CN105582004A - Application of chlorogenic acid and/or chlorogenic acid derivative in tumor stem cell treatment drug - Google Patents
Application of chlorogenic acid and/or chlorogenic acid derivative in tumor stem cell treatment drug Download PDFInfo
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Abstract
The invention provides an application of chlorogenic acid and/or a chlorogenic acid derivative in a tumor stem cell treatment drug and belongs to the technical field of medicine. According to the application of the chlorogenic acid and/or the chlorogenic acid derivative in the tumor stem cell treatment drug, the new application of the chlorogenic acid is provided, and the chlorogenic acid is applied to the tumor stem cell treatment drug, so that the tumor stem cells can be inhibited and killed by the drug and relapse, metastasis and multidrug resistance of tumors are effectively prevented.
Description
Technical field
The present invention relates to medical technical field, derivative in particular to chlorogenic acid and/or itsThe application of thing in the medicine for the treatment of tumor stem cell.
Background technology
The death that 90% tumour causes is all due to tumor recurrence and transfer to other crucial devicesDue to official. The recurrence of tumour and transfer are the existence due to tumor stem cell. American cancer grindsStudy carefully association (AmericanAssociationforCancerResearch) 2006 to Tumor StemThe clearly definition that cell provides is: in tumour, have self-renewal capacity and can produce heterogeneousThe cell of tumour cell. Tumor stem cell has unlimited self-renewal capacity, Multidirectional Differentiation is divedIn energy, higher telomerase activation, strong drug resistance, anti-apoptosis, tumor tissues, ratio is lowerWith the feature of expressing stem cell specific marker thing. Although it is swollen that chemicotherapy can be killed great majorityOncocyte, but tumor stem cell is not but acted on, and tumor stem cell is through propagation,Can cause again eventually tumor recurrence. Therefore, chemicotherapy can not be removed the tumor stem cell in body,And as long as there is the existence of tumor stem cell in body, tumour just likely recurs and shifts.
At present clinical most antineoplastic Main Function is in the tumour cell of differentiation, andNot tumor stem cell, so tumor stem cell is seen as multi-drug resistance of the tumor, recurrenceWith the arch-criminal who shifts, tumor stem cell becomes at present the focus of tumor research in the world,Become the novel targets of oncotherapy, for oncotherapy brings new hope.
Summary of the invention
In order to address the above problem, the object of the present invention is to provide chlorogenic acid and/or its derivativeThe application of thing in the medicine for the treatment of tumor stem cell, so that medicine can suppress and kill is swollenKnurl stem cell, prevents the generation of Preventive and the multidrug resistance of tumour effectively.
The new purposes that the invention provides chlorogenic acid and/or its derivative, its technical scheme is:
The application in the medicine for the treatment of tumor stem cell of chlorogenic acid and/or its derivative.
Further, described tumor stem cell is that liver-cancer stem cell, cancer of the stomach stem cell, lung cancer are dryCell, kidney stem cell, colon cancer stem cell, breast carcinoma stem cell, the white blood of acute myeloidSick stem cell and CML-BC chronic myelogenous leukemia stem cell.
Brain Tumor Stem Cells, liver-cancer stem cell, cancer of the stomach stem cell, lung cancer stem cell, kidneyStem cell, colon cancer stem cell, breast carcinoma stem cell, acute myeloid leukemia stem cell andCML-BC chronic myelogenous leukemia stem cell belongs to different tumor stem cells, because of every kind of tumourThe function difference of stem cell, identification albumen and and the target spot on its inner signal path, surfaceBe different, therefore, can chlorogenic acid act on respectively brain Tumor Stem Cells, liver cancer is dry thinBorn of the same parents, cancer of the stomach stem cell, lung cancer stem cell, kidney stem cell, colon cancer stem cell, mammary glandCancer stem cell, acute myeloid leukemia stem cell and CML-BC chronic myelogenous leukemia stem cellCorresponding target spot, it plays inhibition to corresponding tumor stem cell is also uncertain.
The present invention is through research discovery, and chlorogenic acid not only can act on brain Tumor Stem Cells,Also can act on liver-cancer stem cell, cancer of the stomach stem cell, lung cancer stem cell, kidney stem cell,Colon cancer stem cell, breast carcinoma stem cell, acute myeloid leukemia stem cell and CML-BC are slowThe corresponding target spot of property marrow series leukemia stem cell, can suppress and kill these tumor stem cells,Prevent the generation of Preventive and the multidrug resistance of these tumours.
Further, described chlorogenic acid derivative comprise pharmaceutically acceptable chlorogenic acid salt andThe derivative of chemical synthesis.
Further, described chlorogenic acid salt comprises chlorogenic acid sodium salt, chlorogenic acid sylvite and chlorogenic acidCalcium salt.
In the present invention, described medicine is to have the tumor stem cell of inhibition propagation, lowers Tumor StemCell proportion, weakens the medicine of effect of tumor stem cell self-renewal capacity.
Active component in said medicine is chlorogenic acid and/or its derivative, therefore, and this medicineThere is the tumor stem cell of inhibition propagation, reduce tumor stem cell number, lower tumor stem cellRatio, weakens effect of tumor stem cell self-renewal capacity.
Further, in described medicine, contain chlorogenic acid and/or its derivative and pharmaceutic adjuvant.
Further, described medicine is combination medicine, also contains existing anti-swollen in described medicineTumor medicine.
In said medicine, can adopt chlorogenic acid and/or its derivative action activity composition, also canSo that chlorogenic acid and/or its derivative and existing antineoplastic are combined as combination medicineAnd make this medicine there is better result for the treatment of.
Further, described existing antineoplastic is adriamycin.
Further, in every preparation unit of described medicine, contain chlorogenic acid and/or its derivative1～1000mg。
Preferably, in every preparation unit of described medicine, contain chlorogenic acid and/or its derivative500mg。
Further, the formulation of described medicine is oral formulations or ejection preparation.
Beneficial effect of the present invention:
Chlorogenic acid provided by the present invention and/or its derivative are at the medicine for the treatment of tumor stem cellApplication in thing, for chlorogenic acid provides a kind of new purposes, by chlorogenic acid is applied to and is controlledTreat in the medicine of tumor stem cell, make medicine can suppress and kill tumor stem cell, effectivelyPrevent the generation of Preventive and the multidrug resistance of tumour.
Brief description of the drawings
Fig. 1 is the result that the tumour ball of the cell line H460 described in embodiment 1 forms experimentFigure;
Fig. 2 is the result that the tumour ball of the cell line H466 described in embodiment 1 forms experimentFigure;
Fig. 3 is the result figure that the side population cell described in embodiment 1 (SP) detects;
Fig. 4 is microsphere cultivation results figure after the drug intervention described in embodiment 2;
Fig. 5 is CD44+CD24 in microsphere cell after the drug intervention described in embodiment 2The result of variations figure of ﹣/low cell proportion;
Fig. 6 is side population cell in microsphere cell after the drug intervention described in embodiment 2(SP) testing result figure;
Fig. 7 is MDR1, BCRP in microsphere cell after the drug intervention described in embodiment 2The disparity map of mrna expression.
Detailed description of the invention
Embodiment 1
The impact of chlorogenic acid on lung cancer stem cell growth
Tumour ball forms experiment: the human lung carcinoma cell line H460 of cellar culture and H466's is thinBorn of the same parents respectively after trypsinization with the centrifugal 2min of centrifugal speed of 1000rpm, add after abandoning supernatantEnter 3ml sterile phosphate buffer solution (PBS), softly dispel, washed cell precipitation and fromThe heart. After cyclic washing 3 times, add tumour ball culture medium (serum free medium), be prepared intoSingle cell suspension.
The cell concentration of the single cell suspension of the cell line H460 of mensuration preparation is also adjusted cellDensity is 1500cells/ml, single cell suspension is transferred to equably to 6 orifice plates of ultralow adhesionIn, and set up respectively A, B, C and D group to carry out the cultivation of tumour ball; Measure the cell of preparationThe cell concentration of the single cell suspension of strain H466 to adjust cell density be 1500cells/ml,Single cell suspension is transferred to equably in 6 orifice plates of ultralow adhesion, and set up respectively A, B,C and D group are carried out the cultivation of tumour ball. Wherein, A group is blank group, selects physiological salineProcess; It is the chlorogenic acid processing of 1 μ Mol/L that B group is all selected concentration; C group is all selected concentrationIt is the chlorogenic acid processing of 2 μ Mol/L; It is the chlorogenic acid of 3 μ Mol/L that D group is all selected concentrationProcess. Within every 3 days, change nutrient solution 1 time, after 7 days, observe tumour ball formational situation.
Can in serum free medium, grow and form the characteristic of microballoon according to lung cancer stem cell,These microballoons are formed by minority tumor stem cell self, therefore, and by detecting microspheroidalBecome volume, can indicate the quantity of tumor stem cell and be provided with above-mentioned experiment. Experimental resultAs depicted in figs. 1 and 2, Fig. 1 is the result figure of the tumour ball formation experiment of cell line H460;Fig. 2 is the result figure that the tumour ball of cell line H466 forms experiment. Wherein B, C and D groupTumour sphere volume be all less than blank group, illustrate chlorogenic acid to lung cancer stem cell have suppress doWith; Meanwhile, along with the concentration of chlorogenic acid increases, the volume of tumour ball reduces gradually, explanationAlong with the increase of the concentration of chlorogenic acid, its inhibitory action to tumor stem cell is stronger, canEffectively reduce the quantity of lung cancer stem cell.
Side population cell detects (SP): lung cancer cell line H460 cell is divided into three groups, compilesNumber be A, B and C. A group is blank group, adopts physiological saline to hatch 3 days; B group and CIt is that the chlorogenic acid of 1 μ Mol/L and 3 μ Mol/L is hatched 3 days that group adopts respectively concentration. After 3 days,The cell of A, B and C group is discarded to nutrient solution, and the PBS of 4 DEG C rinses, then through pancreas enzyme-EDTADigestion is also resuspended as single cell suspension taking 2% hyclone 1640 culture mediums, counts and adjustsCell density is 1 × 105cells/ml. Cell adds the Hoechst33342 of debita spissitudo,37 DEG C of slow circumvolves are hatched after 90min in 4 DEG C of centrifugal 5min, and with precooling PBS re-suspended cell.Washed cell 2 times altogether. Cell is kept on ice to suppress the outflow of Hoechst33342 dyestuff.Sample storage is on ice, until upper machine testing.
SP (sidepopulation) cell is a little in cell colony, and they can be byEntering nuclear fluorescent dye discharges outside born of the same parents, at fluorescence microscopy Microscopic observation or fluidic cellWhen detection, show as not painted, therefore be called SP cell. found that SP cell and stem cell have veryMany general character, and very similar to tumor stem cell, therefore, can sentence by detecting SP cellThe growing state of disconnected tumor stem cell.
As shown in Figure 3, the result figure detecting for side population cell (SP). Wherein, B group and CSP cell quantity in group is all less than A group, and C group SP cell quantity is less than B group. CauseThis, illustrate that chlorogenic acid just can play inhibitory action to SP cell under low concentration, and green formerThe depression effect of acid strengthens along with the increase of concentration, and it is dry thin that chlorogenic acid can reduce lung cancerBorn of the same parents' quantity.
Embodiment 2
The effect of chlorogenic acid to breast cancer tumour stem cell
1. the serum-free microactuator suspension spheroid of mouse mammary carcinoma cell line MCF-7 is cultivated---enrichmentBreast carcinoma stem cell
By after conventional the MCF-7 breast cancer cell bought recovery, with containing 10% hycloneDMEM/F12 culture medium (SSM) is cultivated, with 0.25% pancreatin ﹣ 0.02%EDTA digestionPassage. Get the MCF-7 cell of the exponential phase of SSM cultivation, use 0.25% pancreatin﹣ 0.02%EDTA digestion machinery are blown and beaten into single cell suspension, through Trypan Blue countingAfter be inoculated in serum free medium with 2 × 104/ml (SFM, containing hycloneDMEM/F12 culture medium, adds 20ng/mlEGF, 20ng/mlbFGF, 2%B27),Static cultivation in 37 DEG C, 5%CO2 incubator, the 3 days centrifugal liquid that changes, when forming cell ballAfter, be digested to single cell suspension weight with 10 times of dilutions of 0.25% pancreatin ﹣ 0.02%EDTABe suspended from SFM, be still inoculated in SFM with the concentration of 2 × 104/ml, within approximately 6～7 days, go down to posterityOnce.
2. experiment grouping and medication
Get SFM cultivate the 10th generation breast cancer cell ball, with 0.25% pancreatin of 10 times of dilutions﹣ 0.02%EDTA is digested to single cell suspension and is resuspended in SFM, adjusts cell density to be5 × 104/ml, is inoculated in 25ml blake bottle, every bottle of 2ml, totally 20 bottles. 20 bottles of cellsBe divided at random 4 groups, be respectively blank group, chlorogenic acid group, adriamycin group, chlorogenic acid+Adriamycin group. Control group adds physiological saline 20 μ l, and adriamycin group adds 0.1mg/ml Ah mouldElement 20 μ l, chlorogenic acid group adds 1mg/ml chlorogenic acid 20 μ l, and adriamycin+chlorogenic acid group adds0.2mg/ml adriamycin 10 μ l and 2mg/ml chlorogenic acid 10 μ l. 37 DEG C, 5%CO2 trainingSupport static cultivation in case, the centrifugal liquid that changes of 48h, continues SFM and cultivates. Observation of cell after 10 daysBalling-up situation; Collecting cell detects CD44+CD24 ﹣/low cell ratio with flow cytometerExample, side population cell (SP); In RT-PCR technology for detection cell drug resistant gene MDR1 andBCRPmRNA expresses.
3. the MCF-7 cell balling-up situation that after each group drug effect, SFM cultivates
As shown in Figure 4, be microsphere cultivation results figure after drug intervention. Wherein, adriamycinGroup (numbering C) and blank group (numbering A) can be seen the appearance of microsphere, outstandingAfter cultivating 48h, floating cell forms gradually cell mass, visible cell under inverted phase contrast microscopeGroup is made up of to tens neonatal cells that dividing several, along with cell division, and partCell breaks up, and gradually merges with peripheral cell, after 10 days, can see obvious microballoonBody forms. But chlorogenic acid group (numbering B), after the 10th day, be can't see obvious microballoonBody, neonatal cell is also less. Chlorogenic acid+adriamycin group (numbering D) survivaling cell is few,Apoptosis cracking. The cell quantity that can form microballoon reduces the quantity that represents tumor stem cellReduce, illustrate that it can kill tumor stem cell, therefore, illustrate that chlorogenic acid can be remarkableThe microballoon quantity of formation of inhibition cancer cell, the Tumor Stem in can target breast cancer cell is thinBorn of the same parents, suppress it and form microballoon, can suppress tumor stem cell; Chlorogenic acid and adriamycin oneRise to use and can suppress tumor stem cell, also suppress neonatal cell, thereby chlorogenic acid also simultaneouslyCan with adriamycin medication.
The ratio measuring of 4.CD44+CD24 ﹣/low cell
The single cell suspension that the MCF-7 cell that SSM cultivates and SFM condition are cultivated, low speedCentrifugal removal cell fragment, adjusts every pipe 1 × 106/100 μ l of cell density with PBS, experimentGroup adds rat anti-mouse CD44-PE antibody 10 μ l and CD24-FITC antibody 5 μ l, rightAdd the homotype control antibodies of same dosage according to group, normal temperature lucifuge incubation, uses streaming after 60minCell instrument detects CD44+CD24 ﹣/low cell proportion, conventional detection 3 times.
As shown in Figure 5, for CD44+CD24 ﹣/low in microsphere cell after drug intervention is thinThe result of variations figure of born of the same parents' ratio. Wherein, blank group (numbering A), chlorogenic acid group (are compiledNumber B), CD44+CD24 ﹣/low in the plastidogenetic cell ball of adriamycin group (numbering C)Cell proportion is respectively (71.8 ± 1.4) %, (69.1 ± 2.3) %, (11.8 ± 2.7) %.Chlorogenic acid group is starkly lower than blank group and adriamycin group. Adriamycin group and blank groupComparing difference is not remarkable. Chlorogenic acid+adriamycin group cell is (chlorogenic acid and adriamycin connection very littleClose use inhibitory action stronger), fail to carry out the analysis of CD44+CD24 ﹣/low cell proportion.Therefore, illustrate from the expression of tumor stem cell mark, chlorogenic acid can be done by target tumorCell, kills tumor stem cell, avoids recurrence and the transfer of tumour.
5. the detection of side population cell (SP)
Each group of MCF-7 detects after 48h is cultivated in dosing. Cell discards nutrient solution, 4 DEG CPBS rinse; 0.25% trypsinization 3min, discards pancreatin and stops digestion; 4 DEG C centrifugal;The abundant washed cell of PBS of 4 DEG C 2 times; PBS suspension cell, adjusting concentration is 1 × 106/ml,Get the cell suspension of 100 μ l in 5ml streaming pipe, add after antibody 10 μ l mix and keep away in greenhouseLight is hatched 30min, and PBS is again resuspended, flow cytometry analysis.
Corresponding with microsphere formation result, the analysis of flow cytometer dual wavelength shows, as Fig. 6Shown in, be the testing result figure of side population cell (SP) in microsphere cell after drug intervention.Wherein, blank group (numbering A) MCF-7 suspends in glomus cell SP cells ratioHeight, adriamycin group (numbering C) is to SP cell without significant change, and blank group is without obviously poorDifferent, and chlorogenic acid group (numbering B) can't check SP cell substantially, therefore, chlorogenic acid is describedCan targeting tumor stem cells, change the state of tumor stem cell, make cultured cell or tumourTissue stem cell quantity obviously reduces.
6. the detection of drug resistant gene MDR1, BCRP
Get 5 × 106/ml cell extraction cell RNA and carry out RNA Purity and integralityDetect. Adopting RT-PCR technology for detection respectively to organize MDR1 in cell, BCRPmRNA expresses.The expression of gene is expressed as 1 with control group, and all the other each groups compare with relative expression's scale with itShow.
As shown in Figure 7, for the mRNA of MDR1, BCRP in microsphere cell after drug intervention showsThe disparity map reaching. Wherein, MDR1, BCRP phase in chlorogenic acid group (numbering B) cell ballGene expression amount is starkly lower than to control group. Adriamycin group (numbering C) and blank group(numbering A) comparing difference is not remarkable. The generation of tumor multidrug-resistance causes tumourThere is chemoresistance in patient, makes the not good enough even recurrence of curative effect, and Multidrug resistance gene MDR1And breast drug-resistance protein BCRP continued expression and the close phase of multi-drug resistance of the tumorClose; Meanwhile, research shows MDR1 and BCRP high expressed in tumor stem cell, therefore,Illustrate that chlorogenic acid can reduce MDR1 and the BCRP of tumor stem cell high expressed, green formerAcid can, by suppressing or killing tumor stem cell, prevent the generation of multi-drug resistance of the tumor.
All data acquisitions in the present embodiment carry out statistical analysis, tool with SPSS19.0 softwareThere is statistical significance.
Embodiment 3
The impact of chlorogenic acid on leukemic stem cells
Material: acute myeloid leukemia stem cell or CML-BC chronic myelogenous leukemia patient'sPeripheral blood or bone marrow cell.
Method: PBC is removed red blood cell with leucocyte parting liquid, bone marrow cell chlorineChange ammonium and sodium acid carbonate and process removal red blood cell, then cultivate washing 3 with serum free mediumInferior. Be divided into three groups, and be 1 μ g/mL and 5 μ g/mL by physiological saline, concentration respectivelyChlorogenic acid is processed 3 hours, then with serum free medium washing, removes chlorogenic acid, uses methylCellulose I MAM nutrient solution (1% methylcellulose, 30% bovine serum albumin(BSA), 0.2mM sulfydrylEthanol, 2mM glutamy acid amides, 50ng/ml rhMGF, 10ng/ml urge redErythropoietin, 50ng/ml granular leukocyte colony production factor) be made into 50000cells/ml,Put into incubator, cultivate observation of cell colony 10 days.
Colony-forming efficiency is the classics side that evaluates tumor stem cell self and multiplication capacityMethod, its experiment the results are shown in following table 1.
Table 1
As shown in Table 1, chlorogenic acid is inhibited to leukemic stem cells, and can subtractWeak tumor stem cell self-renewal capacity; Meanwhile, the inhibition of chlorogenic acid to leukemic stem cellsEffect improves along with the increase of chlorogenic acid concentration.
According to experimental technique in above-described embodiment, with chlorogenic acid sodium salt, chlorogenic acid sylvite or greenThe pharmaceutically acceptable chlorogenic acid salt such as former acid calcium salt replaces chlorogenic acid and carries out respectively above-mentioned realityTest, find that chlorogenic acid sodium salt, chlorogenic acid sylvite and chlorogenic acid calcium salt all have drug effect.
Hold intelligible, pharmaceutically acceptable chlorogenic acid chemical synthetic derivative, itself andChlorogenic acid has identical mother nucleus structure, thereby can have similar drug effect.
According to the experimental technique in above-described embodiment, also verify respectively that chlorogenic acid is dry to liver cancerCell, cancer of the stomach stem cell, kidney stem cell, colon cancer stem cell etc. also have above-mentioned drug effect.
Embodiment 4
The preparation of chlorogenic acid pill
Prescription: the chlorogenic acid 1g that purity is 98%, the PVP of starch 50g and survival doseK30 and absolute ethyl alcohol.
Method for making: according to the conventional method preparation of pill, adopt stranding ball legal system to obtain chlorogenic acid pill1000, do not have a chlorogenic acid pill containing chlorogenic acid 1mg.
Embodiment 5
The preparation of chlorogenic acid powder
Prescription: the chlorogenic acid 1000g that purity is 99.1% and the auxiliary material of survival dose.
Method for making: according to the conventional method preparation of powder, by chlorogenic acid and auxiliary material through pulverizing, mistakeAfter sieve, mix, be prepared into powder. Under aseptic condition, be distributed into 1000 bags, every bag looseAgent is containing chlorogenic acid 1000mg.
Embodiment 6
The preparation of chlorogenic acid freeze drying powder injection
Prescription: chlorogenic acid 500g, as the sweet mellow wine 55g of caffolding agent, as antioxidantSodium hydrogensulfite 4g.
Method for making: adopt existing freeze drying powder injection method for making, first by each group in above-mentioned prescriptionDivide and be dissolved in purified water completely, then pass through ultrafiltration membrance filter respectively, sterile filling, freezingDry and gland, makes 2ml powder-injection according to the routine operation of sterile powder injection, and totally 1000, every containing chlorogenic acid 500mg.
Hold intelligiblely, above-mentioned chlorogenic acid as medicament active composition according to its method of administration alsoCan make other formulations, such as capsule, tablet and granule etc.
In embodiment 4-6, can also use chlorogenic acid sodium salt, chlorogenic acid sylvite, chlorogenic acid calciumThe pharmaceutically acceptable chlorogenic acid salt derivative such as salt replaces chlorogenic acid thin as treatment Tumor StemActive ingredient in born of the same parents' medicine.
Hold intelligiblely, be used for the treatment of active ingredient in the medicine of tumor stem cell also passableContain in Chlorogenic acid, chlorogenic acid sodium salt, chlorogenic acid sylvite, chlorogenic acid calcium salt two kinds or manyKind.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention,For a person skilled in the art, the present invention can have various modifications and variations. AllWithin the spirit and principles in the present invention, any amendment of doing, be equal to replacement, improvement etc.,Within all should being included in protection scope of the present invention.
Claims (10)
1. chlorogenic acid and/or its derivative application in the medicine for the treatment of tumor stem cell.
2. application according to claim 1, is characterized in that, described tumor stem cell isLiver-cancer stem cell, cancer of the stomach stem cell, lung cancer stem cell, kidney stem cell, colon cancer are done thinThe chronic myelogenous white blood of born of the same parents, breast carcinoma stem cell, acute myeloid leukemia stem cell and CML-BCSick stem cell.
3. application according to claim 1 and 2, is characterized in that, described chlorogenic acid spreads outBiology comprises the derivative of pharmaceutically acceptable chlorogenic acid salt and chemical synthesis.
4. application according to claim 3, is characterized in that, described chlorogenic acid salt comprisesChlorogenic acid sodium salt, chlorogenic acid sylvite and chlorogenic acid calcium salt.
5. application according to claim 1 and 2, is characterized in that, described medicine is toolThere is the tumor stem cell of inhibition propagation, lower tumor stem cell ratio, weaken tumor stem cell certainlyThe medicine of effect of my updating ability.
6. application according to claim 5, is characterized in that, contains green in described medicineOrtho acid and/or its derivative and pharmaceutic adjuvant.
7. application according to claim 6, is characterized in that, described medicine is associating medicineThing, also contains existing antineoplastic in described medicine.
8. application according to claim 7, is characterized in that, described existing antitumorMedicine is adriamycin.
9. application according to claim 8, is characterized in that, every preparation of described medicineIn unit, contain chlorogenic acid and/or its derivative 1～1000mg.
10. application according to claim 9, is characterized in that, the formulation of described medicineFor oral formulations or ejection preparation.
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| CN201610022686.3A CN105582004A (en) | 2016-01-14 | 2016-01-14 | Application of chlorogenic acid and/or chlorogenic acid derivative in tumor stem cell treatment drug |
| PCT/CN2017/071019 WO2017121364A1 (en) | 2016-01-14 | 2017-01-13 | Chlorogenic acid and/or derivative thereof and pharmacotherapeutic application of same for use against cancer stem cell |
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| WO2017121364A1 (en) * | 2016-01-14 | 2017-07-20 | 四川九章生物科技有限公司 | Chlorogenic acid and/or derivative thereof and pharmacotherapeutic application of same for use against cancer stem cell |
| CN109925304A (en) * | 2018-04-16 | 2019-06-25 | 四川九章生物科技有限公司 | Purposes of the chlorogenic acid in preparation prevention and the drug for blocking brain metastasis and/or Bone tumour |
| CN110938001A (en) * | 2018-09-21 | 2020-03-31 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid ethanolamine salt and application thereof |
| CN111138282A (en) * | 2018-11-05 | 2020-05-12 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid L-arginine salt and application thereof |
| CN111297880A (en) * | 2019-12-13 | 2020-06-19 | 北京中医药大学 | A Chinese medicinal composition for inhibiting tumor proliferation and migration |
| CN111568890A (en) * | 2020-05-28 | 2020-08-25 | 刘玉琳 | Application of chlorogenic acid, isomer or pharmaceutically acceptable salt in preparing tumor chemotherapy sensitization medicine |
| CN112778134A (en) * | 2019-11-08 | 2021-05-11 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid calcium salt sesquihydrate and application thereof |
| CN113648300A (en) * | 2021-07-15 | 2021-11-16 | 湖南农业大学 | Application of caffeoylquinic acid derivatives in preparing medicine for treating liver cancer |
| CN114469921A (en) * | 2021-10-11 | 2022-05-13 | 湖南农业大学 | Pharmaceutical composition for reducing drug resistance of hepatoma cells and application thereof |
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| CN104188950A (en) * | 2014-09-15 | 2014-12-10 | 四川九章生物科技有限公司 | Usage of chlorogenic acid in preparation of drug for treating ependymoma |
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| WO2017121364A1 (en) * | 2016-01-14 | 2017-07-20 | 四川九章生物科技有限公司 | Chlorogenic acid and/or derivative thereof and pharmacotherapeutic application of same for use against cancer stem cell |
| CN109925304A (en) * | 2018-04-16 | 2019-06-25 | 四川九章生物科技有限公司 | Purposes of the chlorogenic acid in preparation prevention and the drug for blocking brain metastasis and/or Bone tumour |
| WO2019201219A1 (en) * | 2018-04-16 | 2019-10-24 | 四川九章生物科技有限公司 | Use of chlorogenic acid in preparing drug for preventing or blocking brain and/or bone metastases of lung cancer |
| CN110938001A (en) * | 2018-09-21 | 2020-03-31 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid ethanolamine salt and application thereof |
| CN111138282A (en) * | 2018-11-05 | 2020-05-12 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid L-arginine salt and application thereof |
| CN112778134A (en) * | 2019-11-08 | 2021-05-11 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid calcium salt sesquihydrate and application thereof |
| CN112778134B (en) * | 2019-11-08 | 2022-10-28 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid calcium salt sesquihydrate and application thereof |
| CN111297880A (en) * | 2019-12-13 | 2020-06-19 | 北京中医药大学 | A Chinese medicinal composition for inhibiting tumor proliferation and migration |
| CN111297880B (en) * | 2019-12-13 | 2021-09-21 | 北京中医药大学 | Shuanghuanglian prescription medicine for inhibiting tumor proliferation and migration |
| CN111568890A (en) * | 2020-05-28 | 2020-08-25 | 刘玉琳 | Application of chlorogenic acid, isomer or pharmaceutically acceptable salt in preparing tumor chemotherapy sensitization medicine |
| CN113648300A (en) * | 2021-07-15 | 2021-11-16 | 湖南农业大学 | Application of caffeoylquinic acid derivatives in preparing medicine for treating liver cancer |
| CN114469921A (en) * | 2021-10-11 | 2022-05-13 | 湖南农业大学 | Pharmaceutical composition for reducing drug resistance of hepatoma cells and application thereof |
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