Domb A J, Turovsky L, Nudelman R
Hebrew University of Jerusalem, School of Pharmacy, Department of Pharmaceutical Chemistry, Israel.
Pharm Res. 1994 Jun;11(6):865-8. doi: 10.1023/a:1018985909777.
Chemical reactions between drugs containing reactive amines with hydrolyzable polymers in buffer solutions were investigated. Phenylalkylamines with increasing nucleophilic reactivity were used as model drugs. Solutions of phenylalkylamines were reacted heterogeneously with representative biodegradable polyanhydride and polyester powders in various pH solutions, and the recovery of the amines from the solutions was determined. Poly(sebacic acid), a reactive polyanhydride, reacted by amide formation with the tested amines and their respective HCl salts when exposed to physiologic pH (pH 7.4). However, at pH 5.0 no interaction occurred. The aromatic polyanhydride, PCPP, and the polyesters based on lactic acid and caprolactone did react with the amine derivatives at pH 7.4, but at a slower rate. The reaction can be avoided with appropriate salt derivatives of the amines.
研究了含活性胺的药物与可水解聚合物在缓冲溶液中的化学反应。使用具有递增亲核反应性的苯烷基胺作为模型药物。苯烷基胺溶液在不同pH值的溶液中与代表性的可生物降解聚酐和聚酯粉末进行非均相反应，并测定胺从溶液中的回收率。当暴露于生理pH值（pH 7.4）时，活性聚酐聚（癸二酸）通过酰胺形成与测试的胺及其各自的盐酸盐发生反应。然而，在pH 5.0时未发生相互作用。芳香族聚酐PCPP以及基于乳酸和己内酯的聚酯在pH 7.4时确实与胺衍生物发生反应，但反应速率较慢。使用胺的适当盐衍生物可以避免该反应。
