Preparation and application of seed jade particles

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to preparation and application of seed jade particles. According to the preparation method disclosed by the invention, the preparation process of the seed jade particles is technically upgraded by preferably selecting auxiliary materials and controlling key technical points, and methods and parameters of extraction, concentration, purification, particle forming and the like of the traditional Chinese medicine composition are optimized, so that reliable guarantee is provided for improving the product quality. The finally obtained seed jade particles can meet clinical requirements, all indexes are superior to pharmacopoeia standards, and the seed jade particles are suitable for further expanded production.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to the preparation and application of jade seed particles. Background Art

[0002] Zhongyu granules are composed of astragalus, poria, fried atractylodes, fried coix seed, papaya, antler frost, salted eucommia, dipsacus root, bupleurum, tangerine peel, yam, phellodendron, anemarrhena, vinegar-cured cyperus, amomum, and patchouli. The launch of the product solves the problem of infertility and repeated implantation failure caused by spleen and kidney yang deficiency, dampness, turbidity and blood stasis. It has good safety and compliance, and has good market application prospects.

[0003] The prescription mechanism of Zhongyu Granule is clear and the curative effect is significant. Astragalus and antler frost are the main drugs in the prescription. Astragalus has the effect of invigorating qi and strengthening the exterior, tonifying the spleen and benefiting the lungs. It can help improve the body's immunity and enhance the circulation of qi and blood, especially for people with qi deficiency. Deer antler frost has the effect of invigorating the kidney and strengthening the tendons, replenishing the essence and benefiting the marrow, and can effectively nourish the kidney essence and warm and nourish the kidney yang. The kidney is the foundation of the innate nature. The use of deer antler frost helps to restore the fullness of kidney qi and enhance vitality. It is not dry and can warm and nourish without hurting the yin. It is very suitable for compatibility with astragalus to avoid excessive stimulation of yin fluid by a single yang qi tonic. It warms and nourishes the yang of the kidney and spleen, and benefits the vital energy without being too dry and harsh. Poria, stir-fried Atractylodes macrocephala, Chinese yam, and Patchouli are the assistant drugs, which strengthen the spleen and replenish qi, promote diuresis and eliminate dampness, and have a fragrant aroma to eliminate turbidity. It is assisted by dried tangerine peel, bupleurum, papaya, and Cyperus rotundus to regulate qi and dry dampness, and differentiate the turbidity of phlegm and dampness in the lipid membrane. It is assisted by Chuan Duan and Eucommia ulmoides to nourish the kidney and replenish essence, so as to help conceive the fetus. It is assisted by Amomum villosum, so that Anemarrhena asphodeloides and Phellodendron chinense can dry dampness and strengthen yin, and lead the other drugs downward to control the warm and dry nature of the other drugs, and prevent the disadvantages of damaging yin.

[0004] Zhongyu Granules is a classic Chinese medicine compound that has the effects of tonifying the spleen and replenishing qi and calming the fetus, and is widely used in clinical practice. Its original formula comes from the traditional Chinese medicine recipe for strengthening the spleen and calming the fetus, which contains 16 medicinal materials such as astragalus, Poria, Atractylodes macrocephala, Coix seeds, papaya, and antler frost. Through the modern secondary development of the recipe, the researchers not only innovated in the dosage form, but also improved the production process route to improve the patient's convenience and clinical efficacy. Through innovative dosage forms and production processes, Zhongyu Granules improve the convenience of clinical use while ensuring efficacy and safety, meeting the patient's dual needs for convenience and effectiveness of drug administration. With the continuous development and modernization of traditional Chinese medicine, similar innovative products will provide patients with richer and more efficient treatment options, and also lay the foundation for the future development of the traditional Chinese medicine industry. Summary of the invention

[0005] The present invention further upgrades the preparation process of seed jade particles by optimizing auxiliary materials and controlling key technical points, optimizes the extraction, concentration, purification, molding and other methods and parameters of the Chinese medicine composition, and provides reliable guarantee for improving product quality. The seed jade particles finally obtained can not only meet clinical needs, but also have various indicators that are better than the pharmacopoeia standards. It has good market application prospects.

[0006] Specifically, the technical solution of the present invention is as follows:

[0007] A method for preparing jade seed particles, the preparation of the jade seed particles comprising the following steps:

[0008] a. Extraction and purification process

[0009] 1) Grind patchouli and amomum villosum into finest powder, sieve, and sterilize by irradiation to obtain fine powder A for later use;

[0010] 2) Astragalus, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia bark, Dipsacus asper, Bupleurum, dried orange peel, Chinese yam, Phellodendron amurense, Rhizoma Anemarrhenae and vinegar fragrance are boiled in water, the decoction is combined, filtered and the filtrate is reserved;

[0011] 3) The filtrate of step 2) is concentrated to obtain a clear paste, vacuum dried, and crushed into fine powder B for later use;

[0012] b. Preparation process

[0013] 4) mixing the fine powder A of step 1) with a pharmaceutical excipient to obtain a mixture A, and then mixing it with the fine powder B of step 3) to obtain a seed jade fine powder;

[0014] 5) Adding a binder to the fine powder of seed jade to prepare a soft material, granulating, drying, granulating, sieving, mixing and packaging to obtain seed jade granules.

[0015] Furthermore, the radiation sterilization dose in step 1) is 8 kGy.

[0016] Furthermore, in step 2), 6-10 times the amount of water is added to astragalus, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia ulmoides, Dipsacus asper, bupleurum, tangerine peel, yam, Phellodendron chinense, Anemarrhena asphodeloides and vinegar fragrance, and the mixture is decocted for 60-90 minutes and filtered; 6-10 times the amount of salt water is added to the residue, and the mixture is decocted for 30-60 minutes, filtered, and the secondary filtrates are combined.

[0017] Furthermore, in step 2), the concentration of the saline solution is 0.5-0.9%, the amount used is 8 times the volume of the medicinal residue, and the soaking time is 10-15 hours.

[0018] Furthermore, the filtrate of step 3) is concentrated to a clear paste with a relative density of 1.06-1.11 at 65-75°C, ethanol is added to make the alcohol content 70%-80%, and the mixture is allowed to stand for more than 24 hours, filtered, and the ethanol is recovered under reduced pressure and concentrated to a relative density of 1.20-1.25 to obtain a thick paste. The vacuum degree is -0.08MPa--0.10Mpa, the drying temperature is 65°C-75°C, and the mixture is dried continuously for 6-10 hours. The mixture is crushed under vacuum and passed through an 80-mesh sieve to obtain fine powder B.

[0019] Furthermore, in step 4), the weight ratio of fine powder B to mixture A is 3:0.8-1.2, and more preferably 3:1; in step 5), a proper amount of adhesive is added to the seed jade fine powder to prepare a soft material, the amount of which is 30-40% of the weight of mixture B, granulated with a 16-mesh sieve, dried at 80°C for 3 hours, granulated with a 12-mesh sieve, sieved, mixed, and packaged to obtain the product.

[0020] Furthermore, the pharmaceutical excipient is one or more of maltodextrin, mannitol, microcrystalline cellulose, and sorbitol, more preferably maltodextrin and sorbitol, the dosage ratio is 2-5:1, more preferably, maltodextrin and sorbitol, the dosage ratio is 4:1; the adhesive is an alcohol solution of sodium carboxymethyl cellulose or an alcohol solution of cross-linked sodium carboxymethyl cellulose.

[0021] Furthermore, the medicinal materials are calculated by weight as follows: 213-370 parts of astragalus, 142-247 parts of poria, 142-247 parts of stir-fried atractylodes, 285-494 parts of stir-fried coix seeds, 142-247 parts of papaya, 285-494 parts of antler frost, 142-247 parts of salt eucommia, 142-247 parts of dipsacus root, 142-247 parts of bupleurum, 142-247 parts of tangerine peel, 285-494 parts of yam, 42-74 parts of phellodendron, 42-74 parts of anemarrhena, 142-247 parts of vinegar-soaked cyperus, 42-74 parts of amomum, and 71-123 parts of patchouli.

[0022] Furthermore, the weight ratio of the medicinal materials is as follows: 285 parts of astragalus, 190 parts of poria, 190 parts of stir-fried atractylodes, 380 parts of stir-fried coix seeds, 190 parts of papaya, 380 parts of antler frost, 190 parts of salt eucommia, 190 parts of dipsacus, 190 parts of bupleurum, 190 parts of tangerine peel, 380 parts of yam, 57 parts of phellodendron, 57 parts of anemarrhena, 190 parts of vinegar-cooked cyperus, 57 parts of amomum, and 95 parts of patchouli.

[0023] Compared with the prior art, the preparation process of the present invention has achieved unexpected beneficial effects, which are specifically shown as follows:

[0024] The present invention adopts different preparation processes for different traditional Chinese medicines to ensure the activity and content of effective ingredients, and at the same time utilizes the preferred auxiliary materials of granules, especially the characteristics of maltodextrin and sorbitol, to improve the preparation process of seed jade granules, and the granule molding indexes all meet the requirements of the Chinese Pharmacopoeia, thereby improving the quality of the seed jade granules; the seed jade granules prepared by the present invention have a moisture content of less than 1% after an exposure experiment (24h, temperature 25°C, humidity 40±5%), a newly molded particle size of more than 92%, and no turbidity after the solution is dissolved, and the preparation process is simple and can be further industrialized for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 : Illustration of the granules prepared in Example 7.

[0026] Figure 2 : Illustration of the granules prepared in Example 8.

[0027] Figure 3 : Illustration of the granules prepared in Example 9. DETAILED DESCRIPTION

[0028] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0029] Example 1: Validation of the method for extracting effective substances

[0030] The types and dosages of medicinal materials used are as follows: 28.5g of Astragalus, 19g of Poria, 19g of stir-fried Atractylodes, 38g of stir-fried Coix seeds, 19g of papaya, 38g of antler powder, 19g of salt Eucommia, 19g of Dipsacus asper, 19g of Bupleurum, 19g of dried tangerine peel, 38g of yam, 5.7g of Phellodendron, 5.7g of Anemarrhena, 19g of vinegar-soaked Cyperus rotundus, 5.7g of Amomum, and 9.5g of Patchouli.

[0031] The treatment methods and processes are shown in Table 1.

[0032] Table 1. Processing methods of different medicinal materials and the content of effective substances

[0033]

[0034]

[0035] Experiments have shown that the best extraction process is as follows: add 8-15 times the amount of water to astragalus, Poria, stir-fried Atractylodes, stir-fried Coix seeds, papaya, antler powder, salt Eucommia, Dipsacus asper, bupleurum, tangerine peel, yam, Phellodendron, Anemarrhena and vinegar fragrance, boil for 60-90 minutes, and filter; add 0.5-0.9% saline solution to the residue, and then add 6-10 times the amount of saline solution to the residue, boil for 30-60 minutes, filter, and combine the two filtrates.

[0036] Example 2: Verification of the filtrate treatment method

[0037] Table 2 Verification of filtrate concentration temperature and range

[0038]

[0039] In summary, considering the total amount of astragaloside IV and the transfer rate, the filtrate was concentrated to a clear paste with a relative density of 1.06-1.11 at 70°C.

[0040] Example 3: Study on the ethanol content concentration process

[0041] The main research was on the effect of ethanol content on the content of effective substances, especially the content of astragaloside IV, after reduced pressure concentration at 65℃-75℃. The results are shown in Table 3

[0042] Table 3 Ethanol content for the content of effective substances

[0043]

[0044] From the content of astragaloside IV in Table 3, ethanol was added to make the alcohol content 70%-80%, and the mixture was left to stand for more than 24 hours, filtered, and the ethanol was recovered under reduced pressure.

[0045] Example 3: Study on the concentration process

[0046] The liquid medicine is concentrated by vacuum concentration, and the concentration equipment is basically a single-effect or multi-effect concentrator. Since the main components of each medicinal flavor in the present invention are stable in nature, the temperature can be controlled within the range of 65℃ to 75℃ for vacuum concentration. In the pilot study, the difference in the index components in the concentrated solution after vacuum concentration at 65℃-75℃ was mainly investigated. The results are shown in Table 4

[0047] Table 4 Verification of drying and concentration process parameters

[0048]

[0049] As can be seen from Table 4, after concentration, the process is vacuum degree -0.08MPa--0.10Mpa, drying temperature, 65℃-75℃, concentrated to a relative density of 1.20-1.25 to obtain a thick paste.

[0050] In summary, after the optimization of Examples 1-3, the optimal preparation process of fine powder B is:

[0051] Example 4: Preparation process of fine powder B

[0052] 1) add 8 times the amount of water to Radix Astragali, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia ulmoides, Dipsacus asper, Radix Bupleuri, dried orange peel, Chinese yam, Phellodendron amurense, Rhizoma Anemarrhenae and vinegar fragrance, boil for 75 minutes, filter; add 0.7% saline solution to the residue, the amount is 8 times the volume of the residue, soak for 12 hours, boil for 40 minutes, filter, and combine the secondary filtrates;

[0053] 2) The filtrate was concentrated to a clear paste with a relative density of 1.08 at 70°C, ethanol was added to make the alcohol content 75%, and the mixture was allowed to stand for more than 24 hours, filtered, and the ethanol was recovered under reduced pressure and concentrated to a relative density of 1.22 to obtain a thick paste. The vacuum degree was -0.09 MPa, and the drying temperature was 70°C. The mixture was dried continuously for 8 hours, and then crushed under vacuum to pass through an 80-mesh sieve to obtain fine powder B.

[0054] Preparation: Fine powder B prepared by the optimal preparation process is used for the preparation of granules

[0055] Example 5: Experiment on the influence of pharmaceutical excipients on the preparation of seed jade particles

[0056] 1) Patchouli and Amomum villosum are crushed into the finest powder, sieved, and irradiated for sterilization at a dose of 8 kGy to obtain fine powder A for later use;

[0057] 2) The fine powder A was mixed with the auxiliary materials in Table 5 to obtain a mixture A, and then mixed with the fine powder B in Example 4 to obtain a seed jade fine powder (the weight ratio of the fine powder B to the mixture A was 3:1);

[0058] 3) Add appropriate amount of alcohol solution of sodium carboxymethyl cellulose to the seed jade fine powder to prepare a soft material, the amount used is 35% of the weight of mixture B, granulate through a 16-mesh sieve, dry at 80°C for 3 hours, granulate through a 12-mesh sieve, sieve, mix, and package to obtain the seed jade granules.

[0059] Table 5 Physical effects of different excipient combinations and dosages on particles

[0060]

[0061]

[0062] It can be seen from Table 5 that in terms of auxiliary material selection, maltodextrin, mannitol, microcrystalline cellulose, and sorbitol have better physical properties such as molding properties and solubility properties. Furthermore, the inventor creatively found and adjusted the proportions of thousands of types of auxiliary materials, and finally found that after the mixture of maltodextrin and sorbitol as auxiliary materials, the particle rate was higher. After exposure tests, it was found that the water content was lower than that of other combinations, and the ratio of 2-5:1 was further optimized.

[0063] Example 6: Effect of the ratio of fine powder B to mixture A on seed jade particles in the preparation process

[0064] 1) Patchouli and Amomum villosum are crushed into the finest powder, sieved, and irradiated for sterilization at a dose of 8 kGy to obtain fine powder A for later use;

[0065] 2) Mix the fine powder A with maltodextrin and sorbitol (the weight ratio of maltodextrin and sorbitol is 4:1) to obtain a mixture A, and then mix it with the fine powder B in step 3) to obtain the seed jade fine powder; wherein the weight ratio of the fine powder B to the mixture A is as shown in Table 6.

[0066] 5) Add appropriate amount of alcohol solution of sodium carboxymethyl cellulose to the seed jade fine powder to prepare a soft material, the amount used is 35% of the weight of mixture B, granulate through a 16-mesh sieve, dry at 80°C for 3 hours, granulate through a 12-mesh sieve, sieve, mix, and package to obtain the seed jade granules.

[0067] Table 6 The ratio of fine powder B to mixture A for the type of jade particles

[0068]

[0069] Among them, the method for investigating fluidity is as follows: take an appropriate amount of the particles of this embodiment, and naturally drop them from a funnel at a certain height (H) onto a horizontal plate until no more particles flow out of the funnel, read the radius scale of the horizontal plate from two directions respectively, obtain the diameter of the bottom surface of the cone formed, calculate the average value of the diameter (L), and then calculate the angle of repose (θ) of the particles according to the following formula.

[0070] tanθ=2H / L

[0071] Hygroscopicity investigation method: Place particles of about 2 mm thickness at the bottom of a flat weighing bottle that has been dried to constant weight. After accurate weighing, place it in a constant temperature and humidity chamber at 25°C ± 1°C and 80% ± 2% humidity. Open the lid of the flat weighing bottle, leave it for 24 hours, take it out, quickly weigh it accurately, and then calculate the moisture absorption percentage according to the following formula.

[0072] Moisture absorption rate (%) = (weight of particles after moisture absorption - weight of particles before moisture absorption) / weight of particles before moisture absorption × 100%.

[0073] From Table 6, it can be seen that the weight ratio of fine powder B to mixture A is 3:0.8-1.2, the fluidity is between 30-40°, the particles have a certain fluidity and are easy to process and shape, and the proportion of auxiliary materials has a great influence on hygroscopicity. In addition, in the pilot stage, from the perspective of appearance and shape, the weight ratio of fine powder B to mixture A is 3:0.8-1.2, and the physical properties such as shape and color also show superiority.

[0074] Embodiment 7: A method for preparing seed jade particles, specifically comprising the following steps:

[0075] The weight ratio of the medicinal materials is as follows: 285g of Astragalus, 190g of Poria, 190g of stir-fried Atractylodes, 380g of stir-fried Coix seeds, 190g of papaya, 380g of antler powder, 190g of salt Eucommia, 190g of Dipsacus asper, 190g of Bupleurum, 190g of dried tangerine peel, 380g of Chinese yam, 57g of Phellodendron, 57g of Anemarrhena, 190g of vinegar-cooked Cyperus rotundus, 57g of Amomum, and 95g of Patchouli.

[0076] 1) Patchouli and Amomum villosum are crushed into the finest powder, sieved, and irradiated for sterilization at a dose of 8 kGy to obtain fine powder A for later use;

[0077] 2) Add 8 times the amount of water to Radix Astragali, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia ulmoides, Dipsacus asper, Radix Bupleuri, dried orange peel, Chinese yam, Phellodendron amurense, Rhizoma Anemarrhenae and vinegar fragrance, boil for 75 minutes, filter; add 0.7% salt water in an amount of 8 times the volume of the residue, soak for 12 hours, boil for 45 minutes, filter, combine the secondary filtrates, filter, and set aside the filtrate;

[0078] 3) Concentrate to a clear paste with a relative density of 1.08 at 70°C, add ethanol to make the alcohol content 75%, let stand for more than 24 hours, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.22 to obtain a thick paste, vacuum degree -0.09Mpa, drying temperature, 70°C, continue drying for 8 hours, crush under vacuum to pass through an 80-mesh sieve, and obtain fine powder B for standby use;

[0079] b. Preparation process

[0080] 4) The fine powder A of step 1) is mixed with maltodextrin and sorbitol (the weight ratio of maltodextrin and sorbitol is 4:1) to obtain a mixture A, and then mixed with the fine powder B of step 3) to obtain a seed jade fine powder; wherein the weight ratio of the fine powder B to the mixture A is 3:1.

[0081] 5) Add appropriate amount of alcohol solution of sodium carboxymethyl cellulose to the seed jade fine powder to prepare a soft material, the amount used is 35% of the weight of mixture B, granulate through a 16-mesh sieve, dry at 80°C for 3 hours, granulate through a 12-mesh sieve, sieve, mix, and package to obtain the seed jade granules.

[0082] Figure 1: Illustration of the granules (part) prepared in Example 7.

[0083] Embodiment 8: A method for preparing seed jade particles, comprising the following steps:

[0084] The weight ratio of the medicinal materials is as follows: 285g of Astragalus, 190g of Poria, 190g of stir-fried Atractylodes, 380g of stir-fried Coix seeds, 190g of papaya, 380g of antler powder, 190g of salt Eucommia, 190g of Dipsacus asper, 190g of Bupleurum, 190g of dried tangerine peel, 380g of Chinese yam, 57g of Phellodendron, 57g of Anemarrhena, 190g of vinegar-cooked Cyperus rotundus, 57g of Amomum, and 95g of Patchouli.

[0085] 1) Patchouli and Amomum villosum are crushed into the finest powder, sieved, and irradiated for sterilization at a dose of 8 kGy to obtain fine powder A for later use;

[0086] 2) Add 6 times the amount of water to Radix Astragali, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia bark, Dipsacus asper, Radix Bupleuri, dried orange peel, Chinese yam, Phellodendron amurense, Rhizoma Anemarrhenae and vinegar fragrance, boil for 10 minutes, and filter; add 0.5% salt water to the residue, the amount is 6 times the volume of the residue, soak for 10 hours, boil for 30 minutes, filter, combine the secondary filtrates, filter, and set aside the filtrate;

[0087] 3) Concentrate to a clear paste with a relative density of 1.06 at 65° C., add ethanol to make the alcohol content 70%, let stand for more than 24 hours, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.20 to obtain a thick paste, vacuum degree -0.08 MPa, drying temperature, 65° C., continue drying for 8 hours, crush under vacuum to pass through an 80-mesh sieve, and obtain fine powder B for standby use;

[0088] b. Preparation process

[0089] 4) The fine powder A of step 1) is mixed with maltodextrin and sorbitol (the weight ratio of maltodextrin and sorbitol is 4:1) to obtain a mixture A, and then mixed with the fine powder B of step 3) to obtain seed jade fine powder; wherein the weight ratio of fine powder B to mixture A is 3:0.8.

[0090] 5) Add appropriate amount of alcohol solution of sodium carboxymethyl cellulose to the seed jade fine powder to prepare a soft material, the amount used is 35% of the weight of mixture B, granulate through a 16-mesh sieve, dry at 80°C for 3 hours, granulate through a 12-mesh sieve, sieve, mix, and package to obtain the seed jade granules.

[0091] Figure 2 : Illustration of the granules (part) prepared in Example 8.

[0092] Embodiment 9: A method for preparing seed jade particles, comprising the following steps:

[0093] The weight ratio of the medicinal materials is as follows: 285g of Astragalus, 190g of Poria, 190g of stir-fried Atractylodes, 380g of stir-fried Coix seeds, 190g of papaya, 380g of antler powder, 190g of salt Eucommia, 190g of Dipsacus asper, 190g of Bupleurum, 190g of dried tangerine peel, 380g of Chinese yam, 57g of Phellodendron, 57g of Anemarrhena, 190g of vinegar-cooked Cyperus rotundus, 57g of Amomum, and 95g of Patchouli.

[0094] 1) Patchouli and Amomum villosum are crushed into the finest powder, sieved, and irradiated for sterilization at a dose of 8 kGy to obtain fine powder A for later use;

[0095] 2) Add 10 times the amount of water to Astragalus, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia ulmoides, Dipsacus asper, Bupleurum, Tangerine peel, Chinese yam, Phellodendron amurense, Rhizoma Anemarrhenae and Vinegar, boil for 90 minutes, and filter; add 0.9% salt water in an amount of 10 times the volume of the residue, soak for 15 hours, boil for 60 minutes, filter, combine the secondary filtrates, filter, and set aside the filtrate;

[0096] 3) Concentrate to a clear paste with a relative density of 1.11 at 75°C, add ethanol to make the alcohol content 80%, let stand for more than 24 hours, filter, recover ethanol under reduced pressure and concentrate to a relative density of 1.25 to obtain a thick paste, vacuum degree -0.10Mpa, drying temperature, 70°C, continue drying for 8 hours, crush under vacuum to pass through an 80-mesh sieve, and obtain fine powder B for standby use;

[0097] b. Preparation process

[0098] 4) The fine powder A of step 1) is mixed with maltodextrin and sorbitol (the weight ratio of maltodextrin and sorbitol is 4:1) to obtain a mixture A, and then mixed with the fine powder B of step 3) to obtain a seed jade fine powder; wherein the weight ratio of the fine powder B to the mixture A is 3:1.2.

[0099] 5) Add appropriate amount of alcohol solution of sodium carboxymethyl cellulose to the seed jade fine powder to prepare a soft material, the amount used is 35% of the weight of mixture B, granulate through a 16-mesh sieve, dry at 80°C for 3 hours, granulate through a 12-mesh sieve, sieve, mix, and package to obtain the seed jade granules.

[0100] Figure 3 : Illustration of the granules (part) prepared in Example 9.

[0101] Verification of the therapeutic effect of Example 7: Verification of the clinical effect of Example 6

[0102] 1) Consultation time: 2022-9-9

[0103] Name: Zhang* Registration number: 000*****3

[0104] Chief complaint: 2 IVF failures.

[0105] Current medical history: married for 6 years, using contraceptive tools for 1 year, regular sex life, and failed to conceive after 1 year of natural pregnancy after the removal of contraception. In 2017, she was treated in the General Hospital and diagnosed with polycystic ovary syndrome after relevant examinations. She was given ovulation induction treatment for 3 cycles, with dominant follicle development and normal ovulation. She did not conceive after intercourse guidance. In 2021, 21 eggs were retrieved from the Central Obstetrics and Gynecology Department, 9 eggs were matched, 5 frozen embryos, and 4 blastocysts. One frozen embryo was transplanted in August 2021, and 2 frozen embryos were transplanted in December 2021, but both failed. There are now 2 frozen embryos and 4 blastocysts left. She now intends to transplant again after further treatment with traditional Chinese medicine system, so she came to our department for treatment today.

[0106] Current symptoms: Good appetite, good sleep, dry stool, one bowel movement per day, prone to constipation, normal urination. Usually irritable. Transparent stringy leucorrhea can be seen during ovulation.

[0107] Personal history: Born in Inner Mongolia Autonomous Region, lived in Tianjin for a long time, denied smoking and drinking habits, denied history of contact with infected water, infected areas, toxic and radioactive substances, denied sexually transmitted diseases and travel history.

[0108] Past medical history: denies history of trauma or surgery, hepatitis, tuberculosis, heart disease, diabetes, hypertension, etc. Denies history of drug or food allergy.

[0109] Family history: Both parents are alive, and there are 2 younger sisters, both married and healthy. Denies the same disease and history of tuberculosis, heart disease, diabetes, hypertension, etc.

[0110] Menstrual history: menarche at 12 years old, 6-7 / 30-45 days, moderate flow, red color, blood clots (+), dysmenorrhea (-). LMP: January 9, 2022, clean for 9 days, moderate flow, red color, blood clots (+), dysmenorrhea (-).

[0111] Marital and childbearing history: First marriage 6 years ago, G0.

[0112] Auxiliary examination:

[0113] Initial diagnosis: infertility, polycystic ovary syndrome

[0114] TCM disease name: infertility

[0115] TCM Syndrome Differentiation: Spleen and Kidney Yang Deficiency Syndrome

[0116] Treatment opinion: The granules of Example 7 were taken continuously for 14 days. At the third visit, the patient had amenorrhea for more than 40 days. Blood HCG was detected at another hospital and was elevated. There were no other obvious discomforts. The tongue was pale with white fur and the pulse was stringy and slippery. Chinese medicine was given for pregnancy preservation treatment.

[0117] The current follow-up results are: a boy was born at full term, now one year and six months old and in good health.

[0118] 2) Consultation time: 2022-9-10

[0119] Name: Zhang** Registration number: 000********

[0120] Chief complaint: Failure to conceive for more than 2 years without contraception, and ICSI-ET failure 3 times.

[0121] Current medical history: remarried for 2 and a half years, the current patient has severe oligospermia, and has not been pregnant without contraception since marriage. In June 2019, ICSI was performed at Tianjin Central Obstetrics and Gynecology Hospital, 21 eggs were retrieved, 3 embryos were formed, and 1 ET was performed, but no pregnancy; in September 2021, 2 FETs were performed, but no pregnancy. In 2022, ICSI was performed at Zhongfu Hospital, 12 eggs were retrieved, 7 embryos were formed, and 1 blastocyst was transplanted in February 2022, but no pregnancy. There are currently 6 blastocysts left, and the patient requested systematic treatment of traditional Chinese medicine before transplantation, so she came to our department for treatment.

[0122] Current symptoms: Usually prefer sweet food, like to eat meat, sweat a lot, fear of cold, cold extremities, occasional backache, tinnitus, hair loss. Appetite and sleep are good, urination is regular, stool is unformed, 1-2 times / day. Pale and dark tongue with white and greasy coating, deep and thin pulse.

[0123] Medical history: denied history of trauma or surgery, hepatitis, tuberculosis, heart disease, diabetes, hypertension, etc.

[0124] Allergy history: Denies history of food and drug allergies.

[0125] Family history: Mother is deceased (ectopic pregnancy), father is healthy. Denies the same disease and history of tuberculosis, heart disease, diabetes, hypertension, etc.

[0126] Menstrual history: menarche at age 13, 7 / 26 days, scanty, red, blood clots (-), dysmenorrhea (-). LMP: September 3, 2022, 6 days clean, heavy, red, blood clots (+), dysmenorrhea (-), breast swelling during menstruation, and lower back pain before menstruation.

[0127] Marital and reproductive history: remarried for two and a half years, G4P1, gave birth to a healthy son with her ex-husband in 2013. In June 2016, she had an artificial abortion at 40 days of pregnancy due to her own will. In April 2019, she conceived naturally during downregulation, and then had a biochemical abortion.

[0128] Auxiliary examination: AMH (March 3, 2019, Central Obstetrics and Gynecology): 1.4ng / mL. Six items of sex hormones (March 3, 2019, M2, Central Obstetrics and Gynecology): FSH: 5.83mlU / ml, LH: 4.47mlU / ml, E2: 77.78pg / ml, PRL: 6.64ng / ml, T: 50.35ng / ml, P: 0.43ng / ml.

[0129] Initial diagnosis: secondary infertility; repeated implantation failure

[0130] TCM disease name: infertility

[0131] TCM Syndrome Type: Spleen and Kidney Yang Deficiency Syndrome

[0132] Treatment opinion: The granules of Example 7 were taken continuously for 28 days. At the third visit, the patient had amenorrhea for more than 40 days. Blood HCG was detected at an external hospital and was elevated. There were no other obvious discomforts. The tongue was pale with white fur, and the pulse was stringy and slippery. Chinese medicine was given for pregnancy preservation treatment.

[0133] Follow-up: A healthy baby girl was born at full term.

[0134] 3) Consultation time: 2022-2-5

[0135] Name: Wang* Registration Number: 04*******

[0136] Department of treatment: [South Campus] Reproductive Medicine Clinic

[0137] Chief complaint: No pregnancy for 3 years without contraception, IVF failed once

[0138] Current medical history: 3 years of first marriage, regular sex life, no contraception after marriage, no contraception and no pregnancy for 3 years. In August 2021, I went to the General Hospital for IVF preparation, and in September, 5 eggs were retrieved, and 0 eggs were matched. In January 2022, 4 eggs were retrieved at the First Central Hospital, 1 egg was matched, 1 ET, and no pregnancy. LMP: 2022.1.31, now M6, normal menstrual flow, a small amount of blood clots, no obvious abnormalities in leucorrhea. Now I want to do IVF after further conditioning.

[0139] Current symptoms: Usually has an irritable temperament, likes spicy and stimulating food, easily gets angry, manifested as facial acne, back pain and fatigue, cold hands and feet, breast swelling before menstruation, poor appetite, abdominal distension after eating, staying up late and sleeping late, urination is normal, bowel movements are once every 1-2 days, and the stools are unformed, the tongue is pale with yellow greasy coating, and the pulse is deep and thin.

[0140] Past medical history: denied history of trauma or surgery, hepatitis, tuberculosis, heart disease, diabetes, hypertension, etc.

[0141] Allergy history: Denies any history of drug or food allergy.

[0142] Family history: mother died of lung cancer, father died of cerebral hemorrhage, only daughter. Denies other similar diseases and history of tuberculosis, heart disease, diabetes, hypertension, etc.

[0143] Menstrual history: menarche at age 10, 5-7 / 28 days, moderate flow, dark color, blood clots (+), mild dysmenorrhea (+). LMP: 2022.1.31.

[0144] Marital and childbearing history: first marriage 3 years, G0.

[0145] Auxiliary examination: Sex hormone examination (2021.2.2, M2, General Hospital) FSH: 6.94IU / l, LH: 3.48IU / l, E2: 70pg / ml, PRL: 17.22ng / ml, T: 38.17ng / ml, P: 0.19ng / ml.

[0146] Preliminary diagnosis: Female secondary infertility

[0147] IVF-ET failed 1 time

[0148] TCM disease name: infertility

[0149] TCM Syndrome Type: Spleen and Kidney Yang Deficiency Syndrome

[0150] Treatment opinion: 2022-2-5-April 8, 2022, sixth visit, 44 doses of Chinese medicine, taken in total. April 23, 2022, seventh visit: 29 days of amenorrhea, self-tested urine TT (+), blood HCG test at another hospital: 178IU / L, fatigue relieved after taking 14 doses of medicine, no obvious discomfort now, good appetite and sleep, normal bowel movements. Pale red tongue with thin white fur, fine pulse.

[0151] Later follow-up showed that the full-term twin girls were born, now 15 months old and in good health.

Claims

1. A method for preparing jade seed particles, characterized in that: The preparation of the seed jade particles comprises the following steps: a. Extraction and purification process 1) Grind patchouli and amomum villosum into finest powder, sieve, and sterilize by irradiation to obtain fine powder A for later use; 2) Astragalus, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia bark, Dipsacus asper, Bupleurum, dried orange peel, Chinese yam, Phellodendron amurense, Rhizoma Anemarrhenae and vinegar fragrance are boiled in water, the decoction is combined, filtered and the filtrate is reserved; 3) The filtrate of step 2) is concentrated to obtain a clear paste, vacuum dried, and crushed into fine powder B for later use; b. Preparation process 4) mixing the fine powder A of step 1) with a pharmaceutical excipient to obtain a mixture A, and then mixing it with the fine powder B of step 3) to obtain a seed jade fine powder; 5) Adding a binder to the fine powder of seed jade to prepare a soft material, granulating, drying, granulating, sieving, mixing and packaging to obtain seed jade granules.

2. The method according to claim 1, characterized in that The radiation sterilization dose in step 1) is 8 kGy.

3. The method according to claim 1, characterized in that In the step 2), 6-10 times the amount of water is added to the astragalus, Poria, stir-fried Atractylodes macrocephala, stir-fried Coix seeds, papaya, antler frost, salt Eucommia ulmoides, Dipsacus asper, Bupleurum, dried orange peel, Chinese yam, Phellodendron amurense, Rhizoma Anemarrhenae and vinegar fragrance, and the mixture is decocted for 60-90 minutes and filtered; 6-10 times the amount of salt water is added to the residue, and the mixture is decocted for 30-60 minutes, filtered, and the secondary filtrates are combined.

4. The method according to claim 3, characterized in that The concentration of the saline solution in step 2) is 0.5-0.9% saline solution, the amount used is 8 times the volume of the medicinal residue, and the soaking time is 10-15 hours.

5. The method according to claim 1, characterized in that The filtrate of step 3) is concentrated to a clear paste with a relative density of 1.06-1.11 at 65-75°C, ethanol is added to make the alcohol content 70%-80%, and the mixture is allowed to stand for more than 24 hours, filtered, and the ethanol is recovered under reduced pressure and concentrated to a relative density of 1.20-1.25 to obtain a thick paste. The vacuum degree is -0.08MPa--0.10Mpa, and the drying temperature is 65°C-75°C. The mixture is dried continuously for 6-10 hours, and crushed under vacuum to pass through an 80-mesh sieve to obtain fine powder B.

6. The method according to claim 1, characterized in that In the step 4), the weight ratio of the fine powder B to the mixture A is 3:0.8-1.2, and more preferably 3:1; in the step 5), a proper amount of adhesive is added to the seed jade fine powder to prepare a soft material, the amount of which is 30-40% of the weight of the mixture B, granulated through a 16-mesh sieve, dried at 80°C for 3 hours, sized through a 12-mesh sieve, sieved, mixed, and packaged to obtain the product.

7. The method according to claim 1, characterized in that The pharmaceutical excipient is one or more of maltodextrin, mannitol, microcrystalline cellulose, and sorbitol, more preferably maltodextrin and sorbitol, the dosage ratio is 2-5:1, and more preferably the dosage ratio of maltodextrin and sorbitol is 4:1; the adhesive is an alcohol solution of sodium carboxymethyl cellulose or an alcohol solution of cross-linked sodium carboxymethyl cellulose.

8. The preparation process according to claim 1, characterized in that: The medicinal materials are calculated by weight as follows: 213-370 parts of astragalus, 142-247 parts of poria, 142-247 parts of stir-fried atractylodes, 285-494 parts of stir-fried coix seeds, 142-247 parts of papaya, 285-494 parts of antler frost, 142-247 parts of salt eucommia, 142-247 parts of dipsacus root, 142-247 parts of bupleurum, 142-247 parts of tangerine peel, 285-494 parts of yam, 42-74 parts of phellodendron, 42-74 parts of anemarrhena, 142-247 parts of vinegar-cooked cyperus, 42-74 parts of amomum, and 71-123 parts of patchouli.

9. The preparation process according to claim 1, characterized in that: The medicinal materials are calculated by weight as follows: 285 parts of astragalus, 190 parts of Poria, 190 parts of stir-fried Atractylodes, 380 parts of stir-fried Coix seeds, 190 parts of papaya, 380 parts of antler frost, 190 parts of salt Eucommia, 190 parts of Dipsacus asper, 190 parts of Bupleurum, 190 parts of dried tangerine peel, 380 parts of yam, 57 parts of Phellodendron, 57 parts of Anemarrhena, 190 parts of vinegar-cooked Cyperus rotundus, 57 parts of Amomum, and 95 parts of Patchouli.

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