Compositions of treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination therapy

• US 7,612,093 B2
• Filed: 12/15/2005
• Issued: 11/03/2009
• Est. Priority Date: 02/14/1997
• Status: Expired due to Fees

• Current Assignee: Unither Virology, LLC. (United Therapeutics Corporation)
• Original Assignee: United Therapeutics Corporation
• Inventors: Dwek, Raymond A., Block, Timothy M., Jacob, Gary S.
• Primary Examiner(s): Wang; Shengjun
• Application Number:
  US11/300,464
• Publication Number:
  US 20060094671A1
• Time in Patent Office: 1,419 Days
• Field of Search: 514/315, 514/274, 514/86
• US Class Current: 514/315
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07D 211/46 having a hydrogen atom as the second substituent in position 4

Abstract

Provided are methods and compositions for treating hepatitis virus infections in mammals, especially humans. The methods comprise (1) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/immunostimulating agents, or (2) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, or mixtures thereof, and immunomodulating/immunostimulating agents.

Claims

1. A pharmaceutical composition for treating a hepatitis B virus infection in a human patient, comprising from about 0.1 mg to about 100 mg of N-(n-nonyl-)-1,5-dideoxy-1,5-imino-D-glucitol and from about 0.1 mg to about 500 mg of (−

)-2′

-deoxy-3′

-thiocytidine-5′

-triphosphate.

2. A pharmaceutical composition for treating hepatitis virus infection, comprising a first amount of an N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound of Formula I:

3. The pharmaceutical composition of claim 2, wherein R is a straight chain alkyl having a chain length of C₇ to C₁₂ and W, X, Y, and Z are each hydrogen.

4. The pharmaceutical composition of claim 3, wherein R is nonyl.

5. The pharmaceutical composition of claim 2, wherein R is nonyl and W, X, Y, and Z are each butanoyl.

6. The pharmaceutical composition of claim 2, wherein said N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound is selected from the group consisting of N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol and N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate, and said antiviral compound is (−

)-2′

-deoxy-3′

-thiocytidine-5′

-triphosphate.

7. The pharmaceutical composition of claim 6, wherein said N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound is N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol.

8. The pharmaceutical composition of claim 2, wherein said first amount of said N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound is in the range of from about 0.1 mg to about 100 mg.

9. The pharmaceutical composition of claim 2, wherein said second amount of said nucleoside or nucleotide antiviral compound, or mixture thereof, is in the range of from about 0.1 mg to about 500 mg.