COMPOSITIONS FOR ENHANCED EPITHELIAL PERMEATION OF PEPTIDE YY FOR TREATING OBESITY
Pharmaceutical compositions comprising PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) 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 pharmaceutical composition comprising PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) 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.
2 . The pharmaceutical composition of claim 1 , wherein the phosphatidylcholine is L-α-phosphatidylcholine didecanoyl (DDPC).
3 . The pharmaceutical composition of claim 1 , wherein the cyclodextrin is selected from the group consisting of hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, and methyl-β-cyclodextrin.
4 . The pharmaceutical composition of claim 1 , wherein the cyclodextrin is methyl-β-cyclodextrin.
5 . The pharmaceutical composition of claim 1 , wherein the composition is an aqueous composition having a pH of from about 3 to about 6.
6 . The pharmaceutical composition of claim 5 , wherein the pH is 5.0±0.5.
7 . The pharmaceutical composition of claim 1 , further comprising a chelating agent.
8 . The pharmaceutical composition of claim 7 , wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).
9 . The pharmaceutical composition of claim 7 , wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA).
10 . The pharmaceutical composition of claim 1 , wherein the composition is formulated for nasal mucosal delivery to a mammalian subject.
11 . The pharmaceutical composition of claim 10 , wherein the composition is formulated as an intranasal spray or powder.
12 . The pharmaceutical composition of claim 1 , wherein the composition following mucosal administration to the subject yields a peak concentration (C max ) of PYY(3-36) in a central nervous system (CNS) tissue or fluid or in a blood plasma of the subject that is 25% or greater as compared to a peak concentration of PYY(3-36) in a CNS tissue or fluid or in a blood plasma following subcutaneous injection of an equivalent concentration or dose of PYY(3-36).
13 . The pharmaceutical composition of claim 1 , wherein the composition following mucosal administration to the subject yields an area under concentration curve (AUC) of PYY(3-36) in a CNS tissue or fluid or in a blood plasma of the subject that is 25% or greater compared to an AUC of PYY(3-36) in a CNS tissue or fluid or in a blood plasma following subcutaneous injection of an equivalent concentration or dose of PYY(3-36).
14 . The pharmaceutical composition of claim 1 , wherein the composition following mucosal administration to the subject yields a time to maximal concentration (t max ) of PYY(3-36) in a CNS tissue or fluid or in a blood plasma of the subject between about 0.1 to 1.0 hours.
15 . The pharmaceutical composition of claim 1 , further comprising one or more sustained release-enhancing agent(s).
16 . The pharmaceutical composition of claim 15 , wherein the sustained release-enhancing agent is polyethylene glycol (PEG).
17 . The pharmaceutical composition of claim 1 , wherein the PYY(3-36) is formulated in an effective dosage unit of between about 30 and 250 μg.
18 . The pharmaceutical composition of claim 1 , wherein the PYY(3-36) is formulated in an effective dosage unit of between about 0.1 pmol and 5.0 pmol per kilogram body weight of the subject.