几种抗结核杆菌包合物的制备与活性研究
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摘要
以β-环糊精为药物载体,采用饱和水溶液法制备了吡嗪酰胺-β-环糊精包合物、异烟肼-β-环糊精包合物、异烟肼利福霉素腙-β-环糊精包合物,采用冷冻干燥法制备了胸腺五肽-β-环糊精包合物。吡嗪酰胺与β-环糊精的最佳包合工艺条件为:吡嗪酰胺与β-环糊精物质的量比1.5∶1、包合温度70℃、包合时间1.03 h,此条件下的综合评价为96.18%。异烟肼与β-环糊精的最佳包合工艺条件为:异烟肼与β-环糊精物质的量比1.5∶1、包合温度30℃、包合时间0.5 h,此条件下的综合评价为87.80%。异烟肼利福霉素腙与β-环糊精的最佳包合工艺条件为:异烟肼利福霉素腙与β-环糊精物质的量比1.5∶1、包合温度70℃、包合时间1.08 h,此条件下的综合评价为90.83%。胸腺五肽与β-环糊精的最佳包合工艺条件为:胸腺五肽与β-环糊精物质的量比1.5∶1、包合温度70℃、包合时间1.15 h,此条件下的综合评价为90.03%。包合后药物的水溶解性和热稳定性得到明显改善,具有较好的抗结核杆菌活性。
Using β-cyclodextrin as a drug carrier,we prepared pyrazinamide-β-cyclodextrin inclusion complex,isoniazid-β-cyclodextrin inclusion complex,isoniazid Rifamycin-β-cyclodextrin inclusion complex by a saturated solution method,and prepared thymopentin-β-cyclodextrin inclusion complex by a freeze-drying method.The comprehensive index of assessment is 96.18% under the optimum inclusion conditions of pyrazinamide and β-cyclodextrin as follows:the molar ratio of pyrazinamide and β-cyclodextrin is 1.5∶1,the inclusion temperature is 70 ℃,and the inclusion time is 1.03 h.The comprehensive index of assessment is 87.80% under the optimum inclusion conditions of isoniazid and β-cyclodextrin as follows:the molar ratio of isoniazid and β-cyclodextrin is 1.5∶1,the inclusion temperature is 30 ℃,and the inclusion time is 0.5 h.The comprehensive index of assessment is 90.83% under the optimum inclusion conditions of isoniazid Rifamycin and β-cyclodextrin as follows:the molar ratio of isoniazid Rifamycin and β-cyclodextrin is 1.5∶1,the inclusion temperature is 70 ℃,and the inclusion time is 1.08 h.The comprehensive index of assessment is 90.03% under the optimum inclusion conditions of thymopentin and β-cyclodextrin as follows:the molar ratio of thymopentin and β-cyclodextrin is 1.5∶1,the inclusion temperature is 70 ℃,and the inclusion time is 1.15 h.The water solubility and thermal stability of drug after inclusion improve obviously,and the inclusion complex has good anti-Mycobacterium tuberculosis activity.
Using β-cyclodextrin as a drug carrier,we prepared pyrazinamide-β-cyclodextrin inclusion complex,isoniazid-β-cyclodextrin inclusion complex,isoniazid Rifamycin-β-cyclodextrin inclusion complex by a saturated solution method,and prepared thymopentin-β-cyclodextrin inclusion complex by a freeze-drying method.The comprehensive index of assessment is 96.18% under the optimum inclusion conditions of pyrazinamide and β-cyclodextrin as follows:the molar ratio of pyrazinamide and β-cyclodextrin is 1.5∶1,the inclusion temperature is 70 ℃,and the inclusion time is 1.03 h.The comprehensive index of assessment is 87.80% under the optimum inclusion conditions of isoniazid and β-cyclodextrin as follows:the molar ratio of isoniazid and β-cyclodextrin is 1.5∶1,the inclusion temperature is 30 ℃,and the inclusion time is 0.5 h.The comprehensive index of assessment is 90.83% under the optimum inclusion conditions of isoniazid Rifamycin and β-cyclodextrin as follows:the molar ratio of isoniazid Rifamycin and β-cyclodextrin is 1.5∶1,the inclusion temperature is 70 ℃,and the inclusion time is 1.08 h.The comprehensive index of assessment is 90.03% under the optimum inclusion conditions of thymopentin and β-cyclodextrin as follows:the molar ratio of thymopentin and β-cyclodextrin is 1.5∶1,the inclusion temperature is 70 ℃,and the inclusion time is 1.15 h.The water solubility and thermal stability of drug after inclusion improve obviously,and the inclusion complex has good anti-Mycobacterium tuberculosis activity.
引文
[1] 陈静.结核病的预防与控制[J].基层医学论坛,2015(3):359-360.
[2] 李亚飞,金利群,柳志强,等.吡嗪酰胺的研究进展[J].中国现代应用药学,2010,27(4):307-312.LI Y F,JIN L Q,LIU Z Q,et al.The research progress on pyrazinamide[J].Chinese Journal of Modern Applied Pharmacy,2010,27(4):307-312.
[3] MARISA D,RUDITO M,ZAGITA M G,et al.Hepatotoxicity effect of Rifampicin and isoniazid via chlorinative stress pathway mechanism in-vitro[J].International Journal of Toxicological & Pharmacological Research,2016,8(1):18-22.
[4] 邴林.联合应用异烟肼和胸腺五肽治疗复治菌阳肺结核的效果分析[J].临床医药文献电子杂志,2017,4(36):7053-7054.
[5] 杨阳.环糊精包合技术在药物制剂中的应用[J].黑龙江科技信息,2011(7):63.
[6] 赵永亮,管景帅,温金娥,等.β-环糊精研究及应用进展[J].河南工业大学学报(自然科学版),2014,35(6):97-102.ZHAO Y L,GUAN J S,WEN J E,et al.Progress on research and application of β-cyclodextrin[J].Journal of Henan University of Technology(Natural Science Edition),2014,35(6):97-102.
[7] SAHA S,ROY A,ROY K,et al.Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules[J].Scientific Reports,2016,6:35764.
[8] 张冕.超速离心-HPLC法测定胸腺五肽脂质体的包封率[J].荆楚理工学院学报,2012,27(2):12-14.
[9] 陈亮平,黄颖.紫外分光光度法及毛细管电泳法测定烷基酚与环糊精的包合常数[J].分析测试学报,2015,34(7):836-839.CHEN L P,HUANG Y.Measurement of equilibrium constants between β-cyclodextrin and alkylphenols by UV spectrophotometry and capillary electrophoresis[J].Journal of Instrumental Analysis,2015,34(7):836-839.
[10] 王玮云,邹明,张启迪.恩诺沙星-羟丙基-β-环糊精包合物的制备[J].动物医学进展,2012,33(4):72-75.WANG W Y,ZOU M,ZHANG Q D.Preparation of Enrofloxacin-hydroxypropyl-β-cyclodextrin inclusion complex[J].Progress in Veterinary Medicine,2012,33(4):72-75.
[11] DARTOIS E.CO clathrate hydrate:near to mid-IR spectroscopic signatures[J].Icarus,2010,212(2):950-956.
[12] MASWADEH H M.Incompatibility study of Ibuprofen in ternary interactive mixture by using differential scanning calorimetry[J].Journal of Thermal Analysis & Calorimetry,2016,123(3):1-9.
[2] 李亚飞,金利群,柳志强,等.吡嗪酰胺的研究进展[J].中国现代应用药学,2010,27(4):307-312.LI Y F,JIN L Q,LIU Z Q,et al.The research progress on pyrazinamide[J].Chinese Journal of Modern Applied Pharmacy,2010,27(4):307-312.
[3] MARISA D,RUDITO M,ZAGITA M G,et al.Hepatotoxicity effect of Rifampicin and isoniazid via chlorinative stress pathway mechanism in-vitro[J].International Journal of Toxicological & Pharmacological Research,2016,8(1):18-22.
[4] 邴林.联合应用异烟肼和胸腺五肽治疗复治菌阳肺结核的效果分析[J].临床医药文献电子杂志,2017,4(36):7053-7054.
[5] 杨阳.环糊精包合技术在药物制剂中的应用[J].黑龙江科技信息,2011(7):63.
[6] 赵永亮,管景帅,温金娥,等.β-环糊精研究及应用进展[J].河南工业大学学报(自然科学版),2014,35(6):97-102.ZHAO Y L,GUAN J S,WEN J E,et al.Progress on research and application of β-cyclodextrin[J].Journal of Henan University of Technology(Natural Science Edition),2014,35(6):97-102.
[7] SAHA S,ROY A,ROY K,et al.Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules[J].Scientific Reports,2016,6:35764.
[8] 张冕.超速离心-HPLC法测定胸腺五肽脂质体的包封率[J].荆楚理工学院学报,2012,27(2):12-14.
[9] 陈亮平,黄颖.紫外分光光度法及毛细管电泳法测定烷基酚与环糊精的包合常数[J].分析测试学报,2015,34(7):836-839.CHEN L P,HUANG Y.Measurement of equilibrium constants between β-cyclodextrin and alkylphenols by UV spectrophotometry and capillary electrophoresis[J].Journal of Instrumental Analysis,2015,34(7):836-839.
[10] 王玮云,邹明,张启迪.恩诺沙星-羟丙基-β-环糊精包合物的制备[J].动物医学进展,2012,33(4):72-75.WANG W Y,ZOU M,ZHANG Q D.Preparation of Enrofloxacin-hydroxypropyl-β-cyclodextrin inclusion complex[J].Progress in Veterinary Medicine,2012,33(4):72-75.
[11] DARTOIS E.CO clathrate hydrate:near to mid-IR spectroscopic signatures[J].Icarus,2010,212(2):950-956.
[12] MASWADEH H M.Incompatibility study of Ibuprofen in ternary interactive mixture by using differential scanning calorimetry[J].Journal of Thermal Analysis & Calorimetry,2016,123(3):1-9.