39 results about "Disulfiram" patented technology

The invention discloses a biological medicine application of luwulinine, and provides and verifies that luwulinine can inhibit disulfiram death of cells for the first time, so that luwulinine can be used for preventing or treating hepatic ischemia reperfusion injury. Experimental data show that the luteiniine can relieve liver function injury after reperfusion with cell apoptosis, tissue inflammation infiltration and tissue fibrosis as manifestations, and a new direction is provided for mechanism research and prevention and treatment of hepatic ischemia reperfusion injury.

This invention relates to an injectable hydrogel, its preparation method, and its applications. It solves the technical problems of short half-life, rapid degradation, and inability to directly form bone by direct systemic injection of disulfiram in existing technologies. The hydrogel contains catecholized calcium alginate, disulfiram, and water. The catecholized calcium alginate contains calcium alginate, a catechol group, and calcium ions. The catechol group is coupled to the side chain of the calcium alginate. The mass percentage content of the catecholized calcium alginate is 0.5-5%; the mass percentage content of the disulfiram is 0.25-2%; and the balance is water. This invention can be used to prepare materials that promote alveolar bone repair and regeneration.

The invention provides a nano delivery system based on copper death induction and application of the nano delivery system in preparation of tumor immunotherapy drugs, according to the novel copper death induction nano drug Cu / ZIF-90 (at) DSF, 30 mol% of Cu (acac) 2 and disulfiram are loaded through a high-porosity structure of ZIF-90, and pH / ROS dual-responsiveness copper ion release is achieved. Animal experiments show that the Cu < 2 + > accumulation concentration of the nano-drug at a tumor site reaches 23.7 mu M, and efficient copper death is induced (the apoptosis rate is 41.3% vs and the control group is 9.2%). More importantly, by releasing HMGB1 and ATP, the CD8 < + > T cell infiltration in a tumor microenvironment is increased by 5.8 times, and the CD8 < + > T cell infiltration and the alphaPD-1 antibody generate a synergistic effect, so that the complete remission rate is increased from 18% to 67%. According to the technical breakthrough, a brand new solution is provided for solving the cold tumor immunotherapy drug resistance.

The invention discloses a bionic hybrid nano regulator for enhancing cell copper death and a preparation method and application thereof, and belongs to the technical field of biomedical materials. The invention designs a bionic nano-platform which simultaneously loads a lactic acid regulator cyclostilbene Su 3118 and a copper ion carrier disulfiram DSF, and the bionic nano-platform is combined with hybrid macrophages and tumor cell membranes to construct a nano-regulator SCTDM. The nano regulator can exert multiple functions, including tumor targeting, in-situ photothermal therapy, lactic acid regulation and enhanced copper death. The nano regulator provided by the invention is simple and convenient to manufacture, is combined with in-situ photothermal therapy and lactic acid regulation and is used for enhancing cell death immunotherapy of copper death so as to eliminate primary tumors and delay relapse, and a technical support is provided for regulating immunity by enhancing copper-induced cell death through metabolic reprogramming.

The invention discloses an application of a disulfiram medicine in improving sepsis induced cardiomyopathy. The disulfiram drug is administered in a sepsis mouse model, and the disulfiram drug is proved to have obvious anti-inflammatory effect and myocardial protection effect. The disulfiram medicine can relieve myocardial hypertrophy of mice, relieve the degree of myocardial fibrosis and reduce myocardial interstitial inflammatory exudation, ZO-1 reconstructs continuous linear distribution after administration, and the degree of myocardial edema is obviously relieved. The invention provides a new application of the disulfiram medicine in improving sepsis-induced cardiomyopathy, and provides a new strategy for myocardial protection of sepsis.

The invention provides saCNTF-DSF-LNP composite nanoparticles as well as a preparation method and application of the saCNTF-DSF-LNP composite nanoparticles, and particularly relates to application of the saCNTF-DSF-LNP to preparation of medicines for treating diseases related to optic nerve injury. The method comprises the following steps: S1, preparing self-amplification CNTF RNA, and naming the self-amplification CNTF RNA as saCNTF; s2, preparing lipid nano particles entrapped with the disulfiram DSF; s3, quickly adding the ethanol phase containing the disulfiram DSF-lipid mixture into the aqueous phase containing the saCNTF, and mixing, so that the nanoparticles are formed by self-assembly; s4, purifying the nano particles by using an ultrafiltration centrifugal device to obtain saCNTF-DSF-LNP; the invention provides a preparation method and application of saCNTF-DSF-LNP, the saCNTF-DSF-LNP can inhibit neuroinflammation driven by acute pyroptosis, and continuous neurotrophic support is provided for RGC survival and long-term axon regeneration; according to saCNTF-DSF-LNP, continuous expression of CNTF is achieved through saRNA, efficient targeted delivery is achieved by means of LNP so as to reduce off-target toxicity of DSF, and a new treatment strategy is provided for neuritis and degenerative diseases.

The invention discloses an application of charantin IV in preparation of a tumor treatment medicine. The invention provides and verifies that the charantin IV can significantly inhibit the activity of cancer cells by inducing disulfiram death of cancer cells for the first time, can further promote gefitinib to overcome the drug resistance of cancer cells and inhibit the progress of drug-resistant tumors, and provides a new direction and theoretical basis for drug research, development and treatment of gefitinib drug-resistant non-small cell lung cancer.

The invention provides application of disulfiram in preparation of a medicine for treating calcified aortic valve diseases, and belongs to the field of biological medicine. The disulfiram is used for intervening in-vitro cultured valvular interstitial cells and a mouse in-vivo calcified aortic valve stenosis model, and experimental results show that the disulfiram can inhibit the capability of differentiating the valvular interstitial cells to osteogenic phenotypes, relieve extracellular calcification deposition and relieve aortic valve calcification and stenosis. Therefore, the disulfiram can be used as a medicine for treating the calcified aortic valve disease and has a wide application prospect.

The invention discloses application of disulfiram in preparation of a medicine for treating UMOD gene mutation type autosomal dominant renal tubulointerstitial nephropathy, and belongs to the field of biomedicine. The application comprises the application of the disulfiram in preparation of the medicine for treating the hereditary tubulointerstitial nephropathy. According to the invention, a new pathogenic mutation UMOD c.106Cgt is identified; according to the invention, the pathogenicity of the gene is verified through a UMODH36Y mouse model constructed by CRISPR / Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats / CRISPR associated 9). DSF intervention is adopted, the serum creatinine and glomerular filtration rate (tGFR) of mice can be remarkably improved, and renal interstitial inflammation and fibrosis are relieved. The discovery prompts that the DSF realizes the therapeutic effect of renal function protection-inflammation inhibition-fibrosis relief in an ADTKD-UMOD animal model through targeted regulation of a pyroptosis pathway, a novel therapeutic strategy is provided for ADTKD-UMOD, and the clinical transformation period can be remarkably shortened due to the characteristic of new use of old medicines. The discovery lays an experimental foundation for developing a precise treatment scheme for the hereditary renal tubulointerstitial disease.

The invention relates to the technical field of nano biology, and discloses a nano reactor and a preparation method and application thereof, and the nano reactor comprises nano particles, cell membrane nano particles wrapping the surfaces of the nano particles, and disulfiram loaded on the surfaces of the cell membrane nano particles; and the nano particles are Cu9S8 nano particles. The Cu9S8 nanoparticles are taken as a core, and cell membrane nanoparticles are wrapped outside the nanoparticles, so that homologous tumor targeting is realized, the blood circulation capability is improved, a nanoreactor can be quickly targeted to a tumor part, and the influence on normal tissues / cells is reduced; the chemotherapeutic drug nano-reactor can be combined with photothermal therapy, Cu < 2 + > is quickly converted into Cu < + > under the assistance of the photothermal therapy so as to be chelated with disulfiram, so that the chemotherapeutic drug can be synthesized in situ in a tumor microenvironment by the nano-reactor, and an excellent anti-tumor effect is achieved.

A method of selectively inhibiting aldehyde dehydrogenase 1a1 (ALDH1a1) relative to aldehyde dehydrogenase 2 (ALDH2) in a subject may include administering to the subject in need thereof, an effective amount of a disulfiram derivative having a structure which may be substituted and is optionally a salt, solvate, tautomer, stereoisomer, or mixture thereof, thereby selectively inhibiting the ALDH1A1 relative to ALDH2 in the subject. An aldehyde dehydrogenase 1a1 (ALDH1a1)-selective antagonist composition, may include such a disulfiram derivative and a pharmaceutically acceptable carrier and / or excipient.

The invention provides application of a preparation for activating RIPKs / MLKL mediated necroptosis signal transduction in preparation of a medicine for reversing taxol drug resistance of ovarian cancer, and belongs to the technical field of biological medicine. It is found for the first time that disulfiram (DSF) can reverse ovarian cancer paclitaxel drug resistance and enhance sensitivity of ovarian cancer paclitaxel drug-resistant cells to paclitaxel. A further research discovers that the DSF is used for enhancing RIPKs / MLKL mediated necroptosis signal transduction by combining an apoptosis-inducing factor (AIF), and finally, the chemosensitivity of the paclitaxel drug-resistant ovarian cancer cells is enhanced through a caspase-dependent apoptosis pathway. The invention deeply studies an ovarian cancer paclitaxel drug resistance mechanism, discovers a new application of DSF in reversing ovarian cancer paclitaxel drug resistance, and provides a new choice for treating paclitaxel drug-resistant ovarian cancer.

The invention relates to the technical field of drug nano delivery, and discloses a disulfiram derivative CPD12C15 folic acid targeted liposome as well as a preparation method and application thereof. The lipidosome is of a closed vesicle-shaped structure, and a lipid shell layer of the lipidosome is enclosed by a lipid bilayer which is jointly formed by lecithin, cholesterol and a DSPE lipophilic end of DSPE-PEG2000-Fa; a PEG-folic acid hydrophilic end of the DSPE-PEG2000-Fa extends and is exposed on the outer surface of a lipid shell layer, so that a folic acid receptor is endowed with a targeting function; the inner water phase core is a water-based cavity enclosed by a lipid shell layer, and the active component CPD12C15 is encapsulated in the inner water phase core. Compared with the prior art, the liposome disclosed by the invention has the advantages of high encapsulation efficiency, high drug loading capacity, pH-sensitive controlled release and targeted enrichment in hepatocellular carcinoma tissues, can remarkably inhibit tumor proliferation, migration and angiogenesis and induce apoptosis, and improves the curative effect and reduces the toxicity by regulating a PI3K / AKT pathway.

The invention discloses an application of a small molecule compound covalently bound with GSDMD in preparation of a pyroptosis inhibitor. Through deep research, a novel compound AF-966 / 00547018, called C6 for short, which can specifically target GSDMD protein and effectively inhibit the pore-forming activity of the GSDMD protein is screened, and the structure of the compound AF-966 / 00547018 is shown in the specification. Compared with reported pyroptosis inhibitors such as disulfiram, dimethyl fumarate and Necrosulfenamide (NSA), the C6 shows higher activity of inhibiting the pyroptosis of the cells, and the C6 shows higher activity of inhibiting the pyroptosis of the cells.

A method of selectively inhibiting aldehyde dehydrogenase 1a1 (ALDH1a1) relative to aldehyde dehydrogenase 2 (ALDH2) in a subject may include administering to the subject in need thereof, an effective amount of a disulfiram derivative having a structure which may be substituted and is optionally a salt, solvate, tautomer, stereoisomer, or mixture thereof, thereby selectively inhibiting the ALDH1A1 relative to ALDH2 in the subject. An aldehyde dehydrogenase 1a1 (ALDH1a1)-selective antagonist composition, may include such a disulfiram derivative and a pharmaceutically acceptable carrier and / or excipient.

This invention discloses the application of disulfiram or its pharmaceutical salt in the preparation of radiosensitizers, wherein the radiosensitizer refers to a radiosensitizer for malignant tumors, specifically osteosarcoma. The radiation involved in the radiosensitizer is selected from alpha, beta, gamma, or X-ray radiation. This invention is the first to discover and confirm a novel use of disulfiram in enhancing the radiosensitivity of malignant tumors, significantly inhibiting the proliferation of osteosarcoma cells after radiotherapy and promoting cell death in vitro. It also demonstrates outstanding efficacy in inhibiting the growth of subcutaneously implanted osteosarcoma in mice after radiotherapy.

The present invention discloses a drug combination and application for treating chronic myeloid leukemia, belonging to the field of medical technology. The present invention uses chronic myeloid leukemia cells KBM5, KU-812, and primary cells from clinical patients as research subjects. Disulfiram and TKIs are administered alone or in combination through in vitro drug addition experiments, and cell viability and cell proliferation are measured. The results show that DSF or TKIs alone have certain anti-tumor effects, and the combination of disulfiram and TKIs can significantly enhance the anti-tumor effect of TKIs. Based on this, we speculate that the combination of disulfiram and TKIs can be applied to the clinical treatment of chronic myeloid leukemia.

The invention provides application of disulfiram in preparation of a medicine for preventing and treating CAF-related tumors. Specifically, it is found that disulfiram can affect the formation process of a tumor microenvironment of targeted tumor-related fibroblast cells, development of solid tumors is effectively inhibited from the source, and then increase of the size of CAF-related tumors is inhibited.

The present invention relates to the use of neocuproine, elesclomol, disulfiram and / or dithiocarbamate for use in treatment of cancer, optionally in combination with MAPK-pathway inhibitors in cancers carrying mutations that are recognized as MAPK-pathway activating mutations.

This invention relates to the field of biomedicine, and in particular to the application of disulfiram in the preparation of orthopoxvirus inhibitors. Disulfiram exhibits a significant inhibitory effect on orthopoxvirus by specifically binding to palmitic acid on the MPXV gp045 membrane protein. When the IC50 of disulfiram is 825 nM, it can significantly inhibit the spread of orthopoxvirus. In HeLa and Huh7.5.1 cells, its IC50 is 3022 nM and 7125 nM, respectively, which can significantly inhibit the formation of EEV, thereby preventing the further spread of orthopoxvirus and providing a more comprehensive intervention for anti-orthopoxvirus therapy.

The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit arm-level loss of chromosome 16q, focal copy loss of 16q13 and / or low expression of metallothionein proteins, such as certain uterine, ovarian, gastroesophageal and lung cancers. Three known drugs, disulfiram, elesclomol and thiram, as well as certain disulfiram metabolites, are specifically provided for killing cancer cells characterized by arm-level loss of chromosome 16q, focal copy loss of 16q13 and / or low expression of metallothioneins. The instant disclosure therefore provides for selecting and / or administering disulfiram, elesclomol and thiram and / or active metabolites or derivatives of disulfiram, elesclomol and thiram as a therapeutic agent(s) to target a cancer cell and / or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.

The present invention discloses a dual-responsive phase-change molecular probe for releasing disulfiram, and its preparation method and application, and specifically relates to the field of biomedicine technology. The present invention first performs surface modification on the MMP-2-responsive PEGylated peptide EGPLGVRGK, and obtains a PEGylated MMP-2 peptide segment by covalent coupling; then the PEGylated MMP-2 peptide segment is covalently coupled to the surface of the PLGA-COOH shell layer, and a standard coupling agent method is used to form a PLGA-MMP2-PEG complex; finally, the PLGA-MMP2-PEG complex is reacted with DSF and PFP to obtain PFP@PDM-PEG nanoparticles. The dual-responsive phase-change molecular probe for releasing disulfiram of the present invention paves the way for effective cancer treatment strategies by using LIFU irradiation to destroy the complex microvascular environment in the tumor; it has intelligent design and biocompatible functionalization, and can inhibit tumor growth and metastasis by resisting angiogenic mimicry (VM), providing a strategic and innovative method for cancer treatment.

The invention discloses a medicine for treating bronchial pulmonary dysplasia and application thereof, and relates to the field of medicine. The invention relates to a medicine for treating bronchial pulmonary dysplasia, which comprises a therapeutically effective amount of disulfiram and pharmaceutic adjuvants and is prepared into an injection, and the application of the medicine for treating bronchial pulmonary dysplasia is characterized in that release of lung tissue inflammatory factors IL-1beta and IL-18 is reduced by inhibiting GSDMD-mediated pyroptosis of macrophages, and the dosage is 40-60 [mu] g / (kg.d); the approach is intraperitoneal injection; and the medicine is continuously administrated for 7-10 days for treatment course. According to the application disclosed by the invention, the interaction mechanism between the GSDMD-mediated pyroptosis of macrophages and the chronic hyperxia-induced BPD is determined by constructing a chronic hyperxia-induced newborn mouse BPD model, and the newborn BPD is relieved by regulating the pyroptosis of the macrophages through the disulfiram, so that a new intervention measure and a new drug target are provided for clinical treatment.

Provided herein are methods of treating alcohol use disorder (AUD), opioid use disorder (OUD), and other substance use disorders (SUDs) in a subject, for example by administering an oral transmucosal dosage form of esketamine, such as an oral thin film (OTF) form of esketamine, sublingually or buccally. Disclosed methods may combine one or more therapy modalities provided before, during, and / or after drug administration. In some aspects, the methods comprise administering a dose of esketamine that is sufficient to produce dissociative effects in a subject. In some further aspects, the methods comprise the use of specific therapy modalities or ketamine-assisted psychotherapy (KAP) protocols, including manualized relapse prevention cognitive behavioral therapy (CBT). In yet further aspects, the methods comprise ongoing support, including additional psychotherapy and / or adjunct medication, such as naltrexone, buprenorphine, buprenorphine-naloxone, disulfiram, naloxone, and others.

The invention discloses an application of disulfiram and / or irisin in preparation of a medicine for treating aconitine poisoning. It is found through a large number of attempts that disulfiram can inhibit abnormal expression of alpha-syn in central nervous system caused by aconitine, irisin can inhibit aggregation of alpha-syn, both disulfiram and irisin can rescue PI3K / Akt / mTOR pathway abnormity caused by aconitine, disulfiram or irisin is applied to dyskinesia caused by aconitine, the remarkable improvement effect can be achieved, and the application range of disulfiram or irisin is widened. And an effective strategy is provided for toxicity reduction treatment of clinical aconitine-containing drug poisoning.

The invention provides a preparation method of dextran-modified DSF-loaded Cu-MOF nano-enzyme, which comprises the following steps: dropwise adding a methanol solution of copper chloride into a methanol solution of 3-amino-1, 2, 4-triazole, stirring, adding a methanol solution of disulfiram, continuously stirring, centrifuging, washing the precipitate, and carrying out vacuum drying to obtain DSF-loaded Cu-MOF nano-enzyme powder (D (at) MOF); and dissolving the D (at) MOF in deionized water, then dropwise adding a dextran (DEX) aqueous solution, stirring, centrifuging, washing the precipitate, and carrying out vacuum drying to obtain the dextran-modified DSF-loaded Cu-MOF nano enzyme (D (at) D (at) MOF). The invention also provides an application for preparing a medicine for treating triple negative breast cancer. The D (at) D (at) MOF prepared by the invention can target tumor tissues, simulate SOD, POD and GPx in TME, generate high-level ROS and reduce the GSH level at the same time so as to enhance chemical kinetic therapy (CDT), is combined with DSF-mediated chemical therapy to perform synergistic treatment on triple negative breast cancer (TNBC), and can be used for preparing drugs for triple negative breast cancer.

The invention discloses a micromolecule prodrug co-assembled nano-drug for targeted inhibition of pyroptosis of macrophages as well as a preparation method and application of the micromolecule prodrug co-assembled nano-drug. The preparation method of the micromolecular prodrug co-assembled nano-drug for targeted inhibition of pyroptosis of macrophages comprises the following steps: S1, preparing a Pu-ID prodrug; s2, preparation of MPID NPs: weighing a Pu-ID prodrug, disulfiram, DSPE-PEG-Mannose and DSPE-PEG-COOH, fully dissolving the weighed materials in an organic solvent B, and dropwise adding the obtained mixed solution into pure water in a stirring state to form an MPID NPs solution; then, the obtained MPID NPs solution is transferred into a dialysis bag for dialysis; and after dialysis is finished, collecting the MPID NPs solution in the dialysis bag, so as to obtain the micromolecule prodrug co-assembled nano-drug. The nano-drug provided by the invention can be applied to preparation of drugs for treating atherosclerosis.

Described are analogs of aztreonam and disulfiram of Formula I, II, and III. These compounds can be used to treat bacterial infections in a subject. Also disclosed is the use of aztreonam and disulfiram for treating H. pylori infections. Combinations of the disclosed analogs and / or aztreonam and disulfiram with additional antibiotics and proton pump inhibitors are also disclosed.

The present invention relates to the field of tumor treatment, and specifically to the use of small molecule compounds in the preparation of drugs for treating hepatocellular carcinoma. For the first time, we used disulfiram to reverse the regorafenib resistance of MHCC-97H / REGO cells. The experimental results showed that after using disulfiram, the same concentration of regorafenib inhibited the proliferation, migration and invasion of MHCC-97H / REGO cells more significantly, and could significantly inhibit the tolerance of hepatocellular carcinoma to regorafenib. Therefore, the disulfiram provided by the present invention can be used to prepare drugs for prolonging the life of patients after hepatocellular carcinoma becomes regorafenib-resistant. The present invention provides disulfiram for the preparation of drugs for treating regorafenib-resistant hepatocellular carcinoma.

The invention discloses an application of carnosine in preparation of a medicine for improving pulmonary fibrosis, and belongs to the technical field of medicines. According to the present invention, the puberine VOM can induce disulfiram death by improving the protein expression level of the SLC7A11 of lung fibroblasts so as to alleviate the pulmonary fibrosis symptom, the treatment strategy of the pulmonary fibrosis disease can be further expanded, and the treatment of the pulmonary fibrosis by using the VOM has good application prospects.