Classic famous prescription quality consistency evaluation method based on comparative taste model

Abstract

The invention provides a classical famous prescription quality consistency evaluation method based on a comparative taste model, which comprises the following steps: acquiring a classical famous prescription substance reference and an electronic tongue signal of a sample, carrying out principal component analysis on the electronic tongue signal, constructing the comparative taste model through a variance distance and a distinguishing index, and evaluating the quality consistency of the classical famous prescription. The method comprises the following steps of: evaluating a product obtained in any process step in a classical famous prescription preparation process by adopting a comparative taste model; when a W-Dd value is a positive number, representing that the quality of the classical famous prescription preparation is obviously different from that of a substance reference; when the W-Dd value is a negative number, the quality of the classic famous prescription preparation is close to that of a substance reference, and the quality consistency is achieved. According to the method, the quality consistency of the classic famous prescription is evaluated from the aspect of taste on the basis of the comparative taste model W-Dd value, and the problems that an existing classic famous prescription quality consistency evaluation method is single, complex in process and disjointed with a traditional Chinese medicine theory are solved; and a simple and effective novel method conforming to the traditional Chinese medicine theory is provided for quality consistency evaluation of the classic famous prescription.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and particularly relates to a method for evaluating the quality consistency of classical famous prescriptions based on a reference taste model. Background Art

[0002] Classical famous prescriptions refer to the prescriptions recorded in ancient Chinese medical classics that are still widely used, have definite curative effects, and have obvious characteristics and advantages. The "Regulations on the Simplified Registration and Approval of Traditional Chinese Medicine Compound Preparations of Classical Famous Prescriptions" stipulates that the development of classical famous prescription preparations should be carried out in two stages. The first stage is the development of the material reference of classical famous prescriptions, and the second stage is the preparation of preparations with the material reference as a reference. The "Technical Guidelines for the Pharmaceutical Research of Traditional Chinese Medicine Compound Preparations Managed According to the Catalogue of Classical Famous Prescriptions in Ancient Times (Trial)" states that "benchmark samples should be studied and prepared in accordance with the key information of classical famous prescriptions in ancient times released by the state and the records in ancient medical books, and their key quality attributes should be clarified, with the goal of the preparation quality being basically consistent with the benchmark sample quality". It can be seen that the development of classical famous prescriptions must maintain "quality consistency".

[0003] In terms of the evaluation of the quality consistency of classical famous prescriptions, currently, the quality consistency between the preparations produced on a commercial scale and the benchmark samples is mainly described from aspects such as the dry extract ratio, the content of index components, and fingerprints / characteristic spectra. This evaluation mode mainly focuses on the changes in chemical components in classical famous prescriptions, with a single evaluation method, a complex evaluation process, and being disconnected from traditional Chinese medicine theory. Classical famous prescriptions are the prescriptions recorded in ancient Chinese medical classics, and the evaluation of their quality consistency should be guided by traditional Chinese medicine theory.

[0004] The theory of the properties of traditional Chinese medicine is an important part of traditional Chinese medicine theory, and the five flavors of traditional Chinese medicine are one of the core contents of the theory of the properties of traditional Chinese medicine. It is the result of the long-term practice of Chinese medical scientists in past dynasties and an important theoretical basis for guiding the clinical use of traditional Chinese medicine. The five flavors are not only a true reflection of the taste of traditional Chinese medicine, but also go beyond the scope of taste and are based on efficacy, becoming a highly generalized description of the effects of drugs.

[0005] An electronic tongue is an instrument that simulates the human taste mechanism to detect samples, featuring strong objectivity, good repeatability, rapid detection, dynamic monitoring, standardized control, etc. As an intelligent sensor technology that mimics human taste perception, in recent years, electronic tongue technology has made some progress in the objective evaluation of the five flavors of traditional Chinese medicine (sour, bitter, sweet, pungent, salty). For example, some scholars have successfully distinguished Phellodendri Chinensis Cortex (bitter), Zingiberis Rhizoma (pungent), and Astragali Radix (sweet) using an electronic tongue, with an accuracy rate exceeding 90%. Other scholars have quantified the taste changes of traditional Chinese medicine before and after processing using an electronic tongue. For example, the sweet taste of Rehmanniae Radix (sweet and bitter) is enhanced after steaming. In terms of the quality control and standardization of traditional Chinese medicine, people use an electronic tongue to monitor the taste stability of Chinese medicinal materials or finished products (such as Liuwei Dihuang Pills), and detect adulterated medicinal materials through taste fingerprint recognition (such as the abnormal detection of the sweet taste of honey). Currently, there is no method for evaluating the quality consistency of classical famous prescriptions and their preparations from the perspective of taste / flavor using electronic tongue technology. Summary of the Invention

[0006] The object of the present invention is to address the key issues in the quality consistency evaluation of classical famous prescriptions of traditional Chinese medicine. Starting from the taste of classical famous prescriptions, the electronic tongue technology is applied to the quality consistency evaluation of classical famous prescriptions, and a quality consistency evaluation method that reflects the overall taste of classical famous prescriptions is established, breaking through the limitation of the theory of only focusing on ingredients in the research of classical famous prescriptions of traditional Chinese medicine. Starting from the overall concept of traditional Chinese medicine theory, a new method is provided for the quality consistency evaluation of classical famous prescriptions of traditional Chinese medicine.

[0007] To solve the problems of the theory of only focusing on ingredients, complex evaluation process, and not starting from the overall concept of traditional Chinese medicine theory in the existing quality consistency evaluation methods of classical famous prescriptions, the present invention adopts the following technical solutions.

[0008] A quality consistency evaluation method for classical famous prescriptions based on a reference taste model, characterized in that the reference taste model is used to evaluate the quality consistency between the product obtained from any process step in the preparation process of classical famous prescription preparations and the substance benchmark, including the following steps: (1) Optimize the voltammetric electronic tongue sensor combination and select the optimal sensor combination; (2) Use the voltammetric electronic tongue to detect and compare the distance between the classical famous prescription preparation and the substance benchmark, and perform principal component analysis on the electronic tongue signals; (3) Construct a "reference taste" model (W-Dd): (Formula 1) Where Dd is the variance distance and DI is the discrimination index: in the PCA graph, the classical famous prescription preparation and the substance benchmark are completely separated, and the calculation method of the DI value is shown in formula (2); in the PCA graph, there is an overlapping part between the classical famous prescription preparation and the substance benchmark, and the calculation method of the DI value is shown in formula (3): (Formula 2) (Formula 3) In Formulas (2) and (3), S i is the area of the region of a single sample, and S0 is the total area of all sample regions; (4) Evaluation is performed according to the reference taste model W-Dd value: When the DI value is positive and closer to 100%, the W-Dd value is positive, indicating that the differentiation effect between the classical famous prescription preparation and the material reference is good, that is, there is an obvious difference between the two; when the DI value is negative and the value is smaller, the W-Dd value is negative, indicating that the quality of the classical famous prescription preparation is relatively close to that of the material reference, and it also indicates that the quality of the two is consistent.

[0009] The described method for evaluating the quality consistency of classical famous prescriptions based on the reference taste model is characterized in that the classical famous prescription preparation includes intermediate products and final products obtained from all processes in the preparation process.

[0010] The described method for evaluating the quality consistency of classical famous prescriptions based on the reference taste model is characterized in that the physical object of the classical famous prescription material reference is any one of an extract, a concentrated solution, an extract paste or a powder; the classical famous prescription preparation is any one of tablets, pills, powders, granules, injections, tinctures, solutions, extract pastes, ointments.

[0011] The described preparation process of the classical famous prescription includes any one or more of an extraction process, a purification process, a drying process and a forming process.

[0012] The technical solution of the present invention has the following advantages: The present invention provides a method for evaluating the quality consistency of classical famous prescriptions based on the reference taste model, in which a reference taste model is proposed. This model uses a voltammetric electronic tongue. First, the electronic tongue sensor combination is optimized, and the optimal sensor combination is selected. Through electronic tongue measurement, the PCA diagrams of the sample and the material reference are obtained, the variance distance Dd and the discrimination index DI are obtained, and then the reference taste model W-Dd is constructed by multiplying the two. A method for evaluating the quality consistency of classical famous prescriptions is constructed through the reference taste model. The method provided by the present invention is simple, intuitive, has good discrimination, conforms to the characteristics of traditional Chinese medicine theory, can better ensure the quality consistency between the classical famous prescription preparation product and the reference substance, and further improve the consistency of clinical efficacy. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] By referring to the following drawings, the exemplary embodiments of the present invention can be more completely understood

[0014] Figure 1 is the electronic tongue PCA analysis diagram of the material reference and the sample of the classical famous prescription Qingxin Lianzi Yin in Example 1 of the present invention.

[0015] Figure 2 It is the result diagram of the influence of the extraction times in Example 2 of the present invention on the "reference taste" of Qingxin Lianzi Yin; wherein: Figure 2 In A, it is the PCA diagram of the samples with different extraction times and the substance reference; Figure 2 In B, it is the reference taste diagram of the samples with different extraction times. Compared with the extraction for 2 times, * indicates P < 0.05.

[0016] Figure 3 It is the result diagram of the influence of the extraction water addition amount in Example 2 of the present invention on the "reference taste" of Qingxin Lianzi Yin; wherein: Figure 3 In A, it is the PCA diagram of the samples with different water addition amounts and the substance reference; Figure 3 In B, it is the reference taste diagram of the samples with different water addition amounts. Compared with the 8-fold water addition amount, * indicates P < 0.05.

[0017] Figure 4 It is the result diagram of the influence of the soaking time of the medicinal materials in Example 2 of the present invention on the "reference taste" of Qingxin Lianzi Yin; wherein: Figure 4 In A, it is the PCA diagram of the samples with different soaking times and the substance reference; Figure 4 In B, it is the reference taste diagram of the samples with different soaking times. Compared with the soaking for 0.5 h, * indicates P < 0.05.

[0018] Figure 5 It is the result diagram of the influence of the extraction time of the medicinal materials in Example 2 of the present invention on the "reference taste" of Qingxin Lianzi Yin; wherein: Figure 5 In A, it is the PCA diagram of the samples with different extraction times and the substance reference; Figure 5 In B, it is the reference taste diagram of the samples with different extraction times. Compared with the extraction for 1.0 h, * indicates P < 0.05.

[0019] Figure 6 It is the prediction contour diagram and response surface diagram of the optimal extraction process of Qingxin Lianzi Yin in Example 2 of the present invention.

[0020] Figure 7 It is the result diagram of the influence of the drying method of Qingxin Lianzi Yin in Example 3 of the present invention on the "reference taste"; wherein: Figure 7 In A, it is the PCA diagram of the samples with different drying methods and the substance reference; Figure 7 In B, it is the reference taste diagram of the samples with different drying methods. Compared with freeze-drying, * indicates P < 0.05.

[0021] Figure 8 It is the result diagram of the influence of the spray drying feed rate on the "reference taste" of Qingxin Lianzi Yin in Example 3 of the present invention; wherein: Figure 8 In A, it is the PCA diagram of the samples with different feed rates in spray drying and the substance reference; Figure 8In Figure B, it is the reference taste map of samples with different feeding speeds in spray drying. Compared with 25 rpm, * indicates P < 0.05.

[0022] Figure 9 It is the result diagram of the influence of the outlet air temperature in spray drying on the "reference taste" of Qingxin Lianzi Yin in Example 3 of the present invention; among them: Figure 9 In Figure A, it is the PCA map of samples with different outlet air temperatures in spray drying and the substance reference; Figure 9 In Figure B, it is the reference taste map of samples with different outlet air temperatures in spray drying. Compared with 65 °C, * indicates P < 0.05.

[0023] Figure 10 It is the result diagram of the influence of the inlet air temperature in spray drying on the "reference taste" of Qingxin Lianzi Yin in Example 3 of the present invention; among them: Figure 10 In Figure A, it is the PCA map of samples with different inlet air temperatures in spray drying and the substance reference; Figure 10 In Figure B, it is the reference taste map of samples with different inlet air temperatures in spray drying. Compared with 140 °C, * indicates P < 0.05.

[0024] Figure 11 It is the prediction contour map and response surface map of the optimal spray drying process of Qingxin Lianzi Yin in Example 3 of the present invention. Specific embodiments

[0025] The present invention will be further described in detail below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto.

[0026] Example 1: Establishment and method verification of the "reference taste" model of the classical famous prescription Qingxin Lianzi Yin.

[0027] 1. Preparation of the substance reference solution: Weigh 11.2 g of Scutellaria baicalensis, Ophiopogon japonicus, Cortex Lycii Radicis, Plantago asiatica, and stir-fried Glycyrrhiza uralensis respectively according to the prescription ratio, 16.9 g of Nelumbo nucifera, Poria cocos, Astragalus membranaceus roasted, and Ginseng, crush them into coarse grains, add 30 g of Ophiopogon japonicus, add 4500 ml of water, decoct in a ceramic pot for 1 h, filter the medicinal liquid through a No. 5 sieve, concentrate to 1000 mL, and freeze-dry to obtain the freeze-dried powder of the substance reference. Weigh an appropriate amount of the substance reference, add distilled water, and dissolve it into a substance reference solution of 0.22 mg / mL (0.57 mg of crude drug / mL).

[0028] 2. Preparation of the sample solution: Weigh 6 times the prescription amount of the coarse powder into a round-bottom flask, add 8 times the amount of water, heat under reflux for 2 h, filter through gauze to obtain the extract; measure an appropriate amount of the extract, and dilute it with distilled water to 0.57 mg / mL (calculated by the amount of crude drug).

[0029] 3. Optimization of the electronic tongue sensor combination: The 6 electrodes (S1-S6) of the voltammetric electronic tongue were tested and data were collected at frequency bands of 1, 10, and 100 Hz respectively. The collected sample data were optimized for the sensor, and the electrode and frequency band combination with the largest Discrimination index (DI) was selected for the experiment. The results are shown in Table 1. The results show that the sensor array combination with the highest DI value is S1_10Hz_S2_10Hz_S3_10Hz_S4_100Hz_S5_10Hz. Therefore, the above combination was used in this experiment.

[0030] Table 1 Optimization of Electronic Tongue Sensors 。

[0031] 4. Establishment of the "reference taste" model: The electronic tongue mainly uses chemometrics to reduce the dimension of complex data. After the substance reference and the sample are analyzed by PCA, they each enclose an area in the PCA graph. Therefore, the distance can be used to characterize the similarity between the two. The currently common distances are Euclidean distance (Ed), DiscriminationPower (Dp), and variance distance (Dd). Therefore, in this study, the most stable one was selected as the quality consistency evaluation index. The most stable variance distance (Dd) was selected in this study to evaluate the similarity. The results are shown in Table 2. However, analyzing the data found that when two substances overlap, the Dd value can still be calculated, and the data cannot intuitively reflect whether the two samples are separated; Therefore, this study constructed the "reference taste" (WeightedDifferentialdistance, W-Dd). W-Dd = DI × Dd, where Dd is the variance distance and DI is the discrimination index. When the DI value is positive and closer to 100%, the W-Dd value is positive, indicating good discrimination between substances, that is, there are obvious differences between the two; when the DI value is negative and the value is smaller, the W-Dd value is negative, indicating that the properties of the two substances are relatively close, and also indicating that the properties of the two substances have a certain consistency; The substance reference solution and the sample solution were placed in a special beaker for the electronic tongue, and the electronic tongue was used to repeat the measurement 6 times. After the measurement was completed, PCA analysis was performed between the substance reference and the sample. The results are shown in Figure 1 ; The W-Dd value between the substance reference and the sample was calculated through the PCA graph, and the RSD value was calculated. The results are shown in Table 3. It can be seen from Table 3 that the RSD value of W-Dd is 4.85%, which is relatively stable. Therefore, the reference taste W-Dd can be used as a new index for quality consistency.

[0032] Table 2 Distance Analysis between Substance Reference and Sample 。

[0033] Table 3 Precision analysis of the reference taste model 。

[0034] 5. Precision test, repeatability test and stability test of the determination method of the reference taste model: Take the sample solution under item "2", continuously measure it 6 times, calculate the "reference taste" and its RSD value to obtain the result of the method precision test. According to the method under item "2", prepare 6 portions of sample solutions in parallel, measure them, calculate the "reference taste" and its RSD value to obtain the result of the repeatability test. Take the sample solution under item "2" and measure it at 0, 2, 4, 8, 12, and 24 h after preparation, calculate the "reference taste" and its RSD value to obtain the result of the stability test; The results of the precision investigation show that the RSD of the precision test is 2.36%, indicating that the precision of the method is good; the results of the repeatability test show that among the 6 measurements, the RSD of the "reference taste" is 5.63%, indicating that the repeatability of this method is good. The results of the stability analysis show that among the 6 measurements, the RSD of the "reference taste" is 3.57%, indicating that the stability of the method is good.

[0035] Example 2: Application of the reference taste model in the extraction process of the classical famous prescription Qingxin Lianzi Yin

[0036] 1. Preparation of the material reference of Qingxin Lianzi Yin: Prepare the material reference of Qingxin Lianzi Yin according to the method under item "1" in Example 1, weigh an appropriate amount, and make a material reference solution of 0.57 mg crude drug / mL with distilled water.

[0037] 2. Single-factor investigation of the extraction process of Qingxin Lianzi Yin: 2.1 Investigation of the extraction times: Weigh 6 times the prescription amount of the crude powder, take 3 portions in a round-bottom flask, add 8 times the amount of water, heat under reflux for 1.5 hours, and extract 1, 2, and 3 times respectively. Take an appropriate amount of the extract, dilute it with water to make a solution of 0.57 mg crude drug / mL, and calculate the "reference taste" of the samples with different extraction times. The results are shown in Figure 2 。The results show that with the increase of the extraction times, the "reference taste" decreases; compared with extracting 2 times, the "reference taste" of extracting 1 time increases significantly (P < 0.05), and there is no significant difference between extracting 3 times and extracting 2 times; the results indicate that the quality of the solutions extracted 2 times and 3 times is basically the same as that of the material reference. Therefore, the extraction times are selected as 2 times.

[0038] 2.2 Investigation of the amount of water added: Weigh 6 times the prescription amount of the crude powder, add 6, 8, 10, 12, and 14 times the amount of water respectively, soak for 0.5 hours, extract 2 times, reflux with heating for 1.5 hours each time, and combine the two extraction solutions. Take an appropriate amount of the extraction solution, add water to make a solution with a concentration of 0.57 mg of crude drug / mL, calculate the "reference taste" of the samples with different water addition amounts, and the results are shown in Figure 3 . The results show that as the water addition amount increases, the "reference taste" increases accordingly; compared with the water addition amount of 8 times, when the water addition amounts are 10 times, 12 times, and 14 times, the "reference taste" increases significantly ( P＜0.05 ). When the water addition amount is 6 times, the "reference taste" shows no obvious change, and when the water addition amounts are 6 times and 8 times, the "reference taste" is negative, indicating that its quality is basically consistent with the substance standard.

[0039] 2.3 Investigation of the soaking time: Weigh 6 times the prescription amount of the crude powder, add 8 times the amount of water, and when the soaking times are 0, 0.5, 1, 1.5, and 2 h respectively, the extraction times are 2 times, 1.5 hours each time, and combine the two extraction solutions. Take an appropriate amount of the extraction solution, add water to make a solution with a concentration of 0.57 mg of crude drug / mL, calculate the "reference taste" of the samples with different soaking times, and the results are shown in Figure 4 . The results show that the "reference taste" is the smallest when the soaking time is 0.5 h; compared with the soaking time of 0.5 h, when the soaking times are 1.0 h, 1.5 h, and 2.0 h, the "reference taste" increases significantly ( P＜0.05 ).

[0040] 2.4 Investigation of the extraction time: Weigh 6 times the prescription amount of the crude powder, add 8 times the amount of water, soak for 0.5 hours, the extraction times are 2 times, and extract for 0.5, 1.0, 1.5, 2.0, and 2.5 h respectively each time, and combine the two extraction solutions. Take an appropriate amount of the extraction solution, add water to make a solution with a concentration of 0.57 mg of crude drug / mL, calculate the "reference taste" of the samples with different extraction times, and the results are shown in Figure 5 . The results show that the "reference taste" first decreases and then increases as the extraction time increases; compared with the extraction time of 1.0 h, when the extraction times are 0.5 h, 1.5 h, 2.0 h, and 2.5 h, the "reference taste" increases significantly ( P＜0.05 ). Therefore, it is determined to select the extraction time of 0.5 - 1.5 h as the investigation range.

[0041] 3. Optimization of the extraction process of Qingxin Lianziyin by Box - Behnken design - response surface experiment: 3.1 Experimental design and results: On the basis of single-factor influence experiments, taking the "reference taste" W-Dd(Y) as the dependent variable, the water addition amount (A), soaking time (B), and extraction time (C) as independent variables, a Box-Behnken design-response surface experiment was adopted to optimize the extraction process of Qingxin Lianzi Yin. The investigated factors and levels of the Box-Behnken design are shown in Table 4, and the results of the response surface experiment are shown in Table 5.

[0042] Table 4 Investigated factors and levels of the Box-Behnken design for the extraction process of Qingxin Lianzi Yin 。

[0043] Table 5 Results of the response surface experiment for the extraction process of Qingxin Lianzi Yin 。

[0044] 3.2 Response surface model establishment and variance analysis: The Design Expert 13 software was used for model fitting, and the results of the variance analysis are shown in Table 6. The results show that the quadratic polynomial model is extremely significant, and the lack-of-fit term is not significant, indicating that the model has statistical significance. Among them, the P values of A and B are <0.001, indicating that the water addition amount and soaking time have a significant impact on the "reference taste"; the P values of AC and BC are <0.05, indicating that there are significant interaction effects between the water addition amount and extraction time, and between the soaking time and extraction time; The regression equation of the established evaluation index "reference taste" (Y) for the three factors (A, B, C) is Y = -1.66 + 1.48A + 0.8787B + 0.0688C + 0.3175AB + 0.6725AC + 0.3450BC + 1.80A 2 + 0.9745B 2 + 1.07C 2 ,R 2 = 0.9894. The experimental data were fitted using the quadratic multiple regression equation. One of the factor levels was determined as the center point, and the response surface diagrams with the other two factors were drawn to predict the optimal extraction process of Qingxin Lianzi Yin. The results are shown in Figure 6 ,and its optimal extraction process is to add 6.94 times water, soak for 0.27 h, and extract for 1.06 h.

[0045] Table 6 Regression model and variance analysis of "reference taste" 。

[0046] 3.3 Verification experiment: The optimal extraction process of Qingxin Lianzi Yin is as follows: adding 6.94 times the amount of water, soaking for 0.27 h, and extracting for 1.06 h. Adjusted according to the actual situation to: adding 7 times the amount of water, soaking for 0.3 h, and extracting for 1.1 h. Prepare 3 batches of Qingxin Lianzi Yin extraction solution according to this extraction process, and measure the "reference taste" W-Dd value. The results are shown in Table 7. The results show that the actual value is basically consistent with the predicted value. The verification experiment shows that this extraction process is stable and feasible.

[0047] Table 7 Comparison of predicted and measured values of "reference taste" of the extraction process of Qingxin Lianzi Yin (n = 3) 。

[0048] Example 3: Application of the reference taste model in the drying process of the classical famous prescription Qingxin Lianzi Yin.

[0049] In this example, the "reference taste" was used as the evaluation index to investigate the influence of drying process parameters on the "reference taste". On the basis of single-factor investigation, the Box Behnken design-response surface method was used to optimize the drying process of Qingxin Lianzi Yin.

[0050] Preparation of the reference substance of Qingxin Lianzi Yin: Prepare the reference substance of Qingxin Lianzi Yin according to the method under item "1" of Example 1. Weigh an appropriate amount and make a reference substance solution containing 0.57 mg of crude drug / mL with distilled water.

[0051] Preparation of the decoction of Qingxin Lianzi Yin: Prepare the extraction solution according to the method under item "2" of Example 1, and concentrate it under normal pressure to obtain the concentrated solution.

[0052] 3. Selection of drying methods: 3.1 Preparation of freeze-dried samples: Pour the concentrated solution into a beaker with a thickness of about 5 mm, pre-freeze at -20 °C for 12 h, and then freeze-dry for 72 h to obtain the freeze-dried sample.

[0053] 3.2 Preparation of vacuum-dried samples: Pour the concentrated solution into a beaker with a thickness of about 5 mm, place it in a vacuum drying oven at 70 °C for drying, dry for 48 h, and control the vacuum degree at -0.1 MPa to obtain the vacuum-dried sample.

[0054] 3.3 Preparation of spray-dried samples: Inhale the concentrated solution into the spray dryer, set the inlet air temperature at 140 °C, the outlet air temperature at 65 °C, and the liquid inlet speed at 20 rpm to obtain the spray-dried sample.

[0055] 3.4 Preparation of microwave-dried samples: Pour the concentrated solution into a beaker with a thickness of about 5 mm, and place it in a microwave oven for drying to obtain a microwave-dried sample.

[0056] 3.5 Preparation of samples dried under normal pressure: Pour the concentrated solution into a beaker with a thickness of about 5 mm, and place it in a forced-air drying oven at 70 °C for drying for 72 h to obtain a sample dried under normal pressure.

[0057] 3.6 Preparation of sample solutions: Weigh appropriate amounts of samples dried by freeze-drying, vacuum drying, spray drying, microwave drying, and drying under normal pressure respectively, and add water to make a solution of 0.57 mg of crude drug / mL.

[0058] 3.7 Research results on the influence of drying methods on "reference taste": The results are shown in Figure 7 . The results show that among the five drying methods, the "reference taste" of the freeze-dried sample is the smallest; compared with freeze-drying, the "reference taste" of vacuum drying, spray drying, microwave drying, and drying under normal pressure increases significantly ( P<0.05 ). The "reference taste" of spray drying is only slightly larger than that of freeze-drying, and compared with freeze-drying, spray drying has the advantages of low energy consumption and high efficiency; therefore, in this example, the spray drying process of Qingxin Lianzi Yin will be optimized.

[0059] 4. Single-factor investigation: 4.1 Influence of spray drying feed rate on "reference taste": Fix the outlet air temperature at 60 °C and the inlet air temperature at 140 °C, and investigate the change of "reference taste" when the feed rate is 10 rpm, 15 rpm, 20 rpm, 25 rpm, and 30 rpm. The results are shown in Figure 8 . The results show that when the feed rate is 25 rpm, the "reference taste" is the smallest; compared with 25 rpm, there are significant differences in the "reference taste" of 10 rpm, 15 rpm, 20 rpm, and 30 rpm ( P<0.05 ).

[0060] 4.2 Influence of outlet air temperature on "reference taste": Fix the feed rate at 20 rpm and the inlet air temperature at 140 °C, and investigate the change of "reference taste" when the outlet air temperature is 50 °C, 55 °C, 60 °C, 65 °C, and 70 °C. The results are shown in Figure 9 . The results show that when the outlet air temperature is 65 °C, the "reference taste" is the smallest; compared with 65 °C, there are significant differences in the "reference taste" of 50 °C, 55 °C, 60 °C, and 70 °C ( P<0.05 ).

[0061] 4.3 Influence of inlet air temperature on "reference taste": The fixed feed rate was 20 rpm, and the outlet air temperature was 60 °C. The changes in the "reference taste" were investigated at inlet air temperatures of 110 °C, 120 °C, 130 °C, 140 °C, and 150 °C. The influence of the inlet air temperature on the "reference taste" is shown in Figure 10 . The results showed that the "reference taste" was the smallest at an inlet air temperature of 140 °C. Compared with 140 °C, the "reference tastes" at 110 °C, 120 °C, 130 °C, and 150 °C were significantly different ( P＜0.05 ).

[0062] 5. Box Behnken Design - Response Surface Experiment: 5.1 Experimental Design and Results: On the basis of the single - factor experiment, with the "reference taste" W - Dd (Y) as the dependent variable, and the feed rate (A), outlet air temperature (B), and inlet air temperature (C) as independent variables, the Box Behnken design - response surface method was used to optimize the drying process of Qingxin Lianzi Yin. The factor and level arrangements are shown in Table 8, and the response surface experiment results are shown in Table 9.

[0063] Table 8 Investigation Factors and Levels of Box Behnken Design .

[0064] Table 9 Response Surface Experiment Results of Spray Drying Process .

[0065] 5.2 Response Surface Model Establishment and Variance Analysis: The Design Expert 13 software was used for model fitting, and the variance analysis results are shown in Table 10. The results showed that the quadratic polynomial model P<0.0001 ; the lack - of - fit term was 0.3071, which was not significant, indicating that the model had statistical significance and could be used to represent the relationship between each factor and the response value. Among them, the P<0.01 of C indicated that the influence of the inlet air temperature on the "reference taste" was significant. The P<0.05 of BC indicated that there was a significant interaction between the outlet air temperature and the inlet air temperature; The regression equation of the evaluation index "reference taste" for the three factors was: Y = 1.16 + 0.1736A + 0.0087B - 0.6472C + 0.2112AB - 0.0348AC - 0.4513BC + 0.6044A 2 + 0.9086B 2 + 1.01C 2 , R 2= 0.9768. The experimental data was fitted using a quadratic polynomial regression equation to determine one of the factor levels as the central point, and the response surface plots with the other two factors were drawn to predict the optimal drying process of Qingxin Lianzi Yin. The results are shown in Figure 11 .

[0066] Table 10 Regression Model and Variance Analysis of "Quasi-Taste" .

[0067] 5.3 Verification Experiment: Based on the model generated by the Box Behnken-response surface experiment, the optimal drying process was predicted to be a feeding speed of 24.25 rpm, an outlet air temperature of 65.49 °C, and an inlet air temperature of 143.40 °C, with a quasi-taste of 1.04166. Adjusted according to the actual situation to: feeding speed 25 rpm, outlet air temperature 65 °C, inlet air temperature 145 °C. Three portions of dry powder were prepared according to this extraction process, and the "quasi-taste" was measured. The results are shown in Table 11. The results show that the actual values are basically in line with the predicted values.

[0068] Table 11 Comparison of Predicted Values and Measured Values (n = 3) .

[0069] The above embodiments are used to explain the present invention, rather than limiting the present invention. Any modifications and changes made within the spirit and scope of the protection of the present invention fall within the protection scope of the present invention.

Claims

1. A method for evaluating the quality consistency of classical famous prescriptions based on a reference taste model, characterized in that The quality consistency between the product obtained from any process step in the preparation of a classical famous prescription preparation and the substance reference is evaluated using the reference taste model. The specific steps are as follows: (1) Optimize the voltammetric electronic tongue sensor combination and select the preferred sensor combination; (2) Detect and comparatively analyze the distance between the classical famous prescription preparation and the substance reference using the voltammetric electronic tongue, and perform principal component analysis on the electronic tongue signals; (3) Construct the "reference taste" model (W-Dd): (Formula 1) Among them, Dd is the variance distance and DI is the discrimination index: in the PCA plot, the classical famous prescription preparations and the substance reference are completely separated, and the calculation method of the DI value is shown in formula (2); in the PCA plot, there is an overlapping part between the classical famous prescription preparations and the substance reference, and the calculation method of the DI value is shown in formula (3): (Formula 2) (Formula 3) In Formulas (2) and (3), S i is the area of the region of a single sample, and S0 is the total area of the regions of all samples; (4) Evaluate according to the W-Dd value of the reference taste model: when the DI value is positive and closer to 100%, the W-Dd value is positive, indicating that the differentiation effect between the classical famous prescription preparation and the substance reference is good, that is, there are obvious differences between the two; when the DI value is negative and the value is smaller, the W-Dd value is negative, indicating that the quality of the classical famous prescription preparation is relatively close to that of the substance reference, and also indicating the quality consistency between the two.

2. The quality consistency evaluation method for classical famous prescriptions based on the reference taste model according to claim 1, wherein The classical famous prescription preparation includes the intermediate products and final products obtained from all processes in the preparation process.

3. A method for evaluating the quality consistency of classical famous prescriptions based on a reference taste model according to claim 1 or 2, characterized in that The physical object of the classical famous prescription substance reference is any one of the extract, concentrated solution, extract, or powder; the classical famous prescription preparation is any one of tablets, pills, powders, granules, injections, tinctures, solutions, extractives, ointments.

4. The classical famous prescription preparation process according to claim 2 includes any one or more of the extraction process, purification process, drying process, and forming process.

Images