Details for Patent: 7,910,546
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Title: | Methods and compositions for the treatment of gastrointestinal disorders |
Abstract: | The present invention features compositions and related methods for treating IBS and other gastrointestinal disorders and conditions (e.g., gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, Inflammatory bowel disease, functional heartburn, dyspepsia (including functional dyspepsia or nonulcer dyspepsia), gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudo-obstruction), and disorders and conditions associated with constipation, e.g., constipation associated with use of opiate pain killers, post-surgical constipation (post-operative ileus), and constipation associated with neuropathic disorders as well as other conditions and disorders using peptides and other agents that activate the guanylate cyclase C (GC-C) receptor. |
Inventor(s): | Currie; Mark G. (Sterling, MA), Mahajan-Miklos; Shalina (Stanford, CA), Fretzen; Angelika (Somerville, MA), Sun; Li Jing (New York, NY), Norman; Thea (San Diego, CA), Milne; G. Todd (Brookline, MA) |
Assignee: | Ironwood Pharmaceuticals, Inc. (Cambridge, MA) |
Filing Date: | May 13, 2008 |
Application Number: | 12/120,023 |
Claims: | 1. A method for treating or reducing pain in a patient, wherein the pain is selected from pain associated with a gastrointestinal disorder, abdominal pain, visceral pain or pain associated with a gastrointestinal inflammation disorder, the method comprising administering to the patient an effective amount of a peptide consisting of the amino acid sequence Xaa.sub.1 Xaa.sub.2 Xaa.sub.3 Xaa.sub.4 Xaa.sub.5 Cys.sub.6 Cys.sub.7 Xaa.sub.8 Xaa.sub.9 Cys.sub.10 Cys.sub.11 Asn.sub.12 Pro.sub.13 Ala.sub.14 Cys.sub.15 Xaa.sub.16 Gly.sub.17 Cys.sub.18 Xaa.sub.19 Xaa.sub.20 Xaa.sub.21 (SEQ ID NO: 129) wherein: Xaa.sub.1 Xaa.sub.2 Xaa.sub.3 Xaa.sub.4 Xaa.sub.5 is missing; Xaa.sub.8 is Glu or Asp; Xaa.sub.9 is Leu, Ile, Val, Trp, Tyr or Phe; Xaa.sub.16 is Thr, Ala, Trp; Xaa.sub.19 is Tyr or missing; and Xaa.sub.20 Xaa.sub.21 is missing. 2. The method of claim 1, wherein the gastrointestinal disorder is selected from irritable bowel syndrome (IBS), constipation, disturbed bowel pattern, increased sensitivity of the intestine or increased sensitivity of the colon. 3. The method of claim 1, wherein the IBS is selected from constipation-predominant IBS (c-IBS), diarrhea-predominant IBS (d-IBS) or IBS alternating between c-IBS and d-IBS (a-IBS). 4. The method of claim 1, wherein the pain is visceral pain. 5. The method of claim 1, wherein the pain is abdominal pain. 6. The method of claim 1, wherein the inflammation disorder is selected from inflammatory bowel disease, ischemic bowel disease, intestinal inflammation or allergy, coeliac disease, proctitis or eosinophilic gastroenteritis. 7. The method of claim 6, wherein the inflammatory bowel disease is Crohn's disease. 8. The method of claim 6, wherein the inflammatory bowel disease is ulcerative colitis. 9. The method according to claim 1, wherein Xaa.sub.8 is Glu. 10. The method according to claim 9, wherein Xaa.sub.16 is Thr. 11. The method according to claim 10, wherein Xaa.sub.9 is Trp, Tyr or Phe. 12. A method for treating or reducing pain in a patient, wherein the pain is selected from pain associated with a gastrointestinal disorder, abdominal pain, visceral pain or pain associated with a gastrointestinal inflammation disorder, the method comprising administering to the patient an effective amount of a peptide consisting of the amino acid sequence selected from: Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: 75); Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: 79), Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: 3); Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: 94); Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: 98); or Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: 81). 13. The method of claim 12, wherein the gastrointestinal disorder is selected from irritable bowel syndrome (IBS), constipation, disturbed bowel pattern, increased sensitivity of the intestine or increased sensitivity of the colon. 14. The method of claim 13, wherein the IBS is selected from constipation-predominant IBS (c-IBS), diarrhea-predominant IBS (d-IBS), or IBS alternating between c-IBS and d-IBS (a-IBS). 15. The method of claim 12, wherein the pain is visceral pain. 16. The method of claim 12, wherein the pain is abdominal pain. 17. The method of claim 12, wherein the inflammation disorder is selected from inflammatory bowel disease, ischemic bowel disease, intestinal inflammation or allergy, coeliac disease, proctitis or eosinophilic gastroenteritis. 18. The method of claim 17, wherein the inflammatory bowel disease is Crohn's disease. 19. The method of claim 17, wherein the inflammatory bowel disease is ulcerative colitis. 20. A method for treating or reducing pain in a patient, wherein the pain is selected from pain associated with a gastrointestinal disorder, abdominal pain, visceral pain or pain associated with a gastrointestinal inflammation disorder, the method comprising administering to the patient an effective amount of a peptide consisting of the amino acid sequence Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: 3) or Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: 81). 21. The method of claim 20, wherein the gastrointestinal disorder is selected from irritable bowel syndrome (IBS), constipation, disturbed bowel pattern, increased sensitivity of the intestine or increased sensitivity of the colon. 22. The method of claim 21, wherein the IBS is selected from constipation-predominant IBS (c-IBS), diarrhea-predominant IBS (d-IBS), or IBS alternating between c-IBS and d-IBS (a-IBS). 23. The method of claim 20, wherein the pain is visceral pain. 24. The method of claim 20, wherein the pain is abdominal pain. 25. The method of claim 20, wherein the inflammation disorder is selected from inflammatory bowel disease, ischemic bowel disease, intestinal inflammation or allergy, coeliac disease, proctitis or eosinophilic gastroenteritis. 26. The method of claim 25, wherein the inflammatory bowel disease is Crohn's disease. 27. The method of claim 25, wherein the inflammatory bowel disease is ulcerative colitis. 28. The method of claim 20, wherein the peptide consists of the amino acid sequence Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: 3). |