Quick-release alfacalcidol soft capsule and preparation method thereof

Abstract

The invention provides a quick-release alfacalcidol soft capsule and a preparation method thereof, and relates to the technical field of pharmaceutical preparations, the preparation raw materials comprise a PLGA microsphere content containing vitamin D3 and a capsule shell liquid containing beta-cyclodextrin, the preparation method of the quick-release alfacalcidol soft capsule comprises the following steps: preparing the capsule content and the capsule shell liquid into the soft capsule by using a full-automatic soft capsule machine, shaping in cold air at the temperature of 20 DEG C and the humidity of 45%, washing pills, drying and packaging to obtain the alfacalcidol soft capsule.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a quick-release alfacalcidol soft capsule and a preparation method thereof. Background Art

[0002] Rapid-release Alfacalcidol Soft Capsules are a rapid-release pharmaceutical preparation designed for osteoporosis and other bone diseases. As an analog of active vitamin D3, Alfacalcidol has the functions of regulating calcium-phosphorus balance, promoting bone formation and inhibiting bone resorption. Rapid-release technology is designed to enable drugs to dissolve quickly and be released into the body after oral administration, so as to quickly reach effective concentrations and improve therapeutic effects. However, rapid-release preparations may face stability challenges during preparation and storage, such as drug degradation, excipient interactions, etc., which may affect the efficacy and safety of the drug. With the aging of the population and the increasing number of osteoporosis patients, the market demand for rapid-release alfacalcidol soft capsules is also continuing to grow. Rapid-release preparations have the advantages of rapid onset of effect and improved quality of life of patients. Therefore, they are favored by patients and doctors. Osteoporosis patients are often accompanied by symptoms such as pain and fractures. Rapid-release preparations can quickly relieve these symptoms and improve the quality of life of patients. Rapid-release preparations can ensure the rapid release and effective absorption of drugs in the body, thereby improving the therapeutic effect and reducing drug dosage and side effects. Rapid-release preparations usually have a smaller volume and lighter weight, which is convenient for patients to carry and use. In addition, the method of taking the rapid-release preparation is relatively simple, which helps to improve the patient's medication compliance. In summary, rapid-release alfacalcidol soft capsules have broad market prospects and important clinical application value in the treatment of bone diseases such as osteoporosis. However, in order to overcome the defects of the existing technology and meet market demand, further research and optimization of the preparation process, and improvement of the drug's stability and release control accuracy are needed. Therefore, the market is in urgent need of a new rapid-release alfacalcidol soft capsule and a preparation method thereof. Summary of the invention

[0003] The present invention provides a quick-release alfacalcidol soft capsule and a preparation method thereof, which are used to solve the problems raised in the above background technology.

[0004] In order to solve the above technical problems, the present invention discloses a quick-release alfacalcidol soft capsule and a preparation method thereof. The quick-release alfacalcidol soft capsule comprises PLGA microspheres containing vitamin D3 and a capsule shell liquid containing β-cyclodextrin.

[0005] Furthermore, the raw materials for preparing the contents of the PLGA microspheres containing vitamin D3 include MCT medium-chain triglycerides, alfacalcidol, vitamin E, polyethylene glycol, vitamin E polyethylene glycol succinate, tocopherol acetate and PLGA microspheres containing vitamin D3.

[0006] Further, the raw materials for preparing the contents of the PLGA microspheres containing vitamin D3 include, by weight, 60-80 parts of MCT medium chain triglycerides, 0.01-0.03 parts of alfacalcidol, 0.1-0.3 parts of vitamin E, 1-2 parts of polyethylene glycol, 2-6 parts of vitamin E polyethylene glycol succinate, 0.5-0.8 parts of tocopherol acetate and 2-4 parts of PLGA microspheres containing vitamin D3. Furthermore, the raw materials for preparing the PLGA microspheres containing vitamin D3 include a PVA aqueous solution and a PLGA-dichloromethane solution containing vitamin D3.

[0007] Furthermore, the preparation method of the PLGA microspheres containing vitamin D3 comprises: dissolving 0.01 parts of vitamin D3 in 5 parts of PLGA-dichloromethane solution to obtain a PLGA-dichloromethane solution containing vitamin D3, dropping 10 parts of the PLGA-dichloromethane solution containing vitamin D3 into 25 parts of PVA aqueous solution, ventilating, centrifuging, filtering, and washing to obtain the contents of the PLGA microspheres containing vitamin D3; Preferably, the volume fraction of the PLGA-dichloromethane solution is 5%, and the volume fraction of the PVA aqueous solution is 2%.

[0008] Furthermore, the preparation method of the PLGA microsphere contents containing vitamin D3 comprises mixing MCT medium chain triglycerides and alfacalcidol at a temperature of 30° C. under nitrogen protection, adding vitamin E, polyethylene glycol, vitamin E polyethylene glycol succinate, tocopherol acetate and PLGA microsphere contents containing vitamin D3, stirring, cooling to 25° C., and treating with a homogenizer to obtain the contents of the PLGA microsphere contents containing vitamin D3; Preferably, the stirring speed is 300-400 rpm, the stirring time is 8-12 hours, and the mixture is treated with a homogenizer at a pressure of 12 MPa.

[0009] Furthermore, the raw materials for preparing the capsule shell liquid include glycerol, deionized water, gelatin and β-cyclodextrin.

[0010] Furthermore, the raw materials for preparing the capsule shell liquid include, by weight, 8-12 parts of glycerol, 20-30 parts of deionized water, 35-40 parts of gelatin and 8-15 parts of β-cyclodextrin.

[0011] Furthermore, the preparation method of the capsule shell liquid comprises heating glycerol and deionized water to 70° C., adding gelatin and β-cyclodextrin, stirring and melting, keeping warm for 60 minutes, removing foam, filtering, and obtaining the capsule shell liquid.

[0012] Furthermore, a method for preparing a rapid-release alfacalcidol soft capsule comprises using a fully automatic soft capsule machine to prepare capsule contents and capsule shell liquid into soft capsules, shaping them in cold air at a temperature of 20° C. and a humidity of 45%, washing the pills, drying them, and packaging them to obtain the alfacalcidol soft capsules.

[0013] Compared with the prior art, the present invention provides a rapid-release alfacalcidol soft capsule and a preparation method thereof, which has the following beneficial effects: (1) Combining physical and chemical dual rapid release technologies, physically, porous microspheres PLGA are used as carriers to enable the drug to disintegrate rapidly when it comes into contact with body fluids; chemically, MCT medium-chain triglycerides are used as lipid carriers, and vitamin E polyethylene glycol succinate and polyethylene glycol are compounded in a certain proportion to improve the solubility and permeability of the drug, which helps to quickly release the drug in the body and achieve dual accelerated release; (2) PLGA microspheres can generate lactic acid monomers through ester hydrolysis in the body, and then oxidize into keto acid under the action of lactate dehydrogenase, participate in the tricarboxylic acid cycle in the body, and finally convert into water and carbon dioxide and excrete out of the body; (3) MCT medium-chain triglycerides are the main component of the oil phase, used to dissolve and stabilize other fat-soluble ingredients. Alfacalcidol is the active ingredient, and its content is usually very low because of its strong biological activity. Vitamin E and tocopherol acetate: as antioxidants, they are used to protect the fat-soluble ingredients in the formula from oxidation. Their dosage is usually low, but sufficient to provide effective antioxidant protection. Vitamin E polyethylene glycol succinate is a water-soluble derivative of vitamin E. TPGS is soluble in water and a variety of polar organic solvents and has excellent solubility and stability. It can significantly improve the bioavailability of lipophilic and poorly soluble substances and shows good safety in medicines, cosmetics and foods. Emulsifiers help form stable emulsions or microsphere suspensions. PLGA microspheres containing vitamin D3: This is one of the key ingredients in the formula, and its content depends on the desired vitamin D3 release characteristics and therapeutic dose. Polyethylene glycol 400 is a colorless, odorless, non-toxic, non-volatile liquid at room temperature. It has good water solubility and can be miscible with water in any proportion. This liquid property enables PEG400 to have excellent solubility and mixing capabilities in a variety of applications. In the pharmaceutical field, PEG400 is also an important drug carrier, used to make liquid preparations such as soft capsules, oral solutions, eye drops, etc., which can increase the solubility and stability of drugs and improve the bioavailability and therapeutic effects of drugs. DETAILED DESCRIPTION

[0014] The preferred embodiments of the present invention are described below in combination with the scheme. It should be understood that the preferred embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0015] In addition, in the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes, and do not specifically refer to the order or sequence, nor are they used to limit the present invention. They are only used to distinguish components or operations described with the same technical terms, and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In addition, the technical solutions and technical features between the various embodiments can be combined with each other, but they must be based on the ability of ordinary technicians in the field to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0016] Unless otherwise specified, the examples and comparative examples are parallel tests with the same components, component contents, preparation steps and preparation parameters. The experimental methods in the following examples are conventional methods unless otherwise specified. The test materials used in the following examples are analytical reagents (AR) unless otherwise specified. Parts are parts by weight unless otherwise specified, and the materials are purchased from commercial channels.

[0017] PLGA (FluidicLab, 50 / 50, Mw: 2W); polyvinyl alcohol (PVA, Sigma-Aldrich, P8136-250g); polyethylene glycol is Japanese Aoki, PEG-400 pharmaceutical grade.

[0018] Example 1 1. Preparation of PLGA microspheres containing vitamin D3: 5 mL of 2% PVA aqueous solution and 1 mL of 5% PLGA-dichloromethane solution were added to the microsphere preparation instrument with a pressure of 250 mbar for the aqueous phase and 150 mbar for the oil phase. After being filled with liquid, the pressure control was switched to flow rate control, and the flow rates of channel one (aqueous phase) and channel two (oil phase) were set to 14 μL / min and 3 μL / min, respectively. After the droplets were uniformly generated, they could be received into a glass culture dish containing 2% PVA aqueous solution. After 60 min, the collection was stopped, and the mixture was allowed to stand. Ultrapure water was added at a ratio of V ball: V water = 1:2, and the mixture was shaken and centrifuged at 2500 rpm for 1 min to obtain PLGA microspheres with an average particle size of 65 μm after solidification.

[0019] Dissolve 0.01 parts of vitamin D3 in 5 parts of PLGA-dichloromethane solution to obtain a PLGA-dichloromethane solution containing vitamin D3, add 10 parts of PLGA-dichloromethane solution containing vitamin D3 dropwise into 25 parts of PVA aqueous solution, ventilate in a fume hood, centrifuge, filter, and wash to obtain the PLGA microsphere contents containing vitamin D3.

[0020] 2. Alfacalcidol Soft Capsules (1) Preparing the contents of PLGA microspheres containing vitamin D3: Under nitrogen protection, 70 parts of MCT medium chain triglycerides and 0.02 parts of alfacalcidol were mixed by weight at a temperature of 30° C., 0.2 parts of vitamin E, 1 part of polyethylene glycol, 5 parts of vitamin E polyethylene glycol succinate, 0.6 parts of tocopherol acetate and 3 parts of PLGA microspheres containing vitamin D3 were added, stirred at 400 rpm for 10 hours, naturally cooled to 25° C., and treated twice with a homogenizer at a pressure of 12 MPa to obtain the contents of PLGA microspheres containing vitamin D3; (2) Preparation of capsule shell liquid: heat 10 parts of glycerol and 25 parts of deionized water to 70°C, add 36 parts of gelatin and 10 parts of β-cyclodextrin, stir to melt, keep warm for 60 minutes, remove the foam, filter, and obtain capsule shell liquid; (3) Preparation of Alfacalcidol Soft Capsules: The capsule contents and capsule shell liquid are prepared into soft capsules using a fully automatic soft capsule machine, and the soft capsules are shaped, washed, dried and packaged in cold air at a temperature of 20° C. and a humidity of 45% to obtain the Alfacalcidol Soft Capsules.

[0021] Example 2 The steps for preparing PLGA microspheres containing vitamin D3 are the same as those in Example 1, but different from the preparation of alfacalcidol soft capsules: (1) Preparing the contents of PLGA microspheres containing vitamin D3: Under nitrogen protection, 60 parts of MCT medium chain triglycerides and 0.01 parts of alfacalcidol were mixed by weight at a temperature of 30° C., 0.1 parts of vitamin E, 1 part of polyethylene glycol, 2 parts of vitamin E polyethylene glycol succinate, 0.5 parts of tocopherol acetate and 2 parts of PLGA microspheres containing vitamin D3 were added, stirred at 200 rpm for 8 hours, naturally cooled to 25° C., and treated twice with a homogenizer at a pressure of 12 MPa to obtain the contents of PLGA microspheres containing vitamin D3; (2) Preparation of capsule shell liquid: 8 parts of glycerol and 20 parts of deionized water are heated to 70°C, 35 parts of gelatin and 8 parts of β-cyclodextrin are added, stirred and melted, kept warm for 60 minutes, the foam is removed, and the capsule shell liquid is filtered; (3) Preparation of Alfacalcidol Soft Capsules: The capsule contents and capsule shell liquid are prepared into soft capsules using a fully automatic soft capsule machine, and the soft capsules are shaped, washed, dried and packaged in cold air at a temperature of 20° C. and a humidity of 45% to obtain the Alfacalcidol Soft Capsules.

[0022] Example 3 The steps for preparing PLGA microspheres containing vitamin D3 are the same as those in Example 1, but different from the preparation of alfacalcidol soft capsules: (1) Preparing the contents of PLGA microspheres containing vitamin D3: Under nitrogen protection, 80 parts of MCT medium chain triglycerides and 0.03 parts of alfacalcidol were mixed by weight at a temperature of 30° C., 0.3 parts of vitamin E, 2 parts of polyethylene glycol, 6 parts of vitamin E polyethylene glycol succinate, 0.8 parts of tocopherol acetate and 4 parts of PLGA microspheres containing vitamin D3 were added, stirred at 400 rpm for 12 hours, naturally cooled to 25° C., and treated twice with a homogenizer at a pressure of 12 MPa to obtain the contents of PLGA microspheres containing vitamin D3; (2) Preparation of capsule shell liquid: heat 12 parts of glycerol and 30 parts of deionized water to 70°C, add 40 parts of gelatin and 15 parts of β-cyclodextrin, stir to melt, keep warm for 60 minutes, remove the foam, filter, and obtain capsule shell liquid; (3) Preparation of Alfacalcidol Soft Capsules: The capsule contents and capsule shell liquid are prepared into soft capsules using a fully automatic soft capsule machine, and the soft capsules are shaped, washed, dried and packaged in cold air at a temperature of 20° C. and a humidity of 45% to obtain the Alfacalcidol Soft Capsules.

[0023] Example 4 The steps for preparing PLGA microspheres containing vitamin D3 are the same as those in Example 1, but different from the preparation of alfacalcidol soft capsules: (1) Preparing the contents of PLGA microspheres containing vitamin D3: Under nitrogen protection, 60 parts of MCT medium chain triglycerides and 0.01 parts of alfacalcidol were mixed by weight at a temperature of 30° C., 0.1 parts of vitamin E, 1 part of polyethylene glycol, 3 parts of vitamin E polyethylene glycol succinate, 0.5 parts of tocopherol acetate and 2 parts of PLGA microspheres containing vitamin D3 were added, stirred at 200 rpm for 8 hours, naturally cooled to 25° C., and treated twice with a homogenizer at a pressure of 12 MPa to obtain the contents of PLGA microspheres containing vitamin D3; (2) Preparation of capsule shell liquid: heat 10 parts of glycerol and 27 parts of deionized water to 70°C, add 38 parts of gelatin and 12 parts of β-cyclodextrin, stir to melt, keep warm for 60 minutes, remove the foam, filter, and obtain capsule shell liquid; (3) Preparation of Alfacalcidol Soft Capsules: The capsule contents and capsule shell liquid are prepared into soft capsules using a fully automatic soft capsule machine, and the soft capsules are shaped, washed, dried and packaged in cold air at a temperature of 20° C. and a humidity of 45% to obtain the Alfacalcidol Soft Capsules.

[0024] Example 5 The steps for preparing PLGA microspheres containing vitamin D3 are the same as those in Example 1, but different from the preparation of alfacalcidol soft capsules: (1) Preparing the contents of PLGA microspheres containing vitamin D3: Under nitrogen protection, 80 parts of MCT medium chain triglycerides and 0.03 parts of alfacalcidol were mixed by weight at a temperature of 30° C., 0.3 parts of vitamin E, 2 parts of polyethylene glycol, 6 parts of vitamin E polyethylene glycol succinate, 0.8 parts of tocopherol acetate and 4 parts of PLGA microspheres containing vitamin D3 were added, stirred at 400 rpm for 12 hours, naturally cooled to 25° C., and treated twice with a homogenizer at a pressure of 12 MPa to obtain the contents of PLGA microspheres containing vitamin D3; (2) Preparation of capsule shell liquid: 8 parts of glycerol and 25 parts of deionized water are heated to 70°C, 36 parts of gelatin and 8 parts of β-cyclodextrin are added, stirred and melted, kept warm for 60 minutes, the foam is removed, and the capsule shell liquid is filtered; (3) Preparation of Alfacalcidol Soft Capsules: The capsule contents and capsule shell liquid are prepared into soft capsules using a fully automatic soft capsule machine, and the soft capsules are shaped, washed, dried and packaged in cold air at a temperature of 20° C. and a humidity of 45% to obtain the Alfacalcidol Soft Capsules.

[0025] Based on Examples 1-5, when preparing the capsule shell liquid, experimental analysis is also conducted on the method of adding gelatin and β-cyclodextrin, including: determining the test number of gelatin and β-cyclodextrin, determining different methods of adding gelatin and β-cyclodextrin, wherein the adding methods include: adding all at once, adding sequentially in proportion, adding simultaneously in proportion, etc.; heating glycerol and deionized water to 70°C and then adding them separately according to different heating methods for stirring and melting, and collecting information on the stirring conditions to obtain stirring collection information; analyzing whether the stirring and melting is completed based on the stirring collection information, and determining the stirring and melting time when the stirring and melting is completed; determining the best method of adding gelatin and β-cyclodextrin based on the stirring and melting time, and then adding gelatin and β-cyclodextrin to glycerol and deionized water heated to 70°C for stirring and melting according to the best adding method when preparing the capsule shell liquid.

[0026] The above experimental analysis on the method of adding gelatin and β-cyclodextrin makes it clear that the different effects of the methods of adding gelatin and β-cyclodextrin on stirring and melting, so that when preparing the capsule shell liquid, gelatin and β-cyclodextrin are added according to the optimal adding method, the efficiency of stirring and melting is improved, and the preparation of the capsule shell liquid is completed in a shorter time, thereby improving the preparation efficiency of alfacalcidol soft capsules.

[0027] Furthermore, when preparing alfacalcidol soft capsules, a temperature and humidity control system is used to control the operating environment. The temperature and humidity control system performs temperature and humidity detection on a target area before preparing alfacalcidol soft capsules, and determines whether the temperature data and humidity data of the target area reach the target temperature and target humidity. The target area here refers to the operating area for preparing alfacalcidol soft capsules, and the target temperature is 20°C and the target humidity is 45%. When the temperature data and humidity data of the target area do not reach the target temperature and target humidity, a temperature regulating device or a humidity regulating device is used to regulate the temperature and humidity of the target area until the temperature data and humidity data of the target area reach the target temperature and target humidity, and then shaping, pill washing, drying and packaging are carried out based on the cold wind at the target temperature and target humidity. In addition, during the shaping, pill washing, drying and packaging process based on the cold wind at the target temperature and target humidity, multi-point monitoring is carried out on the target area to obtain temperature monitoring information and humidity monitoring information within the target area, and whether there are temperature and humidity fluctuations in the target area are analyzed based on the temperature monitoring information and humidity monitoring information, the temperature and humidity fluctuation position is locked, the target position is determined, and the temperature and humidity are micro-controlled for the target position, so that the temperature and humidity in the target area always maintain the target temperature and humidity during the preparation of alfacalcidol soft capsules.

[0028] The temperature and humidity control system is used to ensure the stability of the operating environment during the preparation of the alfacalcidol soft capsules, so that the operation and preparation are always carried out in cold wind at a temperature of 20°C and a humidity of 45%, thereby avoiding changes in the properties of the alfacalcidol soft capsules due to fluctuations in temperature or humidity, thereby ensuring the quality of the alfacalcidol soft capsules.

[0029] Comparative Example 1 The difference from Example 1 is that when preparing PLGA microspheres containing vitamin D3, equal weight portions of vitamin D3 are not dissolved in the PLGA-dichloromethane solution, and the other parts are the same.

[0030] Comparative Example 2 The difference from Example 1 is that when preparing the contents of PLGA microspheres containing vitamin D3, an equal weight portion of PLGA microspheres containing vitamin D3 is missing, and the rest is the same.

[0031] Comparative Example 3 The difference from Example 1 is that when preparing the PLGA microspheres containing vitamin D3, vitamin E polyethylene glycol succinate is replaced with an equal weight portion of lecithin, and the rest are the same.

[0032] Comparative Example 4 The difference from Example 1 is that when preparing the PLGA microspheres containing vitamin D3, an equal weight portion of polyethylene glycol is missing, and the rest is the same.

[0033] Comparative Example 5 The difference from Example 1 is that when preparing the PLGA microspheres containing vitamin D3, an equal weight portion of vitamin E is missing, and the rest is the same.

[0034] Comparative Example 6 The difference from Example 1 is that when preparing the PLGA microspheres containing vitamin D3, an equal weight portion of tocopherol acetate is missing, and the rest is the same.

[0035] Comparative Example 7 The difference from Example 1 is that an equal weight portion of β-cyclodextrin is missing when preparing the capsule shell liquid, and the rest is the same.

[0036] Performance Testing 1. Effect of accelerated test on the stability of alfacalcidol soft capsules The quick-release alfacalcidol soft capsules prepared in the example and the alfacalcidol soft capsules prepared in the comparative example were respectively used as test samples and subjected to an accelerated test at a temperature of 40±2°C and a relative humidity of 75%±5%. Samples were taken on the first, eighth and fifteenth days of the test to detect the alfacalcidol content.

[0037] Table 1 Effect of accelerated test on the content of alfacalcidol in alfacalcidol soft capsules

[0038] Table 1 shows that in the accelerated test, the content of alfacalcidol in the rapid-release alfacalcidol soft capsules prepared by the present invention changes relatively little, indicating that the rapid-release alfacalcidol soft capsules prepared by the present invention have high stability under high temperature and high humidity conditions.

[0039] 3. Determination of the release rate of immediate-release alfacalcidol soft capsules According to the "Guidelines for Sustained and Controlled Release Preparations" in the Appendix of the 2010 edition (Part II) of the Pharmacopoeia of the People's Republic of China, 0.25% sodium lauryl sulfate was used as the release medium, and the appropriate amount of alfacalcidol soft capsules prepared in the examples and comparative examples (about 100 mg) were accurately weighed, and the peak area was determined by HPLC according to the first method of Appendix XD of the 2010 edition of the Pharmacopoeia of the People's Republic of China, and the drug concentration and cumulative release percentage (in %) were calculated. The determination results are shown in Table 1 (dissolution medium: 0.25% sodium lauryl sulfate).

[0040] Table 1

[0041] As can be seen from Table 1, the rapid-release alfacalcidol soft capsules prepared in Example 1 have a faster release rate.

[0042] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. If these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A rapid-release alfacalcidol soft capsule, the preparation raw materials of which include PLGA microspheres containing vitamin D3 and capsule shell liquid containing β-cyclodextrin.

2. The rapid-release alfacalcidol soft capsule according to claim 1, characterized in that The raw materials for preparing the content of the PLGA microsphere containing vitamin D3 include MCT medium chain triglyceride, alfacalcidol, vitamin E, polyethylene glycol, vitamin E polyethylene glycol succinate, tocopherol acetate and PLGA microsphere containing vitamin D3.

3. The rapid-release alfacalcidol soft capsule according to claim 1 or 2, characterized in that: The raw materials for preparing the PLGA microspheres containing vitamin D3 include, by weight, 60-80 parts of MCT medium-chain triglycerides, 0.01-0.03 parts of alfacalcidol, 0.1-0.3 parts of vitamin E, 1-2 parts of polyethylene glycol, 2-6 parts of vitamin E polyethylene glycol succinate, 0.5-0.8 parts of tocopherol acetate and 2-4 parts of PLGA microspheres containing vitamin D3.

4. The rapid-release alfacalcidol soft capsule according to any one of claims 1 to 3, characterized in that: The raw materials for preparing the PLGA microspheres containing vitamin D3 include a PVA aqueous solution and a PLGA-dichloromethane solution containing vitamin D3.

5. The rapid-release alfacalcidol soft capsule according to any one of claims 1 to 4, characterized in that: The preparation method of the PLGA microspheres containing vitamin D3 comprises: dissolving 0.01 parts of vitamin D3 in 5 parts of PLGA-dichloromethane solution to obtain a PLGA-dichloromethane solution containing vitamin D3, dropping 10 parts of the PLGA-dichloromethane solution containing vitamin D3 into 25 parts of a PVA aqueous solution, ventilating, centrifuging, filtering, and washing to obtain the contents of the PLGA microspheres containing vitamin D3; Preferably, the volume fraction of the PLGA-dichloromethane solution is 5%, and the volume fraction of the PVA aqueous solution is 2%.

6. The rapid-release alfacalcidol soft capsule according to any one of claims 1 to 3, characterized in that: The preparation method of the PLGA microspheres containing vitamin D3 comprises mixing MCT medium chain triglycerides and alfacalcidol at a temperature of 30° C. under nitrogen protection, adding vitamin E, polyethylene glycol, vitamin E polyethylene glycol succinate, tocopherol acetate and PLGA microspheres containing vitamin D3, stirring, cooling to 25° C., and treating with a homogenizer to obtain the PLGA microspheres containing vitamin D3; Preferably, the stirring speed is 300-400 rpm, the stirring time is 8-12 hours, and the mixture is treated with a homogenizer at a pressure of 12 MPa.

7. The rapid-release alfacalcidol soft capsule according to claim 1, characterized in that: The raw materials for preparing the capsule shell liquid include glycerol, deionized water, gelatin and beta-cyclodextrin.

8. The rapid-release alfacalcidol soft capsule according to claim 1 or 7, characterized in that: The raw materials for preparing the capsule shell liquid include 8-12 parts of glycerin, 20-30 parts of deionized water, 35-40 parts of gelatin and 8-15 parts of beta-cyclodextrin by weight.

9. The rapid-release alfacalcidol soft capsule according to claim 1 or 7, characterized in that: The preparation method of the capsule shell liquid comprises heating glycerol and deionized water to 70° C., adding gelatin and beta-cyclodextrin, stirring and melting, keeping the temperature for 60 minutes, removing the floating foam, filtering, and obtaining the capsule shell liquid.

10. A method for preparing the rapid-release alfacalcidol soft capsules according to claims 1-9, characterized in that: The preparation method of the quick-release alfacalcidol soft capsule comprises the steps of preparing the capsule contents and the capsule shell liquid into soft capsules by using a fully automatic soft capsule machine, shaping in cold wind at a temperature of 20° C. and a humidity of 45%, washing the capsules, drying, and packaging to obtain the alfacalcidol soft capsules.

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