CN108096255B - Deflazacort is used to inhibit or treat the purposes of cancer of pancreas - Google Patents
Deflazacort is used to inhibit or treat the purposes of cancer of pancreas Download PDFInfo
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Abstract
The present invention relates to the scheme for inhibiting or treating cancer of pancreas, preparation and purposes, the program include using a effective amount of deflazacort or its pharmaceutical salt.Therapeutic scheme of the invention can significantly inhibit pancreatic cancer growth, reduce the treatment cost and risk of cancer of pancreas, and without obvious toxic-side effects.
Description
Technical field
The present invention relates to the purposes of deflazacort or its pharmaceutical salt in treatment cancer of pancreas.
Background technique
One of the main reason for cancer (Cancer) is whole world morbidity and is dead, according to the World Health Organization (World
Health Organization, WHO) recent statistics, there are about 8,800,000 cancer related mortalities, account for global death toll within 2015
16% (with reference to from WHO official website http://www.who.int/features/factfiles/cancer/en/).Its
In, it is worst one of the tumour of grade malignancy highest, prognosis that cancer of pancreas, which is a kind of tumor in digestive tract for being difficult to diagnosing and treating,
It has often been in advanced stage after making a definite diagnosis, survival rate is only less than 3% in 5 years.
It mainly include operative treatment, radiotherapy, conventional cell poison at present for the therapeutic strategy of cancer of pancreas than relatively limited
Chemotherapy, the treatment of small molecule targeted drug etc., but progress is very limited, and only the patient less than 20% is suitble to connect
By operative treatment, and most of patients can lead to death because of recurrence after surgery, and the response rate of classic chemotherapy drug is also less than 10%.
Deflazacort (Deflazacort, DFZ) is a kind of artificial synthesized steroid compound, has anti-inflammatory and inhibits
The effects of immune, the diseases such as immunosupress after being widely used in allergy, asthma, inflammation, autoimmune disease, organ transplant
Treatment.DFZ is a kind of prodrug, can absorb rapidly after oral administration and be metabolized as it under the action of blood plasma esterase and mainly live
Property metabolite 21- hydroxyl deflazacort (21-hydroxy deflazacort, 21-OH DFZ).In current existing research
In, it there is no any evidence to show that DFZ has good inhibiting effect to cancer of pancreas.
Summary of the invention
The present inventor has found that DFZ or its pharmaceutical salt have the growth of cancer of pancreas in the therapeutic process of research cancer of pancreas
There is good inhibitory effect, and without obvious drug toxicity.
DFZ is with higher anti-inflammatory with immunosupress efficiency and preferable tolerance, glycometabolism, calcium phosphate to body
Metabolism, hypothalamic function influence very little, so that it is widely used in children and old man.2017, the supervision of U.S.'s food and medicine
Management board (Food and Drug Administration, FDA) has approved DFZ and is applied to treatment Du Shi muscular dystrophy (ginseng
It examines from FDA official website https: //www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm540945.htm).However, all the time its in terms of tumour using extremely limited, especially in cancer of pancreas application
It has not been reported.The present inventor has first carried out cell assay in vitro according to the classical thinking that anticarcinogen is studied at research initial stage, ties
Fruit shows that DFZ, almost without lethal effect (see embodiment 1), but can preferably inhibit cell in vitro to pancreatic cancer cell
Colony forming (see embodiment 2).During testing in animal body, DFZ is had studied respectively and is connect in pancreatic carcinoma SW1990
Antitumor action in the transplantable tumor animal model of kind and the animal model of source of people tumor inoculation, it has unexpectedly been found that DFZ is to pancreas
Cancer has significant inhibitory effect, and effect is even better than clinically used chemotherapeutics gemcitabine in treatment of pancreatic cancer
(Gemcitabine, GEM), and without obvious drug toxicity (see embodiment 3,4).
In view of DFZ is to the potential mechanism of endocrine regulation, the present inventor also have chosen the drug similar with DFZ mechanism he
Former times fragrant (Tamoxifen, TAM) and Letrozole (Letrozole) are not tested, as a result, it has been found that, drug effect of the DFZ in cancer of pancreas
It is substantially better than TAM and LTZ (see embodiment 3,4).
It can be seen from the results above that as endocrine therapeutic agents, in other drugs with similar mechanism to pancreas
In the case that the treatment of cancer is invalid, DFZ can unexpectedly inhibit the growth of cancer of pancreas very well, and without obvious drug toxicity.
Therefore, it is an object of the present invention to provide a kind of treatments that can inhibit cancer of pancreas and do not generate obvious toxic-side effects
Drug, including a effective amount of deflazacort or its pharmaceutical salt.
The pharmaceutical salt is to be synthesized by conventional chemical processes from parent compound, the parent compound packet
Containing alkalinity or acid part.In general, the salt is such as to be worked as by the free acid of these compounds or alkali form and chemistry
The suitable alkali or acid of amount in organic solvent or are reacted in water or in the mixture of water and organic solvent and are prepared.It is logical
Often, non-aqueous media such as ether, ethyl acetate, ethyl alcohol, isopropanol or acetonitrile is preferred.The example of acid-addition salts includes inorganic acid
Addition salts such as hydrochloride, hydrobromate, hydriodate, sulfate, nitrate, phosphate and organic acid addition salt such as acetate,
It is trifluoroacetate, maleate, fumarate, citrate, oxalates, succinate, tartrate, malate, flat
Peach hydrochlorate, analgin and tosilate.The example of base addition salts includes inorganic salts such as sodium, potassium, calcium and ammonium salt and organic
Alkali metal salt such as ethylenediamine, ethanol amine, N, the amino-acid salt of bis- alkylene ethanol amine of N-, triethanolamine and alkalinity.
According to an aspect of the present invention, the cancer of pancreas includes pancreatic sites tumour, tumour is formed and any other evil
Property tissue, preferably pancreas duct carcinoma.
It is a further object of the present invention to provide a kind of anticancer agents comprising deflazacort or its pharmaceutical salt.Into one
Step, anticancer agent provided by the invention further includes auxiliary material pharmaceutically.Wherein, the anticancer agent includes tablet, solution
Agent, suspension, emulsion, powder, granule, capsule, micro-capsule, microballoon, injection, liposome etc., the preparation are slow/controlled release
Preparation is not slow/controlled release preparation.The auxiliary material pharmaceutically include lubricant, filler, surfactant, solubilizer,
Cosolvent etc..
Realization of the invention has following positive effect:
(1) cancer of pancreas is treated by DFZ, can significantly inhibit tumour growth, effect significantly better than Common Chemotherapy drug and
Endocrine therapeutic agents, and without obvious toxic-side effects；
(2) drug safety of the present invention is good, and patient can be greatly reduced under conditions of ensuring good drug effect
Operative risk.
Detailed description of the invention
Fig. 1 is influence result figure (n=6) of the DFZ to human pancreas cancer SW1990 cell survival rate.SW1990 cell is given respectively
The change curve of cell survival rate when giving blank control and various concentration DFZ.
Fig. 2 is influence result figure of the DFZ to human pancreas cancer SW1990 cell colony Forming ability.SW1990 cell is given respectively
The photo that cell colony is formed when giving blank control and various concentration DFZ.
Fig. 3 is influence result figure of the DFZ to human pancreas cancer SW1990 cell colony Forming ability.SW1990 cell is given respectively
The quantitative result that cell colony is formed when giving blank control and various concentration DFZ (with blank control group for 100%).
Fig. 4 is the growth curve (DFZ single dose, n=5) of female tumor bearing nude mice tumour when DFZ is administered.Human pancreas cancer
SW1990 tumor bearing nude mice gives blank control, DFZ 4mg/kg, gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) respectively
The change curve of nude mouse tumor volume when 50mg/kg, Letrozole (LTZ) 0.5mg/kg.
Fig. 5 is the photo (DFZ single dose, n=5) of female tumor bearing nude mice tumour when DFZ is administered.Human pancreas cancer SW1990 lotus
Tumor nude mice give respectively blank control, DFZ 4mg/kg, gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg,
The 22nd day tumour real shooting photo of Letrozole (LTZ) 0.5mg/kg.
Fig. 6 is the variation (DFZ single dose, n=5) of female tumor bearing nude mice weight when DFZ is administered.Human pancreas cancer SW1990 lotus
Tumor nude mice give respectively blank control, DFZ 4mg/kg, gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg,
The change curve of nude mice weight when Letrozole (LTZ) 0.5mg/kg.
Fig. 7 is the organ index (DFZ single dose, n=5) of female tumor bearing nude mice when DFZ is administered.Human pancreas cancer SW1990 lotus
Tumor nude mice give respectively blank control, DFZ 4mg/kg, gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg,
The 22nd day percentage of heart, liver, spleen, lungs, kidney weight relative to nude mice weight of Letrozole (LTZ) 0.5mg/kg.
Fig. 8 is the growth curve (DFZ multi-dose, n=5) of female lotus knurl NOD/SCID mouse tumor when DFZ is administered.Source of people
Pancreatic Adenocarcinoma inoculation tumor-bearing mice give respectively blank control, DFZ 0.5mg/kg, DFZ 2mg/kg, DFZ 4mg/kg,
Mouse tumor volume when gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg, Letrozole (LTZ) 0.5mg/kg
Change curve.
Fig. 9 is the photo (DFZ multi-dose, n=5) of female lotus knurl NOD/SCID mouse tumor when DFZ is administered.Source of people pancreas
The tumor-bearing mice of cancerous tissue inoculation gives blank control, DFZ 0.5mg/kg, DFZ 2mg/kg, DFZ 4mg/kg, Ji Xi respectively
The 34th day tumour of mouse tumor when his shore (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg, Letrozole (LTZ) 0.5mg/kg
Real shooting photo.
Figure 10 is the changes of weight (DFZ multi-dose, n=5) of female lotus knurl NOD/SCID mouse tumor when DFZ is administered.People
The tumor-bearing mice of source Pancreatic Adenocarcinoma inoculation gives blank control, DFZ 0.5mg/kg, DFZ 2mg/kg, DFZ 4mg/ respectively
Mouse weight when kg, gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg, Letrozole (LTZ) 0.5mg/kg
Change curve.
Figure 11 is the organ index (DFZ multi-dose, n=5) of female lotus knurl NOD/SCID mouse tumor when DFZ is administered.People
The tumor-bearing mice of source Pancreatic Adenocarcinoma inoculation gives blank control, DFZ 0.5mg/kg, DFZ 2mg/kg, DFZ 4mg/ respectively
Kg, gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg, Letrozole (LTZ) 0.5mg/kg the 34th day heart, liver
The percentage of dirty, spleen, lungs, kidney weight relative to mouse weight.
Figure 12 is the blood picture index (DFZ multi-dose, n=5) of female lotus knurl NOD/SCID mouse tumor when DFZ is administered.People
The tumor-bearing mice of source Pancreatic Adenocarcinoma inoculation gives blank control, DFZ 0.5mg/kg, DFZ 2mg/kg, DFZ 4mg/ respectively
Mouse when kg, gemcitabine (GEM) 15mg/kg, tamoxifen (TAM) 50mg/kg, Letrozole (LTZ) 0.5mg/kg the 34th day
Blood picture index.
Specific embodiment
In order to better understand the present invention, current inventor provides following embodiments, however, these embodiments are only
Illustratively purpose and provide, and be not interpreted as limitation of the present invention because many variations be it is possible,
Without departing from the spirit and scope of the invention.Although method of the invention is described in specific embodiment, affiliated technology
The technical staff in field is it is clear that the step of can make the method or the sequence of step changes, but without departing from the present invention
Concept and scope.More specifically, it is clear that it is similar with other biologically relevant pharmacology processes in chemistry
Drug can replace drug as described herein, while reach the same or similar effect.The technical personnel in the technical field are aobvious
And what is be clear to should all be considered in scope of the invention and concept all this similar replacements or modification.
Embodiment 1:
The influence that DFZ is proliferated human pancreatic cancer cell
The present embodiment has studied influence of the DFZ to human pancreatic cancer cell in-vitro multiplication.
Logarithmic growth phase cell with 0.25% pancreatin -0.53mmol/L EDTA solution digestion, counts.SW1990 is thin
Born of the same parents are inoculated in 96 porocyte culture plates by 8000/hole respectively.Culture for 24 hours after, be administered, DFZ administration group it is final concentration of
1,10,100,200,400,800,1000 μm of ol/L, every group sets 6 in parallel, continues to be incubated for 48h.Culture is discarded after incubation
10% trichloroacetic acid (TCA, w/v) solution that 100 μ l are pre-chilled in advance, 4 DEG C of fixed 1h are added in base, every hole；TCA solution is discarded, from
Water is rinsed 5 times, naturally dry；100 μ l 0.4% Sulforhodamine B (SRB) dyestuff is added in every hole, dyes 30min at room temperature；
SRB dyestuff is discarded, washes 5 times with 1% acetum, naturally dry；200 μ l 10mmol/L Tris solution (pH are added in every hole
10.5) 20min, is shaken on oscillator dissolves the SRB in conjunction with tumour cell alkaline amino acid residue, microplate reader measurement
Absorbance at 540nm wavelength.The absorbance of blank control group and drug-treated group is expressed as ODcontrol,540And ODsample,540.Its
In one piece of 96 porocyte culture plates not drug treatment, cultivate from inoculation in cell and handled afterwards by above-mentioned steps for 24 hours, it is average to inhale
Luminosity is set as OD0h, 540.Cell survival rate is calculated by formula 1:
IC of (Fig. 1): the DFZ in SW1990 cell as the result is shown50(drug concentration needed for inhibiting 50% cell Proliferation)
Greater than 500 μM, illustrate DFZ to human pancreatic cancer cell without obvious cytotoxicity.
Discuss: the present embodiment has studied DFZ to the cytotoxicity of external pancreatic cancer cell, the results showed that DFZ is to people's pancreas
Adenocarcinoma cell is without apparent direct killing effect.This result can significantly inhibit the result of internal pancreatic cancer growth with DFZ hereinafter
Apparent comparison is formed, illustrates the cytotoxicity that DFZ inhibits the mechanism of tumour growth to be different from classic chemotherapy drug.Due to
In the research of field of antineoplastic medicaments, traditional research method be first carry out the research of cell in vitro poison and select cytotoxicity compared with
Strong compound is studied, and can to illustrate that those skilled in the relevant art are difficult to before making the present invention pre- for the result of this example
Expect that DFZ has significant inhibiting effect to the growth of cancer of pancreas.
Embodiment 2:
Effect of the DFZ to the external Colony forming of human pancreatic cancer cell
The present embodiment has studied influence of the DFZ to human pancreatic cancer cell Colony forming ability in vitro.
The SW1990 pancreatic cancer cell that form is normal, in good condition is taken, the operation digested, be centrifuged, is suspended again is simultaneously
It counts.According to count results, cell suspension is diluted to 1000/mL with culture medium, 6 holes are added to the volume of every hole 2mL
In tissue culture plate, make 2000, every hole cell.6 orifice plates after inoculation are placed in cell incubator.
DFZ titer is diluted with culture medium respectively, respectively obtains that DFZ is 1 μM final concentration of, 10 μM, the training of 100 μM of drug containing
It is spare to support base.Isometric DMSO is added in the culture medium of blank control group, and makes the DMSO concentration in system not higher than 1%.
It after administration for 24 hours, inhales and abandons each hole culture medium, every hole is added 2mL fresh culture, changes the liquid once within every 3 days.Inoculation 8
It after it, inhales and abandons culture medium, 0.5mL PBS rinsing is added once in every hole, inhales every hole after abandoning PBS and 0.5mL methanol is added, solid at room temperature
Determine 10min.It inhales and abandons methanol, dye 10min with 0.5% crystal violet solution.It inhales and abandons crystal violet solution, rinse 6 orifice plates with tap water
To wash away unbonded dyestuff, naturally dry.6 orifice plates after drying are taken pictures, the clone of Amersham Imager600 is utilized
Tally function counts the colony number to be formed, and is compared.
(Fig. 2): DFZ has the Colony forming ability of human pancreatic cancer cell SW1990 in vitro more significant as the result is shown
It influences, DFZ concentration is higher, inhibits the effect of soft agar clonogenic assay stronger.
Discuss: the main individual cells of investigating of Colony forming experiment are proliferated in vitro and form the ability of colony, indirectly
The Tumor formation of tumour cell is reacted；Drug by the way that various dose is added in the medium can investigate cell in drug effect
The lower ability for maintaining fertility, has had researcher to grind the tumor stem cell that the method is used for including cancer of pancreas at present
Study carefully.This chapter research in Colony forming the experimental results showed that, DFZ has significantly under 1 μM, 10 μM and 100 μM of concentration
Inhibit Colony forming ability, there is dose dependent, can illustrate that DFZ has the function of inhibiting tumor development.
Embodiment 3:
Inhibiting effect (DFZ single dose) of the DFZ to tumour growth in internal cancer of pancreas Transplanted tumor model
The present embodiment has studied the inhibiting effect for the nude mouse tumor growth that DFZ is inoculated with human pancreatic cancer cell.
The good SW1990 cell of growth conditions is taken, the DMEM culture medium without FBS on a small quantity is added after digestion, with elbow glass
Glass suction pipe blows down the cell being attached in culture bottle wall, is transferred to 15mL centrifuge tube, and 1000rpm is centrifuged 5min, discards supernatant,
It a small amount of culture medium is added blows and beats cell again and mix and count, according to cell counts by the cell suspension training of no FBS
Feeding base is diluted to 1.5 × 107A/mL.Diluted cell suspension is injected to oxter on the right side of nude mice according to the dimensions subcutaneous of 0.2mL
(about contain 3 × 106A cell), observation inoculation situation.With the major diameter (D of vernier caliper measurement tumourmax) and minor axis (Dmin), meter
Calculate gross tumor volume V (V=Dmax×Dmin 2/2)。
After inoculation, tumour growth to 100~200mm3When mouse is randomly divided into 5 groups, every group 5.Every group give prescription
Case are as follows: (1) blank control group: daily 10% hydroxypropyl-β-cyclodextrin solution of stomach-filling 0.1mL；(2) GEM group: every tail on the three is quiet
Arteries and veins injects physiological saline of the 0.1mL containing GEM, and GEM dosage is 15mg/kg；(3) LTZ group: daily stomach-filling 0.1mL is containing LTZ's
30% hydroxypropyl-β-cyclodextrin solution, LTZ dosage are 0.5mg/kg；(4) TAM group: daily stomach-filling 0.1mL containing TAM 1,
2- propylene glycol solution, the dosage of TAM are 50mg/kg；(5) DFZ 4mg/kg group: daily stomach-filling 0.1mL containing DFZ 10%
Hydroxypropyl-β-cyclodextrin solution, the dosage of DFZ are 4mg/kg.Wherein, blank control group is negative control group, and GEM is Ji
His shore of west, LTZ is Letrozole, and it is positive controls that TAM, which is tamoxifen,.
Since the 0th day, the survival condition of every group of animal of two kinds of animal models is observed, if there is obvious adverse reaction,
And equaled a record its weight with day, as calculating the foundation for being administered daily dosage, and quantify to reflect the survival condition of animal.Administration
The 22nd day afterwards, after completing measurement, animal is put to death, tumour is taken out out of animal body, puts and takes pictures by group.Put to death animal it
Afterwards, completely its heart, liver, spleen, lungs, kidney are taken out in dissection, are cleaned up with physiological saline, and after being dried with filter paper
Weighing calculates the organ index of each internal organs of animal, calculation formula are as follows:
As the result is shown (Fig. 4,5,6,7): DFZ 4mg/kg group gross tumor volume significantly less than blank control group and GEM,
The positive controls such as TAM, LTZ, nude mice weight is without significant changes during administration, and main organs are also without obvious damage.Result above
Show that DFZ can show preferable tumor inhibition effect, and drug safety in the xenograft tumor that human pancreatic cancer cell is inoculated with
Property is good.
Discuss: in the human pancreas cancer xenograft tumor of SW1990 cell inoculation, DFZ has been shown than classic chemotherapy drug
The better antitumor drug effect of GEM and endocrine therapeutic agents TAM, LTZ.Meanwhile weight shows without significant change during administration
DFZ without obvious general toxicity, organ index the result shows that DFZ to main organs without significant toxicity, show that its safety is preferable.
Embodiment 4:
Inhibiting effect (DFZ multi-dose) of the DFZ to tumour growth in internal cancer of pancreas source of people Transplanted tumor model
The present embodiment has studied the inhibiting effect for the mice tumors grew that DFZ is inoculated with clinical patients tumor tissues.
By the obtained Pancreatic Adenocarcinoma of excision of performing the operation out of clinical patients body, take out a part be cut into about 2mm ×
The fritter of 2mm × 3mm is injected into the NOD/SCID right side of mice subcutaneous abdomen of about 6 week old with the medullo-puncture needle of sterilizing, and referred to as
Generation source of people xenograft tumor (Patient-derived xenograft, PDX) model mouse (F1)；To tumour growth to about
500mm3When, it puts to death mouse and takes out tumour rapidly, a part is placed in cryopreservation tube, the FBS containing 10%DMSO is added, is placed in liquid
It is frozen in nitrogen；Another part tumour is cut into 2mm × 2mm × 3mm fritter, is seeded to NOD/SCID mouse skin according to the method described above
Under, referred to as second generation PDX model mouse (F2), and so on.This experiment PDX model mouse used is the third generation (F3).
After third generation inoculation, tumour growth to 100~200mm3When mouse is randomly divided into 7 groups, every group 5.Every group
Dosage regimen is respectively as follows: (1) blank control group: daily 10% hydroxypropyl-β-cyclodextrin solution of stomach-filling 0.1mL；(2) GEM group:
Every physiological saline of the tail vein injection 0.1mL on the three containing GEM, GEM dosage are 15mg/kg；(3) LTZ group: daily stomach-filling
30% hydroxypropyl-β-cyclodextrin solution of the 0.1mL containing LTZ, LTZ dosage are 0.5mg/kg；(4) TAM group: daily stomach-filling
1,2-PD solution of the 0.1mL containing TAM, the dosage of TAM are 50mg/kg；(5) DFZ 0.5mg/kg group: daily stomach-filling
10% hydroxypropyl-β-cyclodextrin solution of the 0.1mL containing DFZ, the dosage of DFZ are 0.5mg/kg；(6) DFZ 2mg/kg group:
Daily 10% hydroxypropyl-β-cyclodextrin solution of the stomach-filling 0.1mL containing DFZ, the dosage of DFZ are 2mg/kg；(7)DFZ 4mg/
Kg group: daily 10% hydroxypropyl-β-cyclodextrin solution of the stomach-filling 0.1mL containing DFZ, the dosage of DFZ are 4mg/kg.Wherein,
Blank control group is negative control group, and GEM is gemcitabine, and LTZ is Letrozole, and it is positive control that TAM, which is tamoxifen,
Group.
Since the 0th day, the survival condition of every group of animal of two kinds of animal models is observed, if there is obvious adverse reaction,
And equaled a record its weight with day, as calculating the foundation for being administered daily dosage, and quantify to reflect the survival condition of animal.Administration
The 34th day afterwards, after completing measurement, blood routine measurement is carried out to control group and test group of animals blood sampling, the side of blood is taken using eye socket
Method takes out 20 μ L of whole blood from mouse right eye, is rapidly added in 5mL dilution, slight oscillatory upper machine measurement after mixing.Animal is put to death,
Tumour is taken out out of animal body, puts and takes pictures by group.After putting to death animal, completely its heart, liver, spleen are taken out in dissection
Dirty, lungs, kidney, are cleaned up with physiological saline, and are weighed after being dried with filter paper, and the organ index of each internal organs of animal is calculated,
Calculation formula is shown in formula 2.
As the result is shown (Fig. 8,9,10,11,12): DFZ each group gross tumor volume is significantly less than blank control group, and DFZ 2mg/
The drug effect of kg group and DFZ 4mg/kg group better than the positive controls such as GEM, TAM, LTZ, the antitumor drug effect of DFZ present dosage according to
Lai Xing.Nude mice weight is without significant changes during administration, and main organs are without obvious damage, blood picture indices Non Apparent Abnormality.With
Above the result shows that DFZ can show preferable tumor inhibition effect, and medicine in the xenograft tumor that source of people tumor tissues are inoculated with
Object good security.
Discuss: source of people xenograft tumor (PDX) model is a kind of model common in preclinical study.PDX model with
Traditional nude mouse xenograft tumor model is compared, and main advantage is to be inoculated with tumor mass from clinical patients, therefore its tumour
The characteristics of growth, is closer with human tumor.Some researches show that until F7~F10, PDX Model Tumor still can be with Primary Tumor
Keep higher similitude.
In the PDX animal model that the present embodiment is established, DFZ has shown preferable antitumor drug effect, meanwhile, administration
Period weight without significant change, show DFZ without obvious general toxicity, organ index the result shows that DFZ to main organs without aobvious
Toxicity is write, the indices and control group of DFZ each group there are no significant difference, show that its safety is preferable in blood picture result.
Claims (3)
1. deflazacort and its pharmaceutically available salt are used to prepare the purposes for inhibiting the drug of pancreas duct carcinoma.
2. purposes according to claim 1, wherein the deflazacort and other kinds of inhibition/treatment tumour medicine
Object is used in combination or deflazacort and its pharmaceutically available salt is used alone.
3. purposes according to claim 1, which is characterized in that the deflazacort and its pharmaceutically available salt are with medicine
The form of object preparation is applied, and the form of the pharmaceutical preparation is tablet, solution, suspension, emulsion, powder, granule, glue
Wafer, micro-capsule, microballoon, injection, liposome are selectively included pharmaceutical excipients in the pharmaceutical preparation.
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| CN102218071A (en) * | 2010-04-06 | 2011-10-19 | 上海安瀚特生物医药技术有限公司 | Micronized deflazacort oral preparation and preparation method thereof |
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