Peptide yy pharmaceutical formulations, compositions, and methods

Abstract

Pharmaceutical compositions comprising PYY (e.g., PYY(3-36) and analogs and variants thereof), satiety peptides, satiety hormones, metabolic hormones, and methods of treating metabolic diseases with such compositions are provided. Aspects include methods of increasing a feeling of fullness in patients treated with pharmaceutical compositions comprising PYY, PYY(3-36), satiety peptides, satiety hormones, metabolic hormones, and analogs, receptor antagonists and variants thereof.

1 . A pharmaceutical composition comprising an agent selected from the group consisting of leptin, amylin, calcitonin, gastric inhibitory peptide (GIP), fibroblast growth factor (FGF21), and insulin, wherein the composition provides satiation to a subject without substantially changing the concentration of the agent in the plasma of the subject, and wherein the composition is formulated as an oral dissolving tablet. 
     
     
         2 . The pharmaceutical composition of  claim 1 , further comprising from about 2.5 ng to about 2.5 mg Peptide YY (PYY). 
     
     
         3 - 9 . (canceled) 
     
     
         10 . A pharmaceutical composition comprising an agent selected from oxyntomodulin (OXM) and cholecystokinin (CCK) in a dose of from about 2.5 ng to about 2.5 mg, wherein the composition provides satiation to a subject without substantially changing the concentration of the agent in the plasma of the subject, and wherein the composition is formulated as an oral dissolving tablet. 
     
     
         11 . The pharmaceutical composition of  claim 10 , further comprising from about 2.5 ng to about 2.5 mg PYY. 
     
     
         12 - 14 . (canceled) 
     
     
         15 . A pharmaceutical composition comprising an agent selected from the group consisting of acetyl-CoA carboxylase inhibitor, a diacylglycerol O-acyltransferase 1 inhibitor, monoacylglycerol O-acyltransferase inhibitors, a phosphodiesterase-10 inhibitor, an AMP-activated protein kinase activator, a sulfonylurea, a meglitinide, an α-amylase inhibitor, an α-glucoside hydrolase inhibitor, an α-glucosidase inhibitor, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, a PPAR α/γ agonist, a biguanide, a protein tyrosine phosphatase-1B inhibitor, sirtuin-1 activator, a dipeptidyl peptidase IV inhibitor, an insulin secreatagogue, a fatty acid oxidation inhibitor, an A2 antagonist, a c-jun amino-terminal kinase inhibitor, glucokinase activators, an insulin mimetic, a glycogen phosphorylase inhibitor, a vasoactive intestinal peptide receptor 2 receptor agonist, a sodium glucose co-transporter 2 inhibitor, a glucagon receptor modulator, a G protein-coupled receptor 19 modulator, a free fatty acid receptor 1 agonist, a free fatty acid receptor 4 modulators, a high affinity nicotinic acid receptor activator, a sodium-D-glucose cotransporter inhibitor, an inhibitor or modulator of a carnitine palmitoyl transferase enzyme, a fructose 1,6-diphosphatase inhibitor, an aldose reductase inhibitor, a mineralocorticoid receptor inhibitor, a target of rapamycin kinase multiprotein complex inhibitor, a C—C chemokine receptor type 2 and/or a C—C chemokine receptor type 5 inhibitor, a protein kinase C inhibitor, a fatty acid synthetase inhibitor, a serine palmitoyl transferase inhibitor, a G protein-coupled receptor 81 modulator, a G protein-coupled receptor 39 modulator, a G protein-coupled receptor 43 modulator, a G protein-coupled receptor 41 modulator, a G protein-coupled receptor 105 modulator, voltage-gated potassium channel, retinal binding protein 4, glucocorticoid receptor, a somatostatin receptor, an inhibitor or modulator of pyruvate dehydrogenase kinase isoform 2 or pyruvate dehydrogenase kinase isoform 4, an inhibitor of mitogen-activated protein kinase kinase kinase kinase 4, an interleukin 1 modulator, a 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, a squalene synthetase inhibitor, a fibrate, a bile acid sequestrant, an acyl-CoA cholesterol acyltransferase, a microsomal triglyceride transfer protein, a lipooxygenase inhibitor, a cholesterol absorption inhibitor, a proprotein convertase subtilisin/kexin type 9 modulator, a cholesteryl ester transfer protein inhibitor, a modulator of retinoid x receptor α, enterostatin or an enterostatin analog, a ghrelin modulator, a pancreatic polypeptide, neuropeptide Y, human growth hormone, prolactin, oxytocin, bovine growth hormone, porcine growth hormone, ghrelin, and glucagon, wherein the composition provides satiation to a subject without substantially changing the concentration of the agent in the plasma of the subject, and wherein the composition is formulated as an oral dissolving tablet. 
     
     
         16 . The pharmaceutical composition of  claim 15 , further comprising from about 2.5 ng to about 2.5 mg PYY. 
     
     
         17 . (canceled) 
     
     
         18 . A method of treating a metabolic disorder in a subject comprising administering the pharmaceutical composition of  claim 1  to the tongue of the subject, wherein the composition provides satiation to a subject without substantially changing the concentration of the agent in the plasma of the subject. 
     
     
         19 . The method of  claim 18 , wherein the pharmaceutical composition further comprises from about 2.5 ng to about 2.5 mg PYY. 
     
     
         20 - 22 . (canceled) 
     
     
         23 . A method of treating a metabolic disorder in a subject comprising administering the pharmaceutical composition of  claim 10  to the tongue of the subject in a dose of from about 2.5 ng to about 2.5 mg, wherein the composition provides satiation to a subject without substantially changing the concentration of the agent in the plasma of the subject. 
     
     
         24 . The method of  claim 23 , wherein the pharmaceutical composition further comprises from about 2.5 ng to about 2.5 mg PYY. 
     
     
         25 - 27 . (canceled) 
     
     
         28 . A method of treating a metabolic disorder in a subject comprising administering the pharmaceutical composition of  claim 15  to the tongue of the subject wherein the composition provides satiation to a subject without substantially changing the concentration of the agent in the plasma of the subject. 
     
     
         29 . The method of  claim 28 , wherein the pharmaceutical composition further comprises from about 2.5 ng to about 2.5 mg PYY. 
     
     
         30 - 32 . (canceled)