72 results about "Ursodesoxycholic acid" patented technology

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 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 present invention discloses a synthesis method of ursodeoxycholic acid by using the plant-derived compound BA as a raw material to synthesize ursodeoxycholic acid through the steps of ethylene glycol or neopentyl glycol protection, oxidation, Wittig reaction, deprotection, reduction and hydrolysis, etc. The raw materials used for the synthesis of ursodeoxycholic acid in the present invention are cheap and easy to get, the synthesis steps are easy to operate, the yield is high, the reaction is environmentally friendly, and the industrial production is convenient.

The invention discloses a biochemical immunodetection device and a biochemical immunodetection method for ursodesoxycholic acid reduzate, and belongs to the technical field of ursodesoxycholic acid reduzate detection. The ursodesoxycholic acid reduzate detection device comprises a detection box and a lifter at the bottom of the detection box, a dissolution preparation part and a centrifugal part are arranged in the detection box, and the dissolution preparation part can fully dissolve an ursodesoxycholic acid reduzate-containing medicament; the centrifugal part is used for carrying out precipitation separation on the dissolved medicament; the detector can accurately collect fluorescence signals of the immune complex; according to the ursodesoxycholic acid reduzate detection device, the integrated operation of detection test tube fixing, cover opening and transferring, medicament adding, cover closing and plug sealing and dissolving is achieved, the steps of automatic medicament filling, sealing and the like are achieved, the medicament preparation efficiency is greatly improved, efficient and accurate detection of ursodesoxycholic acid reduzate is further achieved, and the detection efficiency is improved. And complex and tedious manual operation is avoided, and the situation that the sample is easily polluted by manual operation is avoided.

The invention relates to the technical field of health wine preparation, and discloses a multi-effect synergistic enhanced bear gall body-building wine compound preparation process which comprises the following steps: taking sorghum, corn and fructus lycii as fermentation base materials, and carrying out double-strain synergistic fermentation by adopting saccharomyces cerevisiae and lactobacillus plantarum; adding fresh ursodesoxycholic acid during fermentation, carrying out in-situ enzymatic debinding conversion by using a compound enzyme system generated by a fermentation system, and converting the bound bile acid into free ursodesoxycholic acid; after fermentation, distilling to obtain raw wine; a molecularly imprinted polymer prepared by taking a wolfberry polyphenol key monomer as a template molecule is adopted to carry out targeted anchoring refining on raw wine, selective capture and enrichment of wolfberry polyphenol are carried out, and finally aging is carried out to obtain a finished product. According to the method disclosed by the invention, upstream double-strain fermentation in-situ enzymatic conversion and downstream molecular imprinting targeted refining are systematically integrated, so that the technical contradictions that the conversion rate of combined bile acid is low and a large amount of polyphenol functional components are synchronously lost during purification and impurity removal in a traditional process are solved.

The invention relates to the field of biological catalysis, and discloses a method and a device for generating ursodesoxycholic acid through continuous flow catalysis of chenodeoxycholic acid. Comprising the following steps: (1) in the presence of first immobilized cells, carrying out a first catalytic reaction on a reaction system containing chenodeoxycholic acid to obtain a first product, the first immobilized cells expressing 7 alpha-hydroxysteroid dehydrogenase and lactic dehydrogenase; the concentration of the chenodeoxycholic acid in the reaction system is 40 to 70 mM; (2) adjusting the pH value of the first product to 8-9, and then in the presence of a second immobilized cell, carrying out a second catalytic reaction on the first product after the pH value is adjusted to obtain ursodesoxycholic acid, and the second immobilized cell expresses 7 beta-hydroxysteroid dehydrogenase and glucose dehydrogenase. According to the method, the stable activity of a catalytic system is kept, efficient conversion of high-concentration CDCA is achieved, meanwhile, precipitation of 7-KLCA is thoroughly avoided, and the synthesis efficiency, the product purity and the process continuity of UDCA are remarkably improved.

The invention discloses an ursodesoxycholic acid-pterostilbene conjugate, a preparation method thereof and application of the ursodesoxycholic acid-pterostilbene conjugate in preparation of drugs for treating non-alcoholic fatty liver diseases, and belongs to the technical field of biological medicines. According to the conjugate, ursodesoxycholic acid and pterostilbene are covalently connected through specific chemical bridging, and the structural general formula is shown in the specification. The preparation method comprises the following steps: respectively preparing the alkynyl-containing pterostilbene derivative and the azido-containing ursodesoxycholic acid derivative through esterification and amidation reactions, and then realizing efficient coupling through a click chemical reaction. The conjugate provided by the invention can realize hepatic targeting delivery by virtue of a bile acid transporter, synchronously releases two active components in hepatic cells, plays a therapeutic role through multiple mechanisms such as synergistic regulation of lipid metabolism, inhibition of oxidative stress and inflammation, anti-fibrosis and the like, and is obviously superior to a single component or a physical mixture; and a new strategy is provided for treatment of the non-alcoholic fatty liver disease.

The invention discloses application of hydrotalcite and an ursodesoxycholic acid oral suspension composition, a suspension is composed of two parts, namely a drug-loaded pellet and an inactive particle, the drug-loaded pellet is composed of a drug-loaded pellet core and a taste-masking coating layer, and the taste-masking coating layer comprises zein, hydrotalcite, an anti-sticking agent and a plasticizer; the inactive particles comprise a filling agent, a suspending aid and essence. The drug-loaded pellet of the ursodesoxycholic acid oral suspension composition is composed of a drug-loaded pellet core and a taste-masking coating layer, ursodesoxycholic acid is contained in the drug-loaded pellet core, and hydrotalcite serving as a pore-foaming agent is contained in the taste-masking coating layer. Therefore, when the composition medicine is taken, whether the film-forming material zein or the pore-foaming agent is not dissolved in water during taking, and after the composition medicine reaches the stomach, hydrotalcite can generate neutralization reaction with gastric acid to play a role of the pore-foaming agent, so that quick release of the composition medicine is ensured.

The invention discloses a preparation method of ursodesoxycholic acid capsules. The preparation method comprises the following steps: (1) preparing materials; (2) preparing ursodesoxycholic acid nanocrystals; (3) wet granulation; (4) drying; and (5) total mixing and capsule filling. The ursodesoxycholic acid raw material is pretreated by adopting a nanocrystalline preparation technology (a wet medium grinding method), so that ursodesoxycholic acid particles can still have relatively good fluidity and dissolution rate under the condition of relatively large particle size, the metal adhesion is relatively weak, and the material loss can be reduced; according to the ursodesoxycholic acid capsule, ursodesoxycholic acid is taken as a raw material, lauryl sodium sulfate and povidone K30 are taken as stabilizers, the ursodesoxycholic acid capsule is prepared through wet granulation, drying, total mixing and capsule filling, and the process is simple in step and suitable for industrial production.

The invention discloses a 7alpha-hydroxysteroid dehydrogenase mutant and application thereof in preparation of ursodesoxycholic acid, the enzyme mutant is obtained by mutating a wild type amino acid sequence as shown in SEQ ID NO: 1 through Q31A, H72Q, W111R or A178R, the mutated enzyme activity is high, 7-ketolithocholic acid can be prepared based on catalysis of a high-concentration substrate, and the 7alpha-hydroxysteroid dehydrogenase mutant can be applied to preparation of ursodesoxycholic acid. And the method has a significant meaning for industrial preparation of ursodesoxycholic acid under catalysis of the propulsor.

Improved enantioselective enzymatic processes for preparing ursodeoxycholic acid with high pharmaceutical purity are provided. Also provided are improved enantioselective enzymatic processes for preparing ursodeoxycholic acid with high yield and high pharmaceutical and enantiomeric purity.

The invention belongs to the technical field of medicines and the field of acne treatment, and particularly relates to application of amorphous salt in preparation of a medicine for treating acne and the medicine. The amorphous salt is prepared by reacting ursodesoxycholic acid and matrine, preferably, the ursodesoxycholic acid and the matrine are dissolved in a proper solvent according to the molar ratio of 1: (0.5-2), then the solvent is rapidly removed, and remaining solids are further dried and crushed to obtain the ursodesoxycholic acid / matrine amorphous salt. The solubility and the percutaneous penetration rate of the propionibacterium acnes are remarkably improved, the propionibacterium acnes can be inhibited, the expression of IL-1beta, IL-6, IL-8 and TNF-alpha can be reduced, P65 protein nucleus translocation can be inhibited, and an efficient and safe new scheme is provided for acne treatment.

The application discloses an intelligent response type bear gall powder-based bioactive ceramic hydrogel wound repair system and belongs to the technical field of biomedical materials, and solves the problems of split functions, uncontrollable release and unreasonable interface combination of existing wound dressings. The system innovatively combines intelligent response type hydrogel, bioactive ceramic and active components of bear gall powder through dynamic coordination bonds. The coordination bond formed by the active groups of bear gall powder and metal ions released by the ceramic serves as an intelligent switch, can respond to changes in wound pH / ROS, and accurately controls the release of antibacterial ions and anti-inflammatory components. Meanwhile, the bond realizes the stable and dynamic combination of the ceramic and the gel. The application realizes the organic unity of intelligent response, multiple bioactivity and stable structure, can synergistically resist bacteria, inflammation and promote repair, and improves the quality of wound healing.

The invention belongs to the field of biomedicine, and provides application of bile acid and derivatives thereof in prevention or treatment of intracranial aneurysm. The invention particularly relates to application of ursodesoxycholic acid and bile acid combined with ursodesoxycholic acid in preparation of drugs for preventing or treating intracranial aneurysm. According to the method, metabonomics analysis is carried out on a human blood sample, and the early warning effect of ursodesoxycholic acid and bile acid combined with ursodesoxycholic acid on intracranial aneurysm rupture is found; the verification of the influence effect of ursodesoxycholic acid and bile acid combined with ursodesoxycholic acid on the rupture probability of intracranial aneurysm in a mouse intracranial aneurysm model proves that the substance has a protective effect on intracranial aneurysm, namely the risk of intracranial aneurysm rupture is reduced; and an experimental basis is provided for the drug treatment of intracranial aneurysm and the reduction of clinical rupture risk.

The invention discloses ursodesoxycholic acid and amino acid conjugates (I), pharmaceutically acceptable salts thereof, a preparation method of the ursodesoxycholic acid and amino acid conjugates, a pharmaceutical composition of the ursodesoxycholic acid and amino acid conjugates and application of the ursodesoxycholic acid and amino acid conjugates in preparation of drugs for treating and / or preventing comprising but not limited to vascular dementia, Alzheimer's disease, frontotemporal dementia, Prion disease, dementia with Lewy bodies, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, cerebral arterial thrombosis, hemorrhagic stroke, nerve injury caused by cerebral trauma and other diseases; # imgabs0 #

The invention relates to the technical field of food processing and biology, discloses a genetic analysis bear gall body-building wine liver and stomach maintenance and immunity enhancement process, and solves the problems of unstable quality, low component dissolution rate and fuzzy efficacy orientation caused by fluctuation of raw material components and single soaking process in the prior art. Comprising the following steps: carrying out biochemical fingerprint analysis on fresh ursodesoxycholic acid and fructus lycii, and carrying out efficacy typing according to the contents of ursodesoxycholic acid, lycium barbarum polysaccharide, betaine and the like; carrying out targeted bio-enzyme pretreatment on the specific Chinese wolfberry fruits according to the typing result; raw materials of specific types are subjected to efficacy coupling combination, stepped dynamic alcoholysis soaking is adopted, and components with different dissolution characteristics are fully extracted through low-alcohol pre-dissolution and gradient alcohol rising steps; and finally, filtering, harmonizing and alcoholizing. According to the scheme, raw material standardization and process precision are combined, so that the stability of product quality is ensured, the transfer rate of functional components is increased, and liver and stomach nourishing or immunity enhancing products with definite efficacy can be directionally prepared.

The invention discloses a silanization purification method for ursodesoxycholic acid prepared by a biological enzyme method, and belongs to the field of biological pharmacy. According to the method, the whole-cell reaction liquid is used as a purification object, insoluble macromolecular impurities are removed through preliminary impurity removal and high-concentration acetone-water dissolution, the target content of UDCA is 80% or above successfully, and the product is pure white; the method comprises the following steps: carrying out a reaction on a UDCA silanization derivative and-OH by using a silanization reagent, separating the UDCA silanization derivative from other silanization derivatives, and hydrolyzing the UDCA silanization derivative to realize purification of UDCA. The content of CDCA in the final product is effectively controlled to be 0.5% or below, the purity of the UDCA crude product is improved from 53% to 98.5% or above, and the requirements of UDCA bulk drugs are met. The method is simple in process and low in cost, the obtained product is high in purity, the chenodeoxycholic acid impurity content is low, and the chenodeoxycholic acid can be used as a raw material of a pharmaceutical preparation.

The invention provides application of ursodesoxycholic acid in preparation of a medicament for improving the survival rate of acute hepatopancreatic necrosis of prawns, and belongs to the technical field of disease prevention and control in prawn culture. According to the invention, a lipid metabolism regulator ursodesoxycholic acid (UDCA) is adopted, and the damage of pathogenic vibrio infection to prawns is obviously reduced by regulating and controlling the metabolic pathway of infected prawn bodies. Tests prove that no matter the ursodesoxycholic acid is injected or added into the feed for feeding, the symptoms and the death rate of the prawns infected with the acute hepatopancreatic necrosis disease are remarkably reduced, and the ursodesoxycholic acid has a certain prevention and treatment effect in the prevention and treatment of the acute hepatopancreatic necrosis disease of the prawns.

The invention discloses a bear gall powder preparation method, an instant high-temperature sterilization process and a vacuum freeze-drying process, and the bear gall powder preparation method has the beneficial effects that the traditional sterilization process can be replaced by the bear gall powder preparation method provided by the invention, and the instant high-temperature sterilization work is carried out by using an ultrahigh-temperature sterilizer; according to the method, the bear gall powder can be sterilized and dried on the premise that active ingredients are not damaged, the retention rate of the bezoar ursodesoxycholic acid is increased to be larger than or equal to 50% and the water content of the bezoar ursodesoxycholic acid is smaller than or equal to 2% under the condition that no additive is added, the original luster of the product can be reserved, and the food safety of the product can be improved.

The present invention relates to a pharmaceutical combination comprising 6α-ethyl-3α, 7 a-dihydroxy-24-nor-5 β-cholan-23-ol or a pharmaceutically acceptable salt thereof and a statin and to a combination comprising 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-ol and ursodesoxycholic acid and the use thereof for the treatment of non-alcoholic liver steatosis and non-alcoholic steatohepatitis.

The present invention relates to an artificial bile duct comprising ursodeoxycholic acid (UDCA), and due to comprising UDCA, the artificial bile duct of the present invention is effective in improving differentiation into cholangiocytes and preventing formation of bile stones.

The invention discloses a hepatocyte cryopreservation solution which comprises a first cryopreservation mixed solution, a second cryopreservation mixed solution and fetal calf serum, the first cryopreservation mixed solution is prepared from a Leibovitz's L-15 culture medium, lactobionic acid, raffinose, reduced glutathione, ademetionine, curcumin, bicyclol, ursodesoxycholic acid, silymarin and glycyrrhizic acid; the second cryopreservation mixed solution comprises cane sugar, trehalose, hydroxyethyl starch and polyene phosphatidylcholine. On the other hand, the invention discloses a cryopreservation method and a recovery method of primary mouse hepatocytes based on the hepatocyte cryopreservation liquid. The cryopreservation method comprises the following steps: pre-culturing, re-suspending, slowly dropwise adding DMSO (dimethylsulfoxide) and cooling and cryopreserving step by step. The resuscitation method comprises the steps of rapid unfreezing, centrifugal purification and resuscitation culture. The liver cell cryopreservation liquid and the cryopreservation and resuscitation method can play roles in regulating osmotic pressure, inhibiting ice crystal formation, stabilizing cell membrane structure, resisting oxidation, promoting protein synthesis and the like, and the resuscitated cells are high in survival rate and strong in adherence capability and functional activity.

The present invention relates to compounds that derive from bile acids, such as ursodeoxycholic acid and to their use in the prevention and / or treatment of cancer, in particular of cholangiocarcinoma.

The application discloses a preparation method of tauroursodeoxycholic acid capsules and belongs to the technical field of capsule preparation. The tauroursodeoxyxycholic acid capsules are prepared by using a high-frequency wave vibration device which is precisely driven by a servo motor, and the high-frequency wave vibration device is internally provided with first and second moving blocks which are distributed at intervals and drive a flexible elastic plate to wave and turn over, and a plurality of contact assemblies are uniformly arranged on the elastic plate. In the process of spraying and wetting, particles continuously roll and disperse, water can be rapidly and uniformly distributed on the surfaces of all particles, and the water absorption block can automatically supplement water for dry particles, and will not absorb water from wet particles, so that local over-wetting or over-drying of the particles is effectively avoided. The tauroursodeoxyxycholic acid capsules not only remarkably improve the uniformity of the surface micro-wetting of the particles, and create ideal conditions for efficient coating of the subsequent flow aid, but also combine the high-efficiency airflow disturbance of the fluidized bed mixer, so that the flow aid such as colloidal silicon dioxide is uniformly covered on the surface of the particles, the stickiness of the active ingredient tauroursodeoxycholic acid is reduced, and the flowability of the particles and the consistency of the capsule loading are improved.

The invention relates to the technical field of biomedicine, and particularly discloses an in-vitro diagnosis marker for gall-stone and application thereof.The in-vitro diagnosis marker is jointly composed of a metabolism marker and an inflammation marker, the metabolism marker is the concentration ratio of lithocholic acid to ursodesoxycholic acid (LCA / UDCA), and the inflammation marker is the concentration ratio of CD133 to lipopolysaccharide (CD133 / LPS); the invention further provides a kit containing the marker and a detection method of the kit. The kit integrates specific detection reagents for LCA, UDCA, CD133 and LPS, two specific value markers can be rapidly, sensitively and simultaneously detected through an optimized sample treatment and detection process, and result judgment is carried out based on a preset reference interval upper limit and a composite judgment rule.

The invention relates to the field of biology, in particular to application of tauroursodeoxycholic acid in preparation of a medicine for promoting function maturation of islet organs. The specific effect of tauroursodeoxycholic acid in promoting functional maturation of iPSC-derived islet-like organs is found and verified for the first time, and a brand new treatment thought is represented. The beta cell functional gene expression and glucose stimulation response capability of the sc-islet can be remarkably improved only by performing TUDCA treatment for 96 hours, and the function maturation period is greatly shortened. The obvious effect can be achieved by adopting the low-dose TUDCA with the concentration of 25-100 ng / mL, the cost is reduced, and the potential toxicity risk is reduced. Key indexes (functional gene expression and glucose response) of beta cell maturation are directly targeted, and a high-quality cell model is provided for research and treatment of diabetes mellitus.

The invention provides filling equipment and method for preparing ursodesoxycholic acid capsules, and belongs to the technical field of pharmacy, the filling equipment comprises a storage bin, a transmission mechanism, a feeding bin, a feeding hopper, a dispersing mechanism, a negative pressure machine, a heating dehumidifier and a scraping mechanism; the feeding hopper is fixedly installed on the storage bin, and a pulling-away hole is formed in the side wall of the feeding hopper. The dispersing mechanism is mounted in the feeding hopper, and a multi-surface elastic structure is arranged on the dispersing mechanism; the negative pressure machine is communicated with the extraction hole, and the heating dehumidifier is communicated with the interior of the storage bin; a transpiration cavity is formed in the heating dehumidifier; the scraping mechanism is installed on the feeding bin and provided with a rotator and a centrifugal scraping assembly. The filling equipment for preparing the ursodesoxycholic acid capsules can effectively eliminate negative effects on particle storage and feeding due to high humidity, and ensures that particles are efficiently and accurately filled in capsule filling operation.

The invention relates to the technical field of biological medicine chemical separation, and discloses a separation and purification process of high-purity ursodesoxycholic acid mother liquor, which comprises the following steps: adding alkaline amino acid into the mother liquor containing ursodesoxycholic acid, stirring and dissolving to obtain a water phase system; adding a neutral chiral hydrophobic deep-eutectic solvent formed by complexing L-menthol and long-chain fatty alcohol into the water-phase system, and carrying out mixed extraction; standing for layering, separating to remove an upper-layer oil phase, and collecting a lower-layer water phase; finally, acid is added into the water phase to adjust the pH value, and an ursodesoxycholic acid product is obtained through ultrasonic-assisted crystallization, cleaning and drying. According to the method disclosed by the invention, efficient separation of a target product from chenodeoxycholic acid and lithocholic acid is realized by utilizing the specific hydrophilic anchoring effect of the basic amino acid on ursodeoxycholic acid and cooperating with the chiral hydrophobic recognition effect of the eutectic solvent on impurities. The process is green and environment-friendly, the solvent can be recycled, and the obtained product is high in purity and suitable for industrial application.

The utility model relates to the technical field of chemical separation, and discloses a modularized low-pressure ursodesoxycholic acid separation assembly which comprises a material disc, a partition plate is fixedly connected to the inner wall of the material disc, a connecting disc is rotatably connected to the lower surface of the material disc, and a stirring cabin is fixedly connected to the lower surface of the connecting disc. A second discharging pipe is fixedly connected to the interior of the stirring bin, a first valve is rotationally connected to one side of the outer wall of the second discharging pipe, a filtering bin is fixedly connected to the outer wall of the second discharging pipe, and a filtering assembly is arranged on one side of the inner wall of the filtering bin and comprises a sliding rail. According to the utility model, the effect of enabling materials to enter the filtering cabin is achieved by opening the valve I, the effect of carrying out multi-stage filtering on the materials is achieved by installing the coarse filtering net and the fine filtering net in the filtering cabin, and the effect of effectively improving the purity and the quality of products is achieved by carrying out finer and more thorough separation on the materials.

The invention relates to the field of medicine, in particular to solid dosage forms for the treatment of primary biliary cholangitis (PBC). The invention provides a modified release solid dosage form comprising two active pharmaceutical ingredients, obeticholic acid and ursodeoxycholic acid, arranged to release sequentially over time. The solid dosage form is designed to achieve a controlled, separate release of each API to provide a desired therapeutic profile.