Preparation process of Chinese patent medicine for treating hypertension based on big data analysis

Abstract

The invention discloses a preparation process of a Chinese patent medicine for treating hypertension based on big data analysis, and belongs to the technical field of Chinese patent medicine pharmacy. According to the method, the problems of low preparation efficiency and raw material waste in the existing process are solved, different types of hypertension Chinese patent medicine samples are collected and subjected to chemical component analysis, and the drug effect and action mechanism of each hypertension Chinese patent medicine sample are obtained; designing a pharmacodynamic experiment scheme, and finding out a potential relationship between a preparation process and pharmacological activity of each hypertension Chinese patent medicine sample; the neural network model is trained by using experimental data, so that the model can accurately predict the relationship between the new hypertension Chinese patent medicine preparation process and the pharmacological activity; the condition parameters of the preparation process are adjusted according to the prediction result, so that the preparation process of the new hypertension Chinese patent medicine is optimized; the active ingredients, the efficacy and the action mechanism of the hypertension Chinese patent medicine are comprehensively known, and a scientific basis is provided for reasonable application and preparation of the hypertension Chinese patent medicine.

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese patent medicine pharmaceutical preparation, and in particular to a preparation process of a Chinese patent medicine for treating hypertension based on big data analysis. Background Art

[0002] At present, the most common health problem is the "three highs", namely: high blood pressure, high blood lipids, and high blood sugar. These diseases seriously affect people's physical health and quality of life; therefore, eliminating the "three highs" has become one of the current social concerns.

[0003] In the prior art, Chinese patent medicines for the treatment of hypertension are widely used in clinical practice, but the traditional preparation process has many problems, such as long preparation time and large waste of raw materials, which leads to the insufficient practicality of the preparation process of the existing Chinese patent medicines for hypertension and unsatisfactory development prospects.

[0004] Therefore, the existing needs are not met, and we propose a preparation process for Chinese patent medicine for the treatment of hypertension based on big data analysis. Summary of the invention

[0005] The purpose of the present invention is to provide a preparation process of a traditional Chinese medicine for treating hypertension based on big data analysis. By collecting different types of traditional Chinese medicine samples for hypertension and analyzing their chemical components, the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension are obtained; a pharmacodynamics experiment plan is then designed to find out the potential relationship between the preparation process and pharmacological activity of each traditional Chinese medicine sample for hypertension; and a neural network model is trained using experimental data so that the model can accurately predict the relationship between the preparation process and pharmacological activity of a new traditional Chinese medicine for hypertension; so as to adjust the condition parameters of the preparation process according to the prediction results, thereby optimizing the preparation process of the new traditional Chinese medicine for hypertension; a comprehensive understanding of the active ingredients of the traditional Chinese medicine for hypertension, its efficacy and mechanism of action, provides a scientific basis for the rational application and preparation of traditional Chinese medicine for hypertension, and solves the problems raised in the above-mentioned background technology.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] The preparation process of a traditional Chinese medicine for treating hypertension based on big data analysis includes the following steps:

[0008] Step 1: Collect different types of traditional Chinese medicine samples for hypertension, and organize and analyze each of the collected traditional Chinese medicine samples for hypertension to obtain the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension;

[0009] Step 2: Perform chemical component analysis on each hypertension Chinese patent medicine sample, separate and extract the effective components, purify and identify the effective components, and then record the effective component information of each hypertension Chinese patent medicine sample to evaluate the pharmacological activity of each hypertension Chinese patent medicine sample;

[0010] Step 3: Design a pharmacodynamics experiment plan based on the pharmacological activity data, including: pharmacodynamics experiments at the animal or cell level, find out the potential relationship between the preparation process and pharmacological activity of each hypertension Chinese patent medicine sample, and record the experimental results of each hypertension Chinese patent medicine sample; then use statistical analysis methods to analyze the experimental data and extract the potential relationship between drug dosage and efficacy index;

[0011] Step 4: Based on the chemical composition and pharmacodynamic experimental results of each traditional Chinese medicine for hypertension sample, a neural network model is constructed and trained to predict the relationship between the preparation process and pharmacological activity of the traditional Chinese medicine for hypertension;

[0012] Step 5. Obtain the preparation process parameters of the new Chinese patent medicine for hypertension, use the trained neural network model to predict the pharmacodynamic activity corresponding to the preparation process, and obtain the relationship between the preparation process and the pharmacodynamic activity; and adjust the condition parameters of the preparation process according to the prediction results to optimize the preparation process of the new Chinese patent medicine for hypertension.

[0013] Furthermore, it also includes:

[0014] Step 6. Combine the experimental results with the prediction results of the neural network model and write a preparation process experiment report. The report content includes: experimental part, data processing and analysis part, and neural network model prediction of pharmacodynamic activity part. It explains the intrinsic connection between the preparation process and efficacy of the new traditional Chinese medicine for hypertension, and provides a reference for subsequent research and clinical application.

[0015] Furthermore, in the step 1, the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension are obtained, which specifically includes the following steps:

[0016] Collect literature data on traditional Chinese medicines for hypertension, screen and classify the literature data, and extract information about the active ingredients, efficacy and mechanism of action of the medicines from the literature data; analyze the active ingredients of each traditional Chinese medicine for hypertension sample based on the extracted information to obtain the efficacy and mechanism of action of each traditional Chinese medicine for hypertension sample.

[0017] Furthermore, in the step 2, chemical composition analysis is performed on each traditional Chinese medicine sample for hypertension, which specifically includes the following steps:

[0018] Each sample of traditional Chinese medicine for hypertension is crushed, dried and ground in turn to make the sample fully dispersed; the treated sample is transferred to the extract, and the extract is concentrated, precipitated and solid-phase extracted in turn to obtain a pure extract of active ingredients; the active ingredients are identified by elemental analysis, nuclear magnetic resonance and mass spectrometry to confirm the molecular structure and relative content of the active ingredients; the active ingredients are separated according to molecular size, polarity and affinity, and the separated and purified active ingredients are then tested for purity by high performance liquid chromatography to ensure that the purity and content of the active ingredients meet the requirements.

[0019] Furthermore, in the step 2, the active ingredient information of each hypertension Chinese patent medicine sample is recorded, which specifically includes the following steps:

[0020] The chemical composition and relative content of each traditional Chinese medicine for hypertension sample were recorded. The chemical composition and relative content included: inorganic element composition data, organic matter content determination data and chromatographic analysis data. According to the efficacy of each traditional Chinese medicine for hypertension sample, the chemical composition and index components of each traditional Chinese medicine for hypertension sample were recorded for learning of the neural network model.

[0021] Furthermore, in step 3, a pharmacodynamics experimental scheme is designed according to the pharmacological activity data, which specifically includes the following steps:

[0022] Select experimental subjects, including any one of rats, mice, neurons or cardiomyocytes, to simulate the physiological processes and drug metabolism in the human body; divide the experimental subjects into different groups, including a control group, a low-dose group, a medium-dose group and a high-dose group; select the administration method according to the experimental purpose and the properties of the drug, and then determine the dosage range of each hypertension Chinese patent medicine sample according to the pharmacodynamic data and the experimental purpose; after the preparation of the hypertension Chinese patent medicine samples is completed, convert the samples into a form soluble in physiological saline, and apply different doses of hypertension Chinese patent medicine samples to each group of experimental subjects according to the experimental grouping and administration method, and measure the blood pressure or heart rate of each group of experimental subjects during the administration process; and record the observation indicators of each group of experimental subjects and the experimental results of each hypertension Chinese patent medicine sample to obtain pharmacodynamic experimental data.

[0023] Furthermore, in step three, the experimental data are processed using statistical analysis methods to extract representative and significant effective components, which specifically includes the following steps:

[0024] The drug name, concentration, administration method, intervention time and treatment group of each traditional Chinese medicine for hypertension sample in the pharmacodynamic experiment were recorded, and the recorded experimental data of each group were preprocessed, including: removing duplicates, filling missing values ​​and data conversion; descriptive statistical analysis was performed on the efficacy index data of each traditional Chinese medicine for hypertension sample, including: calculating the mean, median, standard deviation and interquartile range; using the least squares method to calculate the regression equation between the drug dose and the efficacy index of each group, and calculate the pharmacodynamic experimental results: the potential relationship between drug dose and efficacy index.

[0025] Furthermore, if there is a significant positive or negative correlation between the drug dosage and the efficacy index, it indicates that the dosage is effective; conversely, if there is no significant correlation between the two, it indicates that the dosage is not effective enough and the drug dosage needs to be readjusted.

[0026] Furthermore, in the step 4, a neural network model is constructed based on the chemical composition and pharmacodynamics experimental results of each hypertension Chinese patent medicine sample, which specifically includes the following steps:

[0027] The chemical composition information, pharmacodynamic experimental data and experimental results of each traditional Chinese medicine for hypertension sample were collected, and the chemical composition information of each traditional Chinese medicine for hypertension sample and the characteristic information in the pharmacodynamic experimental data were extracted using the principal component analysis method; a neural network model was constructed, and the chemical composition information and the characteristic information of the pharmacodynamic experimental data were imported into the neural network model as input data for training, and the pharmacodynamic experimental results were used as output data to verify the training results of the neural network model and judge the performance of the neural network model; if the verification is passed, a model that can predict the relationship between the preparation process and pharmacological activity of traditional Chinese medicine for hypertension is obtained.

[0028] Furthermore, in step 5, adjusting the condition parameters of the preparation process according to the prediction results specifically includes the following steps:

[0029] Based on the prediction results, the adjustment methods include: adjusting the extraction method of the active ingredient, adjusting the extraction temperature and pressure, adjusting the type, quantity or ratio of the additives, and adjusting the extraction process, drying method or purification steps.

[0030] Furthermore, the step 5 also includes setting a nano-encapsulation layer for controlling the release of drug efficacy for the preparation of various Chinese patent medicine granules, as follows:

[0031] Based on nanotechnology and pharmacological experimental analysis of Chinese patent medicines, the relationship between the thickness of the nano-coating layer of different Chinese patent medicines and the pharmacologically active release rate of the Chinese patent medicines was established, and a curve of the relationship between the thickness of the nano-coating layer and the pharmacologically active release rate was drawn. Based on the curve of the relationship between the thickness of the nano-coating layer and the pharmacologically active release rate, a functional fitting was performed to obtain a fitting function relationship.

[0032] Based on the neural network model in step 4, the relationship between the thickness control of the nano-coating layer and the pharmacological activity in the preparation process of the traditional Chinese medicine for hypertension is obtained, and the fitting function relationship between the thickness of the nano-coating layer and the release rate of the pharmacological activity is combined to output the control scheme for the preparation of the nano-coating layer;

[0033] In the preparation process of traditional Chinese medicine for hypertension, according to the control scheme of nano-coating preparation, pharmaceutical-grade printing materials prepared by nanotechnology are used, and 3D printing technology is adopted to set a nano-coating layer of corresponding thickness on the outer surface of the corresponding traditional Chinese medicine to obtain traditional Chinese medicine particles with nano-coating layer;

[0034] Take some Chinese patent medicine granules with nano-coating layer to carry out pharmacological activity release rate experiment, and verify the pharmacological activity release rate of Chinese patent medicine for hypertension through experimental detection. If the pharmacological activity release rate does not meet the requirements, the fitting function relationship between the thickness of the nano-coating layer and the pharmacological activity release rate will be adjusted accordingly according to the deviation until the pharmacological activity release rate meets the applicable requirements of the pharmacological rate.

[0035] Furthermore, the step 2 further includes:

[0036] Preparation of aldosterone target protein: obtaining a halide by subjecting the carboxyl hydroxyl group of aldosterone to a halogenation reaction, specifically, using lithium chloride (LiCl) and methanesulfonyl halide (MsCl) as halogenation reagents, firstly reacting aldosterone methanesulfonyl halide, and then subjecting it to a chlorination reaction with lithium chloride; using the halide as a substrate, subjecting it to a primary amine halogenation reaction with tert-butyl 4-aminobutyrate, to obtain an intermediate product containing a secondary amine group; using boc anhydride as a protecting agent to protect the secondary amine group in the intermediate product; subjecting the ester group to an ester hydrolysis reaction under acidic conditions, and purifying the aldosterone target protein by silica gel column chromatography;

[0037] The target protein of aldosterone (i.e., induced protein) was used to prepare microplates containing different traditional Chinese medicine samples for hypertension and the target protein. High-throughput screening (HTS) was used to evaluate the biological activity of each traditional Chinese medicine sample for hypertension through microplates.

[0038] According to the concentration-response relationship of the traditional Chinese medicine samples for hypertension, the half-effective active concentration of the traditional Chinese medicine samples for hypertension was estimated using the following formula:

[0039]

[0040] Among them, ω is the half-effective active concentration of the traditional Chinese medicine sample for hypertension, ε max is the maximum effect of the traditional Chinese medicine for hypertension samples, ε minis the minimum effect of the traditional Chinese medicine samples for hypertension, γ is the slope of the concentration-response curve of the traditional Chinese medicine samples for hypertension;

[0041] The calculated half-effective active concentration is used as the key information in the development of traditional Chinese medicines for hypertension.

[0042] The present invention collects different types of traditional Chinese medicine samples for hypertension and performs chemical composition analysis on them to obtain the efficacy and action mechanism of each traditional Chinese medicine sample for hypertension, so as to carry out subsequent big data analysis; then designs a pharmacodynamics experimental scheme to find out the potential relationship between the preparation process and the pharmacological activity of each traditional Chinese medicine sample for hypertension; and uses the above-obtained data to train a neural network model so that the model can accurately predict the relationship between the preparation process and the pharmacological activity of a new traditional Chinese medicine for hypertension in a subsequent preparation process; so as to adjust the condition parameters of the preparation process in time according to the prediction results, thereby optimizing the preparation process of the new traditional Chinese medicine for hypertension; based on this method, the active ingredients of the traditional Chinese medicine for hypertension, its efficacy and action mechanism can be fully understood, and a scientific basis can be provided for the rational application and preparation of the traditional Chinese medicine for hypertension. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 This is a flow chart of the preparation process of a Chinese patent medicine for treating hypertension based on big data analysis according to the present invention. DETAILED DESCRIPTION

[0044] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] In order to solve the technical problems in the prior art that Chinese patent medicines for the treatment of hypertension are widely used in clinical practice, but the traditional preparation process has many problems, such as long preparation time and large waste of raw materials, which leads to the insufficient practicality and unsatisfactory development prospects of the preparation process of the existing Chinese patent medicines for hypertension, please refer to Figure 1 , this embodiment provides the following technical solutions:

[0046] The preparation process of a traditional Chinese medicine for treating hypertension based on big data analysis includes the following steps:

[0047] Step 1: Collect different types of traditional Chinese medicine samples for hypertension to ensure the representativeness and comprehensiveness of the big data, and organize and analyze each type of traditional Chinese medicine sample collected for hypertension to obtain the efficacy and mechanism of action of each traditional Chinese medicine sample for subsequent big data analysis; specifically, the following steps are included:

[0048] Collect literature data on traditional Chinese medicines for hypertension. Specifically, you can use academic search engines such as CNKI or Wanfang Database to search for literature to understand known research progress and reports; screen and classify the literature, and extract the active ingredients, efficacy and mechanism of action of the drugs from the literature; when screening, use keywords such as "hypertension", "traditional Chinese medicine", "active ingredients", "efficacy" and "mechanism of action" as subject terms for search; based on the extracted information, analyze the active ingredients of each traditional Chinese medicine sample for hypertension to obtain the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension; organize the extracted information into a table or document form; then compare the active ingredients and efficacy information extracted from different literature to obtain the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension, so as to facilitate the next step of pharmacodynamic experimental verification.

[0049] It should be noted that in the process of extracting information, it is necessary to distinguish between the quality and credibility of literature to avoid misleading the research results due to low-quality literature;

[0050] Step 2: Perform chemical component analysis on each hypertension Chinese patent medicine sample, separate and extract the effective components, purify and identify the effective components, and then record the effective component information of each hypertension Chinese patent medicine sample to evaluate the pharmacological activity of each hypertension Chinese patent medicine sample; specifically, the following steps are included:

[0051] Each sample of traditional Chinese medicine for hypertension is crushed, dried and ground in turn to make the sample fully dispersed; when necessary, an appropriate amount of anhydrous ethanol, methanol and other solvents can be added to make the sample easy to dissolve; the treated sample is transferred to an extract containing a variety of compounds, such as alkaloids, flavonoids and phenolic acids; during extraction, the extraction conditions and time need to be controlled to ensure that the effective ingredients are extracted to the greatest extent; the extract is then concentrated, precipitated and solid-phase extracted in turn to obtain a pure effective ingredient extract; the effective ingredients are identified by elemental analysis, nuclear magnetic resonance and mass spectrometry to confirm the molecular structure and relative content of the effective ingredients; the effective ingredients are separated according to molecular size, polarity and affinity, such as thin layer chromatography, gel permeation electrophoresis or ultrafiltration; the purity of the separated and purified effective ingredients is then tested by high performance liquid chromatography to ensure that the purity and content of the effective ingredients meet the requirements; during separation and purification, the damage to the effective ingredients should be minimized and appropriate separation technology and conditions should be selected.

[0052] Secondly, the chemical composition and relative content of each traditional Chinese medicine for hypertension sample were recorded. The chemical composition and relative content included: inorganic element composition data, organic matter content determination data and chromatographic analysis data. According to the efficacy of each traditional Chinese medicine for hypertension sample, the chemical composition and index components of each traditional Chinese medicine for hypertension sample were recorded for learning by the neural network model. When recording the chemical composition and relative content, it should be as detailed and accurate as possible. For example, the recording method is as follows: inorganic element composition data include: type of element, atomic number and mass number and other information; organic matter content determination data include: total organic matter content and content of various types of organic matter and other information; chromatographic analysis data include: chromatogram, retention time and peak area ratio and other information, so that the subsequent neural network model can be used for learning and analysis.

[0053] Step 3: Design a pharmacodynamics experiment plan based on the pharmacological activity data, including: pharmacodynamics experiments at the animal or cell level, find out the potential relationship between the preparation process and pharmacological activity of each hypertension Chinese patent medicine sample, and record the experimental results of each hypertension Chinese patent medicine sample; then use statistical analysis methods to analyze the experimental data and extract the potential relationship between drug dosage and efficacy index; specifically include the following steps:

[0054] Select experimental subjects, including any one of rats, mice, neurons or cardiomyocytes, to simulate the physiological process and drug metabolism in the human body; divide the experimental subjects into different groups, including a control group, a low-dose group, a medium-dose group and a high-dose group, to ensure the comparability of the experiment; select the administration method according to the purpose of the experiment and the properties of the drug, including any one of gavage, enema, oral or subcutaneous injection, to ensure that the administration method can accurately reflect the absorption and distribution of the drug in the body; then determine the dosage range of each hypertension Chinese patent medicine sample based on the pharmacodynamic data and the purpose of the experiment; specifically, the initial dose can be determined through a preliminary experiment, and then adjusted according to the results; when the hypertension After the preparation of the hypertension Chinese patent medicine samples is completed, the samples are converted into a form soluble in physiological saline, and different doses of hypertension Chinese patent medicine samples are applied to each group of experimental subjects according to the experimental grouping and administration method, and the blood pressure or heart rate of each group of experimental subjects is measured during the administration process; and the observation indicators of each group of experimental subjects and the experimental results of each hypertension Chinese patent medicine sample are recorded, thereby obtaining the pharmacodynamic experimental data; among which, the observation indicators are as follows: behavioral indicators: athletic ability, food intake, etc., physiological and biochemical indicators: plasma, tissue protein, etc., molecular biology indicators: gene expression, protein level, etc.; experimental results include: survival rate of experimental animals or cell lines, pathological tissue changes and active substance detection.

[0055] In this embodiment, the pharmacodynamics experimental protocol steps are as follows:

[0056] Experimental subjects: Rats were selected as experimental subjects, and mice were selected as alternative subjects to prevent rats from being unable to meet the experimental requirements. Experimental groups: There were control groups, low-dose groups, medium-dose groups, and high-dose groups, and the number of experimental animals in each group was set according to statistical principles, such as 5-10 animals per group. Dosage method: Choose gavage or enema to ensure that the absorption and distribution of the drug in the animal body are more accurately reflected. Dose range: The dose range of each hypertension Chinese patent medicine sample is determined through preliminary experiments, such as: in the preliminary experiment, the dose of each sample is set to 1L / kg, 2L / kg, 3L / kg, 4L / kg, and then the reaction of each group of experimental animals is observed. Observation indicators: According to the purpose of the experiment and existing literature, select from the above-mentioned observation indicators. Experimental results: Record the survival rate, pathological tissue changes, and active substance detection results of each group of experimental animals, so as to understand the mechanism of action of the drug and judge whether the drug has good efficacy. Data analysis: Statistical analysis of experimental results, such as using t-test method to find significant differences between high-dose group and low-dose group, and then analyzing the differences to determine which indicators are most affected, so as to infer the site of action of the drug. Safety assessment: After the experiment, the physical condition of the experimental animals is fully checked to see if there are any abnormalities; if so, the reasons are analyzed and corresponding measures are taken.

[0057] Secondly, according to the drug name, concentration, administration method, intervention time and treatment group of each hypertension Chinese patent medicine sample in the recorded pharmacodynamic experiments, the recorded experimental data of each group were preprocessed, including: removing duplicates, filling missing values ​​and data conversion to ensure the quality and consistency of the data; descriptive statistical analysis was performed on the efficacy index data (such as blood pressure, blood flow, heart rate, etc.) of each hypertension Chinese patent medicine sample, including: calculating the mean, median, standard deviation and interquartile range to understand the distribution of the above indicators; the regression equation between the drug dosage and the efficacy index of each group was calculated using the least squares method. The process calculates the results of the pharmacodynamic experiment: the potential relationship between drug dosage and efficacy index; if there is a significant positive or negative correlation between drug dosage and efficacy index, it indicates that the dosage is effective; conversely, if there is no significant correlation between the two, it indicates that the dosage effect is insufficient and the drug dosage needs to be readjusted; when analyzing the relationship between drug dosage and efficacy index, a multi-factor analysis is required, such as considering factors such as the drug's mechanism of action and biological transport pathways, so as to have a more comprehensive understanding of the drug's effect; at the same time, it should also be compared with other drugs or treatments to have a deeper understanding of its advantages and disadvantages.

[0058] Step 4: Based on the chemical composition and pharmacodynamic experimental results of each traditional Chinese medicine for hypertension sample, a neural network model is constructed and trained to predict the relationship between the preparation process and pharmacological activity of the traditional Chinese medicine for hypertension; specifically, the following steps are included:

[0059] The chemical composition information, pharmacodynamic experimental data and experimental results of each traditional Chinese medicine for hypertension were collected, and the principal component analysis method was used to extract the chemical composition information of each traditional Chinese medicine for hypertension and the characteristic information in the pharmacodynamic experimental data, and the pre-processed data were organized into a data set suitable for neural network model training. Secondly, a neural network model was constructed, and the pre-processed data set was divided into a training set and a test set, such as: 80% of the data was used as a training set and 20% as a test set; the characteristic information of the chemical composition information and the pharmacodynamic experimental data were imported into the neural network model as input data for training, and the pharmacodynamic experimental results were used as output data to verify the training results of the neural network model and judge the performance of the neural network model; specifically, the neural network model was trained by using the data in the training set; and during the training process, the cross-validation method was used to ensure the generalization ability of the neural network model; after the training of the neural network model, the trained neural network model was evaluated using the data in the test set to determine its accuracy and robustness; if the verification passed, a model that can predict the relationship between the preparation process and pharmacological activity of traditional Chinese medicine for hypertension was obtained.

[0060] Step 5: Obtain the preparation process parameters of the new traditional Chinese medicine for hypertension, use the trained neural network model to predict the pharmacodynamic activity corresponding to the preparation process, and obtain the relationship between the preparation process and the pharmacodynamic activity; specifically, by viewing the weight matrix output by the neural network model and observing the weights of the neural network model under different preparation process parameters, the relationship between the preparation process parameters and the pharmacodynamic activity can be obtained; and the condition parameters of the preparation process are adjusted according to the prediction results to optimize the preparation process of the new traditional Chinese medicine for hypertension; for example, the dosage of certain ingredients can be increased or decreased or the formula of the preparation can be changed; the efficacy of the drug can also be further optimized by adjusting the preparation process conditions; specifically, the following steps are included:

[0061] Based on the prediction results, the adjustment methods include: adjusting the extraction method of the active ingredient, such as changing the solvent, number of extractions, extraction time, etc., to optimize the prediction of pharmacodynamic activity; adjusting the extraction temperature and pressure. If the prediction results show that the extraction temperature and pressure have a significant effect on the pharmacodynamic activity, the above conditions can be adjusted to improve the pharmacodynamic activity; adjusting the type, quantity or ratio of additives to observe their effects on the pharmacodynamic activity; if the prediction results show that a certain herb or excipient has an important effect on the pharmacodynamic activity, you can consider adding or reducing this substance in the formula, or replacing other types or sources of substances to optimize the pharmacodynamic activity and adjusting the extraction process, drying method or purification steps to optimize the preparation process.

[0062] Step 6. Combine the experimental results with the prediction results of the neural network model and write a preparation process experiment report. The report content includes: experimental part, data processing and analysis part, and neural network model prediction of pharmacodynamic activity part. It explains the intrinsic connection between the preparation process and efficacy of the new traditional Chinese medicine for hypertension, and provides a reference for subsequent research and clinical application.

[0063] The beneficial effects achieved by the above content: Through the above operations, we can fully understand the active ingredients, efficacy and mechanism of action of traditional Chinese medicines for hypertension, and provide a scientific basis for the rational application and preparation of traditional Chinese medicines for hypertension.

[0064] Working principle: By collecting different types of traditional Chinese medicine samples for hypertension and analyzing their chemical composition, the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension are obtained for subsequent big data analysis; then the pharmacodynamics experiment plan is designed to find out the potential relationship between the preparation process and pharmacological activity of each traditional Chinese medicine sample for hypertension; and the neural network model is trained using the above data so that the model can accurately predict the relationship between the preparation process and pharmacological activity of new traditional Chinese medicines for hypertension in the subsequent preparation process; so as to adjust the condition parameters of the preparation process according to the prediction results, thereby optimizing the preparation process of new traditional Chinese medicines for hypertension.

[0065] On the basis of the above-mentioned embodiment, the step 5 further includes setting a nano-encapsulation layer for controlling the release of drug efficacy for the preparation of various Chinese patent medicine granules, as follows:

[0066] Based on nanotechnology and pharmacological experimental analysis of Chinese patent medicines, the relationship between the thickness of the nano-coating layer of different Chinese patent medicines and the pharmacologically active release rate of the Chinese patent medicines was established, and a curve of the relationship between the thickness of the nano-coating layer and the pharmacologically active release rate was drawn. Based on the curve of the relationship between the thickness of the nano-coating layer and the pharmacologically active release rate, a functional fitting was performed to obtain a fitting function relationship.

[0067] Based on the neural network model in step 4, the relationship between the thickness control of the nano-coating layer and the pharmacological activity in the preparation process of the traditional Chinese medicine for hypertension is obtained, and the fitting function relationship between the thickness of the nano-coating layer and the release rate of the pharmacological activity is combined to output the control scheme for the preparation of the nano-coating layer;

[0068] In the preparation process of traditional Chinese medicine for hypertension, according to the control scheme of nano-coating preparation, pharmaceutical-grade printing materials prepared by nanotechnology are used, and 3D printing technology is adopted to set a nano-coating layer of corresponding thickness on the outer surface of the corresponding traditional Chinese medicine to obtain traditional Chinese medicine particles with nano-coating layer;

[0069] Take some Chinese patent medicine granules with nano-coating layer to carry out pharmacological activity release rate experiment, and verify the pharmacological activity release rate of Chinese patent medicine for hypertension through experimental detection. If the pharmacological activity release rate does not meet the requirements, the fitting function relationship between the thickness of the nano-coating layer and the pharmacological activity release rate will be adjusted accordingly according to the deviation until the pharmacological activity release rate meets the applicable requirements of the pharmacological rate.

[0070] The beneficial effects achieved by the above content are as follows: through the preparation process and experimental analysis of traditional Chinese medicines for hypertension, a nano-coating layer that can control the release of drug efficacy is set on the traditional Chinese medicine particles, ensuring that the active ingredients of the prepared traditional Chinese medicines for hypertension can be better released at the optimal release rate analyzed in theory, so that the drug efficacy can be fully exerted, avoiding the waste of drug efficacy caused by too fast a release rate, ensuring a longer-lasting drug efficacy, and avoiding the unsatisfactory drug efficacy caused by too slow a release rate.

[0071] Working principle: This scheme uses nanotechnology and pharmacological experimental analysis of Chinese patent medicines to establish the relationship between the thickness of the nano-coating layer of different Chinese patent medicines and the pharmacologically active release rate of the Chinese patent medicines, and forms a relationship between the thickness of the nano-coating layer and the pharmacologically active release rate of the Chinese patent medicines. The thickness of the nano-coating layer is determined by the relationship, and control instructions are generated to control the 3D printing equipment for manufacturing the nano-coating layer to print the nano-coating layer on the outer surface of the Chinese patent medicine particles for hypertension, thereby obtaining a nano-coating layer with a pharmacologically active release rate control function; then, some Chinese patent medicine particles with nano-coating layers are extracted to implement pharmacologically active release experimental detection to verify whether the pharmacologically active release rate meets the applicable requirements of the pharmacological rate. If not, corresponding measures are taken to correct and adjust the relationship, and the production and experimental detection are re-implemented until it meets the applicable requirements of the pharmacological rate; by adopting this scheme, the pharmacologically active release rate of Chinese patent medicines can be controlled by setting the thickness of the nano-coating layer according to the need to ensure the efficacy.

[0072] Based on the above embodiment, the step 2 further includes:

[0073] Preparation of aldosterone target protein: obtaining a halide by subjecting the carboxyl hydroxyl group of aldosterone to a halogenation reaction, specifically, using lithium chloride (LiCl) and methanesulfonyl halide (MsCl) as halogenation reagents, firstly reacting aldosterone methanesulfonyl halide, and then subjecting it to a chlorination reaction with lithium chloride; using the halide as a substrate, subjecting it to a primary amine halogenation reaction with tert-butyl 4-aminobutyrate, to obtain an intermediate product containing a secondary amine group; using boc anhydride as a protecting agent to protect the secondary amine group in the intermediate product; subjecting the ester group to an ester hydrolysis reaction under acidic conditions, and purifying the aldosterone target protein by silica gel column chromatography;

[0074] The target protein of aldosterone (i.e., induced protein) was used to prepare microplates containing different traditional Chinese medicine samples for hypertension and the target protein. High-throughput screening (HTS) was used to evaluate the biological activity of each traditional Chinese medicine sample for hypertension through microplates.

[0075] According to the concentration-response relationship of the traditional Chinese medicine samples for hypertension, the half-effective active concentration of the traditional Chinese medicine samples for hypertension was estimated using the following formula:

[0076]

[0077] Among them, ω is the half-effective active concentration of the traditional Chinese medicine sample for hypertension, ε max is the maximum effect of the traditional Chinese medicine for hypertension samples, ε min is the minimum effect of the traditional Chinese medicine samples for hypertension, γ is the slope of the concentration-response curve of the traditional Chinese medicine samples for hypertension;

[0078] The calculated half-effective active concentration is used as the key information in the development of traditional Chinese medicines for hypertension.

[0079] The beneficial effects achieved by the above content are: by introducing high-throughput screening technology and combining it with quantitative analysis using formula calculations, the efficiency of the development of traditional Chinese medicines for hypertension is improved, quantitative analysis of the development of traditional Chinese medicines for hypertension is achieved, and the objectivity and reliability of the data are guaranteed.

[0080] Working principle: By preparing the target protein of aldosterone, which is used to make microtiter plates containing different samples of traditional Chinese medicines for hypertension and the target protein, high-throughput screening technology is introduced to evaluate the biological activity of traditional Chinese medicines for hypertension samples. Specifically, according to the concentration-response relationship of the traditional Chinese medicines for hypertension samples, the above formula is used to estimate the half-effective active concentration of the traditional Chinese medicines for hypertension samples, which is used as the key information for the development of traditional Chinese medicines for hypertension; this key information is used to develop traditional Chinese medicines for hypertension, improve the efficiency of the development of traditional Chinese medicines for hypertension, realize quantitative analysis of the development of traditional Chinese medicines for hypertension, and ensure the objectivity and reliability of the data.

[0081] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "including", "having" or any other variations thereof are intended to cover non-exclusive possessing, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0082] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A preparation process of a Chinese patent medicine for treating hypertension based on big data analysis, characterized in that: The following steps are involved: Step 1: Collect different types of traditional Chinese medicine samples for hypertension, and organize and analyze each of the collected traditional Chinese medicine samples for hypertension to obtain the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension; Step 2: Perform chemical component analysis on each hypertension Chinese patent medicine sample, separate and extract the effective components, purify and identify the effective components, and then record the effective component information of each hypertension Chinese patent medicine sample to evaluate the pharmacological activity of each hypertension Chinese patent medicine sample; Step 3: Design a pharmacodynamics experimental plan based on the pharmacological activity data, find out the potential relationship between the preparation process and pharmacological activity of each traditional Chinese medicine sample for hypertension, and record the experimental results of each traditional Chinese medicine sample for hypertension; then use statistical analysis methods to analyze the experimental data and extract the potential relationship between drug dosage and efficacy index; Step 4: Based on the chemical composition and pharmacodynamic experimental results of each traditional Chinese medicine for hypertension sample, a neural network model is constructed and trained to predict the relationship between the preparation process and pharmacological activity of the traditional Chinese medicine for hypertension; Step 5: Obtain the preparation process parameters of the new traditional Chinese medicine for hypertension, use the trained neural network model to predict the pharmacodynamic activity corresponding to the preparation process, and obtain the relationship between the preparation process and the pharmacodynamic activity; And through the prediction results, the condition parameters of the preparation process are adjusted to optimize the preparation process of new traditional Chinese medicines for hypertension.

2. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: Also includes: Step 6. Combine the experimental results with the prediction results of the neural network model and write a preparation process experiment report. The report content includes: experimental part, data processing and analysis part, and neural network model prediction of pharmacodynamic activity part, explaining the intrinsic connection between the preparation process and efficacy of the new traditional Chinese medicine for hypertension.

3. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: In the step 1, the efficacy and mechanism of action of each traditional Chinese medicine sample for hypertension are obtained, which specifically includes the following steps: Collect literature data on traditional Chinese medicines for hypertension, screen and classify the literature data, and extract information about the active ingredients, efficacy and mechanism of action of the medicines from the literature data; analyze the active ingredients of each traditional Chinese medicine for hypertension sample based on the extracted information to obtain the efficacy and mechanism of action of each traditional Chinese medicine for hypertension sample.

4. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: In the step 2, chemical composition analysis is performed on each traditional Chinese medicine sample for hypertension, which specifically includes the following steps: Each sample of traditional Chinese medicine for hypertension is crushed, dried and ground in turn to make the sample fully dispersed; the treated sample is transferred to the extract, and the extract is concentrated, precipitated and solid-phase extracted in turn to obtain a pure extract of active ingredients; the active ingredients are identified by elemental analysis, nuclear magnetic resonance and mass spectrometry to confirm the molecular structure and relative content of the active ingredients; the active ingredients are separated according to molecular size, polarity and affinity, and the separated and purified active ingredients are then tested for purity by high performance liquid chromatography to ensure that the purity and content of the active ingredients meet the requirements.

5. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: In the step 2, the active ingredient information of each hypertension Chinese patent medicine sample is recorded, which specifically includes the following steps: The chemical composition and relative content of each traditional Chinese medicine for hypertension sample were recorded. The chemical composition and relative content included: inorganic element composition data, organic matter content determination data and chromatographic analysis data. According to the efficacy of each traditional Chinese medicine for hypertension sample, the chemical composition and index components of each traditional Chinese medicine for hypertension sample were recorded for learning of the neural network model.

6. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: In step 3, a pharmacodynamics experiment plan is designed according to the pharmacological activity data, which specifically includes the following steps: Select experimental subjects to simulate the physiological processes and drug metabolism in the human body; divide the experimental subjects into different groups, select the method of administration according to the experimental purpose and the properties of the drugs, and then determine the dosage range of each Chinese patent medicine for hypertension sample according to the pharmacodynamic data and the experimental purpose; after the preparation of the Chinese patent medicine for hypertension samples is completed, convert the samples into a form soluble in physiological saline, and apply different doses of the Chinese patent medicine for hypertension samples to each group of experimental subjects according to the experimental grouping and administration method; during the administration process, measure the blood pressure or heart rate of each group of experimental subjects; and record the observation indicators of each group of experimental subjects and the experimental results of each Chinese patent medicine for hypertension sample to obtain pharmacodynamic experimental data.

7. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: In the step 3, the experimental data are processed by statistical analysis methods to extract representative and significant effective components, which specifically includes the following steps: The drug name, concentration, administration method, intervention time and treatment group of each traditional Chinese medicine for hypertension sample in the pharmacodynamic experiment were recorded, and the recorded experimental data of each group were preprocessed, including: removal of duplicates, missing value filling and data conversion; descriptive statistical analysis was performed on the pharmacodynamic index data of each traditional Chinese medicine for hypertension sample, and the regression equation between the drug dose and the pharmacodynamic index of each group was calculated using the least squares method to obtain the pharmacodynamic experimental results: the potential relationship between drug dose and pharmacodynamic index.

8. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 7, characterized in that: If there is a significant positive or negative correlation between the drug dosage and the efficacy index, it means that the dosage is effective; conversely, if there is no significant correlation between the two, it means that the dosage is not effective enough and the drug dosage needs to be readjusted.

9. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: In the step 4, a neural network model is constructed based on the chemical composition and pharmacodynamics experimental results of each hypertension Chinese patent medicine sample, which specifically includes the following steps: The chemical composition information, pharmacodynamic experimental data and experimental results of each traditional Chinese medicine for hypertension sample were collected, and the characteristic information in the chemical composition information and pharmacodynamic experimental data were extracted using principal component analysis. A neural network model was constructed, and the characteristic information of the chemical composition information and pharmacodynamic experimental data were imported into the neural network model as input data for training. The pharmacodynamic experimental results were used as output data to verify the training results of the neural network model and judge the performance of the neural network model. If the verification is passed, a model that can predict the relationship between the preparation process and pharmacological activity of traditional Chinese medicine for hypertension is obtained.

10. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: In the step 5, adjusting the condition parameters of the preparation process according to the prediction results specifically includes the following steps: Based on the prediction results, the adjustment methods include: adjusting the extraction method of the active ingredient, adjusting the extraction temperature and pressure, adjusting the type, quantity or ratio of the additives, and adjusting the extraction process, drying method or purification steps.

11. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: The step 5 also includes setting a nano-encapsulation layer for controlling the release of drug efficacy for the preparation of various Chinese patent medicine granules, as follows: Based on nanotechnology and pharmacological experimental analysis of Chinese patent medicines, the relationship between the thickness of the nano-coating layer of different Chinese patent medicines and the pharmacologically active release rate of the Chinese patent medicines was established, and a curve of the relationship between the thickness of the nano-coating layer and the pharmacologically active release rate was drawn. Based on the curve of the relationship between the thickness of the nano-coating layer and the pharmacologically active release rate, a functional fitting was performed to obtain a fitting function relationship. Based on the neural network model in step 4, the relationship between the thickness control of the nano-coating layer and the pharmacological activity in the preparation process of the traditional Chinese medicine for hypertension is obtained, and the fitting function relationship between the thickness of the nano-coating layer and the release rate of the pharmacological activity is combined to output the control scheme for the preparation of the nano-coating layer; In the preparation process of traditional Chinese medicine for hypertension, according to the control scheme of nano-coating preparation, pharmaceutical-grade printing materials prepared by nanotechnology are used, and 3D printing technology is adopted to set a nano-coating layer of corresponding thickness on the outer surface of the corresponding traditional Chinese medicine to obtain traditional Chinese medicine particles with nano-coating layer; Take some Chinese patent medicine granules with nano-coating layer to carry out pharmacological activity release rate experiment, and verify the pharmacological activity release rate of Chinese patent medicine for hypertension through experimental detection. If the pharmacological activity release rate does not meet the requirements, the fitting function relationship between the thickness of the nano-coating layer and the pharmacological activity release rate will be adjusted accordingly according to the deviation until the pharmacological activity release rate meets the applicable requirements of the pharmacological rate.

12. The preparation process of the Chinese patent medicine for treating hypertension based on big data analysis according to claim 1, characterized in that: The step 2 further includes: Preparation of aldosterone target protein: by subjecting the carboxyl hydroxyl group of aldosterone to a halogenation reaction to obtain a halide, specifically, using lithium chloride and methanesulfonyl halide as halogenation reagents, firstly reacting aldosterone methanesulfonyl halide, and then subjecting it to a chlorination reaction with lithium chloride; using the halide as a substrate, subjecting it to a primary amine halogenation reaction with tert-butyl 4-aminobutyrate to obtain an intermediate product containing a secondary amine group; using boc anhydride as a protecting agent to protect the secondary amine group in the intermediate product; subjecting the ester group to a hydrolysis reaction under acidic conditions, and purifying it by silica gel column chromatography to obtain the aldosterone target protein; Using the target protein of aldosterone, microplates containing different traditional Chinese medicine samples for hypertension and the target protein were prepared, and the biological activity of each traditional Chinese medicine sample for hypertension was evaluated through the microplate using high-throughput screening technology; According to the concentration-response relationship of the traditional Chinese medicine samples for hypertension, the half-effective active concentration of the traditional Chinese medicine samples for hypertension was estimated using the following formula: Among them, ω is the half-effective active concentration of the traditional Chinese medicine sample for hypertension, ε max is the maximum effect of the traditional Chinese medicine for hypertension samples, ε min is the minimum effect of the traditional Chinese medicine samples for hypertension, and γ is the slope of the concentration-response curve of the traditional Chinese medicine samples for hypertension; The calculated half-effective active concentration is used as the key information in the development of traditional Chinese medicines for hypertension.

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