Pharmaceutical composition containing omega-3 fatty acid and statins and preparation method thereof

Abstract

The invention discloses a pharmaceutical composition containing omega-3 fatty acid and statins and a preparation method of the pharmaceutical composition, and belongs to the technical field of preparation of pharmaceutical compositions. The preparation method comprises the following steps: dissolving the film-forming material in a solvent, adding the statins, the plasticizer and the stabilizer into the solvent to prepare an upper drug layer coating solution, adjusting coating parameters, and preparing an upper drug layer coating outside the capsule core by using the upper drug layer coating solution, or additionally coating a protective layer coating outside the upper drug layer coating to complete the preparation of the composition. The pharmaceutical composition prepared by the invention is of a capsule core / upper drug layer coating structure or a capsule core / upper drug layer coating / protective layer coating structure, and compared with a composition of a capsule core / isolating layer coating / upper drug layer coating structure or a capsule core / isolating layer coating / upper drug layer coating / protective layer coating structure, the pharmaceutical composition has the advantages that the content of the pharmaceutical composition is reduced; the pharmaceutical composition which is not coated with the isolating layer coating is more stable, quick release of omega-3 fatty acid and statins can be realized after stable lofting, the curative effect of drug combination is ensured, and the purpose of synergistically reducing blood fat can be efficiently achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of preparation of pharmaceutical compositions, and in particular to a pharmaceutical composition containing ω-3 fatty acids and statins and a preparation method thereof. Background Art

[0002] Hyperlipidemia is a common dyslipidemia caused by excessively high blood lipid levels in the human body. It has a high incidence rate and can lead to a series of serious vascular diseases such as coronary artery disease, stroke, and peripheral artery disease. At present, statins are routinely used alone in the clinical treatment of hyperlipidemia in my country. However, due to the "6% effect" of statins, that is, when the dose of any statin is doubled, the further reduction in blood lipids is only about 6%, resulting in low treatment efficiency. In order to deal with such problems, the combined use of lipid-lowering drugs is a basic trend in dyslipidemia intervention strategies. The purpose of combined medication is to utilize the pharmacological mechanisms of different drugs to improve treatment efficiency.

[0003] Studies have found that compared with statins alone, the combination of ω-3 fatty acids and statins can significantly reduce the levels of triglycerides (TG), total cholesterol (TC) and very low-density lipoprotein-cholesterol (VLDL-C) in people with dyslipidemia. Omega-3 fatty acid drugs target triglycerides, while statins target cholesterol, and the two can achieve a synergistic effect. At the same time, several clinical studies have shown that the number of adverse events or serious adverse events does not increase significantly when the two are used in combination. The combination of the two has good efficacy and safety in people with dyslipidemia and can be used as a medication option for patients with hypertriglyceridemia.

[0004] There are three main preparation forms of existing ω-3 fatty acid and statin pharmaceutical compositions: one is direct mixing and filling; the second is to mix statins, coating materials and plasticizers to make a coating liquid and then apply it on the core of the ω-3 fatty acid soft capsule; the third is to apply an isolation layer and then apply the statin on the core of the ω-3 fatty acid soft capsule. Among them, the first two combination forms cannot guarantee the stability of statins; this form of coating the isolation layer and then coating the combined drug to prepare the pharmaceutical composition is more common in the prior art, but relevant studies have shown that after coating the ω-3 fatty acid soft capsule core with a common isolation layer liquid, coating the statin on the ω-3 fatty acid soft capsule core has the problem of accelerating the cross-linking of the soft capsule, and cannot guarantee the rapid release of ω-3 fatty acids after the stability of the composite composition, and it is difficult to achieve a good synergistic lipid-lowering effect.

[0005] In order to solve the obvious problems existing in the existing composition preparation scheme, Chinese patent CN 104602684B discloses a multi-layer coated pharmaceutical composition for oral administration containing omega-3 fatty acids or their alkyl esters and statins. The patent improves the isolation shielding layer raw materials used in the preparation of composite capsules to solve the problems of deformation and adhesion of gelatin capsule cores caused by aqueous coating. Specifically, hydroxypropyl methylcellulose and a copolymer of butyl methacrylate, (2-demethylaminoethyl) methacrylate and methyl methacrylate in a weight ratio of 1:2:1 are coated on the gelatin capsule core containing omega-3 fatty acids or their alkyl esters to form a first coating layer, and then a coating solution containing statins is coated on the coating layer to form a second coating layer to complete the preparation of the composition. This scheme improves the stability of the composition by introducing a shielding coating layer, and the disintegration test found that the capsules in the form of multi-layer coatings are similar to the commercially available capsules Omacor TM have similar disintegration time. Therefore, if the pharmaceutical composition containing ω-3 fatty acids and statins is prepared with reference to the scheme disclosed in the patent, it should also be expected to solve the stability problem of statins; but even so, the problem that still needs to be considered is that the test object for the disintegration test in the scheme is a newly prepared composition, and the newly prepared soft capsule itself does not have obvious cross-linking phenomenon, but the soft capsule may cause a huge change in disintegration time due to gelatin cross-linking after stability testing. Therefore, after preparing a pharmaceutical composition containing ω-3 fatty acids and statins based on the scheme disclosed in the patent, it cannot be guaranteed that the ω-3 fatty acids can be quickly released after the stability testing of the composition, and based on the content disclosed in the document, it cannot be inferred without doubt that the corresponding effect can be achieved. Summary of the invention

[0006] One of the purposes of the present invention is to solve the problems existing in the prior art and provide a pharmaceutical composition containing ω-3 fatty acids and statins. Another purpose of the present invention is to provide a method for preparing a pharmaceutical composition having good stability and capable of rapidly and stably releasing ω-3 fatty acids and statins.

[0007] In order to achieve the above technical objectives, the present invention is implemented by the following technical scheme: a method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins, comprising the following steps:

[0008] 1) Preparation of the coating solution for the upper drug layer: adding the coating material into a solvent to dissolve it, and adding the statin or a pharmaceutically acceptable salt thereof, a plasticizer, and a stabilizer into the solvent to dissolve or disperse it;

[0009] 2) Taking ω-3 fatty acid soft capsules as capsule cores, adjusting coating parameters, and using the upper drug layer coating liquid to prepare the upper drug layer coating on the capsule cores.

[0010] Furthermore, the upper drug layer coating liquid includes 5-40 parts of statins or pharmaceutically acceptable salts thereof, 50-95 parts of coating materials, 0.1-10 parts of plasticizers and 0.1-10 parts of stabilizers in terms of weight, and the mass of the upper drug layer coating does not exceed 20% of the capsule core.

[0011] Furthermore, the solvent is one or more of water, acetone, ethanol, and methanol; and the solid-liquid mass ratio of the raw materials and the solvent in the upper drug layer coating liquid is 1:5 to 1:20.

[0012] Furthermore, the coating material is one or more of acrylic resin, hydroxypropyl methylcellulose, methylcellulose, and hydroxypropyl cellulose. Preferably, the coating liquid of the upper drug layer includes 64-93 parts of the coating material, and the coating material is preferably one or more of acrylic resin and hydroxypropyl methylcellulose; the plasticizer is one or more of triethyl citrate, polyethylene glycol, glycerol, triacetin, corn oil, castor oil, acetylated monoglyceride, and phthalate. Preferably, the coating liquid of the upper drug layer includes 0.1-6 parts of the plasticizer, and the plasticizer is preferably selected from one or more of triethyl citrate, glycerol, and triacetin; the stabilizer is one or more of magnesium oxide, magnesium carbonate, sodium hydroxide, sodium citrate, potassium citrate, calcium lactate, sodium carbonate, sodium bicarbonate, and magnesium hydroxide; the statin is selected from rosuvastatin, pravastatin, lovastatin, simvastatin, atorvastatin, fluvastatin, or pitavastatin.

[0013] Furthermore, the coating parameters are: material temperature 20-40°C, main machine speed 5-8rpm, atomization pressure 0.03-0.10MPa, and flattening pressure 0.05-0.15MPa.

[0014] Furthermore, a protective layer coating is provided outside the upper drug layer coating, and the protective layer coating is prepared by secondary coating the capsule core containing the upper drug layer coating with a protective layer coating liquid.

[0015] Furthermore, the protective layer coating solution is composed of 80-100 parts of coating material, 0.1-10 parts of plasticizer and 0-10 parts of stabilizer, and the mass of the protective layer coating does not exceed 20% of the mass of the capsule core.

[0016] Furthermore, the coating material is one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, methylcellulose, and hydroxypropyl cellulose; the plasticizer is one or more of triethyl citrate, polyethylene glycol, glycerol, triacetin, corn oil, castor oil, acetylated monoglyceride, and phthalate; and the stabilizer is one or more of magnesium oxide, magnesium carbonate, sodium hydroxide, sodium citrate, potassium citrate, calcium lactate, sodium carbonate, sodium bicarbonate, and magnesium hydroxide.

[0017] Furthermore, the ω-3 fatty acid soft capsule is made of existing materials, and the relevant contents are not described in detail. By weight, it mainly contains 90-100 parts of ω-3 fatty acids and pharmaceutically acceptable salts thereof, preferably 98-100 parts; contains 0.1-5 parts of antioxidants, the antioxidants are selected from one or more of tocopherol, ascorbic acid, and butylated hydroxytoluene; contains 0.1-10 parts of plasticizers (one or more of glycerol, sorbitol, xylitol, maltitol, mannitol, sorbitol sorbitan, propylene glycol, and polyethylene); and the soft capsule shell material is gelatin.

[0018] The pharmaceutical composition containing ω-3 fatty acids and statins prepared by the above method mainly includes a capsule core containing ω-3 fatty acids and an upper drug layer coating containing statins from the inside to the outside. The pharmaceutical composition with this structure has high stability and can achieve rapid release of drugs after stability is released.

[0019] In order to further improve the material stability without affecting the rapid release of the drug after stability is released, a protective layer coating with a stabilizing effect can be provided outside the upper drug layer coating. Therefore, the pharmaceutical composition containing ω-3 fatty acids and statins disclosed in the present application can also be a composition of capsule core / upper drug layer coating / protective layer coating structure.

[0020] The beneficial effects of the present invention are:

[0021] 1. The pharmaceutical composition containing ω-3 fatty acids and statins prepared in the present application improves the stability of the drug by coating a drug coating layer containing statins and stabilizers on the capsule core containing ω-3 fatty acids, and does not affect the rapid release of the drug after stability release, which helps to effectively achieve the synergistic effect of lowering blood lipids;

[0022] 2. In the preparation of the pharmaceutical composition containing ω-3 fatty acids and statins, in addition to coating the statin-containing upper drug coating layer on the soft capsule core containing ω-3 fatty acids, the present application also attempts to coat the upper drug coating layer with a protective layer having a stabilizing effect. Compared with the composition of the capsule core / upper drug coating structure, the composition of the capsule core / upper drug coating / protective coating structure has better stability and can also achieve rapid release of ω-3 fatty acids after stability is established. In this form, the combined administration of ω-3 fatty acids and statins can better achieve the synergistic effect of lowering blood lipids;

[0023] 3. The pharmaceutical composition prepared in the present application is a composition of a capsule core / upper drug layer coating structure or a capsule core / upper drug layer coating / protective layer coating structure. Compared with a composition prepared by coating the capsule core with an isolation layer before coating the upper drug layer on the pharmaceutical composition of the corresponding structure, the pharmaceutical compositions of the two structures disclosed in the present application can achieve rapid release of ω-3 fatty acids and statins after stability testing, thereby better ensuring the efficacy of combined medication;

[0024] 4. The pharmaceutical composition containing ω-3 fatty acids and statins disclosed in the present application has a simple preparation process, strong operability, a wide range of raw material sources, and is easy to implement and apply on a large scale. It can be used as a clinical medication option for patients with hypertriglyceridemia. DETAILED DESCRIPTION

[0025] The following examples further illustrate the content of the present invention, but should not be construed as limiting the present invention. Without departing from the essence of the present invention, modifications and substitutions made to the methods, steps or conditions of the present invention all fall within the scope of the present invention.

[0026] Example 1

[0027] This embodiment discloses a method for preparing an ω-3 fatty acid and statin pharmaceutical composition, which specifically comprises the following steps:

[0028] 1) Preparation of the drug layer coating solution: Weigh 345 g of acetone and 13.5 g of purified water, mix and slowly add 3.315 g of rosuvastatin calcium and 26.739 g of coating material acrylic resin into the mixed solvent while stirring. After complete dissolution, add 0.557 g of triethyl citrate as a plasticizer and 0.6 g of light magnesium oxide as a stabilizer, and continue stirring until completely uniform.

[0029] 2) Drug layer coating: Place the ω-3 fatty acid soft capsules in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, the flattening pressure to 0.1MPa, and apply the drug layer coating. During the coating process, the coating parameters can be fine-tuned according to the actual situation, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0030] Comparative Example 1

[0031] 1) Preparation of the drug layer coating solution: Weigh 345 g of acetone and 13.5 g of purified water, mix and slowly add 3.315 g of rosuvastatin calcium and 27.339 g of coating material acrylic resin into the mixed solvent while stirring, add 0.557 g of triethyl citrate after complete dissolution, and continue stirring until completely uniform.

[0032] Drug layer coating: Place the ω-3 fatty acid soft capsules in a coating pot, control the material temperature to about 30°C, main engine speed to 6rpm, atomization pressure to 0.06MPa, flattening pressure to 0.1MPa, and apply the drug layer coating. During the coating process, the coating parameters can be fine-tuned according to actual conditions, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0033] The difference between Comparative Example 1 and Example 1 is that in this comparative example, no stabilizer magnesium oxide is added when preparing the upper drug layer coating solution. The compositions prepared in Example 1 and Comparative Example 1 are exposed at 50° C. for 30 days without packaging, and the related substances of rosuvastatin calcium are determined by the United States Pharmacopoeia method. The results are shown in Table 1.

[0034] Table 1 Comparison of the stability of the composition preparations prepared in Example 1 and Comparative Example 1 after being placed at 50°C for 30 days

[0035]

[0036] It can be seen from Table 1 that adding a stabilizer to the upper drug layer coating solution can effectively improve the stability of the final composition preparation.

[0037] Example 2

[0038] In order to further improve the stability of the composition preparation and accelerate the release of ω-3 fatty acids after stability testing, compared with Example 1, this embodiment further provides a protective layer coating outside the upper drug layer coating. The specific preparation process is as follows:

[0039] 1) Preparation of the drug layer coating solution: Weigh 345 g of acetone and 13.5 g of purified water, mix and slowly add 3.315 g of rosuvastatin calcium and 26.739 g of coating material acrylic resin into the mixed solvent while stirring, add 0.557 g of triethyl citrate and 0.6 g of light magnesium oxide after complete dissolution, and continue stirring until completely uniform.

[0040] 2) Drug layer coating: Place the ω-3 fatty acid soft capsules in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, the flattening pressure to 0.1MPa, and apply the drug layer coating. During the coating process, the coating parameters can be fine-tuned according to the actual situation, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0041] 3) Preparation of protective layer coating solution: Weigh 280 g of acetone and 120 g of purified water, mix them, and slowly add 16 g of coating material hydroxypropyl methylcellulose and 1.2 g of plasticizer triethyl citrate into the mixed solvent while stirring until they are completely dissolved.

[0042] 4) Protective layer coating: Place the capsule core containing the upper drug layer coating in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, and the flattening pressure to 0.1MPa for protective layer coating. During the coating process, the coating parameters can be fine-tuned according to actual conditions, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0043] Example 3

[0044] In order to further improve the stability of the composition preparation and accelerate the release of ω-3 fatty acids after stability release, this embodiment, based on the scheme disclosed in Example 2, further added a stabilizer to the protective layer coating solution when preparing the protective layer coating outside the upper drug layer coating. The specific preparation process is as follows:

[0045] 1) Preparation of the drug layer coating solution: Weigh 345 g of acetone and 13.5 g of purified water, mix and slowly add 3.315 g of rosuvastatin calcium and 26.739 g of coating material acrylic resin into the mixed solvent while stirring, add 0.557 g of triethyl citrate and 0.6 g of light magnesium oxide after complete dissolution, and continue stirring until completely uniform.

[0046] 2) Drug layer coating: Place the ω-3 fatty acid soft capsules in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, the flattening pressure to 0.1MPa, and apply the drug layer coating. During the coating process, the coating parameters can be fine-tuned according to the actual situation, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0047] 3) Preparation of protective layer coating solution: Weigh 280 g of acetone and 120 g of purified water, mix them, and slowly add 16 g of coating material hydroxypropyl methylcellulose and 1.2 g of plasticizer triethyl citrate to the mixed solvent while stirring. After complete dissolution, add 0.4 g of stabilizer light magnesium oxide and continue stirring until completely uniform.

[0048] 4) Protective layer coating: Place the capsule core containing the upper drug layer coating in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, and the flattening pressure to 0.1MPa for protective layer coating. During the coating process, the coating parameters can be fine-tuned according to actual conditions, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0049] Comparative Example 2

[0050] The difference between this comparative example and Example 3 is that before coating the ω-3 fatty acid soft capsule with a drug layer, an isolation layer is first coated on the capsule core and no protective layer is additionally coated outside the drug layer. The specific preparation process is as follows:

[0051] 1) Prepare the isolation layer coating solution: weigh 280 g of acetone and 120 g of purified water, mix them, slowly add 16 g of hydroxypropyl methylcellulose and 1.2 g of triethyl citrate into the mixed solvent while stirring, and stir until they are completely dissolved.

[0052] 2) Isolation layer coating: Place the ω-3 fatty acid soft capsules in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, and the flattening pressure to 0.1MPa for isolation layer coating. During the coating process, the coating parameters can be fine-tuned according to actual conditions, and the coating weight gain is controlled to be about 3% of the capsule core weight.

[0053] 3) Preparation of the drug layer coating solution: Weigh 345 g of acetone and 13.5 g of purified water, mix and slowly add 3.315 g of rosuvastatin calcium and 26.739 g of acrylic resin into the mixed solvent while stirring. After complete dissolution, add 0.557 g of triethyl citrate and 0.6 g of light magnesium oxide, and continue stirring until completely uniform.

[0054] 4) Drug layer coating: Place the soft capsules with isolation layer coating in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, the flattening pressure to 0.1MPa, and apply the drug layer coating. During the coating process, the coating parameters can be fine-tuned according to the actual situation, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0055] Comparative Example 3

[0056] The difference between this comparative example and Example 3 is that a layer of isolation layer is first coated on the capsule core before coating the drug layer on the outside of the ω-3 fatty acid soft capsule. The specific preparation process is as follows:

[0057] 1) Prepare the isolation layer coating solution: weigh 280 g of acetone and 120 g of purified water, mix them, slowly add 16 g of hydroxypropyl methylcellulose and 1.2 g of triethyl citrate into the mixed solvent while stirring, and stir until they are completely dissolved.

[0058] 2) Isolation layer coating: Place the ω-3 fatty acid soft capsules in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, and the flattening pressure to 0.1MPa for isolation layer coating. During the coating process, the coating parameters can be fine-tuned according to actual conditions, and the coating weight gain is controlled to be about 3% of the capsule core weight.

[0059] 3) Preparation of the drug layer coating solution: Weigh 345 g of acetone and 13.5 g of purified water, mix and slowly add 3.315 g of rosuvastatin calcium and 26.739 g of acrylic resin into the mixed solvent while stirring. After complete dissolution, add 0.557 g of triethyl citrate and 0.6 g of light magnesium oxide, and continue stirring until completely uniform.

[0060] 4) Drug layer coating: Place the soft capsules with isolation layer coating in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, the flattening pressure to 0.1MPa, and apply the drug layer coating. During the coating process, the coating parameters can be fine-tuned according to the actual situation, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0061] 5) Preparation of protective layer coating solution: Weigh 280 g of acetone and 120 g of purified water, mix them, and slowly add 16 g of coating material hydroxypropyl methylcellulose and 1.2 g of plasticizer triethyl citrate to the mixed solvent while stirring. After complete dissolution, add 0.4 g of stabilizer light magnesium oxide and continue stirring until completely uniform.

[0062] 6) Protective layer coating: Place the capsule core containing the upper drug layer coating in a coating pot, control the material temperature to about 30°C, the main engine speed to 6rpm, the atomization pressure to 0.06MPa, and the flattening pressure to 0.1MPa for protective layer coating. During the coating process, the coating parameters can be fine-tuned according to the actual situation, and the coating weight gain is controlled to be about 4% of the capsule core weight.

[0063] The composition preparations prepared in Examples 1-3 and Comparative Examples 2-3 were exposed to the environment of 40°C / 54%RH for 30 days without packaging, and the related substances of rosuvastatin calcium were determined by the United States Pharmacopoeia method and the capsule rupture test method specified in the United States Pharmacopoeia was used to examine the release rate of ω-3 fatty acids. With reference to the United States Pharmacopoeia, the leakage of the contents was taken as the end point of the investigation, and the capsule rupture time was recorded. If the time was less than 15 minutes, it was recorded as qualified, otherwise it was recorded as unqualified. The results are shown in Table 2.

[0064] Table 2 Stability evaluation of the composite preparations prepared in Examples 1-3 and Comparative Examples 2-3 after being placed at 40°C / 54%RH for 30 days

[0065]

[0066] It can be seen from the data in Table 2 that the addition of a protective layer has a further stabilizing effect on rosuvastatin, and compared with the composition prepared without adding a stabilizer to the protective layer coating solution, adding a certain amount of stabilizer to the protective layer coating solution can further improve the stability of the composition.

[0067] Compared with the composition prepared by adding an isolation layer (referring to the composition of the capsule core / isolation layer coating / upper drug layer coating structure or the composition of the capsule core / isolation layer coating / upper drug layer coating / protective layer coating structure), the composition of the capsule core / upper drug layer coating structure and the composition of the capsule core / upper drug layer coating / protective layer coating structure prepared in the present application can release ω-3 fatty acids faster after stability is established. Therefore, the ω-3 fatty acid and statin compound soft capsule provided in the present application not only has good stability, but also can achieve stable and rapid release of ω-3 fatty acids and statins.

[0068] The above shows and describes the basic principles, main features and advantages of the present invention. However, the above is only a specific embodiment of the present invention, and the technical features of the present invention are not limited thereto. Any other implementation methods derived by any technician in the field without departing from the technical solution of the present invention should be included in the patent scope of the present invention.

Claims

1. A method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins, characterized in that: The steps include: 1) Preparation of the coating solution for the upper drug layer: adding the coating material into a solvent to dissolve it, and adding the statin or a pharmaceutically acceptable salt thereof, a plasticizer, and a stabilizer into the solvent to dissolve or disperse it; 2) Taking ω-3 fatty acid soft capsules as capsule cores, adjusting coating parameters, and using the upper drug layer coating liquid to prepare the upper drug layer coating on the capsule cores.

2. The method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins according to claim 1, characterized in that: By weight, the upper drug layer coating liquid includes 5-40 parts of statins or pharmaceutically acceptable salts thereof, 50-95 parts of coating materials, 0.1-10 parts of plasticizers and 0.1-10 parts of stabilizers. The mass of the upper drug layer coating does not exceed 20% of the capsule core.

3. The method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins according to claim 1, characterized in that: The solvent is one or more of water, acetone, ethanol and methanol; the solid-liquid mass ratio of the raw materials and the solvent in the upper drug layer coating liquid is 1:5 to 1:

20.

4. The method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins according to claim 1, characterized in that: The coating material is one or more of acrylic resin, hydroxypropyl methylcellulose, methylcellulose, and hydroxypropyl cellulose; the plasticizer is one or more of triethyl citrate, polyethylene glycol, glycerol, triacetin, corn oil, castor oil, acetylated monoglyceride, and phthalate; the stabilizer is one or more of magnesium oxide, magnesium carbonate, sodium hydroxide, sodium citrate, potassium citrate, calcium lactate, sodium carbonate, sodium bicarbonate, and magnesium hydroxide; and the statin is selected from rosuvastatin, pravastatin, lovastatin, simvastatin, atorvastatin, fluvastatin, or pitavastatin.

5. The method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins according to claim 1, characterized in that: Coating parameters are: material temperature 20-40℃, main machine speed 5-8rpm, atomization pressure 0.03-0.10MPa, flattening pressure 0.05-0.15MPa.

6. The method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins according to claim 1, characterized in that: A protective layer coating is provided outside the upper drug layer coating, and the protective layer coating is prepared by coating the capsule core containing the upper drug layer coating with a protective layer coating liquid for a second time.

7. The method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins according to claim 6, characterized in that: The protective layer coating liquid is composed of 80-100 parts of coating material, 0.1-10 parts of plasticizer and 0-10 parts of stabilizer. The mass of the protective layer coating does not exceed 20% of the mass of the capsule core.

8. The method for preparing a pharmaceutical composition containing ω-3 fatty acids and statins according to claim 6, characterized in that: The coating material is one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, methylcellulose, and hydroxypropyl cellulose; the plasticizer is one or more of triethyl citrate, polyethylene glycol, glycerol, triacetin, corn oil, castor oil, acetylated monoglyceride, and phthalate; and the stabilizer is one or more of magnesium oxide, magnesium carbonate, sodium hydroxide, sodium citrate, potassium citrate, calcium lactate, sodium carbonate, sodium bicarbonate, and magnesium hydroxide.

9. A pharmaceutical composition containing ω-3 fatty acids and statins, characterized in that: The pharmaceutical composition is prepared based on the preparation method described in any one of claims 1 to 5, and comprises a capsule core containing ω-3 fatty acids and an upper drug layer coating containing statins located on the outside of the capsule core.

10. A pharmaceutical composition containing ω-3 fatty acids and statins, characterized in that: It is prepared based on the preparation method described in any one of claims 6 to 8, and the pharmaceutical composition comprises, from the inside to the outside, a capsule core containing ω-3 fatty acids, an upper drug layer coating containing statins, and a protective layer coating with a stabilizing effect.

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