Method for optimizing extraction process of classic famous prescription Xiaoxiaoxiao decoction based on orthogonal combination benchmark correlation degree and AHP-entropy weight method

Through the combination of orthogonal experimental design and AHP-entropy weight method, the extraction process of Xiaoxianxun Decoction was optimized, and the problem of difficult to guarantee quality consistency in the existing process was solved, and the quality consistency between the extract and the classic benchmark samples was achieved, providing a scientific basis for the development of modern preparations of Xiaoxianxun Decoction.

CN120064481APending Publication Date: 2025-05-30SHAANXI PROVINCIAL HOSPITAL OF CHINESE MEDICINE
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Patent Information

Application Number
CN202510014750.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-01-06
Publication Date
2025-05-30

AI Technical Summary

Technical Problem

The current extraction process of Xiaoxianxiong Decoction lacks a specific description, which makes it difficult to ensure quality consistency in modern clinical applications.

Method used

The extraction process of Xiaoxianxiong Decoction was optimized by using the orthogonal experimental design combined with the benchmark correlation and AHP-entropy weight method. The content of vanillic acid, hypoxanthine, rosine, berberine, bamartin, berberine, fingerprint map similarity and dry paste rate as evaluation indicators.

Benefits of technology

The scientific credibility of the modern extraction process parameters of Xiaoxianxun Tang is achieved, the quality consistency between the extract and the classic benchmark samples is ensured, and the scientific foundation is laid for subsequent preparation development and industrial production.

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Abstract

The invention belongs to the field of traditional Chinese medicine prescription extraction process optimization, and particularly relates to a method for optimizing a classic famous prescription Xiaoxiaoxiao decoction extraction process based on orthogonal combination benchmark correlation degree and an AHP-entropy weight method. According to the invention, quality evaluation is carried out on the extraction process by taking the quality of a reference sample as a reference standard, orthogonal design is selected, and a relatively comprehensive quality control system taking the contents of vanillic acid, hypoxanthine, jateorhizine, coptisine, palmatine and berberine as well as fingerprint similarity and dry extract rate as comprehensive evaluation indexes is established; the limitation of the traditional single index on the quality control of the extraction process is avoided. A combined weighting method combining AHP and an entropy weight method is adopted, the defects caused by single weighting are overcome, and a reference is provided for modern preparation development of the classic famous prescription Xiaoxiaoxi decoction.
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Description

Technical Field

[0001] The present invention belongs to the field of optimization of traditional Chinese medicine prescription extraction technology, and particularly relates to a method for optimizing the extraction technology of the classical famous prescription Xiaoxiaxiong Decoction based on orthogonal combination of benchmark correlation degree and AHP-entropy weight method. Background Art

[0002] The classical famous prescription Xiaoxiaxiong Decoction comes from Treatise on Febrile and Miscellaneous Diseases written by Zhang Zhongjing in the Eastern Han Dynasty. The whole prescription consists of three herbs: Trichosanthes kirilowii Maxim., Pinellia ternata (Thunb.) Breit., and Coptis chinensis Franch. It is mainly used for treating the syndrome of minor chest-binding caused by exogenous pathogenic factors invading the interior, internal invasion of pathogenic heat, and mutual binding of phlegm-heat in the epigastric region. Xiaoxiaxiong Decoction is widely used in modern clinical applications and is often used to treat diseases in multiple systems such as cardiovascular, digestive, respiratory, and gynecological systems, with significant curative effects.

[0003] At present, there are many clinical and mechanism studies on Xiaoxiaxiong Decoction, but few studies on its extraction technology. In the literature, terms such as "decocting" and "boiling" are often used, lacking specific descriptions of the technology. To solve the above problems, the present invention prepares a benchmark sample of Xiaoxiaxiong Decoction by referring to the method recorded in Treatise on Febrile and Miscellaneous Diseases, and then studies the modern extraction technology with the benchmark sample as a reference. The present invention adopts L9(3 4 ) orthogonal design, uses the quality of the benchmark sample as a reference standard to comprehensively evaluate the modern technology, takes the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity, and dry extract ratio as evaluation indicators, calculates the benchmark correlation degree between each sample and the benchmark sample under various evaluation indicators of different extraction parameters, to evaluate the quality consistency between each sample and the benchmark sample under the modern extraction technology, combines the analytic hierarchy process (AHP)-entropy weight method to determine the weight coefficients of each measurement index, combines the subjective weighting method and the objective weighting method, realizes the unity of subjectivity and objectivity, makes the selected modern extraction technology parameters more scientific and credible, and lays a scientific foundation for the subsequent development of related preparations and industrial production of Xiaoxiaxiong Decoction. Summary of the Invention

[0004] The present invention provides a method for optimizing the extraction technology of the classical famous prescription Xiaoxiaxiong Decoction based on orthogonal combination of benchmark correlation degree and AHP-entropy weight method, which is characterized by including the following steps:

[0005] Taking the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity, and dry extract ratio as evaluation indicators, using orthogonal experimental design combined with benchmark correlation degree and AHP-entropy weight method to obtain a process evaluation function model, and then determining the optimal extraction technology of Xiaoxiaxiong Decoction;

[0006] The process evaluation function model is: comprehensive score = relative deviation (SR) i,香草酸 ×36% + SR i,次黄嘌呤 ×14% + SRi,药根碱 × 13% + SR i,黄连碱 × 11% + SR i,巴马汀 × 11% + SR i,小檗碱 × 12% + SR i,指纹图谱相似度 × 2% + SR i,干膏率 × 3%.

[0007] In the above method, the orthogonal experimental design is to weigh 9 portions of the same batch of medicinal herb slices with the same prescription amount as the traditional process. Taking the soaking time (A), extraction time (B), and water addition amount (times) (C) as 3 factors to be investigated, and taking the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity, and dry extract ratio in the extract as evaluation indexes, extraction is carried out according to the L9(3 4 ) orthogonal table. The reference correlation degree is based on the quality of the reference sample as the standard value (S), the content of each sample under the orthogonal experimental design as the measured value (X), and the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity, and extract yield as 7 evaluation indexes. According to the formula: SR ij = 1 - |X ij - S j | / S j , calculate the reference correlation degree. X ij represents the measured value of the jth (j = 1, 2,..., n) index of the ith (i = 1, 2,..., m) sample in the orthogonal experiment, S j represents the measured value of the jth (j = 1, 2,..., n) index of the reference sample, SR ij represents the reference correlation degree of the jth (j = 1, 2,..., n) index of the ith (i = 1, 2,..., m) sample. The closer the SR ij value is to 100%, the higher the similarity between the sample prepared with the process parameters under this index and the reference sample. The AHP-entropy weight method is to substitute W j s obtained by the AHP method and W j o obtained by the entropy weight method into the formula: to obtain the combined weight coefficient W j, See the following table for details

[0008]

[0009] The AHP method includes the following steps:

[0010] According to vanillic acid > hypoxanthine > jatrorrhizine = coptisine = palmatine = berberine > fingerprint similarity ≈ dry extract ratio; relative scores are assigned to each index respectively, and a pairwise comparison priority judgment matrix is constructed. The results are shown in the following table:

[0011]

[0012]

[0013] Applying the AHP method, the weight coefficients (W j s ) of the eight indicators of the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity and dry extract ratio are 0.34, 0.20, 0.09, 0.09, 0.09, 0.09, 0.05 and 0.05 respectively. The consistency index (CI) is 0.004 and the consistency ratio (CR) is 0.003, both of which are less than 0.10, indicating that the judgment matrix has consistency.

[0014] The entropy weight method includes the following steps:

[0015] Establish an original data matrix (R) with the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity and dry extract ratio as the evaluation indicators. According to the formula: Convert the original data matrix R into a probability matrix (P), where P ij represents the probability of the i-th sample under the j-th indicator. According to the formula: Calculate the information entropy H of each indicator j which are 0.8166, 0.8753, 0.7592, 0.7889, 0.7891, 0.7783, 0.9420, 0.8872 in sequence. According to the formula: Calculate the weight coefficients (W j o ) which are 0.18, 0.12, 0.24, 0.21, 0.21, 0.22, 0.06 and 0.11 in sequence.

[0016] Another embodiment of the present invention provides the above method for optimizing the extraction process of the classical famous prescription Xiaoxiaoyin Decoction based on the orthogonal combination of benchmark correlation degree and AHP-entropy weight method, which is characterized in that the W obtained by the AHP-entropy weight method j , it can be known that the proportion of vanillic acid is 0.36, the proportion of hypoxanthine is 0.14, the proportion of jatrorrhizine is 0.13, the proportion of coptisine is 0.11, the proportion of palmatine is 0.11, the proportion of berberine is 0.12, the proportion of fingerprint similarity is 0.02, and the proportion of dry extract ratio is 0.03; according to the comprehensive scoring formula, calculate the extraction process with the highest comprehensive score, which is the best extraction process of Xiaoxiaoyin Decoction. The best extraction process of Xiaoxiaoyin Decoction is to soak it in 10 times the mass of water for 60 min and then decoct it for 2 h.

[0017] In the extraction process of the present invention, the multiple of the amount of added water is the mass multiple. Description of the Drawings

[0018] Figure 1 It is the fingerprint of the reference sample of Xiaoxiaochong Decoction S1 and samples 1-9 of the orthogonal test S2-S10. Detailed Implementation Modes

[0019] For the convenience of further understanding of the present invention, the following provided embodiments make more detailed descriptions of it. However, these embodiments are only for better understanding the invention and are not used to limit the scope or implementation principles of the present invention. The implementation modes of the present invention are not limited to the following content.

[0020] Example 1

[0021] 1. Instruments and Reagents

[0022] 1.1 Instruments

[0023] Agilent 1260 high performance liquid chromatograph (Agilent Technologies); Agilent high performance liquid chromatograph (Agilent Technologies); analytical balance (Sartorius Scientific Instruments Co., Ltd.); water bath (Beijing Kewei Yongxing Instrument Co., Ltd.); ultrasonic instrument (Ningbo Xinyi Ultrasonic Equipment Co., Ltd.).

[0024] 1.2 Reagents

[0025] (Batch number: CHB201107, purity HPLC≥98%); vanillic acid (batch number: 110776-201503, purity HPLC≥99.8%); jatrorrhizine hydrochloride (batch number: 110733-201609, purity HPLC≥89.5%); coptisine hydrochloride (batch number: 112026-201802, purity HPLC≥94.0%); palmatine hydrochloride (batch number: 110732-201913, purity HPLC≥85.7%); berberine hydrochloride (batch number: 110713-202015, purity HPLC≥85.9%), which were purchased from Chengdu Kloma Biotechnology Co., Ltd. and the National Institutes for Food and Drug Control respectively. Potassium dihydrogen phosphate (Tianjin Kemiou Chemical Reagent Co., Ltd.), phosphoric acid (Tianjin Kemiou Chemical Reagent Co., Ltd.), acetonitrile and methanol were of chromatographic grade (Thermo Fisher), and the rest of the reagents were of analytical grade.

[0026] The three medicinal materials of Trichosanthes kirilowii Maxim., Pinellia ternata (Thunb.) Breit., and Coptis chinensis Franch. were all purchased from Shaanxi Xingshengde Pharmaceutical Co., Ltd. and were identified as genuine products by Teacher Meng Xue of Shaanxi Academy of Traditional Chinese Medicine.

[0027] 2. Methods and Results

[0028] 2.1 Preparation of the Reference Sample

[0029] Take 30 g of Trichosanthes kirilowii Maxim. and place it in a decoction vessel. Add 1200 mL of deionized water, soak for 30 min, first decoct with strong fire and then slow fire until the volume reduces to 600 mL, filter to remove the residue; add 6 g of Coptis chinensis Franch. and 12 g of Pinellia ternata (Thunb.) Breit. to the decoction of Trichosanthes kirilowii Maxim., first decoct with strong fire and then slow fire until the volume reduces to 400 mL, filter to remove the residue, and thus obtain the reference sample of Minor Bupleurum Decoction.

[0030] 2.2 Determination of dry extract ratio

[0031] Precisely measure 10 mL of the reference sample of Minor Bupleurum Decoction into an evaporating dish of constant mass. After evaporating to dryness in a water bath, dry at 105 °C for 3 h, record the mass, and calculate the dry extract ratio.

[0032] 2.3 Determination of fingerprint

[0033] 2.3.1 Chromatographic conditions

[0034] Chromatographic column: Spursil C 18 (250 mm × 4.6 mm, 5 μm); Mobile phase: acetonitrile (A) - 0.05 mol / L potassium dihydrogen phosphate (B) (adjust pH = 4 with phosphoric acid), gradient elution: 0 - 10 min, 2% - 10% A; 10 - 17 min, 10% - 15% A; 17 - 23 min, 15% - 37% A; 23 - 27 min, 37 - 40% A; 27 - 37 min, 40% A; 37 - 45 min, 40% - 2% A; Detection wavelength: 0 - 20 min: 290 nm; 20 - 45 min: 300 nm; Flow rate: 0 - 27 min, 0.8 mL / min; 27 - 37 min, 0.6 mL / min, 37 min - 45 min, 0.8 mL / min; Column temperature: 30 °C; Injection volume: 10 μL.

[0035] 2.3.2 Preparation of mixed reference substance solution

[0036] Weigh appropriate amounts of reference substances of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, and berberine respectively, accurately weigh them into a volumetric flask, dissolve and make up the volume with 20% methanol to obtain single reference substance solutions with mass concentrations of 0.39 mg / mL, 2.07 mg / mL, 0.61 mg / mL, 0.40 mg / mL, 0.40 mg / mL, and 0.37 mg / mL respectively; accurately pipette appropriate amounts of the above single reference substance solutions into the same 5 mL volumetric flask, add 20% methanol to make up the volume to obtain a mixed reference substance solution with concentrations of 15.52 μg / mL, 210.63 μg / mL, 41.14 μg / mL, 46.65 μg / mL, 38.03 μg / mL, and 128.83 μg / mL, and store it at 4 °C.

[0037] 2.3.3 Preparation of test solution

[0038] Precisely measure 3 mL of the reference sample of Minor Decoction for Dispersing Chest Binding and the orthogonal water extracts, place them in an evaporating dish dried to a constant weight, evaporate to dryness in a water bath, dissolve the residue in 20% methanol, transfer it to a 10 mL volumetric flask, make up the volume, shake well, filter through a 0.45 μm microporous membrane, and take the subsequent filtrate to obtain the test solution of Minor Decoction for Dispersing Chest Binding.

[0039] 2.3.4 Establishment of fingerprint and similarity analysis

[0040] Respectively take the reference sample solution (S1) of Minor Decoction for Dispersing Chest Binding and the orthogonal test solutions (S2 - S10) prepared by the method under "2.3.3", inject and determine according to the chromatographic conditions under "2.3.1". Import the chromatogram in cdf format into the "Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints (2012 Edition)" for analysis. Using the fingerprint of the reference sample as the reference chromatogram, adopt the median method, with a time window width of 0.1 s, perform full-spectrum peak matching, and calculate the similarity. The chromatograms are shown in Figure 1 .

[0041] 2.4 Orthogonal extraction experiment

[0042] (1) Determination of critical quality attributes (CQAs) and critical process parameters (CPPs): Based on the theoretical basis of monarch, minister, assistant, and envoy and the previous research foundation of the research group, select the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, and berberine, fingerprint similarity, and dry extract ratio as the CQAs of the extraction process of Minor Decoction for Dispersing Chest Binding. Combining relevant literature, select three factors: soaking time (A), extraction time (B), and water addition amount (times) (C) as the CPPs of the preparation process of Minor Decoction for Dispersing Chest Binding.

[0043] (2) Orthogonal experiment design: Weigh 9 portions of the same batch of medicinal herb slices with the same prescription amount as the traditional process. Take three factors: soaking time (A), extraction time (B), and water addition amount (times) (C) as the investigation objects, and take the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity, and dry extract ratio in the extract as the evaluation indexes, and perform extraction according to the L9(3 4 ) orthogonal table. The results are shown in Table 1.

[0044] Table 1 Orthogonal experiment design and response values

[0045]

[0046] 2.5 Calculation of reference correlation degree

[0047] The reference correlation degree uses the quality of the reference sample as the standard value (S), the content of each sample under the orthogonal experimental design as the measured value (X), and the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity, and extract yield as the seven evaluation indicators. The reference correlation degree is calculated according to formula (1), and the results are shown in Table 2. X ij represents the measured value of the j-th (j = 1, 2,..., n) indicator of the i-th (i = 1, 2,..., m) sample in the orthogonal experiment, S j represents the measured value of the j-th (j = 1, 2,..., n) indicator of the reference sample, SR ij represents the reference correlation degree of the j-th (j = 1, 2,..., n) indicator of the i-th (i = 1, 2,..., m) sample. SR ij The closer the value is to 100%, the higher the similarity between the sample prepared under the process parameters of this indicator and the reference sample [5-6] .

[0048] SR ij = 1 - |X ij - S j | / S j (1)

[0049] As can be seen from Table 2, when vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, and berberine are used as evaluation indicators, the one closest to the material reference is Experiment 5; when the fingerprint is used as the evaluation indicator, the one closest to the material reference is Experiment 7; when the dry extract yield is used as the evaluation indicator, the one closest to the material reference is Experiment 3. In summary, when using a single factor as the evaluation indicator, the optimal result obtained from the experiment will change according to the change of the evaluation indicator. Therefore, the extraction process parameters need to be determined after comprehensive scoring

[0050] Table 2 SR of the orthogonal experiment ij

[0051]

[0052] 2.6 Calculation of the combined weight of the AHP-entropy weight method

[0053] 2.6.1 Subjective weighting by AHP

[0054] (1) Construct a judgment matrix: According to the theory of monarch, minister, assistant, and guide compatibility in traditional Chinese medicine theory [7], Trichosanthes kirilowii Maxim. in Minor Decoction for Resolving Glomus is cold in nature and sweet in taste, with the effects of clearing heat and moistening the intestines, and dispersing binds in the chest and regulating qi. It is the monarch drug; Pinellia ternata (Thunb.) Breit. is pungent, dispersing, warm and dry, and is good at dispelling phlegm dampness in the spleen and stomach, and is mainly used to treat diseases caused by phlegm dampness, and is the minister drug; Coptis chinensis Franch. is extremely bitter and cold, clearing heat and purging fire, and is an important drug for treating damp heat and fire toxin, and is the assistant drug. The compatibility of the whole prescription is appropriate, which can not only remove phlegm heat in the chest diaphragm, but also relieve qi stagnation in the heart. It is an excellent prescription for preventing and treating chest impediment and heart pain. According to the prescription composition of Minor Decoction for Resolving Glomus, vanillic acid in Trichosanthes kirilowii Maxim., hypoxanthine in Pinellia ternata (Thunb.) Breit., jatrorrhizine, coptisine, palmatine, and berberine in Coptis chinensis Franch. were selected as 6 index components, and at the same time, the dry extract ratio and fingerprint were considered. The fingerprint can reflect the profile and qualitative characteristics of small molecule components, but compared with the index components for content determination, the quality information it contains is still less, so its importance is regarded as equally important as the extract ratio. Therefore, vanillic acid > hypoxanthine > jatrorrhizine = coptisine = palmatine = berberine > fingerprint similarity ≈ dry extract ratio. Relative scores were assigned to each index, and a pairwise comparison priority judgment matrix was constructed, and the results are shown in Table 3.

[0055] Table 3 Priority judgment matrix for pairwise comparison of indexes

[0056]

[0057] Using the AHP method, the weight coefficients (W j s ) of the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity and dry extract ratio of 8 indexes were 0.34, 0.20, 0.09, 0.09, 0.09, 0.09, 0.05 and 0.05 respectively. The consistency index (CI) was 0.004, and the consistency ratio (CR) was 0.003, both less than 0.10, indicating that the judgment matrix has consistency. [6] .

[0058] 2.6.2 Objective weighting by entropy weight method

[0059] An original data matrix (R) was established with the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity and dry extract ratio of 8 indexes as evaluation indexes. According to formula (2), the original data matrix R was transformed into a probability matrix (P), and P ij represents the probability of the i-th sample under the j-th index. According to formula (3), the information entropy H of each index was calculated j were 0.8166, 0.8753, 0.7592, 0.7889, 0.7891, 0.7783, 0.9420, 0.8872 in turn. According to formula (4), the weight coefficients (W j oThey are 0.18, 0.12, 0.24, 0.21, 0.21, 0.22, 0.06 and 0.11 in sequence.

[0060]

[0061] 2.6.3 Determination of combined weights

[0062] Obtain \(W\) according to AHP j s , and obtain \(W\) by the entropy weight method j o , substitute into formula (5) to calculate the combined weight coefficient \(W\) of each index j , and the results are shown in Table 4.

[0063]

[0064] Table 4 Combined weights

[0065]

[0066] 2.7 Comprehensive scoring

[0067] The \(W\) obtained by the AHP-entropy weight method j , it can be known that the proportion of vanillic acid is 0.36, the proportion of hypoxanthine is 0.14, the proportion of jatrorrhizine is 0.13, the proportion of coptisine is 0.11, the proportion of palmatine is 0.11, the proportion of berberine is 0.12, the proportion of fingerprint similarity is 0.02, and the proportion of dry extract ratio is 0.03. Calculate the comprehensive score according to formula (6), and the results are shown in Table 1. It can be seen from Table 1 that the comprehensive score of Test 9 is the highest, and the result shows that the modern process parameters most similar to the ancient method are A 3 B 3 C 2 , that is, the sample obtained by soaking with 10 times the amount of water for 60 min and decocting for 2 h is the most consistent with the reference sample in quality.

[0068] Comprehensive score = \(SR\) i,香草酸 ×36% + \(SR\) i,次黄嘌呤 ×14% + \(SR\) i,药根碱 ×13% + \(SR\) i,黄连碱 ×11% + \(SR\) i,巴马汀 ×11% + \(SR\) i,小檗碱 ×12% + \(SR\) i,指纹图谱相似度 ×2% + \(SR\) i,干膏率 ×3% (6) 3 Discussions

[0069] The present invention follows the ancient principle of inheritance and innovative development of traditional Chinese medicine, examines the extraction process of the classic famous prescription Xiaoxiaxiong Decoction, and conducts a comprehensive quality evaluation. To ensure the traditional efficacy of the original decoction, the water decoction method is selected for extraction. The present invention takes the quality of the reference sample as the reference standard to evaluate the quality of the extraction process, selects the orthogonal design, and establishes a relatively comprehensive quality control system with the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity, and dry extract ratio as comprehensive evaluation indicators, avoiding the limitations of traditional single indicators for quality control of the extraction process. At the same time, the AHP-entropy weight method is combined to assign weights to the evaluation indicators. The AHP method belongs to the subjective assignment method, and the decision maker determines the weight coefficients of each evaluation indicator, but there is a problem that subjective factors have a greater impact on the whole process; the entropy weight method, as an objective assignment method, obtains the final weight coefficients according to the data change law, but cannot reflect the relationship of monarch, minister, assistant, and guide in traditional Chinese medicine compound prescriptions. Therefore, a combined weighting method combining AHP and entropy weight method is adopted to make up for the deficiencies brought by single weighting, providing a reference for the modern preparation development of the classic famous prescription Xiaoxiaxiong Decoction.

Claims

1. A method for optimizing the extraction process of the classic prescription Xiaoxianxiong Decoction based on orthogonal combination benchmark association degree and AHP-entropy weight method, characterized in that The steps include: Taking the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, bamipine, berberine, fingerprint similarity and dry extract rate as evaluation indicators, orthogonal experimental design combined with benchmark correlation and AHP-entropy weight method was used to obtain the process evaluation function model, and then the optimal extraction process of Xiaoxianxiong Decoction was determined. The process evaluation function model is comprehensive score = relative deviation (SR) i,香草酸 ×36%+SR i,次黄嘌呤 ×14%+SR i,药根碱 ×13%+SR i,黄连碱 ×11%+SR i,巴马汀 ×11%+SR i,小檗碱 ×12%+SR i,指纹图谱相似度 ×2%+SR i,干膏率 ×3%.

2. The method according to claim 1, characterized in that The orthogonal test design is to weigh the same batch of medicinal pieces with the same prescription amount as the traditional process, a total of 9 parts, with soaking time (A), extraction time (B), water addition (times) (C) as the three factors for investigation, and the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine in the extract, fingerprint similarity and dry paste rate as evaluation indicators, according to L9 (3 4 ) orthogonal array for extraction.

3. The method according to any one of claims 1 to 2, characterized in that The benchmark correlation degree is based on the standard value (S) of the benchmark sample mass, the measured value (X) of each sample content under the orthogonal test design, and the evaluation indicators of the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity and cream yield. According to the formula: SR ij =1-|X ij -S j | / S j , calculate the benchmark correlation, X ij represents the measured value of the jth (j=1, 2, ..., n) index of the ith (i=1, 2, ..., m)th sample in the orthogonal test, S j represents the measured value of the jth (j=1, 2, ..., n) index of the reference sample, SR ij represents the benchmark correlation degree under the jth (j=1, 2, ..., n) indicator of the i-th (i=1, 2, ..., m) sample, SR ij The closer the value is to 100%, the more similar the sample made with the process parameters under this index is to the reference sample.

4. The method according to any one of claims 1 to 3, characterized in that The AHP-entropy weight method is to obtain W according to the AHP method. j s , entropy weight method to obtain W j o Substituting into the formula: The combined weight coefficient W of each evaluation index is obtained j, See the table below for details 5. The method according to any one of claims 1 to 4, characterized in that The AHP method described in claim 4 comprises the following steps: According to vanillic acid>hypoxanthine>jatrorrhizine=coptisine=palmatine=berberine>fingerprint similarity≈dry paste rate; give relative scores to each index respectively, and construct a matrix of priority judgment for pairwise comparison. The results are shown in the following table: The AHP method was used to obtain the weight coefficients of eight indicators (W ) including vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine content, fingerprint similarity and dry cream rate. j s ) were 0.34, 0.20, 0.09, 0.09, 0.09, 0.09, 0.05 and 0.05 respectively, the consistency index (CI) was 0.004, and the consistency ratio (CR) was 0.003, all of which were less than 0.10, indicating that the judgment matrix was consistent.

6. The method according to any one of claims 1 to 5, characterized in that The entropy weight method described in claim 4 comprises the following steps: The original data matrix (R) was established with eight indicators, including the contents of vanillic acid, hypoxanthine, jatrorrhizine, coptisine, palmatine, berberine, fingerprint similarity and dry paste rate, as evaluation indicators. According to the formula: Convert the original data matrix R into a probability matrix (P), P ij It is expressed as the probability of the i-th sample under the j-th indicator. According to the formula: Calculate the information entropy H of each indicator j They are 0.8166, 0.8753, 0.7592, 0.7889, 0.7891, 0.7783, 0.9420, and 0.8872, respectively. According to the formula: Calculate the weight coefficient of each indicator (W j o ) are 0.18, 0.12, 0.24, 0.21, 0.21, 0.22, 0.06 and 0.11 respectively.

7. The method according to any one of claims 1 to 6, characterized in that W obtained by AHP-entropy weight method j It can be seen that vanillic acid accounts for 0.36, hypoxanthine accounts for 0.14, jatrorrhizine accounts for 0.13, coptisine accounts for 0.11, bamipine accounts for 0.11, berberine accounts for 0.12, fingerprint similarity accounts for 0.02, and dry paste rate accounts for 0.03; according to the comprehensive scoring formula, the extraction process with the highest comprehensive score is calculated, which is the optimal extraction process of Xiaoxianxiong Decoction.

8. The method according to any one of claims 1 to 7, characterized in that The optimal extraction process of Xiaoxianxiong Decoction is to soak in 10 times the mass of water for 60 minutes and then boil for 2 hours.

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