Chinese patent medicine quality risk assessment method and system

Abstract

The invention discloses a Chinese patent medicine quality risk assessment method and system, and the method specifically comprises the following steps: on the basis that the content of each g of medicinal material decoction pieces extracted by the same extraction process should have a reasonable range, proposing that the component content of each g of preparation is converted into the component content of each g of medicinal material after the preparation, and deducing a data conversion formula; performing data conversion on the content of the to-be-evaluated sample, the content of the reference qualified product and the standard low limit through a data conversion formula; and finally, comparing the content of the target component or the further estimated transfer rate after each gram of medicinal material in the sample to be evaluated is prepared into a preparation with the content of qualified products after data conversion, the standard low limit or the literature transfer rate, and judging whether the sample to be evaluated has a quality risk or not. According to the method, one conversion and three references are taken as a core, fragmented data are converted into a unified quality language, a quantifiable and reusable scientific framework is provided for quality evaluation of Chinese patent medicines, and the industrial pain point of'inspection without data 'is thoroughly solved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine risk assessment, and particularly relates to a traditional Chinese medicine quality risk assessment method and system. BACKGROUND

[0002] Traditional Chinese medicine is a standardized preparation prepared from traditional Chinese medicinal materials. The complexity of its components and the diversity of its production processes pose severe challenges to quality control. Although the legal standard inspection pass rate is relatively high according to the national inspection in recent years, exploratory research has found that the deep-seated quality problems of traditional Chinese medicine are still prominent. Specifically, the following two aspects are manifested: (1) The legal standard defects lead to cost-cutting, that is, the speculative behavior caused by the absence of detection items: if the standard does not specify the content determination of a certain component, some enterprises directly do not add the material; if only identification items are provided, the amount of added material is reduced to reduce the cost. For example, for traditional Chinese medicine without the content determination of platycodon D, there may be a problem of insufficient platycodon medicinal material. This will result in the inability to guarantee the effectiveness of traditional Chinese medicine and the decline of clinical efficacy. (2) The exploratory inspection lacks evaluation criteria, although potential problems can be found by increasing detection items (such as quantitative determination of components of multiple medicinal materials in the prescription), but due to the lack of unified evaluation criteria, the results are difficult to use for quality decision-making. For example, the content expression of the same component in different dosage forms is different (such as “mg / tablet” for tablets, “mg / bag” for granules, and “mg / mL” for liquid preparations), which cannot be compared horizontally; the same medicinal material in different preparations cannot be compared due to different prescription amounts and differences in preparation methods (such as process methods and addition of auxiliary materials).

[0003] In summary, the quality evaluation of traditional Chinese medicine in China at present mainly depends on the legal standard inspection, and some standards lack quality control items, which makes it difficult to reflect the quality “advantages and disadvantages”. In recent years, exploratory research has gradually become an important supplementary means for the quality evaluation of traditional Chinese medicine. The existing technical method cannot solve the problem of evaluation, which is due to the fact that the quality risk evaluation of traditional Chinese medicine has long relied on single dosage form data, and lacks a conversion model for relating the content of preparations to the quality of raw medicinal materials, resulting in the fact that the exploratory test results cannot be converted into effective supervision basis. Therefore, it is urgent to establish a risk evaluation method that breaks through the dosage form limitation and relates the content of preparations to the quality of raw medicinal materials, so as to provide scientific criteria for exploratory testing. SUMMARY

[0004] In view of the deficiencies of the prior art, the present application provides a traditional Chinese medicine quality risk assessment method and system, which compares the content data to be evaluated with the content data of qualified products or the lower limit data of the standard, or further estimates the transfer rate and compares it with the literature transfer rate, to establish a model for quality risk assessment. The evaluation method is not only suitable for quality evaluation of the same traditional Chinese medicine of the same dosage form from different manufacturers, but also suitable for quality evaluation of the same traditional Chinese medicine of different dosage forms or even different kinds of traditional Chinese medicine.

[0005] The application is realized by the following technical solutions:

[0006] A quality risk assessment method for Chinese patent medicines comprises the following steps:

[0007] Step 1) data expression mode conversion, converting the content of target components per g or mL of preparation into the content of target components per g of medicinal materials after preparation, using the following data conversion formula:

[0008]

[0009] In the formula, X is the content of target components per g of medicinal materials after preparation, in mg / g; A is the content of target components per g or mL of preparation, in mg / g or mg / mL; B is the amount of preparation in the standard [preparation method], in g or mL; and C is the weight of medicinal material decoction pieces in the standard [prescription], in g.

[0010] Step 2) using the formula in step 1), converting the content of target components in the sample to be evaluated into the content of target components per g of medicinal materials after preparation;

[0011] Step 3) using the formula in step 1), calculating any one of the following benchmark information:

[0012] Converting the content of qualified products into the content of target components per g of medicinal materials after preparation to obtain qualified product content conversion data;

[0013] Converting the data of the standard lower limit into the lower limit of the content of target components per g of medicinal materials after preparation to obtain standard lower limit conversion data;

[0014] Step 4) for some components, the content data of qualified products for reference or the data of the standard lower limit cannot be obtained, and the estimated transfer rate can be used to evaluate the risk; first, using the formula in step 1), the content of target components in the sample to be evaluated is converted into the content of target components per g of medicinal materials after preparation, and then the content of target components per g of medicinal materials after preparation is divided by the lower limit of the content per g of medicinal materials before processing, which is the estimated transfer rate;

[0015] Step 5) risk assessment: comparing the content of target components per g of medicinal materials after preparation in the sample to be evaluated obtained in step 2) with the qualified product content conversion data or the standard lower limit conversion data obtained in step 3); or comparing the estimated transfer rate obtained in step 4) with the actual transfer rate in the literature to determine whether the sample to be evaluated has risks.

[0016] Preferably, in the formula of step 1), when the sample to be evaluated is a solid preparation, the unit of A is mg / g, the unit of B is g, and the unit of C is g; when the sample to be evaluated is a liquid preparation, the unit of A is mg / mL, the unit of B is mL, and the unit of C is g.

[0017] Preferably, the specific steps of the risk assessment in step 5) are as follows:

[0018] The content of the target component in each g of the medicinal material after the preparation of the sample to be evaluated in step 2) is compared with the content conversion data or the standard lower limit conversion data of the qualified product obtained in step 3), and if the content of the target component in each g of the medicinal material after the preparation of the sample to be evaluated is lower than the lower limit of the content conversion data of the qualified product or the standard lower limit conversion data, it is determined that there is a risk;

[0019] Or, the estimated transfer rate obtained in step 4) is compared with the actual transfer rate in the literature, and if the estimated transfer rate of the sample to be evaluated is lower than the actual transfer rate in the literature, it is determined that there is a risk.

[0020] A traditional Chinese medicine quality risk assessment system, comprising:

[0021] A data standardization module for converting the standard expression of the preparation content diversification into the consistent expression of the component content after the preparation of each g of the medicinal material, the conversion target including the content of the sample to be evaluated, and the content of the qualified product or the standard lower limit for reference;

[0022] An auxiliary data module for further calculating the converted data of the sample to be evaluated into an estimated transfer rate when the content data of the qualified product for reference or the data of the standard lower limit cannot be obtained;

[0023] A risk determination module for comparing the content of the target component in each g of the medicinal material after the preparation of the sample to be evaluated with the content conversion data or the standard lower limit conversion data of the qualified product, or comparing the estimated transfer rate with the actual transfer rate in the literature preset in the system in advance, to determine whether the sample to be evaluated has a risk.

[0024] The beneficial effects of the present application are as follows:

[0025] (1) The present application converts the diversified preparation content into the component content after the preparation of each g of the medicinal material through a data conversion formula, eliminating the interference of dosage forms and prescription amounts. The target component content of different dosage forms, specifications and prescription amounts can be uniformly compared with the standard lower limit, thereby quickly identifying the risk.

[0026] (2) The application integrates multi-source data to generate a general evaluation standard, and establishes a model for quality risk assessment by converting three benchmark data of content data of qualified products, standard lower limit data conversion and actual transfer rate in literature. The exploratory test result data is converted or the transfer rate is further estimated, and if it is lower than the benchmark data, it is determined as a raw material or process defect, which is at risk.

[0027] (3) The application directly relates the content of the preparation and the quality of the medicinal material by standardized conversion, which can effectively improve the supervision efficiency and accurately crack the shortcuts.

[0028] (4) The application takes "one conversion (unifying the content of the preparation to the content of the ingredient after the preparation is made from the medicinal material per g) and three benchmarks (qualified product content, standard lower limit, actual transfer rate)" as the core, converts fragmented data into unified quality language, provides a quantifiable and reusable scientific framework for Chinese medicine effectiveness evaluation, and completely solves the industry pain point of "checking without evidence". BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 The technical roadmap for the quality risk assessment method of Chinese patent medicine;

[0030] Figure 2 The risk assessment based on the qualified sample of Scutellaria preparation in Example 1;

[0031] Figure 3 The risk assessment based on the standard lower limit of Pueraria preparation in Example 2;

[0032] Figure 4 The risk assessment based on the estimated transfer rate of Platycodon preparation in Example 3. DETAILED DESCRIPTION

[0033] The application will be further described in detail below in combination with the drawings and specific examples.

[0034] The drugs involved in the following examples can be obtained from commercial channels unless otherwise specified.

[0035] A quality risk assessment method for Chinese patent medicine, based on the fact that the content of each g of medicinal material decoction piece after the same extraction process should have a reasonable range, proposes to convert the content of each g of preparation ingredient into the content of each g of medicinal material after the preparation is made, such as Figure 1 as shown, the specific steps are as follows:

[0036] (1) Data expression conversion, converting the content of each g or mL of preparation target ingredient into the content of each g of medicinal material target ingredient after the preparation is made, using the following data conversion formula:

[0037]

[0038] In the formula: X is the content of the target component per g of medicinal materials after being made into a preparation, with the unit of mg / g; A is the content of the target component per g or mL of the preparation, with the unit of mg / g or mg / mL; B is the amount of the preparation in the standard [preparation method], with the unit of g or mL; and C is the weight of the medicinal material decoction piece in the standard [prescription], with the unit of g.

[0039] When the sample to be evaluated is a solid preparation, the unit of A is mg / g, the unit of B is g, and the unit of C is g; when the sample to be evaluated is a liquid preparation, the unit of A is mg / mL, the unit of B is mL, and the unit of C is g. The qualified product or the standard lower limit for reference is different in the content expression of different dosage forms, which can be converted to be consistent through the specification, for example, the content of a tablet is usually expressed as mg / tablet, and the specification is expressed as g / tablet, so the content (mg / tablet) is divided by the specification (g / tablet) to convert the expression of the content as A (mg / g) before the result conversion; the content of a capsule is usually expressed as mg / grain, and the specification is expressed as g / grain, so the content (mg / grain) is divided by the specification (g / grain) to convert the expression of the content as A (mg / g) before the result conversion; the content of a granule is usually expressed as mg / bag, and the specification is expressed as g / bag, so the content (mg / bag) is divided by the specification (g / bag) to convert the expression of the content as A (mg / g) before the result conversion. B represents the amount of the preparation in the standard [preparation method], with the unit of g. The amount of the preparation in a tablet is usually expressed as the number of tablets, which needs to be multiplied by the specification (g / tablet) to convert the expression of B (g); the amount of the preparation in a capsule is usually expressed as the number of grains, which also needs to be multiplied by the specification (g / grain) to convert the expression of B (g); the same applies to granules. If it is a liquid preparation, A is in the unit of mg / mL, and B is in the unit of mL.

[0040] (2) Using the above formula, the content of the target component in the sample to be evaluated is converted into the content of the target component per g of medicinal materials after being made into a preparation.

[0041] (3) Using the above formula, any one of the following reference information is calculated:

[0042] Qualified product content conversion data: the content of the qualified product is converted into the content of the target component per g of medicinal materials after being made into a preparation, to obtain the qualified product content conversion data. The qualified product data is derived from the data of the detection agency that has passed the standard inspection; some traditional Chinese medicinal materials do not have a content determination item in the standard of Chinese patent medicines, and the qualified product data can be collected through cooperation with regular production enterprises.

[0043] Standard lower limit conversion data: the data of the standard lower limit is converted into the lower limit of the content of the target component per g of medicinal materials after being made into a preparation, to obtain the standard lower limit conversion data. The standard lower limit is derived from the standard of Chinese patent medicines in the first part of Chinese Pharmacopoeia, the departmental standard of Chinese patent medicines, the standard of formula granules issued by the Pharmacopoeia Commission or the state.

[0044] (4) Estimated transfer rate: In some cases, the content data of qualified products or the data of the standard lower limit cannot be obtained for reference. The risk can be evaluated by using the estimated transfer rate. The transfer rate is calculated by comparing the content data before and after processing per g of medicinal material, i.e. the content per g of medicinal material after processing divided by the content per g of medicinal material before processing. In the exploratory test, the tester cannot directly know the content of each component per g of medicinal material before processing, but can know the lower limit of the content per g of medicinal material in the standard of the medicinal material, so the transfer rate can be estimated.

[0045] First, the content of the target component in the sample to be evaluated is converted into the content of the target component per g of medicinal material after being processed into a preparation by using the above formula, and then the content of the target component per g of medicinal material after being processed into a preparation is divided by the lower limit of the content per g of medicinal material before processing, i.e. the estimated transfer rate. The estimated transfer rate should be higher than the actual transfer rate. On the contrary, if the estimated transfer rate is low, it indicates that the sample may have a quality risk. The data of the actual transfer rate can be obtained by literature search.

[0046] (5) Risk assessment

[0047] The content of the target component per g of medicinal material after being processed into a preparation in the sample to be evaluated obtained in step (2) is compared with the converted data of the content of the qualified product or the converted data of the standard lower limit. If the content of the target component per g of medicinal material after being processed into a preparation in the sample to be evaluated is lower than the lower limit of the converted data of the content of the qualified product or the converted data of the standard lower limit, it is determined that there is a risk.

[0048] Alternatively, the estimated transfer rate obtained in step (4) is compared with the actual transfer rate in the literature. If the estimated transfer rate of the sample to be evaluated is lower than the actual transfer rate in the literature, it is determined that there is a risk.

[0049] Example 1

[0050] The sample to be evaluated in this example is pediatric Xingxing cough granules (XJZG) and cold cough granules (GZG), and the target component is baicalin.

[0051] First, the content of baicalin in the sample to be evaluated is converted into the content of baicalin per g of Huangqin after being processed into a preparation by using the data conversion formula, as shown in Table 1 below.

[0052] Table 1 Conversion results of baicalin content in the sample to be evaluated

[0053]

[0054] The data conversion formula was used to convert the content of the qualified samples containing Scutellaria into the content of baicalin in the prepared preparation per g of Scutellaria, as shown in Table 2 below. The 8 qualified samples containing Scutellaria were respectively: Niuhuang Shangqing tablets (NST), Fangfeng Tongsheng granules (FTG), two batches of Shuanghuanglian oral liquid (SOL1 and SOL2), two batches of Xinqin granules (XG1 and XG2), Yiqing capsules (YC), and Niuhuang Shangqing capsules (NSC). The data of the qualified samples were derived from the sampling test results.

[0055] Table 2 Conversion results of the content of baicalin in the qualified samples containing Scutellaria

[0056]

[0057]

[0058] As can be seen from Table 2, the content of baicalin in the 8 qualified samples containing Scutellaria is converted into the content of baicalin in the prepared preparation per g of Scutellaria, and the content range of baicalin in the prepared preparation is 31-66 mg.

[0059] The data in Tables 1 and 2 are converted into the quality risk assessment results of Figure 2 It can be judged that Xiaoer Jingxinxizhike granules (XJZG) and Ganmaozhike granules (GZG) are both risk-free.

[0060] Example 2

[0061] The judgment basis can also refer to the existing standard of Chinese patent medicines. The standard usually specifies the lower limit of the content, which can prevent shoddy work. After data conversion, it can also be used for risk identification.

[0062] The samples to be evaluated in this example are Fenghan Ganmao granules (FGG), Ganmao Qingre granules (GQG1), and Ganmaozhike capsules (GZG), and the target component is puerarin.

[0063] First, the content of puerarin in the samples to be evaluated was converted into the content of puerarin in the prepared preparation per g of Pueraria using the data conversion formula, as shown in Table 3 below.

[0064] Table 3 Conversion results of the content of puerarin in the samples to be evaluated

[0065]

[0066]

[0067] The standard lower limit of the drug containing Puerariae radix was converted into the standard lower limit of puerarin per g of Puerariae radix prepared into a preparation by using the data conversion formula, as shown in Table 4 below. The four drugs containing Puerariae radix were: Ganmaoqingre granules (GQG2), Gegen granules (GG), Gegen tablets (GT), and Xiaerchaigui granules (XCTG), and the standards came from the Chinese Pharmacopoeia 2020 edition Part I.

[0068] Table 4 Conversion results of puerarin standard lower limit of drugs containing Puerariae radix

[0069]

[0070] As can be seen from Table 4, the minimum limit of puerarin in this embodiment is 9.3 mg / g.

[0071] The data in Tables 3 and 4 were converted into the quality risk assessment results of Figure 3 It can be judged that both Fenghan Ganmao granules (FGG) and Ganmaoqingre granules (GQG1) are not at risk, while the puerarin content of Ganmaoqieke granules (GZG) is 6.69 mg / g, which is lower than the minimum limit, and the quality risk of Puerariae radix in the drug can be evaluated.

[0072] Example 3

[0073] Some components cannot obtain qualified product content data or standard lower limit data, and the judgment method can temporarily refer to the estimated transfer rate to identify the risk. The transfer rate is calculated by comparing the content data before and after processing per g of medicinal material. Although the supervisory inspection personnel cannot directly know the content of each component per g of medicinal material before processing, they can know the content lower limit per g of medicinal material according to the standard, so they can calculate the estimated transfer rate, that is, the content data per g of medicinal material after processing divided by the content lower limit per g of medicinal material before processing. The estimated transfer rate should be higher than the actual transfer rate. On the contrary, if the estimated transfer rate is low, it indicates that the sample may have a quality risk.

[0074] The samples to be evaluated in this embodiment are Qingxuanzhike granules (QZG), Ganmaoqingre granules (GQG), Ganmaoqieke capsules (GZG), and Fenghan Ganmao granules (FGG), and the target component is jiaogulanoside D.

[0075] First, the content of jiaogulanoside D in the samples to be evaluated was converted into the content of jiaogulanoside D per g of Platycodi radix prepared into a preparation by using the data conversion formula, and then the estimated transfer rate of jiaogulanoside D in the samples to be evaluated was calculated, as shown in Table 5 below.

[0076] Table 5 Estimated transfer rate of jiaogulanoside D in samples to be evaluated

[0077]

[0078] Reference (Deng, Y. Preparation and evaluation of jingfang hua-geng-tang lyophilized instant tablets [D]. Chengdu Medical College. 2024.) shows that the actual transfer rate of hua-geng-saponin D in hua-geng is 56%. The data in Table 5 is converted into the mass risk assessment results of Figure 4 The quality risk assessment results of Table 5 show that QZG and GQG are both risk-free, while the estimated transfer rate of GZG is 9.34%, and the estimated transfer rate of FGG is 22.4%, both of which are lower than the actual transfer rate, and the presence of hua-geng in the drug can be evaluated as a quality risk.

[0079] The above-described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. The detailed description of the embodiments of the present application is not intended to limit the scope of the claimed application, but only represents selected embodiments of the present application. The scope of protection of the present application is subject to the scope claimed in the claims, and all other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present application without creative labor fall within the scope of protection of the present application.

Claims

1. A method for quality risk assessment of traditional Chinese medicine preparations, characterized in that, Includes the following steps: Step 1) Data representation conversion: Convert the content of the target component per g or mL of the preparation into the content of the target component per g of medicinal material after preparation. Use the following data conversion formula: In the formula: X is the content of the target component after each gram of medicinal material is made into a preparation, in mg / g; A is the content of the target component in each gram or mL of preparation, in mg / g or mg / mL; B is the amount of the preparation in the standard [preparation method], in g or mL; C is the weight of the medicinal material slices in the standard [prescription], in g. Step 2) Using the formula from Step 1), the content of the target component in the sample to be evaluated is converted into the content of the target component per gram of medicinal material after it is made into a preparation. Step 3) Using the formula from Step 1), calculate any one of the following baseline information: The qualified product content is converted into the content of the target component per gram of medicinal material after it is made into a preparation, and the qualified product content conversion data is obtained. The standard lower limit data is converted into the lower limit of the content of the target component after each gram of medicinal material is made into a preparation, and the standard lower limit conversion data is obtained. Step 4) For some components, if the content data of qualified products or the lower limit of the standard cannot be obtained temporarily, the risk can be assessed by estimating the transfer rate. First, use the formula in Step 1) to convert the content of the target component in the sample to be evaluated into the content of the target component after each gram of medicinal material is made into a preparation. Then divide the content of the target component after each gram of medicinal material is made into a preparation by the lower limit of the content before each gram of medicinal material is processed, which is the estimated transfer rate. Step 5) Risk assessment: Compare the content of the target component per gram of medicinal material in the sample to be evaluated obtained in Step 2) after it is made into a preparation with the content conversion data of qualified products or the standard lower limit conversion data obtained in Step 3); or compare the estimated transfer rate obtained in Step 4) with the actual transfer rate in the literature to determine whether the sample to be evaluated has any risk.

2. The method for quality risk assessment of traditional Chinese medicine preparations according to claim 1, characterized in that, In the formula described in step 1), when the sample to be evaluated is a solid dosage form, the unit of A is mg / g, the unit of B is g, and the unit of C is g. When the sample to be evaluated is a liquid preparation, the unit of A is mg / mL, the unit of B is mL, and the unit of C is g.

3. The method for quality risk assessment of traditional Chinese medicine preparations according to claim 1, characterized in that, The specific steps of the risk assessment described in step 5) are as follows: The content of the target component per gram of medicinal material in the sample to be evaluated obtained in step 2) after being made into a preparation is compared with the content conversion data of qualified product or the standard lower limit conversion data obtained in step 3). If the content of the target component per gram of medicinal material in the sample to be evaluated after being made into a preparation is lower than the lower limit of the content conversion data of qualified product or the standard lower limit conversion data, it is determined that there is a risk. Alternatively, the estimated transfer rate obtained in step 4) can be compared with the actual transfer rate in the literature. If the estimated transfer rate of the sample to be evaluated is lower than the actual transfer rate in the literature, it is determined that there is a risk.

4. A quality risk assessment system for traditional Chinese medicine preparations, characterized in that, include: The data standardization module is used to convert the diverse standard expressions of formulation content into a consistent expression of the component content per gram of medicinal material after it is made into a formulation. The conversion targets include the content of the sample to be evaluated, as well as the content of qualified products or the lower limit of standards for reference. The auxiliary data processing module is used to further calculate the estimated transfer rate by converting the content data of the reference qualified product or the standard lower limit data of the sample to be evaluated when it is not possible to obtain the content data of the sample to be evaluated. The risk assessment module is used to compare the content of the target component per gram of medicinal material in the sample to be evaluated after it is made into a preparation with the content conversion data of qualified product or the standard lower limit conversion data, or to compare the estimated transfer rate with the actual transfer rate in the literature preset in the system in advance, to determine whether the sample to be evaluated has any risk.

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