54 results about "Elemene" patented technology

The invention provides a microneedle preparation for co-delivering photo-thermal nano-enzyme and elemene as well as a preparation method and application of the microneedle preparation. The preparation method comprises the following steps: firstly, preparing a novel photo-thermal nano enzyme Au (at) MoS2 through a two-step water phase synthesis strategy; benefited from the synergistic effect of the hybrid material, the nano-enzyme shows significantly enhanced near-infrared (NIR) photothermal effect, peroxidase-like (POD) activity and glutathione-like peroxidase (GSHOx) activity, and can effectively remodel the tumor microenvironment and destroy the redox steady state. Furthermore, photo-thermal nano enzyme, beta-ELE and hyaluronic acid are used as raw materials, and a novel soluble microneedle preparation is successfully prepared through a template method. The novel composite microneedle is in a sharp rectangular pyramid shape, growth of melanoma can be effectively inhibited through percutaneous delivery of photo-thermal nano-enzyme and beta-ELE, remarkable systemic toxicity is avoided, and an innovative strategy is provided for non-invasive, efficient and safe melanoma combined treatment.

The invention discloses saccharomyces cerevisiae recombinant bacteria for efficiently producing terpenoids as well as a construction method and application of the saccharomyces cerevisiae recombinant bacteria. According to the construction method, saccharomyces cerevisiae rich in terpenoid precursor farnesyl pyrophosphate is taken as a starting strain, the GAL80 protein level in a galactose induction system is regulated and controlled by introducing an N-Degron strategy, and meanwhile, a glucose concentration response type promoter HXT1 is introduced to effectively regulate and control the expression of GAL80 from the transcriptional level; the saccharomyces cerevisiae recombinant strain for efficiently producing the terpenoids can be obtained. The strategy is applied to a saccharomyces cerevisiae engineering strain of beta-elemene and patchouli alcohol, and a remarkable effect is achieved. And in the high-density fermentation process of the saccharomyces cerevisiae, the yield of the beta-elemene is obviously increased and reaches 4818.6 mg / L. The invention provides a solid research basis for sustainable biosynthesis of terpenoids, and has a wide application prospect.

The invention belongs to the technical field of biological medicines, and discloses application of beta-elemonic acid or derivatives thereof or pharmaceutically acceptable salts thereof in preparation of medicines for preventing and / or treating polycystic ovarian syndrome (PCOS). The beta-elemonic acid is screened from a medicinal and edible library, and experiments prove that the beta-elemonic acid can remarkably improve the PCOS ovarian form and the number of mature follicles, normalize the disordered estrus cycle, remarkably improve the serum hormone level and further remarkably improve the sugar tolerance, insulin tolerance and weight of PCOS. The beta-elemonic acid disclosed by the invention is a compound based on homology of medicine and food, can be used as a medicine as well as a natural ingredient of food, is relatively low in toxicity, ensures the safety after long-term use, is relatively low in safety evaluation cost of a relatively brand-new synthetic compound, and can be applied to development and preparation of a medicine or a lead compound thereof for preventing and / or treating PCOS, or a health care product.

The invention discloses a germacene A synthase mutant and application thereof, and belongs to the technical field of enzyme engineering and microbial engineering. Aiming at the bottleneck of the catalytic efficiency of the germacene A synthase, the optimal germacene A synthase mutant DlGASS32H-I97V-Y315F is obtained through semi-rational design based on sequence conservative analysis by taking the germacene A synthase from fungi with a separation wheel layer carbon shell as an object, and the optimal germacene A synthase mutant DlGASS32H-I97V-Y315F is verified through shake flask fermentation in engineering bacteria saccharomyces cerevisiae, so that the yield of beta-elemene is increased by 24%. The combined mutant obtained through a key gene conserved sequence mutation prediction strategy shows remarkably improved catalytic performance, the effectiveness of guiding an enzyme directed evolution strategy based on multi-species sequence conservative analysis is verified, and the yield of germacene A or beta-elemene is remarkably improved. Meanwhile, the method has the advantages of simplicity and convenience in operation, environmental friendliness, mild reaction conditions and the like, and has a very good application prospect in the field of production of germacene A.

The invention discloses a saccharomyces cerevisiae recombinant strain based on a uracil metabolism gene URA3 as well as a construction method and application of the saccharomyces cerevisiae recombinant strain. The construction method comprises the following steps: taking saccharomyces cerevisiae rich in farnesyl pyrophosphate as an original strain, introducing a uracil metabolism gene URA3, synchronously overexpressing a ribosome biosynthetic gene UTP10 and an iron metabolism gene FIT3, and utilizing the uracil metabolism gene URA3 to express up-regulation correlation with the ribosome biosynthetic gene UTP10 and the iron metabolism gene FIT3, so as to obtain the farnesyl pyrophosphate-rich saccharomyces cerevisiae. The metabolic flux of the terpenoids is enhanced, and the saccharomyces cerevisiae recombinant strain for efficiently producing the terpenoids is constructed. According to the method, a metabolic network of yeast is systematically optimized, and combined regulation and control on precursor flux distribution, protein translation capability and metal ion steady state are realized, so that the microbial synthesis efficiency of sesquiterpenoids such as patchouli alcohol and beta-elemene is remarkably improved.

The invention discloses a hydrophobic temperature-sensitive meso-porous silicon drug delivery system and a preparation method and application thereof.The drug delivery system takes copper sulfide nanoparticles as a core and amino-modified hydrophobic meso-porous silicon dioxide as a shell, the surface is coated with a temperature-sensitive polymer PEG-p (AAm-co-AN) coat, and the hydrophobic temperature-sensitive meso-porous silicon drug delivery system is prepared. Wherein the hydrophobic mesoporous silica is prepared from a silane coupling agent A151 containing a carbon-carbon double bond and a silicon source TEOS; the drug delivery system has a photo-thermal effect and upper critical solvent temperature responsiveness, can load a large amount of hydrophobic drugs such as beta-elemene, and can realize controllable release under irradiation of 980nm near-infrared light. The phase change temperature of the delivery system is 43 DEG C, so that the combined application of photo-thermal therapy and chemotherapy can be realized while the drug release is controlled, and a more effective tumor inhibition effect is achieved. In addition, the preparation method is simple and has a wide application prospect.

The invention belongs to the technical field of medicines, and particularly relates to a beta-elemene tryptophan methyl ester derivative and application thereof in preparation of antitumor drugs. According to the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I), on the basis of maintaining a beta-elemene structural framework, a tryptophan methyl ester group is introduced to the 13th site of beta-elemene, and unsubstituted C3-7 heterocycloalkyl, substituted C3-7 heterocycloalkyl, unsubstituted C5-11 hetero-spirocycloalkyl or substituted C5-11 hetero-spirocycloalkyl is introduced to the 14th site of beta-elemene, so that the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) is obtained. The water solubility and the pharmacokinetic property of the compound are effectively improved. Experimental results show that the anti-tumor activity of the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) provided by the invention is obviously enhanced compared with that of beta-elemene. Formula (I).

The application discloses a elemene colon-targeting nano-capsule and a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations, and comprises a core and a pH-sensitive enteric polymer coated on the surface of the core, wherein the core comprises elemene and a self-nanoemulsifying lipid material, and the self-nanoemulsifying lipid material comprises an oil phase, an emulsifier and a co-emulsifier. The nano-capsule has small particle size, uniform dispersion, a clear capsule structure, high drug loading and high encapsulation efficiency, can protect the drug from being released in advance in the stomach and small intestine, and can be effectively delivered to the colon. Animal experiments show that the nano-capsule releases the drug in the form of nanoemulsion in simulated colon fluid, can significantly inhibit the tumor growth of in-situ tumor-bearing mice, has good biological safety, and significantly improves the anti-colorectal cancer therapeutic effect of the drug.

Disclosed are a 14-chloro-β-elemene nitric oxide donor derivative and a preparation method and use thereof in the preparation of anti-tumor drugs. The 14-chloro-β-elemene nitric oxide donor derivative has a general formula shown in formula (I): in formula (I): R1 represents a linear or cyclic alcohol amine structure containing nitrogen and oxygen atoms; and each of R2 and R3 is independently selected from the group consisting of C1-10 alkyl, C3-12 cycloalkyl, C6-12 aryl, 5- to 10-membered cyclic heteroaryl, C2-10 alkenyl, C2-10 alkynyl, and C2-10 alkoxy.

The invention discloses a beta-elemene synthase and an application of the beta-elemene synthase in preparation of beta-elemene. On the basis of EL-Y0 chassis bacteria of high-yield precursor FPP, ERG20 (FPP synthase) and AarTPS72 (beta-elemene synthase) are subjected to fusion expression through flexible linker (GGGS) 2, and the metabolic flux of an MVA pathway is improved by overexpressing genes HIF-1, UPC2-1 and tHMGR, so that the biosynthesis of beta-elemene is improved; the engineering bacterium EL16 for producing the beta-elemene is successfully obtained; the final shake flask yield of the beta-elemene is 748.1 mg / L; in addition, the engineering bacterium EL16 is used for carrying out fed-batch fermentation in a 5L bioreactor, and the final titer of beta-elemene is 14.60 g / L.

The present invention discloses an engineered bacterium for producing β-elemene and its application. The recombinant bacterium provided by the present invention expresses genes for enzymes related to the IPP and DMAPP biosynthesis pathways, as well as farnesyl pyrophosphate synthase, and a mutant of the lettuce-derived germarene A synthase gene in the host Escherichia coli BL21(DE3)star. The recombinant bacterium can obtain a germarene A precursor after IPTG induction in SBMSN medium, and then generate β-elemene after high-temperature conversion. The time-to-yield reaches the highest level reported to date, providing a useful strain for the biosynthesis of β-elemene.

The invention provides the synthetase of the (-)-gemmarene A and the preparation method of the synthetase, and the synthesis of the (+)-beta-elemene is effectively realized.

The invention belongs to the field of biochemical engineering, and discloses a method for producing beta-elemene through microbial fermentation, which comprises the following steps: carrying out high-pressure sterilization on a culture medium for fermentation and a certain amount of solid phase a before fermentation, inoculating a recombinant strain into fermentation liquor after the temperature is reduced, with the inoculation amount of 1-5% (V / V), and adding IPTG for induction after the OD of the recombinant strain grows to 0.8-2.0, the total amount of the solid phase in the whole reaction system does not exceed 20% (W / V), fermenting until the growth of the recombinant strain declines, after the fermentation is finished, carrying out suction filtration, collecting the added solid phase, washing with water, pouring into a beaker, adding a certain amount of an organic solvent, carrying out ultrasonic extraction, and after the extraction is complete, carrying out vacuum drying to obtain the recombinant strain. And concentrating the organic solvent in a distillation or reduced pressure distillation manner to obtain a beta-elemene crude product. According to the invention, the yield of beta-elemene in escherichia coli is increased, and the cost is reduced for subsequent industrial production.

The invention discloses a biosynthesis of elemene and its application in tea tree anti-aphid, belonging to the field of biotechnology, elemene synthase, and its amino acid sequence is shown in SEQ ID No. 1. By increasing the content of elemene in tea trees, the ability of tea trees to avoid tea aphids is improved. The method of the invention can effectively control aphid pests, protect the growth and development of tea trees, improve the quality and yield of crops, and increase farmers' income.

The present invention belongs to the field of enzyme engineering technology, and specifically relates to a mutant of germaene A synthase and its application. The present invention obtains a series of chicory-derived germaene A synthase (CiGASlo) mutants by computer-aided design, constructs CiGASlo mutants by point mutation PCR method, further expresses recombinant protein and purifies, verifies enzyme activity by in vitro enzymatic reaction, and thus screens out CiGASlo mutants with significantly improved relative enzyme activity. The present invention can provide a CiGASlo mutant with significantly improved catalytic activity, which is helpful to promote and apply in the industrial production process of sesquiterpene compounds such as β-elemene. The present invention has the advantages of mild reaction conditions, high stereoselectivity, simple catalyst treatment steps, and environmental friendliness, and reduces equipment requirements, significantly reduces production costs, and shows a wide range of application prospects in industrial applications.

This invention belongs to the field of pharmaceutical technology, specifically relating to a series of novel Procaspase-3 activators and their application in the preparation of various malignant tumor drugs. One novel Procaspase-3 activator is a compound of Formula 1 and its salt. The β-elemene-structured Procaspase-3 activator described in this invention aims to activate the activity of Procaspase-3, which is highly expressed in various tumor cells, and induce tumor cell apoptosis restart. These new compounds exhibit stronger physiological activity and stability.

The application discloses a hydrophobic temperature-sensitive mesoporous silica drug delivery system and a preparation method and application thereof, and the drug delivery system takes copper sulfide nanoparticles as a core, takes amino-modified hydrophobic mesoporous silica as a shell, and is coated with a surface coating of a temperature-sensitive polymer PEG-p(AAm-co-AN), wherein the hydrophobic mesoporous silica is prepared from silane coupling agent A151 containing a carbon-carbon double bond and a silicon source TEOS; the drug delivery system has photothermal effect and upper critical solution temperature responsiveness, can load a large amount of hydrophobic drugs such as beta-elemene, and can realize controllable release under 980nm near-infrared light irradiation. The phase transition temperature of the delivery system is 43 DEG C, so that the combination of photothermal therapy and chemotherapy can be realized while the drug release is controlled, so as to achieve more effective tumor inhibition. In addition, the preparation method is simple and has wide application prospect.

This invention relates to the field of antitumor drug technology, and discloses a cervical cancer treatment composition based on β-elemene and its preparation method. The composition comprises β-elemene, dimethyl sulfoxide (DMSO), and a diluent matrix; wherein the final concentration of β-elemene is 10 μg / mL to 50 μg / mL, and the volume percentage of DMSO is constant at 0.4% to 0.6%. The preparation method includes preparing a stock solution and preparing the final product. By dynamically adjusting the volume of DMSO added, the total amount of solvent in the composition at different drug concentrations remains constant, thus establishing a strict single-variable evaluation system for in vitro drug delivery. This invention effectively eliminates the cytotoxicity additive interference caused by fluctuations in the amount of solubilizer in conventional drug delivery systems, prevents the aggregation and precipitation of poorly soluble components in the aqueous phase, and can objectively and accurately reflect the true pharmacological activity of β-elemene in inhibiting cervical cancer cells and inducing ferroptosis.

The invention relates to the fields of biochemical engineering, synthetic biology and biological medicine, in particular to a gemmarene A synthetase mutant, a fusion protein, an engineering strain and application. According to the invention, the GASX-L1H2H3V436LH4 with the highest catalytic activity is successfully obtained by means of point mutation and structural domain substitution; compared with wild type LTC2 and HaGAS1, the enzyme has the advantages that the catalytic activity is obviously improved, the fusion protein HaGAS1GGGSERG20 is constructed through a flexible linker, and the beta-elemene synthesis efficiency is further improved; on the basis, by strengthening a cytoplasm MVA pathway and constructing a peroxisome MVA pathway, intracellular precursor substances and acetyl coenzyme A are fully utilized, and the yield of elemene is further increased; on the basis, genes related to grease metabolism are screened to find overexpressed TGL4, and the shake flask yield of elemene is further increased.

The invention relates to the field of biochemical engineering, and discloses a post-treatment method for producing beta-elemene through liquid-liquid two-phase fermentation by using a solid drying agent, which comprises the following steps: adding 1-5% W / V of solid drying agent into an emulsion layer after fermentation to carry out step-by-step demulsification, and combining stirring and centrifugal operation, so that the recovery rate of an n-dodecane layer is increased to 79.7-81.6%; the yield of the target product beta-elemene is obviously improved. The method is suitable for the scale of shake flasks and fermentation tanks, has the advantages of simplicity in operation, low cost, high efficiency and the like, and provides an effective technical scheme for industrially producing beta-elemene raw material medicines by adopting microorganisms.

The invention relates to a combined medicine for treating cancer, the combined medicine contains beta elemene, the combined medicine is a single compound preparation or a combination of two single preparations, and the combined medicine effectively realizes the synergism of medicines.

The present invention relates to the technical fields of bioengineering, synthetic biology and computational biology, and in particular to a germacene A synthase mutant, a recombinant engineered bacterium and its use. Y376L The amino acid sequence of the germacrene A synthase mutant is shown in SEQ ID NO. 1. The germacrene A synthase mutant was transformed into Escherichia coli and the yield of the product, β-elemene, was measured, with a yield of 487.46 mg / L. This indicates that the mutant can be used for engineering strain transformation, providing a strong research foundation for high-yield β-elemene production.

The invention discloses a fertilizer for curcuma zedoary and a fertilization method, belongs to the technical field of plant fertilization, and solves the problem of how to increase the content of elemene in the curcuma zedoary. Comprising the following steps: S1, preparing a fertilizer for fertilizing curcuma zedoary in advance; s2, when curcuma zedoary seed stems are planted, base fertilizer is applied to gaps between the adjacent seed stems, soil covering and ridging are carried out, and enzyme liquid fertilizer is sprayed; s3, topdressing is conducted on the curcuma zedoary, topdressing is conducted three times, and when topdressing is conducted each time, corresponding enzyme liquid fertilizer is sprayed. By standardizing curcuma zedoary planting and scientifically fertilizing, the yield of curcuma zedoary is increased, and more high-quality raw materials are provided for elemene extraction, so that the yield of elemene is increased; the fertilizer obtained through a proper proportion promotes growth of curcuma zedoary and improves the yield and quality of curcuma zedoary. The curcuma zedoary is subjected to three times of additional fertilization, corresponding enzyme liquid fertilizer is sprayed during each time of additional fertilization, and the yield of the curcuma zedoary is increased by reasonably matching fertilization.

The invention relates to a beta-elemene concentrated preparation for injection, which has the characteristics of simple process, environmental friendliness, suitability for industrialization, lower cost and the like. The concentrated preparation for beta-elemene injection is prepared from the following components: beta-elemene, soybean oil, polyethylene glycol 15 hydroxystearate, egg yolk lecithin, polysorbate and the balance of absolute ethyl alcohol.

The invention belongs to the technical field of quality control of traditional Chinese medicines, and relates to a thin-layer chromatography identification method and application of bighead atractylodes rhizome and an extract thereof. The invention provides two thin-layer identification methods, one thin-layer identification method takes four components such as atractylenolide I, atractylenolide II, atractylenolide III and beta-eudesmol in bighead atractylodes rhizome as index components, and the other thin-layer identification method takes three components such as atractylenone, geranene B and beta-elemene in bighead atractylodes rhizome as index components. The two methods can be used for rapidly and accurately identifying the rhizoma atractylodis macrocephalae medicinal material, the rhizoma atractylodis macrocephalae volatile oil, the volatile oil clathrate and the rhizoma atractylodis macrocephalae clathrate related preparations, are mild in condition and easy to operate, are favorable for comprehensively improving the quality control level of rhizoma atractylodis macrocephalae related products, provide feasible reference for innovation and research and development related to rhizoma atractylodis macrocephalae in each stage, and have important industrial value.

The invention discloses an application of (1S, 2S, 4R)-1-methyl-2, 4-bis (prop-1-ene-2-yl)-1-vinylcyclohexane (alias, beta-elemene) in preparation of a medicine, and the medicine is used for treating or preventing diseases related to acute inflammation, such as acute inflammation, acute inflammation, acute inflammation, acute inflammation and acute inflammation. Comprise acute lung injury related to sepsis caused by lipopolysaccharide (LPS), acute edema pancreatitis induced by ceratidine and severe necrotizing pancreatitis induced by L-arginine, but are not limited to the inducers, and specifically, the inducers can be used for inducing acute lung injury related to sepsis caused by lipopolysaccharide (LPS), acute edema pancreatitis induced by ceratidine and severe necrotizing pancreatitis induced by L-arginine. The medicine can inhibit or improve pathological injury and inflammatory response of lung tissue and pancreatic tissue of acute lung injury and acute pancreatitis.

The invention relates to application of terpenoids in tobacco leaf baking yellowing, a tobacco fumigation yellowing agent and application thereof, and belongs to the technical field of tobacco processing. A large number of experiments find that in the tobacco leaf baking process, the terpenoids (alpha-pinene, beta-pinene, 1, 8-terpenes, alpha-bisabolol, bisabolol and beta-elemene) can promote smooth proceeding of internal biochemical reaction of tobacco leaves in the flue-cured tobacco fumigation period through the unique chemical properties of the terpenoids, and therefore the tobacco leaf curing effect is improved. Meanwhile, generation of harmful substances is reduced, and the overall quality of the tobacco leaves is improved. A new research direction is provided for accelerating yellowing of tobacco leaves in the tobacco baking process, the problem of yellowing of green stems in the flue-cured tobacco baking process is effectively solved, the quality of flue-cured tobacco is improved, the green and environment-friendly production target is achieved, and the requirement for sustainable development of modern agriculture is met.

The invention discloses application of TRPV1, NUDT9 and MT-ND5 as targets in preparation and screening of drugs for treating brain glioma, and belongs to the technical field of biology. According to the application disclosed by the invention, experiments prove that the expression of NUDT9 and MT-ND5 in brain glioma cells is knocked down, the proliferation of the brain glioma cells is reduced, TRPV1 in the brain glioma cells is knocked down, the proliferation of the brain glioma cells is promoted, the expression of NUDT9 and MT-ND5 in the brain glioma cells is reduced by beta-elemene, and the beta-elemene has the effect of inhibiting tumor growth; the application prospect of the TRPV1, the NUDT9 and the MT-ND5 serving as the target spot in screening the medicine for treating the brain glioma is shown. According to the application disclosed by the invention, the condition that the beta-elemene and the TMZ are combined to enhance DNA damage accumulation through a synergistic effect, continuously activate a cell apoptosis pathway and increase the sensitivity of glioma cells to the TMZ is determined for the first time, so that the curative effect is improved, and the toxicity is reduced.

The present invention discloses a 13-heterocyclic-β-elemene nitric oxide donor derivative, its preparation, and use. The present invention provides a 13-heterocyclic-β-elemene nitric oxide donor derivative having a structure as shown in general formula (I), or a pharmaceutically acceptable salt or solvate thereof, or an enantiomer or diastereomer thereof. The derivative of the present invention surpasses previous β-elemene nitric oxide donor derivatives in design strategy by introducing a nitrogen-containing ring structure and an NO donor that enhance antitumor activity in vivo. This significantly improves the physicochemical properties of the β-elemene nucleus and can be used to treat leukemia, among other diseases for which effective therapeutic agents are currently lacking. #imgabs0#

The invention provides recombinant yarrowia lipolytica for producing beta-elemene in a subcellular compartment and a construction method and application of the recombinant yarrowia lipolytica, and belongs to the field of bioengineering. The recombinant yarrowia lipolytica is prepared by taking yarrowia lipolytica as an original strain, performing localization expression on a germacene A synthase coding gene in a liposome through a liposome localization signal Oleosin, and knocking out a peroxisome biogenic factor 10 in a yarrowia lipolytica genome, so as to obtain the recombinant yarrowia lipolytica. And inserting into a 3-hydroxy-3-methylglutaryl CoA reductase expression cassette, a farnesyl pyrophosphate synthase expression cassette, an isopentenyl pyrophosphate isomerase expression cassette, a diacylglycerol acyltransferase expression cassette and a sterol acyltransferase expression cassette to obtain the recombinant expression vector. The recombinant yarrowia lipolytica disclosed by the invention can be used for efficiently producing beta-elemene.