CN104523967B - 一种柏艾胶囊作为cyp酶抑制剂的应用 - Google Patents

一种柏艾胶囊作为cyp酶抑制剂的应用 Download PDF

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CN104523967B
CN104523967B CN201410772623.0A CN201410772623A CN104523967B CN 104523967 B CN104523967 B CN 104523967B CN 201410772623 A CN201410772623 A CN 201410772623A CN 104523967 B CN104523967 B CN 104523967B
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bai
capsules
cyp
enzyme inhibitors
cyp enzyme
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CN104523967A (zh
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王海盛
闫利颖
蔡正军
龙娜
张素行
张飞鹏
张科之
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Beijing Haiyan Pharmaceutical Industry Co., Ltd., Yangzijiang Pharmaceutical Ind
GUANGDONG ZHONGXI DAYI DRUG DEVELOPMENT CO., LTD.
Yangtze River Pharmaceutical Group Co Ltd
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GUANGDONG ZHONGXI DAYI DRUG DEVELOPMENT Co Ltd
Beijing Haiyan Pharmaceutical Industry Co Ltd Yangzijiang Pharmaceutical Ind
Yangtze River Pharmaceutical Group Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/13—Coniferophyta (gymnosperms)
    • A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/62—Nymphaeaceae (Water-lily family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A61K36/804—Rehmannia

Abstract

本发明公开了一种柏艾胶囊作为CYP酶抑制剂的应用。柏艾胶囊对CYP酶具有非特异性抑制作用，比起常用的非特异性CYP酶抑制剂——1‑ABT，柏艾胶囊的水提物对最常参与药物代谢反应的7个CYP酶亚型均有更强的抑制作用，而且在原代培养的肝细胞上未显示细胞毒。

Description

一种柏艾胶囊作为CYP酶抑制剂的应用
技术领域
本发明涉及一种柏艾胶囊作为CYP酶抑制剂的应用。
背景技术
药物在体内经历吸收、分布、代谢、清除4个过程，决定了药物的给药剂量和间隔时间。研究药物在生物体内的过程，并阐述其动态规律的学科就是药代动力学，其中，药物在体内的代谢是一个重点研究对象。药物在体内主要依靠肝细胞微粒体的药酶，包括一相代谢酶(细胞色素P450黄素蛋白等)和二相代谢酶(UGT和SULT等)。代谢酶表型鉴定(phenotyping)是为了了解参与药物清除的代谢酶类型、数量及所占比例，其对于研究体内药物药物相互作用、规避不良反应以及用药风险皆有重要意义。
代谢酶表型鉴定研究中最常用的手段之一就是使用化学抑制剂，化学抑制剂分特异性P450酶抑制剂和非特异性P450酶抑制剂。其中，后者用于判断细胞色素P450是否参与了药物的代谢反应，报道的最多、最常见的非特异性P450酶抑制剂就是1-Aminobenzotriazole(1-ABT)。然而，1-ABT作为时间依赖性抑制剂，在没有预孵育的情况下，1mM的1-ABT对CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2D6的抑制效果都低于30％；经过30分钟预孵育的情况下，1mM的1-ABT对CYP2C9的抑制效果还是低于50％(Linder CD,RenaudNA,Hutzler JM.Drug Metab Dispos.2004Mar；32(3):333-9.)。
所以，使用1-ABT作为非特异性P450酶抑制剂，判断CYP酶(也称细胞色素氧化酶P450)是否参与代谢的结果并不完全可信。
发明内容
本发明所要解决的技术问题是针对技术现状提供一种柏艾胶囊作为CPY酶抑制剂的应用。
本发明解决上述技术问题所采用的技术方案为：一种柏艾胶囊作为CYP酶抑制剂的应用。
其中，所述柏艾胶囊包括如下重量份数的组分：
其中，所述柏艾胶囊的作用形式为浓度为1.0～1.5mg/mL，例如1.1mg/mL、1.2mg/mL、1.3mg/mL、1.4mg/mL的柏艾胶囊溶液。
其中，所述柏艾胶囊的作用形式为浓度为1.25mg/mL的柏艾胶囊溶液。
与现有技术相比，本发明的优点在于：柏艾胶囊对CYP酶具有较优的非特异性抑制作用，比起常用的非特异性CYP酶抑制剂——1-ABT，柏艾胶囊的水提物对最常参与药物代谢反应的7个CYP酶亚型均有更强的抑制作用，而且在原代培养的肝细胞上未显示细胞毒。因此，在代谢酶表型鉴定(phenotyping)中，柏艾胶囊可以成为一种新型抑制工具药物。
经测试，若不经预孵育，浓度为1.25mg/mL柏艾胶囊的水溶液对CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4的抑制效果皆高达70％以上，其中，对CYP2A6和CYP2E1的抑制效果稍弱，分别为38％和48％，但是其整体效果明显优于1-ABT。
具体实施方式
以下结合实施例对本发明作进一步详细描述。
本实施例的CYP酶抑制剂具体为柏艾胶囊，柏艾胶囊的主要成分包括如下重量份数的组分：
本实施例具体采用的是由扬子江药业集团有限公司生产的批次为13080642的柏艾胶囊，该柏艾胶囊各组分的配比在上述范围内；只要上述四种组分的含量在上述范围内的柏艾胶囊都可作为CYP酶的抑制剂。
柏艾胶囊的作用形式为浓度为1.25mg/mL的柏艾胶囊溶液(即柏艾胶囊的水溶液)，该浓度的柏艾胶囊溶液对CYP酶均具有较优的非特异性抑制作用。
本实施例在没有进行预孵育的前提下，分别采用常用的CYP特异性抑制剂、CYP非特异性CYP抑制剂——1-ABT以及浓度为1.25mg/mL的柏艾胶囊溶液对9个CYP酶亚型进行抑制，抑制结果见表1，表1中，各抑制剂的浓度指其水溶液的浓度。
表1.CYP抑制剂对CYP酶的抑制作用
由表可知，在不经预孵育的情况下，浓度为1.25mg/mL柏艾胶囊的水溶液对CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4的抑制效果皆高达70％以上，其中，对CYP2A6和CYP2E1的抑制效果稍弱，分别为38％和48％，根据2006年FDA颁布的指导原则(Guidance for Industry-Drug Interaction Studies-Study Design.Data Analysis,and Implications for Dosing and Labelling)，CYP2A6和CYP2E1相对于其他7种CYP酶较少参与临床重要的要药物间相互抑制，也就是较少参与药物代谢。综上所述，1.25mg/mL柏艾胶囊的水溶液对CYP药物代谢酶的整体抑制效果明显优于1-ABT。
以上内容仅为本发明的较佳实施例，对于本领域的普通技术人员，依据本发明的思想，在具体实施方式及应用范围上均会有改变之处，本说明书内容不应理解为对本发明的限制。

Claims (3)

1.一种柏艾胶囊在CYP酶抑制剂的制造中的应用；
其中，所述柏艾胶囊按重量百分比计由以下组分组成：
所述CYP酶为CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4、CYP2A6和CYP2E1中的任意一种或至少两种的组合。
2.根据权利要求1所述的应用，其特征在于：所述柏艾胶囊的作用形式为浓度为1.0～1.5mg/mL的柏艾胶囊溶液。
3.根据权利要求2所述的应用，其特征在于：所述柏艾胶囊的作用形式为浓度为1.25mg/mL的柏艾胶囊溶液。
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