135 results about "Deoxycholic acid" patented technology

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

The 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.

This invention belongs to the field of diagnostic testing technology. Addressing the problem that existing gestational diabetes screening methods may miss the optimal time for early intervention, leading to the failure to promptly detect and manage some potentially hyperglycemic pregnant women, increasing the risk of adverse maternal and fetal outcomes, this invention proposes a plasma metabolic biomarker for the early diagnosis or prediction of gestational diabetes and its application. This plasma metabolic biomarker is at least one of L-lysine, propargylglycine, N6-acetyl-L-lysine, cyclic leucine, and glycine-deoxycholic acid. The five plasma metabolic biomarkers provided by this invention can be applied to the early diagnosis or prediction of gestational diabetes, and are of great significance for the prevention or treatment of gestational diabetes.

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.

To provide cellular uptake.SOLUTION: The invention provides a bile acid or a pharmaceutically acceptable salt thereof for use in a method for treating the human or animal body, the method comprises administering to the human or animal body a therapeutic compound, where: a. the bile acid is chenodeoxycholic acid or deoxycholic acid; b. optionally, the bile acid is employed in conjunction with EDTA; c. in the method, the bile acid or salt thereof and EDTA are used to enable or enhance intracellular uptake of the therapeutic compound.SELECTED DRAWING: None

The invention belongs to the technical field of agricultural animal husbandry application, and particularly relates to a feed additive for reducing backfat thickness of fattening Min pigs, a preparation method and application. The feed additive for reducing the backfat thickness of the fattening Min pigs comprises the following components in percentage by weight: 0.25 to 1.0 percent of hyodeoxycholic acid, 21.0 to 31.7 percent of citric acid, 0.7 to 3.2 percent of neutral phytase, 0.1 to 1.4 percent of astragalus membranaceus, 0.3 to 1.4 percent of saccharin sodium salt, 1.0 to 8.2 percent of rice hull powder and 54.0 to 64.7 percent of zeolite powder. The preparation method of the feed additive for reducing the backfat thickness of the fattening Min pigs comprises the following steps: crushing hyodeoxycholic acid, citric acid, neutral phytase, astragalus membranaceus, saccharin sodium salt, rice hull powder and zeolite powder into 80-mesh particles; the preparation method comprises the following steps: weighing the raw material components according to the ratio, stirring in a stainless steel mixer with the mixing uniformity of less than or equal to 5% for 5-10 minutes, and quantitatively packaging to obtain the finished product. The additive in the feed from the late stage of Min pig fattening to slaughtering can effectively reduce the backfat thickness of sows during slaughtering, improve the expression level of related genes of muscle fibers, and further improve the meat quality of Min pigs.

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.

This invention relates to a traditional Chinese medicine combination for treating intrahepatic cholestasis, which is made from the following raw materials in parts by weight: Artemisia capillaris and Glycyrrhiza uralensis 5:1 and 3:1. This invention also provides the preparation of the above-mentioned medicine and its use in treating intrahepatic cholestasis. Its advantages are: the traditional Chinese medicine composition of this invention (Artemisia capillaris and Glycyrrhiza uralensis decoction) has a significant ameliorative effect on intrahepatic cholestasis (non-obstructive type) induced by a 1% CA-containing diet in mice. Artemisia capillaris and Glycyrrhiza uralensis decoction can alleviate weight loss in mice and improve liver necrosis; significantly reduce serum ALT and ALP levels in mice; reduce the content of total bile acids in the liver and decrease the proportion of toxic bile acid taurine deoxycholic acid (TDCA) in the bile acid pool; upregulate liver BSEP protein expression to promote bile acid efflux; and downregulate liver NLRP3 protein expression to alleviate liver necrosis.

The invention provides an impurity removal method of a chenodeoxycholic acid crude product, which comprises the following steps: dissolving the chenodeoxycholic acid crude product and glucose in a solvent, adding alkali to control the pH value of the system to be 8-10, and adding thiourea to react so as to convert 22-ene-chenodeoxycholic acid impurities into chenodeoxycholic acid. According to the impurity removal method provided by the invention, the 22-ene-chenodeoxycholic acid impurity in chenodeoxycholic acid can be effectively removed without adopting a heavy metal catalyst and the like, and the method is convenient to operate, mild in condition, low in production risk and suitable for large-scale industrial production.

The invention relates to a metabolite marker for early diagnosis of colorectal cancer as well as application and a device of the metabolite marker. The marker comprises sulfate, ubiquinone-1, a deoxycholic acid glycine conjugate, demethylchlorophyllin, 3-(3, 5-diiodine-4-hydroxyphenyl) lactate, vitamin K1, O-decanoyl-L-carnitine, sedoheptulose 1, 7-diphosphoric acid, cholesterol-docosahexaenoic acid ester and acyl AMP (adenosine monophosphate). The marker combination has excellent performance in colorectal cancer detection, AUROC can reach 0.97, and noninvasive screening and early diagnosis of colorectal cancer can be accurately, quickly and simply realized.

The application provides a reduction-responsive nano delivery system and application thereof in preparation of a drug for treating drug-resistant tumors, and belongs to the pharmaceutical field. The application constructs a reduction-responsive branched copolymer functionalized by pegylation and deoxycholic acid (DA) (referred to as: pegylated branched poly(HPMA-DA)), which can effectively encapsulate small molecule drugs to form a nano delivery system. Experiments prove that the nano delivery system can be taken up by tumor cells, has good tumor targeting, and exhibits excellent anti-tumor effect in tumor xenografts (CDX) derived from non-small cell lung cancer (NSCLC) chemoresistant cell lines and patient-derived xenograft mouse models (PDX). The pegylated branched poly(HPMA-DA) provided by the application has wide application prospect in preparation of a drug carrier, and the nano delivery system provided by the application has wide application prospect in preparation of a drug for treating cancer.

The present application relates to the application of Hhex agonists in promoting anti-tumor immunity. Specifically, the present application provides a pharmaceutical composition comprising chenodeoxycholic acid and an anti-PD-1 antibody. The present application also provides the use of chenodeoxycholic acid and an anti-PD-1 antibody in the preparation of a drug for promoting anti-tumor immunity. In addition, the present application also provides the use of chenodeoxycholic acid and an anti-PD-1 antibody in the preparation of a drug for treating tumors. The present application uses chenodeoxycholic acid to improve the tumor immune microenvironment and uses it to treat subcutaneous tumors, further verifying that the application of chenodeoxycholic acid can improve the tumor immune microenvironment.

The invention provides a traditional Chinese medicine composition for improving eyesight and removing nebula and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition comprises bear gall powder and borneol in a mass ratio of (1-5): 1. The bear gall powder is prepared from taurodeoxycholic acid and taurodeoxycholic acid arginine salt according to the molar ratio of (0.4 to 0.9) to (0.1 to 0.6). According to the application, taurodeoxycholic acid in the bear gall powder is converted into taurodeoxycholic acid arginine salt, so that the molar ratio of taurodeoxycholic acid to taurodeoxycholic acid arginine salt in the bear gall powder is (0.4-0.9): (0.1-0.6), and the bear gall powder is used for treating cataract after being compounded with borneol. Experimental results show that when the molar ratio of taurodeoxycholic acid to taurodeoxycholic acid arginine salt in the bear gall powder is (0.4-0.9): (0.1-0.6), the effect of treating cataract by compounding the bear gall powder with borneol is obviously superior to that of only taurodeoxycholic acid in the bear gall powder or only taurodeoxycholic acid arginine salt in the bear gall powder; for example, significant differences exist in the aspects of relieving the opacity degree and thickness of the crystalline lens.

The invention discloses application of a reagent for detecting a plasma metabolism marker combination in preparation of a product for diagnosing breast cancer, and belongs to the field of breast cancer markers. According to the application of the reagent for detecting the plasma metabolism marker combination in preparing the product for diagnosing the breast cancer, the plasma metabolism marker combination comprises dehydroepiandrosterone sulfate, acylcarnitine 12: 0 and taurodeoxycholic acid. The plasma metabolism marker combination has high specificity, high sensitivity and non-invasiveness when being used for breast cancer detection, so that a subject can conveniently and safely receive detection, and the plasma metabolism marker combination is suitable for screening and detection of large-scale common people and is beneficial to early screening, early diagnosis and early treatment of breast cancer.

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.

This invention relates to the field of pharmaceutical analysis technology, specifically to a method for determining the content of deoxycholic acid injection. The detection method employs high-performance liquid chromatography (HPLC) with an ultraviolet (UV) detector. The HPLC chromatographic conditions are as follows: the column is an octadecylsilane-bonded silica column; the column dimensions are 4.6 × 150 mm, and the packing diameter is 3 μm; the detection wavelength is 220 nm; the mobile phase is 0.1% formic acid aqueous solution – 0.1% formic acid acetonitrile solution (42:58). Compared with existing technologies, UV detectors are more readily available than CAD detectors. This invention achieves quantitative detection of deoxycholic acid injection content by controlling the HPLC conditions of the UV detector. This method exhibits baseline stability, good specificity, accuracy, and precision, and is of significant importance for the quality control of deoxycholic acid injection.

The invention provides a lipid nanoparticle based on taurochenodeoxycholic acid modification as well as a preparation method and application thereof. The lipid nanoparticle comprises nucleic acid and a lipid carrier encapsulating the nucleic acid, the lipid carrier is prepared from the following components in percentage by mole: 40 to 65 percent of ionized lipid, 5 to 20 percent of structural phospholipid, 20 to 50 percent of sterol component and 0.5 to 5 percent of PEG (Polyethylene Glycol)-lipid, wherein the sterol component comprises cholesterol and taurochenodeoxycholic acid. By replacing cholesterol with taurochenodeoxycholic acid, the membrane order degree and fluidity of the lipid carrier are effectively adjusted, and the targeted delivery and endosome release efficiency of LNP to liver cells is remarkably improved, so that an LNP delivery system can obtain a more remarkable and lasting Lp (a) reduction effect under the same or lower dosage; by optimizing the LNP formula, it is ensured that the LNP preparation has higher controllability and reliability in the production and storage process.

The application provides a kind of antibiotic-loaded nanoemulsion and its preparation method and application, it is related to the technical field of medical adjuvant, antibiotic is mixed with medicinal adjuvant soybean oil, dipalmitoyl phosphatidylcholine and cholesterol, and volatile organic solvent is used to dissolve and form oil phase;Deoxycholic acid sodium and tween are dissolved in sterile liquid to form water phase;Oil phase and water phase are mixed, and are treated by ultrasonic treatment, rotary evaporation treatment and high pressure homogenization treatment, to obtain antibiotic-loaded nanoemulsion.The application adjusts the type of inhalable medicinal adjuvant, the addition ratio of inhalable medicinal adjuvant, the ratio of oil phase and water phase, and the ultrasonic power and homogenization pressure and other factors, so that the prepared nanoemulsion can efficiently load antibiotic, and has good aerosol inhalation performance, better drug stability, the nanoemulsion can be retained in mouse lung tissue for a long time, and the lung drug delivery efficiency is significantly improved.

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 present invention relates to a lipolytic injection composition having excellent effects of alleviating pain during treatment, and improving solubility and maintaining stability of deoxycholic acid by comprising deoxycholic acid (DCA) and cyclodextrin in an optimal composition ratio and adjusting pH to a range of 7.0 to 7.7.

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 present invention provides a fat-dissolving composition and a use thereof. The fat-dissolving composition of the present invention comprises a pharmaceutically active ingredient, an inclusion material, a pH regulator optionally selected from one or more of a buffer, a stabilizer, an osmotic pressure regulator, and a complexing agent, and optionally purified water, wherein the pharmaceutically active ingredient is selected from one or more of deoxycholic acid, a pharmaceutically acceptable salt of deoxycholic acid, and a deoxycholic acid derivative, and the amount of the inclusion material ranges from 4% to 35% on the basis of the total weight of the fat-dissolving composition. Compared with conventional formulations at the same dose, the fat-dissolving composition of the present invention can significantly reduce adverse effects at the administration site while having a good fat-dissolving effect, and has higher safety.

The invention provides a fat-dissolving composition and application thereof. The fat-dissolving composition comprises an active pharmaceutical ingredient, an inclusion material, a pH regulator, one or more optional components selected from a buffering agent, a stabilizing agent, an osmotic pressure regulator and a complexing agent, and optional purified water, the active pharmaceutical ingredient is selected from one or more of deoxycholic acid, pharmaceutically acceptable salts of deoxycholic acid and deoxycholic acid derivatives, and the dosage range of the inclusion material is 4-35% based on the total weight of the fat-dissolving composition. Compared with a conventional preparation with the same dosage, the fat-dissolving composition disclosed by the invention has the advantages that under the condition that a good fat-dissolving effect is achieved, the adverse reaction of an administration part can be obviously relieved, and the fat-dissolving composition has higher safety.

This invention belongs to the field of traditional Chinese medicine technology, and provides the application of Scutellaria baicalensis leaf aqueous extract in the preparation of drugs for improving or treating inflammatory bowel disease (IBD) with depression. The Scutellaria baicalensis leaf aqueous extract improves IBD with depression by increasing the abundance of Akkermansia myxophilus (AKK) bacteria, restoring disordered deoxycholic acid metabolism. The extract increases the abundance of AKK bacteria in the intestine, increases the content of deoxycholic acid (DCA) in the intestine, regulates Th17 / Treg homeostasis, reduces intestinal inflammation, maintains intestinal barrier integrity, reduces the entry of pro-inflammatory factors into the bloodstream and across the blood-brain barrier into the hippocampus, inhibits neuroinflammation, and improves depression. Scutellaria baicalensis leaves can improve IBD with depression by increasing the abundance of AKK bacteria in the intestine, increasing intestinal DCA levels, regulating Th17 / Treg balance, repairing the intestinal barrier, reducing LPS leakage and alleviating nerve damage, and inhibiting the inflammatory response of the gut-brain axis. This provides certain experimental evidence for the development and utilization of related traditional Chinese medicine resources.

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 relates to the field of microbiology and biochemistry, in particular to a 3-ethanone deoxycholic acid compound, a synthetase thereof, a preparation method and application of the 3-ethanone deoxycholic acid compound. According to the present invention, the double-tailed acid compound represented by 3-ethanone deoxybile acid is found, the enzymatic experiment verifies that the ADS sequence can catalyze the generation of the double-tailed acid compound, the bacterial strain capable of generating the double-tailed acid compound is further screened through the experiment, and the growth promotion effect of 3-ethanone deoxycholic acid on lactic acid bacteria is found through detection; the method can be used for intervention of diseases.

The application discloses a deoxycholic acid intermediate and application thereof, and belongs to the technical field of organic synthesis. The deoxycholic acid intermediate has a structural formula as shown in the specification, wherein R1 is -OH or -OAc; R2 is alpha-OH, beta-OH or =O; and R3 is =O or -CHCH3. In addition, the application further provides application of the deoxycholic acid intermediate in preparation of deoxycholic acid. The intermediate can be used for effectively and safely synthesizing deoxycholic acid.

The invention discloses carboxymethyl chitosan nano freeze-dried powder as well as a preparation method and application thereof, and belongs to the technical field of nano medicines. The preparation method of the carboxymethyl chitosan nano freeze-dried powder comprises the following steps: dissolving a carboxymethyl chitosan deoxycholic acid polymer with an alcohol solvent, adding the dissolved carboxymethyl chitosan deoxycholic acid polymer into water to prepare a turbid liquid, and carrying out first dialysis to obtain a carboxymethyl chitosan deoxycholic acid nano particle solution; adding ginsenoside CK powder into the solution, stirring at room temperature to enable ginsenoside CK to be loaded on the nanoparticles, and performing second dialysis with water after stirring to obtain a ginsenoside CK carboxymethyl chitosan-deoxycholic acid nanoparticle suspension; and then freeze-drying to obtain the carboxymethyl chitosan nano freeze-dried powder. The prepared carboxymethyl chitosan nano freeze-dried powder has controllable particle size and high drug loading capacity, can specifically release drugs in a tumor slightly acidic environment, remarkably improves the liver cancer treatment effect and biological safety, and has great market application potential.