Protein Hydrolysate Enriched In Peptides Inhibiting DPP-IV And Their Use

• US 20090075904A1
• Filed: 11/30/2005
• Published: 03/19/2009
• Est. Priority Date: 12/23/2004
• Status: Active Grant

• Current Assignee: Campina Nederland Holding B.V.
• Original Assignee: Campina Nederland Holding B.V.
• Inventors: Boots, Jan-Willem Pieter
• Granted Patent: US 8,273,710 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A23J 1/202 Casein or caseinates
• CPC Class Codes: A23J 1/205 from whey, e.g. lactalbumine
• CPC Class Codes: A23V 2250/5488 Soybean protein
• CPC Class Codes: A61K 38/005 Enzyme inhibitors protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/018 from milk
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: C07K 14/4717 Plasma globulins, lactoglobulin
• CPC Class Codes: C07K 14/4732 Casein in foodstuffs A23J
• CPC Class Codes: C07K 5/0808 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 5/0823 and Pro-amino acid; Derivatives thereof
• CPC Class Codes: C07K 5/1008 the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/101 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 5/1013 the side chain containing O or S as heteroatoms, e.g. Cys, Ser
• CPC Class Codes: C07K 5/1019 : with the first amino acid being basic
• CPC Class Codes: C07K 5/1024 : with the first amino acid being heterocyclic
• CPC Class Codes: C07K 7/06 : having 5 to 11 amino acids
• CPC Class Codes: C12P 21/06 : produced by the hydrolysis of a peptide bond, e.g. hydrolysate products preparing foodstuffs by protein hydrolysis A23J3/00

Abstract

Disclosed is a protein hydrolysate having DPP-IV inhibiting activity, the hydrolysate being enriched in peptides having a length of 2-8 amino acids comprising at least one proline residue, an isolated peptide derivable from such a protein hydrolysate, or a mixture thereof, and the use of such protein hydrolysate or isolated peptide for the manufacture of a medicament, food supplement, beverage or food product for prophylaxis and/or treatment of a DPP-IV mediated condition, in particular chosen from the group of obesity, type 2 diabetes mellitus and an immunological disorder.

Claims

1-14. -14. (canceled)

15. A protein hydrolysate having DPP-IV inhibiting activity, the hydrolysate enriched in peptides of 2-8 amino acids and each peptide comprising at least one proline residue.

16. The protein hydrolysate according to claim 15, wherein the hydrolysate is a protein hydrolysate of milk.

17. The protein hydrolysate according to claim 16, wherein the protein hydrolysate is a hydrolysate of casein.

18. The protein hydrolysate according to claim 15 comprising between 20 and 80 wt. % of peptides having a length of 3-7 amino acids.

19. The protein hydrolysate according to claim 15, wherein the peptides comprise at least one peptide selected from the group consisting of LPL, IPI, PFP, LPLP (SEQ ID NO:

29), HPIK (SEQ ID NO;

     30), LPVP (SEQ ID NO;

     31), MPLW (SEQ ID NO;

     6), GPFP (SEQ ID NO;

     32), PLLQ (SEQ ID NO;

     33), KVLP (SEQ ID NO;

     34), APFPE (SEQ ID NO;

     35), LPQYL (SEQ ID NO;

     36), LPVPQ (SEQ ID NO;

     37), VPYPQ (SEQ ID NO;

     38), APFPEVF (SEQ ID NO;

     39), GPFPIIV (SEQ ID NO;

     22), EMPFPK (SEQ ID NO;

     40), PQSVLS (SEQ ID NO;

     41), YVPEPF (SEQ ID NO;

     42), VPLGTQ (SEQ ID NO;

     43), and LPVPQK (SEQ ID NO;

     44).

20. The protein hydrolysate according to claim 19, wherein the peptides comprise at least one peptide selected from the group consisting of VPYPQ (SEQ ID NO:

38), VPLGTQ (SEQ ID NO;

     43), LPVPQK (SEQ ID NO;

     44), KVLP (SEQ ID NO;

     34), LPL and IPI.

21. An isolated peptide selected from the group consisting of LPL, IPI, PFP, LPLP (SEQ ID NO:

29), HPIK (SEQ ID NO;

     30), LPVP (SEQ ID NO;

     31), MPLW (SEQ ID NO;

     6), GPFP (SEQ ID NO;

     32), PLLQ (SEQ ID NO;

     33), KVLP (SEQ ID NO;

     34), APFPE (SEQ ID NO;

     35), LPQYL (SEQ ID NO;

     36), LPVPQ (SEQ ID NO;

     37), VPYPQ (SEQ ID NO;

     38), APFPEVF (SEQ ID NO;

     39), GPFPIIV (SEQ ID NO;

     22), EMPFPK (SEQ ID NO;

     40), PQSVLS (SEQ ID NO;

     41), YVPEPF (SEQ ID NO;

     42), VPLGTQ (SEQ ID NO;

     43), LPVPQK (SEQ ID NO;

     44), LF, LL, II, LC and VTKCCTE (SEQ ID NO;

     45), wherein said peptide has DPP-IV inhibiting activity.

22. The isolated peptide according to claim 21, wherein the peptide is selected from the group consisting of VPYPQ (SEQ ID NO:

38), VPLGTQ (SEQ ID NO;

     43), LPVPQK (SEQ ID NO;

     44), KVLP (SEQ ID NO;

     34), LPL and IPI.

23. The isolated peptide according to claim 21 wherein the peptide is derived from protein hydrolysate.

24. A method for treatment of a DPP-IV mediated condition comprising administering to a subject in need thereof a protein hydrolysate enriched in peptides of 2-8 amino acids and each peptide comprising at least one proline residue.

25. The method for treatment according to claim 24 wherein the treatment is prophylactic.

26. The method according to claim 24, wherein the DPP-IV mediated condition is obesity, type 2 diabetes mellitus, an immunological disorder, or combinations thereof.

27. The method according to claim 26 for the treatment of obesity.

28. The method according to claim 26 for the treatment of type 2 diabetes mellitus.

29. The method according to claim 26 for the treatment of an immunological disorder.

30. The method according to claim 29 wherein the immunological disorder is an autoimmune disease selected from the group consisting of rheumatoid arthritis, multiple sclerosis, and Graves'"'"' disease.

31. A method for treatment of a DPP-IV mediated condition comprising administering to a subject in need thereof an isolated peptide selected from the group consisting of LPL, IPI, PFP, LPLP (SEQ ID NO:

29), HPIK (SEQ ID NO;

     30), LPVP (SEQ ID NO;

     31), MPLW (SEQ ID NO;

     6), GPFP (SEQ ID NO;

     32), PLLQ (SEQ ID NO;

     33), KVLP (SEQ ID NO;

     34), APFPE (SEQ ID NO;

     35), LPQYL (SEQ ID NO;

     36), LPVPQ (SEQ ID NO;

     37), VPYPQ (SEQ ID NO;

     38), APFPEVF (SEQ ID NO;

     39), GPFPIIV (SEQ ID NO;

     22), EMPFPK (SEQ ID NO;

     40), PQSVLS (SEQ ID NO;

     41), YVPEPF (SEQ ID NO;

     42), VPLGTQ (SEQ ID NO;

     43), LPVPQK (SEQ ID NO;

     44), LF, LL, II, LC and VTKCCTE (SEQ ID NO;

     45), wherein said peptide has DPP-IV inhibiting activity.

32. The method for treatment according to claim 31 wherein the treatment is prophylactic.