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    • 80. 发明专利
    • Method for producing preparation of biodegradable microspheres
    • 生产可生物降解微生物的制备方法
    • JP2014156496A
    • 2014-08-28
    • JP2014114968
    • 2014-06-03
    • Allergan Incアラーガン、インコーポレイテッドAllergan,Incorporated
    • HUGHES PATRICK MSARRAZIN CHRISTIANROSSI ELISABETHBOIX MICHELE
    • A61K47/34A61K9/00A61K9/20A61K9/50A61K9/58A61K31/00A61K31/404
    • A61K9/0051A61K9/1647Y10T428/2985
    • PROBLEM TO BE SOLVED: To provide a method for producing preparation of biodegradable microspheres which can place an intraocular implant releasable of a therapeutic agent at a sustained or controlled rate for long period of time and in an amount with few or no negative side effects.SOLUTION: The method for producing preparation of biodegradable microspheres includes steps of: preparing a viscous organic phase including a TKI (tyrosine kinase inhibitor) having 4 or more of partition coefficients logP in a two-phase system composed of n-octanol and water, a biodegradable polymer, and a solvent; preparing a first aqueous phase so as to have a pH of pH 6-8; forming an emulsion by mixing the viscous organic phase and the first aqueous phase; preparing a second aqueous phase so as to have a pH of pH 4-9, forming a solution by adding the second aqueous phase to the emulsion; stirring the solution; and producing the biodegradable microsphere wherein the TKI is encapsulated by evaporating the solution. The produced biodegradable microsphere releases the TKI at a rate effective to sustain the release of the TKI from the microsphere for the period exceeding one month from when placed in the vitreous of an eye.
    • 要解决的问题:提供一种制备可生物降解的微球的方法,其可以将治疗剂以可持续或受控的速率长时间放置并以少量或没有负面副作用的量放置在眼内植入物中。 制备生物可降解微球的方法包括以下步骤:制备包含TKI(酪氨酸激酶抑制剂)的粘性有机相,其在由正辛醇和水组成的两相体系中具有4或更多的分配系数logP,可生物降解 聚合物和溶剂; 制备第一水相以使pH为6-8; 通过混合粘性有机相和第一水相形成乳液; 制备第二水相以具有pH 4-9的pH,通过将第二水相加入到乳液中形成溶液; 搅拌溶液; 并生产可生物降解的微球,其中通过蒸发溶液来封装TKI。 所生产的可生物降解的微球释放TKI,其速率有效地维持TKI从微球释放超过一个月的时间,从放置在眼睛的玻璃体中。