Mixing uniformity detection method and application

Abstract

The invention discloses a mixing uniformity detection method and application, and belongs to the technical field of traditional Chinese medicines. According to the method, after the to-be-detected sample and the water are uniformly mixed, the solid components and the supernate are separated through centrifugation, and the contents of the solid components at different sampling points are detected by utilizing different loss degrees during centrifugation, washing and filtration when the particle sizes and the components of the solid components are different, so that the measurement of the mixing uniformity can be realized; and the accuracy of the test result can be improved by regulating and controlling the mixing ratio of the to-be-tested sample to the water and the water adding amount during washing. The detection method is easy and convenient to operate, accurate in result, high in detection speed, low in cost and free of environment pollution, the detection accuracy is equivalent to that of a liquid chromatography method, and the method is suitable for measuring the mixing uniformity of traditional Chinese medicine preparations of different dosage forms.

Description

Technical Field

[0001] The present application relates to the technical field of traditional Chinese medicine, and in particular to a method for detecting mixing uniformity and its application. Background Art

[0002] The uniformity of drugs is an important prerequisite for evaluating the safety, stability, effectiveness and controllability of dosage forms, and is also an important indicator for evaluating the processability and scientific rationality of dosage forms. Clinical practice shows that the uniformity of drug preparations will directly affect their clinical use effects, especially for drug preparations with small doses and toxic doses that are very close to the dosage used. The existence of uniformity problems may lead to drug safety accidents such as ineffectiveness, poisoning and side effects. In recent years, people have found in the study of chemical drugs that even if a single chemical preparation is composed, its uniformity may have problems. In the process of drug preparation, uniformity will be affected by factors such as production process and excipient properties. In the field of traditional Chinese medicine preparations, the research on the uniformity of drugs at home and abroad is weaker, and compared with chemical preparations, the situation of traditional Chinese medicine is more complicated. From raw materials to finished products, each process may have a great impact on the uniformity of preparations.

[0003] Mixing uniformity refers to the ability of various raw materials and excipients to be completely mixed without aggregation or uneven distribution in drug production. Mixing uniformity plays a vital role in ensuring the quality and efficacy of drugs. Mixing is a key process step in the production process of pharmaceutical preparations. How to make the mixing uniformity of materials meet production requirements and ensure that each unit dose of materials contains equal active substances is the prerequisite for achieving uniform content of finished products. Currently, there are four methods for testing mixing uniformity: (1) Visual inspection method: divide the sample into several parts and observe the color, texture and uniformity of the mixture. It is mainly suitable for drugs with large differences in color or texture; (2) Weight method: divide the sample into several parts, then weigh and compare the weight differences of each part. It is mainly used for solid particle drugs; (3) Chromatographic method: a method for testing mixing uniformity by detecting the content of drug ingredients in the sample. Commonly used chromatographic methods include high performance liquid chromatography (HPLC) and gas chromatography (GC). It is suitable for situations where the content of active ingredients in the drug is low or the distribution is relatively uniform; (4) Sampling method: randomly select several parts from the sample and then detect the concentration of the relevant ingredients. It is mainly suitable for mixing uniformity testing of large-volume drugs.

[0004] Existing semi-solid preparations mostly use chromatography or chemical analysis to determine the mixing uniformity. For example, Qingyanyin is composed of Chinese medicines Rehmannia root, Scrophularia ningpoensis, Fritillaria balsamina, and Licorice. Rehmannia root, Scrophularia ningpoensis, and Licorice are extracted with water to prepare a clear paste, and Fritillaria balsamina is crushed into fine powder for use as medicine. The addition of Fritillaria balsamina fine powder is the last total mixing process, and the mixing uniformity must be measured before filling. The mixing uniformity measurement index usually selects the lowest content and the most difficult to mix component in the preparation prescription. Fritillaria balsamina is the measurement index of the mixing uniformity of Qingyanyin. The current method stipulates that Fritillaria balsamina is calculated as a dry product, and the total alkaloids contained in the form of Fritillaria balsamina B shall not be less than 0.050%. As a quality control item for Fritillaria cirrhosa, the content of total alkaloids is only 0.050%. However, the raw materials of Qingyanyin, such as Rehmannia glutinosa, Scrophularia ningpoensis, and Licorice, contain different types of alkaloid components. In addition, the content of Fritillaria cirrhosa and Fritillaria cirrhosa is extremely low. Due to different origins and harvesting periods, the content varies greatly. Therefore, using total alkaloids as a detection index cannot accurately evaluate the uniformity of material mixing. In addition, organic chemical reagents such as chloroform and methanol are required in the detection process. The operation steps are complicated and the detection cycle is long, which not only poses a threat to environmental pollution but also greatly reduces production efficiency.

[0005] It can be seen that although chromatography or chemical analysis has the advantages of high accuracy and strong specificity, it also has disadvantages such as complex sample pretreatment steps, long detection time, use of many chemical reagents, expensive reference materials, high equipment precision requirements and environmental pollution.

[0006] Especially in the determination of decoctions, the raw materials are the clear paste and original powder extracted from the slices, and the auxiliary materials are refined honey or sugar (or invert sugar). Due to the low content of the target ingredients and the complex chemical composition, the specificity is poor. In addition, during the production process, it is necessary to ensure that the materials are mixed evenly before the next operation can be carried out. Therefore, the detection speed of mixing uniformity will directly affect the efficiency of drug production.

[0007] Therefore, it is very important to provide a fast, simple, accurate and low-cost method for detecting mixing uniformity. Summary of the invention

[0008] Based on this, the main purpose of this application is to provide a method for detecting mixing uniformity with simple operation, accurate results, fast detection speed, low cost, and no pollution to the environment. The detection accuracy is equivalent to that of liquid chromatography and is suitable for the determination of mixing uniformity of semi-solid and liquid Chinese medicine preparations.

[0009] In a first aspect of the present application, a method for detecting mixing uniformity is provided, comprising the following steps:

[0010] Mix the samples from different sampling points with water, centrifuge, discard 60-80v / v% of the supernatant, wash the remaining solid components with water, filter the washing liquid with filter paper, dry the washed solid components and the filtered filter paper, calculate the solid percentage of the sample at each sampling point, and calculate the average AVG, relative standard deviation RSD and difference DV of the solid percentage of all samples;

[0011] The mixing uniformity of the sample is determined based on the average value AVG, the relative standard deviation RSD and the difference DV from the average value;

[0012] The mass of the sample at different sampling points is m1, the mass of the filter paper is m2, the mass of the washed solid component and the dried filter paper after filtration is m3, and the solid percentage of the sample at each sampling point = (m3-m2) / m1×100%;

[0013] Among them, the number of sampling points is ≥10;

[0014] The volume mass ratio of the mixed water to the sample at each sampling point is (3.5-6) ​​mL:1 g;

[0015] The volume mass ratio of water for washing to the sample at each sampling point is (3-5) mL:1 g.

[0016] In a preferred embodiment, the judgment standard of the mixing uniformity is: when the RSD of all samples is ≤5.0%, and the DV of all samples is within ±10.0% of the RSD, it means that the mixing uniformity meets the requirements.

[0017] In a preferred embodiment, the mass of samples at different sampling points is 2-10 g, optionally 7.8-8.2 g.

[0018] In a preferred embodiment, the volume mass ratio of the water mixed with water to the sample at each sampling point is (4.8-5.2) mL:1 g.

[0019] In a preferred embodiment, the centrifugal speed is ≥4000 r / min; and the centrifugal time is 10-30 min.

[0020] In a preferred embodiment, the centrifugal speed is 4000-8000 r / min, optionally 4800-5200 r / min; the centrifugal time is 18-22 min.

[0021] In a preferred embodiment, the volume mass ratio of water for washing to the sample at each sampling point is (3.4-3.6) mL:1 g.

[0022] In a preferred embodiment, the pore size of the filter paper is 10-30 μm.

[0023] In a preferred embodiment, the drying conditions include: drying temperature 100-120° C., and drying time 4-8 h.

[0024] The second aspect of the present application provides the application of the aforementioned mixing uniformity detection method in the mixing uniformity detection of traditional Chinese medicine preparations.

[0025] In a preferred embodiment, the traditional Chinese medicine preparation comprises a liquid, a semisolid or a solid dosage form.

[0026] In a preferred embodiment, the semisolid dosage form comprises an ointment, a paste or a suppository.

[0027] The beneficial effects of this application are:

[0028] 1. After the sample to be tested is mixed with water evenly, the solid component is separated from the supernatant by centrifugation. When the particle size and composition of the solid component are different, there are different degrees of loss during centrifugation and washing and filtration. The content of the solid component at different sampling points is detected, and the determination of the mixing uniformity can be achieved. By regulating the mixing ratio of the sample to be tested and water, and the amount of water added during washing, the accuracy of the test results can be improved. The detection method is simple to operate, accurate in results, fast in detection speed, low in cost, and does not pollute the environment. The detection accuracy is comparable to that of liquid chromatography, and is suitable for the determination of the mixing uniformity of various Chinese medicine preparations in different dosage forms.

[0029] 2. Traditional detection methods require the use of high-performance liquid chromatography, which is a high-precision instrument with high daily use and maintenance costs. The equipment used in this application is simple equipment with low daily maintenance costs. Liquid chromatography requires organic reagents such as methanol, acetonitrile, and phosphoric acid, and sample pretreatment may also involve flammable and explosive organic reagents. This application does not require the use of high-precision instruments and organic chemical reagents, which not only reduces the cost of detection, but also reduces waste such as organic waste liquid, which can reduce pollution to the environment.

[0030] 3. The traditional detection method uses high-performance liquid chromatography. After pre-treatment, samples need to be queued for measurement in sequence, and it takes 20-60 minutes to measure one sample. In the production process, the determination of mixing uniformity requires the measurement of a large number of samples (n≥30), so the required detection time is long, which greatly affects the production efficiency. This application can measure multiple samples at the same time, greatly reducing the measurement time and shortening the production cycle.

[0031] 4. The high-performance liquid chromatograph used in the traditional method is a high-precision instrument with many operating steps. Operators need to undergo professional training and assessment before using the equipment, which places high demands on operators. The equipment used in the method adopted in this application is simple equipment that can be used after simple training, and has low requirements on operators. DETAILED DESCRIPTION

[0032] In order to facilitate the understanding of the present application, the present application will be described more comprehensively below in conjunction with specific embodiments. Preferred embodiments of the present application are provided hereinafter. However, the present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present application more thorough and comprehensive.

[0033] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0034] In this article, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0035] In this article, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the quantity of the indicated technical features.

[0036] In the description herein, "at least one" means more than one, including one or more than two, for example, one, two, three, etc., unless otherwise clearly defined.

[0037] Herein, when it comes to numerical ranges, unless otherwise specified, the numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as every value between such minimum and maximum values. Further, when a range refers to an integer, every integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0038] In this article, when referring to the unit of a data range, if there is a unit only after the right endpoint, it means that the units of the left and right endpoints are the same. For example, 500-600rpm means that the units of the left endpoint "500" and the right endpoint "600" are both rpm (revolutions per minute).

[0039] The temperature parameters herein, unless otherwise specified, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows for temperature fluctuations within the precision range of instrument control.

[0040] The first aspect of the present application provides a method for detecting mixing uniformity, comprising the following steps:

[0041] Mix the samples from different sampling points with water, centrifuge, discard 60-80v / v% of the supernatant, wash the remaining solid components with water, filter the washing liquid with filter paper, dry the washed solid components and the filtered filter paper, calculate the solid percentage of the sample at each sampling point, and calculate the average AVG, relative standard deviation RSD and difference DV of the solid percentage of all samples;

[0042] The mixing uniformity of the sample is determined based on the average value AVG, the relative standard deviation RSD and the difference DV from the average value;

[0043] The mass of the sample at different sampling points is m1, the mass of the filter paper is m2, the mass of the washed solid component and the dried filter paper after filtration is m3, and the solid percentage of the sample at each sampling point = (m3-m2) / m1×100%;

[0044] Among them, the number of sampling points is ≥10;

[0045] The volume mass ratio of the mixed water to the sample at each sampling point is (3.5-6) ​​mL:1 g;

[0046] The volume mass ratio of water for washing to the sample at each sampling point is (3-5) mL:1 g.

[0047] The present application mixes the sample to be tested with water uniformly, separates the solid component from the supernatant by centrifugation, utilizes the different particle sizes and compositions of the solid component, and has different loss degrees during centrifugation and washing and filtration, and detects the content of the solid component at different sampling points, so as to achieve the determination of the mixing uniformity, and by regulating the mixing ratio of the sample to be tested and water, and the amount of water added during washing, the accuracy of the test result can be improved. The detection method is simple to operate, has accurate results, fast detection speed, low cost, and does not pollute the environment. The detection accuracy is equivalent to that of liquid chromatography, and is suitable for the determination of the mixing uniformity of various Chinese medicine preparations in different dosage forms.

[0048] At present, there is no testing standard for the mixing uniformity of liquid or semi-solid preparations. This application refers to the relevant standards for the mixing uniformity of solid preparations and the uniformity of the central control dosage unit to determine the number of sampling points and the determination standard for mixing uniformity. By applying the detection method of this application to product testing, its detection accuracy is equivalent to that of liquid chromatography, which also confirms the feasibility of the above determination standards.

[0049] Specifically, the judgment standard of the mixing uniformity is: when the RSD of all samples is ≤5.0%, and the DV of all samples is within ±10.0% of the RSD, it means that the mixing uniformity meets the requirements.

[0050] In this application, the amount of water used when the sample is mixed with water mainly affects the mixed dispersion and concentration of the sample. If the amount of water added is too little, the solid components cannot be effectively dispersed. If the amount of water added is too much, the concentration is too low and the test error is large. Therefore, adjusting the amount of water added will affect the test results. Specifically, the volume mass ratio of the water mixed with water to the sample at each sampling point can be specifically 3.5mL:1g, 4mL:1g, 4.5mL:1g, 5mL:1g, 5.5mL:1g, 6mL:1g, etc., preferably, 4.8-5.2mL:1g. It is understandable that the water is purified water, such as distilled water, deionized water, etc.

[0051] In the present application, in the step of washing the solid components with water, the amount of water can be adjusted in combination with the washing effect. The purpose of washing is to transfer all the solid components to the filter paper. If the amount of water is too little, it cannot be effectively transferred. If the amount of water is too much, it is easy to cause the loss of solid components and the detection error is large. Specifically, the volume mass ratio of water to sample is (3-5) mL:1g, and can be (3.4-3.6) mL:1g, such as 3mL:1g, 3.5mL:1g, 4mL:1g, 4.5mL:1g, 5mL:1g, 5.5mL:1g, 6mL:1g, etc. The washing can be a single wash or multiple washes (for example, 2-5 times), and the total amount of water for washing can be maintained.

[0052] It is understandable that there is no particular limitation on the method or instrument for mixing samples from different sampling points with water, as long as a mixing effect can be achieved, such as vortexing, magnetic stirring, mechanical stirring, etc.

[0053] In this application, the amount of samples at different sampling points is not specifically limited. A large amount requires more reagents, which will also increase the process cost, and a small amount will increase the detection error. The amount can be selected according to actual needs. Specifically, the mass of samples at different sampling points is 2-10g, and 7.8-8.2g can be selected, such as 2g, 3g, 4g, 5g, 6g, 7g, 8g, 9g, 10g, etc.

[0054] In the present application, there is no special limitation on the centrifugal speed and the centrifugal time. Increasing the centrifugal time or the centrifugal speed within a certain range can promote the separation of solid components. Specifically, the centrifugal speed is ≥4000r / min, and can be 4000-8000r / min, such as 4000r / min, 5000r / min, 6000r / min, 7000r / min, 8000r / min, etc., preferably 4800-5200r / min; the centrifugal time is 10-30min, and can be 18-22min, such as 10min, 15min, 20min, 25min, 30min, etc.

[0055] In the present application, the pore size of the filter paper is not particularly limited and can be adjusted accordingly according to the product to be tested. Specifically, the pore size of the filter paper is 10-30 μm, for example, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, etc.

[0056] In the present application, there is no special limitation on the drying conditions. Specifically, the drying conditions include: drying temperature of 100-120°C, for example, 100°C, 105°C, 110°C, 115°C, 120°C, etc.; drying time of 4-8h, for example, 4h, 5h, 6h, 7h, 8h, etc.

[0057] In the present application, the step of drying the washed solid component and the filtered filter paper comprises: placing the washed solid component and the filtered filter paper in a container and drying them. The type of container is not particularly limited, such as a beaker, a weighing bottle, a watch glass, etc.

[0058] Specifically, the solid percentage of the sample at each sampling point is calculated as follows:

[0059] The weight of the sample is M1, the weight of the filter paper is M2, the weight of the container is M3, the weight of the container containing the washed solid components and the filtered filter paper after drying is M4, and the solid percentage of the sample at each sampling point is W = (M4-M2-M3) / M1×100%.

[0060] The second aspect of the present application provides the application of the aforementioned mixing uniformity detection method in the mixing uniformity detection of traditional Chinese medicine preparations.

[0061] The present application mixes the sample to be tested with water uniformly, separates the solid component from the supernatant by centrifugation, utilizes the different particle sizes and compositions of the solid component, and has different loss degrees during centrifugation and washing and filtration, and detects the content of the solid component at different sampling points, so as to achieve the determination of the mixing uniformity, and by regulating the mixing ratio of the sample to be tested and water, and the amount of water added during washing, the accuracy of the test result can be improved. The detection method is simple to operate, has accurate results, fast detection speed, low cost, and does not pollute the environment. The detection accuracy is equivalent to that of liquid chromatography, and is suitable for the determination of the mixing uniformity of various Chinese medicine preparations in different dosage forms.

[0062] In a preferred embodiment, the traditional Chinese medicine preparation comprises a liquid, a semisolid or a solid dosage form.

[0063] In a preferred embodiment, the semisolid dosage form comprises an ointment, a paste or a suppository.

[0064] It is worth noting that the raw materials used in the examples of the present application are all common commercially available products, and their sources are not specifically limited.

[0065] The following are specific embodiments.

[0066] Preparation Example 1

[0067] Preparation of sample 1:

[0068] Take Astragalus, Atractylodes and Lycium barbarum (mass ratio 6:4:4), add water and decoct twice, 10 times the amount of water each time, each time for 1.5 hours, combine the decoctions, filter, concentrate the filtrate into a clear paste, add maltitol solution at a mass ratio of 1:2, concentrate to a relative density of 1.28-1.30 (50°C), and cool to room temperature; take white peony slices and grind them into fine powder, add the fine powder into the cooled paste at a mass ratio of 9:1, turn on the stirring paddle, and take a sample at the 5th minute of stirring, which is the sample 1 to be tested.

[0069] Preparation Example 2

[0070] Preparation of sample 2:

[0071] Except for sampling at the 30th minute of stirring, the rest is the same as sample 1.

[0072] Example 1

[0073] 1) Take 8g of the paste from different sampling points (n=10) of the sample 1 to be tested, weigh accurately, place in a 50mL centrifuge tube, add 40mL of purified water (i.e. the amount of water added), and vortex until evenly dispersed. Centrifuge at 5000r / min for 20 minutes, discard 4 / 5 of the supernatant, add 1 / 3 of the total washing water (25mL) to the centrifuge tube containing the solid component (fine powder), stir evenly, pour the washing liquid into the filter paper (pore size of 15-20μm) for filtration, and then add the remaining water into the centrifuge tube to wash the centrifuge tube, and pour the washing liquid into the filter paper for filtration to transfer all the fine powder in the centrifuge tube to the filter paper. Place the fine powder and filter paper in a clean, dry weighing bottle, dry at 105°C for 5 hours, cool to room temperature, weigh the total weight after drying, calculate the percentage of solid (white peony powder) in the paste at different sampling points, and calculate the average AVG and relative standard deviation RSD of the percentage of solid components in the paste at different sampling points. The test results are shown in Table 1.

[0074] Table 1 Test results of sample 1

[0075]

[0076] 2) At the same time, high performance liquid chromatography was used to detect the mixing uniformity of the sample 1, as follows:

[0077] Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel was used as the filler (Waters C18 column, 4.6*250mm, 5µm); acetonitrile-0.1% phosphoric acid solution (14:86) was used as the mobile phase; the detection wavelength was 230nm, the flow rate was 1.0mL / min, and the column temperature was 30℃; the theoretical plate number calculated based on the paeoniflorin peak should be no less than 2000.

[0078] Preparation of reference solution: Take an appropriate amount of paeoniflorin reference substance, weigh accurately, and add methanol to make a solution containing 60 μg per 1 mL.

[0079] Preparation of test solution: Take 2g of the product, accurately weigh it, put it in a centrifuge tube, add 15mL of dilute ethanol (the ethanol content is 49.5v / v%-50.5v / v% at 20℃), vortex until dispersed, pour it into a 50mL volumetric flask, wash the test tube with 20mL of dilute ethanol in batches, add the washing liquid into the volumetric flask, ultrasonically treat (power 240W, frequency 45kHz) for 30 minutes, cool, add dilute ethanol to the scale, shake well, filter, and take the filtrate.

[0080] Determination method: Accurately pipette 10 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine. The determination results are shown in Table 2.

[0081] Table 2 High performance liquid chromatography test results of sample 1

[0082]

[0083] As can be seen from Table 1-2, the RSD test results of the detection method of the present application and the high performance liquid chromatography method are similar. The sample 1 to be tested is a sample mixed for 5 minutes, and its mixing uniformity cannot meet the requirements.

[0084] Example 2

[0085] The mixing uniformity of the sample 2 was tested by the same method as in part 1) of Example 1. The results are shown in Table 3. At the same time, the mixing uniformity of the sample 2 was tested by high performance liquid chromatography. The detection method was the same as in part 2) of Example 1. The results are shown in Table 4.

[0086] Table 3 Test results of sample 2

[0087]

[0088] Table 4 High performance liquid chromatography test results of sample 2

[0089]

[0090] The relative standard deviation RSD of the solid percentage of each sample in Table 3 is 3.1% (≤5%), and the deviation of the solid percentage of each sample from the average value is within ±6% of the average value. Combined with Table 4, it can be seen that the RSD test results of the detection method of the present application and the high performance liquid chromatography method are similar, indicating that the sample 2 to be tested has a good mixing uniformity. It can be seen that the test results of the detection method defined in the present application can evaluate the mixing uniformity of the sample to be tested.

[0091] Example 3

[0092] The influence of specific process parameters on the determination of mixing uniformity

[0093] The mixing uniformity of the sample 2 to be tested is tested. For the specific determination method, see Part 1) of Example 1. For specific parameters and results, see Table 5-6 (parameters not reflected in Table 5-6 are the same as those in Example 1).

[0094] Table 5 Example 3-1 to Example 3-3

[0095]

[0096]

[0097] Table 6 Comparative Examples 1-4

[0098]

[0099]

[0100] It can be seen from Table 5 that the relative standard deviation RSD of the solid percentage of each sample in the detection method of Example 3-1 to Example 3-3 is ≤5%, and the deviation of the solid percentage of each sample from the average value is within ±10% of the average value, indicating that the mixing uniformity of the sample 2 to be tested meets the requirements. It can be seen that the detection results of Example 3-1 to Example 3-3 are consistent with the results of the actual mixing uniformity of the sample 2 to be tested.

[0101] In Comparative Examples 1 and 3, no water was added for washing, and the supernatant was discarded and fine powder flowed out, resulting in large detection errors and inability to perform effective detection. In Comparative Example 2, the amount of water added was increased, and the amount of washing water in Comparative Example 4 was decreased, and the test results did not meet the requirements, and effective detection of mixing uniformity could not be performed. It can be seen that the amount of water added and the amount of washing water both have a great influence on the test results.

[0102] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0103] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.

Claims

1. A method for detecting mixing uniformity, characterized in that: The steps include: Mix the samples from different sampling points with water, centrifuge, discard 60-80v / v% of the supernatant, wash the remaining solid components with water, filter the washing liquid with filter paper, dry the washed solid components and the filtered filter paper, calculate the solid percentage of the sample at each sampling point, and calculate the average AVG, relative standard deviation RSD and difference DV of the solid percentage of all samples; The mixing uniformity of the sample is determined based on the average value AVG, the relative standard deviation RSD and the difference DV from the average value; The mass of the sample at different sampling points is m1, the mass of the filter paper is m2, the mass of the washed solid component and the dried filter paper after filtration is m3, and the solid percentage of the sample at each sampling point = (m3-m2) / m1×100%; Among them, the number of sampling points is ≥10; The volume mass ratio of the mixed water to the sample at each sampling point is (3.5-6) ​​mL:1 g; The volume mass ratio of water for washing to the sample at each sampling point is (3-5) mL:1 g.

2. The detection method according to claim 1, characterized in that The judgment standard of the mixing uniformity is: when the RSD of all samples is ≤5.0%, and the DV of all samples is within ±10.0% of the RSD, it means that the mixing uniformity meets the requirements.

3. The detection method according to claim 1 or 2, characterized in that: The mass of samples at different sampling points is 2-10g, and 7.8-8.2g is optional.

4. The detection method according to claim 1 or 2, characterized in that: The volume mass ratio of water mixed with water to the sample at each sampling point is (4.8-5.2) mL:1g; the volume mass ratio of water washed with water to the sample at each sampling point is (3.4-3.6) mL:1g.

5. The detection method according to claim 1 or 2, characterized in that: The centrifugal speed is ≥4000r / min; the centrifugal time is 10-30min.

6. The detection method according to claim 5, characterized in that The centrifugal speed is 4000-8000 r / min, and can be 4800-5200 r / min; the centrifugal time is 18-22 min.

7. The detection method according to claim 1 or 2, characterized in that: The pore size of the filter paper is 10-30 μm.

8. The detection method according to claim 1 or 2, characterized in that: The drying conditions include: drying temperature 100-120° C., and drying time 4-8 hours.

9. Application of the method for detecting mixing uniformity as described in any one of claims 1 to 8 in detecting mixing uniformity of traditional Chinese medicine preparations.

10. The use according to claim 9, wherein the Chinese medicine preparation comprises a liquid, a semisolid or a solid preparation; Optionally, the semisolid dose includes an ointment, a paste or a suppository.

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