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Combination of ribavirin derivative and alpha-interferon in treating and/or preventing virus infection and related diseases induced by virus infection

A virus infection and derivative technology, applied in the direction of antiviral agents, medical preparations containing active ingredients, peptide/protein components, etc., can solve the problems of long treatment course, obvious side effects, low efficiency, etc., to achieve good virus suppression, no side effects

Active Publication Date: 2019-03-19
江西诺立医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The purpose of the present invention is to overcome the problems of obvious side effects, low efficiency and long course of treatment in the prior art, and provide ribavirin derivatives combined with α-interferon in the manufacture of treatment and / or prevention of viral infection and viral infection Uses in medicines for causing related diseases, pharmaceutical compositions containing ribavirin derivatives and α-interferon and the use of the pharmaceutical compositions in preventing viral infections and related diseases caused by viral infections

Method used

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  • Combination of ribavirin derivative and alpha-interferon in treating and/or preventing virus infection and related diseases induced by virus infection
  • Combination of ribavirin derivative and alpha-interferon in treating and/or preventing virus infection and related diseases induced by virus infection
  • Combination of ribavirin derivative and alpha-interferon in treating and/or preventing virus infection and related diseases induced by virus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Ribavirin derivative A1 was prepared according to the following method.

[0052]

[0053] Ribavirin derivative A1, namely compound 3, was prepared according to the process shown in formula (XII).

[0054] Purchasing dodecaethylene glycol methyl ether (compound 1, 0.5mol) according to the literature "Synthesis and Lubrication and Corrosion Research of Water-Soluble Polyethylene Glycol Phosphate" (Zhao Wei, Yuan Shuai, Yu Ping, Luo Yunbai, Lubrication Compound 2 was prepared by the method in Sealing, 2015, 40(02):64-66).

[0055] Compound 2 (0.1 mol) was treated twice with 50 mL of anhydrous pyridine and concentrated by evaporation. The residue was dissolved in 60 mL of anhydrous pyridine at room temperature, treated with 2,4,6-triisopropyl-benzenesulfonyl chloride (0.15 mol) under nitrogen, and stirred at 25°C for 4 hours. Ribavirin (0.1 mol) was then added immediately and the reaction was stirred under nitrogen for 14 hours. Hydrolysis was performed by adding 20 m...

Embodiment 2

[0057] Ribavirin derivative A2 was prepared according to the following method.

[0058]

[0059] Ribavirin derivative A2, namely compound 6, was prepared according to the process shown in formula (XIII).

[0060] Compound 5 was prepared from compound 4 by referring to the method in the literature "Synthesis of polyphosphate and its application in biomedical materials" (Hu Jian, He Jinlin, Zhang Mingzu, Ni Peihong; Polymer Bulletin, 2015(10):51-65).

[0061] Compound 5 (0.1 mol) was treated twice with 50 mL of anhydrous pyridine and concentrated by evaporation. The residue was dissolved in 60 mL of anhydrous pyridine at room temperature, treated with 2,4,6-triisopropyl-benzenesulfonyl chloride (0.15 mol) under nitrogen, and stirred at 25°C for 4 hours. Ribavirin (0.1 mol) was then added immediately and the reaction was stirred under nitrogen for 14 hours. Hydrolysis was performed by adding 20 mL of water. The solvent in the mixture was evaporated. The resulting crude mat...

Embodiment 3

[0063] Ribavirin derivative A3 was prepared according to the following method.

[0064]

[0065] Ribavirin derivative A3, namely compound 10, was prepared according to the process shown in formula (XIV).

[0066] Compound 7 was prepared by referring to the method in the literature "Synthesis of Novel Phosphate Surfactant and Its Application in Pesticide Preparation" (Pang Wenwen, Shanghai Normal University, 2014).

[0067] Compound 7 (0.8mol) was esterified with ethanol under acidic conditions, and compound 8 was purified.

[0068] Compound 8 (0.5mol) and K 2 CO 3 (5mol) was dissolved in 50mL of tetrahydrofuran, and 1-iododecane (0.5mol) was added thereto, reacted at 80°C for 12h, evaporated the solvent, purified and acidified to obtain compound 9.

[0069] Compound 9 (0.1 mol) was treated twice with 50 mL of anhydrous pyridine and concentrated by evaporation. The residue was dissolved in 60 mL of anhydrous pyridine at room temperature, treated with 2,4,6-triisopropyl-b...

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Abstract

The invention relates to the field of ribavirin derivative resistant virus and discloses an application of combining a ribavirin derivative (shown in a formula (I)) and alpha-interferon in preparing adrug for treating and / or preventing virus infection and related diseases induced by virus infection, a pharmaceutical composition containing the ribavirin derivative and alpha-interferon and an application of the pharmaceutical composition in preventing virus infection and related diseases induced by virus infection. Combination of the ribavirin derivative (shown in a formula (I)) and alpha-interferon has an obvious better virus inhibiting effect and is free of side effects. The formula is as shown in the description.

Description

technical field [0001] The present invention relates to the antiviral field, in particular to the use of ribavirin derivatives in combination with α-interferon in the manufacture of medicines for the treatment and / or prevention of viral infections and related diseases caused by viral infections, containing ribavirin A pharmaceutical composition of Lin derivatives and α-interferon and the use of the pharmaceutical composition in preventing viral infection and related diseases caused by viral infection. Background technique [0002] Ribavirin is a nucleoside analog with spectrum antiviral activity and is used in the treatment of various viral infectious diseases. The combined application of ribavirin and interferon is an effective method for treating chronic hepatitis C caused by hepatitis C virus infection. However, ribavirin is prone to cause hemolytic anemia, and pegylated interferon in interferon can inhibit erythropoiesis, so the combined application of the two may cause...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/21A61P31/12A61P31/14A61K31/7056
CPCA61K31/7056A61K38/212A61P31/12A61P31/14A61K2300/00
Inventor 廖年生眭荣春曾文辉张桂香
Owner 江西诺立医药科技有限公司
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