Microbicidal composition comprising an octoxynol and a quinolizidine alkaloid compound or a source thereof

Abstract

The present invention provides microbicidal compositions comprising an octoxynol and a quinolizidine alkaloid compound or a source thereof, and methods of using the compositions. The quinolizidine alkaloid compound has a structure: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

1 . A method of prevention of conception and/or prevention of transmission of a sexually transmitted disease, said method comprising administering a composition comprising (a) an octoxynol; and (b) a quinolizidine alkaloid compound or a source thereof to a subject,
 wherein the quinolizidine alkaloid compound has a structure:   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: 
         R is H or OH; 
         X and Y are each CH 2  or CH; and 
         Z is N or NO. 
       
     
     
         2 . The method of  claim 2 , wherein the composition is formulated as a gel, and wherein when the subject is a human female, the administration comprises discharging the composition into the vagina or anus of the human female, and when the subject is a human male, the administration comprises discharging the composition into the anus of the human male. 
     
     
         3 . The method of  claim 1 , wherein the quinolizidine alkaloid compound is matrine and/or oxymatrine. 
     
     
         4 . The method of  claim 3 , wherein said matrine, oxymatrine, or mixture thereof, is provided in the form of an extract from  Sophora japonica, Sophora flavescens , or  Euchresta japonica  Benth. 
     
     
         5 . The method of  claim 1 , wherein the octoxynol is octoxynol-9. 
     
     
         6 . The method of  claim 1 , wherein the sexually transmitted disease is caused by infection of human immunodeficiency virus (HIV) or herpes simplex virus 2 (HSV-2). 
     
     
         7 . The method of  claim 3 , wherein the composition comprises about 0.4% of matrine and/or oxymatrine on a weight (g)/volume (mL) basis. 
     
     
         8 . The method of  claim 5 , wherein the composition comprises about 0.1% of octoxynol-9 on a volume/volume (mL) basis. 
     
     
         9 . A kit for prevention of conception and/or prevention of transmission of a sexually transmitted disease, said kit comprising:
 a. a composition comprising (a) an octoxynol; and (b) a quinolizidine alkaloid compound or a source thereof, wherein the quinolizidine alkaloid compound has a structure:   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: 
       R is H or OH; 
       X and Y are each CH 2  or CH; and 
       Z is N or NO;
 b. an applicator; and 
 c. optionally a prophylactic device. 
 
     
     
         10 . The kit of  claim 9 , wherein the prophylactic device is a condom. 
     
     
         11 . The kit of  claim 9 , wherein the quinolizidine alkaloid compound is matrine and/or oxymatrine. 
     
     
         12 . The kit of  claim 11 , wherein said matrine, oxymatrine, or mixture thereof, is provided in the form of an extract from  Sophora japonica, Sophora flavescens , or  Euchresta japonica  Benth. 
     
     
         13 . The kit of  claim 9 , wherein the octoxynol is octoxynol-9. 
     
     
         14 . The kit of  claim 11 , wherein the composition comprises about 0.4% of matrine and/or oxymatrine on a weight (g)/volume (mL) basis. 
     
     
         15 . The kit of  claim 13 , wherein the composition comprises about 0.1% of octoxynol-9 on a volume/volume (mL) basis. 
     
     
         16 . The kit of  claim 9 , wherein the sexually transmitted disease is caused by infection of human immunodeficiency virus (HIV) or herpes simplex virus 2 (HSV-2). 
     
     
         17 . A method of reducing the cytotoxicity of an octoxynol to a mucosal membrane of a subject, said method comprising administering (a) a quinolizidine alkaloid compound or a source thereof; and (b) the octoxynol to the subject, wherein the quinolizidine alkaloid compound or a source thereof reduces the cytotoxicity of the octoxynol to said mucosal membrane, and wherein the quinolizidine alkaloid compound has a structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: 
         R is H or OH; 
         X and Y are each CH 2  or CH; and 
         Z is N or NO. 
       
     
     
         18 . The method of  claim 17 , wherein the composition is formulated as a gel, and wherein when the subject is a human female, the administration comprises discharging the composition into the vagina or anus of the human female, and when the subject is a human male, the administration comprises discharging the composition into the anus of the human male. 
     
     
         19 . The method of  claim 17 , wherein the quinolizidine alkaloid compound is matrine and/or oxymatrine. 
     
     
         20 . The method of  claim 19 , wherein said matrine, oxymatrine, or mixture thereof, is provided in the form of an extract from  Sophora japonica, Sophora flavescens , or  Euchresta japonica  Benth. 
     
     
         21 . The method of  claim 17 , wherein the octoxynol is octoxynol-9. 
     
     
         22 . The method of  claim 19 , wherein the composition comprises about 0.4% of matrine and/or oxymatrine on a weight (g)/volume (mL) basis. 
     
     
         23 . The method of  claim 21 , wherein the composition comprises about 0.1% of octoxynol-9 on a volume/volume (mL) basis.