Compounds, formulations, and methods for treating or preventing rosacea

Abstract

In methods, compounds, and topical formulations for treatment of rosacea incorporating compounds represented by the formulas below: wherein each of R 1 , R 2 , and R 3 is independently hydrogen, hologen, alkyl, or alkoxy; each of R 4 and R 5 is independently hydrogen, alkyl, or alkoxy; and each of R 6 and R 7 is independently hydrogen, nitro, alkyl, or alkoxy; wherein each of A 1 , A 3 , and A 4 is independently hydrogen or alkyl; and A 2 is independently hydrogen or hydroxy; and wherein each of B 1 , B 2 , and B 3 is independently hydrogen, hydroxy, or alkoxy; and each of B 4 and B 5 is independently hydrogen or alkyl, applying such compounds topically as sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions to treat rosacea and its symptoms.

1 . (canceled)  
     
     
         2 . (canceled)  
     
     
         3 . (canceled)  
     
     
         4 . (canceled)  
     
     
         5 . (canceled)  
     
     
         6 . (canceled)  
     
     
         7 . (canceled)  
     
     
         8 . (canceled)  
     
     
         9 . (canceled)  
     
     
         10 . (canceled)  
     
     
         11 . (canceled)  
     
     
         12 . (canceled)  
     
     
         13 . (canceled)  
     
     
         14 . The topical composition according to  claim 167 , wherein the pharmaceutically acceptable carrier is an aqueous gel comprising water, and a water-gelling amount of a pharmaceutically acceptable gelling agent selected from the group including carbomers, glycerine polyacrylate, and mixtures thereof, the topical composition having a physiologically acceptable pH.  
     
     
         15 . The topical composition according to  claim 14 , wherein the brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         16 . The topical composition according to  claim 14 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         17 . The topical composition according to  claim 14 , further comprising a preservative.  
     
     
         18 . The topical composition according to  claim 14 , further comprising a local anesthetic.  
     
     
         19 . The topical composition according to  claim 14 , further comprising a skin humectant.  
     
     
         20 . A package for a topical composition suitable for treating or preventing the symptoms of rosacea comprising brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof and a pharmaceutically acceptable carrier, comprising a container and instructions for use of the topical composition.  
     
     
         21 . The topical composition according to  claim 167 , wherein the pharmaceutically acceptable carrier is at least one of a cream and an ointment, comprising stearic acid, stearyl alcohol, cetyl alcohol, glycerin, and water, the topical composition having a physiologically acceptable pH.  
     
     
         22 . The topical composition according to  claim 21 , wherein the brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         23 . The topical composition according to  claim 21 , wherein the pH value of the composition in the range of about 5 to 8.  
     
     
         24 . The topical composition according to  claim 21 , further comprising a preservative.  
     
     
         25 . The topical composition according to  claim 21 , further comprising a local anesthetic.  
     
     
         26 . The topical composition according to  claim 21 , further comprising a skin humectant.  
     
     
         27 . The topical composition according to  claim 166 , wherein the brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is provided in a concentration sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient to which it is applied.  
     
     
         28 . The topical composition according to  claim 166 , wherein the composition acts locally in the skin of the patient.  
     
     
         29 . A method of treating or preventing rosacea and the symptoms associated therewith, comprising topically administering to the skin of a patient in need of such treatment or prevention a composition comprising: 
 a therapeutically effective amount of at least one of an a adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof; and    a pharmaceutically acceptable carrier.    
     
     
         30 . The method according to  claim 29 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is selected from the group including the compounds shown below:  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently hydrogen, halogen, alkyl, or alkoxy; each of R 4  and R 5  is independently hydrogen, alkyl, or alkoxy; and each of R 6  and R 7  is independently hydrogen, nitro, alkyl, or alkoxy;  
         wherein each of A 1 , A 3 , and A 4  is independently hydrogen or alkyl; and A 2  is independently hydrogen or hydroxy; and  
         wherein each of B 1 , B 2 , and B 3  is independently hydrogen, hydroxy, or alkoxy; and each of B 4  and B 5  is independently hydrogen or alkyl.  
       
     
     
         31 . The method according to  claim 30 , wherein the compounds are selected from the group including brimonidine, naphazoline, tetrahydrozaline, oxymetazoline, xylometazoline, epinephrine, nerepinephrine, phenylephrine, and methoxamine.  
     
     
         32 . The method according to  claim 29 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is a reversible α adrenergic receptor agonist or a pharmaceutically acceptable salt thereof or a prodrug thereof or an active metabolite thereof or a derivative thereof or an analog thereof.  
     
     
         33 . The method according to  claim 29 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         34 . The method according to  claim 29 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         35 . The method according to  claim 29 , wherein the composition acts locally in the skin of the patient.  
     
     
         36 . A topical composition intended for treating or preventing the symptoms of rosacea, comprising: 
 at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof, and    a pharmaceutically acceptable carrier.    
     
     
         37 . The topical composition according to  claim 36 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         38 . The topical composition according to  claim 36 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is selected from the group including the compounds shown below:  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently hydrogen, halogen, alkyl, or alkoxy; each of R 4  and R 5  is independently hydrogen, alkyl, or alkoxy; and each of R 6  and R 7  is independently hydrogen, nitro, alkyl, or alkoxy;  
         wherein each of A 1 , A 3 , and A 4  is independently hydrogen or alkyl; and A 2  is independently hydrogen or hydroxy; and  
         wherein each of B 1 , B 2 , and B 3  is independently hydrogen, hydroxy, or alkoxy; and each of B 4  and B 5  is independently hydrogen or alkyl.  
       
     
     
         39 . The topical composition according to  claim 36 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is selected from the group including brimonidine, naphazoline, tetrahydrozoline, oxymetazoline, xylometazoline, epinephrine, norepinephrine, phenylephrine, and methoxamine.  
     
     
         40 . The topical composition according to  claim 36 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         41 . The topical composition according to  claim 36 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         42 . The topical composition according to  claim 37 , wherein the pharmaceutically acceptable carrier is an aqueous gel comprising water, and a water-gelling amount of a pharmaceutically acceptable gelling agent selected from the group including carbomers, glycerine polyacrylate, and mixtures thereof, the topical composition having a physiologically acceptable pH.  
     
     
         43 . The topical composition according to  claim 42 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         44 . The topical composition according to  claim 42 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         45 . The topical composition according to  claim 42 , further comprising a preservative.  
     
     
         46 . The topical composition according to  claim 42 , further comprising a local anesthetic.  
     
     
         47 . The topical composition according to  claim 42 , further comprising a skin humectant.  
     
     
         48 . A package for a topical composition suitable for treating or preventing the symptoms of rosacea comprising at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof and a pharmaceutically acceptable carrier, comprising a container and instructions for use of the topical composition.  
     
     
         49 . The topical composition according to  claim 37 , wherein the pharmaceutically acceptable carrier is at least one of a cream and an ointment comprising stearic acid, stearyl alcohol, cetyl alcohol, glycerin, and water, the topical composition having a physiologically acceptable pH.  
     
     
         50 . The topical composition according to  claim 49 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         51 . The topical composition according to  claim 49 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         52 . The topical composition according to  claim 49 , further comprising a preservative.  
     
     
         53 . The topical composition according to  claim 49 , further comprising a local anesthetic.  
     
     
         54 . The topical composition according to  claim 49 , further comprising a skin humectant.  
     
     
         55 . The topical composition according to  claim 36 , wherein the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is provided in a concentration sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient to which it is applied.  
     
     
         56 . The topical composition according to  claim 36 , wherein the composition acts locally in the skin of the patient.  
     
     
         57 . A method of reducing or eliminating redness associated with an inflammatory skin disorder comprising topically administering a pharmaceutical composition comprising an effective amount of an alpha adrenergic receptor agonist to the site of the redness on the skin of a patient.  
     
     
         58 . The method of  claim 57 , wherein the disorder is an inflammatory facial skin disorder.  
     
     
         59 . The method of  claim 58 , wherein the disorder is rosacea.  
     
     
         60 . The method of  claim 47 , wherein the alpha adrenergic receptor agonist is an α 2  adrenergic receptor agonist.  
     
     
         61 . The method of  claim 58 , wherein the alpha adrenergic receptor agonist is an α 2  adrenergic receptor agonist.  
     
     
         62 . The method of  claim 59 , wherein the alpha adrenergic receptor agonist is an α 2  adrenergic receptor agonist.  
     
     
         63 . The method of  claim 57 , wherein the α 2  adrenergic receptor agonist is a compound of the formula:  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently hydrogen, halogen, alkyl, or alkoxy; each of R 4  and R 5  is independently hydrogen, alkyl, or alkoxy; and each of R 6  and R 7  is independently hydrogen, nitro, alkyl, or alkoxy;  
         or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
       
     
     
         64 . The method of  claim 58 , wherein the α 2  adrenergic receptor agonist is a compound of the formula:  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently hydrogen, halogen, alkyl, or alkoxy; each of R 4  and R 5  is independently hydrogen, alkyl, or alkoxy; and each of R 6  and R 7  is independently hydrogen, nitro, alkyl, or alkoxy;  
         or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
       
     
     
         65 . The method of  claim 59 , wherein the α 2  adrenergic receptor agonist is a compound of the formula:  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently hydrogen, halogen, alkyl, or alkoxy; each of R 4  and R 5  is independently hydrogen, alkyl, or alkoxy; and each of R 6  and R 7  is independently hydrogen, nitro, alkyl, or alkoxy;  
         or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
       
     
     
         66 . The method of  claim 57 , wherein the α 2  adrenergic receptor agonist is brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
     
     
         67 . The method of  claim 58 , wherein the α 2  adrenergic receptor agonist is brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
     
     
         68 . The method of  claim 59 , wherein the α 2  adrenergic receptor agonist is brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
     
     
         69 . The method of  claim 57 , wherein the alpha adrenergic receptor agonist is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         70 . The method of  claim 57 , wherein the composition acts locally on the skin of the patient.  
     
     
         71 . The method of  claim 57 , wherein the alpha adrenergic receptor agonist is an α 1  adrenergic receptor agonist.  
     
     
         72 . The method of  claim 58 , wherein the alpha adrenergic receptor agonist is an α 1  adrenergic receptor agonist.  
     
     
         73 . The method of  claim 59 , wherein the alpha adrenergic agonist is an α 1  adrenergic receptor agonist.  
     
     
         74 . The method of  claim 71 , wherein the α 1  adrenergic receptor agonist is a compound selected from the following  
       
         
           
           
               
               
           
         
         wherein each of A 1 , A 3 , and A 4  is independently hydrogen or alkyl; and A 2  is independently hydrogen or hydroxy; and  
         wherein each of B 1 , B 2 , and B 3  is independently hydrogen, hydroxy, or alkoxy; and each of B 4  and B 5  is independently hydrogen or alkyl;  
         or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
       
     
     
         75 . The method of  claim 72 , wherein the α 1  adrenergic receptor agonist is a compound selected from the following  
       
         
           
           
               
               
           
         
         wherein each of A 1 , A 3 , and A 4  is independently hydrogen or alkyl; and A 2  is independently hydrogen or hydroxy; and  
         wherein each of B 1 , B 2 , and B 3  is independently hydrogen, hydroxy, or alkoxy; and each of B 4  and B 5  is independently hydrogen or alkyl;  
         or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
       
     
     
         76 . The method of  claim 73 , wherein the α 1  adrenergic receptor agonist is a compound selected from the following  
       
         
           
           
               
               
           
         
         wherein each of A 1 , A 3 , and A 4  is independently hydrogen or alkyl; and A 2  is independently hydrogen or hydroxy; and  
         wherein each of B 1 , B 2 , and B 3  is independently hydrogen, hydroxy, or alkoxy; and each of B 4  and B 5  is independently hydrogen or alkyl;  
         or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
       
     
     
         77 . The method of  claim 71 , wherein the α 1  adrenergic receptor agonist is naphazoline, tetrahydrozaline, oxymetazoline, xylometazoline, epinephrine, nerepinephrine, phenylephrine, or methoxamine, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
     
     
         78 . The method of  claim 72 , wherein the α 1  adrenergic receptor agonist is naphazoline, tetrahydrozaline, oxymetazoline, xylometazoline, epinephrine, nerepinephrine, phenylephrine, or methoxamine, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
     
     
         79 . The method of  claim 73 , wherein the α 1  adrenergic receptor agonist is naphazoline, tetrahydrozaline, oxymetazoline, xylometazoline, epinephrine, nerepinephrine, phenylephrine, or methoxamine, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof.  
     
     
         80 . A method of preventing or reducing the severity of a stress-associated condition in a subject, comprising administering to said subject an effective amount of brimonidine or a pharmaceutically acceptable salt, ester, amide, sterioisomer or racemic mixture thereof, wherein said stress-associated condition is a dermatogical condition.  
     
     
         81 . The method of  claim 80 , wherein said effective amount is administered topically.  
     
     
         82 . The method of  claim 81 , wherein the effective amount acts locally in the skin of the patient.  
     
     
         83 . A method for treating at least one condition selected from the group consisting of rosacea, acne, skin redness or other conditions characterized by discreet erythema of the skin in a subject in need of such treatment, comprising administering topically to said subject, for such period of time as is required to elicit the desired therapeutic response, a therapeutically or cosmetically effective amount of at least one alpha-1 adrenoreceptor agonist.  
     
     
         84 . The method according to  claim 83 , wherein said at least one alpha-1 adrenoreceptor agonist is topically applied to the skin.  
     
     
         85 . The method according to  claim 83 , wherein said at least alpha-1 adrenoreceptor agonist comprises oxymetazoline.  
     
     
         86 . The method according to  claim 83 , wherein said at least alpha-1 adrenoreceptor agonist comprises tetrahydrozoline.  
     
     
         87 . The method according to  claim 83 , wherein said at least alpha-1 adrenoreceptor agonist comprises nephazoline.  
     
     
         88 . The method according to  claim 83 , wherein said at least alpha-1 adrenoreceptor agonist comprises xylometazoline.  
     
     
         89 . The method according to  claim 83 , wherein the treated condition comprises rosacea.  
     
     
         90 . The method according to  claim 83 , wherein the treated condition comprises acne.  
     
     
         91 . The method according to  claim 83 , wherein the treated condition comprises other discreet erythemas.  
     
     
         92 . A composition for topical administration to the skin for treating rosacea comprising oxymetazoline HCl and an inert carrier.  
     
     
         93 . The method according to  claim 83 , wherein at least one alpha-1 adrenoreceptor agonist is co-administered with a therapeutically effective amount of at least one other active agent selected from the group consisting of antibacterial agents, antiparasitic agents, antifungal agents, anti-inflammatory agents, antihistamines, anti-pruriginous agents, anesthetics, antiviral agents, keratolytic agents, anti free-radical agents, antiseborrheic agents, antidandruff agents, antiacne agents, sunscreens and sun blocking agents, and active agents which modify at least one of cutaneous differentiation, proliferation, and pigmentation.  
     
     
         94 . The method according to  claim 83 , wherein said at least one alpha-1 adrenoreceptor agonist is administered in a pharmacologically or cosmetically acceptable form selected from the group consisting of solutions, gels, lotions creams, ointments, foams, emulsions, microemulsions, milks, serums, aerosols, sprays, dispersions, microcapsules, vesicles and microparticles thereof.  
     
     
         95 . The method according to  claim 83 , wherein said at least one alpha-1 adrenoreceptor agonist is administered in a pharmacologically or cosmetically acceptable form selected from the group consisting of soaps and cleansing bars.  
     
     
         96 . The method according to  claim 83 , wherein said skin redness, rosacea, or discreet erythema is elicited by at least one factor selected from the group consisting of intake of food, of hot or alcoholic drinks, temperature variations, heat, exposure to ultraviolet or infrared radiation, exposure to low relative humidity, exposure of the skin to strong winds or currents of air, exposure of the skin to surfactants, irritants, irritant dermatological topical agents, or cosmetics.  
     
     
         97 . A method of treating cutaneous flushing in humans caused by abnormal, endogenously-induced vasomotor instability comprising administering, to said human via topical dermatological application, a composition comprising at least one selective α 2  adrenergic receptor agonist admixed with a dermatologically acceptable carrier, in an amount effective to reduce, inhibit, reverse or prevent cutaneous facial flushing.  
     
     
         98 . The method of  claim 97 , wherein the composition contains at least one (2-imidazolin-2-ylamino) quinoxaline derivative.  
     
     
         99 . The method of  claim 97 , wherein the cutaneous flushing is facial flushing and the flushing re action is caused by acne rosacea.  
     
     
         100 . The method of  claim 98 , wherein the cutaneous flushing is facial flushing and the flushing reaction is caused by acne rosacea.  
     
     
         101 . The method of  claim 97 , wherein the cutaneous flushing is facial flushing and the flushing reaction is caused by menopause-associated hot flashes.  
     
     
         102 . The method of  claim 98 , wherein the cutaneous flushing is facial flushing and the flushing reaction is caused by menopause-associated hot flashes.  
     
     
         103 . The method of  claim 97 , wherein the cutaneous flushing is facial flushing and the flushing reaction is the result of hot flashes following orchiectomy.  
     
     
         104 . The method of  claim 98 , wherein the cutaneous flushing is facial flushing and the flushing reaction is the result of hot flashes following orchiectomy.  
     
     
         105 . The method of  claim 97 , wherein the cutaneous flushing is facial flushing and the flushing reaction is caused by ingestion of a substance capable of inducing cutaneous facial flushing selected from the group consisting of alcohol, chocolate, spice, flavor-enhancing additives and mono-sodium glutamate.  
     
     
         106 . The method of  claim 98 , wherein the cutaneous flushing is facial flushing and the flushing reaction is caused by ingestion of a substance capable of inducing cutaneous facial flushing selected from the group consisting of alcohol, chocolate, spice, flavor-enhancing additives and mono-sodium glutamate.  
     
     
         107 . The method of  claim 98 , wherein the composition further comprises an agent, or combination of agents, selected from the group consisting of antibacterial agents, anthelmintic agents, antioxidant agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, antiangiogenic agents, and derivatives of retinoic acid.  
     
     
         108 . The method of  claim 97 , wherein the composition further comprises an agent, or combination of agents, selected from the group consisting of antibacterial agents, anthelmintic agents, antioxidant agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, antiangiogenic agents, and derivatives of retinoic acid.  
     
     
         109 . The method according to  claim 98 , wherein said at least one (2-imidazolin-2-ylamino)quinoxaline derivative is brimonidine tartrate.  
     
     
         110 . The method of  claim 98 , wherein the composition further comprises: aloe; compounds that act as sunscreens; or a combination of aloe and compounds that act as sunscreens.  
     
     
         111 . The method of  claim 98 , wherein the composition further comprises a preservative.  
     
     
         112 . The method of  claim 98 , wherein the composition further comprises a halogen.  
     
     
         113 . The method of  claim 98 , wherein the (2-imidazolin-2-ylamino)quinoxaline derivative is combined with an acidic group other than tartrate.  
     
     
         114 . The method of  claim 97 , wherein the composition further comprises an agent, or combination of agents, selected from the group consisting of antibacterial agents, anthelmintic agents, antioxidant agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, antiangiogenic agents, and derivatives of retinoic acid.  
     
     
         115 . The method of  claim 114 , wherein the composition further comprises: aloe; compounds that act as sunscreens; or a combination of aloe and compounds that act as sunscreens.  
     
     
         116 . The method of  claim 115 , wherein the composition further comprises a preservative.  
     
     
         117 . The method of  claim 116 , wherein the composition further comprises a halogen.  
     
     
         118 . A composition comprising at least one selective α 2  adrenergic receptor agonist admixed with a dermatologically acceptable carrier and one or more agent selected from the group consisting of antibacterial agents, anthelmintic agents, antioxidant agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, antiangiogenic agents, derivatives of retinoic acid, aloe, compounds that act as sunscreens, a combination of aloe and compounds that act as sunscreens, preservatives, halogens and combinations of said agents.  
     
     
         119 . The composition according to  claim 118 , wherein the selective α 2  adrenergic receptor agonist is a (2-imidazolin-2-ylamino)quinoxaline derivative.  
     
     
         120 . The composition according to  claim 119  wherein said (2-imidazolin-2-ylamino)quinoxaline derivative is brimonidine tartrate.  
     
     
         121 . The composition according to  claim 119 , wherein said at least one selective adrenergic receptor agonist is selected from the group consisting of guanabenz, guanfacine, alpha-methyl DOPA (methydopamine), amphetamine, methylphenidate, lofexidine, moxonidine, dexmedetomidine, mivazerol, (2-imidazolin-2-ylamino)quinoxaline derivatives, brimonidine, and combinations thereof.  
     
     
         122 . A method for the treatment of flushing in an individual comprising the administration of a composition comprising at least one selective α 2  adrenergic receptor agonist and a carrier in an amount sufficient to prevent, reduce, ameliorate, or inhibit facial flushing.  
     
     
         123 . The method of  claim 120 , wherein said at least one selective adrenergic receptor agonist is selected from the group consisting of guanabenz, guanfacine, alpha-methyl DOPA (methydopamine), amphetamine, methylphenidate, lofexidine, moxonidine, dexmedetomidine, mivazerol, (2-imidazolin-2-ylamino) quinoxaline derivatives, brimonidine, and combinations thereof.  
     
     
         124 . The method of  claim 97 , wherein said at least one selective adrenergic receptor agonist is selected from the group consisting of guanabenz, guanfacine, alpha-methyl DOPA (methydopamine), amphetamine, methylphenidate, lofexidine, moxonidine, dexmedetomidine, mivazerol, (2-imidazolin-2-ylamino) quinoxaline derivatives, brimonidine, and combinations thereof.  
     
     
         125 . A method of reducing or eliminating redness associated with rosacea comprising topically administering an effective amount of nephazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof to the site of the redness on the skin of a patient.  
     
     
         126 . The method of  claim 125 , wherein the nephazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         127 . The method of  claim 125 , wherein the nephazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof acts locally on the skin of the patient.  
     
     
         128 . A method of reducing or eliminating redness associated with rosacea comprising topically administering an effective amount of oxymetazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof to the site of the redness on the skin of a patient.  
     
     
         129 . The method of  claim 128 , wherein the oxymetazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         130 . The method of  claim 128 , wherein the oxymetazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof acts locally on the skin of the patient.  
     
     
         131 . A method of reducing or eliminating redness associated with rosacea comprising topically administering an effective amount of xylometazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof to the site of the redness on the skin of a patient.  
     
     
         132 . The method of  claim 131 , wherein the xylometazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         133 . The method of  claim 131 , wherein the xylometazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof acts locally on the skin of the patient.  
     
     
         134 . A topical composition intended for treating or preventing the redness associated with rosacea comprising: 
 nephazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof; and    a pharmaceutically acceptable carrier.    
     
     
         135 . The topical composition according to  claim 134 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         136 . The topical composition according to  claim 134 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         137 . A topical composition intended for treating or preventing the redness associated with rosacea comprising: 
 oxymetazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof; and    a pharmaceutically acceptable carrier.    
     
     
         138 . The topical composition according to  claim 137 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         139 . The topical composition according to  claim 137 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         140 . A topical composition intended for treating or preventing the redness associated with rosacea comprising: 
 xylometazoline or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof; and    a pharmaceutically acceptable carrier.    
     
     
         141 . The topical composition according to  claim 140 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         142 . The topical composition according to  claim 140 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         143 . A topical composition intended for treating or preventing the redness associated with rosacea comprising: 
 at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof; and    a pharmaceutically acceptable carrier.    
     
     
         144 . The topical composition according to  claim 134 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         145 . The topical composition according to  claim 144 , wherein the pharmaceutically acceptable carrier is an aqueous gel comprising water, and a water-gelling amount of a pharmaceutically acceptable gelling agent selected from the group including carbomers, glycerine polyacrylate, and mixtures thereof, the topical composition having a physiologically acceptable pH.  
     
     
         146 . The topical composition according to  claim 145 , wherein the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         147 . The topical composition according to  claim 145 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         148 . The topical composition according to  claim 145 , further comprising a preservative.  
     
     
         149 . The topical composition according to  claim 145 , further comprising a local anesthetic.  
     
     
         150 . The topical composition according to  claim 145 , further comprising a skin humectant.  
     
     
         151 . A package for a topical composition suitable for treating or preventing the symptoms of rosacea comprising at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof, and a pharmaceutically acceptable carrier, comprising a container and instructions for use of the topical composition.  
     
     
         152 . The topical composition according to  claim 144 , wherein the pharmaceutically acceptable carrier is at least one of a cream and an ointments comprising stearic acid, stearyl alcohol, cetyl alcohol, glycerin, and water, the topical composition having a physiologically acceptable pH.  
     
     
         153 . The topical composition according to  claim 152 , wherein the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof, is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         154 . The topical composition according to  claim 152 , wherein the pH value of the composition in the range of about 5 to 8.  
     
     
         155 . The topical composition according to  claim 152 , further comprising a preservative.  
     
     
         156 . The topical composition according to  claim 152 , further comprising a local anesthetic.  
     
     
         157 . The topical composition according to  claim 152 , further comprising a skin humectant.  
     
     
         158 . The topical composition according to  claim 143 , wherein the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof, is provided in a concentration sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient to which it is applied.  
     
     
         159 . The topical composition according to  claim 143 , wherein the composition acts locally in the skin of the patient.  
     
     
         160 . A method of reducing or eliminating redness associated with rosacea comprising topically administering a pharmaceutical composition comprising an effective amount of at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof, to the site of the redness on the skin of a patient.  
     
     
         161 . The method of  claim 160 , wherein the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof, is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         162 . The method of  claim 160 , wherein the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof, acts locally on the skin of the patient.  
     
     
         163 . A topical dermal composition intended for treating or preventing the redness associated with rosacea comprising: 
 at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof; and    a pharmaceutically acceptable carrier.    
     
     
         164 . The topical composition according to  claim 163 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         165 . The topical composition according to  claim 163 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         166 . A topical dermal composition intended for treating or preventing the redness associated with rosacea comprising: 
 brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof; and    a pharmaceutically acceptable carrier.    
     
     
         167 . The topical composition according to  claim 166 , wherein the pharmaceutically acceptable carrier is selected from the group including sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         168 . The topical composition according to  claim 166 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         169 . A method of reducing or eliminating redness associated with rosacea comprising topically administering a pharmaceutical composition comprising an effective amount of brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof to the site of the redness on the skin of a patient.  
     
     
         170 . The method of  claim 169 , wherein the brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         171 . The method of  claim 169 , wherein the brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof acts locally on the skin of the patient.  
     
     
         172 . The topical composition according to  claim 14 , wherein the topical composition comprises a formulation containing a suspension of brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof such that the solubilized portion of the drug is held constant at 100% saturation solubility over the shelf life of the formulation and during application.  
     
     
         173 . The topical composition according to  claim 21 , wherein the topical composition comprises a formulation containing a suspension of brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof such that the solubilized portion of the drug is held constant at 100% saturation solubility over the shelf life of the formulation and during application.  
     
     
         174 . The topical composition according to  claim 36 , wherein the topical composition comprises a formulation containing a suspension of the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof such that the solubilized portion of the drug is held constant at 100% saturation solubility over the shelf life of the formulation and during application.  
     
     
         175 . The topical composition according to  claim 42 , wherein the topical composition comprises a formulation containing a suspension of the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof such that the solubilized portion of the drug is held constant at 100% saturation solubility over the shelf life of the formulation and during application.  
     
     
         176 . The topical composition according to  claim 49 , wherein the topical composition comprises a formulation containing a suspension of the at least one of an α adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof such that the solubilized portion of the drug is held constant at 100% saturation solubility over the shelf life of the formulation and during application.  
     
     
         177 . The topical composition according to  claim 145 , wherein the topical composition comprises a formulation containing a suspension of the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof such that the solubilized portion of the drug is held constant at 100% saturation solubility over the shelf life of the formulation and during application.  
     
     
         178 . The topical composition according to  claim 152 , wherein the topical composition comprises a formulation containing a suspension of the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof such that the solubilized portion of the drug is held constant at 100% saturation solubility over the shelf life of the formulation and during application.  
     
     
         179 . The topical composition according to  claim 14 , wherein the brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is present in a concentration in the range of from about 20% to about 200% of the maximum equilibrium solubility of the drug in a delivery vehicle.  
     
     
         180 . The topical composition according to  claim 21 , wherein the brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is present in a concentration in the range of from about 20% to about 200% of the maximum equilibrium solubility of the drug in a delivery vehicle.  
     
     
         181 . The topical composition according to  claim 36 , wherein the at least one of an a adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is present in a concentration in the range of from about 20% to about 200% of the maximum equilibrium solubility of the drug in a delivery vehicle.  
     
     
         182 . The topical composition according to  claim 42 , wherein the at least one of an a adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is present in a concentration in the range of from about 20% to about 200% of the maximum equilibrium solubility of the drug in a delivery vehicle.  
     
     
         183 . The topical composition according to  claim 49 , wherein the at least one of an a adrenergic receptor agonist, a pharmaceutically acceptable salt thereof, a prodrug thereof, an active metabolite thereof, a derivative thereof, and an analog thereof is present in a concentration in the range of from about 20% to about 200% of the maximum equilibrium solubility of the drug in a delivery vehicle.  
     
     
         184 . The topical composition according to  claim 145 , wherein the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof is present in a concentration in the range of from about 20% to about 200% of the maximum equilibrium solubility of the drug in a delivery vehicle.  
     
     
         185 . The topical composition according to  claim 152 , wherein the at least one of nephazoline, oxymetazoline, and xylometazoline, or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof, is present in a concentration in the range of from about 20% to about 200% of the maximum equilibrium solubility of the drug in a delivery vehicle.  
     
     
         186 . A method of treating or preventing redness associated with rosacea comprising topically administering a pharmaceutical composition comprising an effective amount of brimonidine or a pharmaceutically acceptable salt or prodrug or active metabolite or derivative or analog thereof to a site on the skin of a patient.