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15-羟基紫质-7-内酯二甲酯光动力疗法诱导的新生血管闭塞效果。

The neovessel occlusion efficacy of 15-hydroxypurpurin-7-lactone dimethyl ester induced with photodynamic therapy.

机构信息

Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.

出版信息

Photochem Photobiol. 2010 Mar-Apr;86(2):397-402. doi: 10.1111/j.1751-1097.2009.00684.x. Epub 2010 Jan 13.

Abstract

In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 15(1)-hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 microL volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 microg per embryo of G2 and a light dose of 20 J cm(-2) at a fluence rate of 40 mW cm(-2) filtered at 400-440 nm-a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light-an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer.

摘要

在这项研究中,以鸡胚绒毛尿囊膜血管闭塞为指标,评估了半合成类似物 15(1)-羟基卟啉-7-内酯二甲酯或 G2 的光动力疗法(PDT)疗效,并与维替泊芬进行了比较。早期制剂研究表明,G2 以 2.5%的 Cremophor EL 和 2.5%乙醇在生理盐水中的体系制备,注射体积达 20μL 时具有生物相容性。注射后,G2 在 1 分钟内达到峰值积累,其从血管内向血管外的渗出速度比维替泊芬稍慢。在 PDT 研究中,用胚胎中的 4μg G2 和 20J/cm2 的光剂量(在 400-440nm 处过滤的 40mW/cm2 的辐照度率),观察到毛细血管和小新生血管的闭塞,这一结果可能被认为是治疗年龄相关性黄斑变性(AMD)的最佳结果。此外,使用相同剂量的 G2 和光还观察到了大血管的部分闭塞,这对于癌症治疗是理想的。从这项研究中,我们得出结论,G2 有可能被开发为治疗 AMD 和癌症的光动力治疗药物。

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