Compositions and methods for enhanced mucosal delivery of peptide YY and methods for treating and preventing obesity

• US 20040115135A1
• Filed: 12/17/2002
• Published: 06/17/2004
• Est. Priority Date: 12/17/2002
• Status: Active Grant

• Current Assignee: Mdrna Inc. (Adhera Therapeutics, Inc.)
• Original Assignee: Nastech Pharmaceutical Company Inc. (Adhera Therapeutics, Inc.)
• Inventors: Quay, Steven C.
• Granted Patent: US 7,166,575 B2
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents

Abstract

Pharmaceutical compositions and methods are described comprising at least one peptide YY compound and one or more intranasal delivery-enhancing agents for enhanced nasal mucosal delivery of the peptide YY, for treating a variety of diseases and conditions in mammalian subjects, including obesity. In one aspect, the intranasal delivery formulations and methods provide enhanced delivery of peptide YY to the blood plasma or central nervous system (CNS) tissue or fluid, for example, by yielding a peak concentration (C_max) of the peptide YY in the blood plasma or CNS tissue or fluid of the subject that is 20% or greater compared to a peak concentration of the peptide YY in the blood plasma or CNS tissue or fluid of the subject following administration to the subject of a same concentration or dose of the peptide YY to the subject by subcutaneous injection.

Claims

1. A stable pharmaceutical composition comprising one or more peptide YY compound(s) formulated for mucosal delivery to a mammalian subject wherein said composition is effective to alleviate one or more symptom(s) of obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

2. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields enhanced mucosal delivery of said one or more peptide YY compound(s).

3. The pharmaceutical composition of claim 1, further comprising one or more mucosal delivery-enhancing agent(s).

4. The pharmaceutical composition of claim 3, wherein said composition is formulated for nasal mucosal delivery to a mammalian subject.

5. The pharmaceutical composition of claim 4, wherein said composition is formulated as an intranasal spray or powder.

6. The pharmaceutical composition of claim 1, wherein said composition is effective following mucosal administration to alleviate one or more symptom(s) of obesity in said subject without unacceptable adverse side effects.

7. The pharmaceutical composition of claim 1, wherein said composition is effective following mucosal administration to alleviate one or more symptom(s) of Alzheimer'"'"'s disease, colon adenocarcinoma, pancreatic adenocarcinoma, breast carcinoma, treatment and prevention of malnutrition resulting from iatrogenic causes or cachexia associated with advanced disease, or cancer cachexia in said subject without unacceptable adverse side effects.

8. The pharmaceutical composition of claim 1, further comprising a plurality of different peptide YY compounds.

12. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields enhanced mucosal delivery of said one or more peptide YY compound(s) characterized by:

(i) a peak concentration (C_max) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of said subject that is 15% or greater as compared to a peak concentration of said peptide YY compounds in a CNS tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of said peptide YY compound(s) to said subject;

(ii) an area under concentration curve (AUC) of said peptide YY compound(s) in a CNS tissue or fluid or in a blood plasma of the subject that is 25% or greater compared to an AUC of peptide YY in a CNS tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of said peptide YY compound(s) to said subject;

or (iii) a time to maximal concentration (t_max) of said peptide YY in a CNS tissue or fluid or in a blood plasma of the subject between about 0.1 to 1.0 hours.

13. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields a peak concentration (C_max) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of said subject that is 25% or greater as compared to a peak concentration of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of said peptide YY compound(s) to said subject.

14. The pharmaceutical composition of claim 13, wherein said composition following mucosal administration to said subject yields a peak concentration (C_max) of said peptide YY compound(s) in said CNS tissue or fluid or in a blood plasma of said subject that is 50% or greater as compared to a peak concentration of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of said peptide YY compound(s) to said subject.

15. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields an area under concentration curve (AUC) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of the subject that is 25% or greater compared to an AUC of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of said peptide YY compound(s) to said subject.

16. The pharmaceutical composition of claim 15, wherein said composition following mucosal administration to said subject yields an area under concentration curve (AUC) of said peptide YY compound(s) in said CNS tissue or fluid or in a blood plasma of the subject that is 50% or greater compared to an AUC of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of said peptide YY compound(s) to said subject.

17. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields a time to maximal plasma concentration (t_max) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of the subject between about 0.1 to 1.0 hours.

18. The pharmaceutical composition of claim 17, wherein said composition following mucosal administration to said subject yields a time to maximal plasma concentration (t_max) of said peptide YY compound(s) in said CNS tissue or fluid or in a blood plasma of the subject between about 0.2 to 0.5 hours.

19. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields a peak concentration of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid of the subject that is 10% or greater compared to a peak concentration of said peptide YY compound(s) in a blood plasma of the subject.

20. The pharmaceutical composition of claim 19, wherein said composition following mucosal administration to said subject yields a peak concentration of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid of the subject that is 20% or greater compared to a peak concentration of said peptide YY compound(s) in a blood plasma of the subject.

21. The pharmaceutical composition of claim 20, wherein said composition following mucosal administration to said subject yields a peak concentration of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid of the subject that is 40% or greater compared to a peak concentration of said peptide YY compound(s) in a blood plasma of the subject.

22. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields a peak concentration (C_max) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of said subject that is 110% or greater as compared to a peak concentration of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following mucosal delivery of peptide YY in water or saline of the same or comparable amount of peptide YY to the subject.

23. The pharmaceutical composition of claim 22, wherein said composition following mucosal administration to said subject yields a peak concentration (C_max) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of said subject that is 120% or greater as compared to a peak concentration of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following mucosal delivery of peptide YY in water or saline of the same or comparable amount of peptide YY to the subject.

24. The pharmaceutical composition of claim 1, wherein said composition following mucosal administration to said subject yields an area under concentration curve (AUC) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of the subject that is 110% or greater compared to an AUC of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following mucosal delivery of peptide YY in water or saline of the same or comparable amount of peptide YY to the subject.

25. The pharmaceutical composition of claim 24, wherein said composition following mucosal administration to said subject yields an area under concentration curve (AUC) of said peptide YY compound(s) in a central nervous system (CNS) tissue or fluid or in a blood plasma of the subject that is 120% or greater compared to an AUC of said peptide YY compound(s) in said CNS tissue or fluid or blood plasma following mucosal delivery of peptide YY in water or saline of the same or comparable amount of peptide YY to the subject.

26. The pharmaceutical composition of claim 1, wherein said peptide YY compound(s) formulated for intranasal delivery to said subject in combination with said one or more intranasal delivery-enhancing agent(s) is effective following intranasal administration to alleviate one or more symptom(s) of obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

27. The pharmaceutical composition of claim 3, wherein said mucosal delivery-enhancing agent(s) is/are selected from:

(a) an aggregation inhibitory agent;

(b) a charge-modifying agent;

(c) a pH control agent;

(d) a degradative enzyme inhibitory agent;

(e) a mucolytic or mucus clearing agent;

(f) a ciliostatic agent;

(g) a membrane penetration-enhancing agent selected from (i) a surfactant, (ii) a bile salt, (ii) a phospholipid additive, mixed micelle, liposome, or carrier, (iii) an alcohol, (iv) an enamine, (v) an NO donor compound, (vi) a long-chain amphipathic molecule (vii) a small hydrophobic penetration enhancer;

(viii) sodium or a salicylic acid derivative;

(ix) a glycerol ester of acetoacetic acid (x) a cyclodextrin or beta-cyclodextrin derivative, (xi) a medium-chain fatty acid, (xii) a chelating agent, (xiii) an amino acid or salt thereof, (xiv) an N-acetylamino acid or salt thereof, (xv) an enzyme degradative to a selected membrane component, (ix) an inhibitor of fatty acid synthesis, or (x) an inhibitor of cholesterol synthesis;

or (xi) any combination of the membrane penetration enhancing agents recited in (i)-(x);

(h) a modulatory agent of epithelial junction physiology;

(i) a vasodilator agent;

(j) a selective transport-enhancing agent; and

(k) a stabilizing delivery vehicle, carrier, support or complex-forming species with which the peptide YY is effectively combined, associated, contained, encapsulated or bound resulting in stabilization of the peptide YY for enhanced nasal mucosal delivery, wherein the formulation of said peptide YY with said one or more intranasal delivery-enhancing agents provides for increased bioavailability of the peptide YY in a central nervous system (CNS) tissue or fluid or blood plasma of said subject.

28. The pharmaceutical composition of claim 27, further comprising a plurality of mucosal delivery-enhancing agents.

29. The pharmaceutical composition of claim 27, comprising one or more intranasal delivery-enhancing agents.

30. The pharmaceutical composition of claim 29, further comprising a plurality of intranasal delivery-enhancing agents.

31. The pharmaceutical composition of claim 3, wherein said mucosal delivery-enhancing agent(s) is/are selected from the group consisting of citric acid, sodium citrate, propylene glycol, glycerin, L-ascorbic acid, sodium metabisulfite, EDTA disodium, benzalkonium chloride, sodium hydroxide and mixtures thereof.

32. The pharmaceutical composition of claim 1, further comprising one or more sustained release-enhancing agent(s).

33. The pharmaceutical composition of claim 32, wherein the sustained release-enhancing agent is polyethylene glycol (PEG) in combination with peptide YY.

34. The pharmaceutical composition of claim 1, wherein the peptide YY is human peptide YY or a biologically active analog, fragment, or derivative thereof.

35. The pharmaceutical composition of claim 1, wherein said peptide YY is formulated in an effective dosage unit of between about 30 and 250 μ

g.

36. The pharmaceutical composition of claim 1, wherein said peptide YY is formulated in an effective dosage unit of between about 0.1 pmol and 5.0 pmol per kilogram body weight of the subject.

37. The pharmaceutical composition of claim 7, further comprising vitamin E succinate, and wherein said composition prevents pancreatic adenocarcinoma or breast cancer.

38. The pharmaceutical formulation of claim 1, which is pH adjusted to between about pH 3.0-6.0.

39. The pharmaceutical formulation of claim 1, which is pH adjusted to between about pH 3.0-5.0.

40. The pharmaceutical formulation of claim 1, which is pH adjusted to between about pH 4.0-5.0.

41. The pharmaceutical formulation of claim 1, which is pH adjusted to about pH 4.0-4.5.

42. The pharmaceutical formulation of claim 3, wherein said mucosal delivery-enhancing agent is a permeabilizing peptide that reversibly enhances mucosal epithelial paracellular transport by modulating epithelial junctional structure and/or physiology in a mammalian subject, wherein said peptide effectively inhibits homotypic binding of an epithelial membrane adhesive protein selected from a junctional adhesion molecule (JAM), occludin, or claudin.

9. A stable pharmaceutical composition comprising one or more peptide YY compound(s) formulated for intranasal delivery to a mammalian subject wherein said composition is effective to alleviate one or more symptom(s) of obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

10. The pharmaceutical composition of claim 9, wherein said composition following intranasal administration to said subject yields enhanced intranasal delivery of said one or more peptide YY compound(s).

11. A method for treating or preventing obesity, cancer, or malnutrition or wasting related to cancer in a mammalian subject amenable to treatment by therapeutic administration of a peptide YY compound comprising administering to a nasal mucosal surface of said subject a pharmaceutical composition comprising an effective amount of one or more peptide YY compound(s) formulated for intranasal delivery in an effective dosage regimen-to alleviate one or more symptom(s) of said obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

43. A method for treating or preventing obesity, cancer, or malnutrition or wasting related to cancer in a mammalian subject amenable to treatment by therapeutic administration of a peptide YY compound comprising administering to a mucosal surface of said subject a pharmaceutical composition comprising an effective amount of one or more peptide YY compound(s) formulated for mucosal delivery in an effective dosage regimen to alleviate one or more symptom(s) of said obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

44. The method of claim 43, further comprising administering said pharmaceutical composition in combination with one or more mucosal delivery-enhancing agent(s).

45. The method of claim 43, wherein said peptide YY compound(s) is/are formulated for intranasal delivery to said subject in combination with one or more intranasal delivery-enhancing agent(s), and wherein said method employs an intranasal effective dosage regimen to alleviate one or more symptom(s) of said obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

46. The method of claim 43, wherein said peptide YY compound(s) is/are provided in a multiple dosage unit kit or container for repeated self-dosing by said subject.

47. The method of claim 44, wherein said peptide YY compound(s) is/are repeatedly administered through an intranasal effective dosage regimen that involves multiple administrations of said peptide YY compound(s) to said subject during a daily or weekly schedule to maintain a therapeutically effective baseline level of peptide YY during an extended dosing period.

48. The method of claim 47, wherein said peptide YY compound(s) is/are self-administered by said subject in a nasal formulation between two and six times daily to maintain a therapeutically effective baseline level of peptide YY during an 8 hour to 24 hour extended dosing period.

49. The method of claim 45, wherein said peptide YY compound(s) is/are repeatedly administered through an intranasal effective dosage regimen that involves multiple administrations of said peptide YY compound(s) to said subject during a daily or weekly schedule to maintain a therapeutically effective elevated and lowered pulsatile level of peptide YY during an extended dosing period.

50. The method of claim 49, wherein said peptide YY compound(s) is/are self-administered by said subject in a nasal formulation between two and six times daily to maintain said therapeutically effective elevated and lowered pulsatile level of peptide YY during an 8 hour to 24 hour extended dosing period.

51. The method of claim 43, which yields a peak concentration (C_max) of said peptide YY in a central nervous system (CNS) tissue or fluid or blood plasma of said subject following mucosal administration that is 25% or greater as compared to a peak concentration of peptide YY in a central nervous system (CNS) tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of peptide YY to said subject.

52. The method of claim 51, which yields a peak concentration (C_max) of said peptide YY in a central nervous system (CNS) tissue or fluid or a blood plasma of said subject following mucosal administration that is 50% or greater as compared to a peak concentration of peptide YY in said central nervous system (CNS) tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of peptide YY to said subject.

53. The method of claim 43, which yields an area under concentration curve (AUC) of said peptide YY in a central nervous system (CNS) tissue or fluid or a blood plasma of the subject following mucosal administration that is 25% or greater compared to an AUC of peptide YY in said central nervous system (CNS) tissue or fluid or blood plasma following subcutaneous injection of an equivalent concentration or dose of peptide YY to said subject.

54. The method of claim 53, which yields an area under concentration curve (AUC) of said peptide YY in said central nervous system (CNS) tissue or fluid or said blood plasma of the subject following mucosal administration that is 50% or greater compared to an AUC of peptide YY in said central nervous system (CNS) tissue or fluid or said blood plasma following subcutaneous injection of an equivalent concentration or dose of peptide YY to said subject.

55. The method of claim 43, which yields a time to maximal plasma concentration (t_max) of said peptide YY in a central nervous system (CNS) tissue or fluid or a blood plasma of the subject following mucosal administration of between about 0.1 to 1.0 hours.

56. The method of claim 55, which yields a time to maximal plasma concentration (t_max) of said peptide YY in a central nervous system (CNS) tissue or fluid or a blood plasma of the subject following mucosal administration of between 0.2 to 0.5 hours.

57. The method of claim 43, which yields a peak concentration of said peptide YY in a central nervous system (CNS) tissue or fluid of the subject following mucosal administration that is 10% or greater compared to a peak concentration of said peptide YY in a blood plasma of the subject.

58. The method of claim 57, which yields a peak concentration of said peptide YY in a central nervous system (CNS) tissue or fluid of the subject following mucosal administration that is 20% or greater compared to a peak concentration of said peptide YY in a blood plasma of the subject.

59. The method of claim 57, which yields a peak concentration of said peptide YY in a central nervous system (CNS) tissue or fluid of the subject following mucosal administration that is 40% or greater compared to a peak concentration of said peptide YY in a blood plasma of the subject.

60. The method of claim 43, wherein said mucosal delivery-enhancing agent(s) is/are selected from:

(a) an aggregation inhibitory agent;

(b) a charge-modifying agent;

(c) a pH control agent;

(d) a degradative enzyme inhibitory agent;

(e) a mucolytic or mucus clearing agent;

(f) a ciliostatic agent;

(g) a membrane penetration-enhancing agent selected from (i) a surfactant, (ii) a bile salt, (ii) a phospholipid additive, mixed micelle, liposome, or carrier, (iii) an alcohol, (iv) an enamine, (v) an NO donor compound, (vi) a long-chain amphipathic molecule (vii) a small hydrophobic penetration enhancer;

(viii) sodium or a salicylic acid derivative;

(ix) a glycerol ester of acetoacetic acid (x) a cyclodextrin or beta-cyclodextrin derivative, (xi) a medium-chain fatty acid, (xii) a chelating agent, (xiii) an amino acid or salt thereof, (xiv) an N-acetylamino acid or salt thereof, (xv) an enzyme degradative to a selected membrane component, (ix) an inhibitor of fatty acid synthesis, or (x) an inhibitor of cholesterol synthesis;

or (xi) any combination of the membrane penetration enhancing agents recited in (i)-(x);

(h) a modulatory agent of epithelial junction physiology;

(i) a vasodilator agent;

(j) a selective transport-enhancing agent; and

(k) a stabilizing delivery vehicle, carrier, support or complex-forming species with which the peptide YY is effectively combined, associated, contained, encapsulated or bound resulting in stabilization of the peptide YY for enhanced nasal mucosal delivery, wherein the formulation of said peptide YY with said one or more intranasal delivery-enhancing agents provides for increased bioavailability of the peptide YY in a central nervous system (CNS) tissue or fluid or a blood plasma of said subject.

61. The method of claim 60, wherein said pharmaceutical composition further comprises a plurality of mucosal delivery-enhancing agents.

62. The method of claim 43, wherein said pharmaceutical composition comprises one or more intranasal delivery-enhancing agents.

63. The method of claim 62, wherein said pharmaceutical composition comprises a plurality of intranasal delivery-enhancing agents.

64. The method of claim 43, wherein said mucosal delivery-enhancing agent(s) is/are selected from the group consisting of citric acid, sodium citrate, propylene glycol, glycerin, L-ascorbic acid, sodium metabisulfite, EDTA disodium, benzalkonium chloride, sodium hydroxide and mixtures thereof.

65. The method of claim 43, wherein said pharmaceutical composition further comprises one or more sustained release-enhancing agent(s).

66. The method of claim 65, wherein the sustained release-enhancing agent is polyethylene glycol (PEG).

67. The method of claim 43, wherein the peptide YY is human peptide YY or a biologically active analog, fragment, or derivative thereof.

68. The method of claim 43, wherein said peptide YY is formulated in an effective dosage unit of between about 30 and 250 μ

g.

69. The method of claim 43, wherein said peptide YY is formulated in an effective dosage unit of between about 0.5 pmol and 5.0 pmol per kilogram body weight of the subject.

70. The method of claim 43, which is effective to alleviate one or more symptom(s) of obesity in children or adult subjects without unacceptable adverse side effects.

71. The method of claim 43, which is effective to alleviate one or more symptom(s) of Alzheimer'"'"'s disease, colon adenocarcinoma, pancreatic adenocarcinoma, breast carcinoma, treatment and prevention of malnutrition resulting from iatrogenic causes or cachexia associated with advanced disease, or cancer cachexia in said subject without unacceptable adverse side effects.

72. The method of claim 43, wherein said pharmaceutical composition comprises a plurality of different peptide YY compounds.

73. A stable pharmaceutical composition comprising one or more neuropeptide Y compound(s) formulated for mucosal delivery to a mammalian subject wherein said composition is effective to alleviate one or more symptom(s) of obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

74. The pharmaceutical composition of claim 73, wherein said composition following mucosal administration to said subject yields enhanced mucosal delivery of said one or more peptide YY compound(s).

75. The pharmaceutical composition of claim 73, further comprising one or more mucosal delivery-enhancing agent(s).

76. The pharmaceutical composition of claim 74, wherein said composition is formulated for nasal mucosal delivery to a mammalian subject.

77. The pharmaceutical composition of claim 76, wherein said composition is formulated as an intranasal spray or powder.

78. The pharmaceutical composition of claim 73, wherein said composition is effective following mucosal administration to alleviate one or more symptom(s) of obesity in said subject without unacceptable adverse side effects.

79. A method for treating or preventing obesity, cancer, or malnutrition or wasting related to cancer in a mammalian subject amenable to treatment by therapeutic administration of a neuropeptide Y compound comprising administering to a mucosal surface of said subject a pharmaceutical composition comprising an effective amount of one or more neuropeptide Y compound(s) formulated for mucosal delivery in an effective dosage regimen to alleviate one or more symptom(s) of said obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

80. The method of claim 79, further comprising administering said pharmaceutical composition in combination with one or more mucosal delivery-enhancing agent(s).

81. The method of claim 79, wherein said peptide YY compound(s) is/are formulated for intranasal delivery to said subject in combination with one or more intranasal delivery-enhancing agent(s), and wherein said method employs an intranasal effective dosage regimen to alleviate one or more symptom(s) of said obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

82. A stable pharmaceutical composition comprising one or more pancreatic peptide compound(s) formulated for mucosal delivery to a mammalian subject wherein said composition is effective to alleviate one or more symptom(s) of obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

83. The pharmaceutical composition of claim 82, wherein said composition following mucosal administration to said subject yields enhanced mucosal delivery of said one or more peptide YY compound(s).

84. The pharmaceutical composition of claim 82, further comprising one or more mucosal delivery-enhancing agent(s).

85. The pharmaceutical composition of claim 83, wherein said composition is formulated for nasal mucosal delivery to a mammalian subject.

86. The pharmaceutical composition of claim 85, wherein said composition is formulated as an intranasal spray or powder.

87. The pharmaceutical composition of claim 82, wherein said composition is effective following mucosal administration to alleviate one or more symptom(s) of obesity in said subject without unacceptable adverse side effects.

88. A method for treating or preventing obesity, cancer, or malnutrition or wasting related to cancer in a mammalian subject amenable to treatment by therapeutic administration of a pancreatic peptide compound comprising administering to a mucosal surface of said subject a pharmaceutical composition comprising an effective amount of one or more pancreatic peptide compound(s) formulated for mucosal delivery in an effective dosage regimen to alleviate one or more symptom(s) of said obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

89. The method of claim 88, further comprising administering said pharmaceutical composition in combination with one or more mucosal delivery-enhancing agent(s).

90. The method of claim 88, wherein said peptide YY compound(s) is/are formulated for intranasal delivery to said subject in combination with one or more intranasal delivery-enhancing agent(s), and wherein said method employs an intranasal effective dosage regimen to alleviate one or more symptom(s) of said obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

91. A kit for treatment of a mammalian subject comprising a stable pharmaceutical composition of one or more peptide YY compound(s) formulated for mucosal delivery to said mammalian subject wherein said composition is effective to alleviate one or more symptom(s) of obesity, cancer, or malnutrition or wasting related to cancer in said subject without unacceptable adverse side effects.

92. The kit of claim 91, further comprising a pharmaceutical reagent vial to contain the one or more peptide YY compounds.

93. The kit of claim 92, wherein said pharmaceutical reagent vial is a silanized glass vial.

94. The kit of claim 92, further comprising an aperture for delivery to a nasal mucosal surface of said subject, wherein said aperture comprises silanized glass.