69 results about "Tauroursodeoxycholic acid" patented technology

Endoplasmic reticulum stress has been found to be associated with obesity. Therefore, agents that reduce or prevent ER stress may be used to treat diseases associated with obesity including peripheral insulin resistance, hypergylcemia, and type 2 diabetes. Two compounds which have been shown to reduce ER stress and to reduce blood glucose levels include 4-phenyl butyric acid (PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO). Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide and glycerol. The present invention provides methods of treating a subject suffering from obesity, hyperglycemia, type 2 diabetes, or insulin resistance using ER stress reducers such as PBA, TUDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in ER stressed cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating obesity-associated diseases.

The invention provides compounds and pharmaceutical compositions that can be used to treat or prevent atherosclerosis, stroke, and other ischemic vascular diseases, dyslipidemia and hypercholestcrolemia and prevent complications of these conditions. Agents in accordance with the invention include; tauroursodeoxycholic acid (TUDCA), and analogs and derivatives thereof; 4-phenyl butyric acid (PBA), and analogs and derivatives thereof; and trimethyl N-oxide (TMAO), and analogs and derivatives thereof.

The present invention relates to a artificial bear gall and its preparation method. Its composition includes sodium taurodeoxycholate, mixed bile pigments, amino acid, mineral elements, rice bean oil, cholesterol and lecithin. Said invented artificial bear gall can be substituted for natural bear gall.

The invention discloses pharmaceutical application of tauroursodeoxycholic acid and acceptable salts thereof. The tauroursodeoxycholic acid can reduce the expression and activity of cancer genes Yap and inhibit the activity of a UPR (unfolded protein response) signal channel component; and as verified in two liver cancer models with Yap activation and UPR signal channel activation functions, the tauroursodeoxycholic acid has an effect of preventing and treating a liver cancer, and has a certain application prospect in preparation of a medicament for preventing and treating the liver cancer, particularly in preparation of a medicament for preventing and treating the liver cancer caused by Yap activation or UPR signal channel activation.

The invention discloses a tauroursodeoxycholic acid capsule and a preparation method thereof. The prescription of the tauroursodeoxycholic acid capsule is prepared from the following raw materials by weight: 220-280g of tauroursodeoxycholic acid, 22-28g of starch, 25-35g of lactose, 5-7g of microcrystalline cellulose, 1-2g of hydroxypropyl methylcellulose, 1-2g of magnesium stearate and 2-5g of hydroxy propyl cellulose. Through different proportions of the prescription, a proper adhesive, a stabilizer and a disintegrating agent are adopted, so that the dissolution behavior of the prepared capsule preparation is equivalent to or the same as that of a columnar compression powder capsule.

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 relates to hydroxysteroid dehydrogenase, and in particular to 7alpha-hydroxysteroid dehydrogenase (St-2-2) mutants. The amino acid sequences of the mutants are shown as SEQ ID NO:2, 3, 4, 5, 6, 7, 8, 9 or 10, and are obtained by changing the 255th amino acid of the 7alpha-hydroxysteroid dehydrogenase with an amino acid sequence of SEQ ID NO:1 from Ile to Tyr, Gln, Leu, Thr, Gly, Asn,Ser, Ala or Phe. In the presence of same substrates TCDCA and NADP<+>, enzyme activity of the mutants is respectively 1.49, 1.78, 1.79, 1.79, 1.93, 2.44, 2.58, 2.97 and 3.34 times of enzyme activityof a wild type hydroxysteroid dehydrogenase, and the mutant has a great application potential in a process of obtaining tauroursodeoxycholic acid (TUDCA) through biotransformation of taurochenodeoxycholic acid (TCDCA).

The invention relates to a method for producing and preparing artificial bear gall powder through the optimized engineering bacteria fermentation technology, and belongs to the field of biotechnology. Escherichia coli simultaneously expressing 7alpha-hydroxysteroid dehydrogenase (7alpha-HSDH) and 7beta-hydroxysteroid dehydrogenase (7beta-HSDH) is used for liquid fermentation, taurochenodeoxycholic acid in poultry bile products like chicken gall powder is directly converted into tauroursodeoxycholic acid in a certain proportion, the fermentation process is simple and quick, conditions are mild, and pollution is not caused. Fermentation results are stable and controllable, the conversion rate is high, and the number of intermediate products is small. The method plays an important role in the biotechnology production of bear gall powder substitute resources.

The present invention discloses a tauroursodeoxycholic acid synthesis method, which comprises that chenodeoxycholic acid is adopted as a raw material, the chenodeoxycholic acid and N-hydroxy succinimide or N-hydroxyphthalimide are subjected to condensation under effects of a condensation agent and a catalyst to obtain an active ester, the active ester reacts with sodium taurocholate to obtain taurochenodeoxycholic acid, and further an oxidation reaction and a reduction reaction are performed to synthesize the tauroursodeoxycholic acid. The synthesis method of the present invention adopts the chenodeoxycholic acid as the raw material, and has characteristics of low cost, simple and controllable purification process, high target product purity, and easy industrialization.

The invention relates to a phosphatidyl choline freeze powder injection and relative preparation, wherein said formula is formed by phosphatidyl choline, solubilizer, support agent and other additive components; the phosphatidyl choline content is 10-60%; the solubilizer can colalin, glycocholic acid, cholaic acid, deoxycholic acid, anthrodsoxycholic acid, or taurodeoxycholic acid and relative salt, loxapine and tween; the support agent can be freeze protector. The invention has high stability, which can be stored for 1 year at normal temperature, without allergic and excitation.

The present invention relates to the technical field of biomedicine, and mainly provides new uses of tauroursodeoxycholic acid, wherein the new uses comprise that the tauroursodeoxycholic acid inhibits the virus-entry-host cells adopting endocytosis so as to achieve prevention and treatment of virus infection, anti-injury, and anti-fibrosis. The present invention provides applications of the tauroursodeoxycholic acid in preparation of drugs for treatment of acute lung injury and pulmonary fibrosis, such that the application range of the tauroursodeoxycholic acid is broadened, and the new drug selection is provided for the virus infection patients. According to the present invention, it is confirmed that the tauroursodeoxycholic acid can effectively prevent and treat H5N1 avian influenza virus, human adenovirus and Zaire-type Ebola virus, and it is cleared that the pulmonary fibrosis prevention and control effect of the tauroursodeoxycholic acid is superior to the pulmonary fibrosis prevention and control effect of the chloroquine.

The invention discloses a preparation method of bear bile, which comprises the following steps: incising a wound on the gall bladder of a bear, forming a fistula with muscular tissues and binding up; and extruding a fistula orifice after healing so as to collect the bile. The method can be used for non-continuous, timing, quantitative and long-term collection, and can avoid affecting the utilization of the bile of the bear. The invention discloses high-quality bear bile powder and the preparation method thereof. The bear bile powder shows bright yellow fluorescence under a 365nm ultraviolet lamp and has three chromatographic peaks under 198nm. The preparation method of the powder comprises the steps of standing the bile, separating and drying the powder, and then crushing and screening the powder so as to get the bear bile powder. The prepared bear bile powder is pure in color and luster of appearance, high in the content of tauroursodeoxycholic acid, does not absorb moisture and is convenient to store, transport and process.

The invention relates to a method for synthesizing ursodesoxycholic acid and tauroursodeoxycholic acid from swine bile. The method comprises the following steps: extracting mixed cholic acid, separating the mixed cholic acid and synthesizing the ursodesoxycholic acid and the tauroursodeoxycholic acid; the method is characterized by utilizing the swine bile as a raw material, and carrying out front-end impurity removing by adopting enzymolysis, ultrafiltration and nanofiltration methods, thus extracting the mixed cholic acid; separating the extracted mixed cholic acid; then synthesizing the ursodesoxycholic acid and the tauroursodeoxycholic acid. By adopting the method disclosed by the invention, the raw material is wide and easy to obtain, the purity of the tauroursodeoxycholic acid is high, the conversion rate is high, the repeatability is good, the cost is lower, the operation is simple, the preparation technology is simple, environment friendliness is realized, the method is more suitable for industrial production and is beneficial for saving resources and reducing energy consumption, economic benefit and environmental benefit are obvious, and sustainable development of an industry can be promoted.

The invention discloses a method for detecting five kinds of taurine-bound bile acids in serum by using high performance liquid chromatography tandem mass spectrometry, comprising the following steps: preparation of standard products, separation by high performance liquid chromatography, detection by tandem mass spectrometry, taurine in serum Detection of conjugated bile acids, qualitative and precise quantitative detection of five kinds of taurine-conjugated serum including tauroursodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid and taurolithocholic acid Type bile acid, short detection time, high efficiency, high detection sensitivity, good specificity, and low cost.

It is provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and / or treatment of trans-thyretin-associated amyloidosis. It is also provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and / or treatment of transthyretin-associated amyloidosis in combination therapy with another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline, or epigallocatechin-3-gallate.

The invention discloses a culture solution for a cell source for a bioartificial liver. The culture solution comprises a mixed solution comprising a low-sugar type DMEM culture solution and fetal bovine serum according to the volume ratio of (8-12): 1, wherein the mixed solution further contains 60-140U / L of insulin, 3-9mu g / L of hepatocyte growth factor, 0.5-2g / L of magnesium isoglycyrrhizinate, 3-10mg / L of tauroursodeoxycholic acid and 50-100U / ml of green chain double-antibody. The culture solution for the cell source for the bioartificial liver disclosed by the invention can promote the growth of hepatocytes or hepatocyte-like cells, is conductive to developing the cells to the direction of better realizing liver functions, particularly can effectively improve the survival rate and the survival time of the cells in a hyperbilirubinemia environment and improve the curative effect by improving an existing DMEM culture medium and adding insulin for protecting the hepatocytes, hepatocyte growth factor, magnesium isoglycyrrhizinate and tauroursodeoxycholic acid. The culture solution is suitable for culturing various hepatocytes and hepatocyte-like cells, in particular to L-02 cells.

An artificial medical snake gall for treating cough, asthma, inflammation, etc and resolving phlegm contains at least 3 composite bile acids (taurocholic acid, tauro-chenodeoxycholic acid and taurodeoxycholic acid), as well as mucoprotein, cholesterol, lecithin, free bile acid, pile pigment, amino acid, trace elements, etc.

It is provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and / or treatment of transthyretin-associated amyloidosis. It is also provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and / or treatment of transthyretin-associated amyloidosis in combination therapy with another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline, or epigallocatechin-3-gallate.

The invention discloses a synthetic method of tauroursodeoxycholic acid. The synthetic method comprises the following steps: taking extracted or synthetic taurochenodeoxycholic acid as a raw material,obtaining a target product tauroursodeoxycholic acid crude product through 7 alpha-hydroxyl selective oxidation, 3 alpha-hydroxyl protection, 7-carbonyl selective oxidation, 7 alpha-hydroxyl sulfonylation, detosylation and alkaline hydrolysis reactions of the taurochenodeoxycholic acid, and finally obtaining the high-purity tauroursodeoxycholic acid through recrystallization purification. The tauroursodeoxycholic acid is obtained by using low-cost poultry bile as the raw material, the traditional steps of hydrolyzing and then condensing combined chenodeoxycholic acid are omitted, and a taurylamine structure is obtained directly; the target configuration product is obtained through selective oxidation, selective reduction and stereoselectivity elimination; in the whole technology, using high alkali, metallic sodium or valuable catalysts is avoided, and the whole technology presents a relatively efficient and safe chemical synthetic route. The technological process has the advantages ofbeing simple and controllable, high in purity, efficient, safe, environmentally-friendly and easy for industrialization, and has good application prospects in the field of pharmacy.

An artificial medical snake gall for treating cough, asthma, inflammation, etc and resolving phlegm is prepared from taurocholic acid, extract of chicken bile, cholesterol, mucoprotein, ZnSO4.7H2O, calcium gluconate, sodium bicarbonate, taurine, and optional taurodeoxycholic acid and / or the extract of rabbit gile. Its preparing process is also disclosed.

The invention discloses a primary hepatocyte cryopreservation solution, a hepatocyte cryopreservation method and a hepatocyte recovery method, and belongs to the field of primary hepatocyte cryopreservation and recovery. The primary hepatocyte cryopreservation solution comprises, by volume, 45% of a solution A, 10-45% of fetal bovine serum, 10% of dimethyl sulfoxide, and 0-35% of water, and the solution A comprises D-glucose, hydroxyethyl starch, lactobionic acid, polyvinylpyrrolidone, D-raffinose pentahydrate, potassium hydroxide, potassium dihydrogen phosphate, magnesium sulfate heptahydrate, adenosine, reduced glutathione, allopurinol, tauroursodeoxycholic acid, and diammonium glycyrrhizinate. The invention also discloses the hepatocyte cryopreservation method and the hepatocyte recovery method. The primary hepatocyte cryopreservation solution can reduce the damages of the primary hepatocytes in the cryopreservation process and improve the vitality and adherence efficiency of the primary hepatocytes after thawing, and can be widely used in basic research and new drug development for livers.

The invention discloses application of tauroursodeoxycholic acid salt used as an active ingredient in preparation of a drug for treating echinococcosis. The tauroursodeoxycholic acid salt is used as the active ingredient for killing pathogen-echinococcus granulosus of the echinococcosis; an obvious echinococcosis protoscolex restraining and killing effect is achieved, and thus, the treatment of the echinococcosis is realized.

The invention relates to refined bear gall powder for reducing blood fat and preventing and treating heart cerebrovascular disease and atherosclerosis, in particular to an application of a compound represented as the formula I in preparation of products for reducing blood fat and cholesterol, preventing and / or treating the heart cerebrovascular disease and preventing and / or treating the atherosclerosis. The compound adopts Cu-Kalpha radiation and has diffraction peaks at angles of 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 in a powder X-ray diffraction pattern representedby the 2-theta angle. The compound shows excellent biological performance such as excellent bioavailability and can play physiological activity the same as that of bear gall powder or tauroursodeoxycholic acid. For instance, the refined bear gall powder can be used for reducing blood fat and cholesterol, preventing and / or treating the heart cerebrovascular disease and preventing and / or treating the atherosclerosis.

The invention relates to refined bear gall powder and application thereof in treating cholecystitis gall-stones and improving gall bladder functions. Specifically, on one hand, the invention relates to application of a compound of a formula I shown in the specification in preparing products for preventing or treating gall-stone diseases, preventing or treating cholecystitis and improving gall bladder functions. Under Cu-Ka radiation, the compound has diffraction peaks 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 in a powder X-ray diffraction spectrum expressed with 2theta angles. The compoundhas excellent biological properties such as excellent bioavailability, and in addition, physiological activity identical to that of bear gall powder or tauroursodeoxycholic acid can be taken into play. For example, the compound can be adopted to prevent or treat gall-stone diseases, prevent or treat cholecystitis and improve gall bladder functions.

The invention relates to a feed additive, in particular to a pig feed additive. The additive can significantly enhance the growth and production performance of pigs, improve the nutrition and health of pigs under various emergency states, reduce the diarrhea rate and death rate of pigs, lower the feed-meat ratio, and increase the feed conversion rate. The compound feed additive is prepared from raw materials gamma-aminobutyric acid, tauroursodeoxycholic acid, resveratrol, rabdosiae herba, pyrola, common scouring rush herb, Xuanzhou papaya, Cynanchum glaucescens, Chinese mahonia leaf, Fructus Toosendan, Patrinia heterophylla, Nelumbo nucifera Gaerth, Pouzolzia zeylanica herb with root, Lysimachia clethroides Duby, bacillus licheniformis freeze-dried powder, clostridium butyricum freeze-dried powder, and a carrier, and the carrier is a mixture of corn flour and soybean meal.

The invention discloses a method for preparing poultry artificial bear bile powder. The method comprises the following steps: regulating pH of fresh poultry bile to be 3-4 at normal temperature with diluted hydrochloric acid; slowly adding sodium peroxide into the bile in batches under a slowly stirring state according to the mass ratio of bile to sodium peroxide being 1:(0.013-0.017), and stirring to react for 8-12 hours at normal temperature; adding metal sodium into the bile under a slowly stirring state according to the mass ratio of bile to metal sodium being 1:(0.008-0.010), and reacting for 3.5-4.5 hours at normal temperature; and regulating pH of the bile to 8-9 with diluted hydrochloric acid after the reaction is completed, drying in vacuum and grinding at 55-65 DEG C to obtain the poultry artificial bear bile powder. The preparation method is simple and has high efficiency, the final product of oxidant and reducing agent in the reacting process is sodium chloride, other heavy metal particles are not introduced, and the quality of bear bile powder cannot be influenced. The content of tauroursodeoxycholic acid in a bear bile powder product is more than 38.5 percent.

Provided is a method for preventing or treating a periodontal disease; or a method for improving oral hygiene, including administering a pharmaceutical composition containing tauroursodeoxycholic acid as an active ingredient.

Methods of preventing or retarding or reversing or abolishing the onset and preventing the onset of neurodegenerative disease are discussed. This is achieved through the administration of a bile acid, a salt of the bile acid, an analog of the bile acid or any combinations of these compounds. The bile acid abolishes or interferes or down-regulates metabolic pathways leading to the onset of neurodegenerative diseases. The bile acid also activates metabolic pathways leading to the slowing or reversing or complete abolishment of the progression of neurodegenerative disease.

The invention discloses a process for preparing a tauroursodeoxycholic acid hydrate, which comprises the steps of reacting chenodeoxycholic acid with acyl chloride compound to obtain chenodeoxycholic acid mixed anhydride in an anhydrous organic solvent with ketone groups and in presence of an acid scavenger; reacting the chenodeoxycholic acid mixed anhydride with igepon with water under an alkaling condition to obtain taurine chenodeoxycholic acid; reacting the taurine chenodeoxycholic acid with an oxidizing agent in presence of water under an alkaling condition to obtain taurine-7-ketone group gallstone acid; leading hydrogen into the taurine-7- ketone group gallstone acid under the condition of chiral catalyst and alkalinity and maintaining a certain pressure and temperature for a hydrogenation reduction reaction to obtain the tauroursodeoxycholic acid; mingling the tauroursodeoxycholic acid with the mixed organic solvent to obtain the tauroursodeoxycholic acid hydrate. The tauroursodeoxycholic acid hydrate has the advantages of being low in cost, safe in process, good in production quality, and applicable to industrialization.