正交设计优化磷酸川芎嗪-冰片脂质体的制备工艺
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摘要
目的优化磷酸川芎嗪(TMPP)-冰片(B)脂质体的制备方法。方法采用乙醇注入式(NH_4)_2SO_4梯度法制备TMPP-B脂质体,利用超速离心法测定包封率。以包封率为考察指标,通过正交设计考察磷脂-胆固醇质量比(因素A)、TMPP-(磷脂+胆固醇)质量比(因素B)、水化时间(因素C)和(NH_4)_2SO_4浓度(因素D)对制备工艺的影响。结果对TMPP-B脂质体包封率的影响顺序为A> D> B> C,最佳工艺条件为A_1B_2C_1D_2。按此优化工艺制备3批TMPP-B脂质体,其平均粒径为(136.10±6.30) nm,分布均匀,Zeta电位为(-35.70±3.60)mV,TMPP包封率为(73.14±0.71)%。结论该制备工艺的脂质体包封率高,分布均匀,形态好,质量稳定,该方法简单合理。
Objective To optimize the preparation technology of tetramethylpyrazine phosphate(TMPP)-borneol(B) liposome.Methods The TMPP-B liposomes were prepared by the ethanol injection method combined with the(NH_4)_2SO_4 gradient method.The encapsulation efficiency was determined by ultracentrifugation.With the encapsulation efficiency as index,the effect of the weight ratio of phospholipid to cholesterol(factor A),weight ratio of TMPP to phospholipid and cholesterol(factor B),hydration time(factor C) and concentration of(NH_4)_2SO_4(factor D) on the preparation process were investigated by orthogonal design.Results The order of influence on encapsulation efficiency of TMPP-B liposomes was A > D > B > C,and the optimum preparation technology conditions were A_1B_2C_1D_2.Three batches of TMPP-B liposomes were prepared according to the optimum technology conditions,the average particle size was(136.10 ±6.30) nm with uniform distribution,the average Zeta potential was(-35.70 ± 3.60) mV,and the average encapsulation efficiency of TMPP was(73.14 ± 0.71) %.Conclusion The liposomes prepared by this method have high encapsulation efficiency,uniform distribution,good morphology and stable quality.The method is simple and reasonable.
Objective To optimize the preparation technology of tetramethylpyrazine phosphate(TMPP)-borneol(B) liposome.Methods The TMPP-B liposomes were prepared by the ethanol injection method combined with the(NH_4)_2SO_4 gradient method.The encapsulation efficiency was determined by ultracentrifugation.With the encapsulation efficiency as index,the effect of the weight ratio of phospholipid to cholesterol(factor A),weight ratio of TMPP to phospholipid and cholesterol(factor B),hydration time(factor C) and concentration of(NH_4)_2SO_4(factor D) on the preparation process were investigated by orthogonal design.Results The order of influence on encapsulation efficiency of TMPP-B liposomes was A > D > B > C,and the optimum preparation technology conditions were A_1B_2C_1D_2.Three batches of TMPP-B liposomes were prepared according to the optimum technology conditions,the average particle size was(136.10 ±6.30) nm with uniform distribution,the average Zeta potential was(-35.70 ± 3.60) mV,and the average encapsulation efficiency of TMPP was(73.14 ± 0.71) %.Conclusion The liposomes prepared by this method have high encapsulation efficiency,uniform distribution,good morphology and stable quality.The method is simple and reasonable.
引文
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[12]王勇,张忠义,徐峰,等.冰片对川芎嗪血药浓度和在脑中分布的影响[J].中国药业,2006,15(1):30-31.
[13]张雨曦,李万玉.盐酸川芎嗪脂质体的制备及其理化性质的表征[J].华西药学杂志,2014,29(2):113-115.
[14]杜兆香,鞠建峰.正交试验优选盐酸川芎嗪脂质体的制备工艺[J].中国药房,2011,22(35):3303-3304.
[2]薛梅苓.丹参川芎嗪注射液联合曲美他嗪治疗冠心病心绞痛40例[J].中国药业,2016,25(16):93-96.
[3]朱艳华,王兴刚,李冰菲.盐酸川芎嗪制剂研究综述[J].中国药业,2015,24(3):95-96.
[4]衡卫卫,朱亮,李君.丹参川芎嗪联合前列地尔对急性脑梗死患者神经功能缺损的影响[J].中国药业,2018,27(14):47-50.
[5]LOU YQ,ZHANG H,CAO X,et al.The pharmacokinetics and disposition of tetramethylpyrazine phosphate in dogs and rats[J].Yao Xue Xue Bao,1986,21(7):481-487.
[6]FENG J,LI F,ZHAO Y,et al.Brain pharmacokinetics of tetramethylpyrazine after intranasal and intravenous administration in awake rats[J].Int J Pharm,2009,375(1-2):55-60.
[7]ILLUM L.Nasal drug delivery:new developments and strategies[J].Drug Discov Today,2002,7(23):1184-1189.
[8]吴慧,吴闻折.经鼻给药增加药物靶向的制剂方法[J].世界临床药物,2015,36(1):50-55.
[9]盛竹君,徐维平,徐婷娟,等.脂质体药物传输系统的研究新进展[J].中国药业,2015,24(23):6-9.
[10]晏亦林,周莉玲,叶勇,等.磷酸川芎嗪脂质体大鼠在体鼻黏膜吸收研究[J].中药新药与临床药理,2007,18(5):406-408.
[11]刘煜德,孙寒静,李荣,等.冰片对川芎嗪经鼻腔吸收入脑的影响[J].中国中药杂志,2008,33(3):259-261.
[12]王勇,张忠义,徐峰,等.冰片对川芎嗪血药浓度和在脑中分布的影响[J].中国药业,2006,15(1):30-31.
[13]张雨曦,李万玉.盐酸川芎嗪脂质体的制备及其理化性质的表征[J].华西药学杂志,2014,29(2):113-115.
[14]杜兆香,鞠建峰.正交试验优选盐酸川芎嗪脂质体的制备工艺[J].中国药房,2011,22(35):3303-3304.