CN109453156A - A kind of anti-tumor compositions and its application, anti-tumor drug - Google Patents
A kind of anti-tumor compositions and its application, anti-tumor drug Download PDFInfo
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Abstract
The present invention relates to a kind of anti-tumor compositions and its applications, anti-tumor drug, belong to field of medicine preparing technology.Anti-tumor compositions of the invention include the first Studies on Anticancer Components and the second Studies on Anticancer Components, and first Studies on Anticancer Components is the salt of one or both of docetaxel, Irinotecan or one or both of docetaxel, Irinotecan；Second Studies on Anticancer Components is dihydroartemisinine, and the molar ratio of first Studies on Anticancer Components and dihydroartemisinine is 1:2-100；Or second Studies on Anticancer Components is artemisinin derivatives, the molar ratio for the dihydroartemisinine that first Studies on Anticancer Components and qinghaosu or metabolism generate is 1:2-100, and the antitumoral compounds that can be metabolized generation dihydroartemisinine are the combination of one or more of qinghaosu, Artesunate, Artemether, arteether.Two kinds of Studies on Anticancer Components of anti-tumor compositions of the invention have synergistic function.
Description
Technical field
The present invention relates to a kind of anti-tumor compositions and its applications, anti-tumor drug, belong to field of medicine preparing technology.
Background technique
Malignant tumour can not still cure so far, it has also become current whole world public health problem outstanding.The World Health Organization
Claim, just there is 1 people to die of cancer in average every 8 deaths in the whole world at present, than death caused by AIDS, malaria and tuberculosis
Number summation is taller.International Cancer Research Center (IARC) statistics indicate that, whole world malignant tumour new cases in 2002
About 10,900,000, dead 6,700,000.The research report that IARC is provided is shown, increases cancer patient newly every year to the year two thousand twenty whole world
Number is up to 15,000,000 people.WHO statistics shows that surprising increasing occur in global cancer new cases in 2012 and death toll
Long, China is even more to rank first.A newest phase " Chinese Incidence and the Study on mortality report of National Cancer Center publication
Accuse " display, national de novo malignancy case about 380.4 ten thousand, death 229.6 ten thousand in 2014.China accounts for about respectively
The 21.8% and 27% of global malignant tumour new cases and death occupies medium on the upper side in 184 countries and regions
It is horizontal.This means that average minute clock has 7 people to be diagnosed as cancer, 4 people are because of cancer mortality.The mode for the treatment of of cancer at present is main
There are operative treatment, radiotherapy, chemotherapy, biological therapy etc., wherein chemotherapy is still main therapeutic modality.
In the chemicals for the treatment of cancer, docetaxel (Docetaxel) is primary treatment advanced breast cancer, oophoroma, non-
Small Cell Lung Cancer also has certain curative effect to head-neck carcinoma, Small Cell Lung Cancer, gastric cancer, cancer of pancreas, melanoma etc..
Irinotecan (Irinotecan), for the treatment of adult Metastatic Colorectal Cancer, for failing through chemotherapy containing 5-Fu
Patient, can be used as second line treatment.
Sweet wormwood is conventional Chinese medicine, is the drying overground part of annual compositae plant artemisia annua (Aretemisiaannua L.)
Point." the careless wormwood artemisia " and " sweet wormwood " that ancient herbal medicine describes is no different with " artemisia annua ", and Chinese medicine, which is practised, claims " sweet wormwood ", and botany is commonly referred to as
" artemisia annua ".
Chinese medicine sweet wormwood has effects that clearind deficient heat, except hectic fever due to yin, solution hot summer weather, preventing malaria, removing jaundice, has answer within more than 2,000 years in China
Use history.It slaughters cry of a deer research team and has extracted qinghaosu from Chinese medicine plant Artemisia annua for the first time in China in 1971
(Artemisinin, ART), and its determining chemical structure was sesquiterpenoids in 1972.Qinghaosu be China it is pioneering,
The antimalarial agent of international endorsement.On the basis of qinghaosu, researcher retains peroxide bridge active structure, develops sweet wormwood in succession
A series of artemisinin derivatives such as amber ester, Artemether, arteether, dihydroartemisinine, maleic acid arteether amine (SM934).
The chemical structure of qinghaosu and several frequently seen artemisinin derivative is as follows:
Multinomial research confirms that qinghaosu and its derivative pharmacological action are extensive, not only post malaria, toxoplasma etc. in recent years
Infested disease has therapeutic effect, also has anti-inflammatory, antitumor and immunoregulatory function, has to lupus erythematosus, rheumatism etc.
Significant curative effect, to leukaemia, non-small cell lung cancer, liver cancer, gastric cancer, colon cancer, cancer of pancreas, breast cancer, cervical carcinoma, prostate cancer
Deng there is therapeutic effect.Its mechanism of action is mainly shown as the cell for inhibiting the cell cycle, Apoptosis, iron ion being promoted to mediate
Toxic action, anti-angiogenetic therapy, chemicotherapy enhanced sensitivity and reverse effect of multidrug resistance tumor cells etc..Dihydroartemisinine
(Dihydroartemisinin, DHA) is compound of the qinghaosu through sodium borohydride reduction, is that the active metabolism of qinghaosu produces
Object.DHA anti-tumor activity is good；It is worth noting that, DHA is the shared active metabolite of above-mentioned artemisinin derivatives,
It is the Typical Representative of existing artemisinin derivatives.Potentially clinical new indication meets Present Global for qinghaosu and its derivative
Spectrum of disease development law designs such medicinal application composition and contains for current recruit's entity medicament research and development weakness status
Huge potentiality to be exploited.The pharmaceutical composition of docetaxel and Irinotecan and qinghaosu and its derivative is applied to oncotherapy also
It has not been reported.
Summary of the invention
The purpose of the present invention is to provide a kind of anti-tumor compositions that can be synergistic.The present invention also aims to
One kind is provided and is capable of application of the synergistic anti-tumor compositions in terms of preparing drug that is antitumor or inhibiting cancer cell.
The object of the invention is also to provide a kind of anti-tumor drugs with synergistic function.
To achieve the goals above, The technical solution adopted by the invention is as follows:
A kind of anti-tumor compositions, including the first Studies on Anticancer Components and the second Studies on Anticancer Components, described first antitumor group
It is divided into the salt of one or both of docetaxel, Irinotecan or one or both of docetaxel, Irinotecan；Institute
The second Studies on Anticancer Components is stated as dihydroartemisinine, the molar ratio of first Studies on Anticancer Components and dihydroartemisinine is 1:2-100；
Or second Studies on Anticancer Components be qinghaosu or can be metabolized generate dihydroartemisinine antitumoral compounds, described first
The molar ratio for the dihydroartemisinine that Studies on Anticancer Components and the metabolism of qinghaosu or the second Studies on Anticancer Components generate is 1:2-100, described
Can be metabolized and generate the antitumoral compounds of dihydroartemisinine is one or more of Artesunate, Artemether, arteether
Combination.
The first Studies on Anticancer Components that anti-tumor compositions of the invention use is docetaxel and/or Irinotecan, and second
Studies on Anticancer Components is the antitumoral compounds that dihydroartemisinine or qinghaosu or metabolic energy generate dihydroartemisinine, so that two kinds anti-
Tumour component can be cooperateed with mutually when acting on tumour cell, improve the inhibiting effect to tumour cell.First is antitumor
Group, which is divided into, inhibits purine anti-tumor compounds that can have complementary advantages, subtract with qinghaosu or artemisinin derivative synergy
Few list survival dose avoids toxic reaction, improves anti-tumor activity, expands clinical indication range, reduce or slow down generation drug resistance
Risk.
First Studies on Anticancer Components is docetaxel, and the second Studies on Anticancer Components is dihydroartemisinine, docetaxel and double
The molar ratio of hydrogen arteannuin is 1:100.Studies on Anticancer Components at this time has obvious action to inhibition colon cancer, liver cancer cells.
First Studies on Anticancer Components be docetaxel, the second Studies on Anticancer Components be qinghaosu, Artesunate, Artemether,
Double hydrogen sweet wormwoods that the combination of one or more of arteether, docetaxel and qinghaosu or the metabolism of the second Studies on Anticancer Components generate
The molar ratio of element is 1:100.The second Studies on Anticancer Components at this time can be metabolized generation dihydroartemisinine, and work is cooperateed with docetaxel
With having the function of good inhibition tumour cell.In particular, having obvious action to inhibition colon cancer, liver cancer cells.
First Studies on Anticancer Components is Irinotecan, and the second Studies on Anticancer Components is dihydroartemisinine, Irinotecan and double
The molar ratio of hydrogen arteannuin is 1:2-10.Studies on Anticancer Components at this time has significantly inhibition colon cancer, liver cancer, breast cancer cell
Effect.
First Studies on Anticancer Components be Irinotecan, the second Studies on Anticancer Components be qinghaosu, Artesunate, Artemether,
Double hydrogen sweet wormwoods that the combination of one or more of arteether, Irinotecan and qinghaosu or the metabolism of the second Studies on Anticancer Components generate
The molar ratio of element is 1:2-10.The second Studies on Anticancer Components at this time can be metabolized generation dihydroartemisinine, cooperate with Irinotecan
Effect, has the function of good inhibition tumour cell.In particular, having significantly to inhibition colon cancer, liver cancer, breast cancer cell
Effect.
A kind of application of above-mentioned anti-tumor compositions in terms of preparing anti-tumor drug.Due to above-mentioned antineoplastic combinations
Two kinds of Studies on Anticancer Components in object have synergistic function, which are used to prepare anti-tumor drug, to swollen
Oncocyte has good inhibiting effect, has good antitumous effect.
A kind of application of above-mentioned anti-tumor compositions in terms of the drug that preparation inhibits cancer cell, the cancer cell are knot
At least one of intestinal cancer, liver cancer, breast cancer cell.Anti-tumor compositions of the invention are to colon cancer, liver cancer, breast cancer cell
There is apparent effect, can be used to prepare the drug for inhibiting cancer cell.
A kind of anti-tumor drug, including main ingredient and auxiliary material, the main ingredient include that the first Studies on Anticancer Components and second are antitumor
Component, first Studies on Anticancer Components are one or both of docetaxel, Irinotecan or docetaxel, Irinotecan
One or both of salt；Second Studies on Anticancer Components is dihydroartemisinine, and first Studies on Anticancer Components and double hydrogen are green
The molar ratio of artemisin is 1:2-100；Or second Studies on Anticancer Components for qinghaosu or can be metabolized generation dihydroartemisinine
Antitumoral compounds, the dihydroartemisinine that first Studies on Anticancer Components and qinghaosu or the metabolism of the second Studies on Anticancer Components generate
Molar ratio be 1:2-100, it is described can be metabolized generate dihydroartemisinine antitumoral compounds be Artesunate, Artemether,
The combination of one or more of arteether.
The main ingredient of anti-tumor drug of the invention uses two kinds of Studies on Anticancer Components, both Studies on Anticancer Components can cooperate with
Effect improves antitumous effect.
Detailed description of the invention
Fig. 1 is that the embodiment 1 of anti-tumor compositions of the invention acts on the test result schematic diagram of liver cancer cells；
Fig. 2 is that the embodiment 3 of anti-tumor compositions of the invention acts on the test result schematic diagram of liver cancer cells；
Fig. 3 is that the embodiment 3 of anti-tumor compositions of the invention acts on the test result schematic diagram of breast cancer cell；
Fig. 4 is that the embodiment 1 of anti-tumor compositions of the invention acts on the test result schematic diagram of colon cancer cell；
Fig. 5 is that the embodiment 2 of anti-tumor compositions of the invention acts on the test result schematic diagram of colon cancer cell.
Specific embodiment
Anti-tumor compositions of the invention include the first Studies on Anticancer Components and the second Studies on Anticancer Components, and described first is antitumor
Group is divided into the salt of one or both of docetaxel, Irinotecan or one or both of docetaxel, Irinotecan；
Second Studies on Anticancer Components is dihydroartemisinine, and the molar ratio of first Studies on Anticancer Components and dihydroartemisinine is 1:2-
100；Or second Studies on Anticancer Components is qinghaosu or can be metabolized the antitumoral compounds for generating dihydroartemisinine, it is described
The molar ratio for the dihydroartemisinine that first Studies on Anticancer Components and the metabolism of qinghaosu or the second Studies on Anticancer Components generate is 1:2-100,
The antitumoral compounds that generation dihydroartemisinine can be metabolized are one of Artesunate, Artemether, arteether or several
The combination of kind.
Anti-tumor drug of the invention includes main ingredient and auxiliary material, and wherein main ingredient is above-mentioned anti-tumor compositions.Of the invention
The second Studies on Anticancer Components in anti-tumor compositions and anti-tumor drug can be dihydroartemisinine and/or metabolism generates double hydrogen blueness
The antitumoral compounds of artemisin, when the second Studies on Anticancer Components is dihydroartemisinine, the first Studies on Anticancer Components and second antitumor
The molar ratio of component directlys adopt the mol ratio of the first Studies on Anticancer Components and dihydroartemisinine.When the second Studies on Anticancer Components not
It is dihydroartemisinine but metabolism is when can generate the antitumoral compounds of dihydroartemisinine, is generated with the compound metabolism double
The molal quantity of hydrogen arteannuin is measured.When the second Studies on Anticancer Components be qinghaosu when, directly with the molal quantity of qinghaosu into
Row metering.
One or both of docetaxel, Irinotecan in anti-tumor compositions and anti-tumor drug of the invention
Salt is hydrochloride, oxalates, citrate or mesylate, or sodium salt, sylvite or magnesium salts.
Anti-tumor drug of the invention includes main ingredient and auxiliary material.Auxiliary material can be according to the dosage form of pharmaceutical preparation, and use is existing
Auxiliary material in technology, such as filler, wetting agent, adhesive.For example, auxiliary material can be when dosage form is tablet or capsule
Dextrin, starch, sucrose etc..
There is no limit can directly mix two kinds of Studies on Anticancer Components and be made into the preparation method of anti-tumor drug of the invention
Preparation, or respectively with or corresponding auxiliary material mixing be made into preparation respectively, be then packaged in one according still further to this field usual manner
It rises, or mixes and then remix with corresponding auxiliary material respectively and be made into preparation.
Anti-tumor drug of the invention can be the pharmaceutical preparation suitable for gastrointestinal administration, or parenteral administration
Pharmaceutical preparation.The preferably pharmaceutical preparation of gastrointestinal administration.
The first Studies on Anticancer Components and the second Studies on Anticancer Components in anti-tumor compositions and anti-tumor drug of the invention exist
It can be administered simultaneously, can also be separately administered with any sequencing when administration.The mode of separated administration, the two are administered
Time interval does not specially require, it is preferred that the time interval of the two administration is no more than one day.Or two kinds of groups can also be taken
Divide the mode of alternating delivery.
In the scheme that the first Studies on Anticancer Components and the second Studies on Anticancer Components in anti-tumor drug of the invention are administered simultaneously,
The same preparation comprising both components can be made in first Studies on Anticancer Components and the second Studies on Anticancer Components, such as tablet or glue
Capsule.Two kinds of components can also be made to the two different pharmaceutical preparations for separately including both components, such as tablet or capsule, this
When two kinds of preparations conventionally can be packed or be combined, patient can according to package insert prompt and meanwhile take
With.
It, can in the scheme of first Studies on Anticancer Components of anti-tumor drug of the invention and the second Studies on Anticancer Components consecutive administration
The first Studies on Anticancer Components and the second Studies on Anticancer Components to be made to the two different pharmaceutical preparations for separately including both components,
Such as tablet or capsule, two kinds of preparations conventionally can be packed or be combined at this time, patient can say according to drug
The sequencing of bright book prompt is successively taken.Above two component can also will be made to a kind of system of controlled release using conventional method
Agent first discharges a kind of component, then discharges another component again, and patient only needs to take the controlled release preparation.
It, can in the scheme of first Studies on Anticancer Components of anti-tumor drug of the invention and the second Studies on Anticancer Components alternating delivery
Different preparations is respectively prepared in the first Studies on Anticancer Components and the second Studies on Anticancer Components, two kinds of preparations are conventionally wrapped
It fills or combines, patient can take according to the chi sequence that package insert prompts.Or by above two component
The controlled release preparation for intersecting release is made, patient only needs to take the controlled release preparation.
When anti-tumor drug of the invention is solution, solvent can be castor oil, medical corn oil, ethyl alcohol, Tween-80
One of.Preferably, when the second Studies on Anticancer Components is Artesunate, Studies on Anticancer Components is mixed into system with bicarbonate, water
At injection.
Technical solution of the present invention is further detailed combined with specific embodiments below.
The experimental material and instrument used in following example is as follows:
1) experimental material.
Cell strain:
Tumor cell line human breast cancer cell line Bcap-37 of the present invention is cured purchased from China Concord Medical Science University basis
Learn research institute's preclinical medicine cell centre；Human liver cancer cell HepG2, the colon cancer cell HT29 of use are by Chinese department of traditional Chinese medicine institute
Institute of Chinese materia medica professor Li Qi give.
2) laboratory apparatus:
Carbon dioxide incubator of the present invention is produced by Thermo company, and multi-function microplate reader is by Molecular
The production of Devices company.
3) experiment reagent:
Cell culture medium and fetal calf serum (FBS) of the present invention are purchased from Gibco company, 0.25% pancreatin, blueness
Streptomysin is purchased from Hyclone company, and CCK8 detection reagent is purchased from Japanese colleague chemical reagents corporation.
Dihydroartemisinine (DHA) is purchased from Chongqing Huafang Wulingshan Pharmaceutical Co., Ltd..
Docetaxel (3D), Irinotecan (6I) are purchased from Shanghai Aladdin biochemical technology limited liability company.
The embodiment 1 of anti-tumor compositions
The anti-tumor compositions of the present embodiment are made of the first Studies on Anticancer Components and the second Studies on Anticancer Components, and first is antitumor
Group is divided into docetaxel (3D), and the second Studies on Anticancer Components is dihydroartemisinine (DHA), the first Studies on Anticancer Components and second antitumor
The molar ratio of component is 1:100.
The embodiment 2 of anti-tumor compositions
The anti-tumor compositions of the present embodiment are made of the first Studies on Anticancer Components and the second Studies on Anticancer Components, and first is antitumor
Group is divided into Irinotecan (6I), and the second Studies on Anticancer Components is dihydroartemisinine (DHA), the first Studies on Anticancer Components and second antitumor
The molar ratio of component is 1:2.
The embodiment 3 of anti-tumor compositions
The anti-tumor compositions of the present embodiment are made of the first Studies on Anticancer Components and the second Studies on Anticancer Components, and first is antitumor
Group is divided into Irinotecan (6I), and the second Studies on Anticancer Components is dihydroartemisinine (DHA), the first Studies on Anticancer Components and second antitumor
The molar ratio of component is 1:10.
The embodiment 1 of anti-tumor drug
The anti-tumor drug of the present embodiment is mixture, is resisted by first in the embodiment 1-3 of above-mentioned anti-tumor compositions
Tumour component and the second Studies on Anticancer Components obtain after directly mixing according to corresponding molar ratio.
The embodiment 2 of anti-tumor drug
The anti-tumor drug of the present embodiment is tablet, including main ingredient and auxiliary material, and main ingredient is the reality of above-mentioned anti-tumor compositions
The anti-tumor compositions in a 1-3 are applied, auxiliary material is auxiliary material commonly used in the prior art.
Test example
Dihydroartemisinine (DHA) solution, docetaxel (3D) solution, Irinotecan (6I) solution are in test example below
Culture medium solution, the mass percent of DMSO is not more than 0.5% in culture medium solution.
(1) test of liver cancer cells is acted on
Human hepatoma HepG2 cell is taken to use the RPMI1640 of the mycillin of FBS, 100U/mL containing 10% (mass fraction)
Culture medium is at a temperature of 37 DEG C, the CO of 5% (percent by volume)2It is cultivated in incubator, grows to logarithmic growth phase to cell, used
0.25% pancreatin digestive juice digestion prepares single cell suspension, is inoculated in 96 orifice plates with the concentration of every 5000 cells in hole.
With 200 μm of ol/L, 100 μm of ol/L, 50 μm of ol/L, 25 μm of ol/L, 12.5 μm of ol/L, 6.25 μ after culture 12 hours
Dihydroartemisinine (DHA) solution and 2 μm of ol/L, 1 μm of ol/L, 0.5 μm of ol/L, 0.25 μm of ol/ of mol/L, 3.125 μm of ol/L
L, docetaxel (3D) solution, 20 μm of ol/L, the 10 μm of ol/L, 5 μ of 0.125 μm of ol/L, 0.063 μm of ol/L, 0.031 μm of ol/L
Mol/L, 2.5 μm of ol/L, 1.25 μm of ol/L, 0.63 μm of ol/L, 0.31 μm of ol/L Irinotecan (6I) solution be respectively acting on
Cell after culture, and with above-mentioned dihydroartemisinine (DHA) solution, docetaxel (3D) solution respectively with molar ratio 100:1 connection
Cooperation for after cultivating cell, with above-mentioned dihydroartemisinine (DHA) solution, Irinotecan (6I) solution respectively with molar ratio
10:1 cooperates with the cell after culture.Using the DMSO of same volume score step by step doubling dilution as control.
After acting on 48h, the CCK8 detection reagent of 10 μ L is added in every hole, continues to cultivate 2h.It is detected with all-wave length microplate reader
Light absorption value at OD450nm, then calculates inhibiting rate according to the following formula:
Inhibiting rate (GI)=(C-T)/C*100%, wherein C is control group activity of tumor cells, and T is medication therapy groups tumour
Cell activity.
Drug combination index (Combination Index, CI) is calculated using Calcusyn software, according to Chou-
Talaly definition, CI < 1 indicate that two medicines (component) is synergistic, and CI=1 indicates that two medicines (component) has synergistic effect, CI > 1
Indicate that two medicines (component) has antagonism.
It is CI=(D) that two medicines, which are combined Chou-Talaly formula,1/(Dx)1+(D)2/(Dx)2(meaning of formula and each parameter can
Bibliography: Chou T C.Theoretical basis, experimental design, and computerized
simulation of synergism and antagonism in drug combination studies[J]
.Pharmacological Reviews, 2006,58 (3): 621-681.).
As a result as shown in Table 1 and Fig. 1, Fig. 2.
Table 1 acts on the test result of liver cancer cells
| Types of medicines | Concentration (μM) | Inhibiting rate (%) | CI |
| DHA | 3.125 | 4.89 | - |
| 3D | 0.03125 | 0.11 | - |
| DHA+3D | 3.125+0.03125 | 16 | 0.547 |
| DHA | 25 | 52.48 | - |
| 3D | 0.25 | 3.47 | - |
| DHA+3D | 25+0.25 | 61.39 | 0.467 |
| DHA | 50 | 70.71 | - |
| 3D | 0.5 | 5.48 | - |
| DHA+3D | 50+0.5 | 75.70 | 0.467 |
| DHA | 12.5 | 31.85 | - |
| 6I | 1.25 | 22.70 | - |
| DHA+6I | 12.5+1.25 | 48.74 | 0.53 |
| DHA | 25 | 52.48 | - |
| 6I | 2.5 | 43.65 | - |
| DHA+6I | 25+2.5 | 66.36 | 0.486 |
By table 1 and Fig. 1, Fig. 2 it is found that docetaxel (3D), Irinotecan (6I) have within the scope of debita spissitudo with DHA it is bright
Aobvious synergistic function.
(2) test of breast cancer cell is acted on
Take the MCF-7 Human Breast Cancer Cells DMEM training of the mycillin of FBS, 100U/mL containing 10% (mass fraction)
Base is supported at a temperature of 37 DEG C, the CO of 5% (percent by volume)2It is cultivated in incubator, grows to logarithmic growth phase to cell, used
0.25% pancreatin digestive juice digestion prepares single cell suspension, is inoculated in 96 orifice plates with the concentration of every 5000 cells in hole.
With 200 μm of ol/L, 100 μm of ol/L, 50 μm of ol/L, 25 μm of ol/L, 12.5 μm of ol/L, 6.25 μ after culture 12 hours
Mol/L, dihydroartemisinine (DHA) solution of 3.125 μm of ol/L, 20 μm of ol/L, 10 μm of ol/L, 5 μm of ol/L, 2.5 μm of ol/L,
1.25 μm of ol/L, 0.63 μm of ol/L, 0.31 μm of ol/L Irinotecan (6I) solution be respectively acting on culture after cell, be used in combination
Above-mentioned dihydroartemisinine (DHA) solution and Irinotecan (6I) cooperate with the cell after culture respectively with molar ratio 10:1.
Using the DMSO of same volume score step by step doubling dilution as control.
After acting on 48h, the CCK8 detection reagent of 10 μ L is added in every hole, continues to cultivate 2h.It is detected with all-wave length microplate reader
Light absorption value at OD450nm, then calculates inhibiting rate according to the following formula:
Inhibiting rate (GI)=(C-T)/C*100%, wherein C is control group activity of tumor cells, and T is medication therapy groups tumour
Cell activity.
Drug combination index (Combination Index, CI) is calculated using Calcusyn software, according to Chou-
Talaly definition, CI < 1 indicate that two medicines (component) is synergistic, and CI=1 indicates that two medicines (component) has synergistic effect, CI > 1
Indicate that two medicines (component) has antagonism.
It is CI=(D) that two medicines, which are combined Chou-Talaly formula,1/(Dx)1+(D)2/(Dx)2(meaning of formula and each parameter can
Bibliography: Chou T C.Theoretical basis, experimental design, and computerized
simulation of synergism and antagonism in drug combination studies[J]
.Pharmacological Reviews, 2006,58 (3): 621-681.).
As a result as shown in table 2 and Fig. 3.
Table 2 acts on the test result of breast cancer cell
| Types of medicines | Concentration (μM) | Inhibiting rate (%) | CI |
| DHA | 6.25 | 4.40 | - |
| 6I | 0.625 | 8.54 | - |
| DHA+6I | 6.25+0.625 | 49.32 | 0.044 |
| DHA | 25 | 13.12 | - |
| 6I | 2.5 | 25.9 | - |
| DHA+6I | 25+2.5 | 50 | 0.167 |
| DHA | 50 | 9.99 | - |
| 6I | 5 | 28.63 | - |
| DHA+6I | 50+5 | 59.74 | 0.186 |
| DHA | 100 | 36.08 | - |
| 6I | 10 | 43.59 | - |
| DHA+6I | 100+10 | 70.66 | 0.186 |
By table 2 and Fig. 3 it is found that Irinotecan (6I) has apparent synergistic function within the scope of debita spissitudo with DHA.
(3) test of colon cancer cell is acted on
Take the Human colorectal carcinoma HT29 cells DF-12 training of the mycillin of FBS, 100U/mL containing 10% (mass fraction)
Base is supported at a temperature of 37 DEG C, the CO of 5% (percent by volume)2It is cultivated in incubator, grows to logarithmic growth phase to cell, used
0.25% pancreatin digestive juice digestion prepares single cell suspension, is inoculated in 96 orifice plates with the concentration of every 5000 cells in hole.
With 100 μm of ol/L, 50 μm of ol/L, 25 μm of ol/L, 12.5 μm of ol/L, 6.25 μm of ol/L, 3.125 after culture 12 hours
μm ol/L, dihydroartemisinine (DHA) solution of 1.563 μm of ol/L and 1 μm of ol/L, 0.5 μm of ol/L, 0.25 μm of ol/L, 0.125
μm ol/L, 0.063 μm of ol/L, 0.031 μm of ol/L, 0.015 μm of ol/L docetaxel (3D) solution, 50 μm of ol/L, 25 μm of ol/L,
Irinotecan (6I) the solution difference of 12.5 μm of ol/L, 6.25 μm of ol/L, 3.125 μm of ol/L, 1.56 μm of ol/L, 0.78 μm of ol/L
Cell after acting on culture, and with above-mentioned dihydroartemisinine (DHA) solution and docetaxel (3D) respectively with molar ratio 100:1
Cooperate with culture after cell, with above-mentioned dihydroartemisinine (DHA) solution and Irinotecan (6I) respectively with molar ratio 2:1
Cell after cooperating with culture.Using the DMSO of same volume score step by step doubling dilution as control.
After acting on 48h, the CCK8 detection reagent of 10 μ L is added in every hole, continues to cultivate 2h.It is detected with all-wave length microplate reader
Light absorption value at OD450nm, then calculates inhibiting rate according to the following formula:
Inhibiting rate (GI)=(C-T)/C*100%, wherein C is control group activity of tumor cells, and T is medication therapy groups tumour
Cell activity.
Drug combination index (Combination Index, CI) is calculated using Calcusyn software, according to Chou-
Talaly definition, CI < 1 indicate that two medicines (component) is synergistic, and CI=1 indicates that two medicines (component) has synergistic effect, CI > 1
Indicate that two medicines (component) has antagonism.
It is CI=(D) that two medicines, which are combined Chou-Talaly formula,1/(Dx)1+(D)2/(Dx)2(meaning of formula and each parameter can
Bibliography: Chou T C.Theoretical basis, experimental design, and computerized
simulation of synergism and antagonism in drug combination studies[J]
.Pharmacological Reviews, 2006,58 (3): 621-681.).
As a result as shown in table 3 and Fig. 4, Fig. 5.
Table 3 acts on the test result of colon cancer cell
By table 3 and Fig. 4, Fig. 5 it is found that docetaxel (3D), Irinotecan (6I) have within the scope of debita spissitudo with DHA it is bright
Aobvious synergistic function.
When the second Studies on Anticancer Components be one of qinghaosu, Artesunate, Artemether, arteether when, due to its with it is double
The structural similarity of hydrogen arteannuin also cooperates with increasing with docetaxel (3D), Irinotecan (6I) within the scope of debita spissitudo
Effect effect.
Claims (8)
1. a kind of anti-tumor compositions, which is characterized in that including the first Studies on Anticancer Components and the second Studies on Anticancer Components, described first
Studies on Anticancer Components is one or both of docetaxel, Irinotecan or one of docetaxel, Irinotecan or two
The salt of kind；Second Studies on Anticancer Components is dihydroartemisinine, the molar ratio of first Studies on Anticancer Components and dihydroartemisinine
For 1:2-100；Or second Studies on Anticancer Components is qinghaosu or the antitumor chemical combination that can be metabolized generation dihydroartemisinine
The molar ratio for the dihydroartemisinine that object, first Studies on Anticancer Components and qinghaosu or the metabolism of the second Studies on Anticancer Components generate is 1:
2-100, it is described to be metabolized that generate the antitumoral compounds of dihydroartemisinine be Artesunate, Artemether, one in arteether
Kind or several combinations.
2. anti-tumor compositions according to claim 1, which is characterized in that first Studies on Anticancer Components be more west he
Match, the second Studies on Anticancer Components are dihydroartemisinine, and the molar ratio of docetaxel and dihydroartemisinine is 1:100.
3. anti-tumor compositions according to claim 1, which is characterized in that first Studies on Anticancer Components be more west he
Match, the second Studies on Anticancer Components are the combination of one or more of qinghaosu, Artesunate, Artemether, arteether, docetaxel
The molar ratio of the dihydroartemisinine generated with qinghaosu or the metabolism of the second Studies on Anticancer Components is 1:100.
4. anti-tumor compositions according to claim 1, which is characterized in that first Studies on Anticancer Components replaces for Yi Li
Health, the second Studies on Anticancer Components are dihydroartemisinine, and the molar ratio of Irinotecan and dihydroartemisinine is 1:2-10.
5. anti-tumor compositions according to claim 1, which is characterized in that first Studies on Anticancer Components replaces for Yi Li
Health, the second Studies on Anticancer Components are the combination of one or more of qinghaosu, Artesunate, Artemether, arteether, Irinotecan
The molar ratio of the dihydroartemisinine generated with qinghaosu or the metabolism of the second Studies on Anticancer Components is 1:2-10.
6. a kind of application of anti-tumor compositions as described in claim 1 in terms of preparing anti-tumor drug.
7. a kind of application of anti-tumor compositions as described in claim 1 in terms of preparation inhibits cancer cell drug, feature
It is, the cancer cell is at least one of colon cancer, liver cancer, breast cancer cell.
8. a kind of anti-tumor drug, which is characterized in that including main ingredient and auxiliary material, the main ingredient includes the first Studies on Anticancer Components and the
Two Studies on Anticancer Components, first Studies on Anticancer Components be one or both of docetaxel, Irinotecan or docetaxel,
The salt of one or both of Irinotecan；Second Studies on Anticancer Components is dihydroartemisinine, first Studies on Anticancer Components
Molar ratio with dihydroartemisinine is 1:2-100；Or second Studies on Anticancer Components for qinghaosu or can be metabolized generation pair
The antitumoral compounds of hydrogen arteannuin, first Studies on Anticancer Components and qinghaosu or the metabolism of the second Studies on Anticancer Components generate double
The molar ratio of hydrogen arteannuin be 1:2-100, it is described can be metabolized generate dihydroartemisinine antitumoral compounds be Artesunate,
The combination of one or more of Artemether, arteether.
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|---|---|---|---|---|
| WO2020207257A1 (en) * | 2019-04-08 | 2020-10-15 | 深圳宾德生物技术有限公司 | Application of artemisinin compounds in promoting chimeric antigen receptor t cell treatment, and pharmaceutical composition |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110152289A1 (en) * | 2008-07-29 | 2011-06-23 | Pierre Fabre Medicament | Dimeric derivatives of artemisinin and application in anti-cancer therapy |
| CN102665711A (en) * | 2009-12-23 | 2012-09-12 | 希格马托制药工业公司 | Anticancer combination of artemisinin-based drugs and other chemotherapeutic agents |
| US20160228457A1 (en) * | 2013-04-09 | 2016-08-11 | Stc.Unm | Method for cancer cell reprogramming |
| CN106727494A (en) * | 2016-12-28 | 2017-05-31 | 郑州欧印数字科技有限公司 | A kind of Western medicine for treating Eaton agent pneumonia |
-
2018
- 2018-11-22 CN CN201811401837.1A patent/CN109453156A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110152289A1 (en) * | 2008-07-29 | 2011-06-23 | Pierre Fabre Medicament | Dimeric derivatives of artemisinin and application in anti-cancer therapy |
| CN102665711A (en) * | 2009-12-23 | 2012-09-12 | 希格马托制药工业公司 | Anticancer combination of artemisinin-based drugs and other chemotherapeutic agents |
| US20160228457A1 (en) * | 2013-04-09 | 2016-08-11 | Stc.Unm | Method for cancer cell reprogramming |
| CN106727494A (en) * | 2016-12-28 | 2017-05-31 | 郑州欧印数字科技有限公司 | A kind of Western medicine for treating Eaton agent pneumonia |
Non-Patent Citations (3)
| Title |
|---|
| JIN TAO等: "Co-delivery of dihydroartemisinin and docetaxel in pH-sensitive nanoparticles for treating metastatic breast cancer via the NF-κB/MMP-2 signal pathway", 《RSC ADV.》 * |
| XIAOLONG JIA等: "Application of sequential factorial design and orthogonal array composite design (OACD) to study combination of 5 prostate cancer drugs", 《COMPUTATIONAL BIOLOGY AND CHEMISTRY》 * |
| 周卫等: "NF-κB在肿瘤中的研究进展", 《中国民族民间医药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020207257A1 (en) * | 2019-04-08 | 2020-10-15 | 深圳宾德生物技术有限公司 | Application of artemisinin compounds in promoting chimeric antigen receptor t cell treatment, and pharmaceutical composition |
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