US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
US6051576A (en) * | 1994-01-28 | 2000-04-18 | University Of Kentucky Research Foundation | Means to achieve sustained release of synergistic drugs by conjugation |
DE4403326C1 (de) | 1994-02-03 | 1995-06-22 | Hans Reinhard Prof Dr Koch | Intraokulare Linsenanordnung zur Astigmatismuskorrektur |
US5798349A (en) | 1994-03-14 | 1998-08-25 | The General Hospital Corporation | Use of green porphyrins to treat neovasculature in the eye |
US5516522A (en) * | 1994-03-14 | 1996-05-14 | Board Of Supervisors Of Louisiana State University | Biodegradable porous device for long-term drug delivery with constant rate release and method of making the same |
WO1995027481A1 (en) * | 1994-04-08 | 1995-10-19 | Atrix Laboratories, Inc. | Liquid delivery compositions |
JPH09511666A (ja) * | 1994-04-08 | 1997-11-25 | アトリックス・ラボラトリーズ・インコーポレイテッド | 医療装置で使用する付随的ポリマー系 |
US5466233A (en) | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
US6290991B1 (en) * | 1994-12-02 | 2001-09-18 | Quandrant Holdings Cambridge Limited | Solid dose delivery vehicle and methods of making same |
US6270492B1 (en) | 1994-09-09 | 2001-08-07 | Cardiofocus, Inc. | Phototherapeutic apparatus with diffusive tip assembly |
US5576311A (en) * | 1994-11-30 | 1996-11-19 | Pharmos Corporation | Cyclodextrins as suspending agents for pharmaceutical suspensions |
US5811453A (en) * | 1994-12-23 | 1998-09-22 | Alcon Laboratories, Inc. | Viscoelastic compositions and methods of use |
US5565188A (en) | 1995-02-24 | 1996-10-15 | Nanosystems L.L.C. | Polyalkylene block copolymers as surface modifiers for nanoparticles |
US6369116B1 (en) * | 1995-06-02 | 2002-04-09 | Oculex Pharmaceuticals, Inc. | Composition and method for treating glaucoma |
US5869079A (en) | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
US5906920A (en) * | 1995-08-29 | 1999-05-25 | The Salk Institute For Biological Studies | Methods for the detection of ligands for retinoid X receptors |
US5776699A (en) * | 1995-09-01 | 1998-07-07 | Allergan, Inc. | Method of identifying negative hormone and/or antagonist activities |
US5958954A (en) | 1995-09-01 | 1999-09-28 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
US5877207A (en) * | 1996-03-11 | 1999-03-02 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
IT1288290B1 (it) | 1996-06-21 | 1998-09-11 | Fidia Spa In Amministrazione S | Acido ialuronico autoreticolato e relative composizioni farmaceutiche per il trattamento delle artropatie |
US6066675A (en) * | 1996-09-13 | 2000-05-23 | The Regents Of The University Of California | Method for treatment of retinal diseases |
US5913884A (en) * | 1996-09-19 | 1999-06-22 | The General Hospital Corporation | Inhibition of fibrosis by photodynamic therapy |
US6270749B1 (en) | 1996-12-11 | 2001-08-07 | Pharmacyclics, Inc. | Use of Texaphyrin in ocular diagnosis and therapy |
JP3748970B2 (ja) * | 1997-01-31 | 2006-02-22 | 電気化学工業株式会社 | ヒアルロン酸ナトリウム含有水溶液 |
US6274614B1 (en) | 1997-02-11 | 2001-08-14 | Qlt Inc. | Methods, compositions and articles for reducing or preventing the effects of inflammation |
SE9700827D0 (sv) | 1997-03-07 | 1997-03-07 | Pharmacia & Upjohn Ab | Ophthalmic composition |
US5919970A (en) * | 1997-04-24 | 1999-07-06 | Allergan Sales, Inc. | Substituted diaryl or diheteroaryl methanes, ethers and amines having retinoid agonist, antagonist or inverse agonist type biological activity |
AU727080B2 (en) * | 1997-06-30 | 2000-11-30 | Allergan, Inc. | Calcium blockers to treat proliferative vitreoretinopathy |
US5994309A (en) | 1997-07-25 | 1999-11-30 | Angstrom Pharmaceuticals, Inc. | Anti-invasive and anti-angiogenic compositions and methods |
ES2232005T3 (es) * | 1997-08-11 | 2005-05-16 | Allergan, Inc. | Dispositivo de implante biodegradable esteril que contiene retinoide con biocompatibilidad mejorada y metodo de preparacion. |
US6306426B1 (en) * | 1997-08-11 | 2001-10-23 | Allergan Sales, Inc. | Implant device with a retinoid for improved biocompatibility |
EP0938896A1 (en) | 1998-01-15 | 1999-09-01 | Novartis AG | Autoclavable pharmaceutical compositions containing a chelating agent |
US6271220B1 (en) | 1998-03-11 | 2001-08-07 | Allergan Sales, Inc. | Anti-angiogenic agents |
US6095512A (en) * | 1998-03-25 | 2000-08-01 | Vijuk Equipment, Inc. | Accumulator station with stack height control |
WO1999049846A2 (en) * | 1998-03-30 | 1999-10-07 | Rtp Pharma Inc. | Compositions containing microparticles of water-insoluble substances and method for their preparation |
ATE428345T1 (de) | 1998-07-09 | 2009-05-15 | Curelight Medical Ltd | Vorrichtung und verfahren zur wirkungsvollen hochenergetischen photodynamischen therapie von akne vulgaris und seborrhoe |
EP1104302A4 (en) | 1998-07-10 | 2006-08-09 | Retmed Pty Ltd | PROPHYLACTIC TREATMENTS OF BLOOD VESSEL NEOFORMATION IN MACULAR DEGENERATION |
US6261583B1 (en) * | 1998-07-28 | 2001-07-17 | Atrix Laboratories, Inc. | Moldable solid delivery system |
US20020198174A1 (en) | 2001-05-07 | 2002-12-26 | Allergan Sales, Inc. | Disinfecting and solubilizing steroid compositions |
WO2000012137A1 (en) * | 1998-09-02 | 2000-03-09 | Allergan Sales, Inc. | Preserved cyclodextrin-containing compositions |
US20040152664A1 (en) | 1998-09-02 | 2004-08-05 | Allergan, Inc. | Prednisolone compositions |
US6565874B1 (en) * | 1998-10-28 | 2003-05-20 | Atrix Laboratories | Polymeric delivery formulations of leuprolide with improved efficacy |
US6143314A (en) | 1998-10-28 | 2000-11-07 | Atrix Laboratories, Inc. | Controlled release liquid delivery compositions with low initial drug burst |
CA2351734A1 (en) | 1998-11-20 | 2000-06-02 | University Of Connecticut | Generic integrated implantable potentiostat telemetry unit for electrochemical sensors |
US6217895B1 (en) * | 1999-03-22 | 2001-04-17 | Control Delivery Systems | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US6482854B1 (en) | 1999-03-25 | 2002-11-19 | Massachusetts Eye And Ear Infirmary | Glaucoma treatment |
US6290713B1 (en) | 1999-08-24 | 2001-09-18 | Thomas A. Russell | Flexible illuminators for phototherapy |
US6317616B1 (en) | 1999-09-15 | 2001-11-13 | Neil David Glossop | Method and system to facilitate image guided surgery |
US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
US6461631B1 (en) | 1999-11-16 | 2002-10-08 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
US6319273B1 (en) | 1999-12-16 | 2001-11-20 | Light Sciences Corporation | Illuminating device for treating eye disease |
AUPQ496500A0 (en) * | 2000-01-06 | 2000-02-03 | University Of Sydney, The | Kit |
US6395294B1 (en) * | 2000-01-13 | 2002-05-28 | Gholam A. Peyman | Method of visualization of the vitreous during vitrectomy |
CA2714081C (en) | 2000-02-10 | 2013-08-06 | Massachusetts Eye And Ear Infirmary | Methods and compositions for treating conditions of the eye |
US6726918B1 (en) * | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
PE20020146A1 (es) | 2000-07-13 | 2002-03-31 | Upjohn Co | Formulacion oftalmica que comprende un inhibidor de ciclooxigenasa-2 (cox-2) |
US6357568B1 (en) | 2000-09-27 | 2002-03-19 | Shou Mao Chen | Structure for protecting a luggage shell |
AU2002248284A1 (en) * | 2000-11-01 | 2002-08-06 | Allergan, Inc. | Compositions for treatment of ocular neovascularization |
DE60137960D1 (de) * | 2000-11-15 | 2009-04-23 | Mohan A Chandavarkar | Pharmazeutische zusammensetzungen mit corticosteroiden und antiinfektiva |
US6699493B2 (en) * | 2000-11-29 | 2004-03-02 | Oculex Pharmaceuticals, Inc. | Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor |
US6595945B2 (en) * | 2001-01-09 | 2003-07-22 | J. David Brown | Glaucoma treatment device and method |
US6713081B2 (en) * | 2001-03-15 | 2004-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Ocular therapeutic agent delivery devices and methods for making and using such devices |
TWI298257B (en) * | 2001-05-31 | 2008-07-01 | Allergan Inc | Hypotensive lipid and timolol compositions and methods of using same |
US6713268B2 (en) * | 2001-06-26 | 2004-03-30 | Allergan, Inc. | Methods of identifying ocular hypotensive compounds having reduced hyperpigmentation |
US6765012B2 (en) * | 2001-09-27 | 2004-07-20 | Allergan, Inc. | 3-(Arylamino)methylene-1,3-dihydro-2H-indol-2-ones as kinase inhibitors |
CA2463687A1 (en) | 2001-10-18 | 2003-04-24 | Decode Genetics Ehf | Cyclodextrin complexes |
EA006746B1 (ru) * | 2001-11-09 | 2006-04-28 | Айтек Фармасьютикалз | Способы лечения глазных неоваскулярных заболеваний |
US6885744B2 (en) | 2001-12-20 | 2005-04-26 | Rockwell Electronic Commerce Technologies, Llc | Method of providing background and video patterns |
US6960346B2 (en) | 2002-05-09 | 2005-11-01 | University Of Tennessee Research Foundation | Vehicles for delivery of biologically active substances |
US6899717B2 (en) * | 2002-09-18 | 2005-05-31 | Allergan, Inc. | Methods and apparatus for delivery of ocular implants |
US20040137059A1 (en) * | 2003-01-09 | 2004-07-15 | Thierry Nivaggioli | Biodegradable ocular implant |
WO2004069280A1 (en) | 2003-02-06 | 2004-08-19 | Cipla Ltd | Pharmaceutical inclusion complexes containing a steroid and optionally an antibacterial agent |
BRPI0407693A (pt) * | 2003-02-20 | 2006-03-01 | Alcon Inc | uso de esteróides para preparação de formulações utilizáveis no tratamento de pessoas sofrendo de distúrbios oculares, bem como formulação assim obtidos |
WO2004087043A2 (en) | 2003-02-21 | 2004-10-14 | Sun Pharmaceutical Industries Limited | Stable ophthalmic formulation containing an antibiotic and a corticosteroid |
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 |
CA2539023A1 (en) * | 2003-09-23 | 2005-04-14 | Alcon Inc. | Triamcinolone acetonide and anecortave acetate formulations for injection |
US20050250737A1 (en) * | 2003-11-12 | 2005-11-10 | Allergan, Inc. | Therapeutic ophthalmic compositions containing retinal friendly excipients and related methods |
US20050101582A1 (en) | 2003-11-12 | 2005-05-12 | Allergan, Inc. | Compositions and methods for treating a posterior segment of an eye |
US20060141049A1 (en) * | 2003-11-12 | 2006-06-29 | Allergan, Inc. | Triamcinolone compositions for intravitreal administration to treat ocular conditions |
BRPI0506983A (pt) * | 2004-01-20 | 2007-07-03 | Allergan Inc | composições para terapia localizada dos olhos, compreendendo preferencialmente acetonida de triancinolona e ácido hialurÈnico |
US7589057B2 (en) * | 2004-04-30 | 2009-09-15 | Allergan, Inc. | Oil-in-water method for making alpha-2 agonist polymeric drug delivery systems |
US8425929B2 (en) | 2004-04-30 | 2013-04-23 | Allergan, Inc. | Sustained release intraocular implants and methods for preventing retinal dysfunction |
US20050244478A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Anti-excititoxic sustained release intraocular implants and related methods |
US8119154B2 (en) * | 2004-04-30 | 2012-02-21 | Allergan, Inc. | Sustained release intraocular implants and related methods |
US20050244472A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Intraocular drug delivery systems containing excipients with reduced toxicity and related methods |
US20050244463A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular vasculopathies |
US7771742B2 (en) | 2004-04-30 | 2010-08-10 | Allergan, Inc. | Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods |
US20050244465A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Drug delivery systems and methods for treatment of an eye |
US20050244466A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Photodynamic therapy in conjunction with intraocular implants |
US20050244458A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular neuropathies |
US20050244461A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Controlled release drug delivery systems and methods for treatment of an eye |
US7799336B2 (en) | 2004-04-30 | 2010-09-21 | Allergan, Inc. | Hypotensive lipid-containing biodegradable intraocular implants and related methods |
US20050244462A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Devices and methods for treating a mammalian eye |
US20050244471A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Estradiol derivative and estratopone containing sustained release intraocular implants and related methods |
EP2216026B1 (en) * | 2004-07-12 | 2016-04-20 | Allergan, Inc. | Ophthalmic compositions and uses for treating ophthalmic conditions |
US8802128B2 (en) | 2006-06-23 | 2014-08-12 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
US20070298073A1 (en) | 2006-06-23 | 2007-12-27 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
-
2004
- 2004-10-14 US US10/966,764 patent/US20050101582A1/en not_active Abandoned
- 2004-11-08 EP EP08016371A patent/EP1997497B1/en active Active
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-
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1140988A (zh) * | 1994-02-18 | 1997-01-22 | 希巴-盖古股份公司 | 液体眼科缓释投药系统 |
CN1215589A (zh) * | 1997-10-27 | 1999-05-05 | Ss制药株式会社 | 用于治疗关节病的关节内制剂 |
WO2002100437A2 (en) * | 2001-06-08 | 2002-12-19 | Novartis Ag | Ophthalmic compositions comprising hyaluronic acid |
CN1411814A (zh) * | 2002-08-21 | 2003-04-23 | 王晓伟 | 洗眼液 |
Non-Patent Citations (2)
Title |
---|
刘谊,严密: "曲安奈德玻璃体腔注射的临床应用", 《中华眼底疾病杂志》 * |
陈鹏,等: "透明质酸的应用及制备研究进展", 《上海大学学报(自然科学版)》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024099419A1 (zh) * | 2022-11-11 | 2024-05-16 | 北京华视诺维医疗科技有限公司 | 一种曲安奈德组合物及其制备方法 |
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