1731results about "Glucagons" patented technology

Pharmaceutical compositions comprising a macromolecular pharmaceutical agent in micellar form are disclosed. The micelles are formed from an alkali metal alkyl sulfate, and at least one additional micelle-forming compound as described in the specification. An alkali metal salicylate and a pharmaceutically acceptable edetate are also included in the composition. Micelle size ranges between about 1 and 10 nanometers. Methods for making and using the compositions are also disclosed.

The present invention relates to novel peptide conjugates which have increased stability and are useful in the treatment of excess levels of blood glucose.

Novel modified exendins and exendin agonist analogs having an exendin or exendin agonist analog linked to one or more polyethylene glycol polymers, for example, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonist analogs, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and / or slowing gastric emptying or inhibiting food intake.

Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming lactam bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon / GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, substitution of carboxy terminal amino acids, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (K-RNRNNIA) and SEQ ID NO: 28 (KRNR).

Pharmaceutical compositions comprising 2-[6-(3-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile and pharmaceutically acceptable salts thereof are provided as well as kits and articles of manufacture comprising the pharmaceutical compositions as well as methods of using the pharmaceutical compositions.

Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.

The present invention encompasses compositions wherein a GLP-1 compound is complexed with a basic polypeptide. The compositions provide a prolonged duration of action and can be administered by the pulmonary route.

The present invention provides means to improve the chemical stability of aqueous, parenteral pharmaceutical compositions comprising a polypeptide and glycerin. Reactive aldehydes are identified in commercial glycerins, and means for reducing such are provided. Convenient means are provided to assay for reactive aldehydes in glycerin, and a strong linear correlation between the level of reactive aldehydes in glycerin and chemical stability of compositions comprising a polypeptide and glycerin is demonstrated. The invention includes aqueous compositions comprising a polypeptide and glycerin having improved chemical stability compared to compositions previously known.

The present invention encompasses a method of treating a disease by maintaining chronic steady state serum levels of a GLP-1 compound within a specified range.

The present invention discloses fusion proteins comprising transferrin, lactoferrin or melanotransferrin fused to glucagon-like peptide 1 (GLP-1). In one embodiment of the invention, the fusion protein displays increased serum half-life as compared to a GLP-1 peptide in an unfused state. The invention includes a pharmaceutical composition comprising the GLP-1 fusion protein of the invention and a carrier. The fusion protein of the invention can be administered to a subject for treatment of diseases or conditions treatable by GLP-1, including, but not limited to, diabetes, obesity, congestive heart failure and inflammatory bowel syndrome.

We claim a method of lowering plasma glucagon in a subject in need thereof comprising administering to the subject a composition comprising a modified exendin or modified exendin analog, wherein said modification comprises one or more molecule linked to an exendin or the exendin analog wherein said molecule is selected from the group consisiting of polyethylene glycol, gelatin and / or albumin. The modified exendin or the modified exendin analog has activity of suppressing glucagon secretion and / or lowering glucagon levels in the subject and possesses increased biological half-life compared to unmodified exendin or unmodified exendin analog. The method is useful in treating hyperglucagonemia and other disorders that would be benefited by lowering plasma glucagon or suppressing glucagon secretion.

Methods are provided for treating a subject for a condition. In accordance with the subject methods, at least a portion of a subject's autonomic nervous system is modulated during at least one predetermined phase of the subject's menstrual cycle to alter the parasympathetic activity / sympathetic activity ratio in a manner that is effective to treat the subject for the condition. The subject methods find use in the treatment of a variety of different conditions, including various disease conditions, that increase in severity and / or occurrence during one or more phases of the menstrual cycle. Also provided are systems and kits for use in practicing the subject methods.

The present invention relates generally to novel GIP analogs and GIP hybrid polypeptides with selectable properties, useful as agents for the treatment and prevention of metabolic diseases and disorders, for example those which can be alleviated by control plasma glucose levels, insulin levels, and / or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, critical care, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

The present invention concerns combination of an amount of a GPR119 agonist with an amount of a dipeptidyl peptidase IV (DPP-IV) inhibitor such that the combination provides an effect in lowering a blood glucose level or in increasing a blood GLP-1 level in a subject over that provided by the amount of the GPR119 agonist or the amount of the DPP-IV inhibitor alone and the use of such a combination for treating or preventing diabetes and conditions related thereto or conditions ameliorated by increasing a blood GLP-1 level. The present invention also relates to the use of a G protein-coupled receptor to screen for GLP-1 secretagogues.

This invention relates the use of glucagon-like peptides such as GLP-1, a GLP-1 analog, or a GLP-1 derivative in methods and compositions for reducing body weight.

This invention discloses compositions of chloroquine-coupled active agents such as therapeutic antibodies or insulin, including methods for their preparation. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the drug is delivered, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to a drug directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing the drug for therapeutic or other medical uses. The invention also discloses carrier compositions that are coupled to targeting molecules for targeting the delivery of chloroquine substances and antibody or insulin to their site of action.

The present invention relates generally to novel GIP analogs and GIP hybrid polypeptides with selectable properties, useful as agents for the treatment and prevention of metabolic diseases and disorders, for example those which can be alleviated by control plasma glucose levels, insulin levels, and / or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, critical care, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

The present invention relates generally to novel, selectable hybrid polypeptides useful as agents for the treatment and prevention of metabolic diseases and disorders which can be alleviated by control plasma glucose levels, insulin levels, and / or insulin secretion, such as diabetes and diabetes-related conditions. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

Derivatives of glucagon-like peptide I (GLP-1) and especially GLP-1 (7-37) have been found to have insulinotropic activity. The invention pertains to a composition comprising an acid addition salt of GLP-I (7-37) and to a composition comprising a carboxylate salt of GLP-I (7-37). The invention also pertains to method of treating type II diabetes mellitus by providing derivatives of GLP-I (7-37) to the patient.

The present invention encompasses a method of treating a disease by maintaining chronic steady state serum levels of a GLP-1 compound within a specified range.

The present invention is directed to peptide analogues of glucagon-like peptide-1, the pharmaceutically-acceptable salts thereof, to methods of using such analogues to treat mammals and to pharmaceutical compositions useful therefor comprising said analogues.

This patent discloses compositions and methods of use thereof to normalize the blood glucose levels of patients with type 2 diabetes. It relates particularly to a plasmid comprising a chicken β actin promoter and enhancer; a modified GLP-1 (7-37) cDNA (pβGLP1), carrying a furin cleavage site, which is constructed and delivered into a cell for the expression of active GLP-1.

This invention provides a treatment regimen that is effective in inhibiting chemotherapy-induced apoptosis and promoting cell survival. The invention also relates to a treatment regimen that confers resistance to caspase activation, thereby inhibiting caspase-mediated, proteolytic cleavage of functional cellular enzymes. Specifically, subjects undergoing chemotherapy are first exposed to a pretreatment regimen. Under this regimen, a GLP-2 receptor activator, such as h[GLY2]-GLP2, is administered each day for a predetermined beneficial period, e.g., three consecutive days. Approximately about 1 week following pretreatment, the subjects are exposed to an appropriate chemotherapy treatment regimen. Pretreatment with a GLP-2 receptor activator followed by administration of chemotherapeutic agents improves cell survival, reduces bacteremia, attenuates epithelial injury, and inhibits cellular apoptosis. Moreover, it does not impair the effectiveness of chemotherapy nor result in weight loss. The anti-apoptotic effects of GLP-2 may be useful in the reduction of cytoxicity and bacterial infection induced by chemotherapeutic agents.

The present invention provides phamaceutical compositions comprising at least one delivery agent and GLP-1. These pharmaceutical compositions facilitate the oral delivery of GLP-1, providing improved (e.g. increased) bioavailability of GLP-1 compared to administration of GLP-1 without a delivery agent.

The present invention relates to a pharmaceutical composition comprising a GLP-1 derivative having a lipophilic substituent; and a surfactant.

Pharmaceutical composition comprising both insulin and glucagon can be administered to control and treat diabetes while reducing or eliminating the risk of insulin-induced hypoglycemia.