Novel enteric combination therapy

Abstract

There is disclosed herein a composition for treating gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhea, chronic idiopathic nausea, IBD-associated constipation and diarrhea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinsons disease, MS, Alzheimers Disease, Motor Neurone Disease or autism, the composition comprising: (i) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (ii) at least one anti-clostridial agent selected from the above combined with an opioid blocking agent. There is also disclosed herein a method of treating various gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhea, chronic idiopathic nausea, IBD-associated constipation and diarrhea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinsons disease, MS, Alzheimers Disease, Motor Neurone Disease or autism, the method comprising administering orally, via enema or by suppository: (i) a composition of the invention; (ii) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (iii) at least one anti-clostridial agent selected from the above and an opioid blocking agent to a patient in need of such treatment.

What is claimed: 
     
         1 . A composition for treating gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, traveler's diarrhea, chronic idiopathic nausea, IBD-associated constipation and diarrhea, pseudoobstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, multiple sclerosis (MS), Alzheimer's Disease, Motor Neurone Disease or autism, the composition comprising:
 (i) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or   (ii) at least one anti-clostridial agent selected from the group consisting of vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; with an opioid blocking agent.   
     
     
         2 . The composition of  claim 1 , wherein the vancomycin derivative is carbohydrate-modified vancomycin, vancomycin-disulfide derivative, lapidated vancomycin, chlorobiphenyl-desleucyl-vancomycin, oritavancin, telavancin, or chlorobiphenyl vancomycin. 
     
     
         3 . The composition of  claim 1 , wherein the aminoglycoside is selected from the group consisting of streptomycin, neomycin, framycetin, paromomycin, ribostamycin, kanamycin, amikacin, arbekacin, beanamycin, dibekacin, tobramycin, spectinomycin, hygromycin B, paromomycin sulfate, streptomycin, gentamicin, netilmicin, sisomicin, isepamicin, verdamicin, astromicin and mixtures thereof. 
     
     
         4 . The composition of  claim 1 , wherein the nitroimidazole is selected from the group consisting of metronidazole, tinidazole, nimorazole, secnidazole, ordinazole and mixtures thereof. 
     
     
         5 . The composition of  claim 1 , wherein the ansamycin is selected from the group consisting of rifaximin, rifampicin, rifabutin, rifapentine and mixtures thereof. 
     
     
         6 . The composition of  claim 1 , wherein the prokinetic agents are selected from the group consisting of tegaserod, domperidone, metoclopramide, mosapride, erythromycin and mixtures thereof. 
     
     
         7 . The composition of  claim 1 , wherein the 5-aminosalicylic acid is selected from the group consisting of mesalazine, olsalazine, balsalazide and mixtures thereof. 
     
     
         8 . The composition of  claim 1 , wherein the anti-opioid blocking agent is selected from the group consisting of methyl naltrexone, naloxone hydrochloride and a combination thereof. 
     
     
         9 . The composition of  claim 1 , including the combination of vancomycin and metronidazole. 
     
     
         10 . The composition of  claim 1 , including the combination of vancomycin and rifaximin. 
     
     
         11 . The composition of  claim 1 , including the combination of rifaximin and prucalopride. 
     
     
         12 . The composition of  claim 1 , including the combination rifaximin, metronidazole and colchicine. 
     
     
         13 . The composition of  claim 1 , including the combination vancomycin, metronidazole and colchicine. 
     
     
         14 . The composition of  claim 1 , including the combination vancomycin, aminoglycoside and colchicine. 
     
     
         15 . The composition of  claim 1 , including the combination rifamycin, colchicine and metronidazole. 
     
     
         16 . The composition of  claim 1 , including the combination vancomycin together with a prokinetic agent. 
     
     
         17 . The composition of  claim 1 , including the combination vancomycin, olsalazine and colchicine. 
     
     
         18 . The composition of  claim 1 , including the combination vancomycin and methyl naltrexone or naloxone hydrochloride. 
     
     
         19 . The composition of  claim 1 , including the combination of naloxone hydrochloride, vancomycin and metronidazole. 
     
     
         20 . The composition of  claim 1 , including the combination of naloxone hydrochloride and colchicines. 
     
     
         21 . The composition of  claim 1 , including the combination of naloxone hydrochloride, vancomycin, and rifaximin. 
     
     
         22 . The composition of  claim 1 , including the combination of naloxone hydrochloride and rifaximin. 
     
     
         23 . A method of treating various gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, traveler's diarrhea, chronic idiopathic nausea, IBD-associated constipation and diarrhea, pseudoobstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, multiple sclerosis (MS), Alzheimer's Disease, Motor Neurone Disease or autism, the method comprising administering orally, via enema or by suppository:
 (i) a composition of  claim 1 , or   (ii) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, a prokinetic agent and 5-aminosalicylic acid; or   (iii) (1) at least one anti-clostridial agent selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, a prokinetic agent and 5-aminosalicylic acid, and (2) an opioid blocking agent, to a patient in need of such treatment.   
     
     
         24 . The method of  claim 23 , wherein:
 (a) the agent is administered in doses ranging from 0.01 mg per day to 5000 mg per day;   (b) when present, the colchicine is administered in doses of 0.005 mg to 5 mg per day;   (c) when present, the 5-aminosalicylic acid is administered in doses of 100 mg to 3 gm per day; or   (d) when present, the colchicine is administered in doses of 0.005 mg to 5 mg per day and the 5-aminosalicylic acid is administered in doses of 100 mg to 3 gm per day.