中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (8): 1921-1928.doi: 10.12307/2026.560

• 水凝胶材料Hydrogel materials • 上一篇    下一篇

糖尿病皮肤创面模型小鼠正交实验优选“红黄白”凝胶的处方配比

高艳果1，2，3，郭  旭1，2，3，李晓晗1，2，3，陈仕琦1，2，3，朱海涛1，3，黄良永1，3，叶  方1，3，卢  伟1，3，王启斌1，3，郑  涛1，2，3，陈  黎1，2，3   

  1. 1湖北医药学院药学院，湖北省十堰市  442000；湖北医药学院附属太和医院，2武当中医药研究所，3药学部，湖北省十堰市  442000
  • 收稿日期:2024-11-22 接受日期:2025-01-04 出版日期:2026-03-18 发布日期:2025-07-14
  • 通讯作者: 陈黎，博士，教授，主任药师，湖北医药学院药学院，湖北省十堰市 442000；湖北医药学院附属太和医院，武当中医药研究所，药学部，湖北省十堰市 442000
  • 作者简介:高艳果，女，1999年生，河南省洛阳市人，汉族，硕士在读，主要从事中药药理与制剂方面的研究。
  • 基金资助:
    国家自然科学基金青年基金项目(81703582)，项目负责人：郑涛；湖北省自然科学基金项目(2020CFB713，2016CFB153)，项目负责人：郑涛；湖北省卫生健康科研基金(WJ2021ZH0017，WJ2019M057)，项目负责人：陈黎；“十四五”湖北省高等学校优势特色学科群(生物与医药)项目(2024BMXKQT3，2023BMXKQT3，2022BMXKQT3)，项目负责人：陈黎；湖北医药学院研究生科技创新项目(YC2022056)，项目负责人：郭旭；湖北医药学院研究生科技创新项目(YC2023068)，项目负责人：陈仕琦；湖北医药学院研究生科技创新项目(YC2023069)，项目负责人：李晓晗；吴阶平医学基金会临床科研专项基金(320.6750.2023-25-7)，项目负责人：陈黎

Optimization of prescription ratio of “Honghuangbai” gel by orthogonal test in diabetic skin wound mouse models

Gao Yanguo1, 2, 3, Guo Xu1, 2, 3, Li Xiaohan1, 2, 3, Chen Shiqi1, 2, 3, Zhu Haitao1, 3, Huang Liangyong1, 3, Ye Fang1, 3, Lu Wei1, 3, Wang Qibin1, 3, #br# Zheng Tao1, 2, 3, Chen Li1, 2, 3#br#   

  1. 1School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei Province, China; 2Institute of Wudang Traditional Chinese Medicine,  3Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
  • Received:2024-11-22 Accepted:2025-01-04 Online:2026-03-18 Published:2025-07-14
  • Contact: Chen Li, MD, Professor, Chief pharmacist, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei Province, China; Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China; Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
  • About author:Gao Yanguo, Master candidate, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei Province, China; Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China; Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
  • Supported by:
    National Natural Science Foundation of China Youth Fund Project, No. 81703582 (to ZT); Hubei Natural Science Foundation Project, No. 2020CFB713, 2016CFB153 (to ZT); Hubei Health Research Foundation, No. WJ2021ZH0017, WJ2019M057 (to CL); Hubei Higher Education Institutions Advantageous and Characteristic Disciplines (Biology and Medicine) Project during the “14th Five-Year Plan” Period, No. 2024BMXKQT3, 2023BMXKQT3, 2022BMXKQT3 (to CL); Graduate Science and Technology Innovation Project of Hubei University of Medicine, No. YC2022056 (to GX); Graduate Science and Technology Innovation Project of Hubei University of Medicine, No. YC2023068 (to CSQ); Graduate Science and Technology Innovation Project of Hubei University of Medicine, No. YC2023069 (to LXH); Wu Jieping Medical Foundation Clinical Research Special Fund, No. 320.6750.2023-25-7 (to CL)

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摘要：

文题释义：
糖尿病足溃疡：是慢性疾病糖尿病的严重并发症之一，多因神经性病变和血管病变所致，主要临床表现为下肢溃疡、感染和坏疽。糖尿病足溃疡治疗的关键在于去腐生肌、活血通络和抗菌消炎，现有治疗手段主要为抗感染、局部清创和纠正压力等，治疗效果不理想，故开发有效治疗药物具有重要的研究价值。
正交实验法：是一种用于研究多因素多水平实验设计的科学方法，利用正交表安排实验，通过分析实验结果找出最优组合，具有高效、快速、经济等优点。该文基于糖尿病足溃疡小鼠模型开展正交实验，以优选“红黄白”组方药材的用量。

背景：中药外治法在促创面愈合方面有着悠久的历史，开发有效的中药外用制剂治疗糖尿病足溃疡具有重要意义。“红黄白(红景天、黄柏、白及)”组方药材具有去腐生肌、活血通络和解毒疗疮等功效，可有效促进糖尿病足溃疡愈合，但实际应用中存在久置易分层、换药时不易清理等缺陷。
目的：优选“红黄白”凝胶的处方配比，开发稳定性良好、具有促糖尿病足溃疡愈合作用的凝胶型制剂。
方法：通过腹腔注射链脲佐菌素的方法建立C57BL/6J小鼠糖尿病模型，造模成功4周后在小鼠背部制作直径8 mm的全层皮肤缺损创面，以“红黄白”凝胶组方药材(白及6-15 g、红景天3-6 g和黄柏3-12 g)的用量为考察因素，以创面愈合率及其曲线下面积为评价指标进行L9(34)正交实验，优选“红黄白”凝胶处方的配比。将30只C57BL/6J小鼠随机分为正常对照组、模型对照组和最佳处方配比药物治疗组(平行3组)，每组6只，正常对照组制作全层皮肤缺损，模型对照组制作糖尿病全层皮肤缺损，最佳处方配比药物治疗组制作糖尿病全层皮肤缺损，创面造模3 d后，正常对照组、模型对照组创面涂抹灭菌水，最佳处方配比药物治疗组创面涂抹最佳处方配比“红黄白”凝胶处方，1次/d，连续治疗12 d，以创面愈合率及其曲线下面积为评价指标验证正交实验结果。
结果与结论：正交实验结果显示，“红黄白”凝胶的最佳处方配比为白及6 g、红景天4.5 g、黄柏12 g；验证实验结果显示，最佳处方配比药物治疗组小鼠第4，6天的创面愈合率及其曲线下面积均高于模型对照组。结果表明“红黄白”凝胶的最佳处方配比为白及6 g、红景天4.5 g、黄柏12 g，此处方可有效促进糖尿病小鼠皮肤创面愈合。
https://orcid.org/0009-0000-6461-224X(高艳果)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 红黄白凝胶">, 红景天">, 黄柏">, 白及">, 正交实验">, 处方配比">, 糖尿病足溃疡">, 愈合率">, 工程化皮肤材料

Abstract: BACKGROUND: External treatment of Chinese medicine has a long history in promoting wound healing, and it is of great significance to develop effective Chinese medicine external preparations to treat diabetic foot ulcers. The medicinal materials of the formula “Honghuangbai (Rhodiola crenulata, Phellodendron, and Bletilla striata)” have the effects of removing dead tissue and promoting tissue regeneration, promoting blood circulation and unblocking collaterals, and detoxifying and curing sores, which can effectively promote the healing of diabetic foot ulcers. However, in actual application, there are defects such as easy stratification after long-term storage and difficult cleaning during dressing changes.
OBJECTIVE: To optimize the prescription ratio of “Honghuangbai” gel and develop a gel-type preparation with good stability and the effect of promoting the healing of diabetic foot ulcers. 
METHODS: A diabetic model of C57BL/6J mice was established by intraperitoneal injection of streptozotocin. Four weeks after successful modeling, a full-thickness skin defect with a diameter of 8 mm was made on the back of the mice. The dosage of the medicinal materials in the “Honghuangbai” gel formula (6-15 g of Bletilla striata, 3-6 g of Rhodiola crenulata and 3-12 g of Phellodendron) was used as the investigation factor. The wound healing rate and its area under the curve were used as evaluation indicators to carry out an L9(34) orthogonal experiment to optimize the formulation of the “Honghuangbai” gel. Thirty C57BL/6J mice were randomly divided into a normal control group, a model control group, and an optimal prescription ratio drug treatment group (three parallel groups), with 6 mice in each group. Full-thickness skin defects were made in the normal control group; diabetic full-thickness skin defects were made in the model control group; diabetic full-thickness skin defects were made in the optimal prescription ratio drug treatment group. After 3 days of wound modeling, sterile water was applied to the wounds of the normal control group and the model control group, and the optimal prescription ratio “Honghuangbai” gel was applied to the wounds of the optimal prescription ratio drug treatment group, once a day, for 12 consecutive days. The wound healing rate and its area under the curve were used as evaluation indicators to verify the orthogonal experimental results.
RESULTS AND CONCLUSION: The orthogonal test results showed that the optimal level of each factor was 6 g of Bletilla striata, 4.5 g of Rhodiola crenulata, and 12 g of Phellodendron. The results of the verification experiment showed that the wound healing rate and its area under the curve of the mice in the optimal prescription ratio drug treatment group on days 4 and 6 were higher than those in the model control group. The results showed that the optimal prescription ratio of the “Honghuangbai” gel was 6 g of Bletilla striata, 4.5 g of Rhodiola crenulata, and 12 g of Phellodendron, which could effectively promote the healing of skin wounds in diabetic mice.

Key words: “Honghuangbai” gel">, Rhodiola crenulata">, Phellodendron">, Bletilla striata">, orthogonal test">, prescription ratio">, diabetic foot ulcer">, healing rate">, engineered skin material

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