Method for the treatment or prevention of virus infection using polybiguanide-based compounds

Abstract

An inexpensive, easily available, and convenient method of treating or preventing a virus infection is provided. The present invention relates to a method for the treatment or prevention of virus infections using polybiguanide-based compounds administering a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof The invention relies on the unique biochemical reaction in which polybiguanide-based compounds interfere with the spread of virus within or between organisms. The compositions and formulations described in the present invention are effective means to reduce the infectivity of the human immunodeficiency virus type 1 (HIV-1), and human herpes simplex viruses, and also to kill the causative organisms of many other sexually transmitted diseases (STDs).

1 - 103 . (canceled) 
     
     
         104 . A pharmaceutical composition comprising an active ingredient consisting solely of polyethylene-hexamethylene biguanide (PEHMB) or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier, wherein the PEHMB or salt thereof provides a reduction in the incidence of in-vitro HIV infection of P4R5 cells and/or human CD4(+)T-lymphocyte cells which express CD4 receptor and CXCR4 co-receptor when the PEHMB or salt thereof is tested with the carrier in an in-vitro viral binding/entry assay. 
     
     
         105 . The composition according to  claim 104  wherein the polyethylenehexamethylene biguanide has one or both an amino and a monocyanoguanidine end group. 
     
     
         106 . The composition according to  claim 104  wherein the polyethylenehexamethylene biguanide includes end groups selected from the group consisting of n-octylamine, n-laurylamine, 2-aminothiazole, 2-aminobenzimidazole, 2-aminobenzothiazole, 2-amino-5-chloropyrimidine, 3-amino-1,2,4-triazole, 2-(4-thiazoyl) benzimidazole, p-cholorobenzylamine, 2,4-dichloroaniline, 8-aminoquinoline, Imidizole, Premuline, 2-aminopyrimidine, L-tryptophan, 2-guanidinobenzimidazole and mixtures thereof. 
     
     
         107 . The composition according to  claim 104  wherein the pharmaceutically acceptable salt of PEHMB is a lactate or arginate salt. 
     
     
         108 . (canceled) 
     
     
         109 . The composition of  claim 104  wherein the PEHMB or salt thereof further provides a Therapeutic Index, TI, in the range from 160 to 1000 when the PEHMB or salt thereof is tested with the carrier in assays of in-vitro cytotoxicity and in-vitro HIV-1 antiviral activity using P4R5 cells or T-lymphocyte cells. 
     
     
         110 . The composition of  claim 104  wherein the PEHMB or salt thereof further provides a reduction in availability of CXCR4 receptors on the surface of cells expressing the CXCR4 receptor when tested in-vitro with the carrier by Flouorescence Activated Cell Sorting (FACS) . 
     
     
         111 . The composition of  claim 104  wherein the reduction in the incidence of in-vitro HIV infection of P4R5 cells and/or human CD4(+)T-lymphocyte persists for at least 4 hours after the polyethylenehexamethylene biguanide or salt thereof is removed from a medium in which the cells reside. 
     
     
         112 . A method of treating cells that express a CXCR4 receptor to reduce the availability of the CXCR4 receptor on the cell surface, said method comprising exposing the cells to polyethylenehexamethylene biguanide (PEHMB) at a plasma concentration of 2-50 moles per liter in the medium in which the cells reside. 
     
     
         113 . The method according to  claim 112  wherein the polyethylenehexamethylene biguanide has one or both an amino and a monocyanoguanidine end group. 
     
     
         114 . The method according to  claim 112  wherein the polyethylenehexamethylene biguanide includes end groups selected from the group consisting of n-octylamine, n-laurylamine, 2-aminothiazole, 2-aminobenzimidazole, 2-aminobenzothiazole, 2-amino-5-chloropyrimidine, 3-amino-1,2,4-triazole, 2-(4-thiazoyl) benzimidazole, p-cholorobenzylamine, 2,4-dichloroaniline, 8-aminoquinoline, Imidizole, Premuline, 2-aminopyrimidine, L-tryptophan, 2-guanidinobenzimidazole and mixtures thereof. 
     
     
         115 . The method according to  claim 112  wherein the cells expressing the CXCR4 receptor are human cells. 
     
     
         116 . The method according to  claim 112  wherein the cells expressing the CXCR4 receptor are human T-lymphocyte cells. 
     
     
         117 . The method according to  claim 112  wherein the treatment further comprises exposing the cells to β-cyclodextrin (BCD). 
     
     
         118 . The method of  claim 112  wherein the effective amount of PEHMB is chosen so as to provides a reduction in availability of the CXCR4 receptor on the surface of cells when measured in-vitro by fluorescence activated cell sorting (FACS).