Drug composition for treating HCV (Hepatitis C Virus) infection

A composition and medicine technology, applied in the field of preparing the pharmaceutical composition and unit dosage form, can solve the problems of patient treatment failure, the patient has no treatment alternatives and the like, and achieve the effect of low hygroscopicity

Active Publication Date: 2018-11-30
BEIJING KAWINGREEN BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, even with combination therapy with pegylated IFN-α plus ribavirin, 40% to 50% of patients fail treatment, ie, they are non-responders or relapsers
There are currently no effective treatment alternatives for these patients

Method used

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  • Drug composition for treating HCV (Hepatitis C Virus) infection
  • Drug composition for treating HCV (Hepatitis C Virus) infection
  • Drug composition for treating HCV (Hepatitis C Virus) infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Compound N-[(2S)-1-[(2S)-2-{4-[7-(4-{2-[(2S)-1-[(2S)-2-[(methoxy ylcarbonyl)amino]-3-methylbutyryl]pyrrolidin-2-yl]-1H-imidazol-4-yl}phenyl)-2H-1,3-benzodioxol-4-yl]- 1H-imidazol-2-yl}pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]methyl carbamate (prepared according to the method disclosed in CN102791687B) dihydrochloride salt preparation

[0046] At room temperature, a solution of pure product of structural formula I (800 g, 1.0 eq) and ethyl acetate (8 L) was successively added into a 20 L bottle and stirred. Add dropwise HCl / ethyl acetate solution (839g) with a concentration of about 11.2% into the system, control the temperature of the system at 15°C to 25°C, stir for more than 3 hours, stop the reaction, filter with suction, and filter the cake with ethyl acetate (2L) Wash, control the temperature of the filter cake and bake at 40-60°C, take a sample and test until the residue of ethyl acetate <0.5%, (about 73 hours after drying), the compound of structural...

Embodiment 2

[0047] Example 2 The compound of formula (II) is screened by different crystallization methods

[0048] 1. Slow volatile crystallization

[0049] Weigh about 10mg of the pure product with structural formula II into a 3mL glass bottle, respectively add about 0.5-1.25mL of the following solvents to ensure that the samples are completely dissolved to obtain a clear solution, and the obtained solution is slowly volatilized at room temperature. Solid test XRPD, the results are shown in Table 1. The solids obtained in the volatile crystallization experiment were all amorphous, and no other new crystal forms were obtained.

[0050] Experiment number

Solvent used

temperature

get solid

805301-14-A1

H2O

RT

amorphous

805301-14-A2

MeOH

RT

amorphous

805301-14-A3

EtOH

RT

amorphous

805301-14-A4

IPA

RT

N / A*

805301-14-A5

Acetic acid

RT

amorphous

805301-14-A6

DMSO

RT

...

Embodiment 3

[0073] Example 3 Preparation of Compound Form H of Formula (II)

[0074] (1) In a 100mL three-necked flask, add about 7g of the pure product of structural formula I, 16.8g of methanol, stir to dissolve and then filter. Time is about 10 minutes) dropwise adding 2.8g methanolic hydrochloric acid solution (the concentration of methanolic hydrochloric acid solution is 32%-38%), no need to control the temperature, the solution is a clear solution after the dropwise addition.

[0075] (2) After the hydrochloric acid methanol solution is added dropwise, the temperature of the solution is raised to 60-65° C. to reflux, and the reflux time is about 2 hours. A large amount of white solids are precipitated in the solution.

[0076] (3) Turn off the heating of the solution accompanied by white solid precipitation after reflux, and slowly add ethyl acetate dropwise. After the dropwise addition, first cool down and stir naturally. After reaching room temperature, cool down to 10±5°C and stir ...

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Abstract

The invention relates to a drug composition for treating hepatitis C infection and a unit dosage form. The drug composition and the unit dosage are prepared from KW136(N-[(2S)-1-[(2S)-2-{4-[7-(4-{2-[(2S)-1-[(2S)-2-(methoxycarbonyl)amino]3-methylbutyryl]pyrrolidine-2-yl)-1H-imidazole-4-yl}phenyl}-2H-1,3-benzodioxole-4-yl]-1H-imidazole-2-yl}pyrrolidine-1-yl]-3-methyl-1-oxobutane-2-yl]methyl carbamate dihydrochloride, a compound as shown in a formula (II) and at least one pharmaceutically acceptable excipient which are in therapeutically effective amounts. The invention also discloses a method for preparing the drug composition and the unit dosage form.

Description

technical field [0001] The invention relates to pharmaceutical preparations, and specifically discloses a pharmaceutical composition and unit dosage form for treating hepatitis C virus infection, as well as a method for preparing the pharmaceutical composition and unit dosage form. Background technique [0002] Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the United States. Although the number of new infections has declined, the burden of chronic infection remains substantial, with the Centers for Disease Control estimating that there are 3.9 million infected people (1.8%) in the United States. Chronic liver disease is the tenth leading cause of death among adults in the United States and is responsible for approximately 25,000 deaths each year, or approximately 1% of all deaths. Studies have shown that 40% of chronic liver disease is associated with HCV, causing an estimated 8,000-10,000 deaths per year. HCV-related end-stage liver...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4178A61K9/48A61K45/06A61P1/16A61P31/14
CPCA61K9/1635A61K31/4178A61K45/06A61P1/16A61P31/14
Inventor 杨健周德胜闫甫昆潘海张晓溪刘英明
Owner BEIJING KAWINGREEN BIOTECH CO LTD
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