β-环糊精聚乙二醇羟基喜树碱高聚物的合成及其载药量研究

Synthesis of polymer β-CD-PEG-HCPT and its drug loading capacity

目的合成β-环糊精聚乙二醇羟基喜树碱高聚物(β-CD-PEG-HCPT)并研究其载药量。方法以β-环糊精和4-4′联苯二磺酰氯为起始原料,通过酰化反应、碘代反应、取代反应、酰化反应得到聚乙二醇-β-环糊精(β-CD-PEG)。采用羟基喜树碱(HCPT)为起始原料,利用乙酰基对10位羟基进行保护,再利用二氯甲烷/甲醇/乙酰氯这种温和的系统脱去乙酰基,得到乙酰羟基喜树碱甘氨酸酯(Ac-HCPT-Gly)。β-CD-PEG和Ac-HCPT-Gly反应得到目标产物β-CD-PEG-HCPT。结果合成了目标产物β-CD-PEG-HCPT,其结构通过1H-NMR确证。HCPT的载药量是4.3%。结论改进了β-CD-PEG-HCPT的合成工艺,操作简单、成本低、收率较高。

Objective To synthesize β-CD-PEG-HCPT and study its drug loading capacity. Methods β-Cyclodextrin（β-CD） and biphenyl-4,4＇-disulfonyl chloride were used as the starting materials to synthesize β-CD-PEG by acylation reaction, iodination reaction, substitution reaction, and acylation reaction. HCPT was used as the starting materials, and 10-OH of HCPT was protected by the acetyl group and deprotected by the system of CH2 Cl2/CH3 OH/acetyl chloride to synthesize Ac-HCPT-Gly. β-CD-PEG and Ac-HCPT-Gly were reacted to synthesize the target compound β-CD-PEG-HCPT. Results The target compound β-CD-PEG-HCPT was synthesized, and the structure has been confirmed by 1 H-NMR. The drug loading of HCPT was 4.3%. Conclusion This study improves the synthesis process ofβ-CD-PEG-HCPT with simple operation, low cost, and high yield.