高级检索

    辣椒素-磷脂酰胆碱复合物的制备及其降血糖与抗胃黏膜刺激性作用评价

    Capsaicin-Phosphatidylcholine Complex: Preparation and Evaluation of Its Hypoglycemic Effect and Reduction of Gastric Mucosal Irritation

      摘要
    • 摘要:
      目的 制备辣椒素-磷脂酰胆碱复合物(Cap-PC)，考察Cap-PC体内降血糖药效及抑制胃黏膜刺激性作用。
      方法 以复合率为指标，单因素考察结合Box-Behnken设计-效应面法优化Cap-PC处方工艺。测试Cap-PC溶解度和溶出度，采用傅里叶变换红外光谱、X-射线粉末衍射、扫描电镜对Cap-PC进行表征。一次性腹腔注射链脲佐菌素制作大鼠糖尿病模型，考察Cap-PC药动学行为。将大鼠分为正常组、模型组、二甲双胍组(100 mg·kg−1·d−1)、Cap组(45 mg·kg−1·d−1)及Cap-PC低、中、高剂量组(25、35、45 mg·kg−1·d−1)，检测血糖值和口服糖耐量。采用HE染色法观察Cap和Cap-PC胃黏膜病理变化。
      结果 Cap-PC最佳处方工艺：磷脂酰胆碱与Cap用量比为2.72∶1，制备温度为50.00 ℃，制备时间为4.00 h，平均复合率为(99.69±0.82)%。Cap-PC溶解度提高至13.54倍，12 h累积释放度增加至90.62%。Cap和磷脂酰胆碱以氢键结合在一起形成Cap-PC，并以无定形状态存在于Cap-PC中。Cap-PC的达峰浓度(Cmax)增加至3.26倍，药时曲线下面积(AUC0~t)增加至2.77倍。在给药剂量均为45 mg·kg−1·d−1条件下，Cap-PC显著提高了Cap的降血糖药效及口服糖耐量。Cap-PC避免了Cap的胃黏膜刺激性，提高了用药安全性。
      结论 Cap-PC改善了Cap理化性质缺陷，具有较好的降血糖效果，为进一步应用奠定了基础。

       

      Abstract:
      OBJECTIVE To prepare capsaicin-phosphatidylcholine complex(Cap-PC), and investigate its hypoglycemic effect and inhibitory effect on gastric mucosal irritation in vivo.
      METHOD Recombination rate was employed as evaluation index, single factor study combined with Box-Behnken design-response surface methodology was used to optimize the formulation of Cap-PC. Solubility and dissolution rate were determined. Fourier transform infrared spectrum(FT-IR), X-ray powder diffraction(XRPD) and scanning electron microscope(SEM) were employed to characterize the property of Cap-PC. Diabetic rat model was established by a single intraperitoneal injection of streptozotocin, and then investigated the pharmacokinetic behavior of Cap-PC. Rats were divided into normal group, model group, metformin group(100 mg·kg−1·d−1), Cap group(45 mg·kg−1·d−1), Cap-PC low-, middle- and high-dose(25, 35, 45 mg·kg−1·d−1) group. Blood glucose and oral glucose tolerance were determined. The pathological changes in gastric mucosa of Cap and Cap-PC were observed by HE staining.
      RESULTS Optimized formulation of Cap-PC was as follows: phosphatidylcholine to Cap ratio was 2.72∶1, preparation temperature was 50.00°C and preparation time was 4.00 h, average recombination rate of Cap-PC was (99.69±0.82)%. Solubility of Cap-PC was significantly improved to 13.54 times, and cumulative release rate in 12 h was increased to 90.62%. Cap and phosphatidylcholine were combined together to form Cap-PC by hydrogen bonds, and Cap existed in an amorphous state in Cap-PC. Pharmacokinetic studies showed that the peak concentration(Cmax) and the area under the drug concentration time curve(AUC0~t) of Cap-PC were increased to 3.26 and 2.77 times. Under the condition of a dose of 45 mg·kg−1·d−1, Cap-PC significantly enhanced the hypoglycemic effect and oral glucose tolerance of Cap. Cap-PC avoided the gastric mucosa irritation of Cap and improved the safety of medication.
      CONCLUSION Cap-PC improved the physicochemical properties of Cap and has a better hypoglycemic effect, which lays the foundation for further application.

       

      • HTML全文
      • 参考文献(18)
      • 相关文章
      • 施引文献
    • 资源附件(0)

    /

    返回文章
    返回