Quality control method of traditional Chinese medicine preparation based on Icanteobagrus fulvidraco orifice-dredging formula

Abstract

The invention discloses a quality control method of a traditional Chinese medicine preparation based on an IV-catfish orifice-freeing prescription, and relates to the technical field of analysis of traditional Chinese medicine preparations, and the quality control method comprises the following steps: carrying out microscopic identification on traditional Chinese medicine components in the IV-catfish orifice-freeing prescription, and determining a pharmacodynamic material basis. According to the quality control method for the traditional Chinese medicine preparation based on the IVV orifice-freeing prescription, various evaluation means such as a drug effect equivalent evaluation index, a stability test, a quality test and a clinical test are comprehensively applied, the consistency and reliability of the curative effect of the traditional Chinese medicine preparation can be remarkably improved, and the drug effect equivalent evaluation index is analyzed from the two factors of drug effect intensity and action time; the method ensures the equivalence of the medicinal component group and the original traditional Chinese medicine preparation, comprehensively detects the raw material medicines and the preparation, including characters, identification, inspection and content determination items, and ensures that the quality of each batch of samples meets the standard, so that the curative effect of the traditional Chinese medicine preparation is effectively guaranteed, and the efficacy of the traditional Chinese medicine preparation is improved.

Description

Technical Field

[0001] The invention relates to the technical field of analysis of traditional Chinese medicine preparations, and in particular to a quality control method for traditional Chinese medicine preparations based on the Hanghang Tongqiao recipe. Background Art

[0002] The nasal cavity is the opening of the posterior nasal meatus, approximately where the adenoids are located, and is where the Liver Meridian of Foot-Jueyin passes. Traditional Chinese medicine preparations based on the nasal cavity Tongqiao formula have unique therapeutic effects in the treatment of nasopharyngeal diseases. This formula usually has the effects of clearing away heat and detoxifying, dispersing nodules and opening the orifices. It is suitable for the treatment of nasopharyngeal diseases caused by lung and stomach heat, qi and blood stagnation, etc. Quality control of traditional Chinese medicine preparations of the nasal cavity Tongqiao formula is a key link in ensuring the safety, effectiveness and stability of traditional Chinese medicine. With the acceleration of the modernization and internationalization of traditional Chinese medicine, the quality control requirements for traditional Chinese medicine preparations are becoming increasingly higher. By establishing scientific and standardized quality control methods, it can be ensured that the quality of traditional Chinese medicine preparations meets the prescribed standards, thereby improving their clinical efficacy and safety.

[0003] The pharmacological material basis of Chinese herbal compound preparations is complex, and there are unclear index components, which makes it difficult to determine the key pharmacological effects of the prescription ingredients. Therefore, how to identify the component groups with similar pharmacological effects in Chinese herbal preparations and determine the key pharmacological components in the component groups, and then accurately evaluate the quality of Chinese herbal preparations, is the problem we need to solve. To this end, a quality control method for Chinese herbal preparations based on the Hanghang Tongqiao recipe is proposed. Summary of the invention

[0004] The object of the present invention is to provide a method for quality control of traditional Chinese medicine preparations based on the Hanghang Tongqiao recipe, so as to solve the problems raised in the above-mentioned background technology.

[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0006] A method for quality control of a traditional Chinese medicine preparation based on the Hanghang Tongqiao recipe comprises the following steps:

[0007] Step 1: Microscopically identify the Chinese medicinal ingredients in the Hanghang Tongqiao Recipe to determine the material basis of the efficacy;

[0008] Step 2: Identify the main medicinal materials in the Hanghang Tongqiao Recipe, analyze the specific active ingredients contained in the Hanghang Tongqiao Recipe, determine the content of the medicinal materials in the Hanghang Tongqiao Recipe, establish a component-content characterization sequence, and understand the proportion of the medicinal materials in the preparation by determining the content of the active ingredients;

[0009] Step 3: Based on high performance liquid chromatography technology, the active ingredients in the ingredient-content characterization sequence are comprehensively analyzed to identify the group of effective ingredients with similar pharmacological effects in the Hanhan Tongqiao prescription, and a characteristic spectrum is established. The ingredient group includes multiple active ingredients that act together on specific targets to exert their efficacy;

[0010] Step 4: Using the active ingredient group identified in the characteristic spectrum, conduct pharmacodynamic experiments and bioactivity screening, and conduct equivalence evaluation on key active ingredients;

[0011] Step 5. According to the results of the equivalence evaluation, establish the quality control standard of the Hanghang Tongqiao Recipe, and conduct stability tests, quality tests, and clinical trials on the preparation to comprehensively evaluate its quality;

[0012] Step 6. Based on the evaluation results, optimize the production process and quality control methods of the preparation to ensure the quality stability of the Chinese medicine preparation.

[0013] Preferably, in step 1, the process of determining the drug efficacy substance basis includes:

[0014] Collect all the Chinese medicinal materials in the Han Han Tong Qiao prescription, ensure that the source of each medicinal material is clear, the quality is good, and there is a corresponding quality inspection report, grind the collected Chinese medicinal materials to form powder, and prepare them into slice samples for microscopic identification, wherein the Chinese medicinal material powder is passed through a No. 4 sieve, a small amount is picked and placed on a slide, glycerol acetic acid test solution is added, and a cover glass is covered to prepare the slice sample;

[0015] Observe the prepared samples under a microscope and record their tissue structure, cell shape, and compound characteristics, including but not limited to cell wall structure (such as thickness and texture), cell inclusions (such as pigments and oil droplets), crystal morphology (such as calcium oxalate crystals), starch grains (such as shape, size, and hilum), stone cells (such as shape and hardness), and fiber characteristics (such as length, width, and toughness);

[0016] Compare the observed medicinal material characteristics with the known microscopic characteristic maps of Chinese medicinal materials to confirm the authenticity of the medicinal materials and identify the species and source of the medicinal materials. If the observed characteristics are consistent with the characteristics in the map, the medicinal materials are considered to be authentic. Among them, the known microscopic characteristic maps of Chinese medicinal materials are derived from authoritative books, research papers or professional databases of Chinese medicinal materials;

[0017] Combined with the information on the active ingredients in the known microscopic characteristic maps of traditional Chinese medicines, the observation results are incorporated into the basic database of active substances.

[0018] Preferably, in step 2, the process of establishing the component-content characterization sequence includes:

[0019] The collected medicinal materials of the Hanhan Tongqiao Recipe were identified by properties, microscopic identification, and physical and chemical identification, and the identification characteristics of each medicinal material were recorded, including properties, microscopic characteristics, and physical and chemical characteristics. Among them, property identification was carried out by observing the appearance characteristics of the medicinal materials such as shape, color, smell, and texture. Microscopic identification used a microscope to observe the tissue structure, cell morphology, compound characteristics, etc. of the medicinal materials for a more in-depth identification. Physical and chemical identification identified specific components in the medicinal materials through chemical reactions, spectral analysis, etc.

[0020] According to the identification results of medicinal materials and the known pharmacological effects in the known microscopic characteristic patterns of Chinese medicinal materials, active ingredients are screened out, and the active ingredients in the medicinal materials are qualitatively and quantitatively analyzed using high performance liquid chromatography analysis technology, and a method for determining the content of active ingredients is established to determine the content of active ingredients in the medicinal materials;

[0021] The HPLC wavelength switching technology was used to determine the content of the main effective ingredients in the Hanghang Tongqiao recipe. The determination results were analyzed to determine the specific content of the active ingredients in the medicinal materials. The determined data on the content of the active ingredients in the medicinal materials were combined with the identification results of the medicinal materials, and a component-content characterization sequence was established to clearly display the content and distribution of various components in the medicinal materials, providing strong support for subsequent quality control.

[0022] Preferably, in step 3, the process of establishing the characteristic spectrum includes:

[0023] According to the characteristics of the medicinal materials and the properties of the target active ingredients, the plant materials are mixed and dissolved with an ethanol solvent using ultrasonic extraction technology to promote the release and extraction of the active ingredients, and the medicinal materials are extracted to obtain an extract, which is filtered, concentrated, and purified to obtain a sample to be tested;

[0024] According to the polarity and molecular weight characteristics of the target active ingredients, the HPLC analysis conditions are optimized, the chromatographic column and mobile phase are selected, and the detection wavelength of the fluorescence detector is set according to the properties of the target active ingredients. The chromatographic column types include C18 and C8. The composition and proportion of the mobile phase have a significant impact on the separation effect. The optimal mobile phase composition and gradient elution program need to be determined through experiments;

[0025] The sample to be tested is injected into the HPLC system for chromatographic separation and detection, the chromatogram is recorded, the retention time, peak shape, and peak area parameters of each peak are observed, and the active ingredients in the sample to be tested are identified by comparing with the chromatogram of the standard product;

[0026] According to the pharmacological effects and chemical structure information of the active ingredients, the active ingredients with similar pharmacological effects are classified into the same pharmacological ingredient group, and the position and relative content information of the identified pharmacological ingredient groups on the chromatogram are sorted out to establish a characteristic spectrum. The characteristic spectrum should clearly show the composition, relative content and interaction relationship of each pharmacological ingredient group.

[0027] Preferably, in step 4, the process of equivalence evaluation includes:

[0028] In vitro chemical experimental methods are used to screen biological activities, evaluate the effects of the active ingredient groups on chemical reactions, and select antioxidant activity, antibacterial activity, and anti-inflammatory activity as screening indicators based on the mechanism of action of the active ingredient groups;

[0029] Record the experimental data during the screening process, conduct statistical analysis, compare the screening results of different active ingredient groups, evaluate their biological activities, and verify whether the active ingredient groups identified in the characteristic spectrum have the expected pharmacological effects;

[0030] According to the mechanism of action of the active ingredient group, the efficacy intensity and action time were selected as the efficacy evaluation indicators, and the statistical method of t-test was used to compare the efficacy evaluation indicators of different active ingredient groups;

[0031] Based on the comparison results, the pharmacodynamic equivalence evaluation index is calculated, and the pharmacodynamic ingredient group is evaluated for equivalence with the original Chinese medicine preparation. If the pharmacodynamic ingredient group cannot achieve equivalence with the original Chinese medicine preparation, the pharmacodynamic ingredient group set is readjusted until the pharmacodynamic ingredients achieve equivalence.

[0032] Preferably, the calculation process of the drug efficacy equivalence evaluation index is:

[0033] Based on the experimental results of the original Chinese medicine preparation, the minimum value of the drug effect strength, as well as the maximum value of the drug effect strength and action time are determined, and the measured values ​​of the drug effect strength and action time in the drug effect component group are extracted;

[0034] Analyze the minimum value of drug efficacy and duration of action in the measured values, and standardize the drug efficacy and duration of action to the range of [0,1];

[0035] Calculate the ratio of the smaller value of the drug effect strength and the duration of action to the minimum value to obtain the minimum value ratio, and analyze the potential range of the smaller value of the drug effect strength and the duration of action relative to the drug effect strength;

[0036] The ratio was adjusted by an exponential function to smooth the exponential curve, and the degree of improvement of the potency and duration of action relative to the minimum value was analyzed;

[0037] The combined effects of drug efficacy intensity and duration of action, as well as the relative length of action time, were comprehensively analyzed to calculate the drug efficacy equivalence evaluation index.

[0038] Preferably, the calculation formula of the drug efficacy equivalence evaluation index is:

[0039] ;

[0040] in, is the drug efficacy equivalence evaluation index, is the measured value of drug efficacy, is the measured value of action time, is the minimum value of drug efficacy, is the maximum value of drug efficacy, is the maximum value of the action time, is the adjustment index, The value range is between 0 and 1. and hour, Reaching the maximum value of 1 indicates that the active ingredient group is completely equivalent to the original Chinese medicine preparation. or hour, The value of will be less than 1, indicating that the equivalence of the active ingredient group to the original Chinese medicine preparation is low.

[0041] Preferably, in step 5, the quality assessment process includes:

[0042] According to the results of the drug efficacy equivalence evaluation index, combined with the relevant pharmacopoeia and medicinal material quality control specifications (the regulatory requirements of the "Technical Guiding Principles for Quality Control Research of Chinese Medicine Materials for New Drugs (Trial)"), the quality control standards for the Hanghang Tongqiao Recipe were established, including properties, identification, inspection (impurities, moisture, ash, etc.), and content determination items. The appearance, color, and smell of the Hanghang Tongqiao Recipe were described and specified to ensure that the properties of each batch of preparations remained consistent, the key medicinal materials in the preparations were identified, negative controls and positive controls were set up to ensure the accuracy of the identification results, and the preparations were checked for non-medicinal substances or foreign matter to ensure that the impurity content was within the specified range;

[0043] Conduct stability tests, quality tests, and clinical trials on the preparations. For stability tests, conduct influencing factor tests, accelerated tests, and long-term tests. For quality tests, conduct tests on raw materials and preparations. For clinical trials, conduct randomized controlled trials to evaluate the clinical efficacy and safety of the Hanghang Tongqiao Recipe and provide a basis for further optimization of the drug.

[0044] The results of stability tests, quality tests and clinical trials were combined to comprehensively evaluate the quality of the Hanghang Tongqiao Recipe, including the evaluation of the physical, chemical and biological properties of the preparation, as well as the evaluation of the stability and efficacy of the preparation during storage and use.

[0045] Preferably, the specific process of the stability test, quality test and clinical trial of the preparation is:

[0046] For the test of influencing factors of stability test: the preparation is placed under extreme conditions of high temperature, high humidity and strong light to examine its stability, and sampling is carried out at different time points of 0, 1 and 3 months; accelerated test: the preparation is placed under conditions simulating the marketed packaging, and accelerated stability test is carried out, and sampling is carried out at different time points of 0, 1, 3 and 6 months to evaluate the stability of the preparation under accelerated conditions and predict its shelf life; long-term test: the preparation is placed under actual storage conditions, and long-term stability test is carried out, and sampling is carried out at different time points of 0, 3, 6 and 12 months to evaluate the stability of the preparation under long-term storage conditions, determine its shelf life and storage conditions, and perform content determination, relevant substance inspection and property observation on samples at different time points, and analyze the data through statistical methods to determine the stability of the drug;

[0047] For quality tests, multiple batches of samples are prepared according to the preparation process, and each batch of samples is tested for properties, identification, inspection, and content determination. The test results are summarized and analyzed to assess whether the quality of the samples meets the requirements, and the causes of unqualified samples are analyzed, and corresponding measures are taken to improve them;

[0048] For clinical trials, subjects are selected to clarify the purpose, methods and evaluation criteria of the trial, a control group is set up, medication is given to the subjects and they are observed according to the trial plan, the clinical manifestations and adverse reactions of the subjects are recorded, statistical analysis is performed on the clinical trial data, the efficacy and safety of the drug are evaluated, and comparison is made with the control group to determine the superiority and inferiority of the drug, and problems encountered in the clinical trials are summarized and analyzed.

[0049] Preferably, in step 6, the process of optimizing the preparation production process and quality control method is:

[0050] According to the principle of TCM dialectical treatment, the types, dosage and proportions of Chinese herbal medicines in the prescription are screened to make them meet the pharmacopoeia standards;

[0051] Introduce supercritical extraction technology to enhance extraction efficiency and ingredient purity, optimize the molding process of the preparation, optimize the uniformity of the preparation, and select the sterilization method of irradiation sterilization to ensure the sterility of the preparation;

[0052] Establish a raw material inspection system, conduct comprehensive inspections on the origin, variety, specification, and quality of Chinese medicinal materials, and introduce Chinese medicinal material fingerprint technology to identify the authenticity and evaluate the quality of Chinese medicinal materials. During the preparation production process, set quality standards and conduct regular inspections on the content and purity of extracts.

[0053] Due to the adoption of the above technical solution, the present invention has the following technical advances compared with the prior art:

[0054] 1. The present invention provides a quality control method for Chinese medicine preparations based on the Hanghang Tongqiao Recipe. By comprehensively using a variety of evaluation methods such as a pharmacodynamic equivalence evaluation index, a stability test, a quality test and a clinical trial, the method can significantly improve the consistency and reliability of the efficacy of the Chinese medicine preparations. The pharmacodynamic equivalence evaluation index is analyzed from two factors: efficacy intensity and action time, to ensure the equivalence of the pharmacodynamic component group with the original Chinese medicine preparation. The raw materials and preparations are comprehensively tested, including properties, identification, inspection and content determination items, to ensure that the quality of each batch of samples meets the standards, so that the efficacy of the Chinese medicine preparations is effectively guaranteed and the effectiveness of the Chinese medicine preparations is improved.

[0055] 2. The present invention provides a quality control method for Chinese medicine preparations based on the Hanghang Tongqiao Recipe. Through quality tests and clinical trials, the safety and controllability of the preparations are significantly enhanced. In the quality tests, the raw materials and preparations are comprehensively tested, including properties, identification, inspection and content determination items, to ensure that the content and purity of the active ingredients in the preparations meet the standards and avoid the mixing of impurities and harmful substances. The clinical trials evaluate the clinical efficacy and safety of the preparations through randomized controlled trials, monitor the clinical manifestations and adverse reactions of the subjects, and provide direct evidence for the safety of the preparations, so that the safety of the Chinese medicine preparations is effectively guaranteed, the occurrence of adverse reactions is reduced, and the medication safety of patients is improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For ordinary technicians in this field, other drawings can also be obtained based on these drawings.

[0057] Figure 1 A method flow chart of a method for quality control of a traditional Chinese medicine preparation based on the Hanghang Tongqiao Recipe of the present invention;

[0058] Figure 2 It is a flow chart for establishing the characteristic spectrum of the present invention;

[0059] Figure 3 The figure is a flow chart of the equivalence evaluation of the present invention. DETAILED DESCRIPTION

[0060] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are 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.

[0061] The first embodiment, as Figure 1 , Figure 2 As shown, the present invention provides a technical solution: a method for quality control of traditional Chinese medicine preparations based on the Hanghang Tongqiao recipe, comprising the following steps:

[0062] Step 1: Microscopically identify the Chinese medicinal ingredients in the Hanghang Tongqiao Recipe to determine the material basis of the efficacy, collect all the Chinese medicinal materials in the Hanghang Tongqiao Recipe, ensure that the source of each medicinal material is clear, the quality is excellent, and there is a corresponding quality inspection report, grind the collected Chinese medicinal materials to form powder, and prepare them into slice samples for microscopic identification, wherein the Chinese medicinal material powder is passed through a No. 4 sieve, a small amount is picked and placed on a glass slide, glycerol acetic acid test solution is added, and a cover glass is covered to prepare a slice sample, and the slice sample is observed under a microscope to record its tissue structure, cell shape, and compound characteristics, including but not limited to cell wall structure (such as thickness, texture), cell content The observed medicinal material characteristics are compared with the known microscopic characteristic maps of Chinese medicinal materials to confirm the authenticity of the medicinal materials and identify the varieties and sources of the medicinal materials. If the observed characteristics are consistent with the characteristics in the map, the medicinal materials are considered to be authentic. Among them, the known microscopic characteristic maps of Chinese medicinal materials are derived from authoritative books, research papers or professional databases of Chinese medicinal materials. Combined with the information on the active ingredients in the known microscopic characteristic maps of Chinese medicinal materials, the observation results are included in the database of the basic active substances.

[0063] Step 2: Identify the main medicinal materials in the Hanghang Tongqiao Recipe, analyze the specific active ingredients contained in the Hanghang Tongqiao Recipe, and determine the content of the medicinal materials in the Hanghang Tongqiao Recipe, establish a component-content characterization sequence, and understand the proportion of the medicinal materials in the preparation by determining the content of the active ingredients. Perform property identification, microscopic identification, and physical and chemical identification on the collected Hanghang Tongqiao Recipe medicinal materials, and record the identification characteristics of each medicinal material, including property characteristics, microscopic characteristics, and physical and chemical characteristics. Among them, Characteristic identification is carried out by observing the appearance characteristics of medicinal materials such as shape, color, smell, and texture. Microscopic identification uses a microscope to observe the tissue structure, cell morphology, compound characteristics, etc. of medicinal materials for more in-depth identification. Physical and chemical identification uses chemical reactions, spectral analysis, and other means to identify specific components in medicinal materials. According to the identification results of medicinal materials and the known pharmacological effects in the known microscopic characteristic maps of traditional Chinese medicines, active components are screened out. High-performance liquid chromatography analysis technology is used to conduct qualitative and quantitative analysis of the active components in medicinal materials, and a method for determining the content of active components is established to determine the content of active components in medicinal materials. HPLC wavelength switching technology is used to determine the content of the main effective ingredients in the Han Han Tong Qiao recipe. The determination results are analyzed to determine the specific content of the active components in the medicinal materials. The data on the content of active components of the medicinal materials obtained by the determination are combined with the identification results of the medicinal materials, and a component-content characterization sequence is established to clearly display the content and distribution of various components in the medicinal materials, providing strong support for subsequent quality control.

[0064] Step three, based on high performance liquid chromatography technology, conduct a comprehensive analysis of the active ingredients in the ingredient-content characterization sequence, identify the group of effective ingredients with similar pharmacological effects in the Hanhan Tongqiao recipe, and establish a characteristic spectrum. The ingredient group includes multiple active ingredients that work together on a specific target to exert their efficacy. According to the characteristics of the medicinal materials and the properties of the target active ingredients, use ultrasonic extraction technology to mix and dissolve the plant materials with ethanol solvent to promote the release and extraction of the active ingredients, and extract the medicinal materials to obtain the extract. The extract is filtered, concentrated, and purified to obtain a sample to be tested. According to the polarity and molecular weight characteristics of the target active ingredients, the HPLC analysis conditions are optimized, the chromatographic column and mobile phase are selected, and a fluorescence detector is set according to the properties of the target active ingredients. The detection wavelength is 100 nm, and the chromatographic column types include C18 and C8. The composition and proportion of the mobile phase have a significant impact on the separation effect. The optimal mobile phase composition and gradient elution program need to be determined through experiments. The sample to be tested is injected into the HPLC system for chromatographic separation and detection. The chromatogram is recorded, and the retention time, peak shape, and peak area parameters of each peak are observed. The active ingredients in the sample to be tested are identified by comparing with the chromatogram of the standard product. According to the pharmacological effects and chemical structure information of the active ingredients, the active ingredients with similar pharmacological effects are classified into the same active ingredient group, and the position and relative content information of the identified active ingredient group on the chromatogram are sorted out to establish a characteristic spectrum. The characteristic spectrum should clearly show the composition, relative content, and interaction relationship between each active ingredient group.

[0065] Step 4: Using the active ingredient group identified in the characteristic spectrum, conduct pharmacodynamic experiments and bioactivity screening, and conduct equivalence evaluation on key active ingredients;

[0066] Step 5. According to the results of the equivalence evaluation, establish the quality control standard of the Hanghang Tongqiao Recipe, and conduct stability tests, quality tests, and clinical trials on the preparation to comprehensively evaluate its quality;

[0067] Step 6. Based on the evaluation results, optimize the production process and quality control methods of the preparation to ensure the quality stability of the Chinese medicine preparation.

[0068] The second embodiment is based on the first embodiment. Figure 3 As shown in Figure 4, in step 4, the equivalence evaluation process includes:

[0069] The in vitro chemical experimental method is used to screen the biological activity, evaluate the effect of the active ingredient group on the chemical reaction, and according to the mechanism of action of the active ingredient group, antioxidant activity, antibacterial activity, and anti-inflammatory activity are selected as screening indicators. The experimental data in the screening process are recorded, and statistical analysis is performed to compare the screening results of different active ingredient groups, evaluate their biological activities, and verify whether the active ingredient group identified in the characteristic spectrum has the expected pharmacological effect. According to the mechanism of action of the active ingredient group, the efficacy intensity and action time are selected as the efficacy evaluation indicators, and the statistical method of t-test is used to compare the efficacy evaluation indicators of different active ingredient groups. According to the comparison results, the efficacy equivalence evaluation index is calculated, and the equivalence of the active ingredient group and the original traditional Chinese medicine preparation are evaluated to evaluate the equivalence of the active ingredients. If the active ingredient group cannot achieve equivalence with the original traditional Chinese medicine preparation, the active ingredient group set is readjusted until the active ingredients achieve equivalence;

[0070] Furthermore, the calculation process of the drug efficacy equivalence evaluation index is:

[0071] Based on the experimental results of the original Chinese medicine preparation, the minimum value of the efficacy intensity and the maximum value of the efficacy intensity and the duration of action are determined, and the measured values ​​of the efficacy intensity and the duration of action in the efficacy component group are extracted, the minimum value of the efficacy intensity and the duration of action in the measured values ​​are analyzed, and the efficacy intensity and the duration of action are standardized to the range of [0,1], and the ratio of the smaller value of the efficacy intensity and the duration of action to the minimum value is calculated to obtain the minimum value ratio, and the potential range of the smaller value of the efficacy intensity and the duration of action relative to the efficacy intensity is analyzed, and the ratio is adjusted by an exponential function to smooth the exponential curve, and the degree of improvement of the efficacy intensity and the duration of action relative to the minimum value is analyzed, and the joint influence of the efficacy intensity and the duration of action, as well as the relative length of the duration of action, is comprehensively analyzed, and the efficacy equivalence evaluation index is calculated;

[0072] Furthermore, the calculation formula of the drug efficacy equivalence evaluation index is:

[0073] ;

[0074] in, is the drug efficacy equivalence evaluation index, is the measured value of drug efficacy, is the measured value of action time, is the minimum value of drug efficacy, is the maximum value of drug efficacy, is the maximum value of the action time, is the adjustment index, The value range is between 0 and 1. and hour, Reaching the maximum value of 1 indicates that the active ingredient group is completely equivalent to the original Chinese medicine preparation. or hour, The value of will be less than 1, indicating that the equivalence of the active ingredient group with the original Chinese medicine preparation is low. near and near hour, Close to 1, indicating high equivalence, when Much smaller than or Much smaller than hour, close to 0, indicating low equivalence;

[0075] In step five, the quality assessment process includes:

[0076] According to the results of the drug efficacy equivalence evaluation index and in combination with relevant pharmacopoeias and medicinal materials quality control specifications (regulatory requirements of the "Technical Guidelines for Quality Control Research of Medicinal Materials for New Chinese Medicines (Trial)"), quality control standards for the Hanghang Tongqiao Recipe were established, including properties, identification, inspection (impurities, moisture, ash, etc.), and content determination items. The appearance, color, and odor of the Hanghang Tongqiao Recipe were described and specified to ensure that the properties of each batch of preparations remained consistent, the key medicinal materials in the preparations were identified, negative and positive controls were set up to ensure the accuracy of the identification results, and the preparations were checked for non-medicinal substances or foreign matter to ensure that the impurity content was within the specified range. The preparations were subjected to stability tests, quality tests, Clinical trials: for stability tests, influencing factor tests, accelerated tests and long-term tests are conducted; for quality tests, raw materials and preparations are tested; for clinical trials, randomized controlled trials are conducted to evaluate the clinical efficacy and safety of the Hanhan Tongqiao Recipe, and to provide a basis for further optimization of the drug. For the influencing factor test of the stability test: the preparation is placed under extreme conditions of high temperature, high humidity and strong light to examine its stability, and samples are taken at different time points of 0, 1 and 3 months for testing; accelerated tests: the preparation is placed under conditions that simulate the packaging for marketing, and accelerated stability tests are conducted, and samples are taken at different time points of 0, 1, 3 and 6 months for testing to evaluate the stability of the preparation under accelerated conditions. Qualitative, predict its shelf life; long-term test: place the preparation under actual storage conditions, conduct long-term stability test, select different time points of 0, 3, 6, and 12 months for sampling and testing, evaluate the stability of the preparation under long-term storage conditions, determine its shelf life and storage conditions, perform content determination, related substance inspection, and property observation on samples at different time points, analyze data through statistical methods, and determine the stability of the drug. For quality tests, prepare multiple batches of samples according to the preparation process, and test each batch of samples for properties, identification, inspection, and content determination items. Summarize and analyze the test results, evaluate whether the quality of the samples meets the requirements, and classify the causes of unqualified samples. Analysis and corresponding measures for improvement: for clinical trials, subjects are selected to clarify the purpose, methods and evaluation criteria of the trial, a control group is set up, the subjects are given medication and observed according to the trial plan, the clinical manifestations and adverse reactions of the subjects are recorded, statistical analysis is performed on the clinical trial data, the efficacy and safety of the drug are evaluated, and the drug is compared with the control group to determine the superiority and inferiority of the drug; problems encountered in clinical trials are summarized and analyzed; the results of stability tests, quality tests and clinical trials are comprehensively evaluated to comprehensively evaluate the quality of the Han Han Tong Qiao Recipe, including the evaluation of the physical, chemical and biological properties of the preparation, as well as the evaluation of the stability and efficacy of the preparation during storage and use;

[0077] In step 6, the process of optimizing the preparation production process and quality control method is as follows:

[0078] According to the principles of dialectical treatment in traditional Chinese medicine, the types, dosage and ratios of Chinese herbal medicines in prescriptions are screened to make them conform to the pharmacopoeia standards. Supercritical extraction technology is introduced to enhance the extraction efficiency and ingredient purity, and the molding process of the preparation is optimized. The uniformity of the preparation is optimized, and the sterilization method of irradiation sterilization is selected to ensure the sterility of the preparation. A raw material inspection system is established, and a comprehensive inspection of the origin, variety, specification and quality of Chinese medicinal materials is carried out. The fingerprint technology of Chinese medicinal materials is introduced to identify the authenticity and evaluate the quality of Chinese medicinal materials. During the preparation production process, quality standards are set and the content and purity of the extracts are regularly inspected.

[0079] The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art who is familiar with the present technical field can easily think of changes or substitutions within the technical scope disclosed in the present application, which should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A method for quality control of a traditional Chinese medicine preparation based on the Hanghang Tongqiao Recipe, characterized in that: The following steps are involved: Step 1: Microscopically identify the Chinese medicinal ingredients in the Hanghang Tongqiao Recipe to determine the material basis of the efficacy; Step 2: Identify the main medicinal materials in the Hangang Tongqiao Recipe, analyze the specific active ingredients contained in the Hangang Tongqiao Recipe, determine the content of the medicinal materials in the Hangang Tongqiao Recipe, and establish a component-content characterization sequence; Step 3: Based on high performance liquid chromatography technology, the active ingredients in the component-content characterization sequence are comprehensively analyzed to identify the group of effective ingredients with similar pharmacological effects in the Tongqiao Recipe and establish a characteristic spectrum; Step 4: Using the active ingredient group identified in the characteristic spectrum, conduct pharmacodynamic experiments and bioactivity screening, and conduct equivalence evaluation on key active ingredients; Step 5. According to the results of the equivalence evaluation, establish the quality control standard of the Hanghang Tongqiao Recipe, and conduct stability tests, quality tests, and clinical trials on the preparation to comprehensively evaluate its quality; Step 6. Based on the evaluation results, optimize the production process and quality control methods of the preparation.

2. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 1, characterized in that: In the step 1, the process of determining the drug efficacy material basis includes: Collect all the Chinese medicinal materials in the Hanghang Tongqiao prescription, grind the collected Chinese medicinal materials to form powder, and prepare them into slice samples for microscopic identification; Use a microscope to observe the prepared samples and record their tissue structure, cell shape, and compound characteristics; Compare the observed characteristics of the medicinal material with the known microscopic characteristic maps of Chinese medicinal materials to confirm the authenticity of the medicinal material and identify the variety and source of the medicinal material. If the observed characteristics are consistent with those in the map, the medicinal material is considered to be authentic; Combined with the information on the active ingredients in the known microscopic characteristic maps of traditional Chinese medicines, the observation results are incorporated into the basic database of active substances.

3. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 2, characterized in that: In the step 2, the process of establishing the component-content characterization sequence includes: Carry out property identification, microscopic identification, and physical and chemical identification on the collected medicinal materials of the Han Han Tong Qiao Recipe, and record the identification characteristics of each medicinal material, including property characteristics, microscopic characteristics, and physical and chemical characteristics; According to the identification results of medicinal materials and the known pharmacological effects in the known microscopic characteristic patterns of Chinese medicinal materials, active ingredients are screened out, and the active ingredients in the medicinal materials are qualitatively and quantitatively analyzed using high performance liquid chromatography analysis technology, and a method for determining the content of active ingredients is established to determine the content of active ingredients in the medicinal materials; The HPLC wavelength switching method was used to determine the content of the main effective ingredients in the Hanghang Tongqiao recipe. The determination results were analyzed to determine the specific content of the active ingredients in the medicinal materials. The determined data on the content of the active ingredients in the medicinal materials were combined with the identification results of the medicinal materials, and a component-content characterization sequence was established.

4. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 3, characterized in that: In step 3, the process of establishing the feature map includes: According to the characteristics of the medicinal materials and the properties of the target active ingredients, the plant materials are mixed and dissolved with the ethanol solvent using ultrasonic extraction technology, and the medicinal materials are extracted to obtain the extract, which is filtered, concentrated, and purified to obtain the sample to be tested; According to the polarity and molecular weight characteristics of the target active ingredient, the HPLC analysis conditions are optimized, the chromatographic column and mobile phase are selected, and the detection wavelength of the fluorescence detector is set according to the properties of the target active ingredient; The sample to be tested is injected into the HPLC system for chromatographic separation and detection, the chromatogram is recorded, the retention time, peak shape, and peak area parameters of each peak are observed, and the active ingredients in the sample to be tested are identified by comparing with the chromatogram of the standard product; According to the pharmacological effects and chemical structure information of the active ingredients, the active ingredients with similar pharmacological effects are classified into the same active ingredient group, and the position and relative content information of the identified active ingredient group on the chromatogram are sorted out to establish a characteristic spectrum.

5. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 4, characterized in that: In step 4, the process of equivalence evaluation includes: In vitro chemical experimental methods are used to screen biological activities, evaluate the effects of the active ingredient groups on chemical reactions, and select antioxidant activity, antibacterial activity, and anti-inflammatory activity as screening indicators based on the mechanism of action of the active ingredient groups; Record the experimental data during the screening process, conduct statistical analysis, compare the screening results of different active ingredient groups, evaluate their biological activities, and verify whether the active ingredient groups identified in the characteristic spectrum have the expected pharmacological effects; According to the mechanism of action of the active ingredient group, the efficacy intensity and action time were selected as the efficacy evaluation indicators, and the statistical method of t-test was used to compare the efficacy evaluation indicators of different active ingredient groups; Based on the comparison results, the pharmacodynamic equivalence evaluation index is calculated, and the pharmacodynamic ingredient group is evaluated for equivalence with the original Chinese medicine preparation. If the pharmacodynamic ingredient group cannot achieve equivalence with the original Chinese medicine preparation, the pharmacodynamic ingredient group set is readjusted until the pharmacodynamic ingredients achieve equivalence.

6. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 5, characterized in that: The calculation process of the drug efficacy equivalence evaluation index is: Based on the experimental results of the original Chinese medicine preparation, the minimum value of the drug effect strength, as well as the maximum value of the drug effect strength and action time are determined, and the measured values ​​of the drug effect strength and action time in the drug effect component group are extracted; Analyze the minimum value of drug efficacy and duration of action in the measured values, and standardize the drug efficacy and duration of action to the range of [0,1]; Calculate the ratio of the smaller value of the drug effect strength and the duration of action to the minimum value to obtain the minimum value ratio, and analyze the potential range of the smaller value of the drug effect strength and the duration of action relative to the drug effect strength; The ratio was adjusted by an exponential function to smooth the exponential curve, and the degree of improvement of the potency and duration of action relative to the minimum value was analyzed; The combined effects of drug efficacy intensity and duration of action, as well as the relative length of action time, were comprehensively analyzed to calculate the drug efficacy equivalence evaluation index.

7. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 6, characterized in that: The calculation formula of the drug efficacy equivalence evaluation index is: ； in, is the drug efficacy equivalence evaluation index, is the measured value of drug efficacy, is the measured value of action time, is the minimum value of drug efficacy, is the maximum value of drug efficacy, is the maximum value of the action time, is the adjustment index, The value range is between 0 and 1. and hour, Reaching the maximum value of 1 indicates that the medicinal ingredient group is completely equivalent to the original Chinese medicine preparation.

8. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 7, characterized in that: In step 5, the quality assessment process includes: According to the results of the drug efficacy equivalence evaluation index, combined with relevant pharmacopoeias and medicinal material quality control standards, the quality control standards for the Hanghang Tongqiao prescription were established; Conduct stability tests, quality tests, and clinical trials on the preparations. For stability tests, conduct influencing factor tests, accelerated tests, and long-term tests. For quality tests, conduct tests on raw materials and preparations. For clinical trials, conduct randomized controlled trials to evaluate the clinical efficacy and safety of the Hanghang Tongqiao Recipe. The results of stability tests, quality tests and clinical trials were combined to comprehensively evaluate the quality of the Hanghang Tongqiao Recipe, including the evaluation of the physical, chemical and biological properties of the preparation, as well as the evaluation of the stability and efficacy of the preparation during storage and use.

9. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 8, characterized in that: The specific process of the stability test, quality test and clinical trial of the preparation is as follows: For the influencing factors test of stability test: the preparation is placed under extreme conditions of high temperature, high humidity and strong light to examine its stability, and samples are taken at different time points of 0, 1 and 3 months for testing; Accelerated test: the preparation is placed under conditions simulating the marketed packaging, and accelerated stability test is carried out, and samples are taken at different time points of 0, 1, 3 and 6 months for testing to evaluate the stability of the preparation under accelerated conditions and predict its shelf life; Long-term test: Place the preparation under actual storage conditions and conduct long-term stability tests. Select different time points of 0, 3, 6, and 12 months for sampling and testing to evaluate the stability of the preparation under long-term storage conditions, determine its shelf life and storage conditions, and perform content determination, related substance inspection, and property observation on samples at different time points. Analyze the data through statistical methods to determine the stability of the drug; For quality tests, multiple batches of samples are prepared according to the preparation process, and each batch of samples is tested for properties, identification, inspection, and content determination. The test results are summarized and analyzed to assess whether the quality of the samples meets the requirements, and the causes of unqualified samples are analyzed, and corresponding measures are taken to improve them; For clinical trials, subjects are selected to clarify the purpose, methods and evaluation criteria of the trial, a control group is set up, medication is given to the subjects and they are observed according to the trial plan, the clinical manifestations and adverse reactions of the subjects are recorded, statistical analysis is performed on the clinical trial data, the efficacy and safety of the drug are evaluated, and comparison is made with the control group to determine the superiority and inferiority of the drug, and problems encountered in the clinical trials are summarized and analyzed.

10. A method for quality control of Chinese medicine preparations based on the Hanghang Tongqiao Recipe according to claim 9, characterized in that: In step 6, the process of optimizing the preparation production process and quality control method is as follows: According to the principle of TCM dialectical treatment, the types, dosage and ratio of Chinese herbal medicines in the prescription are screened to make them meet the pharmacopoeia standards; Introduce supercritical extraction technology to enhance extraction efficiency and ingredient purity, optimize the molding process of the preparation, optimize the uniformity of the preparation, and select the sterilization method of irradiation sterilization to ensure the sterility of the preparation; Establish a raw material inspection system, conduct comprehensive inspections on the origin, variety, specification, and quality of Chinese medicinal materials, and introduce Chinese medicinal material fingerprint technology to identify the authenticity and evaluate the quality of Chinese medicinal materials. During the preparation production process, set quality standards and conduct regular inspections on the content and purity of extracts.

Images