METHODS OF TREATING BOWEL DISEASES BY ADMINISTERING A BOWEL CLEANSER AND AN ANTIBIOTIC

• US 20090324736A1
• Filed: 05/07/2009
• Published: 12/31/2009
• Est. Priority Date: 05/07/2008
• Status: Abandoned Application

• Current Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Original Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Inventors: Patton, Stephana, Forbes, William, Johnson, Lorin
• Application Number:
  US12/437,232
• Publication Number:
  US 20090324736A1
• Time in Patent Office: Days
• US Class Current: 424/606
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 33/04 Sulfur, selenium or tellurium; Compounds thereof
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/06 Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to formulations and kits for the treatment of bowel disease, to their use in medicinal preparations and to therapeutic methods thereof.

Claims

1. A method of treating bowel disease (BD), comprising:

administering a gastrointestinal cleanser (GI) to a subject in need thereof; and

administering a therapeutically effective amount of an antibiotic.

2. The method of claim 1, wherein the administering of the GI cleanser and the antibiotic results in from between about 35-70% of subjects with adequate relief of one or more of IBS symptoms, abdominal pain symptoms, or bloating symptoms.

3. The method of claim 1, wherein the antibiotic comprises one or more of a rifamycin, aminoglycoside, amphenicol, ansamycin, β

-Lactam, carbapenem, cephalosporin, cephamycin, monobactam, oxacephem, lincosamide, macrolide, polypeptide, tetracycline, or a 2,4-diaminopyrimidine class antibiotic.

4. The method of claim 1, wherein the GI cleanser comprises one or more of a PEG based composition or a sodium phosphate based composition.

5. The method of claim 1, wherein the GI cleanser comprises polyethylene glycol (PEG), sodium sulfate, sodium chloride, potassium chloride, and ascorbic acid.

6. The method of claim 5, wherein the GI cleanser is supplied as two pouch A'"'"'s comprising 100 grams of PEG 3350, 7.5 grams of sodium sulfate, 2.691 grams of sodium chloride, and 1.015 grams of potassium chloride;

and two pouch B'"'"'s comprising 4.7 grams of ascorbic acid, and 5.9 grams of sodium ascorbate.

7. The method of claim 1, wherein the GI cleanser comprises 32 or 40 tablets comprising sodium phosphate monobasic, sodium phosphate dibasic, PEG 8000, and magnesium sterate.

8. The method of claim 1, wherein the GI cleanser comprises sodium phosphate monobasic, sodium phosphate dibasic, microcrystalline cellulose, colodial silicon dioxide, and magnesium sterate.

9. The method of claim 1, wherein the GI cleanser comprises Fleet®

Phospho-soda®

EZ-Prep;

miraLAX;

a bulk producing purgative;

a serotonin agonist;

a hyperosmotic agent;

GoLytely;

GlycoLax;

CoLyte;

or NuLytely.

10. The method of claim 1, wherein the method further comprises administering an antibiotic prior to the administration of the gastrointestinal cleanser.

11. The method of claim 1 or 10, wherein the method further comprises administering an antibiotic with the administration of the gastrointestinal cleanser.

12. The method of claim 1, 10 or 11, wherein the method further comprises performing a colonoscopy on the subject after the administration of the gastrointestinal cleanser.

13. The method of claim 1, wherein the administration of the gastrointestinal cleanser is within between about 1 to about 90 days before the administration of the antibiotic.

14. The method of claim 1, wherein the administration of the gastrointestinal cleanser is within between about 1 to about 60 days;

between about 1 to about 30 days;

between about 1 to about 24 days;

between about 1 to about 14 days;

between about 1 to about 10 days;

between about 1 to about 7 days;

between about 1 to about 5 days;

between about 1 to about 4 days;

between about 1 to about 3 days;

or between about 1 to about 2 days before the administration of the antibiotic.

15. The method of claim 1, wherein one or more of an anti-inflammatory, one or more additional antibiotics, crofelemer, or metoclopramide is administered to the subject.

16. The method of claim 1, further comprising:

selecting subjects who respond to treatment after being treated for between about 1 and about 52 weeks or longer; and

removing a responding subject from treatment wherein after removal of treatment there is a durability of response.

17. The method of claim 16, wherein the subject is treated for between about 1 and about 24 weeks.

18. The method of claim 1, wherein the bowel disease comprises, one or more of inflammatory bowel disease (IBD), Crohn'"'"'s disease, hepatic encephalopathy, enteritis, colitis, irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), depression, attention deficit/hyperactivity disorder (ADHD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), travelers'"'"' diarrhea, small intestinal bacterial overgrowth, chronic pancreatitis, or pancreatic insufficiency.

19. The method of claim 1, wherein hepatic encephalopathy subject will be administered rifaximin for between about 24 weeks and 24 months or longer.

20. The method of claim 1, wherein the therapeutically effective amount of the antibiotic comprises from between about 100 mg and about 6000 mg;

from between about 50 mg and about 2500 mg BID;

from between about 50 mg and about 2000 mg TID;

550 mg TID;

550 mg BID;

600 mg TID;

600 mg BID;

1650 mg QD;

200 mg TID;

200 mg BID or 200 mg QD.

21. The method of claim 1, wherein the BD comprises uncontrolled diarrhea-associated irritable bowel syndrome (dIBS).

22. The method of claim 2, wherein the rifamycin class antibiotic comprises a compound of Formula I.

23. The method of claim 3, wherein the rifamycin class antibiotic comprises rifaximin.

24. The method of claim 16, wherein subjects are treated from between about 1 and about 12 weeks prior to selection.

25. The method of claim 16, wherein the durability of response comprises from between about 1 and about 24 weeks of adequate relief of symptoms or from between about 1 and about 5 weeks of adequate relief of symptoms.

26. The method of claim 25, wherein symptoms comprise one or more of overall BD symptoms or bloating.

27. A method of treating BD, comprising:

providing a container comprising a gastrointestinal cleanser and a rifamycin class antibiotic, wherein the container comprises printed labeling which describes administering the gastrointestinal cleanser followed by the rifamycin class antibiotic; and

administering the cleanser and the rifamycin class antibiotic from the container to the subject.

28. The method of claim 27, wherein the rifamycin class antibiotic comprises rifaximin.

29. The method of claim 27, wherein the administering of the gastrointestinal cleanser and the rifamycin class antibiotic results in from between about 35-70% of subjects with adequate relief of one or more of IBS symptoms, abdominal pain symptoms, or bloating symptoms.

30. A kit for treating BD comprising a container comprising gastrointestinal cleanser and a rifamycin class antibiotic and a label which describes that administration of the cleanser prior to a therapeutically effective amount of the antibiotic results in from between about 35-70% of subjects with adequate relief of one or more of IBS symptoms, abdominal pain symptoms, or bloating symptoms.

31. A kit for treating BD comprising a container comprising gastrointestinal cleanser and a rifamycin class antibiotic and a label which describes that administration of the cleanser and a colonoscopy prior to a therapeutically effective amount of the antibiotic results in from between about 35-70% of subjects with adequate relief of one or more of IBS symptoms, abdominal pain symptoms, or bloating symptoms.

32. A therapeutic comprising a gastrointestinal (GI) cleanser and a therapeutically effective amount of an antibiotic.

33. The method of claim 32, wherein the therapeutically effective amount of the antibiotic comprises from between about 100 mg and about 6000 mg;

from between about 50 mg and about 2500 mg BID;

from between about 50 mg and about 2000 mg TID;

550 mg TID;

550 mg BID;

600 mg TID;

600 mg BID;

1650 mg QD;

200 mg TID;

200 mg BID or 200 mg QD.

34. The method of claim 32, wherein GI cleanser comprises one or more of a PEG based composition or a sodium phosphate based composition.