Novel enteric combination therapy

Abstract

There is disclosed herein a composition for treating gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome (IBD), diverticulitis, traveler's diarrhoea, chronic idiopathic nausea, IBD-associated constipation and diarrhoea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux esophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, MS, Alzheimer's Disease, Motor Neuron 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, am inoglycosides, 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, traveler's diarrhoea, chronic idiopathic nausea, IBD-associated constipation and diarrhoea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, MS, Alzheimer's Disease, Motor Neuron 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, am inoglycosides, 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.

1 . A for treating or ameliorating a gastrointestinal disorder comprising administering to an individual in need thereof a therapeutic composition comprising:
 (i) vancomycin, a vancomycin derivative, a multi-valent polymer of vancomycin, or a combination thereof,   wherein the vancomycin derivative comprises a carbohydrate-modified vancomycin, a vancomycin-disulfide derivative, a lipidated vancomycin, a chlorobiphenyl-desleucyl-vancomycin or chlorobiphenyl vancomycin; and   (ii) rifaximin.   
     
     
         2 . The method 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 method of  claim 1 , wherein the therapeutic composition further comprises an aminoglycoside, wherein optionally 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 method of  claim 1 , wherein the therapeutic composition further comprises a nitroimidazole, and optionally the nitroimidazole is selected from the group consisting of metronidazole, tinidazole, nimorazole, secnidazole, ordinazole and mixtures thereof. 
     
     
         5 . The method of  claim 1 , wherein the therapeutic composition further comprises an additional ansamycin, and optionally the additional ansamycin is selected from the group consisting of rifampicin, rifabutin, rifapentine and mixtures thereof. 
     
     
         6 . The method of  claim 1 , wherein the therapeutic composition further comprises a prokinetic agent, wherein optionally the prokinetic agent is selected from the group consisting of tegaserod, domperidone, metoclopramide, mosapride, erythromycin and mixtures thereof. 
     
     
         7 . The method of  claim 1 , wherein the therapeutic composition further comprises a 5-aminosalicylic acid, wherein optionally the 5-aminosalicylic acid is selected from the group consisting of mesalazine, olsalazine, balsalazide and mixtures thereof. 
     
     
         8 . The method of  claim 1 , wherein the therapeutic composition further comprises an anti-opioid blocking agent, wherein optionally the anti-opioid blocking agent is selected from the group consisting of methyl naltrexone, naloxone hydrochloride and a combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the therapeutic composition further comprises metronidazole. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the therapeutic composition further comprises prucalopride. 
     
     
         12 . The method of  claim 1 , wherein the therapeutic composition further comprises metronidazole and colchicine. 
     
     
         13 . The method of  claim 1 , wherein the therapeutic composition further comprises metronidazole and colchicine. 
     
     
         14 . The method of  claim 1 , wherein the therapeutic composition further comprises aminoglycoside and colchicine. 
     
     
         15 . The method of  claim 1 , wherein the therapeutic composition further comprises rifamycin, colchicine and metronidazole. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the therapeutic composition further comprises olsalazine and colchicine. 
     
     
         18 . The method of  claim 1 , wherein the therapeutic composition further comprises methyl naltrexone or naloxone hydrochloride. 
     
     
         19 . The method of  claim 1 , wherein the therapeutic composition further comprises the combination of naloxone hydrochloride and metronidazole. 
     
     
         20 . The method of  claim 1 , wherein the therapeutic composition further comprises naloxone hydrochloride and colchicine. 
     
     
         20 . The method of  claim 1 , wherein the therapeutic composition further comprises naloxone hydrochloride and rifaximin. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the gastrointestinal disorder comprises constipation, functional constipation, irritable bowel syndrome (IBD), diverticulitis, IBD-associated constipation, diarrhoea, pseudoobstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, flatulence, halitosis or bloating. 
     
     
         24 . The method of  claim 1 , wherein the vancomycin, vancomycin derivative, multi-valent polymer of vancomycin, or combination thereof, or rifaximin is administered in doses ranging from between about 0.01 mg per day to 5000 mg per day. 
     
     
         25 - 27 . (canceled)