CN105044300A - Method for adjusting dosage of medicinal material coptidis rhizoma on basis of anti-dysentery bacillus effect equivalency factor - Google Patents

Method for adjusting dosage of medicinal material coptidis rhizoma on basis of anti-dysentery bacillus effect equivalency factor Download PDF

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CN105044300A
CN105044300A CN201510341707.3A CN201510341707A CN105044300A CN 105044300 A CN105044300 A CN 105044300A CN 201510341707 A CN201510341707 A CN 201510341707A CN 105044300 A CN105044300 A CN 105044300A
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coptidis rhizoma
coptidis
rhizoma coptidis
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shigella
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肖小河
王伽伯
熊吟
董芹
章从恩
李刚
严桂林
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China Medico Corp
Fifth Medical Center of PLA General Hospital
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Abstract

The invention provides a method for adjusting dosage of a medicinal material coptidis rhizoma on the basis of an anti-dysentery bacillus effect equivalency factor. The method comprises the following steps: (1), measuring the contents of active ingredients in the medicinal material coptidis rhizoma; (2), calculating an anti-dysentery bacillus effect equivalency factor of the coptidis rhizoma; (3), adjusting the dosage of the medicinal material coptidis rhizoma according to the anti-dysentery bacillus effect equivalency factor. According to the invention, a clinical function is used as guidance, the anti-dysentery bacillus effect equivalency factor can represent the coptidis rhizoma anti-dysentery bacillus pharmacological activity, and guide establishment and improvement of a clinical individualized medication standard; the problem of contribution difference of multiple component indexes to the efficacy of the coptidis rhizoma is solved, and comprehensiveness, quantization and integration of the coptidis rhizoma quality evaluation are realized; the efficacy of the coptidis rhizoma can be represented by detecting the contents of the coptidis rhizoma components directly, implementation is simple, easy and repeatable and the operability is high.

Description

一种基于抗痢疾杆菌效应当量因子调节黄连药材用量的方法A method for adjusting the dosage of Coptidis rhizome based on anti-shigella effect equivalent factor

技术领域technical field

本发明涉及一种基于抗痢疾杆菌效应当量因子调节黄连药材用量的方法。The invention relates to a method for adjusting the dosage of coptis chinensis based on the anti-shigella effect equivalent factor.

背景技术Background technique

黄连(CoptidisRhizoma)为毛茛科植物黄连CoptischinensisFranch.、三角叶黄连CoptisdeltoideaC.Y.ChengetHsiao和云连CoptisteetaWall.的干燥根茎。常用于清热燥湿、泻火解毒,与其药效活性相关的成分为生物碱类成分,包括小檗碱、表小檗碱、黄连碱、巴马汀、药根碱等。现代药理研究表明,黄连具有抗菌、抗肿瘤、降血糖、抗病毒、抗炎等作用,其中黄连对痢疾杆菌的抑制作用与其传统功效“止痢”具有重要的相关性。Coptis Rhizoma (Coptidis Rhizoma) is the dry rhizome of Coptis chinensis Franch., Coptis deltoidea C.Y. Chenget Hsiao and Coptisteeta Wall. of Ranunculaceae plants. It is often used for clearing away heat and dampness, purging fire and detoxifying. The ingredients related to its medicinal activity are alkaloids, including berberine, epiberberine, coptisine, palmatine, jatrorrhizine, etc. Modern pharmacological studies have shown that Coptis chinensis has antibacterial, antitumor, hypoglycemic, antiviral, and anti-inflammatory effects, among which the inhibitory effect of Coptis chinensis on Shigella has an important correlation with its traditional effect of "stopping dysentery".

作为临床大宗药材,如何对黄连质量进行有效评控将对保证其临床疗效和促进其产品开发具有重要意义。当前主要以多个指标成分定量分析来实现对黄连品质的评控,但这种方法没有反映出不同成分对药材整体药效的贡献度差异,忽视了不同成分所关联的药效大小有所区别,实际应用时难以评价不同药材的品质优劣情况。对黄连来说,现行标准对其进行质量把关的指标成分包括小檗碱、黄连碱、表小檗碱、巴马汀四个生物碱类成分,在实际检测中发现,两批黄连中,一批的小檗碱含量8.2%,黄连碱为2.7%,另一批的小檗碱含量为9.5%,黄连碱为1.8%时,此时如何通过观察成分含量情况来判断这两批药材的质量差异呢?As a bulk medicinal material in clinical practice, how to effectively evaluate and control the quality of Coptis chinensis will be of great significance to ensure its clinical efficacy and promote its product development. At present, the quantitative analysis of multiple index components is mainly used to realize the evaluation and control of the quality of Coptis chinensis, but this method does not reflect the difference in the contribution of different components to the overall efficacy of the medicinal material, and ignores the difference in the efficacy of different components. , it is difficult to evaluate the quality of different medicinal materials in practical application. For Coptis chinensis, the current standards for its quality control index components include four alkaloid components, berberine, coptisine, epiberberine, and palmatine. The content of berberine in one batch is 8.2%, coptisine is 2.7%, and the content of berberine in another batch is 9.5%, and coptisine is 1.8%, how to judge the quality of these two batches of medicinal materials by observing the content of ingredients What about the difference?

此外,不同于化学药品,其成分结构清楚,构效关系明确,鉴别、检查、含量测定可以直接作为疗效评价的指标。而对于中药来说,其物质内涵复杂,仅检测成分含量就会导致很多局限性,需要将质控指标切实关联药效活性。但若仅在当前成分含测的基础上单纯添加这些药效活性指标,则会增加今后质控标准施行时的难度和复杂度。因为每个药效指标的增添,会导致每种药材有更多要满足的标准,更多繁琐的操作,耗费更多实验材料和实验动物,这势必会造成能源资源的浪费。况且,这种多指标质控模式所带来的贡献度差异问题依然没有解决,无法说明其中哪个指标对药材质量有更重要的关联。In addition, unlike chemical drugs, its component structure is clear and its structure-activity relationship is clear. Identification, inspection, and content determination can be directly used as indicators for efficacy evaluation. For traditional Chinese medicine, its material connotation is complex, and only testing the content of ingredients will lead to many limitations. It is necessary to correlate the quality control indicators with the efficacy and activity of the medicine. However, if these pharmacodynamic and active indicators are simply added on the basis of the current component content test, it will increase the difficulty and complexity of implementing quality control standards in the future. Because the addition of each drug efficacy index will lead to more standards to be met for each medicinal material, more cumbersome operations, and more experimental materials and experimental animals will be consumed, which will inevitably result in a waste of energy resources. Moreover, the problem of difference in contribution caused by this multi-indicator quality control model is still unresolved, and it is impossible to explain which indicator has a more important relationship with the quality of medicinal materials.

因此,若能建立一种综合的既能直接关切“可控有效”,又不会增加质控模式施行难度,同时能指导临床用药的黄连质量评控方法,将对黄连及其他中药质控标准的完善具有重要意义。Therefore, if we can establish a comprehensive quality assessment and control method for Coptis chinensis that can directly concern "controllable and effective" without increasing the difficulty of implementing the quality control model, and can guide clinical medication, it will be of great importance to the quality control standards of Coptis chinensis and other traditional Chinese medicines. perfection is of great significance.

发明内容Contents of the invention

本发明的目的是提供一种基于黄连药材的抗痢疾杆菌效应当量因子(Effectequivalencyfactor,EEF)调节黄连药材用量的方法。The object of the present invention is to provide a method for adjusting the dosage of Coptidis Rhizoma based on the anti-shigella effect equivalent factor (Effectequivalencyfactor, EEF).

本发明的基于黄连药材的抗痢疾杆菌效应当量因子调节黄连药材用量的方法包括以下步骤:The method for regulating the dosage of Coptidis Rhizoma based on the anti-Shigella effect equivalent factor of Coptidis Rhizoma of the present invention comprises the following steps:

(1)测量所述黄连药材中的小檗碱(BER)、表小檗碱(EPI)、黄连碱(COP)、巴马汀(PAL)和药根碱(JAT)的含量,即分别测量XBER、XEPI、XCOP、XPAL、XJAT(1) measure the content of berberine (BER), epiberberine (EPI), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT) in the Coptidis Rhizoma medicinal material, measure respectively X BER , X EPI , X COP , X PAL , X JAT ;

(2)利用公式I来计算待测黄连药材的抗痢疾杆菌效应当量因子:(2) Utilize formula 1 to calculate the anti-shigella effect equivalent factor of Coptidis rhizome medicinal material to be tested:

公式I:EEF=3.352*XBER+1.293*XEPI+6.635*XCOP+0.140*XPAL+0.419*XJAT-0.111;Formula I: EEF=3.352*X BER +1.293*X EPI +6.635*X COP +0.140*X PAL +0.419*X JAT -0.111;

所述EEF为待测黄连药材的抗痢疾杆菌效应当量因子;Described EEF is the anti-Shigella effect equivalent factor of Coptis Rhizoma medicinal material to be tested;

(3)利用公式II计算黄连药材的实际用量:(3) Utilize formula II to calculate the actual consumption of Coptidis medicinal material:

公式II为D=Dtarget/EEF;其中所述D为待测黄连药材的实际用量,Dtarget为黄连药材的目标用量。Formula II is Dmeasure =D target /EEF; wherein Dmeasure is the actual dosage of the Coptidis Rhizoma to be tested , and D target is the target dosage of the Coptidis Rhizoma.

本发明的基于抗痢疾杆菌效应当量因子来调节黄连用量的方法不仅能仅通过测量成分含量来反映其“效”,不会增加质量标准在施行时的难度,具有精准可量化、集成可重现、综合可操作、有效可适用的特点,并且能关联药材临床效用,根据抗痢疾杆菌效应当量因子对黄连用量进行调试,保证效应当量一致性,对黄连药材的品质评控标准的创新整合研究和临床用药指导具有重要意义。The method of adjusting the dosage of Coptis rhizome based on the anti-shigella effect equivalent factor of the present invention can not only reflect its "efficacy" by measuring the content of ingredients, but will not increase the difficulty of implementing quality standards, and is accurate, quantifiable, integrated and reproducible , comprehensively operable, effective and applicable, and can correlate with the clinical efficacy of medicinal materials, adjust the dosage of Coptidis Rhizoma according to the equivalent factor of anti-Shigella effect, to ensure the consistency of effect equivalent, innovative integration research on the quality evaluation and control standards of Coptidis medicinal materials and Clinical medication guidance is of great significance.

具体实施方式Detailed ways

以下结合具体实例来进一步说明发明内容。The content of the invention will be further described below in conjunction with specific examples.

本发明的基于抗痢疾杆菌效应当量因子调节黄连用量的方法可对黄连样品进行活性评价和临床用量调适。The method for adjusting the dosage of Coptis Rhizoma based on the anti-Shigella effect equivalent factor of the present invention can carry out activity evaluation and clinical dosage adjustment of Coptis Rhizoma samples.

试验中所用到的仪器:粉碎机;分析天平(JM-B型,余姚市纪铭称重校验设备有限公司);旋转蒸发仪(R205B,上海申生科技有限公司);电热鼓风干燥箱(DHG9070A,上海一恒科学仪器有限公司);循环水多用真空泵(SHB-B95,郑州长城科工贸有限公司);Agilent1100高效液相色谱仪(DAD检测器),Chemstations色谱工作站(美国Agilent有限公司);BS210S型电子天平(北京Sartorious有限公司);水为蒸馏水。Instruments used in the test: pulverizer; analytical balance (JM-B type, Yuyao Jiming Weighing Calibration Equipment Co., Ltd.); rotary evaporator (R205B, Shanghai Shensheng Technology Co., Ltd.); electric blast drying oven (DHG9070A, Shanghai Yiheng Scientific Instrument Co., Ltd.); circulating water multipurpose vacuum pump (SHB-B95, Zhengzhou Great Wall Technology Industry and Trade Co., Ltd.); Agilent1100 high performance liquid chromatography (DAD detector), Chemstations chromatographic workstation (Agilent Co., Ltd., USA ); BS210S electronic balance (Beijing Sartorious Co., Ltd.); water is distilled water.

(1)测量所收集的黄连药材中的小檗碱、表小檗碱、黄连碱、巴马汀、药根碱的含量:(1) measure the content of berberine, epiberberine, coptisine, palmatine, jatrorrhizine in the collected Coptidis medicinal material:

表1所收集的黄连药材Coptidis medicinal materials collected in Table 1

(i)首先制备黄连水提物:取黄连药材除去杂质,洗净干燥后粉碎成粗粉。称取不同批次的黄连药材粉末各50g,加水浸泡30分钟,水煎提取3次(加水量分别为药材重量的10、10、8倍,各提取1.5、1.0、0.5小时),趁热滤过,合并滤液,减压浓缩,将浸膏转至烘箱中,75℃烘干,即得黄连水提样品干粉。(i) Firstly prepare the water extract of Coptidis rhizome: take Coptidis rhizome medicinal material to remove impurities, wash and dry, then pulverize into coarse powder. Weigh 50g of different batches of Coptidis rhizome medicinal powder, soak in water for 30 minutes, decoct and extract 3 times (the amount of water added is 10, 10, and 8 times the weight of the medicinal material, and the extraction is 1.5, 1.0, and 0.5 hours respectively), and filter while hot. After drying, the filtrates were combined, concentrated under reduced pressure, the extract was transferred to an oven, and dried at 75°C to obtain the dry powder of the water-extracted sample of Coptis chinensis.

(ii)对照品溶液制备:精密称取小檗碱、表小檗碱、黄连碱、巴马汀、药根碱各适量,分别置于棕色量瓶中,加盐酸-甲醇(1:100)分别配制成各对照品储备液。精密量取各对照品储备液适量,置于同一棕色量瓶中,配制成每1ml分别含小檗碱0.4337mg、表小檗碱0.1052mg、黄连0.0606mg、巴马汀0.1160mg、药根碱0.0721mg的混合对照品贮备溶液,备用(10℃以下密封保存)。(ii) Preparation of reference solution: Accurately weigh appropriate amounts of berberine, epiberberine, coptisine, palmatine, and jatrorrhizine, place them in brown measuring bottles, add hydrochloric acid-methanol (1:100) Prepare each reference substance stock solution respectively. Precisely measure the appropriate amount of each reference substance stock solution, put it in the same brown measuring bottle, and prepare it to contain 0.4337mg of berberine, 0.1052mg of epiberberine, 0.0606mg of coptis, 0.1160mg of palmatine, and jatrorrhizine in each 1ml. 0.0721 mg of the mixed reference substance stock solution is set aside (sealed storage below 10°C).

(iii)供试品溶液制备:称取黄连水提浸膏粉末样品约50mg,精密称定,置具塞锥形瓶中,加入盐酸-甲醇(1:100)50ml,称定重量,60℃水浴中加热15分钟,取出,超声处理20分钟,放冷,再称定重量,用盐酸-甲醇(1:100)补足减失的重量,摇匀,用微孔滤膜(0.45μm)滤过,即得。(iii) Preparation of the test solution: Weigh about 50 mg of Coptis chinensis extract powder sample, accurately weigh it, put it in a stoppered conical flask, add 50 ml of hydrochloric acid-methanol (1:100), weigh it, and set the weight at 60°C Heat in a water bath for 15 minutes, take it out, ultrasonically treat it for 20 minutes, let it cool down, weigh it again, make up the lost weight with hydrochloric acid-methanol (1:100), shake well, and filter through a microporous membrane (0.45 μm) , that is.

(iv)液相色谱法测量:(iv) liquid chromatography measurement:

色谱条件:色谱柱:Kromasil100-8C18(250mm×4.6mm);流动相A:乙腈(1.5g十二烷基硫酸钠/500ml)-水(2:1)(磷酸调pH6.0),流动相B:水(3.0g磷酸二氢钾/500ml),线性梯度洗脱程序(0min:38%B,55min:38%B,65min:15%B,70min:0%B);检测波长:345nm;流速:1.0ml/min;柱温:30℃;进样量:10μl。Chromatographic conditions: Chromatographic column: Kromasil100-8C 18 (250mm×4.6mm); mobile phase A: acetonitrile (1.5g sodium dodecyl sulfate/500ml)-water (2:1) (phosphoric acid adjusted to pH 6.0), mobile Phase B: water (3.0g potassium dihydrogen phosphate/500ml), linear gradient elution program (0min: 38%B, 55min: 38%B, 65min: 15%B, 70min: 0%B); detection wavelength: 345nm ; Flow rate: 1.0ml/min; Column temperature: 30°C; Injection volume: 10μl.

测量结果如表2所示。The measurement results are shown in Table 2.

表2:黄连药材中的活性成分含量Table 2: Contents of active ingredients in Coptidis Rhizoma

(2)黄连的抗痢疾杆菌效应当量因子的构建:(2) Construction of Coptidis rhizome anti-shigella effect equivalent factor:

①痢疾杆菌接种:精取1.1mL痢疾杆菌原菌液(第四代),用L.B.培养基稀释成总体积为44mL的接种培养基,即原菌液扩大40倍,痢疾杆菌浓度为1×106CFU/mL。②在洁净无菌的环境下,向每个体积为20mL的玻璃安瓿瓶中精确加入5mL已接种了痢疾杆菌的L.B.培养基,然后向各瓶中分别加入不同体积的活性成分储备液,定容至10mL,使活性成分终浓度分别为0.00mg/mL,0.05mg/mL,0.10mg/mL,0.15mg/mL,0.20mg/mL,0.25mg/mL,加盖瓶塞,密封,放入微量量热仪中,通过仪器自带的记录跟踪软件检测各安瓿瓶中痢疾杆菌生长代谢的“功率-时间(power-time,P-t)”曲线变化。仪器的温度控制于37℃,当所有的曲线全部重新返回基线时,结束实验。通过软件导出相应数据,并将曲线上的数据导入Origin8.5软件(OriginLab公司,美国)作图。③进行抑菌率I%(Inhibitionratio)计算,公式如下:I%=(t2–t0)/t0×100%,其中,t0为未经药物干预时痢疾杆菌生长代谢的第二指数生长期的达峰时间,t2为药物干预时痢疾杆菌生长代谢的第二指数生长期的达峰时间。根据黄连各活性成分作用下痢疾杆菌生长代谢的第二指数生长期的达峰时间t2,计算不同浓度各成分对痢疾杆菌生长的抑制率I%。将抑菌率I%(y)与浓度C(x)进行线性关系分析,计算二者的量效关系方程,结果见表3。① Shigella inoculation: extract 1.1mL of Shigella original bacteria liquid (fourth generation), dilute it with LB medium to form an inoculation medium with a total volume of 44mL, that is, the original bacteria liquid is enlarged by 40 times, and the Shigella concentration is 1×10 6 CFU/mL. ②In a clean and sterile environment, accurately add 5mL of LB culture medium inoculated with Shigella dysenteriae into each glass ampoule bottle with a volume of 20mL, and then add different volumes of active ingredient stock solution to each bottle, and constant volume to 10mL, so that the final concentration of the active ingredient is 0.00mg/mL, 0.05mg/mL, 0.10mg/mL, 0.15mg/mL, 0.20mg/mL, 0.25mg/mL, cap the bottle stopper, seal it, and put it into a micropipette In the calorimeter, the "power-time (Pt)" curve changes of the growth and metabolism of Shigella in each ampoule were detected by the recording and tracking software that comes with the instrument. The temperature of the instrument was controlled at 37°C, and the experiment was terminated when all the curves returned to the baseline. The corresponding data were exported by software, and the data on the curve were imported into Origin8.5 software (OriginLab, USA) for drawing. ③ Calculate the bacteriostatic rate I% (Inhibitionratio), the formula is as follows: I%=(t 2 -t 0 )/t 0 × 100%, wherein, t 0 is the second index of Shigella growth metabolism without drug intervention The peak time of the growth phase, t2 is the peak time of the second exponential growth phase of the Shigella growth metabolism during drug intervention. According to the peak time t 2 of the second exponential growth phase of the growth and metabolism of Shigella with the action of the active ingredients of Coptidis Rhizoma, the inhibitory rate I% of each ingredient at different concentrations on the growth of Shigella was calculated. Bacteriostatic rate I% (y) and concentration C (x) are carried out linear relationship analysis, calculate the dose-effect relationship equation of the two, the results are shown in Table 3.

表3table 3

将五种活性成分的量效关系方程加和得到黄连的抗痢疾杆菌效应加和值,与对照药材成分抗痢疾杆菌效应加和值0.9583之比,即为该批黄连的抗痢疾杆菌效应当量因子方程,即公式I:The sum of the dose-effect relationship equations of the five active ingredients was used to obtain the sum of the anti-Shigella effect of Coptis chinensis, and the ratio of the sum of the anti-Shigella effect of the control medicinal ingredients 0.9583 was the equivalent factor of the anti-Shigella effect of this batch of Coptis chinensis. Equation, which is Formula I:

EEF=3.352*XBER+1.293*XEPI+6.635*XCOP+0.140*XPAL+0.419*XJAT-0.111。EEF=3.352* XBER +1.293* XEPI +6.635* XCOP +0.140* XPAL +0.419* XJAT -0.111.

(3)验证黄连抗痢疾杆菌效应当量因子对其药效活性的代表性:(3) To verify the representativeness of Coptidis rhizome anti-Shigella effect equivalent factor to its medicinal activity:

①痢疾杆菌接种:精取1.1mL痢疾杆菌原菌液(第四代),用L.B.培养基稀释成总体积为44mL的接种培养基,即原菌液扩大40倍,痢疾杆菌浓度为1×106CFU/mL。②采用安瓿法,在洁净无菌的环境下,向每个体积为20mL的玻璃安瓿瓶中精确加入5mL已接种了痢疾杆菌的L.B.培养基,然后向各瓶中分别加入不同体积的黄连样品储备液,定容至10mL,使黄连水提物终浓度分别为0.00mg/mL,0.20mg/mL,0.40mg/mL,0.60mg/mL,0.80mg/mL,1.00mg/mL,加盖瓶塞,密封,放入微量量热仪中,通过仪器自带的记录跟踪软件检测各安瓿瓶中痢疾杆菌生长代谢的P-t曲线变化。仪器的温度控制于37℃,当所有的曲线全部重新返回基线时,结束实验。③以同浓度小檗碱为阳性对照,以0.20mg/mL作为考察不同批次黄连水提物对痢疾杆菌产生抑制作用的浓度,根据t2,计算不同批次黄连样品对痢疾杆菌的抑制率Im%;并以相同浓度的小檗碱抑制率IBER%为对照,计算各批次黄连水提物的相对抑菌率RIm%,公式为RIm%=Im/IBER×100%。④将各批次黄连水提物的活性成分含量值带入公式I,计算它们的EEF,将各批样品的相对抑制率结果与EEF进行相关性分析,结果如表4所示,说明二者具有显著相关性,EEF能较好地代表黄连药材抑菌活性。① Shigella inoculation: extract 1.1mL of Shigella original bacteria liquid (fourth generation), dilute it with LB medium to form an inoculation medium with a total volume of 44mL, that is, the original bacteria liquid is enlarged by 40 times, and the Shigella concentration is 1×10 6 CFU/mL. ②Using the ampoule method, in a clean and sterile environment, accurately add 5 mL of LB culture medium inoculated with Shigella dysenteriae into each glass ampoule bottle with a volume of 20 mL, and then add different volumes of Coptis rhizome sample reserves to each bottle Solution, dilute to 10mL, so that the final concentration of Coptis chinensis water extract is 0.00mg/mL, 0.20mg/mL, 0.40mg/mL, 0.60mg/mL, 0.80mg/mL, 1.00mg/mL, and cap the bottle , sealed, put into a microcalorimeter, and the Pt curve changes of Shigella growth and metabolism in each ampoule were detected by the recording and tracking software that comes with the instrument. The temperature of the instrument was controlled at 37°C, and the experiment was terminated when all the curves returned to the baseline. ③With the same concentration of berberine as the positive control, 0.20 mg/mL was used as the concentration to investigate the inhibitory effect of different batches of Coptis chinensis water extracts on Shigella, and according to t 2 , calculate the inhibition rate of different batches of Coptis chinensis samples against Shigella I m %; and take the berberine inhibition rate I BER % of the same concentration as a contrast, calculate the relative bacteriostatic rate RI m % of the water extract of Coptidis rhizome of each batch, the formula is RI m %=I m /I BER × 100 %. 4. Bring the active ingredient content value of each batch of Coptis chinensis water extract into formula I, calculate their EEF, carry out correlation analysis with the relative inhibition rate result of each batch of samples and EEF, the result is as shown in table 4, illustrates that both There is a significant correlation, and EEF can better represent the antibacterial activity of Coptidis Rhizoma.

表4Table 4

黄连的抗痢疾杆菌效应当量因子EEF的应用:Application of Coptidis rhizome anti-shigella effect equivalent factor EEF:

将按照前述步骤(1)的方法测得的各批次黄连药材的活性成分的含The content of the active ingredients of each batch of Coptidis Rhizoma measured according to the method of the aforementioned step (1)

量值代入公式I中,得到黄连药材的EEF,结果如表5所示:Quantitative value is substituted in the formula I, obtains the EEF of Coptidis rhizome medicinal material, and the result is as shown in table 5:

表5table 5

然后,根据公式II:D=Dtarget/EEF,假设目标剂量Dtarget为1克,则Then, according to the formula II: D=D target /EEF, assuming that the target dose D target is 1 gram, then

待测的黄连药材的实际用量如表6所示:The actual dosage of Coptidis Rhizoma to be tested is shown in Table 6:

表6Table 6

本发明所建立的基于抗痢疾杆菌效应当量因子调节黄连用量的方法经验证能较好地代表黄连抗痢疾杆菌活性。作为化学成分分析与生物活性综合加权的指标,其以集成量化的形式解决了靠多指标评价黄连品质时出现的指标间相悖结果难以评价药材品质差异的问题。由于直接给每个活性成分分配了药效权重系数,系数越大,则该成分对黄连抗痢疾杆菌效应的代表性越强。在临床使用评控黄连品质时,可直接通过检测成分含量去体现该批黄连之“效”,不增加质量标准的施行难度,实现中药质量评控模式的简单易行、科学有效。同时,效应当量因子可在一定程度指导临床用药,指数高的药材在临床使用时可适当降低用量,指数低的药材可增加临床用量,以保证效应当量的一致性。综上,基于效应当量一致性的黄连用量调适方法,使综合量化集成地评控中药品质和指导临床用药成为可能。The method established by the present invention for adjusting the dosage of Coptidis Rhizoma based on the equivalent factor of anti-Shigella effect factor can better represent the anti-Shigella activity of Coptidis Rhizome. As a comprehensive weighted index of chemical composition analysis and biological activity, it solves the problem of inconsistency between indexes when evaluating the quality of Coptis chinensis by multiple indexes in the form of integrated quantification, and it is difficult to evaluate the quality difference of medicinal materials. Since each active ingredient is directly assigned a pharmacodynamic weight coefficient, the larger the coefficient, the stronger the representativeness of the ingredient on the anti-Shigella effect of Coptis chinensis. When evaluating and controlling the quality of Coptis chinensis in clinical use, the "efficacy" of the batch of Coptis chinensis can be directly reflected by detecting the content of ingredients, without increasing the difficulty of implementing quality standards, and realizing a simple, scientific and effective mode of quality assessment and control of traditional Chinese medicine. At the same time, the effect equivalence factor can guide clinical medication to a certain extent. The medicinal materials with high index can be appropriately reduced in clinical use, and the clinical dosage of medicinal materials with low index can be increased to ensure the consistency of effect equivalence. In conclusion, the dosage adjustment method of Coptidis rhizome based on the consistency of effect equivalence makes it possible to evaluate and control the quality of traditional Chinese medicine comprehensively and quantitatively and guide clinical medication.

本发明的方法还可对黄连中不同活性成分进行效应当量因子构建,还可采用不同目标剂量的用量调适,以上仅为说明发明内容所列举的实例,一切基于本发明实质内容所做出的黄连批次、成分、目标用量等简单的变化,均应落在本发明的保护范围内。The method of the present invention can also carry out effect equivalent factor construction to different active components in Coptidis Rhizoma, also can adopt the consumption adjustment of different target doses, the above is only the example enumerated for explaining the content of the invention, all the Coptidis Rhizoma made based on the essential content of the present invention Simple changes such as batches, ingredients, and target dosages should all fall within the protection scope of the present invention.

Claims (3)

1. regulate a method for Rhizoma Coptidis consumption based on anti-shigella dysenteriae effect equivalence factor, said method comprising the steps of:
(1) measure the content of the jamaicin (BER) in described Rhizoma Coptidis, epiberberine (EPI), coptisine (COP), palmatine (PAL) and jateorrhizine (JAT), namely measure X respectively bER, X ePI, X cOP, X pAL, X jAT;
(2) formula I is utilized to calculate the anti-shigella dysenteriae effect equivalence factor of Rhizoma Coptidis to be measured
Formula I:EEF survey=3.352*X bER+ 1.293*X ePI+ 6.635*X cOP+ 0.140*X pAL+ 0.419*X jAT-0.111
Described EEF surveyfor the anti-shigella dysenteriae effect equivalence factor of Rhizoma Coptidis to be measured;
(3) formula II is utilized to calculate the actual amount of Rhizoma Coptidis
Formula II:D survey=D target/ EEF survey; Wherein said D surveyfor the actual amount of Rhizoma Coptidis to be measured, D targetfor the target amount of Rhizoma Coptidis.
2. the method for claim 1, the described measurement wherein in step (1) adopts high performance liquid chromatography.
3. the method for claim 1, wherein said Rhizoma Coptidis is selected from ranunculaceae plant coptis CoptischinensisFranch., triangle leaf coptis CoptisdeltoideaC.Y.ChengetHsiao and Yun Lian CoptisteetaWall.
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