CN105816461B - Application of the Trimetinib on preparing treatment parkinsonism drug - Google Patents
Application of the Trimetinib on preparing treatment parkinsonism drug Download PDFInfo
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- CN105816461B CN105816461B CN201610208591.0A CN201610208591A CN105816461B CN 105816461 B CN105816461 B CN 105816461B CN 201610208591 A CN201610208591 A CN 201610208591A CN 105816461 B CN105816461 B CN 105816461B
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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Abstract
The invention belongs to pharmaceutical technology fields, and it discloses Trimetinibs（Trametinib）Application on preparing treatment Parkinson medicinal is that Trimetinib is used to prepare to the drug for delaying dopaminergic neuron to degenerate.Products obtained therefrom can effectively delay the degeneration of dopaminergic neuron dead, fundamentally have the function that treat Parkinson's disease；And its drug need not be injected, and only can reach therapeutic effect by oral, have good therapeutic effect to Parkinson's disease caused by many reasons, be of great significance to the treatment and healing of Parkinson's disease.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to Trimetinib（Trametinib）Parkinson's medicine is treated preparing
Application on object.
Background technology
Parkinson's disease（Parkinson ' s Disease, PD）Also known as " shaking plasy " is a kind of common central nervous system
System degenerative disease, mainly influences the middle-aged and the old, patient mostly falls ill after 50 years old, but becoming for increasingly rejuvenation has been presented in recent years
Gesture.The chief complaint of Parkinsonian has slow in one's movements, and what trick or body other parts occurred not controlling trembles, body
Become stiff, disequilibrium, so that can't take care of oneself.It shows according to statistics, the trouble of Parkinson in the crowd in China 60 years old or more
Sick rate is about 1.7%, and there are about more than 100 ten thousand patients altogether, and 100,000 new cases of annual at least increase.Substantia nigra of midbrain dopamine
（Dopamine, DA）The denaturation of serotonergic neuron is dead, and striatum DA level substantially reduces, and cannot meet the normal need of human body,
It is one of the main reason for causing Parkinson's disease.
Include mainly that drug therapy and operative treatment ancillary drug are treated to the treatment of Parkinson at present.Common drug master
Will there are three types of：One is dopamine preparations, can directly supplement the dopamine of intracerebral hyposecretion；Second is that inhibiting DOPA amine degradation
Drug, the degradation of dopamine can be reduced, make intracerebral DOPAMINE CONTENT IN RABBIT is opposite to increase；Third, dopamine-receptor stimulant,
Absorption and utilization of the brain to dopamine can be enhanced.But it cannot delay the degeneration of dopaminergic neuron, therefore cannot be from
Fundamentally play the role for the treatment of.
Invention content
Trimetinib（Trametinib）It is a kind of mek inhibitor, the purpose of the present invention is to provide a kind of Trimetinibs
New application.
To achieve the above object, the present invention adopts the following technical scheme that：
A kind of application of Trimetinib on preparing treatment Parkinson medicinal, specifically by Trimetinib individually or and other
Active constituent or auxiliary material prepare into the drug for delaying dopaminergic neuron to degenerate.
The remarkable advantage of the present invention is：The present invention provides a kind of Trimetinibs（Trametinib）New application, be
Trimetinib is used to prepare to the drug for delaying dopaminergic neuron to degenerate.Products obtained therefrom can effectively delay dopaminergic nerve
The degeneration of member is dead, fundamentally has the function that treat Parkinson's disease；And its drug need not be injected, only by oral
Therapeutic effect is can reach, has good therapeutic effect to Parkinson's disease caused by many reasons, the treatment to Parkinson's disease and healing tool
It is significant.
Description of the drawings
Fig. 1 is the schematic diagram of the drosophila local cerebral area dopaminergic neuron state after Trimetinib is handled.
Fig. 2 is the statistical chart of the drosophila local cerebral area dopaminergic neuron quantity after Trimetinib is handled.
Specific implementation mode
In order to make content of the present invention easily facilitate understanding, With reference to embodiment to of the present invention
Technical solution is described further, but the present invention is not limited only to this.
Trimetinib（N-(3-{3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-
dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}
phenyl) acetamide）Chemical formula be：C26H23FIN5O4, structural formula is：,
It is a kind of mek inhibitor.
The present invention provides a kind of Trimetinibs（Trametinib）Application on preparing treatment Parkinson medicinal, specifically
It is that Trimetinib is prepared into individually or with other active components or auxiliary material the drug for delaying dopaminergic neuron to degenerate.
Using 300 medflies as experimental subjects, it is randomly divided into 4 experimental groups and 1 Normal group（Ctrl）, often
Each 60 of group, every group parallel point of experimental group and Normal group are tested again.4 experimental groups are established respectively by a-
Pa caused by synuclein transgenosis overexpression, Lrrk2 transgenosis overexpression, Parkin gene mutations, Pink1 gene mutations
The gloomy disease animal model of gold, and since 5 days adult instars, experimental group persistently feeds 16.24 μM/mL Trimetinibs 30 days respectively,
Normal group feeds 5%DMSO as solvent control.Medicine feed dissects drosophila brain after 30 days, anti-using anti-dopamine hydroxylase
Body carries out full histogenic immunity dye marker dopamine neuron to drosophila brain, and microscopy observes the areas drosophila brain PPL dopamine god
Form and quantity through member, to judge work of the Trimetinib (Trametinib) to drosophila part brain area dopaminergic neuron
With the result is shown in Figure 1,2.
Fig. 1 is the schematic diagram of the local brain area dopaminergic neuron state after Trimetinib is handled, wherein fluorescence part
For the cell body profile of dopaminergic neuron, the state and quantity of dopaminergic neuron can be observed by it；Fig. 2 is through song
The statistical chart of PPL brain area dopaminergic neuron quantity after U.S. is handled for Buddhist nun.
From Fig. 1,2 as it can be seen that 16.24 μM/mL Trimetinibs can effectively reverse different cause parkinsonism Pathological pattern animals
The degeneration and death of middle dopaminergic neuron, or even it can be made to restore normal completely.Therefore, by Trimetinib
（Trametinib）It is prepared into the drug for the treatment of Parkinson, the health of dopaminergic neuron can be safeguarded, be expected to fundamentally control
Treat Parkinson's disease patients.
The foregoing is merely presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with
Modification should all belong to the covering scope of the present invention.
Claims (2)
1. application of the Trimetinib on preparing treatment Parkinson medicinal, it is characterised in that：Trimetinib is used to prepare and is delayed
The drug that dopaminergic neuron is degenerated.
2. application of the Trimetinib on preparing treatment Parkinson medicinal according to claim 1, it is characterised in that：By Sibutramine Hydrochloride
The drug of the treatment Parkinson individually or with other active components or auxiliary material is prepared into for Buddhist nun.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610208591.0A CN105816461B (en) | 2016-04-06 | 2016-04-06 | Application of the Trimetinib on preparing treatment parkinsonism drug |
| US16/091,438 US20190151320A1 (en) | 2016-04-06 | 2016-10-14 | Application of mapk signaling pathway inhibitor in manufacture of drugs for delaying degeneration of dopaminergic neurons |
| EP16897732.0A EP3441066B1 (en) | 2016-04-06 | 2016-10-14 | Mapk inhibitors for the treatment of parkinson's disease |
| PCT/CN2016/102154 WO2017173800A1 (en) | 2016-04-06 | 2016-10-14 | Application using mapk signal pathway inhibitor for preparing pharmaceutical product for delaying dopaminergic neuron degeneration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610208591.0A CN105816461B (en) | 2016-04-06 | 2016-04-06 | Application of the Trimetinib on preparing treatment parkinsonism drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105816461A CN105816461A (en) | 2016-08-03 |
| CN105816461B true CN105816461B (en) | 2018-10-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610208591.0A Active CN105816461B (en) | 2016-04-06 | 2016-04-06 | Application of the Trimetinib on preparing treatment parkinsonism drug |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20190151320A1 (en) * | 2016-04-06 | 2019-05-23 | Fuzhou University | Application of mapk signaling pathway inhibitor in manufacture of drugs for delaying degeneration of dopaminergic neurons |
| CA3041245C (en) * | 2016-11-25 | 2022-12-06 | Shine Biopharma Inc. | Composition for promoting differentiation of and protecting neural stem cells and method for inducing neural regeneration using same |
| CN111374977B (en) * | 2018-12-27 | 2022-03-18 | 浙江大学 | Application of axitinib and analogues thereof in preparation of blood brain barrier permeability regulator |
| KR20230004597A (en) * | 2020-04-14 | 2023-01-06 | 주식회사 지뉴브 | Methods and compositions for evaluating response to therapeutic agents for neurodegenerative diseases |
-
2016
- 2016-04-06 CN CN201610208591.0A patent/CN105816461B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| Forskolin激活MN9D细胞内源性Nurr1表达的信号机制研究;赵咏梅等;《中国药理学通报》;20050830;第21卷(第8期);922-926 * |
| MEK1_2抑制剂曲美替尼的药理作用与临床评价;郑宇静等;《中国新药杂志》;20140915;第23卷(第15期);1723-1726 * |
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| CN105816461A (en) | 2016-08-03 |
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