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    • 6. 发明申请
    • METHOD FOR PROLONGING ACTIVITY OF AUTODEGRADABLE ENZYMES AND COMPOSITIONS THEREOF
    • 用于增强可自由可扩链酶活性的方法及其组合物
    • US20100104551A1
    • 2010-04-29
    • US12603988
    • 2009-10-22
    • Dharmendra M. JaniKai KwokGregory L. McIntireBruce A. PfefferAfshin ShafieeRuiwen ShiSrini VenkateshHongna WangYan HuangStephen R. Davio
    • Dharmendra M. JaniKai KwokGregory L. McIntireBruce A. PfefferAfshin ShafieeRuiwen ShiSrini VenkateshHongna WangYan HuangStephen R. Davio
    • A61K38/48A61P27/02
    • C12N9/50A61K31/198C12N9/6435C12N9/96C12Y304/21007
    • A composition of a long-acting enzyme comprises the enzyme in a formulation comprising a buffer and an additive selected from the group consisting of tranexamic acid, ε-aminocaproic acid, and analogs of L-lysine other than tranexamic acid and ε-aminocaproic acid, combinations thereof, and mixtures thereof. The composition can further comprise another additive selected from the group consisting of L-lysine, L-arginine, L-ornithine (or its pharmaceutically acceptable salts; e.g., L-ornithine hydrochloride), γ-aminobutyric acid, 5-aminovaleric acid, 7-aminoheptanoic acid, glycylglycine, triglycine, N-α-acetyl-L-arginine, betaine, sarcosine, gelatin, HSA, streptokinase, tPA, uPA, non-ionic surfactants, glycerin, D-sorbitol, combinations thereof, and mixtures thereof. A method for prolonging the activity of an autodegradable enzyme comprises storing the enzyme after manufacture at a low pH, and reconstituting the acidified enzyme before use with a solution containing at least one of such additives. The method is useful to provide enzyme for wide use, which otherwise would lose activity upon long storage. In one embodiment the method is applicable to provide enzyme for inducing controlled posterior vitreous detachment.
    • 长效酶的组合物包含在包含缓冲液和添加剂的制剂中的酶,所述缓冲剂和添加剂选自氨甲环酸,氨基己酸和除了氨甲环酸以外的L-赖氨酸和β-氨基己酸 酸,其组合,及其混合物。 所述组合物可以进一步包含选自L-赖氨酸,L-精氨酸,L-鸟氨酸(或其药学上可接受的盐,例如L-鸟氨酸盐酸盐),γ-氨基丁酸,5-氨基戊酸,7 氨基庚酸,甘氨酰甘氨酸,三甘氨酸,N-α-乙酰基-L-精氨酸,甜菜碱,肌氨酸,明胶,HSA,链激酶,tPA,uPA​​,非离子表面活性剂,甘油,D-山梨糖醇,其组合及其混合物。 用于延长自动降解酶的活性的方法包括在低pH下制备后储存酶,并且在使用前将酸化酶与含有至少一种这样的添加剂的溶液重新组合。 该方法对于提供广泛使用的酶是有用的,否则将在长期储存时失去活性。 在一个实施方案中,该方法适用于提供用于诱导受控的后玻璃体脱离的酶。
    • 8. 发明授权
    • Microprecipitation of nanoparticulate pharmaceutical agents using
surface active material derived from similar pharmaceutical agents
    • 使用衍生自相似药剂的表面活性物质微粒沉淀纳米颗粒药剂
    • US5716642A
    • 1998-02-10
    • US370928
    • 1995-01-10
    • Pranab BagchiGregory L. McIntireJohn R. Minter
    • Pranab BagchiGregory L. McIntireJohn R. Minter
    • A61K9/14A61K49/04
    • B82Y5/00A61K49/0428A61K9/146Y10S977/746Y10S977/881Y10S977/90Y10S977/915
    • This invention describes the preparation of nanoparticulate pharmaceutical agent dispersion via a process that comprises the dissolution of the said pharmaceutical agent in an alkaline solution and then neutralizing the said solution with an acid in the presence of suitable surface-modifying, surface-active agents to form a fine particle dispersion of the said pharmaceutical agent. A combination of surface active surface modifying agents comprising a nonionic surface active substance and an anionic surface active material having a chemical structure which is at least on a molecular basis 75% similar to the pharmaceutical agent is used. This process is preferably followed by steps of diafiltration clean-up of the dispersion and then concentration of it to a desired level. This process of dispersion preparation leads to microcrystalline particles of Z-average diameters smaller than 400 nm as measured by photon correlation spectroscopy. Various modifications of precipitation schemes are described, many of which are suitable for large-scale manufacture of these agent dispersions.
    • 本发明描述了纳米颗粒药剂分散体的制备方法,该方法包括将所述药剂溶解在碱性溶液中,然后在合适的表面改性表面活性剂存在下用酸中和所述溶液形成 所述药剂的细颗粒分散体。 使用包含非离子表面活性物质的表面活性表面改性剂和具有与药剂相似至少分子量为75%的化学结构的阴离子表面活性物质的组合。 该方法优选的是通过渗滤清洁分散体的步骤,然后将其浓缩至期望的水平。 这种分散制备过程导致通过光子相关光谱测量的Z平均直径小于400nm的微晶颗粒。 描述了沉淀方案的各种改进,其中许多适用于这些试剂分散体的大规模生产。