CN104817575A - Compound, its extraction method, pharmaceutical composition containing the same and application thereof - Google Patents
Compound, its extraction method, pharmaceutical composition containing the same and application thereof Download PDFInfo
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- CN104817575A CN104817575A CN201510108820.7A CN201510108820A CN104817575A CN 104817575 A CN104817575 A CN 104817575A CN 201510108820 A CN201510108820 A CN 201510108820A CN 104817575 A CN104817575 A CN 104817575A
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- pharmaceutical composition
- changchun
- compound
- agent
- spring alkali
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- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 7
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- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
Abstract
The embodiment of the invention discloses a compound, which has a chemical structural formula as shown in the specification. The compound is called cathachunine. At the same time, the invention also provides an extraction method of the compound, a pharmaceutical composition containing the compound and application of the compound and the pharmaceutical composition in preparation of antitumor drugs. (chemical structural formula).
Description
Technical field
The present invention relates to a kind of compound, the natural compounds particularly extracted from plant Vinca, the extracting method of this compound, the pharmaceutical composition comprising this compound and this compound and pharmaceutical composition are for the preparation of the purposes in antitumor drug.
Background technology
Tumour is one of major reason causing human death.Develop into today in industrial society, the diseases such as liver cancer, mammary cancer, lung cancer have had a strong impact on the healthy living level of the people.Visible prevention and therapy tumour is very critical.Chemotherapy is a kind of effective means for the treatment of tumour, and tumor chemotherapeutic drug conventional clinically at present has tens kinds, effectively extends the life-span of the mankind, but the antitumor drug of synthesis, and toxic side effect is large, seriously limits the performance of the curative effect of these medicines.Chinese medicine and natural drug are the great wealth of China, and it has the features such as toxic side effect is little, so seeking antitumor medicine is the effective way addressed these problems from Chinese medicine and natural drug.
Vinca Catharanthus roseus (L.) G.Don is the herb of Apocynaceae (Apocynaceae) Vinca (Catharanthus) plant Vinca, yellow Vinca, another name Herba amaranthi tricoloris, life spring, four Shi Chun etc.Vinca originates in East Coast of Africa and american torrid zone area, and extensively cultivate in subtropical and tropical zones at present, China's Lingnan area and Jiangsu and Zhejiang Provinces one are with all has cultivation.The Vinca property of medicine is bitter, cold, and poisonous, tool detoxicating and fighting cancer, effect of the flat liver of heat-clearing, cures mainly the illnesss such as multiple cancerous swelling, hypertension, carbuncle sore tumefacting virus and scald.Modern pharmacological research shows, Vinca tool is antitumor, hypotensive, reducing blood-fat, hypoglycemic and expand the effect such as blood vessel.
Summary of the invention
The present inventor extracts and obtains compound Changchun spring alkali (cathachunine) from the dry herb of Vinca, and the present inventor has also found that above-mentioned Changchun spring alkali (cathachunine) can be used for antitumor.Present invention also offers the pharmaceutical composition comprising above-mentioned Changchun spring alkali (cathachunine), and this pharmaceutical composition is for the preparation of the purposes in antitumor drug.Concrete technical scheme is as follows:
A first aspect of the present invention provides compound, and the chemical structural formula of this compound is as follows:
Above-claimed cpd is called Changchun spring alkali (cathachunine).
A second aspect of the present invention provides the extracting method of above-claimed cpd Changchun spring alkali, comprises the following steps:
(1) extract: by dry for Vinca herb, pulverize, with aqueous ethanolic solution refluxing extraction, obtain medicinal extract, adjust pH to 2-3 with HCl solution after thin up, filter, obtain filtrate and filter residue, filtrate adds NH
3h
2o adjusts pH to 9-10, with chloroform extraction, obtains chloroform extract;
(2) be separated: by above-mentioned chloroform extract applying silicon plastic column chromatography, with the chloroform-methanol system gradient elution of volume 100:1 to 2:1, thin-layer chromatography detects, collection obtains the flow point containing Changchun spring alkali (cathachunine), again through ODS column chromatogram chromatography, take volume ratio as the methanol-water system elutions of 20:80, thin-layer chromatography detects, and obtains the sterling of described Changchun spring alkali cathachunine.
In a preferred embodiment of a second aspect of the present invention, above-mentionedly obtain medicinal extract with aqueous ethanolic solution refluxing extraction, be specially: with 95% alcohol reflux 2-4 time, each 2-3 hour, extracting solution is evaporated to medicinal extract.
A third aspect of the present invention provides a kind of pharmaceutical composition, and this pharmaceutical composition comprises above-mentioned compound Changchun spring alkali (cathachunine) and optional pharmaceutically acceptable carrier or vehicle.
In a preferred embodiment of third aspect present invention, based on the gross weight of described pharmaceutical composition, the content of described compound Changchun spring alkali (cathachunine) is 1-99%, is preferably 20-80%, is more preferably 40-60%.
In another preferred embodiment of third aspect present invention, described pharmaceutically acceptable carrier or vehicle are selected from solvent, thinner, dispersion agent, suspending agent, tensio-active agent, isotonic agent, thickening material, emulsifying agent, sanitas, tackiness agent, lubricant, stablizer, hydrating agents, emulsification accelerator, buffer reagent, absorption agent, tinting material, flavouring agent, sweeting agent, ion-exchanger, releasing agent, coating agent, correctives and antioxidant.
In another preferred embodiment of third aspect present invention, the formulation of described pharmaceutical composition is tablet, capsule, pulvis, granule, lozenge, pill, solution, suspensoid, emulsion, syrup, powder, granula subtilis, pilule, elixir, injection, medicinal drops, ointment, lotion, gelifying agent, emulsifiable paste, sprays, suppository or patch.
A fourth aspect of the present invention provides above-mentioned compound Changchun spring alkali (cathachunine) or above-mentioned pharmaceutical composition for the preparation of the purposes in antitumor drug.
In a preferred embodiment of fourth aspect present invention, every per daily dose that described medicine gives object in need counts 0.01-1000mg/kg body weight with compound Changchun spring alkali, is preferably 0.1-100mg/kg body weight, is more preferably 1-100mg/kg body weight.
The present inventor extracts and obtains compound Changchun spring alkali (cathachunine) from the dry herb of Vinca, and this compound is white powder, [α] 20D+22.5 (c 0.2, CHCl
3); By electron spray(ES) ion massspectrum signal m/z:709.33605 [M+H]
+, calculate that its molecular formula is C
41h
48n
4o
7; And pass through
1h and
13c nucleus magnetic resonance and UV spectrum determine its structure.
As used herein, term " ODS post " refers to octadecylsilane post.
The routine techniques in formulation art can be adopted, the effective constituent of the raw material of pharmaceutical composition of the present invention is obtained by extracting method according to the present invention, with one or more of pharmaceutically acceptable carrier or mixed with excipients, then form required formulation, prepare pharmaceutical composition of the present invention.
As used herein, " pharmacy is acceptable " represents when not having tangible toxic action with during usual dosage use, thus by government or the international organization suitable with it approval or can be approved for animal, more specifically to people, or be registered in pharmacopeia.
" pharmaceutically acceptable carrier or vehicle " available in pharmaceutical composition of the present invention can be the carrier of any routine in field of pharmaceutical preparations, and the selection of specific support will depend on the administering mode or disease type and state that are used for the treatment of particular patient.For the preparation method of the said synthetic processes of specific administration pattern completely in the ken of pharmaceutical field technician.Such as, the solvent of pharmaceutical field routine, thinner, dispersion agent, suspending agent, tensio-active agent, isotonic agent, thickening material, emulsifying agent, tackiness agent, lubricant, stablizer, hydrating agents, emulsification accelerator, buffer reagent, absorption agent, tinting material, ion-exchanger, releasing agent, coating agent, correctives and antioxidant etc. can be comprised as pharmaceutically acceptable carrier.If desired, flavouring agent, preservative and sweetener etc. can also be added in pharmaceutical composition.
As used herein, term " pharmaceutical composition " has its general sense.In addition, " pharmaceutical composition " of the present invention can also exist with forms such as healthcare products, functional foodstuff, food, foodstuff additive or provide.The routine techniques of pharmacy field particularly in formulation art can be adopted, the effective constituent of the raw material of pharmaceutical composition of the present invention is obtained by extraction separation and purification means conventional in pharmaceutical production, optionally mix with one or more of pharmaceutically acceptable carrier, then form required formulation, prepare pharmaceutical composition of the present invention.According to pharmaceutical composition of the present invention, it is the pharmaceutical preparation going for oral administration, parenteral admin or topical, topical administration.Pharmaceutical composition of the present invention can make the various ways such as tablet, pulvis, granule, capsule, oral liquid.The medicine of above-mentioned various formulation all can be prepared according to the ordinary method of pharmaceutical field.Specifically, according to pharmaceutical composition of the present invention, described pharmaceutical dosage form includes but not limited to: tablet, capsule, granule, pulvis, injection liquid, injectable powder, transdermal patch, ointment, gelifying agent, suppository, oral liquid, oral administration mixed suspension, injectable emulsion, Orally taken emulsion etc., slow releasing tablet, controlled release tablet.The medicine of above-mentioned various formulation all can be prepared according to the ordinary method of pharmaceutical field.
Such as tablet, pill, hard or soft capsule, solution, suspensoid, emulsion, syrup, powder, pulvis, granula subtilis, granule, pilule, elixir etc. can be comprised for Orally administered formulation, be not limited to this.Except activeconstituents, these preparations also can comprise thinner (such as lactose, dextrose, sucrose, mannitol, Sorbitol Powder, Mierocrystalline cellulose and glycine), lubricant (such as silicon-dioxide, talcum, stearic acid or its magnesium salts, calcium salt and polyoxyethylene glycol).Tablet also can comprise tackiness agent, such as neusilin, starch paste, gelatin, tragacanth, methylcellulose gum, Xylo-Mucine and polyvinylpyrrolidine.If desired, it also can comprise medicinal additive, such as disintegrating agent (as starch, agar, Lalgine or its sodium salt), absorption agent, tinting material, flavouring agent, sweeting agent etc.Tablet can according to the method preparation of conventional mixing, granulation or dressing.
Formulation for using outside enteron aisle can comprise such as injection, medicinal drops, ointment, lotion, gelifying agent, emulsifiable paste, sprays, suspensoid, emulsion, suppository, patch etc., is not limited to this.
According to pharmaceutical composition of the present disclosure can oral or non-bowel such as per rectum, through local, through skin, through intravenously, through intramuscular, through intraperitoneal or through subcutaneous administration.
The acceptable dosage of pharmacy of activeconstituents, i.e. application dosage, can change according to the judgement of the severity of the age of object to be treated, sex and body weight, disease specific to be treated or pathological state, disease or pathological state, route of administration and diagnosis person.Consider that these factor determination application dosages are in the horizontal extent of those skilled in the art.General dosage can be 0.01-1000mg/kg/ day, is preferably 0.1-100mg/kg/ day, is more preferably 1-100mg/kg/ day.But the scope of the present disclosure is limited to described application dosage never in any form.
Accompanying drawing explanation
In order to be illustrated more clearly in the embodiment of the present invention or technical scheme of the prior art, be briefly described to the accompanying drawing used required in embodiment or description of the prior art below, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skill in the art, under the prerequisite not paying creative work, other accompanying drawing can also be obtained according to these accompanying drawings.
Fig. 1 is the fluorescence intensity after the Changchun spring alkali effect HL-60 cell 48h under different concns;
The comparison diagram of the ROS of 48h after Changchun spring alkali effect HL-60 cell under Fig. 2 different concns.
Embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, be clearly and completely described the technical scheme in the embodiment of the present invention, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
The extraction in embodiment 1 compound Changchun spring alkali (cathachunine) and sign
1, instrument and material
X-5 type micro melting point apparatus (Tyke, Beijing instrument company); Jasco FT/IR-480Plus FourierTransform infrared spectrometer (Japan Spectroscopy Corporation); Jasco V-550 UV/visible spectrophotometer (Japan Spectroscopy Corporation); Bruker AV-400MHz nuclear magnetic resonance analyser, TMS is interior mark (German Bruker company); Thermo Finnigan LCQ Advantage MAX mass spectrograph (Thermo company of the U.S.); Dionex analysis mode high performance liquid chromatograph (Dionex company of the U.S.); Cosmosil C-18 chromatographic column (250mm × 4.6mm, 5 μm); Vari an preparative high performance liquid chromatography instrument (Varian company of the U.S.); Column chromatography is with silica gel (Haiyang Chemical Plant, Qingdao); Silica GF254 thin layer precoated plate (Yantai chemical industry institute); Sephadex LH-20 (Pharmacia company); ODS column chromatography material (German Merck company); Agents useful for same is analytical pure and chromatographically pure.
Vinca medicinal material picks up from Haikou City, Hainan Province, is accredited as Vinca (Catharanthus roseus (L.) G.Don) herb by Tianjin University Of Traditional Chinese Medicine doctor Wang Chunhua.Herbarium (No.2012CH0014) deposits in modern Chinese herbal medicine laboratory, Tianjin University Of Traditional Chinese Medicine strand.
2, the extraction in Changchun spring alkali (cathachunine)
The dry herb 3kg of Vinca, pulverizes, and with 95% ethanol 20L refluxing extraction 3 times, each 2 hours, extracting solution was evaporated to medicinal extract 500g, and adjust pH to 2-3 with HCl solution after thin up, filter, obtain filtrate and filter residue, filtrate adds NH
3h
2o adjusts pH to 9-10, with chloroform extraction, obtains chloroform extract, obtains crude product 115g after concentrating under reduced pressure; By above-mentioned chloroform extract applying silicon plastic column chromatography, with the chloroform methanol system gradient elution of volume 100:1 to 2:1, thin-layer chromatography detects, collection obtains the flow point 20g containing Changchun spring alkali (cathachunine), again through ODS column chromatogram chromatography, take volume ratio as the methanol-water system elutions of 20:80, thin-layer chromatography detects, and obtains the sterling 40mg of Changchun spring alkali (cathachunine).
3, characterize
Compound Changchun spring alkali (cathachunine): white powder, [α] 20D+22.5 (c 0.2, CHCl
3); By electron spray(ES) ion massspectrum signal m/z:709.33605 [M+H]
+, calculate that its molecular formula is C
41h
48n
4o
7; UV spectrum has strong absorption at 220nm and 260nm, illustrates that this compound has indole ring structures feature; Infrared spectra is at 3452cm
-1, 1737cm
-1, 1688cm
-1there is absorption peak at place, points out this compound to contain hydroxyl, carbonyl and amide group.
1four fragrant Hydrogen Proton signal [δ 7.53 (1H on H nuclear magnetic resonance spectrum display indole ring, d, J=7.6Hz, 7.16 (1H, m), 7.13 (1H, m) He 7.11 (1H, d, J=7.6Hz)] and four indoline rings on feature Hydrogen Proton signal [δ 6.52 (1H, s), 6.08 (1H, s), 5.67 (1H, dd, J=9.6,4.0Hz) and 5.46 (1H, d, J=9.6Hz)], above nuclear magnetic data points out this compound to be vinealeucoblastine(VLB) (VLB) type alkaloid.Can see that H-3 ' a (δ 3.99)/H-5 ' b (δ 2.99)/H-14 ' (δ 1.54) and C-18 (δ 179.0) has relevant from HMBC spectrum, illustrate that C-20 with N-4 is connected in amido linkage mode, the absolute steric configuration of Changchun spring alkali can be determined in conjunction with ROESY spectrum and CD spectrum.
1h and
13c nuclear magnetic resonance data can the chemical structural formula in deterministic compound Changchun spring alkali (cathachunine) from above-mentioned sign in table 1..
Table 1 Changchun spring alkali (cathachunine)
1h and
13c nuclear magnetic resonance data
1h and
13c nuclear magnetic data records respectively under 400MHz and 100MHz, and J is coupling constant.
The cytotoxic activity test in embodiment 2 Changchun spring alkali (Cathachunine)
1, experiment material
1.1 given the test agent
Changchun spring alkali (cathachunine) of embodiment 1 being extracted is with after DMSO (Merck) dissolving, add PBS (-) and be made into the solution of 100 μMs/ml or uniform mixed solution, then dilute with the PBS (-) containing DMSO.
1.2 cell strain
HL-60 (human leukemia cell, American Type Culture Collection, (ATCC))
K562 (human leukemia cell, American Type Culture Collection, (ATCC))
EA.hy926 (human endothelial cell, American Type Culture Collection, (ATCC))
1.3 nutrient solution
PRMI1640 (Gibco company of the U.S.)+15%NBS (Gibco company of the U.S.)+dual anti-(HyClone company of the U.S.)
1.4 other materials
WST-1 cell proliferation and the full-automatic microplate reader of toxicity test bag (Beyotime institute of biotechnology, China): (BioTek, U.S.A.), import 96 well culture plate etc.
2, experimental technique
Cell survival rate experiment adopts WST-1 cell proliferation and toxicity test bag, adopts the Standard operation procedure SOP of this experiment bag to carry out.The 96 every holes of orifice plate add the cell suspension that concentration is 4-6 × 104/ml, are placed in 37 DEG C, 5%CO2 incubator.Every hole adds the WST solution (comprising the medium of 100 μ l) of 10 μ l, after cultivating 2h, surveys the OD value under 450nm under microplate reader.
3, test-results
The results are shown in Table 2. result display Changchun spring alkali, to human leukemia cell line HL-60 and K562, there is significant cytotoxic activity, to human endothelial cell EAhy926, there is faint cytotoxicity.
The cytotoxicity of table 2. Changchun spring alkali
Embodiment 3 Changchun spring alkali (Cathachunine) is to the impact of active oxygen in tumour cell (Reactive oxygenspecies, ROS) level
1, experiment material
1.1 given the test agent
Changchun spring alkali (cathachunine) adds PBS (-) and is made into the solution of 100 μMs/ml or uniform mixed solution, then dilute with the PBS (-) containing DMSO after dissolving with DMSO (Merck).
1.2 cell strain
HL-60 (human leukemia cell, American Type Culture Collection, (ATCC))
1.3 nutrient solution
PRMI1640 (Gibco company of the U.S.)+15%NBS (Gibco company of the U.S.)+dual anti-(HyClone company of the U.S.)
1.4 other materials
Fluorescent microscope XSP-BM21AY (Shanghai opticinstrument six factory)
2, test method
Common fluorescent probe DCFH-DA, can become the DCFH not having fluorescence by deacetylation in cell, and in time having ROS in cell, DCFH can continue to be oxidized to the DCF with fluorescence, and his fluorescence represents the level of intracellular ROS.This experiment adopts DCFH-DA to have rated Changchun spring alkali (cathachunine) and generates the intracellular ROS of HL-60.Concrete test method is: HL-60 cells rinsed with PBS once, adds DCFH-DA, preserves 30 minutes for 37 DEG C in the dark.Then by cell washing twice, be kept in 1ml substratum.The generation of ROS adopt fluorescent microscope 488 and 530nm excite with emission wavelength under measure respectively.Fluorescence intensity adopt fluorescence microplate reader further 488 and 525nm excite with emission wavelength under analyze and obtain.
3, test-results, as Fig. 1 and Fig. 2.
In Fig. 1 a-d tetra-little figure show respectively Changchun spring alkali respectively under concentration 1,3,10,30 μMs of concentration on the impact producing ROS level in HL-60 cell.It is higher that phosphor dot represents its ROS level more; In Fig. 2 with bar graph form describe equally Changchun spring alkali in concentration 1,3,10,30 μMs of situations on HL-60 produce ROS level and affect.Above two figure all describe compound Changchun spring alkali (cathachunine) under the concentration of 30 μMs, after cultivating 48h, can significantly improve the generation of the intracellular ROS of HL-60.
Embodiment 4: the tablet preparing pharmaceutical composition of the present invention
Mix above composition according to common method and make tablet.
Embodiment 5: the capsule preparing pharmaceutical composition of the present invention
Mix above composition according to common method and load in gelatine capsule.
The foregoing is only preferred embodiment of the present invention, be not intended to limit protection scope of the present invention.All any amendments done within the spirit and principles in the present invention, equivalent replacement, improvement etc., be all included in protection scope of the present invention.
Claims (10)
1. a compound, is characterized in that, chemical structural formula is as follows:
Described compound is called Changchun spring alkali.
2. an extracting method for compound Changchun according to claim 1 spring alkali, is characterized in that, comprise the following steps:
(1) extract: by dry for Vinca herb, pulverize, with aqueous ethanolic solution refluxing extraction, obtain medicinal extract, adjust pH to 2-3 with HCl solution after thin up, filter, obtain filtrate and filter residue, filtrate adds NH
3h
2o adjusts pH to 9-10, with chloroform extraction, obtains chloroform extract;
(2) be separated: by above-mentioned chloroform extract applying silicon plastic column chromatography, with the chloroform-methanol system gradient elution of volume 100:1 to 2:1, thin-layer chromatography detects, collect the flow point obtained containing Changchun spring alkali, again through ODS column chromatogram chromatography, take volume ratio as the methanol-water system elutions of 20:80, thin-layer chromatography detects, and obtains the sterling of described Changchun spring alkali.
3. method as claimed in claim 2, is characterized in that, describedly obtains medicinal extract with aqueous ethanolic solution refluxing extraction, is specially: with 95% alcohol reflux 2-4 time, each 2-3 hour, extracting solution is evaporated to medicinal extract.
4. a pharmaceutical composition, is characterized in that, this pharmaceutical composition comprises compound Changchun according to claim 1 spring alkali and optional pharmaceutically acceptable carrier or vehicle.
5. pharmaceutical composition as claimed in claim 4, it is characterized in that, based on the gross weight of described pharmaceutical composition, the content of described compound Changchun spring alkali is 1-99%.
6. pharmaceutical composition as claimed in claim 5, it is characterized in that, based on the gross weight of described pharmaceutical composition, the content of described compound Changchun spring alkali is 20-80%.
7. pharmaceutical composition as claimed in claim 6, it is characterized in that, based on the gross weight of described pharmaceutical composition, the content of described compound Changchun spring alkali is 40-60%.
8. pharmaceutical composition as claimed in claim 4, it is characterized in that, described pharmaceutically acceptable carrier or vehicle are selected from solvent, thinner, dispersion agent, suspending agent, tensio-active agent, isotonic agent, thickening material, emulsifying agent, sanitas, tackiness agent, lubricant, stablizer, hydrating agents, emulsification accelerator, buffer reagent, absorption agent, tinting material, flavouring agent, sweeting agent, ion-exchanger, releasing agent, coating agent, correctives and antioxidant.
9. compound Changchun spring alkali as claimed in claim 1 or pharmaceutical composition according to claim 3 are for the preparation of the purposes in antitumor drug.
10. purposes as claimed in claim 9, is characterized in that, every per daily dose that described medicine gives object in need is counted 0.01-1000mg/kg body weight with compound Changchun spring alkali, be preferably 0.1-100mg/kg body weight, be more preferably 1-100mg/kg body weight.
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Citations (2)
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WO2007098091A2 (en) * | 2006-02-17 | 2007-08-30 | Novacea, Inc. | Treatment of hyperproliferative diseases with vinca alkaloid n-oxide and analogs |
CN101628916A (en) * | 2009-08-04 | 2010-01-20 | 华中科技大学 | Cathearanthus alkaloid |
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WO2007098091A2 (en) * | 2006-02-17 | 2007-08-30 | Novacea, Inc. | Treatment of hyperproliferative diseases with vinca alkaloid n-oxide and analogs |
CN101628916A (en) * | 2009-08-04 | 2010-01-20 | 华中科技大学 | Cathearanthus alkaloid |
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