CN103948627B - For treating the pharmaceutical composition of small cell carcinoma - Google Patents
For treating the pharmaceutical composition of small cell carcinoma Download PDFInfo
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- CN103948627B CN103948627B CN201410170787.6A CN201410170787A CN103948627B CN 103948627 B CN103948627 B CN 103948627B CN 201410170787 A CN201410170787 A CN 201410170787A CN 103948627 B CN103948627 B CN 103948627B
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
- 208000000649 Small Cell Carcinoma Diseases 0.000 title description 4
- YLRXAIKMLINXQY-ZDUSSCGKSA-O Magnoflorine Chemical compound C1=C(OC)C(O)=C2C3=C(O)C(OC)=CC=C3C[C@@H]3[N+](C)(C)CCC1=C23 YLRXAIKMLINXQY-ZDUSSCGKSA-O 0.000 claims abstract description 34
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 claims abstract description 28
- 229960004316 cisplatin Drugs 0.000 claims abstract description 16
- LXZZYRPGZAFOLE-UHFFFAOYSA-L transplatin Chemical compound [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H] LXZZYRPGZAFOLE-UHFFFAOYSA-L 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 14
- 208000000587 Small Cell Lung Carcinoma Diseases 0.000 claims abstract description 12
- 206010041067 Small cell lung cancer Diseases 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 30
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract description 10
- 230000001629 suppression Effects 0.000 abstract description 6
- 210000004881 tumor cells Anatomy 0.000 abstract description 4
- 230000004663 cell proliferation Effects 0.000 abstract description 3
- 210000004027 cells Anatomy 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 4
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 229940079593 drugs Drugs 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 230000003042 antagnostic Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000012531 culture fluid Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000001225 therapeutic Effects 0.000 description 3
- 210000000170 Cell Membrane Anatomy 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 206010025482 Malaise Diseases 0.000 description 2
- 210000000115 Thoracic Cavity Anatomy 0.000 description 2
- 230000000202 analgesic Effects 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 201000009030 carcinoma Diseases 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000002107 myocardial Effects 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000004083 survival Effects 0.000 description 2
- 230000002195 synergetic Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920000160 (ribonucleotides)n+m Polymers 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N 289-95-2 Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 229940100198 ALKYLATING AGENTS Drugs 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- 108009000097 DNA Replication Proteins 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000033147 ERVK-25 Human genes 0.000 description 1
- 241000417413 Gentiana cephalantha Species 0.000 description 1
- 210000001165 Lymph Nodes Anatomy 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 210000001370 Mediastinum Anatomy 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010025310 Other lymphomas Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 108091005771 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 239000007759 RPMI Media 1640 Substances 0.000 description 1
- 241000218201 Ranunculaceae Species 0.000 description 1
- 229940105648 Soma Drugs 0.000 description 1
- 210000001550 Testis Anatomy 0.000 description 1
- 241000468460 Thalictrum aquilegiifolium Species 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000003509 anti-fertility Effects 0.000 description 1
- 230000003110 anti-inflammatory Effects 0.000 description 1
- 230000000702 anti-platelet Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000001588 bifunctional Effects 0.000 description 1
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- 125000001309 chloro group Chemical group Cl* 0.000 description 1
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- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
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- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-O hydron;2H-tetrazole Chemical compound C1=NN=[NH+]N1 KJUGUADJHNHALS-UHFFFAOYSA-O 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
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- 230000014616 translation Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Abstract
The invention belongs to field of medicaments, relate to the compositions suppressing tumor cell proliferation.The present invention provides one to treat pulmonary carcinoma, especially the pharmaceutical composition of small cell lung cancer, particularly relates to the pharmaceutical composition being made up of cisplatin, magnoflorine with puerarin.In above-mentioned composition, cisplatin, magnoflorine are 10:0.5～5:0.5～5 with the weight ratio of puerarin, preferably 10:1.5～3.5:0.5～1.5, more preferably 10:2:1.
Description
Technical field
The invention belongs to field of medicaments, relate to the compositions suppressing tumor cell proliferation.
Background technology
In recent years, the sickness rate of pulmonary carcinoma, primary hepatocarcinoma, colorectal cancer, gynecologic malignant tumor etc. rises year by year, it has also become the modal malignant tumor of serious harm human health, brings many constant to our society, economy, life.
Pulmonary carcinoma is the higher tumor of current sickness rate, small cell lung cancer (SCLC) is a undifferentiated carcinoma typing of pulmonary carcinoma, ratio about 20～25% shared in pulmonary carcinoma, and small cell lung cancer is divided into Limited-stage and extensive phase, being the extensive phase during most of diagnosis of small cell lung cancer, Limited-stage at most accounts for 1/3.Treatment small cell lung cancer method is mainly chemotherapy at present, and medicine is the DNA synthetic inhibitor of little molecule, the inhibitor of protease and the inhibitor of cell cycle mostly, and these drug toxicitys are high, and poor specificity also kills normal tissue cell while killing tumor cell.When diagnosis, the SCLC patient of about 30% is limited in the tumor of homonymy thoracic cavity, mediastinum and supraclavicular lymph nodes by having, and it is appointed as limited disease.Initially, chemotherapy will be responded by the 70-90% in these patients, but relapse rate is high (75-90%).In the range of 14 to 20 months and two annual survival rates are 40% to suffer from the Median survival time of patient of limited disease.Even if the patient applying X-ray therapy, the most only 6-15% in thoracic cavity and head was survived more than 5 years.
Cis diamino dichloro network platinum (cisplatin) is the heavy metal complex that center combines with two chlorine atoms and two amino molecules with bivalence platinum, is similar to bifunctional alkylating agents, can suppress the reproduction process of DNA.RNA and protein synthesis is suppressed during its high concentration.This product, to anoxic cell effect, may diffuse through charged cell membrane after entering human body.It is now recognized that its Main Function position is at the purine of DNA and pyrimidine bases.It belongs to cell cycle nonspecific agent (CCNSA), has cytotoxicity, can the DNA replication dna process of anticancer, and damage structure on its cell membrane, have stronger broad spectrum anticancer effect.It is clinically used for the multiple entity tumors such as ovarian cancer, carcinoma of prostate, carcinoma of testis, pulmonary carcinoma, nasopharyngeal carcinoma, esophageal carcinoma, malignant lymphoma, G. cephalantha, thyroid carcinoma and osteogenic sarcoma and all can show curative effect.
Magnoflorine is also known as thalictrine, magnoflorine, Magnoflorine etc., and it is naturally occurring in the root street plant of ranunculaceae plant thick fruit Thalictrum aquilegifolium L. var. sibiricum Regel, chemically synthesizes and prepare.It has the effects such as antiinflammatory, blood pressure lowering, antifertility.Concrete structure sees below formula:
Puerarin is present in leguminous plant Radix Puerariae etc., and it is yellow crystal, is dissolved in water, methanol, ethanol, pyridine, is soluble in hot water, is insoluble in benzene, chloroform, ether etc..Modern pharmacology shows that it has raising immunity, strengthens myocardial contraction, protecting myocardial cell, reduces blood pressure, has the effects such as antiplatelet aggregation；Concrete structure sees following formula:
At present, in lung cancer therapy, cisplatin is common chemotherapeutics, but it is bringing preferable curative effect simultaneously, inevitably brings more serious side effect, and cancerous cell can be caused after the treatment of certain time to tolerate it, thus affect therapeutic effect.Therefore, finding the Synergistic compositions of excellent effect, thus reduce conventional chemotherapeutic drugs usage amount, strengthen its therapeutic effect and reduce the cancerous cell purpose to its drug resistance, each medical worker is dreamed of.
Summary of the invention
It is an object of the invention to provide one and treat pulmonary carcinoma, especially the pharmaceutical composition of small cell lung cancer, particularly relate to the pharmaceutical composition being made up of with puerarin cisplatin, magnoflorine.
In above-mentioned composition, cisplatin, magnoflorine are 10:0.5～5:0.5～5 with the weight ratio of puerarin, preferably 10:1.5～3.5:0.5～1.5, more preferably 10:2:1.
It is a further object to provide the application in preparation treatment small cell lung cancer of the described compositions.
In medical usage described above, aforementioned pharmaceutical compositions can be prepared as suitable pharmaceutical preparation to facilitate medication according to the animal state of an illness and agents area, depending on needing according to the concrete diagnostic result of the state of an illness for the administration time of analgesic of the present invention pharmaceutical composition and administration number of times, this is within the technical scope that those skilled in the art grasp.Such as, will be applied to mice analgesic therapeutic scheme on the person, the effective dose of mice can be converted by all medicines by the effective dose of people by this medicine, and this is apparent from for the person of ordinary skill of the art.
Synergism between the medicine of the present invention refers to the biological effect after the combination of each component, compared with the content required by the biological effect given based on expectation generation when being used alone single component, above-mentioned composition can obtain this biological effect by using lesser amount of component, that is the activity of compositions creates synergism apparently higher than between the synergistic effect of single component, i.e. medicine.The pharmaceutical composition of the present invention, in the weight ratio of the present invention, shows obvious synergism in terms of suppression small cell carcinoma.
Detailed description of the invention
To further describe the present invention below in detail.It is pointed out that following description is only the illustration to claimed technical scheme, the not any restriction to these technical schemes.The content that protection scope of the present invention is recorded with appended claims is as the criterion.
Embodiment
1
The synergism that pharmaceutical composition of the present invention suppresses in human tumor cell line growth in vitro
By human small cell lung carcinoma cell strain (NCIH446) cell suspension little containing 10%() in the cell culture fluid of fetal bovine serum, with 5 × 103/ hole is seeded in 96 porocyte culture plates.After 24 hours of incubation, it is separately added into cisplatin, magnoflorine, puerarin or three's compositions to add in culture fluid than mixing with variable concentrations.Make MTT after cultivating 72 hours to measure.Dye by tetrazolium (MTT) method and calculate alone and combination time cell proliferation suppression ratio.The weight proportion of compositions is as follows:
| Weight ratio | Cisplatin | Magnoflorine | Puerarin |
| Compositions 1 | 10 | 0.5 | 0.5 |
| Compositions 2 | 10 | 1.5 | 0.5 |
| Compositions 3 | 10 | 2 | 1 |
| Comparative example 1 | 10 | 2 | |
| Comparative example 2 | 10 | 1 |
Whether having collaborative, addition or antagonism according to T.C. Chou at the specific pharmaceutical composition of standard places that its technical papers proposes, described paper publishing is at magazine Pharmacological
Reviews, Volume 58, pages
In 621-681 (2006).Described multicomponent synergism utilizes equation below to calculate:
A/Ae+B/Be+C/Ce+D/De=CI
A, B, C and D refer to the dosage of Chinese medicine monomer compositions, Ae, Be, Ce and De refer to the dosage of the single component individually using single Chinese medicine monomer to reach needed for the suppression ratio of monomer composition, when X value is less than 1, illustrating that component has synergism, when X value is equal to 1 or more than 1, explanation component has equivalence or antagonism.Data analysis is carried out by CalcuSyn statistical software and drug combination exponential quantity (CI) method.When CI is < when 1, for synergism, during CI=1, for summation action；During CI > 1, for antagonism.Concrete outcome see table:
Medicine is alone and effect to NCIH446 cell strain is used in combination
| Drug level ( mg/L ) | Inhibitory rate of cell growth ( % ) | CI Value |
| Cisplatin ( 2mg ) | 32.4±0.3 | |
| Cisplatin ( 4mg ) | 43.5±0.8 | |
| Cisplatin ( 8mg ) | 62.1±0.7 | |
| Magnoflorine ( 2mg ) | 12.3±0.5 | |
| Magnoflorine ( 4mg ) | 18.4±0.6 | |
| Magnoflorine ( 8mg ) | 33.2±1.0 | |
| Puerarin ( 2mg ) | 1.8±0.3 | |
| Puerarin ( 4mg ) | 2.1±0.2 | |
| Puerarin ( 8mg ) | 3.2±0.3 | |
| Compositions 1 ( 4mg ) | 65.4±1.9 | 0.36 |
| Compositions 1 ( 8mg ) | 88.6±2.4 | 0.12 |
| Compositions 2 ( 4mg ) | 68.3±3.1 | 0.29 |
| Compositions 2 ( 8mg ) | 90.2±1.5 | 0.11 |
| Compositions 3 ( 4mg ) | 75.2±2.3 | 0.08 |
| Compositions 3 ( 8mg ) | 95.3±2.2 | 0.05 |
| Comparative example 1 ( 8mg ) | 63.2±2.7 | 0.87 |
| Comparative example 2 ( 8mg ) | 62.5±3.3 | 0.92 |
Embodiment
2
People small cell carcinoma cell strain NCIH446 is placed in the RPMI-1640 culture fluid containing 10% hyclone at 37 DEG C, 5%CO2Under conditions of cultivate.By being in the NCIH446 cell of exponential phase after digestion, collect counting, every BALB/C nu/nu right butt leather of strain nude mice once injects 1 × 107Individual NCIH446 cell, total amount of liquid 0.2ml, nude inoculation lung carcinoma cell starts after one week to be administered (often group 15), lumbar injection every day 1 time, continuous 1 week.After last is administered, de-cervical vertebra puts to death animal, takes tumor soma, and scales/electronic balance weighing tumor mass, by following equation calculating tumour inhibiting rate: tumour inhibiting rate=(animal drinking water group average tumor weight-experimental group average tumor weight)/model group average tumor weight × 100%.
Concrete outcome is as follows:
| Dosage ( mg/kg ) | Tumour inhibiting rate ( % ) | Dead number |
| Cisplatin ( 2mg/kg ) | 47.2 | 3 |
| Magnoflorine ( 2mg/kg ) | 17.6 | 3 |
| Puerarin ( 2mg/kg ) | 2.3 | 2 |
| Compositions 1 ( 2mg/kg ) | 69.3 | 0 |
| Compositions 2 ( 2mg/kg ) | 71.8 | 0 |
| Compositions 3 ( 2mg/kg ) | 89.6 | 0 |
| Comparative example 1 ( 2mg/kg ) | 55.8 | 2 |
| Comparative example 2 ( 2mg/kg ) | 58.5 | 2 |
Embodiment
3
Use the method study group compound of similar embodiment 1 on the lung cancer cell types/DDP(of cisplatin resistance purchased from Rui Lu bio tech ltd, Shanghai) impact, concrete outcome is as follows:
| Drug level ( mg/L ) | Inhibitory rate of cell growth ( % ) |
| Cisplatin ( 8mg ) | 13.2±0.8 |
| Magnoflorine ( 8mg ) | 27.2±1.4 |
| Puerarin ( 8mg ) | 2.5±0.4 |
| Compositions 1 ( 8mg ) | 79.2±3.1 |
| Compositions 2 ( 8mg ) | 88.5±1.9 |
| Compositions 3 ( 8mg ) | 92.8±3.2 |
| Comparative example 1 ( 8mg ) | 44.2±2.4 |
| Comparative example 2 ( 8mg ) | 42.5±3.5 |
Present invention merely illustrates some claimed specific embodiments; technical characteristic described in one of them or more technical scheme can be combined with arbitrary one or more technical schemes; the technical scheme that these are combined and obtain is also in the application protection domain, technical scheme that is combined just as these and that obtain specifically is recorded in the disclosure of invention.
Claims (2)
1., for treating a pharmaceutical composition for small cell lung cancer, it is made up of cisplatin, magnoflorine and puerarin；Cisplatin, magnoflorine are 10:2:1 with the weight ratio of puerarin.
Pharmaceutical composition the most according to claim 1 is applied in preparation treatment small cell lung cancer medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410170787.6A CN103948627B (en) | 2014-04-27 | For treating the pharmaceutical composition of small cell carcinoma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410170787.6A CN103948627B (en) | 2014-04-27 | For treating the pharmaceutical composition of small cell carcinoma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103948627A CN103948627A (en) | 2014-07-30 |
| CN103948627B true CN103948627B (en) | 2016-11-30 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005012507A1 (en) * | 2003-07-25 | 2005-02-10 | The University Of Melbourne | Production of plant secondary metabolites using adsorption and elicitation in cell suspension culture |
| CN103585237A (en) * | 2013-10-31 | 2014-02-19 | 济南星懿医药技术有限公司 | Application of Berberis fruit extract in preparation of anticancer drugs |
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005012507A1 (en) * | 2003-07-25 | 2005-02-10 | The University Of Melbourne | Production of plant secondary metabolites using adsorption and elicitation in cell suspension culture |
| CN103585237A (en) * | 2013-10-31 | 2014-02-19 | 济南星懿医药技术有限公司 | Application of Berberis fruit extract in preparation of anticancer drugs |
Non-Patent Citations (2)
| Title |
|---|
| 唐松草属植物抗癌有效成分研究进展;陈琪等;《中山大学研究生学刊(自然科学版)》;20001231;第21卷(第2期);第47-50页，第48页第2、7、8段，第49页第1段 * |
| 顺铂联合葛根素纯品和葛根粗提物对H446细胞增殖及Bax、Bcl-2蛋白表达的影响;韩萍等;《郑州大学学报(医学版)》;20100531;第45卷(第3期);第477-480页，第478页左栏第1段，第480页左栏第1-2段 * |
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Inventor after: Wang Xiaoyan Inventor after: Li Jiantian Inventor after: Liu Donglei Inventor after: Xing Zhiyuan Inventor after: Wang Zhiwei Inventor before: Wang Xiaoyan Inventor before: Wang Zhiwei Inventor before: Li Haiying Inventor before: Xu Fei |
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