CN102688489B - Pharmaceutical composition containing triptolide, triptolide derivative and Bc1-2 inhibitor and application thereof - Google Patents
Pharmaceutical composition containing triptolide, triptolide derivative and Bc1-2 inhibitor and application thereof Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition containing triptolide, triptolide derivatives and a Bc1-2 inhibitor, and its applications in preparation of medicaments for treating colon cancer, liver cancer, lung cancer, kidney cancer, stomach cancer, brain tumor, sarcoma, neuroglioma, pancreatic cancer, ovarian cancer, breast cancer, or prostate cancer. The pharmaceutical composition of the invention has significant synergistic effect, can improve medicament curative effect, decrease administration dosage, and reduce the generation of side effect.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and the application in the medicine of preparation treatment cancer thereof, the pharmaceutical composition that is specifically related to contain triptolide and triptolide analog derivative and Bcl-2 inhibitor and the application in the medicine of preparation treatment colon cancer, hepatocarcinoma, pulmonary carcinoma, renal carcinoma, gastric cancer, cerebroma, sarcoma, glioma, cancer of pancreas, ovarian cancer, breast carcinoma or carcinoma of prostate thereof.
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 multiple Diseases In Pancreatic Head of being born in of cancer of pancreas, 90% derives from duct epithelial cells, all the other are from pancreatic acini, for the common malignant tumor of digestive system, sickness rate is ascendant trend year by year, due to onset concealment, lacks effective method of early diagnosis, while making a definite diagnosis, often reach an advanced stage or shift, 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; Glioma is to originate from neurogliocyte, betides neuroectodermal tumor, and its principal character is tumor cell diffuse infiltrating growth, without clear and definite border, infinite multiplication and have Highly invasive.Although in recent years neurosurgery skill constantly perfect, radiotherapy accurately locate and the continuous research and development of chemotherapeutics, patients with gliomas more after still barely satisfactory, the medicine of therefore studying glioma 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 apply to clinical with treatment cancer will have broad prospects.Along with the Study on Molecular Mechanism of the generation development to tumor is more and more clearer, molecular targeted therapy Several Kinds of Malignancy has been subject to paying close attention to widely and paying much attention to.Molecular targeted agents selectivity is high, wide spectrum is effective, and its safety is better than cytotoxicity chemotherapeutics, is the new direction of current therapeutic field of tumor development.
Triptolide (Triptolide) claim again Triptolide, it is isolated a kind of Diterpenoid epoxide class lactone compound from the plants such as Celastraceae Thunder God Calamus Radix Tripterygii Wilfordii, it is Radix Tripterygii Wilfordii main active, its antitumor mechanism may relate to multi-signal approach, comprise that to suppress cell proliferation, inducing apoptosis of tumour cell, inhibition tumor cell DNA synthetic and affect tumor vessel formation etc., there is stronger anti-tumor activity, and there is wide spectrum, the feature such as efficient.In addition, also have the multiple pharmacological effect such as antiinflammatory and immunosuppressant.
Apoptosis (program cell death) is the natural way that body is removed abnormal or unwanted cells, may cause various diseases as the generation of cancer if it is affected.Bcl-2 family protein is the important regulator of apoptosis, wherein Bcl-2 and Bcl-xL overexpression in polytype tumor, being considered to may be relevant with the generation of tumor, development and drug resistance generation, therefore become the study hotspot of antineoplaston in recent years for the drug development of Bcl-2 and Bcl-xL anti-apoptotic proteins.ABT-263 and ABT-737 are the micromolecule Bcl-2 inhibitor by Abbott Laboratories of the U.S. (Abbott) pharmacy exploitation, remarkable to kinds of tumors effect, and can orally use, and have a good application prospect.
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.But the biological behaviour of most of tumor is not arranged by single signal pathway, but multiple signal transduction pathway concurs, and Chinese medicine receives publicity just day by day with the Action advantage of the many target spots of its polygenes.Therefore rational drug combination, there is the incomparable superiority of alone medicine, drug combination carries out targeted therapy for many target spots and will not only be intended to reduce or delay appearance, the reduction toxicity of 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 pharmaceutical composition that contains triptolide and triptolide analog derivative and Bcl-2 inhibitor and the application in the medicine of preparation treatment colon cancer, hepatocarcinoma, pulmonary carcinoma, renal carcinoma, gastric cancer, cerebroma, sarcoma, glioma, cancer of pancreas, ovarian cancer, breast carcinoma or carcinoma of prostate thereof.
In the pharmaceutical composition that the present invention contains triptolide and triptolide analog derivative and Bcl-2 inhibitor, described triptolide and triptolide analog derivative are triptolide; Bcl-2 inhibitor can be ABT-263 or ABT-737, or both corresponding analogs, derivant.
Triptolide in pharmaceutical composition of the present invention and triptolide analog derivative are preferably triptolide, 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 triptolide medicine itself, can also be its pharmaceutically useful salt, hydrate or derivant etc.
In the present invention, described Bcl-2 inhibitor can be the medicine of the Bcl-2 inhibitor of any structure type, is preferably ABT-263 or ABT-737.Wherein ABT-263 is the compound shown in the formula II recording in US 2007027135:
Wherein ABT-737 is the compound shown in the formula III of recording in WO2005049594 and WO2005049593:
In pharmaceutical composition of the present invention, described component is not limited to above-mentioned ABT-263 and ABT-737 itself, can also be the salt of their hydrate, analog, derivant and other organic or inorganic.
In the pharmaceutical composition that the present invention contains triptolide and triptolide analog derivative and Bcl-2 inhibitor, the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.005-0.1: 0.15-4.0; Further preferably the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.01-0.05: 0.3-2.0.
The pharmaceutical composition that the present invention contains triptolide and triptolide analog derivative and Bcl-2 inhibitor can be used for the treatment of various tumors, and described tumor includes but not limited to colon cancer, hepatocarcinoma, pulmonary carcinoma, renal carcinoma, gastric cancer, cerebroma, sarcoma, glioma, cancer of pancreas, ovarian cancer, breast carcinoma or carcinoma of prostate.
The pharmaceutical composition of the preferred triptolide of the present invention and triptolide analog derivative and Bcl-2 inhibitor is for the preparation of the application in Hepatoma therapy, cancer of pancreas, colon cancer and gliomatous medicine.
In the application of pharmaceutical composition of the present invention in the medicine of preparing Hepatoma therapy, the mol ratio of triptolide and triptolide analog derivative and Bc l-2 inhibitor is 0.01-0.025: 0.5-2.0; Preferably the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.015-0.025: 1.5-2.0; Further preferably the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.025: 2.0.
In the application of pharmaceutical composition of the present invention in the medicine of preparation treatment cancer of pancreas, the mol ratio of described triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.02-0.05: 0.75-1.5; Preferably the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.025-0.05: 1.0-1.5; Further preferably the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.05: 1.5.
In the application of pharmaceutical composition of the present invention in the medicine of preparation treatment colon cancer, the mol ratio of described triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.015-0.03: 0.3-2.0.
In the time that described Bcl-2 inhibitor is ABT-263, the mol ratio of described triptolide and triptolide analog derivative and ABT-263 is 0.015-0.03: 0.3-1.0; Further the mol ratio of preferred described triptolide and triptolide analog derivative and ABT-263 is 0.02-0.03: 0.5-1.0; The best mol ratio for described triptolide and triptolide analog derivative and ABT-263 is 0.03: 1.0.
In the time that described Bcl-2 inhibitor is ABT-737, the mol ratio of described triptolide and triptolide analog derivative and ABT-737 is 0.015-0.03: 1.0-2.0; Further the mol ratio of preferred described triptolide and triptolide analog derivative and ABT-737 is 0.02-0.03: 1.5-2.0; The best mol ratio for described triptolide and triptolide analog derivative and ABT-737 is 0.03: 2.0.
In the application of pharmaceutical composition of the present invention in the gliomatous medicine of preparation treatment, the mol ratio of described triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.015-0.05: 0.5-2.0; Preferably the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.025-0.05: 1.5-2.0; Further preferably the mol ratio of triptolide and triptolide analog derivative and Bcl-2 inhibitor is 0.05: 2.0.
Contain triptolide and triptolide analog derivative and Bcl-2 inhibitor combination in preparation treatment colon cancer, hepatocarcinoma, pulmonary carcinoma, renal carcinoma, gastric cancer, cerebroma, sarcoma, glioma, cancer of pancreas, ovarian cancer, in the application of the medicine of breast carcinoma or carcinoma of prostate, in the scheme of medicament of the present composition being made to administration simultaneously, triptolide and triptolide analog derivative and Bcl-2 inhibitor can be contained in same pharmaceutical preparation as in tablet or capsule, also triptolide and triptolide analog derivative and Bcl-2 inhibitor 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 instruction of package insert simultaneously, in the scheme of medicament of the present composition being made to successively administration, triptolide and triptolide analog derivative and Bcl-2 inhibitor 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 instruction, 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, triptolide and triptolide analog derivative and Bcl-2 inhibitor 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 instruction, or this pharmaceutical composition is prepared into the controlled release preparation that triptolide and triptolide analog derivative and Bcl-2 inhibitor intersection discharge.
In the application in the medicine of preparation treatment colon cancer, hepatocarcinoma, pulmonary carcinoma, renal carcinoma, gastric cancer, cerebroma, sarcoma, glioma, cancer of pancreas, ovarian cancer, breast carcinoma or carcinoma of prostate of triptolide and triptolide analog derivative and Bcl-2 inhibitor combination, triptolide in described compositions and triptolide analog derivative and Bcl-2 inhibitor can use or with the using in order of any priority simultaneously, as triptolide and triptolide analog derivative and Bcl-2 inhibitor can taken to patient simultaneously; Also can first Bcl-2 inhibitor be taken, then be taken to triptolide and triptolide analog derivative medicine to patient, or first take Bcl-2 inhibitor, then take triptolide and triptolide analog 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 triptolide of the present invention and triptolide analog derivative and Bcl-2 inhibitor 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 triptolide and triptolide analog derivative and Bcl-2 inhibitor, its dosage form can be conventional tablet or capsule or controlled release, slow releasing preparation.In the pharmaceutical preparation of triptolide of the present invention and triptolide analog derivative and Bcl-2 inhibitor combination, according to different dosage forms and preparation specification, the content of described compositions in preparation can be counted 1-99% for quality, is preferably 10%-90%; The adjuvant that preparation uses can adopt the adjuvant of this area routine, taking the present composition of getting along well react or the curative effect that do not affect medicine of the present invention as 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 is not particularly limited, triptolide and triptolide analog derivative and Bcl-2 inhibitor 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 to ensure that this pharmaceutical composition can reach effective blood drug level as prerequisite in mammalian body.
The present invention has carried out respectively triptolide and triptolide analog derivative and Bcl-2 inhibitor and has combined the test of killing HUH-7 (hepatoma cell strain), E3LZ10 (pancreas cancer cell strain), DLD1 (colon cancer cell line) and U251 (neuroglial cytoma strain), result shows, triptolide of the present invention and triptolide analog derivative and Bcl-2 inhibitor combined therapy pulmonary carcinoma and hepatocarcinoma have significant cooperative effect, improve the curative effect of medicine, reduce dosage, reduced the generation of side effect.
Detailed description of the invention
The invention will be further elaborated with the following Examples, but the present invention is not limited to this.
Embodiment
Reagent and method:
Cell: HUH-7 (hepatoma cell strain), E3LZ10 (pancreas cancer cell strain), DLD1 (colon cancer cell line) and U251 (neuroglial cytoma strain) are 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; Triptolide is purchased from Nanjing Zelang Pharmaceutical Technology Inc.; Bcl-2 inhibitor is all synthesized into by document, and ABT-263 and ABT-737 synthesized reference document are: Synthesis, 15,2398-2404, WO2005049594, WO2005049593 and US 2007027135.
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 DEG C, preserve, when use, be diluted to suitable concentration by fresh culture medium, the solution of each component of 1 microlitre of then respectively asking for, mixes for subsequent use.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 the RPMI1640 culture medium containing 10% calf serum, 100kU/L penicillin, 100mg/L streptomycin, 37 DEG C, 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 adds the medicinal composition solution of preparation as stated above in cell, makes each component reach its working concentration, specifically in 1-9 in table 1.
After drug treating, measure cell death by trypan blue (Trypan Blue), cell turns into 10 minutes by carrying out pancreatin at 37 DEG C 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, count with optical microscope and hematimeter.By the dead cell of counting of dyes au bleu.Choose at random 500 cells and count, dead cell is recently expressed with the percentage that accounts for 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 DEG C.When use, be diluted to suitable concentration by fresh culture medium, 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 DEG C, 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 adds each component solution of the pharmaceutical composition of preparation as stated above with any order in cell, makes each component reach its working concentration, specifically in 10-15 in table 1.
After drug treating, measure cell death by trypan blue (Trypan Blue), cell turns into 10 minutes by carrying out pancreatin at 37 DEG C 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, count with optical microscope and hematimeter.By the dead cell of counting of dyes au bleu.Choose at random 500 cells and count, dead cell is recently expressed with the percentage that accounts for grand total cell.
In drug regimen shown in lower list 1, the combination of 1-9 is prepared by method 1, and the combination of 10-15 is prepared by method 2.
Table 1
The triptolide of embodiment 1 different proportion and the combination Synergistic of ABT-263 promote the test of HUH-7 cell death, in table 2.
Table 2
Cause in the test of hepatoma cell strain HUH-7 cell death at investigation related compound, 10% the cell death of finding only to have an appointment in the time of independent use 0.015 μ M triptolide, 2.0 μ MABT-263 or lower concentration, even if also only have an appointment 20% cell death while using separately 0.025 μ M triptolide; In the time that both share under low concentration, (0.015 μ M triptolide+1.5 μ MABT-263) produces obvious synergism, causes 34% cancer cell death; In the time that both share with the ratio of 0.025 μ M triptolide+2.0 μ MABT-263, produce more significant synergism, cause 90% cancer cell death.
The triptolide of embodiment 2 different proportions and the combination Synergistic of ABT-263 promote the test of E3LZ10 cell death, in table 3.
Table 3
Cause in the test of pancreas cancer cell strain E3LZ10 cell death at investigation related compound, find when using separately only have an appointment 15% cell death of 0.05 μ M triptolide the cell death less than 10% only while using separately 1.5 μ MABT-263 or lower concentration; In the time that both share under low concentration, (0.025 μ M triptolide+1.0 μ MABT-263) produces obvious synergism, causes 31% cancer cell death; In the time that both share with the ratio of 0.05 μ M triptolide+1.5 μ MABT-263, produce more significant synergism, cause 83% cancer cell death.
The triptolide of embodiment 3 different proportions and the combination Synergistic of ABT-263 promote the test of DLD1 cell death, in table 4.
Table 4
Cause in the test of colon cancer cell line DLD1 cell death at investigation related compound, find when using separately 0.03 μ M triptolide or 1.0 μ M ABT-263 approximately to have 15% cell death; In the time that both share under low concentration, (0.02 μ M triptolide+0.5 μ MABT-263) produces obvious synergism, causes 30% cancer cell death; In the time that both share with the ratio of 0.03 μ M triptolide+1.0 μ M ABT-263, produce more significant synergism, cause 79% cancer cell death.
The triptolide of embodiment 4 different proportions and the combination Synergistic of ABT-737 promote the test of DLD1 cell death, in table 5.
Table 5
Cause in the test of colon cancer cell line DLD1 cell death at investigation related compound, find when using separately 0.03 μ M triptolide or 2.0 μ M ABT-737 approximately to have 15% cell death; In the time that both share under low concentration, (0.02 μ M triptolide+1.5 μ M ABT-737) produces obvious synergism, causes 22% cancer cell death; In the time that both share with the ratio of 0.03 μ M triptolide+2.0 μ MABT-737, produce more significant synergism, cause 69% cancer cell death.
The triptolide of embodiment 5 different proportions and the combination Synergistic of ABT-263 promote the test of U251 cell death, in table 6.
Table 6
Cause in the test of neuroglial cytoma strain U251 cell death at investigation related compound, find when using separately 0.05 μ M triptolide or 2.0 μ MABT-263 approximately to have 23% cell death; In the time that both share under low concentration, (0.025 μ M triptolide+1.5 μ MABT-263) produces obvious synergism, causes 43% cancer cell death; In the time that both share with the ratio of 0.05 μ M triptolide+2.0 μ MABT-263, produce more significant synergism, cause 84% 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 (11)
1. a pharmaceutical composition that is used for the treatment of cancer, is characterized in that, described pharmaceutical composition contains triptolide and Bcl-2 inhibitor, and wherein, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.01-0.05:0.3-2.0; Described Bcl-2 inhibitor is ABT-263 or ABT-737; Described cancer is colon cancer, hepatocarcinoma, glioma or cancer of pancreas.
2. pharmaceutical composition according to claim 1, is characterized in that, in the pharmaceutical composition that is used for the treatment of hepatocarcinoma, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.01-0.025:0.5-2.0.
3. pharmaceutical composition according to claim 2, is characterized in that, in the pharmaceutical composition that is used for the treatment of hepatocarcinoma, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.015-0.025:1.5-2.0.
4. pharmaceutical composition according to claim 1, is characterized in that, in the pharmaceutical composition that is used for the treatment of cancer of pancreas, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.02-0.05:0.75-1.5.
5. pharmaceutical composition according to claim 4, is characterized in that, in the pharmaceutical composition that is used for the treatment of cancer of pancreas, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.025-0.05:1.0-1.5.
6. pharmaceutical composition according to claim 1, is characterized in that, in the pharmaceutical composition that is used for the treatment of colon cancer, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.015-0.03:0.3-2.0.
7. pharmaceutical composition according to claim 6, is characterized in that, in the time that described Bcl-2 inhibitor is ABT-263, the mol ratio of described triptolide and ABT-263 inhibitor is 0.015-0.03:0.3-1.0;
In the time that described Bcl-2 inhibitor is ABT-737, the mol ratio of described triptolide and ABT-737 inhibitor is 0.015-0.03:1.0-2.0.
8. pharmaceutical composition according to claim 7, is characterized in that, in the time that described Bcl-2 inhibitor is ABT-263, the mol ratio of described triptolide and ABT-263 is 0.02-0.03:0.5-1.0.
9. pharmaceutical composition according to claim 7, is characterized in that, in the time that described Bcl-2 inhibitor is ABT-737, the mol ratio of described triptolide and ABT-737 is 0.02-0.03:1.5-2.0.
10. pharmaceutical composition according to claim 1, is characterized in that, being used for the treatment of in gliomatous pharmaceutical composition, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.015-0.05:0.5-2.0.
11. pharmaceutical compositions according to claim 10, is characterized in that, the mol ratio of described triptolide and Bcl-2 inhibitor is 0.025-0.05:1.5-2.0.
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| WO2015085447A1 (en) * | 2013-12-11 | 2015-06-18 | 香港浸会大学 | New triptolide derivatives and preparation method and use thereof |
| CN107041875B (en) * | 2017-02-28 | 2019-12-13 | 嘉兴学院 | Fibroin nanoparticles and application thereof |
| CN115364109B (en) * | 2022-09-21 | 2024-02-13 | 黑龙江中医药大学 | Pharmaceutical preparation for treating lung cancer |
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Non-Patent Citations (4)
| Title |
|---|
| 李瀚旻等.雷公藤甲素对人肝癌Bel-7402细胞增殖及凋亡的影响.《中华中医药学刊》.2009,(第01期), |
| 蛋白-蛋白相互作用小分子抑制剂研究进展;闵鉴等;《有机化学》;20101231;第30卷(第11期);1778-1789 * |
| 闵鉴等.蛋白-蛋白相互作用小分子抑制剂研究进展.《有机化学》.2010,第30卷(第11期),第 1778～1789页. |
| 雷公藤甲素对人肝癌Bel-7402细胞增殖及凋亡的影响;李瀚旻等;《中华中医药学刊》;20090110(第01期);8-10 * |
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