Antiviral composition

Abstract

Chemical compounds, being the alkyl sulfate of sulfated saccharides, particularly, dextrin, dextran, and cyclodextrin, and pharmaceutical compositions containing these compounds. The compounds of the invention provide antiviral activity, particularly in the treatment and prevention of sexually-transmitted diseases. Methods of treating viral infection and preventing viral transmission include administration include administration of the compounds of the invention orally, topically, subcutaneously, by muscular injection, by intraperitoneal injection and by intravenous injection.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. patent application Ser. No. 10 / 157,787, filed May 29, 2002, which claims priority to U.S. patent application Ser. No. 10 / 092,021, filed Mar. 6, 2002, which claims priority to U.S. Provisional Patent Application Nos. 60 / 288,032, filed May 2, 2001; and 60 / 273,724, filed Mar. 6, 2001, all of which are incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention relates to the production of the alkyl sulfate of sulfated dextrin, the production of the alkyl sulfate of sulfated dextran, and to the use of these compounds to provide antiviral activity, particularly in the treatment and prevention of sexually-transmitted diseases. [0004] 2. Description of Related Art [0005] Compounds exhibiting activity against viruses may function by a number of mechanisms: they may kill or disable the disease pathogens, they may inhibit the entry of the pa...

AI Technical Summary

Benefits of technology

[0025] The present invention is directed to a new class of compounds, methods for their synthesis, and to the use of these compounds in providing antiviral activity. This class of compounds is produced by alkylsulfation (alkylsulfonation) and sulfation (sulfonation) of dextrin or dextran. The reaction used introduces aliphatic alkyl groups and sulfur groups onto a carbohydrate or polysaccharide. This reaction randomly replaces the reactive hydrogen atoms with a methylsulfate group or a sulfate group and allows for a combinatorial production of sulfate and methylsulfate substitution of dextrin or dextran. The variables of this reaction that can be controlled include the choice of dextrin or dextran as a reactant, the polymeric size of the starting material, the degree of total methylsulfation and sulfation, the degree of methylsulfation and sulfation per saccharide, and position of methylsulfation and sulfation (sulfonation) and the character of the counter ion. Control of these variables, along with the polymeric size of the starting material and degree of hydrolysis during the reaction or work-up, produces a wide range of polymeric compounds. These new compounds are distinctly different from other compounds introduced for anti-HIV therapy. These compounds have a unique synthesis, unique chemical properties and a unique pattern of activity against HIV. Use of these compounds overcomes the absorption obstacles, toxicity obstacles, and efficacy obstacles presented by prior art compounds while retaining the anti-HIV properties of sulfated saccharides. Use of the compounds of the present invention, incorporating alkyl sulfonate groups, embodies the realization that these obstacles are related to the linear sulfated structures and the non-attenuated high degree of anionicity characteristic of these sulfated compounds, and the lack of the presence of an inhibitor to enzymatic sulfate hydrolysis.

[0026] The invention introduces four important changes. First, the crucial structural element required for anti-HIV activity is recognized to be the cluster of sulfate groups presented on the branch point structures. Second, the structural element of toxic side effects is recognized as the sulfate groups on the linear portions. Elimination of linear portions and amplification of branch point sulfated structures decreases toxic side effects and increases therapeutic effects. Third, introduction of the methylsulfate group in synergy with the sulfate group increases efficacy by several possible mechanisms, including the providing of an inhibitor to sulfate hydrolyzing enzymes, the attenuation of the large negative charge and the proposed increase in oral, systemic and cellular absorption and efficacy. Finally, the number of sulfated structures or combinations of structures provides variable sites for binding and enzyme inhibition.

[0028] The comparatively low toxicity and comparative absence of detrimental effects on body tissue allow the use of the compounds of the present invention in a number of applications calling for compounds exhibiting antiviral activity. The compounds may be used directly, alone or in combination with other therapy, as an antiviral or anti-HIV drug. The compounds of the present invention may also be used in preventative treatments for HIV or other viruses. Routes of administration for these uses include oral and topical administration, and sub-cutaneous, muscular, intraperitoneal or intravenous injection. The compounds of the present invention may be used in bound and unbound form to eliminate HIV or other viruses from blood products during dialysis of organ or whole body preparations. They may also be used alone or in combination in cell culture systems or organ preservation systems to destroy or prevent HIV or other viral growth.

Problems solved by technology

Elimination of linear portions and amplification of branch point sulfated structures decreases toxic side effects and increases therapeutic effects.

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