79 results about "Pentanoic Acids" patented technology

The invention discloses a generalized pustular psoriasis diagnosis marker based on metabonomics and application of the generalized pustular psoriasis diagnosis marker. The diagnostic marker is prepared from one or more of the following 35 compounds: pyruvic acid, alpha-ketoisovaleric acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, methane thiophosphoric acid, proline, uracil, tranexamic acid, 4-aminobutyric acid, threonine, scopoletin, dodecanol, N-methyl-L-leucine, L-cysteine-glycine and L-kynurenine. The feed additive is prepared from the following raw materials: 3-hydroxybenzoic acid, allantoin, delta-tocopherol, xylofuranose, glucose-1-phosphoric acid, pyrophosphate, taurine, L-asparagine, phthalic acid, 4-(dimethylamino) azobenzene, 5-tert-butyl-1h-indole-2, 3-dione, quinic acid, glucose, histidine, lysine, palmitic acid, 7-methylguanine, oleic acid and whale acid. The marker can be used for accurately distinguishing patients with generalized pustular psoriasis from healthy people.

The application relates to a preparation method of a crosslinked polymer and belongs to the technical field of polymer preparation. The preparation method of the crosslinked polymer provided by the application comprises the following steps: (1) mixing reactant A and reactant B to perform an esterification reaction to obtain an esterification product; (2) dissolving a crosslinking agent in the obtained esterification product and standing for solidification, so that the crosslinked polymer is obtained; the reactant A is a polyether polyol containing at least three hydroxyl groups; the reactant B is 4-(cyclopenta-2,4-dien-1-ylidene) pentanoic acid; and the crosslinking agent contains a maleimide group. The application constructs a fulvene-maleimide D-A reaction system capable of being rapidly crosslinked under low-temperature conditions by end-capping fulvene at the end of a polyether polyol and then adding a crosslinking agent with a maleimide group.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for efficiently preparing cyclobutane derivatives. Comprising the following steps: dissolving 4-chloro-7H-pyrrolo [2, 3-d] pyrimidine and chloromethyl pivalate in 1, 4-dioxane, and adding an acid binding agent for reaction to obtain a reaction solution; the preparation method comprises the following steps: adding 1-(1-ethoxyethyl)-4-pyrazol boronic acid pinacol ester, purified water, a catalyst and an acid-binding agent into a reaction kettle, carrying out Suzuki reaction, separating liquid, adding activated carbon into an upper organic phase for decoloration, adding an organic solution containing hydrogen chloride for crystallization, and filtering to obtain a wet product; and dissolving the wet product and 2-[1-(ethylsulfonyl)-3-azacyclobutane] acetonitrile in 1, 4-dioxane, and reacting under an alkaline condition to obtain the cyclobutane derivative. According to the preparation method, synthesis is performed through a one-pot four-step reaction, a solvent only relates to 1, 4-dioxane and water, and post-treatment is simple, convenient and efficient.

The invention discloses a method for preparing halogenated fluorine-containing olefin with high yield as well as a product and application of the halogenated fluorine-containing olefin, dihalogenated perfluoroethane (ICF2CF2I or BrCF2CF2Br) and ethylene are taken as raw materials, under the action of a peroxide initiator TAPP (tert-amyl peroxypivalate, the addition amount of which is 0.2%-0.3% of the weight of the perfluorinated halogenated ethane), the ethylene is continuously introduced to maintain the reaction pressure of 0-5 kg, and the halogenated fluorine-containing olefin with high yield is prepared. Carrying out addition reaction to generate a dihalogenated fluorine-containing alkane intermediate; and heating toluene and sodium hydroxide / potassium hydroxide to 60-80 DEG C in a three-neck flask, superposing the intermediate to carry out elimination reaction, and continuously collecting the generated olefin through a distillation head to finally obtain ICF2CF2CH = CH2 or BrCF2CF2CH = CH2. The method is strong in process controllability, high in ethylene utilization rate and high in product separation efficiency, and adapts to iodination and bromination double-system production.

The present invention relates to a pharmaceutical composition for oral administration, the pharmaceutical composition comprising: a) immediate-release granules comprising i. an active ingredient selected from the group consisting of valproic acid, semi-sodium valproic acid, sodium valproic acid, and magnesium valproic acid, and ii. a filler; and b) sustained-release pellets comprising: i. a pellet core comprising (1) an active ingredient selected from the group consisting of valproic acid, semi-sodium valproic acid, sodium valproic acid, and magnesium valproic acid, and (2) a filler; and ii. on the pellet core iii. A sustained-release pellet comprising a subcoat provided on the subcoat, the content of which is 10 to 20% by weight based on the weight of the pellet core and contains a film-forming agent, and iii. a sustained-release coating provided on the subcoat, the content of which is 25 to 100% by weight based on the weight of the pellet core coated with the subcoat and contains a film-forming agent, wherein the amount of active ingredient in the immediate-release granules accounts for 70 to 80% by weight of the total weight of active ingredients in the pharmaceutical composition, and the amount of active ingredient in the sustained-release pellets accounts for 20 to 30% by weight of the total weight of active ingredients in the pharmaceutical composition. In yet another aspect, the present invention relates to a method for producing a pharmaceutical composition and a pharmaceutical composition for use in a method of pretreatment of cancer.

The application discloses a kind of process methods for optimizing control production 5-aminovaleric acid, step one, amino acid fermentation seed is inoculated in culture medium, and aerobic fermentation culture is carried out;During fermentation culture process, fermentation temperature is controlled at 30-35 DEG C, pH value is maintained at 6.5-7.5, and by controlling aeration and stirring, dissolved oxygen level is controlled at 20%-30%;After fermentation, fermentation broth is separated, and 5-aminovaleric acid crude product is obtained;5-aminovaleric acid crude product is sequentially subjected to decolorization, crystallization and refining, and finally 5-aminovaleric acid finished product is obtained.The application uses optimized fermentation conditions, by accurately controlling fermentation temperature, pH value and dissolved oxygen level, to ensure the stability and efficiency of fermentation process, improve product quality and yield.

The invention discloses a high-efficiency transfer hydrogenation method of non-activated olefin, which comprises the following steps: adding a non-activated alkenyl amide compound, nickel acetylacetonate dihydrate, phenylsilane, water and cesium pivalate into an organic solvent 1, 4-dioxane, reacting at room temperature under a nitrogen condition for 12 hours, and after the reaction is completed, filtering to obtain a filtrate, namely the high-efficiency transfer hydrogenation method of the non-activated olefin. And performing post-treatment (extraction and column chromatography separation) to obtain the corresponding alkyl chloride compound. According to the method, phenylsilane and water are directly used as hydrogen sources, direct use of hydrogen can be avoided, operation is easy and convenient, and efficient construction of C (sp3)-C (sp3) bonds can be achieved through transfer hydrogenation of non-activated olefin. The conversion reaction conditions are extremely mild, and the reaction activity is high; the method has the advantages of excellent atom economy and step economy, wide substrate application range, good functional group compatibility and the like. It is worthy that the synthesis method is also suitable for later-stage modification of medicine molecules, and the druggability of the molecules is expected to be further improved.

The invention belongs to the technical field of organic synthetic chemistry, and discloses a method for efficiently synthesizing methyl 2-chloro-3-oxovalerate. According to the method, high-selectivity chlorination is performed on a beta-site C-H bond of methyl 3-oxovalerate under a mild condition by taking sodium chloride as a chlorine source and adopting a dual-catalysis system consisting of engineered halogenase and a visible light-sensitive catalyst under visible light irradiation. The engineered halogenase is a HalB triple mutant, and the affinity and regioselectivity of a substrate are remarkably improved; the photosensitive catalyst is a ruthenium bipyridine complex and synergistically drives generation of chlorine free radicals. According to the invention, a brand new biological-photochemical synergistic catalysis platform is constructed by organically combining the substrate recognition capability of the engineered halogenase and an electron transfer mechanism driven by visible light catalysis, so that the contradiction among selectivity, mildness and atomic efficiency of a traditional chlorination method is solved; and the method can be expanded to precise synthesis of other beta-functionalized ketone ester compounds.

The invention discloses a generalized pustular psoriasis diagnosis marker based on metabonomics and application of the generalized pustular psoriasis diagnosis marker. The diagnostic marker is prepared from one or more of the following 35 compounds: pyruvic acid, alpha-ketoisovaleric acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, methane thiophosphoric acid, proline, uracil, tranexamic acid, 4-aminobutyric acid, threonine, scopoletin, dodecanol, N-methyl-L-leucine, L-cysteine-glycine and L-kynurenine. The feed additive is prepared from the following raw materials: 3-hydroxybenzoic acid, allantoin, delta-tocopherol, xylofuranose, glucose-1-phosphoric acid, pyrophosphate, taurine, L-asparagine, phthalic acid, 4-(dimethylamino) azobenzene, 5-tert-butyl-1h-indole-2, 3-dione, quinic acid, glucose, histidine, lysine, palmitic acid, 7-methylguanine, oleic acid and whale acid. The marker can be used for accurately distinguishing patients with generalized pustular psoriasis from healthy people.

The present application relates to the preparation method of magnesium valproate shown in chemical structural formula I: under the action of potassium carbonate and PTC, dimethyl malonate is subjected to dipropylization with 1-chloropropane in DMF solvent to prepare dimethyl dipropyl malonate shown in formula III; III is subjected to hydrolysis reaction to prepare dipropyl malonic acid shown in formula II; II is uniformly mixed with magnesium oxide, and heated to prepare magnesium valproate shown in formula I by decarboxylation, and the total yield of magnesium valproate is not less than 90.0%; the preparation reaction is as follows: wherein, the PTC for dipropylization is selected from quaternary ammonium salt, the reaction temperature is 50-140 DEG C, the reaction time is 4.0-14.0 h; the hydrolysis temperature is 70-95 DEG C, the time is 2.0-4.0 h; the decarboxylation temperature is 140-158 DEG C, and the time is 3.0-5.0 h.

The application provides a water-triggered self-assembly gel, a use method and application thereof. The water-triggered self-assembly gel comprises 5-aminolevulinic acid hydrochloride 5-15 wt%, phospholipid 5-10 wt%, anionic glycolipid surfactant 0.2-0.8 wt%, polyethylene glycol 50-60 wt%, propylene glycol 20-27 wt% and antioxidant 0.05-0.1 wt%, and water <0.1 wt%; the mass ratio of the polyethylene glycol and the propylene glycol is (2-2.5):1. The water content of the water-triggered self-assembly gel is extremely low, so that the stability is good and the storage is easy; when used, the water-triggered mechanism of transdermal water loss can be used to actively extract water from the stratum corneum, the phase transition of the phospholipid from the disordered lamellar phase to the liposome is quickly completed, the nanometer liposome with uniform particle size and high encapsulation efficiency is spontaneously formed, the 5-ALA hydrochloride is wrapped, and the 5-ALA hydrochloride can be efficiently delivered to the deep layer of the skin.

The invention discloses application of 2-hydroxy-4-methylpentanoic acid in preparation of a product for relieving weaning stress, and belongs to the technical field of feed development. The product is a product for improving slow growth caused by weaning stress, promoting weight gain of animals and improving animal intestinal injury caused by weaning stress. The 2-hydroxy-4-methylpentanoic acid directly intervenes in the fundamental pathological change of jejunum epithelium structure damage, an efficient and safe scheme for relieving weaning stress is provided for animal husbandry, and the 2-hydroxy-4-methylpentanoic acid can be applied to piglets and other animals prone to being affected by weaning stress on a large scale and has remarkable economic and social benefits.

The application relates to the technical field of biomaterials, and particularly discloses a PHA combined microsphere as well as a preparation method and application thereof. The PHA combined microsphere provided by the application contains 10-40 wt% of PHA microspheres with a weight average molecular weight of less than 30000 Da and 1-40 wt% of PHA microspheres with a weight average molecular weight of more than 100000 Da, with the PHA being selected from one or more of poly-beta-hydroxybutyric acid, a copolymer of 3-hydroxybutyric acid ester and 3-hydroxyvaleric acid ester, a copolyester of 3-hydroxybutyric acid and 3-hydroxyhexanoic acid and poly(3-hydroxybutyric acid-co-4-hydroxybutyric acid). After the PHA combined microsphere is filled in the skin, on one hand, the PHA combined microsphere can be rapidly degraded in an early stage and promote the reproduction of fibroblasts and endothelial cells in a short time; on the other hand, the PHA combined microsphere can be continuously degraded within 21 weeks and cannot cause inflammation, so that the effect of persistent filling is achieved.

A method of cell culture comprising providing cells in a cell culture medium to start a cell culture process, and, maintaining at least one metabolite selected from 3-(4-hydroxyphenyl)lactate, 4-hydroxyphenylpyruvate, phenyllactate, indolelactate, indolecarboxylic acid, homocysteine, 2-hydroxybutyric acid, isovalerate and formate below a concentration C1 in the cell culture medium, wherein C1 is 3 mM and / or (ii) maintaining at least one amino acid selected from phenylalanine, tyrosine, tryptophan, methionine, leucine, serine, threonine and glycine below a concentration C2 in the cell culture medium, wherein C2 is 2 mM.

The invention discloses a surfactant for recycling a lithium iron phosphate negative electrode material and a preparation method of the surfactant, and belongs to the technical field of battery recycling. Comprising the following steps: S1, synthesis of PFPE-CTA: carrying out esterification on PFPE-OH and 4-cyano-4-[(dodecyl thiocarbonyl) sulfenyl] valeric acid under the catalysis of DCC / DMAP, so as to obtain PFPE-CTA; s2, copolymerization is carried out on AA and DOPAM under the initiation of PFPE-CTA; s3, grafting 6-amino-beta CD to the carboxyl of the copolymer under the activation of EDC / NHS; s4, modifying the graphene quantum dots with 1-pyrene butyric acid succinimide ester; and the betaCD copolymer and pyrene-GQDs are compounded through an inclusion effect. The surfactant prepared by the invention can realize high recovery rate of graphite, low impurity residue, low foam, easy separation and excellent regeneration performance.

The application discloses a preparation method of 2-ethyl-2-methyl pentanoic acid, wherein in the process of preparing a key intermediate 2-cyanopentanoate (compound B), compound A is removed by using an alkali extraction method, high-purity compound B is separated by using rectification (a yield of 20% and a purity of 98%), and the operation process is simple. In the preparation method, reagents used are sodium methoxide, sodium hydroxide, sulfuric acid, sodium hydride and sodium nitrite, the reagents are simple, the danger is relatively small, and the experimental operation is relatively safe. In the preparation method, the post-treatment processes of alkylation, hydrolysis, deacidification and cyano hydrolysis do not use a chromatographic column purification process, and a conventional extraction distillation operation is adopted, so that the output of unit volume of instrument equipment is high.

The invention discloses a generalized pustular psoriasis diagnosis marker based on metabonomics and application of the generalized pustular psoriasis diagnosis marker. The diagnostic marker is prepared from one or more of the following 35 compounds: pyruvic acid, alpha-ketoisovaleric acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, methane thiophosphoric acid, proline, uracil, tranexamic acid, 4-aminobutyric acid, threonine, scopoletin, dodecanol, N-methyl-L-leucine, L-cysteine-glycine and L-kynurenine. The feed additive is prepared from the following raw materials: 3-hydroxybenzoic acid, allantoin, delta-tocopherol, xylofuranose, glucose-1-phosphoric acid, pyrophosphate, taurine, L-asparagine, phthalic acid, 4-(dimethylamino) azobenzene, 5-tert-butyl-1h-indole-2, 3-dione, quinic acid, glucose, histidine, lysine, palmitic acid, 7-methylguanine, oleic acid and whale acid. The marker can be used for accurately distinguishing patients with generalized pustular psoriasis from healthy people.

The present invention relates to polymorphs of the hydrobromide salt of 5-{2-[({8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}carbonyl)-amino]ethoxy}-5-oxopentanoic acid (linaprazangrate), more specifically Form A, Form B, and Form C of the HBr salt of linaprazangrate. The present invention also relates to pharmaceutical compositions containing such polymorphs and to the use of these polymorphs in the treatment or prevention of gastrointestinal inflammatory or gastric acid-related diseases, particularly erosive gastroesophageal reflux disease (eGERD).

This invention discloses isobutyric acid and isovaleric acid, branched-chain amino acid metabolites of gut microbiota that alleviate aging, and their applications, belonging to the fields of microbial technology and pharmaceutical technology. Animal experiments have demonstrated that isobutyric acid or isovaleric acid, branched-chain amino acid metabolites of gut microbiota, can increase the abundance of the key gene porA in the gut microbiota of aging mice, alter the metabolism of nutrients in the mouse intestine, improve the frailty index in mice, increase liver superoxide dismutase, decrease malondialdehyde, increase glutathione peroxidase (GSH-px) levels, increase catalase levels, decrease the inflammatory factor IL-6, decrease the inflammatory factor TNF-alpha, increase acetylcholine levels in the mouse brain, and improve grip strength in mice. The strains of this invention have great application potential in the preparation of products that improve metabolism and alleviate aging.

The invention provides a preparation method of diethyl malonate and a preparation method of valproic acid, and belongs to the technical field of organic synthesis. According to the method, diethyl carbonate and ethyl acetate are taken as initial raw materials, the ethyl acetate has three alpha-H and loses one alpha-H under the attack of strong base, so that ethyl acetate enol negative ions are formed, and ethyl acetate carbon negative ions are obtained through rearrangement; carrying out nucleophilic addition on carbonyl of diethyl carbonate by using the ethyl acetate carbon negative ions to obtain an addition intermediate, and then removing ethanol negative ions from the addition intermediate to obtain diethyl malonate; by controlling the reaction temperature, ethanol generated in the reaction process is continuously distilled out, so that the reaction is carried out in the forward direction, and side reactions are reduced to the greatest extent; as the condensation catalyst used in the invention has strong nucleophilicity and alkalinity, the use of the aprotic solvent can avoid the consumption of the condensation catalyst by the solvent.

The invention provides a green light-induced stepwise polymerized polymer and a preparation and degradation method thereof. The preparation method of the polymer comprises the following steps: step a, carrying out esterification reaction on 4-cyano-4-[(dodecyl thiocarbonyl) sulfur] valeric acid and trimethylolpropane to obtain a bifunctional chain transfer reagent DCDTPA; and b, mixing the DCDTPA and a vinyl monomer, dissolving in an organic solvent, irradiating with green light under a vacuum condition, and polymerizing to obtain the polymer. The invention solves the problems that the polymer is low in terminal group retention rate and low in molecular weight, and the synthesized polymer is easy to generate a branched structure and is difficult to retain a linear structure, and also solves the technical problem that the monomers applicable to the method are limited to high-cost and low-activity vinyl monomers.

This invention relates to a novel method for preparing ruxolitinib phosphate. Methyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-D]pyrimidin-7-yl)terpentanoate (compound X) is deprotected under alkaline conditions, then directly resolved without separation, alkalized to release the free ruxolitinib, and salted to obtain the ruxolitinib phosphate. The obtained ruxolitinib phosphate has an HPLC purity >99.90%, and the ruxolitinib phosphate isomer has a purity >99.50%. The preparation method of this invention has the advantages of simple operation, controllable impurities, low cost, and suitability for industrial production.

The present invention relates to a polymorph of the maleate salt of 5-{2-[({8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}carbonyl)-amino]ethoxy}-5-oxopentanoic acid (linaprazangrate), more particularly to linaprazangrate maleate Form 1. The present invention also relates to pharmaceutical compositions comprising such polymorph and to the use of this polymorph in the treatment or prevention of gastrointestinal inflammatory or gastric acid-related diseases, particularly erosive gastroesophageal reflux disease (eGERD).

The application provides imidazotetrazine compounds or pharmaceutically acceptable salts thereof, and a preparation method and application thereof, and belongs to the technical field of medicines. The imidazotetrazine compounds or pharmaceutically acceptable salts thereof are obtained by connecting valproic acid, chlorambucil and borneol to an imidazotetrazine group through an ester bond or an amide bond by using a splicing principle. The imidazotetrazine compounds or pharmaceutically acceptable salts thereof have better antitumor activity, and a new generation of powerful antitumor drugs can be developed.

The invention discloses a dicarboxylic acid modifier, a synthesis method thereof and an application of the dicarboxylic acid modifier in modification of recombinant trypsin, the dicarboxylic acid modifier is 2-(3-carboxyl propionamido)-5-[(2, 5-dioxopyrrolidine-1-yl) oxy]-5-oxovalerate, the synthesis method of the dicarboxylic acid modifier comprises the following steps: taking mono-tert-butyl succinate and 1-glutamic acid tert-butyl ester as raw materials, and carrying out one-step reaction to obtain the dicarboxylic acid modifier. The dicarboxylic acid modifier (Suc-Glu-OSU) is successfully prepared through amidation, glutamic acid side chain activation, amidation and tert-butyl ester deprotection. According to the method, Suc-Glu-OSU is adopted as a modifier, and an activated ester group (-OSU) at the tail end of the Suc-Glu-OSU is covalently bound with recombinant trypsin lysine epsilon-NH2 to form a stable amido bond, so that the modified recombinant trypsin TPS-Suc-Glu-OSU is obtained. According to the present invention, the self-cutting site is shielded through the steric hindrance, the stable conformation is reinforced through the hydrophobic interaction, and the self-cutting occurrence is reduced, such that the stability of the recombinant trypsin is enhanced, and the application of the recombinant trypsin in the industrial or scientific research field is further broadened.

The invention relates to a group of metabolic markers and application thereof in preparation of products for screening and / or diagnosing depression. The metabolic marker is prepared from one or more of 4-oxo-2-propyl valeric acid, diethylstilbestrol, cyclo (leucine-valine) peptide, 6-benzylaminopurine and 3-carboxyl-4-methyl-5-pentyl-2-furanpropionic acid, and the metabolic marker is prepared from one or more of the following components: 4-oxo-2-propyl valeric acid, diethylstilbestrol, cyclo (leucine-valine) peptide, 6-benzylaminopurine and 3-carboxyl-4 According to the application, research finds that 4-oxo-2-propyl valeric acid, diethylstilbestrol, cyclo (leucine-valine) peptide, 6-benzylaminopurine and 3-carboxyl-4-methyl-5-pentyl-2-furanpropionic acid can be used as metabolic markers, and high-sensitivity and high-specificity screening diagnosis is carried out on the depression.

The application discloses a kind of synthesis method of dasatinib intermediate in the field of organic synthesis, with 2-aminothiazole-4-carboxylic acid as raw material, first and tert-pivaloyl chloride in situ generates mixed anhydride, further and 2-chloro-6-methylaniline condensation reaction occurs after, the compound 2 obtained is not separated directly hydrolyzed to obtain high-purity 2-amino-N-(2-chloro-6-methylphenyl) thiazole-5-formamide.Due to the mixed anhydride formed by tert-pivaloyl chloride has greater steric hindrance, and the further reaction of corresponding amine is conducive to the regioselectivity, and by-product tert-pivalic acid can be easily removed by post-treatment, so as to solve the disadvantages existing in the prior art, the unit operation involved in the whole preparation process is simpler, and the product purity and yield are higher, with good application prospect.

The present disclosure relates to a combination of valproic acid or a pharmaceutically acceptable salt thereof, a β-lactam compound or a pharmaceutically acceptable salt thereof, and probenecid or a pharmaceutically acceptable salt thereof. The present disclosure also relates to methods of treating or preventing disease using this combination.