Kaixin powder preparation and preparation method thereof

Abstract

The invention discloses a Kaixin powder preparation and a preparation method thereof, and belongs to the field of traditional Chinese medicine preparations. The preparation method comprises the following steps: firstly, respectively cleaning, infiltrating, softening and cutting four medicinal materials, namely ginseng, polygala tenuifolia, poria cocos and rhizoma acori graminei in the Kaixin powder, and then performing high-pressure steam sterilization; drying the sterilized ginseng, polygala tenuifolia and poria cocos under a first drying condition, and drying rhizoma acori graminei under a second drying condition; and finally, respectively performing low-temperature crushing on the dried ginseng, polygala tenuifolia, poria cocos and rhizoma acori graminei according to a specific mass ratio, blending, sieving and packaging to obtain the Kaixin powder preparation. According to the preparation process, the pretreated medicinal materials are sterilized preferentially, only one drying time is carried out in the preparation process, and low-temperature crushing is adopted, so that the loss rate of effective components of the Kaixin powder is effectively reduced, and the pharmacodynamic effect of the obtained Kaixin powder preparation is ensured. The Kaixin powder prepared in the invention meets the microbial limit requirements of powder, and has small toxic and side effects and good safety in non-clinical safety evaluation.

Description

Technical Field

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

[0002] Kaixinsan is one of the first 100 prescriptions selected in the "Catalogue of Ancient Classic Prescriptions (First Batch)" formulated by the State Administration of Traditional Chinese Medicine and the State Food and Drug Administration in 2018. It was first recorded in the "Prescriptions for Emergencies Worth a Thousand Gold Pieces" written by Sun Simiao, a medical scientist in the Tang Dynasty. Kaixinsan is composed of four Chinese medicines: ginseng, polygala, calamus, and poria. The prescription is simple but powerful. Its composition is analyzed according to the basic theory of traditional Chinese medicine. Ginseng in the prescription greatly replenishes vitality, calms the mind and improves intelligence; poria strengthens the spleen and calms the heart, promotes diuresis and eliminates dampness; calamus resolves phlegm, opens the mind, and awakens the spirit; polygala calms the mind and calms the nerves, removes phlegm and opens the mind. It can be combined with calamus to enhance the effect of resolving phlegm and opening the mind, and can be combined with poria to enhance the function of connecting the heart and kidney.

[0003] The preparation method of Kaixin Powder recorded in the Prescriptions for Emergencies is "four ingredients on the right, sieve below", which is similar to the modern powder preparation process of "crushing → sieving → mixing", but does not involve the sterilization method and treatment sequence, and cannot guarantee that the product meets the microbial limit requirements for powders. Although the preparation process of Kaixin Powder has been reported in the prior art, the prescription dosage and preparation method are inconsistent with the key information published by the state, and there is a big gap with the requirements issued by the National Drug Evaluation Center. At present, there is a lack of overall research on the preparation process of the classic prescription "Kaixin Powder".

[0004] At present, Chinese medicine powders are generally sterilized after the Chinese medicine pieces (or coarse particles) are crushed into fine powder and dried twice. However, due to the presence of heat-sensitive components in Kaixin powder (such as Polygala tenuifolia), Ketone III, 3,6'-biserucyl sucrose) and Acorus tatarinowii contain volatile oil components, which are sensitive to the heat treatment process. Improper treatment will have a significant impact on the quality of the fine powder. At the same time, the development of classic prescriptions requires starting from authentic medicinal materials. The medicinal materials need to be dried after purification to facilitate the subsequent crushing process and meet the quality requirement that the moisture content of the powder should not exceed 9.0%. Since the heat-sensitive components in Kaixin Powder are easily lost during sterilization, drying and crushing, the timing and conditions of sterilization, drying and crushing in the Kaixin Powder preparation process are particularly important. Improper selection will seriously reduce the content of effective ingredients in the final powder, thereby affecting the efficacy of Kaixin Powder. Therefore, it is urgent to explore and optimize the process flow and parameter conditions of Kaixin Powder preparation to avoid the loss of heat-sensitive components and adverse effects on the quality of Kaixin Powder preparations, so as to ensure the efficacy of the prepared Kaixin Powder. Summary of the invention

[0005] In view of the fact that there are heat-sensitive ingredients in the classic prescription "Kaixin Powder", it is necessary to optimize the sterilization, drying heat treatment and pulverization process. The contents and microbial limits of seven chemical components, including ketone III, 3,6'-bisinacoylsucrose, polygala tenuifolia saponin, ginsenoside Rb1, pachymic acid, β-asarone and α-asarone, were used as evaluation indicators to optimize the overall preparation process and process parameters of Kaixin Powder, providing a scientific basis for the safe and effective preparation and industrial development of Kaixin Powder. The specific technical solution is as follows:

[0006] In one aspect, the present invention provides a method for preparing a Kaixin powder preparation, comprising the following steps:

[0007] The pretreated ginseng, polygala, poria and calamus are sterilized by high pressure steam at 95-100°C;

[0008] Drying the sterilized ginseng, polygala and poria under the first drying condition, and drying the calamus tatarinowii under the second drying condition;

[0009] The dried ginseng, polygala, poria and calamus are respectively ground at low temperature according to a specific mass ratio;

[0010] The pulverized ginseng fine powder, polygala fine powder, tuckahoe fine powder and calamus fine powder are sequentially blended, sieved and packaged to obtain the Kaixin powder preparation.

[0011] Furthermore, the pretreatment includes: washing, soaking, softening and cutting the four medicinal materials of ginseng, polygala, poria and calamus in Kaixin powder in sequence.

[0012] Furthermore, the conditions for high pressure steam sterilization are 95° C. sterilization for 10 min.

[0013] Furthermore, the conditions for high pressure steam sterilization are 100° C. for 5 min.

[0014] Furthermore, the mass ratio of ginseng, polygala, poria and calamus is 1:1:2:1.

[0015] Furthermore, during the drying process, the first drying condition is drying at 60-80° C. for 4-6 hours.

[0016] Furthermore, during the drying process, the second drying condition is drying at 50-55° C. for 8-10 hours.

[0017] Furthermore, the temperature for low-temperature pulverization is -5-0°C, preferably -5°C.

[0018] On the other hand, the present invention provides a Kaixin powder preparation prepared by the preparation method, wherein the efficacy index components and content ranges in the Kaixin powder preparation include:

[0019] Polygala Ketone III 0.37-0.68 mg / g, 3,6'-dicorinoylsucrose 1.05-1.95 mg / g, Polygala tenuifolia saponin 3.53-6.56 mg / g, ginsenoside Rb1 0.44-0.81 mg / g, pachymic acid 0.08-0.15 mg / g, β-asarone 1.89-3.51 mg / g and α-asarone 0.22-0.40 mg / g.

[0020] Beneficial effects of the present invention:

[0021] The Kaixin powder preparation process proposed in the present invention simplifies the preparation process of Kaixin powder. In the entire preparation process, each medicinal material only needs to be dried once, which consumes low energy. In addition, considering that the medicinal flavors such as Acorus calamus in the Kaixin powder are sensitive to heat, if the powder is sterilized, the fine particle size and large specific surface area of ​​the sample after crushing will have a greater impact on the quality of the fine powder after heating. The present invention directly sterilizes the pretreated medicinal material slices or coarse particles, which can reduce the loss of heat-sensitive and volatile components in Kaixin powder during the sterilization process. At the same time, the high-pressure steam sterilization method adopted by the present invention has better sterilization effect and better animal safety than other sterilization methods. Moreover, the present invention chooses to crush at a low temperature of -5-0°C, which can effectively avoid the hot powder and component loss during the crushing process.

[0022] The optimized sterilization conditions, drying conditions and pulverization conditions in the present invention can effectively reduce the loss rate of effective ingredients, and effectively ensure the pharmacological effect of Kaixinsan preparations. Kaixinsan prepared according to the preparation method and process parameters of the present invention has less loss of index ingredients, less toxic and side effects, and good safety. The present invention respects the past but does not stick to the past, and provides scientific preparation process and technical parameter support for the research and development and industrialization of safe, effective and high-quality Kaixinsan preparations.

[0023] Other features and advantages of the present invention will be described in the following description, and partly become apparent from the description, or understood by practicing the present invention. The purpose and other advantages of the present invention can be realized and obtained by the structures pointed out in the description, claims and drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0025] Figure 1 A flow chart showing the preparation method of Kaixin powder preparation proposed in Example 1 of the present invention is shown;

[0026] Figure 2 A comparison chart of the appearance uniformity of Kaixin powder prepared by two processes in Test Example 1 of the present invention is shown;

[0027] Figure 3 The polygala root prepared in Example 1 and Comparative Example 1 is shown. Chromatogram of determination of ketone III and 3,6'-dicerinoylsucrose content;

[0028] Figure 4 The chromatograms of the determination of saponin content of Polygala tenuifolia in Kaixin powder prepared in Example 1 and Comparative Example 1 are shown;

[0029] Figure 5 The chromatograms of the determination of the content of ginsenoside Rb1 in Kaixin powder prepared in Example 1 and Comparative Example 1 are shown;

[0030] Figure 6 The chromatograms of the determination of the content of pachymic acid in Kaixin powder prepared in Example 1 and Comparative Example 1 are shown;

[0031] Figure 7 The chromatograms of the determination of β-asarone and α-asarone contents in Kaixin Powder prepared in Example 1 and Comparative Example 1 are shown;

[0032] Figure 8 The results show that the polygala in the polygala slices under different sterilization conditions in Example 2 Chromatogram of determination of ketone III and 3,6'-dicerinoylsucrose content;

[0033] Fig. 9 The chromatograms of determination of saponin content of Polygala tenuifolia in Polygala tenuifolia slices under different sterilization conditions in Example 2 are shown;

[0034] Fig.10 The chromatograms of the content determination of ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in ginseng slices under different sterilization conditions in Example 2 are shown;

[0035] Fig.11 The chromatograms of the determination of pachymic acid content in the Poria cocos slices under different sterilization conditions in Example 2 are shown;

[0036] Fig.12 The chromatograms of the determination of β-asarone and α-asarone contents in the Acorus calamus slices under different sterilization conditions in Example 2 are shown. DETAILED DESCRIPTION

[0037] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] Example 1

[0039] This embodiment provides a method for preparing a Kaixin powder preparation, such as Figure 1 As shown, the following steps are included:

[0040] The four medicinal materials of ginseng, polygala, poria and calamus in Kaixinsan are washed, soaked, softened and cut in sequence to obtain ginseng decoction pieces, polygala decoction pieces, poria decoction pieces and calamus decoction pieces;

[0041] Sterilize the ginseng slices, polygala slices, tuckahoe slices and calamus slices with high pressure steam at 100° C. for 5 min;

[0042] The dried ginseng slices, polygala slices, and poria slices were transferred to an oven in a clean area and dried at 70°C for 4 hours, and the calamus slices were transferred to an oven in a clean area and dried at 50°C for 8 hours; it should be noted that the moisture content in the slices was controlled to be lower than 9.0 during the drying process, and the fluctuation range of the index component content in the four slices was ±10%;

[0043] The dried pieces of Polygala tenuifolia, Ginseng, Poria cocos and Acorus calamus were placed in a low-temperature grinder at a mass ratio of 1:1:2:1 and ground into fine powder at -5°C.

[0044] The crushed Polygala powder, ginseng powder, Poria powder and Acorus calamus powder are blended, sieved and packaged to obtain the Kaixin powder preparation.

[0045] The present invention does not specifically limit the shape of the medicinal materials after cutting. For example, in other embodiments of the present invention, the four medicinal materials of ginseng, polygala, poria and calamus can be cut into larger particles in the pretreatment step to obtain ginseng coarse granules, polygala coarse granules, poria cocos coarse granules and calamus coarse granules; and subsequently the ginseng coarse granules, polygala coarse granules, poria cocos coarse granules and calamus coarse granules are sterilized, crushed and mixed.

[0046] Example 2

[0047] Ginseng slices, Polygala slices, Poria slices and Acorus calamus slices were prepared in the same manner as in Example 1. The difference was that the drying conditions of the ginseng slices, Polygala slices and Poria slices were replaced with drying at 60°C for 4 hours, drying at 60°C for 6 hours, drying at 80°C for 4 hours, drying at 80°C for 6 hours and drying at 90°C for 4 hours; the drying conditions of the Acorus calamus slices were replaced with drying at 50°C for 10 hours, drying at 55°C for 8 hours, drying at 55°C for 10 hours and drying at 60°C for 8 hours; and ginseng slices, Polygala slices, Poria slices and Acorus calamus slices were obtained.

[0048] Example 3

[0049] Kaixin powder was prepared according to the same method as Example 1, except that the sterilization conditions were 95°C for 5 minutes, 95°C for 10 minutes, 95°C for 15 minutes, 100°C for 10 minutes, 100°C for 15 minutes, 105°C for 5 minutes, 105°C for 10 minutes, and 105°C for 15 minutes.

[0050] Example 4

[0051] Kaixin powder was prepared in the same manner as in Example 1, except that the pulverization was performed at 0°C to obtain fine powder.

[0052] Comparative Example 1

[0053] Kaixin Powder was prepared in the same manner as in Example 1, except that the sliced ​​ginseng slices, polygala slices, poria slices and calamus slices were placed in an oven for drying, and the dried samples were sterilized and then dried again after sterilization. The method was dried twice.

[0054] Comparative Example 2

[0055] Kaixin powder was prepared in the same manner as in Example 1, except that the sterilization method was irradiation sterilization (6-8 kGy).

[0056] Comparative Example 3

[0057] Kaixin powder was prepared in the same manner as in Example 1, except that the sterilization method was high temperature instantaneous sterilization (160° C. sterilization for 7 seconds).

[0058] Comparative Example 4

[0059] Kaixin powder was prepared in the same manner as in Example 1, except that the pulverization condition was pulverizing into fine powder at 5°C.

[0060] Test Example 1

[0061] The appearance uniformity of the Kaixin powder prepared in Example 1 and Comparative Example 1 was measured. The specific measurement method is as follows:

[0062] Take an appropriate amount of the test sample and place it on a smooth paper, spreading it about 5cm 2 , flatten its surface and observe it in a bright place.

[0063] The test results are as follows Figure 2 As shown, the left side is the Kaixin powder prepared in Comparative Example 1, and the right side is the Kaixin powder prepared in Example 1. By comparison, it can be seen that the Kaixin powder prepared in Example 1 has a more uniform color and no patterns or spots.

[0064] Test Example 2

[0065] The moisture content of Kaixin powder prepared in the examples and comparative examples was determined by the toluene method in the moisture determination method (General Rule 0832) in the 2020 edition of the Chinese Pharmacopoeia. The amount of Kaixin powder was 15 g. The results are shown in Table 1:

[0066] Table 1 Moisture content in Kaixin powder preparation

[0067] Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Moisture (%) 5.0 6.4 6.7 7.1 5.2 7.3

[0068] Test Example 3

[0069] Take 10g of Kaixin powder prepared in the embodiment and the comparative example respectively, weigh accurately, and measure the particle size and particle size distribution according to the particle size and particle size distribution determination method (general rule Chinese Pharmacopoeia 0982 single sieving method). The measurement results are shown in Table 2:

[0070] Table 2 Particle size of Kaixin powder preparation

[0071] Example 1 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 5 granularity(%) 97.6 97.5 96.0 96.7 95.8 95.6

[0072] It can be seen that the particle size distribution of the Kaixin powder preparation prepared by the preparation method of the present invention is uniform, which is more in line with the requirement of not less than 95% stipulated in the "Chinese Pharmacopoeia".

[0073] Test Example 4

[0074] The content of the index components in the Kaixin powder prepared in Example 1 and Comparative Example 1 was measured, and the determination method of each index component was as follows:

[0075] (1) Polygala tenuifolia The contents of ketone III and 3,6'-dicerinoylsucrose were determined by high performance liquid chromatography in accordance with General Chapter 0512 of the 2020 edition of the Chinese Pharmacopoeia; the difference was that the weight of the Kaixin powder in the preparation of the test solution was 5 g.

[0076] (2) The saponin content of Polygala tenuifolia was determined according to the high performance liquid chromatography method in accordance with General Chapter 0512 of the 2020 edition of the Chinese Pharmacopoeia, except that methanol was used as mobile phase A (58%) and 0.05% phosphoric acid aqueous solution was used as mobile phase B (42%) for isocratic elution for 35 min.

[0077] (3) The content of ginsenoside Rb1 was determined according to the high performance liquid chromatography method in accordance with General Chapter 0512 of the 2020 edition of the Chinese Pharmacopoeia, except for the preparation process of the test solution and the mobile phase elution gradient.

[0078] The preparation process of the test solution is as follows: weigh about 5g of Kaixinsan powder, accurately add 50mL of saturated n-butanol with water, seal it, leave it for 30 minutes, ultrasonically treat it (power 250W, frequency 50kHz) for 30 minutes, filter it, discard the initial filtrate, accurately measure 25mL of the subsequent filtrate, evaporate it in an evaporating dish, dissolve the residue in methanol and transfer it to a 5mL volumetric flask, add methanol to dilute it to the scale, shake it well, filter it, take the subsequent filtrate to obtain the test solution.

[0079] The mobile phase elution gradient is shown in Table 3:

[0080] Table 3 Mobile phase elution gradient

[0081]

[0082]

[0083] (4) The method for determining the content of pachymic acid is as follows:

[0084] Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel was used as the chromatographic column filler; methanol was used as the mobile phase A (84%) and 0.05% phosphoric acid aqueous solution was used as the mobile phase B (16%) for isocratic elution for 55 min; the column temperature was 35°C; the flow rate was 1.0 mL per minute, and the detection wavelength of Pachycolic acid was 203 nm.

[0085] Preparation of reference solution: Take the Pachymaranth acid reference substance, weigh it accurately, add methanol to make a solution containing 0.05 mg per 1 mL to obtain the reference solution.

[0086] Preparation of the test solution: weigh about 5 g of Kaixin powder, accurately add 25 mL of methanol, weigh the weight, ultrasonicate (250 W, 50 kHz) for 45 minutes, take out, weigh to make up the weight after cooling, filter with a microporous filter membrane (0.22 μm), and take the filtrate to obtain the test solution.

[0087] Determination: Accurately pipette 10 μL of the reference solution and the test solution respectively and inject into the liquid chromatograph for content determination.

[0088] (5) The method for determining the content of β-asarone and α-asarone is as follows:

[0089] Chromatographic conditions and system suitability test: 5% phenyl-methylpolysiloxane was used as filler; carrier gas was nitrogen with a split ratio of 10:1; injection volume was 1 μL; hydrogen gas flow rate was 35 mL / min; gas flow rate was 1.0 mL / min; injection port temperature was 250°C; detector temperature was 300°C; column oven program temperature conditions are shown in Table 4:

[0090] Table 4 Column oven temperature program conditions

[0091] Rate (℃ / min) Value(℃) Holding time (minutes) Run time (minutes) 50 0 0 11 160 0 10 6 205 3 20.5

[0092] Preparation of mixed reference solution: accurately weigh β-asarone reference substance and α-asarone reference substance, respectively add methanol to prepare 1.0 mg / mL mother solution, take appropriate amount of β-asarone and α-asarone mother solution and add methanol to prepare a mixed reference solution containing 0.400 mg of β-asarone and 0.0344 mg of α-asarone per 1 mL, to obtain a mixed reference solution.

[0093] Preparation of test solution: After extracting the volatile oil from Kaixin Powder by steam distillation, measure 0.01 mL of the volatile oil from Kaixin Powder, place it in a 10 mL volumetric flask, add an appropriate amount of methanol, ultrasonicate for 1 minute, take it out, add methanol to dilute to the scale, shake well, filter with a microporous filter membrane (0.22 μm), and take the filtrate to obtain the test solution.

[0094] Determination: Accurately pipette 1.0 μL of the reference solution and the test solution respectively and inject them into the gas chromatograph for content determination.

[0095] The contents and content change rates of the index components in the Kaixin powder prepared in Example 1 and Comparative Example 1 were determined according to the determination methods in (1)-(5) (based on the preparation process in Example 1).

[0096] Test results such as Figure 3-7 As shown, wherein S1 is the chromatogram of Kaixin powder prepared in Example 1, and S2 is the chromatogram of Kaixin powder prepared in Comparative Example 1, Figure 3 In the middle, 1 is Polygala tenuifolia The peak of ketone III, 2 is the peak of 3,6'-diesinapoylsucrose, Figure 4 In the middle, 1 is the peak of Polygala tenuifolia saponin; Figure 5 Middle 1 is the peak of ginsenoside Rb1; Figure 6 Middle 1 is the peak of pachymic acid; Figure 7 In the figure, 1 is the peak of β-asarone, and 2 is the peak of α-asarone. The specific data are shown in Table 5-6:

[0097] Table 5 Contents of index components of Kaixin powder in two preparation processes

[0098]

[0099]

[0100] Table 6 Change rate of the index component content of Kaixin powder in two preparation processes (%)

[0101]

[0102] It can be seen that the contents of various index components in the Kaixin powder prepared by the preparation method in the embodiment of the present invention vary slightly.

[0103] Test Example 5

[0104] The content and content change rate of the index components in the four kinds of decoction pieces before and after sterilization under different sterilization conditions in Example 2 were determined. The specific determination method is as follows:

[0105] (a) Polygala tenuifolia saponins and Polygala tenuifolia in Polygala tenuifolia slices The contents of ketone III and 3,6'-dicerinoylsucrose components were determined according to the high performance liquid chromatography method (General Rule 0512).

[0106] (b) Ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in ginseng slices were determined by high performance liquid chromatography (General Rule 0512).

[0107] (c) The content of the index components in the Poria cocos slices was determined according to the method of (4) in Test Example 4, except that acetonitrile was used as mobile phase A, 0.05% phosphoric acid solution was used as mobile phase B, and the elution time was 20 min.

[0108] (d) The content of the index components in the Acorus calamus slices was determined according to the method (5) in Test Example 4, except for the column oven temperature program conditions and the preparation of the mixed reference solution. The temperature conditions are shown in Table 7:

[0109] Table 7 Column oven program heating conditions in the determination method of Acorus tatarinowii

[0110] Rate (℃ / min) Value(℃) Holding time (minutes) Run time (minutes) 60 0 0 10 160 0 10 5 205 0 19

[0111] Preparation of mixed reference solution: Prepare a mixed reference solution containing 0.500 mg of β-asarone and 0.043 mg of α-asarone per 1 mL using the same method as that of test example 4 (5).

[0112] According to the determination methods in (a)-(d), the results of the index component content in ginseng slices, polygala slices, tuckahoe slices and calamus slices under different drying conditions are shown in Tables 8-11:

[0113] Table 8 Test results of index component content of three kinds of decoction pieces of ginseng, Polygala and Poria after drying

[0114]

[0115] Table 9 Change rate of index component content of three kinds of decoction pieces of ginseng, Polygala and Poria after drying (%)

[0116]

[0117]

[0118] Table 10 Test results of index component content of Acorus calamus slices after drying

[0119]

[0120] Table 11 Change rate of index component content of Acorus calamus slices after drying (%)

[0121]

[0122] It can be seen from the results in Tables 8-11 that when the ginseng slices, polygala slices and poria slices were dried at 60-80℃ for 4-6h, the change rate of the index component content did not exceed ±8%, while when the drying temperature was 90℃, the index component content decreased significantly. Therefore, the drying conditions for ginseng slices, polygala slices and poria slices were selected as 60-80℃ drying for 4-6h; and when the calamus slices were dried at 50-55℃ for -10h, the change rate of the index component content did not exceed ±7%. Therefore, the drying conditions for the calamus slices were selected as 50-55℃ drying for 8-10h.

[0123] Test Example 6

[0124] According to the determination method in (a)-(d) of Test Example 5, the content spectra of the index components in the ginseng slices, polygala slices, tuckahoe slices and calamus slices under different sterilization conditions in Example 3 and Example 1 are as follows: Figure 8-12 As shown. Among them, S1-S9 represent the 9 sterilization conditions from top to bottom in 18-19 ( Figure 8-10 Except for 5 minutes at 95℃, which starts from 10 minutes at 95℃), Figure 8 In the middle, 1 is Polygala tenuifolia The peak of ketone III, 2 is the peak of 3,6'-diesinapoylsucrose, Fig. 9 In the middle, 1 is the peak of Polygala tenuifolia saponin; Fig.10 In the middle, 1 is the peak of ginsenoside Rg1, 2 is the peak of ginsenoside Re; 3 is the peak of ginsenoside Rb1; Fig.11 Middle 1 is the peak of pachymic acid; Fig.12 In the figure, 1 is the peak of β-asarone, and 2 is the peak of α-asarone. The results are shown in Tables 12 and 13:

[0125] Table 12 Test results of index component content of four kinds of decoction pieces of ginseng, polygala, poria and calamus before and after sterilization

[0126]

[0127] Table 13 Change rate of index component content of four kinds of decoction pieces of ginseng, polygala, poria and calamus after sterilization (%)

[0128]

[0129]

[0130] In Tables 12-13, "-" means that the sample failed the microbial content test under this condition. Except for the case of high-pressure steam sterilization at 95℃ for 5 minutes, the sample failed the microbial content test. Under the other sterilization conditions, the microbial content test was qualified, but the content of the index components under some sterilization conditions changed greatly. When the sterilization conditions were 95℃ for 10 minutes and 100℃ for 5 minutes, the change rate of the index component content did not exceed ±10%. Combined with the stability of the parameters of the high-pressure steam equipment, the preferred sterilization condition of 100℃ for 5 minutes is better.

[0131] Test Example 7

[0132] According to the microbial count method (General Rule 1105) and control bacteria inspection method (General Rule 1106) in the 2020 edition of the Chinese Pharmacopoeia and the microbial limit standard for non-sterile drugs (General Rule 1107), the microbial limits of Kaixin powder prepared in the embodiments and comparative examples were measured, and the results are shown in Table 14:

[0133] Table 14 Results of microbiological examination of Kaixin powder in different preparation processes

[0134]

[0135] It can be seen from the above table that no aerobic bacteria, molds and yeasts, Escherichia coli and Salmonella were detected in the Kaixin powder prepared after sterilization according to the high-temperature steam sterilization method proposed in the present invention, and the number of bile-resistant Gram-negative bacteria was less than 10; while the Kaixin powder prepared after sterilization according to the sterilization method in Comparative Examples 1-3 still contained aerobic bacteria, molds and yeasts. Relatively speaking, the preparation method in the present invention can achieve better sterilization effect.

[0136] Test Example 8

[0137] The GLP (Good Laboratory Practice for Non-clinical Drug Research) safety of the Kaixin powder prepared in the examples and comparative examples was tested, and the test process was as follows:

[0138] Animal grouping and dosing: 40 quarantine-qualified animals were taken, half of which were male and half were female. The weight difference of each sex should be within 20% of the average weight. Females were ranked from small to large, and males were ranked from large to small. They were divided into 5 groups according to the Latin method, namely the vehicle control group and four dosage groups of Kaixinsan test product 1 (0.75g crude drug / kg / d), Kaixinsan test product 2 (1.5g crude drug / kg / d), Kaixinsan test product 3 (3.75g crude drug / kg / d), and Kaixinsan test product 4 (5g crude drug / kg / d), 4 animals / group / sex. Kaixinsan test product was the Kaixinsan preparation prepared in Example 1. Kaixinsan test product 4 group was administered orally twice a day with a volume of 10mL / kg, and the remaining groups were administered orally once a day with a volume of 15mL / kg, and the administration was continued for 4 weeks.

[0139] Observation index: Clinical observation and body weight were performed during the experiment. At the end of the administration, the animals were euthanized and the gross anatomy was performed. The results are shown in Table 15:

[0140] Table 15 GLP adverse reactions of Kaixinsan in three sterilization methods

[0141]

[0142] As can be seen from the above table, under the preparation process conditions proposed by the present invention, Kaixinsan high-pressure steam sterilization test sample 5g crude drug / kg / d and below does not cause abdominal distension or even death in animals, and has better safety. However, Kaixinsan irradiation sterilization test sample (Comparative Example 2) 1.5g crude drug / kg / d and above can cause abdominal distension or even death in some rats. Kaixinsan high-temperature instantaneous sterilization test sample (Comparative Example 3) 5g crude drug / kg / d can cause abdominal distension or even death in some rats. By comparing the mortality rate, abdominal distension rate, etc., it can be seen that the Kaixinsan obtained by the preparation process of the present invention has fewer toxic and side effects and better safety.

[0143] Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent substitutions for some of the technical features therein; and these modifications or substitutions do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a Kaixin powder preparation, characterized in that: The following steps are involved: The pretreated ginseng, polygala, poria and calamus are sterilized by high pressure steam at 95-100°C; Drying the sterilized ginseng, polygala and poria under the first drying condition, and drying the calamus tatarinowii under the second drying condition; The dried ginseng, polygala, poria and calamus are respectively ground at low temperature according to a specific mass ratio; The pulverized ginseng fine powder, polygala fine powder, tuckahoe fine powder and calamus fine powder are sequentially blended, sieved and packaged to obtain the Kaixin powder preparation.

2. The method for preparing a Kaixinsan preparation according to claim 1, characterized in that: The pretreatment comprises: washing, soaking, softening and cutting the four medicinal materials of ginseng, polygala, tuckahoe and calamus in Kaixin powder in sequence.

3. The method for preparing the Kaixinsan preparation according to claim 1, characterized in that: The conditions for high-pressure steam sterilization are 95°C for 10 min.

4. The method for preparing the Kaixinsan preparation according to claim 1, characterized in that: The conditions for high-pressure steam sterilization are 100°C for 5 minutes.

5. The method for preparing the Kaixinsan preparation according to claim 1, characterized in that: The mass ratio of ginseng, polygala, poria and calamus is 1:1:2:

1.

6. The method for preparing the Kaixinsan preparation according to claim 1, characterized in that: During the drying process, the first drying condition is drying at 60-80° C. for 4-6 hours.

7. The method for preparing the Kaixinsan preparation according to claim 1, characterized in that: During the drying process, the second drying condition is 50-55° C. for 8-10 hours.

8. The method for preparing the Kaixinsan preparation according to claim 1, characterized in that: The temperature for low temperature pulverization is -5-0°C.

9. The method for preparing the Kaixinsan preparation according to claim 1, characterized in that: The temperature for low temperature pulverization was -5°C.

10. A Kaixin powder preparation, characterized in that: The invention is prepared by the preparation method according to any one of claims 1 to 9.

Images