A preparation process of peony and liquorice granules

Abstract

The present invention discloses a preparation process of peony and licorice granules, and belongs to the technical field of preparation of traditional Chinese medicine granules. The preparation process comprises the following steps: preparing white peony slices and stir-fried licorice slices, preparing a mixed paste of white peony and stir-fried licorice, preparing a dry paste powder, and preparing peony and licorice granules. The present invention optimizes the preparation, drying and granulation processes to minimize the loss of effective ingredients, and the prepared peony and licorice granules have good consistency in quality with the reference sample of peony and licorice soup. The amount of auxiliary materials added is accurately calculated to ensure the yield of the particles while reducing the amount of auxiliary materials added, thereby restoring the quality of the classic decoctions in ancient books to the maximum extent, ensuring that the daily granules taken by patients are highly consistent with the equivalent amount of medicinal materials or pieces, and the daily dosage is reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of traditional Chinese medicine granules, and particularly relates to a preparation process of peony and liquorice granules. Background Art

[0002] In order to better adapt to the pace of life of modern people and provide better services to people who are sensitive to the taste of traditional Chinese medicine, Chinese medicine formula granules have gradually entered clinical treatment, especially a new dosage form made by extracting and concentrating traditional Chinese medicinal materials through modern technology. It not only retains the efficacy of traditional Chinese medicine, but also overcomes some inconveniences of traditional decoctions, such as time-consuming decoction and difficult to control dosage.

[0003] Peony and Licorice Decoction is a traditional Chinese medicine prescription made by decocting two Chinese medicinal materials, peony and licorice. It tastes slightly bitter and has a wide range of clinical uses. Preparing Peony and Licorice Granules can make it more convenient to take.

[0004] Patent CN115957256A discloses a method for preparing Shaoyao Gancao Tang granules, which comprises boiling peony and licorice with water, combining the filtrate, and concentrating under reduced pressure to prepare Shaoyao Gancao Tang extract, adding excipients and performing fluidized granulation by a fluidized bed granulator to obtain granules. Such fluidized bed granulation method requires a large amount of excipients, which will reduce the efficacy of the drug under the same dosage. The ingredients of Chinese medicine compound preparations are complex, and the effective substances should be retained as much as possible to ensure the efficacy and reduce the dosage. Referring to the technical guidance principle of "Technical Requirements for Quality Control and Standardization of Chinese Medicine Formula Granules", the ratio of excipients / auxiliary materials to intermediates (extracts or dry paste powders, calculated as dry products) is generally not more than 1:1. On the basis of ensuring the formation of particles, the use of excipients and excipients is reduced, the purity of the drug is improved, the efficacy can be improved, and the dosage of the patient can be reduced. Summary of the invention

[0005] The purpose of the present invention is to provide a preparation process of peony and licorice granules, select the best processing process, adopt low-temperature concentration, vacuum belt drying or spray drying, dry granulation and other technologies, minimize the amount of auxiliary materials, restore the quality of classic prescriptions to the maximum extent, improve the purity of the medicine, reduce the dosage of the medicine, and better serve patients.

[0006] The purpose of the present invention can be achieved through the following technical solutions:

[0007] The present invention provides a preparation process of peony root and liquorice granules, comprising the following steps:

[0008] Step 1. Prepare white peony root slices and stir-fried licorice root slices: remove impurities from white peony root, wash it, soak it until the skin is slightly soft, and soak it until it can be slightly bent by the bending method inspection, and there is no dry core on the cross section. Slice and dry it to obtain white peony root slices; remove impurities from licorice root, wash it, soak it, slice it, and stir-fry it in a medicine stir-frying machine until it is slightly yellowish to obtain stir-fried licorice root slices.

[0009] Step 2, prepare a mixed clear paste of white peony root and fried licorice: add white peony root slices and fried licorice slices into an extraction tank in a mass ratio of 1:1, add 2-3 times the amount of water to moisten the medicinal materials for 30 minutes, then add 2-3 times the amount of water, pass saturated water vapor into the jacket of the extraction tank to heat the jacket, heat the medicinal solution in the tank to 70-90°C, circulate until boiling, generate steam in the extraction tank and pass through a condenser, reflux into the extraction tank after condensation, boil, circulate for 10-30 minutes, keep boiling for 10-30 minutes, and circulate for another 10-30 minutes to obtain an extract, pump the extract into a single-effect concentrator for concentration, obtain a concentrated solution after concentration, and filter the concentrated solution through an oscillating sieve to obtain a clear paste, the solid content of the clear paste is 30-50%.

[0010] The concentration to form a clear paste requires strict control of the concentration degree, which not only affects the quality of the finished product, but also has an important impact on the subsequent preparation process of dry paste powder. Since the preparation process provided by the present invention is to dry the clear paste to form a dry paste powder and then dry granulate it, the water content of the clear paste should not be too low. When the water content is too low, the paste is viscous, which can neither achieve uniform distribution on the crawler during vacuum belt drying, nor meet the requirement of thin liquid during spray drying. At this time, the solid content of the clear paste is 30-50%, which can meet the requirements of the drying process and ensure that the water content of the dry paste powder is low.

[0011] Step 3, preparing dry paste powder: the clear paste is placed in a material tank and kept warm at 25-45°C, and dried by vacuum belt drying or spray drying to obtain dry paste powder.

[0012] Step 4, preparation of peony and licorice granules: adding auxiliary materials to the dry paste powder, and directly sucking the mixed powder into the dry granulator after mixing. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by a pressing wheel, and then crushed, granulated and sieved by a crusher to make peony and licorice granules.

[0013] Furthermore, the medicine frying machine is a numerically controlled electromagnetic medicine frying machine or an automatic temperature-controlled electric heating medicine frying machine. The medicine frying machine rotates and heats at the same time, so that the materials in the drum are evenly heated.

[0014] The stir-fried licorice slices prepared by stir-frying have high contents of glycyrrhizin and glycyrrhizic acid, which can improve the efficacy of the product and maintain good efficacy when the dosage is reduced. The licorice needs to be turned over continuously during the stir-frying process to ensure the uniformity of drying the licorice. Uneven heating will cause some licorice to be overheated, reducing the effective ingredients therein. When some licorice is heated to a low degree, the water content therein is higher, and the consistency of the quality of the licorice is reduced. Rotating and stir-frying licorice can make the quality of different batches of medicines uniform.

[0015] Furthermore, the stir-fried licorice slices are stir-fried in a medicine stir-frying machine and the stir-frying is stopped when the moisture content is monitored to be ≤10%.

[0016] According to the quality requirements of the "Chinese Pharmacopoeia 2020 Edition", the moisture content of licorice slices is required to be ≤12%, which has a large range. When the finished product is actually prepared, the presence of moisture in the raw materials will lead to reduced efficacy. Controlling the moisture content below 10% can reduce the moisture ratio and avoid the loss of effective components caused by excessive drying during the actual stir-frying process, thereby increasing the content of effective components in the stir-fried licorice slices.

[0017] Further, in step 2, the quality requirements of the white peony slices and stir-fried licorice slices added to the extraction tank meet the following conditions: each batch of slices is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition", the content of paeoniflorin in each batch of white peony slices is ≥1.2%, the content of liquiritin in stir-fried licorice slices is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%, and the fingerprint spectrum is compared and tested using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System 2012 Edition, and the fingerprint spectrum similarity is ≥0.90;

[0018] Or multiple batches of white peony slices are homogenized, and the homogenized slices are sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in the white peony slices is 2.0%-3.0%, and the fingerprint spectrum comparison test is carried out using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System 2012 Edition, and the fingerprint spectrum similarity of the slices is ≥0.90; multiple batches of stir-fried licorice slices are homogenized, and the content of liquiritin in the stir-fried licorice slices after homogenization is 1.0%-2.0%, and the content of glycyrrhizic acid is 2.5%-4%, and the fingerprint spectrum comparison test is carried out using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System 2012 Edition, and the fingerprint spectrum similarity of the slices is ≥0.90.

[0019] Furthermore, the specific steps of the vacuum belt drying are as follows:

[0020] Turn on the vacuum. Under vacuum conditions, the clear paste in the material tank is continuously spread on the slowly moving crawler belt to form a thin coating. The crawler belt conveys the material into the steam heating section, where the material evaporates due to heat and loses moisture. The material then enters the cooling section, where it cools down and becomes brittle. Finally, it reaches the terminal, where it is automatically discharged through the isolation unloading bin and automatically crushed into powder.

[0021] Compared with other traditional direct oven drying, vacuum belt drying can make the clear paste evenly heated, the degree of drying uniform, and improve the quality of dry paste powder.

[0022] Furthermore, the steam heating section includes first stage heating, second stage heating and third stage heating. The temperature of the first stage heating is 100°C-120°C, the temperature of the second stage heating is 90-100°C, and the temperature of the third stage heating is 80-90°C. The three-stage heating method can reduce the loss of effective components in the clear paste.

[0023] Furthermore, the temperature of the cooling section is 20-40°C.

[0024] Furthermore, the heating pump frequency of the steam heating section is 5-20 Hz.

[0025] Furthermore, the frequency of the transmission motor of the crawler track is 5-30 Hz.

[0026] Furthermore, the angle of the cloth is 20-60°.

[0027] Furthermore, the specific steps of the spray drying are as follows:

[0028] Put the clear paste in the material tank into the spray dryer, set the process parameters of the spray dryer, the air inlet temperature is 170-220℃, the air outlet temperature is 80-110℃, the atomization frequency is 40-60Hz, the diaphragm pump frequency is 10-25Hz, the feed rate is 30-50kg / h, and start the spray dryer for spray drying. Spray drying is to achieve drying by atomizing the liquid into tiny droplets, which quickly evaporate the water after contacting with hot air. The drying process is rapid and can effectively avoid the loss of active ingredients.

[0029] Furthermore, the amount of the auxiliary material added is calculated according to the formula, which is as follows:

[0030] Amount of excipients added = total theoretical batch size × amount of dry paste powder input / [weight of clear paste × solid content of clear paste / (1-water content of dry paste powder)] - amount of dry paste powder input. Among them, the total theoretical batch size is the mass of Peony Glycyrrhiza Granules obtained in step 4 by calculating 20g of Peony Glycyrrhiza Granules according to a single prescription amount (110.4g), the amount of dry paste powder input is the mass of dry paste powder input in step 4, and the weight of clear paste is the weight of clear paste obtained in step 2. The loss during the drying process is eliminated, which can ensure that the equivalent amount of medicinal materials or decoction pieces taken by patients every day is completely consistent.

[0031] Furthermore, the auxiliary material is at least one of sucrose, dextrin, maltodextrin, starch, maltose, lactose and mannitol.

[0032] Furthermore, the mixing standard of the mixed powder is as follows:

[0033] Samples were taken from the mixed powder to test the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of at least 11 different sampling points was ≤5.

[0034] Mixed powders need to undergo strict quality testing to ensure the uniformity of their paeoniflorin, glycyrrhizic acid and liquiritin contents. If the content deviations of different mixed powders are large, it will lead to large differences in the quality of drugs produced in different batches and a lower qualified rate of finished products. Sampling and testing should be carried out at multiple sampling points, and the relative standard deviation (RSD) value should not be too large.

[0035] Furthermore, the drum speed of the dry granulator is 6-15rpm, the screw speed is 5-30rpm, the drum pressure is 4-12MPa, the side sealing pressure is 2-5MPa, the material is pressed into blocks, and the particles are sieved after crushing, the mesh number of the sieve is 10-40 mesh, and the fine powder is then dry-pressed by vacuum feeding until granulation is completed.

[0036] The dry granulator can directly make dry powder into granules without adding any liquid or adhesive, thus maintaining the original characteristics of the raw materials, reducing the generation of wastewater and dust, and meeting environmental protection requirements; the granules produced by dry granulation have uniform particle size and high bulk density.

[0037] Beneficial effects of the present invention:

[0038] (1) The preparation process of the present invention is based on respect for ancient books. Quality inspection is carried out in each process from preparation, feeding, extraction, and drying. The quality of intermediates such as raw materials and clear paste is strictly controlled (raw material quality, clear paste concentration quality); the drying step is omitted in the preparation process of stir-fried licorice, which shortens the preparation time and improves the transfer of effective ingredients; the extraction and concentration process ensures that the clear paste has the same effect as traditional decoction by controlling the amount of water added, the circulating boiling time, and monitoring the concentration degree of the clear paste; the drying process selects appropriate parameters to ensure maximum retention of effective ingredients; the granulation adopts a physical granulation molding process to minimize the loss of effective ingredients; the present invention minimizes the loss of effective ingredients by optimizing the preparation, drying and granulation processes, and the prepared Peony Glycyrrhiza Granules have good consistency in quality with the Peony Glycyrrhiza Decoction benchmark sample.

[0039] (2) The preparation process of the present invention can ensure that the amount of peony and licorice granules taken by the patient daily is completely consistent with the equivalent amount of medicinal materials or decoction pieces by accurately calculating the amount of auxiliary materials added, thereby minimizing the amount of auxiliary materials added. The specifications of the peony and licorice granules with the same amount of raw herbs are much lower than those of the approved varieties, and the daily dosage is significantly reduced.

[0040] (3) The uniformity of the peony and licorice granules prepared by the present invention is good, which is higher than the particle size standard of the Chinese Pharmacopoeia granules (the sum of the particles that cannot pass through the No. 1 sieve and the particles that can pass through the No. 5 sieve shall not exceed 15%). In addition, the particles have good bulk density and particle size uniformity, which is conducive to the stability of the packaging volume. The key quality attributes are consistent with the benchmark sample of the classic prescription Shaoyao Gancao Decoction, which is higher than the quality dispersion requirement of 70%-130% in the "Technical Guiding Principles for Pharmaceutical Research of Traditional Chinese Medicine Compound Preparations Managed According to the Catalog of Ancient Classic Prescriptions". The fingerprint spectrum similarity is greater than 0.95, which restores the quality of the classic prescription decoction in ancient books to the greatest extent. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The present invention will be further described below in conjunction with the accompanying drawings.

[0042] Figure 1 is a comparison chart of the sample fingerprints of Example 1 of the present invention;

[0043] Among them, S1 is the fingerprint of the reference sample, and S2-S7 are the fingerprints of the sampled product particles from 6 different batches in Example 1;

[0044] Figure 2 It is a comparison diagram of the sample fingerprints of Example 1 and Comparative Example 1 of the present invention;

[0045] Wherein, S1 is the fingerprint of the sample of product particles prepared in Example 1, and S2 is the fingerprint of the sample of product particles prepared in Example 2;

[0046] Figure 3 This is a comparison chart of the fingerprint spectrum of the white peony root slices after homogenization in Example 3 of the present invention;

[0047] Among them, S1 is the fingerprint of the reference sample, and S2-S4 are the fingerprints of the homogenized white peony slices of different batches prepared in Example 3;

[0048] Figure 4 This is a comparison chart of the fingerprint spectrum of the homogenized stir-fried liquorice slices according to Example 3 of the present invention;

[0049] Among them, S1 is the fingerprint of the reference sample, and S2-S4 are the fingerprints of different batches of homogenized stir-fried licorice slices prepared in Example 3. DETAILED DESCRIPTION

[0050] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only 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.

[0051] Example 1

[0052] Step 1, prepare white peony slices and stir-fried licorice slices: remove impurities from white peony medicinal materials, wash them, soak them until the skin is slightly soft, soak them until they can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice them, and dry them to obtain white peony slices; remove impurities from licorice medicinal materials, wash them, soak them and slice them, use a CNC electromagnetic medicine stir-frying machine to rotate and heat them at the same time, so that the materials in the drum are evenly heated, stir-fry them until the color is slightly yellow, and the moisture content is 8% when measured by a rapid moisture meter, and take them out to obtain stir-fried licorice slices. The process of preparing stir-fried licorice slices here is shown in Table 1.

[0053] Step 2. Prepare a mixed paste of white peony and fried licorice: Each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. The fingerprint spectrum is compared and tested using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system. Those with a fingerprint spectrum similarity of ≥0.90 can be used as raw materials. The total feed amount is calculated according to the preparation of 6000 single prescriptions and the single prescription feed amount of 110.4g. The white peony pieces and fried Licorice slices were added into an extraction tank at a mass ratio of 1:1, water twice the amount of the feed was added to moisten the medicinal materials for 30 minutes, and then 3 times the amount of water was added, saturated steam was introduced into the jacket of the extraction tank to heat the jacket, and the medicinal solution in the tank was heated to 90°C and circulated to boiling, and steam was generated in the extraction tank and passed through a condenser. After condensation, it was refluxed into the extraction tank, boiled, circulated for 10 minutes, kept boiling for 30 minutes, and circulated for another 20 minutes to obtain an extract, which was pumped into a single-effect concentrator for concentration, and the concentrate was filtered through an oscillating sieve to obtain a clear paste, the solid content of the clear paste was 35%, and the mass of the clear paste was 250 kg.

[0054] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 40°C, the cooling tower and steam valve are opened, and the first, second, third and cooling sections are started in sequence. The first heating temperature is set to 100°C, the second heating temperature is set to 100°C, the third heating temperature is set to 90°C, the cooling section temperature is set to 25°C, and the heating pump frequency of the heating section is set to 20Hz. The vacuum is turned on. Under vacuum conditions, the clear paste is continuously spread on the slowly moving crawler to form a thin coating. The spreading angle is set to 40°, and the transmission motor frequency of the crawler is set to 20Hz; the crawler conveys the material into the steam heating section, so that the material evaporates by heat and removes moisture, and then enters the cooling section to cool the material and make it brittle. Finally, it reaches the terminal and is automatically discharged through the isolation unloading bin, and is automatically crushed into powder to obtain 85kg of dry paste powder, and its moisture content is detected to be 4%.

[0055] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 120 × 85 / [250 × 35% / (1-4%)] - 85 = 26.9kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 2.0. The mixed powder that meets the standard is directly sucked into the dry granulator, and the drum speed is set to 10rpm, the spiral speed is 20rpm, the drum pressure is 8Mpa, and the side seal pressure is 4MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20 mesh) by a crusher to make product particles of uniform size. The 6 different batches of product particles prepared were tested for similarity using the Chinese medicine chromatographic fingerprint similarity evaluation system 2012 version. The similarity of the fingerprints of different batches was greater than 0.98. The specific fingerprints are shown in Figure 1 According to the provisions on granules in the Pharmacopoeia of the People's Republic of China: 2020 Edition, the double screening method was used to test the particle size. The total number of particles that could not pass through the No. 1 sieve and those that could pass through the No. 5 sieve was 2.7%, and the particle yield was 94% (the particle yield is the qualified rate of prepared particles).

[0056] Example 2

[0057] Step 1, prepare white peony slices and stir-fried licorice slices: remove impurities from white peony medicinal materials, wash them, soak them until the skin is slightly soft, soak them until they can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice them, and dry them to obtain white peony slices; remove impurities from licorice medicinal materials, wash them, soak them and slice them, use a CNC electromagnetic medicine stir-frying machine to rotate and heat them at the same time, so that the materials in the drum are evenly heated, stir-fry them until the color is slightly yellow, and the moisture content is 6% when measured by a rapid moisture meter, and take them out to obtain stir-fried licorice slices. The process of preparing stir-fried licorice slices here is shown in Table 1.

[0058] Step 2. Prepare a mixed paste of white peony and fried licorice: Each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. The fingerprint spectrum is compared and tested using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system. Those with a fingerprint spectrum similarity of ≥0.90 can be used as raw materials. The total feed amount is calculated according to the preparation of 6000 single prescriptions and the single prescription feed amount of 110.4g. The white peony pieces and fried Licorice slices were added into an extraction tank at a mass ratio of 1:1, water twice the amount of the feed was added to moisten the medicinal materials for 30 minutes, and then 2 times the amount of water was added, saturated steam was introduced into the jacket of the extraction tank to heat the jacket, and the medicinal solution in the tank was heated to 90°C and circulated to boiling, and steam was generated in the extraction tank and passed through a condenser. After condensation, it was refluxed into the extraction tank, boiled, circulated for 30 minutes, kept boiling for 20 minutes, and circulated for another 30 minutes to obtain an extract, which was pumped into a single-effect concentrator for concentration, and the concentrate was filtered through an oscillating sieve to obtain a clear paste, the solid content of the clear paste was 32%, and the mass of the clear paste was 270 kg.

[0059] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 40°C, and put into a spray dryer. The inlet temperature of the spray dryer is set to 200°C, the outlet temperature is set to 110°C, the atomization frequency is set to 40Hz, the diaphragm pump frequency is set to 20Hz, and the feed rate is set to 40kg / h. The material liquid passes through the high-speed centrifugal atomizer on the top of the tower body and is sprayed into extremely fine mist liquid droplets. It is dried with hot air in a very short time to obtain 84kg of dry paste powder, and its moisture content is detected to be 5%.

[0060] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 120 × 84 / [270 × 32% / (1-5%)] - 84 = 26.8kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 2.5. The mixed powder that meets the standard is directly sucked into the dry granulator, and the drum speed is set to 10rpm, the spiral speed is 20rpm, the drum pressure is 8Mpa, and the side sealing pressure is 4MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin slices by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20 mesh) by a crusher to make product particles of uniform size. The product particles prepared in this embodiment and the product particles prepared in Example 1 are tested for similarity using the Chinese medicine chromatographic fingerprint similarity evaluation system 2012 version. The fingerprint similarity is greater than 0.98. The specific fingerprint comparison diagram is shown in Figure 2 According to the provisions on granules in the Pharmacopoeia of the People's Republic of China: 2020 Edition, the double screening method was used to test the particle size. The sum of particles that could not pass through the No. 1 sieve and those that could pass through the No. 5 sieve was 2.5%, and the particle yield was 96%.

[0061] Example 3

[0062] Step 1, prepare white peony root slices and stir-fried licorice root slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root slices, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and the moisture content is 6% determined by a rapid moisture meter, take out, and obtain stir-fried licorice root slices.

[0063] Step 2. Prepare a mixed paste of white peony root and fried licorice: multiple batches of white peony root slices are homogenized, and the homogenized slices are sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in the white peony root slices is 2.0%-3.0%, and the fingerprint comparison test is performed using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system, and the fingerprint similarity of the slices is ≥0.90; multiple batches of fried licorice slices are homogenized, and the content of liquiritin in the homogenized fried licorice slices is 1.0%-2.0%, and the content of glycyrrhizic acid is 2.5%-4%, and the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system is used for fingerprint comparison test. The fingerprint similarity of the slices is ≥0.90. The fingerprint comparison chart of white peony root slices is shown in Figure 3, the fingerprint comparison chart of stir-fried licorice slices is shown in Figure 4 . The homogenized white peony slices and fried licorice slices were used as raw materials. The total feed amount was calculated according to the preparation of 3000 single prescriptions, with a single prescription feed amount of 110.4g. White peony slices and fried licorice slices were added to the extraction tank at a mass ratio of 1:1. 2.5 times the feed amount of water was added to moisten the medicinal materials for 30 minutes, and then 2 times the water was added. Saturated water vapor was passed into the jacket of the extraction tank to heat the jacket. The liquid in the tank was heated to 90°C and circulated to boiling. Steam was generated in the extraction tank and passed through the condenser. After condensation, it was refluxed into the extraction tank, boiled, circulated for 30 minutes, kept boiling for 30 minutes, and circulated for another 30 minutes to obtain an extract. The extract was pumped into a single-effect concentrator for concentration. The concentrate was filtered through an oscillating sieve to obtain a clear paste. The solid content of the clear paste was 30%, and the mass of the clear paste was 150kg.

[0064] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 30°C, the cooling tower and steam valve are opened, and the first, second, third and cooling sections are started in sequence. The first heating temperature is set to 110°C, the second heating temperature is set to 100°C, the third heating temperature is set to 85°C, the cooling section temperature is set to 30°C, and the heating pump frequency of the heating section is set to 20Hz. The vacuum is turned on. Under vacuum conditions, the clear paste is continuously spread on the slowly moving crawler to form a thin coating. The spreading angle is set to 30°, and the transmission motor frequency of the crawler is set to 20Hz; the crawler conveys the material into the steam heating section, so that the material evaporates by heat and removes moisture, and then enters the cooling section to cool the material and make it brittle. Finally, it reaches the terminal and is automatically discharged through the isolation unloading bin, and is automatically crushed into powder to obtain 43kg of dry paste powder, and its moisture content is detected to be 5%.

[0065] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 60 × 43 / [150 × 30% / (1-5%)] - 43 = 11.43kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 1.8. The mixed powder after reaching the standard is directly sucked into the dry granulator, and the drum speed is set to 8rpm, the spiral speed is 15rpm, the drum pressure is 7Mpa, and the side seal pressure is 3MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin slices by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20 meshes) by a crusher to make product particles of uniform size. The product particles prepared in this embodiment and the product particles prepared in Example 1 are tested for similarity using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system, and the fingerprint similarity is greater than 0.98. According to the provisions of the Pharmacopoeia of the People's Republic of China: 2020 Edition on granules, the double screening method is used to detect the particle size. The sum of particles that cannot pass through the No. 1 sieve and can pass through the No. 5 sieve is 4.2%, and the particle yield is 93%.

[0066] Example 4

[0067] Step 1, prepare white peony root slices and stir-fried licorice root slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root slices, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and the moisture content is 6% determined by a rapid moisture meter, take out, and obtain stir-fried licorice root slices.

[0068] Step 2: Prepare a mixed paste of white peony root and fried licorice root: multiple batches of white peony root slices are homogenized, and the homogenized slices are sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in the white peony root slices is 2.0%-3.0%, and the fingerprint spectrum is compared and tested using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system, and the fingerprint spectrum similarity of the slices is ≥0.90; multiple batches of fried licorice root slices are homogenized, and the content of liquiritin in the homogenized fried licorice root slices is 1.0%-2.0%, and the content of glycyrrhizic acid is 2.5%-4%, and the fingerprint spectrum similarity of the slices is ≥0.90. The homogenized white peony root slices and fried licorice root slices are used as raw materials. The total feed amount was calculated based on the preparation of 6,000 single prescriptions with a single prescription feed amount of 110.4 g. White peony slices and stir-fried licorice slices were added to the extraction tank at a mass ratio of 1:1. Water 3 times the feed amount was added to moisten the medicinal materials for 30 minutes, and then 2 times the water was added. Saturated steam was introduced into the jacket of the extraction tank to heat the jacket. The medicinal liquid in the tank was heated to 90°C and circulated to boiling. Steam was generated in the extraction tank and passed through the condenser. After condensation, it refluxed into the extraction tank, boiled, circulated for 30 minutes, kept boiling for 30 minutes, and circulated for another 30 minutes to obtain an extract. The extract was pumped into a single-effect concentrator for concentration. The concentrate was filtered through an oscillating sieve to obtain a clear paste. The solid content of the clear paste was 32% and the mass of the clear paste was 270 kg.

[0069] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 40°C, and put into a spray dryer. The inlet temperature of the spray dryer is set to 210°C, the outlet temperature is 110°C, the atomization frequency is 40Hz, the diaphragm pump frequency is 20Hz, and the feed rate is 40kg / h. The liquid is sprayed into extremely fine mist liquid droplets through the high-speed centrifugal atomizer on the top of the tower body, and dried with hot air in a very short time to obtain 84kg of dry paste powder. The moisture content is detected to be 5%.

[0070] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 120 × 84 / [270 × 32% / (1-5%)] - 84 = 26.8kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 2.5. The mixed powder that meets the standards is directly sucked into the dry granulator, and the drum speed is set to 10rpm, the spiral speed is 20rpm, the drum pressure is 8Mpa, and the side seal pressure is 4MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20 mesh) by a crusher to make product particles of uniform size. According to the provisions on granules in the "Pharmacopoeia of the People's Republic of China: 2020 Edition", the double screening method is used to test the particle size. The sum of particles that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 3.1%, and the particle yield is 95%.

[0071] Example 5

[0072] Step 1, prepare white peony slices and stir-fried licorice slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and use a rapid moisture meter to determine the moisture content is 7%, take out, and obtain stir-fried licorice slices.

[0073] Step 2. Prepare a mixed paste of white peony and fried licorice: Each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. The fingerprint spectrum is compared and tested using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System 2012 version. Those with a fingerprint spectrum similarity ≥0.90 can be used as raw materials. The total feed amount was calculated according to the preparation of 3000 single prescriptions with a single prescription feed amount of 110.4g. White peony slices and stir-fried licorice slices were added to the extraction tank at a mass ratio of 1:1. Water twice the feed amount was added to moisten the medicinal materials for 30 minutes, and then 3 times the water was added. Saturated steam was introduced into the jacket of the extraction tank to heat the jacket. The medicinal liquid in the tank was heated to 90°C and circulated to boiling. Steam was generated in the extraction tank and passed through the condenser. After condensation, it was refluxed into the extraction tank, boiled, circulated for 30 minutes, kept boiling for 30 minutes, and circulated for another 30 minutes to obtain an extract. The extract was pumped into an MVR evaporator for concentration. The concentrate was filtered through an oscillating sieve to obtain a clear paste. The solid content of the clear paste was 40%, and the mass of the clear paste was 110kg.

[0074] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 30°C, the cooling tower and steam valve are opened, and the first, second, third and cooling sections are started in sequence. The first heating temperature is set to 110°C, the second heating temperature is set to 90°C, the third heating temperature is set to 80°C, the cooling section temperature is set to 35°C, and the heating pump frequency of the heating section is set to 20Hz. The vacuum is turned on. Under vacuum conditions, the clear paste is continuously spread on the slowly moving crawler to form a thin coating. The spreading angle is set to 45°, and the transmission motor frequency of the crawler is set to 30Hz; the crawler conveys the material into the steam heating section, so that the material evaporates by heat and removes moisture, and then enters the cooling section to cool the material and make it brittle. Finally, it reaches the terminal and is automatically discharged through the isolation unloading bin, and is automatically crushed into powder to obtain 42kg of dry paste powder, and its moisture content is detected to be 3%.

[0075] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 60 × 42 / [110 × 40% / (1-3%)] - 42 = 13.5kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 1.2. The mixed powder that meets the standards is directly sucked into the dry granulator, and the drum speed is set to 6rpm, the spiral speed is 12rpm, the drum pressure is 8Mpa, and the side seal pressure is 3MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20) by a crusher to make product particles of uniform size. According to the provisions on granules in the "Pharmacopoeia of the People's Republic of China: 2020 Edition", the double screening method is used to test the particle size. The sum of particles that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 3.4%, and the particle yield is 94%.

[0076] Example 6

[0077] Step 1, prepare white peony root slices and stir-fried licorice root slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root slices, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and the moisture content is 9% as measured by a rapid moisture meter, take out, and obtain stir-fried licorice root slices.

[0078] Step 2. Prepare a mixed paste of white peony root and fried licorice: multiple batches of white peony root slices are homogenized, and the homogenized slices are sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in the white peony root slices is 2.0%-3.0%, and the fingerprint spectrum comparison test is performed using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system, and the fingerprint spectrum similarity of the slices is ≥0.90; multiple batches of fried licorice slices are homogenized, and the content of liquiritin in the homogenized fried licorice slices is 1.0%-2.0%, and the content of glycyrrhizic acid is 2.5%-4%, and the fingerprint spectrum comparison test is performed using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system, and the fingerprint spectrum similarity of the slices is ≥0.90. The homogenized white peony root slices and fried licorice slices are used as raw materials. The total feed amount was calculated according to the preparation of 3000 single prescriptions with a single prescription feed amount of 110.4g. White peony slices and stir-fried licorice slices were added to the extraction tank at a mass ratio of 1:1. Water twice the feed amount was added to moisten the medicinal materials for 30 minutes, and then 3 times the water was added. Saturated steam was introduced into the jacket of the extraction tank to heat the jacket. The medicinal liquid in the tank was heated to 90°C and circulated to boiling. Steam was generated in the extraction tank and passed through the condenser. After condensation, it was refluxed into the extraction tank, boiled, circulated for 15 minutes, kept boiling for 30 minutes, and circulated for another 15 minutes to obtain an extract. The extract was pumped into an MVR evaporator for concentration. The concentrate was filtered through an oscillating sieve to obtain a clear paste. The solid content of the clear paste was 35%, and the mass of the clear paste was 140kg.

[0079] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 30°C, and put into a spray dryer. The inlet temperature of the spray dryer is set to 200°C, the outlet temperature is set to 105°C, the atomization frequency is set to 42Hz, the diaphragm pump frequency is set to 25Hz, and the feed rate is set to 40kg / h. The liquid is sprayed into extremely fine mist liquid droplets through the high-speed centrifugal atomizer on the top of the tower body, and dried with hot air in a very short time to obtain 47kg of dry paste powder. The moisture content is detected to be 5%.

[0080] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 60 × 47 / [140 × 35% / (1-5%)] - 47 = 7.65kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 1.9. The mixed powder that meets the standards is directly sucked into the dry granulator, and the drum speed is set to 12rpm, the spiral speed is 18rpm, the drum pressure is 9Mpa, and the side seal pressure is 2MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20) by the crusher to make product particles of uniform size. According to the provisions on granules in the "Pharmacopoeia of the People's Republic of China: 2020 Edition", the double screening method is used to test the particle size. The sum of particles that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 4.6%, and the particle yield is 95%.

[0081] Example 7

[0082] Step 1, prepare white peony slices and stir-fried licorice slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and determine the moisture content of 10% by a rapid moisture meter, take out, and obtain stir-fried licorice slices.

[0083] Step 2. Prepare a mixed paste of white peony and fried licorice: Each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. The fingerprint spectrum is compared and tested using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System 2012 version. Those with a fingerprint spectrum similarity ≥0.90 can be used as raw materials. The total feed amount was calculated according to the preparation of 4500 single prescriptions with a single prescription feed amount of 110.4g. White peony slices and stir-fried licorice slices were added to the extraction tank at a mass ratio of 1:1. Water twice the feed amount was added to moisten the medicinal materials for 30 minutes, and then 2.5 times the water was added. Saturated steam was introduced into the jacket of the extraction tank to heat the jacket. The medicinal liquid in the tank was heated to 90°C and circulated to boiling. Steam was generated in the extraction tank and passed through the condenser. After condensation, it refluxed into the extraction tank, boiled, circulated for 15 minutes, kept boiling for 30 minutes, and circulated for another 15 minutes to obtain an extract. The extract was pumped into an MVR evaporator for concentration. The concentrate was filtered through an oscillating sieve to obtain a clear paste. The solid content of the clear paste was 40%, and the mass of the clear paste was 160kg.

[0084] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 35°C, the cooling tower and steam valve are opened, and the first, second, third and cooling sections are started in sequence. The first heating temperature is set to 110°C, the second heating temperature is set to 95°C, the third heating temperature is set to 90°C, the cooling section temperature is set to 30°C, and the heating pump frequency of the heating section is set to 30Hz. The vacuum is turned on. Under vacuum conditions, the clear paste is continuously spread on the slowly moving crawler to form a thin coating. The spreading angle is set to 40°, and the transmission motor frequency of the crawler is set to 25Hz; the crawler conveys the material into the steam heating section, so that the material evaporates by heat and removes moisture, and then enters the cooling section to cool the material and make it brittle. Finally, it reaches the terminal and is automatically discharged through the isolation unloading bin, and is automatically crushed into powder to obtain 63kg of dry paste powder, and its moisture content is detected to be 4%.

[0085] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 90 × 63 / [160 × 40% / (1-4%)] - 63 = 22.0kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 1.2. The mixed powder that meets the standards is directly sucked into the dry granulator, and the drum speed is set to 12rpm, the spiral speed is 18rpm, the drum pressure is 9Mpa, and the side seal pressure is 2MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20) by the crusher to make product particles of uniform size. According to the provisions on granules in the "Pharmacopoeia of the People's Republic of China: 2020 Edition", the double screening method is used to test the particle size. The sum of particles that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 3.1%, and the particle yield is 95%.

[0086] Example 8

[0087] Step 1, prepare white peony slices and stir-fried licorice slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and determine the moisture content of 10% by a rapid moisture meter, take out, and obtain stir-fried licorice slices.

[0088] Step 2: Prepare a mixed paste of white peony root and fried licorice root: multiple batches of white peony root slices are homogenized, and the homogenized slices are sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in the white peony root slices is 2.0%-3.0%, and the fingerprint spectrum is compared and tested using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system, and the fingerprint spectrum similarity of the slices is ≥0.90; multiple batches of fried licorice root slices are homogenized, and the content of liquiritin in the homogenized fried licorice root slices is 1.0%-2.0%, and the content of glycyrrhizic acid is 2.5%-4%, and the fingerprint spectrum similarity of the slices is ≥0.90. The homogenized white peony root slices and fried licorice root slices are used as raw materials. The total feed amount was calculated according to the preparation of 4500 single prescriptions with a single prescription feed amount of 110.4g. White peony slices and stir-fried licorice slices were added to the extraction tank at a mass ratio of 1:1. Water 2.5 times the feed amount was added to moisten the medicinal materials for 30 minutes, and then 2 times the water was added. Saturated steam was introduced into the jacket of the extraction tank to heat the jacket. The medicinal liquid in the tank was heated to 90°C and circulated to boiling. Steam was generated in the extraction tank and passed through the condenser. After condensation, it was refluxed into the extraction tank, boiled, circulated for 15 minutes, kept boiling for 30 minutes, and circulated for another 30 minutes to obtain an extract. The extract was pumped into an MVR evaporator for concentration. The concentrate was filtered through an oscillating sieve to obtain a clear paste. The solid content of the clear paste was 32% and the mass of the clear paste was 200kg.

[0089] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 45°C, and put into a spray dryer. The inlet temperature of the spray dryer is set to 200°C, the outlet temperature is set to 105°C, the atomization frequency is set to 50Hz, the diaphragm pump frequency is set to 20Hz, and the feed rate is set to 40kg / h. The liquid is sprayed into extremely fine mist liquid droplets through the high-speed centrifugal atomizer on the top of the tower body, and dried with hot air in a very short time to obtain 64kg of dry paste powder. The moisture content is detected to be 5%.

[0090] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, auxiliary material addition amount = theoretical batch total amount × dry paste powder input amount / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input amount, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin addition amount = 90 × 64 / [200 × 32% / (1-5%)] - 64 = 21.54kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 1.8. The mixed powder that meets the standards is directly sucked into the dry granulator, and the drum speed is set to 12rpm, the spiral speed is 18rpm, the drum pressure is 9Mpa, and the side seal pressure is 2MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20) by a crusher to make product particles of uniform size. According to the provisions on granules in the "Pharmacopoeia of the People's Republic of China: 2020 Edition", the double screening method is used to test the particle size. The sum of particles that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 3.5%, and the particle yield is 96%.

[0091] Comparative Example 1

[0092] Step 1, prepare white peony slices and stir-fried licorice slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and the moisture content is 12% determined by a rapid moisture meter, take out, and obtain stir-fried licorice slices.

[0093] Step 2. Prepare a mixed paste of white peony and fried licorice: Each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. After the test, the qualified pieces are used as raw materials. According to the preparation of 3000 single prescriptions, the total feeding amount is calculated according to the feeding amount of 110.4g per prescription. White peony pieces and fried licorice pieces are added in a mass ratio of 1:1. Put it into the extraction tank, add 6 times the amount of water, pass saturated water vapor into the jacket of the extraction tank to heat the jacket, heat the liquid in the tank to 90°C, circulate until boiling, generate steam in the extraction tank and pass through the condenser, condense and return to the extraction tank, boil, circulate for 30 minutes, keep boiling for 30 minutes, circulate for another 30 minutes to obtain an extract, pump the extract into a single-effect concentrator for concentration, filter the concentrate through an oscillating sieve to obtain a clear paste, the solid content of the clear paste is 32%, and the mass of the clear paste is 140kg.

[0094] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 30°C, and put into a spray dryer. The inlet temperature of the spray dryer is set to 200°C, the outlet temperature is set to 105°C, the atomization frequency is set to 42Hz, the diaphragm pump frequency is set to 25Hz, and the feed rate is set to 40kg / h. The liquid is sprayed into extremely fine mist liquid droplets through the high-speed centrifugal atomizer on the top of the tower body, and dried with hot air in a very short time to obtain 43kg of dry paste powder. The moisture content is detected to be 5%.

[0095] Step 4, preparation of granules: take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, the amount of auxiliary materials added = theoretical batch total amount × dry paste powder input / [clear paste weight × clear paste solid content / (1-dry paste powder moisture content)] - dry paste powder input, the theoretical batch total amount is calculated according to a single prescription amount (110.4g) to make 20g of peony and licorice granules, maltodextrin added = 60 × 43 / [140 × 32% / (1-5%)] - 43 = 11.70kg, mix the auxiliary materials and dry paste powder to obtain a mixed powder, take samples from the mixed powder to detect the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of 11 different sampling points is 1.8. The mixed powder that meets the standards is directly sucked into the dry granulator, and the drum speed is set to 10rpm, the spiral speed is 20rpm, the drum pressure is 8Mpa, and the side seal pressure is 4MPa. According to the principle of physical extrusion granulation process, the mixed powder is squeezed into thin sheets by the pressing wheel, and then crushed, granulated, and sieved (the mesh size is 20 mesh) by a crusher to make product particles of uniform size. According to the provisions on granules in the "Pharmacopoeia of the People's Republic of China: 2020 Edition", the double screening method is used to test the particle size. The sum of particles that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 3.6%, and the particle yield is 94%.

[0096] Upon inspection, the dispersion of the contents of paeoniflorin, glycyrrhizic acid and liquiritin in the product granules prepared in this comparative example exceeded ±30% of the content of the benchmark sample (Technical Guidelines for Pharmaceutical Research of Chinese Herbal Compound Preparations managed according to the catalog of ancient classic prescriptions), which does not meet the technical requirements of the classic prescriptions.

[0097] Comparative Example 2

[0098] Step 1, prepare white peony slices and stir-fried licorice slices: remove impurities from white peony medicinal materials, wash them, soak them until the skin is slightly soft, moisten them until they can be slightly bent by the bending method, and there is no dry core on the cross section, slice them, and dry them to obtain white peony slices; remove impurities from licorice medicinal materials, wash them, moisten them until they can be slightly bent, and there is no dry core on the cross section, slice them, and dry them to obtain white peony slices; remove impurities from licorice medicinal materials, wash them, moisten them until they can be slightly bent, and the cross section has no dry core, slice them, and place the slices in a drying oven to dry them. The rapid moisture meter determines that the moisture content is 10%, and then a CNC electromagnetic medicine frying machine is used to rotate and heat the materials in the drum evenly, stir-fry them until the color is slightly yellow, and the rapid moisture meter determines that the moisture content is 6%, and take them out to obtain stir-fried licorice slices. The process of preparing stir-fried licorice slices here is shown in Table 1.

[0099] Step 2. Prepare a mixed paste of white peony and fried licorice: each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. The fingerprint spectrum is compared and tested using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system. Those with a fingerprint spectrum similarity of ≥0.90 can be used as raw materials. The total feed amount is calculated according to the preparation of 3000 single prescriptions and the single prescription feed amount of 110.4g. The white peony pieces and fried licorice pieces are added in a mass ratio of 1:1. Put it into the extraction tank, add 2 times the amount of water to moisten the medicinal materials for 30 minutes, then add 3 times the amount of water, pass saturated water vapor into the jacket of the extraction tank to heat the jacket, heat the medicinal liquid in the tank to 90°C, circulate until boiling, generate steam in the extraction tank and pass through the condenser, condense and return to the extraction tank, boil, circulate for 10 minutes, keep boiling for 30 minutes, recirculate for 20 minutes to obtain the extract, pump the extract into a single-effect concentrator for concentration, filter the concentrate through an oscillating sieve to obtain a clear paste, the solid content of the clear paste is 40%, the mass of the clear paste is 110kg, and the calculated dry extract amount is 44kg (dry extract amount = 110*40%)

[0100] Step 3, preparation of granules: adopt fluidized bed one-step granulation, refer to the technical guidelines such as "Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules", the ratio of excipients / auxiliary materials to intermediates (extracts or dry paste powders, calculated as dry products) is generally not more than 1:1, 30 kg of auxiliary material dextrin is put into the fluidized bed as the base material excipient, and the clear paste is sprayed into the conventional fluidized bed one-step granulation for granulation, and the granule yield is 78%.

[0101] Comparative Example 3

[0102] Step 1, prepare white peony slices and stir-fried licorice slices: remove impurities from white peony medicinal materials, wash them, soak them until the skin is slightly soft, moisten them until they can be slightly bent by the bending method, and there is no dry core on the cross section, slice them, and dry them to obtain white peony slices; remove impurities from licorice medicinal materials, wash them, moisten them until they can be slightly bent ... the cross section has no dry core, slice them, and dry them to obtain white peony slices; remove impurities from licorice medicinal materials, wash them, moisten them until they can be slightly bent, and the cross section has no dry core, slice them, and place them in a drying oven to dry, and the moisture content is 12% as determined by a rapid moisture meter, and then a CNC electromagnetic medicine frying machine is used to heat while rotating so that the material in the drum is evenly heated, stir-fry them until the color is slightly yellow, and the moisture content is 8% as determined by a rapid moisture meter, and then take them out to obtain stir-fried licorice slices. The process of preparing stir-fried licorice slices here is shown in Table 1.

[0103] Step 2. Prepare a mixed paste of white peony and fried licorice: each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. The fingerprint spectrum is compared and tested using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system. Those with a fingerprint spectrum similarity of ≥0.90 can be used as raw materials. The total feed amount is calculated according to the preparation of 3000 single prescriptions and the single prescription feed amount of 110.4g. White peony pieces and fried licorice pieces are added in a mass ratio of 1:1 In the extraction tank, add 2 times the amount of water to moisten the medicinal materials for 30 minutes, then add 3 times the amount of water, pass saturated water vapor into the jacket of the extraction tank to heat the jacket, heat the medicinal liquid in the tank to 90°C, circulate until boiling, generate steam in the extraction tank and pass through the condenser, condense and return to the extraction tank, boil, circulate for 10 minutes, keep boiling for 30 minutes, and circulate for 20 minutes to obtain an extract, which is pumped into a single-effect concentrator for concentration, and the concentrate is filtered through an oscillating sieve to obtain a clear paste, the solid content of the clear paste is 40%, the mass of the clear paste is 106 kg, and the calculated dry extract amount is 42.4 kg (dry extract amount = 106*40%)

[0104] Step 3, preparation of granules: adopt fluidized bed one-step granulation, refer to the technical guidelines such as "Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules", the ratio of excipients / auxiliary materials to intermediates (extracts or dry paste powders, calculated as dry products) is generally not more than 1:1, 35 kg of auxiliary material dextrin is put into the fluidized bed as the base material excipient, and the clear paste is sprayed into the conventional fluidized bed one-step granulation for granulation, and the yield of granules is 80%.

[0105] Comparative Example 4

[0106] Step 1, prepare white peony root slices and stir-fried licorice root slices: take white peony root, remove impurities, wash, soak until the skin is slightly soft, soak until it can be slightly bent by bending method inspection, and there is no dry core on the cross section, slice, dry, and obtain white peony root slices; take licorice root slices, remove impurities, wash, soak and slice, use a CNC electromagnetic medicine frying machine to rotate and heat at the same time to make the material in the drum evenly heated, stir-fry until the color is slightly yellow, and the moisture content is 8% as measured by a rapid moisture meter, take out, and obtain stir-fried licorice root slices.

[0107] Step 2. Prepare a mixed paste of white peony and fried licorice: Each batch of decoction pieces is sampled and tested according to the content determination method of the "Chinese Pharmacopoeia 2020 Edition". The content of paeoniflorin in each batch of white peony pieces is ≥1.2%, the content of liquiritin in fried licorice pieces is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%. The fingerprint spectrum is compared and tested using the 2012 version of the Chinese medicine chromatographic fingerprint similarity evaluation system. Those with a fingerprint similarity of ≥0.90 can be used as raw materials. The total feed amount is calculated according to the preparation of 3000 single prescriptions and the single prescription feed amount of 110.4g. The white peony pieces and fried Licorice slices were added into an extraction tank at a mass ratio of 1:1, 3 times the amount of water was added to moisten the medicinal materials for 30 minutes, and then 3 times the amount of water was added, saturated steam was introduced into the jacket of the extraction tank to heat the jacket, and the medicinal solution in the tank was heated to 90°C and circulated to boiling, and steam was generated in the extraction tank and passed through a condenser. After condensation, it was refluxed into the extraction tank, boiled, circulated for 10 minutes, kept boiling for 30 minutes, and circulated for another 20 minutes to obtain an extract, which was pumped into a single-effect concentrator for concentration, and the concentrate was filtered through an oscillating sieve to obtain a clear paste, the solid content of the clear paste was 32%, and the mass of the clear paste was 140 kg.

[0108] Step 3, preparation of dry paste powder: the clear paste is placed in a material tank at a constant temperature of 40°C, and put into a spray dryer. The inlet temperature of the spray dryer is set to 200°C, the outlet temperature is set to 105°C, the atomization frequency is set to 42Hz, the diaphragm pump frequency is set to 25Hz, and the feed rate is set to 40kg / h. The liquid is sprayed into extremely fine mist liquid droplets through the high-speed centrifugal atomizer on the top of the tower body, and dried with hot air in a very short time to obtain 43kg of dry paste powder. The moisture content is detected to be 5%.

[0109] Step 4. Preparation of granules: Take dry paste powder, add auxiliary materials (maltodextrin) to the dry paste powder, the amount of auxiliary materials added = theoretical total amount - dry paste powder amount = 60-43 = 17kg, place the auxiliary materials and dry paste powder in a trough mixer, add 70% ethanol for moistening, and make a soft material. The soft material passes through a swing granulator and enters a fluidized bed for drying. The drying temperature is 60°C, dried for 20 minutes, granulated, and sieved to obtain granules. According to the provisions on granules in the "Pharmacopoeia of the People's Republic of China: 2020 Edition", the double screening method is used to detect the particle size. The total amount of particles that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 3.6%, and the yield is 60%.

[0110] Table 1

[0111] Example Example 1 Example 2 Comparative Example 2 Comparative Example 3 Preparation process of stir-fried licorice slices Direct frying Direct frying Drying and frying Drying and frying Drying temperature / / 60℃ 70℃ Drying time / / 5.2h 4.1h Moisture% / / 10 12 Frying temperature 120℃ 120℃ 120℃ 120℃ Frying time 35min 40min 16min 15min Moisture% 8 6 6 8

[0112] According to the above examples 1 and 2, when the vacuum belt drying or spray drying method is used, the difference in the water content of the dry paste powder is small, and the fingerprint of the prepared product particles is compared, and the similarity is greater than 0.98. Both drying methods can achieve the drying of the clear paste, and the influence on the ingredients is small. In Example 3, the screening method of the slices is adjusted to the homogenization method, and the fingerprint of the homogenized slices is compared. It can be seen that the similarity of the fingerprint is ≥ 0.90. The homogenized slices are used as raw materials to prepare product particles. By comparing the fingerprint with the product particles of Example 1, the similarity is greater than 0.98. The raw materials selected by the homogenization method can ensure the effect of the product, and the raw materials screened by the homogenization method can achieve the effective utilization of raw materials of different qualities, thereby improving the utilization rate of raw materials. In Examples 5 and 6, due to the difference in the solid content of the clear paste and the moisture content of the dry paste powder during the preparation process, the amount of auxiliary materials added according to the calculation formula is different, but the yield of the particles is not much different, indicating that the auxiliary materials are added according to the calculation formula of the auxiliary material addition amount of the present invention, and the granulation yield can be guaranteed. Comparative Example 1 is to select the slices that meet the quality requirements of the "Chinese Pharmacopoeia 2020 Edition" as raw materials, and the effective component content of the prepared product particles fluctuates greatly, making it difficult to ensure the stability of the drug effect. Comparative Examples 2 and 3 are to prepare fried licorice slices by first drying and then frying. The process of preparation by this method is time-consuming, which is not conducive to improving production efficiency. The direct frying method in the embodiment is more efficient. And in Comparative Examples 2 and 3, the fluidized bed granulation method is adopted, and the amount of excipient added is large, and the effective component content in the product particles will be reduced. To ensure the drug effect, the dosage will increase, and the yield of its particles is obviously not as good as the embodiment, and the cost increases. In Comparative Example 4, the amount of excipients added is directly calculated according to the amount of excipients added = theoretical total amount - dry paste powder amount, and the amount of excipients added is significantly higher than the amount calculated by the formula provided in the embodiment, and the soft material obtained by the granulation method in Comparative Example 4 is sticky, not easy to granulate, and the particle uniformity is poor.

[0113] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0114] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A preparation process of peony and liquorice granules, characterized in that: The following steps are involved: Step 1, preparing white peony root slices and stir-fried licorice root slices: remove impurities from white peony root, wash it, soak it, and then slice it and dry it to obtain white peony root slices; remove impurities from licorice root, wash it, soak it, and then slice it, and stir-fry it in a stir-frying machine to obtain stir-fried licorice root slices; Step 2, preparing a mixed paste of white peony root and fried licorice root: adding white peony root slices and fried licorice root slices into an extraction tank in a mass ratio of 1:1, adding water and heating to extract, concentrating the extract to obtain a concentrated solution, filtering the concentrated solution to obtain a clear paste, and the solid content of the clear paste is 30-50%; Step 3, preparing dry paste powder: placing the clear paste in a material tank at a constant temperature of 25-45°C, and drying it by vacuum belt drying or spray drying to obtain dry paste powder; Step 4, preparing peony and licorice granules: adding auxiliary materials to the dry paste powder, and the mixed powder after mixing is put into a dry granulator for granulation to obtain peony and licorice granules.

2. The process for preparing the peony and liquorice granules according to claim 1, characterized in that: The stir-fried liquorice slices are stir-fried in a medicine stir-frying machine and the stir-frying is stopped when the moisture content is monitored to be ≤10%.

3. The process for preparing the peony and liquorice granules according to claim 1, characterized in that: In step 2, the quality requirements of the white peony slices and the stir-fried licorice slices added to the extraction tank meet the following conditions: the content of paeoniflorin in each batch of white peony slices is ≥1.2%, the content of liquiritin in the stir-fried licorice slices is ≥0.45%, and the content of glycyrrhizic acid is ≥1.8%; Or multiple batches of white peony slices and stir-fried licorice slices are homogenized. After homogenization, the content of paeoniflorin in the white peony slices is 2.0%-3.0%, the content of liquiritin in the stir-fried licorice slices is 1.0%-2.0%, and the content of glycyrrhizic acid is 2.5%-4%.

4. The process for preparing the peony and liquorice granules according to claim 1, characterized in that: The specific steps of the vacuum belt drying are as follows: Under vacuum conditions, the clear paste in the material tank is evenly distributed on the moving crawler belt to form a coating. The crawler belt conveys the material to the steam heating section and cooling section for drying in turn, and is discharged from the unloading bin.

5. The process for preparing the peony and liquorice granules according to claim 4, characterized in that: The steam heating section includes one stage heating, two stage heating and three stage heating, the temperature of the one stage heating is 100-120°C, the temperature of the two stage heating is 90-100°C, and the temperature of the three stage heating is 80-90°C; the temperature of the cooling section is 20-40°C.

6. The process for preparing the peony and liquorice granules according to claim 1, characterized in that: The specific steps of the spray drying are as follows: Put the clear paste in the material tank into the spray dryer, set the process parameters of the spray dryer, the inlet air temperature is 170-220℃, the outlet air temperature is 80-110℃, the atomization frequency is 40-60Hz, the diaphragm pump frequency is 10-25Hz, the feed rate is 30-50kg / h, and start the spray dryer for spray drying.

7. The process for preparing the Shaoyao Gancao granules according to claim 1, characterized in that: The amount of the auxiliary material added is calculated according to the formula, which is as follows: Amount of auxiliary materials added = total theoretical batch size × amount of dry paste powder input / [weight of clear paste × solid content of clear paste / (1-water content of dry paste powder)] - amount of dry paste powder input, wherein the total theoretical batch size is the estimated mass of the peony licorice granules obtained in step four, the amount of dry paste powder input is the mass of the dry paste powder input in step four, and the weight of the clear paste is the weight of the clear paste obtained in step two.

8. The process for preparing the Shaoyao Gancao granules according to claim 1, characterized in that: The auxiliary material is at least one of sucrose, dextrin, maltodextrin, starch, maltose, lactose and mannitol.

9. The process for preparing the Shaoyao Gancao granules according to claim 1, characterized in that: The mixing standard of the mixed powder is as follows: Samples were taken from the mixed powder to test the contents of paeoniflorin, glycyrrhizic acid and liquiritin, and the RSD of at least 11 different sampling points was ≤5.

10. The process for preparing the Shaoyao Gancao granules according to claim 1, characterized in that: The drum speed of the dry granulator is 6-15 rpm, the drum pressure is 4-12 MPa, and the side sealing pressure is 2-5 MPa.

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