52 results about "Cardiotoxicities" patented technology

The invention discloses an extraction method of safflower leaf exosome-like nano-vesicles and application of the safflower leaf exosome-like nano-vesicles in preparation of drugs for preventing and treating adriamycin-induced cardiotoxicity, fresh safflower leaves are taken and cleaned, a PBS solution is added for crushing and filtering, filtrate is collected and continuously centrifuged, supernate is taken and subjected to ultracentrifugation, precipitates are collected after centrifugation, and the safflower leaf exosome-like nano-vesicles are obtained; and filtering and sterilizing by using a filter membrane to obtain the safflower leaf exosome-like nano-vesicles. The carthamus tinctorius leaf exosome-like nano-vesicles can significantly improve the heart function of doxorubicin-induced cardiotoxic mice; myocardial injury induced by doxorubicin can be repaired, and myocardial fibrosis induced by doxorubicin can be inhibited; the content of a myocardial injury marker lactic dehydrogenase in body serum can be reduced, a new treatment strategy is provided for preventing and treating adriamycin-induced cardiotoxic diseases, and the application prospect is good.

The invention relates to the technical field of biomedical engineering and drug delivery, and particularly discloses a novel targeted drug delivery system based on rose fruit extracellular vesicles, which comprises the following steps: preparing rose fruit source extracellular vesicles; preparing a medicine carrying vesicle; preparing targeted modified drug-loaded vesicles; according to the application disclosed by the invention, a stem related pathway is specifically down-regulated through the components of the rose fruits, and meanwhile, conventional tumor cells are killed by using adriamycin, so that a complementary treatment mechanism is formed, and the tumor recurrence risk is fundamentally reduced. The phenylboronic acid group of DSPE-PEG-PBA is used for specifically recognizing sialic acid over-expressed on the surface of a tumor cell, so that the enrichment of the medicine in tumor tissues is remarkably improved, and meanwhile, the distribution of normal tissues is reduced. By means of the natural biocompatibility and low immunogenicity of the RHNVs and in combination with the long circulation characteristic of a PEG chain, the delivery efficiency is guaranteed, the systemic toxicity is reduced to the maximum extent, and particularly the cardiotoxicity and myelosuppression of adriamycin are relieved.

This invention discloses a compound of formula I, or a pharmaceutically acceptable salt, stereoisomer, ester, prodrug, or solvate thereof. Experimental results show that the compound provided by this invention exhibits high inhibitory activity against PAK4 kinase and PAK I / II selectivity, good liver microsomal stability, and rat PK pharmacokinetic properties, especially with low hERG cardiotoxicity risk, representing a significant improvement over prior art compounds.

Various formulations for combination therapy of liposomes and SR-BI inhibitors that result in enhanced liposome uptake by target cells are provided, exemplified by combination therapy with CPX-351 and BLT-1. Also provided are various formulations for combination therapy of liposomes and ENT inhibitors that result in enhanced uptake of liposome-encapsulated cytarabine by target cells. Also provided are methods for using the formulations in combination therapy. Also provided are methods for reducing cardiotoxicity in age-group patient populations receiving therapy with cytarabine and daunorubicin, and CPX-351.

This invention relates to a method, kit, and application for assessing the cardiotoxicity risk of processed Aconitum carmichaelii products based on NFKB1, PSMB1, and FGR biomarkers, belonging to the field of traditional Chinese medicine processing technology. The invention provides a biomarker specifically any one of the NFKB1, PSMB1, or FGR genes, or any combination thereof. This invention is the first to identify the key causal biomarkers NFKB1, PSMB1, and FGR that cause cardiotoxicity from Aconitum carmichaelii toxic components. A dynamic response model composed of these three genes can accurately quantify the degree of toxicity transformation during Aconitum carmichaelii processing: elevated NFKB1 expression indicates a risk of inflammatory activation, decreased PSMB1 expression reflects the critical point of protein homeostasis collapse, and persistent inhibition of FGR expression indicates the failure of endogenous cardioprotective mechanisms. The predictive model constructed using these three genes can accurately assess the cardiotoxicity of processed Aconitum carmichaelii products and evaluate the Aconitum carmichaelii processing technology.

The invention discloses application of Psammatlysene D and a derivative thereof in preparation of a medicine for resisting chronic liver diseases, and belongs to the technical field of medicines. The technical scheme of the invention comprises the application of the Psammaglyene D in preparation of a product for resisting chronic liver diseases. The Psammatlyene D can inhibit the growth of LX2 cells, reduce liver function indexes ALT and AST, and relieve the degree of hepatic fibrosis in a mouse body; the growth of liver cancer cells can be inhibited in vivo and in vitro, and a synergistic effect can be generated with sorafenib; meanwhile, the anti-proliferation ability is also shown in sorafenib drug-resistant liver cancer. The derivative B12 of the Psammatlysene D has a stronger in-vitro anti-hepatic fibrosis effect, and the C11 has a very weak inhibition capability on hERG (human endothelial growth factor) and has no potential cardiotoxicity. The results show that the Psammaglyene D has relatively strong capabilities of resisting hepatic fibrosis, inhibiting liver cancer development and relieving sorafenib drug-resistant liver cancer, and the Psammaglyene D and C11 can be used as potential lead compounds for the development of anti-hepatic fibrosis and anti-liver cancer drugs, and are finally applied to the treatment of chronic liver diseases.

The application discloses a high-safety tumor treatment preparation based on a prodrug-enzyme-neutralizing antibody three-system, and a preparation method and application thereof. The preparation comprises three core components: (a) a prodrug, which is coupled by an anti-tumor drug (such as doxorubicin) and cephalosporin; (b) an activating enzyme, such as beta-lactamase, which is specifically expressed in the tumor by phage, catalyzes the hydrolysis of the prodrug, and releases the active drug; and (c) a neutralizing antibody, such as an anti-doxorubicin monoclonal antibody, which can specifically bind and neutralize the active drug overflowing into the blood circulation. The application first integrates the precise killing strategy of "prodrug-local activation" and the safety strategy of "neutralizing antibody-systematic protection" into a complete treatment closed loop, utilizes the "differential neutralization" characteristics of the anti-doxorubicin antibody, effectively protects normal tissues from toxic damage under the premise of not affecting the local efficacy of the tumor, and significantly improves the therapeutic index of the chemotherapy drug, reduces the side effects such as cardiotoxicity and bone marrow suppression, and provides a new paradigm with high efficiency and safety for tumor treatment.

The present invention discloses the use of a compound of formula I sertaconazole or a pharmaceutically acceptable salt thereof in the preparation of a pharmaceutical composition for preventing or treating oxidative stress-related cardiovascular diseases. Specifically, the present invention relates to the use of said compound in the preparation of a medicament for preventing or treating oxidative stress-related vascular diseases, including but not limited to acute coronary syndrome, alcoholic heart dysfunction, hypoxic pulmonary arterial hypertension, heart failure, drug-induced cardiotoxicity and stroke, especially acute heart failure.

The Cardio-Tox Tissue Engineered Model (TEEM) invention provides a robust in vitro model for cardiotoxicity evaluation using three-dimensional (3D) human heart microtissues to quantify dose-dependent changes in electromechanical activity, resulting in a comprehensive cardiotoxicity and arrhythmia risk assessment of test compounds. The invention also provides a predictive in vitro screening platform for pro-arrhythmic toxicity testing using human three-dimensional cardiac microtissues. The invention enables the screening of environmental and pharmaceutical compounds, chemicals, and toxicants to establish safe human exposure levels.

The invention belongs to the technical field of biological medicines, and particularly relates to application of przewatanshinone A in preparation of a medicine for treating anti-tumor medicine cardiotoxicity. The traditional Chinese medicine-induced cardiotoxicity disclosed by the invention is cardiotoxicity caused by anthracycline drugs. Experiments prove that przewatanshinone A has a multi-target synergistic effect and can remarkably inhibit myocardial cell oxidative stress, relieve inflammatory response and protect myocardial cell functions, so that cardiotoxicity caused by anthracycline drugs is effectively prevented and treated, and a brand-new solution is provided for clinical prevention and treatment of cardiotoxicity caused by anthracycline drugs.

The invention discloses application of rehmannia D in preparation of a product for preventing and / or treating myocardial injury, and belongs to the technical field of medicines. The myocardial injury comprises myocardial injury induced by doxorubicin (DOX), and experiments prove that the rehmannia D can obviously improve the heart function decline caused by the DOX; the myocardial cell atrophy induced by DOX can be obviously inhibited; the level of myocardial tissue fibrosis induced by DOX can be obviously inhibited; the DOX-induced myocardial tissue oxidative stress level can be obviously inhibited; in addition, DOX-induced myocardial tissue DNA damage (gamma-H2AX is taken as a marker) can be obviously inhibited. The invention proves that the rehmannia glycoside D can be used as a novel treatment means to be applied to treatment of adriamycin-induced myocardial injury, and the risk of treatment interruption or heart failure due to cardiotoxicity caused by chemotherapy of a patient can be possibly reduced, so that the disease burden of the patient and the pressure of a medical system are relieved.

Methods and materials for treating or preventing cardiotoxicity and / or hypertension induced by one or more anti-cancer agents (e.g., tyrosine kinase inhibitor (TKI) -induced cardiotoxicity (e.g., sunitinib-induced cardiotoxicity) and / or TKI-induced hypertension (e.g., sunitinib-induced hypertension)) are provided herein. For example, provided herein are methods for using polypeptides (e.g., chimeric polypeptides) that include (a) one or more natriuretic peptides and (b) one or more angiotensin 1-7 (ANG1-7) polypeptides to treat or prevent cardiotoxicity and / or hypertension induced by one or more anti-cancer agents.

The present invention provides a heteroaromatic ring compound serving as a CDK7 kinase inhibitor, preparation thereof, and a use thereof. The heteroaromatic ring compound is a compound having the structure of formula (I) or a pharmaceutically acceptable salt, ester, stereoisomer, solvent compound or prodrug thereof. The present invention also provides a pharmaceutical composition comprising the compound having the structure of formula (I) or the pharmaceutically acceptable salt, ester, stereoisomer, solvent compound or prodrug thereof. The present invention further provides a use of the compound having the structure of formula (I) or the pharmaceutical composition in the preparation of a CDK7 kinase inhibitor and in the preparation of a drug for treating and / or inhibiting CDK-related diseases. The CDK7 kinase inhibitor compound of the present invention has an enzyme and cell level biological activity superior to that of disclosed similar target compounds and lower cardiotoxicity. The compound of the present invention provides more options for novel antitumor drugs, and has good prospects of application in drugs.

Disclosed in the present invention are a heteroaromatic amine compound, a pharmaceutical composition thereof and the use thereof. Specifically, disclosed are a compound represented by formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of the pharmaceutically acceptable salt thereof. The compound of the present invention has one or more of the following advantages: (1) excellent agonistic activity on 5-hydroxytryptamine 4 receptor; (2) good selective agonistic activity on 5-hydroxytryptamine 4 receptor; (3) capability of significantly reducing the risk of cardiotoxicity caused by hERG channel suppression; and (4) excellent intestinal tissue selectivity and low system exposure, which can reduce the safety risk of the circulatory system.

To provide uses of pertuzumab, which is a first in-class HER2 dimerization inhibitors, and articles of manufacture comprising the same.SOLUTION: A method for extending progression free survival in a population of HER2 + breast carcinoma patients; a method for combining two HER2 antibodies to treat HER2 + breast carcinoma without increasing cardiotoxicity; a method for treating early HER2 + breast carcinoma; a method for treating HER2 + breast carcinoma by co-administering a mixture of pertuzumab and trastuzumab from the same I. v. bag; a method for treating HER2 + metastatic gastric carcinoma; a method for treating HER2 + breast carcinoma with pertuzumab, trastuzumab and vinorelbine; Methods for treating HER2 positive breast cancers with trastuzumab and aromatase inhibitors; and methods for treating low HER3 ovarian, primary peritoneal, or fallopian tube cancers are provided.SELECTED DRAWING: None

The invention discloses a method for detecting scorpion venom-induced cardiotoxicity by fusing metabonomics and an ultrasonic electrocardiogram, the ultrasonic electrocardiogram proves that scorpion venom has cardiotoxicity, then the change of metabolites related to cardiotoxicity is researched through serum metabonomics, and 37 different metabolites are screened out. The kit can find potential damage of scorpion venom to the heart at an early stage, has relatively high sensitivity and specificity, solves the technical problems of high sampling difficulty in traditional pathology, low sensitivity, poor specificity and long period of conventional markers, remarkably improves the timeliness and reliability of scorpion venom cardiotoxicity prediction, and has a good application prospect. And a scientific basis is provided for subsequent preclinical safety evaluation and clinical medication monitoring of scorpion venom preparations.

The invention relates to medical application of IRF9 in prevention and treatment of trastuzumab (TRZ) cardiotoxicity, and belongs to the technical field of biological medicine. The invention reveals that the expression of the interferon regulatory factor 9 (IRF9) in the TRZ cardiotoxic myocardial tissue is up-regulated for the first time, and myocardial damage is aggravated by promoting pyroptosis of myocardial cells. On the basis, the invention provides the IRF9 as a diagnostic marker of TRZ cardiotoxicity, and provides an application of an IRF9 low expression vector or small interfering RNA (siRNA) in preparation of drugs for preventing or treating TRZ cardiotoxicity. Animal experiments show that cardiac function decline, cardiac hypertrophy and fibrosis caused by TRZ can be remarkably improved by myocardial cell specific low-expression IRF9. The invention provides a new target spot and an intervention strategy for clinical prevention and treatment of TRZ cardiotoxicity.

The application discloses application of hydroxyl genkwa flower ketone (HGK) in preparation of a medicine for preventing and treating cardiotoxicity induced by an anti-tumor medicine. The process is as follows: a doxorubicin (DOX) is used to induce and establish a myocardial cell H9C2 injury model, and a minimum concentration of the myocardial cell injury induced by the DOX is determined. After 20 muM of the HGK is added to a treatment group, DOX-induced H9C2 cell apoptosis can be significantly improved. The DOX is used to induce and establish a mouse myocardial injury model, compared with a doxorubicin group, the left ventricular systolic fraction (FS%) and the ejection fraction (EF%) of mice in the doxorubicin+hydroxyl genkwa flower ketone group are significantly increased, the myocardial fiber structure is improved, the cytoplasm vacuolization is reduced, the serum cTnT, CK-MB and BNP levels are reduced, and the heart tissue ROS level is reduced. Therefore, the hydroxyl genkwa flower ketone can significantly reduce the myocardial toxicity induced by the DOX.

This invention discloses the application of MITF inhibitors in the preparation of drugs for the prevention and / or treatment of sorafenib cardiotoxicity, belonging to the field of biomedical technology. This invention is the first to discover that the transcription factor MITF is a core regulatory factor of sorafenib cardiotoxicity. Sorafenib can specifically upregulate the expression and transcriptional activity of MITF in cardiomyocytes, and its expression level is positively correlated with the degree of cardiomyocyte damage. By inhibiting the expression or activity of MITF, sorafenib-induced cardiomyocyte hypertrophy and damage can be significantly reversed. This invention provides a novel specific intervention target for the prevention and treatment of sorafenib cardiotoxicity, and has significant scientific and clinical translational value.

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 15 to 25 parts of radix salviae miltiorrhizae and 15 to 25 parts of radix ginseng rubra according to a weight ratio of 1 to 1. Based on the traditional Chinese medicine theory of tonifying qi, activating blood, detoxifying and dredging collaterals, the traditional Chinese medicine composition is provided for the first time to inhibit neutrophil extracellular traps (NETosis) and inflammatory response in a targeted manner, so as to prevent and treat cardiotoxicity caused by anthracycline drugs. Animal experiments show that the traditional Chinese medicine composition can remarkably improve the heart function, relieve myocardial damage and inhibit release of inflammatory factors, and has good safety. Clinical cases prove that the traditional Chinese medicine can effectively relieve symptoms of patients and guarantee smooth chemotherapy. The invention provides a brand-new, effective and safe traditional Chinese medicine treatment scheme for preventing and treating anthracycline cardiotoxicity.

This invention discloses the application of GW3965 in the preparation of drugs that alleviate cardiac damage caused by doxorubicin. Experiments have demonstrated that GW3965 can, while inhibiting tumor growth, alleviate cardiac dysfunction related to doxorubicin cardiotoxicity, reduce doxorubicin-induced cardiac fibrosis, and inhibit doxorubicin-induced cardiomyocyte atrophy and apoptosis. This suggests that GW3965 can alleviate cardiac damage caused by doxorubicin, increase the safety of doxorubicin chemotherapy, and has promising clinical application prospects.

The Cardiac Tissue Engineered Model (TEEM) invention provides a robust in vitro model for cardiotoxicity evaluation using three-dimensional (3D) human heart microtissues to quantify dose-dependent changes in electromechanical activity, resulting in a comprehensive cardiotoxicity and arrhythmia risk assessment of test compounds. The invention also provides a predictive in vitro screening platform for pro-arrhythmic toxicity testing using human three-dimensional cardiac microtissues. The invention enables the screening of environmental and pharmaceutical compounds, chemicals, and toxicants to establish safe human exposure levels.

To provide methods for forming mature cardiomyocytes.SOLUTION: Disclosed herein are methods of using a cell-derived extracellular matrix derived in-vitro from cells isolated from amniotic fluid (AFC-ECM) for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture, forming mature cardiomyocytes. Also disclosed herein is a cell construct comprising a monolayer of these mature cardiomyocytes on an AFC-ECM useful for cardiotoxicity and / or proarrhythmic screening assays of drug compounds. Also disclosed herein are methods for determining the cardiotoxicity and / or proarrhythmic effect of a drug compound in vitro using such cell constructs.SELECTED DRAWING: None

The present disclosure provides diazaspiro compounds represented by Formula (I), processes for their preparation, and pharmaceutical uses thereof, all within the field of medicinal chemistry. The diazaspiro compounds disclosed herein function as small-molecule agonists of the cholecystokinin-B receptor (CCK-BR). They exhibit excellent agonistic potency and demonstrate marked selectivity for CCK-BR over the cholecystokinin-A receptor (CCK-AR), thereby mitigating off-target effects and associated adverse reactions. No cardiotoxicity or other safety liabilities have been observed to date. The diazaspiro compounds are contemplated for the prophylaxis or treatment of disorders including, without limitation, epilepsy, depression, dementia, anxiety, Alzheimer's disease, tinnitus, amblyopia, schizophrenia, neuropathic pain, amnesia, gastric hyperacidity, obesity, pancreatic carcinoma, and gallbladder carcinoma.

The Cardio-Tox Tissue Engineered Model (TEEM) invention provides a robust in vitro model for cardiotoxicity evaluation using three-dimensional (3D) human heart microtissues to quantify dose-dependent changes in electromechanical activity, resulting in a comprehensive cardiotoxicity and arrhythmia risk assessment of test compounds. The invention also provides a predictive in vitro screening platform for pro-arrhythmic toxicity testing using human three-dimensional cardiac microtissues. The invention enables the screening of environmental and pharmaceutical compounds, chemicals, and toxicants to establish safe human exposure levels.

The application provides a use of Di'ao Xin-xue-kang in preparation of a medicine for preventing doxorubicin-induced cardiac endothelial injury toxicity, and belongs to the field of medicines. The application uses Di'ao Xin-xue-kang for preventive administration, protects early cardiac endothelial injury induced by doxorubicin, and further can rescue or avoid occurrence of subsequent irreversible cardiotoxicity, especially uses Di'ao Xin-xue-kang for prevention or / and intervention of asymptomatic cardiac dysfunction related to cancer treatment, and opens a new use and administration method for clinical use of Di'ao Xin-xue-kang.

The invention belongs to the field of gene drugs, and particularly relates to snoRNA Gm25215 as well as a simulant and application thereof. The invention further discloses the application of the snoRNA Gm25215 serving as the biomarker in preparation of a product for detecting myocardial cell ferroptosis or DIC. When doxorubicin cardiotoxicity occurs, the snoRNA expression activity is increased, so that the application of the snoRNA as a biomarker in preparation of detection products is provided. According to the characteristics of the snoRNA, the snoRNA is named as FERSNO, ferroptosis of myocardial cells is remarkably inhibited by knocking down the FERSNO, the FERSNO simulant and the application of the FERSNO simulant in preparation of drugs for preventing and / or treating heart diseases are provided, the FERSNO simulant is preferably an FERSNO inhibitor, and the application of the FERSNO simulant in preparation of drugs for preventing and / or treating heart diseases in preparation of drugs for preventing and / or treating heart diseases in preparation of drugs for preventing and / or treating heart diseases in preparation of drugs for preventing and / or treating heart diseases in preparation of drugs for preventing and / or treating heart diseases in preparation of drugs for preventing and / or treating heart diseases in preparation of drugs for preventing and / or treating heart diseases in preparation of drugs for preventing and / or treating heart diseases. The reduction of FERSNO expression effectively alleviates the problems of poor prognosis of patients with doxorubicin cardiotoxicity and heart disease treatment. The nucleotide sequence of the FERSNO is as shown in SEQ ID NO. 1.

The invention belongs to the technical field of biological medicines, and discloses a new medical application of an hERG / Kv11.1 channel activator NS-1643, so that new application of old medicines is realized. The NS-1643 is traditionally used for anti-arrhythmia research and development, it is found for the first time that NS-1643 can effectively treat cardiotoxicity induced by anthracycline drugs (such as doxorubicin), and meanwhile NS-1643 can be used for preventing or treating ferroptosis-related cardiovascular diseases such as myocardial ischemia reperfusion injury, myocardial infarction and heart failure. The invention further provides a pharmaceutical composition containing the NS-1643, the NS-1643 or pharmaceutical salt, ester, solvate and the like of the NS-1643 are taken as active ingredients of the composition, and the active ingredients are matched with auxiliary ingredients acceptable in biological pharmacy, so that the composition can be prepared into sterile dosage forms such as injections, oral preparations and the like, and the process is stable and controllable. Cell experiments prove that NS-1643 has a remarkable protective effect on ferroptosis-induced myocardial cell injury (EC50 is approximately equal to 2.7 mu M); animal experiments prove that the doxorubicin-induced mouse death risk can be completely reversed, the heart function is remarkably improved, and myocardial fibrosis and lipid peroxidation damage are relieved. The application expands the clinical application range of NS-1643, has the advantages of high clinical transformation potential, clear treatment effect and the like, provides a new effective strategy for prevention and treatment of anthracycline cardiotoxicity and related cardiovascular diseases, and has important clinical application value and industrial transformation prospect.

The invention discloses application of isoliquiritigenin in preparation of a medicine for treating 5-FU induced cardiotoxicity, and belongs to the technical field of biomedicine.The medicine comprises the isoliquiritigenin, and the isoliquiritigenin improves 5-FU induced oxidative stress and apoptosis by regulating an AhR-CYP1A1 pathway, so that the 5-FU induced cardiotoxicity is improved; the invention systematically reveals the action mechanism of the isoliquiritigenin for improving the 5-FU-induced cardiotoxicity by inhibiting an AhR-CYP1A1 signal channel for the first time from the animal overall level and the cell molecule level to mechanism analysis, and proves the application value of the isoliquiritigenin in preparation of the medicine for treating the 5-FU-induced cardiotoxicity; based on complete analysis of the mechanism, the invention provides a brand new active ingredient and a technical scheme for preparing the medicine for resisting 5-FU cardiotoxicity, lays a theoretical and experimental foundation for research and development of the medicine for relieving the side effect of 5-FU chemotherapy, and has an important medicine development value.