Continuous preparation process of gypenosides capsule

Abstract

The application provides a continuous preparation process of gypenoside capsules, which comprises the following steps: step 1, weighing gypenoside raw materials and silicon dioxide; step 2, feeding the weighed gypenoside raw materials and silicon dioxide into a mixer through a pipeline under vacuum, and fully mixing them; step 3, after mixing, the material is vacuumed into the feeding opening of a dry granulator, the pressure of the pressure roller of the dry granulator, the feeding speed, the rotation speed of the pressure roller, the gap between the pressure rollers are adjusted, so that the material is extruded into a sheet shape, and the whole granulation speed and the mesh number of the screen are controlled, after the sheet material is granulated, the qualified granules are collected, and the unqualified granules are continuously vacuumed into the feeding opening of the dry granulator for continuous granulation. The application adopts dry granulation, avoids the use of more auxiliary materials, greatly reduces the proportion of auxiliary materials in the finished product, and therefore small capsules can be filled, the difficulty of swallowing for patients is reduced, and the patient compliance is improved.

Description

TECHNICAL FIELD

[0001] The application relates to a continuous preparation process of gypenosides capsules. BACKGROUND

[0002] The gypenosides capsule is a listed traditional Chinese medicine. The main functions and indications are as follows: nourishing heart and spleen, benefiting qi and activating blood, removing phlegm and resolving stasis, and reducing blood lipid. The gypenosides capsule is suitable for high blood lipid, and is used for treating heart-spleen qi deficiency, phlegm and blood stasis, such as palpitation, shortness of breath, chest distress, numbness of limbs, dizziness, headache, forgetfulness, tinnitus, self-sweating, fatigue, and abdominal fullness.

[0003] High blood lipid is one of the main risk factors of cardiovascular diseases, which can cause atherosclerosis, coronary heart disease, cerebral infarction and other diseases. The incidence of high blood lipid shows an upward trend in the global range, which seriously threatens human health. The disease is a chronic disease with a long course, and needs long-term treatment through diet adjustment and oral administration of drugs. The gypenosides capsule has a good blood lipid-lowering effect, and thus has a wide application in the field. The current gypenosides capsule is filled with No. 1 capsules. For patients who need long-term medication, reducing the amount of auxiliary materials and lowering the difficulty of swallowing for patients can improve the compliance of patients, which is the demand of patients and the starting point of the application.

[0004] The normal dosage of the gypenosides capsule is 1 capsule once, three times a day. Since the product is a long-term medication, the physical conditions of the patients are different. According to the adverse reaction monitoring data after listing, the adverse reactions of the gypenosides capsule in the gastrointestinal system include nausea, vomiting, abdominal discomfort, gastrointestinal reactions and the like. The adverse reactions of drugs belong to the inherent risk of the drugs (the gypenosides are bitter and cold in nature), which are restricted by the development stage of science and technology and the process level. Through improving the process, improving the quality of raw materials and other measures to reduce the incidence of adverse reactions and improve the efficacy and safety of the drugs, the incidence of adverse reactions can be reduced to a certain extent, and the risk of medication can be reduced.

[0005] The application discloses a preparation method of gypenosides in gypenosides granules. The preparation method comprises the following steps: (1) crushing gypenosides into coarse powder, putting the coarse powder into a multifunctional extraction tank, adding 6-8 times amount of water, adding an emulsifying agent and uniformly mixing, then refluxing and extracting twice, each time for 1 hour, and collecting the extraction liquid; (2) adjusting the Ph value of the collected extraction liquid to 7-8, filtering and precipitating, taking the filtrate, adsorbing the filtrate through a macroporous adsorption resin, chromatographing, washing and eluting the macroporous adsorption resin 1-2 times with 50-70% ethanol, collecting the elution liquid, recovering ethanol, and then reducing pressure and concentrating to obtain a powder extract by spray drying. The method can increase the yield of gypenosides, improve the yield of the extract by more than 30%, reduce the extraction time and the extraction times of gypenosides, greatly shorten the production cycle of gypenosides, and reduce the production cost.

[0006] The invention with publication number CN102600228B discloses a preparation method of total gypenoside in total gypenoside granules, comprising the following steps: (1) crushing gypenoside medicinal materials into coarse powder, putting into a multifunctional extraction tank, adding 6-8 times amount of water, then adding emulsifier and mixing, then refluxing extraction twice, each time for 1 hour, collecting the extraction liquid; (2) adjusting the pH value of the collected extraction liquid to 7-8, filtering the precipitate, taking the filtrate, adsorbing through macroporous adsorption resin, chromatographing, washing and eluting 1-2 times with 50-70% concentration ethanol to collect the eluate, recovering ethanol, then vacuum concentrating, and spray drying to obtain powder extract. The method can increase the yield of total gypenoside, increase the yield of the extract by more than 30%, reduce the extraction time and extraction times of total gypenoside, greatly shorten the production cycle of gypenoside extraction, and reduce the production cost.

[0007] The existing technology for the process of total gypenoside capsules is that total gypenoside raw materials are mixed with excipients, and the capsules are directly filled. Since the filling mode is direct filling, more excipients need to be added. Generally, the proportion of raw materials to excipients needs to be about 1:2 to ensure the flowability of the materials and offset the poor flowability of the raw materials.

[0008] Meanwhile, since the dosage increases after adding more excipients, a larger capsule size (1#) must be used to meet the filling requirements, and thus the patient has a poor swallowing experience. In terms of continuous production, the flowability of the intermediate materials in the existing process is poor, which cannot meet the material transfer requirements, and thus continuous production cannot be realized. SUMMARY

[0009] The purpose of the present application is to provide a continuous preparation process for total gypenoside capsules. The process of the present application uses dry granulation, which avoids the use of more excipients, thereby greatly reducing the proportion of excipients in the finished product. Therefore, small-sized capsules can be used for filling, which reduces the swallowing difficulty of patients and improves patient compliance.

[0010] To solve the above technical problems, the technical solution adopted by the present application is:

[0011] A continuous preparation process for total gypenoside capsules, specifically comprising the following steps:

[0012] Step 1, batching: weighing total gypenoside raw materials and silicon dioxide;

[0013] Step 2, mixing: conveying the weighed and batched total gypenoside raw materials and silicon dioxide to a mixer through a pipeline under vacuum, and fully mixing and uniformizing;

[0014] Step 3, granulation: after mixing, the material is vacuumed to the feeding port of the dry granulator, the pressure of the pressure roller, the feeding speed, the rotation speed of the pressure roller, the gap of the pressure roller are adjusted so that the material is extruded into a sheet, and the screening speed and the mesh size of the screen are controlled, after the sheet material is screened, the qualified particles of 40-65 mesh are collected, and the unqualified particles continue to be vacuumed to the feeding port of the dry granulator for continuous granulation until all the material is granulated into qualified particles;

[0015] Step 4, total mixing: the qualified particles are vacuumed into the total mixing device for mixing;

[0016] Step 5, filling: the total mixed particles are vacuumed into the capsule filling machine feeder for filling capsules;

[0017] Among them, the equipment in each process step is connected by closed pipeline, after the preparation of step 1 is completed, all the materials and intermediates in the process are vacuumed, gravity discharged, and then transported to the next step to realize continuous production.

[0018] Among them, in step 1, the moisture content of the gynostemma total glycoside raw material is controlled to be 5%-7%, and the weight ratio of the gynostemma total glycoside raw material to silicon dioxide is 1:0.005-1:0.05.

[0019] Further, in step 3, the dry granulation parameters are:

[0020] The feeding speed is 30rpm-50rpm;

[0021] The pressure of the pressure roller is 70bar-90bar;

[0022] The gap of the pressure roller is 0.5mm-2.0mm;

[0023] The rotation speed of the pressure roller is 10rpm-20rpm;

[0024] The screening speed is 80rpm-125rpm;

[0025] The mesh size of the screen is 40-65 mesh.

[0026] Preferably, in step 3, the specific parameters are:

[0027] The feeding speed is 40rpm;

[0028] The pressure of the pressure roller is 80bar;

[0029] The gap of the pressure roller is 1.5mm;

[0030] The rotation speed of the pressure roller is 15rpm;

[0031] The screening speed is 100rpm;

[0032] The mesh size of the screen is 50-60 mesh.

[0033] In step 4, the total mixing time is 3-5 min.

[0034] Further, in step 5, the capsule model is 5#.

[0035] In step 1, the moisture content of the gynostemma pentaphyllum total glycoside raw material is controlled to be 6-7%, and the weight ratio of the gynostemma pentaphyllum total glycoside raw material to silicon dioxide is 1:0.04.

[0036] Compared with the prior art, the present application has the following beneficial effects:

[0037] The present application improves the existing gynostemma pentaphyllum total glycoside capsule preparation process, combines the actual situation of each production process, and constructs a continuous production method of gynostemma pentaphyllum total glycoside capsule. For this product, under the existing equipment conditions, through simple modification, vacuum feeding through pipeline, gravity discharge, and under the process conditions of the present application, continuous production can be realized. In the whole production process, closed and continuous production is realized, dust pollution and labor intensity are reduced, occupational health protection is strengthened, production efficiency is improved, and basis for intelligent manufacturing can be provided.

[0038] At the same time, due to the process of the present application, dry granulation is adopted, which avoids the use of more auxiliary materials, thereby greatly reducing the proportion of auxiliary materials in the finished product. Therefore, small capsules can be filled, the difficulty of swallowing for patients is reduced, and patient compliance is improved. In addition, the gynostemma pentaphyllum total glycoside capsule prepared by the present application can reduce the influence on the gastric mucosa barrier function and the stimulation to the stomach compared with the gynostemma pentaphyllum total glycoside capsule sample prepared by the original process, thereby reducing the adverse reactions to the stomach, such as stomach pain and diarrhea. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 Gynostemma pentaphyllum total glycoside capsule sample dissolution curve (water) graph DETAILED DESCRIPTION

[0040] Example 1

[0041] The present embodiment discloses a continuous preparation process of gynostemma pentaphyllum total glycoside capsule, which specifically comprises the following steps:

[0042] Step 1, batching: weighing gynostemma pentaphyllum total glycoside raw material and silicon dioxide;

[0043] Step 2, mixing: the weighed gynostemma pentaphyllum total glycoside raw material and silicon dioxide are conveyed to the mixing machine through the pipeline under vacuum, and are fully mixed and uniformly distributed.

[0044] Step 3, granulation: after mixing, the material is vacuumed to the feeding port of the dry granulator, and the pressure of the pressure roller, the feeding speed, the rotation speed of the pressure roller, the gap of the pressure roller are adjusted so that the material is extruded into a sheet, and the screening speed and the mesh size of the screen are controlled, after the sheet material is screened, the qualified particles of 40-65 mesh are collected, and the unqualified particles are continuously vacuumed to the feeding port of the dry granulator for continuous granulation until all the material is granulated into qualified particles;

[0045] Step 4, total mixing: the qualified particles are vacuumed into the total mixing device for mixing;

[0046] Step 5, filling: the total mixed particles are vacuumed into the capsule filling machine feeder for filling capsules;

[0047] Among them, the equipment in each process step is connected by closed pipeline, after the preparation of step 1 is completed, all the materials and intermediates in the process are vacuumed, gravity discharged, and then transported to the next step to realize continuous production.

[0048] Among them, in step 1, the moisture content of the gynostemma total glycoside raw material is controlled to be 5%-7%, and the weight ratio of the gynostemma total glycoside raw material to silicon dioxide is 1:0.005-1:0.05.

[0049] Further, in step 3, the dry granulation parameters are:

[0050] The feeding speed is 30rpm-50rpm;

[0051] The pressure of the pressure roller is 70bar-90bar;

[0052] The gap of the pressure roller is 0.5mm-2.0mm;

[0053] The rotation speed of the pressure roller is 10rpm-20rpm;

[0054] The screening speed is 80rpm-125rpm;

[0055] The mesh size of the screen is 40-65 mesh.

[0056] Preferably, in step 3, the specific parameters are:

[0057] The feeding speed is 40rpm;

[0058] The pressure of the pressure roller is 80bar;

[0059] The gap of the pressure roller is 1.5mm;

[0060] The rotation speed of the pressure roller is 15rpm;

[0061] The screening speed is 100rpm;

[0062] The mesh number of the screening screen is 50-60.

[0063] In step 4, the total mixing time is 3-5 min.

[0064] In step 5, the capsule model is 5#.

[0065] In step 1, the moisture content of the gynostemma pentaphyllum total glycoside raw material is controlled to be 6-7%, and the weight ratio of the gynostemma pentaphyllum total glycoside raw material to silicon dioxide is 1:0.04.

[0066] Under the process conditions of the present application, continuous production can be realized, and in the entire production process, closed and continuous production is realized, dust pollution and labor intensity are reduced, occupational health protection is strengthened, production efficiency is improved, and basis can be provided for intelligent manufacturing.

[0067] In addition, compared with the gynostemma pentaphyllum total glycoside capsule prepared by the original process, the gynostemma pentaphyllum total glycoside capsule prepared by the present application can reduce the influence on the gastric mucosa barrier function and the stimulation to the stomach, thereby reducing the adverse reactions to the stomach, such as stomach pain and diarrhea.

[0068] In order to facilitate further understanding of the present application by those skilled in the art, the present application will be further described below and in specific implementation cases.

[0069] A continuous preparation process of gynostemma pentaphyllum total glycoside capsules specifically includes the following steps:

[0070] Step 1, batching: weighing gynostemma pentaphyllum total glycoside raw material and silicon dioxide;

[0071] Step 2, mixing: the weighed gynostemma pentaphyllum total glycoside raw material and silicon dioxide are conveyed to a mixer through a pipeline under vacuum, and are fully mixed and uniformly distributed; the moisture content of the gynostemma pentaphyllum total glycoside raw material is controlled to be 7%, and the weight ratio of the gynostemma pentaphyllum total glycoside raw material to silicon dioxide is 1:0.04.

[0072] Step 3, granulation: after mixing, the material is vacuumed to the feeding port of a dry granulator, and the pressure of the pressure roller of the dry granulator, the feeding speed, the rotation speed of the pressure roller, and the gap between the pressure rollers are adjusted, so that the material is extruded into a sheet shape, and the screening mesh number and the screening speed are controlled; after the sheet material is screened, 40-65 mesh qualified particles are collected, and unqualified particles are continuously vacuumed to the feeding port of the dry granulator for continuous granulation until all the material is granulated into qualified particles.

[0073] Specific process parameters are as follows: the feeding speed is 40 rpm; the pressure of the pressure roller is 80 bar; the gap between the pressure rollers is 1.5 mm; the rotation speed of the pressure roller is 15 rpm; the screening mesh number is 50-60.

[0074] Step 4, total mixing: the qualified particles are vacuumed to a total mixing device, and are mixed for 4 min.

[0075] Step 5, filling: the total mixed particles are extracted into the capsule filling machine feeder by vacuum loading to fill the capsule;

[0076] In each process step, the equipment is connected by closed pipes, after the end of step 1, all materials and intermediates in the preparation process are loaded by vacuum, gravity discharged, and then transported to the next step to realize continuous production.

[0077] Compared with the preparation process of gypenoside capsules in the prior art, the present application is completely different; the current process is: gypenoside raw materials are mixed with excipients and directly filled into capsules; the process of the present application is: gypenoside raw materials are mixed with a small amount of excipients, dry granulation, and filled into capsules.

[0078] The present application adopts a continuous preparation method in the process aspect, realizes closed and continuous production in the whole production process, reduces dust pollution and labor intensity, strengthens occupational health protection, and improves production efficiency;

[0079] At the same time, due to the process of the present application, dry granulation is adopted, which avoids the use of more excipients, thereby greatly reducing the proportion of excipients in the finished product, small capsules can be filled, the difficulty of swallowing for patients is reduced, and the patient compliance is improved.

[0080] In addition, surprisingly, the gypenoside capsules prepared by the present application can reduce the influence on the gastric mucosa barrier function compared with the gypenoside capsules prepared by the original process, and can further reduce the adverse reactions on the stomach, such as stomach pain and diarrhea.

[0081] The parameters are optimized by adopting the scheme in the above case 1, and the specific test data are as follows:

[0082] 1. Dry granulation moisture investigation

[0083] The influence of gypenoside raw material moisture on dry granulation is investigated, and the granule yield and the degree of smoothness in the granulation process are evaluated, and the specific conditions are shown in the following table:

[0084]

[0085]

[0086] The moisture of gypenoside raw materials is controlled to be 5%-7%, when the moisture is lower than 5%, dry granulation is not easy to be pressed into shape, resulting in more fine powder, poor flowability during filling, and not meeting the filling requirements; when the moisture is higher than 7%, the adhesion of the pressure roller is difficult, resulting in difficulty in production; when the moisture is in the range of 5%-7%, the granule forming rate is greatly improved, and the adhesion of the pressure roller and the difficulty in discharging are improved.

[0087] 2. Auxiliary amount investigation

[0088] The molding property of dry granulation is improved by increasing the moisture of gypenoside raw material. It is found that the higher the moisture, the stronger the viscosity, but it will also adhere to the pressure roller and hinder dry granulation. It is found that silicon dioxide can significantly improve the adhesion of the material to the pressure roller without reducing the molding property. The specific conditions are as follows:

[0089]

[0090] In actual use, the moisture of gypenoside raw material is in the range of 5%-7%, and the addition of silicon dioxide can improve the adhesion of the material to the pressure roller and the difficulty of discharging, solve the adhesion and flowability of the material, and not affect the molding property of the granules, which is convenient for dry granulation. The weight ratio of the two is 1:0.005-1:0.05. If too little silicon dioxide is added, it cannot solve the flowability of gypenoside material, and it cannot offset the adhesion of gypenoside dry granulation to the pressure roller. If too much silicon dioxide is added, the material will be light after mixing with gypenoside material, and the molding property of dry granulation will be poor.

[0091] By using a small amount of silicon dioxide, the problem of dry granulation by using a large amount of auxiliary materials is avoided, and only 0.5%-5% of auxiliary materials are added on the basis of the dosage of gypenoside raw material, which effectively reduces the dosage of the drug, and then small capsules can be filled.

[0092] 3. Filling investigation

[0093] The samples prepared by the current process and the process in case 1 of the invention were respectively filled into capsules, and the weight difference and disintegration time were used as evaluation indexes.

[0094] After comparing the disintegration time and weight difference of the products, the indexes are as follows:

[0095]

[0096] From the disintegration, the disintegration changes before and after the process change are not obvious, so it will not affect the quality of the product. The weight difference shows that the filling after dry granulation is more stable, and the process is smoother.

[0097] 4. Material property comparison

[0098]

[0099] The total mixed material after the present process is obviously different from the powder characteristics of the total mixed material after the process of the present application. The total mixed material after the present process is relatively loose, while the total mixed material after the process of the present application is compact. Therefore, when the process of the present application is used to fill capsules, smaller 5# capsules can be used, while when the present process is used to fill capsules, larger 1# capsules must be used. The angle of repose also shows that the total mixed material after the process of the present application has a smaller angle of repose, better flowability, smaller difference in filling amount, and is easy to control, which constitutes a necessary condition for realizing continuous production.

[0100] 5. Test of influence on normal rat gastric mucosa function

[0101] Test method: SD rats, body weight 180-220g, half male and half female, randomly divided into 3 groups, namely blank control group, 2 test groups. Each group is given by gavage according to the volume of 10ml / kg. The blank control group uses distilled water, and the test groups are given corresponding drugs and doses respectively. Drug administration is performed once a day, and continuous administration is performed for 10 days. After the last administration, the animals are fasted for 18h, and then sacrificed and the stomach is immediately taken out. The stomach is cut along the greater curvature, the contents are washed out, and then the filter paper is dried and placed on an ice tray to scrape the gastric mucosa. The gastric mucosa tissue homogenate is prepared by adding physiological saline at a ratio of 1:9 in an ice bath. The contents of SOD, MDA and PGE2 are detected by using the kit.

[0102] Influence of gynostemma pentaphyllum total glycoside samples prepared by different processes on the contents of SOD, MDA and PGE2 in normal rat gastric mucosa n=8, as shown in the following table:

[0103]

[0104] *: P<0.05 compared with the blank group

[0105] At a 5-fold dose in clinical use, compared with the blank group, the samples prepared by the present process and the process of the present application both increase the content of SOD in the gastric mucosa, and the sample prepared by the present process has a significant difference, while the sample prepared by the present application has no statistical significance. In terms of MDA content, the samples prepared by the two processes both have an increasing trend, but have no statistical significance. In terms of PGE2 content, compared with the blank group, the samples prepared by the present process and the process of the present application both have a decreasing trend in the content of PGE2 in the gastric mucosa, but have no statistical significance.

[0106] Superoxide dismutase (SOD) can protect the gastric mucosa from oxidative stress damage. When the gastric mucosa is subjected to external stimuli, a large number of reactive oxygen species are produced, which can damage the gastric mucosa. SOD can effectively scavenge these free radicals and maintain the stability of the gastric mucosa. In clinical use at 5 times the dose, both the samples prepared by the current process and the process of this invention increased the SOD content in the gastric mucosa, and the sample prepared by the current process showed a significant difference. This indicates that both the samples prepared by the current process and the process of this invention have a certain degree of irritation to the stomach. The sample prepared by the current process is more irritating than the sample prepared by the process of this invention, suggesting the possibility of stomach damage. Therefore, based on the experimental results, the sample prepared by the process of this invention is less irritating to the stomach than the sample prepared by the current process, thus having the advantage of reducing adverse reactions.

[0107] 6. Analysis of dissolution curves

[0108] To address the difference in gastric irritation between samples prepared using the process of this invention (Case 1) and samples prepared using existing processes, dissolution studies were conducted on samples prepared using different processes. The dissolution curve (water) of the Gynostemma pentaphyllum total glycosides capsule sample is shown below. Figure 1 As shown.

[0109]

[0110]

[0111] According to the test results, the samples prepared by the process of this invention dissolve more slowly than those prepared by the original process, thereby reducing the irritation of the drug to the stomach. Therefore, the samples prepared by the process of this invention are less irritating to the stomach than those prepared by the current process, thus having the advantage of reducing adverse reactions.

[0112] In designing this process, the first step was to have a thorough understanding of the Gynostemma pentaphyllum raw material. A detailed study and verification of the formulation process route was then conducted, ultimately determining the dry granulation process. Simultaneously, a detailed investigation of dry granulation was carried out, and optimal parameters were determined, thus ensuring the stability and controllability of the newly designed process route. The realization of this process is based on extensive research results and creative application of material characteristics; it is not simply a combination or superposition of processes.

[0113] In addition, if the current Gynostemma pentaphyllum total glycosides capsule process route and parameters are directly used, continuous production and small capsule filling cannot be realized. First, the process of the application is consistent with the amount of Gynostemma pentaphyllum total glycosides raw materials in the current Gynostemma pentaphyllum total glycosides capsule preparation process, so that the raw materials taken by patients before and after the application are consistent. However, the auxiliary materials used before and after the application are quite different. Before the application, a large amount of auxiliary materials (the ratio of raw materials to auxiliary materials is about 1:2) is added to ensure the flowability of the materials and offset the poor flowability of the raw materials. At the same time, due to the increase in the amount of auxiliary materials, a larger capsule size (1#) must be used to meet the filling requirements, and the swallowing experience of patients is not good. In terms of continuous production, the flowability of the intermediate materials in the current process cannot meet the requirements, so continuous production cannot be realized.

[0114] The most important thing for realizing continuous production is the convenient transportation of materials and the stability of the preparation process, that is, the flowability of the materials needs to be good. The Gynostemma pentaphyllum total glycosides raw material is amorphous powder with poor flowability, and the current process cannot realize continuous production. At the same time, to meet the subsequent filling requirements and ensure process stability, the current preparation method needs to add auxiliary materials to improve the flowability of the materials, but this will inevitably increase the amount of medication, which is contradictory to reducing the amount of medication. Therefore, in the process of preparing Gynostemma pentaphyllum total glycosides capsules, it is very difficult to ensure good flowability of the materials and easy filling while not using or using less auxiliary materials, which is a technical difficulty of the application.

[0115] In the prior art, to realize Gynostemma pentaphyllum total glycosides dry granulation and improve the forming rate of Gynostemma pentaphyllum total glycosides dry granulation, the method of adding auxiliary materials with good compressibility is usually used to offset the poor forming characteristics of Gynostemma pentaphyllum total glycosides raw materials, but the amount of auxiliary materials is also large, which is contradictory to reducing the amount of medication. Through the study of the properties of Gynostemma pentaphyllum total glycosides materials, the moisture content is controlled to stimulate the adhesion of the materials, thereby improving the granulation forming property. Then, a small amount of specific auxiliary materials is added to solve the problem of adhesion to the press roller and difficult discharging caused by moisture control. Finally, through moisture control and the addition of a small amount of auxiliary materials, Gynostemma pentaphyllum total glycosides capsules are continuously prepared, which reduces the swallowing difficulty of patients and improves patient compliance.

[0116] Surprisingly, the Gynostemma pentaphyllum total glycosides capsules prepared by the application can reduce the impact on the gastric mucosal barrier function compared with the Gynostemma pentaphyllum total glycosides capsules prepared by the original process, thereby reducing adverse reactions such as stomach pain and diarrhea, and having the advantage of reducing adverse reactions.

[0117] While the preferred embodiments of the application have been described, additional variations and modifications can be made to these embodiments by those skilled in the art once they have the benefit of the present disclosure. Therefore, the appended claims are intended to encompass all such variations and modifications as falling within the scope of the application.

[0118] The preferred embodiments of the application described hereinabove are therefore to be considered in all respects as illustrative only and not restrictive in character, since the scope of the application includes any modifications within the spirit and scope of the application as defined in the following claims.

Claims

1. A continuous process for the preparation of Gypenosides capsule, characterized in that, Specifically comprising the following steps: Step 1, batching: weighing the gypenosides raw material and silica; Step 2, mixing: the weighed gypenosides raw material and silica are transported to the mixer through the pipeline under vacuum, and are fully mixed and uniformly distributed; Step 3, granulation: after mixing, the material is vacuumed to the feeding port of the dry granulator, and the pressure of the pressure roller, the feeding speed, the rotation speed of the pressure roller, and the gap between the pressure rollers are adjusted so that the material is extruded into a sheet shape, and the screening speed and the mesh size of the screen are controlled. After the sheet material is screened, the qualified particles of 40-65 mesh are collected, and the unqualified particles are continuously vacuumed to the feeding port of the dry granulator for continuous granulation until all the material is granulated into qualified particles; Step 4, total mixing: the qualified particles are vacuumed to the total mixing equipment for mixing; Step 5, filling: the mixed particles are vacuumed to the capsule filling machine feeder for filling capsules; In each process step, the equipment is connected by closed pipeline. After the batching in step 1 is completed, all the materials and intermediates in the preparation process are vacuumed and gravity discharged, and then are transported to the next step to realize continuous production. In step 1, the moisture content of the gypenosides raw material is controlled to be 5%-7%, and the weight ratio of the gypenosides raw material to silica is 1:0.005-1:0.

05.

2. The continuous preparation process of gypenosides capsules according to claim 1, characterized in that, The dry granulation parameters in step 3 are as follows: The feeding speed is 30rpm-50rpm; The pressure of the pressure roller is 70bar-90bar; The gap between the pressure rollers is 0.5mm-2.0mm; The rotation speed of the pressure roller is 10rpm-20rpm; The screening speed is 80rpm-125rpm; The mesh size of the screen is 40-65 mesh.

3. The continuous preparation process of gypenosides capsules according to claim 2, characterized in that: The specific parameters in step 3 are as follows: The feeding speed is 40rpm; The pressure of the pressure roller is 80bar; The gap between the pressure rollers is 1.5mm; The rotation speed of the pressure roller is 15rpm; The screening speed is 100rpm; The mesh size of the screen is 50-60 mesh.

4. The continuous preparation process of gypenosides capsules according to claim 1, characterized in that: In step 4, the total mixing time is 3-5min.

5. The continuous preparation method of the gypenosides capsule according to claim 1, characterized in that: In step 5, the capsule type is 5#.

6. The continuous preparation process of gypenosides capsules according to claim 2, characterized in that: In step 1, the moisture content of the gypenosides raw material is controlled to be 6-7%, and the weight ratio of the gypenosides raw material to silica is 1:0.04.

Images