48 results about "Ursodeoxycholic acid" patented technology

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.

This invention provides a 7β-HSDH enzyme mutant, its encoding gene, and its applications. Through artificial mutation screening, 7α-HSDH and 7β-HSDH enzyme mutants with specific amino acid sequences were identified, resulting in improved enzyme activity and catalytic efficiency compared to wild-type 7α-HSDH and wild-type 7β-HSDH. This invention also provides a method for preparing ursodeoxycholic acid using the aforementioned 7α-HSDH and 7β-HSDH enzyme mutants, specifically using NADP... + A one-pot catalytic method for the conversion of chenodeoxycholic acid to ursodeoxycholic acid using NADPH-dependent 7α-HSDH enzyme mutants and NADPH-dependent 7β-HSDH enzyme mutants is employed. This method is simple, yields high product conversion, and can also achieve the conversion of the coenzyme NADP. + / NADPH's self-circulating regeneration eliminates the need for auxiliary enzymes and raw materials used in coenzyme regeneration, greatly reducing production costs and environmental pressure, and possessing enormous potential for industrial applications.

The present invention relates to a composition for preventing, alleviating or treating metabolic diseases, the composition comprising a rosuvastatin and ursodeoxycholic acid conjugate or a pharmaceutically acceptable salt thereof, in which the statin conjugates to an ursodeoxycholic acid transporter and has the effects of function inhibition, cholesterol level reduction, antilipid toxicity, body weight reduction, blood lipid reduction, fatty liver alleviation, inflammation alleviation, and kidney damage alleviation. The composition, in the form of a single formulation, has the characteristics of maintaining the therapeutic effects of rosuvastatin and ursodeoxycholic acid while reducing the side effects of existing statins, and thus can be widely used as a substitute for complex formulations in the treatment of metabolic diseases.

Disclosed are a crystalline form of a high-stability nor-ursodeoxycholic berberine salt and a preparation method therefor, while relate to the field of pharmaceutical chemistry. The crystalline form has the following structural formula. In X-ray powder diffraction of the crystalline form, a 2θ diffraction angle has characteristic peaks at 3.54+ / -0.2 degrees, 7.13+ / -0.2 degrees, 13.14+ / -0.2 degrees, 15.95+ / -0.2 degrees, 16.40+ / -0.2 degrees, 18.64+ / -0.2 degrees, 24.90+ / -0.2 degrees, 25.76+ / -0.2 degrees and 26.30+ / -0.2 degrees. Compared with other crystalline forms of the nor-ursodeoxycholic berberine salt, the crystalline form has more excellent stability, and has a good application prospect in the preparation of high-quality solid chemical drugs.

The invention provides a mutant R41D / S193N of 7beta-hydroxysteroid oxidative dehydrogenase, a gene sequence of the mutant enzyme, a recombinant expression vector containing the gene sequence of the enzyme and an engineering strain containing the vector. The invention also provides a construction method of a recombinant expression vector and an engineering strain, a method for preparing the mutant enzyme by using the engineering strain, and application of the mutant enzyme in in-vitro enzyme catalysis of 7-ketolithocholic acid to produce ursodeoxycholic acid. Compared with a wild type, the R41D / S193N mutant provided by the invention shows stronger preference on a cofactor NADH, is more economical than the traditional NADPH utilization, is simple and convenient in preparation process, high in yield and simple in downstream treatment process, does not involve other solvents except water in the preparation process, belongs to a green biosynthesis method, and is suitable for industrial production. Meanwhile, the method has relatively high atom economy and step economy.

This invention relates to the field of traditional Chinese medicine technology, specifically to a composition for clearing heat and detoxifying, protecting the liver and improving eyesight, its pharmaceutical preparation and application. The raw materials of the composition, by weight, include the following components: 10-30 parts ursodeoxycholic acid, 1-5 parts chenodeoxycholic acid, 5-15 parts Lycium barbarum polysaccharide, 5-18 parts betaine, 1-5 parts glycyrrhizic acid, 0.2-5 parts glycyrrhetinic acid, and 1-5 parts glycyrrhizin. This invention combines these components to achieve the effects of clearing heat and detoxifying, protecting the liver and improving eyesight. Pharmacological experiments have demonstrated that it has significant antipyretic effects, prevents and treats eye fatigue, and improves acute liver injury.

The invention discloses application of fungal cytochrome P450 enzyme, and belongs to the technical field of biological enzyme catalysis. The fungal cytochrome P450 enzyme is derived from Gibberella fujikuroi, and the amino acid of the fungal cytochrome P450 enzyme is as shown in SEQ ID NO. 1 or has at least 80% similarity with the sequence as shown in SEQ ID NO. 1; the fungal cytochrome P450 enzyme at least can catalyze 7beta hydroxylation of five steroids L1, L2, L3, L4 and L5, and has excellent selectivity and high yield, and corresponding hydroxylation products can directly or indirectly generate ursodesoxycholic acid. The invention provides a good prospect for synthesizing ursodesoxycholic acid more environmentally and efficiently by using a biological enzyme method.

The application discloses a 7beta-hydroxysteroid dehydrogenase mutant and application thereof, relates to the field of bioengineering technology, and is designed and reformed according to the amino acid sequence of wild-type 7beta-hydroxysteroid dehydrogenase derived from Collinsella aerofaciens, that is, 17 single-mutation sites or 7 combined-mutation sites of 7beta-hydroxysteroid dehydrogenase are provided, the obtained 7beta-hydroxysteroid dehydrogenase mutant has the thermal stability increased by 2-21.5 DEG C and the activity increased by nearly 1.2-2.24 times compared with the wild-type 7beta-hydroxysteroid dehydrogenase. According to the mutation sites with obvious increase in thermal stability and activity, three preferred mutant proteins are further provided, the three preferred mutant proteins have higher yield, activity and thermal stability compared with the wild-type 7beta-hydroxysteroid dehydrogenase, have wider application conditions, are more suitable for the efficient production of ursodeoxycholic acid by the bioconversion method, and are favorable for large-scale production and industrial application.

The invention discloses a ruminococcus torsionosus-sourced 7beta-HSDH enzyme mutant and application thereof, the ruminococcus torsionosus-sourced 7beta-HSDH enzyme is taken as a research object, a series of single-point mutation and combined mutation of the 7beta-HSDH enzyme are provided, and compared with wild type 7beta-HSDH enzyme, the thermal stability of the 7beta-HSDH enzyme mutant is improved by 1-20 DEG C, and the 7beta-HSDH enzyme mutant has the advantages that the 7beta-HSDH enzyme mutant has the advantages that the 7beta-HSDH enzyme mutant can be used for preparing the 7beta-HSDH enzyme mutant; compared with a wild type 7beta-HSDH enzyme, the 7 beta-HSDH enzyme has the advantages that the Tm value of the (C217I and E252K) mutant is improved by 1.2-4.2 times, the enzyme activity of the (C217I and E252K) mutant is 4.2 times that of the wild type 7beta-HSDH enzyme, and the (T103I, D251K, L229K and S161A) mutant has ultrahigh heat stability, the Tm value is close to 68 DEG C, and 50% of enzyme activity is maintained, so that the 7 beta-HSDH enzyme can be used for preparing the 7 beta-HSDH enzyme. Compared with a wild type 7 beta-HSDH enzyme, the 7 beta-HSDH enzyme mutant provided by the invention has wider application conditions, is more suitable for efficiently producing ursodesoxycholic acid from 3 alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KLCA) by a biological conversion method, and is beneficial to large-scale production and industrial application.

The invention provides application of ursodesoxycholic acid in preparation of a medicine for treating peripheral neuropathy. The ursodesoxycholic acid provided by the invention can promote the recovery of sciatic nerve function indexes after the sciatic nerve of a mouse is cut off, and improve the electroneurographic signal conduction function of an injured part; meanwhile, the UDCA can also relieve oxaliplatin-induced ischiadic nerve signal transduction disorder of mice and related crymodynia sensitive symptoms. In addition, the invention further reveals that the relieving effect of the UDCA on the peripheral neuropathy does not depend on promoting Schwann cell migration. According to the discovery, the application value of the UDCA in treating peripheral neuropathy caused by multiple factors is expanded, and a new strategy is provided for clinical treatment of the UDCA.

The invention provides application of ursodesoxycholic acid or a stereoisomer, a prodrug, a crystal form, a pharmaceutically acceptable salt, a pharmaceutically acceptable ester or a pharmaceutically acceptable solvate of ursodesoxycholic acid to preparation of a medicine for treating intrahepatic cholangiocellular carcinoma and a medicine composition for treating the intrahepatic cholangiocellular carcinoma. The invention provides application of ursodesoxycholic acid in treatment of intrahepatic cholangiocellular carcinoma, and application of ursodesoxycholic acid can significantly inhibit growth of tumors and significantly prolong survival time of tested animals. The invention also provides a pharmaceutical composition containing ursodesoxycholic acid and an immune checkpoint inhibitor for treating intrahepatic cholangiocellular carcinoma, and solves the technical problems that in the prior art, an accurate treatment means for reversing CD8 + T cell depletion in intrahepatic cholangiocellular carcinoma is lacked, and an existing treatment method is large in side effect, limited in effect and the like. The invention provides a novel strategy for treating the intrahepatic cholangiocellular carcinoma, and has high clinical application value and wide application prospect.

This application relates to the field of feed, specifically to the application of UDCA in the preparation of formulations that reduce the incidence of intrauterine growth retardation (IUGR) in pregnant sows. According to the technical solution of this application, by adding 0.05% ursodeoxycholic acid to the diet of sows during late gestation (85 days) to the farrowing stage, using a restricted feeding method, at a rate of 2 kg / head / day, twice daily, the incidence of IUGR in sows can be effectively reduced by up to 76.17%, while also increasing the average weaning weight of piglets at 28 days by 9.61%.

The invention discloses a 7beta-HSDH enzyme mutant from active ruminococcus and application thereof, the 7beta-HSDH enzyme from active ruminococcus is taken as a research object, a series of single-point mutations and combined mutations of the 7beta-HSDH enzyme are provided, the thermal stability of the 7beta-HSDH enzyme mutant is improved by 1.3-11.8 DEG C compared with that of wild type 7beta-HSDH enzyme, and the 7beta-HSDH enzyme mutant has the advantages that the 7beta-HSDH enzyme mutant can be used for preparing the 7beta-HSDH enzyme mutant. The 7 beta-HSDH enzyme has the advantages that the activity of the 7 beta-HSDH enzyme is maintained at 90-230%, the thermal stability and the enzyme activity of the (E182L, Q155L and T103I) mutant and the V91N mutant are improved compared with those of the wild type 7 beta-HSDH enzyme, the enzyme activity of the V91N mutant is 2.3 times that of the wild type 7 beta-HSDH enzyme, the Tm value of the (E182L, Q155L and T103I) is close to 60 DEG C, and the activity of the V91N mutant is 1.7 times higher than that of the wild type 7 beta-HSDH enzyme. Therefore, compared with a wild type 7 beta-HSDH enzyme, the 7 beta-HSDH enzyme mutant provided by the invention has wider application conditions, is more suitable for efficiently producing ursodesoxycholic acid from 3 alpha-hydroxy-7-oxo-5beta-cholanic acid by a biological conversion method, and is beneficial to large-scale production and industrial application.

The present application relates to the biomedical field, and specifically provides a copper-based nano-enzyme, a preparation method and application thereof, aiming to solve the problems of diagnosis difficulty and lack of effective treatment drugs in the prior art for the treatment of primary sclerosing cholangitis (PSC) in clinical practice. To this end, the copper-based nano-enzyme comprises: a nano-enzyme carrier, which is a two-dimensional nanosheet formed by coordination bonds between copper ions, gallic acid and ursodeoxycholic acid; and a probe molecule, which is a phycobilin dye molecule connected to the surface of the nano-enzyme carrier by a covalent bond; wherein the copper-based nano-enzyme has enhanced fluorescence intensity after the action of alkaline phosphatase. The present application innovatively integrates alkaline phosphatase-responsive diagnosis, nano-enzyme catalytic treatment and liver targeting of ursodeoxycholic acid into one nano-platform, can perform treatment functions while performing specific imaging diagnosis on diseases, and provides a new strategy for the diagnosis and treatment of PSC and other diseases.

This invention provides a 7α-HSDH enzyme mutant and a 7β-HSDH enzyme mutant, their encoding genes, and their applications. Through artificial mutation screening, 7α-HSDH and 7β-HSDH enzyme mutants with specific amino acid sequences were identified, resulting in improved enzyme activity and catalytic efficiency compared to wild-type 7α-HSDH and wild-type 7β-HSDH. This invention also provides a method for preparing ursodeoxycholic acid using the aforementioned 7α-HSDH and 7β-HSDH enzyme mutants, specifically using NADP... + A one-pot catalytic method for the conversion of chenodeoxycholic acid to ursodeoxycholic acid using NADPH-dependent 7α-HSDH enzyme mutants and NADPH-dependent 7β-HSDH enzyme mutants is employed. This method is simple, yields high product conversion, and can also achieve the conversion of the coenzyme NADP. + / NADPH's self-circulating regeneration eliminates the need for auxiliary enzymes and raw materials used in coenzyme regeneration, greatly reducing production costs and environmental pressure, and possessing enormous potential for industrial applications.

The invention relates to the technical field of biological enzyme engineering, in particular to a 3beta-hydroxysteroid dehydrogenase mutant and application thereof. The 3beta-hydroxysteroid dehydrogenase mutant provided by the invention is obtained by carrying out point mutation on an amino acid sequence shown by wild type 3beta-hydroxysteroid dehydrogenase. Compared with a wild enzyme, the 3beta-hydroxysteroid dehydrogenase mutant constructed by the invention has the advantages that the enzyme activity of the mutant is greatly improved and is 1.68-3.30 times that of a parent, and the use amount of an industrial enzyme can be remarkably reduced. Meanwhile, the mutant can specifically oxidize 3beta-ursodesoxycholic acid to generate 3ketoursodesoxycholic acid, and then the 3ketoursodesoxycholic acid is converted into ursodesoxycholic acid under the action of 3alpha-hydroxysteroid dehydrogenase, so that the defect that 3beta-ursodesoxycholic acid impurities generated in the ursodesoxycholic acid chemical synthesis process are difficult to remove is overcome; and a wide application prospect is provided for industrial production of ursodesoxycholic acid.

The application belongs to the technical field of biological medicine, and particularly relates to application of lenvatinib combined with ursodeoxycholic acid in liver cancer treatment. Specifically, the application constructs a cell strain Huh7R of human liver cancer cell Huh7 cells resistant to lenvatinib to carry out experiments. The results show that lenvatinib and UDCA can produce a synergistic inhibitory effect on HCC at multiple concentrations. Further, animal experiments also confirm the anti-HCC effect of the drug combination. The application provides a method capable of effectively inhibiting HCC progression, thereby overcoming the drug resistance problem of lenvatinib in clinical treatment, bringing new treatment options for liver cancer patients, and hopefully improving tumor treatment effect and improving the quality of life of patients, and therefore has important clinical significance and social value.

The invention provides a biomarker for predicting the prognosis effect of ursodesoxycholic acid for primary biliary cholangitis and application of the biomarker, and belongs to the technical field of biomarkers. The biomarker disclosed by the invention comprises an activating agent AHSA1 of a 90 kDa heat shock protein ATPase homolog 1 and a glycosylated form C4BN226HexNAc (2) Hex( 7) of a complement C4-B. The invention further discloses a preparation method of the biomarker. According to the method, the improvement of the PBC medication efficiency is taken as a starting point, the serum protein and the N-glycopeptide are taken as screening templates, a more accurate non-invasive prediction means for the curative effect of the PBC medication UDCA is provided, and a theoretical basis is provided for personalized treatment of PBC.

This invention discloses genetically engineered bacteria and their applications, belonging to the field of bioengineering technology. By constructing a system that enhances the expression of polyphosphate kinase 2-I, polyphosphate kinase 2-II, and peptide bond synthase, this invention establishes an ATP recycling system, effectively ensuring the continuous execution of enzyme-catalyzed reactions. Using ursodeoxycholic acid or glycine and taurine as substrates, the genetically engineered bacteria expressing these three enzymes generate tauroursodeoxycholic acid or glycoursodeoxycholic acid, increasing the yield of these enzymes and achieving efficient biosynthesis of tauroursodeoxycholic acid or glycoursodeoxycholic acid, demonstrating promising prospects for industrial application.

The present application belongs to the field of aquaculture and nutrition regulation technology, and particularly relates to a ursodeoxycholic acid preparation for inducing the group behavior of juvenile fish, a preparation method and application. The ursodeoxycholic acid preparation for inducing the group behavior of juvenile fish is composed of ursodeoxycholic acid and additives equivalent to 0% to 2% of the mass of ursodeoxycholic acid; the additives are cholic acid or a mixed agent, and the mixed agent is a mixture of taurine and tryptophan in a mass ratio of 1:1. After the ursodeoxycholic acid preparation for inducing the group behavior of juvenile fish is used to feed large yellow croaker juveniles, the juvenile fish olfaction can be stimulated, the group behavior of the juvenile fish can be induced, the growth of the large yellow croaker juveniles can be promoted, the metabolism can be promoted, and the immunity can be improved.

The present invention belongs to the field of bioengineering technologies, and in particular, to a production method of recombinant Escherichia coli (E. coli) and high-purity ursodeoxycholic acid (UDCA). The present invention constructs novel double-enzyme co-expression gene engineered bacteria, that is, recombinant E. coli. The bacteria simultaneously expresses 7β-hydroxysteroid dehydrogenase (7β-HSDH) and glucose dehydrogenase (GDH). The bacteria is applicable to the production of high-purity UDCA. The yield of a target product is increased through the joint expression and application of 7β-HSDH and GDH. The production method of high-purity UDCA in the present invention is simple, generates a small amount of impurities in a production process, is a green process that satisfies environmental protection requirements, and has significant industrial application value.

The invention belongs to the technical field of medical chemistry, and particularly discloses a eutectic salt formed by palmatine hydrochloride and bezoar ursodesoxycholic acid, the chemical structural formula of the eutectic salt is shown as a formula A. The crystal form of the eutectic salt is characterized in that characteristic peaks exist at the positions of 4.3 + / -0.2 degrees, 6.0 + / -0.2 degrees, 8.7 + / -0.2 degrees, 12.2 + / -0.2 degrees, 13.4 + / -0.2 degrees, 14.7 + / -0.2 degrees, 16.3 + / -0.2 degrees, 17.2 + / -0.2 degrees, 21.0 + / -0.2 degrees, 22.1 + / -0.2 degrees, 23.0 + / -0.2 degrees and 24.4 + / -0.2 degrees in an X-ray powder diffraction pattern expressed by a 2theta diffraction angle. The eutectic salt formed through intermolecular interaction can significantly improve the crystallization property of the bezoar ursodesoxycholic acid, thereby enhancing the drug processability and bioavailability. Meanwhile, the eutectic salt disclosed by the invention has excellent crystal stability, and provides basic structure guarantee for subsequent storage, safety and preparation development of the eutectic salt. Formula A

The invention discloses a natural product composition for resisting pulmonary fibrosis. The natural product composition is prepared from baicalin and ursodesoxycholic acid in a mass ratio of 1: (1-10). According to the natural product composition provided by the invention, on the basis of the synergistic anti-pulmonary fibrosis effect of the baicalin and the ursodesoxycholic acid, the optimal anti-fibrosis proportion of the baicalin and the ursodesoxycholic acid is investigated and verified through in-vivo level and in-vitro level experiments, and a new strategy is provided for solving the problem of insufficient curative effect of the existing anti-pulmonary fibrosis medicine.

The application of ursolic acid in the preparation of drugs for treating liver fibrosis can effectively solve the problem of medication for treating liver fibrosis. By regulating the differentiation of immune cells (Th17 cells) and reducing inflammatory damage, ursolic acid intervenes in the liver's immune microenvironment, effectively reversing liver fibrosis, and thus enabling its application in the preparation of drugs for treating liver fibrosis. This invention develops a new drug for treating liver fibrosis, opening up a new avenue for medication in the treatment of liver fibrosis. It represents a major innovation in the treatment of liver fibrosis, demonstrating good efficacy, safety, and practical application value.

The invention relates to a double-dicarboxylic acid diammineplatinum anticancer drug. Specifically, the present invention relates to a pharmaceutical composition for preventing or treating cancer, containing bis-dicarboxylic acid diamineplatinum and N-hydroxyethyl ursodeoxycholic acid amide as active ingredients, and an anti-cancer drug containing the active ingredients. The present invention also relates to methods of providing for the treatment of cancer using diammineplatinum bisdicarboxylate and N-hydroxyethyl ursodesoxycholic acid amide, as well as other various uses using a combination of both diammineplatinum bisdicarboxylate and N-hydroxyethyl ursodesoxycholic acid amide, as well as methods of using diammineplatinum bisdicarboxylate and N-hydroxyethyl ursodesoxycholic acid amide.

The invention discloses a preparation method of high-purity ursodesoxycholic acid, and belongs to the technical field of biological medicines. The method provided by the invention specifically comprises the following steps: carrying out a catalytic oxidation reaction on chenodeoxycholic acid by using 7 alpha-hydroxysteroid dehydrogenase to generate a 7-ketolithocholic acid intermediate, and then carrying out a catalytic reduction reaction on 7 beta-hydroxysteroid dehydrogenase to generate a crude ursodeoxycholic acid product. Further, the crude ursodesoxycholic acid reacts with a triethylamine reagent to generate ursodesoxycholic acid triethylamine salt, and a part of cell impurities are removed; dropwise adding an acid reagent to hydrolyze ursodesoxycholic acid triethylamine salt; and finally, recrystallizing and refining by using ethyl acetate and ethanol to obtain high-purity ursodesoxycholic acid. The method is simple in process and low in cost, the obtained product is high in purity, few organic reagents are used, environmental pollution is little, and industrial production can be achieved.

The invention relates to the technical field of biomedicine, in particular to a nano-composite hirudin protein line capable of remodeling glycolipid metabolism and a preparation method of the nano-composite hirudin protein line. The nano-composite hirudin protein line for remodeling glycolipid metabolism is prepared from the following components in parts by weight: 60 to 85 parts of type I collagen line, 5 to 10 parts of recombinant hirudin, 2 to 5 parts of liraglutide, 1 to 5 parts of ursodesoxycholic acid, 1 to 4 parts of polydopamine and 2 to 5 parts of N-hydroxysuccinimide-polyethylene glycol-maleimide. 2-5 parts of phenylboronic acid modified sodium alginate and 2-5 parts of gallic acid chitosan; according to the invention, on-demand accurate release of drugs in a pathological microenvironment is realized, the intervention efficiency is remarkably improved, the side effects of the system are reduced, meanwhile, a collaborative treatment network is formed, root intervention on complex metabolic disorders is realized, the product can actively remodel a local immune microenvironment while delivering the drugs, the process is controllable, the safety is excellent, and the application prospect is wide. And the benefit of traditional wire embedding weight reduction is greatly improved.

Disclosed in the present invention are a kit for detecting 15 bile acid profiles and three bile acid precursors in serum simultaneously and a detection method therefor. The 15 bile acid profiles comprise: cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, glycoursodeoxycholic acid, glycolithocholic acid, taurocholic acid, taurodeoxycholic acid, taurochenodeoxycholic acid, tauroursodeoxycholic acid and taurolithocholic acid; and the three bile acid precursors comprise: 3α,7α-dihydroxycoprostanic acid, 3α,7α,12α-trihydroxycholestanoic acid and 7α-hydroxy-4-cholesten-3-one. The kit and detection method of the present invention enable the simultaneous and accurate detection of the 15 bile acid profiles and the three bile acid precursors, with a short detection time and a high detection accuracy. This, to a certain extent, meets the clinical need for assessing the enterohepatic cycle composed of the biliary system, intestines, portal venous circulation and hepatocytes.

The invention provides application of taurochenodeoxycholic acid and / or chenodeoxycholic acid and polyinosinic acid combined medicine in preparation of medicine for preventing and / or treating melanoma, and belongs to the field of biological medicine. It is found for the first time that taurochenodeoxycholic acid and / or chenodeoxycholic acid can influence the tumor immune microenvironment by regulating and controlling the antigen presentation function of cDC1, and the treatment effect of polyinosinic-cytidylic acid is improved. The melanoma model experiment directly shows that the combination of chenodeoxycholic acid and polyinosinic-cytidylic acid can better inhibit tumor growth, can effectively promote CD8 + T cell infiltration in tumors, has more cDC1 infiltration in tumor tissues, shows a stronger inhibition effect on tumors, and can be used for preparing drugs for treating tumors. The pharmaceutical composition plays a synergistic role in treatment of melanoma, and provides a new choice for clinical treatment of melanoma.

The application provides an application of ursodeoxycholic acid in preparation of an environmental stress induction caused fish disease related product, and the application comprises one of the following: an application in preparation of a drug for preventing an environmental stress induction related fish disease; an application in preparation of a drug for reducing, treating or assisting in treating an environmental stress induction related fish disease; and an application in preparation of a feed, a feed raw material, a feed additive or a feed composition for improving an environmental stress induction related fish disease. The application proves by experiments that adding a certain dose of ursodeoxycholic acid in the feed can significantly relieve pathological damage of liver of crucian caused by environmental stress factors such as ammonia nitrogen and nitrite, including reducing hepatocyte vacuolization, karyopyknosis and inflammatory cell infiltration, and reducing pathological deposition of liver fat.