41 results about "Carbon monoxide-releasing molecules" patented technology

The invention relates to the use of carbon monoxide (CO) to treat infections. The invention also provides novel carbon monoxide releasing molecules (CORMs).

The invention discloses a photodynamic induced CO releasing method, a CO controlled delivery system and a building method thereof. The CO releasing method is characterized by carrying out controlled release of CO under irradiation of near-infrared light by mixing a photosensitizer responding to the near-infrared light and applied to photodynamic therapy with carbon monoxide releasing molecules CORM-401. The CO controlled delivery system built on the basis of the photodynamic induced CO releasing method comprises a photosensitizer responding to near-infrared light and applied to photodynamic therapy, carbon monoxide releasing molecules CORM-401 and a carrier loaded or integrated with the photosensitizer and the carbon monoxide releasing molecules CORM-401. According to the CO controlled delivery system, the photochemical effect generated by the photosensitizer under induction of the near-infrared light is capable of accelerating the CO controlled delivery system to enter cells for decomposing the nanogel under the action of glutathione in the cells and releasing CORM-401; the near-infrared light activates and simultaneously generates singlet oxygen and CO; the singlet oxygen and COare respectively applied to photodynamic therapy and CO gas therapy; the combined therapy is achieved; the anti-tumor effect is obviously improved.

Provided herein are novel carbon-monoxide releasing molecules (CO-RMs) of the Formula (I): and esters, amides, salts, solvates and hydrates thereof; wherein R1 and R2 are as described herein. Also provided are pharmaceutical compositions comprising these compounds, methods of their preparation, and their use in the treatment of liver disease and inflammation.

The present invention provides novel ruthenium compounds of Formula (I): or salts, isomers, hydrates, or solvates thereof, or combinations thereof; wherein E, R1, R2, R3, R4, R5, X1, and X2 are as defined herein, and pharmaceutical compositions thereof. Also provided are methods of use and treatment. Such compounds have been found useful in the treatment of malaria infection. Such compounds may also be useful in the treatment of inflammatory conditions, such as acute lung injury and acute respiratory distress syndrome, which optionally may be associated with a malaria infection.

Carbon monoxide-releasing organic molecules are described herein. The molecules can be synthesized prior to administration (e.g., ex vivo) or formed in vivo. In those embodiments where the molecules are formed in vivo, reactants are administered under physiological conditions and undergo a cycloaddition reaction to form a product which releases carbon monoxide. In applying such reactions for therapeutic applications in vivo, the cycloaddition and CO release typically occur only under near-physiological or physiological conditions. For example, in some embodiments, the cycloaddition reaction and / or release of carbon monoxide occur at a temperature of about 37 C and pH of about 7.4. Pharmaceutical compositions and methods for release carbon monoxide are also described.

The invention discloses a carbon monoxide releasing molecule with up-conversion nano-phosphor, a method for preparing the carbon monoxide releasing molecule and application of the carbon monoxide releasing molecule as a CO carrier medicine. The method includes synthesizing the up-conversion nano-phosphor from aqueous solution of Y, Yb and Er chloride, organic solvents and methanol solution with sodium hydroxide and ammonium fluoride; uniformly stirring surfactants, cyclohexane and cyclohexane dispersion liquid with the up-conversion nano-phosphor to obtain first mixtures, then adding ammonia water into the first mixtures to obtain second mixtures, sealing the second mixtures and then ultrasonically dispersing the second mixtures in ice bath; adding tetraethyl orthosilicate into mixtures and carrying out reaction; adding silane coupling agents with thiol into mixtures and carrying out reaction; adding dichloromethane solution with iron carbonyl compounds into mixtures, carrying out reaction and centrifuging and washing reaction products to obtain the carbon monoxide releasing molecule with the up-conversion nano-phosphor. The carbon monoxide releasing molecule, the method and the application have the advantages that the UCNPs@SiO2-CORM (up-conversion nano-phosphor@SiO2-carbon monoxide releasing molecule) is excellent in up-conversion luminescence characteristics, and CO can be released under the induction effect of near-infrared light.

The present invention provides novel ruthenium compounds of Formula (I): or salts, isomers, hydrates, or solvates thereof, or combinations thereof; wherein E, R1, R2, R3, R4, R5, X1, and X2 are as defined herein, and pharmaceutical compositions thereof. Also provided are methods of use and treatment. Such compounds have been found useful in the treatment of malaria infection. Such compounds may also be useful in the treatment of inflammatory conditions, such as acute lung injury and acute respiratory distress syndrome, which optionally may be associated with a malaria infection.

The invention discloses application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases. In vivo animal experiments and in vitro cell experiments show that exogenous carbon monoxide can significantly reduce the expression of blood coagulation factors FIB and D-D in sepsis, and reduce the expression of platelet membrane glycoprotein CD 61 and CD 62p in plasma, thereby down-regulating the adhesiveness and aggregation function of platelet, inhibiting the phosphorylation level of platelet HIS of sepsis mice and finally inhibiting over activation of the coagulation system in sepsis. When the carbon monoxide releasing molecules are adopted for inhibiting over activation diseases of the coagulation system in sepsis, the concentration control is relatively easy and accurate, adding is convenient for long-term use, and the requirement of clinical application can be satisfied.

The invention discloses an application of carbon monoxide release molecules in preparing a medicament for treating early sepsis. The invention discovers, according to massive cell and animal tests, that when the carbon monoxide release molecules are dissolved in DMSO solvent and then positioned in cell supernatant or a biological body, CO can be sustainedly released, therefore, the carbon monoxide release molecules can be used as an exogenous CO supplier; in addition, an inflammation model and a mouse CLP sepsis model which are stimulated by cells LPS are adopted for early intervention, and after tests, the carbon monoxide release molecules are dissolved to be capable of serving as a medicament for inhibiting the early sepsis. If the carbon monoxide release molecules are used for inhibiting the sepsis, the control of the concentration thereof is relatively easy and correct, and the superaddition is convenient if the carbon monoxide release molecules are used for a long time. The carbon monoxide release molecules can meet the requirements of clinical application.

The invention discloses a method for promoting carbon monoxide release of carbon monoxide-releasing molecules (CORM) and preventing sedimentation and belongs to the technical field of medical chemistry. The method particularly comprises the following steps: dissolving CO releasing molecules in dimethyl sulfoxide, and adding amino acid, or derivatives thereof, or medicine molecules and an EDTA water solution. After adding of EDTA, generation of CO is effectively promoted, and sedimentation in reaction can be quickly removed. The method has good university; compounds related to the reaction have excellent biocompatibility; and after release of CO, sedimentation can be quickly and effectively prevented, and the CO release time and rate can be easily controlled.

The invention discloses an application of carbon monoxide molecules in inhibition on acute rejection after skin grafting. According to a large number of cell tests, the inventor discovers that after the carbon monoxide molecules are dissolved into a dimethylsulfoxide (DMSO) solvent and placed into an organism, CO can be continuously released, so the carbon monoxide molecules can serve as exogenous CO donors. The skin of ICR mice and BALB / C mice can serve as a donor and a receptor; an allogeneic gene acute rejection model can be established; exogenous CO is injected into the caudal veins of the mice; and early intervention and the test are performed, so that the carbon monoxide release molecules have inhibition effect on the acute rejection after skin grafting. The carbon monoxide release molecules are used for inhibiting the acute rejection after skin grafting; the concentration is controlled relatively easily and correctly; during long-term use, the carbon monoxide release molecules are added conveniently; and the carbon monoxide molecules can serve as an immuno-inhibitor with high specificity, low toxicity and high efficiency.

The invention provides application of carbon monoxide-releasing molecules and heparin in preparing a medicament for treating sepsis. The carbon monoxide-releasing molecules are combined with the ultramicro heparin to improve the coagulation defects of the sepsis, the control of the concentration of the carbon monoxide-releasing molecules and the heparin is relatively easy and correct, the carbon monoxide-releasing molecules and the heparin can be conveniently added when used for a long time, simultaneously the consumption and side effect of the heparin are reduced, and the carbon monoxide-releasing molecules and the heparin can meet the requirement of clinical application. The carbon monoxide-releasing molecules are combined with the ultramicro heparin to improve the coagulation defects ofthe sepsis, the control of the concentration of the carbon monoxide-releasing molecules and the heparin is relatively easy and correct, the carbon monoxide-releasing molecules and the heparin can beconveniently added when used for a long time, and the carbon monoxide-releasing molecules and the heparin can meet the requirement of clinical application.

The invention provides a nanogel drug carrier for targeted delivery and consumption of a large amount of H2O2 and release of CO at the same time, and a preparation method and application thereof. Thenanogel drug carrier is a dendritic polypeptide nanogel drug carrier. The drug carrier comprises dendritic polypeptide nanogel as a carrier, and a carbon monoxide release molecules CORM401 loaded in an internal cavity of the dendritic polypeptide nanogel, and also comprises hyaluronic acid which is modified by folic acid and coats the surface of the dendritic polypeptide nanogel. A multifunctionalanti-inflammatory drug (CPHs) is prepared on the basis of the nanogel drug carrier disclosed by the invention. The drug carrier can enter activated macrophages in a HA-FA targeting manner, and rapidly release a large amount of CO is by consuming excessive H2O2. The generated CO not only can effectively inhibit cell proliferation, but also can obviously inhibit secretion of inflammatory factors byinducing activation (HO-1) of heme oxygenase and down-regulating expression of p38MAPK, NF-kB (p50 / p65) and TLR-2. The CPHs can consume a large amount of ROS at the osteoarthritis joint part, and effectively inhibit degradation of articular cartilage and extracellular matrix.

The invention discloses light induced carbon monoxide release molecules (photoCORMs) and a preparation method thereof. The photoCORMs is of modular design and is synthesized from a CO release unit, support ligand and metal zinc ions, wherein 4-MeOFLH or 4-MeOFLTH is adopted as a CO release unit; 6-Me2TPA is used as the support ligand; the CO release unit and the support ligand independently exist in photoCORMs. The preparation method of the photoCORMs comprises the following steps: (1) by taking methoxybenzaldehyde and 2-phenol acetophenone as initial raw materials, synthesizing 4-MeOFLH or 4-MeOFLTH; (2) by taking 2-(aminomethyl) pyridine as another initial raw material, synthesizing 6-Me2TPA; (3) enabling the CO release unit and the support ligand to react with metal zinc ions, thereby synthesizing photoCORMs. The light induced carbon monoxide release molecules have the beneficial effects that firstly photoCORMs is good in CO release property, and as a CO release medicine, is capable of greatly reducing side effects on bodies, and CO release can be induced through visible light; secondly, the molecule is definite in synthesis step, controllable in process and possible in batched production.

Provided herein are novel carbon-monoxide releasing molecules (CO-RMs) of the Formula (I): and esters, amides, salts, solvates and hydrates thereof; wherein R1 and R2 are as described herein. Also provided are pharmaceutical compositions comprising these compounds, methods of their preparation, and their use in the treatment of liver disease and inflammation.

The invention relates to a method for preparing palladium carbon by using organic carbon monoxide releasing molecule (CORM). According to the method, the palladium carbon is prepared under the ordinary pressure and the low temperature by taking non-toxic and safe formamide liquid carbon monoxide donor as a carbonylation reducing agent, active carbon material as a carrier and palladium chloride, palladium nitrate or palladium acetate as a Pd precursor. According to the method, the preparation method is simple, and the problems of the conventional palladium carbon catalyst that the metal load rate is low, the catalytic activity is not high and the loss quantity of palladium is large after the palladium is circularly utilized are solved. The obtained catalyst can be used for catalyzing cross coupling reaction between aryl halide and phenylboronic acid, wherein the catalyst still presents a high catalytic activity after being repeatedly used, and the recovery rate of the catalyst is above 90%.

The invention discloses a method for preparing alpha, beta-acetylenic ketone compounds through carbon monoxide-releasing molecular carbonylation carbon-carbon bond coupling. According to the method, CO gas is not used, and the method comprises the following steps: by taking palladium chloride as a catalyst, taking 4,5-bis (diphenylphosphino)-9,9-dimethyl xanthenes as a ligand, taking N, N-dimethyl formamide as a solvent, taking pentacarbonyl iron as a CO supply source of a carbon monoxide-releasing molecule, coupling aryl halides and terminal alkyne under alkaline conditions, thereby obtaining the alpha, beta-acetylenic ketone compounds. According to the method disclosed by the invention, usage of high-pressure poisonous gas carbon monoxide is avoided, and the method is simple and safe in experimental operation, mild in conditions and high in substrate applicability and can be widely applied to preparing the alpha, beta-acetylenic ketone compounds.

Carbon monoxide-releasing organic molecules are described herein. The molecules can be synthesized prior to administration (e.g., ex vivo) or formed in vivo. In those embodiments where the molecules are formed in vivo, reactants are administered under physiological conditions and undergo a cycloaddition reaction to form a product which releases carbon monoxide. In applying such reactions for therapeutic applications in vivo, the cycloaddition and CO release typically occur only under near-physiological or physiological conditions. For example, in some embodiments, the cycloaddition reaction and / or release of carbon monoxide occur at a temperature of about 37° C. and pH of about 7.4. Pharmaceutical compositions and methods for release carbon monoxide are also described.

The invention discloses a method of pyrolysis and slow release of carbon monoxide by a metal carbonyl complex. A pentacarbonyl chromium halogenated ion quaternary ammonium compound is used as a carbonmonoxide releasing molecule, the slow release of pure carbon monoxide can be carried out under heating conditions, meanwhile, the physical property is stable, light is not required to be avoided, andair is not required to be isolated, long-term storage can be achieved, so that the pentacarbonyl chromium halogenated ion quaternary ammonium compound is an ideal medical CO-RM. A myoglobin immune test proves that the method can effectively pyrolyze the CO-RM and slow release CO, and the carbonylation process of a micromolar protein solution can be realized. Meanwhile, a complicated air pressurecontrol device required by an existing carbon monoxide release treatment can be avoided, the use of the high-pressure and highly toxic carbon monoxide gas cylinder can be avoided fundamentally, so thesafe, convenient and micro CO release are realized, and the bottleneck problem of the clinical treatment application of CO is solved.

The present invention generally relates to carbon monoxide releasing compounds and compositions, and their use as carbon monoxide prodrugs. The compounds disclosed herein contain a cyclopentadienone moiety, a non-reactive dienophile, and an enzyme-cleavable tethering moiety connecting the cyclopentadienone moiety to the non-reactive dienophile. Cleavage of the enzyme-cleavable tethering moiety results in conversion of the non-reactive dienophile to a reactive dienophile

The present invention generally relates to carbon monoxide releasing compounds and compositions, and their use as carbon monoxide prodrugs.

The invention provides a nanogel drug carrier for targeted delivery and consumption of a large amount of H2O2 and release of CO at the same time, and a preparation method and application thereof. Thenanogel drug carrier is a dendritic polypeptide nanogel drug carrier. The drug carrier comprises dendritic polypeptide nanogel as a carrier, and a carbon monoxide release molecules CORM401 loaded in an internal cavity of the dendritic polypeptide nanogel, and also comprises hyaluronic acid which is modified by folic acid and coats the surface of the dendritic polypeptide nanogel. A multifunctionalanti-inflammatory drug (CPHs) is prepared on the basis of the nanogel drug carrier disclosed by the invention. The drug carrier can enter activated macrophages in a HA-FA targeting manner, and rapidly release a large amount of CO is by consuming excessive H2O2. The generated CO not only can effectively inhibit cell proliferation, but also can obviously inhibit secretion of inflammatory factors byinducing activation (HO-1) of heme oxygenase and down-regulating expression of p38MAPK, NF-kB (p50 / p65) and TLR-2. The CPHs can consume a large amount of ROS at the osteoarthritis joint part, and effectively inhibit degradation of articular cartilage and extracellular matrix.

Provided herein are novel carbon-monoxide releasing molecules (CO-RMs) of the Formula (I):and esters, amides, salts, solvates and hydrates thereof; wherein R1 and R2 are as described herein. Also provided are pharmaceutical compositions comprising these compounds, methods of their preparation, and their use in the treatment of liver disease and inflammation.

The invention discloses a carbon monoxide release molecule-2 preparation, an application of the carbon monoxide release molecule-2 preparation in preparing medicines for resisting porcine reproductive and respiratory syndrome viruses and a detection method of the carbon monoxide release molecule-2 preparation. The carbon monoxide release molecule-2 preparation is Chinese name of CORM-2 (tricarbonyldichlororuthenium (II) dimer). In-vitro experiments prove that the carbon monoxide release molecule-2 has a significant effect of obviously inhibiting replication of the porcine reproductive and respiratory syndrome viruses, therefore a strong support is provided for enhancing prevention and control of the porcine reproductive and respiratory syndrome viruses through drug therapy.

The invention relates to application of carbon monoxide releasing molecules in preparation of an anti-bovine viral diarrhea virus drug, and belongs to the technical field of antiviral researches. The drug contains carbon monoxide releasing molecules and one or more pharmaceutically acceptable adjuvants; the effective concentration of the carbon monoxide releasing molecules for resisting bovine viral diarrhea virus is 50 to 300 [mu] mol / L. According to the application, methods of qPCR, TCID50 and Western Blot are first adopted to detect the influence of the carbon monoxide releasing molecules on the replication of the bovine viral diarrhea virus in MDBK cells so as to further clarify the influence of the carbon monoxide releasing molecules on virus adsorption and internalizationand to detect the influence of treatment of the carbon monoxide releasing molecules with different concentrations on the proliferative activity of the MDBK cells. The role of the carbon monoxide releasing molecules in resistance to the bovine viral diarrhea virus, and a basis is provided for the preparation of the anti-bovine viral diarrhea virus drugs.

The invention discloses a photodynamic induced CO releasing method, a CO controlled delivery system and a building method thereof. The CO releasing method is characterized by carrying out controlled release of CO under irradiation of near-infrared light by mixing a photosensitizer responding to the near-infrared light and applied to photodynamic therapy with carbon monoxide releasing molecules CORM-401. The CO controlled delivery system built on the basis of the photodynamic induced CO releasing method comprises a photosensitizer responding to near-infrared light and applied to photodynamic therapy, carbon monoxide releasing molecules CORM-401 and a carrier loaded or integrated with the photosensitizer and the carbon monoxide releasing molecules CORM-401. According to the CO controlled delivery system, the photochemical effect generated by the photosensitizer under induction of the near-infrared light is capable of accelerating the CO controlled delivery system to enter cells for decomposing the nanogel under the action of glutathione in the cells and releasing CORM-401; the near-infrared light activates and simultaneously generates singlet oxygen and CO; the singlet oxygen and COare respectively applied to photodynamic therapy and CO gas therapy; the combined therapy is achieved; the anti-tumor effect is obviously improved.

The present invention generally relates to carbon monoxide releasing compounds and compositions, and their use as carbon monoxide prodrugs. The compounds disclosed herein contain a cyclopentadienone moiety, a non-reactive dienophile, and an enzyme-cleavable tethering moiety connecting the cyclopentadienone moiety to the non-reactive dienophile. Cleavage of the enzyme-cleavable tethering moiety results in conversion of the non-reactive dienophile to a reactive dienophile.

This invention relates to compositions and methods for treating, ameliorating and preventing the toxic effects of venom poisoning. In particular, the invention provides compositions comprising carbon monoxide releasing molecules (CORM) or compositions comprising CORM and iron releasing molecules (IRM) for one or more of enhancing coagulation, reducing fibrinolysis, and / or inactivating venom related metalloproteinase activity in a subject suffering from or at risk of suffering from venom poisoning.