CN104523665B - Application of double hydroxy benzaldehyde contracting diethylenetriamines of 3 methoxyl group 2 in cancer therapy drug is prepared - Google Patents
Application of double hydroxy benzaldehyde contracting diethylenetriamines of 3 methoxyl group 2 in cancer therapy drug is prepared Download PDFInfo
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Abstract
The invention discloses a kind of new medical use --- application in cancer therapy drug is prepared of double hydroxy benzaldehyde contracting diethylenetriamines of 3 methoxyl group 2, belong to pharmaceutical technology field.Pharmacological experiment shows, in certain concentration range, double hydroxy benzaldehyde contracting diethylenetriamines of 3 methoxyl group 2（VALD）To human liver cancer SMMC7721 and HepG2 cell, the cells of human colon carcinoma HCT 116, the propagation of human gastric cancer SGC 7901 and the cell lines of BGC 823 is respectively provided with significant inhibitory action, therefore, preparation available for cancer therapy drug, i.e. using double hydroxy benzaldehyde contracting diethylenetriamines of 3 methoxyl group 2 as active component, routinely technique and auxiliary material are prepared into pharmaceutically acceptable preparation.
Description
Technical field
The invention belongs to pharmaceutical technology field, it is related to a kind of pair of 3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamine
New medical use --- the application in cancer therapy drug is prepared.
Background technology
Cancer is to threaten one of topmost difficult and complicated illness of human life in the world, and it and angiocardiopathy side by side, turn into
Two hang-ups of medical field, occupy the world and die of illness the front two of reason.Clinically there is stronger poison conventional antineoplastic more
Side effect, normal cell is also injured while tumour cell is killed.Therefore, the efficient, anti-tumor active ingredient of low toxicity is found
Have become an important channel of cancer therapy drug research.
Double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines（(N1,N3-bis(3-methoxysalicylidene)
Diethylenetriamine, Valdien, VALD）, it is a kind of soft chain schiff bases complex, its structural formula is as follows：
Double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines currently as luminous agent be applied to catalytic field, and its
Activity in terms of medicine has not yet to see report.The structure of double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines, synthesis
And performance is referring to JACS/ J. Am. Chem. Soc. 2011,133,5319-5328.
The content of the invention
It is an object of the invention to provide the pharmaceutical of a kind of pair of 3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamine
On the way --- the application in cancer therapy drug is prepared.
Below by inside and outside tumor model, with means such as cell biology, biochemistry, molecular biology, to double
3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamines（Valdien, VALD）Antitumor activity and its mechanism of action carry out it is deep
Enter research, to provide theory in the clinical practice of oncotherapy for double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines
Foundation, the antitumor clinical practice to the medicine plays a role in promoting.
First, the research of the extracorporeal anti-tumor function of double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines
1 material
1.1 medicine：Double 3- methoxyl groups 2- hydroxy-benzaldehyde contractings diethylenetriamine VALD), purity 98%；By Lanzhou University
Chemistry and Chemical Engineering College professor Dou Wei provides.Cis-platinum (cisplatin, CDDP) parenteral solution, purchased from the limited public affairs of Nanjing Pharmaceutical Plant
Department；Fluorouracil Injection (5-fluorouracil, 5-FU), purchased from Shanghai Hai Pu pharmaceutical factories；Adriamycin, the happy medicine in Shenzhen ten thousand
Industry Co., Ltd product.
1.2 reagents and preparation：Newborn calf serum：Hangzhou Chinese holly bioengineering Co., Ltd product, lot number：
120125；The culture mediums of RPMI 1640：Gibco Invitrogen Corporation, U.S.A. products；Tetrazolium bromide（MTT）：
Fluka Products, 5 mg/ml, filtration sterilization packing, 4 DEG C of preservations are configured to the PBS of pH=7.4；Trypsase powder：
Gibco BRL Products, it is 0.25% that concentration is configured to Hank ' S liquid, filtration sterilization packing, and -20 DEG C freeze；Dodecyl
Sodium sulphate（SDS）：For Sigma Products, 10% concentration is configured to 0.01 M HCl.
1.2.1 the preparation of the liquid of RMPI 1640：2.0 g are added after taking the g of RMPI 1,640 10.4, plus distilled water dissolving
NaHCHO3It is set fully to dissolve, volumetric flask, which is added to after 950 ml, adjusts pH value to be 7.4~7.6, and then constant volume is filtered to 1000 ml
Degerming packing, 4 DEG C save backup.
1.2.2 the inactivation of calf serum：Calf serum constant temperature in 56 DEG C of water-baths is put to inactivate 35 minutes, it is aseptic subpackaged ,-
20 DEG C save backup.
1.2.3 trypsase is prepared：The preparation of D-Hanks solution：The g of precise NaCl 8.0 g, KCl 0.4,
KH2PO4 0.06 g, Na2HPO4.H2O 0.06 g（Or Na2HPO4.12H2O 0.134 g）, NaHCO30.35 g, it is phenol red
0.02 g, is dissolved in distilled water and stirs frequently, be settled to 1000 ml successively, in the volumetric flask for being sub-packed in 100 ~ 250 ml,
Autoclaving, 4 DEG C save backup.Trypsase is prepared：The g of enzyme powder 0.25 is dried in beaker plus a little D-Hanks liquid exists into pasty state
100 ml, the rearmounted h of room temperature 4 are settled to DHanks liquid（Or 4 DEG C of refrigerator overnights, mix）, filtration sterilization, packing 20-25
Ml/ bottles, -20 DEG C save backup.
1.2.4 dispense paddy propionamide：Weigh the g of glutamine 3, the g of Sodium Pyruvate 1.1, distilled water constant volume in 100 ml,
Fully, after dissolving, seitz filter filtration sterilization is used, 2 ml/- 20 DEG C of bottle is distributed into and stores for future use, indicate title, date.Note：
Paddy propionamide is unstable after being configured 2 weeks 1640, and the composition in original 1640 has been lost, and should supplement again.
1.2.5 it is dual anti-to prepare：Blue or green G Na salt 1,600,000u/, streptomycin sulphate 1,000,000u/, blue or green G+1.6 ml are double to be steamed
1 ml is taken after water, dissolving；Take 1（1000000 u）Streptomycin sulphate, a little distilled water dissolving, the two is settled to distilled water
100 ml seitz filter filtration sterilizations are distributed into 1-2 ml/- 20 DEG C of bottle and preserved（1 year effectively）It is standby, indicate title, day
Phase.
1.3 instruments and material
CO2Incubator：Shellab 2306, shellab 2323 is U.S.A products；Superclean bench：SW-CJ-
IFD Purifying Equipment Co., Ltd., Suzhou product；ELX800 type enzyme-linked immunosorbent assay instruments：U.S.A. product；Inverted microscope：
OLYMPUS products；Centrifuge：DL4000, Anting Scientific Instrument Factory, Shanghai's product.
1.4 cell line
SMMC-7721 human hepatocarcinoma cell and HepG2, human colon cancer cell strain HCT-116, SGC-7901 cells
And BGC-823 is purchased from Shanghai Inst. of Cytobiology, Chinese Academy of Sciences.With containing 10% calf serum, 1 × 105 IU/L moulds
The culture mediums of RPMI 1640 of element and 100 mg/L streptomysins, in 37 DEG C, 5% CO2And trained under the conditions of saturated humidity in incubator
Support, above-mentioned cell is attached cell, digested during passage with 0.25% tryptic digestive juice, passage in 2 ~ 3 days is once.
2 experimental methods
2.1 mtt assay determine double 3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamines（VALD）It is alone to different tumours
The inhibitory action of cell propagation
MTT colorimetric method for determining VALD is to human liver cancer cell SMMC7721 and HepG2, human colon cancer cell HCT-116, people
The inhibitory action of stomach cancer cell SGC-7901 and BGC-823 cell propagation.Experiment sets negative control group（Cell suspension+solvent）、
Blank control group（1640 complete culture solutions of RPMI+solvent）, alone group of VALD（Cell suspension+VALD）, VALD color comparator groups
（Complete culture solution+the VALD of RPMI 1640）And positive controls（Cell suspension+chemotherapeutics）If positive drug has color,
Positive drug color comparator group is set again（1640 complete culture solutions of RPMI+chemotherapeutics）.Each concentration sets the hole of multiple holes 3, every 3 hole
The average of OD values is as once testing.Exploitative experiment is at least carried out 1 time, and effect confirms that experiment is at least repeated 3 times the above.
Take the logarithm SMMC7721, HepG2, HCT-116, SGC-7901 and BGC-823 cell in growth period, use RPMI
1640 culture medium adjusts cell concentration respectively to 1 × 105 / mL, cell suspension is added in 96 well culture plates with 90 μ L/hole；24
Medicine is added with 10 μ l/hole after h, 48 h are cultivated.Preceding 4 h, which is terminated, in experiment adds MTT（10 μ L/hole）, add during experiment termination
Enter 10 %SDS（100 μ L/hole）, 10 min are shaken, light absorption value is determined at the nm of wavelength 570.
2.2 statistical analysis
All experiments are all provided with 3 parallel groups or are repeated 3 times, and are as a result represented, are examined using t with mean scholar standard deviation (± SD)
Test (variance is same together) and r is examined（Heterogeneity of variance）Significant difference compares between being organized, with P<0.05 is that difference has statistics
Meaning,P<0.01 is that difference tool is statistically significant.
3. result
The alone inhibitory action bred to human liver cancer SMMC7721 and HepG2 cell of VALD of 3.1 various doses
VALD has significant inhibitory action to the propagation of human liver cancer SMMC7721 and HepG2 cell, is in concentration
It is in obvious concentration dependent and time dependence, Fig. 1, Fig. 2 in the range of the mg/L of 0.5mg/L ~ 10.SMMC7221 exists
24h, 48h and 72h IC50Respectively 6.87mg/L, 5.56 mg/L, 4.32 mg/L.HepG2 is in 24h, 48h and 72h
IC50Respectively 6.95mg/L, 5.27 mg/L, 3.34 mg/L.
The alone inhibitory action bred to human colon carcinoma HCT-116 cells of VALD of 3.2 various doses
VALD has significant inhibitory action to the propagation of human colon carcinoma HCT-116 cells, concentration be 0.5mg/L ~
It is in obvious concentration dependent and time dependence in the range of 10 mg/L, sees Fig. 3：HCT-116 is in 24h, 48h and 72h
IC50Respectively 4.06 mg/L, 2.43 mg/L, 1.65 mg/L.
The alone inhibitory action bred to human gastric cancer SGC-7901 and BGC-823 cell of VALD of 3.3 various doses
VALD has significant inhibitory action to the propagation of human gastric cancer SGC-7901 and BGC-823 cell, is in concentration
It is in obvious concentration dependent and time dependence in the range of the mg/L of 0.5mg/L ~ 10, sees Fig. 4.SGC-7901 in 24h,
48h and 72h IC50Respectively 5.26 mg/L, 4.38 mg/L, 3.38 mg/L.BGC-823 is in 24h, 48h and 72h
IC50Respectively 4.65 mg/L, 2.94 mg/L, 2.13 mg/L.
4 conclusions
This experiment observes VALD to human liver cancer SMMC7721 and HepG2 cell, human colon carcinoma HCT- by MTT colorimetric methods
116 cells, human gastric cancer SGC-7901 and BGC-823 CDCC.Experiment is found, in certain concentration range, VALD pairs
Human liver cancer SMMC7721 and HepG2 cell, human colon carcinoma HCT-116 cells, human gastric cancer SGC-7901 and BGC-823 cell line
Propagation be respectively provided with significant inhibitory action, and with the increase of concentration, inhibitory action enhancing, with obvious dose-effect relationship, its
In it is most strong to HCT-116 action effect.
2nd, the research of double 3- methoxyl groups 2- hydroxy-benzaldehydes contracting diethylenetriamine Anticancer effect in vivo
1. material
1.1 animal：Kunming mouse, ♀, body weight：18~22 g, SPF grade, purchased from Lanzhou University's Experimental Animal Center,
Credit number：SCXK (sweet) 2008-0007；BALB/c mouse, ♀, body weight：18~22 g, SPF grade, it is real purchased from Lanzhou University
Test animal center, credit number：SCXK (sweet) 2008-0008；BALB/c Female nude mices, SPF grades, tonneau China is tieed up purchased from Beijing
Experimental animal Co., Ltd, up-to-standard licensing numbering is SCXK (capital) 2009-0005, and the raising of experimental animal exists
The college of traditional Chinese medicine of Gansu Province SPF laboratories are carried out.
1.2 cell line：The strain of S180 sarcoma knurl, the strain of H22 knurls are tested by Gansu Province's new drug preclinical study emphasis
Room（Lanzhou University）Professor Wu Yongjie gives.The strain of human colon carcinoma HCT-116 knurls is purchased from Chinese Academy of Sciences's Shanghai cell biology
Research institute.
2. experimental method
The foundation of 2.1 tumor models
2.1.1 the foundation of S180 sarcoma subcutaneous transplantation tumor model：Recovery euphorbia egg decoctum cell, takes healthy KM
Number of mice only, passed on 2 times by intraperitoneal inoculation, in 7d after last intraperitoneal inoculation, and mouse cervical dislocation is put to death, the leaching of 75% alcohol
Bubble sterilization, with the syringe extraction ascites of No. 7 syringe needles of 5 mL bands under aseptic condition, then with N.S by S180 sarcoma ascites
Oncocyte is diluted to inoculum density（5.0×106 Individual/only, 0.2 ml/ is only）, plus it is dual anti-（Containing the U/mL of penicillin 100 and streptomysin
100 U/mL）, be inoculated into the right armpit of KM mouse it is subcutaneous after, mouse is randomly divided into 5 groups：Solvent（Physiological saline）Control group, change
Treat medicine control（5-Fu）Group, double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines（Valdien）It is low（5 mg/kg）, in
（10 mg/kg）, high dose group（20 mg/kg）.Each concentration of Valdien and 5-Fu are administered in intraperitoneal injection.Wherein
Valdien, once a day, 5-Fu, the next day once, give normal saline when not to 5-Fu.During experiment：Body weight was every 2 days
Claim 1 time.5-Fu dosages press 20 mg/kg.After the d of Valdien successive administrations 7, mouse is put to death, lump is peeled off.
2.1.2 the foundation and administration of rat liver cancer H22 subcutaneous transplantations knurl model：Recovery rat liver cancer H22 cells, take strong
Health KM number of mice only, passed on 2 times by intraperitoneal inoculation, in 7d after last intraperitoneal inoculation, and mouse cervical dislocation is put to death, 75% wine
Ascites is extracted with the syringe of No. 7 syringe needles of 5 mL bands under smart soaking disinfection, aseptic condition, then with N.S by rat liver cancer H22 abdomens
Hydatoncus cell is diluted to inoculum density（5.0×106 Individual/only, 0.2 mL/ is only）, plus it is dual anti-（Containing the U/mL of penicillin 100 and strepto-
100 U/mL of element）, it is inoculated into the right armpit of BALB/c mouse subcutaneous.Mouse is grouped and gives drug therapy at random in inoculation next day,
Mouse is randomly divided into 5 groups：Physiological saline group, 5-Fu groups, Valdien are low（5 mg/kg）, in（10 mg/kg）, high dose group
（20 mg/kg）.Each concentration of Valdien and 5-Fu are administered in intraperitoneal injection.Wherein Valdien, once a day, 5-Fu,
The next day once, give normal saline when not to 5-Fu.During experiment：Body weight claimed 1 time every 2 days.5-Fu dosages press 20
mg/kg.After the d of Valdien successive administrations 7, mouse is put to death, tumor mass is peeled off.
2.1.3 the foundation and administration of human colon carcinoma HCT-116 subcutaneous transplantations knurl model：Collect exponential phase people knot
Intestinal cancer HCT-116 cells, cell concentration is adjusted to 4 × 10 with physiological saline7Individual/mL.By 0.2 mL tumour cells（I.e. 8
×106It is individual）It is inoculated in the right armpit of BALB/c nude mices subcutaneous, observes tumour growth situation.Experiment sets vehicle control group（Physiology
Salt solution）, chemotherapeutic positive controls, Valdien groups.BALB/c nude mices are grouped at random in inoculation next day, and medicine is given after 4d
Treatment.Wherein Valdien groups, once a day（20mg/kg）；Cis-platinum, every two days once, normal is given when not to cis-platinum
Salt solution（Cisplatin administration totally 4 times）.During experiment：Body weight claimed 1 time every 2 days.Cisplatin administration dosage presses 5 mg/kg.Valdien connects
After 14 d of continuous administration, mouse is put to death, tumor mass is peeled off.
2.2 observation index and effective criterion
1. tumor weight inhibiting rate（IR）And drug interaction index（CDI）Calculating：Claim in next day after last dose
Body weight, puts to death animal, and dissection strips tumor mass, claims knurl weight.Tumour inhibiting rate and drug interaction index is calculated as follows（CDI）：
Tumour inhibiting rate（IR）=（The average knurl weight of the average knurl weight-administration group of negative control group）The average knurl weight of/negative control group ×
100%
2. solid tumor criterion：The average knurl weight of negative control group tumour is less than 1 g, or 20% tumor weight is less than 400
Mg, represents that tumour growth is bad, experiment is cancelled.By reagent curative effect：Tumour inhibiting rate（That is tumor weight inhibiting rate）<40% is invalid；Suppression
Ratio of outflow >=40%, and be statistically analyzedP<0.05 is effective, and repeats to be judged to effectively when 1-2 result is consistent.
2.3 statistical analysis：Data are usedRepresent,Use multigroup meantMethod of inspection is analyzed.
3. result
The influence grown when 3.1 Valdien are alone to S180 sarcoma subcutaneous transplantation knurl：Each dosage pair of Valdien
The growth of S180 sarcoma subcutaneous transplantation knurl has inhibitory action, with vehicle control group ratio, Valdien middle dosages and high dose group
Knurl weight is substantially reduced（p<0.01）, tumor control rate respectively reaches 48.7% and 55.5%, is shown in Table 1.
The influence grown when 3.2 Valdien are alone to rat liver cancer H22 subcutaneous transplantations knurl
Each dosage of Valdien has inhibitory action to the growth of rat liver cancer H22 subcutaneous transplantations knurl, and vehicle control group ratio,
Each dosage group knurl weights of Valdien are substantially reduced（p<0.05 orp<0.01）, tumor control rate respectively reaches 33.0%, 50.4%
With 60.1%, 2 are shown in Table.
The influence grown when 3.3 Valdien are alone to human colon carcinoma HCT-116 nude mouse subcutaneous transplantations knurl
Each dosage of Valdien has inhibitory action to the growth of human colon carcinoma HCT-116 nude mouse subcutaneous transplantations knurl, with solvent
Control group ratio, Valdien group knurl weights are substantially reduced（P<0.01）, tumor control rate reaches 57.8%, is shown in Table 3.
4. conclusion
Valdien is alone to have obvious therapeutic action to S180 sarcoma, rat liver cancer H22 subcutaneous transplantation knurls, wherein,
High dose group tumour inhibiting rate is up to more than 40%, and wherein high dose is up to more than 50%.Valdien is alone to human colon carcinoma
HCT-116 nude mouse subcutaneous transplantation knurls have obvious therapeutic action, and its tumour inhibiting rate is up to 57.8%.
In summary, the double 3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamines of soft chain schiff bases complex（VALD）It is right
Human liver cancer SMMC7721 and HepG2 cell, human colon carcinoma HCT-116 cells, human gastric cancer SGC-7901 and BGC-823
The propagation of cell line is respectively provided with significant inhibitory action, therefore, available for the preparation of cancer therapy drug, i.e., with double 3- methoxyl groups 2- hydroxyls
Base-benzaldehyde contracting diethylenetriamine is active component, and routinely technique and auxiliary material are prepared into pharmaceutically acceptable preparation.
Brief description of the drawings
Fig. 1 is the VALD of various dose in inhibited proliferation of the different time to SMMC7721 cells（, n=3）；Figure
In, every group is from left to right followed successively by Control, 0.5 mg/L, 1 mg/L, 2.5 mg/L, 5 mg/L, 8 mg/L.
Fig. 2 is the VALD of various dose in inhibited proliferation of the different time to HepG2 cells（, n=3）, in figure, often
Group is from left to right followed successively by Control, 0.5 mg/L, 1 mg/L, 2.5 mg/L, 5 mg/L, 8 mg/L.
Fig. 3 is the VALD of various dose in inhibited proliferation of the different time to HCT-116 cells（, n=3）, figure
In, every group is from left to right followed successively by Control, 0.5 mg/L, 1 mg/L, 2.5 mg/L, 5 mg/L, 8 mg/L.
The inhibitory action that Fig. 4 VALD breed to SGC-7901gastriccarcinomacellline（, n=3）, in figure, every group from left to right according to
Secondary is Control, 0.5 mg/L, 1 mg/L, 2.5 mg/L, 5 mg/L, 8 mg/L.
The inhibitory action that Fig. 5 VALD breed to human gastric cancer（, n=3）, in figure, every group from left to right according to
Secondary is Control, 0.5 mg/L, 1 mg/L, 2.5 mg/L, 5 mg/L, 8 mg/L.
Embodiment
The method that cancer therapy drug is prepared to Valdien below by specific embodiment is described further.
The preparation of embodiment 1, capsule cancer therapy drug
Raw material proportioning：Double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines（Valdien）200 mg, 10% starch
Slurry is appropriate, and hard capsule 100 is made in appropriate food coloring altogether；
Preparation technology：Valdien is crossed after 80 mesh sieves, plus 10% starch, food coloring and suitable quantity of water, is well mixed, system
Softwood, crosses the granulation of 14 mesh nylon mesh, below 3%, inserts in capsulae vacuus, produces to moisture in 70 DEG C of dryings；
Dose：2 times on the one, one time 1.
The preparation of embodiment 2, granule cancer therapy drug
Raw material proportioning：The mg of Valdien 200, the g of Icing Sugar 500, the g of starch 500；
Preparation technology：After Valdien sievings, plus starch, Icing Sugar and suitable quantity of water, it is well mixed, softwood processed, crosses 14 mesh Buddhist nuns
Imperial sieve series grain, wet granular is in 60 DEG C of dryings, and dry particl crosses 14 mesh sieve whole grains, after No. 4 sieves（65 mesh）Fine powder is weeded out, then
Packing, sealing, packaging is produced.Specification：2mg/10g ；
Dose：2 times on the one, one time 1 bag.
The preparation of embodiment 3, anti-cancer injection
Raw material proportioning：The mg of Valdien 200, sodium chloride 850mg, the mL of tween 1, water for injection adds to 100 mL；
Preparation technology：In with container, plus the % of recipe quantity 80 water for injection, add Valdien and sodium chloride
And tween, stirring is completely dissolved it, filters, embedding, and 100 DEG C of 30 min of sterilizing are produced.The mg/1mL of specification 2；
Dosage：2 times on the one, one time 1.
The preparation of embodiment 4, pill cancer therapy drug
Raw material proportioning：Valdien 200 mg, PEG-6000 1800mL；
Preparation technology：Take PEG-6000 to be heated to about 135 DEG C in oil bath, add the mg of Valdien fine powders 200,
Being stirred continuously makes whole meltings, filters while hot, puts in reservoir, is incubated at 135 DEG C, is respectively with the inside and outside footpath of the mouth of pipe
9.0mm, 9.8mm dropper titration, drip fast 80 drops/min, instill in the atoleine coolant containing 43% kerosene, condensation
Pelletization, ball is washed with atoleine, to without kerosene taste, the atoleine of adhesion is sucked with writing paper made from bamboo, is produced；
Dose：2 times on the one, one time 1.
Claims (3)
1. pair application of the 3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamines in cancer therapy drug is prepared, it is characterised in that：Institute
Cancer is stated for liver cancer, colon cancer, stomach cancer.
2. double 3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamines answering in cancer therapy drug is prepared as claimed in claim 1
With, it is characterised in that：Using double 3- methoxyl groups 2- hydroxy-benzaldehyde contracting diethylenetriamines as active component, routinely technique and auxiliary
Material is prepared into pharmaceutically acceptable preparation.
3. double 3- methoxyl group 2- hydroxy-benzaldehyde contracting diethylenetriamines answering in cancer therapy drug is prepared as claimed in claim 2
With, it is characterised in that：The preparation is granule, capsule, pill or parenteral solution.
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