67 results about "Triptolide" patented technology

The present application relates to a kind of cytochrome P450 oxidase CYP716C52 protein, and the CYP716C52 protein coding gene, the protein can catalyze hydroxylation of maytenic acid C2 position to generate triptolide acid C, in turn participate in triptolide biosynthesis.

The invention belongs to the field of new application of medicines, and particularly relates to application of triptolide in preparation of medicines for treating diabetic vascular obstruction complications. Diabetes vascular obstruction is a common serious complication of diabetes and can cause various tissue injuries such as cardiovascular diseases, nephropathy and retinopathy. Experiments prove that the triptolide can remarkably improve the problems of blood vessel blockage, blood flow slowing, abnormal neovascularization and the like caused in a high-glucose environment, and meanwhile, the expression of blood glucose related indexes (such as Glucose and HbA1c) and inflammatory factors (such as TNF-alpha and IL-1beta) is reduced. In addition, triptolide can also protect pancreas from high glucose damage and improve functions of pancreatic beta cells. According to the invention, the clinical application range of the triptolide is expanded, and a new candidate substance is provided for drug treatment of diabetic vascular complications.

The present disclosure provides triptolide conjugates, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat conditions / diseases, such as those related to cancer, immune modulation, and / or inflammation.

The application discloses a triptolide nano-micelle, a synthesis method and application thereof. The nano-micelle is formed by self-assembly of triptolide, metal ions and a modular functional polymer through metal coordination; and the high molecular polymer is covalently connected by a metal coordination group R1, a hydrophilic polymer main chain R2 and a functional end-capping group R3. The application constructs a micelle system by relying on the coordination of three components without an exogenous carrier, avoids potential biological safety risks accompanied by traditional nano-carriers, reduces the complexity of the synthesis process of the medicament, and significantly improves the storage stability of the preparation after freeze-drying. The obtained micelle has good water solubility, can be quickly reconstituted after freeze-drying without a freeze-drying protective agent, has an ATP response drug release characteristic in a tumor microenvironment, and can be used for antitumor drug delivery.

This invention provides the application of triptolide in the preparation of drugs for treating microglial inflammation-related neuroimmunological disorders. Experiments show that triptolide significantly inhibits the expression, migration, phagocytosis, and morphological activation of microglial inflammatory factors, and exerts an anti-microglial inflammatory effect in animal models. Through DARTS technology combined with siRNA screening, ACOX1 was identified as its key target, and the direct binding between the two was verified by CETSA, SPR, and molecular docking.

The invention provides a tripterine sulfated metabolite and application thereof in preparation of a medicine for resisting rheumatoid arthritis, and belongs to the technical field of biological medicine. The tripterine sulfated metabolite is 10-sulfated tripterine which is formed by connecting a HSO3 <-> to the 10-position carbon of the tripterine. Compared with the tripterine, the 10-sulfonated tripterine has no obvious difference in anti-rheumatoid arthritis pharmacological activity, however, the hepatotoxicity in vivo and the cytotoxicity in vitro of the 10-sulfonated tripterine are obviously reduced. The tripterine sulfated metabolite is efficient and low in toxicity, and a wide application prospect is developed for treatment of rheumatoid arthritis.

The invention belongs to the field of biological medicine, and relates to application of triptolide in preparation of a medicine for preventing and treating calcified aortic valve diseases. The triptolide is found to be capable of promoting expression and maturation of CTSD and activating enzyme activity of the CTSD, meanwhile, biogenesis of lysosome in valvular interstitial cells can be promoted by regulating and controlling AKT / mTOR / TFEB signal axes, lysosome functions are improved, autophagy flux is recovered, and finally the effect of treating the calcified aortic valve disease is achieved. A novel treatment medicine is provided for the calcified aortic valve disease.

The invention belongs to the technical field of medicines, and particularly relates to tripterine-loaded nano-particles as well as a preparation method and application thereof, and the tripterine-loaded nano-particles (Cel-GDNPs) comprise ginger exosome (GDNPs) and tripterine (Cel) encapsulated in the ginger exosome. According to the invention, the Cel is used as a therapeutic drug, and the adopted carrier GDNPs has anti-inflammatory activity, so that when the Cel and the GDNPs are used for treating inflammatory diseases such as colitis and the like, the Cel and the GDNPs can play a multi-component synergistic therapeutic effect, and compared with the single use of the Cel or the GDNPs, the expression of proinflammatory factors (such as TNF-alpha, IL-1beta and IL-6) can be more effectively inhibited, so that the synergistic therapeutic effect is realized; a new strategy is provided for developing a novel natural compound preparation.

The present invention relates to the technical field of pharmaceutics, and in particular to a triptolide lignocerate, a liposome thereof and a preparation method therefor. The chemical structural formula of the triptolide lignocerate is represented by formula (I). The triptolide lignocerate provided by the present invention is obtained by esterification of triptolide C14-OH and lignoceric acid. The anti-tumor effectiveness, safety and the like of the triptolide lignocerate liposome are further improved with respect to the prior art, so that a foundation is laid for providing safer and more effective triptolide-related clinical preparations.

The invention discloses application of triptolide ketone in preparation of a medicine for treating sepsis lung injury, and belongs to the technical field of biological medicine. Aiming at the problems that traditional chemical synthetic drugs may cause a large amount of sequelae and antibiotic abuse, and triptolide may cause liver and kidney injury when treating sepsis, research finds that triptolide can be used for treating sepsis lung injury, and can be used for treating sepsis lung injury. According to the application, the protein expression level of HIF-1alpha in proinflammatory activated macrophages is lowered, so that aerobic glycolysis is inhibited, and the effect of treating sepsis lung injury is achieved. Compared with the triptolide alcohol, the triptolide ketone does not cause liver and kidney injury while playing a role in treating the sepsis lung injury, and the curative effect of the triptolide ketone is equivalent to that of the existing medicine 2ME2 for treating the sepsis lung injury, so that the triptolide ketone has important application potential clinically, and can be used for preparing medicines for treating the sepsis lung injury. And a theoretical basis is provided for clinically developing medicines for treating sepsis lung injury.

This invention belongs to the field of biomedical technology, specifically relating to triptolide liposomes (TP-lipo), their combined use, and their application in the prevention and treatment of tumors. To enhance the efficacy of triptolide in the treatment and prevention of tumors such as pancreatic cancer, cervical cancer, ovarian cancer, and colorectal cancer, and to improve its bioavailability and clinical application while reducing toxicity, this invention uses HSPC, DOPS, and cholesterol as liposome components to encapsulate triptolide monomers, thus preparing TP-lipo. Experiments have shown that TP-lipo exhibits anti-tumor activity: it directly kills tumor cells and reverses the immunosuppressive microenvironment, making it a potential drug for tumor treatment. TP-lipo, when used in combination with PD-1 antibodies, or in combination with radiotherapy, chemotherapy, or surgery, demonstrates a potent and synergistic anti-tumor effect with low toxicity. Therefore, the TP-lipo of this invention provides more clinical strategies for tumor treatment.

The invention discloses triptolide hydrogel, a preparation method thereof and application of the triptolide hydrogel in preparation of a medicine for treating hepatocellular carcinoma, and belongs to the field of biological medicine. The stable injectable hydrogel drug is prepared by utilizing the self-assembly capability of glycyrrhizic acid saponins and loading triptolide, and while the anti-tumor effect of triptolide is played, the toxic and side effects are reduced by virtue of the targeting and anti-inflammatory effects of glycyrrhizic acid, and accurate treatment of liver cancer is realized.

The invention belongs to the technical field of biological medicine, and particularly relates to a rheumatism immune disease treatment composition combining traditional Chinese medicine active ingredients and immune regulation and application of the rheumatism immune disease treatment composition, and the rheumatism immune disease treatment composition comprises the following components in parts by weight: 10-50 parts of a traditional Chinese medicine active ingredient compound; 0.01 to 1 part of an immune regulation factor; 50 to 90 parts of pharmaceutic adjuvants; wherein the traditional Chinese medicine active component compound is prepared from the following components: astragaloside, artemisinin, curcumin and triptolide in a weight ratio of (2-5): (1-3): (1-4): (0.5-2); the immunoregulation factor is composed of recombinant human interleukin-10 (rhIL-10), a transforming growth factor-beta1 (TGF-beta1) and a CTLA4-Ig fusion protein according to a weight ratio of (1-3): (0.5-2): (1-4). The active ingredients of the traditional Chinese medicine cover a plurality of links of anti-inflammation, anti-oxidation, immunoregulation and the like, and immunoregulatory factors accurately intervene in immune cell activation and a cell factor network to jointly inhibit abnormal immune response.

The application discloses application of triptolide-loaded ZIF-8 sustained-release material in preparation of a forest and farm harmful animal control agent. The triptolide-loaded ZIF-8 sustained-release material is composed of a ZIF-8 carrier and triptolide loaded on the ZIF-8 carrier. Through loading of triptolide by the ZIF-8, the concentration of free triptolide in the system is effectively reduced, the release rate of triptolide is slowed down, the inhibition of triptolide on soil self-nitrogen fixation bacteria can be relieved, and soil urease activity can be adjusted, and the harmful animal control effect and soil ecological environment safety are considered.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an angiotensin II receptor antagonist in preparation of a medicine for preventing and treating renal tubular injury caused by triptolide. According to the invention, the upstream key target protein of the TPL-induced renal tubule injury is determined to be HSPA1 through experiments for the first time, and the problem that the key target spot of TPL toxicity is not determined in the prior art is solved. Based on a key target spot of TPL toxicity, through molecular screening and parallel pharmacodynamic verification on various sartan drugs such as irbesartan, losartan, olmesartan and valsartan, it is determined that the angiotensin II receptor antagonist has a general protection effect on TPL toxicity. Wherein the protective efficacy of irbesartan as a preferable embodiment is obviously superior to that of losartan of the same kind (the efficiency slope is 2.451 to 1.584).

The application discloses a kind of nanomedicine for treating rheumatoid arthritis, including triptolide, Y6 fluorescent probe and poloxamer, triptolide and Y6 fluorescent probe are polymerized by poloxamer to form triptolide nanomedicine Y6@TPL, the average particle size of the triptolide nanomedicine Y6@TPL is 20~300nm.The application combines triptolide with Y6 fluorescent probe, constructs a new type of nano delivery system, the system not only realizes the accurate control release of drug, but also can be enhanced by photo-thermal response Targeted accumulation of rheumatoid arthritis lesion site, significantly improve the selective killing effect of triptolide on inflammatory synoviocytes, while greatly reducing the toxic side effects on normal joint tissue.The nano system integrates photo-thermal therapy, photo-thermal imaging and targeted drug delivery functions, and provides an integrated solution for the diagnosis and treatment of RA.

The invention discloses a nano-drug for treating rheumatoid arthritis, the nano-drug comprises triptolide, a Y6 fluorescent probe and poloxamer, the triptolide and the Y6 fluorescent probe are polymerized by the poloxamer to form a triptolide nano-drug Y6 at TPL, and the average particle size of the triptolide nano-drug Y6 at TPL is 20-300 nm. The triptolide and the Y6 fluorescent probe are combined to construct a novel nano delivery system, the system not only realizes precise controlled release of drugs, but also can enhance targeted accumulation of rheumatoid arthritis focus parts through photo-thermal response, the selective killing effect of the triptolide on inflammatory synovial cells is remarkably improved, and the application prospect is broad. Meanwhile, the toxic and side effects on normal joint tissues are greatly reduced. According to the nano system, photo-thermal treatment, photo-thermal imaging and targeted drug delivery functions are integrated, and an integrated solution is provided for diagnosis and treatment of RA.

The invention belongs to the technical field of biological medicines, and particularly relates to a drug-loaded nano-micelle as well as a preparation method and application thereof. According to the invention, bromoalkanes with different chain lengths are introduced to a leonurine phenolic hydroxyl group by adopting a total synthesis method to prepare a leonurine derivative, and the drug-loaded nano-micelle is prepared by applying triptolide (TP) and the leonurine derivative. The embodiment of the invention verifies that the drug-loaded nano-micelle can reduce in-vivo and in-vitro toxicity caused by triptolide and improve the treatment effect on a mouse arthritis model induced by type II collagen. The novel triptolide compatible medicine prepared by the invention is small in toxic and side effects and has a good curative effect on rheumatoid arthritis.

The invention discloses application of brusatrolactone A in preparation of a medicine for treating HIV infectious diseases, and belongs to the technical field of biological medicine. The invention provides an application of gall gall lactone A in preparation of a medicine for treating human immunodeficiency virus infectious diseases. The invention also relates to a pharmaceutical composition for treating the HIV infection disease, and the pharmaceutical composition comprises the brusatrolactone A and pharmaceutically acceptable auxiliary materials. A cell model experiment proves that the brusatrolactone A has a remarkable effect on inhibiting HIV (human immunodeficiency virus) from invading cells and inhibiting the replication of the HIV in host cells. The medicament not only expands the medicament selection of HIV infection, but also further expands the application range of the brusatrolactone A.

The invention relates to the technical field of biological medicine, in particular to application of tripterine or medicinal salt thereof in preparation of medicine for treating ketoacidosis or symptoms caused by ketoacidosis. The invention provides application of tripterine or medicinal salt thereof in preparation of a medicine for treating ketoacidosis or symptoms caused by ketoacidosis. The result of the specific embodiment of the invention shows that the tripterine can obviously reduce the mouse serum beta-hydroxybutyric acid level caused by hunger; the tripterine can be used for remarkably reducing the expression of HMGCS2 in the liver of a mouse; the dapagliflozin remarkably promotes the level of beta-hydroxybutyric acid, and the tripterine remarkably reduces the level of mouse serum beta-hydroxybutyric acid caused by treatment of the dapagliflozin. Therefore, tripterine can be used for treating or improving ketoacidosis or symptoms caused by ketoacidosis. The invention provides a new technical scheme for treatment and improvement of ketoacidosis or symptoms caused by ketoacidosis.

The application relates to the technical field of extraction equipment, and particularly discloses a high-energy triptolide extraction and separation equipment and an extraction process, which solves the problem of poor extraction of triptolide in the prior art; the equipment comprises a base, a premixing box is arranged above the base, a feeding assembly for feeding is arranged at the upper end of the premixing box, a separation cylinder is arranged at the discharging position of the lower end of the premixing box, a second piston plate and a first piston plate are slidably arranged in the separation cylinder, and the lower end of the second piston plate is rotationally connected with a central shaft at the middle position, the application is designed according to the existing needs, the extraction liquid can be preliminarily mixed with bitter gourd raw materials, then the two piston plates moving up and down are used to mix and extrude the mixed materials, centrifugal separation is completed by cooperating with high-speed rotation of the materials, and residual materials are discharged at the end of the reciprocating movement, so that the extraction effect of the bitter gourd is greatly improved.

The application discloses a preparation method of a triptolide sesquiterpene alkaloid purity standard sample, and belongs to the technical field of natural product separation and purification and standard substance preparation. The method comprises the following steps: obtaining total alkaloid crude products through ethanol extraction and acid-dissolution alkalinization extraction, enriching the total alkaloid crude products through methanol grading, pre-separating the total alkaloid crude products through a specific two-phase system of petroleum ether (60-90 DEG C)-ethyl acetate-isopropyl alcohol-water HSCCC, and finally obtaining monomer products with purity greater than or equal to 99.0% through reverse-phase preparation HPLC refining and low-temperature multiple recrystallization. The obtained standard sample has water content less than or equal to 0.5%, residual solvents meet the requirements of ICH Q3C and the Chinese Pharmacopoeia, and the impurity spectrum fingerprint similarity is greater than or equal to 0.98 under different raw material batches and amplification conditions, so that the batch consistency, traceability and storage stability are significantly improved, and the strict requirements of standard substances in quality control and analytical detection are met.

The present application relates to a cytochrome P450 oxidase, and a gene encoding the cytochrome P450 oxidase, the enzyme is involved in the final key step of the biosynthesis of important active ingredients of Tripterygium wilfordii, triptolide and / or neo-triptolide, and can be used for biosynthesis of triptolide and / or neo-triptolide.

This invention belongs to the field of pesticide technology and discloses a synergistic ant-killing powder based on traditional Chinese medicine extracts. This powder uses aminated modified biochar as a bifunctional carrier, loading a complex of active ingredients including triptolide and rotenone. It addresses the problems of short duration of action and poor targeting of existing plant-derived ant killers through an electrostatic adsorption-slow-release synergistic mechanism. Its components include 65%–85% aminated modified biochar, 3%–8% triptolide, 2%–6% rotenone, 5%–15% flow aid, and 1%–3% anti-caking agent. The carrier is prepared from agricultural waste through oxygen-limited pyrolysis and silane grafting, possessing a high specific surface area and controllable pore size, which can stably anchor the active ingredients and trigger release in the alkaline microenvironment of ants. This ant-killing powder extends the duration of action, improves efficacy utilization, and has low toxicity to non-target organisms, making it suitable for green pest control in various scenarios.

This application relates to the field of natural product chemistry, specifically disclosing a method for extracting triptolide and its application. The extraction method for triptolide includes the following steps: S1, pretreatment: After washing and drying the roots of Tripterygium wilfordii, it is subjected to ultrafine pulverization and plasma treatment to obtain Tripterygium wilfordii powder; S2, enzymatic hydrolysis: After enzymatic hydrolysis of the Tripterygium wilfordii powder, the enzyme is inactivated, centrifuged, concentrated, and dried to obtain crude triptolide; S3, purification: The crude triptolide is purified by high-speed countercurrent chromatography and vacuum dried to obtain refined triptolide. The above extraction method is simple and safe to operate, and the purity and extraction rate of the obtained triptolide are improved. The obtained triptolide can be mixed with total glucosides of paeony, glycyrrhizic acid, papain, poloxamer, xanthan gum, and propylene glycol to prepare a drug for treating rheumatoid arthritis, which has significant efficacy, high safety, and broad clinical application prospects.

The invention discloses a new application of tripterine, namely application of the tripterine in preparation of bladder cancer resisting drugs, in-vitro cell experiments prove that the tripterine shows remarkable proliferation inhibition activity on various bladder cancer cell strains including cell strains UM-UC-3, TCCSUP and T24 and a cis-platinum drug-resistant strain T24CDDP, the median inhibitory concentration (IC50) of the tripterine is 0.2688-0.5870 mu M, and the tripterine shows remarkable proliferation inhibition activity on various bladder cancer cell strains including cell strains UM-UC-3, TCCSUP and T24 and a cis-platinum drug-resistant strain T24CDDP. The further mechanism research shows that the tripterine can regulate and control the cell cycle by down-regulating the expression levels of CDK1 and CDC5L proteins in bladder cancer cells and up-regulating the expression of phosphorylated p53 (p-p53) proteins at the same time, thereby playing a role in resisting bladder cancer; the invention provides a new effective candidate drug for clinical treatment of bladder cancer, especially cis-platinum resistant bladder cancer, and has important clinical application value.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tripterine prodrug compound as well as a preparation method and application thereof. The tripterine prodrug compound provided by the invention has a structure as shown in a formula I. The tripterine prodrug compound designed by utilizing the unique high expression characteristic of nitrate reductase in a tumor microenvironment can be specifically activated by the nitrate reductase at a tumor part, so that accurate release of tripterine at the tumor part is realized; the tripterine prodrug compound is kept relatively stable in normal tissues, so that the toxic effect on tissues such as normal livers is greatly reduced, and an innovative and potential solution is provided for solving the hepatotoxicity problem of the tripterine and improving the anti-tumor treatment effect of the tripterine; and breakthrough is hopefully brought to tumor treatment and the clinical application value is improved. Formula I.

The invention discloses a recombinant bacterium and application thereof in production of triptolic acid C or a precursor friedelin thereof. The recombinant strain expresses a gene TwOSC1T502E for synthesizing a tripterygium wilfordii C precursor friedelin, so that de novo synthesis of friedelin is realized, and the yield of the precursor friedelin is increased through MVA (Mycopoeic Acid) pathway optimization and peroxisome metabolism-form collaborative optimization; the method comprises the following steps: by taking tripterygium wilfordii as a raw material, firstly synthesizing tripterygium wilfordii in saccharomyces cerevisiae, then expressing tripterygium wilfordii C synthesis related genes ThCYP712K1 and TrCYP716C52 and TwCPR3, realizing de novo synthesis of tripterygium wilfordii C in saccharomyces cerevisiae, obtaining the ThCYP712K1 mutant ThCYP712K1I124V with improved activity through enzyme engineering, and remarkably improving the yield of tripterygium wilfordii C through lipid droplet engineering modification and cofactor engineering modification. The recombinant strain provided by the invention can be used for efficiently producing the triptolide C and the precursor friedelin of the triptolide C, and has an important application value.

The invention discloses a preparation method of L-echinacea A and an acid salt thereof. The preparation method of the L-echinacea A acid salt comprises the following synthetic route. And carrying out alkalization treatment on the L-inclusion canine A acid salt, so as to obtain the L-inclusion canine. According to the invention, pyridinium salt and chiral N-acryloyl oxazolidinone are taken as initial raw materials, a (2R, 5R, 6S) core skeleton of the obtuseline A is selectively constructed through a 1, 3-dipolar cycloaddition reaction, then introduction of all carbon atoms in the obtuseline A is completed through processes of hydrogenation reduction, transamination, hydroboration reduction reaction, methylation and the like, and the novel preparation method of the obtuseline A is realized. The preparation method comprises the following steps: by taking L-echinokimene as a raw material, carrying out protection group replacement, oxidation rearrangement reaction, protection group removal and other processes to prepare L-echinokimene acid salt, and carrying out alkalization treatment on the L-echinokimene acid salt to obtain the L-echinokimene with optical activity, the whole route is simple and convenient, the yield is good, the selectivity is relatively good, and the reaction conditions are mild and controllable.

This disclosure provides triptolide-conjugates, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, as well methods of using such compounds in the treatment of conditions / diseases, such as those relating to cancer, immunomodulation and / or inflammation.