IP Library › Patent Application 12598792
Patent Application
App. No. 12/598,792

Compositions and Methods for Treating Disorders Associated with Salt or Fluid Retention

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Quick Facts
Patent No.
US None
App. No.
12/598,792
Abstract

Methods for reducing the risk of or treating a disorder associated with fluid and/or salt retention in a patient are described. The methods include administering to the patient an agent selected from: a) an agent that reduces sodium absorption in the intestine; b) an agent that increases anion secretion in the intestine; or c) an agent that both reduces sodium absorption in the intestine and increases anion secretion in the intestine.

Claims (233)

1 - 355 . (canceled)

356 . A method of reducing the risk of or treating a disorder associated with fluid and/or salt retention in a patient, the method comprising administering to the patient an agent selected from: a) an agent that reduces sodium absorption in the intestine; b) an agent that increases anion secretion in the intestine; or c) an agent that both reduces sodium absorption in the intestine and increases anion secretion in the intestine.

357 . The method of claim 356 , wherein the agent reduces sodium absorption in the intestine.

358 . The method of claim 356 , wherein the agent increases anion secretion in the intestine.

359 . The method of claim 356 , wherein the agent both reduces sodium absorption in the intestine and increases anion secretion in the intestine.

360 . The method of claim 356 , wherein the agent is selected from: a) a guanylate cyclase receptor C agonist, b) a soluble guanylate cyclase modulator, c) a prostanoid, d) a chloride channel activator, e) a 5HT4 agonist, f) a cyclic nucleotide, g) a sodium transport inhibitor, h) a laxative, i) a cystic fibrosis transmembrane conductance regulator (CTFR) modulator, j) an agent that affects cAMP levels, k) a renin inhibitor, and l) an aldosterone antagonist.

361 . The method of claim 360 , wherein the agent is a guanylate cyclase receptor C agonist.

362 . The method of claim 360 , wherein the agent is a soluble guanylate cyclase modulator.

363 . The method of claim 360 further comprising administering an anti-diabetic agent.

364 . The method of claim 360 further comprising administering an anti-obesity agent.

365 . The method of claim 360 further comprising administering an antihypertensive agent.

366 . The method of claim 360 further comprising administering potassium or salt thereof.

367 . The method of claim 360 further comprising administering a PDE inhibitor.

368 . The method of claim 360 further comprising administering a polymer resin.

369 . The method of claim 360 further comprising administering a lipid altering agent.

370 . The method of claim 356 , wherein the agent comprises a peptide that activates the guanylate cyclase C receptor.

371 . The method of claim 370 further comprising administering psyllium.

372 . The method of claim 370 wherein the peptide is selected from:

Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Asn Asp Asp Cys Glu Leu Cys Val Asn Val Ala Cys

Thr Gly Cys Leu;

Asn Asp Glu Cys Glu Leu Cys Val Asn Val Ala Cys

Thr Gly Cys Leu;

Phe Lys Thr Leu Arg Thr Ile Ala Asn Asp Asp Cys

Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu;

Phe Lys Thr Leu Arg Thr Ile Ala Asn Asp Glu Cys

Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu;

Val Tyr Ile Gln Tyr Gln Gly Phe Arg Val Gln Leu

Glu Ser Met Lys Lys Leu Ser Asp Leu Glu Ala Gln

Trp Ala Pro;

Ser Pro Arg Leu Gln Ala Gln Ser Leu Leu Pro Ala

Val Cys His His Pro Ala Leu Pro Gln Asp Leu Gln

Pro Val Cys;

Ala Ser Gln Glu Ala Ser Ser Ile Phe Lys Thr Leu

Arg Thr Ile Ala Asn Asp Asp Cys Glu Leu Cys Val

Asn Val Ala Cys Thr Gly Cys Leu;

Val Tyr Ile Gln Tyr Gln Gly Phe Arg Val Gln Leu

Glu Ser Met Lys Lys Leu Ser Asp Leu Glu Ala Gln

Trp Ala Pro;

Ser Pro Arg Leu Gln Ala Gln Ser Leu Leu Pro Ala

Val Cys His His Pro Ala Leu Pro Gln Asp Leu Gln

Pro Val Cys;

Ala Ser Gln Glu Ala Ser Ser Ile Phe Lys Thr Leu

Arg Thr Ile Ala Asn Asp Glu Cys Glu Leu Cys Val

Asn Val Ala Cys Thr Gly Cys Leu;

Pro Gly Thr Cys Glu Ile Cys Ala Tyr Ala Ala Cys

Thr Gly Cys;

Val Thr Val Gln Asp Gly Asn Phe Ser Phe Ser Leu

Glu Ser Val Lys Lys Leu Lys Asp Leu Gln Glu Pro

Gln Glu Pro;

Arg Val Gly Lys Leu Arg Asn Phe Ala Pro Ile Pro

Gly Glu Pro Val Val Pro Ile Leu Cys Ser Asn Pro

Asn Phe Pro;

Glu Glu Leu Lys Pro Leu Cys Lys Glu Pro Asn Ala

Gln Glu Ile Leu Gln Arg Leu Gln Glu Ile Ala Glu

Asp Pro Gly Thr Cys Glu Ile Cys Ala Tyr Ala Ala

Cys Thr Gly Cys;

Met Pro Ser Thr Gln Tyr Ile Arg Arg Pro Ala Ser

Ser Tyr Ala Ser Cys Ile Trp Cys Thr Thr Ala Cys

Ala Ser Cys His Gly Arg Thr Thr Lys Pro Ser Leu

Ala Thr;

Ala Asp Leu Cys Glu Ile Cys Ala Phe Ala Ala Cys

Thr Gly Cys Leu;

Val Gln Val Glu Glu Gly Gly Phe Ser Phe Pro Leu

Asp Ala Val Lys Lys Leu Glu Glu Leu Met Gly Val

Asp Met;

Thr Val Lys Gln Ser Pro Arg Leu Ala Lys Thr Ser

Thr Thr Ala Val Cys Thr Asn Pro Asp Leu Pro Ala

Val Phe Leu;

Pro Leu Cys Lys Ser Lys Gly Ala Ala Asn Ser Phe

Phe Arg Leu Gly Phe Val Ala Ala Arg Ala Asp Leu

Cys Glu Ile Cys Ala Phe Ala Ala Cys Thr Gly Cys

Leu;

Gln Glu Glu Cys Glu Leu Cys Ile Asn Met Ala Cys

Thr Gly Tyr;

Val Tyr Ile Gln Tyr Glu Gly Phe Gln Val Asn Leu

Asp Ser Val Lys Lys Leu Asp Lys Leu Leu Glu Gln

Leu Arg Gly;

Phe His His Gln Met Gly Asp Gln Arg Asp Pro Ser

Ile Leu Cys Ser Asp Pro Ala Leu Pro Ser Asp Leu

Gln Pro Val;

and

Cys Glu Asn Ser Gln Ala Val Asn Ile Phe Arg Ala

Leu Arg Tyr Ile Asn Gln Glu Glu Cys Glu Leu Cys

Ile Asn Met Ala Cys Thr Gly Tyr.

373 . The method of claim 370 , wherein the peptide comprises the amino acid sequence Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr

374 . The method of claim 370 , wherein the peptide consisting of the amino acid sequence Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr

375 . The method of claim 356 , wherein the disorder is associated with fluid retention.

376 . The method of claim 356 , wherein the disorder is associated with salt retention.

377 . The method of claim 356 , wherein the disorder is a cardiovascular disorder.

378 . The method of claim 377 , wherein the cardiovascular disorder is selected from cardiomyopathy, hypertension, congestive heart failure, cardiac hypertrophy, heart attack, or stroke.

379 . A pharmaceutical composition comprising: a first agent selected from: an anti-hypertensive agent; an anti-diabetic agent; an anti-obesity agent; potassium or a salt thereof; a PDE inhibitor; a polymer resin; or a lipid altering agent; and

a second agent selected from: a) an agent that reduces sodium absorption in the intestine; b) an agent that increases anion secretion in the intestine; or c) an agent that both reduces sodium absorption in the intestine and increases anion secretion in the intestine.

380 . The pharmaceutical composition of claim 379 , wherein the second agent reduces sodium absorption in the intestine.

381 . The pharmaceutical composition of claim 379 , wherein the second agent increases anion secretion in the intestine.

382 . The pharmaceutical composition of claim 379 , wherein the second agent both reduces sodium absorption in the intestine and increases anion secretion in the intestine.

383 . The pharmaceutical composition of claim 379 , wherein the second agent is selected from: a) a guanylate cyclase receptor C agonist, b) a soluble guanylate cyclase modulator, c) a prostanoid, d) a chloride channel activator, e) a 5HT4 agonist, f) a cyclic nucleotide, g) a sodium transport inhibitor, h) a laxative, i) a cystic fibrosis'transmembrane conductance regulator (CTFR) modulator, j) an agent that affects cAMP levels, k) a phosphodiesterase inhibitor, l) a renin inhibitor, m) an aldosterone antagonist, n) potassium, and o) a polymer resin.

384 . The pharmaceutical composition of claim 379 , wherein the second agent is a guanylate cyclase receptor C agonist.

385 . The pharmaceutical composition of claim 379 , wherein the second agent is a soluble guanylate cyclase modulator.

386 . The pharmaceutical compositions of claim 379 , wherein the second agent comprises a peptide that activates the guanylate cyclase C receptor.

387 . The pharmaceutical composition of claim 386 further comprising psyllium.

388 . The pharmaceutical composition of claim 386 , wherein the peptide comprises an amino acid sequence selected from:

Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys Tyr;

d-Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

d-Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly

Cys;

Asn Asp Asp Cys Glu Leu Cys Val Asn Val Ala Cys

Thr Gly Cys Leu;

Asn Asp Glu Cys Glu Leu Cys Val Asn Val Ala Cys

Thr Gly Cys Leu;

Phe Lys Thr Leu Arg Thr Ile Ala Asn Asp Asp Cys

Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu;

Phe Lys Thr Leu Arg Thr Ile Ala Asn Asp Glu Cys

Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu;

Val Tyr Ile Gln Tyr Gln Gly Phe Arg Val Gln Leu

Glu Ser Met Lys Lys Leu Ser Asp Leu Glu Ala Gln

Trp Ala Pro;

Ser Pro Arg Leu Gln Ala Gln Ser Leu Leu Pro Ala

Val Cys His His Pro Ala Leu Pro Gln Asp Leu Gln

Pro Val Cys;

Ala Ser Gln Glu Ala Ser Ser Ile Phe Lys Thr Leu

Arg Thr Ile Ala Asn Asp Asp Cys Glu Leu Cys Val

Asn Val Ala Cys Thr Gly Cys Leu;

Val Tyr Ile Gln Tyr Gln Gly Phe Arg Val Gln Leu

Glu Ser Met Lys Lys Leu Ser Asp Leu Glu Ala Gln

Trp Ala Pro;

Ser Pro Arg Leu Gln Ala Gln Ser Leu Leu Pro Ala

Val Cys His His Pro Ala Leu Pro Gln Asp Leu Gln

Pro Val Cys;

Ala Ser Gln Glu Ala Ser Ser Ile Phe Lys Thr Leu

Arg Thr Ile Ala Asn Asp Glu Cys Glu Leu Cys Val

Asn Val Ala Cys Thr Gly Cys Leu;

Pro Gly Thr Cys Glu Ile Cys Ala Tyr Ala Ala Cys

Thr Gly Cys;

Val Thr Val Gln Asp Gly Asn Phe Ser Phe Ser Leu

Glu Ser Val Lys Lys Leu Lys Asp Leu Gln Glu Pro

Gln Glu Pro;

Arg Val Gly Lys Leu Arg Asn Phe Ala Pro Ile Pro

Gly Glu Pro Val Val Pro Ile Leu Cys Ser Asn Pro

Asn Phe Pro;

Glu Glu Leu Lys Pro Leu Cys Lys Glu Pro Asn Ala

Gln Glu Ile Leu Gln Arg Leu Glu Glu Ile Ala Glu

Asp Pro Gly Thr Cys Glu Ile Cys Ala Tyr Ala Ala

Cys Thr Gly Cys;

Met Pro Ser Thr Gln Tyr Ile Arg Arg Pro Ala Ser

Ser Tyr Ala Ser Cys Ile Trp Cys Thr Thr Ala Cys

Ala Ser Cys His Gly Arg Thr Thr Lys Pro Ser Leu

Ala Thr;

Ala Asp Leu Cys Glu Ile Cys Ala Phe Ala Ala Cys

Thr Gly Cys Leu;

Val Gln Val Glu Glu Gly Gly Phe Ser Phe Pro Leu

Asp Ala Val Lys Lys Leu Glu Glu Leu Met Gly Val

Asp Met;

Thr Val Lys Gln Ser Pro Arg Leu Ala Lys Thr Ser

Thr Thr Ala Val Cys Thr Asn Pro Asp Leu Pro Ala

Val Phe Leu;

Pro Leu Cys Lys Ser Lys Gly Ala Ala Asn Ser Phe

Phe Arg Leu Gly Phe Val Ala Ala Arg Ala Asp Leu

Cys Glu Ile Cys Ala Phe Ala Ala Cys Thr Gly Cys

Leu;

Gln Glu Glu Cys Glu Leu Cys Ile Asn Met Ala Cys

Thr Gly Tyr;

Val Tyr Ile Gln Tyr Glu Gly Phe Gln Val Asn Leu

Asp Ser Val Lys Lys Leu Asp Lys Leu Leu Gln Gln

Leu Arg Gly;

Phe His His Gln Met Gly Asp Gln Arg Asp Pro Ser

Ile Leu Cys Ser Asp Pro Ala Leu Pro Ser Asp Leu

Gln Pro Val;

and

Cys Glu Asn Ser Gln Ala Val Asn Ile Phe Arg Ala

Leu Arg Tyr Ile Asn Gln Glu Glu Cys Glu Leu Cys

Ile Asn Met Ala Cys Thr Gly Tyr.

389 . The pharmaceutical composition of claim 386 , wherein the peptide comprises the amino acid sequence Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr.

390 . The pharmaceutical composition of claim 386 , wherein the peptide consisting of the amino acid sequence Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 22, 2010
From: CURRIE, MARK G.; ZIMMER, DANIEL P.
To: IRONWOOD PHARMACEUTICALS, INC.
Reel/Frame 023971/0939 →