CN102440987A - Drug compound of apigenin, apigenin-like derivants, artemisinin and artemisinin-like derivants and application thereof - Google Patents
Drug compound of apigenin, apigenin-like derivants, artemisinin and artemisinin-like derivants and application thereof Download PDFInfo
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- CN102440987A CN102440987A CN2010105064891A CN201010506489A CN102440987A CN 102440987 A CN102440987 A CN 102440987A CN 2010105064891 A CN2010105064891 A CN 2010105064891A CN 201010506489 A CN201010506489 A CN 201010506489A CN 102440987 A CN102440987 A CN 102440987A
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Abstract
The invention relates to a drug compound of apigenin, apigenin-like derivants, artemisinin and artemisinin-like derivants and application thereof in the preparation of drugs for curing lung cancer, pancreas cancer, colon cancer, liver cancer, prostate gland cancer, kidney cancer, stomach cancer, encephaloma, sarcoma, ovarian cancer or breast cancer. The drug compound has a remarkable coordination effect, improves the curative effect of the drugs, reduces the drug dosage, and reduces the side effects.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and the application in the medicine of preparation treatment cancer thereof, be specifically related to contain the pharmaceutical composition and the application in the medicine of preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, ovarian cancer or breast carcinoma thereof of apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives.
Background technology
World Health Organization's investigation report shows that global cancer condition is serious day by day, and 20 years from now on new patients' number will be increased to 1,500 ten thousand by present every year 1000 ten thousand, because of the number that cancer is dead also will be by increasing to 1,000 ten thousand 6,000,000 of every year.Wherein pulmonary carcinoma is one of common malignancy, comes from bronchiolar epitheliums at different levels, is divided into small cell lung cancer and nonsmall-cell lung cancer; The cancer of pancreas pilosity is born in head of pancreas portion, and 90% derives from the ductus pancreaticus epithelial cell, and all the other are from pancreatic acini; Be the digestive system common malignancy; Sickness rate is ascendant trend year by year, because the onset concealment lacks effective method of early diagnosis; Often reach an advanced stage when making a definite diagnosis or shift, the patients with terminal median survival interval is no more than six months; The morbidity of colon cancer and environment, living habit, especially diet style is relevant, it is generally acknowledged that high fat diet and cellulose deficiency are main pathogenic factors.Along with growth in the living standard, the change of dietary structure, the sickness rate of colon cancer is ascendant trend year by year.Carcinoma of prostate is most important a kind of in the male genitourinary system tumor, is human distinctive disease.Carcinoma of prostate is a senile disease, mostly at 50 years old with sequela.Along with the prolongation of human average life, the raising of diagnostic techniques, the change of life style, the sickness rate of carcinoma of prostate is in continuous rising, and it is extremely urgent therefore to study the treatment of prostate cancer medicine.
The antitumor drug that has gone on the market at present is more, and like alkylating agent medicine, antimetabolite, AGPM, immunomodulator etc., but medicine is because toxicity is bigger mostly, and patient does not tolerate.Lots of clinical facts have proved that malignant tumor can be effectively treated in the Chinese medicine or the combination of Chinese and Western medicine, can alleviate the toxic and side effects of chemicotherapy simultaneously.Utilization modern medicine means find that some bioactive natural products can effectively suppress the growth of tumor cell, have the effect of cell death inducing.Numerous antibiotic and the antitumor drug that uses at present or be directed to natural product, or get through its structure of modification.Therefore, safe bioactive natural product applies to clinically will have broad prospects with the treatment cancer, also is the new direction of present oncotherapy field development.
Arteannuin is the sesquiterpene lactone that contains peroxide bridge, and its derivant has artesunate, Artemether, arteether and dihydroarteannuin etc.Arteannuin and derivant thereof are the antimalarial agents of one type of efficient, low toxicity; Along with going deep into of research; It is found that arteannuin and artemisine compounds also have other a lot of important pharmacologically actives; Like schistosomicide, immunomodulating, arrhythmia, antitumor etc., especially its antitumor action more and more causes the attention of researcheres.A lot of experimentatioies show; Arteannuin and artemisine compounds have significant inhibitory effect to the growth of kinds of tumor cells; And it is very low to normal histiocytic toxicity; Mechanism of action maybe with the generation and the oxidative stress of free radical in the tumor cell, postpone cell cycle, cell death inducing is relevant with the antineoplastic vascular generation.Dihydroarteannuin is an active stronger derivant in the artemisinin-based drug; Artesunate is one of most important derivant of arteannuin; Has good water solubility; Artesunate antitumor mechanism has direct killing effect or relevant with cell death inducing with it to tumor cell line, also maybe be relevant with its inhibition tumor tissues angiogenesis etc.Arteannuin and artemisinin-based drug can the selective killing tumor cells, and do not have crossing drug resistant with traditional chemotherapeutic, multidrug resistance phenomenon that can the reversing tumor cell.
Apigenin is a kind of flavone compound, extensively is present in the multiple fruits and vegetables, has various biological effects such as antitumor, antioxidation and antiinflammatory.Pass through pharmacological research in recent years and find that the apigenin antitumor action is obvious, can suppress growth of tumour cell, inducing apoptosis of tumour cell, and can suppress tumor vessel formation, invasion and attack and transfer, in addition, go back the signal transduction path of interfere tumor cell.Apigenin receives much concern in the application of anti-tumor aspect.
Along with the progress of oncomolecularbiology, the molecular targeted treatment of tumor has become the focus of tumor research, in the treatment of kinds of tumors, has brought into play important effect.Yet the biological behaviour of most of tumor is not to be arranged by single signal transduction pathway, but a plurality of signal transduction pathway concurs.Chinese medicine receives publicity with the effect advantage of the many target spots of its polygenes just day by day; Therefore drug combination carries out targeted therapy to many target spots and will not only be intended to reduce or delay chemical sproof appearance, reduce toxicity, and through multiple medicine the synergism that cancerous cell kills and wounds is obtained better therapeutic.
Summary of the invention
To above technological deficiency; The present invention provides a kind of pharmaceutical composition and the application in the medicine of preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, ovarian cancer or breast carcinoma thereof, is specially the application of pharmaceutical composition in the medicine of preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, ovarian cancer or breast carcinoma that contains apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives.
The present invention contains in the pharmaceutical composition of apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives, and said apigenin and apigenin analog derivative are apigenin; Said arteannuin and artemisinin derivatives can be arteannuin, artesunate, dihydroarteannuin, Artemether or arteether, or their corresponding derivative.
Arteannuin and artemisinin derivatives in the pharmaceutical composition of the present invention are preferably: artesunate, dihydroarteannuin, its corresponding structure formula are respectively suc as formula shown in I, the formula II.
Apigenin in the pharmaceutical composition of the present invention and apigenin analog derivative are preferably apigenin, and its structural formula is shown in formula III.
In the pharmaceutical composition of the present invention, said component is not limited to apigenin itself, can also be its pharmaceutically useful salt, hydrate or derivant etc.
In the pharmaceutical composition of the present invention, said component is not limited to artesunate and dihydroarteannuin medicine itself, can also be its pharmaceutically useful salt, hydrate or derivant etc.
The present invention contains in the pharmaceutical composition of apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives, and the mol ratio of apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 5.0-60.0: 0.3-20.0; Further the mol ratio of preferred said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 10.0-30.0: 0.75-10.0.
The pharmaceutical composition that the present invention contains apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives can be used to treat various tumors, and said tumor includes but not limited to pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, ovarian cancer or breast carcinoma.
The pharmaceutical composition of preferably celery element of the present invention and apigenin analog derivative and arteannuin and artemisinin derivatives is used for preparing the application of the medicine of treating pulmonary carcinoma, cancer of pancreas, colon cancer and carcinoma of prostate.
Be used for preparing in the application of treating lung cancer drugs at pharmaceutical composition of the present invention, the mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 20.0-30.0: 5.0-10.0; The mol ratio that is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 25.0-30.0: 7.5-10.0; The mol ratio that further is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 30.0: 10.0.
Be used for preparing in the application of the medicine of treating cancer of pancreas at pharmaceutical composition of the present invention, the mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 15.0-25.0: 4.0-7.5; The mol ratio that is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 20.0-25.0: 5.0-7.5; The mol ratio that further is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 25.0: 7.5.
Be used for preparing in the application of the medicine of treating colon cancer at pharmaceutical composition of the present invention, the mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 10.0-17.0: 4.0-7.0; The mol ratio that is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 13.0-17.0: 5.0-7.0; The mol ratio that further is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 17.0: 7.0.
Be used for preparing in the application of the medicine of treating carcinoma of prostate at pharmaceutical composition of the present invention, the mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 20.0-30.0: 0.75-1.5; The mol ratio that is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 25.0-30.0: 1.0-1.5; The mol ratio that further is preferably apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 30.0: 1.5.
The pharmaceutical composition that contains apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is in the application of the medicine of preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, ovarian cancer or breast carcinoma; In the scheme of the medicament of the present composition being processed administration simultaneously; Arteannuin and artemisinin derivatives and apigenin and apigenin analog derivative can be contained in in a kind of pharmaceutical preparation such as tablet or the capsule; Also can arteannuin and artemisinin derivatives and apigenin and apigenin analog derivative be made preparation respectively; As make tablet or capsule respectively; And adopting the conventional mode in this area with their packings or combine, the patient takes according to the indication of package insert then simultaneously; In the scheme of the medicament of the present composition being processed administration successively; Can arteannuin and artemisinin derivatives be made different preparations respectively with apigenin and apigenin analog derivative; And adopt the conventional mode in this area with their packings or combine; The patient takes according to the sequencing of package insert indication then; Or two kinds of compositions in the above-mentioned composition are processed a kind of preparation of controlled release, and a kind of composition in the first release composition and then the another kind of composition in the release composition, the patient only need take this controlled release composition preparation; In the scheme of the medicament that the present composition is prepared into the intersection administration; Can arteannuin and artemisinin derivatives be made different preparations respectively with apigenin and apigenin analog derivative; And adopt the conventional mode in this area with their packings or combine; The patient takes according to the chi sequence of package insert indication then, perhaps this preparation of pharmaceutical compositions is become the controlled release preparation of arteannuin and artemisinin derivatives and apigenin and the release of apigenin analog derivative intersection.
In the application of the pharmaceutical composition of apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives in the medicine of preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, ovarian cancer or breast carcinoma; Arteannuin in the said compositions and artemisinin derivatives and apigenin and apigenin analog derivative can use or with the using in order of any priority simultaneously, as can arteannuin and artemisinin derivatives and apigenin and apigenin analog derivative being taken to the patient simultaneously; Also can earlier apigenin and apigenin analog derivative taken, taken then to arteannuin and artemisinin derivatives medicine to the patient; Or take apigenin and apigenin analog derivative earlier, take arteannuin and artemisinin derivatives medicine then; The interval of taking for both does not have special demands, but the interval of preferably taking two kinds of medicines is no more than one day; Perhaps two kinds of medicines replace administration.
Among the present invention; Can the method for arteannuin of the present invention and artemisinin derivatives and apigenin and apigenin analog derivative employing this area routine be prepared into the pharmaceutical preparation that is suitable for gastrointestinal administration or parenteral administration; The pharmaceutical preparation that the present invention preferably processes gastrointestinal administration with arteannuin and artemisinin derivatives and apigenin and apigenin analog derivative, its dosage form can be conventional tablet or capsule or controlled release, slow releasing preparation.In the pharmaceutical preparation of arteannuin of the present invention and artemisinin derivatives and apigenin and apigenin analog derivative compositions; According to different dosage forms and preparation specification; The content of said compositions in preparation can be counted 1-99% for quality, is preferably 10%-90%; The adjuvant that preparation uses can adopt the conventional adjuvant in this area, reacts or the curative effect that do not influence medicine of the present invention is a prerequisite with the discord present composition; The method for preparing of said preparation can adopt the conventional method for preparing in this area to prepare.
Among the present invention; The preparation of compositions method does not have any restriction; Arteannuin and artemisinin derivatives and apigenin and apigenin analog derivative can directly mix makes preparation then; Or respectively and/or corresponding auxiliary material mix and to make preparation respectively, and then packaging together, or mix and then mix and make preparation with corresponding auxiliary material respectively according to the conventional mode in this area.
The dosage of the pharmaceutical composition among the present invention can carry out suitable variation according to the dosage form difference of administration object, route of administration or medicine, but is prerequisite to guarantee that this pharmaceutical composition can reach effective blood drug level in mammalian body.
The present invention has carried out the test that apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives combination kill H460 (lung cancer cell line), Panc-1 (pancreas cancer cell strain), HCT-116 (colon cancer cell line) and LNCaP (prostate gland cancer cell strain) respectively; Results suggest; Apigenin of the present invention and apigenin analog derivative and arteannuin and artemisinin derivatives combined therapy pulmonary carcinoma, cancer of pancreas, colon cancer and carcinoma of prostate have significant cooperative effect; Improved the curative effect of medicine; Reduce dosage, reduced the generation of side effect.
The specific embodiment
In conjunction with following examples the present invention is done further elaboration, but the present invention is not limited to this.
Embodiment
Reagent and method:
Cell: H460 (lung cancer cell line), Panc-1 (pancreas cancer cell strain), HCT-116 (colon cancer cell line) and LNCaP (prostate gland cancer cell strain) are all available from American Type Culture Collection (ATCC), Rockville, MD, USA.
Medicine: institute's pharmaceutical composition is all by following method 1 or 2 said preparations of method in following examples; Artemisinin derivatives artesunate and dihydroarteannuin are all available from Sigma, and apigenin is available from Nanjing Zelang Pharmaceutical Technology Inc..
Method 1: each component of accurate weighing corresponding pharmaceutical compositions, dissolve respectively with dimethyl sulfoxide, be made into the stock solution of 10mM separately; Preserve down at-20 ℃; Be diluted to suitable concentration with fresh culture medium during use, the solution of each component of 1 microlitre of respectively asking for then mixes subsequent use.In all tests, the ultimate density of dimethyl sulfoxide is answered≤5g/L, so that do not influence cell activity.
With all cells in RPMI 1640 culture medium that contain 10% calf serum, 100kU/L penicillin, 100mg/L streptomycin, 37 ℃, 5%CO
2Damp condition cultivate down, in the previous day of dosing, on six orifice plates, carry out cell inoculation 2 * 10
5/ hole adds the pharmaceutical composition solution of preparation as stated above then in cell, make each component reach its working concentration, specifically sees 1-12 in the table.
After the drug treating, measure cell death through trypan blue (Trypan Blue), cell turns into 10 minutes through carrying out pancreatin at 37 ℃ with trypsin sodium/EDTA.Get into the culture medium because dead cell comes off from incubator,, and then, mix with the trypan blue dyestuff with culture medium suspended sediment again through all cells of centrifugal collection under 1200 rev/mins.After the dyeing, count with optical microscope and hematimeter.Dyed the blue dead cell of counting by dyestuff.500 cells of picked at random are counted, and dead cell is recently expressed with the percentage that accounts for the grand total cell.
Method 2: each component of accurate weighing corresponding pharmaceutical compositions, dissolve respectively with dimethyl sulfoxide, be made into the stock solution of 10mM separately, preserve down at-20 ℃.Be diluted to suitable concentration with fresh culture medium during use, the solution for standby of each component of 1 microlitre of respectively asking for then.In all tests, the ultimate density of dimethyl sulfoxide is answered≤5g/L, so that do not influence cell activity.
With all cells in RPMI 1640 culture medium that contain 10% calf serum, 100kU/L penicillin, 100mg/L streptomycin, 37 ℃, 5%CO
2Damp condition cultivate down, in the previous day of dosing, on six orifice plates, carry out cell inoculation 2 * 10
5/ hole adds each component solution of the pharmaceutical composition of preparation as stated above with any order then in cell, make each component reach its working concentration, specifically sees 13-24 in the table.
After the drug treating, measure cell death through trypan blue (Trypan Blue), cell turns into 10 minutes through carrying out pancreatin at 37 ℃ with trypsin sodium/EDTA.Get into the culture medium because dead cell comes off from incubator,, and then, mix with the trypan blue dyestuff with culture medium suspended sediment again through all cells of centrifugal collection under 1200 rev/mins.After the dyeing, count with optical microscope and hematimeter.Dyed the blue dead cell of counting by dyestuff.500 cells of picked at random are counted, and dead cell is recently expressed with the percentage that accounts for the grand total cell.
Tabulate down in the drug regimen shown in 1, the combination of 1-12 is by method 1 preparation, and the combination of 13-24 is by method 2 preparations.
Table 1
The artesunate of embodiment 1 different proportion and the combination Synergistic of apigenin promote the test of H460 cell death, see table 2.
Table 2
Cause in the test of lung cancer cell line H460 cell death at the investigation related compound, find when using 10.0 μ M artesunate separately or using 30.0 μ M apigenins that 25% cell death is arranged approximately separately; (7.5 μ M artesunate+25.0 μ M apigenins) then produce than the obvious synergistic effect when both share under low concentration, cause about 40% cancer cell death; When both share with the ratio of 10.0 μ M artesunate+30.0 μ M apigenins, then produce significant more synergism, cause 73% cancer cell death.
The dihydroarteannuin of embodiment 2 different proportions and the combination Synergistic of apigenin promote the test of H460 cell death, see table 3.
Table 3
Cause in the test of lung cancer cell line H460 cell death at the investigation related compound, find when using 10.0 μ M dihydroarteannuins separately or using 30.0 μ M apigenins that 25% cell death is arranged approximately separately; (7.5 μ M dihydroarteannuins+25.0 μ M apigenins) then produce than the obvious synergistic effect when both share under low concentration, cause 42% cancer cell death; When both share with the ratio of 10.0 μ M dihydroarteannuins+30.0 μ M apigenins, then produce significant more synergism, cause 77% cancer cell death.
The artesunate of embodiment 3 different proportions and the combination Synergistic of apigenin promote the test of Panc-1 cell death, see table 4.
Table 4
Cause in the test of pancreas cancer cell strain Panc-1 cell death investigating related compound, find when using 7.5 μ M artesunate, 25.0 μ M apigenins 20% cell death of only having an appointment separately; (5.0 μ M artesunate+20.0 μ M apigenins) then produce the obvious synergistic effect when both share under low concentration, cause 61% cancer cell death; When both share with the ratio of 7.5 μ M artesunate+25.0 μ M apigenins, then produce significant more synergism, cause 92% cancer cell death.
The dihydroarteannuin of embodiment 4 different proportions and the combination Synergistic of apigenin promote the test of Panc-1 cell death, see table 5.
Table 5
Cause in the test of pancreas cancer cell strain Panc-1 cell death investigating related compound, find, use 25.0 μ M apigenins, 15% cell death of also only having an appointment separately when using 7.5 μ M dihydroarteannuins, 25% cell death of only having an appointment separately; (5.0 μ M dihydroarteannuins+20.0 μ M apigenins) then produce the obvious synergistic effect when both share under low concentration, cause 63% cancer cell death; When both share with the ratio of 7.5 μ M dihydroarteannuins+25.0 μ M apigenins, then produce significant more synergism, cause about 90% cancer cell death.
The artesunate of embodiment 5 different proportions and the combination Synergistic of apigenin promote the test of HCT-116 cell death, see table 6.
Table 6
Cause in the test of colon cancer cell line HCT-116 cell death at the investigation related compound; Find when use 5.0 μ M artesunate or lower concentration separately, to have only the cell death of very small amount, even use 7.0 μ M artesunate, 25% cell death of also only having an appointment separately; Use separately 17.0 μ M apigenins, 20% cell death of only having an appointment; (5.0 μ M artesunate+13.0 μ M apigenins) then produce the obvious synergistic effect when both share under low concentration, cause 51% cancer cell death; When both share with the ratio of 7.0 μ M artesunate+17.0 μ M apigenins, then produce significant more synergism, cause 99% cancer cell death.
The dihydroarteannuin of embodiment 6 different proportions and the combination Synergistic of apigenin promote the test of HCT-116 cell death, see table 7.
Table 7
Cause in the test of colon cancer cell line HCT-116 cell death at the investigation related compound; Find when use 5.0 μ M dihydroarteannuins or lower concentration separately, to have only the cell death of very small amount, even only have an appointment 20% cell death when using 7.0 μ M dihydroarteannuins or 17.0 μ M apigenins separately; (5.0 μ M dihydroarteannuins+13.0 μ M apigenins) then produce the obvious synergistic effect when both share under low concentration, cause 55% cancer cell death; When both share with the ratio of 7.0 μ M dihydroarteannuins+17.0 μ M apigenins, then produce significant more synergism, cause 99% cancer cell death.
The artesunate of embodiment 7 different proportions and the combination Synergistic of apigenin promote the test of LNCaP cell death, see table 8.
Table 8
Cause in the test of prostate gland cancer cell strain LNCaP cell death at the investigation related compound; Find when use 1.5 μ M artesunate or lower concentration separately, to have only the cell death of very small amount, even use 30.0 μ M apigenins, 25% cell death of only having an appointment separately; (1.0 μ M artesunate+25.0 μ M apigenins) then produce the obvious synergistic effect when both share under low concentration, cause 59% cancer cell death; When both share with the ratio of 1.5 μ M artesunate+30.0 μ M apigenins, then produce significant more synergism, cause 82% cancer cell death.
The dihydroarteannuin of embodiment 8 different proportions and the combination Synergistic of apigenin promote the test of LNCaP cell death, see table 9.
Table 9
Cause in the test of prostate gland cancer cell strain LNCaP cell death investigating related compound, find, use 30.0 μ M apigenins, 25% cell death of only having an appointment separately when using only have an appointment 10% cell death of 1.5 μ M dihydroarteannuins separately; (1.0 μ M dihydroarteannuins+25.0 μ M apigenins) then produce the obvious synergistic effect when both share under low concentration, cause 52% cancer cell death; When both share with the ratio of 1.5 μ M dihydroarteannuins+30.0 μ M apigenins, then produce significant more synergism, cause 88% cancer cell death.
Although the foregoing description describes in detail technical scheme of the present invention; But technical scheme of the present invention is not limited to above embodiment; Under the situation that does not break away from thought of the present invention and aim, any change that technical scheme of the present invention is done all will fall into claims of the present invention institute restricted portion.
Claims (10)
1. a pharmaceutical composition is characterized in that, said compositions contains apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives.
2. pharmaceutical composition according to claim 1; It is characterized in that; The mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 5.0-60.0: 0.3-20.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 10.0-30.0: 0.75-10.0.
3. pharmaceutical composition according to claim 2 is characterized in that, said apigenin and apigenin analog derivative are apigenin; Said arteannuin and artemisinin derivatives are arteannuin, artesunate, dihydroarteannuin, Artemether or arteether.
4. the application of the arbitrary described pharmaceutical composition of claim 1-3 in the medicine of preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, ovarian cancer or breast carcinoma.
5. application according to claim 4; It is characterized in that; In the application in preparation treatment lung cancer drugs; The mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 20.0-30.0: 5.0-10.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 25.0-30.0: 7.5-10.0.
6. application according to claim 4; It is characterized in that; In the application in the medicine of preparation treatment cancer of pancreas; The mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 15.0-25.0: 4.0-7.5, and the mol ratio of preferred said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 20.0-25.0: 5.0-7.5.
7. application according to claim 4; It is characterized in that; In the application in the medicine of preparation treatment colon cancer; The mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 10.0-17.0: 4.0-7.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 13.0-17.0: 5.0-7.0.
8. application according to claim 4 is characterized in that, in the application in the medicine of preparation carcinoma of prostate, the mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 20.0-30.0: 0.75-1.5.
9. application according to claim 8 is characterized in that, in the application in the medicine of preparation carcinoma of prostate, the mol ratio of said apigenin and apigenin analog derivative and arteannuin and artemisinin derivatives is 25.0-30.0: 1.0-1.5.
10. application according to claim 4 is characterized in that, apigenin in the said pharmaceutical composition and apigenin analog derivative and arteannuin and artemisinin derivatives use or using in order with any priority simultaneously.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104188953A (en) * | 2014-08-01 | 2014-12-10 | 南京伊度医疗技术有限公司 | Application of apigenin to preparation of medicines for inhibiting scaffolding protein expression and cancer cell metastasis |
| CN104840456A (en) * | 2014-02-13 | 2015-08-19 | 复旦大学附属肿瘤医院 | Application of apigenin to prepare medicine for treating pancreatic cancer |
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| CN1895244A (en) * | 2006-06-09 | 2007-01-17 | 江秉华 | Medicinal composition for preventing and treating cancer diseases |
| CN101756957A (en) * | 2008-12-26 | 2010-06-30 | 鼎泓国际投资（香港）有限公司 | Pharmaceutical composition containing artemisinin, artemisinin derivatives and histon deacetylase (HDAC) inhibitor and application thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104840456A (en) * | 2014-02-13 | 2015-08-19 | 复旦大学附属肿瘤医院 | Application of apigenin to prepare medicine for treating pancreatic cancer |
| CN104188953A (en) * | 2014-08-01 | 2014-12-10 | 南京伊度医疗技术有限公司 | Application of apigenin to preparation of medicines for inhibiting scaffolding protein expression and cancer cell metastasis |
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