666 results about "Methyl Donors" patented technology

The present disclosure relates to pharmaceutically acceptable salts, cocrystals, and crystalline forms thereof, of a compound which is N—((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2- ((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-TH-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide, which is useful in the treatment of a Retroviridae viral infection including an infection caused by the HIV virus.

The invention relates to a high-water-solubility denitroflavin covalent complex as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis and medicinal chemistry. Comprising the following steps: (1) firstly, carrying out bromination reaction on 3-methyl-10-ethyl denitroflavin, so as to obtain 3-methyl-10-(1-bromoethyl) denitroflavin; and (2) coupling the 3-methyl-10-(1-bromoethyl) denitroflavin with vitamin C, so as to obtain the high-water-solubility denitroflavin covalent complex. According to the present invention, the prepared highly water-soluble denitrificin covalent complex has the two-phase solubility of the organic solvent and the water, such that the water solubility of the 3-methyl-10-ethyl-denitrificin is substantially enhanced, and the application range of the denitrificin is expanded. And meanwhile, the denitrified flavin covalent compound also has good antioxidant activity, and the antioxidant duration can be prolonged.

Described herein are pharmaceutical formulations of a farnesoid X receptor agonist, 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, and methods of using such pharmaceutical formulations in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.

The invention belongs to the technical field of biological detection, and particularly relates to a method for synchronously and quantitatively detecting various folic acid metabolism related substances in trace plasma or serum, which comprises the following steps of: detecting a pretreated trace plasma or serum sample by adopting a liquid chromatography-tandem mass spectrometry method; the following nine folic acid metabolism related substances are synchronously and quantitatively detected: 5-formyl tetrahydrofolic acid, folic acid, 5-methyl tetrahydrofolic acid, S-adenosine-L-methionine, S-adenosine-L-homocysteine, vitamin B12, pyridoxamine, pyridoxine and pyridoxal. The invention further relates to application of the detection method in related detection of child neurodevelopment. According to the detection method, only trace plasma or serum is used, methotrexate is used for replacing an expensive isotope internal standard for more economical detection, and nine folate metabolism related substances can be accurately quantified at the same time. Therefore, the detection method disclosed by the invention has important clinical significance and wide market application prospect.

The invention discloses a photocuring microneedle with ginseng exosome loaded berberine, a preparation method of the photocuring microneedle and application of the photocuring microneedle to tissue repair. A ginseng exosome loaded berberine compound is prepared through a microfluidic technology; filling a needle cavity of a microneedle mold with a needle tip layer preparation solution containing the compound, methylacryloylated hyaluronic acid and methylacryloylated gelatin through a centrifugal method; covering a backing layer preparation solution composed of hyaluronic acid and povidone K90, and centrifuging again; and finally, carrying out light curing, drying and demolding. The prepared composite microneedle is complete and sharp in needle shape and high in forming rate; the efficient entrapment of the active medicine is realized; the biocompatibility is good, and the irritation is low; a cross-linked network structure formed by photocuring is beneficial to realizing controlled release of drugs, the targeted repair function of the ginseng exosome is combined with the hypoglycemic effect of berberine, and a new strategy and technical approach with a prospect are provided for painless, efficient and long-acting treatment of diabetes mellitus.

Methods for treating patients with wAIHA comprising administering at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (rilzabrutinib) and pharmaceutically acceptable salts thereof are disclosed.

The invention provides a programmable hydrogel wound dressing with rotation contraction force and application thereof, and belongs to the technical field of biomedical materials, the programmable hydrogel wound dressing comprises a dual-network hydrogel main body, a first hydrogel layer, a second hydrogel layer, a first hydrogel layer and a second hydrogel layer, and the dual-network hydrogel main body is composed of a first network and a second network; the first network is a chemically cross-linked methacrylated hyaluronic acid network and forms a cross-linked network structure through photopolymerization; the second network is a physical cross-linked polyvinyl alcohol network, and forms an instantaneous cross-linking point with a crystal region through a hydrogen bond, so that the hydrogel is endowed with shape memory performance; the surface is modified with an N-hydroxysuccinimide ester functional group, and the N-hydroxysuccinimide ester functional group and amino of wound tissue protein can form a covalent bond; the dual-network hydrogel main body is subjected to pre-stretching or pre-twisting treatment and then is dried and shaped into a preset shape, the initial shape is recovered after moisture is absorbed, and rotary contraction mechanical force is output. Rapid wound healing and scar-free regeneration are achieved by dynamically regulating and controlling wound edge mechanical force and enhancing tissue adhesion, and then application to regulation and control of wound microenvironment to promote scar-free healing is achieved.

The application relates to a cartilage organoid based on a DNA-silk fibroin hybrid hydrogel sustained-release system and a preparation method and application thereof. The DNA-silk fibroin hybrid hydrogel sustained-release system is a hydrogel system after a DNA-silk fibroin hybrid hydrogel sustained-release system premixing solution is printed through a digital light processing system, wherein the DNA-silk fibroin hybrid hydrogel sustained-release system premixing solution contains DNA, silk fibroin, acrylated RGD peptide, acrylated polyethylene glycol NHS ester, glucosamine, TD-198946 and 2,4,6-trimethylbenzoyl lithium phosphate. Compared with the prior art, the glucosamine and TD-198946 introduced in the DNA-silk fibroin hybrid hydrogel sustained-release system can significantly improve the cartilage differentiation efficiency of bone marrow mesenchymal stem cells; and the application can be transplanted to a cartilage defect as a cartilage graft to promote cartilage regeneration and repair.

Described herein is the farnesoid X receptor agonist, 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, including crystalline forms and pharmaceutically acceptable salts, solvates, and formulations thereof.

The invention discloses a compound rumen bypass guanidinoacetic acid additive as well as a preparation method and application thereof, and belongs to the technical field of animal feed additives. The compound rumen bypass guanidinoacetic acid additive provided by the invention is prepared from the following components in parts by mass: 40 to 60 parts of guanidinoacetic acid, 0.1 to 0.5 part of selenium yeast, 5 to 10 parts of nicotinamide, 5 to 12 parts of DL-methionine, 0.01 to 0.05 part of vitamin B12, 1 to 3 parts of compound probiotics, 3 to 5 parts of hydroxypropyl methyl cellulose, 1 to 2 parts of ethyl cellulose, 15 to 25 parts of hydrogenated palm oil and 3 to 5 parts of glyceryl monostearate. The compound probiotics comprise bacillus subtilis and saccharomyces cerevisiae. The compound additive provided by the invention can significantly improve the daily gain of ruminants and reduce the feed-gain ratio, and meanwhile, due to the improvement of the energy utilization efficiency and the enhancement of the antioxidant ability, the immunity of animals is improved, the morbidity is reduced, and the meat quality is improved.

The invention discloses a thiochromanone derivative containing a thiosemicarbazone structure and application of the thiochromanone derivative, relates to the technical field of medicines, and particularly relates to the technical field that the compound has better oxidation resistance and alpha-glucosidase resistance activity, the IC50 value of the compound 1-(7-chloro-4, 4-dioxothiochromanone-3-N-propyl) thiosemicarbazone to ABTS clearance activity is 2.86 [mu] g / mL, the IC50 value of the compound 1-(7-chloro-4, 4-dioxothiochromanone-3-N-propyl) thiosemicarbazone to alpha-glucosidase inhibition activity is 9.51 [mu] g / mL, and the effect is the best and is superior to that of a control agent vitamin E and acarbose. The thiochromanone derivative containing the thiosemicarbazone structure has a general formula shown in the specification,

The invention discloses an ergothioneine-producing recombinant engineering bacterium as well as a construction method and application thereof, and belongs to the technical field of gene recombination fermentation. The method comprises the following steps: by taking escherichia coli as a starting bacterium, carrying out recombinant expression on a histidine trimethyl inner salt cysteine sulfoxide synthetase egt1 gene, an L-histidine methyltransferase egtD gene, a histidine trimethyl inner salt cysteine sulfoxide lyase egt2 gene, a methionine adenosine transferase metK gene, an adenylate kinase adK gene and an adenine phosphoribose transferase apt gene; on this basis, supply of precursor substances including histidine, cysteine and methionine is further improved through metabolic transformation, the yield of the finally obtained recombinant engineering bacterium for producing ergothioneine reaches 2.54 g / L after 48 h of shake-flask culture, the yield of a 5L fermentation tank reaches 18 g / L after further enlarged culture, the yield of ergothioneine is guaranteed while energy consumption and cost are reduced, and the method is suitable for industrial production. The method is suitable for practical popularization.

The present invention relates to salts of aminopyrimidine compounds and uses thereof. In particular, the present invention relates to salts of (S)-2-(1-((6-amino-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-4-yl)amino)ethyl)-5-(3-hydroxyprop-1-yn-1-yl)-3-phenylquinazolin-4(3H)-one and pharmaceutical compositions comprising said salts, further to their use in the manufacture of a medicament for the treatment and prevention of diseases associated with PI3K kinase abnormalities.

The invention relates to the technical field of skin care essence, in particular to double-layer essence with an anti-aging effect and a preparation method thereof.The double-layer essence with the anti-aging effect is composed of a water phase layer and an oil phase layer; the water-phase layer is prepared from the following raw materials in percentage by mass: 3-8% of hydroxypropyl tetrahydropyrantriol, 0.1-0.5% of tetrahydromethylpyrimidine carboxylic acid, 0.01-0.1% of a pepper kava extract, 1-5% of lactobacillus / soybean milk fermentation product filtrate, 1-5% of vitamin C ethyl ether, 1-5% of acetylchitosamine, 3-8% of 1, 3-butanediol and the balance of water. The invention relates to an anti-aging mask which comprises the following components in percentage by weight: 1-10% of 1, 3-butanediol, 0.01-0.1% of sodium hyaluronate, 0.1-0.5% of a buffer system, 5-10% of glycerol and the balance of deionized The oil phase layer is prepared from the following raw materials: 0.5-2% of ascorbyl tetraisopalmitate, 11-44% of compound plant-derived grease and 0.05-0.3% of tocopheryl acetate, and the problems that existing essence oil is lack of a multi-dimensional synergistic anti-aging effect, and the stability and transdermal absorption efficiency of water-soluble active ingredients and oil-soluble ingredients are difficult to consider are solved.

The present invention includes novel compositions and methods for treating comprising a compound with the Formula I:wherein n=0, 1, 2, 3, 4, or 5; X=NH or O or S; Y=phenyl, or a phenyl group substituted with at least one methyl, a phenyl group substituted with at least one nitro, a phenyl group substituted with at least one nitrogen, a phenyl group substituted with at least one boron, aryl, substituted aryl, heteroaryl, four to six membered cycloalkyl, four to six membered heterocycloalkyl; R=H, C(O)R2, SO2R2; R1=H, C(O)R2, SO2R2; R2=Ethyl, methyl, isopropyl, n-propyl, t-butyl, n-butyl, NH2, NR3R4; R3, R4=Ethyl, methyl, isopropyl, n-propyl, t-butyl, n-butyl, three to six membered cycloalkyl, and Z=NH, or O, or none, and optionally wherein both X and Z are not both S, and wherein the amount of the compound is selected to either inhibit or activate the immune response.

The invention discloses a recombinant bacterium capable of increasing the yield of alpha-bisabolol as well as a preparation method and application of the recombinant bacterium, and belongs to the technical field of microorganisms. The invention aims to improve the yield of alpha-bisabolol and enhance the tolerance of a host to an organic solvent. The invention provides a recombinant bacterium for improving the yield of alpha-bisabolol. Escherichia coli is used as a starting strain; the method comprises the following steps of: overexpressing an acetyl CoA acyltransferase / HMG-CoA reductase mvaE gene, an HMG-CoA synthetase mvaS gene, a 2-methyl citrate dehydratase prpD gene, a mevalonate kinase ERG12 gene, a mevalonate 5-phosphate kinase ERG8 gene, a mevalonate 5-diphosphate decarboxylase ERG19 gene and an isopentenyl diphosphate isomerase idi gene, so as to obtain a recombinant vector; the gene is obtained from an alpha-bisabolol synthase gene of artichoke, a farnesyl diphosphate synthase ispA gene and an alpha-bisabolol synthase CcBOS gene of artichoke. The industrial process of synthesizing alpha-bisabolol by a biological method is promoted.

The invention provides a method for the analysis of a biological sample to determine multiple types of information therefrom in a streamlined, combined workflow, where all information is obtained in a sequencing-based analysis. The information includes the presence and concentration of specific plasma proteins in a blood sample: the number, location, and types of histone modifications associated with cell-free DNA obtained from the same sample: the sequence of cfRNA and cfDNA in the cell-free DNA sample; and epigenetic information pertaining to the cell-free DNA, such as hydroxy methylation and methylation profiles, i.e., the distribution of 5-hydroxymethylcytosine (5hmC) and 5-methylcy tosine (5mC) residues, respectively. The invention additionally pertains to a classical sequencing-based method for analyzing a biological sample to determine one or more non-classical sequence features of the sample. Compositions, kits, and related methods are also provided, including an embodiment in which truncated sequencing adapters are used in conjunction with barcoded PCR primers.

The application discloses a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative and a synthesis method and application thereof, and relates to a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative which is a compound with the following general formula (I): wherein R1 is selected from,,,,,,,,, and R2 is selected from,,, and. The compound can significantly inhibit the proliferation of leukemia, multiple myeloma, lymphoma, breast cancer, liver cancer and the like at a low dose (nanomole), can effectively degrade IKZF1, IKZF3, BRD4, GSPT1 and CK1 alpha, and has the prospect of being developed into an anti-tumor drug. The application solves the problem that the existing malignant hematological disease treatment drugs have a high safety risk.

The invention provides a high-protein feed raw material and a preparation method thereof, and belongs to the field of protein feeds.The preparation method comprises the steps that animal-derived organs are selected, an animal-derived organ enzyme solution is obtained through a pretreatment means, and natural protein components in the animal-derived organ enzyme solution are reserved to serve as crude protein nutritional ingredients; step 2, adding a substrate and a methyl donor into the animal-derived visceral organ enzyme liquid, and generating guanidinoacetic acid and creatine through an enzymatic synthesis reaction to obtain a mixed liquid; and step 3, carrying out enzyme system inactivation, centrifugal filtration, drying and crushing on the mixed solution to obtain a finished product. According to the invention, guanidinoacetic acid and creatine are synthesized by in-situ catalysis of animal-derived visceral organ natural enzyme systems, and can be naturally fused with protein components, so that the problem of compatibility is avoided, and growth functional factors do not need to be added from an external source; natural enzyme systems of animal livers and kidneys are directly utilized, industrial enzymes do not need to be purchased, and the natural enzyme systems are more adaptive to a raw material system; protein, natural enzyme systems and mineral substances in the raw materials are synchronously utilized, so that one material has multiple purposes.

The invention relates to a traditional Chinese medicine composition which comprises more than 1.09 permillage of ephedrine hydrochloride, more than 0.86 permillage of pseudoephedrine hydrochloride, more than 0.17 permillage of peiminine, more than 0.03 permillage of peimine, more than 0.17 permillage of chrysin-7-O-glucuronide, more than 0.002 permillage of glycyrrhetinic acid, more than 11.87 permillage of amygdalin and more than 0.01 permillage of neotuberostemonine. The oral liquid is prepared from more than 2.16 per mill of glycyrrhizic acid, more than 1.97 per mill of oroxylin A, more than 1.97 per mill of oroxylin B, more than 1.23 per mill of liquiritin, more than 0.59 per mill of apiose liquiritin, more than 0.55 per mill of baicalin, more than 0.23 per mill of chlorogenic acid, more than 0.18 per mill of praeruptorin A, more than 0.15 per mill of wild melanosin, more than 0.14 per mill of methyephedrine hydrochloride, more than 0.13 per mill of isoliquiritin, more than 0.13 per mill of neochlorogenic acid and more than 0.13 per mill of cryptochlorogenic acid. The composition is prepared from more than 0.10% of peimine, more than 0.08% of baicalein, more than 0.05% of praeruptorin B, more than 0.04% of praeruptorin C, more than 0.011% of xanthoxylin and more than 0.0006% of formononetin.

The present invention relates to processes to obtain methyl (E)-2-[2-halomethyl)-3-methyl- phenyl]-3-hydroxy-prop-2-enoates and intermediates thereof. These compounds are used as intermediates for preparing strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution F129L in the mitochondrial cytochrome b protein (also referred to as F129L mutation in the mitochondrial cytochrome b gene) conferring resistance to Qo inhibitors.

To provide a type I receptor tyrosine kinase inhibitor.SOLUTION: Or a pharmaceutically acceptable salt thereof. Specific examples thereof include N - (4 - ([1,2,4] triazolo [1, 5-c] pyrimidin-7-yloxy) - 3-methylphenyl) - 5 - (3 - (dimethylamino) azetidin-1-yl) - 6-methoxyquinazolin-4-amine.SELECTED DRAWING: None

The present invention refers to compounds of formula (I). The present invention also relates to compounds of formula (I) for use as G Protein coupled Receptor 139 (GPR139) antagonists in methods of medical treatment of e.g. depression, Alzheimer's disease, schizophrenia, drug addiction, sleep disorders, pain, and attention deficit hyperactivity disorder. Exemplary compounds are e.g. 3-((1H-pyrazol-4-yl)methyl)-6′-(phenyl)-2H-(1,2′-bipyridin)-2-one derivatives and related compounds. The present description discloses the synthesis and characterisation of exemplary compounds, pharmacological data thereof, as well as exemplary tablet formulations comprising the compounds of the invention (e.g. page 83 to page 110; examples 1 to 33; reference example 1; test examples 1 and 2; tables 1 to 4).

Disclosed herein is a method of treating pemphigus in a human patient in need thereof, comprising administering to the human patient a dose of at least 400 mg of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (PRN1008) once daily (QD) or twice daily (BID).

The invention relates to a preparation method and application of nitric oxide gas release hydrogel for chronic wound repair of diabetes mellitus, and belongs to the technical field of biomedical materials. According to the invention, hyaluronic acid is modified by tris (hydroxymethyl) aminomethane with mechanical properties and structural stability, so that the stability of the hydrogel is improved, and the problem that traditional hydrogel is fragile and easy to collapse is solved; the epsilon-polylysine is introduced, so that the hydrogel has a sterilization effect, and infectious bacteria at chronic wounds can be efficiently sterilized; nitric oxide donor small molecules are introduced into hydrogel, and on-demand release in a pathological environment is realized by combining a high active oxygen response mechanism; through dynamic inclusion of the hollow meso-porous silicon-selenium hybrid nanostructure and cyclodextrin, the drug loading efficiency and release stability of the nanoparticles are further improved, and the nanoparticles are endowed with good responsiveness, controllability and synergistic function. The prepared nitric oxide gas release hydrogel can significantly accelerate healing of chronic wound surfaces of diabetes, the preparation process is mild, simple and convenient, and large-scale production is easy.

The present disclosure provides methods for generating mbias corrected sequence fragment data comprising correcting one or more strand displacement mbias instances in one or more nucleic acid fragments from a sample obtained from a subject, performing a methylation analysis, and correcting one or more end-repair bias instances in sequence fragment data from the methylation analysis.

The present disclosure provides methods of treating multiple sclerosis (MS) using Compound 1 represented by the following structure, or a pharmaceutically acceptable salt thereof, in combination with dihydroxymethyl fumarate (DRF).