CN102688228B - Pharmaceutical composition containing apigenin, apigenin derivative, rubescensin and rubescensin derivative, and application thereof - Google Patents
Pharmaceutical composition containing apigenin, apigenin derivative, rubescensin and rubescensin derivative, and application thereof Download PDFInfo
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- CN102688228B CN102688228B CN201110080494.5A CN201110080494A CN102688228B CN 102688228 B CN102688228 B CN 102688228B CN 201110080494 A CN201110080494 A CN 201110080494A CN 102688228 B CN102688228 B CN 102688228B
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Abstract
The present invention relates to a pharmaceutical composition containing apigenin, an apigenin derivative, rubescensin, and a rubescensin derivative, and applications of the pharmaceutical composition for preparing pharmaceuticals to cure lung cancer, pancreas cancer, colorectal carcinoma, liver cancer, prostate cancer, kidney cancer, stomach cancer, brain tumor, sarcoma, mesothelioma, head and neck squamous cancer, ovary cancer or breast cancer. The pharmaceutical composition has an obvious synergistic effect, increases the pharmic curative effect, reduces the administration dosage and reduces the adverse reactions.
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 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, mesothelioma, head and neck squamous cell carcinoma, ovarian cancer or breast carcinoma thereof that contain apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative.
Background technology
World Health Organization's investigation report shows, global cancer condition is day by day serious, and 20 years new patients' number will be increased to 1,500 ten thousand by current annual 1000 ten thousand from now on, because the dead number of cancer also will be increased to 1,000 ten thousand by annual 6000000.Wherein, primary hepatocarcinoma is the canceration that occurs in hepatocyte and intrahepatic biliary epithelium cell, is one of modal malignant tumor of the mankind; 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.Mesothelioma is the tumor occurring on thoracic cavity or abdominal cavity inwall, can be divided into optimum or pernicious.Mesothelioma of pleura is pleural neoplasm, has dividing of topical type (mostly being optimum) and diffuse type (being all pernicious).Wherein diffuse type malignant mesothe is one of chest the worst rear tumor.Most patient is at 40-70 between year, and male is more than women.The treatment of malignant pleural mesothelioma, does not still have effective radical cure method at present.Peritoneal mesothelioma refers to the tumor that is primary in Peritoneal Mesothelial Cells.Clinical manifestation does not have characteristic, and peritoneal mesothelioma accounts for 20% of all mesothelioma cases, and most of cases are at 45-64 between year.A specificity is not had in peritoneal mesothelioma clinical manifestation.Up to now, peritoneal mesothelioma still lacks the Therapeutic Method of specially good effect.Squamous cell carcinoma of the head and neck is common head and neck diseases, and its sickness rate occupies the 6th of malignant tumor, and annual nearly 4,000,000 new cases, particularly become male's the 3rd common cancer in developing country.Original site is mainly incidence 4 common site-oral cavities, nasopharynx, oropharynx, hypopharynx and larynxs.At present, operation combined radiotherapy, chemotherapy are the primary treatment means of squamous cell carcinoma of the head and neck.Carcinoma of prostate is most important a kind of in male genitourinary system tumor, is the distinctive diseases of the mankind.Carcinoma of prostate is senile disease, mostly at 50 years old with sequela.Along with the prolongation of mankind's average life, the raising of diagnostic techniques, the change of life style, the sickness rate of carcinoma of prostate is in continuous rising, and the medicine of therefore studying carcinoma of prostate is extremely urgent.
The antitumor drug having gone on the market is at present more, and as alkylating agent medicine, antimetabolite, antitumor antibiotics, immunomodulator etc., but medicine is because toxicity is larger mostly, and patient does not tolerate.A large amount of clinical practices prove, malignant tumor can be effectively treated in Chinese medicine or the combination of Chinese and Western medicine, can alleviate the toxic and side effects of chemicotherapy simultaneously.Use modern medicine means, find the effectively growth of inhibition tumor cell of some bioactive natural products, have the effect of cell death inducing.Numerous antibiotic and the antitumor drug using at present or be directed to natural product, or obtain through its structure of modification.Therefore, safe bioactive natural product applies to clinically with treatment cancer, will have broad prospects, and is also the new direction that current therapeutic field of tumor develops.
Rubescensine A (Oridonin, Ori) is that isolated chemical constitution is ent-kaurene Diterpenes organic compound from Labiatae Rabdosia (Rabdosia) plant.For a long time China, Korea S and Japan etc. ground among the people extensively by Rabdosia rubescens for antiinflammatory, antibacterial and treatment tumor.Research shows, rubescensine A is by inducing apoptosis of tumour cell, retardance tumor cell proliferation cycle and reduce the performance antitumor actions such as telomerase activation.Rubescensine A is because toxic and side effects is compared with little and have compared with strong anti-tumor activity and paid close attention to widely.
Apigenin (Apigenin) is a kind of flavone compound, is extensively present in various fruits and vegetable, has the various biological effects such as antitumor, antioxidation and antiinflammatory.By pharmacological research, find in recent years, apigenin antitumor action is obvious, can grow by inhibition tumor cell, and inducing apoptosis of tumour cell, and can suppress tumor vessel formation, invasion and attack and shift, in addition, can also disturb the signal transduction path of tumor cell.Apigenin receives much concern in the application of anti-tumor aspect.
Along with the progress of oncomolecularbiology, tumor molecular targeted therapy has become the focus of tumor research, has brought into play important effect in the treatment of kinds of tumors.Yet the biological behaviour of most of tumor is not arranged by single signal pathway, but a plurality of signal transduction pathway concurs.Chinese medicine receives publicity just day by day with the Action advantage of the many target spots of its polygenes, therefore drug combination carries out for many target spots appearance, the reduction toxicity that targeted therapy will not only be intended to minimizing or delay drug resistance, and synergism cancerous cell being killed and wounded by multi-medicament is obtained better curative effect.
Summary of the invention
For above technological deficiency, the invention provides a kind of pharmaceutical composition and the application in the medicine of preparation treatment cancer thereof, be 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, mesothelioma, head and neck squamous cell carcinoma, ovarian cancer or breast carcinoma that contains apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative.
In the pharmaceutical composition that the present invention contains apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative, described apigenin and apigenin analog derivative are apigenin; Described rubescensine A and Oridonin derivative are rubescensine A.
Rubescensine A and Oridonin derivative in pharmaceutical composition of the present invention are preferably rubescensine A, and its corresponding structural formula is suc as formula shown in I.
In pharmaceutical composition of the present invention, described component is not limited to rubescensine A itself, can also be its pharmaceutically useful salt, hydrate or derivant etc.
Apigenin in pharmaceutical composition of the present invention and apigenin analog derivative are preferably apigenin, and its structural formula is suc as formula shown in II.
In pharmaceutical composition of the present invention, described component is not limited to apigenin itself, can also be its pharmaceutically useful salt, hydrate or derivant etc.
In the pharmaceutical composition that the present invention contains apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative, the mol ratio of apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 5.0-60.0: 3.5-30.0; Further the mol ratio of preferred described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 10.0-30.0: 7.5-15.0.
The pharmaceutical composition that the present invention contains apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative can be used for the treatment of various tumors, and described tumor includes but not limited to pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, mesothelioma, head and neck squamous cell carcinoma, ovarian cancer or breast carcinoma.
The pharmaceutical composition of preferably celery element of the present invention and apigenin analog derivative and rubescensine A and Oridonin derivative is for the preparation of the application in the medicine for the treatment of colon cancer, hepatocarcinoma, carcinoma of prostate, mesothelioma and head and neck squamous cell carcinoma.
Pharmaceutical composition of the present invention for the preparation for the treatment of colon cancer medicine in application in, the mol ratio of described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 12.5-20.0: 7.5-15.0; The mol ratio that is preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-20.0: 10.0-15.0; The mol ratio that is further preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0: 15.0.
Pharmaceutical composition of the present invention for the preparation of the application in the medicine of Hepatoma therapy in, the mol ratio of described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 10.0-25.0: 7.5-15.0.
Wherein, in the application of medicine of preparing treatment HUH-7 type hepatocarcinoma, the mol ratio of preferred described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is preferably 15.0-25.0: 10.0-15.0; The best mol ratio for described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 25.0: 15.0.
In the application of medicine of preparing treatment SK-Hep-1 type hepatocarcinoma, the mol ratio of described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-25.0: 7.5-15.0; Further the mol ratio of preferred described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0-25.0: 10.0-15.0; The best mol ratio for described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 25.0: 15.0.
Pharmaceutical composition of the present invention for the preparation for the treatment of carcinoma of prostate medicine in application in, the mol ratio of described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-25.0: 7.5-15.0; The mol ratio that is preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0-25.0: 10.0-15.0; The mol ratio that is further preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 25.0: 15.0.
Pharmaceutical composition of the present invention for the preparation for the treatment of mesothelioma medicine in application in, the mol ratio of described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 12.5-20.0: 7.5-15.0; The mol ratio that is preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-20.0: 10.0-15.0; The mol ratio that is further preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0: 15.0.
Pharmaceutical composition of the present invention for the preparation of the application in the medicine for the treatment of head and neck squamous cell carcinoma in, the mol ratio of described apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-30.0: 7.5-15.0; The mol ratio that is preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0-30.0: 10.0-15.0; The mol ratio that is further preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 30.0: 15.0.
The pharmaceutical composition that contains apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is in preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, mesothelioma, head and neck squamous cell carcinoma, in the application of the medicine of ovarian cancer or breast carcinoma, in the scheme of medicament of the present composition being made to administration simultaneously, rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative can be contained in same pharmaceutical preparation as in tablet or capsule, also rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative can be made respectively to preparation, as made respectively tablet or capsule, and adopt the mode of this area routine that their are packed or are combined, then patient takes according to the indication of package insert simultaneously, in the scheme of medicament of the present composition being made to successively administration, rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative can be made respectively to different preparations, and adopt the mode of this area routine that their are packed or are combined, then patient takes according to the sequencing of package insert indication, or two kinds of compositions in above-mentioned composition are made to a kind of preparation of controlled release, a kind of composition in first release composition, and then the another kind of composition in release composition, patient only need to take this controlled release composition preparation, in the scheme of medicament that the present composition is prepared into intersection administration, rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative can be made respectively to different preparations, and adopt the mode of this area routine that their are packed or are combined, then patient takes according to the chi sequence of package insert indication, or this pharmaceutical composition is prepared into the controlled release preparation of rubescensine A and Oridonin derivative and apigenin and the release of apigenin analog derivative intersection.
The pharmaceutical composition of apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is in preparation treatment pulmonary carcinoma, cancer of pancreas, colon cancer, hepatocarcinoma, carcinoma of prostate, renal carcinoma, gastric cancer, cerebroma, sarcoma, mesothelioma, head and neck squamous cell carcinoma, in application in the medicine of ovarian cancer or breast carcinoma, rubescensine A in described compositions and Oridonin derivative and apigenin and apigenin analog derivative can be used or using in order with any priority simultaneously, as rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative can taken to patient simultaneously, also can first apigenin and apigenin analog derivative be taken, then be taken to rubescensine A and Oridonin derivative medicine to patient, or first take apigenin and apigenin analog derivative, then take rubescensine A and Oridonin derivative medicine, the interval of taking for both does not have special requirement, but the interval of preferably taking two kinds of medicines is no more than one day, or two kinds of medicines replace administration.
In the present invention, the method of rubescensine A of the present invention and Oridonin derivative and apigenin and apigenin analog derivative employing this area routine can be prepared into the pharmaceutical preparation that is suitable for gastrointestinal administration or parenteral administration, the pharmaceutical preparation that the present invention preferably makes gastrointestinal administration by rubescensine A and Oridonin derivative 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 rubescensine A of the present invention and Oridonin derivative and apigenin and apigenin analog derivative compositions, according to different dosage forms and preparation specification, the content of described compositions in preparation can be 1-99% in mass, is preferably 10%-90%; The adjuvant that preparation is used can adopt the adjuvant of this area routine, and the curative effect of getting along well that the present composition reacts or not affecting medicine of the present invention of take is prerequisite; The preparation method of described preparation can adopt the preparation method of this area routine to be prepared.
In the present invention, the preparation method of compositions does not have any restriction, rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative can carry out direct mixing and then make preparation, or respectively and/or corresponding adjuvant mix and make respectively preparation, and then be packaging together according to the mode of this area routine, or mix and then mix and make preparation with corresponding adjuvant respectively.
The dosage of the pharmaceutical composition in the present invention can carry out suitable variation according to the dosage form difference of administration object, route of administration or medicine, but take, guarantees that this pharmaceutical composition can reach effective blood drug level as prerequisite in mammalian body.
The present invention has carried out respectively apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative combination and has killed HCT-116 (colon cancer cell line), HUH-7 and SK-Hep-1 (hepatoma cell strain), LNCaP (Prostatic cancer cell lines), the test of H-28 (mesothelioma cell strain) and SCC-1 (strain of head and neck squamous cancer cell), results suggest, the present invention is treating colon cancer containing the pharmaceutical composition of apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative, hepatocarcinoma, carcinoma of prostate, mesothelioma and head and neck squamous cell carcinoma aspect have significant cooperative effect, improved the curative effect of medicine, reduced dosage, reduced the generation of side effect.
The specific embodiment
Below in conjunction with specific embodiment, the invention will be further elaborated, but the present invention is not limited to this.
Embodiment
Reagent and method:
Cell: HCT-116 (colon cancer cell line), HUH-7 and SK-Hep-1 (hepatoma cell strain), LNCaP (Prostatic cancer cell lines), H-28 (mesothelioma cell strain) and SCC-1 (strain of head and neck squamous cancer cell), all purchased from American Type Culture Collection (ATCC), Maryland, USA Rockwell.
Medicine: in following examples, institute's pharmaceutical composition is all prepared described in following method 1 or method 2; Rubescensine A is purchased from Xi'an Xu Huang Bioisystech Co., Ltd, and apigenin is purchased from Nanjing Zelang Pharmaceutical Technology Inc..
Method 1: accurately weigh each component of corresponding pharmaceutical composition, dissolve respectively with dimethyl sulfoxide, be made into separately the stock solution of 10mM, at-20 ℃, preserve, during use, by fresh culture medium, be diluted to suitable concentration, the solution of each component of 1 microlitre of then respectively asking for, mixes standby.In all tests, answer≤5g/L of the ultimate density of dimethyl sulfoxide, to do not affect the activity of cell.
By all cells in RPMI 1640 culture medium containing 10% calf serum, 100kU/L penicillin, 100mg/L streptomycin, 37 ℃, 5%CO
2damp condition under cultivate, in the previous day of dosing, on six orifice plates, carry out cell inoculation 2 * 10
5/ hole, then, to adding the medicinal composition solution of preparation as stated above in cell, makes each component reach its working concentration, specifically in Table in 1-9.
After drug treating, by trypan blue (Trypan Blue), measure cell death, cell turns into 10 minutes by carrying out pancreatin at 37 ℃ with trypsin sodium/EDTA.Because dead cell comes off and enters in culture medium from incubator, by all cells of centrifugal collection under 1200 revs/min, and then with culture medium Eddy diffusion precipitate, mix with trypan blue dyestuff.After dyeing, with optical microscope and hematimeter, count.By the dead cell of counting of dyes au bleu.Choose at random 500 cells and count, dead cell is recently expressed to account for the percentage of grand total cell.
Method 2: accurately weigh each component of corresponding pharmaceutical composition, dissolve respectively with dimethyl sulfoxide, be made into separately the stock solution of 10mM, preserve at-20 ℃.During use, by fresh culture medium, be diluted to suitable concentration, the solution for standby of each component of 1 microlitre of then respectively asking for.In all tests, answer≤5g/L of the ultimate density of dimethyl sulfoxide, to do not affect the activity of cell.
By all cells in RPMI 1640 culture medium containing 10% calf serum, 100kU/L penicillin, 100mg/L streptomycin, 37 ℃, 5%CO
2damp condition under cultivate, in the previous day of dosing, on six orifice plates, carry out cell inoculation 2 * 10
5/ hole, then with any order to adding each component solution of the pharmaceutical composition of preparation as stated above in cell, make each component reach its working concentration, specifically in Table in 10-18.
After drug treating, by trypan blue (Trypan Blue), measure cell death, cell turns into 10 minutes by carrying out pancreatin at 37 ℃ with trypsin sodium/EDTA.Because dead cell comes off and enters in culture medium from incubator, by all cells of centrifugal collection under 1200 revs/min, and then with culture medium Eddy diffusion precipitate, mix with trypan blue dyestuff.After dyeing, with optical microscope and hematimeter, count.By the dead cell of counting of dyes au bleu.Choose at random 500 cells and count, dead cell is recently expressed to account for the percentage of grand total cell.
In drug regimen shown in lower list 1, the combination of 1-9 is by method 1 preparation, and the combination of 10-18 is by method 2 preparations.
Table 1
The apigenin of embodiment 1 different proportion and the combination Synergistic of rubescensine A promote the test of HCT-116 cell death, in Table 2.
Table 2
At investigation related compound, cause in the test of colon cancer cell line HCT-116 cell death, find approximately has 23% cell death when using 20.0 μ M apigenin separately, uses separately 15.0 μ M rubescensine A approximately to have 14% cell death; When both share under low concentration, (15.0 μ M apigenin+10.0 μ M rubescensine A) produces obvious synergism, causes 57% cancer cell death; When both share with the ratio of 20.0 μ M apigenin+15.0 μ M rubescensine A, produce more significant synergism, cause 99% cancer cell death.
The apigenin of embodiment 2 different proportions and the combination Synergistic of rubescensine A promote the test of HUH-7 cell death, in Table 3.
Table 3
At investigation related compound, cause in the test of hepatoma cell strain HUH-7 cell death, find almost acellular death when using 25.0 μ M apigenin separately, while using separately 15.0 μ M rubescensine A, also only less than 10% cell death; When both share under low concentration, (15.0 μ M apigenin+10.0 μ M rubescensine A) produces obvious synergism, causes 61% cancer cell death; When both share with the ratio of 25.0 μ M apigenin+15.0 μ M rubescensine A, produce more significant synergism, cause 99% cancer cell death.
The apigenin of embodiment 3 different proportions and the combination Synergistic of rubescensine A promote the test of SK-Hep-1 cell death, in Table 4.
Table 4
At investigation related compound, cause in the test of hepatoma cell strain SK-Hep-1 cell death, finding, when using separately 25.0 μ M apigenins or using separately 15.0 μ M rubescensine A, approximately has 10-15% cell death; When both share under low concentration, (20.0 μ M apigenin+10.0 μ M rubescensine A) produces obvious synergism, causes 43% cancer cell death; When both share with the ratio of 25.0 μ M apigenin+15.0 μ M rubescensine A, produce more significant synergism, cause 81% cancer cell death.
The apigenin of embodiment 4 different proportions and the combination Synergistic of rubescensine A promote the test of LNCaP cell death, in Table 5.
Table 5
At investigation related compound, cause in the test of Prostatic cancer cell lines LNCaP cell death, find almost acellular death when using 15.0 μ M rubescensine A separately, while using separately 25.0 μ M apigenin, also only less than 10% cell death; When both share under low concentration, (20.0 μ M apigenin+10.0 μ M rubescensine A) produces obvious synergism, causes 44% cancer cell death; When both share with the ratio of 25.0 μ M apigenin+15.0 μ M rubescensine A, produce more significant synergism, cause 81% cancer cell death.
The apigenin of embodiment 5 different proportions and the combination Synergistic of rubescensine A promote the test of H-28 cell death, in Table 6.
Table 6
At investigation related compound, cause in the test of mesothelioma cell strain H-28 cell death, find almost acellular death when using 15.0 μ M rubescensine A separately, while using separately 20.0 μ M apigenin, approximately have 20% cell death; When both share under low concentration, (15.0 μ M apigenin+10.0 μ M rubescensine A) produces obvious synergism, causes 46% cancer cell death; When both share with the ratio of 20.0 μ M apigenin+15.0 μ M rubescensine A, produce more significant synergism, cause approximately 80% cancer cell death.
The apigenin of embodiment 6 different proportions and the combination Synergistic of rubescensine A promote the test of SCC-1 cell death, in Table 7.
Table 7
At investigation related compound, cause in the test of head and neck squamous cancer cell strain SCC-1 cell death, finding, when using separately 30.0 μ M apigenins or using separately 15.0 μ M rubescensine A, approximately has 15% cell death; When both share under low concentration, (20.0 μ M apigenin+10.0 μ M rubescensine A) produces obvious synergism, causes 68% cancer cell death; When both share with the ratio of 30.0 μ M apigenin+15.0 μ M rubescensine A, produce more significant synergism, cause 99% cancer cell death.
Although above-described embodiment describes in detail technical scheme of the present invention, but technical scheme of the present invention is not limited to above embodiment, in the situation that not departing from thought of the present invention and aim, any change that technical scheme of the present invention is done all will fall into claims limited range of the present invention.
Claims (15)
1. a pharmaceutical composition, is characterized in that, described compositions contains apigenin and rubescensine A, it is characterized in that, the mol ratio of described apigenin and rubescensine A is 10.0-30.0:7.5-15.0.
2. the application of pharmaceutical composition claimed in claim 1 in the medicine of preparation treatment cancer, is characterized in that, described cancer is colon cancer, hepatocarcinoma, carcinoma of prostate, mesothelioma or head and neck squamous cell carcinoma.
3. application according to claim 2, is characterized in that, in the application in the medicine of preparation treatment colon cancer, the mol ratio of described apigenin and rubescensine A is 12.5-20.0:7.5-15.0.
4. application according to claim 3, is characterized in that, in the application in the medicine of preparation treatment colon cancer, the mol ratio of described apigenin and rubescensine A is 15.0-20.0:10.0-15.0.
5. application according to claim 2, is characterized in that, in the application in preparing the medicine of Hepatoma therapy, the mol ratio of described apigenin and rubescensine A is 10.0-25.0:7.5-15.0.
6. application according to claim 5, is characterized in that, described hepatocarcinoma is HUH-7 type hepatocarcinoma, and the mol ratio of described apigenin and rubescensine A is 15.0-25.0:10.0-15.0.
7. application according to claim 5, is characterized in that, described hepatocarcinoma is SK-Hep-1 type hepatocarcinoma, and the mol ratio of described apigenin and rubescensine A is 15.0-25.0:7.5-15.0.
8. application according to claim 7, is characterized in that, the mol ratio of described apigenin and rubescensine A is 20.0-25.0:10.0-15.0.
9. application according to claim 2, is characterized in that, in the application in the medicine of preparation treatment carcinoma of prostate, the mol ratio of described apigenin and rubescensine A is 15.0-25.0:7.5-15.0.
10. application according to claim 9, is characterized in that, in the application in the medicine of preparation treatment carcinoma of prostate, the mol ratio of described apigenin and rubescensine A is 20.0-25.0:10.0-15.0.
11. application according to claim 2, is characterized in that, in the application in the medicine of preparation treatment mesothelioma, the mol ratio of described apigenin and rubescensine A is 12.5-20.0:7.5-15.0.
12. application according to claim 11, is characterized in that, in the application in the medicine of preparation treatment mesothelioma, the mol ratio of described apigenin and rubescensine A is 15.0-20.0:10.0-15.0.
13. application according to claim 2, is characterized in that, in the application in the medicine of preparation treatment head and neck squamous cell carcinoma, the mol ratio of described apigenin and rubescensine A is 15.0-30.0:7.5-15.0.
14. application according to claim 13, is characterized in that, in the application in the medicine of preparation treatment head and neck squamous cell carcinoma, the mol ratio of described apigenin and rubescensine A is 20.0-30.0:10.0-15.0.
15. according to the application described in claim 2-14 any one, it is characterized in that, the apigenin in described pharmaceutical composition and rubescensine A are used or using in order with any priority simultaneously.
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| 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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