Treatments for Gastrointestinal Disorders

A method of preventing, treating or ameliorating a disorder selected from inflammatory bowel disease (IBD), diverticulitis, colorectal cancer, an inflammatory disorder, obesity, congestive heart failure, benign prostatic hyperplasia (BPH), pain, salt retention or fluid retention, wherein the method comprises administering a pharmaceutical composition comprising a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide comprises the amino acid sequence:

• Xaa1 Xaa2 Xaa3 Xaa4 Cys5 Xaa6 Xaa7 Xaa8 Cys9 Asn10 Pro11 Ala12 Cys13 Xaa14 Gly15 Xaa16 Xaa17, (SEQ ID NO:1) or a pharmaceutically acceptable salt thereof;
• wherein
• Xaa1 is Asn, D-Asn, Gln, D-Gln, Pro, D-Pro, Ala, β-Ala, D-Ala, Val, D-Val, Gly, Thr, D-Thr, Asp, D-Asp, β-carboxylated Asp, Glu, D-Glu, γ-carboxylated Glu, α-aminosuberic acid (Asu), α-aminoadipic acid (Aad), or α-aminopimelic acid (Apm);
• Xaa2 is Asp, β-carboxylated Asp, Glu, γ-carboxylated Glu, Asu, Aad, Apm, or is absent;
• Xaa3 is Asp, β-carboxylated Asp, Glu, γ-carboxylated Glu, Asu, Aad, Apm, or is absent;
• Xaa4 is Cys or D-Cys;
• Xaa6 is Asp or Glu;
• Xaa7 is Tyr, Leu, Phe or Ile;
• Xaa8 is Cys or D-Cys;
• Xaa14 is Thr, Ala or Phe;
• Xaa16 is Cys or D-Cys;
• and
• Xaa17 is Tyr, D-Tyr, or is absent;
• wherein:
• Xaa1 may be modified on its amino group by methyl, ethanedioic acid, propanedioic acid, butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid or octanedioic acid;
• and
• if both Xaa2 and Xaa3 are absent, then Xaa1 must be β-carboxylated Asp or γ-carboxylated Glu, or Xaa1 must be Asp, D-Asp, Glu, D-Glu, Asu, Aad, Apm and must be modified on its amino group by ethanedioic acid, propanedioic acid, or butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid or octanedioic acid.

A method of preventing, treating or ameliorating a disorder selected from inflammatory bowel disease (IBD), diverticulitis, colorectal cancer, an inflammatory disorder, obesity, congestive heart failure, benign prostatic hyperplasia (BPH), pain, salt retention or fluid retention, wherein the method comprises administering a pharmaceutical composition comprising a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide consists of the amino acid sequence:

• Xaa1 Xaa2 Xaa3 Xaa4 Cys5 Xaa6 Xaa7 Xaag Cys9 Asn10 Pro11 Ala12 Cys13 Xaa14 Gly15 Xaa16 Xaa17, (SEQ ID NO:1) or a pharmaceutically acceptable salt thereof;
• wherein
• Xaa1 is Asn, D-Asn, Gln, D-Gln, Pro, D-Pro, Ala, β-Ala, D-Ala, Val, D-Val, Gly, Thr, D-Thr, Asp, D-Asp, β-carboxylated Asp, Glu, D-Glu, γ-carboxylated Glu, α-aminosuberic acid (Asu), α-aminoadipic acid (Aad), or α-aminopimelic acid (Apm);
• Xaa2 is Asp, β-carboxylated Asp, Glu, γ-carboxylated Glu, Asu, Aad, Apm, or is absent;
• Xaa3 is Asp, β-carboxylated Asp, Glu, γ-carboxylated Glu, Asu, Aad, Apm, or is absent;
• Xaa4 is Cys or D-Cys;
• Xaa6 is Asp or Glu;
• Xaa7 is Tyr, Leu, Phe or Ile;
• Xaa8 is Cys or D-Cys;
• Xaa14 is Thr, Ala or Phe;
• Xaa16 is Cys or D-Cys;
• and
• Xaa17 is Tyr, D-Tyr, or is absent;
• wherein:
• Xaa1 may be modified on its amino group by methyl, ethanedioic acid, propanedioic acid, butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid or octanedioic acid;
• and
• if both Xaa2 and Xaa3 are absent, then Xaa1 must be β-carboxylated Asp or γ-carboxylated Glu, or Xaa1 must be Asp, D-Asp, Glu, D-Glu, Asu, Aad, Apm and must be modified on its amino group by ethanedioic acid, propanedioic acid, or butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid or octanedioic acid.