769 results about "Cholic acid" patented technology

The invention discloses a liver-targeting drug liposome and application thereof, and relates to the field of drug delivery, cholate and mannose are used for respectively modifying phospholipid molecules DSPE-PEG2000, two raw materials DSPE-PEG2000-CA and DSPE-PEG2000-MAN composed of the liposome are synthesized, and then the liposome is prepared into the liver-targeting drug liposome. The liposome with liver targeting property is obtained from the liposome, cholesterol, DSPC, DC-cholesterol and a water-soluble therapeutic drug according to a certain proportion, the liposome has relatively high cell safety and liver targeting property, and the therapeutic effect of the corresponding drug can be remarkably improved after the drug is embedded.

The invention discloses a streptomyces-derived cytochrome P450 enzyme mutant and an application of the streptomyces-derived cytochrome P450 enzyme mutant in synthesis of ursodesoxycholic acid. The cytochrome P450 enzyme mutant is obtained by carrying out single mutation or multiple mutation on the 181st site, the 192nd site, the 249th site or the 288th site of an amino acid sequence shown in SEQ ID NO.2. The cytochrome P450 enzyme mutant has high activity and regioselectivity, low-cost lithocholic acid is used as a substrate, efficient cytochrome P450 enzyme is used for hydroxylating the 7beta site of the lithocholic acid, ursodesoxycholic acid is synthesized in one step, the industrial production cost is greatly reduced, and the cytochrome P450 enzyme mutant has good application prospects in industrial production of ursodesoxycholic acid.

The invention belongs to the technical field of polymer biomaterials, and particularly relates to a multi-drive composite dual-response gel system and a preparation method thereof, and the gel system has good adhesion and thermosensitivity and excellent comprehensive performance. The preparation method comprises the following steps: taking a poly (N-isopropylacrylamide)-acrylamide gel solution and a polyvinyl alcohol-cyclodextrin gel solution as a first layer of gel; one or more of a polyvinyl alcohol-bile acid gel solution, a polyethylene glycol-bile acid gel solution, a polyvinyl alcohol-deoxycholic acid gel solution, a polyvinyl alcohol-taurocholic acid gel solution and a polyvinyl alcohol-glycine gel solution is or are used as a second layer of gel. The two gel solutions are mixed together and are intertwined and cross-linked in a physical space, so that the gel has a large-hole structure; and the mixed gel has two response characteristics due to the double gel solutions, and can be applied to wider fields.

The invention relates to the technical field of inorganic non-metallic materials, in particular to a quaternized cholic acid polyurethane modified polyvinyl chloride material, a preparation method and application. The quaternized cholic acid polyurethane polymer is based on a polyurethane elastomer developed by using cholic acid molecules with a rigid skeleton as a hard segment unit and flexible oligomeric ethylene glycol as a soft segment unit, hydroxyl on cholic acid polyurethane is quaternized to prepare cation modified cholic acid polyurethane, and the cation modified cholic acid polyurethane simulates amphiphilic characteristics of natural peptides. The quaternized cholic acid polyurethane is introduced into a polyvinyl chloride (PVC) matrix as an antibacterial agent, so that the growth of microorganisms such as bacteria and molds can be effectively inhibited, the antibacterial property is achieved, bacteria breeding on the inner surface of a pipeline is avoided, and the composite material is endowed with better biocompatibility and antibacterial property; meanwhile, the quaternized cholic acid polyurethane can effectively improve the strength and toughness of the PVC material; wide application prospects are realized.

Provided is the use of a conjugated cholic acid, tryptophan-conjugated bile acids (TrpCA) or a TrpCA-producing strain for preventing and / or treating a metabolic disease. The present disclosure relates to the use of tryptophan-conjugated cholic acid or its producing bacteria strain in the preparation of a composition for preventing and / or treating a metabolic disease, or for promoting GLP-1 and / or insulin production. The inventors have discovered for the first time that the tryptophan-conjugated cholic acid can significantly promote the secretion of GLP-1 in both in vivo animal model and in vitro cell model, thereby reducing weight, lowering blood glucose and relieving symptoms of non-alcoholic fatty liver disease. Moreover, colonization of the selected probiotics can also have the same metabolic improvement effects.

There is provided the use of Lactobacillus paracasei or a afterbiogen in the preparation of a pharmaceutical composition or a food composition for the production of tryptophan-binding cholic acid. The Lactobacillus paracasei or the afterbiogen thereof can be used to prevent and / or treat metabolic diseases or to promote the production of GLP-1 and / or insulin, or to maintain blood glucose healthy levels, to maintain blood lipid health and / or to control fat in the body.

The invention provides application of combined cholic acid TrpCA and producing bacteria thereof in treating and preventing metabolic diseases. The present invention relates to the use of tryptophan-binding cholic acid or a producing bacterium thereof in the preparation of a composition for preventing and / or treating a metabolic disease or for promoting the production of GLP-1 and / or insulin. The inventor finds for the first time that tryptophan-bound cholic acid can remarkably promote secretion of GLP-1 on an in-vivo animal model and an in-vitro cell model, the effects of reducing weight, reducing blood sugar and relieving the symptoms of the non-alcoholic fatty liver disease are achieved, and the same metabolism improvement effect can also be achieved through planting of probiotics capable of generating cholic acid TrpCA.

The invention discloses a culture solution for reducing lipid of animal embryos before freezing as well as a preparation method and application of the culture solution. The culture solution is prepared by adding bezafibrate and cholic acid into an NCSU23 culture solution. The invention also discloses a preparation method of the culture solution, which comprises the following steps: preparing an NCSU23 culture solution, and adding bezafibrate and cholic acid into the NCSU23 culture solution. Compared with a conventional NCSU23 culture solution, the culture solution provided by the invention has the advantages that the added bezafibrate and cholic acid have a synergistic lipid-lowering effect, so that the content of lipid in an embryo can be remarkably reduced, and the survival rate and the blastocyst hatching rate after the embryo is frozen and unfrozen are finally effectively improved. The culture solution provided by the invention has application prospects in the aspects of animal embryo lipid reduction, frozen embryo survival and development and the like.

The invention relates to application of 12-ketolithocholic acid in preparation of a medicine for preventing or treating acute ischemic intestinal injury. According to the application, 12-ketolithocholic acid (12-KLCA) is used for preventing or treating acute ischemic intestinal injury and is verified on a constructed classical intestinal ischemia reperfusion model, and a verification result shows that the 12-KLCA obviously improves intestinal histopathologic injury induced by intestinal ischemia reperfusion of a mouse, improves the survival rate of the mouse, and has a good application prospect in prevention or treatment of acute ischemic intestinal injury. The protein expression level of the apoptosis factor activated caspase-3 is reduced, the effect is obvious, safety and non-toxicity are achieved, and the side effect is small.

The invention discloses hawthorn leaf pectic polysaccharide with lipid-lowering activity and a preparation method and application thereof, and belongs to a preparation method of plant polysaccharide, the preparation method comprises the following steps: refluxing hawthorn leaves with ethanol, discarding monosaccharide and small molecule compounds, refluxing with hot water to extract medicinal materials, removing protein through an enzymolysis method and a Sevage reagent method, decolorizing with polyamide resin, and drying to obtain the hawthorn leaf pectic polysaccharide with lipid-lowering activity. The crude polysaccharide is separated through DEAE-52 column chromatography, and finally, the crude polysaccharide is further purified through Sephadex G-100, so that the uniform purified polysaccharide is obtained. Tests on pancreatic lipase inhibition, taurocholate binding capacity and glycocholate binding rate show that the compound has remarkable lipid-lowering activity and is expected to become a potential natural lipid-lowering preparation.

Provided here is use of Lacticaseibacillus paracasei or postbiotics thereof for the manufacture of a pharmaceutical or a food composition for generating a cholic acid conjugated to tryptophan. The Lacticaseibacillus paracasei or the postbiotics thereof can be used for preventing and / or treating a metabolic disease, or for promoting GLP-1 and / or insulin production, or for maintaining healthy blood glucose level, maintaining healthy lipid level and / or controlling body fat.

The invention relates to the field of biomedicine, particularly provides a copper-based nano-enzyme as well as a preparation method and application thereof, and aims to solve the problems that in the prior art, clinical treatment on primary sclerosing cholangitis (PSC) is difficult in diagnosis and lacks of effective treatment drugs. The copper-based nano-enzyme comprises a nano-enzyme carrier and a copper-based nano-enzyme, wherein the nano-enzyme carrier is a two-dimensional nanosheet formed by copper ions, gallic acid and ursodesoxycholic acid through coordinate bonds; the probe molecule is a cyanine dye molecule connected to the surface of the nano-enzyme carrier through a covalent bond; wherein the fluorescence intensity of the copper-based nano enzyme is enhanced after the action of the alkaline phosphatase. The three functions of alkaline phosphatase responsive diagnosis, nano-enzyme catalytic treatment and ursodesoxycholic acid hepatic targeting are innovatively and synergistically integrated into one nano platform, the treatment function can be executed while specific imaging diagnosis is performed on diseases, and a new strategy is provided for diagnosis and treatment of diseases such as PSC.

The invention relates to the technical field of pharmaceutical separation, and discloses a device, method and application of ursodeoxycholic acid preparation and purification. The device comprises a separation tank, wherein a batching center cylinder is rotatably installed inside the separation tank, and a plurality of elution tubes are arranged around the batching center cylinder. The batching center cylinder rotates forward, and centrifugal force is used to load adsorption resin into each elution tube. Then, the batching center cylinder rotates reversely, and the volume of each elution tube is poured out by anti-centrifugal force, so as to achieve a more convenient effect of replacing the adsorption resin. The replaced adsorption resin is cleaned outside the device and reused. The purification method and application thereof realize column loading, sample loading and elution in the separation tank in sequence without stopping the machine for operation, and simplify the column loading and column replacement operations, so as to solve the problem that the separation and purification process in the prior art is complicated and not suitable for batch production, so as to meet the industrial production requirements of solvent recycling.

The invention discloses efficient synthesis of ursodesoxycholic acid by improving the positive enzyme activity of 7 beta-hydroxysteroid dehydrogenase through directed evolution, and belongs to the field of biological catalysis engineering. According to the invention, the 7beta-hydroxysteroid dehydrogenase mutant TEAE / F152L / W101N with improved positive reaction activity and improved affinity with a substrate is obtained. Compared with TEAE, the forward enzyme activity of the mutant enzyme is improved by 2.9 times, the reverse activity of the mutant enzyme is reduced by 3.6 times, the catalytic efficiency kcat / Km of the mutant enzyme to 7K-LCA is improved by 4.3 times, and compared with a wild type mutant TEAE / F152L / W101N, the enzyme activity of the mutant enzyme is improved by 206.23 times, and the catalytic efficiency of the mutant enzyme to 7K-LCA is improved by 58.56 times. The invention provides a universal technical platform for directed evolution of hydroxysteroid dehydrogenase, provides an excellent mutant enzyme for biological efficient synthesis of ursodesoxycholic acid, and lays a solid research foundation for efficient and low-cost preparation of ursodesoxycholic acid.

The invention relates to the technical field of polypeptides, and discloses a soybean polypeptide with an antibacterial function and a preparation method thereof.The soybean polypeptide with the antibacterial function is obtained by adding soybean polypeptide, quaternized cholic acid and modified chitosan into N, N-dimethylformamide and stirring for reaction. A chitosan group, a quaternary ammonium salt group, an imidazole group and a cholic acid group contained in the soybean polypeptide with the antibacterial function jointly form an antibacterial system, and a good antibacterial effect is achieved; wherein the chitosan group can destroy bacterial cell walls to death bacteria, so that the antibacterial effect is achieved, and the cholic acid group also has a relatively good antibacterial effect; the imidazole group rapidly kills bacteria by destroying bacterial cell membranes, affecting bacterial metabolism and inhibiting formation of biological membranes, a good antibacterial effect is achieved, quaternary ammonium salt is adsorbed to the negatively charged bacterial cell membranes through the cationic characteristics of quaternary ammonium salt, the cell membranes are broken, and therefore the bacteria are rapidly killed.

The disclosure relates to a traditional Chinese medicine composition, comprising active ingredients derived from Cornu caprae or Cornu saigae tataricae, Radix scutellariae, Bulbus fritillariae ussuriensis, Radix glycyrrhizae, Radix et rhizoma rhei, Gypsum fibrosum, Calculus bovis artifactus and Lapis Chloriti, the said active ingredients comprise in parts by weight: at least 1600 parts of amino acids; at least 120 parts of gallic acid; at least 130 parts of liquiritin; at least 20 parts of liquiritigenin; at least 400 parts of baicalin; at least 40 parts of oroxyloside; at least 120 parts of wogonoside; at least 280 parts of glycyrrhizic acid; at least 12 parts of chrysin-7-O-β-D-glucoronic acid; at least 50 parts of aloe-emodin-8-O-β-D-glucopyranoside; at least 30 parts of chrysophanol-1-O-β-D-glucopyranoside; at least 45 parts of chrysophanol-8-O-β-D-glucopyranoside; at least 260 parts of hyodeoxycholic acid; at least 150 parts of cholic acid. The traditional Chinese medicine composition in the present invention possess antipyretic, anti-inflammatory and antitussive effects.

The invention belongs to the field of medicinal chemistry, and particularly discloses application of oxime cholic acid analogues as TGR5 allosteric agonists. The preparation method comprises the following steps: by taking cholic acid as a raw material, obtaining cholic acid intermediates of which the 12th site or the 7th site and the 12th site are oximes through a series of reactions, and then carrying out a series of modification on the 24th site and oximes of the intermediates to obtain the cholic acid analogue as shown in a formula 1 or a formula 2. According to the invention, a GloSensor cAMP accumulation experiment is adopted to test the functional activity and allosteric regulation mechanism of all compounds on TGR5 on a G protein dependent signal channel. Pharmacological results show that all the synthesized target compounds have relatively good agonist activity on TGR5, and can positively allosteric regulate the functional activity of chenodeoxycholic acid CDCA, that is, the target compounds disclosed by the invention are all TGR5 positive allosteric modulators or allosteric agonists. # imgabs0 # imgabs1 #

Provided are methods of treating diabetes and / or obesity in a subject in need thereof, and methods of increasing the amount of cholic acid-7-sulfate (CA7S) in a subject. Further provided herein are methods of administering CA7S to a subject. Also provided are compositions and kits comprising cholic acid-7-sulfate, or a salt thereof for use in the treatment of diabetes and / or obesity.

The present invention relates to antisense oligonucleotides (AONs) that can mediate RNA editing by binding to a target RNA nucleic acid molecule, preferably an RNA transcript molecule, in a cell and recruiting an endogenous deaminating enzyme in the cell to deaminate a target adenosine in the target RNA molecule to an inosine. The target RNA molecule is a transcript molecule form the SLC10A1 gene that encodes the Na+ / Taurocholate Co-transporting Polypeptide (NTCP), and the target adenosine is the adenosine in the GAC codon coding for aspartic acid (D) at position 24 of the NTCP protein. The deamination of the adenosine changes the amino acid to a glycine (G). The RNA editing of the adenosine will result in a loss-of-function of the NTCP protein, which will result in lowered uptake of bile acids from the portal circulation into the liver, thereby lowering the risk of suffering from disorders related to bile accumulation in the liver.

The invention belongs to the technical field of microorganisms, and particularly relates to bacillus cereus as well as a culture and application thereof. The preservation number of the bacillus cereus AK-LY1 is CCTCC (China Center For Type Culture Collection) NO: M 2025756. The bacillus cereus AK-LY1 disclosed by the invention is excellent in trypsin resistance, good in cholate resistance, acid resistance and high temperature resistance, good in inhibition performance on antibiotics such as strong penicillin and chloramphenicol, and relatively good in adhesion capacity in intestinal tracts, and provides a relatively good microecological preparation reference basis for expanding a bacillus cereus resource library and applying the bacillus cereus.

The invention relates to an exosome fusion liver targeting liposome drug delivery system as well as a preparation method and application thereof, and belongs to the field of high polymer material science and pharmaceutical preparations. The invention discloses an exosome-fused liver-targeted liposome drug delivery system, which combines high-concentration PEG8000 and Nycodenz in a breakthrough manner, synergistically improves the fusion efficiency of exosome and liposome, and forms bionic vesicles with uniform size and high drug loading capacity. The exosome not only can exert the anti-inflammatory and anti-oxidation characteristics, but also plays a role in resisting a severe gastrointestinal environment and crossing a biological barrier. In addition, liposome is modified by cholic acid derivatives through EDC / NHS mediated amidation reaction, precise targeting of the liver is achieved, and the liposome is fully accumulated in the liver. The effects synergistically realize the treatment of type II diabetes and non-alcoholic steatohepatitis.

The invention discloses a method for analyzing and identifying anti-inflammatory active ingredients of Xinhuang tablets based on a UPLC-Tripe-TOF-MS (Ultra Performance Liquid Chromatography-Tripe-TOF-Mass Spectrometry) spectrum-effect relationship. According to the method, an active extract is obtained from Xinhuang tablets through a dichloromethane liquid-liquid extraction method, a fingerprint spectrum of 10 batches of samples is established by using UPLC-Tripe-TOF-MS, a double-target evaluation system is constructed by combining an LPS-induced RAW264.7 cell inflammation model and COX-2 enzyme inhibition detection, and spectrum-effect relationship research is performed through gray correlation analysis and an OPLS-DA data mining technology. Four chemical components, namely indomethacin, 7-ketolithocholic acid, erucyl amide and pyranoapigenin, which are highly related to the anti-inflammatory activity are identified; the quality control method of the Xinhuang tablets based on the key chemical markers is established, a scientific basis is provided for quality evaluation and standardization of the traditional Chinese medicine compound Xinhuang tablets, and meanwhile a new thought is provided for development of anti-inflammatory drugs.

The invention provides a 7beta-hydroxysteroid dehydrogenase mutant and application thereof in synthesis of ursodesoxycholic acid by a biological enzyme method, through a genetic engineering technology and computer-aided design, phosphoric acid coordination residues of protein are modified, the 7beta-hydroxysteroid dehydrogenase (7beta-HSDH) mutant with higher activity under an NADH (Nicotinamide Adenine Dinucleotide Hydroxide) system is constructed, and the 7beta-hydroxysteroid dehydrogenase (7beta-HSDH) mutant can be used for synthesizing ursodesoxycholic acid. The modification strategy is suitable for other proteins for modifying cofactor preference and improving enzyme activity, and has remarkable industrial value when being used for efficiently catalyzing CDCA to be converted into UDCA through a one-pot one-step method.

The invention discloses a lactobacillus rhamnosus GYX-9 strain and an application of the lactobacillus rhamnosus GYX-9 strain. The lactobacillus rhamnosus GYX-9 disclosed by the invention can be used for regulating the problems of blood lipid metabolism disorder, liver lipid accumulation or pathological injury and the like caused by high-fat diet. The lactobacillus rhamnosus GYX-9 disclosed by the invention can be used for reducing the level of TNF-alpha, increasing the content of IL-10 and regulating colonic immune disorder; the abundance of intestinal microbiome communities is adjusted; according to the invention, the lactobacillus rhamnosus GYX-9 is combined to regulate and control the metabolic disorder caused by high-fat diet on the basis of'intestinal flora-intestine-liver axis'. The normal-temperature viable bacterium fermented milk with the viable bacterium number not less than 108 cfu / mL is also prepared, the normal-temperature viable bacterium fermented milk has remarkable capabilities of lowering cholesterol, combining taurocholate and inhibiting pancreatic lipase, and the pancreatic lipase inhibition rate can reach 67.06%.

A model that closely resembles human excessive myopia can be prepared by mounting a minus lens (2) and a protector (4) to a juvenile mouse, the minus lens having an angle and a width adjustable in response to growth of the mouse. Further, this model analysis shows that myopia induction causes endoplasmic reticulum stress in a sclera and the endoplasmic reticulum stress induces myopia. Furthermore, it is revealed that an endoplasmic reticulum stress suppressant, particularly, phenylbutyrate and tauroursodeoxycholic acid act as a myopia prevention / suppression agent.

The invention discloses an application of 12-ketolithocholic acid in preparation of an anti-Vihonor coccus product. The first test proves that the 12-ketolithocholic acid has good activity of inhibiting atypical Wehonor coccus, specifically, the minimum inhibitory concentration required for inhibiting 50% of tested ATCC 17744 strain is measured, and the result shows that bacteria in a blank control hole containing no medicine grow obviously, and the MIC50 of the 12-ketolithocholic acid for the atypical Wehonor coccus is 294.7 mu g / ml. Therefore, the new application of the 12-ketolithocholic acid provided by the invention provides reference for clinical prevention and control of epidemic diseases caused by Wehonor coccus.

The invention provides a silibinin mixed micelle injection as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. The cholate / lecithin mixed micelle system constructed by adopting specific cholic acid and phospholipid has good stability, can be well compatible with the silibinin so as to well encapsulate the silibinin, can obviously improve the solubility of the silibinin, has higher safety under the condition of ensuring the stability of the silibinin, and can be used for preparing a medicine for treating the silibinin. Therefore, the bioavailability of the silibinin is greatly improved. According to the invention, a shearing dispersion method is adopted to prepare the mixed micelles, and the mixed micelles with high drug loading capacity, clarification and good stability for silibinin are formed by destroying and shearing the raw and auxiliary materials in a molecular level, so that the mixed micelles have better physical and chemical stability, the drug quality is easier to control, the process is more simplified, the clinical medication is safer and the cost is lower; and the accessibility of the medicine is improved.

Methods for stereo-selectively crystallizing 3-keto-5β-cholanic acid ("3-KCA") and 3-keto ursodeoxycholic acid ("3-KUDCA") of exceptional purity, salts useful in carrying out such methods, particularly the t-butylamine and cyclohexylamine salts of 3-KCA, the t-butylamine salt of 3-KUDCA, and crystalline forms of such salts, and methods of making commercial steroids from such purified materials.

The invention provides poly-zwitterion-cholic acid, synthesis thereof and application of the poly-zwitterion-cholic acid in drug delivery. Specifically, the invention provides a polymer, the polymer is formed by connecting polycholic acid and one or more zwitterionic polymers through covalent bonds, and the polycholic acid is a main chain (skeleton) of the polymer; and a nano-drug using a micelle or particle formed by the polymer as a carrier.

The present disclosure relates to stable pharmaceutical compositions comprising fixed dose combination of obicetrapib and ezetimibe, or their salts, solvates or derivatives thereof. The disclosure further describes the use of ezetimibe and obicetrapib, e.g. in the form of such fixed dose combinations, for preparation of medicaments and method of treatment of subjects requiring reduction in LDL-cholesterol or those suffering from hyperlipidemia or mixed dyslipidemia.