穿心莲超微粉有效成分溶出及药物代谢动力学研究
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摘要
目的:研究超微粉碎技术对穿心莲有效成分溶出量及对家兔体内药物代谢动力学参数和生物利用度的影响;对穿心莲超微粉进行其在家兔和猪体内的比较药物代谢动力学研究,为穿心莲超微粉的,临床应用提供有益借鉴和科学依据。
方法:
1、穿心莲制成细粉和超微粉,分别用水和甲醇提取,高效液相色谱法(HPLC)测定细粉和超微粉中有效成分穿心莲内酯(Andrographalide)和脱水穿心莲内酯(Dehydroandrographolide)的含量,比较穿心莲细粉和超微粉中两种成分溶出量的差异。
2、将穿心莲细粉和超微粉以2g·Kg~(-1)体重的剂量给家兔灌服,HPLC测定家兔体内穿心莲内酯和脱水穿心莲内酯的血药浓度,数据经PKS(PharmaceuticalKinetics Software)药代动力学分析软件处理,比较穿心莲细粉和超微粉中两种成分的药代动力学参数和生物利用度差异。
3、将穿心莲超微粉以4g·Kg~(-1)体重的剂量给家兔和猪灌服,比较穿心莲超微粉中穿心莲内酯和脱水穿心莲内酯在家兔和猪体内的药代动力学参数和生物利用度差异。
结果:
1、分别用水和甲醇提取后,穿心莲超微粉中的穿心莲内酯含量分别比细粉提高30.30%、92.45%,脱水穿心莲内酯含量分别提高31.00%、125.00%。
2、家兔分别灌服2g·Kg~(-1)体重穿心莲细粉和超微粉后,穿心莲内酯和脱水穿心莲内酯在体内的代谢过程均符合一级吸收二室模型。与细粉相比,家兔灌服超微粉后,穿心莲内酯的药时曲线下面积(AUC)提高59.86%,达峰时间(T_(peak))提前7.14min,达峰浓度(C_(max))增大0.60%;脱水穿心莲内酯的AUC提高124.64%,T_(peak)提前1.433min,C_(max)增大88.34%。
3、家兔灌服4g·Kg~(-1)体重穿心莲超微粉后,穿心莲内酯和脱水穿心莲内酯在体内的代谢过程均符合一级吸收二室模型;猪灌服4g·Kg~(-1)体重穿心莲超微粉后,穿心莲内酯和脱水穿心莲内酯在体内的代谢过程均符合一级吸收一室模型。与猪灌服穿心莲超微粉相比,家兔灌服穿心莲超微粉后,穿心莲内酯的AUC提高19.74%,T_(peak)提前26min,C_(max)增大12.47%;脱水穿心莲内酯的AUC提高2651.10%,T_(peak)提前10min,C_(max)提高2174.42%。
结论:
1、超微粉碎技术可显著提高穿心莲药材中有效成分穿心莲内酯和脱水穿心莲内酯的溶出量。
2、与灌服细粉相比,家兔灌服穿心莲超微粉后,体内穿心莲内酯和脱水穿心莲内酯的生物利用度均有提高,其中,脱水穿心莲内酯的生物利用度有明显提高。
3、家兔和猪分别灌服穿心莲超微粉,家兔对其有效成分穿心莲内酯和脱水穿心莲内酯的生物利用度高于猪,其中,脱水穿心莲内酯的生物利用度提高显著。
Objective:To study the effects of dissolution contents and Pharmacokinetics parameters and the bioavailability in rabbits of the components in ultramicro pulverization of Andrographis paniculata.Pharmacokinetics characteristics in rabbits and piglets were compared after they were administered with ultramicro-pulverised powder to provide useful reference and scientific testify for the clinical application of the ultramicro-pulverised powder of Andrographis paniculata in rabbits and piglets.
Metheds:
1.The Andrographis paniculata was made into ordinary powder and ultramicro-pulverised powder.High performance liquid chromatography(HPLC)was applied to determine the contents of Andrographalide and Dehydroandrographolide from ordinary powder and ultramicro-pulverised powder treated with water and methanol to compare the dissolution differences.
2.The plasma concentration of Andrographalide and Dehydroandrographolide was determined by HPLC in two groups of rabbits after they were administered with ultramicro-pulverised powder and with ordinary powder of Andrographis paniculata 2g·Kg~(-1)·BW dosage by gastrogavage,respectively.The plasma concentration-time data of Andrographalide and Dehydroandrographolide was analyzed by Pharmaceutical Kinetics Software(PKS).Pharmacokinetic parameters and the bioavailabilities in both groups were compared.
3.HPLC was applied to determine the plamsa concentrations in rabbits and piglets after they were administered with ultramicro-pulverised powder of Andrographis paniculata 4g·Kg~(-1)·BW dosage by gastrogavage,respectively. Pharmacokineties parameters and the bioavailabilities in both groups were compared.
Results:
1.Compared with ordinary powder,the contents of Andrographalide from ultramicro-pulverised powder of Andrographis paniculata raised 30.30%and 92.45% after treated with water and methanol,while the contents of Dehydroandrographolide raised 31.00%and 125.00%.
2.Both the concentration-time curves of Andrographalide and Dehydroandrographolide were Confirmed to two compartment model after the rabbits were administered with.the ordinary powder and ultramicro-pulverised powder of Andrographis paniculata 2g·Kg~(-1)·BW dosage by gastrogavage,respectively. Compared with taking ordinary powder,the Andrographalide's area under concentration-time(AUC)raised 59.86%,the tisne reach the maximum consistency (T_(peak))was 7.14 minutes premature,and the maximum consistency(C_(max))enlarged 0.60%after the rabbits were administered with ultramicro-pulverised powde;the Dehydrographolide's AUC raised 124.64%,T_(peak)was 1.433 minutes premature,and C_(max)enlarged 88.34%.
3.Both the concentration-time curves of Andrographalide and Dehydroandrographolide were confirmed to two compartment model after the rabbits were administered with ultramicro-pulverised powder of Andrographis paniculata 4g·Kg~(-1)·BW dosage by gastrogavage,while the two components above were confirmed to one compartment model after the piglets were administered with ultramicro-pulverised powder 4g·Kg~(-1)·Bw dosage by gastrogavage,respectively. Compared with piglets,the Andrographolide's AUC raised 19.74%,T_(peak)was 26 minutes premature,and C_(max)enlarged 12.47%after the rabbits were administered with ultramicro-pulverised powder;the Dehydrographolide's AUC raised 2651.10%, T_(peak)was 10 minutes premature,and C(max)enlarged 2174.42%.
Conclusion:
1.The technique of ultromicro-pulverization promotes the dissolution contents of Andrographalide and Dehydroandrographolide of Andrographis paniculata.
2.Compared with ordinary powder,the bioavailabilites of Andrographalide and Dehydroandrographolide were higher after the rabbits were administered with ultramicro-pulverised powder of Andrographis paniculata,especially,the bioavailability of Dehydroandrographolide raised obviously.
3.The bioavailabilities of Andrographalide and Dehydroandrographolide after the rabbits were administered with ultramicro-pulverised powder were higher than piglet,especially,the bioavailability of Dehydroandrographolide raised obviously.
方法:
1、穿心莲制成细粉和超微粉,分别用水和甲醇提取,高效液相色谱法(HPLC)测定细粉和超微粉中有效成分穿心莲内酯(Andrographalide)和脱水穿心莲内酯(Dehydroandrographolide)的含量,比较穿心莲细粉和超微粉中两种成分溶出量的差异。
2、将穿心莲细粉和超微粉以2g·Kg~(-1)体重的剂量给家兔灌服,HPLC测定家兔体内穿心莲内酯和脱水穿心莲内酯的血药浓度,数据经PKS(PharmaceuticalKinetics Software)药代动力学分析软件处理,比较穿心莲细粉和超微粉中两种成分的药代动力学参数和生物利用度差异。
3、将穿心莲超微粉以4g·Kg~(-1)体重的剂量给家兔和猪灌服,比较穿心莲超微粉中穿心莲内酯和脱水穿心莲内酯在家兔和猪体内的药代动力学参数和生物利用度差异。
结果:
1、分别用水和甲醇提取后,穿心莲超微粉中的穿心莲内酯含量分别比细粉提高30.30%、92.45%,脱水穿心莲内酯含量分别提高31.00%、125.00%。
2、家兔分别灌服2g·Kg~(-1)体重穿心莲细粉和超微粉后,穿心莲内酯和脱水穿心莲内酯在体内的代谢过程均符合一级吸收二室模型。与细粉相比,家兔灌服超微粉后,穿心莲内酯的药时曲线下面积(AUC)提高59.86%,达峰时间(T_(peak))提前7.14min,达峰浓度(C_(max))增大0.60%;脱水穿心莲内酯的AUC提高124.64%,T_(peak)提前1.433min,C_(max)增大88.34%。
3、家兔灌服4g·Kg~(-1)体重穿心莲超微粉后,穿心莲内酯和脱水穿心莲内酯在体内的代谢过程均符合一级吸收二室模型;猪灌服4g·Kg~(-1)体重穿心莲超微粉后,穿心莲内酯和脱水穿心莲内酯在体内的代谢过程均符合一级吸收一室模型。与猪灌服穿心莲超微粉相比,家兔灌服穿心莲超微粉后,穿心莲内酯的AUC提高19.74%,T_(peak)提前26min,C_(max)增大12.47%;脱水穿心莲内酯的AUC提高2651.10%,T_(peak)提前10min,C_(max)提高2174.42%。
结论:
1、超微粉碎技术可显著提高穿心莲药材中有效成分穿心莲内酯和脱水穿心莲内酯的溶出量。
2、与灌服细粉相比,家兔灌服穿心莲超微粉后,体内穿心莲内酯和脱水穿心莲内酯的生物利用度均有提高,其中,脱水穿心莲内酯的生物利用度有明显提高。
3、家兔和猪分别灌服穿心莲超微粉,家兔对其有效成分穿心莲内酯和脱水穿心莲内酯的生物利用度高于猪,其中,脱水穿心莲内酯的生物利用度提高显著。
Objective:To study the effects of dissolution contents and Pharmacokinetics parameters and the bioavailability in rabbits of the components in ultramicro pulverization of Andrographis paniculata.Pharmacokinetics characteristics in rabbits and piglets were compared after they were administered with ultramicro-pulverised powder to provide useful reference and scientific testify for the clinical application of the ultramicro-pulverised powder of Andrographis paniculata in rabbits and piglets.
Metheds:
1.The Andrographis paniculata was made into ordinary powder and ultramicro-pulverised powder.High performance liquid chromatography(HPLC)was applied to determine the contents of Andrographalide and Dehydroandrographolide from ordinary powder and ultramicro-pulverised powder treated with water and methanol to compare the dissolution differences.
2.The plasma concentration of Andrographalide and Dehydroandrographolide was determined by HPLC in two groups of rabbits after they were administered with ultramicro-pulverised powder and with ordinary powder of Andrographis paniculata 2g·Kg~(-1)·BW dosage by gastrogavage,respectively.The plasma concentration-time data of Andrographalide and Dehydroandrographolide was analyzed by Pharmaceutical Kinetics Software(PKS).Pharmacokinetic parameters and the bioavailabilities in both groups were compared.
3.HPLC was applied to determine the plamsa concentrations in rabbits and piglets after they were administered with ultramicro-pulverised powder of Andrographis paniculata 4g·Kg~(-1)·BW dosage by gastrogavage,respectively. Pharmacokineties parameters and the bioavailabilities in both groups were compared.
Results:
1.Compared with ordinary powder,the contents of Andrographalide from ultramicro-pulverised powder of Andrographis paniculata raised 30.30%and 92.45% after treated with water and methanol,while the contents of Dehydroandrographolide raised 31.00%and 125.00%.
2.Both the concentration-time curves of Andrographalide and Dehydroandrographolide were Confirmed to two compartment model after the rabbits were administered with.the ordinary powder and ultramicro-pulverised powder of Andrographis paniculata 2g·Kg~(-1)·BW dosage by gastrogavage,respectively. Compared with taking ordinary powder,the Andrographalide's area under concentration-time(AUC)raised 59.86%,the tisne reach the maximum consistency (T_(peak))was 7.14 minutes premature,and the maximum consistency(C_(max))enlarged 0.60%after the rabbits were administered with ultramicro-pulverised powde;the Dehydrographolide's AUC raised 124.64%,T_(peak)was 1.433 minutes premature,and C_(max)enlarged 88.34%.
3.Both the concentration-time curves of Andrographalide and Dehydroandrographolide were confirmed to two compartment model after the rabbits were administered with ultramicro-pulverised powder of Andrographis paniculata 4g·Kg~(-1)·BW dosage by gastrogavage,while the two components above were confirmed to one compartment model after the piglets were administered with ultramicro-pulverised powder 4g·Kg~(-1)·Bw dosage by gastrogavage,respectively. Compared with piglets,the Andrographolide's AUC raised 19.74%,T_(peak)was 26 minutes premature,and C_(max)enlarged 12.47%after the rabbits were administered with ultramicro-pulverised powder;the Dehydrographolide's AUC raised 2651.10%, T_(peak)was 10 minutes premature,and C(max)enlarged 2174.42%.
Conclusion:
1.The technique of ultromicro-pulverization promotes the dissolution contents of Andrographalide and Dehydroandrographolide of Andrographis paniculata.
2.Compared with ordinary powder,the bioavailabilites of Andrographalide and Dehydroandrographolide were higher after the rabbits were administered with ultramicro-pulverised powder of Andrographis paniculata,especially,the bioavailability of Dehydroandrographolide raised obviously.
3.The bioavailabilities of Andrographalide and Dehydroandrographolide after the rabbits were administered with ultramicro-pulverised powder were higher than piglet,especially,the bioavailability of Dehydroandrographolide raised obviously.
引文
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