CN103191144A - Medicine composition for treating cancers and application - Google Patents
Medicine composition for treating cancers and application Download PDFInfo
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- CN103191144A CN103191144A CN2013101448082A CN201310144808A CN103191144A CN 103191144 A CN103191144 A CN 103191144A CN 2013101448082 A CN2013101448082 A CN 2013101448082A CN 201310144808 A CN201310144808 A CN 201310144808A CN 103191144 A CN103191144 A CN 103191144A
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- Prior art keywords
- decitabine
- cancer
- clavulanate potassium
- leukemia
- medicine composition
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- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 29
- 239000003814 drug Substances 0.000 title claims abstract description 24
- 239000000203 mixture Substances 0.000 title abstract description 11
- 229940079593 drug Drugs 0.000 title description 2
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 claims abstract description 29
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 claims abstract description 28
- 229960003603 decitabine Drugs 0.000 claims abstract description 26
- 201000011510 cancer Diseases 0.000 claims description 27
- 229940038649 clavulanate potassium Drugs 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 208000032839 leukemia Diseases 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 8
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 abstract description 11
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 abstract description 11
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 abstract description 10
- 230000012010 growth Effects 0.000 abstract description 9
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 abstract description 8
- 229930002330 retinoic acid Natural products 0.000 abstract description 8
- 229960001727 tretinoin Drugs 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 6
- 230000004614 tumor growth Effects 0.000 abstract description 3
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 abstract 2
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 229940126673 western medicines Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 16
- 206010059866 Drug resistance Diseases 0.000 description 7
- 230000001154 acute effect Effects 0.000 description 7
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000002607 hemopoietic effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002132 β-lactam antibiotic Substances 0.000 description 3
- 229940124586 β-lactam antibiotics Drugs 0.000 description 3
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 2
- 230000007067 DNA methylation Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 2
- 229960003324 clavulanic acid Drugs 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- NCMVOABPESMRCP-SHYZEUOFSA-N 2'-deoxycytosine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 NCMVOABPESMRCP-SHYZEUOFSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 230000030933 DNA methylation on cytosine Effects 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 229930182507 Neplanocin Natural products 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229940123468 Transferase inhibitor Drugs 0.000 description 1
- 229940038195 amoxicillin / clavulanate Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003558 transferase inhibitor Substances 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a medicine composition for treating cancers, relating to the technical field of Western medicines. The active ingredients of the medicine composition include decitabine and potassium clavulanate. Compared with the prior art, the medicine composition has higher activity of inhibiting the tumor growth rate and can not only inhibit growth of human acute promyelocytic leukemia NK4 cells and chronic granulocytic leukemia K562 cells but also inhibit growth of retinoic acid medicine-resistant promyelocytic leukemia MR-2 cells.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of pharmaceutical composition and application for the treatment of cancer.
Background technology
At present, cancer is that current serious influences human health, threatens one of principal disease of human life.Cancer constitutes world today's All Countries three big causes of death with cardiovascular and cerebrovascular disease and contingency.Therefore, World Health Organization (WHO) and hygiene department of national governments all classify capture cancer as a top priority as.Treat method for cancer in the world and mainly contain three kinds, the one, adopt surgical excision, removal lesion tissue prevents the cancerous cell diffusion; But adopt chemotherapy or radiotherapy, with kill cancer cell; The 3rd, heal with medicine.The method of employing excision has increased patient's misery, hinders its vigour, and expense is huge.With the method for radiotherapy, in kill cancer cell, also injure erythrocyte and leukocyte, patient suffers untold misery.
Leukemia is the hemopoietic system malignant tumor of serious harm human life health, is the malignant disease that a class originates from hemopoietic (or lymph) stem cell.Because stem cell is impaired, the leukaemia loses the ability of further differentiation and maturation, perhaps increment and differentiation capability imbalance, and stop at cytocerastic different phase, be embodied in cell infinitely increment in vivo, and its differentiation and maturation and apoptosis are obstructed.Therefore, leukemic treatment can be started with from three aspects: cell death inducing, inducing cell differentiation and stem cell transplantation reconstitute hematopoiesis function.Traditional combined chemotherapy is still mainly adopted in leukemic treatment so far, but this therapy side effect is very big, and the relapse rate height especially has bigger infringement to immunity of organism and hemopoietic system.
Decitabine is a kind of demethylation medicine, has the treatment mechanism of unique methylated transferase inhibitor.Decitabine (decitabine, 5-azepine-2-dCMP 1beta-Deoxyribofuranosylcytosine-5'-phosphate) is a kind of neplanocin of natural dCMP 1beta-Deoxyribofuranosylcytosine-5'-phosphate, cytosine and dna methylation transferring enzyme covalent bond in the alternative tumor of decitabine fusion of low concentration, make dna methylation transferring enzyme inactivation, reach the effect of demethylation.2006, U.S. food and FAD have been ratified decitabine and have been used for the treatment of myelodysplastic syndrome (myelodysplasia syndrome, MDS), to other malignant hematologic diseases such as acute myeloid leukemia (acute myeloid leukemia, AML) and chronic myelocytic leukemia (chronic myelocyticleukemia, CML), decitabine all has obvious curative effects.Clavulanic acid is the natural beta-lactamase inhibitor that clavuligerus produces, can the irreversible activity of protecting beta-lactam antibiotic in conjunction with the serine avtive spot of beta-lactamase.Normal and the composite use of beta-lactam antibiotic of clavulanic acid clinically can strengthen the antibacterial activity of beta-lactam antibiotic effectively and enlarge antimicrobial spectrum.Wherein with the amoxicillin/clavulanate potassium compound preparation use the most extensive, ranked world's best-selling drugs ranking list in once continuous 13 years.
At present, also clavulanate potassium is not used for anticancer bibliographical information, more decitabine is not united clavulanate potassium and be used for anticancer bibliographical information.
Summary of the invention
The inventor is surprised to find that clavulanate potassium to Leukemia Patients has certain therapeutical effect in a long-term line clinical application.Therefore, the present invention furthers investigate by a large amount of tests, and a kind of pharmaceutical composition and application of Synergistic treatment cancer are provided.
In order to realize purpose of the present invention, the inventor has finally obtained following technical scheme by a large amount of experimental studies:
A kind of pharmaceutical composition for the treatment of cancer of the present invention, active component contains decitabine and clavulanate potassium.
Preferably, the pharmaceutical composition of above-mentioned treatment cancer, wherein said decitabine is 1:1-60 with the mole dosage ratio of clavulanate potassium.
Further preferably, the pharmaceutical composition of above-mentioned treatment cancer, wherein said decitabine is 1:2-30 with the mole dosage ratio of clavulanate potassium.
Again further preferably, the pharmaceutical composition of above-mentioned treatment cancer, wherein said decitabine is 1:4-10 with the mole dosage ratio of clavulanate potassium.
Pharmaceutical composition of the present invention, wherein has the anti-tumor synergetic effect after the associating of active component decitabine and clavulanate potassium, namely not only can suppress the growth of people's acute promyelocytic leukemic NK4 cell and chronic myelocytic leukemia K562 cell, more amazing is that it can suppress the growth of children's grain leukemia MR-2 cell early of retinoic acid drug resistance.Therefore, the present invention does further preferred to the indication of described pharmaceutical composition, and namely described cancer is leukemia.
Two of purpose of the present invention provides the medical usage of chemical compound, specifically, and the application of clavulanate potassium in the medicine of preparation treatment cancer.And: the application of decitabine associating clavulanate potassium in the medicine of preparation treatment cancer.
More preferably a kind of technical scheme is: the purposes of compositions in the medicine of preparation treatment acute promyelocytic leukemic that active component is made up of decitabine and clavulanate potassium.
More preferably another kind of technical scheme is: the purposes of compositions in the medicine of preparation treatment chronic myelocytic leukemia that active component is made up of decitabine and clavulanate potassium.
More preferably another kind of technical scheme is: the purposes of compositions in the leukemic medicine of preparation treatment retinoic acid drug resistance children's morning grain that active component is made up of decitabine and clavulanate potassium.
Compared with prior art, the activity that the pharmaceutical composition that the present invention relates to suppresses the tumor growth rate is higher, not only can suppress the growth of people's acute promyelocytic leukemic NK4 cell and chronic myelocytic leukemia K562 cell, can also suppress the growth of children's grain leukemia MR-2 cell early of retinoic acid drug resistance, this is for acute promyelocytic leukemic, chronic myelocytic leukemia and retinoic acid drug resistance children's morning grain leukemia have deep directive significance clinically.
The specific embodiment
With people's acute promyelocytic leukemic NK4 cell, chronic myelocytic leukemia K562 cell, retinoic acid drug resistance early children's grain leukemia MR-2 cell is inoculated in respectively in the RPMI-1640 culture fluid, contains 5%CO in 37 ℃
2Incubator in cultivate and to go down to posterity, be inoculated in 96 well culture plates, add the medicine of respective concentration during inoculation by group, parallel 5 holes of every concentration, the MTT reduction reaction is measured inhibition rate of tumor growth behind the 48h, and test data carries out statistical analysis with the Excel system, and concrete result of the test is referring to table 1.
The test grouping is as follows with the administration final concentration:
Blank group: isopyknic excipient
Decitabine group: 3.2mmol/L decitabine
Clavulanate potassium group: 20mmol/L clavulanate potassium
Compositions A group: 0.8mmol/L decitabine+5mmol/L clavulanate potassium
Compositions B group: 3.2mmol/L decitabine+20mmol/L clavulanate potassium
Table 1 compositions is to the influence of leukaemia's growth
Compare with the decitabine group,
* P＜0.05,
* P＜0.01;
Compare with the clavulanate potassium group,
$ P＜0.05,
$$ P＜0.01.
Result by above-mentioned table 1 as can be seen, compositions A group of the present invention and B organize and compare with single medicine group (decitabine group and clavulanate potassium group) and to have significant difference (
P＜0.05) or utmost point significant difference (
P＜0.01), this shows, decitabine and clavulanate potassium can be worked in coordination with the growth that suppresses people's acute promyelocytic leukemic NK4 cell and chronic myelocytic leukemia K562 cell, even can suppress the growth of children's grain leukemia MR-2 cell early of retinoic acid drug resistance, this result is for acute promyelocytic leukemic, chronic myelocytic leukemia and retinoic acid drug resistance children's morning grain leukemia have deep directive significance clinically.
Claims (9)
1. pharmaceutical composition for the treatment of cancer, it is characterized in that: active component contains decitabine and clavulanate potassium.
2. according to the pharmaceutical composition of the described treatment cancer of claim 1, it is characterized in that: described decitabine is 1:1-60 with the mole dosage ratio of clavulanate potassium.
3. according to the pharmaceutical composition of the described treatment cancer of claim 2, it is characterized in that: described decitabine is 1:2-30 with the mole dosage ratio of clavulanate potassium.
4. according to the pharmaceutical composition of the described treatment cancer of claim 3, it is characterized in that: described decitabine is 1:4-10 with the mole dosage ratio of clavulanate potassium.
5. according to the pharmaceutical composition of each described treatment cancer of claim 1-4, it is characterized in that: described cancer is leukemia.
6. according to the application of the described clavulanate potassium of claim 1 in the medicine of preparation treatment cancer.
7. application according to claim 6 is characterized in that: described cancer is leukemia.
8. according to the application of the described decitabine associating of claim 1 clavulanate potassium in the medicine of preparation treatment cancer.
9. application according to claim 8 is characterized in that: described cancer is leukemia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310144808.2A CN103191144B (en) | 2013-04-25 | 2013-04-25 | Medicine composition for treating cancers and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310144808.2A CN103191144B (en) | 2013-04-25 | 2013-04-25 | Medicine composition for treating cancers and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103191144A true CN103191144A (en) | 2013-07-10 |
| CN103191144B CN103191144B (en) | 2014-06-18 |
Family
ID=48714080
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310144808.2A Expired - Fee Related CN103191144B (en) | 2013-04-25 | 2013-04-25 | Medicine composition for treating cancers and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103191144B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014246A (en) * | 2004-07-13 | 2007-08-08 | 苏伯俭股份有限公司 | Compositions and formulations of decitabine polymorphs and methods of use thereof |
| CN102088969A (en) * | 2008-06-09 | 2011-06-08 | 西克拉塞尔有限公司 | Combination of spacitabine (CNDAC) and DNA methyltransferase inhibitors such as decitabine and procaine |
-
2013
- 2013-04-25 CN CN201310144808.2A patent/CN103191144B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014246A (en) * | 2004-07-13 | 2007-08-08 | 苏伯俭股份有限公司 | Compositions and formulations of decitabine polymorphs and methods of use thereof |
| CN102088969A (en) * | 2008-06-09 | 2011-06-08 | 西克拉塞尔有限公司 | Combination of spacitabine (CNDAC) and DNA methyltransferase inhibitors such as decitabine and procaine |
Non-Patent Citations (1)
| Title |
|---|
| 刘娟等: "阿莫西林_克拉维酸钾治疗恶性血液病化疗后白细胞减少期并发感染", 《中国新药与临床杂志》 * |
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| Publication number | Publication date |
|---|---|
| CN103191144B (en) | 2014-06-18 |
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