Traditional Chinese medicine composite granules and production method thereof
By encapsulating cordycepin and traditional Chinese medicine combinations using microencapsulation technology, traditional Chinese medicine combination granules were prepared, which solved the problems of cordycepin instability and the side effects of Western medicine, achieving long-term lipid-lowering and improved safety.
Patent Information
- Application Number
- CN202510910692.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-02
- Publication Date
- 2025-11-07
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Existing Western lipid-lowering drugs cause adverse reactions with long-term use, while cordycepin is unstable and has low bioavailability, making it difficult to effectively lower high blood lipids.
Cordycepin was encapsulated using microencapsulation technology, and gelatin was used as the wall material to form a sustained-release component. Combined with traditional Chinese medicines such as Poria cocos, hawthorn, cassia seed, and salvia miltiorrhiza, a combination of traditional Chinese medicine granules was prepared to achieve sustained release and improved stability of cordycepin.
Traditional Chinese medicine granules have a long retention time in the body, which improves the stability and bioavailability of cordycepin, reduces serum cholesterol and triglycerides, reduces the frequency of administration, and improves the convenience of medication.
Smart Images
Figure SMS_1 
Figure SMS_2 
Figure SMS_3
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine combined granule and a production method thereof. BACKGROUND
[0002] Traditional Chinese medicine has a long history and is a valuable cultural heritage, has a unique theoretical system and rich clinical experience, and is mainly derived from natural animals and plants, minerals and other drugs or processed products of natural drugs, has different effects and various active ingredients, can be used for targeted treatment of different diseases and different populations, has multiple target points, and has the advantages of prevention and treatment, small side effects, less adverse reactions, safety and reliability.
[0003] With the continuous improvement of living standards and changes in dietary structure, the number of people with high blood lipids is increasing, high blood lipids mainly refer to one or more of serum triglyceride (TG), total cholesterol (TC) and low-density lipoid cholesterol (LDL-C) being higher than the normal level, and in traditional Chinese medicine, high blood lipids are mainly related to qi stagnation, blood stasis and phlegm-dampness, and are mainly related to the spleen, liver and kidney, and high blood lipids can cause cardiovascular diseases, and high blood lipids are also a cause of cerebral thrombosis, coronary heart disease, myocardial infarction, hypertension, diabetes, fatty liver and gallstones, and seriously endanger health; currently, commonly used lipid-lowering drugs are mainly western medicines such as statins and fibrates, which have significant effects, but long-term use can cause adverse reactions, and have toxic and side effects on the liver, muscles and gastrointestinal tract, can easily cause headache, nausea, diarrhea, skin rash and the like, and can even cause rhabdomyolysis, while traditional Chinese medicine resources are abundant, and many natural drugs have lipid-lowering effects, have sustained effects, small toxic and side effects, and cordyceps sinensis, as a traditional Chinese medicine, has various effects and functions, and can separate effective active ingredients cordycepin therefrom, and has good prevention and treatment effects on various diseases, and cordycepin also has good lipid-lowering effects on high blood lipids, but cordycepin is unstable and has low bioavailability, therefore, the present application provides a traditional Chinese medicine combined granule, in which effective cordycepin is coated with microcapsules, has a sustained release effect, can stay in the body for a long time, prolongs the action time, improves the stability and bioavailability, has obvious lipid-lowering effects, can reduce the frequency of administration, and improves the convenience of medication. SUMMARY
[0004] In order to solve the problems mentioned in the background art, the purpose of the present application is to provide a traditional Chinese medicine combined granule and a production method thereof.
[0005] The purpose of the present application can be achieved by the following technical solutions. A traditional Chinese medicine combined granule comprises the following raw materials by weight: 10-20 parts of poria cocos, 10-20 parts of hawthorn, 20-35 parts of dextrin, 10-15 parts of cassia seed, 10-15 parts of salvia miltiorrhiza, and 2-5 parts of cordycepin sustained-release components.
[0006] Further, the preparation method of the cordycepin slow-release component comprises the following steps: S1, take Cordyceps militaris and put it into a forced air drying oven, dry it at a constant temperature of 50-60℃ for 10-30min, grind and crush it, sieve it, then add distilled water, then put it into a microwave extraction tank, set the temperature to 60-80℃, extract it for 10-20min, then place it in a centrifuge, centrifuge it at 4000-4500r / min, take the supernatant, filter it, concentrate it by reduced pressure distillation, and obtain cordycepin; S2, add gelatin to distilled water, increase the temperature to 40-50℃, stir until it dissolves, prepare a gelatin solution with a mass fraction of 3-5%, then add cordycepin and Tween-60, stir until they are evenly distributed, then immediately add a sodium sulfate solution, stir at 300-500r / min for 25-35min, then reduce the temperature to room temperature, and obtain a microcapsule suspension; S3, place the microcapsule suspension in an ice bath environment, control the temperature below 10℃, add genipin to the microcapsule suspension, solidify it for 5-8h, then let it stand and settle, wash it with cold distilled water, then freeze-dry it, and obtain a cordycepin slow-release component.
[0007] By using the above technical solution, cordycepin is extracted by microwave method, which has the advantages of simple operation, high extraction efficiency, and short extraction time. Gelatin is used as the wall material, and cordycepin is used as the core material. The addition of sodium sulfate reduces the solubility of gelatin, so that gelatin can be deposited on the surface of cordycepin and form a microcapsule structure to prepare a cordycepin slow-release component. After solidification, the microcapsule can only be dissolved in neutral and slightly alkaline conditions, and the solubility in acidic conditions is greatly reduced. Therefore, the cordycepin slow-release component can slowly release in gastric juice, stay in the body for a long time, prolong the action time, improve the stability and bioavailability of cordycepin, improve the treatment effect, reduce the frequency of administration, and improve the convenience of medication.
[0008] Further, in step S1, the number of sieving is 40-60 mesh.
[0009] Further, in step S1, the mass ratio of Cordyceps militaris to distilled water is 1-2:20.
[0010] Further, in step S2, the mass fraction of the sodium sulfate solution is 15-20%.
[0011] A production method of a traditional Chinese medicine combined granule comprises the following steps: Step one, mix Fuling, Shanzha, Semen Cassiae, and Danshen, and dry them in a vacuum drying oven for 30-60min to obtain a mixture; Step two, the mixture is placed in a pulverizer, crushed, screened, and wormgrassin sustained-release components, dextrin and distilled water are added, stirred evenly, granulated, and wet granules are obtained; Step three, the wet granules are placed in a spray dryer and dried for 1-3 hours, and then, after the temperature drops to room temperature, the granules are sized using a vibrating screen, packaged, and sealed.
[0012] By using the above technical solution, the Fuling is flat, and is distributed to the heart, lung, spleen and kidney, and has the effects of promoting water and removing dampness, strengthening the spleen and calming the heart; the Shanzha is slightly warm, and is distributed to the spleen, stomach and liver, and can be used for blood stasis and amenorrhea; the Semen Cassiae is slightly cold, and is distributed to the liver and kidney, and can clear heat, moisten the intestines, promote metabolism and reduce fat accumulation; the Danshen is slightly cold, and is distributed to the heart and liver, and can promote blood circulation and phlegm, calm the liver and protect the liver, and inhibit atherosclerosis; the Fuling, Shanzha, Semen Cassiae and Danshen are combined with wormgrassin sustained-release components to obtain a traditional Chinese medicine combined granule with the effects of removing blood stasis, clearing heat and removing dampness, promoting defecation and metabolism, strengthening the viscera, and effectively reducing lipid.
[0013] Further, in step two, the number of screens is 50-80 meshes.
[0014] Further, in step three, the inlet air temperature of the spray dryer is 60-80 DEG C.
[0015] The beneficial effects of the present application are: The traditional Chinese medicine combined granule prepared by adding Fuling, Shanzha, Semen Cassiae, Danshen and wormgrassin sustained-release components has excellent lipid-lowering effect, wormgrassin can effectively reduce the content of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL-C) in serum, and the wormgrassin is coated to form a microcapsule structure to achieve sustained-release effect, so that the wormgrassin can stay in the body for a long time, prolong the action time, improve the stability and bioavailability of wormgrassin, and fully exert the lipid-lowering effect.
[0016] Of course, implementing any product of the present application does not necessarily require all the advantages described above. DETAILED DESCRIPTION
[0017] The technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present application.
[0018] Embodiment 1 Preparation of cordycepin sustained-release component S1, 2.5 g of cordyceps militaris was weighed and placed in a forced air drying oven, and dried at 50 DEG C for 10 min, and then ground and crushed, and sieved through a 40 mesh sieve, and then added to 50 mL of distilled water, and then placed in a microwave extraction tank, and the temperature was set to 60 DEG C, and extracted for 10 min, and then placed in a centrifuge, and centrifuged at 4000 r / min, and the supernatant was taken, and filtered, and concentrated by reduced pressure distillation, to obtain cordycepin; S2, 6 g of gelatin was added to distilled water, and the temperature was raised to 40 DEG C, and stirred until it was dissolved, to prepare a gelatin solution with a mass fraction of 3%, and then 1 g of cordycepin and 2 mL of Tween-60 with a concentration of 3% were added, and stirred until uniform, and then 25 mL of a sodium sulfate solution with a mass fraction of 15% was added, and stirred at 300 r / min for 25 min, and then cooled to room temperature, to obtain a microcapsule suspension; S3, 4 g of the microcapsule suspension was placed in an ice bath environment, and the temperature was controlled below 10 DEG C, and 0.3 g of genipin was added to the microcapsule suspension, and solidified for 5 h, and then allowed to stand and settle, and washed with cold distilled water, and freeze-dried, to obtain a cordycepin sustained-release component.
[0019] Embodiment 2 Preparation of cordycepin sustained-release component S1, 3 g of cordyceps militaris was weighed and placed in a forced air drying oven, and dried at 55 DEG C for 20 min, and then ground and crushed, and sieved through a 50 mesh sieve, and then added to 40 mL of distilled water, and then placed in a microwave extraction tank, and the temperature was set to 70 DEG C, and extracted for 15 min, and then placed in a centrifuge, and centrifuged at 4250 r / min, and the supernatant was taken, and filtered, and concentrated by reduced pressure distillation, to obtain cordycepin; S2, 9 g of gelatin was added to distilled water, and the temperature was raised to 45 DEG C, and stirred until it was dissolved, to prepare a gelatin solution with a mass fraction of 4%, and then 1.5 g of cordycepin and 2.5 mL of Tween-60 with a mass fraction of 3% were added, and stirred until uniform, and then 25 mL of a sodium sulfate solution with a mass fraction of 18% was added, and stirred at 400 r / min for 30 min, and then cooled to room temperature, to obtain a microcapsule suspension; S3, 5g of the microcapsule suspension was placed in an ice bath environment, the temperature was controlled below 10℃, 0.4g of genipin was added to the microcapsule suspension, and after 6.5h of solidification, it was allowed to settle, washed with cold distilled water, and then freeze-dried to obtain the cordycepin slow-release component.
[0020] Example 3 Preparation of the cordycepin slow-release component S1, 3.5g of cordyceps militaris was weighed and placed in a forced air drying oven, dried at 60℃ for 30min, ground and crushed, passed through a 60 mesh sieve, then added to 35mL of distilled water, and then placed in a microwave extraction tank, the temperature was set to 80℃, extracted for 20min, then placed in a centrifuge at 4500r / min, the supernatant was taken, filtered, and concentrated under reduced pressure to obtain cordycepin; S2, 12g of gelatin was added to distilled water, the temperature was increased to 50℃, and stirred until it dissolved to prepare a gelatin solution with a mass fraction of 5%, then 2g of cordycepin and 3mL of Tween-60 with a mass fraction of 3% were added, stirred uniformly, then 25mL of sodium sulfate solution with a mass fraction of 20% was added, stirred at 500r / min for 35min, and then cooled to room temperature to obtain a microcapsule suspension; S3, 6g of the microcapsule suspension was placed in an ice bath environment, the temperature was controlled below 10℃, 0.5g of genipin was added to the microcapsule suspension, and after 8h of solidification, it was allowed to settle, washed with cold distilled water, and then freeze-dried to obtain the cordycepin slow-release component.
[0021] Example 4 Production of the traditional Chinese medicine combined granules Step one, 10g of poria cocos, 10g of hawthorn, 10g of cassia seed, and 10g of salvia miltiorrhiza were mixed and placed in a vacuum drying oven for drying for 30min to obtain a mixture; Step two, the mixture was placed in a pulverizer and crushed, passed through a 50 mesh sieve, 2g of the cordycepin slow-release component prepared in Example 2, 20g of dextrin, and distilled water were added, stirred uniformly, and then granulated to obtain wet granules; Step three, the wet granules were placed in a spray dryer, the inlet temperature of the spray dryer was 60℃, and the drying time was 1h, after the temperature was reduced to room temperature, the granules were sized using a vibrating screen, and then packaged after sizing and sealing to obtain the traditional Chinese medicine combined granules.
[0022] Example 5 Production of the traditional Chinese medicine combined granules Step one, 14g of poria cocos, 14g of hawthorn, 12g of cassia seed, and 13g of salvia miltiorrhiza were mixed and placed in a vacuum drying oven for drying for 40min to obtain a mixture; Step two, put the mixture into a pulverizer to be pulverized, pass through a 60-mesh sieve, add 3 g of the cordycepin sustained-release component prepared in Example 2, 25 g of dextrin and distilled water, stir uniformly, granulate, and obtain wet granules; Step three, dry the wet granules in a spray dryer, the inlet air temperature of the spray dryer is 65°C, the drying time is 2 h, after the temperature drops to room temperature, use a vibrating screen to size, after sizing is completed, perform packaging and bagging, and obtain the traditional Chinese medicine combined granules.
[0023] Example 6 Production of the traditional Chinese medicine combined granules Step one, mix 18 g of poria cocos, 18 g of hawthorn, 13 g of cassia seed and 14 g of salvia miltiorrhiza and dry them in a vacuum drying oven for 50 min to obtain a mixture; Step two, put the mixture into a pulverizer to be pulverized, pass through a 70-mesh sieve, add 4 g of the cordycepin sustained-release component prepared in Example 2, 30 g of dextrin and distilled water, stir uniformly, granulate, and obtain wet granules; Step three, dry the wet granules in a spray dryer, the inlet air temperature of the spray dryer is 75°C, the drying time is 2.5 h, after the temperature drops to room temperature, use a vibrating screen to size, after sizing is completed, perform packaging and bagging, and obtain the traditional Chinese medicine combined granules.
[0024] Example 7 Production of the traditional Chinese medicine combined granules Step one, mix 20 g of poria cocos, 20 g of hawthorn, 15 g of cassia seed and 15 g of salvia miltiorrhiza and dry them in a vacuum drying oven for 60 min to obtain a mixture; Step two, put the mixture into a pulverizer to be pulverized, pass through an 80-mesh sieve, add 5 g of the cordycepin sustained-release component prepared in Example 2, 35 g of dextrin and distilled water, stir uniformly, granulate, and obtain wet granules; Step three, dry the wet granules in a spray dryer, the inlet air temperature of the spray dryer is 80°C, the drying time is 3 h, after the temperature drops to room temperature, use a vibrating screen to size, after sizing is completed, perform packaging and bagging, and obtain the traditional Chinese medicine combined granules.
[0025] Comparative Example 1 Production of the traditional Chinese medicine combined granules Step one, mix 14 g of poria cocos, 14 g of hawthorn, 12 g of cassia seed and 13 g of salvia miltiorrhiza and dry them in a vacuum drying oven for 40 min to obtain a mixture; Step two, put the mixture into a pulverizer to be pulverized, pass through a 60-mesh sieve, add 3 g of the cordycepin prepared in Example 2, 25 g of dextrin and distilled water, stir uniformly, granulate, and obtain wet granules; Step three, the wet granules are dried in a spray dryer, the inlet temperature of the spray dryer is 65℃, the drying time is 2h, after the temperature drops to room temperature, the granules are sized by a vibrating screen, and after the sizing is completed, the granules are packed and sealed to obtain the traditional Chinese medicine combined granules.
[0026] Comparative example 2 Production of the traditional Chinese medicine combined granules Step one, 14g of Poria cocos, 14g of hawthorn, 12g of cassia seed and 13g of Salvia miltiorrhiza are mixed and dried in a vacuum drying oven for 40min to obtain a mixture; Step two, the mixture is crushed in a pulverizer and sieved through a 60 mesh sieve, 25g of dextrin and distilled water are added, stirred uniformly, and then granulated to obtain wet granules; Step three, the wet granules are dried in a spray dryer, the inlet temperature of the spray dryer is 65℃, the drying time is 2h, after the temperature drops to room temperature, the granules are sized by a vibrating screen, and after the sizing is completed, the granules are packed and sealed to obtain the traditional Chinese medicine combined granules.
[0027] Detection A. Safety detection: 140mg of cordycepin sustained-release components prepared in examples 1-3 are immersed in 15mL of DMEM medium containing 10% fetal bovine serum, and after 24h of extraction, centrifugation is performed, the supernatant is taken, 10% fetal bovine serum-containing DMEM medium is added and diluted, rat osteoblasts are cultured, and the second-generation cells are inoculated on a 96-well culture plate at 1×10 3 6 / mL, 100μL per well, and cultured at 37℃ in 5% carbon dioxide for 24h, the negative control group is DMEM medium containing 10% fetal bovine serum, after two days of culture, 20μL of 3-(4,5-dimethylthiazole-2)-2,5-diphenyl tetrazolium bromide (MTT) is added, 150μL of dimethyl sulfoxide is added after 2h, and the A value in examples 1-3 is measured at 490nm wavelength by using an enzyme-linked immunoassay instrument, the relative growth rate RGR (%) of the cells is calculated, RGR= test group A value / negative control group A value×100%, to judge the safety of the cordycepin sustained-release components, and the results are shown in the following table:
[0028] From the above table, it can be seen that the cordycepin sustained-release components prepared in examples 1-3 of the present application have good safety and can be applied to the traditional Chinese medicine combined granules.
[0029] B. Release detection: the release detection of the cordycepin sustained-release components prepared in Example 1-Example 3 was carried out, 0.5 g of the cordycepin sustained-release components was added into a dialysis bag, stirred in an artificial gastric juice for 3 h, after standing overnight, the solution volume of the dialysis bag was supplemented, 100 μL was taken for high performance liquid chromatography analysis to measure the mass concentration of cordycepin, and the release rate was calculated, and the results are shown in the following table:
[0030] From the above table, it can be seen that the cordycepin sustained-release components prepared in Example 1-Example 3 have good sustained-release effect in the artificial gastric juice, can make the cordycepin stay in the body for a long time, prolong the action time, improve the bioavailability of cordycepin, reduce the frequency of administration, and improve the convenience of medication.
[0031] C. Lipid-lowering effect detection: 4 g of the traditional Chinese medicine combined granules prepared in Example 4-Example 7 and Comparative Example 1-Comparative Example 2 were added into 200 mL of distilled water for standby; 80 healthy SPF male SD rats were fed with basic feed for 7 days of adaptation period, and randomly divided into 8 groups, 10 rats in each group, one group was fed with basic feed and set as a normal control group, one group was fed with high-fat feed and set as a high-fat control group, and the remaining groups were fed with high-fat feed and subjected to gavage treatment, the gavage volume was 1 mL / 100 g·bw of the traditional Chinese medicine composition prepared in Example 4-Example 7 and Comparative Example 1-Comparative Example 2, after 7 weeks of feeding, the tail blood was taken without fasting, and the content of triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL-C) in the serum of the rats was detected by 70220 type automatic biochemical analyzer, and the test results are shown in the following table:
[0032] From the above table, it can be seen that the traditional Chinese medicine combined granules prepared in Example 4-Example 7 have excellent lipid-lowering effect, and the lipid-lowering effect of Example 5 is the best, Comparative Example 1 added cordycepin, and the lipid-lowering effect is relatively poor, which may be caused by the instability of cordycepin in the body and the low bioavailability; Comparative Example 2 did not add the cordycepin sustained-release component, so the lipid-lowering effect is poor.
[0033] The above content is only an example and description of the concept of the present application, and those skilled in the art can make various modifications or supplements or use similar ways to replace the described specific embodiments, as long as they do not deviate from the concept of the present application or exceed the scope defined by the present claims, which shall belong to the protection scope of the present application.
Claims
1. A traditional Chinese medicine combination granule, characterized in that, The raw materials include the following weight parts: 10-20 parts of poria cocos, 10-20 parts of hawthorn, 20-35 parts of dextrin, 10-15 parts of cassia seed, 10-15 parts of salvia miltiorrhiza, and 2-5 parts of cordycepin sustained-release component.
2. The traditional Chinese medicine combined granule according to claim 1, characterized in that, The preparation method of the cordycepin sustained-release component includes the following steps: S1, weigh the cordyceps militaris and put it into the air blower drying oven, constant temperature drying at 50-60℃ for 10-30min, grinding and crushing, sieving, then adding distilled water, then putting it into the microwave extraction tank, setting the temperature to 60-80℃, extracting for 10-20min, then placing in the centrifuge, centrifuging at 4000-4500r / min, taking the supernatant, filtering, vacuum distillation and concentration, obtaining cordycepin; S2, add gelatin to distilled water, increase the temperature to 40-50℃, stir until it dissolves, configure a gelatin solution with a mass fraction of 3-5%, then add cordycepin and tween-60, stir uniformly, then add sodium sulfate solution, stir at 300-500r / min for 25-35min, then reduce to room temperature, obtaining microcapsule suspension; S3, place the microcapsule suspension in an ice bath environment, control the temperature below 10℃, add genipin to the microcapsule suspension, solidify for 5-8h, then stand and settle, wash with cold distilled water, then freeze-dry, obtaining cordycepin sustained-release component.
3. The traditional Chinese medicine combined granule according to claim 2, characterized in that, In step S1, the sieving number is 40-60 mesh.
4. The traditional Chinese medicine combined granule according to claim 2, characterized in that, In step S1, the mass ratio of cordyceps militaris to distilled water is 1-2:
20.
5. The traditional Chinese medicine combined granule according to claim 2, characterized in that, In step S2, the mass fraction of sodium sulfate solution is 15-20%.
6. The production method of the traditional Chinese medicine combination granules according to claim 1, characterized in that, The method comprises the following steps: Step one, mix poria cocos, hawthorn, cassia seed and salvia miltiorrhiza, and place them in a vacuum drying oven for drying for 30-60min, obtaining mixed material; Step two, crush the mixed material in a pulverizer, sieve, add cordycepin sustained-release component, dextrin and distilled water, stir uniformly, then granulate, obtaining wet granules; Step three, dry the wet granules in a spray dryer, the drying time is 1-3h, after the temperature drops to room temperature, use a vibrating screen to size, after sizing, package and seal, obtaining traditional Chinese medicine combined granules.
7. The production method of the traditional Chinese medicine combination granules according to claim 6, characterized in that, In step two, the sieving number is 50-80 mesh.
8. The production method of the traditional Chinese medicine combination granules according to claim 6, characterized in that, In step three, the inlet air temperature of the spray dryer is 60-80℃.