Vitamin D2 soft capsule and preparation method thereof

Abstract

The invention discloses a vitamin D2 soft capsule and a preparation method thereof, and relates to the technical field of pharmaceutical preparations. The vitamin D2 soft capsule comprises contents and a capsule shell; the contents comprise 0.004-0.15 parts of vitamin D2, 0.03-4 parts of a stabilizer and 80-280 parts of a dispersant in parts by weight; the capsule shell comprises 20-50 parts of gelatin, 20-50 parts of sodium alginate, 10-50 parts of glycerol, 0.03-0.2 parts of a sunscreen and 40-100 parts of purified water in parts by weight. The present invention improves the vitamin D2 content and capsule quality under long-term storage by preparing a vitamin D2 soft capsule with high stability.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a vitamin D2 soft capsule and a preparation method thereof. Background Art

[0002] Vitamin D is a fat-soluble steroid derivative and an important drug for treating rickets in children and osteoporosis in the elderly. Studies have shown that the onset of asthma is related to vitamin D metabolism, and abnormalities in multiple links in the vitamin D metabolic pathway can lead to abnormal embryonic development and immune system disorders. In addition, vitamin D has many new biological functions, such as preventing cardiovascular disease, autoimmune diseases, diabetes and anti-tumor. Vitamin D2, a member of the vitamin family, is mainly found in vegetable oils or yeast. Ergosterol is converted into vitamin D2 after exposure to sunlight or ultraviolet rays. It is also called calciferol and ergocalciferol. It is an essential element for the growth, development, reproduction, maintenance of life and health of humans and animals. It can regulate the metabolism of calcium and phosphorus and promote bone health. In clinical practice, it is used to prevent and treat diseases such as rickets, osteomalacia and hypoparathyroidism.

[0003] Vitamin D2, chemical name is 9,10-secoeciated ergoster-5,7,10(19),22-tetraene-3β-ol, the structural formula is as follows:

[0004] .

[0005] Vitamin D2 has poor stability and is easily deteriorated when exposed to light or air. Therefore, it is particularly important to prepare vitamin D2 preparations with stable quality.

[0006] Chinese patent application CN113546062A discloses a vitamin D soft capsule and a preparation method thereof. The raw materials of the soft capsule content include: vitamin D, a dispersant and a suspending agent; the raw materials of the soft capsule shell include: glycerol, gelatin, carrageenan and hydroxypropyl starch; the invention uses vegetable oil as a dispersion medium for vitamin D and uses it as a content to prepare the vitamin D soft capsule, thereby avoiding contact of vitamin D with the external environment during storage and preventing it from being oxidized and decomposed, thereby improving the stability of vitamin D.

[0007] The soft capsule has the problem of capsule shell aging after storage. This is due to the cross-linking reaction between gelatin in the capsule shell and aldehyde compounds. The cross-linking mechanism may be that a free amino group of lysine reacts with the aldehyde group to generate an imine group, and then undergoes a series of polycondensation reactions to finally generate a cross-linked compound. The cross-linked compound blocks the entry of water molecules, causing a water-insoluble film to form on the inner wall of the capsule shell, thereby preventing the release of the contents of the soft capsule.

[0008] At present, there are few studies on high-stability vitamin D2 soft capsules. In view of this, the present application provides a high-stability vitamin D2 soft capsule, while taking into account the easy aging characteristics of the soft capsule shell, and optimizing the quality stability of the capsule shell. Summary of the invention

[0009] The purpose of the present invention is to provide a vitamin D2 soft capsule with high stability, so as to improve the vitamin D2 content and capsule quality under long-term storage.

[0010] To achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows:

[0011] In one aspect, the present invention provides a vitamin D2 soft capsule, comprising contents and a capsule shell;

[0012] The contents include, by weight, 0.004-0.15 parts of vitamin D2, 0.03-4 parts of stabilizer, and 80-280 parts of dispersant; the capsule shell includes, by weight, 20-50 parts of gelatin, 20-50 parts of sodium alginate, 10-50 parts of glycerol, 0.03-0.2 parts of sunscreen, and 40-100 parts of purified water;

[0013] in,

[0014] The stabilizer includes vitamin E acetate, vitamin E polyethylene glycol succinate and tert-butyl p-hydroxyanisole;

[0015] The dispersants include soybean oil, walnut oil and grape seed oil;

[0016] The sunscreens include brilliant blue and tartrazine.

[0017] Preferably, the contents include 0.004-0.12 parts of vitamin D2, 0.05-3 parts of stabilizer and 100-250 parts of dispersant by weight; the capsule shell includes 20-40 parts of gelatin, 20-40 parts of sodium alginate, 20-40 parts of glycerol, 0.05-0.15 parts of sunscreen and 50-80 parts of purified water by weight.

[0018] Most preferably, the contents include, by weight, 0.1 parts of vitamin D2, 1 part of stabilizer and 120 parts of dispersant; the capsule shell includes, by weight, 30 parts of gelatin, 30 parts of sodium alginate, 30 parts of glycerol, 0.1 parts of sunscreen and 60 parts of purified water.

[0019] Preferably, in the stabilizer, the mass ratio of vitamin E acetate, vitamin E polyethylene glycol succinate and butylated p-hydroxyanisole is 1-3:1-3:3-8, and most preferably 2:2:5.

[0020] Preferably, in the dispersant, the mass ratio of soybean oil, walnut oil and grape seed oil is 5-10:4-8:2-4, most preferably 8:2:3.

[0021] Preferably, in the sunscreen, the mass ratio of brilliant blue to lemon yellow is 2-5:1-2, more preferably 3:2.

[0022] On the other hand, the present invention provides a method for preparing the above-mentioned vitamin D2 soft capsule, comprising the following steps:

[0023] (1) Mix the dispersant, take part of the dispersant and mix it with the formulated amount of stabilizer, heat it to 80-95°C, add the formulated amount of vitamin D2 until it is completely dissolved, and then mix it with the remaining dispersant to obtain the content material;

[0024] (2) Dissolving the formulated amount of sunscreen in purified water to obtain a sunscreen solution, mixing the formulated amount of glycerin and the remaining formulated amount of purified water, heating to 70-85° C., adding the sunscreen solution and the formulated amounts of gelatin and sodium alginate, maintaining the temperature at 60-80° C., and evacuating the gelatin particles after they are completely dissolved, maintaining the temperature at 60-80° C., to obtain a capsule shell material;

[0025] (3) pelletizing the content material and the capsule shell material to obtain the vitamin D2 soft capsule.

[0026] Preferably, step (1) is specifically:

[0027] Mix the formulated amount of stabilizer and part of the dispersant in a stainless steel container, heat to 90°C, add the formulated amount of vitamin D2, stir until completely dissolved, continue stirring for 1 hour, mix evenly with the remaining dispersant, and obtain the content material.

[0028] Preferably, in step (1), the mass ratio of the partial dispersant to vitamin D2 is 1-2:1-2, and more preferably 1:1.

[0029] Preferably, step (2) is specifically:

[0030] Dissolve the formulated amount of sunscreen agent in purified water to obtain a sunscreen solution, suck the formulated amount of glycerin and the remaining formulated amount of purified water into the sol tank in sequence, start stirring, open the steam valve and heat to 70-80°C, slowly add the sunscreen solution, gelatin and sodium alginate into the sol tank, control the steam heating to keep the temperature in the tank at 60-80°C, after all the gelatin particles in the tank are evenly dissolved and there are no particles, evacuate and maintain it at -0.07 ~ -0.09MPa, adjust the steam valve to keep the temperature in the tank at 60°C-80°C, and when there is no obvious foam on the surface of the glue solution, turn off the vacuum and stop stirring.

[0031] The operation time of step (2) is 1-2.5h.

[0032] Preferably, in step (3), a YWJ250-II fully automatic soft capsule machine is used.

[0033] Further preferably, in step (3), a lubricant not less than 2 / 3 of the height of the sight glass is injected into the lubricating oil tank, and the lubricant is a mixture of caprylic and capric glycerides and acetylated monoglycerides.

[0034] Further preferably, in the lubricant, the volume ratio of caprylic and capric glycerides to acetylated monoglyceride is 1-2:1-2, most preferably 1:1.

[0035] Preferably, the vitamin D2 soft capsule of the present invention has a content weight of 235-255 mg / pill and a capsule shell weight of 210-240 mg / pill.

[0036] Preferably, step (3) is specifically:

[0037] A. Wipe the inside and outside of the hopper, plastic box, container, measuring tool, and feeding oil pipe with 75% ethanol solution;

[0038] B. Assemble the insulation sleeve, upper rubber hose and left and right rubber boxes, and inject lubricant into the lubricating oil tank to a height not less than 2 / 3 of the sight glass;

[0039] C. Set the main machine speed to 2.0-3.0 rpm. After the gelatin box is heated to the set value, turn on "automatic loading" to allow the glue to enter the left and right glue boxes through the glue feeding tube;

[0040] D. Turn on "main machine operation", turn on the glue wind wheel, put the leather board out of the glue box into the leather rolling roller, use the thickness gauge to check whether the leather board is standard, control the thickness of the rubber, if it does not meet the standard, adjust the knob on the glue distribution box, turn on the left and right lubricating oils, and turn on the air pressure;

[0041] E. After the spray temperature reaches the set value, push the spray switch, turn on the pill feeder, tighten the lower net shaft slightly, and start to adjust the content weight and capsule shell thickness. Take 10 pills each time and weigh them one by one. The content weight is controlled at 235-255mg / pill and the capsule shell weight is controlled at 210-240mg / pill. If it does not meet the standard, turn on the "Automatic Content Adjustment" in the auxiliary operation page to adjust it. When the content weight and capsule shell weight are within the standard range, flush the pipeline 3 times;

[0042] F. Send the balls into the shaping cage through the fan duct. The shaping temperature shall not exceed 25℃ and the shaping time shall be controlled at 2-4h.

[0043] G. Put the shaped wet pills into the drying cage. The drying temperature should be controlled not to exceed 35℃ and the drying time should be 6-15h.

[0044] The beneficial effects of the present invention are:

[0045] (1) The present invention selects vitamin E acetate, vitamin E polyethylene glycol succinate and butylated p-hydroxyanisole as stabilizers to synergistically improve the quality stability of the contents of vitamin D2 soft capsules.

[0046] (2) The present invention selects soybean oil, walnut oil and grape seed oil as dispersants, which can further improve the stability of the contents.

[0047] (3) The present invention selects brilliant blue and tartrazine to be added to the capsule shell in a specific ratio as a sunscreen to improve the quality stability of the soft capsule.

[0048] (4) The present invention uses a compound of gelatin and sodium alginate as the capsule shell material, which reduces the defect of easy aging caused by gelatin and improves the quality of the capsule shell itself.

[0049] (5) The present invention uses a mixture of caprylic and capric glycerides and acetylated monoglycerides to replace the liquid paraffin in the prior art as a lubricant, which can avoid the influence of liquid paraffin on the absorption of vitamin D2, improve the absorption rate, avoid adhesion, and reduce the impact on production.

[0050] (6) The vitamin D2 soft capsule provided by the present invention has good stability and is suitable for the prevention and treatment of cardiovascular and cerebrovascular diseases. DETAILED DESCRIPTION

[0051] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and they should also fall within the scope of the present application.

[0052] The present invention is further described below by way of specific examples. The various chemical reagents used in the embodiments of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all mass contents. Unless otherwise specified, it is understood that it is carried out at room temperature. The vitamin D2 content is determined according to the 2020 edition of the Chinese Pharmacopoeia.

[0053] In the following examples, vitamin D2 is 40 million international units / g;

[0054] Vitamin E acetate is from DSM, CAS: 7695-91-2;

[0055] Vitamin E polyethylene glycol succinate was from Spreadtrum Biotechnology, product number ZX-HZPYL-0158, CAS: 9002-96-4;

[0056] Tert-butyl-p-hydroxyanisole is chemerin, CAS: 25013-16-5.

[0057] Examples 1-5

[0058] The vitamin D2 soft capsule formula of embodiment 1-5 is as follows:

[0059]

[0060] Wherein, the stabilizer is a mixture of vitamin E acetate, vitamin E polyethylene glycol succinate and tert-butyl hydroxyanisole in a mass ratio of 2:2:5;

[0061] The dispersant is a mixture of soybean oil, walnut oil and grape seed oil in a mass ratio of 8:2:3;

[0062] The sunscreen is a mixture of brilliant blue and lemon yellow in a mass ratio of 3:2.

[0063] The preparation method is as follows:

[0064] (1) Mix the formulated amount of stabilizer and part of the dispersant in a stainless steel container, heat to 90°C, add the formulated amount of vitamin D2, the mass ratio of the part of the dispersant to vitamin D2 is 1:1, stir until completely dissolved, continue stirring for 1 hour, mix evenly with the remaining dispersant, and obtain the content material;

[0065] (2) Dissolve the formulated amount of sunscreen in purified water to obtain a sunscreen solution, suck the formulated amount of glycerol and the remaining formulated amount of purified water into the sol tank in sequence, start stirring, open the steam valve to heat to 75°C, slowly add the sunscreen solution, gelatin, and sodium alginate into the sol tank, control the steam heating to keep the temperature in the tank at 60-80°C, and after all the gelatin particles in the tank are evenly dissolved and there are no particles, evacuate and maintain the temperature at -0.07 to -0.09MPa, adjust the steam valve to keep the temperature in the tank at 60°C-80°C, and after there is no obvious foam on the surface of the gelatin solution, turn off the vacuum and stop stirring. The operation time is controlled within 1.5h;

[0066] (3) Put the content material and capsule shell material into the YWJ250-II fully automatic soft capsule machine to prepare soft capsules:

[0067] A. Wipe the inside and outside of the hopper, plastic box, container, measuring tool, and feeding oil pipe with 75% ethanol solution;

[0068] B. Assemble the insulation sleeve, upper rubber tube and left and right rubber boxes, and inject lubricant into the lubricating oil tank to a height not lower than 2 / 3 of the sight glass; the lubricant is a mixture of caprylic and capric glycerides and acetylated monoglycerides in a volume ratio of 1:1;

[0069] C. Set the main machine speed to 2.0-3.0 rpm. After the gelatin box is heated to the set value, turn on "automatic loading" to allow the glue to enter the left and right glue boxes through the glue feeding tube;

[0070] D. Turn on "main machine operation", turn on the glue wind wheel, put the leather board out of the glue box into the leather rolling roller, use the thickness gauge to check whether the leather board is standard, control the thickness of the rubber, if it does not meet the standard, adjust the knob on the glue distribution box, turn on the left and right lubricating oils, and turn on the air pressure;

[0071] E. After the spray temperature reaches the set value, push the spray switch, turn on the pill feeder, tighten the lower net shaft slightly, and start to adjust the content weight and capsule shell thickness. Take 10 pills each time and weigh them one by one. The content weight is controlled at 235-255mg / pill and the capsule shell weight is controlled at 210-240mg / pill. If it does not meet the standard, turn on the "Automatic Content Adjustment" in the auxiliary operation page to adjust it. When the content weight and capsule shell weight are within the standard range, flush the pipeline 3 times;

[0072] F. Send the balls into the shaping cage through the fan duct. The shaping temperature shall not exceed 25℃ and the shaping time shall be controlled for 3 hours.

[0073] G. Put the shaped wet pills into the drying cage. The drying temperature should be controlled not to exceed 35℃ and the drying time should be 10h.

[0074] Embodiment 6-8

[0075] Examples 6-8 observed the effect of the stabilizer composition on the stability of the contents. The stabilizer composition is as follows, and the rest is the same as Example 3.

[0076] Example 6: The mass ratio of vitamin E acetate, vitamin E polyethylene glycol succinate and tert-butylparahydroxyanisole is 1:1:8.

[0077] Example 7: The mass ratio of vitamin E acetate, vitamin E polyethylene glycol succinate and tert-butylparahydroxyanisole is 1:1:1.

[0078] Example 8: The mass ratio of vitamin E acetate, vitamin E polyethylene glycol succinate and tert-butylparahydroxyanisole is 1:1:10.

[0079] Examples 9-10

[0080] Examples 9-10 observed the effect of the dispersant composition on the stability of the contents. The dispersant composition is as follows, and the rest is the same as in Example 3.

[0081] Example 9: The mass ratio of soybean oil, walnut oil and grape seed oil is 5:4:4.

[0082] Example 10: The mass ratio of soybean oil, walnut oil and grape seed oil is 5:4:1.

[0083] Examples 11-12

[0084] Examples 11-13 observed the effect of the composition of the sunscreen on the stability of the contents. The composition of the sunscreen is as follows, and the rest is the same as in Example 3.

[0085] Example 11: The mass ratio of brilliant blue to lemon yellow is 1:1.

[0086] Example 12: The mass ratio of brilliant blue to lemon yellow is 5:1.

[0087] Example 13: The mass ratio of brilliant blue to lemon yellow is 7:1.

[0088] Comparative Example 1

[0089] The difference from Example 3 is that the stabilizer is a mixture of vitamin E acetate and butylated hydroxyanisole in a mass ratio of 2:5, and the rest are the same.

[0090] Comparative Example 2

[0091] The difference from Example 3 is that the stabilizer is a mixture of vitamin E polyethylene glycol succinate and butylated hydroxyanisole in a mass ratio of 2:5, and the rest are the same.

[0092] Comparative Example 3

[0093] The difference from Example 3 is that the dispersant is soybean oil, and the rest is the same.

[0094] Comparative Example 4

[0095] The difference from Example 3 is that the dispersant is a mixture of soybean oil and grape seed oil in a mass ratio of 8:3, and the rest is the same.

[0096] Comparative Example 5

[0097] The difference from Example 3 is that the sunscreen is brilliant blue, and the rest is the same.

[0098] Comparative Example 6

[0099] The difference from Example 3 is that the lubricant injected into the lubricating oil tank is caprylic and capric glyceride, and the rest is the same. During the preparation process, the adhesion phenomenon is more serious than that of Example 3, which is not conducive to the preparation.

[0100] Results

[0101] (1) Accelerated stability test: Ten qualified capsules were taken from each group of capsules of Examples 1-13 and Comparative Examples 1-6 and placed at a temperature of 50°C ± 2°C and a relative humidity of RH 75% ± 5% for 1 month. The vitamin D2 content and the vitamin D2 retention rate were determined by high performance liquid chromatography (the average value was taken).

[0102] Among them, retention rate = vitamin D2 content after placement / initial vitamin D2 content × 100%.

[0103] The results are as follows:

[0104]

[0105] The results show that after the accelerated experiment, the vitamin D2 content of Examples 1-7, 9-13 and Comparative Example 5 is still above 90%, and the stability is good. Among them, Example 3 has the best stability, and the retention rate reaches 99.6%. Example 8 shows that the mass ratio of vitamin E acetate, vitamin E polyethylene glycol succinate and butylated hydroxyanisole can affect the high temperature stability of the content. Comparative Examples 1 and 2 show that the composition of the stabilizer can affect the high temperature stability of the content. In the present invention, the applicant finds that the combination of vitamin E acetate, vitamin E polyethylene glycol succinate and butylated hydroxyanisole as stabilizers has an effect better than other stabilizers for improving the quality stability of the vitamin D2 soft capsule content. Comparative Examples 3 and 4 show that the composition of the dispersant can affect the high temperature stability of the content. In the comprehensive formula of the present invention, soybean oil, walnut oil and grape seed oil are selected as dispersants, which has a significant improvement effect.

[0106] (2) Light stability test: Ten qualified capsules were taken from each group of capsules of Examples 1-13 and Comparative Examples 1-6 and irradiated under a fluorescent lamp of 3000 lux for 240 hours. The vitamin D2 content and the vitamin D2 retention rate were determined using a high performance liquid chromatograph (the average value was taken).

[0107] Among them, retention rate = vitamin D2 content after illumination / initial vitamin D2 content × 100%.

[0108] The results are as follows:

[0109]

[0110] The results show that after the illumination experiment, the vitamin D2 content of embodiments 1-7 and 9-12 is still above 90%, and the stability is good. Among them, embodiment 3 has the best stability, and the retention rate reaches 99.8%. Embodiment 8 shows that the mass ratio of vitamin E acetate, vitamin E polyethylene glycol succinate and butylated hydroxyanisole can affect the high temperature stability of the content, and embodiment 13 shows that the composition of sunscreen can affect the stability under illumination, and the influence on the high temperature stability is not as sensitive as under illumination, and comparative example 5 shows that the composition of sunscreen can affect the light stability of the content. The applicant finds that the combination of brilliant blue and lemon yellow in a specific ratio, relative to brilliant blue as a sunscreen, is better for improving the light stability of the vitamin D2 soft capsule content. Comparative examples 1-2 and comparative examples 3-4 respectively prove the influence of the composition of stabilizer and dispersant on light stability.

[0111] (3) Disintegration time measurement: 10 qualified capsules were taken from each group of capsules in Examples 1-5 and placed under conditions of temperature 50°C ± 2°C and relative humidity RH 75% ± 5% for observation. The average disintegration time after 1 week, 2 weeks, 3 weeks, and 4 weeks was measured:

[0112]

[0113] Since aging of the capsule skin will lead to an extension of the disintegration time, the disintegration time reflects the anti-aging performance of the capsule skin. Examples 1-5 verify that the formulation composition under different proportions leads to different anti-aging performance of the capsule skin. The formulations of Examples 1-5 still maintained a disintegration time of less than 60 minutes after 4 weeks of accelerated testing, and Examples 2-4 maintained a disintegration time of less than 30 minutes, indicating that the capsule shell material of the present invention has good anti-aging performance.

[0114] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A vitamin D2 soft capsule, characterized in that: The capsule comprises contents and a capsule shell; the contents comprise, by weight, 0.004-0.15 parts of vitamin D2, 0.03-4 parts of a stabilizer and 80-280 parts of a dispersant; the capsule shell comprises, by weight, 20-50 parts of gelatin, 20-50 parts of sodium alginate, 10-50 parts of glycerol, 0.03-0.2 parts of a sunscreen and 40-100 parts of purified water; in, The stabilizer includes vitamin E acetate, vitamin E polyethylene glycol succinate and tert-butyl hydroxyanisole; in the stabilizer, the mass ratio of vitamin E acetate, vitamin E polyethylene glycol succinate and tert-butyl hydroxyanisole is 1-3:1-3:3-8; The dispersant comprises soybean oil, walnut oil and grape seed oil; in the dispersant, the mass ratio of soybean oil, walnut oil and grape seed oil is 5-10:4-8:2-4; The sunscreen comprises brilliant blue and lemon yellow; in the sunscreen, the mass ratio of brilliant blue to lemon yellow is 2-5:1-2.

2. The vitamin D2 soft capsule according to claim 1, characterized in that The content comprises, by weight, 0.004-0.12 parts of vitamin D2, 0.05-3 parts of stabilizer and 100-250 parts of dispersant; the capsule shell comprises, by weight, 20-40 parts of gelatin, 20-40 parts of sodium alginate, 20-40 parts of glycerol, 0.05-0.15 parts of sunscreen and 50-80 parts of purified water.

3. The vitamin D2 soft capsule according to claim 2, characterized in that The content comprises, by weight, 0.1 parts of vitamin D2, 1 part of stabilizer and 120 parts of dispersant; the capsule shell comprises, by weight, 30 parts of gelatin, 30 parts of sodium alginate, 30 parts of glycerol, 0.1 parts of sunscreen and 60 parts of purified water.

4. The method for preparing the vitamin D2 soft capsule according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) Mix the dispersant, take part of the dispersant and mix it with the formulated amount of stabilizer, heat it to 80-95° C., add the formulated amount of vitamin D2 until it is completely dissolved, and then mix it with the remaining dispersant to obtain the content material; (2) dissolving the formulated amount of sunscreen in purified water to obtain a sunscreen solution, mixing the formulated amount of glycerin and the remaining formulated amount of purified water, heating to 70-85° C., adding the sunscreen solution and the formulated amount of gelatin and sodium alginate, maintaining the temperature at 60-80° C., and evacuating the gelatin particles after they are completely dissolved, maintaining the temperature at 60-80° C., to obtain a capsule shell material; (3) pelletizing the content material and the capsule shell material to obtain the vitamin D2 soft capsule; In step (3), a lubricant is injected into the lubricating oil tank to a level not lower than 2 / 3 of the height of the sight glass, wherein the lubricant is a mixture of caprylic and capric glycerides and acetylated monoglycerides.

5. The preparation method according to claim 4, characterized in that: The operation time of step (2) is 1-2.5h.

6. The preparation method according to claim 4, characterized in that: In the lubricant, the volume ratio of caprylic and capric glycerides to acetylated monoglyceride is 1-2:1-2.

7. The preparation method according to claim 4, characterized in that: Step (3) is specifically as follows: A. Wipe the inside and outside of the hopper, plastic box, container, measuring tool, and feeding oil pipe with 75% ethanol solution; B. Assemble the insulation sleeve, upper rubber hose and left and right rubber boxes, and inject lubricant into the lubricating oil tank to a height not less than 2 / 3 of the sight glass; C. Set the main machine speed to 2.0-3.0 rpm. After the gelatin box is heated to the set value, turn on "automatic loading" to allow the glue to enter the left and right glue boxes through the glue feeding tube; D. Turn on "main machine operation", turn on the glue wind wheel, put the leather board out of the glue box into the leather rolling roller, use the thickness gauge to check whether the leather board is standard, control the thickness of the rubber, if it does not meet the standard, adjust the knob on the glue distribution box, turn on the left and right lubricating oils, and turn on the air pressure; E. After the spray temperature reaches the set value, push the spray switch, turn on the pill feeder, tighten the lower net shaft slightly, and start to adjust the content weight and capsule shell thickness. Take 10 pills each time and weigh them one by one. The content weight is controlled at 235-255mg / pill and the capsule shell weight is controlled at 210-240mg / pill. If it does not meet the standard, open the "Automatic Content Adjustment" in the auxiliary operation page to adjust it. When the content weight and capsule shell weight are within the standard range, flush the pipeline 3 times; F. Send the balls into the shaping cage through the fan duct. The shaping temperature shall not exceed 25℃ and the shaping time shall be controlled at 2-4h. G. Put the shaped wet pills into the drying cage. The drying temperature should be controlled not to exceed 35℃ and the drying time should be 6-15h.

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