葛根素固体分散体温敏灌肠凝胶的处方优化及表征

doi:10.3976/j.issn.1002-4026.2025181

摘要/Abstract

摘要： 制备了一种葛根素固体分散体温敏灌肠凝胶，以解决葛根素溶解度差、生物利用度低的问题。通过单因素试验与Box-Behnken响应面法，以胶凝温度、胶凝时间等多个指标进行综合评价，确定的最佳处方（质量分数）组成为：泊洛沙姆407为17.74%，泊洛沙姆188为1.36%，海藻酸钠0.96%，以及无水氯化钙0.06%。对该优化处方进行材料学表征的结果表明，所制备的凝胶其胶凝温度介于36~39℃之间，与生理温度接近，能在体温条件下迅速转变为半固体凝胶状态。扫描电子显微镜（SEM）观察显示，凝胶具有规整的三维多孔网络结构。傅里叶红外光谱（FTIR）分析表明，葛根素在固体分散体及凝胶中均以无定形态存在，且与载体材料相容性良好，未发生明显的化学相互作用。流变学测试进一步揭示，凝胶在发生相变后表现出以弹性为主的特性，具备良好的凝胶强度。体外溶胀与降解实验评价显示，该凝胶在模拟生理环境中具有优良的吸水膨胀能力，其最大溶胀率可达80%以上；同时在降解过程中，凝胶在24小时后的质量残留率仍保持在20%以上，且降解曲线呈现先快后慢的趋势，显示出其具备可持续的药物释放潜力。结果表明，本研究制备的葛根素固体分散体温敏灌肠凝胶，具备适宜的温敏胶凝特性、良好的溶胀与降解性能以及稳定的三维多孔结构，为改善葛根素的递送提供了一种有前景的新策略。

关键词: 葛根素, 固体分散体, 温敏凝胶, 灌肠, 溃疡性结肠炎

Abstract: In this study, a thermosensitive enema gel containing puerarin in solid dispersion form was prepared to address the poor solubility and low bioavailability of puerarin. Through single-factor experiments and using the Box-Behnken response surface methodology, we evaluated multiple indicators of the gel such as gelation temperature and gelation time, and identified its optimal formulation: 17.74% poloxamer 407, 1.36% poloxamer 188, 0.96% sodium alginate, and 0.06% anhydrous calcium chloride. Material characterization of this optimized formulation showed that the gel had a gelation temperature ranging from 36°C to 39°C, which is close to physiological body temperature, allowing the gel to rapidly transform into a semi-solid gel state at body temperatures. Scanning electron microscopy indicated that the gel possessed a regular three-dimensional porous network structure. Fourier transform infrared spectroscopy analysis showed that Puerarin existed in an amorphous state in both the solid dispersion and the gel, and showed good compatibility with the carrier materials without significant chemical interactions. Rheological tests further demonstrated that the gel exhibited elastic properties after the phase transition, indicating good gel strength. In vitro swelling and degradation experiments showed that the gel had excellent water absorption and swelling capacity in a simulated physiological environment, with a maximum swelling rate of over 80%. Additionally, during the degradation process, the mass retention rate of the gel remained above 20% after 24 h, and the degradation curve showed a trend of initial rapidity followed by gradual degradation, indicating its potential for sustained drug release. In conclusion, these results suggest that the enema gel containing puerarin in a solid dispersion form possessed marked temperature-sensitive gelation properties, favorable swelling and degradation characteristics, and a stable three-dimensional porous structure, providing a promising novel strategy for improving the delivery of puerarin.

Key words: , puerarin, solid dispersion, thermosensitive gel, enema, ulcerative colitis

中图分类号:

R943

魏荟霖, 付艳, 代安琳, 陈雅娟, 张曾妮, 周霞, 万军. 葛根素固体分散体温敏灌肠凝胶的处方优化及表征[J]. 山东科学, 0, (): 1-.

WEI Huilin, FU Yan, DAI Anlin, CHEN Yajuan, ZHANG Zengni, ZHOU Xia, WAN Jun. Formulation optimization and characterization of a thermosensitive enema gel containing puerarin in a solid dispersion[J]. Shandong Science, 0, (): 1-.

参考文献

[1] Wangchuk P, Yeshi K, Loukas A. Ulcerative colitis: Clinical biomarkers, therapeutic targets, and emerging treatments[J]. Trends in Pharmacological Sciences, 2024, 45(10): 892-903. DOI:10.1016/j.tips.2024.08.003.

[2] 陈秋伶, 罗锐, 王利宏, 等. 凝胶剂在溃疡性结肠炎中的应用进展[J]. 药学学报, 2025, 60(6): 1654-1660. DOI:10.16438/j.0513-4870.2024-1278.

[3] 余紫依, 郝蕾蕾, 李培强, 等. 原位凝胶在多种给药途径中的应用[J]. 中国医药工业杂志, 2024, 55(8): 1061-1068. DOI:10.16522/j.cnki.cjph.2024.08.003.

[4] Tao Qing, Liang Qiao, Fu Yu, et al. Puerarin ameliorates colitis by direct suppression of macrophage M1 polarization in DSS mice[J]. Phytomedicine, 2024, 135: 156048. DOI:10.1016/j.phymed.2024.156048.

[5] Jelić D. Thermal stability of amorphous solid dispersions[J]. Molecules, 2021, 26(1): 238. DOI:10.3390/molecules26010238.

[6] Garg A, Agrawal R, Singh Chauhan C, et al.In-situgel: A smart carrier for drug delivery[J]. International Journal of Pharmaceutics, 2024, 652: 123819. DOI:10.1016/j.ijpharm.2024.123819.

[7] Le T P, Yu Yang, Cho I S, et al. Injectable poloxamer hydrogel formulations for intratympanic delivery of dexamethasone[J]. Journal of Korean Medical Science, 2023, 38(17): e135. DOI:10.3346/jkms.2023.38.e135.

[8] Febriyenti F, Rahmi S, Halim A. Study of gliclazide solid dispersion systems using PVP K-30 and PEG 6000 by solvent method[J]. Journal of Pharmacy & Bioallied Sciences, 2019, 11(3): 262-267. DOI:10.4103/jpbs.JPBS_87_18.

[9] Fan Yilin, Hong Ran, Sun Xiaoli, et al. Gastric acid-responsive deformable sodium alginate/Bletillastriatapolysaccharidein situgel for the protection and treatment of alcohol-induced peptic ulcers[J]. International Journal of Biological Macromolecules, 2024, 258: 128815. DOI:10.1016/j.ijbiomac.2023.128815.

[10] Dong Ziyi, Zhang Qing, Wang Changhai, et al. Combined thermosensitive gel co-loaded with dermaseptin-PP and PTX liposomes for effective local chemotherapy[J]. International Journal of Nanomedicine, 2023, 18: 413-424. DOI:10.2147/IJN.S385470.

[11] 孙静莹, 王玉霞, 王婷, 等. 滴通鼻炎温敏凝胶的工艺研究[J]. 华西药学杂志, 2020, 35(3): 249-255. DOI:10.13375/j.cnki.wcjps.2020.03.004.

[12] Niranjan R, Koushik C, Saravanan S, et al. A novel injectable temperature-sensitive zinc doped chitosan/β-glycerophosphate hydrogel for bone tissue engineering[J]. International Journal of Biological Macromolecules, 2013, 54: 24-29. DOI:10.1016/j.ijbiomac.2012.11.026.

[13] Yuan Baoming, Zhang Yanfeng, Wang Qian, et al. Thermosensitive vancomycin@PLGA-PEG-PLGA/HA hydrogel as an all-in-one treatment for osteomyelitis[J]. International Journal of Pharmaceutics, 2022, 627: 122225. DOI:10.1016/j.ijpharm.2022.122225.

[14] Chen I C, Su Chenying, Chen Peiyu, et al. Investigation and characterization of factors affecting rheological properties of poloxamer-based thermo-sensitive hydrogel[J]. Polymers, 2022, 14(24): 5353. DOI:10.3390/polym14245353.

[15] Zhao Shiyi, Zhang Junbo, Qiu Mengyu, et al. Mucoadhesive and thermosensitiveBletillastriatapolysaccharide/chitosan hydrogel loaded nanoparticles for rectal drug delivery in ulcerative colitis[J]. International Journal of Biological Macromolecules, 2024, 254(Pt 1): 127761. DOI:10.1016/j.ijbiomac.2023.127761.

[16] Chang Kaiyi, Chou Y N, Chen Weiyu, et al. Mussel-inspired adhesive and self-healing hydrogel as an injectable wound dressing[J]. Polymers, 2022, 14(16): 3346. DOI:10.3390/polym14163346.

[17] Yi Yihu, Chen Guo, Gong Song, et al. Injectable temperature-sensitive hydrogel loaded with IL-36Ra for the relief of osteoarthritis[J]. ACS Biomaterials Science & Engineering, 2023, 9(3): 1672-1681.

[18] 国家药典委员会. 中华人民共和国药典-一部——2020年版[M]. 北京: 中国医药科技出版社, 2020.

[19] 马培元, 陈欣欣, 陈善坦, 等. 百草伤膏凝胶贴膏的制备及其对骨关节炎的药效学评价[J]. 中国现代应用药学, 2024, 41(20): 2839-2849. DOI:10.13748/j.cnki.issn1007-7693.20242243.

[20] 顾秀梅. 改变灌肠液温度对治疗溃疡性结肠炎疗效的影响[J]. 医学理论与实践, 2016, 29(8): 1047-1048. DOI:10.19381/j.issn.1001-7585.2016.08.036.

[21] Jeon Y D, Lee J H, Lee Y M, et al. Puerarin inhibits inflammation and oxidative stress in dextran sulfate sodium-induced colitis mice model[J]. Biomedicine & Pharmacotherapy, 2020, 124: 109847. DOI:10.1016/j.biopha.2020.109847.

[22] Zhang Yijia, Wang Xinji, Gu Qin, et al. Two-in-one: Multifunctional poloxamer hydrogel accelerates endometrial regeneration and fertility restoration through synergistic regulation of KGF-2 and NO[J]. Regenerative Biomaterials, 2025, 12: rbaf062. DOI:10.1093/rb/rbaf062.

[23] 王启龙, 刘鹏飞, 董潇, 等. 熊果苷调控STAT3/NF-κB通路对溃疡性结肠炎大鼠肠道菌群及肠道黏膜的影响[J]. 中国病原生物学杂志, 2025, 20(8): 1041-1045. DOI:10.13350/j.cjpb.250813.

[24] 杨玥, 周靖惟, 邹佳良, 等. 基于QbD理念的煅赭石炮制工艺优化及健康风险评估[J]. 中国实验方剂学杂志, 2025, 31(13): 187-196. DOI:10.13422/j.cnki.syfjx.20251466.