41 results about "10-hydroxycamptothecine" patented technology

The invention provides a preparation method of a target compound nano particle, relating to a preparation method of target treatment integration compound nano particles. The invention solves the technical problems of poor carrier stability and small drug-loading quantity of the traditional antineoplastic drugs. The method comprises the following steps of: preparing a methanol solution of an integrated nano particle of a Fe3O4-HCPT@SiO2 coupling porphyrin photosensitizer; and stirring the methanol solution of the integrated nano particle of the Fe3O4-HCPT@SiO2 coupling porphyrin photosensitizer, N,N-dimethylformamide and target biomolecule or antitumor drug for reacting at the room temperature, and centrifuging to obtain the target compound nano particle. Polystyrolsulfon acid (PSS) and 10-hydroxycamptothecine are absorbed on a Fe3O4 magnetic nano particle through a self-assembly mode. The preparation method is high feasibility; the target compound nano particle has a physical target function of the magnetic nano particle and an active target function of further functionally modifying the biomolecule on the surface; and the medicine concentration can be increased under a dual-target function.

The invention discloses a 7-ethyl-10-hydroxycamptothecine drug precursor, a preparation method and an application thereof. A structure formula of the drug precursor is represented as the formula I or II. The drug precursor is prepared through an esterification reaction between a C-10 hydroxyl group or a C-20 hydroxyl group of 7-ethyl-10-hydroxycamptothecine and a hydrophobic molecule. The drug precursor has excellent anti-tumor activity and can directly release active components in vivo in a hydrolysis manner without catalytic hydrolysis of carboxylesterase, thereby achieving a high bioavailability. The drug precursor not only has excellent solubility in water but also has great solubility in amphipathic surfactants, such as tween-80 and the like, wherein the solubility can reach more than 30 mg / ml, and a high stability is achieved even that the drug precursor is diluted in water. The drug precursor can be prepared just through a one-step esterification method, is high in yield and low in preparation cost, is high in stability and good in safety, satisfies requirements in clinical medication and in large-scale industrial production, and has excellent market prospect and clinical application value.

A 10-hydroxy camptothecine lipoid is disclosed, which has high anticancer function and curative effect and high water solubility and stability. Its preparing process is also disclosed, in which phosphatide and cholesterin are used as filming material, the chloroform, alcohol or ether is used as solvent, and the mannitol or glucose is used as the protectant for freeze drying.

The invention discloses a novel water-soluble targeted nano drug carrier based on carboxymethyl chitosan, and a preparation method of the novel water-soluble targeted nano drug carrier. The method comprises the following steps: linking targeted molecular folic acid with polyethylene glycol by using an amido bond; coupling the obtained folic acid-polyethylene glycol conjugate with the carboxymethylchitosan by means of an amidation reaction; enabling the product to be subjected to an esterification reaction with ursolic acid; enabling the prepared folic acid-polyethylene glycol-carboxymethyl chitosan-ursolic acid conjugate to be wrapped with another medicine, i.e., 10-hydroxycamptothecine by means of self-assembling in water so as to obtain nanoparticles loaded with two anticancer medicines. The nanoparticles have two-layer structures, the outer layer is hydrophilic carboxymethyl chitosan-polyethylene glycol, and the inner layer is the hydrophobic drug ursolic acid and the 10-hydroxycamptothecine. The novel water-soluble targeted nano drug carrier has the advantages that the nano drug carrier improves the water solubility, stability and half-life period of the ursolic acid and the 10-hydroxycamptothecine, so that the drug loading capacity is greatly increased; the folic acid is linked for enhancing the targeting effect of the medicines on tumor sites; the method is simple in preparation process and easy to operate.

The invention provides an intermediate of Irinotecan with the advantages of simple synthetic process, mild condition and easy control and the preparation method thereof, and a method for preparing Irinotecan from the same, wherein the intermediate is 4-piperidino piperidine-1-formic acid. The preparation method of the intermediate comprises an acylation step and a hydrolysis step. Irinotecan is prepared by condensing the intermediate and 7-ethyl-10-hydroxycamptothecine. The preparation method avoids the defects of the prior art, reduces the impurity content, and shortens the production period, and can directly synthesize the target product with high purity, therefore, the preparation method is of great significance and of huge economic benefit in reducing the production cost, widening the clinical application of the Irinotecan, reducing therapeutic cost, etc.

The invention belongs to the medical technical field, and discloses 7-ethyl-10-hydroxycamptothecine liposome freeze-dried powder injection and a preparation method thereof. The 7-ethyl-10-hydroxycamptothecine liposome freeze-dried powder injection comprises the following components: 1-10g of 7-ethyl-10-hydroxycamptothecine, 30-60g of phospholipids, 10-40g of cholesterol, 2-8g of VE, 100-300g of a freeze drying protectant, 2000-8000ml of an organic solvent, 1000-4000ml of alkaline buffer salt solution and 1000-4000ml of acid buffer salt solution. The preparation method comprises the following steps: dissolving liposoluble components in the organic solvent and water-soluble components in the alkaline buffer salt; transferring the organic solvent, and then adding the alkaline buffer salt for hydration; and carrying freeze drying in vacuum, re-dissolving with the acid buffer salt, incubating, filtering, sterilizing, and carrying out freeze drying again to obtain the 7-ethyl-10-hydroxycamptothecine liposome freeze-dried powder injection for injection. The invention solves the problems of low solubility and fast in-vivo metabolism of the 7-ethyl-10-hydroxycamptothecine, thus lowering toxic reaction, eliminating side reaction, having higher target distribution characteristics, prolonging metabolism time and improving solubility and bioavailability.

The invention discloses a 7-ethyl-10-hydroxycamptothecine (SN38) conjugated polymer, a preparation method, a nano-preparation of the conjugated polymer and an anti-tumor application. C-10 position or C-20 position hydroxy of a 7-ethyl-10-hydroxycamptothecine compound is conjugated with different molecular weight terminal carboxyl group polymers through covalent bonds to obtain an SN38 series conjugated prodrug, and then amphiphilic polymer materials and the SN38 prodrug are prepared into a nano-drug. The nano-drug solves the problem of poor water solubility of SN38, and slow release of the SN38 is achieved in vitro. Besides, the particle diameter of the nano-drug is mainly distributed within the range of 20-50nm, high permeability and EPR (enhanced permeation and retention) effects of nano-particles through solid tumors are achieved, and passive targeting functions of the nano-particles are enhanced. The nano-drug has good effects in vitro and vivo and accordingly has a good application prospect.

The invention relates to a cancer compound 10-hydroxycamptothecine and crizotinib for treating lung cancer and application. Active components of the medicinal composition include a chemotherapy medicine 10-hydroxycamptothecine and a targeting medicine crizotinib. The invention also relates to application of 10-hydroxycamptothecine and crizotinib in the field of cancer treatment drugs. According tothe cancer compound 10-hydroxycamptothecine and crizotinib for treating lung cancer, the anti-tumor medicine 10-hydroxycamptothecine and the targeting medicine crizotinib are used in match; the in vitro experiment verifies that the chemotherapy medicine 10-hydroxycamptothecine and the targeting medicine crizotinib are obviously synergistically interacted in killing malignant cells. The new application of the drug combination helps reducing the toxic and side effects of chemotherapy medicines; the drug resistance of the targeting medicine can also be reduced; the tumor inhibiting effect is improved; and scientific foundation is supplied to develop new drugs.

The invention belongs to technical filed of biology, in particular to a method for promoting biosynthesis of 10-hydroxycamptothecine. The method comprises the following steps of: constructing a suspension culture system of camptotheca acuminata cells for an explant by using leaves of camptotheca acuminata plants; adding three kinds of exogenous substances such as cobalt nitrate, lanthanum nitrate and salicylic acid to regulate and control the secondary metabolism of the camptotheca acuminata cells; and inoculating two kinds of microorganisms such as Mucor spinosus and Aspergillus niger for biotransformation at the later stage of cell culture, placing the treated camptotheca acuminata cell culture into a pulp refiner, into which an ethanol solution is added, for homogenating, and filtering to obtain filtrate containing 10-hydroxycamptothecine. The method has the characteristics of short production period, low production cost and high yield of 10-hydroxycamptothecine, and is beneficial to the protection of the camptotheca acuminata plant resources.

The invention discloses a method for preparing a nano-drug common delivery system based on a pectin and multi-arm polyethylene glycol and particularly relates to a novel pectin nano-drug. A pectin (PET) and eight-arm polyethylene glycol (8 ARM-PEG-COOH) serve as carriers and load dihydroartemisinin (DHA) and betulinic acid (BA) together; firstly, eight-arm polyethylene glycol reacts with betulinic acid (BA) to form polyethylene glycol-dihydroartemisinin (8 ARM-PEG-BA), the pectin reacts with a certain amount of dihydroartemisinin to form pectin-dihydroartemisinin (PET-DHA), then 8 ARM-PEG-BA reacts with PET-DHA to form BA-PEG-PET-DHA, then BA-PEG-PET-DHA and 10-hydroxycamptothecine (HCPT) are self-assembled to form nano particles BA-PEG-PET-DHA (HCPT).NPs, drug loading efficiency is high, and targeting performance is high. The method for preparing the nano-drug common delivery system based on the pectin and multi-arm polyethylene glycol has the sustained release function, pectin and multi-arm polyethylene glycol are good in biocompatibility, and the formed nano-drug is low in toxicity. The method belongs to the fields of biopharmacy and nanotechnology. The preparation process is simple, operation is convenient, and the experiment period is short.

The invention relates to application of degalactotigonin and a derivative thereof in preparation of an antitumor medicine. The nightshade Solanum Linn is extracted and separated from the compound. A pharmacological experiment proves that the degalactotigonin has high inhibition rate on tumor cells at a certain concentration; the anti-patent activity of degalactotigonin is obviously higher than that of a positive medicine 10-hydroxycamptothecine; the desgalactotigonin has relatively low toxicity on normal cells, and can be used for treating tumor diseases such as liver cancer, lung cancer, gastric cancer, colon cancer, breast cancer, ovarian cancer, oral cancer, esophagus cancer, bile duct cancer and leukemia. The invention further discloses a method for extracting degalactotigonin from plants. The method is simple and feasible, and has a good industrial prospect.

A 10-hydroxy camptothecine lipoid is disclosed, which has high anticancer function and curative effect and high water solubility and stability. Its preparing process is also disclosed, in which phosphatide and cholesterin are used as filming material, the chloroform, alcohol or ether is used as solvent, and the mannitol or glucose is used as the protectant for freeze drying.

The invention discloses a preparation method of a multi-component nanometer medicine with a collaborative treatment effect and high drug loading. The preparation method comprises the following steps of: 1) dissolving three hydrophobic cancer-fighting medicines, namely, methotrexate, 10-hydroxycamptothecine and taxol which are in a mass ratio of 1: 1: 1, into dimethylsulfoxide; ultrasonically treating for 5 minutes to produce mixed solution with concentration of 3mg / mL; 2) dropwise adding 400 micro-millimeters of the mixed solution into ultrapure water; and magnetically stirring to obtain suspension liquid of the multi-component nanometer medicine; and 3) adding 300 micro-millimetres of polymaleic anhydride 18 carbene-polyethylene glycol with concentration of 1mg / mL to the suspension liquid of the multi-component nanometer medicine; ultrasonically dispersing for 5 minutes; and standing for 3 minutes. The preparation method is simple, efficient, high in repeatability, excellent in controllability and high in universality, and provides experimental bases for preparing the nanometer medicine applied to multi-medicine collaborative treatment in the cancer field.

The invention provides application of a curcumin on preparation of a medicine for preventing or / and treating a late diarrhea caused by an anti-tumor medicine, wherein the anti-tumor medicine is irinotecan or an active metabolite 7-thyl-10-hydroxycamptothecine (SN-38), and the late diarrhea is a severe diarrhea capable of lasting for 7 days appeared after the irinotecan is administrated for 24 hours. The curcumin provided by the invention is definite in efficacy; and with the adoption of the curcumin, the late diarrhea can be effectively relieved and the intestinal mucosa is protected.

The invention relates to 10-hydroxycamptothecine derivatives and applications thereof and belongs to the field of pesticides. The 10-hydroxycamptothecine is spliced with active sites of a conventional chemical pesticide, namely, a pyrethroid pesticide to obtain a series of pyrethroid-10-hydroxycamptothecine derivatives, so that the pyrethroid-10-hydroxycamptothecine derivatives maintain the original excellent antifeedant activity of the 10-hydroxycamptothecine to beet armyworms, can also be endowed with the excellent contact toxicity of the pyrethroid pesticide to the beet armyworms and have important research significance for the development of new high-efficiency low-toxicity pesticides with a unique targeting effect.

The invention relates to an amphiphilic polymer prodrug for reducing responsive 7-ethyl-10-hydroxycamptothecine and a preparation method thereof. The amphiphilic polymer prodrug has the molecular structure as shown in the specification, wherein the polymerization degree n is 5-1000 and m is 1 or 2. According to the prodrug, targeted drug delivery can be realized, and therefore the advantages of anano drug carrier system are kept, and meanwhile, the characteristic that a disulfide bond is specifically degraded in a tumor site can be achieved. Compared with conventional 2,2'-disulfanediyldiacetic acid, 3,3'-dithiodipropionic acid and other connecting arms, the prodrug and the preparation method thereof have the advantage that an anticancer drug in an active compound molecular form can be obtained without further hydrolysis.

The invention provides a 10-hydroxycamptothecine invisible nano-particle sustained release preparation and a preparation method thereof, relating to a new preparation of medical antitumor medicaments. The invention provides the 10-hydroxycamptothecine invisible nano-particle sustained release preparation which has long sustained drug release time, stable drug release and high bioavailability, and the preparation method thereof. The 10-hydroxycamptothecine invisible nano-particle sustained release preparation is composed of 10-hydroxycamptothecine and a medical carrier, wherein the mass ratio of the 10-hydroxycamptothecine to the medical carrier is 1:(2-20). The preparation method comprises the steps of: dissolving the 10-hydroxycamptothecine and the medical carrier in the mass ratio of 1:(2-20) in an organic solvent to obtain a solution A; transferring the solution A into a dialysis bag to dialyze; and freeze drying the obtained suspension to obtain the 10-hydroxycamptothecine invisible nano-particle sustained release preparation.

The invention relates to a preparation method of irinotecan hydrochloride. The method comprises the steps that a mother ring reacts with propionaldehyde by taking camptothecin as a raw material to generate 7-ethylcamptothecin, and then hydrogen peroxide is used for oxidization to generate N-oxide-7-ethylcamptothecin; illumination rearrangement is carried out to generate 7-ethyl-10-hydroxycamptothecine; 4-piperidinopiperidine reacts with dimethyl carbonate to generate 4-piperidinopiperidine methyl carbonate; 7-ethyl-10-hydroxycamptothecine reacts with 4-piperidinopiperidine methyl carbonate togenerate irinotecan monomer; the irinotecan monomer and hydrochloric acid are salified to obtain an irinotecan hydrochloride finished product. Compared with the prior art, in the reaction process, phosgene, chloroform and other toxic substances are prevented from being used, and the irinotecan hydrochloride has the advantages of being safe, convenient to use, little in pollution and the like during production. Besides, the synthesis method avoids the defect that a chromatographic column is needed for separation and purification in the prior art, the production cost of irinotecan is reduced, and huge economic benefits are achieved.

The invention discloses a conjugate of 10-hydroxycamptothecine-butanedioic acid and adenovirus. The preparation method of the conjugate comprises the following steps of: catalyzing 10-hydroxycamptothecine and succinic anhydride in anhydrous pyridine by virtue of 4-dimethylamino-pyridine so that a hydroxyl on the 10-hydroxycamptothecine reacts with a carboxyl on the succinic anhydride to generate HCPT-SA; reacting the HCPT-SA with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in N,N-dimethyl formamide through N-hydroxysuccinimide, and then adding adenovirus for a dark reaction; then reacting the carboxyl on the HCPT-SA with the amino group of adenovirus capsidprotein to form the conjugate of 10-hydroxycamptothecine-butanedioic acid and adenovirus. The conjugate of 10-hydroxycamptothecine-butanedioic acid and adenovirus provided by the invention is applied to preparation of anti-tumor drugs.

The invention relates to a method used for producing camptothecin and 10-hydroxycamptothecine with camptotheca acuminate suspension cells, and belongs to the field of medical biotechnology. The method comprises following steps: 1, MS liquid medium is inoculated with camptotheca acuminate suspension cells for culturing, wherein sorbitol is added in culturing process; 2, corresponding suspension cells and cell culture fluid are collected; and 3, separation extraction of camptothecin and 10-hydroxycamptothecine are carried out. The method used for producing camptothecin and 10-hydroxycamptothecine with camptotheca acuminate suspension cells is simple, and is convenient to control. Compared with a conventional camptothecin and 10-hydroxycamptothecine preparation method, the method comprises following advantages: sorbitol is taken as an inducible factor, and is capable of increasing camptothecin and 10-hydroxycamptothecine yield by more than 100 to 500 times.

A self-microemulsifying 10-hydroxycamptothecine composition applied by injection or orally features that its self-microemulsifier is prepared from oil phase, surfactant and cosurfactant. After it is taken into human body, it can automatically microemulsifying for higher biologic utilization rate.

The invention relates to a method for carrying out liposome modification on compound with free hydroxyl groups, in particular to liposome modified taxol and analogues thereof, as well as nanoparticlescontaining the liposome modified drug. According to the method disclosed by the invention, the taxol modified by liposome N,N'-di-dodecyl-L-glutamate diamide (LG-C12), 10-hydroxycamptothecine, irinotecan and epothilone B are specifically designed and successfully prepared, and the hydrophobicity of drugs is improved; then NH2-mPEG-DSPE bonded by mPEG-DSPE and mitochondrial targeted molecular triphenylphosphonium bromide (TPP) is utilized to coat liposome modified drugs to assemble into nanoparticles which improve the cytotoxic effect of the drugs on cancer cells and also reduce the toxic andside effects of the drugs on humans or animals.

The invention discloses a 7-ethyl-10-hydroxycamptothecine drug precursor, a preparation method and an application thereof. A structure formula of the drug precursor is represented as the formula I or II. The drug precursor is prepared through an esterification reaction between a C-10 hydroxyl group or a C-20 hydroxyl group of 7-ethyl-10-hydroxycamptothecine and a hydrophobic molecule. The drug precursor has excellent anti-tumor activity and can directly release active components in vivo in a hydrolysis manner without catalytic hydrolysis of carboxylesterase, thereby achieving a high bioavailability. The drug precursor not only has excellent solubility in water but also has great solubility in amphipathic surfactants, such as tween-80 and the like, wherein the solubility can reach more than 30 mg / ml, and a high stability is achieved even that the drug precursor is diluted in water. The drug precursor can be prepared just through a one-step esterification method, is high in yield and low in preparation cost, is high in stability and good in safety, satisfies requirements in clinical medication and in large-scale industrial production, and has excellent market prospect and clinical application value.

The invention provides a method for producing irinotecan, which comprises the following steps of: (1) purifying an initial raw material SN-38 to obtain a pure SN-38, and controlling the impurities in the pure SN-38 till the single impurity is less than 0.1 percent; and (2) condensing the pure SN-38 and free 4-piperidyl piperidine formyl chloride base and then refining to obtain the irinotecan, wherein column chromatography does not need to be adopted in the refining. Preferably, in the step (1), the initial raw material SN-38 is sequentially treated by adopting methanol, acetic acid and ethanol re-crystallization so as to obtain the pure SN-38; 10-hydroxycamptothecine in the impurities is controlled to be less than 0.05 percent; and the ratio of the free 4-piperidyl piperidine formyl chloride base to the pure SN-38 is at least 1.2:1. Because the column chromatography is not needed in the irinotecan refining process, the method for producing the irinotecan shortens the production period, simplifies the operation, reduces the cost, improves the yield and is suitable for industrialized scale production.

The invention relates to 7-ethyl-10-hydroxycamptothecine crystal forms II and III, and a preparation method and application thereof. The crystal form II uses Cu-K alpha radiation; the X-ray powder diffraction represented by 2theta angle has characteristic peaks when the diffraction angle is 5.64, 10.80, 12.55, 13.48, 17.09, 17.65, 18.21, 18.79, 24.52 and 26.84 degrees; and the error range of 2theta is + / -0.2 degree. The crystal form III uses Cu-K alpha radiation; the X-ray powder diffraction represented by 2theta angle has characteristic peaks when the diffraction angle is 4.58, 9.34, 10.42, 11.12, 12.30, 13.40, 14.40, 16.34, 16.86, 17.20, 17.70, 18.72, 19.32, 21.48, 22.44, 24.90, 25.40, 25.68 and 27.44 degrees; and the error range of 2theta is + / -0.2 degree. The two crystal forms of 7-ethyl-10-hydroxycamptothecine have high solubility and favorable stability.

The invention provides a method for synthesizing and purifying irinotecan. The method prepares irinotecan that is an antineoplastic compound with high purity quotient through the purification of 7-ethide-10-hydroxycamptothecine that is an intermediate for synthesizing irinotecan and crystallization for impurity removal of hydrochloric piperidyl piperidine formyl chloride; secondary reaction is reduced, and the purity quotient as well as the yield of products are increased through improving the reaction condition at the same time, especially through cryoconcentration evolution; the purity quotient of the obtained products is more than 99.5 percent, and the single hetero is less than 0.1 percent. In addition, the method overcomes the disadvantages that the cycle is long, the solvent quantity is large, etc. caused by column chromatography that is used for purifying the products, and large scale production is easy to realize.

The invention provides a preparation method and application of a 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation, relates to a preparation method and application of a porphyrinphotosensitizer composite preparation and aims at solving the technical field of poor survival rate effect of the existing porphyrin compound photosensitizer on cancer cells. The method comprises thefollowing steps of 1, preparing dimerization L-glutamic acid; 2, preparing tetramerization L-glutamic acid; 3, preparing hexameric L-glutamic acid; 4, preparing hexameric glutamic acid bonding porphyrin dimers; 5, preparing the 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation. The 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation is applied to inhibition of the cancer cell survival rate. The 10-hydroxycamptothecine / porphyrin photosensitizer composite preparation can lower the cancer cell survival rate to 10 percent under the condition of the illumination for 40 min.

The invention provides a preparation method of a target compound nano particle, relating to a preparation method of target treatment integration compound nano particles. The invention solves the technical problems of poor carrier stability and small drug-loading quantity of the traditional antineoplastic drugs. The method comprises the following steps of: preparing a methanol solution of an integrated nano particle of a Fe3O4-HCPT@SiO2 coupling porphyrin photosensitizer; and stirring the methanol solution of the integrated nano particle of the Fe3O4-HCPT@SiO2 coupling porphyrin photosensitizer, N,N-dimethylformamide and target biomolecule or antitumor drug for reacting at the room temperature, and centrifuging to obtain the target compound nano particle. Polystyrolsulfon acid (PSS) and 10-hydroxycamptothecine are absorbed on a Fe3O4 magnetic nano particle through a self-assembly mode. The preparation method is high feasibility; the target compound nano particle has a physical target function of the magnetic nano particle and an active target function of further functionally modifying the biomolecule on the surface; and the medicine concentration can be increased under a dual-target function.

The invention provides an intermediate of Irinotecan with the advantages of simple synthetic process, mild condition and easy control and the preparation method thereof, and a method for preparing Irinotecan from the same, wherein the intermediate is 4-piperidino piperidine-1-formic acid. The preparation method of the intermediate comprises an acylation step and a hydrolysis step. Irinotecan is prepared by condensing the intermediate and 7-ethyl-10-hydroxycamptothecine. The preparation method avoids the defects of the prior art, reduces the impurity content, and shortens the production period, and can directly synthesize the target product with high purity, therefore, the preparation method is of great significance and of huge economic benefit in reducing the production cost, widening theclinical application of the Irinotecan, reducing therapeutic cost, etc.

The invention discloses a method for preparing high-purity 9-allyl-10-hydroxycamptothecine (compound 1). The method comprises the following steps of: (1) reacting 10-hydroxycamptothecine with a halogenated reagent to obtain 9-bromine-10-hydroxycamptothecine and 9-iodine-10-hydroxycamptothecine; (2) protecting 10-position hydroxyl; (3) introducing a Suzuki reaction into the allyl; and (4) removingthe protective group to obtain the compound 1. The product has the characteristics of high purity and capability of meeting the clinical requirement.