Pharmaceutical formulation comprising an immune response modifier

Abstract

Pharmaceutical formulations comprising an immune response modifier (IRM) chosen from imidazoquinoline amines, imidazotetrahydroquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazolo-quinolineamines, oxazolo-quinolinamines, thiazolo-pyridinamines, oxazolo-pyridinamines, imidazonaphthyridine amines, tetrahydroimidazonaphthyridine amines, and thiazolonaphthyridine amines; a fatty acid; and a hydrophobic, aprotic component miscible with the fatty acid are useful for the treatment of dermal associated conditions. Novel topical formulations are provided. In one embodiment, the topical formulations are advantageous for treatment of actinic keratosis, postsurgical scars, basal cell carcinoma, atopic dermatitis, and warts.

What is claimed is:  
     
         1 . A pharmaceutical formulation comprising: 
 an immune response modifier (IRM) compound selected from imidazoquinoline amines, imidazotetrahydroquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazoloquinoline amines, oxazoloquinoline amines, thiazolopyridine amines, oxazolopyridine amines, imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, and thiazolonaphthyridine amines;    a fatty acid;    a hydrophobic, aprotic component miscible with the fatty acid and comprising a hydrocarbyl group of 7 or more carbon atoms; and    a hydrophilic viscosity enhancing agent selected from cellulose ethers and carbomers.    
     
     
         2 . The formulation according to  claim 1  wherein the formulation further comprises a preservative system and an emulsifier.  
     
     
         3 . The formulation according to  claim 1  wherein the hydrophobic, aprotic component has a hydrophilic lipophilic balance of less than 2.  
     
     
         4 . The formulation according to  claim 1  wherein the hydrophobic, aprotic component has a pKa greater than 14.2.  
     
     
         5 . The formulation according to  claim 1  wherein the ratio of the hydrophobic, aprotic component to the fatty acid is 0.025:1 to 600:1.  
     
     
         6 . The formulation according to claim I wherein the combined weight percent of the hydrophobic, aprotic component and the fatty acid is 2 to 50.  
     
     
         7 . The formulation according to  claim 1  wherein the fatty acid is isostearic acid.  
     
     
         8 . The formulation according to  claim 1  wherein the hydrophobic, aprotic component is selected from aprotic fatty acid esters, hydrocarbons of 8 or more carbon atoms, and waxes.  
     
     
         9 . The formulation according to  claim 8  wherein the aprotic fatty acid ester is isopropyl myristate, isopropyl palmitate, diisopropyl dimer dilinoleate, caprylic/capric triglyceride, cetyl esters wax, or a combination thereof.  
     
     
         10 . The formulation according to  claim 8  wherein the hydrocarbon of 8 or more carbon atoms is mineral oil or petrolatum.  
     
     
         11 . The formulation according to  claim 1  wherein the hydrophilic viscosity enhancing agent comprises a carbomer.  
     
     
         12 . The formulation according to  claim 2  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and propylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         13 . The formulation according to  claim 2  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and ethylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         14 . The formulation according to  claim 2  wherein the preservative system comprises iodopropynyl butylcarbamate.  
     
     
         15 . The formulation according to  claim 2  wherein the preservative system comprises iodopropynyl butylcarbamate and one or more of methylparaben, ethylparaben, propylparaben, or phenoxyethanol.  
     
     
         16 . The formulation according to  claim 2  wherein the preservative system comprises iodopropynyl butylcarbamate, methylparaben, and ethylparaben.  
     
     
         17 . The formulation according to  claim 2  wherein the preservative system comprises phenoxyethanol and one or both of methylparaben and ethylparaben.  
     
     
         18 . The formulation according to  claim 2  wherein the preservative system comprises a preservative enhancing solubilizer.  
     
     
         19 . The formulation according to  claim 18  wherein the preservative enhancing solubilizer comprises diethylene glycol monoethyl ether, propylene glycol or a combination thereof.  
     
     
         20 . The formulation of  claim 2  comprising: 
 (a) 0.001 to 5% w/w  
 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 N-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-N′-cyclohexylurea,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,8]naphthyridin-4-amine,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-methylthiazolo[4,5-c]quinolin-4-amine,  
 2-ethoxymethyl-1-phenylmethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-ethylthiazolo[4,5-c]quinolin-4-amine,  
 4-amino-2-butyl-α,α-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridine-1-ethanol,  
 1-{2-[3-(3-pyridyl)propoxy]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-[(R)-1-phenylethyl]-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 1-{2-[3-(1,3-thiazol-2-yl)propoxy]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-[2-(pyridin-4-ylmethoxy)ethyl]-1H-imidazo[4,5-c]quinolin-4-amine,  
 N-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]cyclohexanecarboxamide,  
 2-butyl-1-{2-[(1-methylethyl)sulfonyl]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}ethanesulfonamide,  
 N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}propanamide,  
 1-[2-(methylsulfonyl)ethyl]-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-ethyl-1-{4-[(1-methylethyl)sulfonyl]butyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-ethyl-1-[4-(ethylsulfonyl)butyl]-1H-imidazo[4,5-c]quinolin-4-amine,  
 N-{3-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclopentanecarboxamide,  
 1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine,  
 8,9,10,11-tetrahydropyrido[1′,2′:1,2]imidazo[4,5-c]quinolin-6-amine,  
 4-amino-α,α,2-trimethyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinoline-1-ethanol,  
 2-hydroxymethyl-1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 or a combination thereof; 
 (b) 0.05 to 40% w/w isostearic acid;  
 (c) 1 to 30% w/w hydrophobic, aprotic component;  
 (d) 0.5 to 10% w/w emulsifier;  
 (e) 0.01 to 30% w/w preservative system; and  
 (f) 0.1 to 10% carbomer.  
 
 
     
     
         21 . The formulation of  claim 20  comprising: 
 (a) 0.03 to 3% w/w 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, N-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-yl)butyl]-N′-cyclohexylurea, 2-butyl-1-{2-[(1-methylethyl)sulfonyl]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine, or a combination thereof;  
 (b) 3 to 25% w/w isostearic acid;  
 (c) 3 to 15% w/w hydrophobic, aprotic component;  
 (d) 0.75 to 3.5% w/w emulsifier;  
 (e) 0.1 to 25% w/w preservative system; and  
 (f) 0.5 to 5% w/w carbomer.  
 
     
     
         22 . A method of treating a dermal associated condition, the method comprising a step of: 
 applying to skin a formulation comprising an immune response modifier (IRM) selected from imidazoquinoline amines, imidazotetrahydroquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazoloquinoline amines, oxazoloquinoline amines, thiazolopyridine amines, oxazolopyridine amines, imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, and thiazolonaphthyridine amines; a fatty acid; a hydrophobic, aprotic component miscible with the fatty acid and comprising a hydrocarbyl group of 7 or more carbon atoms; and a hydrophilic viscosity enhancing agent selected from cellulose ethers and carbomers.    
     
     
         23 . The method according to  claim 22  wherein the ratio of the hydrophobic, aprotic component to the fatty acid is 0.025:1 to 600:1.  
     
     
         24 . The method according to  claim 22  wherein the combined weight percent of the hydrophobic, aprotic component and the fatty acid is 2 to 50.  
     
     
         25 . The method according to  claim 22  wherein the hydrophobic, aprotic component is selected from the group consisting of aprotic fatty acid esters, hydrocarbons of 8 or more carbon atoms, and waxes.  
     
     
         26 . The method according to  claim 25  wherein the aprotic fatty acid ester is isopropyl myristate, isopropyl palmitate, diisopropyl dimer dilinoleate, caprylic/capric triglyceride, cetyl esters wax, or combinations thereof.  
     
     
         27 . The method according to  claim 22  wherein the hydrophilic viscosity enhancing agent comprises a carbomer.  
     
     
         28 . The method according to  claim 22  wherein the topical formulation further comprises: 
 a preservative system; and  
 an emulsifier.  
 
     
     
         29 . The method according to  claim 22  wherein the IRM is 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, N-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-N′-cyclohexylurea, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine, 
 2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,8]naphthyridin-4-amine,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-methylthiazolo[4,5-c]quinolin-4-amine,  
 2-ethoxymethyl-1-phenylmethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-ethylthiazolo[4,5-c]quinolin-4-amine,  
 4-amino-2-butyl-α,α-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridine-1-ethanol,  
 1-{2-[3-(3-pyridyl)propoxy]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-[(R)-1-phenylethyl]-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 1-{2-[3-(1,3-thiazol-2-yl)propoxy]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-[2-(pyridin-4-ylmethoxy)ethyl]-1H-imidazo[4,5-c]quinolin-4-amine,  
 N-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]cyclohexanecarboxamide,  
 2-butyl-1-{2-[(1-methylethyl)sulfonyl]ethyl}-1 H-imidazo[4,5-c]quinolin-4-amine,  
 N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}ethanesulfonamide,  
 N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}propanamide,  
 1-[2-(methylsulfonyl)ethyl]-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-ethyl-1-{4-[(1-methylethyl)sulfonyl]butyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-ethyl-1-[4-(ethylsulfonyl)butyl]-1H-imidazo[4,5-c]quinolin-4-amine,  
 N-{3-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclopentanecarboxamide,  
 1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine,  
 8,9,10,11-tetrahydropyrido[1′,2′: 1,2]imidazo[4,5-c]quinolin-6-amine,  
 4-amino-α,α,2-trimethyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinoline-1-ethanol,  
 2-hydroxymethyl-1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, or a combination thereof.  
 
     
     
         30 . The method according to  claim 22  wherein the dermal associated condition is selected from actinic keratosis, postsurgical scars, basal cell carcinoma, atopic dermatitis, and warts.  
     
     
         31 . The method according to  claim 30  wherein the IRM is 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, 
 N-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-N′-cyclohexylurea,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,8]naphthyridin-4-amine,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-methylthiazolo[4,5-c]quinolin-4-amine,  
 2-ethoxymethyl-1-phenylmethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-ethylthiazolo[4,5-c]quinolin-4-amine,  
 4-amino-2-butyl-α,α-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridine-1-ethanol,  
 1-{2-[3-(3-pyridyl)propoxy]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-[(R)-1-phenylethyl]-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 1-{2-[3-(1,3-thiazol-2-yl)propoxy]ethyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 1-[2-(pyridin-4-ylmethoxy)ethyl]-1H-imidazo[4,5-c]quinolin-4-amine,  
 N-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]cyclohexanecarboxamide,  
 2-butyl-1-{2-[(1-methylethyl)sulfonyl]ethyl} -1H-imidazo[4,5-c]quinolin-4-amine,  
 N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}ethanesulfonamide,  
 N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethyl}propanamide,  
 1-[2-(methylsulfonyl)ethyl]-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-ethyl-1-{4-[(1-methylethyl)sulfonyl]butyl}-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-ethyl-1-[4-(ethylsulfonyl)butyl]-1H-imidazo[4,5-c]quinolin-4-amine,  
 N-{3-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}cyclopentanecarboxamide,  
 1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine,  
 8,9,10,11-tetrahydropyrido[1′,2′:1,2]imidazo[4,5-c]quinolin-6-amine,  
 4-amino-α,α,2-trimethyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinoline-1-ethanol,  
 2-hydroxymethyl-1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine,  
 2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, or a combination thereof.  
 
     
     
         32 . The method according to  claim 30  wherein the formulation further comprises a preservative system and an emulsifier.  
     
     
         33 . The method according to  claim 32  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and propylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         34 . The method according to  claim 32  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and ethylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         35 . The method according to  claim 32  wherein the preservative system comprises iodopropynyl butylcarbamate.  
     
     
         36 . The method according to  claim 32  wherein the preservative system comprises iodopropynyl butylcarbamate and one or more of methylparaben, ethylparaben, propylparaben, or phenoxyethanol.  
     
     
         37 . The method according to  claim 32  wherein the preservative system comprises iodopropynyl butylcarbamate, methylparaben, and ethylparaben.  
     
     
         38 . The method according to  claim 32  wherein the preservative system comprises phenoxyethanol and one or both of methylparaben and ethylparaben.  
     
     
         39 . The method according to  claim 32  wherein the preservative system comprises a preservative enhancing solubilizer.  
     
     
         40 . The method according to  claim 39  wherein the preservative enhancing solubilizer comprises diethylene glycol monoethyl ether, propylene glycol or a combination thereof.  
     
     
         41 . A method for delivering an immune response modifier (IRM) to a dermal surface, the method comprising the steps of: 
 selecting a formulation comprising: 
 (a) an immune response modifier selected from imidazoquinoline amines, imidazotetrahydroquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazoloquinoline amines, oxazoloquinoline amines, thiazolopyridine amines, oxazolopyridine amines, imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, and thiazolonaphthyridine amines;  
 (b) a fatty acid;  
 (c) a hydrophobic, aprotic component miscible with the fatty acid and comprising a hydrocarbyl group of 7 or more carbon atoms; and  
 (d) a hydrophilic viscosity enhancing agent selected from cellulose ethers and carbomers; and  
   applying the selected topical formulation to the dermal surface.    
     
     
         42 . A pharmaceutical formulation comprising: 
 an immune response modifier (IRM) compound selected from the group consisting of imidazonaphthyridine amines, tetrahydroimidazonaphthyridine amines, and thiazolonaphthyridine amines;    a fatty acid; and    a hydrophobic, aprotic component miscible with the fatty acid and comprising a hydrocarbyl group of 7 or more carbon atoms.    
     
     
         43 . The formulation according to  claim 42  wherein the formulation further comprises a preservative system.  
     
     
         44 . The formulation according to  claim 42  wherein the hydrophobic, aprotic component has a hydrophilic lipophilic balance of less than 2.  
     
     
         45 . The formulation according to  claim 42  wherein the hydrophobic, aprotic component has a pKa greater than 14.2.  
     
     
         46 . The formulation according to  claim 42  wherein the ratio of the hydrophobic, aprotic component to the fatty acid is 0.025:1 to 600:1.  
     
     
         47 . The formulation according to  claim 42  wherein the combined weight percent of the hydrophobic, aprotic component and the fatty acid is 2 to 50.  
     
     
         48 . The formulation according to  claim 42  wherein the fatty acid is isostearic acid.  
     
     
         49 . The formulation according to  claim 42  wherein the hydrophobic, aprotic component is selected from aprotic fatty acid esters, hydrocarbons of 8 or more carbon atoms, and waxes.  
     
     
         50 . The formulation according to  claim 49  wherein the aprotic fatty acid ester is isopropyl myristate, isopropyl palmitate, diisopropyl dimer dilinoleate, caprylic/capric triglyceride, cetyl esters wax, or combinations thereof.  
     
     
         51 . The formulation of  claim 49  wherein the hydrocarbon of 8 or more carbon atoms is mineral oil or petrolatum.  
     
     
         52 . The formulation according to  claim 43  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and propylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         53 . The formulation according to  claim 43  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and ethylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         54 . The formulation according to  claim 43  wherein the preservative system comprises iodopropynyl butylcarbamate.  
     
     
         55 . The formulation according to  claim 43  wherein the preservative system comprises iodopropynyl butylcarbamate and one or more of methylparaben, ethylparaben, propylparaben, or phenoxyethanol.  
     
     
         56 . The formulation according to  claim 43  wherein the preservative system comprises iodopropynyl butylcarbamate, methylparaben, and ethylparaben.  
     
     
         57 . The formulation according to  claim 43  wherein the preservative system comprises phenoxyethanol and one or both of methylparaben and ethylparaben.  
     
     
         58 . The formulation according to  claim 43  wherein the preservative system comprises a preservative enhancing solubilizer.  
     
     
         59 . The formulation according to  claim 58  wherein the preservative enhancing solubilizer comprises diethylene glycol monoethyl ether, propylene glycol or a combination thereof.  
     
     
         60 . The formulation of  claim 43  comprising: 
 (a) 0.001 to 5% w/w imidazonaphthyridine amine, imidazotetrahydronaphthyridine amine, thiazolonaphthyridine amine, or a combination thereof;  
 (b) 0.05 to 40% w/w isostearic acid;  
 (c) 1 to 30% w/w hydrophobic, aprotic component; and  
 (d) 0.01 to 30% w/w preservative system.  
 
     
     
         61 . The formulation of  claim 43  further comprising an emulsifier and a hydrophilic viscosity enhancing agent.  
     
     
         62 . The formulation of  claim 60  further comprising an emulsifier and a hydrophilic viscosity enhancing agent.  
     
     
         63 . The formulation of  claim 62  wherein the viscosity enhancing agent comprises a carbomer.  
     
     
         64 . The formulation of  claim 63  comprising: 
 (a) 0.03 to 3% w/w  
 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 N-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-N′-cyclohexylurea,  
 2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,8]naphthyridin-4-amine,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-ethoxymethyl-1-phenylmethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 4-amino-2-butyl-α,α-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridine-1-ethanol,  
 1-[(R)-1-phenylethyl]-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 or a combination thereof; 
 (b) 3 to 25% w/w isostearic acid;  
 (c) 3 to 15% w/w hydrophobic, aprotic component;  
 (d) 0.1 to 25% w/w preservative system;  
 (e) 0.75 to 3.5% w/w emulsifier; and  
 (f) 0.5 to 5% w/w carbomer.  
 
 
     
     
         65 . A method of treating a dermal associated condition, the method comprising a step of: 
 applying to skin a formulation comprising an immune response modifier (IRM) chosen from imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, and thiazolonaphthyridine amines; a fatty acid; and a hydrophobic, aprotic component miscible with the fatty acid and comprising a hydrocarbyl group of 7 or more carbon atoms.    
     
     
         66 . The method according to  claim 65  wherein the ratio of the hydrophobic, aprotic component to the fatty acid is 0.025:1 to 600:1.  
     
     
         67 . The method according to  claim 65  wherein the combined weight percent of the hydrophobic, aprotic component and the fatty acid is 2 to 50.  
     
     
         68 . The method according to  claim 65  wherein the hydrophobic, aprotic component is selected from the group consisting of aprotic fatty acid esters, hydrocarbons of 8 or more carbon atoms, and waxes.  
     
     
         69 . The method according to  claim 68  wherein the aprotic fatty acid ester is isopropyl myristate, isopropyl palmitate, diisopropyl dimer dilinoleate, caprylic/capric triglyceride, cetyl esters wax, or combinations thereof.  
     
     
         70 . The method according to  claim 65  wherein the formulation further comprises: 
 a preservative system; and  
 an emulsifier.  
 
     
     
         71 . The method according to  claim 65  wherein the IRM is 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, N-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-N′-cyclohexylurea, 
 2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,8]naphthyridin-4-amine,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-ethoxymethyl-1-phenylmethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 4-amino-2-butyl-α,α-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridine-1-ethanol,  
 1-[(R)-1-phenylethyl]-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, or a combination thereof.  
 
     
     
         72 . The method according to  claim 65  wherein the dermal associated condition is actinic keratosis, postsurgical scars, basal cell carcinoma, atopic dermatitis, and warts.  
     
     
         73 . The method according to  claim 72  wherein the IRM is 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, N-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]-N′-cyclohexylurea, 
 2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,8]naphthyridin-4-amine,  
 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-ethoxymethyl-1-phenylmethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 4-amino-2-butyl-α,α-dimethyl-1H-imidazo[4,5-c][1,5]naphthyridine-1-ethanol,  
 1-[(R)-1-phenylethyl]-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine,  
 2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine, or a combination thereof.  
 
     
     
         74 . The method according to  claim 72  wherein the formulation further comprises: a preservative system; and 
 an emulsifier.  
 
     
     
         75 . The method according to  claim 74  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and propylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         76 . The method according to  claim 74  wherein the preservative system comprises methylparaben at 0.01 to 0.5% w/w of the formulation and ethylparaben at 0.01 to 0.5% w/w of the formulation.  
     
     
         77 . The method according to  claim 74  wherein the preservative system comprises iodopropynyl butylcarbamate.  
     
     
         78 . The method according to  claim 74  wherein the preservative system comprises iodopropynyl butylcarbamate and one or more of methylparaben, ethylparaben, propylparaben, or phenoxyethanol.  
     
     
         79 . The method according to  claim 74  wherein the preservative system comprises iodopropynyl butylcarbamate, methylparaben, and ethylparaben.  
     
     
         80 . The method according to  claim 74  wherein the preservative system comprises phenoxyethanol and one or both of methylparaben and ethylparaben.  
     
     
         81 . The method according to  claim 74  wherein the preservative system comprises a preservative enhancing solubilizer.  
     
     
         82 . The method according to  claim 81  wherein the preservative enhancing solubilizer comprises diethylene glycol monoethyl ether, propylene glycol or a combination thereof.  
     
     
         83 . A method for delivering an immune response modifier (IRM) to a dermal surface, the method comprising the steps of: 
 selecting a formulation comprising: 
 (a) an immune response modifier selected from imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, and thiazolonaphthyridine amines;  
 (b) at fatty acid;  
 (c) a hydrophobic, aprotic component miscible with the fatty acid and comprising a hydrocarbyl group of 7 or more carbon atoms; and  
   applying the selected formulation to the dermal surface.