35 results about "Uncoupling Agents" patented technology

An invention relating to therapeutic pharmacological agents and methods to chemically induce intracellular hyperthermia and / or free radicals for the diagnosis and treatment of infections, malignancy and other medical conditions. The invention relates to a process and composition for the diagnosis or killing of cancer cells and inactivation of susceptible bacterial, parasitic, fungal, and viral pathogens by chemically generating heat, and / or free radicals and / or hyperthermia-inducible immunogenic determinants by using mitochondrial uncoupling agents, especially 2,4 dinitrophenol and, their conjugates, either alone or in combination with other drugs, hormones, cytokines and radiation.

An invention relating to therapeutic pharmacological agents and methods to chemically induce intracellular hyperthermia and / or free radicals for the diagnosis and treatment of infections, malignancy and other medical conditions. The invention relates to a process and composition for the diagnosis or killing of cancer cells and inactivation of susceptible bacterial, parasitic, fungal, and viral pathogens by chemically generating heat, and / or free radicals and / or hyperthermia-inducible immunogenic determinants by using mitochondrial uncoupling agents, especially 2,4 dinitrophenol and, their conjugates, either alone or in combination with other drugs, hormones, cytokines and radiation.

Novel 3-vinylsulfonyl indole derivatives are chemical uncouplers useful e.g. for treatment of obesity.

The invention discloses a method for producing methane through anaerobic digestion of high-solid content sludge, belonging to the technical field of sludge treatment. The method comprises the steps of regulating the carbon nitrogen ratio of a treatment object, namely the dehydrated high-solid content sludge of a municipal sewage treatment plant, carrying out intermediate temperature pretreatment, adding inoculated sludge in a proportion, then adding waste scrap iron, rhamnolipid, alkyl polyglucoside, 3,3,4,5-tetrachlorosalicylanilide (TCS) and the like in a phased manner, turning and stirring at regular intervals, controlling the temperature at 34-38 DEG C, and carrying out anaerobic digestion. After the high-solid content sludge is treated, the internal mass transfer efficiency of the sludge is increased in the anaerobic digestion process, and the yield of methane is increased. Medicament materials used in the method include production waste, a biodegradable surfactant and a low-toxicity chemical uncoupling agent, so that the production of the methane through the anaerobic digestion of the high-solid content sludge can be effectively promoted, the environmental risk is reduced, and the utilization degrees of the recycling and energy regeneration of the sludge are increased.

The present invention relates to therapeutic compositions for treating or preventing obesity and obesity-related disorders in a subject. The present invention also relates to the use of PGC-1 expression levels to determine the safe dosage range for known or putative respiration uncoupling agents for use as anti-obesity therapeutics. The present invention further relates to methods for identifying new compounds that have respiration uncoupling activity.

The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase cellular NAD+ levels and enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a mitochondrial uncoupler or / and a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, metabolic disorders, and other disorders and conditions.

Xanthosine-5'-monophosphate is produced by cultivating the bacterium which has a resistance to growth inhibition by an inhibitor selected from the group consisting of inhibitors of cell membrane biosynthesis and / or functioning, phosphorylation inhibitors, uncoupling agents, RNA-polymerase inhibitors and methionine analogs, and has an ability to produce xanthosine-5'-monophosphate according to produce and accumulate xanthosine-5'-monophosphate in the culture, and recovering the xanthosine-5'-monophosphate therefrom.

The present invention relates to therapeutic compositions for treating or preventing obesity and obesity-related disorders in a subject. The present invention also relates to the use of PGC-1 expression levels to determine the safe dosage range for known or putative respiration uncoupling agents for use as anti-obesity therapeutics. The present invention further relates to methods for identifying new compounds that have respiration uncoupling activity.

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca2+ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

The invention provides methods for screening for agents that modulate mitochondrial function and in particular mitochondrial regulation of intracellular calcium. The methods may be used to detect agents that bind to a mitochondrial calcium uniporter and may also detect inhibitors or uncouplers of mitochondrial respiration. Agents identified using the screens provided herein have application in the prevention and treatment of a variety of diseases associated with abnormal mitochondrial function.

The invention provides a method for reducing sludge in sewage treatment, and the method is capable of greatly reducing the sludge quantity. The method comprises the following steps of: filling a biocarrier enriched with a plurality of trace elements for the growth of microbe in a sewage treatment main process, the DO changeable environment can be formed through the unique form of the biocarrier, the sludge retention time (SRT) is long, the variety is abundant, the food cycle is long, and the newly produced sludge is gradually re-degraded by a plurality of microbes to achieve the aim of reducing the sludge quantity. According to the method for reducing sludge in sewage treatment, the mud yield of the sewage treatment process is reduced to 0.1-0.15% from the 0.8-1% of the sewage quantity without adding an uncoupling agent and producing the secondary pollution; the microbe types and number can be conveniently controlled with obvious effect, and the application range is wide; the organic wastewater of municipal administration, garden, industry and life can be treated, the operation is stable, the water force and water quality change can be born, and the adjusting working quantity is small.

The present invention relates to an organophosphonium derivative of the mean general formula (1), wherein n is a number between 4 and 20, preferably between 5 and 10, m is a number between 0 and 10, preferably between 0 and 1, and Y is an anion. The invention also relates to a method for preparing same, and to a method for controlling the growth of bacterial biomass in an aqueous system, including adding to said aqueous system or contacting said aqueous system with an efficient amount of an uncoupling agent selected from an organophosphonium derivative as defined above.

The invention relates to the field of plant disease control, in particular to application of amitriptyline as a bactericide synergist in plant disease control. The occurrence of oomycete disease resistance to fungicides and even multi-drug resistance in the field is reported, resistance including an uncoupling agent is often associated with the multi-drug resistance, the management of such resistant groups is very difficult, and great harm is brought to agricultural production. According to the application of amitriptyline as the bactericide synergist in plant disease control, the amitriptyline and a diarylamine bactericide, substituted benzene bactericides or piperidinothiazole isoxazoline bactericides, are found to have good synergism on the combined toxicity of phytophthora resistant mutants after being mixed, the toxicity of the bactericides can be effectively improved, the sensitivity of drug resistant strains to the bactericides is restored, the usage amount of the bactericides is reduced, and a new method is provided for the development and application of new preparations of existing bactericides. The application provides a new application of farm chemical, can be used for disease control in the agricultural field, and provides a new way for disease resistance management in the field.

The present invention provides a method capable of substantially reducing the sludge amount in sludge treatment. According to the method, the filler for filling the biological carrier in the sewage treatment main process is rich in a variety of trace elements for microorganism growth, the unique form of the biological carrier can form the DO changeable environment, the sludge retention time (SRT) is long, the variety is rich, the food chain is long, and the newly-generated sludge is progressively re-degraded by a variety of microorganisms so as to achieve the sludge reduction purpose. According to the present invention, the sludge generation amount of the sewage treatment process is reduced to 0.1-0.15% of the sewage amount from 0.8-1% of the sewage amount, the uncoupling agent adding is not required, no secondary pollution is generated, the variety and the quantity of the microorganisms can be easily controlled, the control is easy, the effect is significant, the application range is wide, the method can be used for treating municipal wastewater, park wastewater, industrial wastewater, domestic wastewater and other organic wastewater, the operating is stable, the changes of the hydropower and the water quality can be bore, and the adjust workload is low.

The invention belongs to the fields of biology and medicine and discloses a method for generating mitochondria uncoupling and activating adenosine monophosphate activated protein kinase (AMPK). The method is characterized in that horizontal reversed electron transfer of a mitochondrial respiratory chain complex I is caused by oxidation of a sulfur-containing compound through SQR, cross-mitochondrial inner membrane potential is reduced, and thereby mitochondrial uncoupling is generated; by the mitochondrial uncoupling, the synthesis level of ATP in cells can be reduced and further the AMPK is activated. The invention also discloses a method for obtaining a mitochondria uncoupling agent and an AMPK activator based on the SQR. The experiment verifies that the method disclosed by the inventionhas the advantages that firstly, oxidation of the sulfur-containing compound by the SQR is a novel method for generating the mitochondria uncoupling or activating the AMPK; secondly, a novel mitochondria uncoupling agent or the AMPK activator can be obtained on the basis of the SQR; thirdly, an obtained compound has the mitochondria uncoupling of cell specificity or AMPK activating effect as wellas low toxic and side effects, and can be used for treating related diseases.

The invention relates to a composite uncoupling agent for reducing excess sludge in a sewage treatment process by an activated sludge method, which comprises the following components: 3,3,4,5-tetrachloro salicylamide, soluble copper salt and an adsorbent, wherein the soluble copper salt is one of copper sulfate, copper chloride or copper acetate; the adsorbent is one of refined diatomite or zeolite powder or a mixture of the refined diatomite and the zeolite powder; the weight ratio of the 3,3,4,5-tetrachloro salicylamide to the soluble copper salt is 1:0.05-0.25; and the weight ratio of the total of the 3,3,4,5-tetrachloro salicylamide and the soluble copper to the adsorbent is 1:0.05-1.00. The composite uncoupling agent has obvious positive effect, particularly stronger sludge reductionperformance. If the same weight reduction rate of the sludge is achieved, the added TCS (tetrachloro salicylamide) can be reduced by 25 to 75 percent, and after the TCS is added into a system, the removing rate of the COD (chemical oxygen demand) is basically not influenced.

The invention discloses a compound uncoupling agent which is used for deweighting treatment of residual sludge in the sewage treatment technology with the activated sludge process. The compound uncoupling agent comprises 3,3,4,5- tetrachlorosalicyloylaniline, refined diatomite and zeolite. When one part by weight of 3,3,4,5-tetrachlorosalicyloylaniline is provided, 0.05-1.0 part by weight of refined diatomite is provided, and 0.05-1.0 part by weight of zeolite is provided. The compound uncoupling agent provided by the invention can obviously lower attenuation on sludge activity while keeping favorable sludge decrement performance and has obvious active effect, which embodies on the aspect that the sludge decrement performance is enhanced, for example, the added TCS can be reduced by 20-60% for reaching the same sludge decrement ratio; after TCS is added in a system, COD strainaway rate is not affected on the whole.

The invention provides a pharmaceutical composition used for preventing or treating metabolism or damage-related diseases. The pharmaceutical composition comprises at least one mitochondrial uncoupling agent and at least one artemisinin compound; and the pharmaceutical composition can effectively and remarkably improve symptoms of polydipsia, polyphagia and polyuria of diabetes, reduces various metabolic indexes related to blood glucose and insulin, reduces metabolic disorders brought by insulin defects, relieves islet damage or insulin resistance, exerts a protective effect on kidneys, can effectively prevent or treat diabetic nephropathy and kidney damage related diseases, meanwhile, has certain protection and improvement effects on liver damage and lipid metabolism, can effectively adjust and stabilize the body temperature, and takes effect quickly.

The present invention relates to novel compounds that act as chemical uncouplers. Compounds of the invention are useful, inter alia, in the treatment, including prevention, of obesity, diabetes and a number of diseases or conditions associated therewith.

The invention discloses a pyridine phenyl coupling compound and a pharmaceutical composition and application thereof. The pyridine phenyl coupling compound is a PSD-95-nNOs uncoupling agent, can selectively inhibit combination between PSD-95 and nNOs to achieve the pharmaceutical effect, has the important potential treatment effect and has wide application in preparation of drugs for treating stroke, neuropathic pain and an alzheimer disease or vascular dementia.

The invention provides a diagnosis method for promoting the sludge uncoupling effect through an uncoupling agent, and relates to a diagnosis method for the uncoupling effect. The method aims to solve the technical problem that diagnosis achieved through an existing method can not directly represent the uncoupling effect in microorganisms. The method includes the following steps that firstly, part of sludge mixed liquid is uniformly mixed, a trichloroacetic acid solution is added for ultrasonic processing, and homogeneous mixed liquid is obtained; the homogeneous mixed liquid is obtained and added into a buffering solution to be mixed; filtering is carried out; the fluorescence intensity of filtered liquid is measured; sludge concentration of a solution to be tested is measured; the sludge concentration is divided by the fluorescence intensity to obtain the specific ATP concentration; the sludge uncoupling effect is diagnosed according to the specific ATP concentration, when the specific ATP concentration is smaller than 60 RLU.L / mg, ATP synthesis in sludge is obviously inhibited, and metabolic uncoupling is generated. The method can be suitable for judging the effects, for promoting uncoupling in the sludge, of different uncoupling agents, and the test method is simple and accurate. The method belongs to the field of uncoupling effect diagnosis of the uncoupling agents.

The invention discloses a compound uncoupling agent which is used for deweighting treatment of residual sludge in the sewage treatment technology with the activated sludge process. The compound uncoupling agent comprises 3,3,4,5-tetrachlorosalicylamide, refined diatomite and zeolite. When one part by weight of 3,3,4,5-tetrachlorosalicylamide is provided, 0.05-1.0 part by weight of refined diatomite is provided, and 0.05-1.0 part by weight of zeolite is provided. The compound uncoupling agent provided by the invention can obviously lower attenuation on sludge activity while keeping favorable sludge decrement performance and has obvious active effect, which embodies on the aspect that the sludge decrement performance is enhanced, for example, the added TCS can be reduced by 20-60% for reaching the same sludge decrement ratio; after TCS is added in a system, COD strainaway rate is not affected on the whole.

The disclosure provide compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables, R1, R2, R3, X1, X2, and Z are defined herein. Certain compounds of Formula I act as selective mitochondrial protonophore uncouplers that do not affect the plasma membrane potential. Compounds and salts of Formula I are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as cancer, obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH). Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, compounds of Formula I are useful for increasing lifespan. Compounds and salts of Formula I are also useful for regulating glucose homeostasis or insulin action in a patient.

The present invention relates to an organophosphonium derivative of the mean general formula (1), where n is a number comprised between 4 and 20, preferably between 5 and 10, m is a number between 0 and 10, preferably between 0 and 1, and Y is an anion.The invention also relates to a method for preparing same, and to a method for controlling the growth of bacterial biomass in an aqueous system, including adding to said aqueous system or contacting said aqueous system with an efficient amount of an uncoupling agent selected from an organophosphonium derivative as defined above.

The invention relates to a method for reducing excess sludge of an aerobic unit of a sewage treatment system by an activated sludge process, which comprises a step of adding a chemical uncoupling agent into water inlet of the aerobic unit of the sewage treatment system, wherein the chemical uncoupling agent comprises the following components: 3,3,4,5-tetrachloro salicylamide, soluble copper salt and an adsorbent; the soluble copper salt is one of copper sulfate, copper chloride or copper acetate; the adsorbent is one of refined diatomite or zeolite powder or a mixture of the refined diatomite and the zeolite powder; the weight ratio of the 3,3,4,5-tetrachloro salicylamide to the soluble copper salt is 1:0.05-0.25; the weight ratio of the total of the 3,3,4,5-tetrachloro salicylamide and the soluble copper to the adsorbent is 1:0.05-1.00; and in the water inlet, the addition amount of the chemical uncoupling agent accounted by the 3,3,4,5-tetrachloro salicylamide is controlled in the range of 0.6 to 3.8mg / l. The method has stronger sludge reduction performance. If the same weight reduction rate of the sludge is achieved, the added TCS (tetrachloro salicylamide) can be reduced by 25 to 75 percent, and the removing rate of the COD (chemical oxygen demand) is basically not influenced.

The disclosure provides compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables, R1, R2, R3, R4, R5, X1, X2, and Z are defined herein. Certain compounds of Formula I act as selective mitochondrial protonophore uncouplers that do not affect the plasma membrane potential. The disclosure includes pharmaceutical composition comprising a compound or salt Formula I, and apharmaceutically acceptable carrier. Compounds and salts of Formula I are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as obesity, cancer, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH). Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, compounds of Formula I are useful for increasing lifespan. Compounds and salts of Formula I are also useful for regulating glucose homeostasis or insulin action in a patient.

The invention discloses a composite uncoupling agent and a preparation method thereof, and belongs to the technical field of uncoupling agents. The composite uncoupling agent comprises bishydroxycoumarin (3,3'-methylene bis(4-hydroxycoumarin) and tourmaline, wherein the weight ratio of the bishydroxycoumarin to the tourmaline is 1 to (1,000 to 5,000). The preparation method of the composite uncoupling agent comprises the following steps: proportionally taking the bishydroxycoumarin and the tourmaline, and uniformly mixing the two in a solid form to obtain the composite uncoupling agent. The uncoupling agent provided by the invention maintains good sludge reduction property, and also can significantly relieve the decline of sludge activity, showing a noticeable positive effect; to reach thesame sludge reduction rate, the sludge activity can be improved by 20%, and the water treatment effect can be improved by 40%; after the composite uncoupling agent is added into the system, the COD removal rate is basically not influenced.

The current technology is related to methods for rapidly determining the metabolic baseline and potential of living cells. Embodiments relate to measuring the activity of each of the two major energy-generating pathways within the cell: mitochondrial respiration and glycolysis, first under baseline conditions, and again after applying a stress to the cells to demand increased energy supply. In some embodiments the stress may be applied by exposing the cells to a combination of two chemical compounds: a mitochondrial uncoupler and an ATP synthase inhibitor. In one embodiment, the metabolic energy generating activity of the mitochondrial respiration pathway is determined by measuring the rate of oxygen consumption by the living cells, and the metabolic energy generating activity of the glycolysis pathway is determined from a measurement of extracellular acidification caused by secretion of protons from the cell. Other embodiments are related to an apparatus for determining a metabolic potential of a cell sample in a well of a multiwell plate.

The invention relates to a novel insecticide combination. The combination comprises: an oxidative phosphorylated uncoupling agent selected from the group consisting of chlorfenapyr, DNOC and fipronilor derivatives thereof; a voltage dependent sodium channel blocker selected from metaflumizone, indoxacarb, or derivatives thereof; and a mitochondrial ATP synthase inhibitor selected from azocyclotin, cyhexatin, fenbutatin oxide, acaricidal sulfone trichloride, propargite, diafenthiuron, or derivatives thereof. The combination enhances greening and yield increase of crops to which it is applied and late-aging the crops to which it is applied, thereby increasing the yield of the crops, resulting in a reduction in pest stress in the crops to which it is applied, enhancing pesticidal activity and enhancing protection of plants from attack or infestation by insects, mites or nematodes.