辣椒素-磷脂酰胆碱复合物的制备、降血糖及抑制胃黏膜刺激性研究

Capsaicin-phosphatidylcholine complex: preparation, hypoglycemic effects and inhibition of gastric mucosa

关键词:  辣椒素  复合物  溶解度  溶出度  降血糖

Key words:  capsaicin, complex, solubility, dissolution  rate, hypoglycemic

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。将大鼠分为空白组，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最佳处方工艺为：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，时间-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 spectrometer (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, control group, metformin group (100 mg·kg-1·d-1), Cap group (45 mg·kg-1·d-1), Cap-PC high, middle and low dose (25, 35, 45 mg·kg-1·d-1) group, and 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 formulations of Cap-PC 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 90.69%. Cap and phosphatidylcholine are 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 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 laying the foundation for further application.