Kaixin powder and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparation, in particular to Kaixin powder and a preparation method thereof.The preparation method comprises the steps that medicinal materials are smashed, ground, screened and mixed to prepare powder, and a plurality of parts of test samples are periodically taken from set positions; carrying out content uniformity inspection on the test sample, carrying out primary test to judge the content uniformity of the test sample or carrying out secondary test to judge the content uniformity of the test sample; performing comprehensive test according to the primary test result and the retest result, and judging the content uniformity of the test sample; predicting the change trend of the standard deviation when the uniformity does not meet the specification, and judging whether the mixing time length needs to be adjusted or the cause that the uniformity does not meet the standard; the crushing degree of the medicinal material powder is judged, and the reason for determining that the crushing degree does not meet the standard is that the charging coefficient exceeds the range or the crushing and grinding process does not meet the standard; and sterilizing the powder conforming to the specification, judging the adjustment state of the process parameter duration, and determining the sterilization duration of the sterilization process. By determining and adjusting the mixing uniformity of the medicine powder in real time, the dissolution rate of the medicinal materials is improved, and the taking compliance is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparation, and particularly relates to a KaiXinSan and a preparation method thereof. Background Art

[0002] KaiXinSan is a traditional Chinese medicine prescription with the effects of tonifying qi and nourishing the heart, calming the mind and stabilizing the will, and is commonly used to treat diseases such as depression, anxiety, insomnia, and cognitive impairment. It was first recorded in Volume 14 of "Emergency Prescriptions Worth a Thousand Gold" by Sun Simiao in the Tang Dynasty. The prescription, preparation, and usage of KaiXinSan described in the "Key Information Table of Ancient Classic Prescriptions (25 Prescriptions)" announced by the State Administration of Traditional Chinese Medicine are as follows: Polygala tenuifolia and Ginseng, each four fen, Poria cocos two liang, Acorus tatarinowii one liang; the above four flavors are ground into powder, and taken one square spoonful with water, three times a day. As a classic traditional Chinese medicine prescription, KaiXinSan is composed of four medicinal materials: Polygala tenuifolia, Ginseng, Poria cocos, and Acorus tatarinowii. Each medicinal material has its unique properties and effects in terms of medicinal properties, and the compatibility has a synergistic effect; Polygala tenuifolia is used as the monarch drug to nourish the heart and kidney and calm the mind; Ginseng is used as the minister drug to enhance the qi-tonifying effect and communicate the heart and kidney; Poria cocos and Acorus tatarinowii are used as assistant drugs. Poria cocos strengthens the spleen and promotes diuresis, and Acorus tatarinowii opens the orifices and resolves phlegm, jointly enhancing the efficacy of the whole prescription.

[0003] Chinese Patent Publication No.: CN116983356A discloses a preparation method of KaiXinSan. By adopting an intermittent microwave sterilization process, the processing temperature is low, the time is short, the damage to the active ingredients in the medicinal materials is very small, and the medicinal value of the medicinal materials themselves is effectively preserved; the cleanliness of traditional Chinese medicine is improved, and at the same time, the sterilized traditional Chinese medicine is collected in a clean area to avoid recontamination of traditional Chinese medicine. Thus, the following problems exist in the described preparation method of KaiXinSan:

[0004] Uneven mixing after the medicinal materials are pulverized will cause uneven distribution of active ingredients, thereby affecting the medicinal effect, and may cause a large amount of precipitation in the medicinal liquid during taking, affecting the compliance and treatment effect of patients. Summary of the Invention

[0005] Therefore, the present invention provides a KaiXinSan and a preparation method thereof to overcome the problems in the prior art that uneven mixing after the medicinal materials are pulverized will cause uneven distribution of active ingredients, thereby affecting the medicinal effect, and may cause a large amount of precipitation in the medicinal liquid during taking, affecting the compliance and treatment effect of patients.

[0006] To achieve the above object, the present invention provides a KaiXinSan and a preparation method thereof, including:

[0007] Pre-treat the raw medicinal materials of KaiXinSan, pulverize and grind the pre-treated medicinal materials into medicinal powders according to preset pulverizing and grinding parameters, and screen the medicinal powders;

[0008] Mix the screened medicinal material powders according to a preset charging coefficient to prepare a powder, and take samples periodically from a set position during the mixing process to obtain several test samples of KaiXinSan

[0009] Check the content uniformity of several test samples at different set positions. In the initial test, determine whether the content uniformity of the test samples meets the regulations, or conduct a re-test for a second determination;

[0010] Conduct a comprehensive test based on the results of the initial and re-tests to determine whether the content uniformity of the test samples meets the regulations;

[0011] When the content uniformity does not meet the regulations, draw a standard deviation change curve, predict the change trend of the standard deviation, and determine whether it is necessary to adjust the mixing duration, or determine the reason for the non-compliance of the uniformity;

[0012] Detect the powder particle size of the medicinal material powders, determine the degree of pulverization of the medicinal material powders, and based on the degree of pulverization, determine that the reason for the non-compliance of the uniformity is that the charging coefficient exceeds the range, or the pulverization and grinding process does not meet the standard, and determine the pulverization and grinding parameters;

[0013] Sterilize the powder with compliant content uniformity, and determine the adjustment status of the process parameter duration according to the mixing duration and the pulverization and grinding parameters, and determine the sterilization duration of the sterilization process;

[0014] Among them, the set positions include the upper part of the mixer, the corner edge, and the discharge port inside the square cone mixer.

[0015] Furthermore, the process of determining the content uniformity of the test samples in the initial test includes,

[0016] For the test samples at different set positions, respectively measure the relative content of each single dose in several test samples, calculate the mean value, standard deviation and absolute value, and compare the absolute value and the standard deviation with the specified values;

[0017] Determine that the content uniformity of the test samples does not meet the regulations, meets the regulations, or the content uniformity of the test samples needs to be re-determined according to the sum of the product of the initial test determination coefficient and the standard deviation and the absolute value, and take the test samples for re-test;

[0018] Among them, the single dose is the medicinal material powders of Polygala tenuifolia, Panax ginseng, Poria cocos, and Acorus tatarinowii.

[0019] Furthermore, conduct a comprehensive test according to the results of the initial and re-tests, calculate the mean value, standard deviation and absolute value of several test samples in the initial and re-tests,

[0020] Compare the absolute value with the specified value, and adopt the first determination condition and the second determination condition according to the comparison result.

[0021] Further, the first determination condition is to compare the sum of the square of the absolute value and the square of the standard deviation with the square of a specified value to determine whether the content uniformity of the test sample meets the requirements;

[0022] The second determination condition is to compare the product of the comprehensive test determination coefficient and the standard deviation and the sum of the absolute values with a specified value to determine whether the content uniformity of the test sample meets the requirements.

[0023] Further, when the uniformity does not meet the standard, the test data of the test sample at the corner edge of the square cone mixer is extracted, and a standard deviation change curve is plotted to predict the change of the standard deviation;

[0024] If the derivative value of the standard deviation change curve corresponding to the current detection period is less than zero, it is determined that the standard deviation is continuously decreasing, and it is predicted whether the uniformity can meet the requirements within the required duration and whether the mixing duration needs to be adjusted;

[0025] If the absolute value of the derivative value of the standard deviation change curve corresponding to the current detection period is less than the difference evaluation value, it is determined that the standard deviation fluctuation tends to zero, and the reason for the non - compliance of the uniformity with the standard is judged.

[0026] Further, the process of judging the reason for the non - compliance of the uniformity with the standard includes,

[0027] Obtain the powder particle size of the medicinal material powder, compare the powder particle size with the standard particle size, and judge whether the pulverization degree of the corresponding medicinal material powder is at the first pulverization degree or the second pulverization degree;

[0028] Calculate the powder proportion of the medicinal material powder at the second pulverization degree in the test sample, compare the powder proportion with the critical proportion, and judge whether the content of over - fine powder is within the normal range or exceeds the normal range.

[0029] Further, when the content of over - fine powder is within the normal range, it is judged that the reason for the non - compliance of the uniformity with the standard is that the loading coefficient of the square cone mixer exceeds the range, and the loading coefficient is adjusted;

[0030] When the content of over - fine powder exceeds the normal range, it is judged that the reason for the non - compliance of the uniformity with the standard is that the pulverization and grinding process does not meet the standard, and the process parameters of pulverization and grinding are adjusted

[0031] Further, the process of determining the adjustment state of the process parameter duration includes,

[0032] If the pulverization and grinding duration, or, the mixing duration is adjusted, it is determined that the process parameter duration is in the first adjustment state;

[0033] If the pulverization and grinding duration, and, the mixing duration are adjusted, it is determined that the process parameter duration is in the second adjustment state;

[0034] Furthermore, in the first adjustment state, the sterilization time of the sterilization process is adjusted according to the ratio of the crushing and grinding time or mixing time after adjustment to the crushing and grinding time or mixing time before adjustment;

[0035] In the second adjustment state, the sterilization time of the sterilization process is adjusted according to the ratio of the sum of the crushing and grinding time and the mixing time after adjustment to the sum of the crushing and grinding time and the mixing time before adjustment.

[0036] A Kaixin powder, characterized in that the Kaixin powder is a powder in an oral solid preparation;

[0037] The powder contains 13.80g of Polygala, 13.80g of Ginseng, 27.60g of Poria, and 13.80g of Acorus calamus;

[0038] The mass fraction ratio of Polygala tenuifolia, ginseng, Poria cocos and Acorus calamus in the powder is 1:1:2:1.

[0039] Compared with the prior art, the beneficial effect of the present invention lies in that the medicinal powder is mixed with materials in a square cone mixer, and the medicinal powder in the hopper will not only flip as the hopper rotates, but also move tangentially along the hopper wall. The combination of flipping and tangential movement allows the material to be fully moved and exchanged in multiple directions, effectively avoiding the stratification and segregation of the material. Compared with traditional mixers, the mixing effect of the square cone mixer is more ideal, and can ensure that each component material is evenly distributed in the entire mixture; at the same time, in order to improve the cross-mixing degree and mixing speed of the intermediate materials, the present invention is provided with guide blades under the top cover of the square cone mixer; this method evenly distributes sampling points in the mixing equipment to avoid the influence of the dead corners of the mixing equipment on the results, and samples are taken at different time points during the mixing process to ensure the dynamic evaluation of the mixing uniformity.

[0040] Furthermore, when taking the powder, if it is not fully mixed and uniform, it may cause a large amount of precipitation in the medicine solution, affecting the patient's compliance and therapeutic effect. The uniformity, sterilization effect and hygroscopicity of the powder should be strictly tested to ensure that the product quality meets the standards and strengthen quality inspection. According to the characteristics of the consistent content of most medicinal materials in Kaixin Powder, the present invention detects the content uniformity of Kaixin Powder in the mixture, more accurately controls the uniformity of the medicine, and improves the accuracy of drug quality control. At the same time, there is no need to check the weight difference after the inspection. The method can directly reflect the distribution of medicinal materials in the preparation through the content uniformity inspection. The weight difference pays more attention to the change in total weight and cannot reflect the uniformity of the medicinal materials. It simplifies the inspection process and ensures the quality consistency of key components, which helps to improve the quality of Kaixin Powder and reduce precipitation problems when taking.

[0041] Furthermore, during the process of mixing the medicinal herb powder by the square cone mixer, the uniformity of the medicinal herb powder becomes higher and higher, and the standard deviation shows a downward trend over time and then gradually tends to a fixed value. This method analyzes the changing trend of the standard deviation through the derivative value of the change curve. When the uniformity does not meet the standard, it detects whether the standard deviation is still changing, that is, determines whether the content uniformity is changing. When the standard deviation is continuously decreasing, it adjusts the mixing duration of the square cone mixer. At the same time, when the standard deviation fluctuates towards zero, it determines that the standard deviation has been fixed, that is, the determined content uniformity has been fixed. For the situation where the uniformity does not meet the standard, it inspects whether the crushing and grinding process of the medicinal herbs meets the standard, which helps to ensure that patients obtain the same dose of active ingredients each time they take the medicine, thereby improving the stability and predictability of the drug efficacy, and can timely detect possible problems of uneven mixing or filling difference in the production process, thereby reducing the quality risk and improving the production efficiency.

[0042] Furthermore, the polygala tenuifolia, ginseng, poria cocos, and acorus tatarinowii in the KaiXinSan are soft medicinal herbs, which are easy to become powder after being crushed. Attention should be paid to the proportion of too fine powder. This method determines the crushing degree of the medicinal herb powder, calculates the proportion of too fine powder in the medicinal herb powder, determines whether the reason for the non-compliance of the uniformity standard is that the crushing and grinding process does not meet the standard, and correspondingly adjusts the process parameters of crushing and grinding or the loading coefficient of the square cone mixer, increasing the accuracy and adaptability of the preparation method of KaiXinSan, improving the drug efficacy and taking compliance of KaiXinSan, and enhancing the dissolution rate and drug efficacy consistency of the medicinal herbs.

[0043] Furthermore, Chinese medicinal materials may contain microorganisms during the collection and processing process, and these microorganisms affect the safety and stability of the drugs. During the preparation process of KaiXinSan, in the crushing and grinding process and the mixing and crushing process, the medicinal herb powder is in an aerobic environment. Any change in the duration parameters of the grinding duration and the mixing duration will affect the contact duration between the medicinal powder and the air, resulting in a change in the content of the microorganisms generated. This method determines the adjustment state of the process parameter duration according to the change situation of the duration parameters, and correspondingly adopts different ways to adjust the sterilization duration of the sterilization process, increasing the accuracy of sterilizing the prepared KaiXinSan. At the same time, since KaiXinSan contains heat-sensitive ingredients such as ginseng and poria cocos, as well as volatile ingredients of acorus tatarinowii, over-sterilization that may damage the active ingredients is avoided. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 It is a schematic flow chart of a preparation method of a KaiXinSan in an embodiment of the present invention;

[0045] Figure 2 It is a schematic diagram of the positions of the sampling points of the conical mixer in an embodiment of the present invention;

[0046] Figure 3Schematic structural diagram of the diversion blade at the top of the conical mixer in the embodiment of the present invention;

[0047] Figure 4 Schematic flow diagram for determining whether the content uniformity of the test sample meets the requirements in the embodiment of the present invention. Detailed implementation manners

[0048] In order to make the objectives and advantages of the present invention clearer, the present invention will be further described below in conjunction with embodiments; it should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0049] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are only used to explain the technical principles of the present invention and do not limit the protection scope of the present invention.

[0050] It should be noted that in the description of the present invention, the terms indicating directions or positional relationships such as "upper", "lower", "left", "right", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings. This is only for convenience of description and does not indicate or imply that the device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the present invention.

[0051] In addition, it should be noted that in the description of the present invention, unless otherwise clearly specified and limited, the terms "installation", "connection", and "coupling" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0052] Please refer to Figures 1-4 as shown Figure 1 Schematic flow diagram of a preparation method of KaiXinSan in the embodiment of the present invention; Figure 2 Schematic diagram of the positions of the sampling points of the conical mixer in the embodiment of the present invention; Figure 3 Schematic structural diagram of the diversion blade at the top of the conical mixer in the embodiment of the present invention; Figure 4 Schematic flow diagram for determining whether the content uniformity of the test sample meets the requirements in the embodiment of the present invention.

[0053] The present invention provides a KaiXinSan, which is characterized by comprising:

[0054] The KaiXinSan is a powder in oral solid preparations;

[0055] The powder contains 13.80 g of Polygala tenuifolia, 13.80 g of Ginseng radix, 27.60 g of Poria cocos, and 13.80 g of Acorus tatarinowii;

[0056] In the powder, the mass fraction ratio of Polygala tenuifolia, Ginseng radix, Poria cocos, and Acorus tatarinowii is 1:1:2:1.

[0057] The present invention provides a preparation method of KaiXinSan, including:

[0058] Step S1, pre-treat the Polygala tenuifolia, Ginseng radix, Poria cocos, and Acorus tatarinowii herbs in KaiXinSan, grind the pre-treated herbs into herb powders according to preset crushing and grinding parameters, and screen the herb powders;

[0059] Step S2, put the screened herb powders into a square conical mixer according to a preset charging coefficient for mixing to prepare the powder. During the mixing, periodically take samples from the set positions of the square conical mixer, and take several test samples of KaiXinSan

[0060] Step S3, check the content uniformity of the test samples at different set positions, initially determine whether the content uniformity of the test samples meets the regulations, or, conduct a re-test for secondary determination;

[0061] Step S4, conduct a comprehensive test according to the results of the initial and re-tests to determine whether the content uniformity of the test samples meets the regulations;

[0062] Step S5, when the content uniformity does not meet the regulations, draw a standard deviation change curve, predict the change trend of the standard deviation, and judge whether it is necessary to adjust the mixing duration, or, judge the reason why the uniformity does not meet the standard;

[0063] Step S6, detect the powder particle size of the herb powders, determine the crushing degree of the herb powders, and judge that the reason for the non-compliance of the uniformity with the standard is that the charging coefficient exceeds the range, or, the crushing and grinding process does not meet the standard, and determine the crushing and grinding parameters;

[0064] Step S7, sterilize the powder with the content uniformity meeting the regulations, determine the adjustment state of the process parameter duration according to the mixing duration and the crushing and grinding parameters, and determine the sterilization duration of the sterilization process;

[0065] Among them, the set positions include the upper part of the mixer, the corner edge, and the discharge port in the square conical mixer.

[0066] In this embodiment, a square conical mixer is used to mix the crushed and ground herb powders;

[0067] The square-cone mixer loads materials into a square-cone-shaped sealed mixing barrel, and the axis of symmetry of the hopper forms an angle with the axis of the rotating shaft. During operation, materials of different components perform three-dimensional motion in the sealed hopper. This motion generates strong flipping and diffusive contraction effects, enabling the materials to be fully mixed.

[0068] Below the cover top inside the square-cone mixer, there are guide vanes arranged. The guide vanes are approximately cross-shaped, and a feed inlet is correspondingly arranged at the center of the guide vanes;

[0069] The square-cone mixer is loaded according to a preset filling coefficient, and the filling coefficient of the square-cone mixer is set to 80%.

[0070] For the mixed KaiXinSan, samples are taken from the set positions of the square-cone mixer according to the initial detection period. 10 test samples of KaiXinSan are taken, and the set positions are 11 positions including the upper part of the mixer, the corner edge, and the discharge port inside the square-cone mixer.

[0071] Specifically, when using the square-cone mixer to mix medicinal herb powders, the medicinal herb powders in the hopper will not only flip with the rotation of the hopper but also move tangentially along the hopper wall. The combination of this flipping and tangential movement enables the materials to move and exchange sufficiently in multiple directions, effectively avoiding the phenomena of material stratification and segregation. Compared with traditional mixers, the mixing effect of the square-cone mixer is more ideal, which can ensure that each component material is evenly distributed throughout the mixture; at the same time, in order to improve the degree of cross-mixing and mixing speed of the intermediate materials, guide vanes are arranged below the cover top inside the square-cone mixer in the present invention; this method avoids the influence of the dead corners of the mixing equipment on the results by evenly distributing the sampling points in the mixing equipment, and samples are taken at different time points during the mixing process to ensure the dynamic evaluation of the mixing uniformity.

[0072] In this embodiment, the labeled amount of the reference sample of KaiXinSan is M,

[0073] Content uniformity inspections are carried out on 10 test samples at different set positions. The relative content xi of each single dose in several test samples is measured respectively, and the mean value X, the standard deviation S, and the absolute value A of the difference between the labeled amount and the mean value are calculated. The single dose is the medicinal herb powders of Polygala tenuifolia, Panax ginseng, Poria cocos, and Acorus tatarinowii;

[0074]

[0075] In the initial test, the absolute value A and the standard deviation S are compared with the specified values. If the sum of the absolute value A and α1 times the standard deviation S is less than or equal to the specified value L, it is determined that the content uniformity of the test sample meets the requirements;

[0076] If the sum of the absolute value of A and α0 times the standard deviation S is greater than the specified value L, it is determined that the content uniformity of the test sample does not meet the requirements;

[0077] If the sum of the absolute value of A and α1 times the standard deviation S is greater than the specified value L, and the sum of the absolute value of A and the standard deviation S is less than or equal to the specified value L, then it is determined that the content uniformity of the test sample requires a second determination, and another 20 test samples are taken for retesting.

[0078] Based on the results of the initial and retest, a comprehensive test is carried out. Calculate the mean X, the standard deviation S of 30 single doses, and the absolute value A of the difference between the labeled amount and the mean, and then calculate and determine according to the following formula;

[0079] When the absolute value of A is less than or equal to 0.25 times the specified value L, the first determination condition is adopted.

[0080] If the sum of the square of the absolute value of A and the square of the standard deviation S is less than or equal to 0.25 times the square of the specified value L, it is determined that the content uniformity of the test sample meets the requirements;

[0081] If the sum of the square of the absolute value of A and the square of the standard deviation S is greater than 0.25 times the square of the specified value L, it is determined that the content uniformity of the test sample does not meet the requirements.

[0082] When the absolute value of A is greater than 0.25 times the specified value L, the second determination condition is adopted.

[0083] If the sum of the absolute value of A and α2 times the standard deviation S is less than or equal to the specified value L, it is determined that the content uniformity of the test sample meets the requirements;

[0084] If the sum of the absolute value of A and α2 times the standard deviation S is greater than the specified value L, it is determined that the content uniformity of the test sample does not meet the requirements.

[0085] In this embodiment, the specified value L is equal to 15.0, α is the determination coefficient, α0 and α1 are the initial determination coefficients, α2 is the comprehensive determination coefficient, α0 = 1, α1 = 2.2, α2 = 1.7.

[0086] Specifically, during administration, if the powder is not fully and evenly mixed, it may lead to a large amount of precipitation in the liquid medicine, affecting the compliance and treatment effect of patients. Therefore, the uniformity, sterilization effect, and hygroscopicity of the powder should be strictly detected to ensure that the product quality meets the standards and strengthen quality inspection. According to the characteristic that the contents of most medicinal materials in KaiXinSan are consistent, the present invention detects the content uniformity of KaiXinSan during mixing to more precisely control the uniformity of the medicine and improve the accuracy of drug quality control. At the same time, after inspection, there is no need to check the weight difference anymore. This method can directly reflect the distribution of medicinal materials in the preparation through the content uniformity inspection. The weight difference focuses more on the change in the total weight and cannot reflect the uniformity of the medicinal materials, which simplifies the detection process and ensures the quality consistency of key components, helps to improve the quality of KaiXinSan, and reduces the precipitation problem during administration.

[0087] When the uniformity does not meet the standard, extract the test data of the test sample at the corner edge of the conical mixer. According to the standard deviation S of the test sample sampled according to the initial detection cycle, draw a curve of the change of the standard deviation over time, and derive the derivative function of the standard deviation change curve to predict the change of the standard deviation.

[0088] If the derivative value of the standard deviation change curve corresponding to the current detection cycle is less than zero, it is determined that the standard deviation is continuously decreasing, and predict whether the uniformity can meet the requirements within the predicted demand time and whether it is necessary to adjust the mixing time.

[0089] Specifically, when the standard deviation is continuously decreasing, increase the mixing time of the preset conical mixer.

[0090] If the absolute value of the derivative value of the standard deviation change curve corresponding to the current detection cycle is less than the difference evaluation value, it is determined that the standard deviation fluctuation tends to zero, determine the reason why the uniformity does not meet the standard, and detect whether the crushing and grinding process of the medicinal materials meets the standard.

[0091] Specifically, during the process of mixing medicinal material powders by a square-cone mixer, the uniformity of the medicinal material powders becomes higher and higher, and the standard deviation generally shows a downward trend over time and then gradually tends to a fixed value. This method analyzes the changing trend of the standard deviation through the derivative value of the change curve. When the uniformity does not meet the standard, it detects whether the standard deviation is still changing, that is, whether the determined content uniformity is changing. When the standard deviation is continuously decreasing, the mixing duration of the square-cone mixer is adjusted. At the same time, when the standard deviation fluctuates and tends to zero, it is determined that the standard deviation has been fixed, that is, the determined content uniformity has been fixed. For the situation where the uniformity does not meet the standard, it is necessary to inspect whether the crushing and grinding process of the medicinal materials meets the standard, which helps to ensure that patients obtain the same dose of active ingredients each time they take the medicine, thereby improving the stability and predictability of the drug efficacy, and can timely detect possible problems of uneven mixing or filling quantity differences during the production process, thereby reducing the quality risk and improving the production efficiency.

[0092] Inspect whether the crushing and grinding process of the medicinal materials meets the standard. Use a laser particle size analyzer to obtain the particle size of the medicinal material powders in the crushed medicinal materials and divide the particle size of the powders.

[0093] If the particle size of the powder is smaller than the standard particle size, it is determined that the crushing degree of the corresponding medicinal material powder is at the second crushing degree.

[0094] If the particle size of the powder is greater than or equal to the standard particle size, it is determined that the crushing degree of the corresponding medicinal material powder is at the first crushing degree.

[0095] Calculate the powder proportion of the medicinal material powders at the second crushing degree in the test sample. If the powder proportion is less than or equal to the critical proportion, it is determined that the content of the overly fine powder is within the normal range, and the reason for the non-compliance of the uniformity is that the loading coefficient of the square-cone mixer exceeds the range, and the loading coefficient is adjusted.

[0096] Specifically, the loading coefficient of the square-cone mixer is reduced according to the ratio of the powder proportion to the critical proportion.

[0097] If the powder proportion is greater than the critical proportion, it is determined that the content of the overly fine powder exceeds the normal range, and the reason for the non-compliance of the uniformity is that the crushing and grinding process does not meet the standard, and the process parameters of the crushing and grinding are adjusted.

[0098] Specifically, the crushing and grinding duration in the crushing and grinding process is reduced according to the ratio of the critical proportion to the powder proportion.

[0099] Among them, the critical proportion is 5%, and the standard particle size is a preset value set according to the particle size of the medicinal material powder required by the KaiXinSan.

[0100] Specifically, polygala tenuifolia, ginseng, poria cocos, and acorus tatarinowii in the KaiXinSan are soft medicinal materials. After being crushed, they are easily turned into powder, and attention should be paid to the proportion of overly fine powder. By determining the crushing degree of the medicinal material powder, calculating the proportion of the overly fine powder in the medicinal material powder, and determining whether the reason for the non-compliance of the uniformity standard is the substandard crushing and grinding process, the process parameters of crushing and grinding or the loading coefficient of the conical mixer are adjusted accordingly, which increases the accuracy and adaptability of the preparation method of KaiXinSan, improves the efficacy and compliance of taking KaiXinSan, and enhances the dissolution rate and efficacy consistency of the medicinal materials.

[0101] Chinese medicinal materials may contain microorganisms such as bacteria and fungi during the collection and processing. These microorganisms may affect the safety and stability of drugs. Especially during long-term storage, the reproduction of microorganisms may increase. According to the Chinese Pharmacopoeia and relevant regulations, traditional Chinese medicine preparations need to meet certain microbial limit standards to ensure the safety of medication.

[0102] In this embodiment, the irradiation sterilization method is used for sterilization, and the sterilization parameters are determined according to different states of the process parameter duration.

[0103] If the crushing and grinding duration or the mixing duration is adjusted, it is determined that the process parameter duration is in the first adjustment state, and the sterilization duration of the sterilization process is adjusted.

[0104] Specifically, the sterilization duration of the sterilization process is adjusted according to the ratio of the adjusted crushing and grinding duration or mixing duration to the crushing and grinding duration or mixing duration before adjustment.

[0105] If the crushing and grinding duration and the mixing duration are adjusted, it is determined that the process parameter duration is in the second adjustment state, and the sterilization duration of the sterilization process is adjusted.

[0106] Specifically, the sterilization duration of the sterilization process is adjusted according to the ratio of the sum of the adjusted crushing and grinding duration and mixing duration to the sum of the crushing and grinding duration and mixing duration before adjustment.

[0107] Specifically, Chinese medicinal materials may contain microorganisms during the collection and processing, and these microorganisms affect the safety and stability of drugs. During the preparation process of KaiXinSan, in the crushing and grinding process and the mixing and crushing process, the medicinal material powder is in an aerobic environment. Any change in the duration parameters of the grinding duration and the mixing duration will affect the contact duration between the medicinal powder and the air, resulting in a change in the content of the microorganisms generated. This method determines the adjustment state of the process parameter duration according to the change situation of the duration parameters, and correspondingly adopts different methods to adjust the sterilization duration of the sterilization process, which increases the accuracy of the sterilization treatment of the prepared KaiXinSan. At the same time, since KaiXinSan contains heat-sensitive components such as ginseng and poria cocos, as well as the volatile components of acorus tatarinowii, over-sterilization that may damage the active ingredients is avoided.

[0108] So far, the technical solution of the present invention has been described in conjunction with the preferred embodiments shown in the accompanying drawings. However, it is easy for those skilled in the art to understand that the protection scope of the present invention is obviously not limited to these specific embodiments. Without departing from the principle of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will fall within the protection scope of the present invention.

[0109] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing Kaixin powder, characterized in that: include: Pre-treating the medicinal material raw materials of Kaixin Powder, crushing and grinding the pre-treated medicinal materials into medicinal material powder according to preset crushing and grinding parameters, and screening the medicinal material powder; The screened medicinal material powders are mixed according to a preset loading factor to prepare a powder, and samples are periodically taken from a set position during the mixing process to take out several portions of the test sample of the Xinsan; Conduct content uniformity checks on several test products at different set positions, and conduct a preliminary test to determine whether the content uniformity of the test products meets the requirements, or conduct a retest for a second determination; Conduct comprehensive tests based on the initial and retest results to determine whether the content uniformity of the test product meets the requirements; When the content uniformity does not meet the requirements, draw a standard deviation change curve to predict the trend of the standard deviation and determine whether the mixing time needs to be adjusted, or determine the reason why the uniformity does not meet the standards; Detect the powder particle size of the medicinal material powder, determine the degree of crushing of the medicinal material powder, and determine the reason why the uniformity does not meet the standard based on the degree of crushing, such as the charging factor exceeds the range, or the crushing and grinding process does not meet the standard, and determine the crushing and grinding parameters; Sterilize the powders whose content uniformity meets the requirements, determine the adjustment state of the process parameter time according to the mixing time and crushing and grinding parameters, and determine the sterilization time of the sterilization process; Wherein, the set position includes the upper part of the mixer, the corner edge and the discharge port in the square cone mixer.

2. The method for preparing Kaixinsan according to claim 1, characterized in that: The process of initial testing to determine the uniformity of the content of the test product includes: For the test samples at different set positions, the relative content of each single dose in several test samples is determined, the mean, standard deviation and absolute value are calculated, and the absolute value and standard deviation are compared with the specified value; According to the product of the initial determination coefficient and the standard deviation and the sum of the absolute values, it is determined that the content uniformity of the test sample does not meet the requirements, or meets the requirements, or the content uniformity of the test sample needs to be determined again, and the test sample is taken for retesting; Wherein, the single dose is the medicinal material powder of Polygala tenuifolia, Ginseng, Poria cocos and Acorus calamus.

3. The method for preparing Kaixinsan according to claim 2, characterized in that: Carry out a comprehensive test based on the results of the initial test and the retest, calculate the mean, standard deviation and absolute value of several test samples in the initial test and the retest, compare the absolute value with the specified value, and adopt the first judgment condition and the second judgment condition based on the comparison result.

4. The method for preparing Kaixinsan according to claim 3, characterized in that: The first determination condition is to compare the sum of the square of the absolute value and the square of the standard deviation with the square of the specified value to determine whether the content uniformity of the test sample meets the requirements; The second determination condition is to compare the product of the comprehensive test determination coefficient and the standard deviation and the sum of the absolute values ​​with the specified value to determine whether the content uniformity of the test sample meets the requirements.

5. The method for preparing Kaixinsan according to claim 4, characterized in that: When the uniformity does not meet the standard, extract the test data of the test product at the corner edge of the square cone mixer, draw the standard deviation change curve, and predict the change of the standard deviation; If the derivative value of the standard deviation change curve corresponding to the current detection period is less than zero, it is judged that the standard deviation is continuously decreasing, and it is predicted whether the uniformity within the required time can meet the demand and whether the mixing time needs to be adjusted; If the absolute value of the derivative value of the standard deviation change curve corresponding to the current detection period is less than the difference evaluation value, it is judged that the standard deviation fluctuation tends to zero, and the reason why the uniformity does not meet the standard is judged.

6. The method for preparing Kaixinsan according to claim 5, characterized in that: The process of determining why uniformity does not meet the standard includes: Obtaining the powder particle size of the medicinal material powder, comparing the powder particle size with the standard particle size, and determining whether the crushing degree of the corresponding medicinal material powder is at the first crushing degree or the second crushing degree; Calculate the powder ratio of the medicinal material powder at the second degree of crushing in the test sample, compare the powder ratio with the critical ratio, and determine whether the content of excessively fine powder is within the normal range or exceeds the normal range.

7. The method for preparing Kaixinsan according to claim 6, characterized in that: When the content of overfine powder is within the normal range, it is judged that the uniformity does not meet the standard because the filling coefficient of the square cone mixer is out of range, and the filling coefficient is adjusted; When the content of excessively fine powder exceeds the normal range, it is judged that the uniformity does not meet the standard because the crushing and grinding process does not meet the standard, and the crushing and grinding process parameters are adjusted.

8. The method for preparing Kaixinsan according to claim 1, characterized in that: The process of determining the adjustment state of the process parameter duration includes: If the crushing and grinding time or the mixing time is adjusted, it is determined that the process parameter time is in the first adjustment state; If the crushing and grinding time and the mixing time are adjusted, it is determined that the process parameter time is in the second adjustment state.

9. The method for preparing Kaixinsan according to claim 8, characterized in that: In the first adjustment state, the sterilization time of the sterilization process is adjusted according to the ratio of the crushing and grinding time or mixing time after adjustment to the crushing and grinding time or mixing time before adjustment; In the second adjustment state, the sterilization time of the sterilization process is adjusted according to the ratio of the sum of the crushing and grinding time and the mixing time after adjustment to the sum of the crushing and grinding time and the mixing time before adjustment.

10. A kind of Kaixin powder, prepared by the preparation method according to any one of claims 1 to 9, characterized in that: The Kaixin powder is a powder in an oral solid preparation; The powder contains 13.80g of Polygala, 13.80g of Ginseng, 27.60g of Poria, and 13.80g of Acorus calamus; The mass fraction ratio of Polygala tenuifolia, ginseng, Poria cocos and Acorus calamus in the powder is 1:1:2:1.

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