162 results about "Podophyllotoxin" patented technology

The invention relates to conjugates of anti-integrin specific antibodies with cytotoxic compounds, the synthesis, selection, and use of such conjugates for use in cancer therapy or other diseases mediated by cell proliferation, cell migration, or inflammation and which pathology involves angiogenesis or neovascularization of new tissue. In addition the invention relates to combination therapy of such diseases wherein the treatment comprises use of said conjugates in combination with one or more other treatment modalities including but not limited to: chemotherapy, surgery or radiation therapy. The preferred conjugates contain maytansinoid compounds linked to the antibody by a disulfide linkage, and preferred chemotherapeutic agents are doxorubicin, a taxane, a camptothecin, a podophyllotoxin, a nucleoside analog, or a pyrimidine analog.

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and / or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant.

[PROBLEMS] A novel podophyllotoxin derivative, which is capable of releasing a drug without depending on biological enzymes and can be expected to have an effective therapeutic effect and is soluble in water has been demanded.[MEANS FOR SOLVING PROBLEMS] A polymer having a polyethyleneglycol structural unit and two or more succinic monoamide structural units, particularly a polymer conjugate of a podophyllotoxin in which a carboxylic acid group of polyethyleneglycol / polyaspartic acid copolymer and a hydroxyl group of podophyllotoxin and linked via an ester bond is provided.

The present invention discloses compositions comprising podophyllotoxins, analogs thereof, or derivatives thereof, and a surfactant. The invention also discloses a podophyllotoxin composition further comprising a targeting moiety. The present invention also discloses a method of delivering a podophyllotoxin, an analog thereof or a derivative thereof, to a cell by administering the described podophylootoxin compositions. Further, the present invention discloses a method of making the podophyllotoxin compositions.

The invention discloses a Chinese traditional medicine composition for treating cancer and its preparation. The composition comprises the following traditional Chinese medicines by weight ratio: 500 to 1000 of American ginseng, 500 to 1000g of radix astragali, 500 to 1000g of Radix aristolochiae, 200 to 1200 of cordyceps sinensis, 120 to 1000 of sappan wood, podophyllotoxin, radix bupleuri, turmeric, heydyotis, common pleione pseudobulb, tulipa edulis and barbat skullcap, 500 to 1500 of airpotato yam rhizome, curcuma rhizome, rhizoma paridis, pseudo-ginseng, salvia chinensis and mythic fungus, 50 to 100 of licorice, 1 to 20 of gamboge and 500 to 2000 of ligustrum lucidum. A traditional Chinese medicine preparation prepared by the invention has the advantages of controllable and stable quality, convenient taking, and is used for the treatment and the auxiliary treatment of various types of cancers, the composition provided in the invention has definite therapeutic effect and small toxicity and side effect.

The invention relates to a podophyllotoxin vesicle and a preparation method thereof. The preparation method takes a non-ionic surfactant and modification lipids as vesicle materials, and adds cholesterol, dicetyl phosphate and the like as stabilizers. The vesicle having the advantage of good preparation stability is a novel preparation easy to industrialize.

The invention discloses a sulfur-substituted podophyllotoxin derivative as well as a synthetic method and application thereof. The podophyllotoxin derivative, shown by a formula (V), with significantly improved anti-tumor activity and reduced toxic or side effect is obtained by introducing an aromatic heterocyclic compound with rigidity and a further sulfonamide product of 3-amino-5-mercapto-1,2,4-triazole, 2-amino-5-mercapto-1,3,4-thiadiazole, and 4-methyl benzenesulfonyl chloride or 4-methoxy benzenesulfonyl chloride, serving as substituent groups, into the fourth position of a C ring of podophyllotoxin or 4'-demethylepipodophyllotoxin respectively. An activity inhibition experiment of tumor cells in vitro shows that the anti-tumor activity of the compound shown by the formula (V) is significantly improved as compared with that of podophyllotoxin or 4'-demethylepipodophyllotoxin.

The invention relates to a method for extracting podophyllotoxin from dysosma versipellis. The method comprises the steps as follows: extracting with waveform to obtain extract; adding the extract to macroreticular resin column to absorb; eluting; recovering alcohol in a pressure reduced way; concentrating; adding the concentrate to polyamide chromatographic column; eluting; carrying out support detection with homogenous polyamide film by utilizing the eluant; collecting; recovering the solvent in a pressure reduced way; adding acetone to crystallize; separating and crystallizing; washing; and drying to obtain the product. The method provided by the invention is simple in operation, less in consumption of solvent, low in production cost, stable in technology, low in energy consumption and pollution, and high in purity of the obtained product (99%), and is suitable for experiment and industrial preparation and preparative production.

Etoposide analogs with improved water-solubility such as 4′-O-Demethyl-4′-(N′,N′-dimethyl-glycyl)-4β-(4″-nitroanilino)-4-desoxy-podophyllotoxin (8) and 4′-O-Demethyl-4′-(N′,N′-dimethyl-glycyl)-4β-(4″-fluoroanilino)-4-desoxy-podophyllotoxin (9) are described, along with pharmaceutical formulations containing the same, methods of use thereof, and intermediates and methods of making the same.

The invention discloses a 4-amino oxadiazole epipodophyllotoxin derivative and a preparation method and application thereof. The 4-amino oxadiazole epipodophyllotoxin derivative has a structure shown as a Formula (1), wherein R1 represents hydrogen or methyl, and R2 represents hydrogen, alkyl, aryl, heteroaryl or heteroaryl alkyl. The derivative is prepared according to the following steps of: firstly, subjecting podophyllotoxin serving as a raw material to azido reaction, reduction, addition and elimination to obtain isothiocyanate epipodophyllotoxin; secondly, reacting an isothiocyanate epipodophyllotoxin intermediate with a hydrazide compound to obtain a thiosemicarbazide derivative; and finally, subjecting to cyclization, and thus obtaining a corresponding 4-amino oxadiazole derivative. The preparation method is simple and is easy to operate. Initial in-vitro screening tests show that the toxicity of the derivative on normal cells is obviously reduced, meanwhile, certain compounds have better anti-tumor activity, and high-efficiency and low-toxicity anti-tumor drugs can be expected to be prepared.

The invention discloses a method for preparing desoxy-podophyllotoxin, which comprises the following steps of: 1) smashing radix podophylli raw material into middlings, quenching and percolating or extracting in a backflow way to obtain radix podophylli extract liquid; 2) concentrating the radix podophylli extract liquid obtained by the step 1) to obtain the concentration liquid of the radix podophylli extract liquid, evenly mixing with silica gel, drying, grinding, and filling into a chromatographic column, wherein the chromatographic column is filled with blank silica gel for column chromatography; and 3) eluting the chromatographic column with eluent, taking effluent liquid, the volume of which is equal to that of blank silica gel in the chromatographic column, as one fraction, collecting desoxy-podophyllotoxin-containing fraction, removing the eluent in the desoxy-podophyllotoxin-containing fraction, dissolving residue with dichloromethane or trichloromethane, and recrystallizing to obtain the desoxy-podophyllotoxin. The purity of the desoxy-podophyllotoxin obtained by the method is more than 70%, so that the method is suitable for not only laboratory preparation in small scale but also industrial preparation in large scale.

The invention relates to a prodrug of a compound podophyllotoxin PPT with an anti-tumour activity and a preparation method thereof. The preparation method comprises the following steps: converting the hydroxyl group of C4 of the C-ring of the PPT to chloro-carbonic ester, and reacting the group with the addition product DCM-S of 2-hydroxyethyl disulphide and a benzopyranyl nitrile amino derivative DCM-NH2 to generate a GSH-sensitive PPT-S-DCM prodrug compound. The compound obtained by the preparation method disclosed by the invention has the characteristic of selectively releasing the PPT in vitro and in vivo through tumour cell targeting (GSH sensitivity), and a clinical application prospect; meanwhile, the release behaviour of the PPT prodrug compound can be detected and researched by virtue of the near-infrared fluorophore of benzopyranyl nitrile.

The invention relates to a method for extracting podophyllotoxin from umbrella leaves, comprising the following steps of: using the umbrella leaves as raw materials; ultrasonically extracting 75-85 percent of methanol; decompressing and condensing to obtain extract; ultrasonically extracting by using ethyl acetate; concentrating an extracting solution; placing crystals; dissolving the crystals by using absolute ethyl alcohol; refluxing and decoloring by adding active carbon; filtering, extracting an organic solvent; concentrating, crystallizing; and recrystallizing and drying absolute methanol to obtain the podophyllotoxin. The invention has simple technical operation and low cost.

The invention discloses a nitrogen-substituted podophyllotoxin derivative with anti-tumor activity and a preparation method and use thereof. According to the method, 2-aminopyrimidine, 2-aminopyridine, 2-amino-3-methylpyridine, 2-amino-4-methylpyridine, 2-amino-5-methylpyridine, 2-amino-4,6-dimethyl pyridine, 3-aminopyridine, 3-amino-4-methylpyridine, 5-amino-2-methylpyridine, 3-amino-2-chloropyridine or 4-amino-2-chloropyridine is respectively introduced to an activated C-ring fourth position of a podophyllotoxin compound through nitrogen substitution reaction, so as to obtain the nitrogen-substituted podophyllotoxin derivative, represented by a formula (V) shown in the specification, with excellent anti-tumor activity. The nitrogen-substituted podophyllotoxin derivative disclosed by the invention acts on tumor cells through multiple ways and multiple target points, and the anti-tumor activity of the nitrogen-substituted podophyllotoxin derivative is remarkably improved compared with that of the podophyllotoxin compound. The compound disclosed by the invention can be used for preparing anti-tumor drugs and is clinically applied to anti-tumor treatment.

The invention provides a deoxidized podophyllotoxin polymer micelle freeze-drying preparation. Polymer micelle consists of an amphiphilic block polymer, and a polyethylene glycol monomethyl ether-poly (D,L) lactide block copolymer is optimal. A preparation method of the preparation comprises the steps that deoxidized podophyllotoxin and the block polymer are dissolved in an organic solvent; the solvent is flooded to be gel; the gel is hydrated; the micelle is obtained; and the freeze-drying preparation is prepared further. The freeze-drying preparation can be used for treating a tumor; a medicine carrying encapsulation rate is above 90%; the particle size of the redissolved micelle is 40-70nm; and a redissolved micelle solution can be stabilized for 4-24h at 25 DEG C.

The invention relates to a preparation method for natural product podophyllotoxin, which comprises the following steps of pulverizing raw materials into 20 to 60 meshes; taking CO2 and chloroform as solvents; super-critically extracting for 1 to 3 hours; washing analytic matters by utilizing deionized water; dissolving by utilizing chloroform; carrying out a medium-pressure alumina column chromatography; carrying out gradient elution by utilizing a petroleum ether-methanol chloroform mixing solution; collecting high-concentration fraction, concentrating and crystallizing; and recrystallizing the methanol chloroform mixing solution. The method for producing the podophyllotoxin has the advantages of less pollution, high extraction efficiency and less usage of organic solvents.

The invention discloses a deoxy-podophyllotoxin type compound, and a preparation method and a use of the compound. The structural formula of the compound is as shown in formula I, and a substituting group NR1R2 in the formula I is a piperazine type compound as shown in formula II, or the NR1R2 is an amino acid amide type compound as shown in formula III. The compound of the invention can be applied in the preparation of anti-tumor medicaments. The formula I, the formula II and the formula III are as follows.

An application of the solid liposome nanoparticles as the carrier of podophyllotoxin and its derivative and a composite medicine containing podophyllotoxin or its derivative and said solid liposome nanoparticles as carrier are disclosed. Its advantages are higher curative effect, high stability and low cost.

The invention relates to a process for extracting and purifying podophyllotoxin from Dysosma difformis, which comprises the following steps: crushing rhizomes of the Dysosma difformis into coarse powder, pretreating the Dysosma difformis coarse powder with organic solvents, extracting with hot water by reflux, continuously extracting filter residue by hot reflux, filtering again, merging the two filtrates, recovering the organic solvents, adding a defined amount of water to maintain a constant volume so as to obtain a podophyllotoxin extracting solution; and preparing the podophyllotoxin extracting solution into a solution the crude drug content of which is 0.12-0.18g / mL, selecting a purified macroporous adsorptive resin as the adsorption column resin to sufficiently adsorb the solution acting as a sample solution, respectively and sequentially washing off impurities with water and 10% ethanol, eluting with a strippant, collecting the eluted part, recovering the strippant, and adding a defined amount of water to maintain a constant volume so as to obtain a podophyllotoxin purified solution. The organic solvents used in the process are nonpoisonous and can be recovered, and no three wastes polluting the environment are produced. The whole process is green and environment friendly and has the advantages of simple operation and easy industrialization, and the purity of the podophyllotoxin obtained by the process is above 98%.

The invention discloses a podophyllotoxin preparation formula for external use for the treatment of condyloma acuminatum and genital herpes, a series of formulations and a preparation method, and belongs to the field of pharmacy. The weights or the volumes of all the ingredients of the formula of 100ml of the podophyllotoxin preparation for external use are as follows: 0.5g of podophyllotoxin, 20ml-80ml of main solvent, 1ml-3ml of penetration enhancer 1, 0.5g-2.5g of penetration enhancer 2, 20ml-80ml of cosolvent and 0.03-0.5g of preservative. The podophyllotoxin preparation for external use has the advantages that the types and the amount of excipients and the proportion of main drugs are reasonable, the drug administration is carried out by a liniment, a spray or other formulations which are applicable to the external use, the main drug can be rapidly absorbed by the horny layer and the epidermis, the efficacy is significant, the local toxicity or side effects are small, the skin acute toxicity is very low, and the podophyllotoxin preparation has no irritation and weak allergy and does not hinder the skin normal functions; the podophyllotoxin preparation has no systemic toxicity or side effects, thereby being safe and effective. The preparation prepared by the formula has the advantages of good appearance, moderate viscosity, easy coating, spraying drug administration, feasible process, controllable quality, simple preparation process, and suitability for industrial batch production.

The invention relates to the field of natural drugs and chemical drugs, in particular to a manufacturing method for deoxypodophyllotoxin. The manufacturing method provided by the invention has the characteristics that the deoxypodophyllotoxin can be obtained through the reaction of podophyllotoxin with NaBH4 and CF3COOH, namely, podophylotoxin is reduced to deoxypodophyllotoxin by addition of with a reducing reagent and protonic acid. According to the invention, the applied materials have wide source and low price, so that the manufacturing method is applicable in industrial production.

The invention relates to a dysosma versipellis extract, a medicine composite containing the extract as well as a preparation method and application thereof. The dysosma versipellis extract with specific chemical components contains active components, such as general lignans, general flavones and the like; and the impurities of the extract are reduced, and contents of effective components are high. The dysosma versipellis extract comprises the following components in percentage by weight: 20-50 percent of podophyllotoxin, 3-8 percent of kaempferol and 8-15 percent of general flavones. The dysosma versipellis extract is high in contents of the effective components and low in impurities; and the dysosma versipellis extract or the medicine composite containing the extract is obvious in effect and low in side effects during skin sterilization and treatment in verruca acuminate. Compared with the prior art, the preparation method has the advantages of advanced process, high production, high practicability, relatively low cost and low environment pollution.

The invention relates to a podophyllotoxin-retinoic acid heterocomplex synthesis method and application of a podophyllotoxin-retinoic acid heterocomplex in a medicine for preventing and curing tumors. The podophyllotoxin-retinoic acid heterocomplex has a structural formula as shown in a formula I (shown in the description); a preparation method of the compound as shown in the formula (I) is as follows (shown in the description), wherein a to b represent reaction conditions: a: a reagent is oxalyl chloride, a solvent is methylbenzene, and reaction temperature is 20 to 35 DEG C; b: a solvent is dichloromethane, a catalyst is triethylamine, and reaction temperature is 10 to 30 DEG C. A solvate is a complex prepared from the compound as shown in the formula (I), ethyl alcohol, diethyl ether, n-butyl alcohol, water, acetone or an isopropanol solvent. An experimental result shows that the podophyllotoxin-retinoic acid heterocomplex has a strong inhibiting effect on two human gastric cancer cell strains, and has an IC50 value in a nano-mole level, which is remarkably better than that of positive control agents: retinoic acid and etoposide. The compound as shown in the general formula (I) has the highest antiproliferative activity on human gastric cancer BGC-823 cells, is used for preventing and curing cell proliferation abnormity related diseases, and is particularly applied in the medicine for preventing or curing the tumors.

The invention relates to a pH and temperature dual responsive copolymer and a preparation method and an application thereof, which belong to the technical field of pharmaceutical polymers. A molecular structure of the copolymer is shown as follows, and the molecular weight is 10000 to 30000. The copolymer is prepared in the following steps of (a) preparing a copolymer of diethyl allylmalonate and N-vinylcaprolactam; (b) preparing a copolymer of allylmalonic acid and N-vinylcaprolactam. The copolymer is used for self assembly in water to form nanomicelles as controlled release carriers of podophyllotoxin drugs. Raw materials are low in price and are easy to obtain, a synthetic method is simple, products are easy to separate and purify, and the operability is strong. The copolymer can be assembled by self in a water solution to form stable spherical nanomicelles which have high drug loading capacity and encapsulation efficiency on podophyllotoxin and have pH and temperature dual responsive controlled release performance on the podophyllotoxin, and the copolymer can be used for constructing an intelligent drug controlled release system.

The present invention provides genetic engineering technological process of transforming Tibetan Dysosma versipellis to obtain hairy roots of Tibetan Dysosma versipellis for producing podophyllotoxin. The technological process includes genetic transformation of rooting agrobacterium to Tibetan Dysosma versipellis to obtain hairy roots of Tibetan Dysosma versipellis. The hairy roots of Tibetan Dysosma versipellis is, molecular detection shows, genetically transformed hairy roots, and may be, HPLC detection shows, used in producing podophyllotoxin. The present invention provides one new way of producing podophyllotoxin.

The invention discloses a series of new 2beta-chloropodophyllotoxin aromatic acid ester compounds, a preparation method and application in preparing botanical pesticide by using the compounds. Chemical general formulas of the 2beta-chloropodophyllotoxin aromatic acid ester compounds are as figures. The series of compounds are prepared by using podophyllotoxin as a raw material, the material is prepared into 2beta-chloropodophyllotoxin through C-4 site hydroxy group protection, C-2 site beta-chloro substitution and C-4 site protection removal, and then the 2beta-chloropodophyllotoxin reacts with eight aromatic acids to form the 2beta-chloropodophyllotoxin aromatic acid ester compounds. Proved by experiments, the 2beta-chloropodophyllotoxin aromatic acid ester compounds of the invention have good insecticidal activities which are partially higher than that of podophyllotoxin, and the insecticidal activities of some compounds are higher than those of the prior commercial botanical pesticide toosendanin; and proved by the experiments, the compounds can be used for preparing the botanical pesticide with high efficiency and low toxicity.

The invention relates to the multi-drug resistance (MDR) of Lapatinib (formula 1) in reversing tumour cells which are mediated by membrane transport proteins (ABC) families such as P-glycoprotein (P-gp), multi-drug resistance related protein (MRP1), breast cancer multi-drug resistance related proteins (ABCG2 and BCRP) and the like. The Lapatinib is used together with anti-cancer drugs such as anthracyclines, catharanthines, taxols, podophyllotoxins, camptothecins and the like to restore the sensitivity of MDR tumor cells to the anticancer drugs. The Lapatinib is applied to combination chemotherapy of drug-resistant patients in clinical chemotherapy or the prevention of drug-resistance generation for the tumor cells.

An insecticide in the form of microemulsion is prepared from the sand-land cypress' extract containing podophyllotoxin, emulsifier, antifreezing agent and water through adding emulsifier to said extract, high-speed stirring while adding others, and stirring while heating at 70-80 deg.C. Its advantages are high effect and high safety.