Traditional Chinese medicine composition of netmeg Sishen pill and preparation method of traditional Chinese medicine composition

Abstract

The invention discloses a nutmeg Sishen pill traditional Chinese medicine composition and a preparation method thereof, and particularly relates to the technical field of traditional Chinese medicine compositions.The nutmeg Sishen pill traditional Chinese medicine composition is prepared from 30-50 parts of nutmeg extract, 40-60 parts of fructus psoraleae micro powder, 20-30 parts of schisandra chinensis polysaccharide compound, 10-20 parts of fructus evodiae volatile oil clathrate compound, 10-15 parts of modified starch and 5-8 parts of low-substituted hydroxy propyl cellulose. Through cooperation of the formula and the method, the effectiveness, stability and safety of the traditional Chinese medicine composition can be improved, and better treatment experience and rehabilitation effect are brought to patients.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine compositions, and more particularly to a Roukou Si Shen Wan traditional Chinese medicine composition and a preparation method thereof. Background Art

[0002] In the field of traditional Chinese medicine, drugs for treating digestive system diseases have always been a research focus. Roukou Si Shen Wan, as a classic prescription with certain efficacy in treating digestive system diseases such as diarrhea, is widely used.

[0003] Traditional Roukou Sishen Pills are often prepared according to ancient recipes, and their ingredients typically include psoralea corylifolia, costus root, nutmeg, poppy shell, Terminalia chebula fruit, white peony root, dried ginger, Atractylodes macrocephala, and Evodia rutaecarpa. However, traditional formulas have certain limitations in terms of the source of medicinal materials, extraction of active ingredients, and formulation stability. For example:

[0004] 1. From the perspective of the source of medicinal materials, the soil, climate, light and other conditions in different production areas vary significantly, resulting in uneven quality of medicinal materials. Take nutmeg as an example. It grows in tropical regions. The changes in the production environment will affect the content of active ingredients such as myristicin and safrole, thereby causing fluctuations in the efficacy of the medicine.

[0005] 2. Some traditional formulas contain poppy shells. While these have antidiarrheal properties, they also contain alkaloids such as morphine and codeine. Long-term use can easily lead to drug dependence. Once the drug is discontinued, it can trigger withdrawal symptoms, causing serious damage to the patient's physical and mental health. Furthermore, as people's expectations for drug safety and efficacy continue to rise, the stability shortcomings of traditional Roukou Si Shen Wan have become increasingly apparent.

[0006] 3. Conventional preparation processes are difficult to effectively inhibit the volatilization and degradation of drug ingredients. During storage, the content of active ingredients in drugs is prone to decrease, resulting in a decline in drug quality and a shortened shelf life, which cannot meet the needs of long-term clinical medication.

[0007] In view of the above situation, the present invention provides a Roukou Si Shen Wan Chinese medicine composition and a preparation method thereof. Summary of the Invention

[0008] In order to overcome the above-mentioned defects of the prior art, the present invention provides a Chinese medicine composition of Roukou Sishen Pills and a preparation method thereof, so as to solve the problems raised in the above-mentioned background technology.

[0009] To achieve the above objectives, the present invention provides the following technical solution: a Chinese medicine composition of Roukou Sishen Pills, composed of the following raw materials in parts by weight: 30-50 parts of nutmeg extract, 40-60 parts of psoralea corylifolia powder, 20-30 parts of Schisandra chinensis polysaccharide complex, 10-20 parts of Evodia rutaecarpa volatile oil inclusion compound, 10-15 parts of modified starch and 5-8 parts of low-substituted hydroxypropyl cellulose.

[0010] Preferably, the nutmeg extract is prepared by supercritical carbon dioxide extraction technology, specifically, the nutmeg raw material is crushed to 40-60 mesh, and the nutmeg is separated and concentrated under reduced pressure under the conditions of extraction pressure of 20-30 MPa, temperature of 40-50° C., and extraction time of 2-3 hours.

[0011] Preferably, the psoralea corylifolia powder is made by airflow pulverization technology, the airflow pressure during pulverization is 0.6-0.8 MPa, the feed rate is 10-15 g / min, and the powder particle size is 1-10 μm.

[0012] Preferably, the preparation method of the Schisandra polysaccharide complex is:

[0013] Take Schisandra chinensis, add 10-15 times the amount of water, and boil 2-3 times, each time for 1-2 hours;

[0014] Combine the decoctions, filter, and concentrate to a relative density of 1.1-1.2 and a temperature of 60°C;

[0015] Slowly add 95% ethanol to make the alcohol content reach 70-80%, and let it stand for 12-24 hours to precipitate polysaccharides;

[0016] The precipitate was collected by centrifugation, washed with anhydrous ethanol, and dried to obtain crude polysaccharide;

[0017] The crude polysaccharide was purified by 100 kDa ultrafiltration membrane;

[0018] The purified schisandra polysaccharide and selenomethionine are mixed in an aqueous solution at a molar ratio of 1:0.05-0.1, 0.1% by weight of tea polyphenols are added, the pH is adjusted to 6-7, and the mixture is stirred and reacted at 40-50° C. for 2-3 hours to form a schisandra polysaccharide complex, which is then freeze-dried for later use.

[0019] Preferably, the Evodia rutaecarpa volatile oil inclusion compound is prepared by the following method:

[0020] The volatile oil was extracted from Evodia rutaecarpa by steam distillation.

[0021] Prepare a saturated aqueous solution of β-cyclodextrin at a ratio of 10:1-15:1 between β-cyclodextrin and Evodia rutaecarpa essential oil, slowly add Evodia rutaecarpa essential oil dropwise at 40-50°C, and stir for 2-3 hours;

[0022] Refrigerate for 12-24 hours, filter, wash with anhydrous ethanol, and dry to obtain the Evodia rutaecarpa volatile oil inclusion compound.

[0023] Preferably, the traditional Chinese medicine composition further comprises 0.3-0.5% by weight of probiotics, wherein the probiotics are Bacillus coagulans or Bacillus subtilis, and the probiotics are in the form of sodium alginate-chitosan microcapsules, the microcapsule particle size is 20-50 μm, and the encapsulation efficiency is ≥90%.

[0024] Preferably, the nutmeg extract and schisandra polysaccharide complex form nanoscale composite particles, 0.5% by weight of poloxamer 188 is added during the formation process, and the nanoscale composite particles are homogenized three times at 60 MPa high pressure, and the particle size of the nanoscale composite particles is 80-150 nm.

[0025] Preferably, the modified starch is prepared from corn starch by the following method: mixing corn starch with sodium hydroxide solution, stirring at 30-40° C. for 1-2 hours for alkalization, then adding chloroacetic acid for etherification, the reaction temperature is controlled at 50-60° C., the reaction time is 3-4 hours, and after the reaction is completed, neutralizing with hydrochloric acid to neutrality, filtering, washing, and drying to obtain a degree of substitution of 0.45-0.55 and a viscosity of 50-100 cPa·s;

[0026] The low-substituted hydroxypropyl cellulose is prepared by reacting cotton cellulose with propylene oxide under the catalysis of sodium hydroxide at 50-70° C. for 6-8 hours, followed by washing and drying. The hydroxypropyl substitution degree is 7-9%.

[0027] The present invention also provides a preparation method for preparing the above-mentioned Roukou Si Shen Wan Chinese medicine composition, which specifically comprises the following steps:

[0028] S1. Mix nutmeg extract, psoralea corylifolia powder, schisandra chinensis polysaccharide complex, modified starch, and low-substituted hydroxypropyl cellulose, add 40-60% by weight of purified water to form a soft material, and granulate through a 16-20 mesh sieve; dry the wet granules at 50-60°C.

[0029] S2. Vibrate and mix the dry particles obtained in step S1, the Evodia rutaecarpa volatile oil inclusion compound, and the probiotic microcapsules at 5-10° C., with a vibration frequency of 30-50 Hz and a mixing time of 15 min;

[0030] S3. The particles mixed in step S2 are subjected to nanoliposome coating treatment, specifically comprising the following steps: dissolving soybean lecithin and cholesterol in ethanol at a mass ratio of 3:1 to prepare a coating solution with a mass concentration of 5%, placing the particles in a coating pot, spraying the coating solution at a temperature of 35-40° C. and a rotation speed of 15-20 r / min, removing ethanol under reduced pressure after coating to a residual ethanol content of ≤0.5%, and finally using an automatic pill making machine to prepare pills weighing 0.5 g per pill.

[0031] Preferably, the surface of the nanoliposome-coated pills is smooth and uniform without adhesion or cracks.

[0032] The technical effects and advantages of the present invention are as follows:

[0033] 1. The Roukou Sishen Pills Chinese medicine composition of the present invention adopts a unique raw material ratio and uses advanced technologies such as supercritical carbon dioxide extraction and airflow milling to accurately extract and prepare ingredients such as nutmeg extract and psoralea corylifolia powder, significantly increasing the content of effective ingredients such as myristicin and psoralea corylifolia. At the same time, new ingredients such as Schisandra chinensis polysaccharide complex and probiotics are introduced, and nano-scale composite particles are formed by intermolecular hydrogen bonding, which expands the drug's mechanism of action and the synergistic effect of multiple ingredients, laying a solid material foundation for improving drug efficacy.

[0034] 2. The present invention adopts innovative technologies in the preparation process, from raw material processing to formulation molding. For example, modified starch and low-substituted hydroxypropyl cellulose are prepared by a specific method, which have excellent properties. The application of technologies such as low-temperature vibration grinding and mixing, and nano-liposome coating makes the preparation have a short disintegration time, high solubility, strong stability, high retention rate of active ingredients, reliable drug quality, and extended shelf life.

[0035] 3. The Chinese medicine composition of Roukou Si Shen Wan of the present invention has a good effect in treating diseases such as diarrhea, and has a lower incidence of adverse reactions, reflecting a good therapeutic effect and high safety. It has more advantages in clinical applications and can bring better treatment experience and rehabilitation effects to patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 It is a preparation flow chart of the present invention. DETAILED DESCRIPTION

[0037] Example 1

[0038] The present invention provides a Chinese medicine composition of Roukou Sishen Wan, which is specifically composed of the following raw materials in parts by weight:

[0039] 30 parts of nutmeg extract, 40 parts of psoralea corylifolia powder, 20 parts of schisandra chinensis polysaccharide complex, 10 parts of evodia rutaecarpa volatile oil inclusion compound, 10 parts of modified starch and 5 parts of low-substituted hydroxypropyl cellulose, and 0.3% by weight of probiotics, wherein the probiotics are Bacillus coagulans, and the probiotics are in the form of sodium alginate-chitosan microcapsules, the microcapsule particle size is 20 μm, and the encapsulation efficiency is ≥90%.

[0040] The above raw materials are prepared as follows:

[0041] The nutmeg extract comprises the following steps: crushing nutmeg raw material into 40 meshes, placing the nutmeg raw material into an extraction kettle of a supercritical carbon dioxide extraction device, setting the extraction pressure to 20 MPa, the temperature to 40° C., and the extraction time to 2 hours, wherein the carbon dioxide is pressurized by a high-pressure pump and heated in a heating furnace before entering the extraction kettle, extracting the nutmeg raw material under the set conditions, and the mixed fluid after extraction entering a separation kettle, wherein the carbon dioxide and the nutmeg extract are separated by decompression separation, the carbon dioxide is compressed, condensed, and then recycled, and the separated nutmeg extract is concentrated to obtain a high-purity nutmeg extract;

[0042] Psoralea corylifolia fine powder: the dried Psoralea corylifolia is put into an air flow mill, the air flow pressure is set to 0.6 MPa, and the feeding rate is 10 g / min. Under the action of the high-speed air flow, the Psoralea corylifolia collides and rubs against each other in the grinding chamber to achieve grinding. The Psoralea corylifolia fine powder with a particle size of 1-10 μm is collected by a cyclone separator and a bag dust collector to prevent the powder from being lost;

[0043] The schisandra polysaccharide complex is prepared by taking schisandra medicinal material, adding 10 times the amount of water, placing the mixture in a stainless steel reactor, heating to boiling, maintaining a slightly boiling state and decocting for 1 hour, decocting twice in total, combining the two decoctions, filtering with a 200-mesh sieve to remove the medicinal residue, transferring the filtrate to a vacuum concentration tank, concentrating at 60° C. to a relative density of 1.1, slowly adding 95% ethanol while stirring until the alcohol content reaches 70%, and standing for 12 hours to allow the polysaccharide to precipitate. The mixture is centrifuged at a speed of 3000 r / min for 10 minutes. The precipitate was collected and washed three times with anhydrous ethanol to remove residual ethanol and impurities. The precipitate was placed in a vacuum drying oven and dried at 50°C to constant weight to obtain a crude polysaccharide. The crude polysaccharide was purified by a 100 kDa ultrafiltration membrane. The purified schisandra polysaccharide was mixed with selenomethionine in an aqueous solution at a molar ratio of 1:0.05, and 0.1% by weight of tea polyphenols was added. The pH was adjusted to 6 with sodium hydroxide solution and hydrochloric acid solution. The mixture was stirred at 40°C for 2 hours to form a schisandra polysaccharide complex, and finally freeze-dried for use.

[0044] The volatile oil inclusion complex of Evodia rutaecarpa is extracted from Evodia rutaecarpa using a steam distillation apparatus. The Evodia rutaecarpa medicinal material is crushed and placed in a distillation flask. 8 times the amount of water is added and heated for distillation for 6 hours. The volatile oil is collected through an oil-water separator. β-cyclodextrin is added to distilled water at a ratio of β-cyclodextrin to Evodia rutaecarpa volatile oil of 10:1, and stirred at 40°C to prepare a saturated aqueous solution. The volatile oil of Evodia rutaecarpa is slowly added dropwise to the saturated aqueous solution of β-cyclodextrin, with the addition time controlled to be more than 30 minutes. After the addition is completed, stirring is continued for 2 hours. The mixed solution is placed in a refrigerator for 12 hours to allow the inclusion complex to fully form, and then filtered through a suction filtration device. The filter cake is washed with anhydrous ethanol 3 times to remove the unincluded volatile oil and impurities, and finally dried at 40°C to obtain the volatile oil inclusion complex of Evodia rutaecarpa.

[0045] To modify starch, corn starch and 10% sodium hydroxide solution were mixed in a mass ratio of 1:2, placed in a reactor, and stirred at 30°C for 1 hour for alkalization. Then, chloroacetic acid was added at a mass ratio of 1:0.5 to corn starch, and the temperature was raised to 50°C for etherification reaction. The reaction time was 3 hours. After the reaction, the pH was adjusted to neutral with hydrochloric acid, and the mixture was filtered and separated through a plate and frame filter press. The filter cake was washed with deionized water until neutral. Finally, the filter cake was placed in a forced air drying oven, dried at 60°C, and crushed to obtain modified starch with a degree of substitution of 0.45 and a viscosity of 50 cPa·s.

[0046] Low-substituted hydroxypropyl cellulose is prepared by mixing cotton cellulose with a 20% sodium hydroxide solution at a mass ratio of 1:3 and soaking at room temperature for 30 minutes to swell. Propylene oxide is then added at a mass ratio of 1:0.3 to cotton cellulose, and the mixture is heated to 50°C and reacted for 6 hours under the catalysis of sodium hydroxide. After the reaction, the mixture is repeatedly washed with deionized water until neutral, centrifuged, and the separated solid is placed in a vacuum drying oven, dried at 50°C, and pulverized to obtain low-substituted hydroxypropyl cellulose with a hydroxypropyl substitution degree of 7%.

[0047] The embodiment of the present invention provides a preparation method. Based on the raw materials prepared above, the specific preparation method further includes the following steps:

[0048] Mixing and granulation: the prepared nutmeg extract, psoralea corylifolia powder, schisandra chinensis polysaccharide complex, modified starch, and low-substituted hydroxypropyl cellulose are uniformly mixed, and purified water accounting for 40% of the total weight of the raw materials is added, and the mixture is stirred while adding water at a stirring speed of 50 r / min to prepare a soft material with suitable plasticity. The soft material is passed through a 16-mesh sieve and granulated using a rocking granulator to obtain uniform wet granules. The wet granules are dried at 50° C. The dried granules are vibrated with the Evodia rutaecarpa volatile oil inclusion compound and the probiotic microcapsules at 5° C. at a vibration frequency of 30 Hz for 15 minutes.

[0049] For coating, dissolve soybean lecithin and cholesterol in an appropriate amount of ethanol at a mass ratio of 3:1 to prepare a coating solution with a mass concentration of 5%. Place the particles in a high-efficiency coating pot, set the temperature of the coating pot to 35°C and the speed to 15r / min. Use a peristaltic pump to spray the coating solution onto the particle surface at a rate of 2mL / min. At the same time, turn on the hot air system and control the hot air temperature to 40°C to quickly evaporate the ethanol. After coating, continue to rotate the coating pot for 10 minutes to further solidify the coating film. Then, remove the residual ethanol under reduced pressure to a residual ethanol level of ≤0.5%. Check that the surface of the nanoliposome-coated pills is smooth and uniform, without adhesion or cracks. Finally, use an automatic pill making machine to produce pills weighing 0.5g each.

[0050] Example 2

[0051] The present invention provides a Chinese medicine composition of Roukou Sishen Wan, which is specifically composed of the following raw materials in parts by weight:

[0052] 40 parts of nutmeg extract, 50 parts of psoralea corylifolia powder, 25 parts of schisandra chinensis polysaccharide complex, 15 parts of evodia rutaecarpa volatile oil inclusion compound, 12 parts of modified starch and 6 parts of low-substituted hydroxypropyl cellulose, and 0.4% by weight of probiotics, wherein the probiotics are Bacillus subtilis, and the probiotics are in the form of sodium alginate-chitosan microcapsules, the microcapsule particle size is 35 μm, and the encapsulation efficiency is ≥90%.

[0053] The above raw materials are prepared as follows:

[0054] Nutmeg extract: nutmeg raw material is crushed into 50 mesh, extraction pressure is 25 MPa, temperature is 45°C, extraction time is 2.5 h, and other operations are the same as in Example 1;

[0055] Psoralea corylifolia powder, air flow pressure 0.7 MPa, feed rate 12 g / min, other operations are the same as in Example 1;

[0056] Schisandra polysaccharide complex: add 12 times the amount of water to Schisandra medicinal material, decoct 3 times, each time for 1.5 hours, concentrate to a relative density of 1.15, and add ethanol to make the alcohol content reach 75% at 60°C. Let it stand for 18 hours. Purify the crude polysaccharide through a 100kDa ultrafiltration membrane. Mix the purified Schisandra polysaccharide and selenomethionine in an aqueous solution at a molar ratio of 1:0.08, add 0.1% by weight of tea polyphenols, adjust the pH to 6.5, and react with stirring at 45°C for 2.5 hours. The remaining operations are the same as those in Example 1.

[0057] The inclusion compound of Evodia rutaecarpa volatile oil was prepared in a ratio of β-cyclodextrin to Evodia rutaecarpa volatile oil of 12:1, stirred at 45°C for 2.5h, and refrigerated for 18h. The remaining operations were the same as those in Example 1.

[0058] Modified starch, alkalization temperature 35 ° C, stirring 1.5 hours, etherification temperature 55 ° C, reaction 3.5 hours, to obtain modified starch with a degree of substitution of 0.5 and a viscosity of 75 cPa s. The remaining operations are the same as in Example 1;

[0059] Low-substituted hydroxypropyl cellulose was prepared at a reaction temperature of 60° C. for 7 h to obtain low-substituted hydroxypropyl cellulose with a hydroxypropyl substitution degree of 8%. The remaining operations were the same as those in Example 1.

[0060] The embodiment of the present invention provides a preparation method. Based on the raw materials prepared above, the specific preparation method further includes the following steps:

[0061] Mixing and granulation: add purified water (50% by weight of the total weight of the raw materials), granulate using a vertical wet mixing granulator, pass through an 18-mesh sieve, dry the wet granules at 55° C., and vibrate the dried granules with the Evodia rutaecarpa volatile oil inclusion compound and the probiotic microcapsules at 8° C. at a vibration frequency of 40 Hz and a mixing time of 15 min. Other procedures are the same as in Example 1.

[0062] Coating, the coating liquid was prepared as in Example 1, the coating pot temperature was 38 ° C, the speed was 18 r / min, the spray speed was 3 mL / min, and the ethanol was removed under reduced pressure after the coating was completed to make the ethanol residue ≤ 0.5%. The surface of the pills after the nanoliposome coating was checked to be smooth and uniform, without adhesion or cracks. Finally, pills weighing 0.5 g per pill were made using an automatic pill making machine.

[0063] Example 3

[0064] The present invention provides a Chinese medicine composition of Roukou Sishen Wan, which is specifically composed of the following raw materials in parts by weight:

[0065] 50 parts of nutmeg extract, 60 parts of psoralea corylifolia powder, 30 parts of schisandra chinensis polysaccharide complex, 20 parts of evodia rutaecarpa volatile oil inclusion compound, 15 parts of modified starch and 8 parts of low-substituted hydroxypropyl cellulose, and 0.5% by weight of probiotics, wherein the probiotics are Bacillus coagulans, and the probiotics are in the form of sodium alginate-chitosan microcapsules, the microcapsule particle size is 50 μm, and the encapsulation efficiency is ≥90%.

[0066] The above raw materials are prepared as follows:

[0067] Nutmeg extract: nutmeg raw material is crushed into 60 mesh, extraction pressure is 30 MPa, temperature is 50°C, extraction time is 3 h, and other operations are the same as in Example 1;

[0068] Psoralea corylifolia powder, air flow pressure 0.8 MPa, feed rate 15 g / min, other operations are the same as in Example 1;

[0069] Schisandra polysaccharide complex: add 15 times the amount of water to Schisandra medicinal material, decoct 3 times, each time for 2 hours, concentrate to a relative density of 1.2, and add ethanol to make the alcohol content reach 80% at 60°C. Let it stand for 24 hours. Purify the crude polysaccharide through a 100kDa ultrafiltration membrane. Mix the purified Schisandra polysaccharide and selenomethionine in an aqueous solution at a molar ratio of 1:0.1, add 0.1% by weight of tea polyphenols, adjust the pH to 7, and react at 50°C with stirring for 3 hours. The remaining operations are the same as those in Example 1.

[0070] The inclusion compound of Evodia rutaecarpa volatile oil was prepared in a ratio of β-cyclodextrin to Evodia rutaecarpa volatile oil of 15:1, stirred at 50°C for 3 hours, and refrigerated for 24 hours. The remaining operations were the same as those in Example 1.

[0071] Modified starch, alkalization temperature 40 ° C, stirring for 2 hours, etherification temperature 60 ° C, reaction for 4 hours, to obtain modified starch with a degree of substitution of 0.55 and a viscosity of 100 cPa s. The remaining operations are the same as in Example 1;

[0072] Low-substituted hydroxypropyl cellulose was prepared at a reaction temperature of 70° C. for 8 h to obtain low-substituted hydroxypropyl cellulose with a hydroxypropyl substitution degree of 9%. The remaining operations were the same as in Example 1.

[0073] The embodiment of the present invention provides a preparation method, based on the raw materials prepared above, the specific preparation method further includes the following steps:

[0074] Mixing and granulation: Add 60% of the total weight of the raw materials in purified water, mix and granulate using a wet mixing granulator, and pass through a 20-mesh sieve. Dry the wet granules at 60°C, and vibrate the dried granules with the Evodia rutaecarpa volatile oil inclusion complex and the probiotic microcapsules at 10°C at a vibration frequency of 50 Hz for 15 minutes. All other procedures are the same as in Example 1.

[0075] Coating, the coating liquid was prepared as in Example 1, the coating pan temperature was 40 ° C, the rotation speed was 20 r / min, the spray speed was 4 mL / min, and the ethanol was removed under reduced pressure after the coating was completed to make the ethanol residue ≤ 0.5%. The surface of the pills after the nanoliposome coating was checked to be smooth and uniform, without adhesion or cracks.

[0076] The following is a test of the active ingredient content of the raw materials of the Chinese medicine compositions of Examples 1-3, using the following method:

[0077] Determination of components in nutmeg extract: The contents of myristicin and safrole were determined by HPLC using a C18 column, a mobile phase of acetonitrile-water (60:40, v / v), a flow rate of 1.0 mL / min, a detection wavelength of 220 nm, and a column temperature of 30°C.

[0078] Determination of the components of Psoralea corylifolia powder: The contents of psoralen and isopsoralen were determined by HPLC using a C18 column, a mobile phase of methanol-water (60:40, v / v), a flow rate of 1.0 mL / min, a detection wavelength of 246 nm, and a column temperature of 35°C.

[0079] Determination of Schisandra polysaccharide complex: The polysaccharide content was determined by sulfuric acid-phenol method, and the zinc content was determined by atomic absorption spectrophotometry;

[0080] Determination of inclusion complexes in Evodia rutaecarpa volatile oil: The content of main components in Evodia rutaecarpa volatile oil, such as evodiene, was determined by gas chromatography. Chromatographic conditions: capillary column, nitrogen carrier gas, flow rate 1.5 mL / min, injection port temperature 250°C, detector temperature 280°C, and programmed temperature rise.

[0081] The final test results are shown in the following table:

[0082]

[0083] From the data table, it can be seen that with the increase of the raw material ratio in the examples, the content of each active ingredient shows a corresponding growth trend. In Examples 1-3, the content of myristyl ether is increased from 8.2±0.5 mg / g to 10.8±0.7 mg / g, safrole is increased from 3.1±0.3 mg / g to 4.0±0.5 mg / g, psoralen is increased from 12.5±0.8 mg / g to 15.5±1.0 mg / g, etc. This shows that the present invention can effectively increase the content of key active ingredients in the traditional Chinese medicine composition through precise raw material ratios and advanced extraction and preparation processes. In the present invention, supercritical carbon dioxide extraction technology, airflow milling technology, etc. fully play the role of retaining and enriching active ingredients in the raw material processing process, laying a material foundation for the drug to exert its therapeutic effect.

[0084] The Chinese medicine compositions of Examples 1-3 above were subjected to preparation quality testing in the following manner:

[0085] Disintegration time determination: According to the disintegration time determination method specified in the Chinese Pharmacopoeia, the pills were placed in a disintegration apparatus and the time required for complete disintegration was recorded;

[0086] Dissolution determination: The paddle method was used, with 900 mL of 0.1 mol / L hydrochloric acid solution as the dissolution medium and a rotation speed of 50 r / min. Samples were taken at different time points, and the amount of dissolved active ingredients was detected using the corresponding content determination method.

[0087] Stability testing:

[0088] Accelerated test: Place the pills in an environment with a temperature of 40℃±2℃ and a relative humidity of 75%±5%. Take samples at 0, 1, 2, 3, and 6 months to test indicators such as appearance, active ingredient content, and disintegration time.

[0089] Long-term test: Place the pills in an environment with a temperature of 25℃±2℃ and a relative humidity of 60%±10%, and take samples for testing at 0, 3, 6, 9, 12, 18, and 24 months.

[0090] The final test results are shown in the following table:

[0091]

[0092] From the above table data, we can see that:

[0093] Disintegration time: The disintegration time of Examples 1-3 gradually shortened, from 12 ± 1 min to 8 ± 1 min. This is due to the rational use of modified starch and low-substituted hydroxypropyl cellulose, as well as the optimization of process parameters such as granulation and drying. The shorter disintegration time means that the drug can release the active ingredient faster in the body, improving the drug's onset of action.

[0094] Dissolution: The 1-hour dissolution rates were 65±3%, 72±4%, and 78±5%, respectively, showing an upward trend. This indicates that with the adjustment of the raw material ratio and preparation process, the release efficiency of the drug in the dissolution medium has been improved, which is beneficial to the absorption and utilization of the drug in the body.

[0095] Stability: In the accelerated test and the long-term test, the active ingredient retention rate was high. In Example 3, the active ingredient retention rate reached 95±4% after 6 months of accelerated testing and 92±3% after 12 months of long-term testing, which was significantly better than that of Examples 1 and 2. This shows that the formulation process of the present invention can ensure the stability of the drug under different environmental conditions, extend the shelf life of the drug, and improve the reliability of the drug quality.

[0096] The pharmacodynamics test of the Chinese medicine compositions of Examples 1-3 is carried out as follows:

[0097] Animal experiment: Healthy SD rats were selected and randomly divided into a model group, a positive control group (traditional Roukou Sishen Pills), and Example 1-3 groups, with 20 rats in each group. Except for the normal group, the other groups were given a decoction of senna leaves by gavage to establish a diarrhea model. After successful modeling, each drug group was given the corresponding drug by gavage, and the normal group and the model group were given an equal volume of normal saline. The drugs were given for 7 consecutive days, and the diarrhea symptoms of the rats (diarrhea frequency, stool characteristics, etc.) were observed. After the experiment, the rats were killed, and the intestinal tissues were obtained for pathological observation.

[0098] Clinical trial: 200 patients who met the diagnostic criteria for diarrhea were selected and randomly divided into 4 groups, with 50 cases in each group, namely the traditional Roukou Si Shen Wan control group and the Example 1-3 groups. The patients in each group took the drug according to the prescribed dosage. The treatment course was 2 weeks. The changes in symptoms such as the number of diarrhea, abdominal pain severity, and stool characteristics of the patients before and after treatment were observed, and the occurrence of adverse reactions was recorded.

[0099] The results of animal experiment tests are shown in the following table:

[0100]

[0101]

[0102] From the data in the above table, it can be seen that the diarrhea frequency reduction rate and intestinal pathology improvement rate of Examples 1-3 groups are higher than those of the positive control group (traditional Roukou Si Shen Wan). The diarrhea frequency reduction rate of Example 3 reaches 85±8%, and the intestinal pathology improvement rate is 92±9%, indicating that the Chinese medicine composition of the present invention has a more significant effect in treating diarrhea and can effectively improve intestinal pathological conditions. The improvement in efficacy may be closely related to factors such as the increase in the content of effective ingredients and the optimization of preparation quality.

[0103] The clinical trial test results are shown in the following table:

[0104] Total effective rate (%) Incidence of adverse reactions (%) Traditional Roukou Sishen Pills control group 75 8 Example 1 group 82 5 Example 2 group 88 3 Example 3 group 93 2

[0105] From the data in the above table, it can be seen that in terms of the total effective rate, the groups of Examples 1-3 were 82%, 88% and 93% respectively, which were higher than the 75% of the control group of the traditional Roukou Si Shen Wan. The incidence of adverse reactions was significantly reduced, and the incidence of Example 3 was only 2%. This fully proves that the Chinese medicine composition of the present invention not only has significant clinical efficacy, but also has higher safety, and has greater advantages in practical applications.

[0106] Summarize:

[0107] The Roukou Si Shen Wan Chinese medicine composition of the present invention has excellent performance in terms of active ingredient content, preparation quality and pharmacodynamics due to its unique raw material ratio and advanced preparation process. The increase in the active ingredient content provides material guarantee for the drug to exert its therapeutic effect. The optimization of the preparation quality, such as shortened disintegration time, improved solubility and enhanced stability, is conducive to better release and absorption of the drug in the body. The excellent therapeutic effect and low incidence of adverse reactions demonstrated in animal experiments and clinical trials further verify the innovation and practicality of the Chinese medicine composition, and it has good application prospects and market value.

[0108] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A Chinese medicine composition of Roukou Sishen Wan, characterized in that: The invention is composed of the following raw materials in parts by weight: 30-50 parts of nutmeg extract, 40-60 parts of psoralea corylifolia powder, 20-30 parts of schisandra chinensis polysaccharide complex, 10-20 parts of evodia rutaecarpa volatile oil inclusion compound, 10-15 parts of modified starch and 5-8 parts of low-substituted hydroxypropyl cellulose.

2. The Chinese medicine composition of Roukou Sishen Wan according to claim 1, characterized in that: The nutmeg extract is prepared by supercritical carbon dioxide extraction technology, specifically, the nutmeg raw material is crushed into 40-60 meshes, and the nutmeg is separated and concentrated under reduced pressure under the conditions of extraction pressure of 20-30 MPa, temperature of 40-50° C., and extraction time of 2-3 hours.

3. The Chinese medicine composition of Roukou Sishen Wan according to claim 2, characterized in that: The psoralea corylifolia micropowder is prepared by air flow pulverization technology. During pulverization, the air flow pressure is 0.6-0.8 MPa, the feed speed is 10-15 g / min, and the particle size of the micropowder is 1-10 μm.

4. The Chinese medicine composition of Roukou Sishen Wan according to claim 3, characterized in that: The preparation method of the Schisandra polysaccharide complex is as follows: Take Schisandra chinensis, add 10-15 times the amount of water, and boil 2-3 times, each time for 1-2 hours; Combine the decoctions, filter, and concentrate to a relative density of 1.1-1.2 and a temperature of 60°C; Slowly add 95% ethanol to make the alcohol content reach 70-80%, and let it stand for 12-24 hours to precipitate polysaccharides; The precipitate was collected by centrifugation, washed with anhydrous ethanol, and dried to obtain crude polysaccharide; The crude polysaccharide was purified by 100 kDa ultrafiltration membrane; The purified schisandra polysaccharide and selenomethionine are mixed in an aqueous solution at a molar ratio of 1:0.05-0.1, 0.1% by weight of tea polyphenols are added, the pH is adjusted to 6-7, and the mixture is stirred and reacted at 40-50° C. for 2-3 hours to form a schisandra polysaccharide complex, which is then freeze-dried for later use.

5. The Chinese medicine composition of Roukou Sishen Wan according to claim 4, characterized in that: The Evodia rutaecarpa volatile oil inclusion compound is prepared by the following method: The volatile oil was extracted from Evodia rutaecarpa by steam distillation. Prepare a saturated aqueous solution of β-cyclodextrin at a ratio of 10:1-15:1 between β-cyclodextrin and Evodia rutaecarpa essential oil, slowly add Evodia rutaecarpa essential oil dropwise at 40-50°C, and stir for 2-3 hours; Refrigerate for 12-24 hours, filter, wash with anhydrous ethanol, and dry to obtain the Evodia rutaecarpa volatile oil inclusion compound.

6. The Chinese medicine composition of Roukou Sishen Wan according to claim 5, characterized in that: The traditional Chinese medicine composition further comprises 0.3-0.5% by weight of probiotics, wherein the probiotics are Bacillus coagulans or Bacillus subtilis. The probiotics are in the form of sodium alginate-chitosan microcapsules, the particle size of the microcapsules is 20-50 μm, and the encapsulation rate is ≥90%.

7. The Chinese medicine composition of Roukou Sishen Wan according to claim 6, characterized in that: Nano-scale composite particles are formed between the nutmeg extract and the schisandra polysaccharide complex. During the formation process, 0.5% by weight of poloxamer 188 is added, and the nano-scale composite particles are homogenized three times at 60 MPa high pressure. The particle size of the nano-scale composite particles is 80-150 nm.

8. The Chinese medicine composition of Roukou Sishen Wan according to claim 7, characterized in that: The modified starch is prepared from corn starch by the following method: mixing corn starch with sodium hydroxide solution, stirring at 30-40° C. for 1-2 hours for alkalization, then adding chloroacetic acid for etherification, controlling the reaction temperature at 50-60° C. for 3-4 hours, neutralizing with hydrochloric acid to neutrality after the reaction, filtering, washing, and drying to obtain a degree of substitution of 0.45-0.55 and a viscosity of 50-100 cPa·s; The low-substituted hydroxypropyl cellulose is prepared by reacting cotton cellulose with propylene oxide under the catalysis of sodium hydroxide at 50-70° C. for 6-8 hours, followed by washing and drying. The hydroxypropyl substitution degree is 7-9%.

9. A preparation method for preparing the Roukou Si Shen Wan Chinese medicine composition according to claim 8, characterized in that: The specific steps include: S1. Mix nutmeg extract, psoralea corylifolia powder, schisandra chinensis polysaccharide complex, modified starch and low-substituted hydroxypropyl cellulose, add 40-60% of purified water by weight of the total raw materials to form a soft material, granulate through a 16-20 mesh sieve, and dry the wet granules at 50-60°C; S2. Vibrate and mix the dry particles obtained in step S1, the Evodia rutaecarpa volatile oil inclusion compound, and the probiotic microcapsules at 5-10° C., with a vibration frequency of 30-50 Hz and a mixing time of 15 min; S3. The particles mixed in step S2 are subjected to nanoliposome coating treatment, specifically comprising the following steps: dissolving soybean lecithin and cholesterol in ethanol at a mass ratio of 3:1 to prepare a coating solution with a mass concentration of 5%, placing the particles in a coating pot, spraying the coating solution at a temperature of 35-40° C. and a rotation speed of 15-20 r / min, removing ethanol under reduced pressure after coating to a residual ethanol content of ≤0.5%, and finally using an automatic pill making machine to prepare pills weighing 0.5 g per pill.

10. The preparation method according to claim 9, characterized in that: The surface of the pills coated with the nanoliposomes is smooth and uniform without adhesion or cracks.

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