Topical amlodipine salts for the treatment of anorectal diseases

Abstract

Provided is a topical pharmaceutical gel composition of an amlodipine salt and methods for its use in the treatment of anorectal disease.

1 - 20 . (canceled) 
     
     
         21 . A method for treating an anorectal disease, comprising topically applying a topical pharmaceutical gel composition to a skin surface of a patient in need thereof, wherein the topical pharmaceutical gel composition comprises:
 about 0.01-1% w/w of an amlodipine salt, as measured as the free base;   about 5-75% w/w of at least one glycol solvent;   about 0.1-10% w/w of at least one gelling agent;   about 5-75% w/w of glycerin;   about 1-20% w/w of ethanol; and   about 10-40% w/w of water,   wherein the anorectal disease is chronic anal fissure, and the topical pharmaceutical gel composition is topically applied to an affected area of the skin.   
     
     
         22 . A method for treating an anorectal disease, comprising topically applying a topical pharmaceutical gel composition to a skin surface of a patient in need thereof, wherein the topical pharmaceutical gel composition comprises:
 about 0.01-1% w/w of an amlodipine salt, as measured as the free base;   about 5-75% w/w of at least one glycol solvent;   about 0.1-10% w/w of at least one gelling agent;   about 5-75% w/w of glycerin;   about 1-20% w/w of ethanol;   about 10-40% w/w of water; and   a local anesthetic.   
     
     
         23 . The method of  claim 22 , wherein the local anesthetic is lidocaine. 
     
     
         24 . A method for treating an anorectal disease, comprising topically applying a topical pharmaceutical gel composition to a skin surface of a patient in need thereof, wherein the topical pharmaceutical gel composition comprises:
 about 0.01-1% w/w of an amlodipine salt, as measured as the free base;   about 5-75% w/w of at least one glycol solvent;   about 0.1-10% w/w of at least one gelling agent;   about 5-75% w/w of glycerin;   about 1-20% w/w of ethanol;   about 10-40% w/w of water; and   an anti-inflammatory agent,   wherein the anti-inflammatory agent is a COX-1 or COX-2 inhibitor, or a mixture thereof.   
     
     
         25 . The method of  claim 21 , wherein the anorectal disease is selected from hemorrhoids, anal fissure (acute or chronic), painful conditions after anorectal surgery, prolapsed thrombosed piles, perianal haematoma, or proctalgia fugax. 
     
     
         26 . The method of  claim 21 , wherein the anorectal disease is acute anal fissure, and the topical pharmaceutical gel composition is topically applied to an affected area of the skin. 
     
     
         27 . The method of  claim 21 , wherein the amlodipine salt is amlodipine besylate. 
     
     
         28 . The method of  claim 21 , wherein the topical pharmaceutical gel composition further comprises at least one preservative, wherein the at least one glycol solvent is propylene glycol, wherein the at least one gelling agent is hydroxyethyl cellulose. and wherein the at least one preservative is methyl parahydroxybenzoate. 
     
     
         29 . The method of  claim 21 , wherein the amlodipine salt is amlodipine besylate, wherein the ethanol is present in a concentration of about 5-15% w/w, wherein the at least one gelling agent is hydroxyethyl cellulose, and wherein the water is present in a concentration of about 15-35% w/w. 
     
     
         30 . The method of  claim 21 , wherein the at least one gelling agent is hydroxyethyl cellulose. 
     
     
         31 . The method of  claim 21 , wherein the amlodipine salt is present in in a dissolved state in the gel and is stable against degradation at a temperature of 2-8° C. for a period of at least 24 months, as demonstrated by an assay limit of between 95% and 105%. 
     
     
         32 . The method of  claim 21 , wherein the amlodipine salt is amlodipine besylate, and wherein the amlodipine besylate is present in a dissolved state in the gel and is stable against degradation at a temperature of 2-8° C. for a period of at least 24 months, as demonstrated by an assay limit of between 95% and 105%. 
     
     
         33 . The method of  claim 21 , wherein the degradation impurities of the amlodipine salt in the topical pharmaceutical gel composition is less than about 2.5% for a storage period of 24 months at room temperature. 
     
     
         34 . The method of  claim 32 , wherein the degradation impurities of the amlodipine besylate in the topical pharmaceutical gel composition is less than about 2.5% for a storage period of 24 months at a temperature of about 2-8° C. 
     
     
         35 . The method of  claim 21 , wherein the amlodipine salt is amlodipine besylate, wherein the at least one glycol solvent is propylene glycol, wherein the at least one gelling agent is hydroxyethyl cellulose, wherein the topical pharmaceutical gel composition further comprises at least one preservative present in a concentration of about 0.01-5% w/w, wherein the at least one preservative is methyl parahydroxybenzoate, wherein the glycerin is present in a concentration of about 30-50% w/w, wherein the ethanol is present in a concentration of about 5-15% w/w, and wherein the water is present in a concentration of about 15-35% w/w. 
     
     
         36 . The method of  claim 21 , wherein the topical pharmaceutical gel composition has an active ingredient consisting essentially of the amlodipine salt. 
     
     
         37 . The method of  claim 21 , wherein the amlodipine salt is present at a concentration of about 0.1-1% w/w, as measured as the free base. 
     
     
         38 . The method of  claim 21 , wherein the topical pharmaceutical gel composition causes no erythema, edema, inflammation, hypersensitivity, infection, biofilm formation, ischemia, necrosis, erysipelas, cellulitis at the skin surface. 
     
     
         39 . The method of  claim 21 , wherein the anorectal disease is anal fissure, and wherein the method treats pain associated with the anal fissure.