郝天云, 魏元锋, 钱帅, 张建军, 高缘. 改善紫杉烷类药物低水溶性和低渗透性的策略探讨J. 药学学报, 2018,53(1): 54-61. doi: 10.16438/j.0513-4870.2017-0863
引用本文: 郝天云, 魏元锋, 钱帅, 张建军, 高缘. 改善紫杉烷类药物低水溶性和低渗透性的策略探讨J. 药学学报, 2018,53(1): 54-61. doi: 10.16438/j.0513-4870.2017-0863
HAO Tian-yun, WEI Yuan-feng, QIAN Shuai, ZHANG Jian-jun, GAO Yuan. Advances in strategies of improving solubility and permeability of taxanesJ. Acta Pharmaceutica Sinica, 2018,53(1): 54-61. doi: 10.16438/j.0513-4870.2017-0863
Citation: HAO Tian-yun, WEI Yuan-feng, QIAN Shuai, ZHANG Jian-jun, GAO Yuan. Advances in strategies of improving solubility and permeability of taxanesJ. Acta Pharmaceutica Sinica, 2018,53(1): 54-61. doi: 10.16438/j.0513-4870.2017-0863

改善紫杉烷类药物低水溶性和低渗透性的策略探讨

Advances in strategies of improving solubility and permeability of taxanes

  • 摘要: 紫杉烷类药物作为新一代抗肿瘤药物,对卵巢癌、乳腺癌、非小细胞肺癌及头颈癌等恶性肿瘤均具有良好的临床疗效,然而低水溶性和低渗透性导致的低口服生物利用度严重限制了其口服制剂的开发。目前,已上市制剂均非口服,所开发成的注射剂,因含有大量表面活性剂和有机溶媒,存在体液潴留、超敏反应等不良反应,且注射给药患者用药顺应性差,将其开发成口服制剂是未来紫杉烷类药物发展的方向。作者结合所在课题组对紫杉烷类药物的研究和近几年相关文献,探讨并分析改善该类药物的水溶性和渗透性进而提高其口服生物利用度的技术策略,其中着重探讨了制剂晶体学技术在该领域的应用前景,最终为紫杉烷类药物口服制剂的开发提供理论基础和研究方向。

     

    Abstract: As a new generation of anti-tumor drugs, taxanes has a good clinical efficacy in the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, head and neck cancer. However, low bioavailability of oral administration from low water solubility and low permeability significantly limited the development of their oral applications. Currently, the marketed preparations were non-oral drug preparations, and the injection contained a large number of surfactants (cremophor EL or Tween 80) and organic solvents (ethanol), which could result in fluid retention, hypersensitivity and other side effects, as well as poor compliance. Oral preparation will be an ideal form for development of taxanes medicines. According to the research by our and other groups in recent years, we investigate the technical strategies enhancing the water solubility and absorptive permeability to improve their oral bioavailability. Among them, we emphasize the application prospects of crystallography technology, and provide a theoretical basis to guide future research in the development of oral preparations for taxanes.

     

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