Claims
- 1. A modified Neuropeptide Y, having blood pressure lowering activity and consisting of a fragment of 8 to 18 amino acids of a Neuropeptide Y, which fragment comprises an amino acid segment selected from the group consisting of amino acids 28 to 35 of a Neuropeptide Y, wherein D-Thr is substituted for Thr at position 32;
- pharmaceutically acceptable salts thereof; and
- mixtures thereof.
- 2. The modified Neuropeptide Y of claim 1, comprising 9 to 17 amino acids.
- 3. The modified Neuropeptide Y of claim 2, comprising 10 to 16 amino acids.
- 4. The modified Neuropeptide Y of claim 3, comprising 15 amino acids.
- 5. The modified Neuropeptide Y of claim 4, which is selected from the group consisting of
- D-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH.sub.2 (SEQ ID NO: 1);
- D-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH.sub.2 (SEQ ID NO: 2);
- D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH.sub.2 (SEQ ID No: 3);
- Ac-D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH2 (SEQ ID No: 4);
- D-Phe(NO2)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO2)-NH2 (SEQ ID NO: 5);
- Ac-D-Phe(NO2)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO2)-NH2 (SEQ ID NO: 6);
- D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH2 (SEQ ID NO: 7);
- Ac-D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH2 (SEQ ID NO: 8);
- D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH2 (SEQ ID NO: 9);
- Ac-D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH2 (SEQ ID NO: 10);
- D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH2 (SEQ ID NO: 11); and
- D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH2 (SEQ ID NO: 12);
- wherein Ac represents acetyl, Phe(NO.sub.2) represents NO.sub.2 substituted phenylalanine, Phe(pCl) represents phenylalanine substituted by Cl on the phenylalanine ring, and Phe(pF) represents phenylalanine substituted by F on the phenylalanine.
- 6. The modified Neuropeptide Y of claim 5, which is freeze-dried or lyophilized.
- 7. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 1, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 8. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 2, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 9. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 3, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 10. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 4, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 11. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 5, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 12. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 6, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 13. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 7, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 14. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 8, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 15. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 9, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 16. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 10, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 17. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 11, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 18. The modified Neuropeptide Y of claim 5, which is SEQ. ID NO: 12, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 19. A peptide, comprising the modified Neuropeptide Y of claim 1, and a Neuropeptide Y unrelated amino acid segment, a pharmaceutically acceptable salt thereof or mixtures thereof.
- 20. A composition, comprising the modified Neuropeptide Y of claim 1, and a carrier.
- 21. The composition of claim 8, wherein the carrier is a physiologically acceptable carrier.
- 22. The composition of claim 9, wherein the carrier is a pharmaceutically acceptable carrier.
- 23. The composition of claim 8, comprising about 0.5 to about 99% of the modified Neuropeptide Y.
- 24. The composition of claim 8, in unit dosage form.
- 25. The composition of claim 8, in multi-dosage form.
- 26. The composition of claim 8, in bulk.
- 27. The composition of claim 8, wherein the carrier is selected from the group consisting of solid and liquid carriers.
- 28. The composition of claim 8, further comprising an agent selected from the group consisting of other therapeutic agents, flavorings, lubricants, suspending and thickening agents, binders, inert diluents, surface active agents, dispersants, antioxidants, buffers, bacteriostats and solutes to attain isotonicity.
- 29. The composition of claim 28, comprising a therapeutic agent is a tubercular agent.
- 30. A formulation, comprising the composition of claim 8, which is selected from the group consisting of inhalation, oral, rectal, topical, parenteral, and transdermal formulations.
- 31. The formulation of claim 30, which is selected from the group consisting of buccal, sublingual, dermal, intraocular, subcutaneous, intradermal, intramuscular, intravenous, intraarticular, and transdermal formulations.
- 32. The formulation of claim 30, in a form selected from the group consisting of capsules, cachets, pastilles, lozanges, powder, granules, solution, suspension, emulsion and tablets.
- 33. The formulation of claim 32, comprising a suspension or solution in an aqueous or non-aqueous liquid or an oil-in-water or water-in-oil emulsion.
- 34. The formulation of claim 32, provided in a capsule.
- 35. The formulation of claim 30, which is a parenteral formulation.
- 36. The parenteral formulation of claim 35, comprising an injectable formulation.
- 37. The formulation of claim 30, which is an oral formulation.
- 38. The oral formulation of claim 37, which is a solution or suspension selected from the group consisting of aqueous and non-aqueous liquid solutions and suspensions.
- 39. The oral formulation of claim 37, which is an emulsion selected from the group consisting of oil-in-water and water-in-oil emulsions.
- 40. The oral formulation of claim 30, which is a buccal or sub-lingual formulation selected from the group consisting of
- lozenges further comprising a flavoring agent selected from the group consisting of sucrose, acacia and tragacanth; and
- pastilles further comprising an inert base selected from the group consisting of gelatin, glycerin, sucrose and acacia.
- 41. The oral formulation of claim 30, further comprising an enteric coating.
- 42. The parenteral formulation of claim 30, comprising a solution, suspension or emulsion.
- 43. The injectable formulation of claim 36, selected from the group consisting of injectable solutions or suspensions, and which may further comprise an agent selected from the group consisting of antioxidants, buffers, bacteriostatic agents and solutes which render the solution or suspension isotonic with the blood of a recipient.
- 44. The injectable formulation of claim 43, wherein the solutions and suspensions are selected from the group consisting of sterile aqueous and non-aqueous injection solutions and suspensions, which may further comprise suspending agents and thickening agents.
- 45. The formulation of claim 38, in unit-dose form.
- 46. The formulation of claim 30, which is in bulk or multi-dose form.
- 47. The formulation of claim 35, which is provided in multi-dose or bulk form selected from the group consisting of sealed ampoules and vials, respectively.
- 48. The formulation of claim 30, which is freeze-dried or lyophilized.
- 49. The formulation of claim 30, which is a topical formulation selected from the group consisting of ointments, creams, lotions, pastes, gels, sprays, aerosols and oils; and may further comprise a carrier selected from the group consisting of vaseline, lanoline, polyethylene glycols, alcohols and trans-dermal enhancers.
- 50. The formulation of claim 30, which is a transdermal formulation.
- 51. The transdermal formulation of claim 50, which is an iontophoretic formulation selected from the group consisting of iontophoretic solutions and suspensions, and which may further comprise a buffer.
- 52. A sub-lingual formulation comprising the composition of claim 30, wherein the flavoring and inert diluent are selected from the group consisting of sucrose, acacia, tragacanth, gelatin and glycerin.
- 53. An ampoule or vial comprising the formulation of claim 30.
- 54. A rectal formulation comprising the composition of claim 30, in unit dosage form.
- 55. A transdermal formulation comprising the composition of claim 30, and an iontophoretic medium.
- 56. A transdermal device, comprising a patch which comprises the formulation of claim 55.
- 57. An iontophoretic device comprising the transdermal device of claim 56, and means for iontophoretic delivery.
- 58. A method of lowering blood pressure, comprising administering to a subject in need of such treatment a blood pressure lowering amount of the modified Neuropeptide Y of claim 1.
- 59. The method of claim 58, wherein the agent is administered as a composition further comprising a pharmaceutically acceptable carrier.
- 60. The method of claim 58, which is a prophylactic method.
- 61. The method of claim 58, which is a therapeutic method.
- 62. The method of claim 58, wherein the agent is administered parenterally.
- 63. The method of claim 58, wherein the agent is administered orally.
- 64. The method of claim 58, wherein the agent is administered transdermally.
- 65. The method of claim 58, wherein the agent is administered in an amount of about 400 to about 4000 nmole/kg body weight.
- 66. The method of claim 58, wherein the subject is human.
- 67. The method of claim 58, wherein the subject is an animal.
- 68. A method of treating a disease or condition associated with high blood pressure, comprising administering to a subject in need of such treatment the method of claim 48, wherein the modified Neuropeptide Y is administered in an anti-disease or condition effective amount.
- 69. The method of claim 58, wherein the agent is administered anally.
- 70. The method of claim 58, wherein the agent is administered transdermally.
- 71. The method of claim 58, wherein the modified Neuropeptide Y is administered by inhalation.
- 72. The method of claim 58, wherein the modified Neuropeptide Y is administered intraocularly.
- 73. The method of claim 58, wherein the modified Neuropeptide Y is administered sublingually.
- 74. The method of claim 58, wherein the modified Neuropeptide Y is administered buccally.
- 75. The method of claim 58, wherein the modified Neuropeptide Y is administered by a route selected from the group consisting of subcutaneous, intradermal, intramuscular, intravenous and intraarticular.
- 76. The method of claim 58, wherein the modified Neuropeptide Y is administered dermally.
- 77. The method of claim 76, wherein the modified Neuropeptide Y is administered by means of a patch.
- 78. The method of claim 58, wherein the modified Neuropeptide Y is administered by iontophoresis.
- 79. The modified Neuropeptide Y of claim 5, which is selected from the group consisting of SEQ. ID NO: 3 and SEQ. ID NO: 4, pharmaceutically acceptable salt thereof and mixtures thereof.
Government Interests
This invention was made with Government support under Grant No. RO1 CA47217-06 from the National Cancer Institute. The Government may have certain rights in this invention.
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