CN102397547B - Anti-cancer pharmaceutical composition - Google Patents
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Abstract
The invention relates to an anti-cancer pharmaceutical composition comprising arctigenin and a tyrosine kinase inhibitor. Compared to single-component medicines, the pharmaceutical composition provided by the invention has synergic anti-cancer activity in the aspect of non-small-cell lung carcinoma inhibiting. The invention also provides a micro emulsion preparation of the pharmaceutical composition.
Description
Technical field
The present invention relates to a kind of anticancer pharmaceutical composition, particularly a kind of pharmaceutical composition that contains aretigenin and tyrosine kinase inhibitor.
Background technology
Nonsmall-cell lung cancer is modal pulmonary carcinoma histological type, accounts for 85% left and right of pulmonary carcinoma.Nonsmall-cell lung cancer comprises again the several types such as squamous cell cancer, adenocarcinoma and large cell carcinoma, and the growth of cancer cells of non-small cell carcinoma is slow, and grade malignancy is relatively low, and it is more late that diffusion transfer occurs.The treatment of nonsmall-cell lung cancer mainly comprises surgical operation therapy, radiotherapy, chemotherapy, Chinese medicine and the novel method for the treatment of take molecular targeted therapy as representative clinically, but nonsmall-cell lung cancer is poor to the sensitivity of chemotherapy, radiotherapy, and seeking effective Therapeutic Method is the problem that current Treatment for Non-small Cell Lung is needed solution badly.
Aretigenin (arctigenin) belongs to Lignanoids compounds, has antibiotic, antiviral, antitumor, anti-paf receptor and calcium antagonistic activity significantly.Wang Lu etc. disclose at " Advance on Pharmacological Activities of arctiin and the sub-aglycon of Arctiin " (Chinese herbal medicine, the 39th the 3rd phase of volume,, 467-450 page in 2008) activity that aretigenin has anti-pulmonary carcinoma.Take 4-nitroquinoline-N-oxidant as initiator, bring out rat pulmonary carcinoma take glycerol as promoter, carry out the two-phase canceration test of rat pulmonary carcinoma, result shows that aretigenin has the activity of Chinese People's Anti-Japanese Military and Political College's Mus pulmonary carcinoma.But the document and other existing document do not disclose the activity that aretigenin has the treatment nonsmall-cell lung cancer.
Tyrosine kinase is the enzyme of one group of catalytic proteins tyrosine residue phosphorylation, and the phosphate group on energy catalysis ATP is transferred on many important tyrosine residues, makes its residue phosphorylation.Erlotinib is a kind of epidermal growth factor recipient tyrosine kinase inhibitor, transduces by the autophosphorylation Inhibitory signal that suppresses epidermal growth factor recipient tyrosine kinase, thus the propagation of inhibition tumor cell and activation.Gefitinib is a kind of orally active selectivity tyrosinase inhibitor, by with the extracellular ligand binding of ATP competitive binding, the activation process of blocking-up tryrosinase suppresses EGFR and activates, thereby suppress cell increment and angiogenesis, promote apoptosis of tumor cells.
Use clinically above-mentioned tyrosine kinase inhibitor all to have some common problems.At first, toxic and side effects is very large.Such as significant feel sick, vomiting or diarrhoea etc.Take Erlotinib as example, skin adverse reaction and digestive system disease etc. in various degree all can occur in the clinical user more than 50%.For a kind of medicine, the size of toxic and side effects is closely-related with the using dosage of this kind medicine.The oral dose of Erlotinib is 150mg/d, and the oral dose of gefitinib is 250mg/d, and the oral dose of imatinib mesylate is especially up to 400mg-600mg/d.Secondly, drug resistance is poor.The cancer therapy drug life-time service of high dose will certainly produce drug resistance.Take imatinib mesylate as example, long-term, high-dose is taken imatinib mesylate, can cause the point mutation in BCR-ABL protein kinases territory, causes imatinib affinity with it to descend, thereby produces the drug resistance of imatinib.When the chemotherapy drugs in combination of imatinib mesylate and high dose uses, the liver toxicity of a property crossed can occur, raise and hyperbilirubinemia as the transaminase.
The drug combination of cancer therapy drug is based on the drug resistance of single medicine generation and the consideration that reduces toxic and side effects, but be not the form that all cancer therapy drugs all are fit to take drug combination, select the drug combination overriding concern can promote curative effect of medication exactly the time reduce toxic and side effects.Giaccone G etc. are at " Gefitinib in combination with gemcitabine andcisplatin in advanced non-small-cell lung cancer:a phase III trial-INTACT 1 " (J Clin Oncol.Mar 1,2004vol.22no.5, the technical scheme of gefitinib, cisplatin and gemcitabine drug combination treatment advanced Non-small cell lung 777-784) is disclosed in a literary composition.Ulrich Gatzemeier etc. are at " Phase III Study of Erlotinib inCombination With Cisplatin and Gemcitabine in Advanced Non-Small-Cell Lung Cancer:TheTarceva Lung Cancer Investigation Trial " (JCO April 20,2007vol.25no.12,1545-1552) technical scheme that Erlotinib, cisplatin and gemcitabine drug combination are used for the treatment of advanced Non-small cell lung is disclosed in a literary composition.
The compound of selecting to unite use with tyrosine kinase inhibitor in numerous cancer therapy drugs is very necessary to obtaining to promote curative effect, make side effect be down to minimum work simultaneously, and difficulty is also sizable.
Summary of the invention
In order to reduce toxic and side effects, to improve tyrosine kinase inhibitor to the curative effect of nonsmall-cell lung cancer, the present invention unites use with aretigenin and tyrosine kinase inhibitor, obtained good expection, the invention provides a kind ofly to treatment nonsmall-cell lung cancer effectively pharmaceutical composition for this reason, contain following active component in this pharmaceutical composition:
(1) aretigenin; With
(2) tyrosine kinase inhibitor.
The present invention finds that aretigenin has certain therapeutic effect to the nonsmall-cell lung cancer of mice after separately gastric infusion is used for the treatment of the mice nonsmall-cell lung cancer respectively with aretigenin, tyrosine kinase inhibitor, compares with model group to have significant difference.The invention provides aretigenin in a kind of new application of field of medicaments, namely aretigenin can be used as the drug use for the treatment of nonsmall-cell lung cancer for this reason, and the effective dose that the independent gastric infusion of aretigenin is used for the treatment of nonsmall-cell lung cancer is 0.1-500mg/kg.
The present invention is used for the treatment of the aforementioned pharmaceutical compositions gastric infusion nonsmall-cell lung cancer of mice, contains aretigenin and tyrosine kinase inhibitor in this pharmaceutical composition, and the weight ratio of tyrosine kinase inhibitor and aretigenin is (0.005-100): 1.Above-mentioned tyrosine kinase inhibitor is gefitinib, imatinib mesylate or Erlotinib.Administration time and administration number of times need to be decided the diagnostic result of the state of an illness according to the doctor.To the therapeutic scheme of the nonsmall-cell lung cancer of mice be applied on the person, all medicines can convert by the effective dose of this medicine to mice to people's effective dose, and this is apparent for the person of ordinary skill of the art.
Preferably, in aforementioned pharmaceutical compositions, the weight ratio of gefitinib and aretigenin is (0.005-50): 1, this moment, compositions effect aspect the inhibition nonsmall-cell lung cancer of aretigenin and gefitinib was extremely remarkable, compare with individually dosed aretigenin or gefitinib, suppressing to have synergism aspect nonsmall-cell lung cancer.
Preferably, in aforementioned pharmaceutical compositions, the weight ratio of Erlotinib and aretigenin is (0.05-25): 1, this moment, compositions effect aspect the inhibition nonsmall-cell lung cancer of aretigenin and Erlotinib was extremely remarkable, compare with individually dosed aretigenin or Erlotinib, suppressing to have synergism aspect nonsmall-cell lung cancer.
Preferably, in aforementioned pharmaceutical compositions, the weight ratio of imatinib mesylate and aretigenin is (0.01-100): 1, this moment, compositions effect aspect the inhibition nonsmall-cell lung cancer of aretigenin and imatinib mesylate was extremely remarkable, compare with individually dosed aretigenin or imatinib mesylate, suppressing to have synergism aspect nonsmall-cell lung cancer.
In addition, the discovery that the inventor is surprised, the dosage of gefitinib, Erlotinib or imatinib mesylate height no matter, even in the situation that their drug dose is very low, this pharmaceutical composition to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth all very obviously, and be significantly higher than gefitinib, Erlotinib or the imatinib mesylate of the high dose of independent use.Aspect the reduction poisonous side effect of medicine, individually dosed tyrosine kinase inhibitor adverse reaction rate is generally greater than 50%, and after aretigenin associating tyrosine-kinase enzyme preparation, adverse reaction rate decreases, and compare with individually dosed group, drug combination group adverse reaction rate significantly reduces, this may have with the dosage of tyrosine kinase inhibitor very large relation, because drug combination has reduced the dosage of tyrosine kinase inhibitor.
In order better to express the form of this pharmaceutical composition, the present invention has prepared the microemulsion formulation of this pharmaceutical composition.Described microemulsion formulation can be prepared according to conventional preparation method, and the mean diameter of the microemulsion formulation of preparation is 15-80nm.Described ejection preparation can be prepared according to conventional formulation.The present invention has also studied the microemulsion formulation of pharmaceutical composition provided by the invention to people's lung cancer A549 cell transplanted tumor in nude mice affects on the growth, in microemulsion formulation, the weight ratio of tyrosine kinase inhibitor and aretigenin is (0.005-100): 1, adopt gastric infusion mode or drug administration by injection.More specifically, the weight ratio of gefitinib and aretigenin is (0.005-50): 1, the weight ratio of Erlotinib and aretigenin is (0.05-25): 1, the weight ratio of imatinib mesylate and aretigenin is (0.01-100): 1, result of the test has obtained unexpected effect, tumour inhibiting rate is all more than 90%, and suppressing to have good synergism aspect nonsmall-cell lung cancer.
In a word, pharmaceutical composition provided by the invention is compared with prior art, has following outstanding advantage:
The first, prior art mostly adopts the successively administration successively in order of two or more cancer therapy drugs, and the present invention is prepared into a kind of pharmaceutical preparation administration simultaneously with two kinds of cancer therapy drugs, greatly facilitates the patient to use, and has improved the compliance of disease treatment.
The second, to compare with single medicine or other drug combination, pharmaceutical composition provided by the invention has significant Synergistic anti-cancer effect aspect the treatment nonsmall-cell lung cancer.
The 3rd, this pharmaceutical composition has outstanding characteristics.Extract the aretigenin that obtains from the natural plants Fructus Arctii, toxicity is low, and in case be used in combination with gefitinib, Erlotinib or imatinib mesylate, under the prerequisite that guarantees stronger active anticancer, can significantly reduce the using dosage of gefitinib, Erlotinib or imatinib mesylate, reduce toxic and side effects, improve the drug resistance of cancer therapy drug.
The specific embodiment
Below further describe the present invention by the specific embodiment, the present invention is not limited only to following examples.
Embodiment 1 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 10g
Gefitinib 0.05g
Soybean oil 35g
Polyoxyethylene-23-lauryl ether 60g
1,2-PD 30g
Preparation technology: take recipe quantity soybean oil, polyoxyethylene-23-lauryl ether, 1, the 2-propylene glycol, stir after mixing, then add aretigenin, gefitinib dissolving, also can ultrasonic Treatment with accelerate dissolution, concentrated solution be must clarify, aretigenin and gefitinib microemulsion concentrate are.Laser granulometry is measured its particle diameter, and mean diameter is 15nm.
Embodiment 2 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 0.1g
Gefitinib 5g
Hydrogenation cocos nucifera oil glyceride 5g
Lauroyl Polyethylene Glycol-32-glyceride 20g
1,2-PD 5g
PEG3350 20g
Preparation technology: take recipe quantity hydrogenation cocos nucifera oil glyceride, lauroyl Polyethylene Glycol-32-glyceride, 1; 2-propylene glycol, PEG3350; stir after mixing; then add aretigenin, gefitinib dissolving; also can ultrasonic Treatment with accelerate dissolution; concentrated solution be must clarify, aretigenin and gefitinib microemulsion concentrate are.Laser granulometry is measured its particle diameter, and mean diameter is 40nm.
Embodiment 3 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 10g
Gefitinib 5g
Safflower oil 35g
Polyoxyethylene-23-lauryl ether 60g
1,2-PD 30g
Preparation technology is with embodiment 2.Laser granulometry is measured its particle diameter, and mean diameter is 36nm.
Embodiment 4 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 10g
Erlotinib 0.5g
Oleum Gossypii semen 30g
SY-Glyster MSW 750 55g
1,2-PD 25g
Preparation technology: take recipe quantity Oleum Gossypii semen, SY-Glyster MSW 750,1,2-PD, stir after mixing, then add aretigenin, Erlotinib dissolving, also can ultrasonic Treatment with accelerate dissolution, get the clarification concentrated solution, be the microemulsion concentrate of aretigenin and Erlotinib.Laser granulometry is measured its particle diameter, and mean diameter is 76nm.
Embodiment 5 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 2g
Erlotinib 2g
Soybean oil 30g
SY-Glyster MSW 750 55g
1,2-PD 25g
Preparation technology is with embodiment 4.Laser granulometry is measured its particle diameter, and mean diameter is 47nm.
Embodiment 6 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 1g
Erlotinib 25g
Soybean oil 30g
SY-Glyster MSW 750 55g
1,2-PD 25g
Preparation technology is with embodiment 4.Laser granulometry is measured its particle diameter, and mean diameter is 58nm.
Embodiment 7 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 10g
Imatinib mesylate 0.1g
Soybean oil 30g
SY-Glyster MSW 750 55g
1,2-PD 25g
Preparation technology: take recipe quantity soybean oil, SY-Glyster MSW 750,1, the 2-propylene glycol, stir after mixing, then add aretigenin, imatinib mesylate dissolving, also can ultrasonic Treatment with accelerate dissolution, must clarify concentrated solution, be the microemulsion concentrate of aretigenin and imatinib mesylate.Laser granulometry is measured its particle diameter, and mean diameter is 56nm.
Embodiment 8 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 2g
Imatinib mesylate 2g
Soybean oil 30g
SY-Glyster MSW 750 55g
1,2-PD 25g
Preparation technology is with embodiment 7.Laser granulometry is measured its particle diameter, and mean diameter is 39nm.
Embodiment 9 pharmaceutical composition microemulsion formulation of the present invention
Aretigenin 0.1g
Imatinib mesylate 10g
Soybean oil 30g
SY-Glyster MSW 750 55g
1,2-PD 25g
Preparation technology is with embodiment 7.Laser granulometry is measured its particle diameter, and mean diameter is 58nm.
Embodiment 10 pharmaceutical composition of the present invention is to people's lung cancer A549 cell transplanted tumor in nude mice affects on the growth
1 materials and methods
1.1 cell strain
Lung cancer cell line A549 cell strain is available from Wuhan University's Chinese Typical Representative culture collection center (Wuhan, China city).
1.2 medicine and reagent
The RPMI-1640 culture medium, Gibeo company product; Newborn calf serum, Hangzhou Sijiqing Biological Engineering Material Co., Ltd. produces; 0.25% trypsin, Sigma company produces.
1.3 people's pulmonary carcinoma transplanted tumor in nude mice treatment experiment
192 of SPF level BALB/c-nu mices, Nat'l Pharmaceutical ﹠ Biological Products Control Institute provides [SCXKII-00-0010], 6 ages in week, weight 16g-18g.The trophophase A549 cell of taking the logarithm, adjusting the A549 cell concentration with aseptic PBS is 3 * 10
7Individual/mL at BALB/c-nu mouse back subcutaneous vaccination A549 cell 0.1ml, treats that subcutaneous transplantation tumor volume reaches 75mm
3During the left and right (approximately l0d), be divided into 16 groups by tumor volume and mice with tumor body weight homeostatic principle, 12 every group.
Model control group: the normal saline of gastric infusion equivalent;
Aretigenin hangs down the amount group: gastric infusion 0.1mg/kgd aretigenin;
Amount group in aretigenin: gastric infusion 25mg/kgd aretigenin;
Aretigenin a large amount group: gastric infusion 100mg/kgd aretigenin;
Gefitinib group: gastric infusion 25mg/kgd
Erlotinib group: gastric infusion 25mg/kgd
Imatinib group: gastric infusion 25mg/kgd
Aretigenin+gefitinib A group: gastric infusion 0.1mg/kgd aretigenin+5mg/kgd gefitinib;
Aretigenin+gefitinib B group: gastric infusion 40mg/kgd aretigenin+40mg/kgd gefitinib;
Aretigenin+gefitinib C group: gastric infusion 100mg/kgd aretigenin+0.5mg/kgd gefitinib;
Aretigenin+Erlotinib A group: gastric infusion 0.1mg/kgd aretigenin+2.5mg/kgd Erlotinib;
Aretigenin+Erlotinib B group: gastric infusion 25mg/kgd aretigenin+25mg/kgd Erlotinib;
Aretigenin+Erlotinib C group: gastric infusion 100mg/kgd aretigenin+5mg/kgd Erlotinib;
Aretigenin+imatinib A group: gastric infusion 0.1mg/kgd aretigenin+10mg/kgd imatinib mesylate;
Aretigenin+imatinib B group: gastric infusion 70mg/kgd aretigenin+70mg/kgd imatinib mesylate;
Aretigenin+imatinib C group: gastric infusion 100mg/kgd aretigenin+1mg/kgd imatinib mesylate;
Administration every day 1 time amounts to 8 times, during administration every 4 days with the major diameter (L) of vernier caliper measurement transplanted tumor and minor axis (w).After last administration 48h, mice is put to death in dislocation, and excision transplanted tumor takes tumor heavy.Tumour inhibiting rate (%) IR=(1-experimental group tumor weight-average value/matched group tumor weight-average value) * 100%.The medicine that relatively embodies that weighs by tumor suppresses the tumor affects on the growth to people's lung cancer A549 cell nude mice.A situation arises to record untoward reaction, untoward reaction for vomiting, feel sick, diarrhoea, skin pruritus and edema, according to the time course for the treatment of, a situation arises especially to record the untoward reaction of common diarrhoea and edema, calculates adverse reaction rate.The number of animals of adverse reaction rate=appearance diarrhoea or edema/this experimental group animal number * 100%.
1.4 statistical procedures
(x ± s) expression adopts SPSS15.0 software to carry out variance analysis to data with mean ± standard deviation.
2 results
Result of the test shows (seeing Table 1):
(1) compare with model control group, each treatment group all has significant difference to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth.
(2) compare with gefitinib group, each single medicine group of aretigenin, the pharmaceutical composition of aretigenin and gefitinib has utmost point significant difference (p＜0.01) to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth, and has synergism.In addition, the discovery that we are surprised, the dosage of gefitinib height no matter, even in the situation that gefitinib dosage is very low, so long as aretigenin and gefitinib are united use, this pharmaceutical composition to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth all very obviously, and be significantly higher than the gefitinib of the high dose of independent use.
(3) compare with Erlotinib group, each single medicine group of aretigenin, the pharmaceutical composition of aretigenin and Erlotinib has utmost point significant difference (p＜0.01) to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth, and has synergism.In addition, the discovery that we are surprised, the dosage of Erlotinib height no matter, even in the situation that Erlotinib dosage is very low, so long as aretigenin and Erlotinib are united use, this pharmaceutical composition to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth all very obviously, and be significantly higher than the Erlotinib of the high dose of independent use.
(4) compare with imatinib mesylate group, each single medicine group of aretigenin, the pharmaceutical composition of aretigenin and imatinib mesylate has significant difference (p＜0.05) to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth, and has synergism.In addition, the discovery that we are surprised, the dosage of imatinib mesylate height no matter, even in the situation that imatinib mesylate dosage is very low, so long as aretigenin and imatinib mesylate are united use, this pharmaceutical composition to the inhibitory action of people's lung cancer A549 cell transplanted tumor in nude mice growth all very obviously, and be significantly higher than the imatinib mesylate of the high dose of independent use.
(5) individually dosed tyrosine kinase inhibitor adverse reaction rate is generally greater than 50%, and after aretigenin associating tyrosine-kinase enzyme preparation, adverse reaction rate decreases, and compare with individually dosed group, drug combination group adverse reaction rate significantly reduces, this may have with the dosage of tyrosine kinase inhibitor very large relation, because drug combination has reduced the dosage of tyrosine kinase inhibitor.
Table 1 pharmaceutical composition of the present invention is to people's lung cancer A549 cell transplanted tumor in nude mice affects on the growth
*Compare p＜0.05 with model control group;
*Compare p＜0.01 with model control group;
##Compare p＜0.01 with the gefitinib group;
$ $Compare p＜0.01 with the Erlotinib group;
﹠amp; ﹠amp;Compare p＜0.01 with the imatinib group;
﹠amp;Compare p＜0.05 with the imatinib group;
■ ■Compare p＜0.01 with the low amount group of aretigenin;
▲ ▲Compare p＜0.01 with amount group in aretigenin;
◆ ◆Compare p＜0.01 with aretigenin a large amount group.
Owing to having described the present invention by above embodiment, any to be equal to replacement be all apparent for the present invention and be included among the present invention.
Claims (1)
1. anticancer pharmaceutical composition is characterized in that it contains aretigenin and tyrosine kinase inhibitor, and wherein tyrosine kinase inhibitor is selected from imatinib mesylate, gefitinib or Erlotinib.
2. pharmaceutical composition as claimed in claim 1, is characterized in that the weight ratio of described tyrosine kinase inhibitor and aretigenin is (0.005-100): 1.
3. pharmaceutical composition as claimed in claim 1, is characterized in that the weight ratio of described imatinib mesylate and aretigenin is (0.01-100): 1.
4. pharmaceutical composition as claimed in claim 1, is characterized in that the weight ratio of described gefitinib and aretigenin is (0.005-50): 1.
5. pharmaceutical composition as claimed in claim 1, is characterized in that the weight ratio of described Erlotinib and aretigenin is (0.05-25): 1.
6. described pharmaceutical composition as arbitrary in claim 1-5, is characterized in that it is microemulsion formulation.
7. pharmaceutical composition as claimed in claim 6, the mean diameter that it is characterized in that described microemulsion formulation is 15-80nm.
8. the application of the arbitrary described pharmaceutical composition of claim 1-5 in preparation treatment non-small cell lung cancer drug.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102853689A CN102397547B (en) | 2010-09-19 | 2010-09-19 | Anti-cancer pharmaceutical composition |
| PCT/CN2011/079822 WO2012034540A1 (en) | 2010-09-19 | 2011-09-19 | Anti-tumor pharmaceutical composition |
| CN201180044842.1A CN103179967B (en) | 2010-09-19 | 2011-09-19 | Antineoplastic pharmaceutical compositions |
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| CN2010102853689A CN102397547B (en) | 2010-09-19 | 2010-09-19 | Anti-cancer pharmaceutical composition |
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| CN102397547B true CN102397547B (en) | 2013-06-12 |
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| CN201180044842.1A Active CN103179967B (en) | 2010-09-19 | 2011-09-19 | Antineoplastic pharmaceutical compositions |
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| WO2015156409A1 (en) * | 2014-04-10 | 2015-10-15 | クラシエ製薬株式会社 | Anticancer agent and side-effect-alleviating agent |
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| CN102397547B (en) * | 2010-09-19 | 2013-06-12 | 山东新时代药业有限公司 | Anti-cancer pharmaceutical composition |
| CN107412777B (en) * | 2017-08-08 | 2021-03-09 | 四川九章生物科技有限公司 | Anti-tumor combined medicine and application thereof in preparing anti-cancer medicine |
| CN108498575B (en) * | 2018-05-30 | 2021-06-22 | 南阳市中心医院 | Medicine for treating esophageal squamous carcinoma and preparation method thereof |
| CN111110685A (en) * | 2018-10-31 | 2020-05-08 | 正大天晴药业集团股份有限公司 | Pharmaceutical composition containing ibrutinib and application thereof |
| CN113491771A (en) * | 2020-03-18 | 2021-10-12 | 苏州大学 | Application of small molecular compound in preparation of GLUT5 inhibitor for uptake and transportation of fructose |
| CN114470216B (en) * | 2020-10-23 | 2024-08-06 | 和记黄埔医药（上海）有限公司 | Pharmaceutical combinations of multiple receptor tyrosine kinase inhibitors with chemotherapeutic agents and methods of use thereof |
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| CN101036643A (en) * | 2006-03-13 | 2007-09-19 | 海南盛科天然药物研究院有限公司 | Pharmaceutical composition containing arctigenin and preparation method |
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| CN102397547B (en) * | 2010-09-19 | 2013-06-12 | 山东新时代药业有限公司 | Anti-cancer pharmaceutical composition |
| CN102440986B (en) * | 2010-10-08 | 2014-12-03 | 鲁南制药集团股份有限公司 | Application of arctigenin in preparation of medicines for preventing and treating bone marrow suppression caused by radiation or chemicals |
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| CN101036643A (en) * | 2006-03-13 | 2007-09-19 | 海南盛科天然药物研究院有限公司 | Pharmaceutical composition containing arctigenin and preparation method |
Non-Patent Citations (2)
| Title |
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| 牛蒡子苷及牛蒡子苷元的药理作用研究进展;王潞等;《中草药》;20080331;第39卷(第3期);第467-470页 * |
| 王潞等.牛蒡子苷及牛蒡子苷元的药理作用研究进展.《中草药》.2008,第39卷(第3期), |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015156409A1 (en) * | 2014-04-10 | 2015-10-15 | クラシエ製薬株式会社 | Anticancer agent and side-effect-alleviating agent |
| JPWO2015156409A1 (en) * | 2014-04-10 | 2017-04-13 | クラシエ製薬株式会社 | Anticancer agent and side effect reducing agent |
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| Publication number | Publication date |
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| WO2012034540A1 (en) | 2012-03-22 |
| CN103179967A (en) | 2013-06-26 |
| CN102397547A (en) | 2012-04-04 |
| CN103179967B (en) | 2016-03-02 |
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