Compositions for enhanced epithelial permeation of neuropeptide Y for treating obesity
View Patent ↗Pharmaceutical compositions comprising PYY(3-36) or Neuropeptide Y (NPY), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) or Neuropeptide Y (NPY) is present in an amount effective to alleviate one or more symptom(s) of obesity in a subject, and the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation.
1. A composition comprising a Y2-receptor selective agonist, a solubilizing agent, a chelating agent, and L-α-phosphatidylcholine didecanoyl (DDPC).
2. The composition of claim 1 , wherein the Y2-receptor selective agonist is PEGylated.
3. The composition of claim 1 , wherein the Y2-receptor selective agonist is selected from the group consisting of neuropeptide Y (SEQ ID NO:795), ([ 125 I]-Tyr)-neuropeptide Y (SEQ ID NO:802), biotinyl-neuropeptide Y (SEQ ID NO:803), (Leu 31 ,Pro 34 )-neuropeptide Y (SEQ ID NO:804), (D-Trp 32 )-neuropeptide Y (SEQ ID NO:805), (Tyr(Me) 21 )-neuropeptide Y (SEQ ID NO:806), (A 1 a 31 ,Aib 32 )-neuropeptide Y (SEQ ID NO:807), (Leu 31 ,Pro 34 )-neuropeptide Y (SEQ ID NO:808), (Pro 34 )-neuropeptide Y (SEQ ID NO:809), (D-Trp 32 )-neuropeptide Y (SEQ ID NO:810), neuropeptide Y 1-24 amide (SEQ ID NO:811), (Cys 2 )-neuropeptide Y 1-4 -8-aminooctanoyl-(D-Cys 27 )-neuropeptide Y 25-32 (SEQ ID NO:812), neuropeptide Y 2-36 (SEQ ID NO:813), neuropeptide Y 3-36 (SEQ ID NO:814), neuropeptide Y 13-36 (SEQ ID NO:815), (Leu 31 ,Pro 34 )-neuropeptide Y 13-36 (SEQ ID NO:816), neuropeptide Y 18-36 (SEQ ID NO:817), pancreatic polypeptide 1-17 -A 1 a 31 ,Aib 32 )-neuropeptide Y 18-36 (SEQ ID NO:818), neuropeptide Y 22-36 (SEQ ID NO:819), Tyr-Lys-Gly-Arg-(Glu 26 ,Lys 29 ,Pro 34 )-neuropeptide Y 26-36 (SEQ ID NO:820), (D-Tyr 27,36 ,D-Thr 32 )-neuropeptide Y 27-36 (SEQ ID NO:821), ((Cys 31 ,Nva 34 )-neuropeptide Y 27-36 ) 2 (SEQ ID NO:822), (Pro 30 ,Tyr 32 ,Leu 34 )-neuropeptide Y 28-36 (SEQ ID NO:823), (His 32 ,Leu 34 )-neuropeptide Y 32-36 (SEQ ID NO:824), ([ 125 I]-Tyr)-(Leu 31 ,Pro 34 )-neuropeptide Y (SEQ ID NO:825), (Gly 1 ,Ser 3,22 ,Gln 4,34 ,Thr 6 ,Ala 19 , Tyr 21 ,Ala 23,31 ,Aib 32 )-pancreatic polypeptide (human) (SEQ ID NO:826), and Y2A (N-acetyl [Leu 28 , Leu 31 ]NPY 24-36 ) (SEQ ID NO:827).
4. The composition of claim 1 , wherein the solubilizing agent is selected from the group consisting of hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, and methyl-β-cyclodextrin.
5. The composition of claim 1 , wherein the chelating agent is selected from the group consisting of ethylene diamine tetraacetic acid (EDTA) and ethylene glycol tetraacetic acid (EGTA).
6. The composition of claim 1 , wherein the composition is a dry powder.
7. The composition of claim 1 , further comprising a pH control agent.
8. The composition of claim 7 , wherein the pH control agent is selected from the group consisting of arginine, sodium hydroxide, glycine, hydrochloric acid, and citric acid.
9. The composition of claim 1 , wherein the composition is an aqueous composition having a pH from about 3 to about 6.
10. The composition of claim 1 , wherein the composition is an aqueous composition having a pH of about 5.
11. The composition of claim 1 , wherein the composition is an aqueous composition having a pH of about 4.
12. The composition of claim 1 , further comprising a preservative.
13. The composition of claim 12 , wherein the preservative is selected from the group consisting of methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, phenol, methyl paraben, paraben, m-cresol, thiomersal, benzylalkonimum chloride, and chlorobutanol.
14. The composition of claim 1 , further comprising a release-enhancing agent.
15. The composition of claim 14 , wherein the release-enhancing agent is polyethylene glycol (PEG).