35 results about "Haem Oxygenase" patented technology

Disclosed are compounds of the general formula (I):TCnD  (I),compositions comprising an effective amount of said compounds either alone or in combination with other chemotherapeutic agents, and methods useful for treating or preventing cancer and for inhibiting tumour tissue growth. These compounds attenuate the oxidative damage associated with increased heme-oxygenase activity and can reduce cell proliferation in transformed cells. In addition, the described compounds and compositions are useful as neuroprotectants and for treating or preventing neurodegenerative disorders and other diseases of the central nervous system.

Substituted fused imidazole derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted fused imidazole derivative, and methods of use in treating inflammation are provided. The substituted fused imidazole derivatives may control the activity or the amount or both the activity and the amount of heme-oxygenase.

Anticancer agents which contain as the active ingredient, a heme oxygenase inhibitory metalloporphyrin derivatives which are conjugated with amphipathic or water-soluble polymers (in particular, Zn-protoporphyrin (ZnPP) conjugated with polyethylene glycol). Because of being conjugated to amphipathic or water-soluble polymers, such as polyethylene glycol, the active ingredient can be administered by intravenous injection and can exert a remarkable anticancer effect owing to tumor selective delivery.

Substituted fused imidazole derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted fused imidazole derivative, and methods of use in treating inflammation are provided. The substituted fused imidazole derivatives may control the activity or the amount or both the activity and the amount of heme-oxygenase.

The present invention provides a method for evaluating an inclination of a subject to lung cancer, the method comprising preparing a DNA, from the sample, containing at least one allele which comprises a GT repeat located upstream to a heme oxygenase-1 gene, and determining the repeat number of the GT repeat in each allele in the sample wherein the presence of at least one allele comprising a GT repeat whose repeat number is not less than 33 being an indication for an inclination of a subject to lung cancer. In addition, the present invention provides a kit for evaluating an inclination of a subject to lung cancer, by means of the method.

The invention relates to a bismuth sulfide-zinc protoporphyrin composite material with a tumor photodynamic therapy (PDT) property under excitation of near-infrared light as well as a preparation method and application and belongs to the field of composite materials, aiming at solving the problem that the PDT efficiency is relatively low, caused by photoelectron-hole compounding in a photodynamictherapy process of bismuth sulfide and an anti-oxidization stress capability of heme oxygenase (HO-1) in cells. The composite material is the bismuth sulfide-zinc protoporphyrin composite material which is obtained by synthesizing a polyN-isopropylacrylamide-acrylamide copolymer modified bismuth sulfide nano-material and then carrying out condensation reaction of carboxyl and amino. The prepared composite material has the effect of enhancing the photodynamic therapy efficiency through two ways of inhibiting the activity of the heme oxygenase and promoting electron-hole separation; meanwhile, the material provided by the invention has good biocompatibility, light stability, CT (Computed Tomography) imaging capability and enhanced PDT efficiency; a thought is provided for designing a novel nano diagnosis and treatment integrated system and the material has important meaning on early-stage diagnosis and treatment of cancers.

Substituted pyridine derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted pyridine derivative, and methods of use in treating inflammation are provided. The substituted pyridine derivatives may control of the activity or the amount or both the activity and the amount of heme-oxygenase.

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 present invention relates to a method for the prevention of allograft rejection in clinical transplantation. Specifically, the method of the present invention relates to the prevention of transplant arteriosclerosis and interstitial fibrosis by stable and long-term expression of HO-1 in grafts. The present invention represents a novel therapeutic approach to prevent allograft rejection in clinical transplantation.

The invention discloses a medicine for treating lipopolysaccharide / D-aminogalactose (LPS / GalN) induced liver injury. The medicine for treating lipopolysaccharide / D-aminogalactose (LPS / GalN) induced liver injury is forsythiaside A. The forsythiaside A is capable of alleviating liver pathological injury induced by lipopolysaccharide / D-aminogalactose (LPS / GalN), reducing content of malonaldehyde (MDA) and serum ALT (Alanine Aminotransferase) and AST (Aspartate Amino Transferase) levels. In addition, the forsythiaside A is capable of inhibiting NF-chiB activation, serum TNF-alpha and liver TNF-alpha levels caused by LPS / GalN. In addition, the forsythiaside A is capable of increasing expression of Nrf2 and haem oxygenase 1. Results show that the protection function of the forsythiaside A on LPS / GalN induced liver injury is achieved by activating Nrf2 and inhibiting NF-chiB activation.

The present invention relates to hybrid fumarate-CO-releasing molecules capable of increasing heme oxygenase-1 (HO-1) activity and HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory or cardiovascular diseases.

The invention belongs to the field of molecular biological diagnosis and treatment of radiation-induced lung injury, and particularly relates to application of heme oxygenase-1 in diagnosis and treatment of radiation-induced lung injury. It is found that serious radiation-induced lung injury is caused by insufficient HO-1 content, so that for a patient subjected to large-dose X-ray radiation therapy, if HO-1 in blood is reduced, radiation-induced lung injury is caused. A drug such as Hemin for enhancing the expression and function of HO-1 can be used as a new method for treating radiation-induced lung injury.

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 relates to cobalt porphyrin / porous silicon dioxide composite particle with photoacoustic imaging performance and a cytoprotection function and a preparation method and application thereof. The preparation method comprises the steps that a cobalt ion-centered metallic porphyrin compound and porous silicon dioxide nano particles are mixed and stirred, particles are centrifugally collected and dried, and the multifunctional cobalt porphyrin / porous silicon dioxide composite particle is obtained. According to the preparation method, the metallic porphyrin compound is carried by the porous silicon dioxide nano particles, an optical absorption property of a porphyryl compound is changed, the absorption of molecule near an infrared light area is promoted, and an expressed photoacoustic imaging radiography performance is good. According to the composite material, haem oxygenase-1 can be up-regulated to generate a cytoprotection effect, and the survival rate of a cell after cell transplantation is improved. The adopted preparation method is simple, quick, economical, applicable and has high repeatability, the photoacoustic imaging and the cytoprotection are successfully combined, a new method for an imaging mark is provided and improves the cell survival rate.

The invention relates to the technical field of medicines and in particular relates to a composition as well as a preparation method and application thereof. The composition is prepared from herba polygoni salicifolii and folium et ramulus evodiae, wherein the herba polygoni salicifolii is a sovereign drug and the folium et ramulus evodiae is an assistant and guide drug. The two drugs are reasonably matched to realize the effects of clearing away heat and dispelling dampness, and promoting blood circulation and stopping pain. A pharmacodynamic research shows that the composition has a remarkable protection effect on gastric mucosal injuries and can be used for effectively improving the cell survival rate of H2O2 or ethanol caused cell injuries, promoting the multiplication of normal GES-1cells, improving the expression of an important transcription factor Nrf2 capable of adjusting cell anti-oxidization stress, inducing the expression of downstream haem oxygenase-1 (HO-1) and eliminating surplus oxygen free radicals, so that the anti-oxidization capability of gastric mucosa is enhanced; the composition can be used for preparing a medicine for preventing and / or treating the gastricmucosal injuries.

The invention discloses an exosome delivery carrier as well as a preparation method and application thereof, and relates to the field of medical treatment. The exosome can target heme oxygenase 1 (HMOX1) through HSSP polypeptide modification, HMOX1 protein is highly expressed in various tumor cells and neurodegenerative diseases, especially drug-resistant glioma, based on this, the exosome modified with HSSP can specifically target tumors and neurodegenerative diseases, and therefore, the exosome delivery carrier can also be applied to targeted therapy or prevention of tumors and / or neurodegenerative diseases, and a new solution is provided for the problem of drug resistance of glioma drugs TMZ. The exosome has extremely low immunogenicity, so that the safety of the delivery carrier is improved; meanwhile, the exosome also has good blood-brain barrier penetrating ability, so that the problem that the medicine is difficult to penetrate through the blood-brain barrier is solved.

The invention relates to a haem oxygenase drug eluting stent. The haem oxygenase drug eluting stent comprises a stent body, and haem oxygenase is adsorbed to the surface of the stent body. According to the haem oxygenase drug eluting stent, HO is adsorbed to the surface of an intravascular stent, After the stent is placed in an embolism blood vessel, enzymolysis and lesion are conducted on abundant heme at the blood vessel, CO is generated, CO can be freely diffused to adjacent vascular endothelial cells and smooth muscles to generate a biological effect, proliferation of smooth muscle cells can be inhibited, restoration of the endothelial cells can be promoted, meanwhile, the effects of inhibiting the inflammatory reaction, inhibiting the foreign matter rejection reaction and resisting to platelet aggregation are achieved, the efficacy of preventing post-stenting restenosis and stent throbosis formation is achieved, and the haem oxygenase is an ideal stent coating drug integrating multiple functions.

The invention relates to a bismuth sulfide-zinc protoporphyrin composite material with a tumor photodynamic therapy (PDT) property under excitation of near-infrared light as well as a preparation method and application and belongs to the field of composite materials, aiming at solving the problem that the PDT efficiency is relatively low, caused by photoelectron-hole compounding in a photodynamictherapy process of bismuth sulfide and an anti-oxidization stress capability of heme oxygenase (HO-1) in cells. The composite material is the bismuth sulfide-zinc protoporphyrin composite material which is obtained by synthesizing a polyN-isopropylacrylamide-acrylamide copolymer modified bismuth sulfide nano-material and then carrying out condensation reaction of carboxyl and amino. The prepared composite material has the effect of enhancing the photodynamic therapy efficiency through two ways of inhibiting the activity of the heme oxygenase and promoting electron-hole separation; meanwhile, the material provided by the invention has good biocompatibility, light stability, CT (Computed Tomography) imaging capability and enhanced PDT efficiency; a thought is provided for designing a novel nano diagnosis and treatment integrated system and the material has important meaning on early-stage diagnosis and treatment of cancers.

According to the invention, experimental autoimmune neuritis is used as an experimental environment to research intervention effect of zidovudine on the immune system. It is found through experiments that zidovudine can increase expression quantity of nuclear transcription factor 2 and heme oxygenase 1 so as to induce differentiation of M1-type macrophage to M2-type macrophage and furthermore promote neighboring cell proliferation and tissue repairing by the utilization of cytokines released by the M2-type macrophage. In addition, it is found that oral administration of zidovudine can down-regulate messenger RNA level of pro-inflammatory cytokines gamma-interferon, tumor necrosis factor alpha, interleukin 6 and interleukin 17 and up-regulate messenger RNA level of anti-inflammatory cytokines interleukin 4 and 10 so as to improve inflammatory injury in an EAN model. Based on the above positive discovery, the new application of zidovudine for preparation of a medicine for treating autoimmune neuritis is determined. The invention is of positive clinical significance.

The invention relates to the technical field of bilirubin production methods and discloses a method for synthesizing bilirubin by utilizing an immobilized enzyme. The method comprises the following steps of: a) respectively cloning haem oxygenase genes and biliverdin reductase genes; b) respectively expressing the recombinant haem oxygenase and biliverdin reductase in escherichia coli; c) extracting a crude extract or pure enzyme of haem oxygenase and a crude extract or pure enzyme of biliverdin reductase; d) immobilizing the crude extract or pure enzyme of haem oxygenase and the crude extract or pure enzyme of biliverdin reductase; and e) preparing bilirubin in the assistance of an oxidized coenzyme II by catalyzing with the immobilized haem oxygenase and the immobilized biliverdin reductase and taking haem and oxygen as substrates.

Disclosed are compounds of the general formula (I):compositions comprising an effective amount of said compounds either alone or in combination with other chemotherapeutic agents, and methods useful for treating or preventing cancer and for inhibiting tumour tissue growth. These compounds attenuate the oxidative damage associated with increased heme-oxygenase activity and can reduce cell proliferation in transformed cells. In addition, the described compounds and compositions are useful as neuroprotectants and for treating or preventing neurodegenerative disorders and other diseases of the central nervous system.

Heme released as a result of sustained injury leads to toxicity and triggers an inflammatory response and tissue damage. Heme oxygenase, an enzyme, recognizes, binds free heme and breaks it down as a part of the anti-inflammatory response. The present disclosure relates to a class of peptide amphiphiles that mimic the heme oxygenase function, and have shown that the designed peptide is able to bind and break down heme thus validating its potential as an anti-inflammatory agent that promotes tissue repair and useful in wound healing. The disclosed peptide sequence design provides control of amphiphile peptides' supramolecular structure and function. Applicants have shown that the incorporated heme molecule can transport CO, which suggests that the peptides can also transport NO, O2 and reactive oxygens, the molecules which are responsible for vasodilation, neurotransmission and cell death. Besides heme oxygenase function, it is believed that the designed peptides can recognize normal tissue adjacent to the damaged area and the peptide can self-assemble into fibers that promote healthy cell growth.

The present invention relates to hybrid fumarate-CO-releasing molecules capable of increasing heme oxygenase-1 (HO-1) activity and HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory or cardiovascular diseases.

Increased viral particle maturation and production can be achieved in various methods for producing viral particles from viral proteins, in general, by inhibiting or preventing Heme Oxygenase 2 (HO-2) from binding to the group-specific antigen (Gag) of the viral proteins, thus allowing delivery of the viral proteins to plasma membranes where they can replicate and mature without interference from HO-2. The increase in viral particle maturation and production can also be achieved by minimizing or eliminating the presence of HO-2 to thus reduce or prevent binding of HO-2 to the group-specific antigen (Gag) of the viral proteins. The invention is particularly applicable to the production of lentiviruses from viral proteins wherein the Matrix domain (MA) of the Gag is myristoylated.

The present invention relates to dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs) comprising a polymer core comprising a heme oxygenase 1 inhibitor and a lipid membrane (shell) comprising a targeting moiety, a kit for preparing the dual-targeting lipid-polymer hybrid nanoparticles, a pharmaceutical composition comprising the dual-targeting lipid-polymer hybrid nanoparticles as an active ingredient, and a method of preventing or treating cancer comprising administering the pharmaceutical composition to a subject in need thereof. Accordingly, the present invention can provide the dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs) comprising a polymer core comprising a heme oxygenase 1 inhibitor and a lipid membrane (shell) comprising a targeting moiety, the kit for preparing the dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs), the pharmaceutical composition comprising the dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs) as an active ingredient, and the method of preventing or treating cancer comprising administering the pharmaceutical composition to a subject in need thereof.

The invention belongs to the technical field of gene engineering, and particularly discloses a heme oxygenase gene and an effect of the heme oxygenase gene in regulation and control of ganoderma lucidum polysaccharide biosynthesis. According to the invention, a ganoderma lucidum HMX1 gene is silenced through a gene silencing technology, so that ganoderma lucidum polysaccharide biosynthesis amountcan be increased. Besides, an RNA interference means is adopted so as to provide an important genetic manipulation means for improving the biosynthesis of the ganoderan by silencing the heme oxygenasegene; and thus, a theoretical basis is provided for improving the ganoderma lucidum polysaccharide biosynthesis by using a genetic engineering technical means.

Increased viral particle maturation and production can be achieved in various methods for producing viral particles from viral proteins, in general, by inhibiting or preventing Heme Oxygenase 2 (HO-2) from binding to the group-specific antigen (Gag) of the viral proteins, thus allowing delivery of the viral proteins to plasma membranes where they can replicate and mature without interference from HO-2. The increase in viral particle maturation and production can also be achieved by minimizing or eliminating the presence of HO-2 to thus reduce or prevent binding of HO-2 to the group-specific antigen (Gag) of the viral proteins. The invention is particularly applicable to the production of lentiviruses from viral proteins wherein the Matrix domain (MA) of the Gag is myristoylated.

The invention relates to cobalt porphyrin / porous silicon dioxide composite particle with photoacoustic imaging performance and a cytoprotection function and a preparation method and application thereof. The preparation method comprises the steps that a cobalt ion-centered metallic porphyrin compound and porous silicon dioxide nano particles are mixed and stirred, particles are centrifugally collected and dried, and the multifunctional cobalt porphyrin / porous silicon dioxide composite particle is obtained. According to the preparation method, the metallic porphyrin compound is carried by the porous silicon dioxide nano particles, an optical absorption property of a porphyryl compound is changed, the absorption of molecule near an infrared light area is promoted, and an expressed photoacoustic imaging radiography performance is good. According to the composite material, haem oxygenase-1 can be up-regulated to generate a cytoprotection effect, and the survival rate of a cell after cell transplantation is improved. The adopted preparation method is simple, quick, economical, applicable and has high repeatability, the photoacoustic imaging and the cytoprotection are successfully combined, a new method for an imaging mark is provided and improves the cell survival rate.