CN104436194B - Anti-cancer composition with synergistic function - Google Patents
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Abstract
The present invention relates to a kind of anti-cancer composition with synergistic function, the composition of at least one VEGF/VEGFR inhibitor and dopamine specially including effective dose.The composition of the present invention can substantially suppress the growth of tumour cell, greatly reduce the use of anticarcinogen, reduce Operative risk and cost, have broad application prospects.
Description
Technical field
The present invention relates to a kind of anti-cancer composition with synergistic function, preparation method and the usage.
Background technology
Cancer, also known as malignant tumour are a kind of by the not normal caused disease of control growth and proliferation of cell mechanism.Cancer cell removes
Growth is out of control outer, can also locally invade arround tissue or even be transferred to body other parts.The tradition side for the treatment of cancer at present
Method includes radiotherapy or chemotherapy, and the method that can use electrotherapy for some local entities's knurls, these conventional methods have the effect of certain,
But the secondary work of its poison is quite big, and during treatment, great pain is brought to patient.In tumor disease, entity tumor accounts for
The overwhelming majority, and the generation of entity tumor, development and Preventive depend on tumor neovasculature formation.Tumour blood
Pipe generation is the necessary requirement of implanted solid tumor growth and transfer.Suppress Tumor angiogenesis, block the swollen of tumor tissues blood supply
Knurl " hunger cure ", it is considered to be one for the treatment of most promising new method of solid tumor.
VEGF (Vascular Endothelial Growth Factor, vascular endothelial growth factor) is tumour blood
A kind of angiogenesis factor in pipe generating process, it is the hormone regulator of endothelial cell differentiation, the development of solid tumor and VEGF
Expression in closely related, VEGF is used as the key angiogenic growth factor in tumor angiogenesis, it with it is specific
Height expression combines in the vegf receptor tyrosine kinase of neovascular endothelium cell surface, activates EGFR-TK so as to play life
Thing function.Thus the tumor vascular targeted treatment using vegf receptor tyrosine kinase as target spot (refers to using vegf receptor junket
Histidine kinase inhibitor) as the new way of oncotherapy in recent years.In addition, prior art have been disclosed using antibody with
VEGF multivalence chelates and caused VEGF antagonisms can suppress tumour growth (Kim, 1993, Nature362,841-844).
Therefore, itself and acceptor VEGFR (Vascular Endothelial Growth Factor of VEGF VEGF
Receptor the important target spot of cancer therapy drug antiangiogenic therapy) is already become, such medicine includes multiple small molecules
The monoclonal antibody of VEGFR inhibitor and VEGF, the former includes Sutent (Sunitinib, SN), Sorafenib
(Sorafenib), pazopanib (Pazopanib) and Axitinib (Axitinib) etc..The latter includes bevacizumab
And ranibizumab (Ranibizumab) etc. (Bevacizumab).These medicines can be referred to as VEGF/VEGFR suppression by we
Agent.
Endogenous dopamine (Dopamine, DA) be central nervous system (central nervous system, CNS) most
Important Catecholamines Neurotransmitters in Blood, its acceptor are dopamine receptor (Dopamine Receptor, DR).DR is mainly distributed
In central nervous system, it controls many CNS functions such as motion, cognition, emotion, endocrine metabolic diseases；DR is also distributed about painstaking effort
The peripheral tissues such as pipe, kidney, pancreas, adrenal gland, research increasing in recent years show that there is also DR signal in peripheral tissues
Path, secretion of myocardium output quantity, blood pressure, renal function, insulin and hormone etc. can be adjusted, this is DR periphery function.But
Effects and DR of the DA to tumour are very limited always for a long time in the research of tumor cells expression situation.
Hematopoietic Malignancies originate from stem cell-like cell, and this theoretical foundation changes people and sent out for tumour
The conventional wisdom of raw and chemotherapy.Then, in the entity tumor of breast cancer, nervous system neoplasm and other non-hemopoietic systems
In, also confirm successively, there is thin into more abilities of the various constituents of organ with self-renewal capacity energy specific differentiation
Born of the same parents, people are promoted to carry out the biological study of tumor stem cell deeper into ground.These have and normal stem cell similar characteristic
Stem cell-like cell, or the presence for tumor stem cell colony, imply that the real source of tumour.
Although the chemotherapy of tumour now can successfully reduce the load of many entity tumors, the thin of fast breeding is eliminated
Born of the same parents, it may be exactly that have ignored the removing for tumor proliferation pond to be but difficult to reach the root for effecting a radical cure its failure, for recurrence in the future
Hidden some dangers for transfer.Tumour is for chemotherapeuticsDrug resistance is related to the characteristic of tumor stem cell.Tumor stem cell is unique
Resistance medicine and poisonous substance infringement mechanism, be likely to become the intractable basis of tumour so that the drug resistance of tumour be considered as chemistry
Biggest obstacle in treatment.Research for drug resistance of tumor, tumor stem cell and the relation between it are especially analyzed, for
Promote the development of tumor chemical therapy significant.It is believed thatThe drug resistance and tumor stem cell of tumour have close Relation。
The content of the invention
The present inventor has now surprisingly been found that during treatment of cancer is studied, VEGF VEGF or
Its acceptor VEGFR inhibitor (herein alternatively referred to as " VEGF/VEGFR inhibitor ") and dopamine is used in combination and can shown
Fabulous tumor inhibitory effect is shown.After we have surprisingly found that both combinations, its active anticancer greatly enhances.
Therefore, it is an object of the present invention to provide a kind of anti-cancer composition with synergistic function, including it is effective
At least one cancer therapy drug of amount and a kind of non-cancer therapy drug of effective dose, the cancer therapy drug is VEGF/VEGFR inhibitor；
The non-cancer therapy drug is dopamine；Described dopamine can make using VEGF VEGF or its acceptor as target spot
The therapeutic effect of cancer therapy drug produces synergistic function.
According to an aspect of the present invention, the VEGFR inhibitor of described VEGF/VEGFR inhibitor, preferably small molecule
With VEGF monoclonal antibody, wherein, the VEGFR inhibitor of small molecule is preferably Sorafenib (Sorafenib, Bayer/
Onyx, 2005), Sutent (Sunitinib, pFizer, 2006), pazopanib (Pazopanib, GSK, 2009), A Xi
For Buddhist nun (Axitinib, pFizer, 2012) and its pharmaceutically one or more in acceptable salt, Buddhist nun of most preferably relaxing replace
Buddhist nun (Sunitinib, SN) and its pharmaceutically acceptable salt.VEGF monoclonal antibody is preferably bevacizumab
(Bevacizumab, Genentech, 2004), ranibizumab (Ranibizumab, Genentech, 2006).
Described pharmaceutically acceptable salt is to be synthesized by the chemical method of routine from parent compound, the parent
Compound includes alkaline or acid part.Generally, the salt is such as by the free acid or alkali form of these compounds
In organic solvent or react in water or in the mixture of water and organic solvent and make with stoichiometric suitable alkali or acid
Standby.Generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile is preferable.The example bag of acid-addition salts
Containing inorganic acid addition salt such as hydrochloride, hydrobromate, hydriodate, sulfate, nitrate, phosphate, and organic acid addition salt
Such as acetate, trifluoroacetate, maleate, fumarate, citrate, oxalates, succinate, tartrate, apple
Tartaric acid salt, mandelate, analgin and tosilate.The example of base addition salts includes inorganic salts such as sodium, potassium, calcium and ammonium
Salt, and organically alkali metal salt such as ethylenediamine, monoethanolamine, N, the amino of the alkylene monoethanolamines of N- bis-, triethanolamine and alkalescence
Hydrochlorate.
According to an aspect of the present invention, the cancer means to include tumour, neoplasia and any other malignant tissue
Or cell.Specifically include colon cancer or the carcinoma of the rectum, metastatic colorectal cancer, lung cancer, non-squamous non-small cell lung cancer, mammary gland
Cancer, metastatic breast cancer, metastatic HER2 negative breast cancers, the cancer of the brain, spongioblastoma of being grown up, children's spongioblastoma,
Child-resistance spongioblastoma, glioma, ependymoma, astrocytoma, medulloblastoma, children are into nerve channel
Cytoma, glioma, oligodendroglioma or meningioma, kidney such as advanced renal cell carcinoma, carcinoma of urinary bladder, cervical carcinoma, knot
Intestinal cancer (including colorectal cancer), the cancer of the esophagus, stomach cancer, incidence cancer, liver cancer, lung cancer (ED-SCLC and non-small cell lung
Cancer), squamous non-small cell lung cancer, melanoma, myeloma, neuroblastoma, oophoroma, cancer of pancreas, prostate cancer, sarcoma
(including osteosarcoma), cutaneum carcinoma (including squamous cell carcinoma), stomach cancer, carcinoma of testis, thyroid cancer, uterine cancer, celiothelioma, bile duct
Cancer, leiomyosarcoma, embryonal-cell lipoma, nasopharyngeal carcinoma, neuroendocrine carcinoma, oophoroma, salivary-gland carcinoma, or carcinoma sarcomatodes.
According to an aspect of the present invention, at least one cancer therapy drug of the effective dose and the non-cancer therapy drug of effective dose
Applied in same time or different time.When same time is applied, each component in the composition is with same or independent
Dosage form uses.In different time in use, identical or different formulation can be used in each component of the composition.
According to an aspect of the present invention, specification uses in the whole text term " joint " or " combination " or " administering drug combinations " or
" drug combination " refers to the therapeutic agent that is included in identical or independent pharmaceutical preparation in same time or different time
Use.
It is a further object of the present invention to provide a kind of anticancer preparation, and it includes the described anticancer with synergistic function
Composition and customary adjuvant pharmaceutically.The customary adjuvant includes lubricant, filler, surfactant, solubilizer, hydrotropy
Agent etc..
According to an aspect of the present invention, every kind of medicine in the anticancer preparation can be separately or cooperatively tablet, capsule
Agent, supensoid agent, solution, injection etc..
The present invention realizes following beneficial effect：
(1) controlling for certain tumour is combined by one or more anticarcinogens (VEGF/VEGFR inhibitor) and dopamine
Treat, the growth of tumour cell can be significantly inhibited in vitro, the increase of gross tumor volume can be significantly inhibited in vivo and be obviously prolonged and investigated
The life cycle of object, it is alone that its significant effect is better than anticarcinogen.
(2) drug combination of the invention can greatly reduce making for anticarcinogen in the case where ensureing the basis of identical active anticancer
With reducing Operative risk under larger dose caused by cancer therapy drug and the toxic side effect (toxic side effect of usual alone anticarcinogen
It is all bigger).
(3) non-anticarcinogen uses so that the treatment cost of patient substantially reduces.Because usual cancer therapy drug is all somewhat expensive,
The dosage when dosage required when reaching identical drug effect is significantly less than alone anticarcinogen after combination, therefore patient spends and controlled in medicine
Therefore expense in treatment can substantially reduce.
(4) anti-cancer composition with synergistic function of the invention is (close with drug resistance of tumor to tumor stem cell
It is related) growth there is obvious inhibitory action, illustrate that the present invention can be as good solution solution field of cancer treatment
Make us intractable tumor drug resistance sex chromosome mosaicism.
Brief description of the drawings
Fig. 1 is Sutent (A, B, C) and dopamine (D, E, F) respectively to human breast cancer cell (MCF-7), adriamycin-resistant
Human breast cancer cell (MCF-7/Adr) and breast carcinoma stem cell propagation inhibitory action.Medicine suppresses to the half of cell
Concentration (IC50) it is respectively 8.27,8.97,9.41,17.69, ＞ 100 from A to F, 12.59 μM.
Fig. 2 is Sutent and dopamine administering drug combinations human breast cancer cell (MCF-7/Adr) and breast to adriamycin-resistant
The synergy that gland cancer stem cells hyperplasia suppresses.A and B represents that two prescriptions are used and different combination modes are to MCF-7/ respectively in figure
Adr and breast carcinoma stem cell propagation inhibitory action, numerical value are less than killing effect of 0 expression to cell.C and D is then represented respectively
Index of cooperation of the different combination modes in two kinds of cells, index of cooperation, which represents two kinds of medicines less than 1, has synergy.
Fig. 3 is the growth (n=3) that Sutent and dopamine combination suppress female tumor bearing nude mice tumour.A, adriamycin-resistant
Human breast cancer cell (MCF-7/Adr) tumor bearing nude mice give blank control, Sutent (gavage middle dosage), dopamine respectively
The growth curve of gross tumor volume when (intraperitoneal injection) and two kinds of Drug combinations；B, each group tumour photo；C, each group nude mice
Life cycle；D, each group nude mice weight versus time curve.
Fig. 4 is the human breast cancer cell (MCF-7/ that various dose Sutent and dopamine combination suppress adriamycin-resistant
Adr) the tumor growth delay (n=5) of mice with tumor.A, the tumor volume growth curve of tumor bearing nude mice under 9 kinds of administering modes；B, respectively
The time graph of group nude mice weight；C, each group tumour be administered 21 days after tumour real shooting photo.
Embodiment
In order to be better understood from 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 of which change is possible,
Without departing from the spirit and scope of the invention.Although the compositions and methods of the invention are described in particular,
Person of ordinary skill in the field is it is clear that the step of can make the composition or/and method or the order of step occurs
Change, but without departing from idea of the invention and category.More particularly, it is clear that in chemistry to it is biologically related
The similar medicine of other pharmacology processes can substitute medicine as described herein, while reach same or analogous effect.The skill
The technical staff in art field obviously should be considered as in scope of the invention to all this similar replacements or modification
In concept.
The present invention have studied VEGFR inhibitor Sutent (SN) and dopamine (DA) is alone and both are shared to mammary gland
The inhibitory action of cancer cell multiplication and the inhibitory action grown to the nude mouse tumor that human breast cancer cell is inoculated with.
Embodiment 1
The alone inhibitory action to Cells Proliferation of Human Breast Cancer of SN and DA。
Take the logarithm growth period cell, with 0.25% pancreatin -0.53mmol/L EDTA solution digestions, count.By MCF-7 (people
Breast cancer cell), MCF-7/Adr (to the MCF-7 cells of Adriamycin resistant), breast carcinoma stem cell press 1 × 104Individual/hole inoculation
In 96 porocyte culture plates.Cultivate 24h after, be administered, the mono- medicine administration groups of SN final concentration of 0,0.01,0.1,1,2,5,
10、100μM；Final concentration of 0,0.01,0.1,1,10,20,50,100 μM of the mono- medicine administration groups of DA, every group sets 6 parallel, continuation
It is incubated 48h.When investigating administering drug combinations, for 4 96 parallel orifice plates, DA concentration is set gradually as 0,2,20,100 μM,
And in every 1 96 orifice plate, SN concentration is disposed as 0,1,2,5,10 μM, every group set 6 it is parallel.Continue to be incubated 48h.It is incubated
Culture medium is discarded after end, 10% trichloroacetic acid (TCA, w/v) solution of the 100 advance precoolings of μ l, 4 DEG C of fixed 1h are added per hole；
TCA solution is discarded, running water rinses 5 times, naturally dry；100 μ l0.4% Sulforhodamines B (SRB) dyestuffs, room are added per hole
The lower dyeing 30min of temperature；SRB dyestuffs are discarded, wash 5 times with 1% acetum, naturally dry；200 μ l10mmol/ are added per hole
LTris solution (pH10.5), shaking 10min makes the SRB dissolvings combined with tumour cell alkaline amino acid residue, enzyme on oscillator
Mark absorbance at instrument measure 540nm wavelength.The absorbance of blank control group and drug-treated group is expressed as ODControl, 540With
ODSample, 540.Processing is not administered for one of 96 porocyte culture plates, by above-mentioned steps after other Tissue Culture Plates give SN
Processing, its mean light absorbency are set to OD0h, 540.Cell survival rate is calculated by formula 1-1：
If the OD of drug-treated groupSample, 540Less than OD0h, 540, i.e., cell survival rate be less than 0, illustrate that medicine not only may be used
To suppress the propagation of tumour cell, and tumour cell can be killed.Cell lethality is calculated by formula 1-2.
As a result display is (referring to Fig. 1)：ICs of the SN in MCF-7, MCF-7/Adr and three cell lines of breast carcinoma stem cell50
(suppressing the drug concentration needed for 50% cell propagation) is respectively 8.27,8.97,9.41 μM (Figure 1A), and DA IC50 is respectively：
17.69th, 100,12.59 μM of ＞ (Figure 1B), it is seen that mono- without significant difference, DA used in suppression when SN is alone to three kinds of cells in vitro
Used time is significantly less than other two kinds of cells to the inhibitory action of MCF-7/Adr cells.
Embodiment 2
The inhibitory action that SN and DA combinations are bred to MCF-7/Adr cells and tumor stem cell。
The inhibitory action of cell proliferation after various concentrations SN and various concentrations DA combinations is investigated by SRB methods, and is divided
Analyse the size of index of cooperation (combination index, CI).Index of cooperation is calculated using the method for document report, according to public affairs
Formula 1-3 calculates the theoretical absorbance of administering drug combinations group, and the absorbance of actual measurement and the ratio of theoretical value are index of cooperation (formula 1-
4).CI values are less than, equal to and more than 1, show that SN and DA has collaboration plus and and antagonism respectively.
As a result display is (referring to Fig. 2), no matter to MCF-7/Adr cells or tumor stem cell, DA combinations significantly strengthen
Inhibitory action of the SN to cancer cell, and with the rise of DA concentration strengthen (Fig. 2A), while index of cooperation after the combination of two medicines
(CI) 1 is respectively less than, illustrates that two medicines are combined no antagonism (CI ＞ 1), nor simple addition (CI=1), but cooperate with
Synergistic effect.
Embodiment 3
Inhibitory action (single dose) of the SN and DA combinations to tumour in internal breast carcinoma resistance Transplanted tumor model
BALB/c nude mices are inoculated with MCF-7/Adr cells after raising one week.Take the logarithm the MCF-7/Adr cells in growth period, warp
0.25% pancreatin -0.53mmol/L EDTA solution digestions are prepared into single cell suspension, 1,000rpm centrifugation 5min, cell PBS
Wash twice, be 1 × 10 with PBS adjustment cell densities7Individual/ml.Aseptically second pair of mammary subcutaneous fat on the left of nude mice
0.2ml cell suspensions (about 2 × 10 are subcutaneously injected in fat pad6Individual cell).With the major diameter (D of vernier caliper measurement tumourmax) and minor axis
(Dmin), calculate gross tumor volume V (V=Dmax×Dmin 2/2)。
MCF-7/Adr cell in-situs are inoculated into 12 BALB/c nude mice mammary gland positions, obtain the breast cancer of heterograft
Tumor model, when the mean tumour volume of nude mice is about 100mm3When, it is randomly divided into 4 groups, every group 3.SN administering modes are mouth
Gavage is taken, drug solvent is 1,2-PD；DA administering modes are intraperitoneal injection, and drug solvent is physiological saline, dosage regimen
It is as follows：(1) blank control group：Intraperitoneal injection 0.1ml physiological saline daily, gavage 0,2ml1,2- propylene glycol solutions；(2) SN groups：
Intraperitoneal injection 0,1ml physiological saline daily, gavage 0.2ml SN 1,2-PD solution, dosage 40mg/kg；(3)
The normal saline solution of DA groups, daily intraperitoneal injection 0.1ml DA, gavage 0,2ml1,2- propylene glycol solutions, dosage are
50mg/kg；(4) administering drug combinations group, 0.1ml DA normal saline solution, gavage 0.2ml SN 1,2- third are injected intraperitoneally daily
Glycol solution, DA dosage is 50mg/kg, and SN dosage is 40mg/kg.Each group is administered once a day, administration
Preceding measure gross tumor volume simultaneously weighs nude mice body weight, until nude mice is dead, records life span.
As a result show that DA is alone (referring to Fig. 3) and do not have significant inhibitory action, but DA and SN combination to gross tumor volume
The size (Fig. 3 A and Fig. 3 B) of tumour can be significantly reduced, extends nude mice life cycle (Fig. 3 C), and does not have notable shadow to nude mice weight
Ring (Fig. 3 D), illustrate two medicines toxic side effect relatively low after being combined.
Embodiment 4
Inhibitory action (multiple dose) of the SN and DA combinations to tumour in internal breast carcinoma resistance Transplanted tumor model。
Above is pharmacodynamic results (n=3) inside first time, in order to ensure the authenticity of result, we are carried out again
The bigger experiment of sample size, the quantity of every group of tumor bearing nude mice for being inoculated with drug resistance MCF-7/Adr cells are at least 5, and
The SN of two dosage of 20mg/Kg and 80mg/Kg is added in addition, and difference is alone and is combined with 50mg/kg DA (in whole experiment
DA dosage keeps constant), increase by 4 experimental groups (totally 8 groups) altogether.
As a result it is as shown in Figure 4.It can be seen that after being combined with DA, gross tumor volume is all more alone conspicuousness decline, 20mg/kg
The effect that SN and DA are shared is better than or close to the alone effect of 40mg/kg SN, and the effect that 40mg/kg SN and DA are shared is better than
The alone effects of 80mg/kg SN, the result of gross tumor volume is astonishing after 80mg/kg SN and DA combination, and tumour growth is complete
Restrain, while nude mice weight does not have significant changes, illustrates that the general toxicity of the drug combination is smaller.
From above inside and outside, result can be seen that SN and DA combination no matter in vitro or in vivo to tumour growth
Suppress the effect for being all significantly better than alone SN, especially vivo results highly significant；IllustrateThis combination scheme is not only to common Tumour is effective, also has good result to resistant tumors, advantageously accounts for the drug resistance of tumor being clinically widely present at present With metastases problem (closely related with tumor stem cell)。
According to the knowledge of prior art, Sutent is produced by suppressing the signal path of the VEGFR on tumour cell
Anticancer effect.VEGF/VEGFR inhibitor Sutent and the dopamine meeting of being used in combination are confirmed by experiment of the present invention
Produce unexpected anticancer effect.Because VEGF/VEGFR inhibitor can suppress tumor neovasculature life from mechanism
Into, the nutrition supply for carrying out autoblood needed for blocking tumor cell proliferation, and this kind of medicine that each major company has listed at present
Thing all shows obvious antitumor activity, therefore thus those skilled in the art easily predict and Sutent antitumaous effect
Mechanism identical other VEGF/VEGFR inhibitor (such as Sorafenib, pazopanib, Axitinib and bevacizumab, blue Buddhist nun
Monoclonal antibody), and after dopamine is used in combination, it will also produce according to the unexpected anticancer effect of prior art, the effect can be by
Those skilled in the art pass through (for example with the method in above-described embodiment) verified.
Situation occurred based on current cancer understands that the present invention has broad application prospects.
Claims (13)
1. a kind of anti-cancer composition with synergistic function, it is characterised in that said composition includes at least the one of effective dose
Kind of VEGFR inhibitor and dopamine, described VEGFR inhibitor are VEGFR micromolecular inhibitors, described VEGFR small molecules
Inhibitor selected from Sutent, pazopanib, Axitinib, Sorafenib and its pharmaceutically one kind in acceptable salt or
It is several.
2. the anti-cancer composition according to claim 1 with synergistic function, it is characterised in that the VEGFR suppressions
Preparation is Sutent or its pharmaceutically acceptable salt.
3. the anti-cancer composition according to claim 1 with synergistic function, it is characterised in that the cancer is entity
Cancer.
4. according to the anti-cancer composition with synergistic function described in claim 3, it is characterised in that described entity
One or more of the cancer in the combination of following disease：Breast cancer, carcinoma of urinary bladder, cervical carcinoma, colon cancer, the cancer of the esophagus, incidence cancer,
Liver cancer, lung cancer, melanoma, myeloma, neuroblastoma, oophoroma, cancer of pancreas, prostate cancer, kidney, late period nephrocyte
Cancer, sarcoma, cutaneum carcinoma, stomach cancer, carcinoma of testis, thyroid cancer, uterine cancer, celiothelioma, cholangiocellular carcinoma, nasopharyngeal carcinoma, interior point of nerve
Secrete cancer, salivary-gland carcinoma, or carcinoma sarcomatodes.
5. according to the anti-cancer composition with synergistic function described in claim 4, it is characterised in that described lung cancer
For ED-SCLC, non-small cell lung cancer, non-squamous non-small cell lung cancer.
6. according to the anti-cancer composition with synergistic function described in claim 4, it is characterised in that described sarcoma
Including osteosarcoma, embryonal-cell lipoma, leiomyosarcoma.
7. according to the anti-cancer composition with synergistic function described in claim 4, it is characterised in that described skin
Cancer includes squamous cell carcinoma.
8. the anti-cancer composition according to claim 1 with synergistic function, it is characterised in that described cancer is breast
Gland cancer.
9. the anti-cancer composition according to claim 1 with synergistic function, it is characterised in that described anticancer group
Compound has the prevention or therapeutic activity for Common tumors.
10. the anti-cancer composition according to claim 1 with synergistic function, it is characterised in that described anticancer
Composition has the prevention or therapeutic activity for drug resistant cancer.
11. the anti-cancer composition according to claim 1 with synergistic function, it is characterised in that described cancer
For drug resistant breast cancer.
12. a kind of pharmaceutical preparation with antitumaous effect, including the anti-cancer composition of claim 1 and the routine of pharmacy it is auxiliary
Material, the formulation of the pharmaceutical preparation are the regular dosage form of art of pharmacy, wherein different types of medicine is individually packed or common bag
Dress, different types of medicine are with one dosage type low temperature or different dosage forms.
13. the anti-cancer composition with synergistic function any one of claim 1-11 is in cancer therapy drug is prepared
Application.
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| AU2016256470B2 (en) | 2015-04-29 | 2020-10-15 | Radius Pharmaceuticals, Inc. | Methods of treating cancer |
| CN107126563B (en) * | 2016-02-26 | 2021-09-10 | 博生吉医药科技(苏州)有限公司 | Composition containing low-dose antibody for blocking VEGF signal path and application thereof |
| CN109715149A (en) * | 2016-09-27 | 2019-05-03 | 雷迪厄斯健康公司 | The method for treating oophoroma |
| CN106963948A (en) * | 2017-05-12 | 2017-07-21 | 顾艳宏 | A Pa is combined the application in colon cancer drug is prepared for Buddhist nun with the antibody of Anti PD 1 |
| CN107261145B (en) * | 2017-08-08 | 2021-03-09 | 四川九章生物科技有限公司 | Anti-tumor combined medicine and application thereof in preparing anti-cancer medicine |
| CN109771658B (en) * | 2017-11-14 | 2021-12-10 | 博瑞生物医药（苏州）股份有限公司 | Targeted multi-arm conjugates |
| CN108187055B (en) * | 2018-03-06 | 2019-12-27 | 北京大学 | Anticancer composition with synergistic effect |
| CN111166758A (en) * | 2019-12-10 | 2020-05-19 | 安徽瀚海博兴生物技术有限公司 | A combined anticancer medicine prepared from ouabain |
| CN113893350B (en) * | 2020-07-06 | 2023-09-15 | 诺未科技（北京）有限公司 | Composition for treating cancer and application and medicine thereof |
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