A kind of Jinshuibao micropill capsule and preparation method thereof

Abstract

The invention discloses a Jinshuibao micropill capsule and a preparation method thereof, and relates to the field of medicine, specifically comprising: 630 parts of fermented cordyceps powder (CS-4), 126 parts of hydrophilic adjuvants, 15-25 parts of hydrophilic gel skeleton materials, and 15-23 parts of coating materials. Fermented cordyceps powder (CS-4) is mixed with hydrophilic adjuvants and then crushed by an ultrafine grinder to obtain an extremely fine powder mixed powder, and a 40-60 mesh screened micropill mother core is prepared with an aqueous solution of 3-5wt% of the skeleton material, and the above-mentioned mixed powder is added by a powder layering method to prepare a 18-24 mesh screened micropill, dried, coated, and filled, and the present invention adopts hydrophilic adjuvants, hydrophilic gel skeleton materials, and Chinese medicine sustained-release micropill coating materials to change the surface activity of poorly soluble drugs, promote the precipitation and dissolution of poorly soluble drugs in the human body, improve drug dissolution and release, and make the drug absorption rate uniform, thereby improving the absorption and utilization efficiency of drugs in the gastrointestinal mucosa of patients.

Description

Technical Field

[0001] The invention relates to the field of medicine, and in particular to a Jinshuibao micropill capsule and a preparation method thereof. Background Art

[0002] Jinshuibao Capsule is a national first-class new drug, which has the functions of nourishing lung and kidney, retaining essence and replenishing Qi. It is used for lung and kidney deficiency, lack of essence and Qi, chronic cough and asthma, fatigue, insomnia and forgetfulness, soreness of waist and knees, irregular menstruation, impotence and premature ejaculation, etc. The product has significant efficacy and is well received by pharmaceutical companies and patients, with sales volume and output value increasing year by year.

[0003] The main raw material of Jinshuibao Capsule, fermented Cordyceps sinensis powder (Cs-4), is a raw material obtained by drying and crushing the mycelium obtained by fermenting the matrix with Paecilomyces cerevisiae (Cs-4) and then drying and crushing it. It has strong hydrophobicity. The drug can only be absorbed by the gastrointestinal epithelial cell mucosa when it is dissolved. When the drug has poor solubility and is difficult to absorb, it will result in low oral bioavailability, and its application will be greatly limited.

[0004] The existing preparation method of Jinshuibao capsule is as follows: fermented Cordyceps sinensis powder (Cs-4) is taken and filled into a gelatin hollow capsule to obtain the capsule.

[0005] The above preparation method is powder filling. A large amount of dust is generated during the filling production process. If inhaled into the respiratory tract of the production operator, it will cause bronchial asthma, pneumonia, pneumoconiosis, etc. In addition, it will also damage the defense system and cause allergic rhinitis and other hazards. It is well known that Chinese medicine powder has strong hygroscopicity and a short shelf life. It is very easy to be unqualified during the validity period, thus affecting the efficacy. After the powder in the capsule enters the gastrointestinal tract, it is not conducive to dissolution and release, which is easy to cause adverse reactions and local irritation due to excessive local drug concentration.

[0006] In order to solve the above problems, the inventors have obtained a new method for preparing Jinshuibao micropill capsules, a traditional Chinese medicine preparation, through a large number of experiments, thereby improving the efficacy and quality of Jinshuibao capsules, improving drug dissolution and release, making drug absorption rate uniform, and reducing adverse drug reactions and local irritation in patients. The preparation process of the present invention is convenient, suitable for large-scale production, and has good control of product quality. Summary of the invention

[0007] The purpose of the present invention is to solve at least one of the technical problems existing in the prior art and to provide a Jinshuibao micropill capsule and a preparation method thereof.

[0008] The technical solution of the present invention is as follows:

[0009] A Jinshuibao micropill capsule, comprising the following raw materials in parts by weight:

[0010] 630 parts of fermented Cordyceps sinensis powder (Cs-4), 126 parts of hydrophilic auxiliary materials, 15-25 parts of hydrophilic gel skeleton materials, and 15-23 parts of coating materials.

[0011] Preferably, the hydrophilic auxiliary material is at least one of starch, dextrin, sodium carboxymethyl starch, lactose and talc.

[0012] Preferably, the hydrophilic gel skeleton material is at least one of sodium carboxymethylcellulose (CMC-Na), methylcellulose (CM), hydroxypropyl methylcellulose (HPMC), polyvidone (PVP), carbomer (acrylic resin), and deacetylated chitosan (chitosan).

[0013] Preferably, the aqueous solution concentration of the hydrophilic gel skeleton material is 3-5 wt %.

[0014] Preferably, the ultrafinely crushed fermented Cordyceps sinensis powder (Cs-4) is mixed evenly with a hydrophilic auxiliary material to obtain an ultrafine powder mixture, a micropellet core is prepared with an aqueous solution of a hydrophilic gel skeleton material, and the micropellet core is added to the mixture by a powder layering method to prepare micropellets, which are then dried, coated, and filled.

[0015] Preferably, the micropellet core is obtained by sieving with 40-60 mesh.

[0016] Preferably, the micropellets are obtained by sieving with 18-24 mesh.

[0017] Preferably, the coating material is at least one of Type II acrylic resin, cellulose acetate titanate (CAP), hydroxypropyl methylcellulose titanate (HPMCP), and hydroxypropyl methylcellulose acetate succinate (HPMCAS).

[0018] Powder layering method refers to depositing dry drug powder, or mixed powder of drug and excipients, on the surface of prefabricated pellet cores in the presence of adhesive and rolling conditions, so that the powder is gradually layered to form pellets of appropriate size.

[0019] The beneficial effects of the present invention are:

[0020] The present invention changes the surface activity of poorly soluble drugs by optimizing skeleton-type sustained-release materials, adding hydrophilic excipients and traditional Chinese medicine sustained-release micropill coating materials, promotes the precipitation and dissolution of poorly soluble drugs in the human body, makes the drug absorption rate uniform, and thus improves the absorption and utilization efficiency of drugs in the patient's gastrointestinal mucosa. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is the dissolution curve diagram of the original process and the process of the present invention. DETAILED DESCRIPTION

[0022] Microcapsules are spherical or quasi-spherical solid dosage forms with a diameter of less than 2.5 mm. Compared with powders and granules, microcapsules have the advantages of beautiful appearance, good fluidity, stable drug release, uniform drug absorption rate, high bioavailability, reduced drug irritation to the digestive tract, masking the unpleasant taste of certain drugs and moisture resistance.

[0023] There are many methods for preparing micropellets, and the most common methods at home and abroad are extrusion spheronization, fluidized bed method, coating pan method, centrifugal granulation method, etc. Among them, centrifugal granulation method is a more advanced micropellet preparation technology, which has the characteristics of simple operation, high production efficiency, automatic operation and large-scale production.

[0024] The object of the present invention is to provide a method for preparing Jinshuibao micropill capsules. The present invention reduces the health hazards of production personnel and improves the stability of drugs by changing the preparation method. The present invention also improves the dissolution and release of drugs and reduces the risk of adverse reactions of patients by optimizing hydrophilic gel skeleton materials and adding hydrophilic excipients. The present invention also achieves the purpose of moisture-proofing, odor-masking, increasing the stability of preparations, improving mechanical properties and controlling the release rate of drugs by optimizing the film coating materials of traditional Chinese medicine sustained-release micropills. The present invention also provides a centrifugal granulation method.

[0025] The object of the present invention is achieved in this way: by continuously optimizing the process of the prescription, the stability of the drug is improved.

[0026] The Jinshuibao micropill capsule of the present invention is prepared from the following Chinese medicinal raw materials in parts by weight:

[0027] 630 parts of fermented Cordyceps sinensis powder (CS-4), 126 parts of sodium carboxymethyl starch, 15-25 parts of hypromellose, and 15-23 parts of hypromellose titanate;

[0028] The fermented Cordyceps powder (C S -4) and sodium carboxymethyl starch in a drug-excipient mass ratio of 5:1 to obtain a fine powder mixture, a 3-5% mass concentration of hydroxypropyl methylcellulose aqueous solution is used as a hydrophilic gel skeleton material to prepare a micropellet mother core with a 40-60 mesh sieve, and the above-mentioned mixed powder is added by powder layering method to prepare micropellets with a 18-24 mesh sieve, and the mixture is dried, coated, and filled to obtain the product.

[0029] (1) Prescription design and prescription screening

[0030] The purpose of the present invention is achieved in this way: water solubility is an important physicochemical property that affects drug absorption and efficacy, and only dissolved drugs can be absorbed into the circulatory system through transcellular pathways or paracellular pathways; because the main raw material of Jinshuibao Capsule, fermented Cordyceps sinensis powder (Cs-4), has strong hydrophobicity, it causes low oral bioavailability, and low bioavailability is the main reason why pharmacologically active substances cannot become therapeutic drugs; therefore, the present invention changes the surface activity of poorly soluble drugs by optimizing hydrophilic gel skeleton materials and adding hydrophilic excipients, promotes the precipitation and dissolution of poorly soluble drugs in the human body, thereby improving the absorption and utilization efficiency of drugs in the patient's gastrointestinal mucosa; the present invention also optimizes the film coating material of traditional Chinese medicine sustained-release micropills to achieve the purposes of moisture-proofing, odor-masking, increasing preparation stability, improving mechanical properties and controlling the release rate of drugs.

[0031] Hydrophilic excipients: starch, dextrin, sodium carboxymethyl starch, lactose, talc, etc.

[0032] Hydrophilic gel skeleton materials: sodium carboxymethyl cellulose (CMC-Na), methyl cellulose (CM), hydroxypropyl methyl cellulose (HPMC), polyvidone (PVP), carbomer (acrylic resin), deacetylated chitosan (chitosan), etc.

[0033] Coating materials for Chinese medicine sustained-release micropellets: Type II acrylic resin, cellulose acetate titanate (CAP), hydroxypropyl methylcellulose titanate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), etc.

[0034] Experimental research equipment and model: LBZ-315 multifunctional centrifugal granulator.

[0035] Original prescription process: Take fermented Cordyceps sinensis powder (Cs-4) and put it into gelatin hollow capsules.

[0036] (2) Selection of auxiliary materials

[0037] The original prescription of Jinshuibao capsule is directly filled with the raw material fermented Cordyceps powder (Cs-4); since the raw material has strong hydrophobicity and poor solubility, it leads to certain difficulties in drug absorption; and adding appropriate amounts of hydrophilic excipients such as starch, dextrin, sodium carboxymethyl starch and other fine powders to the solid preparation prescription to prepare micropills can promote drug dissolution, improve product quality, and improve product fluidity, making the filling amount more stable; therefore, in view of the problems of the original prescription of Jinshuibao capsule, the process of the present invention respectively adds starch, dextrin, sodium carboxymethyl starch, lactose and talcum powder as excipients to prepare micropills for excipient type selection research, and conducts a single factor investigation on the excipient type based on the quality indicators such as micropill sticking and wall sticking, 18-24 mesh micropill yield, properties, roundness and micropill condition and dissolution, and synchronously conducts a comparative study on the quality indicators such as product filling amount difference and disintegration time limit with the original prescription process. The prescription design and experimental results are shown in Tables 1 and 2 below.

[0038] Table 1 Excipient types, prescription design and experimental results

[0039]

[0040]

[0041] From the test results in Table 1 above, it can be seen that when pellets are prepared with starch and lactose as excipients, there are more sticky pellets and sticky walls, the yield of 18-24 mesh pellets is low, the color is uneven, there are flower colors, the pellets are not round, there are slightly irregular and deformed pellets, and the solubility is low; when pellets are prepared with dextrin and talcum powder as excipients, although the sticky pellets and sticky walls, properties, roundness and pellet conditions are in line with experimental expectations, the yield and solubility of 18-24 mesh pellets are low; and when pellets are prepared with sodium carboxymethyl starch as an excipient, the yield and solubility of 18-24 mesh pellets are high, and the quality indicators such as sticky pellets and sticky walls, properties, roundness and pellet conditions are in line with experimental expectations. Therefore, sodium carboxymethyl starch is selected as the best excipient type.

[0042] Table 2 Original recipe process and recipe design of the present invention and experimental results

[0043] Technology Difference in filling volume Disintegration time Original prescription process +2.8% to -3.6% 9 minutes Process of the present invention +1.5% to -1.1% 8 minutes

[0044] It can be seen from the test results in Table 2 above that the filling amount difference of the inventive process is better than that of the original prescription process, indicating that the filling process of the inventive process is more stable, the product quality uniformity is good, and it is more conducive to production control.

[0045] (3) Selection of drug-excipient ratio

[0046] According to the above preferred excipient type (sodium carboxymethyl starch powder), fermented Cordyceps sinensis powder (Cs-4) powder was taken, and the drug-excipient mass ratio was 3:1, 5:1, 7:1, 9:1, and 11:1 as the drug-excipient ratio, respectively. The drug-excipient ratio was investigated by single factor based on quality indicators such as pellet sticking and wall sticking, 18-24 mesh pellet yield, properties, roundness, pellet condition, and dissolution. The prescription design and experimental results are shown in Table 3 below.

[0047] Table 3 Drug-excipient ratio prescription design and experimental results

[0048]

[0049] From the test results in Table 3 above, it can be seen that when the drug-excipient ratio is 11:1, the pellets are prepared according to the above-mentioned optimized process, and there are slight sticky pellets and sticky walls. The yield of 18-24 mesh pellets is low, the pellets are not round, there are slightly irregular and deformed pellets, and the solubility is low; when the drug-excipient ratios are 7:1 and 9:1, the pellets are prepared. Although the quality indicators such as sticky pellets and sticky walls, properties, roundness and pellet conditions are in line with the experimental expectations, the yield and solubility of 18-24 mesh pellets are low; and when the drug-excipient ratios are 3:1 and 5:1, the pellets are prepared. The yield and solubility of 18-24 mesh pellets are high, and the quality indicators such as sticky pellets and sticky walls, properties, roundness and pellet conditions are in line with the experimental expectations. Considering the principle of less excipients, 5:1 is selected as the best drug-excipient ratio.

[0050] (4) Selection of material particle size

[0051] According to the above preferred excipient type (sodium carboxymethyl starch) and drug-excipient ratio (5:1), the medium powder, fine powder, finest powder and ultrafine powder of the drug-excipient were sieved after being crushed by a universal grinder and an ultrafine grinder respectively. The material particle size was investigated by single factor based on quality indicators such as pill sticking, wall sticking, 18-24 mesh pellet yield, properties and roundness, and pellet condition. The prescription design and experimental results are shown in Table 4 below.

[0052] Table 4 Material particle size prescription design and experimental results

[0053]

[0054] Note: The powder classification in the table is in accordance with the provisions of the first volume of the 2020 edition of the Chinese Pharmacopoeia.

[0055] It can be seen from the test results in Table 4 that when the material particle size is medium powder, the micropellets are prepared according to the above-mentioned optimized process. Although the sticky pills and sticky wall conditions meet the experimental expectations, the yield of 18-24 mesh micropellets is low, the color of the micropellets is uneven, and the micropellets are not round, and there are many special-shaped and deformed micropellets; when the micropellets are prepared with the material particle size of fine powder and the finest powder, although the sticky pills and sticky wall conditions, properties and roundness and micropellet conditions meet the experimental expectations, the yield of 18-24 mesh micropellets is low; and when the micropellets are prepared with the material particle size of ultrafine powder, the yield of 18-24 mesh micropellets is high, and the quality indicators such as sticky pills, sticky wall conditions, properties and roundness and micropellet conditions meet the experimental expectations, so the material particle size is selected as ultrafine powder.

[0056] (5) Selection of skeleton material

[0057] According to the above preferred excipient type (sodium carboxymethyl starch), drug-excipient ratio (5:1) and material particle size (ultrafine powder), sodium carboxymethyl cellulose (CMC-Na), methyl cellulose (CM), hydroxypropyl methylcellulose (HPMC), polyvidone (PVP), carbomer (acrylic resin) and deacetylated chitosan (chitosan) were used as skeleton materials, and the type of skeleton material was investigated by single factor based on quality indicators such as pellet sticking and wall sticking, 18-24 mesh pellet yield, properties and roundness, and pellet condition. The prescription design and experimental results are shown in Table 5 below.

[0058] Table 5 Framework material type prescription design and experimental results

[0059]

[0060] From the test results in Table 5, it can be seen that when povidone, carbomer and deacetylated chitosan are used as skeleton materials, there are more sticky pellets and wall-sticking situations, the yield of 18-24 mesh micropellets is low, the color is uneven, there are flower colors, and the roundness of micropellets is poor, and there are more special-shaped and deformed micropellets; when sodium carboxymethyl cellulose and methyl cellulose are used as skeleton materials, there are slight sticky pellets and wall-sticking situations, the yield of 18-24 mesh micropellets is low, the micropellets are relatively round, and there are a small number of special-shaped micropellets, while when hydropropyl methyl cellulose is used as skeleton material, the yield of 18-24 mesh micropellets is high, the sticky pellets and wall-sticking situations, the properties and roundness and micropellet situation are all in line with the experimental expectations, so hydropropyl methyl cellulose is selected as the best skeleton material type.

[0061] (6) Selection of skeleton material concentration

[0062] According to the above preferred excipient type (sodium carboxymethyl starch), drug-excipient ratio (5:1), material particle size (ultrafine powder) and skeleton material type (hydroxypropyl methylcellulose), 2%, 3%, 4%, 5% and 6% by mass of hydroxypropyl methylcellulose aqueous solution were used as skeleton materials, and the concentration of the skeleton material was investigated by single factor based on quality indicators such as pellet sticking and wall sticking, 18-24 mesh pellet yield, properties and roundness, and pellet condition. The prescription design and experimental results are shown in Table 6 below.

[0063] Table 6 Framework material concentration prescription design and experimental results

[0064]

[0065] From the test results in Table 6 above, it can be seen that when the 2wt% hydroxypropyl methylcellulose aqueous solution is used as the skeleton material concentration, although the sticky pills, sticky wall conditions and properties meet the experimental expectations, the yield of 18-24 mesh micro-pellets is low, and there are a small number of fragile micro-pellets; when the 6% hydroxypropyl methylcellulose aqueous solution is used as the skeleton material concentration, there are slight sticky pills and sticky walls, the yield of 18-24 mesh micro-pellets is low, and there are a small number of irregular micro-pellets; and when the 3%, 4% and 5% hydroxypropyl methylcellulose aqueous solution is used as the skeleton material concentration, the yield of 18-24 mesh micro-pellets is high, and the sticky pills, sticky wall conditions, roundness and micro-pellets conditions all meet the experimental expectations, so the optimal concentration of the hydroxypropyl methylcellulose aqueous solution is selected as 3%-5%.

[0066] (7) Investigation of preparation process

[0067] According to the above preferred excipient type (sodium carboxymethyl starch), drug-excipient ratio (5:1), material particle size (ultrafine powder), skeleton material type (hydroxypropyl methylcellulose), and skeleton material concentration (3wt%), the preparation process was investigated by single factor based on quality indicators such as pellet sticking, wall sticking, 18-24 mesh pellet yield, properties, roundness, and pellet condition. The preparation process design and experimental results are shown in Tables 7 and 8 below.

[0068] Table 7 Experimental design of preparation process

[0069]

[0070] Table 8 Preparation process experimental results

[0071]

[0072] From the test results in Tables 7 and 8 above, it can be seen that the 18-24 mesh micropellets prepared by the processes of Test No. 1, Test No. 2 and Test No. 3 have low yields, slightly sticky pellets and wall-sticking conditions, the micropellets are relatively round, and there are a small number of irregular micropellets; while the micropellets prepared by the process of Test No. 4, the quality indicators such as sticky pellets and wall-sticking conditions, 18-24 mesh micropellets yield, properties and roundness, and micropellets conditions all meet the experimental expectations, so Test No. 4 is selected as the best micropellet preparation process.

[0073] (8) Screening of coating materials

[0074] The 18-24 mesh pellets prepared by the above preferred prescription process were respectively used as film coating materials using type II acrylic resin, cellulose acetate titanate (CAP), hydroxypropyl methylcellulose titanate (HPMCP), and hydroxypropyl methylcellulose acetate succinate (HPMCAS). The film coating materials were investigated by single factor based on quality indicators such as coating operation, coating forming rate, properties, and taste masking. The prescription design and experimental results are shown in Table 9 below:

[0075] Table 9: Coating material formulation design and experimental results

[0076]

[0077] From the above test results, it can be seen that when Type II acrylic resin and cellulose acetate titanate are used as coating materials, the micropills are slightly adhered to each other, the coating time is long, the coating formation rate is low, the color is more uniform, the pellet surface is rough, and the taste masking is poor; when hydroxypropyl methylcellulose acetate succinate is used as the coating material, the micropills are easy to stick to each other, the coating time is long, the coating formation rate is low, there are pitting, the pellet surface is rough, and the taste masking is poor; when hydroxypropyl methylcellulose titanate is used as the coating material, the quality indicators such as coating operation, coating formation rate, properties and taste masking are in line with the experimental expectations, so hydroxypropyl methylcellulose titanate is selected as the best film coating material.

[0078] (9) Therefore, the optimal process is selected as:

[0079] 630 parts of fermented cordyceps powder (CS-4), 126 parts of sodium carboxymethyl starch, 15-25 parts of hypromellose, and 15-23 parts of hypromellose titanate.

[0080] The fermented Cordyceps powder (C S -4) mixing with sodium carboxymethyl starch in a drug-excipient mass ratio of 5:1 to obtain a fine powder mixture, using a 3-5wt% hydroxypropyl methylcellulose aqueous solution as a skeleton material to prepare a 40-60 mesh pellet mother core, adding the above mixed powder by powder layering method to prepare 18-24 mesh pellets, drying, coating, filling, and obtaining;

[0081] The test results of products prepared by the invented optimal prescription process and other processes are shown in Table 10.

[0082] Table 10 Test results of products prepared by the invention prescription process and other processes:

[0083]

[0084] From the above test results, it can be seen that the product prepared according to the invention prescription process has various indicators of capsules that meet the requirements, the process is feasible, the overall process is easy to operate, and is suitable for promotion and application; while the product prepared according to patent application number 200610200325.X has high water content, and the content of uridine, guanosine and adenosine and the content of ergosterol are much lower than those of the invention process.

[0085] (10) Accelerated stability data of original process, invented process and other processes

[0086] The products prepared by the original process, the invented process and other processes were respectively taken and placed in commercial packaging for accelerated stability test. The test conditions were: temperature 40℃±2℃, relative humidity 75%±5% for 6 months. During the test period, samples were taken once in the 0th month, 1st month, 2nd month, 3rd month and 6th month respectively for testing. The experimental results are shown in Table 11 below.

[0087] Table 11 Accelerated stability data of original process, invented process and other processes

[0088]

[0089] From the above results, it can be seen that the product prepared by the original process and patent application number: 200610200325.X has a large upward trend in moisture content and a significant decrease in ergosterol content after the high temperature accelerated test; while the product prepared by the process of the present invention has good moisture stability after the high temperature accelerated test, and the uridine, guanosine and adenosine content and ergosterol content are basically not degraded. Therefore, the stability of the product prepared by the process of the present invention is significantly better than that of the original process, and it has strong antioxidant capacity and stable therapeutic effect.

[0090] (11) Comparison of dissolution curves between the original process and the invented process

[0091] Dissolution method: Adenosine was determined by high performance liquid chromatography (General Rule 0512) and dissolution method 1 (General Rule 0931).

[0092] Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel as filler; methanol-0.01 mol / L potassium dihydrogen phosphate solution (10:90) as mobile phase; column temperature 25°C; detection wavelength 254 nm. The theoretical plate number calculated based on the adenosine peak should be no less than 3000.

[0093] Preparation of reference solution: Take adenosine reference substance and add dissolution medium to prepare a mixed solution containing 4 μg per 1 ml as the reference solution.

[0094] Preparation of test solution: Take 6 capsules of the product into a dissolution cup, add 900 ml of dissolution medium with a pH of 1.2 (7.65 ml of hydrochloric acid plus water to 1000 ml), temperature 37 ± 0.5 ° C, rotation speed 50 r / min, and test according to the first method (basket method) in the general rule (0931). Sampling is carried out at 0.5h, 1h, 2h, 3h, and 4h, and filtering is performed.

[0095] Determination method: Accurately pipette 20μl of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0096] The products prepared by the original process and the invented process of this product were respectively taken to refer to the above dissolution test method. The experimental results are shown in Table 12 below. Figure 1 .

[0097] Table 12 Comparative data of dissolution between original process and invented process

[0098]

[0099] It can be seen from the above test results that the product prepared by the original process is quickly dissolved and released in 0.5h, which is easy to cause adverse reactions and local irritation due to excessive local drug concentration, and the cumulative dissolution rate is low. The product prepared by the process of the present invention has a solubility of 40.6%, 58.5%, 73.2%, 87.6% and 99.8% at 0.5h, 1h, 2h, 3h and 4h, respectively. The dissolution rate is uniform, the drug release is stable, the bioavailability is high, the irritation of the drug to the digestive tract is reduced, and the cumulative dissolution rate is significantly higher than the original process, thereby improving the product quality and making the drug efficacy more stable.

[0100] The following are specific embodiments of the present invention.

[0101] Embodiment 1:

[0102] Fermented Cordyceps powder (Cs-4) and sodium carboxymethyl starch were mixed evenly in a drug-excipient mass ratio of 5:1, and a 3wt% hydroxypropyl methylcellulose aqueous solution was used as a skeleton material to prepare a manually sieved 40-60 mesh micropellet mother core, and then the mixed powder was added by powder layering method to prepare 18-24 mesh micropellets.

[0103] Embodiment 2:

[0104] Fermented Cordyceps powder (Cs-4) and sodium carboxymethyl starch were mixed evenly in a drug-excipient mass ratio of 5:1, and a 4wt% hydroxypropyl methylcellulose aqueous solution was used as a skeleton material to prepare a 40-60 mesh micropellet mother core that was manually sieved, and then the above mixed powder was added using a powder layering method to prepare 18-24 mesh micropellets.

[0105] Embodiment 3:

[0106] Fermented Cordyceps sinensis powder (Cs-4) and sodium carboxymethyl starch were mixed evenly at a drug-excipient mass ratio of 5:1, a 5wt% hydroxypropyl methylcellulose aqueous solution was used as a skeleton material, and a 40-60 mesh micro-pellet mother core was prepared by manual sieving, and then the mixed powder was added by powder layering method to prepare 18-24 mesh micro-pellets;

[0107] Embodiment 4:

[0108] The fermented Cordyceps sinensis powder (Cs-4) with a particle size distribution of extremely fine powder was crushed by an ultrafine grinder and mixed evenly with sodium carboxymethyl starch at a drug-excipient mass ratio of 5:1. A 3wt% hydroxypropyl methylcellulose aqueous solution was used as a skeleton material to prepare a manually sieved 40-60 mesh micropill mother core, and then the mixed powder was added by powder layering method to prepare 18-24 mesh micropills.

[0109] Embodiment 5:

[0110] The fermented Cordyceps sinensis powder (Cs-4) with a particle size distribution of extremely fine powder was crushed by an ultrafine grinder and mixed evenly with sodium carboxymethyl starch at a drug-excipient mass ratio of 5:1. A 4wt% hydroxypropyl methylcellulose aqueous solution was used as a skeleton material to prepare a manually sieved 40-60 mesh micropill mother core, and then the mixed powder was added by powder layering method to prepare 18-24 mesh sieved micropills.

[0111] Embodiment 6:

[0112] The fermented Cordyceps sinensis powder (Cs-4) with a particle size distribution of extremely fine powder was crushed by an ultrafine grinder and mixed evenly with sodium carboxymethyl starch at a drug-excipient mass ratio of 5:1. A 5wt% hydroxypropyl methylcellulose aqueous solution was used as a skeleton material to prepare a manually sieved 40-60 mesh micropill mother core, and then the mixed powder was added by powder layering method to prepare 18-24 mesh micropills.

[0113] Embodiment 7:

[0114] The fermented Cordyceps sinensis powder (Cs-4) with a particle size distribution of extremely fine powder was crushed by an ultrafine grinder and mixed evenly with sodium carboxymethyl starch at a drug-excipient mass ratio of 5:1. A 3wt% hydroxypropyl methylcellulose aqueous solution was used as a skeleton material to prepare a manually sieved 40-60 mesh micropill mother core, and then the mixed powder was added by a powder layering method to prepare 18-24 mesh micropills; and then hydroxypropyl methylcellulose titanate was used as a coating material for coating.

[0115] Under the premise that no conflict occurs, those skilled in the art may freely combine and superimpose the above-mentioned additional technical features.

[0116] The above-mentioned embodiments only express the preferred implementation modes of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the present invention. It should be pointed out that, for ordinary technicians in this field, various other corresponding changes and deformations can be made according to the technical solutions and concepts described above, and all these changes and deformations should fall within the scope of protection of the claims of the present invention.

Claims

1. A Jinshuibao micropill capsule, characterized in that: Including the following raw materials by mass: 30 parts of fermented Cordyceps sinensis powder Cs-46, 126 parts of hydrophilic auxiliary materials, 15-25 parts of hydrophilic gel skeleton materials, and 15-23 parts of coating materials; The hydrophilic auxiliary material is sodium carboxymethyl starch; The hydrophilic gel skeleton material is hydroxypropyl methylcellulose; The coating material is hypromellose titanate; The aqueous solution concentration of the hydrophilic gel skeleton material is 3-5w%; The preparation method of the Jinshuibao micro-pill capsule comprises the following steps: taking ultrafinely pulverized fermented Cordyceps sinensis powder Cs-4 and mixing it evenly with a hydrophilic auxiliary material to obtain an ultrafine powder mixture, preparing a micro-pill mother core with an aqueous solution of a hydrophilic gel skeleton material, adding the micro-pill mother core to the mixture by a powder layering method to prepare micro-pills, drying, coating, and filling; The micropellet core is obtained by sieving with 40-60 mesh; The micropellets are obtained by sieving with 18-24 meshes.

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