Fopitasvir-containing triple compound preparation for treating hepatitis C and preparation method of Fopitasvir-containing triple compound preparation

Abstract

The invention discloses a Fopitasvir-containing triple compound preparation for treating hepatitis C and a preparation method of the Fopitasvir-containing triple compound preparation, the compound preparation is a tablet prepared from Sofosbuvir, Amphihevir, Fopitasvir, lactose, microcrystalline cellulose, croscarmellose sodium, povidone and magnesium stearate, and the mass ratio of Sofosbuvir to Amphihevir to Fopitasvir is (6-7): (1-0.5): (2-2.6). The preparation can effectively solve the problems of great side effect and poor treatment effect of the existing preparation.

Description

Technical Field

[0001] The present invention relates to the technical field of medicines, and in particular to a compound preparation for treating hepatitis C and a preparation method thereof. Background Art

[0002] Hepatitis C is primarily transmitted through blood transfusions, needle sticks, and drug use. It is a viral hepatitis caused by infection with the hepatitis C virus (HCV). HCV is a major human pathogen, infecting approximately 170 million people worldwide, which is roughly five times the number of infections with human immunodeficiency virus type 1. Once infected, approximately 20% of people can clear the virus, but the rest carry HCV for the rest of their lives. 10 20% of chronically infected individuals eventually develop cirrhosis or cancer that damages the liver, posing a serious threat to the patient's health and life.

[0003] Currently, the drugs used to treat hepatitis C are mainly those containing interferon α. ​​These drugs have serious side effects after use, which seriously affect the daily life of patients. Therefore, it is particularly important to develop a drug with fewer side effects. Summary of the invention

[0004] In view of the above-mentioned deficiencies in the prior art, the present invention provides a compound preparation for treating hepatitis C and a preparation method thereof, which can effectively solve the problems of large side effects and poor therapeutic effects of the existing preparations.

[0005] To achieve the above purpose, the technical solution adopted by the present invention to solve the technical problem is: a compound preparation for treating hepatitis C, comprising the following components Sofosbuvir, Amphihevir, and Fopitasvir, wherein the mass ratio of Sofosbuvir, Amphihevir, and Fopitasvir is 6-7:1-0.5:2-2.6.

[0006]

[0007] Further, the structural formula of Sofosbuvir is:.

[0008] Further, the structural formula of Amphihevir is:

[0009] Further, the structural formula of Fopitasvir is:

[0010] Furthermore, the invention further comprises the following auxiliary materials in parts by weight: 10-30 parts of lactose, 30-50 parts of microcrystalline cellulose, 20-30 parts of cross-linked sodium carboxymethyl cellulose, 30-40 parts of povidone and 5-10 parts of magnesium stearate, wherein the mass ratio of the lactose to the fopitasvir is 0.75-1.5:1.

[0011] Furthermore, the dosage form of the compound preparation is tablets.

[0012] The preparation method of the compound preparation for treating hepatitis C comprises the following steps:

[0013] (1) mixing Fopitasvir and lactose and then ultrafine grinding to obtain a mixed powder;

[0014] (2) mixing the mixed powder in step (1) with Sofosbuvir, microcrystalline cellulose, and cross-linked sodium carboxymethyl cellulose to obtain a mixed material;

[0015] (3) dissolving povidone to obtain a povidone solution with a mass concentration of 3-10%, and then adding the povidone solution to the mixed material of step (2) to prepare a soft material, and then granulating, drying, and granulating;

[0016] (4) adding magnesium stearate to the granules after granulation in step (3), mixing the whole granules and then tableting to obtain a product.

[0017] Furthermore, the particle size of the material after ultrafine grinding in step (1) is ≤25nm.

[0018] Furthermore, the drying temperature in step (3) is 45-65°C.

[0019] Furthermore, the drying temperature in step (3) is 50°C.

[0020] In the above scheme, the drying temperature is too high, which will cause the loss of effective ingredients.

[0021] Furthermore, the mesh size of the sieve used for granulation in step (3) is 20 meshes.

[0022] The beneficial effects of the present invention are as follows: the preparation of the present invention is a dual compound preparation, wherein Sofosbuvir is an NS5B protease inhibitor, Amphetamine is an NS4B protease inhibitor, and Fopitasvir is an NS5A protease inhibitor. The combination of the three can cure hepatitis C from the root, and the cure rate of hepatitis C is as high as 90%, with excellent sustained viral response. The side effects of both are small, which can solve the problem of large side effects caused by interferon a. DETAILED DESCRIPTION

[0023] The specific implementation modes of the present invention are described in detail below.

[0024] Example 1

[0025] A compound preparation for treating hepatitis C, each 1000 tablets includes 4kg of Sofosbuvir, 1.2kg of Amphihevir, 0.6kg of Fopitasvir, 1kg of lactose, 0.44kg of microcrystalline cellulose, 0.26kg of cross-linked sodium carboxymethyl cellulose, 0.33kg of povidone, and 0.07kg of magnesium stearate.

[0026] The preparation method of the above-mentioned compound preparation for treating hepatitis C is as follows:

[0027] (1) Mixing Fopitasvir, Amphihevir and lactose and then ultrafine grinding them to control the particle size D90 ≤ 25 nm to obtain a mixed active ingredient for later use;

[0028] (2) Weighing the calculated amount of co-micronized powder and lactose, the formulated amount of sofosbuvir, microcrystalline cellulose, cross-linked carboxymethyl cellulose sodium, and povidone, mixing and stirring to obtain a mixed material for later use;

[0029] (3) adding an appropriate amount of water for injection to the mixed material obtained in step (2), adding an appropriate amount of water for injection to make a soft material, and drying the wet granules at 55° C. to form granules;

[0030] (4) adding magnesium stearate to the granulated material in step (3), mixing, and tableting to obtain the product.

[0031] Example 2

[0032] A compound preparation for treating hepatitis C, each 1000 tablets includes 4kg of Sofosbuvir, 1.2kg of Amphihevir, 0.6kg of Fopitasvir, 1kg of lactose, 0.44kg of microcrystalline cellulose, 0.26kg of cross-linked sodium carboxymethyl cellulose, 0.33kg of povidone, and 0.07kg of magnesium stearate.

[0033] The preparation method of the above-mentioned compound preparation for treating hepatitis C is as follows:

[0034] (1) Mixing Fopitasvir, Amphihevir and lactose and then ultrafine grinding them to control the particle size D90 ≤ 25 nm to obtain a mixed active ingredient for later use;

[0035] (2) weighing the calculated amount of co-micronized powder and lactose, the formulated amount of sofosbuvir, microcrystalline cellulose, and cross-linked sodium carboxymethyl cellulose, and mixing and stirring to obtain a mixed material for later use;

[0036] (3) dissolving povidone in water for injection to prepare a povidone solution with a mass concentration of 5%, and then adding the solution to the mixed material in step (2) to prepare a soft material, granulate and dry the granules, and then pass through a 20-mesh sieve to size the granules;

[0037] (4) adding magnesium stearate to the granulated material in step (3), mixing, and tableting to obtain the product.

[0038] Comparative Example 1

[0039] A compound preparation for treating hepatitis C, each 1000 tablets comprising 4kg of Sofosbuvir, 1kg of lactose, 0.44kg of microcrystalline cellulose, 0.26kg of cross-linked carboxymethyl cellulose sodium, 0.33kg of povidone, and 0.07kg of magnesium stearate.

[0040] The preparation method of the above-mentioned compound preparation for treating hepatitis C is as follows:

[0041] (1) Weighing the formulated amount of Sofosbuvir, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, and povidone, mixing and stirring evenly to obtain a mixed material, and setting aside;

[0042] (2) adding an appropriate amount of water for injection to the mixed material obtained in step (2), adding an appropriate amount of water for injection to make a soft material, and drying the wet granules at 55° C. to form granules;

[0043] (3) adding magnesium stearate to the granulated material in step (2), mixing, and tableting to obtain the product.

[0044] Comparative Example 2

[0045] A compound preparation for treating hepatitis C, each 1000 tablets comprising 1.2 kg of Amphihevir, 1 kg of lactose, 0.44 kg of microcrystalline cellulose, 0.26 kg of cross-linked sodium carboxymethyl cellulose, 0.33 kg of povidone, and 0.07 kg of magnesium stearate.

[0046] The preparation method of the above-mentioned compound preparation for treating hepatitis C is as follows:

[0047] (1) mixing Fopitasvir and lactose and then ultrafine grinding them to control the particle size D90≤25nm to obtain a mixed effective ingredient for later use;

[0048] (2) Weighing the calculated amount of the co-micronized powder, lactose microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, and povidone, mixing and stirring to obtain a mixed material for later use;

[0049] (3) adding an appropriate amount of water for injection to the mixed material obtained in step (2), adding an appropriate amount of water for injection to make a soft material, and drying the wet granules at 55° C. to form granules;

[0050] (4) adding magnesium stearate to the granulated material in step (3), mixing, and tableting to obtain the product.

[0051] A compound preparation for treating hepatitis C, each 1000 tablets comprising 4kg of Sofosbuvir, 1kg of lactose, 0.44kg of microcrystalline cellulose, 0.26kg of cross-linked carboxymethyl cellulose sodium, 0.33kg of povidone, and 0.07kg of magnesium stearate.

[0052] Comparative Example 3

[0053] A compound preparation for treating hepatitis C, each 1000 tablets comprising 0.6 kg of Fopitasvir, 1 kg of lactose, 0.44 kg of microcrystalline cellulose, 0.26 kg of cross-linked carboxymethyl cellulose sodium, 0.33 kg of povidone, and 0.07 kg of magnesium stearate.

[0054] The preparation method of the above-mentioned compound preparation for treating hepatitis C is as follows:

[0055] (1) Weighing the formulated amount of Sofosbuvir, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, and povidone, mixing and stirring evenly to obtain a mixed material, and setting aside;

[0056] (2) adding an appropriate amount of water for injection to the mixed material obtained in step (1), adding an appropriate amount of water for injection to make a soft material, and drying the wet granules at 55° C. to form granules;

[0057] (3) adding magnesium stearate to the granulated material in step (2), mixing, and tableting to obtain the product.

Claims

1. A triple compound preparation for treating hepatitis C comprising Fopitasvir, characterized in that: The invention comprises the following components: Sofosbuvir, Amphihevir and Fopitasvir, wherein the mass ratio of Sofosbuvir to Fopitasvir is 6-7:1-0.5:2-2.

6.

2. The compound preparation for treating hepatitis C according to claim 1, characterized in that: The structural formula of Sofosbuvir is:

3. The compound preparation for treating hepatitis C according to claim 1, characterized in that: The structural formula of Amphihevir is:

4. The compound preparation for treating hepatitis C according to claim 1, characterized in that: The structural formula of the Fopitasvir is:

5. The compound preparation for treating hepatitis C according to claim 1, characterized in that: The invention also includes the following auxiliary materials in parts by weight: 10-30 parts of lactose, 30-50 parts of microcrystalline cellulose, 20-30 parts of cross-linked sodium carboxymethyl cellulose, 30-40 parts of povidone and 5-10 parts of magnesium stearate, and the mass ratio of the lactose to the fopitasvir is 0.75-1.5:

1.

6. The compound preparation for treating hepatitis C according to claim 5, characterized in that: The dosage form of the compound preparation is tablet.

7. The method for preparing the compound preparation for treating hepatitis C according to claim 6, characterized in that: The following steps are involved: (1) mixing Fopitasvir, Amphihevir and lactose and then ultrafine grinding to obtain a mixed powder; (2) mixing the mixed powder in step (1) with Sofosbuvir, microcrystalline cellulose, and cross-linked sodium carboxymethyl cellulose to obtain a mixed material; (3) dissolving povidone to obtain a povidone solution with a mass concentration of 3-10%, and then adding the povidone solution to the mixed material of step (2) to prepare a soft material, and then granulating, drying, and granulating; (4) adding magnesium stearate to the granules after granulation in step (3), mixing the whole granules and then tableting to obtain a product.

8. The compound preparation for treating hepatitis C according to claim 7, characterized in that: The particle size of the material after ultrafine grinding in step (1) is ≤25nm.

9. The compound preparation for treating hepatitis C according to claim 7, characterized in that: The drying temperature in step (3) is 45-65°C.

10. The compound preparation for treating hepatitis C according to claim 7, characterized in that: The mesh size of the sieve used for granulation in step (3) is 10-20 meshes.

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