张依, 李晓洁, 颜云松, 张楚, 白雪婷, 申艳光, 刘毓东, 颜炎, 张家雯, 陈卫衡, 林娜, 张彦琼. 新型杜仲水凝胶促进骨折愈合的药效评价及其优势表征J. 药学学报, 2025, 60(8): 2518-2527. DOI: 10.16438/j.0513-4870.2025-0232
引用本文: 张依, 李晓洁, 颜云松, 张楚, 白雪婷, 申艳光, 刘毓东, 颜炎, 张家雯, 陈卫衡, 林娜, 张彦琼. 新型杜仲水凝胶促进骨折愈合的药效评价及其优势表征J. 药学学报, 2025, 60(8): 2518-2527. DOI: 10.16438/j.0513-4870.2025-0232
ZHANG Yi, LI Xiao-jie, YAN Yun-song, ZHANG Chu, BAI Xue-ting, SHEN Yan-guang, LIU Yu-dong, YAN Yan, ZHANG Jia-wen, CHEN Wei-heng, LIN Na, ZHANG Yan-qiong. Pharmacological evaluation and advantage characterization of a novel Eucommia ulmoides Hydrogel in promoting fracture healingJ. Acta Pharmaceutica Sinica, 2025, 60(8): 2518-2527. DOI: 10.16438/j.0513-4870.2025-0232
Citation: ZHANG Yi, LI Xiao-jie, YAN Yun-song, ZHANG Chu, BAI Xue-ting, SHEN Yan-guang, LIU Yu-dong, YAN Yan, ZHANG Jia-wen, CHEN Wei-heng, LIN Na, ZHANG Yan-qiong. Pharmacological evaluation and advantage characterization of a novel Eucommia ulmoides Hydrogel in promoting fracture healingJ. Acta Pharmaceutica Sinica, 2025, 60(8): 2518-2527. DOI: 10.16438/j.0513-4870.2025-0232

新型杜仲水凝胶促进骨折愈合的药效评价及其优势表征

Pharmacological evaluation and advantage characterization of a novel Eucommia ulmoides Hydrogel in promoting fracture healing

  • 摘要: 骨折后延迟愈合及骨不连仍是骨伤临床的难点和痛点。针对现有骨折治疗药物存在疗效不稳定、药效发挥慢和不良反应等问题, 本研究采用BanGel专利技术, 将具有补肝肾强筋骨功效的传统中药杜仲与水凝胶相结合, 制备了一种新型杜仲水凝胶。通过建立横断性胫骨中段骨折大鼠模型, 采用行为学、血清学、影像学和组织病理学等方法, 观察骨折发生及愈合过程中的动态变化特征, 评价杜仲水凝胶促进骨折愈合的药效特点, 并与含相同杜仲药物浓度的口服给药和直接涂抹给药对比, 考察其药效优势。所有动物实验经中国中医科学院中医基础理论研究所实验动物中心实验动物福利伦理委员会批准, 且实验均按照相关指导原则和规定进行(批准号: IBTCMCACMS21-2406-03)。研究结果表明, 杜仲水凝胶能够显著减轻骨折大鼠的早期症状, 促进骨痂形成, 改善骨小梁参数及皮质骨连续性, 调控骨形成与吸收的动态平衡。相较于含等量杜仲的口服及涂抹给药, 水凝胶具有起效快、渗透性强的优势。进一步的机制挖掘与验证结果显示, 杜仲可通过激活丝氨酸/苏氨酸蛋白激酶1/β-连环蛋白(AKT1/β-catenin) 信号轴调控Runt相关转录因子2 (RUNX2) 及核因子κB受体活化因子配体/骨保护素(RANKL/OPG) 表达促进骨折愈合。综上, 本研究开发的新型杜仲水凝胶在促进骨折愈合方面展现出显著优势, 具备潜在临床应用价值。

     

    Abstract: Delayed fracture healing and nonunion continue to pose substantial challenges in orthopedic clinical practice. Existing medications for fracture treatment can, to a certain degree, promote fracture healing. However, they are plagued by problems such as unstable efficacy, slow onset, and frequent adverse effects. In this study, leveraging BanGel patented technology, we developed a novel Eucommia ulmoides-based hydrogel. This was achieved by integrating Eucommia ulmoides, a traditional Chinese medicine renowned for its liver and kidney tonifying and bone-strengthening properties, with a hydrogel delivery system. A transverse mid-shaft tibial fracture rat model was established. Behavioral assessments, serological analysis, radiological and histopathological examinations were employed to observe the dynamic changes during the fracture and subsequent healing processes. The efficacy of the Eucommia ulmoides hydrogel in promoting fracture healing was objectively evaluated. Moreover, the therapeutic advantages of the hydrogel were compared with those of oral and direct topical administrations containing the same dosage of Eucommia ulmoides. All animal experiments were approved by the Laboratory Animal Welfare Ethics Committee of the Laboratory Animal Center of the Institute of Basic Theory of Chinese Medicine, China Academy of Traditional Chinese Medicine, and were conducted in accordance with the relevant guidelines and regulations (approval No. IBTCMCACMS21-2406-03). The results showed that Eucommia hydrogel can significantly alleviate the early symptoms of fractured, promote callus formation, improve trabecular parameters and cortical bone continuity, and regulate the dynamic balance of bone formation and absorption. Compared with oral and topical applications of the same dose of Eucommia ulmoides, the Eucommia ulmoides hydrogel exhibited a faster onset and stronger permeability. Further mechanism exploration and verification results showed that Eucommia ulmoides can promote fracture healing by activating the serine/threonine protein kinase 1/β-catenin (AKT1/β-catenin) signaling axis to regulate the expression of Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG). In summary, the novel Eucommia ulmoides hydrogel shows distinct advantages in promoting fracture healing and has potential clinical application value.

     

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