37 results about "Tauroursodesoxycholic acid" patented technology

The invention relates to high-purity tauro ursodesoxy cholic acid and a preparation method thereof. The content of taurochenodeoxycholic acid in the tauro ursodesoxy cholic acid is less than 0.7%. The tauro ursodesoxy cholic acid is safe and effective and does not have toxic and side effects in clinical application. The invention further provides a mixed anhydride reaction of ursodesoxycholic acid and ethyl chloroformate by taking acetone as a solvent. By means of control of a reaction condition and a reaction solvent, the tauro ursodesoxy cholic acid has the advantages of simple process, low cost, environmental friendlessness and industrial production; furthermore, the high-purity tauro ursodesoxy cholic acid can be obtained.

The invention discloses a method of preparing tauroursodeoxycholic acid by biotransformation and application of the method. Biotransformation includes genetic codon optimization, engineered bacteria construction, engineered bacteria cultivation, substrate transformation and product preparation. Tauroursodeoxycholic acid is prepared by transforming a substrate through direct fermentation of engineered bacteria; the substrate is taurochenodeoxycholic acid. The substrate may reach 250 g / L in concentration; the reaction time is short; substrate transformation rate reaches 98% and above; the obtained product reaches 99% and above in purity; cyclic regeneration of NAD+ (nicotinamide adenine dinucleotide +) in the reaction system helps greatly reduce the usage of the coenzyme NAD+; the cost of enzymic catalytic reaction is reduced; industrial amplification is benefited. hydroxysteroid dehydrogenase and the regenerated coenzyme are connected via a flexible polypeptide sequence to form a protein fusion polymer; binding distances to the substrate and coenzyme are shorter; transformation progress is more facilitated; the number of fermenting times in industrial production is decreased; the process is simplified; time cost and material cost are saved.

The invention provides an artificial bear bile. The formula of the artificial bear bile comprises the following ingredients by mass percent: 35-48 of tauroursodeoxycholic acid, 50-63 of mixed choline, 1-3 of amino acid and 0.5-1 of trace element, wherein the mixed choline is an avian bile or a mixture of a plurality of avian biles and one or a mixture of a plurality of ox bile, sheep bile, rabbit bile and dog bile. The whole pharmacological tests prove that the artificial bear bile powder has the pharmacological functions which are similar to natural bear bile in the aspects of analgesia, sedation, convulsion prevention, inflammatory prevention, liver and gallbladder protection and the like, and can be used for completely substituting for the natural bear bile, the industrial production can be realized; and moreover, the price of the artificial bear bile is lower than that of the natural (drainage) bear bile, so the artificial bear bile is easily accepted. In addition, the molecular pharmacology also proves that the artificial bear bile has the functions of inhibiting MGc80-3 cancer cell growth and proliferation.

The invention relates to refined bear gall powder and application to physique enhancement treatment and prevention of tumors and cancer thereof, in particular to application of a compound as shown ina formula I as shown in the specification to production of products used for preventing or treating tumors and cancer on one hand. Cu-K alpha radiation is used for the compound, and in a powder X-raydiffraction spectrum expressed in 2theta degrees, diffraction peaks exist at 8.53+ / -0.20 degrees, 10.96+ / -0.20 degrees, 12.03+ / -0.20 degrees, 13.14+ / -0.20 degrees, 14.82+ / -0.20 degrees, 17.26+ / -0.20 degrees, 22.53+ / -0.20 degrees, 24.21+ / -0.20 degrees, 26.68+ / -0.20 degrees, 29.42+ / -0.20 degrees and 31.24+ / -0.20 degrees. The compound shows excellent biological performance, for example, the compoundhas excellent bioavailability, and physiological activity the same as that of bear gall powder or tauroursodeoxycholic acid can be given play to. For example, the compound can be used for preventing or treating tumors and cancer.

The invention relates to the field of biological medicine, relates to a preparation process of bear gall powder, and in particular relates to a preparation process of artificial bear gall powder. According to the scheme, a conversion solution containing cell active substances is used, so that the technical problems that the purification step of enzyme is complex, the cost is high and the enzyme activity is not easy to maintain are solved. According to the preparation process, after bioconversion is performed on livestock gall powder, the ratio of tauroursodeoxycholic acid to taurochenodeoxycholic acid of the obtained artificial bear gall powder is similar to that of natural bear gall powder. The artificial bear gall powder in the scheme can be used as a substitute of the natural bear gallpowder for deep processing and further application. The artificial bear gall powder product produced by adopting the preparation process is small in batch difference, the production process can be standardized, the conversion efficiency is improved, and industrial large-scale production can be achieved.

The invention relates to refined bear gall powder with improved bioavailability and a preparation method thereof. Specifically, the invention relates to a compound represented by a formula (I). The diffraction peaks represented by 2[theta] angles of the compound in a powder X-ray diffraction spectrogram under the alpha irradiation of Cu-K are 8.53 + / - 0.20 degrees, 10.96 + / - 0.20 degrees, 12.03 + / - 0.20 degrees, 13.14 + / - 0.20 degrees, 14.82 + / - 0.20 degrees, 17.26 + / - 0.20 degrees, 22.53 + / - 0.20 degrees, 24.21 + / - 0.20 degrees, 26.68 + / - 0.20 degrees, 29.42 + / - 0.20 degrees, and 31.24 + / - 0.20 degrees. The compound has excellent biological properties such as excellent bioavailability and has the same physiological activity of bear gall powder or tauroursodeoxycholic acid.

The invention relates to a method for detecting related substance in tauroursodeoxycholic acid, and especially relates to a method using a HPLC-ELSD technology to simultaneously detect eight related substances in tauroursodeoxycholic acid. According to the method, an octyl bonded silica gel chromatographic column and an evaporative light-scattering detector are adopted; and a mobile phase (A) and a mobile phase (B) are mixed to carry out isocratic elution or gradient elution, wherein the mobile phase (A) is an ammonium salt buffer solution with a concentration of 2.5 to 50 mmol / L, and the mobile phase (B) is methanol or acetonitrile. The provided method has the advantages of simpleness, rapidness, accuracy, reliability, and good resolution of chromatographic peaks, and is capable of simultaneously detecting eight related substances in tauroursodeoxycholic acid quantitatively or qualitatively.

The invention discloses a method for preparing tauro ursodesoxy cholic acid. The synthetic method comprises the following steps: a step (1) of adding ursodeoxycholic acid and phenolic compounds into chloralkane organic solvent at room temperature, performing cooling to 10-20 DEG C, adding a condensing agent; after the condensing agent is added dropwise, reacting completely at 5-45 DEG C, performing filtration and then concentrating filtrate to obtain a crude product, performing recrystallization and then obtaining high-finished product ursodesoxycholic acid phenolic ester as shown in a formula (II); a step (2) of adding the high-finished product ursodesoxycholic acid phenolic ester and taurine salt into an organic alcohol solvent to undergo the reaction completely, lowering the temperature to room temperature and then performing filtration, dissolving filter cake in water, using acid to adjust the pH to 1.0-3.0, and performing stirring and crystallization to obtain tauro ursodesoxy cholic acid as shown in a formula (I). The synthetic method is low cost, simple to operate, controllable and high in product yield and purity, an isomer impurity taurochenodeoxycholic acid of tauro ursodesoxy cholic acid can be controlled well, and the method is suitable for industrial production.

The invention relates to the technical field of drug synthesis, and discloses a method for synthesizing tauroursodeoxycholic acid under the catalysis of boric acid ester. Ursodeoxycholic acid and taurine react under the action of boric acid ester to obtain tauroursodeoxycholic acid, and the molecular formula of boric acid ester is B (OCH (CF3) 2) 3. Boric acid ester is used as a catalyst to synthesize tauroursodeoxycholic acid, the method is high in atom utilization rate, a product with a single structure is obtained, the application range of a substrate is wide, and the tolerance of functional groups is high; the problems of high synthesis cost and difficulty in industrial application in the prior art are solved.

The invention relates to the field of biotechnology and medicine, in particular to a method for preparing artificial bear bile powder by biocatalysis of active substances expressed by engineering saccharomyces cerevisiae. The method comprises the following steps: performing liquid culture on saccharomyces cerevisiae which simultaneously expresses 7alpha-hydroxysteroid dehydrogenase (7alpha-HSDH) and 7beta-hydroxysteroid dehydrogenase (7beta-HSDH) genes to prepare a crude enzyme extract; directly converting taurochenodeoxycholic acid in poultry bile products such as chicken gall powder into tauroursodeoxycholic acid with a certain proportion. According to the method, in-vitro double-enzyme catalysis is used, NADP+ is added as an auxiliary factor to promote the reaction, the crude enzyme preparation process is simple, the catalytic reaction condition is mild, the result is stable, the whole process is green, safe, rapid, environment-friendly, pollution-free and controllable, and great significance is achieved by utilizing the biotechnology to replace resources with bear bile powder.

The invention discloses an application of tauroursodeoxycholic acid in preparation of chicken feed additive, and a chicken feed, and particularly relates to the feed additive which is prepared from the tauroursodeoxycholic acid and can alleviate chicken heat stress. The tauroursodeoxycholic acid is found to have the function of alleviating the stress of a chicken in the environment with high temperature and high humidity, thus being capable of improving the organism redox state of the chicken and improving the conversion efficiency of the chicken feed; the tauroursodeoxycholic acid is a safe feed and does not contain the substances which are poisonous and harmful to the growth and the health of chicken flocks. The feed additive is less in adding amount of the tauroursodeoxycholic acid, and premix can be directly added into the feed additive, so that the adding process is convenient and fast; the feed additive is simple in preparation method and does not have special equipment requirement, thus having good popularization and application prospect.

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.

Provided herein is a method for treating a human subject afflicted with ALS by administering to the subject a therapeutically effective amount of pridopidine as monotherapy or together with riluzole, edaravone, combination of dextromethorphan / quinidine, sodium phenylbutyrate (PB), tauroursodeoxycholic acid or combination of sodium phenylbutyrate (PB) / tauroursodeoxycholic acid (i.e. AMX0035) as combination or add-on therapy.

The invention relates to the field of synthesis of tauroursodeoxycholic acid, and discloses application of silane and synthesis of tauroursodeoxycholic acid under catalysis of the silane. The synthesis method of tauroursodeoxycholic acid under catalysis of the silane comprises the following steps: synthesis of tauroursodeoxycholic acid: under the action of hydrosilane and aminosilane, taurine andursodeoxycholic acid react to obtain a system I containing tauroursodeoxycholic acid in tetrahydrofuran. According to the application, hydrosilane firstly reacts with carboxyl of ursodeoxycholic acidin situ to obtain silicon-based carboxylate, amino silane is beneficial to conversion of silicon-based carboxylate, silicon-based carboxylate quickly reacts with taurine to obtain tauroursodeoxycholicacid, one-pot direct synthesis of tauroursodeoxycholic acid is realized, the synthesis process is simplified, the reaction conditions are mild, and the operation is simple; the method is low in cost,economical, environment-friendly and suitable for industrial production.

It is disclosed a method for the treatment of neurodegenerative disorders, such as ALS, Alzheimer's disease, Parkinson's disease, Huntington's disease and / or retinitis pigmentosa, which method comprises administering to a patient tauroursodeoxycholic acid or a pharmaceutically acceptable salt thereof.

The invention relates to a determination method of a capsule fingerprint spectrum for dredging collaterals and reducing phlegm, which comprises the following steps: (1) test solution prepartion: taking capsule contents for dredging collaterals and reducing phlegm, adding methanol, carrying out ultrasonic extraction, filtering, and taking the subsequent filtrate to obtain the test solution; (2) preparation of reference substance solutions: taking tauroursodeoxycholic acid, gastrodin, sodium tanshinol, tanshinone IIA, salvianolic acid B, protocatechuic aldehyde, ginsenoside Rb1, ginsenoside Rg1,notoginsenoside R1, rheum emodin and rheinic acid reference substances which are dried under reduced pressure to constant weight, and respectively adding methanol to prepare the reference substance solutions; (3) determination: precisely measuring the test solution and the reference solution respectively, injecting the solutions into a high performance liquid chromatograph for determination, andrecording chromatograms; and (4) performing comparison according to the chromatogram and the standard comparison fingerprint, and determining that the product is qualified if the chromatogram and thestandard comparison fingerprint are consistent.

The invention relates to the technical field of medicine synthesis, and provides a cholic acid derivative as well as a preparation method and application thereof. The cholic acid derivative provided by the invention has a remarkable effect of inhibiting hepatocyte apoptosis, can effectively inhibit hepatocyte damage induced by glycochenodeoxycholic acid, and the inhibition rate of part of the derivative is superior to that of a positive control tauroursodeoxycholic acid; the cholic acid derivative provided by the invention provides a reference for research and development of liver protection drugs, and has a wide application prospect in preparation of the liver protection drugs.

The invention discloses a method for efficiently preparing tauroursodesoxycholic acid from multiple cells, and relates to the technical field of biological enzyme catalysis. The method solves the technical problems of low conversion rate, high cost, long reaction time, difficulty in industrial production and the like of an existing method for preparing the tauroursodesoxycholic acid. According to the method, a mixed enzyme solution is adopted as an enzyme system required in the reaction process to directly react to prepare the tauroursodeoxycholic acid, the mixed enzyme solution is enzyme-containing whole cells, the enzyme-containing whole cells are adopted, so that the enzyme activity is ensured, and the enzyme cost is greatly reduced; a micro-reaction concept is introduced, so that the reaction time is shortened to 30 minutes, and the time is saved; according to the preparation method, the preparation process is simplified, enzyme is recycled, the cost is saved, the preparation efficiency is also remarkably improved, and the content and the purity of a prepared TUDCA product are relatively high and reach 98% or above.

The invention relates to a method for producing tauro-ursodesoxycholic acid with 98.5 percent ursodesoxycholic acid. The method comprises the following steps: carrying out reaction of 98.5 percent ursodesoxycholic acid, ethyl acetate, ethyl chlorocarbonate, taurine and the like; and obtaining tauro-ursodesoxycholic acid, of which the effective components are the same as those of natural bear bile, through steps including delaminating, filtration, recovery, drying and the like. The method has the advantages that the problems that the herb bear bile is scarce and taking bile from a living bear is difficult are solved; the manufacturing process is simple; the raw material sources are wide; the production cost is low; the production reaches international advanced level; risks in production, transportation and storage are avoided; and the market prospect is wide.

The invention discloses a preparing method for tauro ursodesoxy cholic acid. The method comprises the following steps that firstly, ursodesoxycholic acid and a phenolic compound are added into a chloralkane organic solvent at the room temperature, the temperature is lowered to 10-20 DEG C, a condensing agent is added, thorough reaction is carried out under the temperature of 5-45 DEG C in a heat preservation mode after dripping is completed, filter liquor is concentrated after filtering to obtain a crude product, and the crude product is recrystallized to obtain a ursodesoxycholic acid phenolic ester refined product; secondly, taurine salt and a crown ether complexing agent are added into water to be dissolved, a taurine salt crown ether complex is obtained after concentration, the ursodesoxycholic acid phenolic ester refined product and the taurine salt crown ether complex are added into an organic solvent to be reacted, acid is added after thorough reaction and stirred, solids are separated out and filtered, a filter cake is dissolved in water, stirred and subjected to crystallization, and tauro ursodesoxy cholic acid is obtained. The synthetic method is low in cost, operation is simple and controllable, the product is high in yield and purity, meanwhile, the isomer impurity taurochenodeoxycholic acid of tauro ursodesoxy cholic acid can be well controlled, and the preparing method is suitable for industrial production.

The invention discloses the use of a bile acid combined marker in the preparation of a detection reagent or a detection object for predicting or diagnosing diabetes. The bile acid combined marker consists of glycocholic acid, sodium glycochenodeoxycholate, taurocholic acid, Composed of sodium taurochenodeoxycholate and sodium tauroursodeoxycholate, by detecting the concentration level of the above bile acid joint markers, the data calculated based on the above ROC curve is used to predict the risk of diabetes, with high detection sensitivity and low detection cost Low, good repeatability.

The invention discloses the application of tauroursodeoxycholic acid in anti-hand-foot-mouth virus and vesicular stomatitis virus drugs. At the stage of HFMD and vesicular stomatitis virus adsorbing and invading host cells, tauroursodeoxycholic acid can inhibit the infection of host cells by HFMD and vesicular stomatitis viruses by changing the activity of the virus itself. The HFMD virus is EV71 virus and / or CA16 virus. The tauroursodeoxycholic acid of the present invention can be used to prepare drugs against adsorption and invasion of hand-foot-mouth virus and vesicular stomatitis virus, especially drugs for hand-foot-mouth disease caused by EV71 and CA16. The invention discovers new medicinal value of TUDCA, It opens up new ideas for antiviral, prevention and / or treatment of virus adsorption invasion.

The invention relates to a method for producing tauro-ursodesoxycholic acid with 98.5 percent ursodesoxycholic acid. The method comprises the following steps: carrying out reaction of 98.5 percent ursodesoxycholic acid, ethyl acetate, ethyl chlorocarbonate, taurine and the like; and obtaining tauro-ursodesoxycholic acid, of which the effective components are the same as those of natural bear bile, through steps including delaminating, filtration, recovery, drying and the like. The method has the advantages that the problems that the herb bear bile is scarce and taking bile from a living bear is difficult are solved; the manufacturing process is simple; the raw material sources are wide; the production cost is low; the production reaches international advanced level; risks in production, transportation and storage are avoided; and the market prospect is wide.

The invention belongs to the technical field of drug quality determination methods, and in particular relates to a method for detecting impurities in tauroursodeoxycholic acid by high performance liquid chromatography. Impurity separation and limit requirements steps, in the test results, if ursodeoxycholic acid impurity ≤ 0.1%; taurochenodeoxycholic acid ≤ 0.1%, tauro nutria cholic acid ≤ 0.1%, p-nitrophenol ≤ 0.1% , the intermediate is less than or equal to 0.1%, it is a qualified quality product. The detection method in the present invention can comprehensively detect impurities in tauroursodeoxycholic acid under the same chromatographic conditions, so as to ensure the quality of the product; the operation is simple, the time is fast, the accuracy is high, the data is stable, and the cost is reduced.

The invention belongs to the technical field of chemical drug analysis, and discloses a detection method of gold-gallbladder powder. According to the detection method, high performance liquid chromatography is adopted for detection, and the conditions of the high performance liquid chromatography are as follows: a mobile phase: a mobile phase A: a tetrahydrofuran aqueous solution; and the mobile phase B is a trifluoroacetic acid methanol solution. The detection method can be used for simultaneously detecting six cholic acid substances such as tauroursodeoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, tauro-7-ketocholic acid, ursodeoxycholic acid and chenodeoxycholic acid, has the advantages of high detection accuracy, good repeatability, good stability and the like, and can meet the actual detection requirements of the quality of the golden bile powder.

The invention discloses a preparation method of mixed anhydride and an industrial preparation method of tauroursodesoxycholic acid dihydrate, ursodesoxycholic acid and alkyl chloroformate are used as raw materials to react in an organic solvent to generate the mixed anhydride, and the alkyl chloroformate comprises propyl chloroformate and / or isopropyl chloroformate; the organic solvent comprises propyl alcohol and / or isopropyl alcohol. Furthermore, the mixed anhydride is prepared by adopting the preparation method of the mixed anhydride; the method comprises the following steps: carrying out alkaline water-soluble reaction on mixed anhydride and taurine to prepare a TUDCA crude product, and refining to obtain high-quality TUDCA dihydrate. The method disclosed by the invention is beneficial to reducing impurities, improving the quality of the TUDCA, reducing the cost and being beneficial to industrial production of the TUDCA.

The invention relates to a high-purity tauroursodeoxycholic acid and a preparation method thereof. The content of tauroursodeoxycholic acid in the tauroursodeoxycholic acid of the present invention is less than 0.7%, which is safe and effective in clinical application and has no toxic or side effects; The reaction of cholic acid and ethyl chloroformate to form a mixed anhydride, through the control of reaction conditions and reaction solvents, not only realizes the advantages of simple process, low cost, environmental friendliness, and suitability for industrial production, but also can obtain high-purity taurine bear deoxycholic acid.

The invention relates to refined bear bile powder with improved bioavailability and a preparation method thereof. Specifically, one aspect of the present invention relates to the compound shown in formula I: the compound, which uses Cu-Kα radiation, in the powder X-ray diffraction pattern represented by 2θ angle, at 8.53±0.20°, 10.96±0.20°, 12.03 There are diffraction peaks at ±0.20°, 13.14±0.20°, 14.82±0.20°, 17.26±0.20°, 22.53±0.20°, 24.21±0.20°, 26.68±0.20°, 29.42±0.20°, 31.24±0.20°. The compound exhibits excellent biological properties such as excellent bioavailability, and can exert the same physiological activity as bear bile powder or tauroursodeoxycholic acid.

The invention relates to a method for detecting related substance in tauroursodeoxycholic acid, and especially relates to a method using a HPLC-ELSD technology to simultaneously detect eight related substances in tauroursodeoxycholic acid. According to the method, an octyl bonded silica gel chromatographic column and an evaporative light-scattering detector are adopted; and a mobile phase (A) and a mobile phase (B) are mixed to carry out isocratic elution or gradient elution, wherein the mobile phase (A) is an ammonium salt buffer solution with a concentration of 2.5 to 50 mmol / L, and the mobile phase (B) is methanol or acetonitrile. The provided method has the advantages of simpleness, rapidness, accuracy, reliability, and good resolution of chromatographic peaks, and is capable of simultaneously detecting eight related substances in tauroursodeoxycholic acid quantitatively or qualitatively.