A stomach-soothing and analgesic composition capsule and large-scale preparation method thereof

Abstract

The present invention relates to the technical field of production process of traditional Chinese medicine composition, and discloses a stomach-relieving and analgesic composition capsule and a large-scale preparation method thereof, wherein the medicinal raw materials include 80-120 parts of coptis root, 50-70 parts of amomum villosum, 80-120 parts of bupleurum, 80-120 parts of dandelion, 80-120 parts of corydalis, 40-60 parts of evodia rutaecarpa, 80-120 parts of rhubarb, 80-120 parts of costusroot and 25-35 parts of clove. The present invention adopts acidic conditions percolation extraction, cyclodextrin inclusion of volatile oil, alkali precipitation and filtrate drying in sequence, and fills the capsules after mixing the inclusion compound and powder. In the whole process, no large-scale energy consumption is required, which reduces the production cost and greatly improves the production efficiency; it also solves the technical problems of low yield of berberine in the existing extraction of coptis root, and reducing the berberine content in the product and the utilization rate of coptis root due to the compatibility reaction of berberine with other components, effectively improving the content of berberine in the medicine, and improving the quality and efficacy of the medicine.

Description

Technical Field

[0001] The invention relates to the technical field of production technology of traditional Chinese medicine compositions, and in particular to a stomach-soothing and analgesic composition capsule and a large-scale preparation method thereof. Background Art

[0002] Hewei Zhitong Capsule has the effects of clearing the liver and harmonizing the stomach, relieving nausea and vomiting, regulating qi and relieving pain; its main ingredients are Coptis chinensis, Evodia rutaecarpa, Bupleurum chinense, Rhubarb, Corydalis yanhusuo, costusroot, clove, Amomum villosum and Taraxacum mongolicum.

[0003] At present, high-temperature processes such as decoction extraction, concentration, wet granulation, and boiling drying are often used to prepare medicines; the existing process uses water extraction, and due to the poor water solubility of berberine, the extraction efficiency is low, and the high-temperature decoction during the production process causes serious compatibility reactions between berberine hydrochloride and other ingredients in Coptis chinensis, resulting in a very low transfer rate of berberine hydrochloride to the finished product, which not only makes it difficult for the content of the finished product to meet the quality standard requirements, but also leads to waste of medicinal materials. For example, studies have shown that in the water decoction of Coptis chinensis and Evodia rutaecarpa, alkaloid components such as berberine in Coptis chinensis react with flavonoid compounds in Evodia rutaecarpa to form precipitated macromolecules, making it difficult to decoctine, reducing the dissolution rate of berberine, and then reducing the utilization rate of Coptis chinensis, resulting in waste of medicinal materials. In addition, the existing production process divides the raw medicinal materials into three units for separate decoction, extraction and concentration; after the extracts are combined, the preparations are produced, and the preparation units also require wet granulation and boiling drying. As a result, the total energy consumption in the production process is very large, and the production cost is quite high, which is not conducive to improving the market competitiveness of the products. In addition, the total mixture prepared by the existing process has poor fluidity and strong hygroscopicity, resulting in large differences in the filling amount during the capsule filling process.

[0004] In order to solve the above problems, the prior art CN1056078C discloses a stomach-soothing analgesic. When preparing the stomach-soothing analgesic, water and 0.2% to 0.7% acetic acid solution are added to acidify, soak, and then decocted to extract the effective components of the four medicinal materials of coptis chinensis, evodia rutaecarpa, costusroot, and yanhusuo. However, the transfer rate of berberine hydrochloride extracted from coptis chinensis by the above decoction method is still very low (the transfer rate of berberine is about 20 to 30%), and the berberine hydrochloride content in the finished product is low, thereby significantly reducing the quality of the stomach-soothing analgesic composition capsule.

[0005] Therefore, developing a stomach-soothing and analgesic composition product with high drug quality and reduced energy consumption and a large-scale preparation method thereof can not only effectively make up for the shortcomings of existing stomach-soothing and analgesic composition products and production processes, but also has important significance for improving product quality, medicinal material utilization rate and product market competitiveness. Summary of the invention

[0006] The present invention aims to provide a stomach-soothing and analgesic composition capsule and a large-scale preparation method thereof, so as to solve the technical problems in the existing process that the berberine extraction transfer rate in Coptis chinensis is low and it is easy to react with other ingredients, resulting in low content of berberine and other ingredients in the drug, strong fluidity and hygroscopicity of the total mixture, thereby reducing the quality and stability of the drug.

[0007] To achieve the above object, the present invention adopts the following technical scheme: a stomach-soothing and analgesic composition capsule, wherein the medicinal raw materials include 80-120 parts of coptis root, 50-70 parts of amomum villosum, 80-120 parts of bupleurum root, 80-120 parts of dandelion, 80-120 parts of corydalis root, 40-60 parts of evodia rutaecarpa, 80-120 parts of rhubarb, 80-120 parts of costus root and 25-35 parts of clove;

[0008] The medicinal raw materials are crushed, extracted by percolation with an acidic ethanol solution, the upper volatile oil in the percolation liquid is separated and a volatile oil inclusion compound is prepared; the lower oil-free percolation liquid in the percolation liquid is alkalized and the solid-liquid separation is performed to obtain a precipitate and a filtrate; the precipitate is dried and then crushed to obtain a first medicinal powder; the filtrate is concentrated, dried and crushed to obtain a second medicinal powder; the first medicinal powder, the volatile oil inclusion compound and the second medicinal powder are mixed and filled into capsules to obtain stomach-soothing and analgesic composition capsules.

[0009] The principles and advantages of this solution are:

[0010] In this scheme, the medicinal raw materials are extracted by percolation under an acidic ethanol solution of appropriate acidity and concentration to extract the medicinal ingredients of the medicinal materials. The percolation liquid is separated from the volatile oil and a cyclodextrin inclusion compound is prepared with the volatile oil (the percolation liquid needs to be concentrated. If the volatile oil is not separated, the volatile oil in the percolation liquid will be lost due to heating and concentration, reducing the efficacy of the finished product). The de-oiled percolation liquid is then alkalized and allowed to stand to precipitate berberine and other insoluble substances under weak alkaline conditions (to prevent berberine from having a strong compatibility reaction in subsequent concentration, thereby improving the quality of the product), and the precipitate is dried and crushed to obtain the first medicinal powder; the filtrate is further concentrated, conventionally dried, and crushed to prepare a dry paste powder (also called the second medicinal powder), and the above two medicinal powders and the volatile oil cyclodextrin inclusion compound are combined to fill and prepare capsules. Under this process condition, the total material basis remains unchanged. The percolation extraction of acidic ethanol and simple process control solve the problems of drug component extraction transfer rate and compatibility reaction, greatly improving the quality of the product. In particular, the berberine hydrochloride extraction transfer rate effect is solved. Different types of active ingredients in the medicinal materials are processed in different steps and processes, effectively increasing the content of each active ingredient in the finished product, thereby improving the quality and efficacy of the finished product. Specifically, the present invention first separates the volatile oil from the percolation liquid and forms a cyclodextrin inclusion complex by encapsulating it with cyclodextrin, thereby effectively increasing the stability of the volatile oil and facilitating its stable transfer to the finished product to exert its medicinal effect; then, berberine and other weakly alkaline insoluble components are separated by alkali precipitation at low temperature, and the other components are then prepared into dry paste powder by conventional concentration and drying methods, thereby preventing berberine from reacting strongly with other components by conventional concentration and drying methods, thereby greatly increasing the content of medicinal components in the finished product; the process also unexpectedly found that the spots of thin layer identification (including coptis root, clove, rhubarb, evodia rutaecarpa and corydalis) were significantly larger than the spots of thin layer identification by the existing process, indicating that the transfer rate of these components has also been greatly improved; furthermore, the first drug powder obtained by phase separation, alkali precipitation, drying and pulverization in the process has a good flow-aiding effect and hygroscopic sealing effect, thereby improving the fluidity of the total mixture and greatly reducing the hygroscopicity, thereby solving the problems of fluidity and hygroscopicity of the total mixture in the process, and solving the problem of large differences in capsule filling amount due to poor fluidity and rapid hygroscopicity in the process.

[0011] According to the applicant's test, the berberine hydrochloride content in the capsules prepared by this scheme is as high as 18.9 mg / capsule, which is significantly higher than the minimum standard of berberine hydrochloride content in the national drug standard for Hewei Zhitong Capsules (standard number WS-5307-(B-0307)-2002) (berberine hydrochloride is not less than 6 mg / capsule), thereby effectively improving the quality and efficacy of the drug. Secondly, this scheme adopts the method of percolation extraction and alkali precipitation, and no large-scale energy is required in the preparation stage. The preparation method is green and environmentally friendly, and the production efficiency is greatly improved, which greatly reduces the production cost. In addition, the process has simple production conditions and strong practicality, and the total mixture produced has good fluidity and low moisture absorption rate. The material is smoothly transported on the production line, which helps to improve the production efficiency of large-scale preparation.

[0012] This solution also provides a large-scale preparation method of a stomach-soothing and analgesic composition capsule, comprising the following steps:

[0013] S1: preparing a percolation liquid: mixing coptis root, evodia rutaecarpa, yanhusuo, costusroot, clove, rhubarb, bupleurum root, dandelion and amomum villosum, crushing the mixture, and then extracting the mixture by percolation with acidic ethanol to obtain a percolation liquid;

[0014] S2 Preparation of volatile oil inclusion compound: the percolate is phase-separated to obtain an upper layer of volatile oil and a lower layer of de-oiled percolate, the upper layer of volatile oil, ß-cyclodextrin and water are mixed and dried to obtain a volatile oil inclusion compound;

[0015] S3 Preparation of the first medicinal powder: alkalizing the deoiled percolate, separating the solid and the liquid after standing, filtering to obtain a precipitate and a filtrate; drying and pulverizing the precipitate to obtain the first medicinal powder;

[0016] S4: preparing the second medicinal powder: the filtrate is concentrated to obtain an ointment, and the ointment is dried and crushed to obtain a second medicinal powder;

[0017] S5 Preparation of the total mixture: taking the first drug powder, the volatile oil inclusion compound and the second drug powder and mixing them to obtain the total mixture;

[0018] S6 filling into finished medicine: filling the total mixture into capsules to obtain stomach-soothing and analgesic composition capsules.

[0019] Beneficial effects: This solution solves the problem of berberine extraction transfer rate and effectively avoids the compatibility reaction between berberine and other components (such as flavonoids in Evodia rutaecarpa) during the concentration and drying process by percolating the raw materials of medicinal materials under acidic conditions and precipitating them with alkali to preferentially separate berberine from the percolation liquid, thereby effectively increasing the content of berberine in the product and improving the product quality and efficacy. The applicant found through experiments that the berberine content in the finished product obtained by using other extraction methods (such as Comparative Examples 1-2) and directly concentrating the percolation liquid after percolation extraction (such as Comparative Example 8) was reduced, and a capsule product with a higher berberine content could not be obtained, thereby reducing the quality of the capsule product.

[0020] Preferably, in S1, the medicinal material raw material is crushed into 16-20 mesh medicinal material coarse powder, and then subjected to percolation extraction.

[0021] Beneficial effects: The use of the above-mentioned coarse and fine particle sizes of medicinal raw materials can effectively improve the percolation extraction effect and improve the product quality. The applicant has found through experiments that during percolation extraction, using too fine medicinal raw materials is easy to block the gaps and hinder the passage of solvents; while using too coarse medicinal raw materials will reduce the percolation extraction effect, reduce the content of effective ingredients in the product, and thus reduce the product quality.

[0022] Preferably, in S1, the percolation extraction method is: using an acidic ethanol solution 2 to 3 times the total mass of the medicinal material raw material to wet the medicinal material coarse powder to obtain a wetted material; the wetted material is placed in a sealed manner for 3 to 4 hours; then the acidic ethanol solution is added to submerge the wetted material after placement; percolation extraction is performed at a rate of 1 to 3 ml / min / kg of medicinal material, and a percolation liquid of 32 to 40 times the total mass of the medicinal material is collected.

[0023] Beneficial effect: The above-mentioned percolation extraction parameter setting can significantly increase the berberine content in the product. The applicant found in the experiment that when the submerged standing time is short, berberine reacts less with hydrochloric acid to form berberine hydrochloride which is insoluble in water, thereby reducing the extraction effect of berberine; and when the percolation extraction speed is too fast or the percolation liquid is collected too little, it is easy to cause the content of effective ingredients in the percolation liquid to be low and reduce the product quality. When the percolation extraction speed is too slow or the percolation liquid is collected too much, the content of medicinal ingredients in the percolation liquid is not greatly increased, but the extraction efficiency is significantly reduced, thereby affecting the overall production efficiency of the product.

[0024] Preferably, in the acidic ethanol solution, the volume concentration of ethanol is 60% to 75%, and the concentration of hydrochloric acid is 0.5 to 1 mol / L.

[0025] Beneficial effects: The use of the above-mentioned concentrations of ethanol and hydrochloric acid can effectively increase the content of berberine in the powder and improve the product quality. The use of organic weak acid (such as comparative example 3), too high a hydrochloric acid content or no hydrochloric acid (such as comparative examples 4-5), and too high or too low an ethanol concentration (such as comparative examples 6-7) will reduce the content of berberine in the percolate obtained by these treatments, and it is impossible to obtain a capsule product with a higher berberine content, thereby reducing the quality of the capsule product.

[0026] Preferably, in S3, the percolation liquid is alkaline treated by adjusting the pH value of the percolation liquid to 7.5-8.0; then standing for more than 12 hours, filtering to obtain a filter cake; drying the filter cake at 40-60°C until the moisture content is less than 5.0%; and crushing and passing through an 80-mesh sieve after drying to obtain a first drug powder.

[0027] Beneficial effect: The first drug powder obtained by this step has good lubricity and strong hydrophobicity. After mixing with other drug powders, it has strong water sealing and flow-aiding effects, ensuring smooth capsule filling and small filling volume differences. Using too high alkaline precipitation pH (such as comparative example 9) and too low alkaline precipitation pH (such as comparative example 10) will lead to a decrease in the content of berberine in the finished product, and a capsule product with a higher berberine content can be obtained, thereby reducing the quality of the capsule product. The inventor analyzed that the reason is that the alkaline precipitation step in this scheme is mainly convenient for quickly separating and precipitating weakly alkaline medicinal ingredients such as berberine, shortening the time for it to react with other components, thereby increasing its content in the finished product. However, the alkaline precipitation pH in comparative examples 9-10 is not suitable, which reduces the berberine content in the first drug powder obtained by alkaline precipitation; the berberine that is not precipitated remains in the filtrate, and reacts with other medicinal ingredients in the subsequent concentration and drying process, thereby reducing the overall content of berberine in the finished product.

[0028] Preferably, in S3, a 0.1 mol / L sodium hydroxide solution is used to adjust the pH value of the percolate.

[0029] Beneficial effects: The pH value of the percolate is adjusted by using the sodium hydroxide solution of the above concentration. On the one hand, the pH value of the percolate changes slowly, which is convenient for accurately controlling the pH value of the percolate. On the other hand, a lower concentration of sodium hydroxide is added to the percolate to slowly precipitate weakly alkaline insoluble components such as berberine, thereby avoiding the situation where a higher concentration of sodium hydroxide is added to the percolate and the precipitation is too fast, resulting in the precipitation enveloping other components and reacting with berberine, thereby increasing the berberine content in the product and improving the product quality.

[0030] Preferably, in S4, the filtrate is decompressed to recover ethanol, and is further concentrated to an ointment with a relative density of 1.2-1.25 at 60°C, and then dried under reduced pressure at a vacuum degree of more than -0.09 MPa and 60-70°C, and the dried product is crushed and passed through a 60-80 mesh sieve to obtain a second medicinal powder.

[0031] Beneficial effects: The above drying conditions are used to dry the concentrated ointment of the filtrate. On the one hand, the drying temperature required is low and the drying speed is fast, which is convenient for improving the overall production efficiency of the product; on the other hand, vacuum drying reduces the adverse effects of air on the medicinal ingredients in the product, especially the heat-sensitive or high-temperature easily oxidized ingredients, effectively improving the content and quality of the active ingredients in the product; furthermore, the material obtained by drying in this scheme is in a crisp sponge state and is easy to crush to obtain a second drug powder with good fluidity, thereby reducing the difference in product filling amount and improving product quality.

[0032] Preferably, in S5, the first drug powder, the volatile oil cyclodextrin inclusion compound and the second drug powder are mixed for 5 to 10 minutes.

[0033] Beneficial effects: The first drug powder can be used as a lubricant and a hygroscopic protective agent without adding other excipients, which can effectively ensure that the content of the active ingredient in the total mixture is at a high level, and significantly improve the fluidity of the total mixture and significantly reduce the moisture absorption, which is convenient for smooth transmission during the production process and improves production efficiency. At the same time, the total mixture has good fluidity, which solves the problem of large differences in filling volume in the capsule filling process caused by poor fluidity and strong hygroscopicity of the total mixture in the existing process. DETAILED DESCRIPTION

[0034] The present invention is further described in detail below in conjunction with the examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following examples and experimental examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used can be obtained from commercial channels. Unless otherwise specified, the technical means used in the following examples are conventional means well known to those skilled in the art.

[0035] Example 1

[0036] This scheme provides a stomach-soothing and analgesic composition capsule and a preparation method thereof. The raw material formula is shown in Table 1.

[0037] Table 1: Raw material formula of stomach-regulating and analgesic composition capsules

[0038]

[0039] This solution also provides a large-scale preparation method of a stomach-soothing and analgesic composition capsule, comprising the following steps:

[0040] S1: preparing percolation liquid: mixing coptis root, evodia rutaecarpa, yanhusuo, costusroot, clove, rhubarb, bupleurum, dandelion and amomum villosum, and grinding through a 16-20 mesh sieve to obtain crude powder of medicinal materials. The crude powder of medicinal materials is subjected to percolation extraction with acidic ethanol, and the specific process is as follows;

[0041] The above crude powder of medicinal materials is moistened with an acidic ethanol solution of 2 to 3 of the total mass of the medicinal material raw materials, and then the soaked crude powder of the medicinal materials (called wetted material) is taken out and placed in a percolation tank, and placed in a sealed state for 3 to 4 hours. Then, the acidic ethanol solution is added to submerge the wetted material, and the percolation extraction is performed at a rate of 1 to 3 ml / min / kg of medicinal materials. The percolation solvent is added at any time to submerge the medicinal materials, and the percolation liquid of 32 to 40 times the total amount of the medicinal materials is collected. Among them, the acidic ethanol solution refers to an ethanol solution containing 0.5 to 1 mol / L hydrochloric acid with a volume percentage of 60% to 75%.

[0042] Preparation of S2 volatile oil inclusion compound: The volatile oil in the upper layer of the percolate is separated by standing phase separation to obtain two parts, volatile oil and de-oiled percolate. The ingredients are included in a weight ratio of volatile oil: ß-cyclodextrin: purified water = 1:4:30, and dried to a moisture content of less than 5.0% to obtain the volatile oil inclusion compound.

[0043] S3 Preparation of the first drug powder: Add 0.1 mol / l sodium hydroxide solution to the deoiled percolate, adjust the pH value of the percolate to 7.5-8.0, let it stand for more than 12 hours, filter, and reserve the filtrate. Dry the filter cake in an oven at 40-60°C until the moisture content is less than 5.0%, and then grind it through an 80-mesh sieve to obtain the first drug powder.

[0044] Preparation of S4 second medicinal powder: the filtrate is subjected to conventional decompression to recover ethanol, and is further concentrated to an ointment with a relative density of 1.20~1.25 (60°C) at 60°C, and then dried under reduced pressure at 60~70°C (vacuum degree above -0.09MPa) until the moisture content is less than 5.0%, and then crushed and passed through an 80-mesh sieve to obtain the second medicinal powder.

[0045] Preparation of S5 total mixture: Take the first drug powder, the volatile oil inclusion compound and the second drug powder, mix them in a conventional three-dimensional motion mixer for 5 to 10 minutes to obtain the total mixture.

[0046] S6 Filling the finished drug: Fill the above-mentioned total mixture into capsules to obtain the stomach-regulating and analgesic composition capsules. As an example, a No. 0 hollow capsule is used, with a filling amount of 0.4 g / capsule and a filling amount range of 0.364 g / capsule to 0.436 g / capsule; check the filling amount difference every 30 minutes, take 10 capsules each time, remove the dust on the surface, and weigh them.

[0047] Example 2

[0048] This embodiment is basically the same as embodiment 1, wherein the raw material formula is:

[0049] 120 parts of coptis root, 70 parts of amomum villosum, 120 parts of bupleurum, 120 parts of dandelion, 120 parts of corydalis, 60 parts of evodia rutaecarpa, 120 parts of rhubarb, 120 parts of costusroot and 35 parts of cloves.

[0050] The preparation process is:

[0051] S1: preparing percolation liquid: mixing coptis root, evodia rutaecarpa, yanhusuo, costusroot, clove, rhubarb, bupleurum, dandelion and amomum villosum, and grinding through a 20-mesh sieve to obtain crude powder of medicinal materials. The crude powder of medicinal materials is subjected to percolation extraction with acidic ethanol, and the specific process is as follows;

[0052] The above crude medicinal material powder is moistened with an acidic ethanol solution of 2% of the total mass of the medicinal material raw materials, and then the soaked crude medicinal material powder (called wet material) is taken out and placed in a percolation tank, and sealed for 4 hours. Then, the acidic ethanol solution is added to submerge the wet material, and percolation extraction is performed at a rate of 3ml / min / kg of medicinal material. The percolation solvent is added at any time to submerge the medicinal material, and the percolation liquid of 40 times the total amount of the medicinal material is collected. Among them, the acidic ethanol solution refers to an ethanol solution containing 1mol / L hydrochloric acid with a volume percentage of 75%.

[0053] Preparation of S2 volatile oil inclusion compound: separate the volatile oil in the upper layer of the percolate, saturate it with the ingredients according to the weight ratio of volatile oil: ß-cyclodextrin: purified water = 1:4:30, and dry it to obtain the S2 volatile oil inclusion compound.

[0054] S3 Preparation of the first medicinal powder: Add 0.1 mol / l sodium hydroxide solution to the percolate, adjust the pH value of the percolate to 7.5, let it stand for more than 14 hours, filter, and reserve the filtrate. Dry the filter cake in a 60°C oven, and then crush it through an 80-mesh sieve to obtain the first medicinal powder.

[0055] Preparation of S4 second medicinal powder: the filtrate is subjected to conventional decompression to recover ethanol, and the ointment with a relative density greater than 1.20 (60°C) is further concentrated, and then dried under reduced pressure at 70°C (vacuum degree above -0.09MPa), and the dried product is crushed and passed through an 80-mesh sieve to obtain the second medicinal powder.

[0056] S5 Preparation of the total mixture: Preparation of the total mixture: Take the first drug powder, the volatile oil cyclodextrin inclusion compound and the second drug powder, mix them in a conventional three-dimensional motion mixer for 10 minutes to obtain the total mixture.

[0057] S6 filling into finished medicine: filling the total mixture into capsules to obtain stomach-soothing and analgesic composition capsules.

[0058] Example 3

[0059] This embodiment is basically the same as embodiment 1, wherein the raw material formula is:

[0060] 80 parts of coptis root, 50 parts of amomum villosum, 80 parts of bupleurum, 80 parts of dandelion, 80 parts of corydalis, 40 parts of evodia rutaecarpa, 80 parts of rhubarb, 80 parts of costusroot and 25 parts of cloves.

[0061] The preparation process is:

[0062] S1: preparing percolation liquid: mixing coptis root, evodia rutaecarpa, yanhusuo, costusroot, clove, rhubarb, bupleurum, dandelion and amomum villosum, and grinding through a 16-mesh sieve to obtain crude powder of medicinal materials. The crude powder of medicinal materials is subjected to percolation extraction with acidic ethanol, and the specific process is as follows;

[0063] The above crude medicinal material powder is moistened with an acidic ethanol solution of 2% of the total mass of the medicinal material raw materials, and then the soaked crude medicinal material powder (called wet material) is taken out and placed in a percolation tank, and sealed for 3 hours. Then, the acidic ethanol solution is added to submerge the wet material, and percolation extraction is performed at a rate of 1-3 ml / min / kg of medicinal material. The percolation solvent is added at any time to submerge the medicinal material, and the percolation liquid of 32 times the total amount of the medicinal material is collected. Among them, the acidic ethanol solution refers to an ethanol solution containing 0.5 mol / L hydrochloric acid with a volume percentage of 60%.

[0064] Preparation of S2 volatile oil inclusion compound: separate the volatile oil in the upper layer of the percolate, saturate it with the ingredients according to the weight ratio of volatile oil: ß-cyclodextrin: purified water = 1:4:30, and dry it to obtain the S2 volatile oil inclusion compound.

[0065] S3 Preparation of the first medicinal powder: Add 0.1 mol / l sodium hydroxide solution to the percolate, adjust the pH value of the percolate to 7.5, let it stand for more than 14 hours, filter, and reserve the filtrate. Dry the filter cake in a 60°C oven, and then crush it through an 80-mesh sieve to obtain the first medicinal powder.

[0066] Preparation of S4 second medicinal powder: the filtrate is subjected to conventional decompression to recover ethanol, and the ointment with a relative density greater than 1.25 (60°C) is further concentrated, and then dried under reduced pressure at 70°C (vacuum degree above -0.09MPa), and the dried product is crushed and passed through an 80-mesh sieve to obtain the second medicinal powder.

[0067] Preparation of S5 total mixture: take the first drug powder, the volatile oil cyclodextrin inclusion compound and the second drug powder, mix them in a conventional three-dimensional motion mixer for 10 minutes to obtain the total mixture.

[0068] S6 filling into finished medicine: filling the total mixture into capsules to obtain stomach-soothing and analgesic composition capsules.

[0069] Comparative Example 1

[0070] This comparative example adopts the conventional decoction process of the prior art to prepare the stomach-regulating analgesic capsule (refer to patent CN1056078C, a stomach-regulating analgesic drug), and the specific operation process is as follows:

[0071] The raw material formula is the same as that of Example 2. First, four medicinal materials of Rhizoma Coptidis, Fructus Evodiae, Radix Aucklandiae, and Rhizoma Corydalis are selected, and after being immersed in 0.5% acetic acid solution for 45 minutes, they are heated and extracted twice, the first time for 2 hours and the second time for 1.5 hours, and the liquid is filtered and concentrated under reduced pressure to obtain a thick paste 1 (relative density 1.30-1.35, 80°C). Two medicinal materials of Clove and Fructus Amomi are selected, and they are heated and decocted twice, the first time for 2 hours and the second time for 1.5 hours, and volatile oil is collected, and the filtrate is combined, and the volatile oil is collected at the same time, and the oil is dehydrated and encapsulated with β-cyclodextrin for standby use. Three medicinal materials of Radix Bupleuri, Herba Taraxaci, and Radix Rhei are selected, and they are immersed in deionized water for 45 minutes, and they are heated and decocted twice, the first time for 2 hours and the second time for 1.5 hours, and the filtrate is combined, mixed with the extraction filtrate of Clove and Fructus Amomi, and concentrated under reduced pressure to obtain a thick paste 2 (relative density 1.30-1.35, 80°C). Add appropriate amount of starch to the two groups of thick pastes and stir evenly, vacuum dry (50°C), crush, and pass through a 40-mesh sieve to obtain dry paste powder. Mix the dry paste powder, β-cyclodextrin inclusion compound and appropriate amount of starch to obtain a total mixture, and fill capsules to obtain the mixture.

[0072] Comparative Example 2

[0073] This comparative example adopts the method previously patented by our company to prepare the Hewei Zhitong Capsules (refer to Example 1 of the patent CN115137706A, an industrialized preparation method of Hewei Zhitong Capsules, the raw material formula is the same as Example 2 of this patent application), and the general operation process is as follows:

[0074] Extraction liquid I: Take glycerol solution, moisten and ferment the coptis powder with the glycerol solution to obtain coptis moistened powder, mix the coptis moistened powder, Evodia rutaecarpa, Corydalis yanhusuo and costusroot, and perform decocting and extraction treatment to obtain Group I liquid.

[0075] Extraction of medicinal solution II and volatile oil: After decocting and extracting cloves and Amomum villosum, medicinal solution and volatile oil are obtained, and after extracting rhubarb, bupleurum and dandelion, they are incorporated into the medicinal solution extracted from cloves and Amomum villosum to obtain Group II medicinal solution.

[0076] Concentration: The drug solution of group I and the drug solution of group II are concentrated and collected into extracts to obtain extracts I and II.

[0077] Volatile oil inclusion and drying: the volatile oil and β-cyclodextrin are mixed and filtered to obtain a filtered inclusion compound, and the filtered inclusion compound is dried to obtain a volatile oil inclusion compound.

[0078] Extract drying: extract I, extract II and corn starch are placed in a container, stirred and mixed, and dried to obtain the Hewei Zhitong Capsule dry paste.

[0079] Total mixing: crush the dry paste of Hewei Zhitong Capsules to obtain dry paste powder, sieve the dry paste powder, volatile oil inclusion compound and corn starch respectively, and then mix the sieved dry paste powder, volatile oil inclusion compound and corn starch in turn to obtain Hewei Zhitong Capsules powder.

[0080] Capsule filling: Take a hollow capsule, and fill the Hewei Zhitong Capsule powder into the hollow capsule to obtain the Hewei Zhitong Capsule.

[0081] Comparative Example 3

[0082] This comparative example is basically the same as Example 2, except that in S1, the acidic ethanol solution is an ethanol solution containing 0.5% acetic acid in a volume percentage of 75%.

[0083] In this comparative example, acetic acid (organic weak acid) was used instead of hydrochloric acid to increase the solubility of berberine, but the effect was not obvious, and the berberine content in the obtained finished product was low, which seriously affected the quality and efficacy of the finished product.

[0084] Comparative Example 4

[0085] This comparative example is basically the same as Example 2, except that in S1, the acidic ethanol solution is an ethanol solution containing 1.5 mol / L hydrochloric acid in a volume percentage of 75%.

[0086] In this comparative example, the excessively high hydrochloric acid concentration not only fails to further increase the berberine content in the finished product, but reduces the berberine content in the finished product; the inventors analyzed that the reason is that after the acidity of the extract exceeds a certain value, the solubility of berberine becomes worse, which ultimately leads to a decrease in the berberine content in the percolate.

[0087] Comparative Example 5

[0088] This comparative example is basically the same as Example 2, except that in S1, an ethanol solution with a volume percentage of 75% is used instead of an acidic ethanol solution.

[0089] In this comparative example, hydrochloric acid was not used during the percolation extraction, and the berberine content in the obtained finished product was significantly reduced, resulting in a lower efficacy. The inventors analyzed that the reason was that hydrochloric acid was not used to dissolve the berberine during the percolation process, resulting in a smaller amount of berberine dissolved in the percolation liquid, thereby significantly reducing the berberine content in the finished product, thereby reducing the efficacy of the finished product.

[0090] Comparative Example 6

[0091] This comparative example is basically the same as Example 2, except that in S1, the acidic ethanol solution is an ethanol solution containing 1 mol / L hydrochloric acid with a volume percentage of 80%.

[0092] In this comparative example, an ethanol solution of too high a concentration was used to perform percolation extraction on the medicinal ingredients in the medicinal materials, and the berberine content in the obtained finished product did not continue to increase. Therefore, the use of an 80% concentration ethanol solution would only increase the cost of percolation extraction, and would not improve the berberine content in the finished product or the efficacy of the finished product.

[0093] Comparative Example 7

[0094] This comparative example is basically the same as Example 2, except that in S1, the acidic ethanol solution is an ethanol solution containing 1 mol / L hydrochloric acid in a volume percentage of 50%.

[0095] In this comparative example, the medicinal ingredients in the medicinal materials were extracted by percolation using an ethanol solution of too low a concentration, and the content of berberine in the obtained finished product was significantly reduced, thereby reducing the quality and efficacy of the finished product.

[0096] Comparative Example 8

[0097] This comparative example is basically the same as Example 2, except that S2 and S3 are omitted, and the percolate in S1 is directly concentrated, dried and crushed into powder, and the powder is mixed in a conventional three-dimensional motion mixer to obtain a total mixture.

[0098] In this comparative example, the berberine in the percolate was not separated and dried in steps, so that the berberine reacted with other ingredients during the drying process, thereby reducing the berberine content in the finished product; and in this comparative example, the volatile oil and other medicinal ingredients were dried together, resulting in a higher angle of repose and moisture absorption rate of the finished product, thereby reducing the fluidity of the total mixture and further reducing the large-scale production efficiency of the product.

[0099] Comparative Example 9

[0100] This comparative example is basically the same as Example 2, except that in S3, the pH value of the percolate is adjusted to 8.5.

[0101] Comparative Example 10

[0102] This comparative example is basically the same as Example 2, except that in S3, the pH value of the percolate is adjusted to 7.0.

[0103] In addition, the inventors have also tried to omit the step of adding alkali to precipitate in S3, directly concentrate the deoiled percolate in S2, dry it into a dry paste and grind it into a powder, and mix the powder with the volatile oil inclusion compound to obtain a total mixture. This process step does not separate the first powder and the second powder, resulting in poor fluidity and hygroscopicity of the total mixture. The experimental results of the angle of repose and the 24h moisture absorption rate of the total mixture at RH55% are similar to those of Comparative Example 8. In addition, since the deoiled percolate is directly concentrated and dried, berberine hydrochloride is easily reacted with other ingredients in the above environment, resulting in the content of berberine hydrochloride in the finished product being lower than that of Example 2.

[0104] Experimental Example 1: Quality Testing of Examples and Comparative Examples

[0105] The quality inspection of the embodiments and comparative examples was carried out with reference to the relevant provisions in the National Drug Standard for Hewei Zhitong Capsules (Standard No. WS-5307-(B-0307)-2002), which specifically includes the following contents:

[0106] [Properties] This product is a hard capsule, the contents are brown to brown granules or powder; it has a light fragrance and a bitter taste.

[0107]

Detection of berberine hydrochloride

[0108] Determined according to the high performance liquid chromatography method (General Chapter 0512) in the 2020 edition of the "Chinese Pharmacopoeia".

[0109] (1) Chromatographic conditions and system suitability test: Octadecylsilane bonded silica gel was used as the filler; methanol-acetonitrile-water (50:20:30) (containing 0.1% sodium dodecyl sulfate and 0.1% phosphoric acid solution) was used as the mobile phase; the detection wavelength was 265 nm, and the theoretical plate number calculated based on the berberine hydrochloride peak should be no less than 5000.

[0110] (2) Preparation of reference solution: Take an appropriate amount of berberine hydrochloride reference substance, accurately weigh it, and add 60% methanol to make a solution containing 5 μg per 1 ml.

[0111] (3) Preparation of test solution: Take the contents of the product under the item of filling volume difference, grind it into powder, take out 0.25 g, weigh it accurately, put it in a stoppered conical flask, add 50 ml of 60% methanol accurately, weigh it, treat it ultrasonically (power 200 W, frequency 40 kHz) for 30 minutes, let it cool, weigh it again, make up the lost weight with 60% methanol, shake it well, filter it, and take the filtrate to obtain the product.

[0112] (4) Determination method: Accurately pipette 20 μl of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0113] [Blend Flowability Test] Test the angle of repose of the blend. The angle of repose characterizes the flowability of the blend. The smaller the angle of repose, the more ideal the blend flowability, the smoother the material transmission on the production line, and the better the production efficiency.

[0114] [Hygroscopicity test] The hygroscopicity of the total mixture after being placed for 24 hours under RH55% conditions is tested. The moisture absorption rate is expressed by the following calculation formula: Moisture absorption rate = (m1-m0) / m0×100%

[0115] Wherein, m0 is the weight of the total mixture before placement; m1 is the weight of the total mixture after being placed at a relative humidity of RH55% for 24 hours.

[0116] The test results of the stomach-regulating and analgesic composition capsules obtained in the examples and comparative examples are shown in the following table (Table 2):

[0117] Table 2: Test results of the embodiments and comparative examples with reference to quality standards

[0118] Detection indicators Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Capsule filling status Good fluidity and small difference in filling volume Good fluidity and small difference in filling volume Poor fluidity and large differences in filling volume Poor fluidity and large differences in filling volume Poor fluidity and large differences in filling volume Good fluidity and small difference in filling volume Characteristics Brown granules or powder Brown granules or powder Brown granules or powder Brown granules or powder Brown granules or powder Brown granules or powder Identification of Coptis chinensis Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Clove identification Spots of the same color as the control medicinal material and the reference substance appear at the same position Spots of the same color appear at the same position as the control medicinal material and the reference substance Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Identification of Evodia rutaecarpa Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small Identification of Rhubarb There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. Identification of Corydalis Fluorescent spots of the same color as those of the control medicinal materials and reference substances appear at the same position Fluorescent spots of the same color as those of the control medicinal materials and reference substances appear at the same position Fluorescent spots of the same color as those of the control medicinal materials and reference substances appear at the same position, and the spots are relatively small Fluorescent spots of the same color appear at the same position as the control medicinal materials and reference substances, and the spots are relatively small Fluorescent spots of the same color as those of the control medicinal materials and reference substances appear at the same position, and the spots are relatively small Fluorescent spots of the same color appear at the same position as the control medicinal materials and reference substances, and the spots are relatively small Berberine hydrochloride content (not less than 6.0 mg / capsule) 18.9 18.2 4.5 7.9 6.3 8.5 Flowability (angle of repose) 38.2° 38.6° 43.2° 44.2° 41.2° 38.5° 24h moisture absorption rate of total mixture at RH55% (%) 2.5 2.4 8.1 8.5 5.6 3.8 Detection indicators Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Comparative Example 9 Comparative Example 10 Capsule filling status Good fluidity and small difference in filling volume Good fluidity and small difference in filling volume Good fluidity and small difference in filling volume Poor fluidity and large differences in filling volume The fluidity is slightly poor, and the filling volume difference is slightly large The fluidity is slightly poor, and the filling volume difference is slightly large Properties: Brown granules or powder Brown granules or powder Brown granules or powder Brown granules or powder Brown granules or powder Brown granules or powder Identification of Coptis chinensis Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Fluorescent spots of the same color as the control medicinal material at the same position Clove identification Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Spots of the same color appear at the same position as the control medicinal material and the reference substance, and the spots are relatively small Identification of Evodia rutaecarpa The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small The same color fluorescent spots are shown at the same position as the control medicinal material, and the spots are relatively small Identification of Rhubarb There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. There are 5 orange-yellow spots at the same position as the control medicinal material. After ammonia fumigation, the spots turn red and are relatively smaller. Identification of Corydalis Fluorescent spots of the same color as those of the control medicinal materials and reference substances appear at the same position Fluorescent spots of the same color as those of the control medicinal materials and reference substances appear at the same position Fluorescent spots of the same color as those of the control medicinal materials and reference substances appear at the same position Fluorescent spots of the same color appear at the same position as the control medicinal materials and reference substances, and the spots are relatively small Fluorescent spots of the same color appear at the same position as the control medicinal materials and reference substances, and the spots are relatively small Fluorescent spots of the same color appear at the same position as the control medicinal materials and reference substances, and the spots are relatively small Berberine hydrochloride content (not less than 6.0 mg / capsule) 7.6 18.2 13.1 15.2 15.3 15.8 Flowability (angle of repose) 44.9° 38.5° 38.4° 44.6° 39.6° 38.8° 24h moisture absorption rate of total mixture at RH55% (%) 3.6 3.9 3.7 8.9 4.6 4.7

[0119] The inventors encountered the following technical difficulties in producing the gastric analgesic composition capsules: the content of the characteristic ingredient in the capsules was low, resulting in low capsule quality; and the medicinal powder in the finished product had poor fluidity and strong hygroscopicity (easy to absorb moisture), and the easy moisture absorption of the medicinal powder further hindered the fluidity of the powder (total mixture), all of which would lead to the inability to carry out large-scale production smoothly; and the easy moisture absorption of the drug would also affect the quality of the product after long-term storage or storage in a humid environment.

[0120] The inventor explored the reasons for the above phenomenon and tried various means to solve the above problems. Finally, it was found that the reasons for the unsatisfactory content of the characteristic components (such as berberine hydrochloride) in the powder are as follows: the method and conditions of extracting medicinal materials, and the method of preparing the powder with the marker. Referring to Table 2 and the embodiments and comparative examples, in terms of the method of extracting medicinal materials, the traditional extraction method (Comparative Example 1 and Comparative Example 2) was used to obtain the powder and fill the capsules. The berberine hydrochloride content in the finished product was low, and the fluidity of the total mixture used for filling the capsules was poor, which reduced the efficiency of the large-scale production of the product; the hygroscopicity of the total mixture used for filling the capsules increased, affecting the long-term storage of the finished product. Although the method of percolation extraction with an acidic ethanol solution effectively assisted in dissolving berberine and increased the transfer rate of the useful components in the medicinal materials to the percolation solution, the content of berberine hydrochloride in the finished product can be increased to a certain extent, and the efficacy of the finished product can be improved. However, if the appropriate medicinal material extraction conditions are not selected (specifically, such as selecting the appropriate acid, acid concentration, drying method of the active ingredient in the percolate, etc.), the berberine hydrochloride content in the finished product is still reduced. For example, the inventor tried to use organic weak acid (such as comparative example 3), too high hydrochloric acid content or no hydrochloric acid (such as comparative examples 4-5), too high or too low ethanol concentration (such as comparative examples 6-7), too high or too low alkaline precipitation pH (such as comparative examples 9-10), and the finished products prepared by these methods could not obtain a higher berberine hydrochloride content, thereby reducing the quality and efficacy of the finished product.

[0121] Comparing Example 2 and Example 3 with Comparative Example 1 and Comparative Example 2, it can be seen that the use of appropriate percolation extraction can reduce the compatibility reaction between materials and increase the extraction efficiency of the functional components, so the preparation process of this scheme can greatly increase the content of berberine hydrochloride in the finished product. In addition, the use of an appropriate preparation process can simultaneously improve the fluidity and moisture resistance of the total mixture. In addition, the type of acid (such as Comparative Example 3) and the amount (such as Comparative Examples 4-7) in the percolation extraction will also significantly affect the extraction efficiency of the functional components.

[0122] Comparative Example 8 did not separate the percolate into volatile oil, the first drug powder and the second drug powder. The pH value used in the process of separating the first drug powder and the second drug powder in Comparative Examples 9 and 10 was not appropriate, which would lead to poor fluidity and hygroscopicity of the total mixture. In addition, the inventor tried to omit the alkali precipitation step of S3, which would also lead to poor fluidity and hygroscopicity of the total mixture. This shows that: in this scheme, the first drug powder can be used as a lubricant and hygroscopic protective agent, and no other excipients are added, which can effectively ensure that the content of the active ingredient in the total mixture is at a high level, and significantly improve the fluidity of the total mixture and significantly reduce the hygroscopicity, which is convenient for smooth transmission in the production process and improves production efficiency; at the same time, the total mixture has good fluidity, which solves the problem of large differences in the amount of filling in the capsule filling process caused by the poor fluidity and strong hygroscopicity of the total mixture in the existing process.

[0123] In summary, Examples 2 to 3 prove that the use of acidic ethanol solution for percolation extraction can effectively improve the dissolution and extraction effect of medicinal ingredients in medicinal materials. This scheme adopts the method of alkali precipitation of weak alkaline components such as berberine and drying the remaining effective components to obtain powder or inclusion complexes in steps, which effectively prepares the powder according to the characteristics of different medicinal ingredients, thereby effectively improving the content and stability of each medicinal ingredient in the finished product, and thus effectively improving the efficacy of the finished product; in addition, the various medicinal ingredients are separated in steps, which effectively improves the fluidity of the powder and reduces the hygroscopicity of the powder, which is convenient for large-scale production of capsules to improve production efficiency, reduce the difference in loading, and further improve product quality. In addition, the berberine hydrochloride content in the capsules prepared by this scheme is as high as 18.9 mg / capsule, which is significantly higher than the minimum standard of berberine hydrochloride content in the national drug standard for Hewei Zhitong Capsules (standard number WS-5307-(B-0307)-2002) (berberine hydrochloride is not less than 6 mg / capsule), thereby effectively improving the quality and efficacy of the drug. Finally, the drugs in this scheme only contain cyclodextrin and medicinal extracts, and the amount of medicinal excipients in the drugs is reduced, thereby significantly reducing the risk of stress reactions in patients when taking the drugs and improving the safety of the drugs.

[0124] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions and / or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A stomach-soothing and analgesic composition capsule, characterized in that: The medicinal raw materials are composed of 80-120 parts of coptis root, 50-70 parts of amomum villosum, 80-120 parts of bupleurum root, 80-120 parts of dandelion, 80-120 parts of corydalis, 40-60 parts of evodia rutaecarpa, 80-120 parts of rhubarb, 80-120 parts of costusroot and 25-35 parts of cloves by weight. It is prepared by the following method: S1. Preparing percolation liquid: mixing coptis root, evodia rutaecarpa, yanhusuo, costusroot, clove, rhubarb, bupleurum root, dandelion and amomum villosum, crushing and then extracting by acidic ethanol percolation to obtain percolation liquid; the percolation extraction method is: using an acidic ethanol solution of 2 to 3 of the total mass of the medicinal raw materials to wet the crude powder of the medicinal materials to obtain a wetted material; placing the wetted material in a sealed container for 3 to 4 hours; then adding the acidic ethanol solution to submerge the wetted material after placement; percolating and extracting at a speed of 1 to 3 ml / min / kg of medicinal materials, and collecting a percolation liquid of 32 to 40 times the total mass of the medicinal materials; in the acidic ethanol solution, the volume concentration of ethanol is 60% to 75%, and the concentration of hydrochloric acid is 0.5 to 1 mol / L; S2 Preparation of volatile oil inclusion compound: the percolate is phase-separated to obtain an upper layer of volatile oil and a lower layer of de-oiled percolate, the upper layer of volatile oil, ß-cyclodextrin and water are mixed and dried to obtain a volatile oil inclusion compound; S3 Preparation of the first drug powder: alkalinizing the deoiled percolate to adjust the pH value of the percolate to 7.5-8.0; then standing for more than 12 hours, filtering to obtain a filter cake; drying the filter cake at 40-60° C. until the moisture content is less than 5.0%, and then crushing and passing through an 80-mesh sieve to obtain the first drug powder; S4 Preparation of the second medicinal powder: the filtrate is subjected to reduced pressure to recover ethanol, and is further concentrated to an ointment having a relative density of 1.20 to 1.25 at 60°C, and then dried under reduced pressure at a vacuum degree of more than -0.09 MPa and 60 to 70°C, and the dried product is crushed and passed through a 60 to 80 mesh sieve to obtain a second medicinal powder; S5 Preparation of the total mixture: taking the first drug powder, the volatile oil inclusion compound and the second drug powder and mixing them to obtain the total mixture; S6 filling into finished medicine: filling the total mixture into capsules to obtain stomach-soothing and analgesic composition capsules.

2. The stomach-soothing and analgesic composition capsule according to claim 1, characterized in that: In S1, the medicinal material raw material is crushed into 16-20 mesh medicinal material coarse powder, and then subjected to percolation extraction.

3. The stomach-soothing and analgesic composition capsule according to claim 1, characterized in that: In S2, the weight ratio of volatile oil, ß-cyclodextrin and water was 1:4:

30.

4. The stomach-soothing and analgesic composition capsule according to claim 1, characterized in that: In S3, the pH value of the percolate is adjusted using a 0.1 mol / l sodium hydroxide solution.

5. The stomach-soothing and analgesic composition capsule according to claim 1, characterized in that: In S5, the first drug powder, the volatile oil inclusion compound and the second drug powder are mixed for 5 to 10 minutes.

Images