Pharmaceutical composition

Abstract

A topical composition comprises at least 5 wt % metronidazole or a pharmacologically acceptable derivative thereof in a non-aqueous vehicle. The composition may be used in the treatment of conditions of the colon, rectum, anorectum and perianal region, in particular inflammatory bowel disease and perianal Crohn's disease. The composition also relieves pain and inflammation and promotes healing of the colon, rectum, anorectum and perianal region following surgical operations. One advantage of the composition is that topical administration of metronidazole results in a primarily local effect and thus side effects observed from systemic administration are avoided.

1 . A topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle, wherein the vehicle comprises at least one hydrocarbon compound.  
   
   
       2 . A topical composition as claimed in  claim 1  wherein the concentration of metronidazole is between from about 5 wt % to about 50 wt %.  
   
   
       3 . A topical composition as claimed in  claim 1  wherein the concentration of metronidazole is between from about 5 wt % to about 15 wt %.  
   
   
       4 . A topical composition as claimed in  claim 1  wherein the concentration of metronidazole is about 10 wt %.  
   
   
       5 . (canceled)  
   
   
       6 . (canceled)  
   
   
       7 . A topical composition as claimed in  claim 1  wherein the vehicle comprises a mixture of at least two semi-solid saturated hydrocarbon compounds.  
   
   
       8 . A topical composition as claimed in  claim 1  wherein the vehicle comprises white petrolatum (USP).  
   
   
       9 . A topical composition as claimed in  claim 1  further comprising a therapeutically effective amount of at least one steroid.  
   
   
       10 . A topical composition as claimed in  claim 9  wherein the steroid is hydrocortisone or a pharmacologically acceptable derivative thereof.  
   
   
       11 . A topical composition as claimed in  claim 1  further comprising a therapeutically effective amount of at least one analgesic agent.  
   
   
       12 . A topical composition as claimed in  claim 11  wherein the or at least one analgesic agent is an amide or an ester.  
   
   
       13 . A topical composition as claimed in  claim 11  wherein the or at least one analgesic agent is selected from the group consisting of pramoxine and benzocaine  
   
   
       14 . A topical composition as claimed in  claim 1  further comprising a therapeutically effective amount of at least one antimicrobial agent.  
   
   
       15 . A topical composition as claimed in  claim 14  wherein the or at least one antimicrobial agent is an antibiotic selected from the group consisting of ciprocfloxacin, amoxicillin-clavulonic acid, erythromycin, tetracyclin, clindamycin and doxycyclin.  
   
   
       16 . A topical composition as claimed in  claim 1  further comprising a therapeutically effective amount of at least one substance that either promotes skin integrity or inhibits skin breakdown.  
   
   
       17 . A topical composition as claimed in  claim 16  wherein the or at least one of said substances is selected from the group consisting of vitamin E, aloe, zinc oxide and other barrier cream.  
   
   
       18 . A topical composition as claimed in  claim 1  further comprising a therapeutically effective amount of least one anti-inflammatory agent.  
   
   
       19 . A topical composition as claimed in  claim 18  wherein the or at least one anti-inflammatory agent is a non-steroidal anti-inflammatory agent selected from the group consisting of aminosalicylic acid, ibuprofen, sulindac, piroxicam and diflunisal.  
   
   
       20 . A topical composition as claimed in  claim 1  further comprising a therapeutically effective amount of at least one antidiarrheal compound.  
   
   
       21 . A topical composition as claimed in  claim 20  wherein the or at least one antidiarrheal compound is a bismuth salt.  
   
   
       22 . A topical composition as claimed in  claim 1  in a form suitable for direct application to the colon, rectum, anorectum, perianal region or anal canal.  
   
   
       23 . A topical composition as claimed in  claim 1  in the form of an enema, suppository, ointment, lotion, gel, foam or cream.  
   
   
       24 . A topical composition as claimed in  claim 1  in the form of an ointment.  
   
   
       25 . A topical composition as claimed in  claim 1  in the form of an enema.  
   
   
       26 . A topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of about 10 wt % in white petrolatum (USP).  
   
   
       27 . A topical composition as claimed in  claim 26  consisting essentially of metronidazole at a concentration of about 10 wt % in white petrolatum (USP).  
   
   
       28 . A topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle for use in the treatment of the human or animal body.  
   
   
       29 .- 47 . (canceled)  
   
   
       48 . A method of relieving pain caused by conditions of colon, rectum, anorectum and perianal region of the human or animal body comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       49 . A method of relieving pain following a surgical operation to the colon, rectum, anorectum and perianal region of the human or animal body comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       50 . A method of reducing inflammation following a surgical operation to the colon, rectum, anorectum and perianal region of the human or animal body comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       51 . A method of promoting healing following a surgical operation to the colon, rectum, anorectum and perianal region of the human or animal body comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       52 . A method of reducing edema following a surgical operation to the colon, rectum, anorectum and perianal region of the human or animal body comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       53 . A method of reversing tissue induration and granulation following a surgical operation to the colon, rectum, anorectum and perianal region of the human or animal body comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       54 . A method as claimed in any one of  claims 49  to  53  wherein the surgical operation is selected from the group consisting of a hemorrhoidectomy, a fistulotomy, a fissurectomy, a sphincterotomy, sphincteroplasty and incision and drainage of an abscess.  
   
   
       55 . A method of treatment of conditions of the colon, rectum, anorectum and perianal region comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       56 . A method as claimed in  claim 55  wherein the condition is selected from the group consisting of inflammatory bowel disease, ulcerative colitis, perianal Crohn's disease, radiation proctitis, idiopathic proctocolitis of and pouchitis.  
   
   
       57 . A method of treatment of anorectal or perianal ulcers comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       58 . A method of treatment of perianal infective or inflammatory processes comprising application of a topical composition comprising metronidazole or a pharmacologically acceptable derivative thereof at a concentration of at least about 5 wt % in a pharmacologically acceptable non-aqueous vehicle directly to the affected area.  
   
   
       59 . A method of treatment of conditions of the colon, rectum, anorectum and perianal region comprising application of a topical composition as defined in  claim 1  to the affected area.  
   
   
       60 . A method as claimed in  claim 48  wherein the dose of metronidazole for each application is between from about 125 mg to about 1250 mg.  
   
   
       61 . A method as claimed in  claim 48  wherein the dose of metronidazole for each application is between from about 125 mg to about 375 mg.  
   
   
       62 . A method as claimed in  claim 48  wherein the dose of metronidazole for each application is about 250 mg.  
   
   
       63 . A method as claimed  claim 48  wherein the composition is applied between from 2 to 4 times daily.  
   
   
       64 . A method as claimed in  claim 48  wherein the composition is applied 3 times daily.