59 results about "Betulic acid" patented technology

This invention features betulinic acid derivatives having the formula: wherein the variables are defined herein. The invention also provides related compounds and intermediates thereof, as well as pharmaceutical compositions, kits, and articles of manufacture comprising such compounds. Treatment methods and methods of manufacture are also provided.

A kind of modified 23-hydroxy betulic acid derivatives, their preparing process, the medicinal composition containing them and their application in preventing and treating tumor are disclosed.

The invention discloses a method for synthesizing betulic acid by microbial cell bioconversion of betulin comprising the following steps: inoculating an Armillaria luteo-virens Sacc. ZJUQH to sterilized culture solution and obtaining a pre reaction system; adding a substrate solution containing the betulin and reacting for 5-7 days at between 25 and 30 DEG C, processing the converted culture solution and obtaining the betulic acid, wherein the betulin dosage is 0. 01-0. 1 g per each litre of culture solution. Comparing with the direct plant extraction of the betulic acid method and the chemical synthesis of the betulic acid method The method of the invention has advantages of short microbial cell culture time, easy operation and control, short whole bioconversion period, safe and reliable conversion process, low cost and is suitable for the industrial production.

The invention relates to a method for extracting betulic acid from cornus officinalis stones. The method comprises the steps: firstly, the cornus officinalis stones are crushed, the crushed stones are degreased by using petroleum ether, then paste extracts are extracted by using organic solvent, the paste extracts are added to a weak-polarity or non-polar adsorption column made from macroporous adsorbent resin, high-concentration ethanol is used for elution and crude extracts of betulic acid are obtained, methanol or ethanol is used for recrystallization, and finally high-purity betulic acid is obtained. By adopting the method, betulic acid is extracted from cornus officinalis stones, not only is the extract source of betulic acid widened, but also the utilization problem of the cornus officinalis stones is loved; and simultaneously, compared with the prior art, the method has the advantages that the process is less, the production cycle is shortened by 10-30 percent, the extract purity can be up to 99 percent, and the operation is simple, thereby being favorable for mass production.

The invention discloses a method for synthesizing betulic acid by carrying out biocatalysis on betulin, comprising the following steps: (1) preparing armillaria luteo-uirens ZJUQH wet cells; (2) adding armillaria luteo-uirens ZJUQH wet cells into ionic liquid or a two-phase system for pre-culture to obtain a pre-culture system; (3) adding betulin solution in the pre-culture system for fermentation culture for 6-24 hours at 25-30 DEG C to obtain transformed culture solution; (4) processing the transformed culture solution to obtain betulic acid. The two-phase system is mixed solvent of ionic liquid and normal hexane, or mixed solvent of ionic liquid and phosphoric acid buffer solution. Compared with a conventional method, the inventive method has higher product yield, shorter catalytic reaction time, simple product separation, lower volatility of ionic liquid system, better biocompatibility and no pollution to the environment.

The invention discloses a method for synthesizing betulic acid by carrying out biocatalysis on betulin, comprising the following steps: (1) preparing armillaria luteo-uirens ZJUQH wet cells; (2) adding armillaria luteo-uirens ZJUQH wet cells into ionic liquid or a two-phase system for pre-culture to obtain a pre-culture system; (3) adding betulin solution in the pre-culture system for fermentation culture for 6-24 hours at 25-30 DEG C to obtain transformed culture solution; (4) processing the transformed culture solution to obtain betulic acid. The two-phase system is mixed solvent of ionic liquid and normal hexane, or mixed solvent of ionic liquid and phosphoric acid buffer solution. Compared with a conventional method, the inventive method has higher product yield, shorter catalytic reaction time, simple product separation, lower volatility of ionic liquid system, better biocompatibility and no pollution to the environment.

The present invention relates to the application of 23-hyroxy betulic acid in inhibiting vascularization, and relates to Chinese medicine application technology. The present invention discloses the new use of 23-hyroxy betulic acid in inhibiting vascularization, and research shows that 23-hyroxy betulic acid has vascularization inhibiting effect. The effective dosage of 23-hyroxy betulic acid in preventing and treating medicine for inhibiting vascularization is 3-50 mg each kg of body weight each day. The present invention adopts vascularization as disease treating target, and has the advantages of specificity; direct action of medicine to blood vessel endothelial cell resulting in small dosage, high curative effect and less side effect; and less drug resistance.

The invention discloses a betulinic acid derivative shown by the formula (I) and a synthesis method and application thereof, the betulinic acid derivative comprises a betulinic acid part which is in covalent binding with a 1,2,3-triazole linker in the C-2 position the betulinic acid part, and the linker is in covalent binding with the fludarabine part. According to the compound, the problem of lowwater solubility of the betulinic acid is solved by medical method design, and the betulinic acid is connected with a nucleoside compound by the stable 1,2,3-triazole liker.

The present invention is the method of extracting betulic acid, and features that common jujube seed as material is crushed into coarse powder, deoiled with petroleum ether to obtain common jujube seed oil, with the petroleum ether being recovered; the medicine residue is reflux extracted with methane dichloride to obtain brown viscous paste after the solvent is recovered; and the paste is further processed through complexing, decomplexing, re-crystallization, column separation and other steps to obtain betulic acid in different purity. The said method is simple, high in product purity and suitable for industrial production, and the extracted betulic acid is one kind of antitumor active component.

The present invention provides a method for preparing an ester of betulin at the 3-position, e.g., betulin-3-acetate, including the selective alcoholysis of a betulin-3,28-diester, e.g., betulin-3,28-diacetate; a method for preparing betulin-3-acetate including (1) acetylating betulin to provide betulin-3,28-diacetate and (2) the alcoholysis of betulin-3,28-diacetate to provide betulin-3-acetate; and a method for preparing betulinic acid (1) acetylating betulin to provide betulin-3,28-diacetate, (2) the alcoholysis of betulin-3,28-diacetate to provide betulin-3-acetate, (3) oxidizing betulin-3-acetate to provide betulinic aldehyde-3-acetate, (4) oxidizing betulinic aldehyde-3-acetate to provide betulinic acid-3-acetate, and (5) deprotecting betulinic acid-3-acetate to provide betulinic acid.

The invention discloses recombined saccharomyces cerevisiae and a construction method and application thereof. The recombined saccharomyces cerevisiae is named (Saccharomyces cerevisiae) W303-1b, the preservation number is CCTCC NO:M 2015662, and the preservation data is November 5th, 2015. The invention further discloses a method for preparing microsome protein from the recombined saccharomyces cerevisiae. The method includes the following steps that firstly, inoculation is performed; secondly, thallus cells are cultured and collected; thirdly, the thallus cells are broken; fourthly, supernate is obtained through first-time centrifugation; fifthly, precipitant is added into the supernate, and a precipitate (namely the microsome protein) is obtained through second-time centrifugation. The invention discloses application of the microsome protein to the reaction generating betulinic acid by converting betulin. Betulinic acid can be generated by converting betulin through the microsome protein prepared by culturing recombined saccharomyces cerevisiae, the period of the method is short, post processing is convenient, and the maximum yield of betulinic acid can reach 27.5%.

The invention belongs to the technical field of biological medicines, and discloses a betulinic acid derivative, a preparation method and application thereof. The preparation method comprises the following steps: preparing biotin esterification coupled oligomerization ethylene glycol carboxylic acid or biotin amide coupled oligomerization ethylene glycol carboxylic acid; dissolving betulinic acidin a solvent, and carrying out a stirring reaction at 0 DEG C for 1-6 hours under the action of a dehydrating agent and a catalyst; adding biotin or the biotin esterification coupled oligomerization ethylene glycol carboxylic acid or biotin amide coupled oligomerization ethylene glycol carboxylic acid according to a betulinic acid molar ratio of 1:1-3, heating to room temperature from an ice bath,and stirring in a dark place overnight; and concentrating the filtrate, re-crystallizing with ice diethyl ether or isopropanol, carrying out chromatography or preparative liquid phase purification, and freeze-drying to obtain the betulinic acid derivative. The betulinic acid derivative, the pharmaceutically acceptable salt and the isotope marker thereof can be applied to preparation of anti-cancer drugs and drugs for treating obesity or non-alcoholic fatty liver disease.

The invention provides a method for extracting betulinic acid by subcritical water and belongs to the technical field of extraction and separation of active ingredients of natural products. The method includes the steps of smashing materials, placing the smashed materials in a subcritical water extracting device, extracting raw material powder by taking water as extracting liquid, adding sodium hydroxide in extract after the extractive is subjected to alcohol washing, dissolving out crude betulinol, adding the sodium hydroxide in alkali liquor to dissolve out rough betulinic acid, and recrystallizing to obtain the betulinic acid. By means of utilizing an advanced subcritical water extracting technology, the method for extracting the betulinic acid by the subcritical water has the advantages of high extracting efficiency, short extracting time, no pollution, high betulinol and betulinic acid production rate and the like, and industrial application of the method is easy to achieve.

A betulinic acid nano-liposome wrapped with a nanogold spherical shell is a nano drug-loading system with the particle size being 130-200 nm, a layer of nanogold spherical shell is formed on the surface of the betulinic acid nano-liposome modified by glutathione, and the surface plasma resonant absorption wavelength ranges from 750 nm to 850 nm. A preparation method of the betulinic acid nano-liposome mainly includes the steps that glutathione serves as a raw material to prepare the betulinic acid nano-liposome, and the surface of the betulinic acid nano-liposome has mercapto functional groups; the liposome and gold nanoparticles are inoculated under mild conditions, then a gold chloride solution is added, the mixture stands still for 15-40 min at room temperature and then placed in ice bath, and finally a sodium borohydride solution is added for inoculation for 4-9 h. The method can be implemented under normal-temperature, normal-pressure and mild conditions, operation is easy, and reaction is easy to control. The prepared betulinic acid nano-liposome wrapped with the nanogold spherical shell has good photo-thermal conversion performance, and release is controllable.

The invention belongs to the field of medicines, and discloses a betulinic acid derivative or pharmaceutically acceptable salts thereof, and an application of the betulinic acid derivative or pharmaceutically acceptable salts in preparation of antitumor drugs. The betulinic acid is successfully subjected to structural modification by utilizing a microbial conversion technology to obtain a plurality of novel compounds, and in-vitro anti-tumor cell tests prove that the compounds have better anti-tumor activity, can be used as active ingredients of anti-tumor drugs and have wide application.

An anti-tumor Chinese medicine product comprises medicine, reagent, food and drink and is characterized in that the effective component of the Chinese medicine product is a betulic acid liposome containing betulic acid. The entrapment rate of the betulic acid liposome reaches over 90 percent and particle diameter is 100 to 1000 nanometers. Firstly, the betulic acid plastid is obtained by membrane process; and then the single betulic acid liposome or the betulic acid liposome as well as other chemical substances comprising a pharmaceutically acceptable carrier, the food, a natural product, synthetic chemicals or medicine composition for human are made into the medicine, the food or the drink by general process.

The invention discloses betulinic acid derivative and a synthesis method and application thereof as indicated by formula (I). The betulinic acid derivative covalently bonds with the linker 1, 2, 3-triazole at the C-2 node of the betulinic acid part contained in the betulinic acid derivative, the linker further covalently bonds with 2-fluoride-sugar nucleotides part. The compound provided by the synthesis method is to solve the low water solubility problem of betulinic acid, and bonds the betulinic acid with nucleoside compound via the stable linker 1,2,3-triazole.

The invention relates to the field of biological medicines and in particular relates to betulinic acid 28-O-beta-D-glucopyranoside (I). The invention discloses a preparation method of the betulinic acid 28-O-beta-D-glucopyranoside. The preparation method comprises the following step of carrying out biotransformation onto the betulinic by a bacterial strain with a preservation number of NRRL1086. The invention further discloses a use of the betulinic acid 28-O-beta-D-glucopyranoside in anti-inflammation.

The invention discloses a method for extracting betulinic acid from persimmon leaves. The method comprises the steps that dry persimmon leaves are taken to be ground, added with water to mix and wet, added with bio-enzyme for natural enzymolysis for 4-7 days, the enzymolysis raw material is added with 70-90% ethanol and extracted under refluxing for 1-3 times, the extract is concentrated under reduced pressure until the alcohol concentration is 50-60%, and stood for crystallization, crystal substances are dissolved with 5-7 times of amount of alkaline ethanol solution, undissolved substances are filtered out, filtrate is regulated through hydrochloric acid or sulfuric acid solution to be neutral and centrifuged, crude extract is dissolved with ethanol for recrystallizing, and the betulinic acid is obtained after drying. By adopting the method for extracting the betulinic acid, the raw material resources are abundant, the method is simple to operate, and the industrialization production is benefited.

Disclosed are large-scale industrial processes for obtaining highly pure betulinic acid from ground plane bark. Betulinic acid is 3β-hydroxy-lup-20(29)-ene-28-oic acid of formula

The invention belongs to the field of medicines, and discloses betulinic acid derivatives or pharmaceutically acceptable salts thereof, and application of the betulinic acid derivatives or pharmaceutically acceptable salts in preparation of the anti-nephropathy drug The betulinic acid is successfully subjected to structural modification by utilizing a microbial conversion technology, a plurality of novel betulinic acid derivatives are obtained, and in-vitro TGF-[beta]1 induced HK-2 cell tests prove that the compounds have a better effect of protecting HK-2 cells from being damaged. The betulinic acid derivatives can be used as active ingredients of the drug for preventing or treating nephropathy, and have wide application.

The invention discloses a method for synthesizing betulic acid by microbial cell bioconversion of betulin comprising the following steps: inoculating an Armillaria luteo-virens Sacc. ZJUQH to sterilized culture solution and obtaining a pre reaction system; adding a substrate solution containing the betulin and reacting for 5-7 days at between 25 and 30 DEG C, processing the converted culture solution and obtaining the betulic acid, wherein the betulin dosage is 0. 01-0. 1 g per each litre of culture solution. Comparing with the direct plant extraction of the betulic acid method and the chemical synthesis of the betulic acid method The method of the invention has advantages of short microbial cell culture time, easy operation and control, short whole bioconversion period, safe and reliableconversion process, low cost and is suitable for the industrial production.

The invention discloses an endophytic fungus strain for efficient biotransformation of betulinic acid and application of the endophytic fungus strain. The invention firstly provides a Phomopsis sp. WDS2 strain, and the preservation number of the Phomopsis sp. WDS2 in China Center for Type Culture Collection is CCTCC NO: M 20199394. The invention further provides a microbial inoculum containing thePhomopsis sp. WDS2 and application of the microbial inoculum. The Phomopsis sp. WDS2 disclosed by the invention has the capability of efficiently and biologically converting betulin into betulinic acid; the betulinic acid conversion amount reaches 23.5 mg / L, so that the Phomopsis sp. WDS2 provides an excellent bacterial strain material for the development of anticancer and antiviral products in the future, and has an important value.

The invention discloses a preparation method of triterpenic acid in a jujube material. According to the preparation method of the triterpenic acid in the jujube material, by using alcohols as an extracting agent and alcohol-acid as an eluant, the jujube material is heated, refluxed and extracted; the purity of the triterpenic acid obtained by using two separation methods of macroporous absorbent resin column chromatography and preparative liquid chromatography is high, the content of the triterpenic acid exceeds 90%, and main components are betulinic acid, ursolic acid and oleanolic acid. In the preparation process, organic solvents are all recycled, so that the preparation method of the triterpenic acid in the jujube material is economic and environmentally friendly. The preparation method of the triterpenic acid in the jujube material, disclosed by the invention, has the advantages that AB-8 or HPD100 adsorption resin is adopted, the AB-8 adsorption resin and the HPD100 adsorption resin are polystyrene low polar or nonpolar polymers, the service life is relatively long, and the triterpenic acid elution efficiency is relatively high. The preparation method of the triterpenic acidin the jujube material, disclosed by the invention, has the advantages that the preparative liquid chromatography is a maximum technical characteristic different from the characteristic of the conventional technology, and online monitoring and targeted separation are adopted, so that the separation efficiency is high.

The invention relates to a method for simultaneously detecting five triterpene acid components in Cornus officinalis by utilizing a UFLC method. The method comprises the following steps: firstly, configuring reference solutions of ursolic acid, oleanolic acid, maslinic acid, korosorbic acid and betulinic acid respectively; performing chromatographic analysis on the reference solutions to obtain a peak area of each component respectively; using a sample volume of each reference solution as the abscissa and the peak area of each component in the reference solutions as the ordinate to draw a standard curve respectively; adding an extracting agent to Cornus officinalis powder, and extracting to obtain a sample solution; extracting and filtering the sample solution to obtain a filtrate as a test solution; performing chromatographic analysis on the test solution to obtain the peak area of each detected component in the test solution; and calculating to obtain the content of each component, so as to complete the simultaneous detection of five triterpene acid components in Cornus officinalis by utilizing the UFLC method. The method provided by the invention is used for analyzing and reaching components of Cornus officinalis by utilizing the UFLC method, significantly reduces analysis time, can obtain a good separation effect within 9 min, and also reduces the consumption of solvents and samples correspondingly.

The invention belongs to the field of medicines, and particularly provides a betulinic acid derivative as shown in a formula (I), and pharmaceutically acceptable salts, hydrates or prodrugs thereof. The invention also provides a pharmaceutical composition, a synthetic method and application of the betulinic acid derivative.

The present invention relates to 23-hyroxy betulic acid fat emulsion as anticancer medicine and its preparation process, and belongs to the field of Chinese medicine and medicament preparation technology. The fat emulsion consists of 23-hyroxy betulic acid as active component and medicinal supplementary material, and includes 23-hyroxy betulic acid in 0.5-5 g / L, emulsifier for injection in 5-20 g / L, vegetable oil for injection in 100-250 g / L and osmotic pressure regulator in 18-25 g / L except water for injection. The present invention has simple preparation process, and the prepared 23-hyroxy betulic acid fat emulsion with antitumor effect may be orally taken or intravenously injected. The prepared 23-hyroxy betulic acid fat emulsion has low toxicity, high bioavailability, slow releasing, targeting, and body energy providing effect.

The invention belongs to the field of medicines, and discloses betulinic acid derivatives or pharmaceutically acceptable salts thereof, and application of the betulinic acid derivatives or pharmaceutically acceptable salts thereof in preparation of anti-liver lesion medicines. The betulinic acid is successfully subjected to structural modification by a microbial conversion technology, a pluralityof novel compounds are obtained, and in-vitro anti-hepatic fibrosis cell tests prove that the compounds have better anti-hepatic fibrosis activity, can be used as active ingredients of anti-hepatic fibrosis medicines and have wide application.

The invention discloses recombinant yarrowia lipolytica for heterogenous synthesis of betulinic acid and a construction method of the recombinant yarrowia lipolytica. The construction method comprisesthe following steps: by using a homologous recombination method, introducing an optimized lupeol synthase encoding gene opAtLUP1, an optimized cytochrome P450 enzyme encoding gene opCYP716A12 and anoptimized cytochrome P450 reductase 1 encoding gene opAtCPR1 into yarrowia lipolytica so as to obtain a recombinant bacterium 1; and introducing a shortcut 3-hydroxy-3-methylglutaryl coenzyme A reductase encoding gene tHMG1, a squalene synthase encoding gene Erg9 and the optimized lupeol synthase encoding gene opAtLUP1 into the recombinant bacterium 1, so as to obtain a recombinant bacterium 2. Experiments show that the recombinant yarrowia lipolytica which is constructed by using the method disclosed by the invention and applied to heterogenous synthesis of betulinic acid has a high yield ofbetulinic acid.