一种新型的可注射药物缓释材料研究

Have certain liquidity, room-temperature fast curing of biodegradable polymeric materials and drug preparation method of slow release agents available injection, implant lesion under temperature fast curing, is expected to achieve solid tumor, easy recurrence of disease such as osteomyelitis non-surgical or small local slow-release chemotherapy, surgery, and difficult to surgically resected cancerous tumors, conventional treatment method is difficult to cure terminal local drug delivery of chemotherapy. But the present study of injectable drugs slow-release materials for various defects such as easy to loss, toxicity, unstable and sudden release drugs and make its use is restricted. Physi CAL was prepared on the basis of the pilot study of a certain fluidity, biodegradable in the body to absorb and biocompatibility good modified unsaturated polyester resin, the resin is not easy to scatter, good stability in body fluids, not sudden release drugs, fast curing at room temperature, the hydrophilic drug has good slow release performance. And then to its physical and chemical properties were characterized, in vitro degradation of performance; To the model in vitro drug release properties of ciprofloxacin hydrochloride, a new modified unsaturated polyester material in mice subcutaneous injection of biocompatibility, and can be injected adriamycin - modified unsaturated polyester slow-release preparation in mice sarcoma S180 rat model to study the antitumor activity.

有一定流动性的、室温快速固化的可降解高分子材料与药物配制的缓释药剂可用注射的方法植入病灶部位，体温下迅速固化，有望实现实体瘤、骨髓炎等易复发病的非手术或小手术局部缓释给药化疗，及难于手术切除的、常规治疗方法难以治愈的晚期癌瘤进行局部给药化疗。但目前研究的可注射药物缓释材料因存在各种缺陷如易流失、毒性大、不稳定、突释药物等而使其利用受到限制。本课题组在前期研究的基础上制备出一种具有一定流动性的、在体内可降解吸收的以及生物相容性好的改性不饱和聚酯树脂，本树脂不易流散、在体液中稳定性好、不突释药物、室温快速固化的、对亲水性药物具有良好缓释性能。然后对其理化性质进行表征，在体外降解性能；体外对模型药物盐酸环丙沙星的释放性能,新型可注射改性不饱和聚酯材料在小鼠皮下的生物相容性,及可注射的阿霉素-改性不饱和聚酯缓释制剂对小鼠S180鼠肉瘤模型的抗癌活性进行研究。

在过去的二十年中，聚酯类材料广泛用于化疗剂、抗生素药物、多肽和蛋白质制剂（如胰岛素、生长因子）、麻醉剂、多糖（如肝素）等药物的控释研究，用作骨固定材料、高分子药物的新型聚酯类材料也屡见报道。聚酯类材料在临床医学领域越来越受到重视。. 以马来酸酐或富马酸为不饱和酸单体，以癸二酸、月桂二酸、十三烷二酸之一为饱和酸单体，与乙二醇共聚，制备得到了新型不饱和聚酯材料,并进行了表征。结果表明作为药物缓释材料具有良好的降解性能和药物控释性能。. 合成的新型不饱和聚酯材料在小鼠皮下具有良好的组织相容性。在小鼠皮下的吸收代谢证实，合成的新型不饱和聚酯材料在生物体内具有良好的生物可降解吸收特性。因此，该大类不饱和聚酯材料作为一类新型可降解皮下植入药物缓释材料，有广阔的应用前景。. 载药量5﹪的盐酸阿霉素-不饱和聚酯缓释制剂在体外和小鼠皮下均具有较好的持续释药性能和释药安全性，在体内对小鼠S180鼠肉瘤模型具有较好的治疗效果，配合5-氟尿嘧啶（5-Fu）-不饱和聚酯缓释制剂治疗效果更好。该类盐酸阿霉素-不饱和聚酯缓释制剂作为新型可注射缓释化疗制剂，对实体瘤的治疗具有明显的潜在应用前景。