Compositions containing alpha-2-adrenergic agonist components

Abstract

Compositions useful for improving effectiveness of alpha-2-adrenergic agonist components include carrier components, alpha-2-adrenergic agonist components, solubility enhancing components which aid in solubilizing the alpha-2-adrenergic agonist components. In one embodiment, the alpha-2-adrenergic agonist components include alpha-2-adrenergic agonists. In another embodiment, the solubility enhancing components include carboxymethylcellulose.

What is claimed is:  
     
         1 . A composition comprising: 
 an alpha-2-adrenergic agonist component 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 alpha-2-adrenergic agonist component in the composition relative to the solubility of an identical alpha-2-adrenergic agonist component in a similar composition without the solubility enhancing component; and    a liquid carrier component.    
     
     
         2 . The composition of  claim 1  wherein the alpha-2-adrenergic agonist component is selected from the group consisting of imino-imidazolines, imidazolines, imidazoles, azepines, thiazines, oxazolines, guanidines, catecholamines, derivatives thereof and mixtures thereof.  
     
     
         3 . The composition of  claim 1  wherein the therapeutically active component includes a quinoxaline component.  
     
     
         4 . The composition of  claim 3  wherein the quinoxaline component is selected from the group consisting of quinoxaline, derivatives thereof, and mixtures thereof.  
     
     
         5 . The composition of  claim 3  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.  
     
     
         6 . The composition of  claim 1  wherein the therapeutically active component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline.  
     
     
         7 . The composition of  claim 1  wherein the alpha-2-adrenergic agonist component is substantially unionized.  
     
     
         8 . The composition of  claim 1  wherein the alpha-2-adrenergic agonist component is substantially unionized in a biological environment to which the composition is administered.  
     
     
         9 . The composition of  claim 1  wherein the alpha-2-adrenergic agonist component has increased diffusion through a lipid membrane relative to an identical alpha-2-adrenergic agonist component in a similar composition without the solubility enhancing component.  
     
     
         10 . The composition of  claim 1  wherein the alpha-2-adrenergic agonist component is selected from the group consisting of agonists of alpha-2A-adrenergic receptors, agonists of alpha-2B-adrenergic receptors, agonists of alpha-2D-adrenergic receptors and mixtures thereof.  
     
     
         11 . The composition of  claim 1  wherein the solubility enhancing component is effective to increase the solubility in a biological environment of the alpha-2-adrenergic agonist component relative to the solubility in a biological environment of an identical alpha-2-adrenergic agonist 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 component 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 derivatives 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 liquid carrier component is an aqueous liquid carrier component.  
     
     
         20 . The composition of  claim 1  which is a solution.  
     
     
         21 . The composition of  claim 1  which has a pH of about 7 or greater.  
     
     
         22 . The composition of  claim 1  which has a pH in a range of about 7 to about 9.  
     
     
         23 . The composition of  claim 1  which is ophthalmically acceptable.  
     
     
         24 . A composition comprising: 
 an alpha-2-adrenergic agonist component 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 alpha-2-adrenergic agonist component; and    an aqueous liquid carrier component.    
     
     
         25 . The composition of  claim 24  wherein the alpha-2-adrenergic agonist component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline.  
     
     
         26 . The composition of  claim 24  wherein the anionic cellulose derivative comprises carboxymethylcellulose.  
     
     
         27 . The composition of  claim 24  wherein the anionic cellulose derivative is present in an amount in a range of about 0.2% (w/v) to about 0.6% (w/v).  
     
     
         28 . 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; and    an aqueous liquid carrier component.    
     
     
         29 . The composition of  claim 28  wherein the solubility enhancing component comprises a carboxymethylcellulose.  
     
     
         30 . The composition of  claim 28  which is ophthalmically acceptable.  
     
     
         31 . A complex comprising monomer units derived from one or more quinoxaline components.  
     
     
         32 . The complex of  claim 31  wherein the quinoxaline component is selected from the group consisting of a quinoxaline, a (2-imidozolin-2-ylamino) quinoxaline, a 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline, a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline, derivatives thereof and mixtures thereof.  
     
     
         33 . The complex of  claim 31  wherein the quinoxaline component is a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline.  
     
     
         34 . An oligomer comprising monomer units derived from a quinoxaline component.  
     
     
         35 . The oligomer of  claim 34  wherein the quinoxaline component is selected from the group consisting of a quinoxaline, a (2-imidozolin-2-ylamino)quinoxaline, a 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline, a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline, derivatives thereof and mixtures thereof.  
     
     
         36 . The oligomer of  claim 34  wherein the quinoxaline component is a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino)quinoxaline.  
     
     
         37 . The oligomer of  claim 34  which is a dimer.  
     
     
         38 . The oligomer of  claim 35  which is a dimer.  
     
     
         39 . The oligomer of  claim 36  which is a dimer.  
     
     
         40 . A composition comprising: 
 an alpha-2-adrenergic agonist component in an amount effective to provide a 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.    
     
     
         41 . The composition of  claim 40  wherein the alpha-2-adrenergic agonist component is selected from the group consisting of imino-imidazolines, imidazolines, imidazoles, azepines, thiazines, oxazolines, guanidines, catecholamines, derivatives thereof and mixtures thereof.  
     
     
         42 . The composition of  claim 40  wherein the therapeutically active component includes a quinoxaline component.  
     
     
         43 . The composition of  claim 42  wherein the quinoxaline component is selected from the group consisting of quinoxaline, derivatives thereof, and mixtures thereof.  
     
     
         44 . The composition of  claim 40  which further includes a solubility enhancing component in an amount effective to increase the solubility of the alpha-2-adrenergic agonist component in the composition relative to the solubility of an identical alpha-2-adrenergic agonist component in a similar composition without the solubility enhancing component.  
     
     
         45 . The composition of  claim 44  wherein the solubility enhancing component is effective to increase the solubility in a biological environment of the alpha-2-adrenergic agonist component relative to the solubility in a biological environment of an identical alpha-2-adrenergic agonist component in a similar composition without the solubility enhancing component.  
     
     
         46 . The composition of  claim 44  wherein the solubility enhancing component comprises a polyanionic component.