CN102688228A - 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
- Publication number
- CN102688228A CN102688228A CN2011100804945A CN201110080494A CN102688228A CN 102688228 A CN102688228 A CN 102688228A CN 2011100804945 A CN2011100804945 A CN 2011100804945A CN 201110080494 A CN201110080494 A CN 201110080494A CN 102688228 A CN102688228 A CN 102688228A
- Authority
- CN
- China
- Prior art keywords
- apigenin
- derivative
- rubescensine
- cancer
- oridonin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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 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, mesothelioma, head and neck squamous cell carcinoma, ovarian cancer or breast carcinoma thereof of apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative.
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, primary hepatocarcinoma is one of human modal malignant tumor for occurring in the epithelial canceration of hepatocyte and stones in intrahepatic bile duct; 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 that occurs on thoracic cavity or the abdominal cavity inwall, can be divided into optimum or pernicious.Mesothelioma of pleura is the pleura primary tumo(u)r, and the branch of topical type (being mostly optimum) and diffuse type (all being pernicious) is arranged.Wherein the diffuse type malignant mesothe is one of tumor the worst after chest is healed.Between year, the male is more than the women at 40-70 for most patient.The treatment of malignant pleural mesothelioma does not still have effective radical cure method at present.Peritoneal mesothelioma is meant the tumor that is primary in the peritoneal mesothelium cell.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 the peritoneal mesothelioma clinical manifestation.Up to now, peritoneal mesothelioma still lacks specific Therapeutic Method.SCCHN 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.Former position mainly is incidence 4 common site-oral cavities, nasopharynx, oropharynx, hypopharynx and larynxs.At present, operation combined radiotherapy, chemotherapy are the main treatment meanss of SCCHN.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.
(Oridonin is that isolated chemical constitution is an ent-kaurene Diterpenes organic compound from Labiatae Rabdosia (Rabdosia) plant Ori) to rubescensine A.Ground such as China, Korea S and Japan are among the people for a long time extensively is used for antiinflammatory, antibiotic and treatment tumor with Rabdosia rubescens.Research shows that rubescensine A is through performance antitumor actions such as inducing apoptosis of tumour cell, retardance tumor cell proliferation cycle and reduction telomerase activations.Rubescensine A is less and have stronger anti-tumor activity and paid close attention to widely because of toxic and side effects.
Apigenin (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 cancer 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, 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.
The present invention contains in the pharmaceutical composition of apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative, and said apigenin and apigenin analog derivative are apigenin; Said rubescensine A and Oridonin derivative are rubescensine A.
Rubescensine A and Oridonin derivative in the pharmaceutical composition of the present invention are preferably rubescensine A, and its corresponding structure formula is suc as formula shown in the I.
In the pharmaceutical composition of the present invention, said component is not limited to rubescensine A itself, can also be its pharmaceutically useful salt, hydrate or derivant etc.
Apigenin in the pharmaceutical composition of the present invention and apigenin analog derivative are preferably apigenin, and its structural formula is suc as formula shown in the II.
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.
The present invention contains in the pharmaceutical composition of apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative, and 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 said 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 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, 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 used for preparing the application of the medicine of treating colon cancer, hepatocarcinoma, carcinoma of prostate, mesothelioma and head and neck squamous cell carcinoma.
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 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 further is preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0: 15.0.
Be used for preparing in the application of the medicine of treating hepatocarcinoma at pharmaceutical composition of the present invention, the mol ratio of said 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 the medicine for preparing treatment HUH-7 type hepatocarcinoma, the mol ratio of preferred said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is preferably 15.0-25.0: 10.0-15.0; Best mol ratio for said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 25.0: 15.0.
In the application of the medicine for preparing treatment SK-Hep-1 type hepatocarcinoma, the mol ratio of said 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 said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0-25.0: 10.0-15.0; Best mol ratio for said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 25.0: 15.0.
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 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 further is preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 25.0: 15.0.
Be used for preparing in the application of the medicine of treating mesothelioma at pharmaceutical composition of the present invention, the mol ratio of said 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 further is preferably apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0: 15.0.
Be used for preparing in the application of the medicine of treating the head and neck squamous cell carcinoma at pharmaceutical composition of the present invention, the mol ratio of said 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 further is 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 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, mesothelioma, head and neck squamous cell carcinoma, ovarian cancer or breast carcinoma; In the scheme of the medicament of the present composition being processed administration simultaneously; Rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative can be contained in in a kind of pharmaceutical preparation such as tablet or the capsule; Also can rubescensine A and Oridonin derivative 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 rubescensine A and Oridonin derivative 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 rubescensine A and Oridonin derivative 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 rubescensine A and Oridonin derivative and apigenin and the release of apigenin analog derivative intersection.
In the application of the pharmaceutical composition of apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative 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; Rubescensine A in the said compositions and Oridonin derivative and apigenin and apigenin analog derivative can use or with the using in order of any priority simultaneously, as can rubescensine A and Oridonin derivative and apigenin and apigenin analog derivative being taken to the patient simultaneously; Also can earlier apigenin and apigenin analog derivative taken, taken then to rubescensine A and Oridonin derivative medicine to the patient; Or take apigenin and apigenin analog derivative earlier, take rubescensine A and Oridonin derivative 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 rubescensine A of the present invention and Oridonin derivative 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 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 said compositions in preparation can be 1-99% in mass, 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; Rubescensine A and Oridonin derivative 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 rubescensine A and Oridonin derivative combination kill HCT-116 (colon cancer cell line), HUH-7 and SK-Hep-1 (hepatoma cell strain), LNCaP (prostate gland cancer cell strain), H-28 (mesothelioma cell strain) and SCC-1 (strain of head and neck squamous cancer cell) respectively; Results suggest; The pharmaceutical composition that the present invention contains apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative has significant cooperative effect aspect treatment colon cancer, hepatocarcinoma, carcinoma of prostate, mesothelioma and the head and neck squamous cell carcinoma; Improved the curative effect of medicine; Reduce dosage, reduced the generation of side effect.
The specific embodiment
Below in conjunction with concrete embodiment the present invention is done further elaboration, 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 (prostate gland cancer cell strain), H-28 (mesothelioma cell strain) and SCC-1 (strain of head and neck squamous cancer cell); All available from American Type Culture Collection (ATCC), Maryland, USA Rockwell.
Medicine: institute's pharmaceutical composition is all by following method 1 or 2 said preparations of method in following examples; Rubescensine A is available from the bright Bioisystech Co., Ltd of the Xi'an rising sun, 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 1-9 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 10-18 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 1-9 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, see table 2.
Table 2
Cause in the test of colon cancer cell line HCT-116 cell death at the investigation related compound, finding has 23% cell death approximately when using 20.0 μ M apigenins separately, use 15.0 μ M rubescensine A that 14% cell death is arranged approximately separately; (15.0 μ M apigenins+10.0 μ M rubescensine A) then produce the obvious synergistic effect when both share under low concentration, cause 57% cancer cell death; When both share with the ratio of 20.0 μ M apigenins+15.0 μ M rubescensine A, then produce significant more 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, see table 3.
Table 3
Cause in the test of hepatoma cell strain HUH-7 cell death at the investigation related compound, find almost acellular death when using 25.0 μ M apigenins separately, when using 15.0 μ M rubescensine A separately, also only less than 10% cell death; (15.0 μ M apigenins+10.0 μ M rubescensine A) then produce the obvious synergistic effect when both share under low concentration, cause 61% cancer cell death; When both share with the ratio of 25.0 μ M apigenins+15.0 μ M rubescensine A, then produce significant more 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, see table 4.
Table 4
Cause in the test of hepatoma cell strain SK-Hep-1 cell death at the investigation related compound, finding has the 10-15% cell death approximately when using 25.0 μ M apigenins separately or using 15.0 μ M rubescensine A separately; (20.0 μ M apigenins+10.0 μ M rubescensine A) then produce than the obvious synergistic effect when both share under low concentration, cause 43% cancer cell death; When both share with the ratio of 25.0 μ M apigenins+15.0 μ M rubescensine A, then produce significant more 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, see table 5.
Table 5
Cause in the test of prostate gland cancer cell strain LNCaP cell death at the investigation related compound, find almost acellular death when using 15.0 μ M rubescensine A separately, when using 25.0 μ M apigenins separately, also only less than 10% cell death; (20.0 μ M apigenins+10.0 μ M rubescensine A) then produce the obvious synergistic effect when both share under low concentration, cause 44% cancer cell death; When both share with the ratio of 25.0 μ M apigenins+15.0 μ M rubescensine A, then produce significant more 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, see table 6.
Table 6
Cause in the test of mesothelioma cell strain H-28 cell death at the investigation related compound, find almost acellular death when using 15.0 μ M rubescensine A separately, 20% cell death is arranged when using 20.0 μ M apigenins separately approximately; (15.0 μ M apigenins+10.0 μ M rubescensine A) then produce the obvious synergistic effect when both share under low concentration, cause 46% cancer cell death; When both share with the ratio of 20.0 μ M apigenins+15.0 μ M rubescensine A, then produce significant more synergism, cause about 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, see table 7.
Table 7
Cause in the test of head and neck squamous cancer cell strain SCC-1 cell death at the investigation related compound, finding has 15% cell death approximately when using 30.0 μ M apigenins separately or using 15.0 μ M rubescensine A separately; (20.0 μ M apigenins+10.0 μ M rubescensine A) then produce the obvious synergistic effect when both share under low concentration, cause 68% cancer cell death; When both share with the ratio of 30.0 μ M apigenins+15.0 μ M rubescensine A, then produce significant more synergism, cause 99% 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 (13)
1. a pharmaceutical composition is characterized in that, said compositions contains apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative.
2. pharmaceutical composition according to claim 1; It is characterized in that; The mol ratio of said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 5.0-60.0: 3.5-30.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 10.0-30.0: 7.5-15.0.
3. pharmaceutical composition according to claim 2 is characterized in that, said apigenin and apigenin analog derivative are apigenin; Said rubescensine A and Oridonin derivative are rubescensine A.
4. the application of each described pharmaceutical composition of claim 1-3 in the medicine of preparation treatment cancer.
5. application according to claim 4 is characterized in that, said cancer is 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.
6. application according to claim 5; 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 rubescensine A and Oridonin derivative is 12.5-20.0: 7.5-15.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-20.0: 10.0-15.0.
7. application according to claim 5 is characterized in that, in the application in the medicine of preparation treatment hepatocarcinoma, the mol ratio of said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 10.0-25.0: 7.5-15.0.
8. application according to claim 7 is characterized in that, said hepatocarcinoma is HUH-7 type hepatocarcinoma, and the mol ratio of said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-25.0: 10.0-15.0.
9. application according to claim 7; It is characterized in that; Said hepatocarcinoma is SK-Hep-1 type hepatocarcinoma; The mol ratio of said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-25.0: 7.5-15.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0-25.0: 10.0-15.0.
10. application according to claim 5; It is characterized in that; In the application in the medicine of preparation treatment carcinoma of prostate; The mol ratio of said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-25.0: 7.5-15.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0-25.0: 10.0-15.0.
11. application according to claim 5; It is characterized in that; In the application in the medicine of preparation treatment mesothelioma; The mol ratio of said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 12.5-20.0: 7.5-15.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-20.0: 10.0-15.0.
12. application according to claim 5; It is characterized in that; In the application in the medicine of preparation treatment head and neck squamous cell carcinoma; The mol ratio of said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 15.0-30.0: 7.5-15.0, and the mol ratio of preferred said apigenin and apigenin analog derivative and rubescensine A and Oridonin derivative is 20.0-30.0: 10.0-15.0.
13., it is characterized in that apigenin in the said pharmaceutical composition and apigenin analog derivative and rubescensine A and Oridonin derivative use or using in order with any priority simultaneously according to each described application of claim 4-12.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110080494.5A CN102688228B (en) | 2011-03-25 | 2011-03-25 | Pharmaceutical composition containing apigenin, apigenin derivative, rubescensin and rubescensin derivative, and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110080494.5A CN102688228B (en) | 2011-03-25 | 2011-03-25 | Pharmaceutical composition containing apigenin, apigenin derivative, rubescensin and rubescensin derivative, and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102688228A true CN102688228A (en) | 2012-09-26 |
| CN102688228B CN102688228B (en) | 2014-05-07 |
Family
ID=46854074
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110080494.5A Expired - Fee Related CN102688228B (en) | 2011-03-25 | 2011-03-25 | Pharmaceutical composition containing apigenin, apigenin derivative, rubescensin and rubescensin derivative, and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102688228B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014047780A1 (en) * | 2012-09-25 | 2014-04-03 | 鼎泓国际投资（香港）有限公司 | Pharmaceutical composition containing apigenin and apigenin derivative and oridonin and oridonin derivative and use thereof |
| 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 |
| CN115364109A (en) * | 2022-09-21 | 2022-11-22 | 黑龙江中医药大学 | Pharmaceutical preparation for treating lung cancer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1895244A (en) * | 2006-06-09 | 2007-01-17 | 江秉华 | Medicinal composition for preventing and treating cancer diseases |
| CN101953839A (en) * | 2010-10-19 | 2011-01-26 | 中国药科大学 | Compound medicinal composition with effect of resisting acute myeloid leukemia |
-
2011
- 2011-03-25 CN CN201110080494.5A patent/CN102688228B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1895244A (en) * | 2006-06-09 | 2007-01-17 | 江秉华 | Medicinal composition for preventing and treating cancer diseases |
| CN101953839A (en) * | 2010-10-19 | 2011-01-26 | 中国药科大学 | Compound medicinal composition with effect of resisting acute myeloid leukemia |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014047780A1 (en) * | 2012-09-25 | 2014-04-03 | 鼎泓国际投资（香港）有限公司 | Pharmaceutical composition containing apigenin and apigenin derivative and oridonin and oridonin derivative and use thereof |
| 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 |
| CN115364109A (en) * | 2022-09-21 | 2022-11-22 | 黑龙江中医药大学 | Pharmaceutical preparation for treating lung cancer |
| CN115364109B (en) * | 2022-09-21 | 2024-02-13 | 黑龙江中医药大学 | Pharmaceutical preparation for treating lung cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102688228B (en) | 2014-05-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103371991A (en) | Application of dimethyldiguanide in preparation of medicaments for preventing or treating hepatocellular carcinoma | |
| CN102552908B (en) | Pharmaceutical composition containing artemisinin, artemisinin derivatives and Bcl-2 inhibitor and application thereof | |
| CN102688493B (en) | Pharmaceutical composition containing resveratrol, resveratrol derivative and Bc1-2 inhibitor, and application thereof | |
| CN102441168B (en) | Medicine composition containing apigenin, apigenin derivant and Bc1-2 inhibitor and application thereof in preparation of medicines capable of treating cancer | |
| CN102688228B (en) | Pharmaceutical composition containing apigenin, apigenin derivative, rubescensin and rubescensin derivative, and application thereof | |
| CN102688489B (en) | Pharmaceutical composition containing triptolide, triptolide derivative and Bc1-2 inhibitor and application thereof | |
| CN101836989B (en) | Medicament composition containing tetrandrine, tetrandrine derivatives and histone deacetylase inhibitor and application thereof | |
| CN101940569B (en) | Medicament composition containing sorafenib, artemisinin and artemisinin derivative and application thereof in preparing medicament for treating cancer | |
| CN100443080C (en) | Medicinal composition for preventing and treating cancer diseases | |
| CN101837129A (en) | Medicament composition containing cMet inhibitor, HDAC (Histone Deacetylases) inhibitor and EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitor and application thereof | |
| CN106974908A (en) | Pharmaceutical composition and purposes containing hdac inhibitor and IRE1 inhibitor | |
| CN102441167B (en) | Pharmaceutical composition having apiolin and apiolin derivant as well as histone deaceylase inhibitors and application thereof | |
| CN108295085B (en) | Application of protodioscin in preparation of drug-resistant osteosarcoma drug | |
| CN101836991B (en) | Medicament composition containing sorafenib, cMet inhibitors and EGFR tyrosine kinase inhibitors and application thereof | |
| CN102688490B (en) | Pharmaceutical composition containing evodiamine, evodiamine derivative and Bc1-2 inhibitor, and the application | |
| CN102440987B (en) | Drug compound of apigenin, apigenin-like derivants, artemisinin and artemisinin-like derivants and application thereof | |
| CN113440519A (en) | Application of mycophenolic acid and derivatives thereof in preparation of drugs for targeted therapy of cancers | |
| CN101653607B (en) | Pharmaceutical composition containing hepatocyte growth factor receptor inhibitor and mitogen extracellular kinase inhibitor and application thereof | |
| CN101757626B (en) | Pharmaceutical composition containing insulin-like growth factor-I receptor inhibitor and histon deacetylase (HDAC) inhibitor and application thereof | |
| CN112618569A (en) | Medicine for treating urothelial cancer | |
| CN113209149A (en) | Application of mitoxantrone and total ginsenoside combined medicine in preparation of medicine for treating gastric cancer | |
| CN115089570B (en) | Pharmaceutical composition for treating tumors and preparation and application thereof | |
| CN103127510A (en) | Medicine composition containing hepatic cell growth factor receptor inhibitor and Bcl-2 inhibitor and application thereof | |
| CN109045052A (en) | For treating pharmaceutical formulation and the application of colon cancer | |
| CN115837051B (en) | Composite cordycepin preparation, preparation method thereof and application thereof in preparation of small cell lung cancer resistant products |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140507 Termination date: 20180325 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |