Compositions and methods for enhanced mucosal delivery of Y2 receptor-binding peptides and methods for treating and preventing obesity
View Patent ↗Pharmaceutical compositions and methods are described comprising at least one Y2 receptor-binding peptide, such as peptide YY(PYY), Neuropeptide Y (NPY) or Pancreatic Peptide (PP) and one or more mucosal 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.
1. A PYY composition comprised of a solubilizing agent, a chelating agent, a polyol, L-α-phosphatidylcholine didecanoyl (DDPC) and a PYY peptide wherein the PYY peptide is comprised of the amino acid sequence of SEQ ID NO: 2.
2. The PYY composition of claim 1 wherein the composition is further comprised of at least two polyols.
3. The PYY composition of claim 2 wherein the polyols are selected from the group consisting of sucrose, mannitol, sorbitol, lactose, L-arabinose, D-erythrose, D-ribose, D-xylose, D-mannose, trehalose, D-galactose, lactulose, cellobiose, gentibiose, glycerin and polyethylene glycol.
4. The PYY composition of claim 3 wherein the polyols are lactose and sorbitol.
5. The PYY compostion of claim 1 wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).
6. The PYY composition of claim 5 wherein the chelating agent is ethylenediamine tetraacetic acid (EDTA).
7. The PYY composition of claim 1 wherein the solubilizing agent is selected from the group consisting of a cyclodextran, hydroxypropyl-β-cyclodextran, sulfobutylether-β-cyclodextran and methyl-β-cyclodextrin.
8. The PYY composition of claim 7 wherein the solubilizing agent is a methyl-β-cyclodextrin.
9. The PYY composition of claim 1 wherein the composition is an aqueous PYY composition further comprised of water.
10. The PYY composition of claim 9 wherein the aqueous PYY composition has a pH of about of about 3–6.
11. The PYY composition of claim 10 wherein the pH of the aqueous PYY composition is 5.0±0.3.
12. A PYY composition comprised of methyl-β-cyclodextrin, EDTA, lactose, sorbitol, DDPC and a PYY peptide wherein the PYY peptide is comprised of the amino acid sequence of SEQ ID NO: 2.
13. A PYY composition comprised of water, sodium citrate, citric acid, methyl-β-cyclodextrin, EDTA, lactose, sorbitol, DDPC and PYY(3–36) (SEQ ID NO: 2), wherein the formulation has a pH of about 5.0±0.3.
14. The PYY composition of claim 13 further comprised of a preservative selected from the group consisting of chlorobutanol and benzalkonium chloride.
15. The composition of claim 14 wherein the preservative is chlorobutanol.
16. A PYY composition comprised of water, chlorobutanol, sodium citrate, citric acid, methyl-β-cyclodextrin, EDTA, lactose, sorbitol, DDPC and PYY(3–36) (SEQ ID NO: 2), wherein the formulation has a pH of about 5.0±0.3.
17. A PYY composition comprised of water, benzalkonium chloride, sodium citrate, citric acid, methyl-β-cyclodextrin, EDTA, lactose, sorbitol, DDPC and PYY(3–36) (SEQ ID NO: 2), wherein the formulation has a pH of about 5.0±0.3.
18. A PYY composition comprised of water, chlorobutanol at a concentration of 5 mg/ml, sodium citrate at a concentration of 1.62 mg/ml, citric acid at a concentration of 0.86 mg/ml, methyl-β-cyclodextrin at a concentration of 45 mg/ml, EDTA at a concentration of 1 mg/ml, lactose at a concentration of 9 mg/ml, sorbitol at a concentration of 18.2 mg/ml, DDPC at a concentration of 1 mg/ml and PYY(3–36) (SEQ ID NO: 2) at a concentration of 1 mg/ml, wherein the formulation has a pH of about 5.0±0.3.
19. A PYY composition comprised of water, chlorobutanol at a concentration of 5 mg/ml, sodium citrate at a concentration of 1.62 mg/ml, citric acid at a concentration of 0.86 mg/ml, methyl-β-cyclodextrin at a concentration of 45 mg/ml, EDTA at a concentration of 1 mg/ml, lactose at a concentration of 9 mg/ml, sorbitol at a concentration of 18.2 mg/ml, DDPC at a concentration of 1 mg/ml and PYY(3–36) (SEQ ID NO: 2) at a concentration of 15 mg/ml, wherein the formulation has a pH of about 5.0±0.3.