[关键词]
[摘要]
目的 采用溶剂浇铸法制备口腔溃疡双层膜剂,研究青黛表面改性前后对膜剂质量与药效的影响。方法 通过单因素实验设计和响应面优化法优选膜剂最佳处方,并对膜剂表面形貌、黏附时间、抗拉强度、含量测定以及体外药物释放等性能进行评估。进一步采用化学灼烧法建立大鼠口腔溃疡模型,考察膜剂对溃疡组织肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6以及口腔溃疡组织形态的影响。结果 空白隔离层确定为25 mg/mL的乙基纤维素乙醇溶液,载药膜最佳处方为63 mg/mL PVA17-88、55 mg/mL PVP K30、3.0 mg/mL明胶与0.047 mL/mL甘油。青黛表面改性后,双层膜剂比未改性双层膜剂具有更加光滑均一的外观、更高的含量均匀性和有效成分靛蓝释放率。药效学结果表明,与模型组相比,阳性组与青黛改性膜剂组显著降低了溃疡组织TNF-α、IL-1β、IL-6的含量(P<0.05),并减少了炎症细胞的浸润,溃疡组织愈合程度较高。结论 青黛改性之后的口腔溃疡双层膜剂具有更好的质量与更佳的疗效,具有较好的应用前景。
[Key word]
[Abstract]
Objective To prepare the bilayer film for oral ulcer by solvent casting method, and study the effect of surface modification on film quality and efficacy of Qingdai (Indigo Naturalis). Methods The optimal formulation of the film was optimized by single-factor experimental design and response surface optimization method, and the properties of the film such as surface morphology, adhesion time, tensile strength, content determination and drug release in vitro were evaluated. A rat oral ulcer model was further established by the chemical burning method, and the effects of film preparations on tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and oral ulcer tissue morphology were investigated. Results The blank isolation layer was determined to be 25 mg/mL ethyl cellulose ethanol solution, and the best formulation of the drug-loaded film was as follow: 63 mg/mL PVA17-88, 55 mg/mL PVP K30, 3.0 mg/mL gelatin and 0.047 mL/mL glycerin. After the surface modification of Indigo Naturalis, the double-layer film preparation had a smoother and more uniform appearance, higher content uniformity and release rate of active ingredient indigo than the unmodified Indigo Naturalis double-layer film preparation. The pharmacodynamic results showed that compared with the model group, the contents of TNF-α, IL-1β, and IL-6 (P < 0.05) were significantly reduced in the positive group and the modified film group and the infiltration of inflammatory cells was reduced, and the healing degree of ulcer tissue was higher. Conclusion The double-layer film for oral ulcers of modified Indigo Naturalis has better quality and curative effect, and has a better application prospect.
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[基金项目]
国家自然科学基金面上项目(82173976);国家自然科学基金面上项目(81773918)