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US 2024/0199697 A1Published application
Compositions for Colon Cleansing and the Treatment of Gastrointestinal Disorders
AssigneeIronwood Pharmaceuticals, Inc.
InventorsMark G. Currie, Robert Solinga, Christopher Leitheiser
Life of this patent
Estimating the term…
Abstract
The present invention provides peptides and compositions that are useful for the treatment of gastrointestinal disorders or for colon cleansing. The present invention also provides compositions and methods of treating gastrointestinal disorders and pharmaceutical compositions for accomplishing the same. In some embodiments, these pharmaceutical compositions include oral dosage forms.
Claims53
A peptide or a pharmaceutically acceptable salt thereof, wherein the peptide comprises the amino acid sequence
- Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO:
- 1), or a pharmaceutically acceptable salt thereof;
- wherein
- Xaa1 is BE or is absent;
- Xaa2 is BK, Asn or is absent;
- Xaa3 is Asn, Ser or is absent;
- Xaa4 is Ser or is absent;
- Xaa5 is Ser, Asn, Ile, BE or is absent;
- Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
- Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), Hag, or Asp;
- Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
- Xaa9 is Glu, Asp, Ser, Thr, or Gln;
- Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
- Xaa11 is Cys, Ag, or penicillamine (Pen);
- Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
- Xaa13 is Asn or Leu;
- Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
- Xaa16 is Cys, Ag, Pen or Cth;
- Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
- Xaa19 is Cys, Ag or Pen;
- Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
- Xaa21 is absent or Asn;
- wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro;
- and
- wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16 and Xaa11 and Xaa19.
22 more elements
A peptide or a pharmaceutically acceptable salt thereof, wherein the peptide consists of the amino acid sequence
- Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO:
- 1), or a pharmaceutically acceptable salt thereof;
- wherein
- Xaa1 is BE or is absent;
- Xaa2 is BK, Asn or is absent;
- Xaa3 is Asn, Ser or is absent;
- Xaa4 is Ser or is absent;
- Xaa5 is Ser, Asn, Ile, BE or is absent;
- Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
- Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), Hag, or Asp;
- Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
- Xaa9 is Glu, Asp, Ser, Thr, or Gln;
- Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
- Xaa11 is Cys, Ag, or penicillamine (Pen);
- Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
- Xaa13 is Asn or Leu;
- Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
- Xaa16 is Cys, Ag, Pen or Cth;
- Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
- Xaa19 is Cys, Ag or Pen;
- Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
- Xaa21 is absent or Asn;
- wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro;
- and
- wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16 and Xaa11 and Xaa19.
22 more elements
A peptide or a pharmaceutically acceptable salt thereof, wherein the peptide comprises the amino acid sequence:
- Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Cys11 Xaa12 Asn13 Xaa14 Ala15 Cys16 Xaa17 Gly18 Cys19 Xaa20 Xaa21 (SEQ ID NO:
- 93), or a pharmaceutically acceptable salt thereof;
- wherein
- Xaa1 is BE or is absent;
- Xaa2 is BK or is absent;
- Xaa3 is Asn or is absent;
- Xaa4 is Ser or is absent;
- Xaa5 is Ser, Asn, Ile, or is absent;
- Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), or is absent;
- Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), Hag, or Asp;
- Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
- Xaa9 is Glu, Asp, Ser, Thr, or Gln;
- Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
- Xaa12 is Cys, allylglycine (Ag), Hag, or Val;
- Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
- Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, or Ala;
- Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
- Xaa21 is absent or Asn;
- wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, or OH-Pro;
- and
- wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Cys16, and Cys11 and Cys19.
18 more elements
A pharmaceutical composition comprising a peptide or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, diluent or carrier, wherein the peptide or pharmaceutically acceptable salt thereof comprises the amino acid sequence:
- Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO:
- 1), or a pharmaceutically acceptable salt thereof;
- wherein
- Xaa1 is BE or is absent;
- Xaa2 is BK, Asn or is absent;
- Xaa3 is Asn, Ser or is absent;
- Xaa4 is Ser or is absent;
- Xaa5 is Ser, Asn, Ile, BE or is absent;
- Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
- Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), 4-pentenoic acid (Pent), Hag, or Asp;
- Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
- Xaa9 is Glu, Asp, Ser, Thr, or Gln;
- Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
- Xaa11 is Cys, Ag, or penicillamine (Pen);
- Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
- Xaa13 is Asn or Leu;
- Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
- Xaa16 is Cys, Ag, Pen or Cth;
- Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
- Xaa19 is Cys, Ag or Pen;
- Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
- Xaa21 is absent or Asn;
- wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro;
- and
- wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19.
22 more elements
A method of cleansing the colon of a subject in preparation for a colonoscopy procedure comprising administering to the subject an effective dose of a colon cleansing composition;
- wherein the colon cleansing composition comprises a pharmaceutically acceptable excipient, diluent or carrier, and a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide or a pharmaceutically acceptable salt thereof comprises the amino acid sequence:
- Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO:
- 1), or a pharmaceutically acceptable salt thereof;
- wherein
- Xaa1 is BE or is absent;
- Xaa2 is BK, Asn or is absent;
- Xaa3 is Asn, Ser or is absent;
- Xaa4 is Ser or is absent;
- Xaa5 is Ser, Asn, Ile, BE or is absent;
- Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
- Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), 4-pentenoic acid (Pent), Hag, or Asp;
- Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
- Xaa9 is Glu, Asp, Ser, Thr, or Gln;
- Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
- Xaa11 is Cys, Ag, or penicillamine (Pen);
- Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
- Xaa13 is Asn or Leu;
- Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
- Xaa16 is Cys, Ag, Pen or Cth;
- Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
- Xaa19 is Cys, Ag or Pen;
- Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
- Xaa21 is absent or Asn;
- wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro;
- and
- wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19.
23 more elements
The method of claim 51, further comprising administering to the subject a pharmaceutical composition comprising an active ingredient selected from opioids, tramadol, beta-3 adrenergic receptor agonists, anti-cholinergic agents, and tricyclic antidepressants.
A pharmaceutical composition for use in cleansing the colon in a subject in preparation for a colonoscopy procedure, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient, diluent or carrier, and a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide or a pharmaceutically acceptable salt thereof comprises the amino acid sequence:
- Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO:
- 1), or a pharmaceutically acceptable salt thereof;
- wherein
- Xaa1 is BE or is absent;
- Xaa2 is BK, Asn or is absent;
- Xaa3 is Asn, Ser or is absent;
- Xaa4 is Ser or is absent;
- Xaa5 is Ser, Asn, Ile, BE or is absent;
- Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
- Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), 4-pentenoic acid (Pent), Hag, or Asp;
- Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
- Xaa9 is Glu, Asp, Ser, Thr, or Gln;
- Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
- Xaa11 is Cys, Ag, or penicillamine (Pen);
- Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
- Xaa13 is Asn or Leu;
- Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
- Xaa16 is Cys, Ag, Pen or Cth;
- Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
- Xaa19 is Cys, Ag or Pen;
- Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
- Xaa21 is absent or Asn;
- wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro;
- and
- wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19.
22 more elements
Dependencies are inferred from the claim text.