116 results about "Endothelins" patented technology

The invention relates to a composition with whitening and skin tendering effects, essence lotion and a preparation method and application of the essence lotion, in the composition with the whitening and skin tendering effects, the weight ratio of achillea millefolium extract to hydroxyethyl piperazine ethanesulfonic acid to ormosia henryi bark extract is (0.1-1): (0.5-8): (0.05-0.5). The essence lotion is prepared from the following components in percentage by weight: 0.75 to 6 percent of composition with skin whitening and tendering effects, 3 to 8 percent of emollient, 0.5 to 2 percent of emulsifier, 0.01 to 1 percent of filler, 0.5 to 2 percent of thickener, 0.8 to 1.5 percent of preservative, 0.02 to 0.2 percent of daily essence, 0.1 to 10 percent of skin conditioner, 0.1 to 10 percent of humectant and the balance of deionized water. The main components have a synergistic effect, can effectively regulate and control the information network effect of endothelin and reduce the differentiation, proliferation and the like of melanocytes in the first step of melanin generation by inhibiting the activity of tyrosinase, can promote cell autophagy and effectively metabolize melanin and lipofuscin generated in the skin, and achieves the effects of whitening, whitening, whitening and the like. The skin tendering effect is realized.

The present invention relates to a monoclonal antibody or a fragment thereof that recognizes and binds specifically to the extracellular domain of endothelin receptor type A as an antigen. The monoclonal antibody of the present invention is suitable for use in a therapeutic agent for hypertension or cancer associated with endothelin receptor type A.

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

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 method for making a non-human primate model of cerebral infarction comprising a step of administering endothelin to the brain basal nucleus-thalamic region of a non-human primate, thereby inducing brain basal nucleus disorders, thalamic disorders and endocystic disorders, and a method for treating subacute stages-containing NeuroD1 protein or a polynucleotide encoding a NeuroD1 protein The pharmaceutical composition can be used for treating chronic cerebral infarction, transbronchial infarction or cerebral infarction with brain disorder in a transbronchial dominating region.

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 invention provides biphenyl sulfonamide compounds which are combined angiotensin and endothelin receptor antagonists useful in the treatment of conditions such as diabetic nephropathy and other diseases.

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.

A method of treating IgA nephropathy and a pharmaceutical composition comprising an endothelin receptor antagonist and a glucocorticoid.

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.

The present invention concerns endothelin receptor antagonists for use in the treatment or the prevention of muscle fibrosis.

The present invention relates to a novel crystalline form of an aprocetentan sodium salt, processes for their preparation, pharmaceutical compositions comprising said crystalline form, pharmaceutical compositions prepared from such crystalline forms and their use as endothelin receptor antagonists.

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 present invention concerns the compound aprocitentan, {5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-sulfamide:and its use as endothelin receptor antagonist, in combination with an SGLT-2 inhibitor. The invention further relates to pharmaceutical compositions comprising aprocitentan in combination with said SGLT-2 inhibitor. The invention further relates to such pharmaceutical compositions comprising crystalline forms of aprocitentan.

The proinflammatory and vasoconstrictor agent endothelin-1 (ET-1) is a pathogenic molecule involved in an array of cardiovascular diseases. Different from ET-1 signaling for vasoconstriction in large arteries, we demonstrate herein that the coronary microvasculature exhibits unique signaling mechanisms (independent of PKC, CPI-17, and intracellular calcium storage) for constriction. The pathophysiological levels of ET-1 preferentially act on the microvasculature to exert long-lasting vasoconstriction through the activation of Rho kinase after binding to the ET-1 receptor ETAR. The ETAR antagonist BQ123 only blocks but is not able to reverse the vasoconstriction to ET-1. In contrast, ROCK inhibitors (e.g., H-1152) effectively reverse arteriolar constriction to ET-1. Therefore, ROCK inhibition is a potent and specific choice for treating coronary ischemic diseases (abnormal vasoconstriction) associated with microvascular dysfunction with overproduced ET-1. ROCK inhibitors may also be used to treat microvascular diseases related to diabetic retinopathy and microvascular dysfunction from cancer therapy or immunosuppressive medications. Since H-1152 can also reduce the basal tone of the microvasculature, ROCK inhibitors are also good diagnostic agent(s) when used during angiogram or by noninvasive methods.

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.

The present invention relates to the compound alpoxivan, {5-(4-bromophenyl)-6 [2 (5-bromopyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-sulfonamide: # imgabs0 # and their use as an endothelin receptor antagonist in a method of treating hypertension, including refractory hypertension, in a subject in need thereof, the method comprises administering to the subject a pharmaceutical composition comprising a clinically proved effective amount of alpoxivan or a pharmaceutically acceptable salt thereof.

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 present disclosure relates to a combination of zipotentan and dapagliflozin, i.e., the endothelin receptor antagonist (ERA) zipotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin, for use in the treatment of certain endothelin-related diseases.