116 results about "Taxane Compound" patented technology

The invention discloses a preparation method of a taxanes compound shown as the formula I in the specification, relating to the field of pharmaceutical chemistry. The preparation method comprises the following steps of: under the water isolating condition, with docetaxel as a raw material and benzene alcohol, ketons or ethers compounds as a solvent, dropwise adding dimethyl sulfate, carrying out the alkylation reaction for 0.5 to 10 hours at the temperature of 10 to 60 DEG C, controlling the PH value of the reaction solution between 7 and 8 by an alkalescent organic solvent during the alkylation reaction, and adding water for separate out crystals after the alkylation reaction, wherein the crystals are the compound shown as the formula I. In the preparation method, a one-step method is adopted to prepare the taxanes compound cabazitaxel shown as the formula I. The preparation method has the advantages of few reaction steps, mild reaction condition, short reaction time and high reaction efficiency, and is favorable for industrial production. Meanwhile, through controlling the dropping speed of an alkylating agent and the PH value of the reaction solution, the docetaxel can be prevented from decomposing and the purity of the reaction product can be enhanced.

The present invention is broadly directed to novel compounds useful for the synthesis of biologically active compounds. More particularly, the present embodiments disclosed herein relate to novel side chains, that when coupled to a taxane, are useful for the synthesis of pharmaceutically useful taxanes. Methods of forming the novel side chains and coupling them to hindered alcohols, namely taxanes resulting in useful esters are also disclosed. Various taxanes compounds are known to exhibit anti-tumor activity.

The invention discloses a method for extracting and separating taxol and other taxane compounds from yew. The method includes the steps of extraction, degreasing, crude separation to an organic phase and an aqueous phase respectively, refined separation with reverse-phase chromatography, and crystallization. The invention sequentially adopts the ethanol of 80 to 95 percent, 60 to 75 percent and 20 to 55 percent to carry out gradient extraction to the yew material and also to fully extract taxane compounds with different polarities so as to lead the total extraction rate of the taxane compounds to be raised to more than 90 percent from 70 percent of the traditional art; the simultaneous extracting of 8 different tazane compound monomers from one set of the yew material is realized by the invention and the purity of each monomer can reach more than 98 percent; an aqueous phase substance which is generated in the extraction process abandoned by the traditional art is fully utilized to raise the utilization rate of the taxane compounds in the yew by 10 to 20 times, therefore, the bottleneck problem of industrial production of the lack of yew material is effectively solved.

The invention discloses a taxane medicinal precursor, which is a conjugate formed by bonding a hydroxyl group at C-2' or C-7 position of a taxane compound and water-soluble targeting peptide through a conjugation bridge, wherein the conjugation bridge contains at least one of an ester bond, a carbonic ester bond, a urea bond and a disulfide bond. Compared with the taxane compound, the medicinal precursor has the advantages that the medicinal precursor has extremely high water solubility capable of reaching 2mg/ml, so that the problem that the taxane compound can only be dissolved by using an unsafe substance such as an organic solvent and tween 80 in the prior art is solved; due to the adoption of a covalent coupling mode, the taxane medicinal precursor is ensured to have high stability when being stored in vitro, and the taxane compound can be rapidly released to achieve medicinal effects after the taxane medicinal precursor enters cells; the taxane compound can be carried to a specific tumor cell through the targeting peptide to reduce killing ability to normal cells; a decomposed product of the targeting peptide in the cells is amino acid, so that high biocompatibility is ensured.

The invention provides a self-emulsifying medical composition for delivering taxane medicaments and a preparation method thereof. The self-emulsifying medical composition is transparent liquid, comprises an effective dose of taxane compound, an oil component, a surface active agent and alcohol and preferentially comprises lactic acid, wherein the surface active agent consists of phospholipid and polyoxyethylenated castor oil. After the self-emulsifying composition is added to a glucose injection, the composition can self-emulsify into micro emulsion the mean grain size of which is 50-300nm, and the micro emulsion can stabilize for more than 12 hours at room temperature. The preferential taxane compound in the invention is taxol.

The invention relates to a method for preparing a water-soluble taxane medicament and application thereof. In the water-soluble taxane compounds with a formula I structure, R1 is phenyl or alkoxide, R2 is acetyl or hydrogen atoms, and R3 is directly directed or 4-amino benzyloxy formyl.

The invention relates to a method for using specific resin and silicon gel column chromatography purification via negative pressure cavitation water extraction to high-efficiency produce 10-deacetylbaccatin III and 7-xylose-10-deacetylpaclitaxel, which uses taxus branch leaves as raw material, dries and breaks to process negative pressure cavitation water extraction, filters and uses AB-8 resin to process dynamic absorption on filter liquor to concentrate 10-deacetylbaccatin III and 7-xylose-10-deacetylpaclitaxel and process further purification via middle pressure silicon gel column chromatography, to obtain the 10-deacetylbaccatin III of at least 60% purity and 7-xylose-10-deacetylpaclitaxel of at least 67% purity. The invention can use renewable taxus branch leaves to protect ecological resource and effectively extract effective component and biological semi synthesis precursor materials, with simple operation, support for industrial application and important industrial production value.

The invention discloses a taxus chinensis cell strain with high yield of 10-DAB, is named taxuswallichianavar. mairei plant cell line N12#, and is preserved in CGMCC, and the preservation number is CGMCC No.10001. The invention further discloses screening and establishment of a 10-DAB high-yield cell line (10-DeacetylbaccatinIII, CASNO: 32981-86-5). A high-yield 10-DAB cell line is induced and screened from taxuswallichianavar. mairei explant. Experimental results prove that the cell line can highly produce taxane diterpenoids such as secondary metabolites 10-DAB and can be used for production of crude drug precursors of paclitaxel and docetaxel.

The invention relates to a taxane compound and a preparation method thereof and in particular relates to an intermediate compound for preparing cabazitaxel, a preparation method of the intermediate compound and a method for preparing cabazitaxel with the compound. The intermediate compound is shown in the formula V in the specification. In each step in the process of preparing cabazitaxel with the intermediate, the reaction time is greatly shortened and the reaction yield is substantially increased, thus greatly lowering the synthesis cost of cabazitaxel. The formula V is shown in the specification.

The present invention relates to cultivation method of increasing taxol content in Chinese yew. The method is to apply lanthanum containing compound as fertilizer additive under proper Chinese yew growing condition. In the root part of soil cultivated Chinese yew, lanthanum containing compound in 0.00015-0.0015 mole is applied for each plant, or, in the water culture liquid for Chinese yew, lanthanum containing compound is added to La ion concentration of 0.001-0.01 mol/L. The present invention can raise taxol content in Chinese yew and increase yield of taxane compounds with extremely high economic value. The present invention has wide application foreground.

The invention provides a method for purifying a taxane compound. The method comprises the processes of solvent drying, double recrystallization, once pulping and drying, can effectively remove impurities, water, ignition residues, mechanical and inorganic impurities and a residual solvent generated in the processes of preparing and storing the taxane compound; and the method has mild condition, simple and convenient operation and higher yield and is easy to control. The content of any single impurity of a refined product is lower than 0.1 percent by the detection of a high performance liquid chromatograph, and the total impurity content is lower than 0.5 percent; and the obtained refined product is the anhydrous crystallization taxane compound with high stability and content.

The invention discloses a drug composition of taxanes, which comprises taxane compounds with effective dosage for treatment, a surfactant, a cosolvent and a stabilizer, wherein the cosolvent is selected from one or a mixture of more of polyethylene glycol, propylene glycol, glycerine or ethylene glycol; and the stabilizer is selected from hydrochloride, carbonate, phosphate and nitrate or a mixture of hydrochloride, carbonate, phosphate and nitrate. The composition can be an injection, a frozen dry powder needle or a kit for combined use. The composition can improve the solubility and stability of the taxane compounds. The invention also discloses a method for preparing the drug composition and application of the drug composition.

The invention relates to a method for preparing polyhydroxy taxane and paclitaxel, which pertains to the manufacturing method of natural medical chemical substances or drug raw materials, aims at the tight source of paclitaxel, and selectively converts the multi-acetyl taxane with high abundance in the alcohol extract of yew plant material or cell culture into corresponding polyhydroxy taxane while separating the paclitaxel. The invention comprises the steps of resin column separation, alumina chromatographic column separation, hydrolysis reaction, the solid phase extraction of polyhydroxy taxane, the elution of polyhydroxy taxane, the purification of paclitaxel and the purification of polyhydroxy taxane, thus obtaining the paclitaxel with the purity approaching to 99.5 percent and the polyhydroxy taxane with the purity being more than 98 percent. The invention selectively converts the multi-acetyl taxane with high abundance into corresponding polyhydroxy taxane, produces raw materials which can be used in the pharmaceuticals industry, significantly reduces the loss of taxane compounds in the raw materials and improves the availability of biological resources.

The present invention relates to a method of forming taxane diterpene by difference transformation 7- taxane using microorganisms. The present invention comprised the following steps: 1. Completely dissolve the 7- taxane compound which has a content of over 1% into the organic solvent that can be mixed with water at any ratio; 2. Add the solution of step 1 into the microbes biological culture, or abstraction enzyme from themicro-organism. An alternative is that after the extractenzyme immobilization, the solution of step 1 is added and the conversion time is 3-100 hours; 3. Extract taxane diterpene using conventional methods from the convert product of step 2. The technical problem solved in this invention is that the no valueble 7- taxane is converted into a valuble enantiomer, so as to save the resources of Yew.

This invention is directed to a method for isolating and/or purifying one or more taxanes from materials comprising taxanes. In one embodiment, the method comprises the steps of: (a) treating a taxane containing material with an amino containing material attached to a solid matrix, such as a polyethyleneimine-bonded silica chromatographic resin; (b) eluting the desired taxane compound from the resin; and (c) recovering the eluted taxane compound.

The invention discloses a taxus chinensis cell strain (Taxus wallichiana var.mairei) with the high-yield paclitaxel characteristic. The taxus chinensis cell strain is named taxus chinensis var.mairei plant cell system NO51-3 which is preserved in the China General Microbiological Culture Collection Center, and the preservation number is CGMCCNo.10002. The invention further discloses a method for screening and establishing a paclitaxel high-yield cell system (Paclitaxel, CASNO:33069-62-4, with a trade name Taxol as a common name). The cell system with the high yield of paclitaxel is induced and screened from taxus chinensis explants, and the experiment result shows that the cell system is high in yield of taxane compounds such as secondary metabolite paclitaxel, and can be used as a raw material medicine for treating ovarian cancer, breast cancer and the like.

This invention provides a novel cancer treatment method in which plinabulin (t-butyl-dehydrophenylahistin or NPI-2358) and a taxane compound (such as docetaxel) are used in combination. Our study has shown that the optimum combination of injecting plinabulin after taxane compound has unexpected enhanced efficacy in large tumor populations in animal model and in NSCLC cancer patients compared to taxane compound treatment alone. In addition, this optimum combination can achieve unexpected safety effect in lowering unbearable side effects of taxane compound, including decreasing its neutropenia rates at all grades and decreasing G-CSF use in cancer patients.

The invention relates to a method for removing protective groups and preparing a dimethoxy taxane compound. The invention belongs to the technical field of medicines used for treating prostate cancer. According to the invention, an acid is dissolved in methanol; silica gel with a specification of 100-800 meshes is added to the solution, and the solution is sufficiently stirred under room temperature; the solution is dried by rotary evaporation, such that acid-activated silica gel is obtained; the acid-activated silica gel is dissolved in an organic solvent; a compound 3-Boc-2-p-methoxy phenyl-4-phenyl-(2R,4S,5R)-1,3-oxazolidine-5-carboxylate 4alpha-acetoxy-2alpha-benzoyloxy-5beta,20-epoxy-1beta-hydroxyl-9-oxygen-7beta,10beta-dimethoxy-11-taxadiene-13alpha ester is added to the solution; the mixture is continuously stirred, and is subject to a reaction; an obtained reaction liquid is processed through pump filtration; an obtained filtrate is dried by condensation, and is processed through silica gel column chromatography, such that the product dimethoxy taxane compound is obtained. According to the invention, the protective groups are removed in an acidic environment, such that the dimethoxy taxane compound is prepared. The method is advantaged in simple operation, suitability for industrialized productions, no by-product during the reaction process, improved reaction yield, and improved product purity.

This invention is based on the discovery that the administration of a sphingosine-1-phosphate receptor antagonist (S1P) and at least one chemotherapeutic agent selected from the the group of antimicrotubule agents provides an unexpectedly superior treatment for cancer. Antimicrobial agents such as the taxane compounds are known in the art, for example, paclitaxel (available as TAXOL® from Bristol-Myers Squibb, Princeton, N.J.), docetaxel (available as TAXOTERE® from Sanofi-aventis, Bridgewater, N.J.) and the like and other compounds that act as antimicrotubule agents, such as Vincristine (ONCOVIN®, VINCASAR PFS®, VCR), Vinblastin (VELBAN®, VELSAR®) and Vinorelbine, and similar compounds. The present invention also provides methods of modulating the growth of selected cell populations, such as cancer cells, by administering a therapeutically effective amount of at least one sphingosine-1-phosphate 1 (S1P1R) receptor antagonists, and at least one antimicrotubule agent.

The invention discloses a water-soluble polymer containing taxol and taxol ester and actively targeting a tumor and a preparation method of the polymer. The water-soluble polymer is prepared by conjugating a polymer containing taxol or docetaxel with polyglutamic acid, and tumor actively-targeted molecular folic acid is modified on the structure basis of polyglutamic acid-taxane compounds. The water-soluble polymer disclosed by the invention can be used for treatment of tumors.

The invention discloses a method for preparing taxol, docetaxel and other taxanes. The taxanes synthesized or semi-synthesized or extracted from the plants are used as the raw materials, the waterborne solvent is used to dissolve the materials, and the macroporous absorption resins such as Diaion Hp resins, Amberlite XAD resins are used as the stationery phase, the organic solvents such as THF, N, N-DMF and other solvents are used as the eluent, the atmospheric pressure column chromatography is adopted, one step is enough to extract the taxanes with the purity above 99.90% with high yield above 99.0%. The invention has the advantages of simple method, convenient operation, favorableness to production expansion, small amount and recyclability of organic solvent and environmental friendliness.

The invention relates to a 'one-pot' method which is suitable for industrial application, which is used for preparing taxol and derivatives thereof. The method adopts 10-deacetyl- taxane compounds simultaneously containing hydroxyls at the sites of C(2') and C(10) as raw material; under the catalytic function of metal element salt, by using acetic oxide, the hydroxyls at the sites C(2') and C(10) are selectively acetylated, and then peroxidate and alkaline matter are added into the reaction system; the acetyl is selectively hydrolyzed at the site of C(2'), thereby obtaining the taxane compounds with acetylated hydroxyl at C(10) site.

The invention relates to a plant cell culture technology, in particular to a method for inducible production of taxane by utilization of Chinese yew cells. The method comprises the following steps that: the Chinese yew cells are placed into a commonly used culture medium for culture, and the cell inoculum size is between 50 and 200 grams per liter green weight; in the initial stage of the exponential growth of the cells, a revulsant with a concentration of between 1 and 2,000 micrometers, 50 to 200 grams of sterile absorbent and 10 to 50 grams of sugar are added into per liter of the culture medium; and in the intermediate stage of the exponential growth of the cells, the revulsant with a concentration of between 1 and 2,000 micrometers is added for the second time; and the revulsant is an abiological revulsant or a fungal elicitor. Because a large part of taxane compounds are externally secreted to the outsides of the cells and absorbed on the absorbent, the operation of separation and purification is greatly simplified, thereby the cost is reduced and the industrialized production is easy to realize. Moreover, because the method can produce novel taxane compounds by means of induction, the taxane is taken as a precursor compound of a first-line anticarcinogenic drug, namely paclitaxel, and the technology has important commercial application prospect.