39 results about "Diabetes type i" patented technology

The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and / or long term regulation of energy balance; short-, medium- and / or long term regulation (stimulation and / or inhibition) of food intake; adipogenesis, adiposity and / or obesity; body weight gain and / or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and / or gastrectomy (ghrelin replacement therapy).

The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and / or long term regulation of energy balance; short-, medium- and / or long term regulation (stimulation and / or inhibition) of food intake; adipogenesis, adiposity and / or obesity; body weight gain and / or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and / or gastrectomy (ghrelin replacement therapy).

The present invention is related to the use of oxindole hydrazide derivatives of formula (I) for the treatment and / or prevention of metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of oxindole hydrazide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs, in particular of PTP1B, TC-PTP, SHP and GLEPP-1. The present invention is furthermore related to novel oxindole hydrazide derivatives and method of preparation thereof.(I).

The present invention provides novel triazole derivatives with improved receptor activity and bioavailability properties as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular alcohol disorder, drug abuse, growth retardation, cachexia, short-, medium-, and / or long term regulation of energy balance, short-, medium-, and / or long term regulation (stimulation and / or inhibition) of food intake, intake of rewarding food, adipogenesis, adiposity and / or obesity, body weight gain and / or reduction, diabetes, diabetes type I, diabetes type II, tumor cell proliferation, inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and / or gastrectomy (ghrelin replacement therapy).

The present invention is related to substituted methylene amide derivatives of formula (I) and use thereof for the treatment and / or prevention of metabolic disorders mediated by insulin resistance or pyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of substituted methylene amide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs. Also the present invention relates to a method of treating diabetes type II, obesity and to regulate the appetite of mammals. The present invention is furthermore related to novel substituted methylene amide derivatives and method of preparation thereof. Formula (I).

The invention belongs to the technical field of medicine, and particularly relates to C-indican derivative as shown in general formula (I), the pharmaceutically acceptable salt of the C-indican derivative, the easily-hydrolyzed ester of the C-indican derivative, and the stereoisomer and the intermediate of the C-indican derivative. The invention specifically relates to the C-indican derivative taken as sodium-dependent glucose transporters (SGLT) inhibitor, the pharmaceutically acceptable salt of the C-indican derivative, the easily-hydrolyzed ester of the C-indican derivative, and the stereoisomer and the intermediate of the C-indican derivative. The C-indican derivative provided by the invention not only can be used for the diabetes mellitus such as the insulin dependent diabetes mellitus (I type diabetes mellitus), the non-insulin dependent diabetes mellitus (II type diabetes mellitus) and the like, but also can be used for the treatment and the prevention of various mellitus-related diseases such as the insulin-resistant disease and the fatness. R1, R2, R3, R4, R5, R6a, R6b, R6c, W, M, n and A are defined in the specification.

The present invention is related to aryl dicarboxamides of formula (I) and use thereof for the treatment and / or prevention of obesity and / or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholes-terolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of aryl dicarboxamides of formula (I) to modulate, notably to inhibit the activity of PTPs. A is an aminocarbonyl moiety; Cy is an aryl, heteroaryl, aryl-heteroaryl, heteroaryl-aryl, aryl-aryl, cycloalkyl or heterocycle group; n is either 0 or 1; R1 and R2 are independently from each other is selected from the group consisting of hydrogen or C1-C6-alkyl; R4 and R5 are each independently from each other selected from the group consisting of H, hydroxy, C1-C6 alkyl, carboxy, C1-C6 alkoxy, C1-C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl

The present invention is related to alkynyl aryl carboxamides of Formula (I′) and use thereof for the treatment and / or prevention of an inflammatory disorder, obesity and / or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia-hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of alkynyl aryl carboxamides of Formula (I′) to modulate, notably to inhibit the activity of PTPs. (I′) A is a C2-C15 alkynyl, C2-C6-alkynyl aryl, C2-C6-alkynyl heteroaryl. Cy is an aryl, heteroaryl, cycloalkyl or heterocycle group; n is either 0 or 1. Cy′ is an aryl, which may optionally be fused by a 3-8 membered cycloalkyl. R1 and R2 are independently from each other is selected from the group consisting of hydrogen or (C1-C6)alkyl. R4 and R5 are each independently from each other selected from the group consisting of H, hydroxy. C1-C6 alkyl, carboxy, C1-C6 alkoxy, C1-C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl.

The present invention relates to a medicine composition for preventing and curing diabetes type I and its application. Said medicine composition includes (1), polypeptide capable of curing diabetes type I and (2), nucleic acid vaccine possesses the polypeptide which has 50% of homology respectively with proinsulin, GAD65 and B7-1 wa polypeptide which can be combined with T cell negative regulator CTLA-4. The invented medicine composition can effectively prevent and cure diabetes type I.

The invention relates to an aminopyrimidine derivative used as a PPAR-gamma regulator, specifically to a 2,4-diamino-6-chloropyrimidone derivative as shown in a formula I which is described in the specification, and / or medicinal salts thereof, a preparation method thereof, and application of the derivatives and / or medicinal salts thereof in treatment and / or prevention of disease related to peroxidase proliferator-activated acceptor subtype PPAR-gamma, e.g., inflammations (including rheumatoid arthritis), atherosclerosis, diabetes type I or II, diabetic complications, obesity, hyperlipidemia, impaired glucose tolerance, cerebral ischemia, Parkinson's disease, insulin resistance and osteoporosis. The invention also relates to a pharmaceutical composition containing the derivative. In the formula I, two substituents, i.e., R1 and R2 are defined in the specification.

The present invention is related to carboxylic acids of Formula (I) and use thereof for the treatment and / or prevention of obesity and / or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of carboxylic acids of Formula (I) to modulate, notably to inhibit the activity of PTPs.

The invention discloses a preparation method of Coxsackie virus B3 virus-like particles. The method provided by the invention comprises the following steps: 1) cloning a VP1 gene and a VP4 gene of the Coxsackie virus B3 to a target plasmid 1 to obtain a recombinant expression vector 1; and cloning a VP2 gene and a VP3 gene to a target plasmid 2 to obtain a recombinant expression vector 2; 2) cotransforming the recombinant expression vector 1 and the recombinant expression vector 2 obtained in the step 1 ) to a yeast cell to obtain a recombinant yeast cell expressing the VP1 gene, the VP2 gene, the VP3 gene and the VP4 gene; and 3) cracking the recombinant yeast cell obtained in the step 2 ), and separating to obtain the Coxsackie virus B3 virus-like particles. Experiments show that Coxsackie virus B3 virus-like particles are successfully prepared by the method provided by the invention in the yeast expression system, and can be further used in candidate preventive vaccines and pharmaceutical compositions for virus myocarditis and diabetes type I.

This invention pertains to the use of steroid compounds including spirosteroid analogues in treating, preventing or ameliorating the symptoms of inflammatory conditions. The steroid compounds are useful for treating a range of inflammatory conditions, including, but not limited to asthma, lung inflammation, retinal inflammatory conditions, autoimmune diseases such as rheumatoid arthritis, diabetes type I, systemic lupus erythematosus, ulcerative colitis and inflammatory bowel diseases and myopathies, as well as multiple sclerosis. The active compounds are represented by Formula (I): wherein R1, R2, R3, R4, R5, R6, R7, A, B, X, Y and Z are defined in the description of the invention.

The present invention is related to aryl dicarboxamides of formula (I) and use thereof for the treatment and / or prevention of obesity and / or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholes-terolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of aryl dicarboxamides of formula (I) to modulate, notably to inhibit the activity of PTPs. A is an aminocarbonyl moiety; Cy is an aryl, heteroaryl, aryl-heteroaryl, heteroaryl-aryl, aryl-aryl, cycloalkyl or heterocycle group; n is either 0 or 1; R1 and R2 are independently from each other is selected from the group consisting of hydrogen or C1-C6-alkyl; R4 and R5 are each independently from each other selected from the group consisting of H, hydroxy, C1-C6 alkyl, carboxy, C1-C6 alkoxy, C1-C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl.

The technical problem to be solved by the present invention is to prolong the half-life of an Exendin-4 polypeptide and to improve the stability and the safety of the existing Exendin-4 polypeptide-containing fusion protein. The scheme for solving the technical problem is to provide a new fusion protein containing the Exendin-4 polypeptide, wherein the structure of the fusion protein sequentially comprises Exendin-4, a connecting peptide, Exendin-4, a connecting peptide and an IgG4Fc mutant from the nitrogen terminal. According to the present invention, the provided fusion protein containing the Exendin-4 has characteristics of good stability, long half-life and low toxic-side effect; and the fusion protein of the invention can be used for treatment of diabetes type I and diabetes type II, and has high clinical application value.

Disclosed herein are compositions and methods to differentiate pancreatic cells into functional insulin-producing CD133 / Ki-67-positive activated islet proliferating cells (AIPCs) derived from isolated pancreatic islets and expand derived-AIPCs in in vitro cultures using a culture medium comprising an active agent. Also disclosed herein is the use of the AIPCs for implantation into a mammal for in vivo therapy, specifically for pancreatic disorders, including diabetes type I.

The present invention is related to alkynyl aryl carboxamides of Formula (I′) and use thereof for the treatment and / or prevention of an inflammatory disorder, obesity and / or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia-hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of alkynyl aryl carboxamides of Formula (I′) to modulate, notably to inhibit the activity of PTPs. (I′) A is a C2-C15 alkynyl, C2-C6-alkynyl aryl, C2-C6-alkynyl heteroaryl. Cy is an aryl, heteroaryl, cycloalkyl or heterocycle group; n is either 0 or 1. Cy′ is an aryl., which may optionally be fused by a 3-8 membered cycloalkyl. R1 and R2 are independently from each other is selected from the group consisting of hydrogen or (C1-C6)alkyl. R4and R5 are each independently from each other selected from the group consisting of H, hydroxy. C1-C6 alkyl, carboxy, C1-C6 alkoxy, C1-C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl.

The present invention is related to the use of oxindole hydrazide derivatives of formula (I) for the treatment and / or prevention of metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of oxindole hydrazide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs, in particular of PTP1B, TC-PTP, SHP and GLEPP-1. The present invention is furthermore related to novel oxindole hydrazide derivatives and method of preparation thereof.(I).

The present invention is related to carboxylic acids of Formula (I) and use thereof for the treatment and / or prevention of obesity and / or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of carboxylic acids of Formula (I) to modulate, notably to inhibit the activity of PTPs.

The present invention provides novel triazole derivatives with improved receptor activity and bioavailability properties as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular alcohol disorder, drug abuse, growth retardation, cachexia, short-, medium-, and / or long term regulation of energy balance, short-, medium-, and / or long term regulation (stimulation and / or inhibition) of food intake, intake of rewarding food, adipogenesis, adiposity and / or obesity, body weight gain and / or reduction, diabetes, diabetes type I, diabetes type II, tumor cell proliferation, inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and / or gastrectomy (ghrelin replacement therapy).

The invention provides an external use medicine for treating diabetes, which is prepared by the raw materials with by weight proportion: 15-25 parts of yam, 15-25 parts of radix astragali, 3-9 parts of rhizoma anemarrhenae, 1-5 parts of endothelium corneum gigeriae galli, 1-5 parts of calamus, 2-8 parts of Chinese magnoliavine fruit, 1-5 parts of mongolian snakegourd root, 7-13 parts of myrrh, 7-13 parts of amber, 7-13 parts of frankincense, 3-9 parts of cornucervi pantotrichum, 3-9 parts of radix curcumae and 7-13 parts of Chinese asafetida; when the medicine is prepared, the raw materials are taken according to the proportion and ground to be screened by 40-500 meshes, and then is mixed into paste by using honey or vaseline; the medicines in the invention are reasonably matched, has good treatment effect on diabetes type I and diabetes type II can remarkably reduce the blood sugar of patients after dinner for 2 hours, fasting blood-glucose and glycolated hemoglobin; when in use, themedicine is externally used without toxicity and side effects as well as irritation to gastrointestinal tract.

Disclosed herein are compositions and methods to differentiate pancreatic cells into functional insulin-producing CD133 / KI-67-positive activated islet proliferating cells (AIPCs) derived from isolated pancreatic islets and expand derived-AIPCs in in vitro cultures using a culture medium comprising an active agent. Also disclosed herein is the use of the AIPCs for implantation into a mammal for in vivo therapy, specifically for pancreatic disorders, including diabetes type I.

The invention provides an immunosuppressive drug and a preparation method thereof. The immunosuppressive drug comprises dendritic cells with an immunity negative regulating effect induced by pancreasstroma cells. The invention further provides a method for preparing the immunosuppressive drug. The method comprises the following steps: 1) to obtain a mononuclear cell from blood of a mammal, and inducing the mononuclear cell as a mature dendritic cell; 2) co-culturing the pancreas stroma cells and the dendritic cells, and inducing regulatory dendritic cells; and 3) collecting the regulatory dendritic cells for playing the immunity negative regulating effect. The immunosuppressive drug provided by the invention has the good immunosuppressive action, can be used for treating rheumatoid arthritis and diabetes type I, and has good using safety.

The present invention relates to a pharmaceutical composition for preventing or treating metabolic diseases, in which a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative and at least another active ingredient, which is selected from the group consisting of dipeptidyl peptidase-4 (DPPIV) inhibitor-based, sulfonylurea-based, thiazolidinedione (TZD)-based, biguanide-based, and sodium / glucose cotransporter 2 (SGLT2) inhibitor-based drugs, may be administered in combination or in the form of a composite preparation. The use of the composition of the present invention can provide a remarkably excellent blood sugar reducing effect in various animal diabetic disease models, and the composition of the present invention can be favorably used as a pharmaceutical composition for preventing or treating metabolic diseases, such as obesity, diabetes type I, diabetes type II, glucose intolerance symptoms, insulin resistance symptoms, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X.

The invention discloses novel liquid medicine capable of treating cancer and having many other effects. The novel liquid medicine is prepared by using disodium hydrogen phosphate, carbonized hair andwater according to a certain proportion. The novel liquid medicine has the advantages that the new liquid medicine can be intermittently taken by cancer patients for a long time to treat cancer and prevent massive hemorrhage caused by tissue wounds formed after the cancer is dissolved, can be taken by patients with diabetes type I to inhibit the complication of the diabetes type I, can be taken bypatients with diabetes type II to lower blood sugar concentration, can be taken by hypertension patients to lower blood pressure, can be taken by hypotension patients to increase blood pressure, canbe taken by patients who have a cold to inhibit cold viruses, can be taken by patients with in-vivo herpes viruses and hepatitis B viruses to inhibit the herpes viruses and hepatitis B viruses, and can treat various other chronic diseases; the novel liquid medicine can also be intermittently taken by common people to achieve a healthcare effect, and the people who take the liquid medicine can havephysical and psychological health and pleasure and can be rejuvenated; the people who begin taking the liquid medicine need to be guided by staff with professional knowledge and skills and can take the liquid medicine by themselves after they master the main points; the effective liquid medicine is prepared on the basis of the scientific theoretical knowledge of the inventor and through constantmassive interest observation, logical highly-initiative analysis, judgment and reasoning, self-trial and trials on other people and constant improvement by the inventor, and the novel liquid medicineis an updated and original invention of the inventor.

The invention discloses a preparation method of Coxsackie virus B3 virus-like particles. The method provided by the invention comprises the following steps: 1) cloning a VP1 gene and a VP4 gene of the Coxsackie virus B3 to a target plasmid 1 to obtain a recombinant expression vector 1; and cloning a VP2 gene and a VP3 gene to a target plasmid 2 to obtain a recombinant expression vector 2; 2) cotransforming the recombinant expression vector 1 and the recombinant expression vector 2 obtained in the step 1 ) to a yeast cell to obtain a recombinant yeast cell expressing the VP1 gene, the VP2 gene, the VP3 gene and the VP4 gene; and 3) cracking the recombinant yeast cell obtained in the step 2 ), and separating to obtain the Coxsackie virus B3 virus-like particles. Experiments show that Coxsackie virus B3 virus-like particles are successfully prepared by the method provided by the invention in the yeast expression system, and can be further used in candidate preventive vaccines and pharmaceutical compositions for virus myocarditis and diabetes type I.

The invention provides a medicament for gene therapy of recombinant adeno-associated virus mediated diabetes type I. The recombinant adeno-associated virus vector carries an oFat-1(optimized Fat-1, for short oFat-1) gene cassette containing human a miR-142-3p target sequence. An in vivo experiment shows that the recombinant adeno-associated virus vector can be efficiently introduced into bodies aswell as continuously and stably express Fat-1 protein, in order to increase content of omega-3 polyunsaturated fatty acid, increase content of insulin in vivo, and maintain stabilization of blood sugar. A result shows that the recombinant adeno-associated virus vector is hopeful to be developed into a novel medicament for treating diabetes type I.

The present invention relates to a pharmaceutical composition for preventing or treating metabolic diseases, in which a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative and at least another active ingredient, which is selected from the group consisting of dipeptidyl peptidase-4 (DPPIV) inhibitor-based, sulfonylurea-based, thiazolidinedione (TZD)-based, biguanide-based, and sodium / glucose cotransporter 2 (SGLT2) inhibitor-based drugs, may be administered in combination or in the form of a composite preparation. The use of the composition of the present invention can provide a remarkablyexcellent blood sugar reducing effect in various animal diabetic disease models, and the composition of the present invention can be favorably used as a pharmaceutical composition for preventing or treating metabolic diseases, such as obesity, diabetes type I, diabetes type II, glucose intolerance symptoms, insulin resistance symptoms, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X.

The present invention relates to a novel bicyclic derivative that has an inhibitory activity against sodium-glucose linked transporters (SGLTs) present in the intestines and kidneys, or a pharmaceutically acceptable salt, isomer, hydrate or solvate thereof, and a pharmaceutical composition including the same as an active ingredient, which effectively inhibit the SGLT activity, and thus can be used as a therapeutic agent to treat diseases caused by hyperglycemia, such as diabetes including insulin-dependent diabetes (type I diabetes mellitus) and non-insulin-dependent diabetes (type II diabetes mellitus), diabetic complications, and obesity.

The invention relates to an aminopyrimidine derivative used as a PPAR-gamma regulator, specifically to a 2,4-diamino-6-chloropyrimidone derivative as shown in a formula I which is described in the specification, and / or medicinal salts thereof, a preparation method thereof, and application of the derivatives and / or medicinal salts thereof in treatment and / or prevention of disease related to peroxidase proliferator-activated acceptor subtype PPAR-gamma, e.g., inflammations (including rheumatoid arthritis), atherosclerosis, diabetes type I or II, diabetic complications, obesity, hyperlipidemia, impaired glucose tolerance, cerebral ischemia, Parkinson's disease, insulin resistance and osteoporosis. The invention also relates to a pharmaceutical composition containing the derivative. In the formula I, two substituents, i.e., R1 and R2 are defined in the specification.