169 results about "Deoxycholic acid" patented technology

The invention discloses a preparation method of a doxorubicin-loaded ginseng selenium polysaccharide nano-carrier with immunoregulation and liver cancer cell inhibition functions, and aims to solve the problems of toxic injury of tissues and organs and inhibition of an immune system caused by an antitumor drug doxorubicin. According to the invention, deoxycholic acid is grafted on the ginseng selenium polysaccharide, so that the ginseng selenium polysaccharide is hydrophobized and forms an amphiphilic polysaccharide polymer, and the limitations of large molecular weight, low bioavailability and the like of the ginseng selenium polysaccharide are overcome. The self-assembled ginseng selenium polysaccharide nanoparticles are used as carriers for delivering antitumor drugs, so that the self-assembled ginseng selenium polysaccharide nanoparticles have an immunoregulation effect and can effectively improve side effects such as immunosuppression caused by the antitumor drugs; and the carrier also has a pH sensitive response release characteristic, so that the targeting effect of the medicine in a tumor area is enhanced, and the innovative carrier has a good clinical application prospect.

The invention relates to the technical field of pharmaceutical separation, and discloses a device, method and application of ursodeoxycholic acid preparation and purification. The device comprises a separation tank, wherein a batching center cylinder is rotatably installed inside the separation tank, and a plurality of elution tubes are arranged around the batching center cylinder. The batching center cylinder rotates forward, and centrifugal force is used to load adsorption resin into each elution tube. Then, the batching center cylinder rotates reversely, and the volume of each elution tube is poured out by anti-centrifugal force, so as to achieve a more convenient effect of replacing the adsorption resin. The replaced adsorption resin is cleaned outside the device and reused. The purification method and application thereof realize column loading, sample loading and elution in the separation tank in sequence without stopping the machine for operation, and simplify the column loading and column replacement operations, so as to solve the problem that the separation and purification process in the prior art is complicated and not suitable for batch production, so as to meet the industrial production requirements of solvent recycling.

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.

The present invention provides a recombinant Bacillus subtilis engineering strain and its application in the biological preparation of ursodeoxycholic acid, belonging to the field of bioengineering technology. The present invention provides a recombinant Bacillus subtilis engineering strain that simultaneously and efficiently and stably expresses 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenase (7β-HSDH). During biosynthesis, chenodeoxycholic acid is used as a substrate and combined with oxidized coenzyme NADP under the action of 7α-HSDH. + , the 7α-hydroxyl group in chenodeoxycholic acid is oxidized to a carbonyl group, and the resulting intermediate 7-keto-lithocholic acid is reduced to ursodeoxycholic acid under the action of 7β-HSDH and NADPH. The recombinant Bacillus subtilis engineered strain can efficiently and stably biosynthesize ursodeoxycholic acid, and greatly reduces the purification work of the product in industrial applications, greatly reducing production costs.

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.

An embodiment of the present invention relates to: a cancer antigen peptide nanostructure comprising an assembly of cancer antigen peptides conjugated with deoxycholic acid; a method for preparing same; and use thereof. The inventors of the present invention confirmed that the nanostructure of the present invention effectively stimulates the maturation of dendritic cells, migrates to lymph nodes, and activates T cells. Also, in a cancer cell model, significant infiltration of cytotoxic T lymphocytes into primary tumors was observed, and an anti-metastatic effect was confirmed. Therefore, the nanostructure according to the present invention can be effectively used as a promising immunotherapy platform that can be applied to various intractable cancers.

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 present invention relates to the field of animal breeding technology, and in particular to the use of porcine deoxycholic acid in reducing animal fat deposition. The present invention uses UCP1 genetically modified pigs with a low-fat phenotype to conduct targeted metabolic analysis in feces, and discovers and identifies a pig intestinal endogenous metabolite that can reduce fat deposition, porcine deoxycholic acid, whose chemical formula is C 24 H 40 O4. The present invention finds that the content of swine deoxycholic acid can indicate the fat deposition ability of pigs, and oral administration of swine deoxycholic acid to mice can significantly reduce the fat deposition of mice. The swine deoxycholic acid provided by the present invention has the effect of reducing fat deposition, and can be developed as a feed additive for reducing pig fat deposition in the future. At the same time, it can be applied to the research and development of drugs for reducing human obesity, providing a scientific basis for the treatment of human obesity and other diseases.

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 present invention provides a method for separating hyodeoxycholic acid and chenodeoxycholic acid. The method of the present invention comprises fractionating and extracting a raw material liquid containing hyodeoxycholic acid and chenodeoxycholic acid using an extractant containing an ionic liquid and / or a polar solvent. The method has good stability and high separation selectivity, and is simple in process, easy to scale up, safe and environmentally friendly, and suitable for industrial production.

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 invention provides a method for separating and detecting impurities in a metronidazole-ursodesoxycholic acid conjugate and application of the metronidazole-ursodesoxycholic acid conjugate. The method comprises the following steps: preparing a metronidazole-ursodesoxycholic acid conjugate solution to obtain a test solution; performing high performance liquid chromatography detection on the test solution by adopting a high performance liquid chromatograph with an electrified spray detector; wherein the chromatographic conditions of the high performance liquid chromatography detection are as follows: a mobile phase is a mixed solution of a 0.1% formic acid aqueous solution, methanol and acetonitrile in a volume ratio of 40: 35: 25; and the power law of the electrospray detector is 1.4. According to the application, an electrospray detector is adopted for detection, so that the problem of low sensitivity under an ultraviolet detector due to few conjugated systems in an ursodesoxycholic acid structure and large terminal absorption interference is solved; the electrospray detector serves as a mass type detector, the detection of the electrospray detector is irrelevant to the molecular structure of a detected substance, the response value of the detected substance is determined by the absolute mass of a detected sample, and the detection requirements of ursodesoxycholic acid and metronidazole can be met.

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.