CN107088194A - The new application of medicine Amlodipine - Google Patents
The new application of medicine Amlodipine Download PDFInfo
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- CN107088194A CN107088194A CN201610089010.6A CN201610089010A CN107088194A CN 107088194 A CN107088194 A CN 107088194A CN 201610089010 A CN201610089010 A CN 201610089010A CN 107088194 A CN107088194 A CN 107088194A
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- amlodipine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
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Abstract
The invention discloses the new application of medicine Amlodipine.Disclosed new application be Amlodipine or its pharmaceutically acceptable salt, ester, solvate it is following 1) or 2) in application：1) application in eucaryote tumor cell proliferation inhibitor is prepared；2) application in prevention and/or tumor is prepared.Using Amlodipine as tumor cell proliferation inhibitor or antineoplastic, with following two advantages：(1) compared to other tumor chemical therapy medicines, toxic side effect is low.(2) because Amlodipine has been the marketed drug of the diseases such as treatment hypertension, therefore as anti-tumor medicine, the research cost in preclinical study can be substantially reduced, economizes on resources, shortens the R＆D cycle.It is demonstrated experimentally that Amlodipine can effectively suppress activity of tumor cells, with potential potential applicability in clinical practice.
Description
Technical field
The present invention relates to the new application of medicine Amlodipine.
Background technology
Amlodipine (Amlodipine) is a class cerebrocrast thing, and molecular formula is：C20H25ClN2O5；Chemistry
It is entitled：(RS) -3- ethyls -5- methyl -2- (2- ammonia ethoxymethyl) -4- (2- chlorphenyls) -1,4- dihydro -6- methyl -3,5- pyridines two
Carboxylic acid；English name is (RS) -3-ethyl-5-methyl-2- [2-aminoethoxy) methyl] -4- (2-chlorophenyl)
-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate；Shown in chemical structural formula such as formula (I)：
Amlodipine is used to treat hypertension and angina pectoris, has been put into clinical treatment use.As shown by data, in day
With the Amlodipine few side effects in dosage range, most of adverse reactions are light moderate.It is more typical cause headache,
The milds such as insomnia, nausea, rare indigestion, fash etc..As cerebrocrast thing, adult's is daily
Consumption 5-10mg.
With the increasing of new drug development difficulty, development cost it is high, the emphasis of drug development is shifted all over the world
To the secondary development of product, new indication, the exploitation novel form of old medicine are such as expanded, to obtain new effective treatment
Medicine.The clinical observation of old medicine prolonged a large amount of cases after listing, its security is guaranteed, adverse reaction
Understanding is comprehensive, and cheap.Old medicine develops new application, and the cost that its preclinical and pre-clinical assay expends is also
Relative it can save.Therefore, old medicine is studied, its new indication is expanded, is not only greatly promoted the hair of clinical therapeutics
Exhibition, also produces important value in market to save the cycle of health resources and the old medicine life of extension.
The content of the invention
It is an object of the invention to provide the new application of medicine Amlodipine.
One new application of the medicine Amlodipine that the present invention is provided is：Amlodipine or its pharmaceutically acceptable salt,
The application of ester, solvate in eucaryote tumor cell proliferation inhibitor is prepared.
In above-mentioned application, the eucaryote can be mammal.
The tumour cell can be cancer cell；The cancer cell includes but is not limited to：Glioma cell, leukaemia
(blood cell), breast cancer cell, lung carcinoma cell, liver cancer cells, ovarian cancer cell, stomach cancer cell, the cancer of the esophagus are thin
Born of the same parents, colon-cancer cell, cervical cancer cell, malignant lymphom cells and nasopharyngeal carcinoma cell.
Wherein, the breast cancer cell concretely human breast cancer cell SUM159, MDA-MB-231；It is described white
The blood disease cell concretely acute T _ Lymphoid Leukemic Cells Jurkat of people；Concretely people is neural for the colloid cancer cell
Colloid cancer cell U118MG.
Another new application that the present invention is provided is：Amlodipine or its pharmaceutically acceptable salt, ester, solvent are closed
Application of the thing in prevention and/or tumor is prepared.
In above-mentioned application, the tumour can be cancer；The cancer includes but is not limited to：Brain tumor, leukaemia, breast cancer,
Lung cancer, liver cancer, oophoroma, stomach cancer, the cancer of the esophagus, intestinal cancer, cervical carcinoma, malignant lymphoma and nasopharyngeal carcinoma.
It is thin by the eucaryote tumour of active component of Amlodipine or its pharmaceutically acceptable salt, ester, solvate
Born of the same parents' antiblastic, also within the scope of the present invention.
In above-mentioned eucaryote tumor cell proliferation inhibitor, the eucaryote can be mammal.
The tumour cell can be cancer cell；The cancer cell can for glioma cell, leukaemia's (blood cell),
Breast cancer cell, lung carcinoma cell, liver cancer cells, ovarian cancer cell, stomach cancer cell, esophageal cancer cell, colon-cancer cell,
Cervical cancer cell, malignant lymphom cells or nasopharyngeal carcinoma cell.
In above-mentioned eucaryote tumor cell proliferation inhibitor, the eucaryote tumor cell proliferation inhibitor can pass through
Injection, injection, collunarium, eye drip, infiltration, absorption, method importing the body such as muscle, skin physically or chemically mediated
Interior, subcutaneous, vein, mucosal tissue；Or imported body after other material mixings or parcel.
When needs, one or more pharmaceutically acceptable carriers can also be added in said medicine；It is described to carry
Body includes the conventional diluent of pharmaceutical field, excipient, filler, adhesive, wetting agent, disintegrant, absorption rush
Enter agent, surfactant, absorption carrier, lubricant etc..
It is that active component prepares eucaryote tumour with Amlodipine or its pharmaceutically acceptable salt, ester, solvate
Parenteral solution, tablet, pulvis, granule, capsule, oral liquid, paste, creme can be made in inhibition of cell proliferation
Etc. diversified forms；The medicine of above-mentioned various formulations can be prepared according to the conventional method of pharmaceutical field.
It is that the prevention of active component and/or treatment are swollen using Amlodipine or its pharmaceutically acceptable salt, ester, solvate
Tumor medicine, also within the scope of the present invention.
In above-mentioned prevention and/or tumor, the tumour can be cancer；The cancer can be brain tumor, leukaemia, breast
Gland cancer, lung cancer, liver cancer, oophoroma, stomach cancer, the cancer of the esophagus, intestinal cancer, cervical carcinoma, malignant lymphoma or nasopharyngeal carcinoma.
In above-mentioned prevention and/or tumor, it is described prevention and/or tumor can by injection, injection,
Collunarium, eye drip, infiltration, absorption, the method that physically or chemically mediates import body such as muscle, intracutaneous, subcutaneous, quiet
Arteries and veins, mucosal tissue；Or imported body after other material mixings or parcel.
When needs, one or more pharmaceutically acceptable carriers can also be added in said medicine；It is described to carry
Body includes the conventional diluent of pharmaceutical field, excipient, filler, adhesive, wetting agent, disintegrant, absorption rush
Enter agent, surfactant, absorption carrier, lubricant etc..
It is that active component prepares prevention and/or treatment with Amlodipine or its pharmaceutically acceptable salt, ester, solvate
It is a variety of that parenteral solution, tablet, pulvis, granule, capsule, oral liquid, paste, creme etc. can be made in tumour medicine
Form；The medicine of above-mentioned various formulations can be prepared according to the conventional method of pharmaceutical field.
The present invention proves that Amlodipine is a kind of potential antineoplastic by the test of various kinds of cell system.With Amlodipine
As antineoplastic, with following two advantages：(1) compared to other tumor chemical therapy medicines, toxic side effect
It is low.(2) because Amlodipine has been the marketed drug of the diseases such as treatment hypertension, therefore as anti-tumor medicine,
The research cost in preclinical study can be substantially reduced, economizes on resources, shorten the R＆D cycle.All experimental data cards
Bright Amlodipine can effectively suppress activity of tumor cells, with potential potential applicability in clinical practice.
Embodiment
Experimental method used in following embodiments is conventional method unless otherwise specified.
Material, reagent used etc., unless otherwise specified, are commercially obtained in following embodiments.
Embodiment 1, by cell in vitro proliferation inhibition test detect Amlodipine to inhibiting tumour cells effect
Cell in vitro proliferation inhibition test uses mtt assay, by it is following represent cell exemplified by：Human breast cancer cell
SUM159, MDA-MB-231, people acute T _ Lymphoid Leukemic Cells Jurkat, human neuroglia cancer cell U118
MG。
Above cell pearl obtains from Nanjing KaiJi Biology Science Development Co., Ltd's cell bank purchase.
Cell culture processes：SUM159 adds 5ug/ml in the DMEM/F12 culture mediums containing 10% hyclone
Insulin and 1ug/ml hydrocortisones, Jurkat in containing 10% hyclone RPMI-1640 culture mediums, 37 DEG C,
Volume fraction is 5% CO2Under the conditions of cellar culture cultivated.MDA-MB-231 is containing 10% hyclone
In Leibovitz ' s-15 culture mediums, U118MG is in containing 10% hyclone DMEM culture mediums in 37 DEG C, nothing
CO2Under the conditions of cellar culture cultivated.
Amlodipine handles cell：By pending cell, 24h is spread into 96 orifice plates before drug-treated, 5000-10000
Individual/hole.Cultivate after 24h, discard culture medium.Complete mediums of the 200uL dissolved with 2 μ L Amlodipines is replaced by, is made
Medicine effect it is final concentration of 100 μM, 50 μM, 25 μM, 12.5 μM, 6 μM, 3 μM, 1.5 μM, 0.75 μM,
0.4μM、0.2μM、0.1μM、0.05μM.Every kind of sample sets 3 multiple holes, sets positive control and blank control, makees
Use time 72h.
MTT methods detect cell proliferation inhibition rate：The MTT diluted with PBS is added per Kong Zhongzhi final concentrations
0.5mg/mL.Lucifuge, is put into cell culture incubator 4-6h.Cell culture medium is discarded, 100 μ L DMSO are added per hole,
Concussion, purple crystal all dissolves, and 490nM, which absorbs, measures OD values under light.Cell propagation suppression is calculated as follows
Rate (Inhibition Rate, IR%) processed：
IR%=[(control OD- blank OD)-(sample OD- blank OD)]/(control OD- blank OD) × 100%；
It is computed, the inhibiting rate result and 50 3nhibitory dose IC of Amlodipine tumour cell50It is shown in Table 1.
Table 1, Amlodipine cause kinds of tumor cells system cytotoxicity experiment result
Claims (10)
1. Amlodipine or its pharmaceutically acceptable salt, ester, solvate are preparing the increasing of eucaryote tumour cell
Grow the application in inhibitor.
2. application according to claim 1, its feature exists：The eucaryote is mammal；It is described swollen
Oncocyte is cancer cell.
3. application according to claim 2, it is characterised in that：The cancer cell be selected from it is following any one：
Glioma cell, leukaemia, breast cancer cell, lung carcinoma cell, liver cancer cells, ovarian cancer cell, stomach cancer are thin
Born of the same parents, esophageal cancer cell, colon-cancer cell, cervical cancer cell, malignant lymphom cells and nasopharyngeal carcinoma cell.
4. Amlodipine or its pharmaceutically acceptable salt, ester, solvate are preparing prevention and/or treatment tumour medicine
Application in thing.
5. application according to claim 4, it is characterised in that：The tumour is cancer.
6. application according to claim 5, it is characterised in that：The cancer be brain tumor, leukaemia, breast cancer,
Lung cancer, liver cancer, oophoroma, stomach cancer, the cancer of the esophagus, intestinal cancer, cervical carcinoma, malignant lymphoma or nasopharyngeal carcinoma.
7. a kind of eucaryote tumor cell proliferation inhibitor, its active component be Amlodipine or its can pharmaceutically connect
Salt, ester, the solvate received.
8. eucaryote tumor cell proliferation inhibitor according to claim 7, it is characterised in that：It is described true
Core biology is mammal；The tumour cell is cancer cell；The cancer cell is specially glioma cell, leukaemia
Cell, breast cancer cell, lung carcinoma cell, liver cancer cells, ovarian cancer cell, stomach cancer cell, esophageal cancer cell, intestines
Cancer cell, cervical cancer cell, malignant lymphom cells or nasopharyngeal carcinoma cell.
9. one kind prevention and/or tumor, its active component be Amlodipine or its pharmaceutically acceptable salt,
Ester, solvate.
10. medicine according to claim 9, it is characterised in that：The tumour is cancer；The cancer is specially brain
Knurl, leukaemia, breast cancer, lung cancer, liver cancer, oophoroma, stomach cancer, the cancer of the esophagus, intestinal cancer, cervical carcinoma, pernicious pouring
Bar knurl or nasopharyngeal carcinoma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610089010.6A CN107088194A (en) | 2016-02-17 | 2016-02-17 | The new application of medicine Amlodipine |
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| CN201610089010.6A CN107088194A (en) | 2016-02-17 | 2016-02-17 | The new application of medicine Amlodipine |
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| CN201610089010.6A Pending CN107088194A (en) | 2016-02-17 | 2016-02-17 | The new application of medicine Amlodipine |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101569624A (en) * | 2008-04-29 | 2009-11-04 | 石药集团中奇制药技术（石家庄）有限公司 | Application of amlodipine to preparation of medicaments for curing phoproliferative diseases |
| CN103930132A (en) * | 2011-09-27 | 2014-07-16 | 拜奥迈德瓦利探索有限公司 | Compositions and methods of treating gliomas |
-
2016
- 2016-02-17 CN CN201610089010.6A patent/CN107088194A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101569624A (en) * | 2008-04-29 | 2009-11-04 | 石药集团中奇制药技术（石家庄）有限公司 | Application of amlodipine to preparation of medicaments for curing phoproliferative diseases |
| CN103930132A (en) * | 2011-09-27 | 2014-07-16 | 拜奥迈德瓦利探索有限公司 | Compositions and methods of treating gliomas |
Non-Patent Citations (1)
| Title |
|---|
| 徐兴华，等: "氨氯地平对人乳腺癌细胞株MDA_MB_231侵袭影响的体外实验", 《第三军医大学学报》 * |
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Application publication date: 20170825 |