Compositions containing therapeutically active components having enhanced solubility

Abstract

Compositions which include therapeutically active components, solubility enhancing components other than cyclodextrins, and oxy-chloro components, wherein the oxy-chloro components are substantially effective as preservatives. In one embodiment, the oxy-chloro components are useful for preserving the therapeutically active components. In one embodiment, the oxy-chloro components include chlorite components. In a useful embodiment, the solubility enhancing components include carboxymethylcellulose.

What is claimed is:  
     
         1 . A composition comprising: 
 a therapeutically active component in an amount effective to provide a desired therapeutic benefit to a patient to whom the composition is administered;    a solubility enhancing component, other than a cyclodextrin, in an amount effective to increase the solubility of the therapeutically active component in the composition relative to the solubility of an identical therapeutically active component in a similar composition without the solubility enhancing component;    an oxy-chloro component in an effective amount to at least aid in preserving the composition; and    a liquid carrier component.    
     
     
         2 . The composition of  claim 1  wherein the therapeutically active component is selected from the group consisting of antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, derivatives thereof and mixtures thereof.  
     
     
         3 . The composition of  claim 1  wherein the therapeutically active component is selected from the group consisting of adrenergic agonists and mixtures thereof.  
     
     
         4 . The composition of  claim 1  wherein the therapeutically active component is selected from the group consisting of alpha-2-adrenergic agonists and mixtures thereof.  
     
     
         5 . The composition of  claim 1  wherein the therapeutically active component selected from the group consisting of imino-imidazolines, imidazolines, imidazoles, azepines, thiazines, oxazolines, guanidines, catecholamines, derivatives thereof and mixtures thereof.  
     
     
         6 . The composition of  claim 1  wherein the therapeutically active component includes a quinoxaline component.  
     
     
         7 . The composition of  claim 6  wherein the quinoxaline component is selected from the group consisting of quinoxaline, derivatives thereof, and mixtures thereof.  
     
     
         8 . The composition of  claim 6  wherein the quinoxaline component is selected from the group consisting of quinoxaline, (2-imidozolin-2-ylamino) quinoxaline, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, and tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, derivatives thereof and mixtures thereof.  
     
     
         9 . The composition of  claim 1  wherein the therapeutically active component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline.  
     
     
         10 . The composition of  claim 1  wherein the therapeutically active component has increased diffusion through a lipid membrane relative to an identical therapeutically active component in a similar composition without the solubility enhancing component.  
     
     
         11 . The composition of  claim 1  wherein the solubility enhancing component is effective to increase the solubility in a biological environment of the therapeutically active component relative to the solubility in a biological environment of an identical therapeutically active component in a similar composition without the solubility enhancing component.  
     
     
         12 . The composition of  claim 1  wherein the solubility enhancing component comprises a polyanionic component.  
     
     
         13 . The composition of  claim 12  wherein said polyanionic components is selected from the group consisting of anionic cellulose derivatives, anionic polymers derived from acrylic acid, anionic polymers derived from methacrylic acid, anionic polymers derived from alginic acid, anionic polymers derived from amino acids and mixtures thereof.  
     
     
         14 . The composition of  claim 1  wherein the solubility enhancing component is selected from the group consisting of anionic cellulose derivatives and mixtures thereof.  
     
     
         15 . The composition of  claim 1  wherein the solubility enhancing component is selected from the group consisting of carboxymethylcelluloses and mixtures thereof.  
     
     
         16 . The composition of  claim 1  wherein the solubility enhancing component is present in an amount in a range of about 0.1% (w/v) to about 30% (w/v).  
     
     
         17 . The composition of  claim 1  wherein the solubility enhancing component is present in an amount in a range of about 0.2% (w/v) to about 10% (w/v).  
     
     
         18 . The composition of  claim 1  wherein the solubility enhancing component is present in an amount in a range of about 0.2% (w/v) to about 0.6% (w/v).  
     
     
         19 . The composition of  claim 1  wherein the oxy-chloro component is selected from the group consisting of hypochlorite components, perchlorate components, chlorite components and mixtures thereof.  
     
     
         20 . The composition of  claim 1  wherein the oxy-chloro component comprises a chlorite component.  
     
     
         21 . The composition of  claim 1  wherein the oxy-chloro component comprises stabilized chlorine dioxide.  
     
     
         22 . The composition of  claim 1 , wherein the oxy-chloro component is present in an amount of about 500 ppm (w/v) or less.  
     
     
         23 . The composition of  claim 1  wherein the oxy-chloro component is present in an amount in a range of about 10 ppm (w/v) to about 200 ppm (w/v).  
     
     
         24 . The composition of  claim 1  which further comprises an additional preservative component other than the oxy-chloro component in an amount effective to at least aid in preserving the composition.  
     
     
         25 . The composition of  claim 24 , wherein the additional preservative component is selected from the group consisting of sorbic acid, benzalkonium chloride, chlorbutol and alkyl esters of p-hydroxybenzoic acid and mixtures thereof.  
     
     
         26 . The composition of  claim 1  wherein the liquid carrier is an aqueous liquid carrier component.  
     
     
         27 . The composition of  claim 1  which is a solution.  
     
     
         28 . The composition of  claim 1  which, has a pH of about 7 or greater.  
     
     
         29 . The composition of  claim 1  which has a pH in a range of about 7 to about 9.  
     
     
         30 . The composition of  claim 1  which is ophthalmically acceptable.  
     
     
         31 . A composition comprising: 
 a therapeutically active component selected from the group consisting of alpha-2-adrenergic agonists and mixtures thereof in an amount effective to provide a therapeutic benefit to a patient to whom the composition is administered;    an anionic cellulose derivative in an amount effective to increase the solubility of the therapeutically active component;    a chlorite component in an effective amount to at least aid in preserving the composition; and    an aqueous liquid carrier component.    
     
     
         32 . The composition of  claim 31  wherein the therapeutically active component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline.  
     
     
         33 . The composition of  claim 31  wherein the anionic cellulose derivative comprises carboxymethylcellulose.  
     
     
         34 . The composition of  claim 31  wherein the anionic cellulose derivative is present in an amount in a range of about 0.2% to about 0.6% (w/v).  
     
     
         35 . A composition comprising: 
 a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline in an amount effective to provide a therapeutic benefit to a patient to whom the composition is administered;    a solubility enhancing component in an amount effective to increase the solubility of the tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline;    a chlorite component in an effective amount to at least aid in preserving the composition; and    an aqueous liquid carrier component.    
     
     
         36 . The composition of  claim 35  wherein the solubility enhancing component comprises a carboxymethylcellulose.  
     
     
         37 . The composition of  claim 35  which is ophthalmically acceptable.  
     
     
         38 . A composition comprising: 
 a therapeutically active component in an amount effective to provide a desired therapeutic benefit to a patient to whom the composition is administered;    an oxy-chloro component in an effective amount to at least aid in preserving the composition; and    a liquid carrier component, wherein the composition is substantially free of cyclodextrins.    
     
     
         39 . The composition of  claim 38  wherein the therapeutically active component is selected from the group consisting of antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, derivatives thereof and mixtures thereof.  
     
     
         40 . The composition of  claim 38  wherein the therapeutically active component is selected from the group consisting of adrenergic agonists and mixtures thereof.  
     
     
         41 . The composition of  claim 38  wherein the therapeutically active component is selected from the group consisting of alpha-2-adrenergic agonists and mixtures thereof.  
     
     
         42 . The composition of  claim 38  wherein the therapeutically active component selected from the group consisting of imino-imidazolines, imidazolines, imidazoles, azepines, thiazines, oxazolines, guanidines, catecholamines, derivatives thereof and mixtures thereof.  
     
     
         43 . The composition of  claim 38  wherein the therapeutically active component includes a quinoxaline component.  
     
     
         44 . The composition of  claim 43  wherein the quinoxaline component is selected from the group consisting of quinoxaline, derivatives thereof, and mixtures thereof.  
     
     
         45 . The composition of  claim 43  wherein the quinoxaline component is selected from the group consisting of quinoxaline, (2-imidozolin-2-ylamino) quinoxaline, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, and tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, derivatives thereof and mixtures thereof.  
     
     
         46 . The composition of  claim 38  wherein the therapeutically active component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline.  
     
     
         47 . The composition of  claim 38 , which further includes a solubility enhancing component, other than a cyclodextrin, in an amount effective to increase the solubility of the therapeutically active component in the composition relative to the solubility of an identical therapeutically active component in a similar composition without the solubility enhancing component.  
     
     
         48 . The composition of  claim 47  wherein the solubility enhancing component comprises a polyanionic component.  
     
     
         49 . The composition of  claim 38  wherein the oxy-chloro component is selected from the group consisting of hypochlorite components, perchlorate components, chlorite components and mixtures thereof.  
     
     
         50 . The composition of  claim 38  wherein the oxy-chloro component comprises a chlorite component.  
     
     
         51 . The composition of  claim 38  wherein the oxy-chloro component comprises stabilized chlorine dioxide.  
     
     
         52 . The composition of  claim 38  which is ophthalmically acceptable.