Kai xin san and a preparation method thereof

Abstract

The present invention relates to the technical field of traditional Chinese medicine preparation, and particularly to a KaiXinSan and its preparation method, which includes crushing, grinding, screening and mixing medicinal materials to prepare a powder, periodically taking several portions of test samples from a set position; checking the content uniformity of the test samples, initially determining the content uniformity of the test samples or conducting a re-test for a second determination; conducting a comprehensive test based on the results of the initial and re-tests to determine the content uniformity of the test samples; predicting the change trend of the standard deviation when the regulations are not met, and judging whether it is necessary to adjust the mixing duration or the reason for the non-compliance of the uniformity; determining the degree of pulverization of the medicinal material powder, and determining that the reason for non-compliance is that the charging coefficient exceeds the range or the pulverization and grinding process does not meet the standard; sterilizing the powder that meets the regulations, judging the adjustment state of the process parameter duration, and determining the sterilization duration of the sterilization process. The present invention improves the dissolution rate of medicinal materials and enhances the compliance of taking medicine by determining and adjusting the mixing uniformity of medicinal powder in real time.

Description

Technical Field

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

[0002] KaiXinSan is a traditional Chinese medicine prescription with the effects of replenishing 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, taken with water, one square spoonful each time, 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 characteristics in terms of medicinal properties and effects, 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 invigorates 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, effectively preserving the medicinal value of the medicinal materials itself; improving the cleanliness of traditional Chinese medicine, and at the same time collecting the sterilized traditional Chinese medicine 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 lead to uneven distribution of active ingredients, thereby affecting the medicinal effect, and may cause a large amount of precipitation in the liquid medicine during taking, affecting the compliance of patients and the treatment effect. Summary of the Invention

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

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

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

[0008] The screened medicinal powders were mixed according to a preset filling coefficient to prepare a powder. During the mixing process, samples were periodically taken from a set location, and several portions of the Kaixin powder were collected as test samples.

[0009] For several test samples at different set locations, the content uniformity is checked. The initial test determines whether the content uniformity of the test samples meets the requirements, or a second test is conducted to determine whether the content uniformity meets the requirements.

[0010] Based on the results of the initial and retests, a comprehensive test is conducted to determine whether the content uniformity of the test sample meets the requirements.

[0011] When the content uniformity does not meet the requirements, plot the standard deviation change curve, predict the trend of the standard deviation change, and determine whether the mixing time needs to be adjusted, or determine the reason why the uniformity does not meet the standard.

[0012] The particle size of the medicinal powder is tested to determine the degree of pulverization. Based on the degree of pulverization, the reason why the uniformity does not meet the standard is that the loading coefficient is out of range or the pulverization and grinding process is not up to standard. The pulverization and grinding parameters are then determined.

[0013] For powders with uniform content that meet the requirements, sterilization is carried out. The adjustment status of the process parameters is determined based on the mixing time and grinding parameters, and the sterilization time of the sterilization process is determined accordingly.

[0014] The designated locations include the upper part of the mixer, the corner edge, and the discharge port within the square cone mixer.

[0015] Furthermore, the initial determination of the uniformity of the content of the test sample includes,

[0016] For test samples at different designated locations, the relative content of each single agent in several test samples was determined, the mean, standard deviation, and absolute value were calculated, and the absolute value and standard deviation were compared with the specified value.

[0017] The content uniformity of the test sample is determined by the sum of the product and absolute value of the initial test judgment coefficient and standard deviation. If 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 judged a second time, the test sample is taken for retesting.

[0018] The single-dose formulation consists of powdered medicinal materials of Polygala tenuifolia, ginseng, Poria cocos, and Acorus tatarinowii.

[0019] Furthermore, based on the results of the preliminary and final tests, a comprehensive test is conducted, and the mean, standard deviation, and absolute value of several test samples from the preliminary and final tests are calculated.

[0020] The absolute value is compared with the specified value, and the first and second judgment conditions are adopted based on the comparison results.

[0021] Furthermore, the first judgment 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.

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

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

[0024] If the derivative 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. It is then determined whether the uniformity can meet the requirements within the predicted time period and whether the mixing time needs to be adjusted.

[0025] If the absolute value of the derivative of the standard deviation change curve corresponding to the current testing cycle is less than the difference evaluation value, it is determined that the standard deviation fluctuation tends to zero, and the reason why the uniformity does not meet the standard is determined.

[0026] Furthermore, the process of determining why uniformity does not meet the standard includes,

[0027] Obtain the particle size of the medicinal powder, compare the particle size with the standard particle size, and determine whether the corresponding medicinal powder is in the first or second degree of pulverization.

[0028] Calculate the proportion of medicinal powder at the second stage of pulverization in the test sample, compare the powder proportion with the critical proportion, and determine whether the content of excessively fine powder is within or exceeds the normal range.

[0029] Furthermore, when the content of excessively fine powder is within the normal range, the reason for the non-compliance of uniformity is that the loading coefficient of the cone mixer is out of range, and the loading coefficient should be adjusted.

[0030] When the content of excessively fine powder exceeds the normal range, the reason for the non-compliance with uniformity standards is that the grinding process is substandard. The grinding process parameters should be adjusted accordingly.

[0031] Furthermore, the process of determining the adjustment status of the process parameters duration includes,

[0032] If the grinding time or the mixing time is adjusted, then the process parameter time is determined to be in the first adjustment state.

[0033] If the grinding time and the mixing time are adjusted, then the process parameter time is determined to be 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 adjusted grinding or mixing time to the grinding 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 adjusted grinding and mixing time to the sum of the grinding and mixing time before adjustment.

[0036] A kind of Kaixin powder, characterized in that the Kaixin powder is a powder in oral solid dosage form;

[0037] The powder contains 13.80g of Polygala tenuifolia, 13.80g of ginseng, 27.60g of Poria cocos, and 13.80g of Acorus tatarinowii.

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

[0039] Compared with existing technologies, the advantages of this invention are that it uses a cone-shaped mixer to mix medicinal powders. The powders not only tumble as the hopper rotates, but also move tangentially along the hopper wall. This combination of tumbling and tangential movement allows the material to move and exchange fully in multiple directions, effectively preventing stratification and segregation. Compared with traditional mixers, the cone-shaped mixer achieves a more ideal mixing effect, ensuring that each component is evenly distributed throughout the mixture. Furthermore, to enhance the cross-mixing degree and mixing speed of intermediate materials, this invention incorporates guide vanes below the top cover inside the cone-shaped mixer. This method avoids the influence of dead zones on the results by evenly distributing sampling points within the mixing equipment, and sampling at different time points during the mixing process ensures dynamic evaluation of the mixing uniformity.

[0040] Furthermore, if the powder is not thoroughly mixed during administration, it may lead to a large amount of sediment in the liquid, affecting patient compliance and therapeutic effect. Therefore, the uniformity, sterilization effect, and hygroscopicity of the powder should be strictly tested to ensure product quality meets standards and to strengthen quality control. Based on the characteristic that most medicinal materials in Kaixin San have consistent content, this invention tests the uniformity of Kaixin San content in the mixture, more precisely controlling the homogeneity of the drug and improving the accuracy of drug quality control. Simultaneously, after the test, it is no longer necessary to check for weight differences. This method directly reflects the distribution of medicinal materials in the preparation through content uniformity testing, while weight differences focus more on changes in total weight and cannot reflect the uniformity of medicinal materials. This simplifies the testing process, ensures the quality consistency of key components, helps improve the quality of Kaixin San, and reduces sedimentation problems during administration.

[0041] Furthermore, during the mixing of medicinal powders using a cone-shaped mixer, the uniformity of the powders increases, and the standard deviation shows a decreasing trend over time, eventually tending towards a fixed value. This method analyzes the trend of standard deviation using the derivative of the variation curve. When uniformity does not meet the standard, it checks whether the standard deviation is still changing, i.e., whether the determined content uniformity is changing. When the standard deviation is continuously decreasing, the mixing time of the cone-shaped mixer is adjusted. Simultaneously, when the standard deviation fluctuation tends to zero, it is determined that the standard deviation has been fixed, i.e., the determined content uniformity has been fixed. For cases where uniformity does not meet the standard, the pulverization and grinding process of the medicinal materials is inspected to ensure that patients receive the same dose of effective ingredients each time they take the medication, thereby improving the stability and predictability of drug efficacy. It can also promptly detect potential mixing unevenness or dosage differences during the production process, thereby reducing quality risks and improving production efficiency.

[0042] Furthermore, the ingredients in Kaixin San, such as Polygala tenuifolia, ginseng, Poria cocos, and Acorus tatarinowii, are soft medicinal materials that are easily pulverized into powder. Therefore, attention must be paid to the proportion of excessively fine powder. This method determines the degree of pulverization of the medicinal material powder, calculates the proportion of excessively fine powder in the medicinal material powder, and determines whether the reason for non-standard uniformity is due to substandard pulverization and grinding process. Accordingly, the pulverization and grinding process parameters or the loading coefficient of the square cone mixer are adjusted, which increases the accuracy and adaptability of the Kaixin San preparation method, improves the efficacy and compliance of Kaixin San, and enhances the dissolution rate and efficacy consistency of the medicinal materials.

[0043] Furthermore, Chinese medicinal materials may contain microorganisms during the collection and processing, which can affect the safety and stability of the drug. In the preparation of Kaixin San, the powdered medicinal materials are in an aerobic environment during the pulverization and grinding processes and the mixing and pulverization processes. Changes in the grinding and mixing time parameters will affect the contact time between the powder and the air, leading to changes in the content of microorganisms. This method determines the adjustment status of the process parameters based on the changes in the time parameters and adopts different methods to adjust the sterilization time of the sterilization process accordingly, which increases the accuracy of sterilization treatment of the prepared Kaixin San. At the same time, since Kaixin San contains heat-sensitive components such as ginseng and poria, as well as volatile components of acorus tatarinowii, it avoids excessive sterilization that could destroy the effective components. Attached Figure Description

[0044] Figure 1 This is a schematic flowchart of a method for preparing Kaixin San in an embodiment of the present invention;

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

[0046] Figure 3This is a schematic diagram of the top flow divider blades of the conical mixer in an embodiment of the present invention;

[0047] Figure 4 This is a schematic diagram illustrating the process for determining whether the content uniformity of the test sample meets the specified requirements in an embodiment of the present invention. Detailed Implementation

[0048] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0049] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

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

[0051] Furthermore, it should be noted that, in the description of this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0052] Please see Figures 1-4 As shown, Figure 1 This is a schematic flowchart of a method for preparing Kaixin San in an embodiment of the present invention; Figure 2 This is a schematic diagram showing the location of the sampling points of the conical mixer in an embodiment of the present invention; Figure 3 This is a schematic diagram of the top flow divider blades of the conical mixer in an embodiment of the present invention; Figure 4 This is a schematic diagram illustrating the process for determining whether the content uniformity of the test sample meets the specified requirements in an embodiment of the present invention.

[0053] This invention provides a remedy for relieving unhappiness, characterized in that it comprises:

[0054] Kaixin San is a powder in oral solid dosage forms;

[0055] The powder contains 13.80g of Polygala tenuifolia, 13.80g of ginseng, 27.60g of Poria cocos, and 13.80g of Acorus tatarinowii.

[0056] The mass fraction ratio of Polygala tenuifolia, ginseng, Poria cocos and Acorus tatarinowii in the powder is 1:1:2:1.

[0057] This invention provides a method for preparing Kaixin San (a traditional Chinese medicine formula), comprising:

[0058] Step S1: Pre-treat the medicinal materials of Polygala tenuifolia, ginseng, Poria cocos and Acorus tatarinowii in Kaixin San. Grind the pre-treated medicinal materials into powder according to the preset grinding parameters and screen the powder.

[0059] Step S2: The screened medicinal powder is placed into a cone-shaped mixer according to a preset loading coefficient to prepare the powder. During the mixing process, samples are periodically taken from a set position in the cone-shaped mixer to obtain several samples of the Kaixin powder for testing.

[0060] Step S3: Check the content uniformity of the test samples at different set locations. Initially determine whether the content uniformity of the test samples meets the requirements, or conduct a second test to determine whether the content uniformity of the test samples meets the requirements.

[0061] Step S4: Based on the results of the initial and retests, conduct a comprehensive test to determine whether the content uniformity of the test sample meets the requirements.

[0062] Step S5: When the content uniformity does not meet the requirements, plot the standard deviation change curve, predict the trend of standard deviation change, determine whether the mixing time needs to be adjusted, or determine the reason why the uniformity does not meet the standard.

[0063] Step S6: Detect the particle size of the medicinal powder, determine the degree of pulverization of the medicinal powder, and determine the reason why the uniformity does not meet the standard based on the degree of pulverization: the loading coefficient is out of range, or the pulverization and grinding process is not up to standard, and determine the pulverization and grinding parameters.

[0064] Step S7: Sterilize the powder with the specified content uniformity, determine the adjustment status of the process parameter time based on the mixing time and grinding parameters, and determine the sterilization time of the sterilization process.

[0065] The designated locations include the upper part of the mixer, the corner edge, and the discharge port within the square cone mixer.

[0066] In this embodiment, a square cone mixer is used to mix the pulverized and ground medicinal powder;

[0067] A cone mixer loads materials into a sealed cone-shaped mixing hopper, with the axis of symmetry of the hopper forming an angle with the axis of rotation. During operation, the different components of the materials undergo three-dimensional spatial movement within the sealed hopper. This movement generates strong tumbling, diffusion, and contraction effects, thereby ensuring thorough mixing of the materials.

[0068] The cone-shaped mixer has guide vanes below the top cover inside. The guide vanes are approximately cross-shaped, and the feed inlet is located in the center of the guide vanes.

[0069] The square cone mixer is loaded with materials according to the preset loading coefficient, which is set to 80%.

[0070] For the Kaixin San in the mixture, samples were taken from the set positions of the square cone mixer according to the initial detection cycle. Ten samples of Kaixin San were taken. The set positions were the upper part of the mixer, the corner edge and the discharge port, a total of 11 positions.

[0071] Specifically, a cone-shaped mixer is used to mix medicinal powders. The powders not only tumble as the hopper rotates but also move tangentially along the hopper wall. This combination of tumbling and tangential movement allows for sufficient movement and exchange of materials in multiple directions, effectively preventing stratification and segregation. Compared to traditional mixers, the cone-shaped mixer achieves a more ideal mixing effect, ensuring that all components are evenly distributed throughout the mixture. Furthermore, to enhance cross-mixing and mixing speed, guide vanes are installed below the top cover inside the cone-shaped mixer. This method avoids the influence of dead zones on the results by evenly distributing sampling points within the mixing equipment, and sampling at different time points during the mixing process ensures dynamic evaluation of mixing uniformity.

[0072] In this embodiment, the labeled amount of the reference sample of the Kaixin San is M.

[0073] The content uniformity of 10 test samples at different locations was checked. The relative content xi of each single agent in several test samples was measured, and the mean X and standard deviation S, as well as the absolute value A of the difference between the labeled amount and the mean were calculated. The single agent was the medicinal powder of Polygala tenuifolia, 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 value. If the sum of the absolute value A and the standard deviation S (α1 times the standard deviation S) is less than or equal to the specified value L, then the content uniformity of the test sample is determined to meet the requirements.

[0076] If the sum of the absolute value A and the standard deviation S of α0 times is greater than the specified value L, then the content uniformity of the test sample is determined to be non-compliant.

[0077] If the sum of the absolute value A and the standard deviation S (α1 times) is greater than the specified value L, and the sum of the absolute value A and the standard deviation S is less than or equal to the specified value L, then the content uniformity of the test sample needs to be determined a second time, and another 20 test samples should be taken for retesting.

[0078] Based on the results of the initial and retests, a comprehensive test is conducted, and the mean X, standard deviation S, and absolute value A of the difference between the labeled amount and the mean are calculated for 30 single doses. Then, the results are calculated and determined according to the following formula.

[0079] When the absolute value A is less than or equal to 0.25 times the specified value L, the first criterion applies.

[0080] If the sum of the square of the absolute value 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, then the uniformity of the content of the test sample is deemed to meet the requirements.

[0081] If the sum of the square of the absolute value A and the square of the standard deviation S is greater than 0.25 times the square of the specified value L, then the uniformity of the content of the test sample is deemed to be non-compliant.

[0082] When the absolute value A is greater than 0.25 times the specified value L, the second criterion applies.

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

[0084] If the sum of the absolute value A and α² times the standard deviation S is greater than the specified value L, then the uniformity of the content of the test sample is determined to be non-compliant.

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

[0086] Specifically, if the powder is not thoroughly mixed during administration, it may lead to a large amount of sediment in the liquid, affecting patient compliance and treatment efficacy. Therefore, the uniformity, sterilization effect, and hygroscopicity of the powder should be rigorously tested to ensure product quality meets standards and to strengthen quality control. Based on the characteristic that most medicinal materials in Kaixin San have consistent content, this invention tests the uniformity of Kaixin San content in the mixture, more precisely controlling the homogeneity of the drug and improving the accuracy of drug quality control. Furthermore, after the test, it is no longer necessary to check for weight differences. This method directly reflects the distribution of medicinal materials in the preparation through content uniformity testing, while weight differences focus more on changes in total weight and cannot reflect the uniformity of medicinal materials. This simplifies the testing process while ensuring the quality consistency of key components, helping to improve the quality of Kaixin San and reduce sedimentation problems during administration.

[0087] When the uniformity does not meet the standard, the test data of the sample at the corner edge of the square cone mixer is extracted. Based on the standard deviation S of the sample taken according to the initial test cycle, the curve of the standard deviation changing with time is plotted. The derivative function of the standard deviation change curve is derived to predict the change of standard deviation.

[0088] If the derivative 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. It is then determined whether the uniformity can meet the requirements within the predicted time period and whether the mixing time needs to be adjusted.

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

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

[0091] Specifically, during the mixing of medicinal powders using a cone-shaped mixer, the uniformity of the powders increases, and the standard deviation shows a decreasing trend over time, eventually tending towards a fixed value. This method analyzes the trend of standard deviation using the derivative of the variation curve. When uniformity does not meet the standard, it checks whether the standard deviation is still changing, i.e., whether the determined content uniformity is changing. When the standard deviation is continuously decreasing, the mixing time of the cone-shaped mixer is adjusted. Simultaneously, when the standard deviation fluctuation approaches zero, it is determined that the standard deviation has been fixed, i.e., the determined content uniformity has been fixed. For cases where uniformity does not meet the standard, the pulverization and grinding process of the medicinal materials is inspected to ensure compliance. This helps ensure that patients receive the same dose of effective ingredients each time they take the medication, thereby improving the stability and predictability of drug efficacy. It can also promptly detect potential mixing inconsistencies or dosage differences during the production process, thereby reducing quality risks and improving production efficiency.

[0092] To test whether the pulverization and grinding process of medicinal materials meets the standards, a laser particle size analyzer is used to obtain the particle size of the pulverized medicinal materials and classify the particle size.

[0093] If the powder particle size is smaller than the standard particle size, the powder is judged to be in the second degree of pulverization.

[0094] If the powder particle size is greater than or equal to the standard particle size, then the powder of the corresponding medicinal material is judged to be in the first degree of pulverization.

[0095] Calculate the proportion of the medicinal powder in the test sample that is in the second stage of grinding. If the proportion of powder is less than or equal to the critical proportion, it is determined that the content of excessively fine powder is within the normal range. The reason why the uniformity does not meet the standard is that the loading coefficient of the square cone mixer is out of range. Adjust the loading coefficient.

[0096] Specifically, the loading coefficient of the cone mixer is reduced based on the ratio of powder proportion to critical proportion;

[0097] If the powder ratio is greater than the critical ratio, it is determined that the content of excessively fine powder exceeds the normal range and the uniformity does not meet the standard. The reason is that the grinding process is not up to standard, and the grinding process parameters should be adjusted.

[0098] Specifically, the grinding time in the grinding process is reduced based on the ratio of the critical proportion to the powder proportion.

[0099] The critical percentage is 5%, and the standard particle size is a preset value set according to the required particle size of the medicinal powder for Kaixin San.

[0100] Specifically, the ingredients in Kaixin San, such as Polygala tenuifolia, ginseng, Poria cocos, and Acorus tatarinowii, are soft medicinal materials that are easily pulverized into powder, so attention must be paid to the proportion of excessively fine powder. This method determines the degree of pulverization of the medicinal material powder, calculates the proportion of excessively fine powder in the medicinal material powder, and determines whether the reason for non-standard uniformity is due to substandard pulverization and grinding process. Accordingly, the process parameters of pulverization and grinding or the loading coefficient of the square cone mixer are adjusted, which increases the accuracy and adaptability of the preparation method of Kaixin San, improves the efficacy and compliance of Kaixin San, and enhances the dissolution and efficacy consistency of the medicinal materials.

[0101] Traditional Chinese medicinal materials may contain microorganisms, such as bacteria and fungi, during the harvesting and processing. These microorganisms may affect the safety and stability of the medicine, especially during long-term storage, when their reproduction may increase. According to the Chinese Pharmacopoeia and related regulations, traditional Chinese medicine preparations must meet certain microbial limit standards to ensure medication safety.

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

[0103] If the grinding or mixing time is adjusted, the process parameter time is determined to be in the first adjustment state, and the sterilization time of the sterilization process is adjusted.

[0104] Specifically, the sterilization time of the sterilization process is adjusted according to the ratio of the adjusted grinding or mixing time to the original grinding or mixing time.

[0105] If the grinding and mixing time is adjusted, the process parameter time is determined to be in the second adjustment state, and the sterilization time of the sterilization process is adjusted.

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

[0107] Specifically, Chinese medicinal herbs may contain microorganisms during the collection and processing of medicinal materials. These microorganisms can affect the safety and stability of the drugs. In the preparation of Kaixin San, the powdered herbs are in an aerobic environment during the pulverization and grinding processes and the mixing and pulverization processes. Changes in the grinding and mixing time parameters will affect the contact time between the powder and the air, leading to changes in the content of microorganisms. This method determines the adjustment status of the process parameters based on the changes in the time parameters and adopts different methods to adjust the sterilization time of the sterilization process accordingly. This increases the accuracy of sterilization treatment of the prepared Kaixin San. At the same time, since Kaixin San contains heat-sensitive components such as ginseng and poria cocos, as well as volatile components of acorus tatarinowii, it avoids excessive sterilization that could destroy the effective components.

[0108] The technical solution of the present invention has been described above with reference to the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles 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 all fall within the scope of protection of the present invention.

[0109] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A process for the preparation of Kaempferia galanga Linn. characterized in that, The method comprises the following steps: Pretreat the medicinal material of Kai Xin San, and grind the pretreated medicinal material into medicinal powder according to preset grinding parameters, and screen the medicinal powder; Mix the screened medicinal powder according to a preset loading coefficient to prepare a powder, and periodically sample from a set position during the mixing process to obtain several test samples of Kai Xin San; Check the content uniformity of the several test samples at different set positions, and determine whether the content uniformity of the test samples meets the requirements in a preliminary test, or determine in a second test; Determine whether the content uniformity of the test samples meets the requirements according to the results of the preliminary test and the second test; When the content uniformity does not meet the requirements, draw a standard deviation change curve, predict the change trend of the standard deviation, and determine whether the mixing time needs to be adjusted or the reason why the uniformity does not meet the standard; When the uniformity does not meet the standard, extract the detection data of the test sample at the corner edge of the conical mixer, draw a 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 determined that the standard deviation is continuously decreasing, and it is predicted whether the uniformity can meet the requirements within the required time 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 determined that the standard deviation fluctuates towards zero, and the reason why the uniformity does not meet the standard is determined; Obtain the powder particle size of the medicinal powder, compare the powder particle size with the standard particle size, and determine whether the grinding degree of the corresponding medicinal powder is in the first grinding degree or the second grinding degree; Calculate the powder proportion of the medicinal powder in the second grinding degree in the test sample, compare the powder proportion with the critical proportion, and determine whether the content of the fine powder is within the normal range or exceeds the normal range; When the content of the fine powder is within the normal range, it is determined that the reason why the uniformity does not meet the standard is that the loading coefficient of the conical mixer exceeds the range, and the loading coefficient is adjusted; When the content of the fine powder exceeds the normal range, it is determined that the reason why the uniformity does not meet the standard is that the grinding and milling process is not up to standard, and the grinding and milling process parameters are adjusted; Detect the powder particle size of the medicinal powder, determine the grinding degree of the medicinal powder, and determine whether the reason why the uniformity does not meet the standard is that the loading coefficient exceeds the range or that the grinding and milling process is not up to standard according to the grinding degree, and determine the grinding and milling parameters; Sterilize the powder whose content uniformity meets the requirements, determine the sterilization time of the sterilization process according to the adjustment state of the process parameter time, and determine the sterilization time of the sterilization process; The process of determining the adjustment state of the process parameter time comprises: If the grinding and milling time or the mixing time is adjusted, it is determined that the process parameter time is in a first adjustment state; If the grinding and milling time and the mixing time are adjusted, it is determined that the process parameter time is in a second adjustment state; In the first adjustment state, adjust the sterilization time of the sterilization process according to the ratio of the adjusted grinding and milling time or the adjusted mixing time to the unadjusted grinding and milling time or the unadjusted mixing time. In the second adjustment state, the sterilization time length of the sterilization process is adjusted according to the ratio of the sum of the adjusted pulverizing and grinding time length and the mixing time length to the sum of the unadjusted pulverizing and grinding time length and the mixing time length. The set position comprises a mixing machine upper portion, a corner edge and a discharge port in the square-cone-shaped mixing machine.

2. The process for the preparation of Kaphvacika according to claim 1, wherein, The process of determining the content uniformity of the test sample in the preliminary test comprises, The relative content of each single dose in several test samples is determined for the test sample in different set positions, and the mean value, standard deviation and absolute value are calculated, and the absolute value and standard deviation are compared with the specified value; The content uniformity of the test sample is determined to be not in conformity with the regulation, in conformity with the regulation or in need of secondary determination according to the product of the preliminary test determination coefficient and the standard deviation and the sum of the absolute values. The single dose is the medicinal material powder of Polygala, Panax, Poria cocos and Acorus.

3. The preparation method of the Kai Xin Powder according to claim 2, characterized in that, The preliminary test and the retest results are summarized, the mean value, standard deviation and absolute value of several test samples in the preliminary test and the retest are calculated, the absolute value is compared with the specified value, and the first determination condition and the second determination condition are adopted according to the comparison result.

4. The preparation method of the Kai Xin Powder 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, and determine whether the content uniformity of the test sample conforms to the regulation; The second determination condition is to compare the product of the summary determination coefficient and the standard deviation and the sum of the absolute value with the specified value, and determine whether the content uniformity of the test sample conforms to the regulation.

5. An open heart powder prepared according to the method of any one of claims 1 to 4, characterized in that, The Kai Xin Powder is a powder in oral solid preparations; The powder comprises 13.80g of Polygala, 13.80g of Panax, 27.60g of Poria cocos and 13.80g of Acorus; The mass fraction ratio of Polygala, Panax, Poria cocos and Acorus in the powder is 1:1:2:1.

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