| 摘要: |
| 目的:探讨0. 5%马来酸噻吗洛尔(TM)凝胶的皮肤刺激性及治疗婴幼儿血管瘤(IH)的体内药效与作用机制。方法:制
备TM 凝胶,通过新西兰兔和SD 大鼠完整/ 破损皮肤模型考察TM 凝胶单次及多次给药的刺激性。使用EOMA 小鼠血管瘤细
胞建立小鼠血管瘤模型考察TM 凝胶药效。免疫组化检测给药后瘤体组织缺氧诱导因子1α( HIF-1α)、血管内皮生长因子
(VEGF)、血管内皮细胞特异性抗原CD34 表达水平。结果:TM 凝胶单次和多次给药对新西兰兔和SD 大鼠皮肤无刺激性。药
效学实验表明,TM 凝胶能抑制小鼠血管瘤生长(P<0. 01),且用药对小鼠组织脏器无病理损伤。免疫组化结果显示,TM 凝胶可
降低瘤体组织HIF-1α、VEGF 和CD34 的表达水平(P<0. 01)。结论:TM 凝胶安全无刺激,用于治疗IH 的疗效优于参比制剂,有
望为临床治疗IH 提供新思路。 |
| 关键词: 婴幼儿 血管瘤 马来酸噻吗洛尔凝胶 体内 药效学 作用机制 |
| DOI：doi:10.13407/j.cnki. jpp.1672-108X.2025.08.002 |
|
| 基金项目:基金项目:江苏省药学会—恒瑞医院药学基金项目,编号H202309;苏州市科技发展计划项目,编号SKYD2023175;苏州市吴江区“科教兴
卫”项目,编号WWK202206;江苏省研究型医院学会-精益化用药专项科研项目,编号JY202240。 |
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| Preclinical Study on Efficacy and Safety of Timolol Maleate Gel in the Treatment of Hemangioma |
| Hang Xiaoxing1, Yang Mei2, Gao Xiaoning2, Chen Haoran2, Jin Taiwei2, Zhang Xuenong1, Song Wenlin2 |
| (1.College of Pharmacy, Suzhou University, Jiangsu Suzhou 215123, China; 2. Children’s Hospital of Suzhou Wujiang District, Jiangsu
Suzhou 215000, China) |
| Abstract: |
| Objective: To investigate the skin irritation of 0. 5% timolol maleate (TM) gel and its in vivo pharmacodynamics and
mechanism in the treatment of infantile hemangiomas (IH). Methods: The TM gel was prepared, and its skin irritation with single and
multiple administrations were investigated by using intact/ broken skin models of New Zealand rabbits and SD rats. A mouse hemangioma
model was established by using EOMA mouse hemangioendothelioma cells to investigate the therapeutic effect of TM gel.
Immunohistochemistry was performed to detect the expression levels of hypoxia-inducible factor 1α (HIF-1α), vascular endothelial
growth factor (VEGF) and vascular endothelial cell-specific antigen CD34 in tumor tissues after administration. Results: Single and
multiple administrations of TM gel had no irritation on the skin of New Zealand rabbits and SD rats. In vivo pharmacodynamic study
demonstrated that TM gel could significantly inhibit the growth of hemangiomas in mice (P<0. 01) without causing pathological damage
to tissues or organs. Immunohistochemical results indicated that TM gel significantly reduced the expression of HIF-1α, VEGF, and
CD34 in tumor tissues (P <0. 01). Conclusion: TM gel is safe and non-irritating, and its efficacy for IH is higher than reference
product, which is expected to provide a new idea for the clinical treatment of IH. |
| Key words: infants hemangioma timolol maleate gel in vivo pharmacodynamics mechanism |
