CN106353469B - A kind of integrated evaluating method of Quality Evaluation of Chinese Medicinal - Google Patents
A kind of integrated evaluating method of Quality Evaluation of Chinese Medicinal Download PDFInfo
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Abstract
A kind of integrated evaluating method of Quality Evaluation of Chinese Medicinal, the method is using the size of the quality composite index of sample as the quantizating index of evaluation sample quality superiority and inferiority, it wherein uses gore area method and calculates quality composite index: first, data are normalized using ratio method, eliminate dimension, numerical value different evaluation result data converted between 0-1；Secondly, carrying out integrated processing using data of the gore area method to experience, chemistry, biological 3 dimensions, the quality intension value (triangle area numerical value) of different batches sample is obtained；Finally, the triangle area is maximum, using the triangle area of each sample divided by maximum triangle area to get quality composite index when the data of three dimensions are 1.According to the present processes, quality composite index embodies traditional Chinese medicine Overall View, has merged traditional cognitive and Contemporary Cognition, is associated with effect and safety.
Description
Technical field
This application involves the field of Chinese medicines, and in particular to a kind of integrated evaluating method of Quality Evaluation of Chinese Medicinal.
Background technique
As the saying goes " medicinal material is good, and medicine is better ", the good premise of medicinal material are to have the evaluation method and index of " good " medicinal material first.Mesh
Preceding index component content measurement is the main method and index of Quality Evaluation of Chinese Medicinal evaluation, however surveyed index ingredient is not necessarily
Effective component, individual index ingredients are also difficult to represent the quality of Chinese medicine overall quality.Traditional genunie medicinal materials character specification is commented
Valence is the empirical evaluation method formed over the past thousands of years, still plays a significant role in practice so far that document confirms tradition in recent years
Empirical evaluation has scientific and repeatability.The core of medicinal material " good " is meant that clinical efficacy is excellent, but in view of Medical Ethics and
The problems such as operability, using clinical laboratory evaluations medical material quanlity and unrealistic, therefore using association clinical efficacy, take into account it is accurate
Property and operability biological assessment method can be used as Quality Evaluation of Chinese Medicinal evaluation important method supplement.However different evaluation method
Evaluation result it is sometimes not consistent, even conflicting, be unfavorable for holding and evaluating Quality Evaluation of Chinese Medicinal on the whole.
Due to the complex material attribute of Chinese medicine, single method, single index have certain one-sidedness.Comprehensive a variety of evaluations
Index evaluates Quality Evaluation of Chinese Medicinal on the whole, avoids the deficiency for only discussing quality with ingredient, is increasingly becoming the weight of Quality Evaluation of Chinese Medicinal evaluation
Want developing direction.More comprehensive index, quality comment control power stronger, can more reflect the overall quality of Chinese medicine.
Currently, although this field has had scholar to use by determining weight with expert opinion to index importance assessment
Weighting marking carrys out the quality of quantitatively evaluating Chinese medicine, but due to the unit of Character Evaluation, Chemical Evaluation, biological assessment result etc.
Dimension is inconsistent, is difficult to illustrate the difference of importance of various methods.
Therefore, there are still the urgent needs of the other methods to overall merit Quality Evaluation of Chinese Medicinal for this field.
Summary of the invention
A kind of integrated evaluating method for being designed to provide Quality Evaluation of Chinese Medicinal of the application.
The further object of the application is to provide the above method in the assessment of Chinese medicine genuineness, elite germplasm breeding, essence mark
Purposes in medicine materical crude slice exploitation, market circulation high quality and favourable price or clinical rational drug use.
Specifically, the application provides a kind of integrated evaluating method of Quality Evaluation of Chinese Medicinal, and the method is comprehensive with the quality of sample
Quantizating index of the size of index (IQI) as evaluation sample quality superiority and inferiority, the quality composite index pass through following acquisition:
Empirical evaluation, Chemical Evaluation and biological assessment are carried out to sample, respectively obtain empirical evaluation, the Chemical Evaluation of sample
And the absolute figure E of biological assessmenti、CiAnd Bi, by all measured values of empirical evaluation and a collection of sample of Chemical Evaluation most
Big value is respectively as empirical evaluation maximum value EmaxWith Chemical Evaluation maximum value Cmax, and if the toxicity of sample is obvious, it will be biological
Minimum value in all measured values of a collection of sample of evaluation is as biological assessment minimum value Bmin, or if the toxicity of sample not
Obviously, using the maximum value in all measured values of a collection of sample of biological assessment as biological assessment maximum value Bmax,
With EiDivided by empirical evaluation maximum value EmaxEmpirically evaluation coefficient E, with CiDivided by Chemical Evaluation maximum value CmaxMake
For Chemical Evaluation coefficient C, and if the toxicity of sample is obvious, with biological assessment minimum value BminDivided by BiAs biological assessment system
Number B, or if the toxicity of sample is unobvious, with BiDivided by biological assessment maximum value BmaxAs biological assessment coefficient B,
X-axis, Y using Chemical Evaluation coefficient C, biological assessment coefficient B and empirical evaluation coefficient E as space coordinate
Point on axis, Z axis constructs triangle, calculates quality intension value of the area as sample of the triangle, and
Using empirical evaluation coefficient E, Chemical Evaluation coefficient C and biological assessment coefficient B be 1 triangle as maximum triangle
Shape and the maximum triangle area of calculating, the quality intension value of sample is comprehensive to get the quality of sample divided by maximum triangle area
Hop index,
Wherein, if the toxicity of sample is obvious, the biological assessment be based on toxicity in terms of detection, or if sample
Toxicity is unobvious, the biological assessment be based on drug effect in terms of detection.
Wherein, using Chemical Evaluation coefficient C, biological assessment coefficient B and empirical evaluation coefficient E as the X of space coordinate
Axis, Y-axis, triangle is as follows constructed by the point on Z axis:
Those skilled in the art can be according to the area of its mathematics common sense reasonable computation triangle, such as the face of triangle
Product can calculate as follows:
Formula 2
P=(a+b+c)/2 formula 3
Formula 4
In formula, a, b, c are respectively three sides of triangle, and p is the average of three edge lengths, and S is the area of triangle.
The calculation formula of quality composite index (IQI) are as follows: IQI=Si/Smax, wherein SiFor the area of each batch sample, Smax
For maximum triangle area.
In some embodiments, the empirical evaluation can be carried out by weighing the weight of sample, and with sample
The absolute figure E that average weight is empirically evaluatedi。
It will be appreciated by those skilled in the art that empirical evaluation method may include size dimension, weight, quality, face
Color, smell etc..Such as fructus lycii, Radix Ophiopogonis, monkshood, Radix Notoginseng head more great tradition think that quality is better, frequently with per kilogram number,
Head number carrys out opinion rating, and objectively evaluating can be using average weight as index；Agalloch eaglewood quality is more heavy, and density is greater than water, then quality is more
Good, objectively evaluating can be using density as index；The redder quality of Radix Salviae Miltiorrhizae is better, and the redder quality of color is better after Rhubarb meets buck,
Objectively evaluating can be measured in a manner of color evaluating, colorimetric card etc., and objectively evaluating being averaged with the value of chromatism of average measurement
Value is index；The root of Dahurain angelica, the stronger quality of aroma of Rhizoma Chuanxiong are better, and objectively evaluating can be measured with electronic nose；Radix Astragali gets over sweet tea, product
Matter is better, and objectively evaluating can be evaluated with electronic tongues.Therefore, those skilled in the art completely can be according to the sample specifically evaluated
Product select suitable empirical evaluation method.
Those skilled in the art will be further understood that empirical evaluation can be according to methods known in the art or with reference to existing
There is the pertinent literature in technology to carry out, such as referring to document Wang JB, Zeng LN, Zang QC, et
al.Colorimetric grading scale can promote the standardization of experiential
and sensory evaluation in quality control of traditional Chinese
medicines.PLoS One.2012；7 (11): e48887 is measured.
In some embodiments, weigh sample weight can according to " 76 kinds of medicinal material commodity specification standards " come into
Row.
In some embodiments, if the toxicity of sample is obvious, the Chemical Evaluation can be by using chemical method
The content of effective component in measurement sample and the content of toxic component carry out, and with the average value of active constituent content with
Absolute figure C of the ratio of the average value of toxic component content as Chemical EvaluationiAnd by a collection of sample of the Chemical Evaluation
All measured values in maximum value as Chemical Evaluation maximum value Cmax。
It will be appreciated by those skilled in the art that using the ratio of effective component and toxic component as evaluation index, it should
Numerical value is bigger, and security window is wider, and the safe coefficient of medication is higher.
In some embodiments, if the toxicity of sample is unobvious, the Chemical Evaluation can pass through measurement sample
The sum of content of effective component carries out, and using the average value of the sum of active constituent content as the absolute figure of Chemical Evaluation
CiAnd using the maximum value in all measured values of a collection of sample of the Chemical Evaluation as Chemical Evaluation maximum value Cmax.For example,
Rheum officinale toxicity is unobvious, can be referred to rushing down the sum of lower ingredient cassia angustifolia methods of glycosides and combined anthraquinone constituents total amount for evaluation
Mark；Ginseng toxicity is unobvious, can be with the sum of a variety of content of ginsenoside for evaluation index.
In some embodiments, the chemical method is UHPLC-Q-TOF/MS or HPLC method.Certainly, this field
Technical staff understands that the chemical method can also be known in the art its other party that can measure sample composition content
Method.
In some embodiments, if the toxicity of sample is obvious, in terms of the biological assessment can be based on toxicity
Detection and the biological assessment are carried out by the minimum lethal malicious valence of biology of measurement, and with the lethal biology poison valence of minimum
Absolute figure B of the average value as biological assessmentiAnd with the minimum value in all measured values of a collection of sample of biological assessment
As biological assessment minimum value Bmin。
Wherein, the measurement of the minimum malicious valence of lethal biology can be with bibliography Qin Y, Wang JB, Zhao YL, et
al.Establishment of a bioassay for the toxicity evaluation and quality
control of Aconitum herbs[J].J Hazard Mater,2012,199-200:350-357。
In some embodiments, if the toxicity of sample is unobvious, the biological assessment be can be based in terms of drug effect
Detection and the biological assessment be to be carried out by measuring the biological value of sample, and with the average value of the biological value
Absolute figure B as biological assessmentiAnd using the maximum value in all measured values of a collection of sample of biological assessment as biology
Evaluate maximum value Bmax。
Wherein, the measurement of biological value can refer to such as document Wang Jia primary, Jin Cheng, Li Huifang, and is waited to rush down lower class Chinese medicine matter
Biological control method and Research on basic problems [J] Acta Pharmaceutica Sinica of amount, 2009,44 (5): 500-505；Li Hanbing, Yan Dan, king
Jia Bai, biological assessment [J] the Acta Pharmaceutica Sinica for the Radix Isatidis quality for waiting to detect based on neuraminidase activity, 2009,44 (2):
162-166；Luo Yun, Jin Cheng, Zhou Jian wait to study [J] based on muscone's quality evaluating method of cyclooxygenase inhibiting effect
Acta Pharmaceutica Sinica, 2011,46 (4): 438-442；Liu Xingxing, Dong Li, Zhang Xiaohong wait hemostasis biological value to comment for bletilla quality
Research [J] CHINA JOURNAL OF CHINESE MATERIA MEDICA of valence, 2014,39 (19): 3764-3767；Chen Guangyun, Wu Qinan, Wang Xinsheng wait biology to imitate
Valence measuring method is used for research [J] CHINA JOURNAL OF CHINESE MATERIA MEDICA of blood-activating and stasis-removing trigone quality evaluation, 2012,37 (19): 2913-
2916；Dai little Jiao, Song Jun, Yan Liangchun, wait the Sichuan monkshood quality biomass calibration method pilot study [J] Chinese medicine, and 2013,31
(9):43-46；And Wang Xiaoxiao, Zhang Lihong, Li Xi, wait Radix Angelicae Sinensis medicinal material to enrich blood active quantitative determination [J] CHINA JOURNAL OF CHINESE MATERIA MEDICA,
2015,40 (7): 1381-1387 etc..
It will be understood by those skilled in the art that biological assessment mainly includes biological value and malicious two aspect of valence of biology；Before
Person is used for pharmacodynamic assessment, such as rushes down lower potency, promoting blood circulation potency, anti-inflammatory potency, antiviral activity, heart tonifying potency, inhibitory potency, hemostasis
Potency, antitumor potency etc.；The latter is used for toxicity evaluation, such as minimum lethal dose poison valence, the poison based on cell growth inhibition model
Valence etc..
In some embodiments, the sample can for monkshood, rheum officinale, the coptis, ginseng, Radix Notoginseng, fructus lycii, Radix Salviae Miltiorrhizae,
Radix Glycyrrhizae, radix scutellariae, Schisandra chinensis, the fleece-flower root, cordyceps sinensis.
According to the present processes, quality composite index (IQI) embodies traditional Chinese medicine Overall View, merged traditional cognitive with
Contemporary Cognition is associated with effect and safety, is benefited our pursuits to building evaluation of traditional Chinese medicine standard, for science, thoroughly evaluating
Quality Evaluation of Chinese Medicinal provide technical support and demonstration, while also for the evaluation of Chinese medicine genuineness, elite germplasm breeding, essence mark medicine materical crude slice open
Hair, market circulation high quality and favourable price and clinical rational drug use provide Technical Reference.
Detailed description of the invention
Attached drawing is used to provide further understanding of the present application, constitutes part of this application, the schematic reality of the application
Example and its explanation are applied for explaining the application, but it is not constituted an undue limitation on the present application.In the accompanying drawings:
Fig. 1 shows the structural formula of 10 kinds of active constituents in the monkshood of embodiment 1；
Fig. 2 shows the average weight measurement result (n=100) of the monkshood in embodiment 1；
Fig. 3 A shows measurement knot of the sum of the toxic component of monkshood in embodiment 1 with the average value of the sum of effective component
Fruit；
Fig. 3 B shows effect/poison ratio of the monkshood in embodiment 1；
Fig. 4 shows the malicious valence measurement result (n=6) of the biology of the monkshood in embodiment 1；
Fig. 5 shows the quality composite index of the different sources monkshood of the embodiment 1 integrated based on three-dimensional data；
Fig. 6 shows the measurement result of the average value of the composite index of the different sources monkshood of embodiment 1；
Fig. 7 shows the HPLC figure of 14 batches of monkshoods, wherein 1 represents benzoylmesaconine, 2 represent benzoyl aconite original
Alkali, 3 represent benzoyl time aconine, and 4 represent mesaconine, and 5 represent aconitine, and 6 represent Hypaconitine.
Specific embodiment
Presently filed embodiment is described below by embodiment, it will be appreciated by the person skilled in the art that these
Specific embodiment only indicates to achieve the purpose that the application and the implementation technical solution that selects, is not to technical solution
Limitation.According to teachings of the present application, be to the improvement of technical scheme in conjunction with the prior art it is obvious, belong to the application
The range of protection.
Material employed in following instance is as follows:
14 parts of monkshood samples of drug are adopted in Sichuan, Hanzhong, Sichuan Butuo, Weishan and Sichuan An County,
Ranunculaceae plant rhizome of Chinese monkshood Aconitum carmichaelii Debx. is accredited as through the 302nd hospital Xiao little He researcher of liberation army
Sub- root.Wherein Sichuan (JY), Hanzhong (HZ), Sichuan Butuo (BT), Weishan (WS) monkshood sample respectively adopt
3 parts of collection, every part of 15-30kg；The monkshood sample of Sichuan An County (AX) acquires 2 parts, every part of about 20kg monkshood.Sample, which keeps sample, to be stored in
Chinese medicine study institute of the entire PLA.
Reagent mesaconine, aconitine, Hypaconitine, benzoylmesaconine, benzoyl aconine and benzoyl
Secondary aconine reference substance is purchased from Chinese food drug identification research institute, and lot number is respectively 110799-201106,110720-
201111,110798-201106,111795-200901,111794-200901 and 111796-201303；Neoline, monkshood
Spirit, songorine and talastisamine reference substance are purchased from Chengdu Puffy moral Bioisystech Co., Ltd, lot number difference 131214,
140315,140420,131112；The structural formula of 10 ingredients is as shown in Figure 1.Methylene chloride, ethyl acetate, isopropanol, acetic acid
Ammonium, dense ammonia, ethyl alcohol are that analysis is pure, are purchased from Beijing Chemical Plant；Deionized water (self-control)；Formic acid (chromatographically pure, Sigma), acetonitrile
(chromatographically pure, Fisher).
Instrument Agilent Technology 1290Infinity UPLC Ultra Performance Liquid Chromatography instrument, Agilent1200
Type high performance liquid chromatograph (quaternary pump, autosampler and UV detector), Agilent TechnologyiFunnel
6550Q-TOF LC/MS level four bars time-of-flight mass spectrometry, 1,290 2 aurora array detectors (G4212A), Agilent
Masshunter work station；Gradient A10Mill-Q Superpure water machine (French Millipore company)；Sartorius-
BS110S one thousandth assay balance, ten a ten thousandth assay balances (Sartorius AG), (Beijing is rich for desk freeze-dryer
Yi Kang laboratory apparatus Co., Ltd), BYZ-810T syringe pump (Changsha ratio raises Medical Devices Co., Ltd.).
Animal SD rat, SPF grades, male, 6-8 week old, 180 ± 20g of weight, by Chinese People's Liberation Army's military medicine
Academy of sciences's Experimental Animal Center provides, animal credit number: SCXK- (army) 2007-004.
1 overall merit of embodiment is adopted in Sichuan, Hanzhong, Sichuan Butuo, Weishan and Sichuan An County
Monkshood sample
1. empirical evaluation
Regulation according to " 76 kinds of medicinal material commodity specification standards " evaluates monkshood quality with head weight, attached with each batch
The average weight of son is as Character Evaluation index.
Calculation method measures the weight after mud monkshood sample is cleaned.From every batch of mud monkshood medicinal material, 100 samples are randomly selected
This, cleans the weight for using assay balance to weigh each mud monkshood after removal soil, calculates average value, measurement result such as Fig. 2 institute
Show.
As shown in Fig. 2, there is some difference for the mud monkshood weight of different sources.In terms of average weight, 5 place of production grades are commented
Valence result is successively quality assay, towering mountain monkshood, Monkshood, Hanzhong monkshood and An County monkshood.
2. Chemical Evaluation
In order to compare the otherness of different producing area monkshood chemical component more fully hereinafter, 3 kind are had detected shown in Fig. 1 altogether
The diester-type alkaloids (mesaconine, aconitine, Hypaconitine) of strong toxicity, and figure remaining 7 kinds of drug activity therein compared with
(monoester alkaloid is benzoylmesaconine, benzoyl aconine, benzene for strong monoester alkaloid and ester alkaloid
Formyl time aconine, ester alkaloid are neoline, Fuziline, songorine, talastisamine), calculate effect/(7 kinds of poison ratio
Monoester type and ester biology total alkali content/3 kind diester-type alkaloids total content).Effect/poison ratio is bigger, reflects monkshood drug effect
Stronger, the weaker feature of toxicity, drug safety are higher, it is believed that its quality is also relatively more excellent.
According to document, (Chen Dongan, Yi Jinhai, HUANG Zhifang wait the research of tag finger-print and 6 kinds of ester alkaloid contents
Measure [J] CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2010,35 (21): 2829-2833) in documented method, using HPLC method measurement mud it is attached
Mesaconine, aconitine, Hypaconitine, benzoylmesaconine, benzoyl aconine and benzoyl time rhizome of Chinese monkshood are former in son
The content of alkali.Containing for neoline in mud monkshood, Fuziline, songorine and talastisamine is measured using UHPLC-Q-TOF/MS method
Amount.Concrete operations are as follows:
HPLC measuring method
Using mesaconine, aconitine, Hypaconitine, benzoylmesaconine, benzene first in HPLC method measurement mud monkshood
The content of acyl aconine and benzoyl time aconine.
Chromatographic condition chromatographic column: Phenomenex Gemini C18column (250 × 4.6mm, 5 μm), mobile phase: A phase
For acetonitrile -0.04mol/L ammonium acetate solution (liquor ammoniae fortis tune pH 10.0) (1:3), B phase is acetonitrile -0.04mol/L ammonium acetate
Solution (liquor ammoniae fortis tune pH 10.0) (65:35), linear gradient elution program: 0-20min, 10-22%B；20-30min, 22-
37%B；30-40min,；40-45min, 47.5-52%B；45-65min, 52-60%B；65-75min, 60-75%B；75-
80min, 75-95%B；Flow velocity 0.8mLmin-1；Detection wavelength is 235nm；Column temperature: 30 DEG C；Sample volume: 10 μ L.
The preparation precision of reference substance solution weighs mesaconine, aconitine, Hypaconitine, benzoylmesaconine, benzene
Formyl aconine and benzoyl time aconine are appropriate, and the dissolution of 0.05% hydrochloric acid-methanol solution is added, and concentration is made in constant volume
The mixed reference substance solution of respectively 101.6,49.2,100.0,40.4,43.6,43.2 μ g/ml.
The preparation of test solution takes fresh mud monkshood, cleans and removes mud, and shave, freeze-drying is dehydrated for 24 hours, obtains dried mud
Monkshood sample.Sample comminution crosses No. 3 sieves.This product powder (crossing No. three sieves) about 2g is taken, it is accurately weighed, it sets in stuffed conical flask, adds
Isopropanol-ethyl acetate (1:1) mixed solution 50ml is added in ammonia solution 3ml, precision, and weighed weight is ultrasonically treated (power
300W, frequency 40kHz, water temperature is at 25 DEG C or less) 30 minutes, it lets cool, then weighed weight, it is mixed with isopropanol-ethyl acetate (1:1)
The weight that solution supplies less loss is closed, is shaken up, is filtered.Precision measures subsequent filtrate 20ml, and for recycling design to doing, residue is smart in draught cupboard
Close addition isopropanol-methylene chloride (1:1) mixed solution 3ml dissolution, crosses 0.22 μm of miillpore filter to get test solution.
Assay prepares 14 batches of mud monkshoods according to " preparation of test solution " item, measures peak area and brings standard into
The content of 6 kinds of alkaloids is calculated in curve.Measurement result is as shown in Figure 7.
UHPLC-Q-TOF/MS measuring method
Containing for neoline in mud monkshood, Fuziline, songorine and talastisamine is measured using UHPLC/MS-Q-TOF method
Amount.
Chromatographic condition using chromatographic column Zorbax RRHD 300SB-C18column (100mm × 2.1,1.8 μm,
Agilent, USA), 30 DEG C of column temperature, flow velocity 0.3ml/min, 1 μ l of sample volume；Mobile phase A: 0.1% aqueous formic acid, mobile phase
B:0.1% formic acid acetonitrile solution, gradient elution (0-1min:2%B；1-2min:2-5%B；2-5min:5-11%B；5-
10min:11-15%B).
Mass Spectrometry Conditions use electrospray ionisation ion source (electrospray ionization, ESI), positive ion mode
Detection: m/z range 100-900, scanning speed 1.00spectra/sec, capillary voltage 3500V, orifice potential 1000V, from
200 DEG C of source temperature, 350 DEG C, sheath gas 14l/min of sheath temperature degree, mass calibration matter composition and division in a proportion is TFANH4-Purine-HP
0921 solution [(M+H)+m/z121.0509 and 922.0098].
The preparation precision of reference substance solution weighs neoline, Fuziline, songorine and appropriate talastisamine, is added
The dissolution of 0.05% hydrochloric acid-methanol solution, constant volume, obtained concentration is respectively the mixing of 1.38,1.285,1.125,1.115 μ g/ml
Reference substance solution.
The mud monkshood for preparing of test solution is cleaned, is freeze-dried after slice, and crushing is prepared into powder.Precision weighs powder
Hplc grade methanol 25ml is added in 1g, and ultrasonic extraction 30min is let cool, and supplies weight, filters, and subsequent filtrate dilutes 100 times, crosses 0.22
Test sample is made in μm miillpore filter.
Assay prepares 14 batches of mud monkshoods according to " preparation of test solution " item, and ion stream peak face is extracted in measurement
Product, calculates the content of 4 kinds of alkaloids.
Wherein, the active constituent content of monkshood and the measurement result of toxic component content are as shown in Figure 3A, wherein in Fig. 3 A
Hypertoxic component content be 3 kinds of toxic components average content summation and active constituent content be being averaged for 7 kinds of effective components
The summation of content.
It finds during the test, the content of monoester alkaloid is extremely low in mud monkshood, mainly the new rhizome of Chinese monkshood of benzoyl
Former alkali, in addition to the monkshood of An County, remaining monkshood can not quantitative determine benzoyl aconine and benzoyl time aconine.Dibasic acid esters
The content of type alkaloid (mesaconine, aconitine, Hypaconitine) has a certain difference, Monkshood and towering mountain monkshood
Content is higher than quality assay and Hanzhong monkshood, and 2 times of left sides of An County monkshood content highest, almost Hanzhong monkshood and quality assay
The right side, toxicity are extremely strong.It is raw that 4 kinds of ester alkaloid (neoline, Fuziline, songorine, talastisamine) contents are higher than 3 kinds of diester-types
Alkaloids (mesaconine, aconitine, Hypaconitine), but the content difference of different sources is big, the content of quality assay is most on the whole
Height, followed by Hanzhong monkshood, An County monkshood content are minimum.Calculate separately the average content summation and effective component of toxic component
The sum of average content is divided by by the two and calculates effect/poison ratio, as a result sees Fig. 3 B.
The effect of Genuine producing area monkshood/poison ratio shows poison in 6:1 or so in chemical composition it can be seen from Fig. 3 B
Inefficient high feature；Effect/poison ratio of Butuo and towering mountain monkshood is contracted to 2.5:1 or so, and effect weakens, poison enhances；And An County is attached
Effect/poison ratio of son is only 1:1 or so, shows as malicious efficiently low feature.
3. biological assessment
Monkshood toxicity is extremely strong, and alcohol extract is injected by tail vein can quickly result in rats death, is caused greatly by calculating
The minimum lethal dose of mouse death, evaluates its Difference In Toxicity.Minimum lethal dose is smaller, and toxicity is stronger.
Measuring method is according to document (Qin Y, Wang JB, Zhao YL, et al.Establishment of a
bioassay for the toxicity evaluation and quality control of Aconitum herbs
[J] .J Hazard Mater, 2012,199-200:350-357.) the malicious valence evaluation method of minimum lethal dose biology recorded, with
10μg·ml-1Rhizome of Chinese monkshood aqueous slkali be standard solution, using 70% ethanol extract of mud monkshood as test solution (5mg crude drug amount/
Ml, normal saline dilution are prepared), every group of 6 SD rats.The intoxicating potency for defining 1mg aconitine is 1000U, the traditional Chinese medicines in
" direct measuring method " of allusion quotation biological standardization statistics program BS2000 software calculates malicious valence.
The measurement result of biological poison valence is as shown in Figure 4.As can be seen from the results, aconitine standard items have very strong lethal,
10μg·ml-1(U·ml-1) titer tail vein inject 1.2-1.5ml and can make rats death.And different sources mud monkshood
Alcohol extract also can make rats death, but there is some difference for toxicity.Generally speaking, strong toxicity weak ordering are as follows: An County monkshood, towering
Mountain monkshood, Monkshood, quality assay, Hanzhong monkshood；The toxicity of An County monkshood is significantly stronger than other places of production, and malicious valence reaches
3000U·g-1More than；Hanzhong monkshood and quality assay toxicity are most weak, average in 2000-2200Ug-1Left and right；Monkshood and
Towering mountain monkshood toxicity is closer to, average in 2300-2500Ug-1Left and right.
4. the normalization of data and the calculating of quality composite index
The application uses gore area method and calculates quality composite index.Firstly, being returned using ratio method to data
One change processing, eliminates dimension, the numerical value converted different evaluation result data between 0-1；Secondly, using gore area method
Integrated processing is carried out to the data of character, chemistry, biological 3 dimensions, obtains the quality intension value (triangle of different batches sample
Area figures)；Finally, the triangle area is maximum when the data of three dimensions are 1, the gore of each sample is utilized
Product is divided by maximum triangle area to get quality composite index.Computing Principle is as follows:
Data normalization, integrated calculation formula are as follows:
Data normalization calculation formula:
Formula 1
In formula, E, C, B respectively represent empirical evaluation coefficient (Empirical evaluation coefficient, E), change
Learn evaluation coefficient (Chemical evaluation coefficient, C) and biological assessment coefficient (Biological
evaluation coefficient,B)。Ei、Ci、BiEach batch monkshood empirical evaluation, Chemical Evaluation and biology is respectively represented to comment
The absolute figure of valence；EmaxWith CmaxRespectively represent empirical evaluation, the maximum value in a collection of sample measures in Chemical Evaluation, Bmin
Represent the minimum value in biological assessment in a collection of sample measures.
Triangle area calculation formula:
Formula 2
P=(a+b+c)/2 formula 3
Formula 4
In formula, a, b, c are respectively three sides of triangle, and p is the average of three edge lengths, and S is the area of triangle.
Quality composite index calculation formula:
IQI=Si/0.866 formula 5
In formula, IQI is quality composite index, and Si is the area of each batch sample, and 0.866 is the maximum by being calculated
Triangle area.
The calculating of the empirical evaluation coefficients of 14 batches of monkshoods, Chemical Evaluation coefficient, biological assessment coefficient and quality composite index
As a result shown in such as table 1, Fig. 5 and Fig. 6.
1 quality composite index measurement result of table
As shown in Figure 5, different sources monkshood has larger difference in terms of experience (or shape), chemistry and biological assessment.From
Triangle area can be seen that quality assay area maximum, followed by Hanzhong monkshood, and An County monkshood area is minimum.Pass through product
Matter composite index (IQI) calculates (as shown in Figure 6), quality assay, Hanzhong monkshood, Monkshood, towering mountain monkshood, An County monkshood
Average value is respectively 0.842 ± 0.091,0.597 ± 0.047,0.442 ± 0.033,0.454 ± 0.038,0.170 ± 0.021,
I.e. quality assay is best in quality, hence it is evident that is better than other producing region monkshoods (p < 0.05), this genuineness understanding one traditional with monkshood
It causing, followed by Hanzhong monkshood, Monkshood is suitable with towering mountain monkshood quality, it is inferior to quality assay and Hanzhong monkshood on the whole, and
The quality of An County monkshood is worst.
The genuineness of Chinese medicine is the high abstraction and summary about herbal species, quality and brand, objective essence tool
Have duality, genunie medicinal materials are not only to have become but also constant, it is genuine with it is non-it is genuine be it is not only continuous but also intermittent, be Chinese medicine integrated quality
Embodiment.Thus, single, isolated evaluation index is all difficult to objective comprehensive reflection genuineness.The monkshood of embodiments herein 1
Quality composite index evaluation result shows that quality assay medicinal material is of fine quality greatly, effect is virulent weak, and overall merit is optimal, passes with monkshood
The genuineness cognitive consonance of system, it was demonstrated that the reasonability of the present processes and scientific can be used for the evaluation of medicinal material genuineness,
Such as provide that the quality composite index of genunie medicinal materials must be higher than specific numerical value, index is higher, and genuineness is stronger.Meanwhile quality is comprehensive
Hop index also provides scientific basis to instruct the addressing of the fine-variety breeding, the base GAP of natural resources of Chinese medicinal materials to plan with demonstration.
Equally, the present processes are also to be suitable for the prepared slices of Chinese crude drugs.The curative effect that good Chinese medicine has added Chinese medicine that could generate.When
Modern The Quality of Sliced Herbal Medicine is irregular, the good and bad jumbled together, and clinic needs the high-quality medicine materical crude slice of Chinese medicine.For this purpose, present inventor just mentions
Quality genuineness, specification homogeneity, adjustment accuracy, performance uniformity, the Chinese medicine essence mark medicine materical crude slice for being associated with effect and toxicity are gone out.
It is integrated by the comprehensive quantification to medicine materical crude slice character, chemical component, biological work/toxicity, is conducive to establish the clinical evaluation side of association
Method provides technology for scientific evaluation prepared slice quality and guarantees.
In addition, the present processes can be also used for the guidance of high quality and favourable price.High quality and favourable price is the plantation of guidance Chinese medicine, adds
The important channel of work and circulation.Quality evaluation and price are mainly foundation commercial specification grade in Chinese medicine circulation at present, for
Some extraction type medicinal materials also refer to index components content height.The division of Chinese medicine specification grade is based primarily upon traditional experience and comments
Valence, such as head, color, smell, quality, section, need to be furtherd elucidate with the correlation of interior quality.It is single chemically at
Divided by the tailing content of many root and rhizome class medicinal materials is higher, is unfavorable for scientific guidance Producing medicinal herbs.It can be said that
The missing of integrated evaluating method more causes market circulation adulterate, is adulterated so that high-quality medicinal material lacks the appraisement system of science
Of inferior quality means are made to remain existing despite repeated prohibition, the policy of favorable price for good quality also because lacking specific referential, is difficult landing and implements.However, the application
Quality composite index (IQI) can for medicinal material market circulate high quality and favourable price objective, quantifiable comprehensive reference index be provided；?
Specific reference standard is provided for hospital pharmacy and medicine enterprise buying medicinal material, it is preferential to purchase if specified quality composite index is bigger
Higher grade.
Furthermore the present processes can also be used to guide clinical rational drug use." traditional Chinese medicine is not broken up the family from ancient times ".In ancient times
Doctor continues to use always the mode of " preceding shop Hou Fang ", and doctor is pharmacist again, grasps drug and gathers and processes, is familiar with medical material quanlity, and can be according to right
The criticism result of medical material quanlity correspondingly adjusts dosage, reaches ideal therapeutic effect, i.e., so-called " pressing matter stoichiometric ".
However, modern medicine is broken up the family, doctor but prescription of feeling the pulse is known, do not know drug quality, more appearance " thousand people, one medicine, ten thousand people, one amount " shows
As；Ignore quality of medicinal material factor, clinical efficacy is necessarily affected.And it relies only on chemical component detection and is difficult to characterize the whole of medicinal material
Body quality cannot achieve the clinical rational drug use based on medical material quanlity.The quality composite index (IQI) of the application is Chinese medicine
Quality evaluation provides new means, by the relationship research of medicinal material comprehensive effect power and dosage, may be implemented to be based in the future
The personalized medicine of quality of medicinal material, helps to improve clinical therapeutic efficacy.
The foregoing is merely preferred embodiment of the present application, not to the application make in any form with substantial limit
System.Those skilled in the art, in the range of not departing from technical scheme, in using disclosed above technology
Hold and the equivalent variations of a little change, modification and differentiation made is the equivalent embodiment of the application；Meanwhile it is all according to this Shen
Change, modification and differentiation of any equivalent variations to the above embodiments of substantial technological please etc. are in the application by weighing
Benefit requires in the range of defining.
Claims (10)
1. a kind of integrated evaluating method of Quality Evaluation of Chinese Medicinal, the method is using the size of the quality composite index of sample as evaluation sample
The quantizating index of product quality, the quality composite index pass through following acquisition:
Empirical evaluation, Chemical Evaluation and biological assessment are carried out to sample, respectively obtain the empirical evaluation, Chemical Evaluation and life of sample
The absolute figure E of object evaluationi、CiAnd Bi, by the maximum value in all measured values of empirical evaluation and a collection of sample of Chemical Evaluation
Respectively as empirical evaluation maximum value EmaxWith Chemical Evaluation maximum value Cmax, and if the toxicity of sample is obvious, by biological assessment
A collection of sample all measured values in minimum value as biological assessment minimum value Bmin, or if the toxicity of sample is unobvious,
Using the maximum value in all measured values of a collection of sample of biological assessment as biological assessment maximum value Bmax,
With EiDivided by empirical evaluation maximum value EmaxEmpirically evaluation coefficient E, with CiDivided by Chemical Evaluation maximum value CmaxAs change
Evaluation coefficient C is learned, and if the toxicity of sample is obvious, with biological assessment minimum value BminDivided by BiAs biological assessment coefficient B,
Or if the toxicity of sample is unobvious, with BiDivided by biological assessment maximum value BmaxAs biological assessment coefficient B,
Using Chemical Evaluation coefficient C, biological assessment coefficient B and empirical evaluation coefficient E as the X-axis, Y-axis, Z axis of space coordinate
On point construct triangle, calculate quality intension value of the area as sample of the triangle, and
Using empirical evaluation coefficient E, Chemical Evaluation coefficient C and biological assessment coefficient B be 1 triangle as maximum triangle simultaneously
Maximum triangle area is calculated, the quality intension value of sample is referred to divided by maximum triangle area to get the quality synthesis of sample
Number,
Wherein, if the toxicity of sample is obvious, the biological assessment be based on toxicity in terms of detection, or if sample toxicity
It is unobvious, the biological assessment be based on drug effect in terms of detection.
2. according to the method described in claim 1, wherein, the empirical evaluation is carried out by weighing the weight of sample,
And the absolute figure E empirically evaluated with the average weight of samplei。
3. according to the method described in claim 1, wherein, if the toxicity of sample is obvious, the Chemical Evaluation be by using
The content of effective component in chemical gauging sample and the content of toxic component carry out, and with active constituent content
Absolute figure C of the ratio of average value and the average value of toxic component content as Chemical EvaluationiAnd by the Chemical Evaluation
Maximum value in all measured values of a collection of sample is as Chemical Evaluation maximum value Cmax。
4. according to the method described in claim 1, wherein, if the toxicity of sample is unobvious, the Chemical Evaluation is to pass through survey
It measures the sum of content of effective component of sample to carry out, and using the average value of the sum of active constituent content as Chemical Evaluation
Absolute figure CiAnd using the maximum value in all measured values of a collection of sample of the Chemical Evaluation as Chemical Evaluation maximum value
Cmax。
5. according to the method described in claim 1, wherein, if the toxicity of sample is obvious, the biological assessment is based on toxicity
The detection of aspect and the biological assessment are carried out by the minimum lethal malicious valence of biology of measurement, and with the lethal life of minimum
Absolute figure B of the average value of object poison valence as biological assessmentiAnd in all measured values of a collection of sample of biological assessment
Minimum value is as biological assessment minimum value Bmin。
6. according to the method described in claim 1, wherein, if the toxicity of sample is unobvious, the biological assessment is based on medicine
The detection in efficacious prescriptions face and the biological assessment are carried out by measuring the biological value of sample, and with the biological value
Absolute figure B of the average value as biological assessmentiAnd made with the maximum value in all measured values of a collection of sample of biological assessment
For biological assessment maximum value Bmax。
7. the method according to claim 3 or 4, wherein the chemical method is UHPLC-Q-TOF/MS or HPLC method.
8. according to the method described in claim 1, wherein, the sample be monkshood, rheum officinale, the coptis, ginseng, Radix Notoginseng, fructus lycii,
Radix Salviae Miltiorrhizae, Radix Glycyrrhizae, radix scutellariae, Schisandra chinensis, the fleece-flower root or cordyceps sinensis.
9. according to the method described in claim 8, wherein, the sample is monkshood.
10. if method according to any one of claims 1 to 9 is in the assessment of Chinese medicine genuineness, elite germplasm breeding, essence mark drink
Purposes in piece exploitation, market circulation high quality and favourable price or clinical rational drug use.
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| CN115340953A (en) * | 2021-05-14 | 2022-11-15 | 四川省中医药科学院 | Efficient screening method of new lucid ganoderma strains |
| CN115479993B (en) * | 2021-05-31 | 2023-09-08 | 中国中医科学院中药研究所 | Quality consistency evaluation method for Chinese patent medicines |
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