63 results about "Endothelins" patented technology

The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin related diseases.

The present invention relates to a composition for promoting the efficiency of somatic cell replication, comprising endothelin as an active ingredient. When somatic cells are treated with the composition of the present invention, H3K9me3, which is suspected to be a factor for the lowering success rate of nuclear substitution, is inhibited, and H3K4me3, which has the opposite effect, is increased to increase the success rate of nuclear substitution. Accordingly, the composition of the present invention increases the efficiency of somatic cell replication, thereby increasing the efficiency of producing pluripotent stem cells derived from nuclear substitution, and ultimately, the composition is expected to contribute to the development of cell therapeutic agents.

A pro-inflammatory and vasoconstrictor and endothelin-1 (ET-1) are pathogenic molecules related to a series of cardiovascular diseases. Unlike ET-1 signaling for vasoconstriction of the main artery, we have proven herein that coronary microvessels exhibit a unique signaling mechanism for constriction (independent of PKC, CPI-17, and intracellular calcium storage). The pathophysiological level of ET-1 acts preferentially on the microvessels to exert persistent vasoconstriction by activating Rho kinase upon binding to ETAR of the ET-1 receptor. The ETAR antagonist BQ123 only blocks but cannot reverse vasoconstriction against ET-1. In contrast, ROCK inhibitors (e.g., H-1152) are effective to reverse arteriolar systole against ET-1. Thus, ROCK inhibition is a potent and specific choice for the treatment of coronary ischemic disease (abnormal vasoconstriction) associated with microvascular dysfunction due to excessive production of ET-1. The ROCK inhibitors may also be used to treat microvascular diseases associated with diabetic retinopathy as well as microvascular dysfunction caused by cancer therapy or immunosuppressive drugs. Since H-1152 can also reduce the basal tension of microvessels, a ROCK inhibitor is also a good diagnostic agent when used during angiography or by a non-invasive method.

The present disclosure provides methods for identifying therapeutic agents for treating ejection fraction preserved heart failure. The method may comprise: contacting a cardiac tissue or cardiac organoid with an effective amount of transforming growth factor-pi and an effective amount of endothelin-1 (ET-1) to induce ejection fraction preserved heart failure in the cardiac tissue; exposing the cardiac tissue or cardiac organoid exhibiting heart failure with preserved ejection fraction to a candidate therapeutic agent; and if the cardiac tissue or cardiac organoid induces a reduction in any one or more of the following characteristics of the cardiac tissue or cardiac organoid if the candidate therapeutic agent induces a reduction in any one or more of the following characteristics of the cardiac tissue or cardiac organoid, if yes, identifying the candidate therapeutic agent as a therapeutic agent for ejection fraction preserved heart failure: passive strain, stiffness, myocardial cell hypertrophy, or fibrosis. In some embodiments, the candidate therapeutic agent identified as a therapeutic agent for treating ejection fraction preserved heart failure induces an increase in contraction kinetics or relaxation kinetics. Additional embodiments of the disclosed methods identify therapeutic agents that induce any combination of the above altered characteristics of cardiac tissue and / or cardiac organoids.

This invention discloses an endothelin A receptor antagonist-albumin fusion protein and its application in preventing and treating hypotension during anesthesia induction. The fusion protein is formed by chemically coupling BQ-123 with human serum albumin (HSA). BQFu significantly enhances its antihypertensive effect by prolonging the half-life of BQ-123 and improving plasma stability. Experiments show that BQFu dose-dependently inhibits the decrease in mean arterial pressure (MAP) in a propofol-induced hypotension model, with a sustained and stable effect in the high-dose group (30 mpk), shortening the recovery time to 20.8 ± 10.5 min, while maintaining BQ-123 activity. This invention provides a long-acting and safe prevention and treatment strategy for hypotension during anesthesia induction.

Provided are T cell compositions and endothelin receptor antagonists for treating cancer and methods of making the same. In some embodiments, the present technology comprises methods of preventing or reducing a cancer in a subject in need thereof relative to a control, comprising administering to the subject (a) a T cell composition specific to at least a portion of one or more cancer antigens and (b) an endothelin receptor antagonist. In some embodiments, the methods further comprise administering (c) an immune checkpoint inhibitor to the subject.

This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind endothelin A receptor (ETAR). These ETAR antibodies, or antigen-binding fragments thereof, have a high affinity for ETAR, function to effectively block ET-1 binding to ETAR, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat ETAR-associated disorders. Importantly, compared to small molecule ETAR antagonists, the antibodies of the present invention have advantages of longer serum half-life, higher target specificity, thereby limiting the risk of off-target toxicity and improving therapeutic window.

The invention provides a culture medium for culturing heart tissue, a method for inducing diabetic cardiomyopathy disease phenotype in heart tissue, diseased heart tissue and a kit. An exemplary culture medium for culturing cardiac tissue comprises 100 to 300 M of palmitic acid / salt / ester, 100 to 300 M of oleic acid / salt / ester, and 0.5 to 15 nM of endothelin-1.

The application discloses a chemical structural formula of a biphenyl sulfonamide compound of a bis-benzimidazole, and also discloses application of the compound in preparation of a pharmaceutically acceptable salt or solvate, application of the compound and the pharmaceutically acceptable salt or solvate in preparation of a medicine for treating endothelin-dependent or angiotensin II-dependent diseases. Meanwhile, the biphenyl sulfonamide compound of the bis-benzimidazole can also be used in combination by changing substituted functional groups. The biphenyl sulfonamide compound of the bis-benzimidazole, the prepared pharmaceutically acceptable salt or solvate and the medicine prepared by the compound have pharmacological activities, and have pharmacological effects in animals including human beings, and are particularly useful in treatment or prevention of IgA nephropathy, focal segmental glomerulosclerosis, nephrotic syndrome, chronic kidney disease, diabetic nephropathy, hypertension, coronary heart disease and myocardial infarction.

The invention discloses application of scopalactone in treatment of pulmonary arterial hypertension, and relates to the technical field of medicinal chemistry. The scoparone is applied to preparation of the medicine for treating pulmonary arterial hypertension. The medicine comprises scopalactone, a pharmaceutically acceptable carrier, a diluent and an excipient, the medicine further comprises other medicines for treating the pulmonary arterial hypertension, and the other medicines for treating the pulmonary arterial hypertension are selected from a prostacyclin medicine, an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. The scopalactone is applied to preparation of the medicine for treating pulmonary arterial hypertension, right heart insufficiency caused by hypoxia can be remarkably reversed, and the right heart function is effectively improved by reducing the transverse diameter of the right ventricle and the transverse diameter of the right atrium and improving the indexes such as tricuspid valve ring plane contraction displacement; the average pulmonary arterial pressure and right ventricular systolic pressure can be obviously reduced, and hemodynamic parameters are improved; the area and thickness of a blood vessel wall can be remarkably reduced, the blood vessel structure is improved, and pulmonary arteriole reconstruction is relieved.

To provide novel drugs effective in improving pain associated with osteoarthritis of the knee and periarthritis of the shoulder. [Solution] According to the present invention, a synovial pain reliever for arthritis is provided, comprising an endothelin A receptor antagonist as an active ingredient, wherein the arthritis is osteoarthritis of the knee or periarthritis of the shoulder. According to the present invention, it is possible to improve joint pain caused by movements that put a load on the knee joint and joint pain at rest in patients with osteoarthritis of the knee, and it is possible to improve joint pain caused by movements that put a load on the shoulder joint and joint pain at rest in patients with periarthritis of the shoulder.

The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin related diseases.

The invention provides application of endothelin in oocyte in-vitro maturation and embryo in-vitro culture. New application of endothelin is found, the endothelin can improve the polar body discharge rate of oocytes matured in vitro, promote cytoplasm maturing and improve the normal arrangement proportion of organelles after maturing, certain promotion is provided for improvement of oocyte fertilization, and meanwhile subsequent blastocyst development is promoted. The invention further provides an in-vitro maturation culture solution of the sheep oocytes and an in-vitro maturation method of the sheep oocytes, the in-vitro maturation culture solution contains endothelin, and after the sheep oocytes are treated with the in-vitro maturation culture solution containing the endothelin concentration, the mitochondrial membrane potential level of the oocytes can be remarkably improved, and the survival rate of the sheep oocytes is increased. ROS (reactive oxygen species) in the oocytes is remarkably reduced, and the ATP (adenosine triphosphate) and GSH (glutathione) levels of the oocytes and the normal proportion level of spindles are improved; the maturation rate, the fertilization efficiency, the blastocyst number and the blastocyst rate are remarkably increased, in-vitro maturation of sheep oocytes and in-vitro development of early embryos are promoted, and the production efficiency of the sheep in-vitro embryos is effectively improved.

The application discloses a kind of serum-free epidermal melanocyte culture medium and its application, method includes by dissolving adenine, hepatocyte growth factor (HGF), glutamine, retinoic acid, vitamin E, nicotinic acid, sodium selenite, sodium hyaluronate and recombination human type XVII collagen are configured into initial culture medium;Preparation of melanocyte stimulating hormone, endothelin-3, transferrin, triiodothyronine, cholesterol, neuroregulin 1 (NRG1), 3-isobutyl-1-methyl purine (IBMX), dibutyryl cyclic adenosine monophosphate (db-cAMP), cholera toxin, hydrocortisone and recombination human insulin mother liquor;Step three: according to culture and concentration, a certain amount of mother liquor of step two is added to initial culture medium.The culture medium can effectively promote human epidermal melanocyte proliferation, melanin accumulation and help to promote human umbilical cord mesenchymal stem cells into human epidermal melanocyte, provide key advantage for obtaining functional melanocyte with high activity and therapeutic potential.

This invention belongs to the field of medicinal chemistry, specifically relating to a dimeric compound with endothelin A (ETA) receptor antagonist activity and its applications. The compound of this invention is rapidly metabolized to atrasentan in human liver microsomes. In rats, after oral administration, it exhibits excellent absorption, high bioavailability, and a long half-life, significantly lowering blood pressure and improving kidney injury. Furthermore, its weak binding to P-GP and its non-substrate nature further enhance its bioavailability. The compound of this invention, or its pharmaceutically acceptable salt, holds promise for use in the preparation of drugs for the treatment and prevention of ETA receptor antagonist-related diseases, such as chronic kidney disease and hypertension.

The description provides compositions and methods for treating ETBR-related cancer. In certain aspects, the description provides a delivery system for the controlled, systemic release of at least one of ETBR antagonists, caspase-8 inhibitors, or a combination thereof, optionally including an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide or a combination thereof. The compositions described are useful for the treatment of certain cancers, including, e.g., breast cancer, malignant melanoma, squamous cell carcinoma, glioblastoma, as well as others. In addition, the description provides a delivery system for the controlled release of at least one of ETBR antagonists, caspase-8 inhibitors or a combination thereof, optionally including at least one of an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide, or a combination thereof, to the central nervous system that are useful for treating cancers that have spread to the brain.

The present application relates to a kind of compositions for improving skin color and its application, belong to the field of cosmetics.The present application provides a kind of composition, the composition includes recombinant humanization type IV collagen and lavender exosome, the amino acid sequence of the recombinant humanization type IV collagen is as shown in SEQ ID NO.1, both compound use, can increase the expression of heat shock protein, improve cell viability under heat stress, inhibit the expression of endothelin and the production of glycation product, to improve the effect of skin skin color, and both have synergistic effect.The composition of the present application reduces the amount of recombinant humanization type IV collagen under the premise of achieving similar effects by using lavender exosome, significantly reduces the application cost of recombinant humanization type IV collagen.

The invention discloses a traditional Chinese medicine formula for preventing and treating body artery and blood vessel diseases, and relates to the technical field of pharmacy, in particular to a traditional Chinese medicine formula for preventing and treating body artery and blood vessel diseases, the traditional Chinese medicine composition is prepared from the following raw material medicines: 100g of radix puerariae, 100g of herba epimedii, 100g of herba leonuri, 50g of dioscorea panthaica, 50g of raw endothelium corneum gigeriae galli, 50g of fructus aurantii immaturus, 50g of rhizoma dioscoreae nipponicae, 50g of lumbricus and 50g of kapok leaves. Pharmacodynamic tests prove that compared with related traditional Chinese medicine prescriptions in the prior art, the traditional Chinese medicine composition can significantly reduce the intima-media thickness of blood vessels, reduce the area proportion of plaques, improve the blood vessel stenosis rate, and improve the curative effect. 0.05 in terms of prolonging thrombosis time, increasing microcirculation blood flow velocity, regulating blood lipid level (reducing total cholesterol, triglyceride and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol), protecting vascular endothelial function (increasing the content of vascular endothelial relaxation factor NO and reducing endothelin ET level) and the like, and the pharmaceutical composition is superior to the prior art group (Plt: 0.05) in terms of prolonging thrombosis time, increasing microcirculation blood flow velocity, regulating blood lipid level (reducing total cholesterol, triglyceride, low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol).

The disclosure relates to methods of reducing the risk of disease progression in a patient with pulmonary arterial hypertension (PAH), comprising administering to a patient in need thereof, an initial triple combination therapy of an endothelin receptor antagonist (ERA), a phosphodiesterase type 5 (PDE-5) inhibitor, and a prostacyclin receptor agonist (IP receptor agonist).

The application discloses a kind of serum-free medium for efficiently enriching tumor stem cells and application thereof, belong to the technical field of cell biology.The serum-free medium includes basic medium, basic additive factor, functional additive component;Among them, functional additive component includes: 1 μM-1mM of alpha-ketoglutaric acid dimethyl ester, 10nM-10 μM of butyl benzyl phthalate, 0.01 μM-1 μM of endothelin-1, 0.01mM-1mM of uridine diphosphate glucose, 1nM-100nM of tetrabromobisphenol A.The application provides stable stemness maintenance conditions for tumor stem cells by adding functional additive component to serum-free medium;At the same time, the synergistic effect between functional additive component and other components significantly improves the enrichment efficiency of tumor stem cells, and has the advantage of low cost;Therefore, it has good application prospect in efficient enrichment of tumor stem cells.

The present invention relates to a culture medium for efficiently and rapidly culturing primary mouse pulmonary artery endothelial cells, belonging to the technical field of culture medium preparation, and well solving the problems such as high price, slow cell crawling speed and poor cell state of the primary mouse pulmonary artery endothelial cell culture medium on the current market. The culture medium comprises the following components: glucose, L-glutamine, sodium pyruvate, sodium bicarbonate, fetal bovine serum, heparin, vascular endothelial growth factor, epidermal growth factor, vasopressin, endothelin, phenol red, Earle's balanced salt solution, and ultrapure water. This culture medium can culture primary mouse pulmonary artery endothelial cells economically, rapidly and efficiently, and has the characteristics of good cell growth, stable phenotype and meeting the requirements of subsequent experiments.

A pharmaceutical composition comprising an endothelin A (ETA) receptor antagonist and an SGLT-2 inhibitor and use thereof in the preparation of a drug for preventing and / or treating a disease selected from nephropathy and hypertension, wherein the ETA receptor antagonist is a compound of formula (I) or a salt thereof, and the SGLT-2 inhibitor is selected from dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin, and salts thereof. (I)

The application discloses a kind of compound insect oil and its application in cardiovascular and cerebrovascular repair, the compound insect oil is composed of palmitoleic acid-enriched pentatomidae oil and olive oil, wherein the content of palmitoleic acid in palmitoleic acid-enriched pentatomidae oil is ≥20g / 100g.The application obtains pentatomidae crude oil by supercritical CO2 extraction, then directional enrichment is carried out by low-temperature distillation and molecular rectification, the content of palmitoleic acid is increased to more than 20g / 100g, then the enriched pentatomidae oil is compounded with olive oil, and the compound insect oil is prepared by low-temperature homogenization emulsification, deodorization, sterilization process.The compound insect oil prepared by the application can significantly reduce the levels of TC, TG and LDL-C, while significantly increasing the level of HDL-C, showing excellent hypolipidemic effect.In addition, the compound insect oil can also significantly reduce the level of endothelin-1 and increase the level of nitric oxide, effectively improve the function of vascular endothelium, and can be used for the prevention and adjuvant therapy of cardiovascular and cerebrovascular diseases, with good application prospect.

The invention provides a series of endothelin A (ETA) receptor antagonist compounds, and a preparation method and a pharmaceutical composition thereof. The invention also relates to application of the compound or the pharmaceutical composition in preparation of drugs for preventing or treating endothelin A (ETA)-mediated related diseases.

The present invention belongs to the technical field of chemical medicines and provides a salt of an endothelin A (ETA) receptor antagonist compound and a preparation method and application thereof.

The present invention belongs to the technical field of chemical drugs. Provided are a salt of an endothelin A (ETA) receptor antagonist compound, and a preparation method therefor and the use thereof.

Provided herein are an ETAR antibody and a pharmaceutical composition thereof, also provided herein is a method for treating, preventing or ameliorating one or more symptoms of diabetic nephropathy and one or more symptoms of chronic nephropathy.

The present invention belongs to the technical field of chemical medicines and provides a pharmaceutically acceptable salt crystal form of an endothelin A (ETA) receptor antagonist compound and a preparation method thereof.

The present invention concerns novel crystalline forms of aprocitentan sodium salt, processes for the preparation thereof, pharmaceutical compositions comprising said crystalline forms, pharmaceutical compositions prepared from such crystalline forms, and their use as endothelin receptor antagonists.

This application provides antibodies and functional equivalents thereof which are capable of neutralizing endothelin-1, as well as their use in the treatment of disease conditions associated with endothelin-1 activation, such as Alport syndrome.