复方中药痤疮凝胶的制备工艺与药效作用研究

Study on the preparation process and pharmacodynamic effect of a compound traditional Chinese medicine Gel for Acne

关键词:  中药复方  痤疮  凝胶  卡波姆940  工艺优化  药效学评价  安全性评价

Key words:  compound traditional Chinese medicine  acne  gel  carbomer 940  process optimization  pharmacodynamic evaluation  safety evaluation

摘要:

[目的] 基于中医“清热化瘀”理论，针对痤疮治疗常用药物的耐药性及皮肤刺激难题，开发安全有效的复方中药痤疮凝胶并明确其药效与安全性。[方法] 以黄芩、丹参等9味中药组成的传统方剂为核心，通过基质筛选与正交试验优化凝胶处方，3批次验证工艺稳定性；建立兔耳痤疮模型，设不同剂量组并以维A酸乳膏为阳性对照，观察病理变化及血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）水平；开展单次/多次皮肤刺激性试验及致敏性试验评价安全性。[结果] 确定卡波姆-940为最佳基质（综合评分41.2），优化处方为卡波姆-940 3 g、甘油37.5 g、丙二醇75 g，3批次验证平均评分48.8，工艺稳定；各剂量组兔耳表皮增厚、角栓增多及炎症浸润明显好转，血清 TNF-α、IL-6、IL-1β水平显著降低（P<0.05），疗效与维A酸乳膏无差异（P>0.05）；皮肤刺激评分均为0，致敏发生率0%。[结论] 该复方中药痤疮凝胶工艺稳定，可通过改善痤疮病理损伤、抑制炎症因子异常升高发挥治疗作用，且无刺激性与致敏性，安全性良好，为痤疮治疗提供新制剂。

Abstract:

[Objective] Guided by the traditional Chinese medicine theory of “clearing heat and resolving stasis”， and to address the common issues of drug resistance and skin irritation associated with conventional acne treatments，this study aimed to develop a safe and effective compound traditional Chinese medicine gel for acne and to elucidate its pharmacodynamic effects and safety profile. [Methods] Based on a classical prescription composed of nine herbs，including Scutellaria baicalensis Georgi and Salvia miltiorrhiza Bge.，the gel formulation was optimized through matrix screening and orthogonal experiments. The stability of the preparation process was verified in three consecutive batches. A rabbit ear acne model was established. Different dose groups of the gel were set up，with tretinoin cream as the positive control. Pathological changes in the model tissue were observed，and serum levels of tumor necrosis factor-α（TNF-α），interleukin-6（IL-6），and interleukin-1β（IL-1β） were measured. Safety was evaluated through single and repeated cutaneous irritation tests and a skin sensitization test. [Results] Carbomer-940 was determined to be the optimal gel matrix（comprehensive score：41.2）. The optimized formulation consisted of Carbomer-940（3 g），glycerol（37.5 g），and propylene glycol（75 g）. The average score from the three-batch validation was 48.8，indicating a stable preparation process. Compared with the model group，all dose groups showed significant improvements in epidermal thickening，follicular hyperkeratosis（comedone formation），and inflammatory cell infiltration in the rabbit ear. Serum levels of TNF-α，IL-6，and IL-1β were significantly reduced（P<0.05）. The therapeutic efficacy was comparable to that of tretinoin cream（P>0.05）. The scores for both skin irritation tests were 0，and the incidence of skin sensitization was 0%. [Conclusion] The preparation process for this compound traditional Chinese medicine acne gel is stable. It exerts therapeutic effects by ameliorating acne-related pathological damage and inhibiting the abnormal elevation of inflammatory cytokines. The gel exhibits no skin irritation or sensitization potential，demonstrating a favorable safety profile，and thus offers a new option for acne treatment.