枳壳总黄酮的质量控制及肠吸收研究
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摘要
本文针对中药有效部位的特点,进一步完善了有效部位的质量控制方法;初步探讨了有效部位的肠吸收特性和吸收动力学,为有效部位中药的剂型设计及体内过程研究提供依据。
采用指标性成分、总成分含量测定及指纹图谱分析结合的方法,建立了枳壳有效部位质量控制体系。对10个批次的枳壳总黄酮分析结果显示,不同批次样品的柚皮苷、新橙皮苷和总黄酮含量有一定的波动,但批次间指纹图谱相似度具有高度一致性,说明产品质量稳定。该分析方法能有效控制有效部位产品的稳定性,全面反映产品内在质量。
采用大鼠离体肠囊外翻模型,考察了枳壳总黄酮主要成分柚皮苷和新橙皮苷的肠吸收机制,以及不同肠段、药物浓度和维拉帕米等因素对它们吸收的影响,比较了柚皮苷和新橙皮苷在单体给药和枳壳总黄酮给药时的吸收差异。结果表明,柚皮苷和新橙皮苷在大鼠肠道各段均有吸收,吸收百分率按十二指肠、空肠、回肠和结肠依次下降;在试验时间和浓度范围内,按一级吸收动力学特征,符合被动扩散的特征;随着pH值的增加,柚皮苷和新橙皮苷的累积吸收量都有下降的趋势;维拉帕米的存在使柚皮苷和新橙皮苷从黏膜面向浆膜面的转运有明显增加。枳壳总黄酮中的共存物质会促进柚皮苷和新橙皮苷的吸收。
采用大鼠在体肠灌流模型,考察了枳壳总黄酮和赤芍总苷两个有效部位合用时,其中主要成分柚皮苷、新橙皮苷和芍药苷的肠吸收动力学,并比较了两个有效部位合用和单用时的吸收差异。结果显示,柚皮苷、新橙皮苷和芍药苷不同浓度时的K_a无显著性差异,符合被动扩散的吸收特征,属于一级动力学过程。在两个有效部位单用和合用时,柚皮苷、新橙皮苷和芍药苷的K_a无显著性差异,说明合用对其中成分的吸收无显著影响。
In this thesis, the method for the quality control of the effective fraction of Traditional Chinese Medicines was further developed. Moreover, the absorption characteristics and kinetics of the effective fraction were also studied. The research results will provide information for dosage form design and physiological disposition of the effective fraction.
Based on index components content, overall composition content and finger-print analysis, an approach was proposed and applied to the quality control of the total flavonoids of Fructus Aurantii. The contents of naringin, neohesperidin and the total flavonoids, and fingerprinting analysis for different batches of the effective fractions of Fructus Aurantii. were investigated. The results showed that the contents of the index compounds and the total flavonoids in different batches of the effective fraction were fluctuated, but the similarities of their fingerprints were high conformity. It indicates that the proposed method can effectively control the quality of effective fraction
The intestinal absorption mechanism of naringin and neohesperidin was studied by the everted rat gut sacs. According to the absorption parameters, it was a first-order process with the passive diffusion mechanism in the range of the tested concentration, and could be absorbed in all segment of intestine in rat The absorption decreased with the raise of pH, and increased as verapamil existed. Other substances in the total flavonoids would promote the absorption of these two compounds.
The absorption kinetics of the total flavonoids of Fructus Aurantii and the total glycosides of Radix Paeoniae Rubra was studied by in situ recirculation. as well as the difference between them when using co-administratively and exclusively. The results indicated that there was no significant difference of K_a's value of naringin, neohesperidin and paeoniflofin in different concentrations, their absorptions in rat intestinal were fit to a first-order process with the passive diffusion mechanism. No significant absorption difference was found between co-administration and exclusive situations too.
采用指标性成分、总成分含量测定及指纹图谱分析结合的方法,建立了枳壳有效部位质量控制体系。对10个批次的枳壳总黄酮分析结果显示,不同批次样品的柚皮苷、新橙皮苷和总黄酮含量有一定的波动,但批次间指纹图谱相似度具有高度一致性,说明产品质量稳定。该分析方法能有效控制有效部位产品的稳定性,全面反映产品内在质量。
采用大鼠离体肠囊外翻模型,考察了枳壳总黄酮主要成分柚皮苷和新橙皮苷的肠吸收机制,以及不同肠段、药物浓度和维拉帕米等因素对它们吸收的影响,比较了柚皮苷和新橙皮苷在单体给药和枳壳总黄酮给药时的吸收差异。结果表明,柚皮苷和新橙皮苷在大鼠肠道各段均有吸收,吸收百分率按十二指肠、空肠、回肠和结肠依次下降;在试验时间和浓度范围内,按一级吸收动力学特征,符合被动扩散的特征;随着pH值的增加,柚皮苷和新橙皮苷的累积吸收量都有下降的趋势;维拉帕米的存在使柚皮苷和新橙皮苷从黏膜面向浆膜面的转运有明显增加。枳壳总黄酮中的共存物质会促进柚皮苷和新橙皮苷的吸收。
采用大鼠在体肠灌流模型,考察了枳壳总黄酮和赤芍总苷两个有效部位合用时,其中主要成分柚皮苷、新橙皮苷和芍药苷的肠吸收动力学,并比较了两个有效部位合用和单用时的吸收差异。结果显示,柚皮苷、新橙皮苷和芍药苷不同浓度时的K_a无显著性差异,符合被动扩散的吸收特征,属于一级动力学过程。在两个有效部位单用和合用时,柚皮苷、新橙皮苷和芍药苷的K_a无显著性差异,说明合用对其中成分的吸收无显著影响。
In this thesis, the method for the quality control of the effective fraction of Traditional Chinese Medicines was further developed. Moreover, the absorption characteristics and kinetics of the effective fraction were also studied. The research results will provide information for dosage form design and physiological disposition of the effective fraction.
Based on index components content, overall composition content and finger-print analysis, an approach was proposed and applied to the quality control of the total flavonoids of Fructus Aurantii. The contents of naringin, neohesperidin and the total flavonoids, and fingerprinting analysis for different batches of the effective fractions of Fructus Aurantii. were investigated. The results showed that the contents of the index compounds and the total flavonoids in different batches of the effective fraction were fluctuated, but the similarities of their fingerprints were high conformity. It indicates that the proposed method can effectively control the quality of effective fraction
The intestinal absorption mechanism of naringin and neohesperidin was studied by the everted rat gut sacs. According to the absorption parameters, it was a first-order process with the passive diffusion mechanism in the range of the tested concentration, and could be absorbed in all segment of intestine in rat The absorption decreased with the raise of pH, and increased as verapamil existed. Other substances in the total flavonoids would promote the absorption of these two compounds.
The absorption kinetics of the total flavonoids of Fructus Aurantii and the total glycosides of Radix Paeoniae Rubra was studied by in situ recirculation. as well as the difference between them when using co-administratively and exclusively. The results indicated that there was no significant difference of K_a's value of naringin, neohesperidin and paeoniflofin in different concentrations, their absorptions in rat intestinal were fit to a first-order process with the passive diffusion mechanism. No significant absorption difference was found between co-administration and exclusive situations too.
引文
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