CN107088191A - The new application of medicine taractan - Google Patents
The new application of medicine taractan Download PDFInfo
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- CN107088191A CN107088191A CN201610089259.7A CN201610089259A CN107088191A CN 107088191 A CN107088191 A CN 107088191A CN 201610089259 A CN201610089259 A CN 201610089259A CN 107088191 A CN107088191 A CN 107088191A
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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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
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Abstract
The invention discloses the new application of medicine taractan.Disclosed new application be taractan 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.The present invention has advantages below：1) resistance phenomenon occurs in clinic is used for a long time in tumour medicine, and one of the main reasons is exactly that medicine pumps out effect, and taractan is not the substrate specificity of glycoprotein, can avoid pumping out for medicine, increase curative effect；2) the most of kinase inhibitor clinically used is difficult to break through blood-brain barrier, thus is difficult to play a role to brain tumor, and taractan is easy to break through blood-brain barrier, has potential antitumor activity to brain tumor；3) because taractan has been antipsychotic marketed drug, the research cost in preclinical study can be substantially reduced, is economized on resources, shorten the R＆D cycle.
Description
Technical field
The present invention relates to the new application of medicine taractan.
Background technology
Taractan (Chlorprothixene) is a class major tranquilizer thing, molecular formula：C18H18ClNS；Chemical name is：
(Z) -3- (2- diurils ton)-N, N- dimethyl-propane -1- amine；English name is：
(Z)-3-(2-chlorothioxanthen-9-ylidene)-N,N-dimethyl-propan-a-amine；Chemical structural formula such as formula (I)
It is shown：
In China, taractan has been put into clinical treatment and used.As shown by data, taractan has potent antipsychotic symptom
With calm effect, antiadrenergic drug and cholinolytic effect be weak, is generally used for the spirit with diseases such as anxiety or depression
The treatment of Split disease.As antipsychotic class medicine, taractan has very strong to dopamine receptor and 5-hydroxytryptamine receptor
Affinity interaction, can effectively suppress its activity.The toxic side effect of taractan is weaker, only causes outside extremely low centrum and is
Adverse reaction, the day usual amounts 5-800mg of adult.
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 taractan.Taractan has good suppression to kinds of tumor cells
Effect processed, is a kind of potential antineoplastic, with potential potential applicability in clinical practice.
The new application for the medicine taractan that the present invention is provided is：Taractan or its pharmaceutically acceptable salt, ester,
Application of the 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 are thin
Born of the same parents' (blood cell), breast cancer cell, lung carcinoma cell, liver cancer cells, ovarian cancer cell, stomach cancer cell, the cancer of the esophagus
Cell, colon-cancer cell, cervical cancer cell, malignant lymphom cells and nasopharyngeal carcinoma cell；
Wherein, the breast cancer cell concretely human breast cancer cell SUM159；The leukaemia specifically may be used
Behave acute T _ Lymphoid Leukemic Cells Molt-4, CCRF-CEM, chronic myeloid leukemia cell K562；Institute
State colloid cancer cell concretely human neuroglia cancer cell U118MG.
The new application for another medicine taractan that the present invention is provided is：Taractan or its pharmaceutically acceptable salt, ester,
Application of the solvate 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 a kind of using taractan or its pharmaceutically acceptable salt, ester, solvate as the eucaryote tumour of active component
Inhibition of cell proliferation, 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 includes but is not limited to：Glioma cell, leukaemia are thin
Born of the same parents' (blood cell), breast cancer cell, lung carcinoma cell, liver cancer cells, ovarian cancer cell, stomach cancer cell, the cancer of the esophagus
Cell, colon-cancer cell, cervical cancer cell, malignant lymphom cells and 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 preparation eucaryote tumour is thin with taractan or its pharmaceutically acceptable salt, ester, solvate
Parenteral solution, tablet, pulvis, granule, capsule, oral liquid, paste, creme etc. can be made in born of the same parents' antiblastic
Diversified forms；The medicine of above-mentioned various formulations can be prepared according to the conventional method of pharmaceutical field.
It is a kind of using taractan or its pharmaceutically acceptable salt, ester, solvate as the prevention of active component and/or treatment
Tumour medicine, also within the scope of the present invention.
In above-mentioned prevention and/or tumor, 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.
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 is swollen with taractan or its pharmaceutically acceptable salt, ester, solvate
A variety of shapes such as parenteral solution, tablet, pulvis, granule, capsule, oral liquid, paste, creme can be made in tumor medicine
Formula；The medicine of above-mentioned various formulations can be prepared according to the conventional method of pharmaceutical field.
The present invention has the advantages that：
The present invention proves that taractan is a kind of potential antineoplastic by the test of kinds of tumor cells system.With taractan
There is three below advantage in particular for brain tumor as antineoplastic：(1) tumour medicine is in clinic is used for a long time
Occur resistance phenomenon, one of the main reasons is exactly that medicine pumps out effect, and taractan is not the effect of glycoprotein
Substrate increases curative effect so as to avoid pumping out for medicine；(2) the most of kinase inhibitor clinically used is difficult
Blood-brain barrier is broken through, thus is difficult to play a role to brain tumor, and taractan is easy to break through blood as antipsychotics
Brain barrier, therefore more likely there is potential antitumor activity to brain tumor.(3) because taractan has been treatment mental disease
Marketed drug, therefore as anti-tumor medicine, the research cost in preclinical study can be substantially reduced, saved
Resource, shortening R＆D cycle.Therefore, taractan has 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, cell in vitro proliferation inhibition test detect taractan to inhibiting tumour cells effect
Cell in vitro proliferation inhibition test uses mtt assay, by it is following represent cell line exemplified by：Human breast cancer cell
SUM159, people acute T _ Lymphoid Leukemic Cells Molt-4, CCRF-CEM, chronic myeloid leukemia cell K562,
People's colloid cancer cell U118MG.
Above cell pearl obtains from Nanjing KaiJi Biology Science Development Co., Ltd's cell bank purchase.
Cell culture processes：SUM159 is added in the DMEM/F12 culture mediums containing 10% hyclone
5 μ g/mL insulin and 1 μ g/mL hydrocortisones, CCRF-CEM, Molt-4, K562 are containing 10% tire ox blood
In clear RPMI-1640 culture mediums, U118MG is in containing 10% hyclone DMEM culture mediums in 37 DEG C, body
Fraction is 5% CO2Under the conditions of cellar culture cultivated.
Taractan 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 200 μ L dissolved with 2 μ L taractans 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, 100ul 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, taractan cause kinds of tumor cells system cytotoxicity experiment result
Claims (10)
1. taractan or its pharmaceutically acceptable salt, ester, solvate are preparing eucaryote tumor cell proliferation
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. taractan or its pharmaceutically acceptable salt, ester, solvate are preparing prevention and/or tumor
In application.
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 is taractan or its is pharmaceutically acceptable
Salt, ester, solvate.
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 be glioma cell, leukaemia,
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.
9. one kind prevention and/or tumor, its active component be taractan or its pharmaceutically acceptable salt,
Ester, solvate.
10. medicine according to claim 9, it is characterised in that：The tumour is cancer；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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610089259.7A CN107088191A (en) | 2016-02-17 | 2016-02-17 | The new application of medicine taractan |
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| CN201610089259.7A CN107088191A (en) | 2016-02-17 | 2016-02-17 | The new application of medicine taractan |
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| CN107088191A true CN107088191A (en) | 2017-08-25 |
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| CN201610089259.7A Pending CN107088191A (en) | 2016-02-17 | 2016-02-17 | The new application of medicine taractan |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110585197A (en) * | 2019-09-26 | 2019-12-20 | 上海交通大学 | Application of dopamine receptor antagonist telfon in treating acute myeloid leukemia |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008054354A2 (en) * | 2005-08-11 | 2008-05-08 | Albert Einstein College Of Medecine Of Yeshiva University | Assays for s1oo inhibitors |
-
2016
- 2016-02-17 CN CN201610089259.7A patent/CN107088191A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008054354A2 (en) * | 2005-08-11 | 2008-05-08 | Albert Einstein College Of Medecine Of Yeshiva University | Assays for s1oo inhibitors |
Non-Patent Citations (3)
| Title |
|---|
| JAMES M. FORD等: "Cellular and Biochemical Characterization of Thioxanthenes for Reversal of Multidrug Resistance in Human and Murine Cell Lines", 《CANCER RESEARCH》 * |
| JOHN S.DRISCOLL: "Psychotropic drugs as potential antitumor agents: a selective screening study", 《CANCER TREATMENT REPORTS》 * |
| SUSAN J. FRIEDMAN等: "Membrane-active drugs potentiate the killing of tumor cells by D-glucosamine", 《PROC. NATL. ACAD. SCI. USA》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110585197A (en) * | 2019-09-26 | 2019-12-20 | 上海交通大学 | Application of dopamine receptor antagonist telfon in treating acute myeloid leukemia |
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Application publication date: 20170825 |
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