Film-forming compositions of antihyperalgesic opiates and method of treating hyperalgesic conditions therewith

A topical anti-hyperalgesic film-forming composition for coating an injured/inflamed site on the mammalian patient to reduce hyperalgesia of said injured/inflamed site comprising:

• a) of from about 1 to about 65% w/w of an anti-hyperalgesic compound selected from the group consisting of
• 2-[4-(4-hydroxy-4-phenylpiperidino)-2,2-diphenylbutyryl]-piperidine;
• 4-{4-[4-hydroxy-4-(3-trifluoromethylphenyl)piperidinol]-2,2-diphenylbutyryl }morpholine;
• 1-{4-[4-hydroxy-4-(3-trifluoromethylphenyl)-piperidino]-2,2-diphenylbutyl}p iperidine;
• 4-(p-chlorophenyl)-4-hydroxy-N-N-,y-trimethyl-.alpha.,.alpha.-diphenylpiper idine-1-butyramide;
• 4-(p-chlorophenyl)-4-hydroxy-N-N-dimethyl-.alpha.,.alpha.-diphenylpiperidin e-1-butyramide[loperamide];
• 4-(3,4-dichlorophenyl)-N-N-diethyl-4-hydroxy-.alpha.,.alpha.-diphenylpiperi dine-1-butyramide;
• 4-(3,4-dichlorophenyl)-4-hydroxy-N-N-dimethyl-.alpha.,.alpha.-diphenylpiper idine-1-butyramide
• 4-(chloro-3-trifluoromethylphenyl)-4-hydroxy-N-N-dimethyl-.alpha.,.alpha.-d iphenylpiperidine-1-butyramide;
• 4-(p-fluorophenyl)-4-hydroxy-N-N-,y-trimethyl-.alpha.,.alpha.-diphenylpiper idine-1-butyramide;
• 4-(p-bromophenyl)-4-hydroxy-N-N-dimethyl-.alpha.,.alpha.-diphenylpiperidine -1-butyramide;
• 1-{4-[4-(3,4-dichlorophenyl)-4-hydroxypiperidine]-2,2-diphenylbutyl}pyrroli dine;
• 4-(p-chlorophenyl)-N-ethyl-4-hydroxy-N-methyl-.alpha.,.alpha.-diphenylpiper idine-1-butyramide;
• 5-[1,1-diphenyl-3-(exo-5-hydroxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-met hyl-1,3,4-oxadiazole;
• 5-[1,1-diphenyl-3-(exo-5-acetoxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-met hyl-1,3,4-oxadiazole;
• 5-[1,1-diphenyl-3-(endo-5-acetoxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-me thyl-1,3,4-oxadiazole;
• 5-[1,1-diphenyl-3-(endo-5-hydroxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-me thyl-1,3,4-oxadiazole;
• 5-[1,1-diphenyl-3-(endo-6-acetoxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-me thyl-1,3,4-oxadiazole;
• 5-[1,1-diphenyl-3-(endo-6-hydroxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-me thyl-1,3,4-oxadiazole;
• 5-[1,1-diphenyl-3-(exo-6-acetoxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-met hyl-1,3,4-oxadiazole;
• 5-[1,1-diphenyl-3-(exo-6-hydroxy-2-azabicyclo[2,2-2]oct-2-yl)-propyl]-2-met hyl-1,3,4-oxadiazole;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-piperidinecarboxylic acid hydrochloride;
• ethyl 1-(3,3,3-triphenylpropyl)-4-phenyl-4-piperidinecarboxylate;
• potassium 1-(3,3,3-triphenylpropyl)-4-phenyl-4-piperidinecarboxylate;
• sodium 1-(3,3,3-triphenylpropyl)-4-phenyl-4-piperidinecarboxylate;
• 1-[3,3-diphenyl-3-(2-pyridyl)propyl]-4-phenyl-4-piperidinecarboxylic acid hydrochloride;
• sodium 1-[3,3-diphenyl-3-(2-pyridyl)propyl]-4-phenyl-4-piperidinecarboxylate;
• ethyl 1-[3,3-diphenyl-3-(2-pyridyl)propyl]-4-phenyl-4-piperidinecarboxylate;
• potassium 1-[3,3-diphenyl-3-(2-pyridyl)propyl]-4-phenyl-4-piperidinecarboxylate;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-piperidinemethanol;
• 1-[3,3-diphenyl-3-(2-pyridyl)propyl-4-phenyl-4-piperidinemethanol;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-acetoxymethyl-piperidine;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-methoxymethyl-piperidine;
• 1-(3,3,3-triphenylpropyl)-4-(4-chlorophenyl)-4-piperidinemethanol;
• 1-[3-(p-chloropheny)-3,3-diphenylpropyl]-4-(phenyl)-4-piperidinemethanol;
• 1-[3-(p-tolyl)-3,3-diphenylpropyl]-4-(phenyl)-4-piperidinemethanol;
• 1-[3-(p-bromophenyl)-3,3-diphenylpropyl]-4-(phenyl)-4-piperidinemethanol;
• 1-[3,3-diphenyl-3-(4-pyridyl)-propyl]-4-phenyl-4-piperidinemethanol;
• 1-[3,3-diphenyl-3-(3-pyridyl)propyl]-4-phenyl-4-piperidinemethanol;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-hexoxymethyl-piperidine;
• 1-(3,3,3-triphenylpropyl)-4-(p-tolyl)-4-piperidinemethanol;
• 1-(3,3,3-triphenylpropyl)-4-(p-trifluoromethyl)-4-piperidinemethanol;
• 1-(3,3,3-triphenylbutyl)-4-(phenyl)-4-piperidinemethanol;
• 1-(3,3,3-triphenylpropyl)-4-(phenyl)-4-piperidinemethanol;
• 1-(3,3,3-triphenylpropyl)-4-(phenyl)-4-methoxyethylpiperidine;
• 1-[3,3-diphenyl-3-(2-pyridyl)propyl]-4-phenyl-4-methoxyethylpiperidine;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-piperidinemethanol;
• 1-[3,3-diphenyl-3-(2-pyridyl)propyl]-4-phenyl-4-piperidinemethanol;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-acetoxymethylpiperidine;
• 1-(3,3,3-triphenylpropyl)-4-phenyl-4-methoxymethylpiperidine;
• 1-(3,3,3-triphenylpropyl)-4-(chlorophenyl)-4-piperidinemethanol;
• 1-(3,3,3-triphenylpropyl)-4-hydroxy-4-benzylpiperidine and 1-(3,3,3-triphenylpropyl)-4-hydroxy-4-benzylpiperidine;
• hydrochloride;
• 1-(3,3,3-triphenylpropyl)-4-hydroxy-4-p-chlorobenzylpiperidine;
• 1-(3,3,3-triphenylpropyl)-4-hydroxy-4-p-methylbenzylpiperidine;
• 1-[3,3,3-(2-pyridyl)propyl]-4-benzyl-4-hydroxypiperidine;
• m-chlorophenylamidinourea;
• p-chlorophenylamidinourea;
• 3. 4-dichlorophenylamidinourea;
• m-bromophenylamidinourea;
• p-bromophenylamidinourea;
• 3,4-dibromo-phenylamidinourea;
• 3-chloro-4-bromophenylamidinourea;
• 3-bromo-4-chlorophenylamidinourea;
• 3-chloro-4-fluorophenylamidinourea;
• 3-bromo-4-fluorophenylamidinourea;
• 3-fluoro-4-chlorophenylamidinourea;
• 2,6-dimethylphenylamidinourea;
• 2,6-diethylphenylamidinourea;
• 2-methyl-6-ethylphenylamidinourea;
• 2-methyl-6-methoxyphenylamidinourea;
• 2-methyl-6-ethoxyphenylamidinourea;
• 2-ethyl-6-methoxyphenylamidinourea;
• 2-ethyl-6-ethoxyphenylamidinourea;
• 3,4-dimethoxyphenylamidinourea;
• 3,4-dihydroxyphenylamidinourea;
• 3,4,5-trimethoxyphenylamidinourea;
• 3,4,5-trihydroxyphenylamidinourea;
• 2-[(2-methyl-3-aminophenyl)amino]-1-pyrroline, dihydrochloride;
• 2-[(2-methyl-3-acetamidophenyl)amino]-1-pyrroline, hydrochloride;
• 2-[(2-methyl-3-(ethoxycarbonylamino)phenyl-)amino]-1-pyrroline, hydrochloride;
• 2-(2,2-diphenylpentyl)-1-azabicylo[2,2,2]octane;
• 2-(2,2-diphenylhexyl)-1-azabicylo[2,2,2]octane;
• 2-(2,2-diphenylpropyl)-1-azabicylo[2,2,2]octane;
• 2-(2,2-diphenyloctyl)-1-azabicylo[2,2,2]octane;
• and
• 2-(2,2-diphenylheptyl)-1-azabicylo[2,2,2]octane,
• said anti-hyperalgesic compound incorporated in a film-forming material, said anti-hyperalgesic compound being devoid of central nervous system side effects when topically delivered to the mammalian patient;
• b) said film-forming polymeric material being present in said composition of from about 1 to about 76% w/w and is capable of forming an essentially continuous film in the pH environment of about 5.5 to 8.5, said polymeric material having atoms contain polarizable electrons thereon, said atoms being selected from the group consisting of oxygen, nitrogen, sulfur, in combination with a divalent cation, said divalent cation selected from the group consisting of CA.sup.++, MG.sup.++, Zn.sup.++ and Ba.sup.++, wherein the ratio of said atoms containing the polarizable electrons to said divalent catons is in the range of from about 7.7 to about 1, said film-forming material selected from the group consisting of
• sodium ethylcellulose sulfate,
• sodium cellulose acetate sulfate,
• sodium carboxyethyl cellulose,
• chondroitin sulfate,
• dermatan sulfate,
• keratosulfate,
• lyaluronic acid,
• heparin,
• chitin,
• polyinyl pyrrolidone,
• polyvinyl alcohol,
• polyethylene oxide;
• and
• c) of from about 23 to about 34% w/w of an aqueous pharmaceutically acceptable carrier.