92 results about "Aklanonic acid" patented technology

The application discloses a specific palmitoyl transferase inhibitor and application thereof, and an active ingredient of the palmitoyl transferase inhibitor is 4-(3-(2-(trifluoromethyl)-9H-thioxanthene-9-ylidene)propyl)-1-piperazine ethanol or a salt thereof. Current palmitoylation inhibitors, 2-bromohexadecanoic acid (2-BP), cerulenin and tunicamycin can all inhibit protein palmitoylation in cells, but all are not selective. And the existing palmitoylation inhibitors are similar to endogenous fatty acids, and inevitably affect lipid metabolism in the body, which limits the clinical application. The application discloses, for the first time, the application of 4-(3-(2-(trifluoromethyl)-9H-thioxanthene-9-ylidene)propyl)-1-piperazine ethanol as a specific palmitoyl transferase inhibitor, and the palmitoyl transferase inhibitor is better in specificity and reversible in inhibition.

Provided are a recombinant human interleukin-11 mutant, and a conjugate of the mutant conjugated to a chemical molecule and a use thereof. The recombinant human interleukin-11 mutant achieves soluble expression in an Escherichia coli expression system by means of an SUMO sequence tandem fusion method. The conjugate is obtained by the site-specific conjugation of the mutant to the chemical molecule at a mutant amino acid residue in position W147 by means of a covalent bond. The chemical molecule is at least one of polyethylene glycol, an alkanoic acid aliphatic chain, and a hydrophilic high-molecular polymer containing an alkanoic acid aliphatic chain. The conjugate retains the binding capacity to human interleukin-11 receptor A while demonstrating significantly reduced binding capacity to human IL-6 signal transducer receptor. The conjugate shows the ability to block the signaling between human IL-11 and IL-11 RA and between human IL-11 and GP130 either in vivo or in vitro and can be used for the treatment of associated diseases with tissue fibrosis as a clinical manifestation caused by elevated primary or secondary IL-11.

The invention provides a preparation method of an efficient selective antagonist BQ-788, and relates to the technical field of preparation of antagonists. A solid-liquid combination method is adopted for synthesis, due to the fact that dimethyl dialkanoate on a side chain of tryptophan (DTrp) is difficult, Fmoc-DTrp (CO2Me)-OH is obtained through liquid-phase synthesis, p-methoxybenzyl is selected for protecting carboxyl in the synthesis process, the carboxyl can be removed through trifluoroacetic acid subsequently, and the risk that an indole ring of tryptophan is reduced due to hydrogenation can be successfully avoided. According to the present invention, by using the solid phase synthesis method, the fragment can be rapidly and efficiently obtained, the racemization problem during the condensation process can be effectively avoided, the urea is formed on the solid phase, the operation is simple and convenient, the hydrogen and the diphosgene are not used during the preparation process, the production is safe, the obtained product has characteristics of high yield and high purity, and the preparation steps are less.

An oral suspension pharmaceutical composition is disclosed for water soluble salts of arylalkanoic acid (NSAID) drugs such as ibuprofen and naproxen. When mixed with glyceryl esters such as glyceryl caprate / caprylate and water, the resulting combination forms a “liquid scaffold” structure that reliably enables the suspension of significant quantities of said arylalkanoic acid drugs. For example, suspensions containing 25% w / w arylalkanoic acid may be obtained using the aforementioned combination. Suspensions comprising further pharmaceutically active agents, in addition to said arylalkanoic acids, may also be prepared. Also disclosed is a binary blend of glyceryl caprate / caprylate and the sodium salt of ibuprofen and a ternary blend of glyceryl caprate / caprylate and the potassium salt of ibuprofen.

The invention discloses an application of a pyroptosis inhibitor in preparation of a product for treating biliary atresia, the pyroptosis inhibitor 2-bromohexadecanoic acid has a certain treatment effect on biliary atresia mice, can significantly prolong the survival time of the mice, improve jaundice, improve the liver function of the mice, reduce the infiltration quantity of inflammatory cells around intrahepatic bile ducts, and can be used for treating the biliary atresia. A new potential target and a treatment strategy are provided for treatment of biliary atresia.

The present invention relates to compounds according to general formula (I) which are metabolically robust analogues of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs) for use in treating or reducing the risk of developing or preventing: (i) neovascularization and / or (ii) inflammatory disorder, in particular, ophthalmic disorders associated with neovascularization and / or inflammation.

The present invention discloses a method and kit for analyzing endotoxins in complex matrix samples based on liquid chromatography-mass spectrometry. 3-hydroxydecanoic acid, 3-hydroxydodecanoic acid, 3-hydroxytetradecanoic acid, 3-hydroxyhexadecanoic acid or 3-hydroxyoctadecanoic acid characteristic of endotoxins are released by KOH methanol solution for quantitative analysis of various types of endotoxin content; the hydrolyzate is derivatized with isoquinoline-1-carboxylic acid hydrazine to significantly improve the ionization efficiency of the hydrolyzate; using optimized liquid chromatography and mass spectrometry parameters, high stability, high sensitivity and broad spectrum detection of endotoxins from different bacterial sources are achieved. The method has strong anti-interference ability, is applicable to complex matrices, and solves the problem of high false negative rate caused by matrix interference in the prior art.

The invention relates to the field of biological medicine, and discloses a pTH long-acting polypeptide compound as well as preparation and application thereof. According to the polypeptide, at least one amino acid residue of the 13th, 26th and 27th amino acid residues of a pTH (1-34) parent peptide sequence is connected with octadecanedioic acid or eicosanoic acid and a derivative modification group of octadecanedioic acid or eicosanoic acid, and the polypeptide is covalently combined with a polypeptide skeleton through an AEA-AEA-gamma-Glu connecting unit. The binding capacity of the polypeptide and serum albumin is remarkably enhanced by utilizing a fatty acid side chain modification means, and meanwhile, the half-life period is prolonged. The pTH long-acting polypeptide compound disclosed by the invention has remarkable osteogenic activity promoting effect, can promote proliferation of MC3T3-E1 cells and generate osteogenic markers and calcium nodules under osteogenic induction conditions, and the binding capacity of the pTH long-acting polypeptide compound and serum albumin is improved by 2-6 times. The invention further provides a solid-phase synthesis method of the polypeptide compound and a pharmaceutical composition containing the polypeptide compound, the polypeptide compound can be used for treating osteoporosis and parathyroid hypofunction, and the compliance problem that an existing medicine needs to be injected every day is effectively solved.

This invention discloses a method for synthesizing cefotiam, using 7-aminocephalosporanic acid (7-ACA) as the parent nucleus and introducing a 4-dimethylaminopyridine-dimethyl carbonate composite catalytic system. The reaction is carried out in a one-pot process involving 3-position nucleophilic substitution, 7-position amidation, and simultaneous deprotection in a green mixed solvent of ionic liquid [BMIM]BF₄-water with 1-(2-dimethylaminoethyl)-1H-5-mercapto-tetrazole and compound I. This method simplifies the process, improves selectivity, produces a high-purity product with stable yield, and is suitable for industrial production.

The invention discloses an agonist of a retinoic acid receptor beta and application of the agonist in preparation of a non-small cell lung cancer medicine in the technical field of biological medicine. The agonist of the retinoic acid receptor beta is saturated odd fatty acid heptadecanoic acid C17: 0; according to the research, the expression of a retinoic acid receptor beta can be up-regulated by adding heptadecanoic acid into the NSCLC cells, so that the sensitivity of the NSCLC cells to retinoic acid treatment is improved. When heptadecanoic acid and retinoic acid are combined for use, the activity and migration ability of NSCLC cells can be further inhibited, and apoptosis of the cells is promoted. The result shows that the heptadecanoic acid plays an important role in controlling the sensitivity of the NSCLC cells to the retinoic acid, the combined use of the heptadecanoic acid and the retinoic acid provides a new drug treatment means for treating the NSCLC, and the heptadecanoic acid and the retinoic acid have potential application value in preparing the drug for treating the non-small cell lung cancer.

The invention relates to a continuous preparation method and system of 7-aminocephalosporanic acid, and the method comprises the following steps: regulating a CPC concentrated solution to a preset concentration and a preset temperature to obtain a CPC diluent; the CPC diluent is introduced into a first filter to be filtered, and CPC filtrate is obtained; the CPC filtrate is introduced into a plurality of continuous reaction modules filled with cephalosporin C acylase, the continuous reaction modules automatically adjust reaction liquid to preset parameters, feeding is carried out while stirring is carried out for dynamic continuous reaction, 7-ACA lysate is obtained after the filtrate passes through the continuous reaction modules, and 7-ACA filtrate is obtained after the 7-ACA lysate is introduced into a second filter to be filtered; and pumping the obtained 7-ACA filtrate into a 7-ACA storage device. The CPC concentrated solution is taken as a preparation starting point, the temperature and pH of the feed liquid are automatically regulated and controlled after the feed liquid enters the continuous reaction module for cracking reaction, operations such as feeding, discharging and manual regulation and control are omitted, and a foundation is laid for comprehensive automatic continuous production of 7-aminocephalosporanic acid.

Provided is an engineered bacterium for inhibiting the synthesis of dodecanedioic acid. The expression of a related redox gene is knocked out or down-regulated in the genome of the engineered bacterium. The engineered bacterium can effectively reduce the production of the by-product dodecanedioic acid and prevent the peroxidation of 12-hydroxydodecanoic acid during the synthesis of nylon 12 monomer. Further provided is a method for constructing an engineered bacterium for inhibiting the synthesis of dodecanedioic acid. The method involves synthesizing nylon 12 monomer in Escherichia coli by using a quorum-sensing system in Vibrio fischeri. The established Escherichia coli containing a self-induction system can produce the nylon 12 monomer from glucose, and the generation of the by-product dodecanedioic acid can be effectively reduced. After fermentation in a shake flask for 72 h, the yield of the nylon 12 monomer is more than 100 mg / L, and the yield of the by-product dodecanedioic acid is reduced to less than 200 mg / L (the proportion in the product is less than 20%).

The present invention relates to a liquid cleansing composition. Particularly, the present invention relates to a liquid cleansing composition that provides improved deposition of an active, an octadecanoic acid, when applied on to a surface. The composition comprises an octadecanoic acid and an organic acid with pKa from 2.5 to 4.9 wherein the organic acid is other than the octadecanoic acid.

The invention discloses application of a marker to preparation of a kit for diagnosing chronic obstructive pulmonary diseases. According to the application disclosed by the invention, the accuracy of diagnosing the chronic obstructive pulmonary disease by using (R)-3-hydroxytetradecanoic acid alone or in combination with the azelayl platelet activating factor is relatively high; on the basis of combination of (R)-3-hydroxytetradecanoic acid and an azelayl platelet activating factor, the compound is prepared. The compound can be further combined with one or two of 1-hexadecyl-2-(5-oxovaleryl)-sn-glycerol-3-phosphorylcholine, 1-O-hexadecyl-SN-glycerol-3-choline phosphoric acid, lauroyl-L-carnitine and beta-acetyl-gamma-O-alkyl-L-alpha-phosphatidylcholine to be used for diagnosing the chronic obstructive pulmonary disease. Therefore, a diagnostic kit for diagnosing the chronic obstructive pulmonary disease can be prepared on the basis of the scheme, and the kit contains a compound standard substance corresponding to the scheme and can also contain an internal standard compound for mass spectrum quantitative analysis.

This invention provides a physiological age prediction model that predicts the physiological age of a subject by detecting urinary proteins and metabolites in a urine sample. The aforementioned urinary proteins and metabolites are those that change significantly with age, including one or more selected from the following: cartilage intermediate layer protein (CILP2), collagen Alpha 1 chain (COFA1), myristic acid, 12-methyltridecanoic acid, CN family member 5 (CCN5), Sushi domain-containing protein 5 (SUSD5), procollagen C endopeptidase enhancer 1 (PCOLCE), and L-lactate oxidase (LOX), preferably including all of the aforementioned urinary proteins and metabolites.

This disclosure relates to hyaluronic acid nanoparticles containing an anticancer agent such as a NADPH oxidase (NOX) inhibitor for targeted delivery to cancerous cells or tumors. In certain embodiments, the nanoparticles are made up of hyaluronic acid conjugated to hydrophobic moieties. In certain embodiments, the hydrophobic moieties are steroid based compounds, such as 5beta-cholanic acid.

This invention relates to the biotechnological production of ω-functionalized carboxylic acids and their esters. Microbial cells are provided for the production of at least one ω-functionalized carboxylic acid ester from at least one alkane, wherein the cells are genetically modified relative to wild-type cells to increase the expression of: (i) an enzyme E1 capable of converting the alkane to the corresponding 1-alkanol; (ii) an enzyme E2 capable of converting the 1-alkanol of (i) to the corresponding 1-alkanal; (iii) an enzyme E3 capable of converting the 1-alkanal of (ii) to the corresponding alkanoic acid; (iv) an enzyme E4 capable of converting the alkanoic acid of (iii) to the corresponding alkanoic acid ester; and (iv) an enzyme E5 capable of converting the alkanoic acid ester of (iv) to the corresponding ω-hydroxy-alkanoic acid ester, and wherein the cells do not contain an increase relative to wild-type cells of the expression of the following enzymes selected from the group consisting of: 20 -E 24 Genetic modification of expression of at least one of them: -E 20 Acyl-ACP thioesterase, -E 21 Acyl-CoA thioesterase, -E 22 Acyl-CoA:ACP transacylase, -E 23 Polyketide synthase, and -E 24 Hexanoic acid synthase.

Compositions for activating mucosal repair pathways and methods of treatment are provided. For example, octadecanoid compositions that include an intermediate of C-18 fatty acid metabolism of gastrointestinal microbes as an activator of mucosal repair pathways, and methods of using the compositions for treating an illness, disease, disorder, or condition associated with mucosal dysfunction are described. Also provided are methods and compositions for using an octadecanoid composition in a supplement at a level sufficient to treat symptoms of metabolic syndrome.

The present invention discloses a hair metabolite marker combination for diagnosing Alzheimer's disease and its application. The hair metabolite marker combination includes triacontanes, erucic acid, heneicosane, behenic acid, tetracosane, 3-hydroxybutyric acid, 15-methylhexadecanoic acid, arachidic acid, heptadecanoic acid, melatonin, stearic acid, tetracosanoic acid, heneicosanoic acid, and docosane. The present invention uses metabolomics methods to study, compare, and analyze the hair metabolites of AD patients, MCI patients, and cognitively normal subjects, explores potential biomarkers that may be contained therein, obtains a group of hair metabolite differences among AD patients, and evaluates the sensitivity and specificity of this group of substances for diagnosing AD. The present invention provides a new marker for the accurate diagnosis of AD and can be used in clinical auxiliary diagnosis of AD to improve diagnostic accuracy.

The present invention describes novel drug-carrying nanoparticles called bionanocarriers capable of modulating the cellular redox system and targeting the cancerous tumor.Specifically, the invention relates to a nanomedicine strategy for combating cancerous tumor cells, a strategy that aims to target the tumor, and consists of providing quercetin-linked magnetite nanoparticles (Q): (MNPs Q), and 3,5-dimaleylbenzoic acid-linked magnetite nanoparticles (A3'5DMB): (MNPs A3'5DMB)M; both types of nanoparticles were subsequently encapsulated with chitosan (Qs) and O-carboxymethyl chitosan (O-CMQs), functionalized with 11-mercaptoundecanoic acid (MUDA), and finally the anti-ABCC3 antibody was attached to the polymer phase, which was used as a selective driver of the delivery process of the encapsulated nanoparticles, thus carrying out the construction of the bionanocarriers: BNC-1: MNPs-Q-Ab; BNC-2: MNPs-a3'5DMB-Ab.Its manufacturing method and the tests of its biological functionality, its stability, the degradation of the encapsulation for the tumor microenvironment, the controlled release profile of the drugs Q and A3'5DMB, selective cell uptake, intracellular localization, cytotoxic effect on steroids of hepatocellular carcinoma cells with altered redox balance and induction of apoptosis, as well as its safety on normal cells, are described.

The application discloses citrullinated collagen type II polypeptide and application thereof. The amino acid sequence of the polypeptide is Ste-QYMCitADQAAGGLR (SEQ ID NO. 1), wherein the N terminal of glutamine Q in the sequence is connected with octadecanoic acid Ste, and the fourth position in the sequence is modified by citrullination. The citrullinated collagen type II polypeptide has a long drug half-life, can effectively treat rheumatoid arthritis, and has small side effects.

The present application relates to the field of cefoperazone acid, and discloses a preparation method of cefoperazone impurity A, which comprises the following steps: (1) performing acyl chloride treatment on oxypiperazine acid in the presence of an acyl chloride reagent to generate an acyl chloride compound of oxypiperazine acid; (2) performing silylation treatment on 7-aminocephalosporanic acid in the presence of a silylation reagent to generate a silylated compound of 7-aminocephalosporanic acid; (3) reacting the acyl chloride compound of oxypiperazine acid with the silylated compound of 7-aminocephalosporanic acid to generate an intermediate compound (I); (4) hydrolyzing the intermediate compound (I) under the action of penicillin acylase to generate an intermediate compound (II); and (5) performing esterification and cyclization reaction on the intermediate compound (II) in the presence of a first crystallization solvent, a first organic solvent and a cyclization reagent to obtain the cefoperazone impurity A. The method disclosed by the present application is simple in process, and can obtain the cefoperazone impurity A with high purity, which can be used as a control sample for cefoperazone detection.

This invention relates to the field of drug synthesis and microchemical technology, and discloses a method for synthesizing 6-bromopenicillinic acid based on continuous flow microreactors. The method includes dissolving 6-aminopenicillinic acid in ethanol and stirring until clear to obtain liquid A; preparing an aqueous solution of sodium nitrite and hydrobromic acid to obtain liquid B; mixing liquid A and liquid B in a first micromixer and then passing them into a microreactor pipeline for diazotization and bromination reactions, with inert gas purging the pipeline online to obtain a reaction effluent; extracting the reaction effluent with dichloromethane online in a second micromixer, then separating the organic phase using a membrane phase separator, and concentrating to obtain 6-bromopenicillinic acid. This invention utilizes the advantages of efficient mixing and precise temperature control in a continuous flow microreactor, combined with inert gas purging, to achieve continuous and stable preparation. It features safe operation, good batch stability, high production efficiency, and environmental friendliness, making it suitable for industrial production.

The application discloses a new type of hapten and fatty acid double modified long-acting hypoglycemic BimBH3 mimetic peptide compound targeting PTP1B as well as a preparation method and application thereof. The structural general formula of the Bim BH3 mimetic peptide is shown as formula I: wherein the compound is derived from a core region peptide segment of a Bim-BH3 domain, a non-natural amino acid is used to replace the second amino acid by site-specific substitution to increase the stability of the peptide segment against DPP-4 enzyme, and a long-chain fatty acid (hexadecanoic acid or octadecanedioic acid) is conjugated to the N terminal to modify to ensure better PTP1B inhibitory activity, so that the BimBH3 mimetic peptide has longer duration and higher activity and plays a role in hypoglycemia by inhibiting the target PTP1B. The compounds are prepared by using 2-CTC resin by polypeptide solid-phase synthesis method, and the crude product is cut, purified and freeze-dried to obtain a pure target compound.

The invention relates to the technical field of analysis and testing, and discloses a quality detection method for 6-aminopenicillanic acid, which can effectively detect coporphyrin I which is generated in a penicillin fermentation-enzyme method process and causes the 6-aminopenicillanic acid to become powder, and can be used for detecting the content of porphyrin in each main step of the process. The generation reasons and the effective removal steps are known, so that the technical process control is better guided; meanwhile, the chromatographic conditions can also be used for detecting the content of porphyrin in each main step of the process for producing 6-aminopenicillanic acid so as to understand the generation reasons and effective removal steps of the porphyrin, so that the process control is better guided.

The present invention relates to a novel aminoalkanoic acid derivative compound into which a biphenyl group is introduced and an anti-inflammatory composition comprising the same. The purpose of this invention is to provide a pharmaceutical composition for preventing or treating fibrotic diseases, inflammatory diseases, autoimmune diseases, and / or allergic diseases containing a novel aminoalkanoic acid derivative compound into which a biphenyl group a biphenyl, its salt and / or a solvent as active ingredient.

Disclosed is a method and oral composition for treating a plurality of End stage diseases such as end-stage renal disease, chronic kidney disease, liver cirrhosis, chronic liver failure, end stage liver disease, Cancer, congestive Heart failure, pulmonary fibrosis, chronic obstructive pulmonary disease. In an embodiment of the invention, the composition comprises testosterone duodecanoate.

The invention relates to a pyridazinic acid unit-containing cyclic ester peptide compound, a preparation method thereof, a pharmaceutical composition containing the compound, application of the compound in preparation of a medicine for inducing rupture and death of a tumor cell membrane, and application of the compound in preparation of a medicine for activating tumor immune response, and particularly relates to a pyridazinic acid unit-containing cyclic ester peptide compound and a pharmaceutical composition containing the pyridazinic acid unit-containing cyclic ester peptide compound. The invention also relates to application of the compound in preparation of medicines for treating diseases related to cell death in organisms.

The object of the present invention is to provide an absorption enhancer capable of introducing high-molecular weight compounds into cells.The object can be solved by a composition of the present invention comprising a polymer compound having a group represented by the following general formula (1) or the following general formula (2) at a side chain, and a compound to be administered with a molecular weight of 1,000 to 1,200,000.wherein X1 is a residue of neutral amino acid or ω-aminoalkanoic acid in which an end amino group and an end carboxyl group are removed, X2 is a residue of cell-penetrating peptide in which an end amino group and an end carboxyl group are removed, X3 is a hydroxyl group, an amino group, an alkoxyl group having 1 to 4 carbon atoms or a benzyloxy group, a is an integer of 0 to 50, and * denotes a bonding site.wherein X4 is a residue of neutral amino acid or ω-aminoalkanoic acid in which an end amino group and an end carboxyl group are removed, X5 is a residue of cell-penetrating peptide in which an end amino group and an end carboxyl group are removed, X6 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a benzyl group, an acyl group having 1 to 6 carbon atoms, an arylsulfonyl group or an oxycarbonyl group, b is an integer of 0 to 50, and * denotes a bonding site.