162 results about "PPAR agonist" patented technology

A method and composition for blood lipid therapy that comprises administering to the subject an effective amount of a PPAR agonist and / or antagonist and an omega-3 fatty acid. The methods and compositions include combination products or concomitant therapy for the treatment of subjects with hypertriglyceridemia, hypercholesteremia, mixed dyslipidemia, vascular disease, artherosclerotic disease and related conditions, obesity, the prevention or reduction of cardiovascular and vascular events, the reduction of insulin resistance, fasting glucose levels and postprandial glucose levels, and / or the reduction of incidence and / or the delay of onset of diabetes.

The present invention relates to a combination comprising a substance with inhibiting effect on the ileal bile acid transport system (I BAT) and at least one other active substance selected from an IBAT inhibitor; an enteroendocrine peptide or enhancer thereof; a dipeptidyl peptidase-IV inhibitor; a biguanidine; an incretin mimetic; a thiazolidinone; a PPAR agonist; a HMG Co-A reductase inhibitor; a bile acid binder; and a TGR5 receptor modulator; wherein the IBAT inhibitor compound and the at least one other active substance are adminstered simultaneously, sequentially or separately.

The invention provides methods and pharmaceutical compositions for administering a PPARα agonist (e.g., OEA-like agonist, OEA-like compound), an OEA-like appetite reducing compound, or a FAAH inhibitor and a CB1 cannabinoid receptor antagonist to a subject in order to reduce the consumption or ingestion of food, ethanol or other appetizing substances as well as in treating appetency disorders related to the excess consumption of food, ethanol, and other appetizing substances. The combination therapy can also be useful for reducing body fat or body weight and modulating lipid metabolism.

The present invention relates to a combination comprising a substance with inhibiting effect on the ileal bile acid transport system (I BAT) and at least one other active substance selected from an IBAT inhibitor; an enteroendocrine peptide or enhancer thereof; a dipeptidyl peptidase-IV inhibitor; a biguanidine; an incretin mimetic; a thiazolidinone; a PPAR agonist; a HMG Co-A reductase inhibitor; a bile acid binder; and a TGR5 receptor modulator; wherein the IBAT inhibitor compound and the at least one other active substance are administered simultaneously, sequentially or separately.

The present invention relates to pharmaceutical compositions comprising a combination of a particular dipeptidyl peptidase-IV (DPP-IV) inhibitor and a particular PPAR-α / γ dual agonist, kits containing such combinations and methods of using such compositions for the treatment of diabetes, diabetes associated with obesity, diabetes-related disorders, obesity, and obesity-related disorders.

The present invention provides a novel compound having an excellent PPAR agonist action. More specifically, it provides a compound represented by the following formula, a salt thereof, an ester thereof or a hydrate of them. Wherein a, b and c are the same as or different from one another and each represents 0 to 4; R1 to R6 are the same as or different from one another and each represents a hydrogen atom, a hydroxyl group, a cyano group, a halogen atom, etc.; A1 and A2 are the same as or different from each other and each represents a single bond, an oxygen atom, etc.; L, M and T each represent a single bond, an alkylene group having one to six carbon atoms, etc.; W represents a carboxyl group; the partial structure represented by the formula:  represents a single bond or a double bond; X represents a single bond, an oxygen atom, —NRX1CQ1O—, etc.; Y represents Y1—Y2— (wherein Y1 represents a 5 to 14-membered aromatic ring having one to four substituents, etc.; and Y2 represents a single bond or a 5 to 14-membered aromatic ring); and the ring Z represents a 5 to 14-membered aromatic ring which have one to four substituents selected form the above-mentioned Group A, may have one or more hetero atoms and may be partially saturated.

Nutritional compositions are provided containing at least one PPAR agonist, at least one PGC-1alpha agonist, and at least one creatine derivative. Methods of promoting anabolism and improving or enhancing physical performance using the compositions are provided. The compositions and methods can be combined with physical training or exercise.

A method of treating a PPARγ and / or RXR related disease or disorder in a subject includes adminstering to the subject an RXR agonist alone or in combination with a PPARγ agonist.

This invention features methods for treating diseases associated with mutations in the CFTR gene by administering PPAR agonists, specifically PPARγ, PPARα, and PPARδ agonists, PPAR inducers, and / or antioxidants. Also disclosed are screening methods for identifying therapeutically useful candidate compounds.

Methods for treating diabetes by increasing the insulin secretion by administration of a GLP-1 receptor agonist and / or a DPP-IV inhibitor in combination with a proton pump inhibitor and optionally a PPAR agonist are provided.

In accordance with the invention, a compound with a protective action for nerve cell can be reselected by adding PPARδ agonist to a culture cell system where toxic substances such as thapsigargin, MPP+ and staurosporine are preliminarily allowed to react and reselecting a compound improving the survival rate. The compound selected by such method can be used as an active ingredient of a therapeutic agent for neurodegenerative diseases such as cerebral infarction and Parkinson's disease. Thus, the invention is very useful for research works for creating novel pharmaceutical agent.

Provided, among other things, is a formulation or kit comprising: (a) a pharmaceutically effective dosage of one or more a glucose-level-controlling bioactive agents selected from an α-glucodase inhibitor, sulfonylurea, meglitinide, thiazolidinediones, biguanide, insulin, dual PPARα / γ agonist, PPARγ agonist or insulin secretagogue; and (b) a pharmaceutically effective dosage of (i) one or more of an antihypertensive bioactive agent selected from an ACE inhibitor, calcium channel blocker, beta blocker, angiotension II receptor antagonist or diuretic, or (ii) one or more of an anti-dyslipidemia bioactive agent selected from a HMG-CoA reductase inhibitor, bile acid sequestrant, fibric acid derivative, sterol, cholesterol absorption inhibitor, MTP inhibitor or nicotinic acid derivative; wherein: in the case of (i) a combination of a first bioactive agent of group (a) that is metformin with a second bioactive agent of group (b), or (ii) a combination of a first bioactive agent of group (a) that is a thiazolidinedione or dual PPARα / γ agonist with an angiotension II receptor antagonist, one or more of the following applies: (I) one of the first bioactive agent or the second bioactive agent is formulated for sustained release, and the other is formulated for immediate release, each formulated for once-a-day dosing; or (II) the co-formulation or kit comprises (A) a biguanide and a thiazolidinedione and (B) one or more group (b) bioactive agents.

The present invention provides methods and compositions for the consistent and quantitative differentiation of human preadipocytes isolated from adipose tissue into adipocytes bearing biochemical, genetic, and physiological characteristics similar to that observed in isolated primary adipocytes. The methods of the invention comprise incubating isolated human preadipocytes, plated at least about 25,000 cells / cm2, in a medium containing, glucose, a cyclic AMP inducer such as isobutylmethylxanthine or forskolin, a glucocorticoid or glucocorticoid analogue, insulin or an insulin analogue and a PPARγ agonist or a RXR agonist. The compositions of the invention include media for the differentiation of human preadipocytes, human adipocytes differentiated by the methods of the invention and transfected adipocytes.The present invention also provides methods for determining the ability of a compound to affect the differentiation of human preadipocytes to adipocytes, for determining the ability of a compound to act as a PPARγ antagonist. a glucocorticoid, a glucocoticoid analogue, or an insulin analogue, for transfecting cultured human adipocytes, and as a means to identify novel polypeptides secreted from human adipocytes into the conditioned medium. The methods and compositions have use in the drug discovery of compounds having relevance to the disease states of diabetes, obesity, and cardiovascular disease and in the studies of these diseases.

Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, aryl-alkyl, heteroaryl-alkyl or cycloalkyl-alkyl, R2 is H, alkyl or haloalkyl, the polymethylene chain (II), is saturated or may contain a carbon-carbon double bond, while n is 2, 3, 4, W is O or S, Y is an unsubstituted phenylene, naphthylene or 1, 2, 3, 4 tetrahydronaphthylene, R3 is II, alkyl or haloalkyl, R4 is II, alkyl, haloalkyl or a substituted or unsubstituted benzyl, are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.

Insulin or a peroxisome proliferator-activated receptor (PPAR) agonist provides reliable and effective prevention of scarring in human skin, or at least a reduction in the severity of scarring. The application of insulin or the PPAR agonist to wounds topically or by local injection is particularly advantageous since it simultaneously reduces / prevents scarring whilst enhancing re-epithelialisation of the wound and thus provides a dual action wound healing treatment. The present invention accordingly provides a highly effective prophylactic treatment for any individual suffering tissue trauma to reduce and / or prevent normal and / or pathological scarring.

The invention concerns an endovascular implant, in particular a stent, with an at least portion-wise active coating. The object of the present invention is to provide locally therapeutic formulations for the treatment of stenosis or restenosis. The implants modified in accordance with the invention are to ensure improved compatibility, in particular in regard to any inflammatory and proliferative processes in the tissue environment. That is achieved in that the active coating includes, as an active substance: 1) PPARα-agonists, PPARδ-agonists or a combination thereof; 2) an RXR-agonist; or 3) a combination of PPAR-agonists and RXR-agonists.

A method of treating a dermatological disorder in a subject includes the step of administering a therapeutically effective amount of at least one PPARγ agonist or derivative thereof to the subject.

The present invention provides compositions and methods for reducing flushing in a patient. In addition, compositions and methods are provided for increasing HDL and / or HDL-2b levels in a patient. In some embodiments, the compositions include an adipocyte G-protein antagonist, a PPAR-α agonist, and a PPAR-γ agonist in amounts effective in to provide a synergistic therapeutic HDL increasing effect, and / or a synergistic therapeutic HDL-2b increasing effect.

This invention features methods for treating diseases associated with mutations in the CFTR gene by administering PPAR agonists, specifically PPARγ, PPARα, and PPARδ agonists, PPAR inducers, and / or antioxidants. Also disclosed are screening methods for identifying therapeutically useful candidate compounds.

Insulin or a peroxisome proliferator-activated receptor (PPAR) agonist provides reliable and effective prevention of scarring in human skin, or at least a reduction in the severity of scarring. The application of insulin or the PPAR agonist to wounds topically or by local injection is particularly advantageous since it simultaneously reduces / prevents scarring whilst enhancing re-epithelialisation of the wound and thus provides a dual action wound healing treatment. The present invention accordingly provides a highly effective prophylactic treatment for any individual suffering tissue trauma to reduce and / or prevent normal and / or pathological scarring.

The invention relates to a pharmaceutical composition comprising an SGLT2 inhibitor and a PPARγ agonist which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.

PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and / or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, aryl-alkyl, heteroaryl-alkyl or cycloalkyl-alkyl, R2 is H, alkyl or haloalkyl, the polymethylene chain (H), is saturated or may contain a carbon-carbon double bond, while n is 2, 3, 4, W is O or S, Y is an unsubstituted phenylene, naphthylene or 1, 2, 3, 4 tetrahydronaphthylene, R3 is H, alkyl or haloalkyl, R4 is H, alkyl, haloalkyl or a substituted or unsubstituted benzyl, are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.

Disclosed is the preparation and pharmaceutical use of substituted arylalcanoic acid derivatives of Formula I, wherein ring A, ring B, R1, R2, R3, R4, R5, X, Alk1, Alk2, Ar1, and Ar2 are as defined in the specification. These compounds, as selective agonists activating peroxisome proliferator-activated receptors (PPAR), in particularly the RXR / PPARalpha, RXR / PPARgamma, and RXR / PPARdelta heterodimers, are useful in the treatment and / or prevention of type 2 diabetes and associated metabolic syndrome such as hypertension, obesity, insulin resistance, hyperlipidemia, hyperglycemia, hypercholesterolemia, atherosclerosis, coronary artery disease, and other cardiovascular disorders with improved side effects profile commonly associated with conventional PPARgamma agonists.

The present invention relates to methods of treating or preventing addiction and relapse use of addictive agents, and treating or preventing addictive or compulsive behaviour and relapse practice of an addictive behaviour or compulsion, by administering a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, alone or in combination with another therapeutic agent, such as, for example, an opioid receptor antagonist or an antidepressant. The present invention also includes pharmaceutical compositions for treating or preventing addiction or relapse that include a PPARγ agonist and one or more other therapeutic agents, as well as unit dosage forms of such pharmaceutical compositions, which contain a dosage effective in treating or preventing addiction or relapse. The methods and compositions of the invention are useful in the treatment or prevention of addiction to any agent, including alcohol, nicotine, marijuana, cocaine, and amphetamines, as well as compulsive and addictive behaviours, including pathological gambling and pathological overeating.

Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: n is 2, 3, or 4 and W is CH2, CH(OH), C(O) or O; R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aryl-alkyl, heteroaryl-alkyl, cycloalkyl-alkyl, or t-butyl; R2 is H, alkyl, haloalkyl or phenyl; Y is an unsubstituted or substituted thiophen-2,5-diyl or phenylene; R3 is alkyl or haloalkyl; R4 is a substituted or unsubstituted phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, quinolyl, pyridyl or benzo[1,3]dioxol-5-yl group; and R5 is H, alkyl, or aminoalkyl; are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.