COMPOSITIONS USEFUL FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS
원문보기
IPC분류정보
국가/구분
United States(US) Patent
공개
국제특허분류(IPC7판)
A61K-038/10
A61K-038/04
A61K-047/64
A61K-047/55
A61K-045/06
A61K-031/196
C07K-014/00
C07K-007/08
A61K-031/4402
출원번호
16275641
(2019-02-14)
공개번호
20190262420
(2019-08-29)
발명자
/ 주소
SHAILUBHAI, Kunwar
출원인 / 주소
SHAILUBHAI, Kunwar
인용정보
피인용 횟수 :
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0
초록▼
This invention provides novel peptides and methods to prevent, control, and treat an inflammation, cancer and other disorders, particularly of the gastrointestinal tract and the lung by administering at least one agonist of guanalyte cyclase receptor either alone or in combination with a compound se
This invention provides novel peptides and methods to prevent, control, and treat an inflammation, cancer and other disorders, particularly of the gastrointestinal tract and the lung by administering at least one agonist of guanalyte cyclase receptor either alone or in combination with a compound selected from i) 5-aminosalicyclic acid (5-ASA) or a derivative or a pharmaceutically acceptable salt thereof; ii) mercaptopurine; or iii) an anti-TNF therapy.
대표청구항▼
1. A composition comprising a guanylate cyclase receptor agonist (GCRA) peptide consisting essentially of the sequence of any one of Tables 1-8 and a compound selected from i) 5-aminosalicyclic acid (5-ASA) or a derivative or a pharmaceutically acceptable salt thereof; ii) mercaptopurine; iii) an an
1. A composition comprising a guanylate cyclase receptor agonist (GCRA) peptide consisting essentially of the sequence of any one of Tables 1-8 and a compound selected from i) 5-aminosalicyclic acid (5-ASA) or a derivative or a pharmaceutically acceptable salt thereof; ii) mercaptopurine; iii) an anti-TNF therapy; or iv) an antibiotic. 2. The composition of claim 1, wherein said 5-ASA or derivative or pharmaceutically acceptable salt thereof is covalently linked to the N terminus and/or the C terminus of said peptide. 3. The composition of claim 2, wherein said peptide is selected from the group consisting of [5-ASA]-GCRA (formula A),GCRA-[5-ASA] (formula B), and[5-ASA]-GCRA-[5-ASA] (formula C), 4. The composition of claim 1, further comprising a pharmaceutical carrier, excipient or diluent. 5. The composition of claim 1, wherein said derivative is sulfasalazine. 6. The composition of claim 1, wherein said peptide is a bicyclic peptide comprising the sequence of any one of Tables 1, 3, 4, 5, and 8. 7. A formulation comprising an inert carrier coated with composition of claim 2 and an enteric coating which releases said composition at pH5 or pH7. 8. The formulation of claim 7, wherein said inert carrier is a selected from mannitol, lactose, a microcrystalline cellulose, or starch. 9. A method for treating a condition that responds to enhanced cGMP levels in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a composition of claim 1, wherein said composition is administered in an amount sufficient to increase water transport in the gastrointestinal tract and induce cGMP production in a gastrointestinal epithelial cell. 10. A method for preventing or treating a condition selected from the group consisting of ulcerative colitis, Crohn's disease, irritable bowel syndrome (IBS), non-ulcer dyspepsia, chronic intestinal pseudo-obstruction, functional dyspepsia, colonic pseudo-obstruction, duodenogastric reflux, constipation, constipation associated with use of opiate pain killers, post-surgical constipation, constipation associated with neuropathic disorders, gastroesophageal reflux disease (GERD), Celiac disease, gastroparesis, heartburn, poor gastrointestinal motility, congestive heart failure, hypertension, benign prostatic hyperplasia (BPH), colon cancer, lung cancer, bladder cancer, liver cancer, salivary gland cancer or skin cancer, bronchitis, tissue inflammation, organ inflammation, respiratory inflammation, asthma, COPD, lipid metabolism disorders, biliary disorders, cardiovascular disease, obesity and an endocrine disorder comprising administering to a subject in need thereof a therapeutically effective amount of a composition of claim 1. 11. A method of colonic cleansing, comprising administering to a subject in need thereof an effective amount of a composition of claim 2. 12. The method of claims 9, 10, or 11, further comprising administering a therapeutically effective amount of a cGMP-dependent phosphodiesterase inhibitor. 13. The method of claim 12, wherein said cGMP-dependent phosphodiesterase inhibitor is administered either concurrently or sequentially with said peptide. 14. The method of claim 12, wherein said cGMP-dependent phosphodiesterase inhibitor is selected from the group consisting of sulindac sulfone, zaprinast, motapizone, vardenafil, and sildenafil. 15. The method of claim 9 or 10, further comprising administering a therapeutically effective amount of at least one anti-inflammatory agent. 16. The method of claim 15, wherein said anti-inflammatory agent is a steroid or nonsteroid anti-inflammatory drug (NSAID). 17. The composition of claim 1, wherein said anti-TNF therapy is selected from the group consisting of infliximab (Remicade®), adalimumab (Humira®), certolizumab pegol (Cimzia®), golimumab (Simponi®), etanercept (Enbrel®), xanthine derivatives (e.g., pentoxifylline) and bupropion.
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