26 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 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 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 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.

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 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 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.

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.

The present invention belongs to the technical field of tumor treatment, and particularly relates to a pharmaceutical composition and its application, as well as a composition for treating prostate cancer and its application. The pharmaceutical composition comprises a soluble copper salt and a copper ion carrier, wherein the copper ion carrier is at least one of ilisimol and disulfiram. The pharmaceutical composition can inhibit cancer cell proliferation and reduce the size of solid tumors. When used in combination with chemotherapy drugs at specific concentrations, it has a synergistic effect in inhibiting cancer cell proliferation and reducing cancer cell activity. The pharmaceutical composition can also inhibit chemotherapy-induced autophagy and improve chemotherapy drug resistance. Therefore, the pharmaceutical composition can enable chemotherapy drugs to produce ideal therapeutic effects even at a reduced dosage, thereby reducing the dosage of chemotherapy drugs and alleviating the side effects of chemotherapy without significantly increasing adverse reactions, providing a new combination drug regimen for tumor treatment.

The invention discloses a hydrogel microsphere for treating drug-resistant ovarian cancer and a preparation method of the hydrogel microsphere. The pharmaceutical composition is prepared from a 2, 5-dihydroxy bibenzyl acetate derivative, a lycorine N-demethylated derivative, a chemotherapeutic drug (paclitaxel / cis-platinum / carboplatin), hyaluronic acid, glycerol, glutaraldehyde and a copper death mixture (disulfiram-copper-carrier and quercetin nanocrystal). The hydrogel is formed by a micro-fluidic technology, and has the characteristics of multi-mechanism synergy (inhibition of drug-resistant genes, induction of copper death and chemotherapy), efficient targeting (chitosan enhances biocompatibility) and controllable slow release (hyaluronic acid-glutaraldehyde crosslinking). In-vitro / in-vivo experiments show that the tumor inhibition rate reaches up to 75%, the safety is good, the process is mature, and the method is suitable for large-scale production.

There is provided pharmaceutical compositions comprising disulfiram (DSF) or copper di-ethyldithiocarbamate (CuET), an indirubin compound such as 6-bromo-indirubin-3'-oxime (BIO), and a stabilizer, wherein the disulfiram or CuET, the indirubin compound, and the stabilizer are associated with a lipid nanoparticle. The pharmaceutical compositions are particularly suitable for treating a cancer overexpressing p97 and NPLOC4.

The invention provides a GLUT inhibitor based on a disulfide death mechanism, the molecular formula of the GLUT inhibitor is C17H18N4O2S2, the molecular weight is 378.48, the GLUT inhibitor comprises a core structure containing a sulfur group, and the core structure and specific amino acid residues in GLUT protein form covalent bonds; the preparation method of the GLUT inhibitor comprises the following steps: S1, mixing sodium diethyldithiocarbamate and copper chloride in absolute ethyl alcohol, and reacting at the temperature of 25 DEG C for 24 hours to obtain a disulfiram copper compound; and S2, mixing the disulfiram copper compound and glucose transporter in a phosphate buffer solution, and reacting at 37 DEG C for 12 hours to obtain the GLUT inhibitor based on the disulfide death mechanism. The core structure of the inhibitor can form a covalent bond with a specific amino acid residue in a GLUT protein, so that the activity of the GLUT is irreversibly inhibited, the activity of the GLUT is easily approached to the GLUT protein, and due to the structural characteristics, the inhibitor can efficiently and specifically recognize and inhibit the GLUT protein and induce tumor cells to generate dithio death.

The present invention is directed to methods of treating ophthalmic conditions comprising administration of disulfiram or a metabolite of disulfiram selected from the group consisting of sodium diethyldithiocarbamate, copper diethyldithiocarbamate, zinc diethyldithiocarbamate, lead diethyldithiocarbamate, nickel diethyldithiocarbamate, cadmium diethyldithiocarbamate, S-methyl-N,N-diethylthiocarbamate, S-methyl N,N-diethylthiocarbamate sulfoxide, S-methyl-N,N-diethylthiocarbamate sulfone, diethyldithiocarbamate and methyl diethyldithiocarbamate and hydrates thereof.

The invention provides a vascular intervention device and a preparation method and application thereof. In a first aspect, the present invention provides a vascular intervention device comprising an expandable balloon and a drug coating located on a surface of the balloon, the drug coating comprising a disulfiram (DSF). The disulfiram-containing drug coating is coated on the surface of the expandable balloon, the disulfiram can be efficiently transferred to a target blood vessel while the disulfiram-containing drug coating has stability, the disulfiram-containing drug coating plays a regulating role in an inflammatory microenvironment after a vascular intervention operation so as to resist restenosis, and the disulfiram-containing drug coating vascular intervention device is more targeted, more effective and safer.

The invention discloses an application of disulfiram in preparation of a medicine for treating lysosomal storage diseases. The drug disulfiram screened by the invention can inhibit phenotypes of lysosomal storage diseases, including inhibition of increase of lysosomal volume, inhibition of cholesterol storage, substantial recovery of inhibited lysosomal tubulation, substantial recovery of repeated hunger tolerance and reduction of cell death rate, thereby achieving the purposes of alleviating injury and inhibiting disease development. Therefore, the disulfiram has the prospect of being developed into the broad-spectrum medicine for treating the lysosomal storage disease.

The invention belongs to the technical field of medicines, and particularly relates to a method for enhancing tumor radiotherapy / chemotherapy sensitivity by combining a low-temperature plasma activating solution with disulfiram. The invention discloses an application of a composition containing a low-temperature plasma activating solution and disulfiram or a compound thereof in preparation of a medicine for enhancing the sensitivity of tumor radiotherapy or chemotherapy, and discloses a medicine composition for enhancing the sensitivity of tumor radiotherapy or chemotherapy, which comprises disulfiram or the compound thereof and the low-temperature plasma activating solution. According to the invention, after the tumor cells are pretreated by adopting the low-temperature plasma activating solution, the killing capability on the tumor cells can be obviously enhanced by adopting disulfiram combined with radiotherapy / chemotherapy, so that cancer patients can benefit from the tumor cells, and a new treatment means is provided for clinically overcoming the tolerance of advanced tumor radiotherapy / chemotherapy.

The disclosure provides disulfiram containing compositions and methods of using disulfiram for activating transcription, and / or protein synthesis, and / or tubulin tyrosination and / or histone serine- ADP-ribosylation, and / or increasing TyrRS protein levels in presence of elevated tyrosine / phenylalanine levels. Compositions may be used prophy lactically, to delay neurodegeneration or reduce the expected severity. Disulfiram-containing compositions of this disclosure may be used for treating neurodegradation that leads to constitutive aging and age-associated neurocognitive and metabolic disorders. In particular, compositions disclosed herein are neuroprotective at nanomolar concentrations against tyrosine or its metabolites-mediated transcription inhibition.