883 results about "Cholic acid" patented technology

New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure:

wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof.

Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided. Novel methods of treating prostate tumors or of delaying the progression of prostate tumors are also provided, including, methods of treating bone or soft tissue metastases of prostate cancer, methods for treating hormone sensitive and hormone refractory prostate cancer, methods for delaying the progression of hormone sensitive prostate cancer, for facilitating combination therapy in patients with hormone sensitive prostate cancer and for decreasing aberrant vascular permeability in patients with hormone sensitive prostate cancer.

The invention discloses a decellularized pericardial tissue via chemical treatment with cholic acid or bile salts as a medical device and process of manufacture.

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 a preparation method of a 7-keto-6[alpha]-alkyl cholanic acid derivative. According to the preparation method provided by the invention, a 7-keto-6[beta]-alkyl cholanic acid derivative, as shown by a formula II, is used as a raw material, and the 7-keto-6[alpha]-alkyl cholanic acid derivative is prepared by converting a 6[beta] configuration into a 6[alpha] configuration under an acid or alkali condition. The invention also provides a 7-keto-6[beta]-alkyl cholanic acid derivative and an application thereof in preparation of 3[alpha],7[alpha]-dihydroxy-6[alpha]-alkyl-5[beta]-cholanic acid. The preparation method provided by the invention is simple and convenient, and is high in configuration conversion rate, and the product, the 7-keto-6[alpha]-alkyl cholanic acid derivative, is easy to purify, so that the purification difficulty for preparing the 3[alpha],7[alpha]-dihydroxy-6[alpha]-alkyl-5[beta]-cholanic acid is reduced.

Process for preparing 3α-7α(β)-di-hydroxy-6α(β)-alkyl-5β-cholanic acid (I) in which R is a linear or branched C₁-C₅ alkyl and the relative intermediates 3α-hydroxy-6β-alkyl-7-keto-5β-cholanic (VIII) and 3α-hydroxy-6α-alkyl-7-keto-5β-cholanic (IX).

The invention provides a method for preparing a cholic acid coupler therapeutic medicine (I). The method adopts a taurine or glycinate compound as an initial material, and carries out a reaction to obtain the medicine (I) with the condensating agent of 2-chlorine-4,6-dimethoxy-1,3, 5-triazine or chloridized 4-(4,6- dimethoxy-1,3, 5-triazine-2-group)-4-methyl morpholine. The method has cheap and easily obtained raw material, gentle reaction conditions, solvent without water treatment, simple operation, high yield and friendly reaction environment. (in the formula, R1, R2, R3 represent H, alpha-OH, beta-OH, =O; R1, R2 and R3 can be the same or not the same; R represents CH2CH2SO3H, CH2COOH, CH2CH2SO3M, and CH2COOM; M represents metallic ions).

A chemically amplified resist composition comprising a base polymer, an acid generator, and a basic compound which is a cholanoate having an acid labile group-protected amino group has a high contrast of alkaline dissolution rate before and after exposure and high resolution and forms a pattern of satisfactory profile with minimal roughness.

The invention provides a mutant of 7 beta-hydroxyl steroid dehydrogenase, application of the mutant and a synthesis method. The mutant of the 7 beta-hydroxyl steroid dehydrogenase is characterized in that amino acid sequences of the mutant are Seq ID NO:4, and coded nucleotide sequences are Seq ID NO:3; or amino acid sequences of the mutant are Seq ID NO:6, and coded nucleotide sequences are Seq ID NO:5. The mutant, the application and the synthesis method have the advantages that cholic acid compounds, particularly ursodeoxycholic acid, can be catalytically synthesized by the efficient 7 beta-hydroxyl steroid dehydrogenase, mutant enzymes of the 7 beta-hydroxyl steroid dehydrogenase and coenzyme regeneration systems, accordingly, the substrate concentration can reach 100 g/L, the conversion rate is 99.2-99.5%, and the weight yield can reach 94-96%; and the enzymes can be inexpensively and easily obtained by the aid of a fermentation process, accordingly, the production cost and the product quality are superior to the production cost and the product quality of chemical synthesis methods, and the mutant and the synthesis method are applicable to industrial production.

The invention provides a preparation method of ursodeoxycholic acid. Commercial available chenodeoxycholic acid is taken as raw materials, the ursodeoxycholic acid is obtained by four steps including selective oxidation, esterification, deoxidation and hydrolyzation, and the total yield is 85.7%. In a mixture of acetone and water, NBS is used for selective oxidation of hydroxy at C- 7 bit of the chenodeoxycholic acid, and the selective oxidation possesses excellent selectivity and high yield. NaBH14/CeC13 may be used to deoxidize carbonyl at C-7 bit into hydroxy, and the ratio of alpha/beta is as high as 5/95.

The invention relates to an obeticholic acid (OCA) isomer namely an OCA-alpha alpha beta body, a synthetic method of the OCA-alpha beta alpha body, and a method adopting the reversed phase liquid chromatography condition to separate the OCA isomer. With adoption of the technical scheme disclosed by the invention, the OCA-alpha alpha beta body and the OCA-alpha beta alpha body with the HPLC purity greater than 98% can be obtained to meet quality control of the isomer in OCA.

The invention discloses a preparation method of ursodesoxycholic acid, which comprises the flowing steps of: a. carrying out 3-bit esterification on chenodeoxycholic acid to obtain 3-esterification protected chenodeoxycholic acid; b. carrying out 7-bit oxidation reaction on 3-bit ester to obtain 3-estergroup-7-oxocompounds; c. carrying out hydrolysis reaction or reduction reaction on the 3-estergroup-7-oxocompounds; d, carrying out 7-bit reduction reaction on 3a-hydroxy-7-oxo-5 beta-cholic acid or hydrolysis reaction on 3a-estergroup-7 beta- hydroxyl-5 beta-cholic acid to obtain crude products of the ursodesoxycholic acid; e. forming salt through the crude products of the ursodesoxycholic acid and organic base; and f. carrying out steps such as water adding dissolution, acid adding crystallization and the like on ursodesoxycholate to obtain pure ursodesoxycholic acid products with the purity higher than 99.0 percent. The invention aims at overcoming the defects in the prior art to provide a novel method for preparing the ursodesoxycholic acid, and the ursodesoxycholic acid prepared by the method has high yield and high purity.

The present invention relates to process of extracting cholic acid, deoxycholic acid and bilirubin from bile of pig, ox and sheep. Bile of pig, ox and sheep consists of water in about 97 %, bile acid in about 2.5 % and bilirubin in about 0.4 %; and contains also phospholipid, cholesterol, Na, K, Ca, phosphate, carbonate, small amount of protein, and other components. Fresh bile is treated through cooling, filtering to defat, basic hydrolysis, acidification and organic solvent extracting to obtain bilirubin; the rest solution is further treated through deep saponification, acidification and organic solvent precipitation to obtain the mixture of cholic acid and deoxycholic acid; and the mixture is re-crystallization separated to obtain high purity cholic acid and deoxycholic acid.

The feature of the invention includes: adopting frozen chicken gallbladder slicing, heating to 70 degree centigrade, adding 10% weight of the bile boiling for 24 hours, reflux cooling, adjusting the pH value by hydrochloric acid to gain cream, washing to neutrality; adding 95% alcohol and 10% diatomite, reflux cooling and adding active carbon, reflux, cooling and filtering, adding petrol to the filtrate to take degreasing, reflux, standing, separating alcohol liquid and washing to neutrality in reaction kettle, adding 95% alcohol, after resolving, adding barium chloride and active carbon, reflux, hot filtering, concentrating white crystal from the filtrate, washing, and adding water and sodium carbonate water solution, heating and reflux, filtering, adjusting the pH value, drying. The invention has simple technology, low cost, and could drastically separate cholesterol, lithocholic acid, and cholic acid from gall, and improves the purity.

The invention relates to a stable compound containing a plurality of vitamins and the method for preparing same. The compound comprises at least four kinds of fat-soluble vitamin, cholate, phosphatide and carriers or findings acceptable by pharmacy. The compound also comprises water soluble vitamins. The compound is a clear and transparent solution. The preparing method comprises: (1) dissolving the fat-soluble vitamin with liquid containing ethanol; (2) removing ethanol. The compound is used as nutriment for patients.

The invention relates to a biodegradable amphiphilic albumin derivative and a pharmaceutical composition thereof. In the biodegradable amphiphilic albumin derivative, hydrophilic long-chain polyethyleneglycol and alkyl (acyl) group or (deoxidized) cholic acid are led to an albumin skeleton so that the amphiphilic albumin derivative is amphipathic and is self-assembled in water to form nano-micelle. The biodegradable amphiphilic albumin derivative is characterized in that medicament can be encapsulated through the double actions of a hydrophobic group and an albumin molecule chain with the medicament, and the capacity of the albumin encapsulating the medicament is markedly improved; in addition, a hydrophilic long-chain can reduce the immunogenicity of the albumin and improve the nano-micelle surface hydrophilicity so that the stability of the nano-micelle in aqueous medium can be improved and the nano-micelle has long-circulation characteristics in a body. The pharmaceutical composition of the biodegradable amphiphilic albumin derivative can be used as the carrier of organic medicament, water-insoluble or insoluble medicament and amphiphilic medicament, can be used for intravascular administration, intramuscular injection administration, oral administration, cavitary administration or external administration. The invention can be prepared with simple method and mature process and is suitable of large-scale continuous production.

The invention discloses a method to manufacturing high purity chemocholic acid from fowl bile that belongs to refinement chemical and medicine field. It includes the following steps: a. saponification reaction: mixing the fowl bile and sodium hydroxide and reacting for 20-30 hours under the certain temperature; b. neutral reaction: adding dilute hydrochloric acid after saponification reaction and gaining raw cholic acid after filtering; c. column chromatography: adding dilute sodium hydroxide into raw cholic acid and injecting into chromatography column, uniting the eluent; super filtering: taking super filtering by super filtering film; e. gaining chemocholic acid that the purity is over 96% after adding dilute acid, filtering and drying. The invention has simple technology, high purity, low cost and environment protection.

A process for separating the chenodeoxycholic acid from pig's gall and purifying it includes such steps as preparing general cholic acid from the mother liquid generated by extracting the cholerythrin from pig's gall, saponifying, regulating pH value to obtain crude chenodeoxycholic acid, decoloring, defatting, preparing the deposit of barium chenodeoxycholate, reacting on potassium carbonate to remove Ba, regulating pH value, and purifying by silicon gel column.

The invention relates to a chenodeoxycholic acid (3 alpha, 7 alpha-dihydroxyl-5 belta-cholestane-24-acid) chemical synthesis method, belonging to the field of organic chemical synthesis. Chenodeoxycholic acid is prepared by the following steps of: (1) preparing cholate; (2) preparing 3 alpha, 7 alpha-acetyl-12 alpha-hydroxy cholate; (3) preparing 3 alpha, 7 alpha-acetyl-12-oxo-chenodeoxycholic acid ester; (4) preparing 12-oxo-chenodeoxycholic acid; and (5) preparing chenodeoxycholic acid. The application of the method for synthesizing chenodeoxycholic acid has the advantages of high yield rate, low cost and no pollution and is particularly convenient for industrial production.

The present invention relates to stabilised <99m>Tc radiopharmaceutical compositions, which include both a radioprotectant and one or more antimicrobial preservative(s), and hence have an extended lifetime of use. The radioprotectant is ascorbic acid, para-aminobenzoic acid, gentisic acid or a salt thereof with a biocompatible cation, and the antimicrobial preservative is one or more compound from the paraben series of preservatives. The invention is particularly useful for cationic, lipophilic <99m>Tc heart imaging agents such as Myoview(TM).

The invention provides a group of biomarkers which can be used for detecting liver fibrosis and cirrhosis. The biomarkers refer to metabolite components existing in a biological sample of a subject body and comprise a plurality of metabolites, wherein the metabolites are selected from cholic acid, amino acid and fatty acid. Metabolite combination comprises at least one amino acid, fatty acid and cholic acid, the metabolite combination is differentially expressed in at least one target plasma or serum and in a control plasma or serum. The biomarkers can optionally be combined with clinical indicators for diagnosis of liver fibrosis in the subject body. The biomarker composition has the characteristics of high sensitivity and specificity for pathological staging diagnosis of liver fibrosis patients, and can be clinically applied as a non-invasive means to improve clinical diagnosis and reduce puncture pain of the patients. The invention further provides a use method of the biomarkers andkits containing the biomarkers.

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 a glycogen phosphorylase inhibitor cholic acid derivative, a preparation method thereof and a pharmaceutical composition containing the same. The glycogen phosphorylase inhibitor cholic acid derivative is a liver-targeted pro-drug for glycogen phosphorylase; compared with a glycogen phosphorylase inhibitor, the concentration of the glycogen phosphorylase inhibitor in a liver can be increased after the glycogen phosphorylase inhibitor cholic acid derivative is taken orally, so that the glycogen phosphorylase inhibitor cholic acid derivative can serve as a preferred drug for lowering blood sugar, particularly for treating impaired fasting glucose. The compound can be used for preventing and treating diabetes and complications thereof, hyperlipidemia, obesity, high-glucagon disease, insulin resistance, impaired fasting glucose, hypertension and complications thereof, atherosclerosis, metabolic syndrome or tumor.