51 results about "Type i diabetes mellitus" patented technology

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 relates to the field of biomedicine, in particular to a preparation method of a mesenchymal stem cell artificial pancreas islet. The preparation method of a mesenchymal stem cell artificial pancreas islet comprises the following steps of (1) culturing mesenchymal stem cells, and performing inducing to generate ancreas islet like cells; (2) performing extraction and culture of vascular endothelial cells; (3) preparing temperature-sensitive chitosan hydrogel; (4) preparing composite hydrogel; and (5) performing partial transplantation on the composite hydrogel obtained in the step(4), and rapidly performing agglutination under the 37 DEG C body temperature environment to form the artificial pancreas islet. According to the preparation method of the mesenchymal stem cell artificial pancreas islet disclosed by the invention, the problems of insulin resistance in the insulin treatment course, large number of pancreas islets required during pancreas islet transplantation and high immunological rejection reactions during pancreas islet transplantation are solved, and new donors are provided for pancreas islet transplantation for treating type I diabetes mellitus.

The invention provides a kit and method for detecting an autoimmune antibody of the type-I diabetes mellitus and belongs to the technical field of biochemical medicine detection. The method comprises the following steps of: adding a luciferase as an antibody fusion protein, wherein the luciferase as the antibody fusion protein is generated by 293 cell culture and can be specifically combined with a diabetes mellitus autoantibody in serum of a patient; then, adding protein-A agarose, depositing a fusion protein as an antibody compound, centrifuging, and then, absorbing the uncombined fusion protein from a supernatant liquid; and then, adding a luciferase substrate, and detecting the fluorescence intensity by using a fluorescence detection instrument to finally measure the content of the diabetes mellitus autoantibody in a sample to be detected. Compared with the traditional HPLC (High Performance Liquid Chromatography), a micro-quantitative fluorescence detection instrument used for detecting in the method has the advantages of simplicity in operation, no need of uncovering to block a pollution way, high sensitivity and signal to noise ratio, stable and reliable measured value and capability of ensuring reliable experiment result and safety of operating personnel and meeting the requirements of micro quantity and regent saving.

The present invention relates to salts of 2-(2-((4-(((4-chlorophenyl)(phenyl)-carbamoyloxy)methyl)cyclohexyl)methoxy)acetamido)ethanesulfonic acid (Compound 1) and crystalline forms, solvates and hydrates thereof. The present invention further relates to processes and intermediates useful in the preparation of Compound I and salts, solvates and hydrates thereof. Crystalline forms, salts, solvates and hydrates of the present invention and pharmaceutical compositions thereof are useful in the treatment of for example, pulmonary arterial hypertension (PAH); platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack; angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; atherosclerosis; acne; type I diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

The invention is directed to thiocarbonate compounds of Formula (I)-(III) and methods of treating atherosclerosis, neuropathy, nephropathy, retinopathy, inflammatory disorders, COPD, cardiovascular diseases, metabolic disorders, type I diabetes mellitus, type II diabetes mellitus, LADA, Wolfram Syndrome 1, Wolcott-Rallison syndrome, metabolic syndrome, dyslipidemia, hyperglycemia, or insulin resistance. The compounds of the invention are also useful for protecting pancreatic beta-cells and for reducing free fatty acids, triglycerides, advanced glycated end products, ROS, lipid peroxidation, tissue and plasma TNFalpha and IL6 levels, or for delaying or preventing cardiovascular complications associated with atherosclerosis.

The present invention relates to the use of glycogen synthase kinase 3(GSK3) inhibitors, especially inhibitors of GSK-3α, GSK-3β and GSK-3β2, preferably, inhibitors of GSK-3β, in patients having autoimmune diseases and / or immune dysfunction / dysregulation to induce immune tolerance. Inhibition of GSK leads to activation of a pathway of dendritic cell maturation which leads to a dendritic phenotype which attenuates, rather than induces, immune responses. The immune responses and mature dendritic cells produced by the method of the present invention redirect or attenuate the immune response in individuals, thus leading to effective therapies for a number of autoimmune diseases and / or diseases of immune dysfunction / dysregulation (immune inflammatory diseases), including systemic lupus erythematosus (SLE), autoimmune diabetes (type I diabetes mellitus), asthma, rheumatoid arthritis, inflammatory bowel disease, among numerous others.

The invention discloses an extraction method of gypenoside XLIX and a medicine for treating diabetes and hyperlipidemia, belongs to the technical field of pharmaceutical chemicals, and provides a medicine taking gypenoside XLIX which is extracted and purified from gynostemma pentaphylla total saponins as a single active component, and applications of the extracted gypenoside XLIX in preparation ofthe medicine used for treating patients with diabetes and cardiovascular diseases. The medical curative effect is definite, the medicine is safe and free of toxic and side effects. The method for extracting gypenoside XLIX comprises the following steps: by taking gynostemma pentaphylla total saponins as a raw material, carrying out column chromatography, recovering a solvent to obtain a gypenoside XLIX crude product, dissolving the crude product with methanol, purifying by adopting preparative liquid chromatography, and repeatedly recrystallizing to obtain gypenoside XLIX with the purity of 90% or higher. The medicine for treating diabetes and hyperlipidemia is prepared by adding medical auxiliary materials into gypenoside XLIX with the content of 90% or higher. According to the method, amodern extraction and purification technology is adopted, and the purity of the extracted gypenoside XLIX reaches 90% or above; the medicine prepared from the gypenoside XLIX is used for treating diseases including type I diabetes mellitus, type II diabetes mellitus and diabetic nephropathy.

The invention is to use camel milk and rosiglitazone maleate for combined treatment of type II diabetes, and relates to the field of medicine. It was reported that camel milk can reduce trypsin dosage for patients with type I diabetes mellitus. But there is no report about the effect of camel milk on type II diabetes. The experiment of the invention indicates that drinking camel milk alone has the same effect with rosiglitazone maleate in reducing blood sugar, blood lipid, and trypsin. Combined drinking of rosiglitazone maleate 4mg and camel milk 8ml once each day has better therapeutic effect than exclusive use of rosiglitazone maleate in reducing blood sugar, blood lipid, and trypsin. The invention has the advantages of convenient administration and low cost, and also is benefit for the economical development of pastoral zone.

Compound of a compound of formula (I) or a salt, N-oxide, hydrate or solvate thereof, in the preparation of a composition for inhibition of HSP90 activity: wherein ring A is an aromatic or non-aromatic carbocyclic or heterocyclic ring having 5 ring atoms, for example 1,2,3-triazolyl or a 1,2,4-triazolyl or a tetrazolyl ring; and R1 R2 R3 are as defined in the specification are inhibitors of HSP90 and therefore of use in the treatment of, for example, cancers, viral disease, inflammatory diseases such as rheumatoid arthritis, asthma, multiple sclerosis, Type I diabetes, lupus, psoriasis and inflammatory bowel disease; cystic fibrosis angiogenesis-related disease such as diabetic retinopathy, haemangiomas, and endometriosis; or for protection of normal cells against chemotherapy-induced toxicity; or diseases where failure to undergo apoptosis is an underlying factor, or protection from hypoxia-ischemic injury due to elevation of Hsp70 in the heart and brain; scrapie / CJD, Huntingdon's and Alzheimer's disease.

Provided is a prophylactic agent for an autoimmune disease, including a fraction of a milk-derived basic protein, lactoperoxidase, and lactoferrin as active ingredients. The agent can be taken on a daily basis, and even if it is taken over a long period of time, its safety is high, and hence, an autoimmune disease such as type I diabetes mellitus or rheumatoid arthritis, which could not be effectively prevented or treated by a conventional method, can be prevented.

Provided is a novel JAK3 inhibitor useful as a preventive and / or therapeutic agent for organ transplant rejection, graft versus host disease (GvHD), rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Sjogren's syndrome, Behcet's disease, type I diabetes mellitus, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, ulcerative colitis, Crohn's disease, asthma, allergic conjunctivitis, atopic dermatitis, contact dermatitis, urticaria, eczema, psoriasis, allergic conjunctivitis, uveitis, cancer, leukemia, etc. A pyridine-3-carboxyamide derivative represented by general formula (1) or a salt thereof or a solvate thereof are also provided.

The invention provides an expression method, a special expression vector, engineering bacteria and an application for recombinant human insulin. According to the expression method, recombinant human insulin genes can be subjected to induced expression in food-grade lactobacillus, and the recombinant human insulin is presented on the surface of the lactobacillus. The engineering bacteria, the expression vector and an inducer, which are used in the expression method, all meet food-grade requirements, so that the potential hazard caused by existence of resistance genes of the expression vector and non-food-grade inducers is avoided. Lactobacillus engineering bacteria containing cell-wall presentation insulin obtained according to the invention can stimulate an NOD (Non-obese diabetic) rat to produce specific antibodies for the recombinant human insulin, so that the level of a cell factor IL-4 related to immune tolerance is obviously increased, and the generation of immune tolerance is induced; a microbial agent can be taken as an oral vaccine for type I diabetes mellitus as long as the induced lactobacillus engineering bacteria are prepared into the microbial agent, complicated post-processing processes, such as purification, are unnecessary, and wide application prospects are obtained.

Disclosed is a solid dispersion and a preparation method therefor. The solid dispersion contains a glucokinase activator, an isotopic label thereof, or a medicinal salt thereof and a polymer support. Further disclosed is a solid dispersion composition containing the solid dispersion and an excipient. Also disclosed is an oral preparation of the glucokinase activator, containing the solid dispersion or the solid dispersion composition. Also disclosed is a tablet and a capsule of the glucokinase activator and a preparation method therefor. In addition, also disclosed is the uses of the solid dispersion, the solid dispersion composition and the oral preparations comprising the tablet and the capsule, which can be used for treating and / or preventing selected diseases or medical conditions and especially one or more diseases selected from type I diabetes mellitus, type II diabetes mellitus, impaired glucose tolerance, impaired fasting glucose and hyperglycemia.

The invention discloses a traditional Chinese medicine for treating diabetes mellitus and a preparation method thereof. According to the invention, the traditional Chinese medicine for treating diabetes mellitus is suitable for treating type I diabetes mellitus and type II diabetes mellitus in clinical practice; especially, the traditional Chinese medicine shows substantial efficacy in treating the type II diabetes mellitus with no adverse reaction as well as no toxic and side effects. The traditional Chinese medicine for treating the diabetes mellitus, which can be made in a form of powder, pill, and tablet, is easy to carry and to take as well as is cheap. Therefore, the traditional Chinese medicine for treating the diabetes mellitus has a bright prospect on clinical application.

The invention belongs to the technical field of biological medicine, and particularly relates to a recombinant expression vector for specifically and highly expressing SIA in muscle-derived cells and application of the recombinant expression vector. A recombinant expression vector promoter is PEMS, and the nucleotide sequence of the recombinant expression vector promoter is shown as SEQ ID NO.1; and the nucleotide sequence for coding the SIA is as shown in SEQ ID NO. 2. A flexible peptide (GGGGS) 3 is used for replacing a C peptide to modify proinsulin, a high-activity single-chain insulin analogue SIA is obtained, an enhanced muscle specific promoter PEMS is used for regulating and controlling the expression of the SIA, specific efficient expression of the high-activity single-chain insulin analogue SIA in skeletal muscle cells is achieved, the high-activity single-chain insulin analogue SIA is secreted out of cells to enter a blood circulation system, the effects of effectively reducing blood sugar can be achieved, and meanwhile, unnecessary side effects caused by ectopic expression can also be avoided. The recombinant expression vector provided by the invention can be used for preparing medicines for treating type I diabetes mellitus.

The invention discloses enteromorpha margin oligosaccharide with a blood glucose reducing function as well as a preparation method and application thereof. The invention provides an enteromorpha margin oligosaccharide mixture with the blood glucose reducing effect; enteromorpha margin from the production place of Qingdao is degraded into enteromorpha margin oligosaccharide with the molecular weight range being 1000Da to 10000Da; the efficacy of improving the diabetes is achieved; the enteromorpha margin oligosaccharide can be used for medicine preparations for relieving type I diabetes mellitus or health care food in various modes or paths.

A method of treating diabetes by administering Carvedilol in patients and diabetes mellitus. This method of treatment will eliminate the need for insulin and other blood sugar controlling agents in hypertensive patients with Type II diabetes mellitus, and will significantly reduce the required dosage of insulin and eliminate the need for other blood controlling agents in patients with Type I diabetes mellitus. This method will also delay and / or prevent the progression of non-insulin dependent Type II diabetes mellitus to insulin-dependent Type II diabetes mellitus. Moreover, this method has been shown to preserve improve insulin receptor sensitivity such that patient's HbA1c level reaches and is maintained at or near 7% or less.

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.

Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations that include them. Also disclosed are methods of preparing and using novel capsid-protein-mutated rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more diseases, disorders, or dysfunctions of the mammalian vascular system, and complications from Type I diabetes. Also disclosed are methods for systemic and tissue-localized delivery of therapeutic rAAV-based gene expression cassettes to vascular endothelial cells, tissues, and organs, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and / or in vivo applications including the treatment of vasculitis, and complications arising from Type I diabetes, such as macular edema, nephropathy, diabetic retinopathy, and the like.

The invention belongs to the field of medicines and pharmacy, and provides a polypeptide, a derivative and hydrogel thereof, and an application of the polypeptide in preparation of medicines for preventing and / or treating type I diabetes mellitus. The invention provides a polypeptide of which the sequence is shown as SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3, and provides a derivative of the polypeptide and hydrogel thereof. The polypeptide, the derivative thereof and the hydrogel provided by the invention are simple in preparation process, the chemical structure of the product is clear, theused raw materials are amino acids necessary for a human body every day, the cost is low, and the biocompatibility is good; the polypeptide, the derivative thereof and the hydrogel can simulate insulin antigen epitopes, recover the immune tolerance to insulin antigens, have high ability to remove blood sugar, keep blood sugar stable in a normal range, and can effectively reduce the incidence of type I diabetes mellitus.

The invention concerns bifunctional fusion molecules, and novel, safer and more efficacious methods for the treatment of immune disorders resulting from excessive or unwanted immune responses. The invention provides methods for the suppression of type I hypersensitive (i.e., IgE-mediated) allergic conditions, methods for the prevention of anaphylactic responses that occur as a result of traditional peptide immunotherapies for allergic and autoimmune disorders, and provides novel methods for the treatment of autoimmune conditions, where the methods have reduced risk of triggering an anaphylactic response. The invention provides novel therapeutic approaches for the treatment of allergic responses, including the prevention of anaphylactic response that can occur from environmental allergen exposure. The invention also provides methods for the treatment of autoimmune disorders such as multiple sclerosis, autoimmune type I diabetes mellitus, and rheumatoid arthritis. The invention also provides methods for preventing anaphylactic response during traditional antigen therapies.

The invention discloses a muscle-derived cell blood glucose response type expression SIA promoter, a recombinant vector and a construction method and application thereof, and belongs to the technical field of biological medicine.The blood glucose response type muscle specific promoter pGREMS is used for regulating and controlling expression of SIA, high-activity single-chain insulin analogues SIA3 and SIA4 are obtained, and the expression of the SIA is regulated and controlled. SIA7 is specifically and efficiently expressed at the skeletal muscle part and secreted into blood, so that the effect of effectively reducing blood sugar can be achieved. Meanwhile, the designed and screened promoter has a blood glucose responsive function, so that insulin expression can be closed when the blood glucose is relatively low, and the side effect of hypoglycemia caused by overexpression of insulin is avoided. The recombinant expression vector provided by the invention can be applied to preparation of medicines for treating diabetes mellitus and is particularly suitable for type I diabetes mellitus, and the provided recombinant expression vector is simple in construction method, convenient to operate and suitable for industrial large-scale production.

The invention is directed to thiocarbonate compounds of Formula (I)-(III) and methods of treating atherosclerosis, neuropathy, nephropathy, retinopathy, inflammatory disorders, COPD, cardiovascular diseases, metabolic disorders, type I diabetes mellitus, type II diabetes mellitus, LADA, Wolfram Syndrome 1, Wolcott-Rallison syndrome, metabolic syndrome, dyslipidemia, hyperglycemia, or insulin resistance. The compounds of the invention are also useful for protecting pancreatic beta-cells and for reducing free fatty acids, triglycerides, advanced glycated end products, ROS, lipid peroxidation, tissue and plasma TNFalpha and IL6 levels, or for delaying or preventing cardiovascular complications associated with atherosclerosis.

Disclosed are compositions and methods for detecting, isolating, and / or characterizing a T cell or autoantibody associated with type I diabetes. The composition and methods comprise the use of a hybrid insulin peptide having an N-terminal amino acid sequence taken from the human insulin peptide and a C-terminal amino acid sequence taken from a secretory granule protein that are joined through a peptide bond to form an autoimmune antigen. The detecting, isolating and characterization step further includes performing an immunoassay and / or T cell proliferation assay with the disclosed hybrid insulin peptides, where preferably, the immunoassay is an ELISPOT assay.

Provided are isolated complexes comprising a major histocompatibility complex (MHC) class II and a type I diabetes-associated autoantigenic peptide, the isolated complex having a structural conformation which enables isolation of a high affinity entity which comprises an antigen binding domain capable of specifically binding to a native conformation of a complex composed of the MHC class II and the type I diabetes-associated autoantigenic peptide; and isolated high affinity entities comprising an antigen binding domain capable of specifically binding the complex, wherein the isolated high affinity entity does not bind to the MHC class II in an absence of the diabetes-associated autoantigenic peptide, wherein the isolated high affinity entity does not bind to the diabetes-associated autoantigenic peptide in an absence of the MHC class II; and methods and kits using same for diagnostic and therapeutic purposes.

The invention discloses a gene combination, a primer and a probe for detecting susceptibility to type I diabetes mellitus and an application, wherein the gene combination comprises the combination of three genes close related to the type I diabetes mellitus, including a PTPN22 gene, a CTLA-4 gene and a VDR gene, and the following SNPs (Single Nucleotide Polymorphism) loci including a locus rs2476601 of the PTPN22 gene, a locus rs231775 of the CTLA-4 gene and a locus rs2228570 of the VDR gene are comprised. By detecting a group of genes and loci related to the susceptibility to the type I diabetes mellitus, populations susceptible to the type I diabetes mellitus are screened out by synthetically detecting and analyzing whether detected populations carry susceptive genes to the type I diabetes mellitus by utilizing specific primers and probes through the combination of a single nucleotide elongation technology and a microarray chip technology, so as to achieve the purpose of prevention by changing unhealthy lifestyles.

The invention is concerned with use of oral inorganic pyrophosphate for preventing and / or reducing tissue calcification, particularly soft tissue calcification, and / or diseases or disorders characterized by low plasma PPi levels, as, e.g., occurs in chronic kidney disease (CKD), end-stage renal disease (ESRD), generalized arterial calcification of infancy (GACI), Pseudoxanthoma elasticum (PXE), Arterial Calcification Due to Deficiency of CD73 (ACDC), Ehlers-Danlos syndrome, arteriosclerosis obliterans, venous calcifications, crystal deposition disorders, calcification resulting from neurological disorders, calcinosis universalis, calcinosis circumscripta, scleroderma, dermatomyositis, systemic lupus erythematosus, hyperparathyroidism, neoplasms, milk-alkali syndrome, hypervitaminosis D, tumoral calcinosis, hypophosphatemic rickets, ossification of the posterior longitudinal ligament of the spine, myocardial ischemia, joint calcification, heterotropic ossification of traumatized muscle, angioid streaks, diabetes mellitus type II, cardiovascular disorder, or atherosclerosis.

The present invention provides a method of diagnosing or predicting susceptibility to an autoimmune disease in an individual by determining the presence or absence in the individual of a 2-2-4 haplotype at the Notch4, HSP70-HOM and D6S273 loci, where the presence of the haplotype diagnoses or predicts susceptibility to the autoimmune disease. The methods of the invention can be particularly useful for diagnosing or predicting susceptibility to Crohn's disease, rheumatoid arthritis or type I diabetes mellitus. In a preferred embodiment, a method of the invention is used to diagnose or predict susceptibility to Crohn's disease in an individual of Ashkenazi Jewish ethnicity.

The invention discloses a gas-sensitive nano material based on a carbon particle modified mesoporous iron oxide nanorod structure as well as a preparation process and application of the gas-sensitivenano material. A template material FeMOF nanorod prepared by a solvothermal method is subjected to a one-step calcining process by adopting a self-sacrificing template method, so that the carbon particle modified mesoporous iron oxide nanorod heterostructure is obtained. The preparation method of the material has the advantages of being low in cost, simple in synthesis process, high in preparationefficiency, capable of achieving large-scale production and the like. The prepared heterogeneous gas-sensitive nano material can realize ultra-sensitive and high-selectivity detection of ppb-grade trace acetone gas, can be widely applied to monitoring of gas leakage and emission in chemical industry, laboratories and the like, can realize screening of type I diabetes mellitus when being applied to detection of exhaled breath of human bodies, and is applied to the fields of environmental detection and medical treatment and health.