张小飞,杨强,张雅昕,邓意辉
ZHANG Xiao-fei1,YANG Qiang2,ZHANG Ya-xin3,DENG Yi-hui2(1.School of Pharmacy

• 1:陕西中医学院中药制药重点学科
• 2:沈阳药科大学药学院
• 3:洛阳市第六人民医院药剂科

摘要(Abstract)：

目的制备低分子质量肝素-枸橼酸铵混合离子梯度的阿霉素脂质体,并对其处方和制备工艺进行优化。方法采用离子交换树脂法建立脂质体内外水相低分子量肝素与枸橼酸铵的混合离子梯度,考察建立离子梯度的不同方法、脂质体处方及水化介质种类对阿霉素脂质体包封率的影响。结果最终优化的处方为m(hydrogenated soybean phosphatidylcholine,HSPC)∶m(cholesterol,CH)∶m(polyethylene glycol 2000-cholesteryl hemisuccinate,mPEG2000-CHEMS)=3.0∶1.0∶1.5;制备工艺为以100 mmol.L-1枸橼酸铵联同10 g.L-1低分子质量肝素铵为水化介质,除盐时间为15 min。加入低分子量肝素后,可使枸橼酸铵阿霉素脂质体的包封率由78.0%提高到95.5%。结论低分子量肝素的加入可显著提高枸橼酸铵阿霉素脂质体的包封率。
Objective To prepare doxorubicin liposomes by low molecular weight heparin combined with ammonium citrate ion gradients and optimize the method of preparation.Methods The mixed ion exchange resin method was used to remove combine gradients which in the exterior aqueous space of the liposome.Different methods were investigated,including establishment of ion gradients,prescriptions and hydration medium which influence encapsulation efficiency of doxorubicin liposome. Results The final optimized prescription was as follow:m(HSPC)∶m(CH)∶m(mPEG2000-CHEMS)=3.0∶1.0∶1.5,and the hydration medium was 100 mmol·L-1 ammonium citrate with 10 mg·mL-1 of low molecular weight heparin ammonia,the time of establishing ion gradients was 15 min.After addition of low molecular weight heparin,the encapsulation efficiency of ammonium citrate doxorubicin liposome was increased from 78.0% to 95.5%. Conclusions Low molecular weight heparin could improve encapsulation efficiency of ammonium citrate doxorubicin liposome.

关键词(KeyWords)： 低分子量肝素;阿霉素;脂质体;离子交换树脂;离子梯度法
low molecular weight heparin;doxorubicin;liposome;ion exchange resin;ion gradient method

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 张小飞,杨强,张雅昕,邓意辉
ZHANG Xiao-fei1,YANG Qiang2,ZHANG Ya-xin3,DENG Yi-hui2(1.School of Pharmacy

DOI: 10.14066/j.cnki.cn21-1349/r.2012.07.010

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