CN106727537A - A kind of pharmaceutical composition and its application for senile dementia - Google Patents
A kind of pharmaceutical composition and its application for senile dementia Download PDFInfo
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- CN106727537A CN106727537A CN201611093832.8A CN201611093832A CN106727537A CN 106727537 A CN106727537 A CN 106727537A CN 201611093832 A CN201611093832 A CN 201611093832A CN 106727537 A CN106727537 A CN 106727537A
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- senile dementia
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- piracetam
- western medicine
- pharmaceutical composition
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
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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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition for senile dementia and its application, the Western medicine compound is made up of levamisole hydrochloride bolt and Piracetam, wherein, levamisole hydrochloride bolt is 20 28 with the mass ratio of Piracetam：1.Present invention selection APP/PS1 bi-transgenic mices are the animal model of senile dementia, the index for keeping away learning memory of the dark latency as measurement mouse to keep away dark experiment behaviouristics detection mouse, using the resolving index of new object recognition test detection mouse as the cognitive ability of measurement mouse.Result is proved, what Western medicine compound of the present invention extremely can significantly shorten APP/PS1 bi-transgenic mices keeps away dark latency, the resolving index of APP/PS1 bi-transgenic mices is improved, there is preferable therapeutic effect to the senile dementia of APP/PS1 bi-transgenic mices.
Description
Technical field
The present invention relates to technical field of western medicines, specifically a kind of pharmaceutical composition and its application for senile dementia.
Background technology
Alzheimer disease (Alzheimer ' sdisease, AD) is senile dementia, is common a kind of multiple of the elderly
Chronic progressive neurodegenerative disorders, clinical signs are memory disorders, agnosia, spatial memory capacity infringement, abstract thinking
With the feature such as computing capability infringement, personality and behavior change.With population in the world aging, the incidence of disease of AD is in what is risen year by year
Trend.Due to lacking effective treatment means, AD has turned into the 4th harm mankind after Cardial or cerebral vascular diseases and tumour and has been good for
The fatal disease of health.Therefore, the active drug for finding preventing and treating AD has become problem demanding prompt solution in life science.
At present, treatment senile dementia medicine mainly have cholinesterase inhibitor, cerebral vasodilator, calcium antagonist,
Prevent A β from depositing medicine, suppress β, gamma secretase medicine and anti-inflammatory agent and the natural component with the effect of potential anti-senile dementia.Though
Right said medicine has shown that certain curative effect in clinical practice, but exists during long-term use and serious can not keep away
The side effect exempted from, and therapeutic effect is not notable.Therefore, find and a kind of treat senile dementia effect is significant, Small side effects
Medicine is the problem of current urgent need to resolve.
Levamisole hydrochloride bolt, is the levo form of tetramisole, optionally suppresses the butanedioic acid dehydrogenation in polypide muscle
Enzyme, prevents fumaric acid from the anaerobic metabolism for being reduced to butanedioic acid so as to influence polypide muscle, reduces energy production.When polypide with
Contact when, can depolarize neuromuscular, muscle occur contracts last and cause paralysis；The plan choline effect of medicine is conducive to worm
The discharge of body.Its activity is about 1~2 times of tetramisole (raceme), but toxic and side effect is then relatively low.In addition, medicine is to polypide
Micro-tubular structure may have inhibitory action.Levamisol also has immunological regulation and immune excitement function.
The present invention is by research discovery, the combination that levamisole hydrochloride bolt and Piracetam are formed according to a certain ratio
Thing, can effectively treat senile dementia.
The content of the invention
It is an object of the invention to provide a kind of evident in efficacy pharmaceutical composition and its application for senile dementia.
To achieve the above object, the present invention provides following technical scheme：
A kind of pharmaceutical composition for senile dementia, is made up of levamisole hydrochloride bolt and Piracetam, wherein, salt
Sour levamisol bolt is 20-28 with the mass ratio of Piracetam：1.
As further scheme of the invention：Described levamisole hydrochloride bolt is 23-26 with the mass ratio of Piracetam：
1。
As further scheme of the invention：Described levamisole hydrochloride bolt is 24 with the mass ratio of Piracetam：1.
Application of the described pharmaceutical composition for senile dementia in treatment senile dementia is prepared.
As further scheme of the invention：Adult's dosage of described Western medicine compound is 3.5-4.5mg/kg/
Day.
As further scheme of the invention：Adult's dosage of described Western medicine compound is 4.0mg/kg/ days.
Compared with prior art, the beneficial effects of the invention are as follows：
Present invention selection APP/PS1 bi-transgenic mices are the animal model of senile dementia, to keep away dark experiment behaviouristics
That detects APP/PS1 bi-transgenic mices keeps away learning and memory of the dark latency as measurement APP/PS1 bi-transgenic mices
The index of power.Result proves that it is dark latent that Western medicine compound of the present invention extremely can significantly shorten keeping away for APP/PS1 bi-transgenic mices
Time phase, the learning memory of APP/PS1 bi-transgenic mices is greatly improved, the old age to APP/PS1 bi-transgenic mices is crazy about
Slow-witted disease has preferable therapeutic effect.
In addition, the present invention is using the resolving index of new object recognition test detection APP/PS1 bi-transgenic mices as measurement
The cognitive ability of APP/PS1 bi-transgenic mices.Result finds that Western medicine compound of the present invention can improve APP/PS1 pairs and turn base
Because of the resolving index of mouse, the cognitive ability of APP/PS1 bi-transgenic mices is improved, there is preferably treatment to senile dementia
Effect.
Specific embodiment
Below in conjunction with the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described,
Obviously, described embodiment is only a part of embodiment of the invention, rather than whole embodiments.Based in the present invention
Embodiment, the every other embodiment that those of ordinary skill in the art are obtained under the premise of creative work is not made, all
Belong to the scope of protection of the invention.
Embodiment 1
In the embodiment of the present invention, a kind of pharmaceutical composition for senile dementia is drawn by levamisole hydrochloride bolt and pyrrole
Western smooth composition, wherein, levamisole hydrochloride bolt is 20 with the mass ratio of Piracetam：1.
Embodiment 2
In the embodiment of the present invention, a kind of pharmaceutical composition for senile dementia is drawn by levamisole hydrochloride bolt and pyrrole
Western smooth composition, wherein, levamisole hydrochloride bolt is 28 with the mass ratio of Piracetam：1.
Embodiment 3
In the embodiment of the present invention, a kind of pharmaceutical composition for senile dementia is drawn by levamisole hydrochloride bolt and pyrrole
Western smooth composition, wherein, levamisole hydrochloride bolt is 23 with the mass ratio of Piracetam：1.
Embodiment 4
In the embodiment of the present invention, a kind of pharmaceutical composition for senile dementia is drawn by levamisole hydrochloride bolt and pyrrole
Western smooth composition, wherein, levamisole hydrochloride bolt is 26 with the mass ratio of Piracetam：1.
Embodiment 5
In the embodiment of the present invention, a kind of pharmaceutical composition for senile dementia is drawn by levamisole hydrochloride bolt and pyrrole
Western smooth composition, wherein, levamisole hydrochloride bolt is 24 with the mass ratio of Piracetam：1.
In above-described embodiment, the preparation process of the described pharmaceutical composition for senile dementia is：It is left-handed with hydrochloric acid
Imidazoles bolt and Piracetam are active ingredient, and using acceptable technique and auxiliary material in pharmacy, being made can in various pharmacies
The peroral dosage form of receiving.
Test example 1
Influence experiment of the Western medicine compound of the present invention to the memory capability of APP/PS1 bi-transgenic mices
1st, subjects
100 APP/PS1 bi-transgenic mices are chosen, is provided by Ze Sheng Bioisystech Co., Ltd of BeiJing ZhongKe.
2nd, experiment packet
Take 100 APP/PS1 bi-transgenic mices and be randomly divided into 10 groups, every group 10, respectively model group, 1 group of experiment,
Test 2 groups, experiment 3 groups, experiment 4 groups, experiment 5 groups, contrast 1 group, contrast 2 groups, experiment 5 subtract dosage group, experiment 5 increase dosage groups.
The administering mode of each group rat is rear tail vein injection, and once a day, continuous 4 weeks, each packet dosage was as follows：
Model group：The isometric physiological saline of injection；
Test 1 group：The Western medicine compound of the embodiment 1 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 2 groups：The Western medicine compound of the embodiment 2 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 3 groups：The Western medicine compound of the embodiment 3 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 4 groups：The Western medicine compound of the embodiment 4 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 5 groups：The Western medicine compound of the embodiment 5 of 4.0mg/kg is given, parenteral solution injection is configured to；
Contrast 1 group：The levamisole hydrochloride bolt of 3.84mg/kg is given, parenteral solution injection is configured to；
Contrast 2 groups：The Piracetam of 0.16mg/kg is given, parenteral solution injection is configured to；
Experiment 5 subtracts dosage group：The Western medicine compound of the embodiment 5 of 2.0mg/kg is given, parenteral solution injection is configured to；
Experiment 5 increases dosage group：The Western medicine compound of the embodiment 5 of 8.0mg/kg is given, parenteral solution injection is configured to.
3rd, test method
Detected using dark auto testing instrument is kept away, clearly demarcated dark two Room of active box of dark auto testing instrument is kept away, between two Room
There is a hole, bottom passes to copper grid.Each group APP/PS1 bi-transgenic mices are trained before formal test, APP/PS1 is double
Transgenic mice head carries hole and is put into bright room, first adapts to environment 2min, then gives the darkroom logical 36V electric currents of copper grid, and APP/PS1 is double
Into being subject to behind darkroom electric shock to run away to bright room, copper grid are persistently powered 5min transgenic mice, as training process.After 24h
The test of memory of APP/PS1 bi-transgenic mices is carried out, record APP/PS1 bi-transgenic mices enter the time in darkroom for the first time
(keeping away dark incubation period), if being still introduced into darkroom in APP/PS1 bi-transgenic mices 5min, its incubation period is counted as 300s.
4th, result of the test
Result of the test is as shown in table 1.
Each administration group of table 1 keeps away APP/PS1 bi-transgenic mices dark preclinical influence (± SD)
Compared with model group, * P ＜ 0.05, * * P ＜ 0.01.
As can be seen from Table 1：
(1) compared with 2 groups of model group, 1 group of contrast and contrast, the Western medicine compound for testing 1-5 groups can significantly shorten
APP/PS1 bi-transgenic mices keep away dark latency, especially test that 5 groups of Western medicine compound is double to APP/PS1 to turn base
Because the dark latency of keeping away of mouse shortens with extremely significant difference (p ＜ 0.01)；
(2) compared with 2 groups of 1 group of contrast and contrast, the Western medicine compound of 5 groups of experiment extremely can significantly shorten APP/PS1
Bi-transgenic mice keeps away dark latency, illustrates that levamisole hydrochloride bolt and Piracetam turn the APP/PS1 for shortening is double
The dark latency aspect of keeping away of DNA murine has significant synergy, can significantly recover APP/PS1 double transgenics small
The memory capability of mouse；
(3) compared with experiment 5 subtracts dosage group, the Western medicine compound of 5 groups of experiment and the increasing dosage group of experiment 5 can significantly shorten
Keeping away between dark latency, but 5 groups of experiment and the increasing dosage group of experiment 5 for APP/PS1 bi-transgenic mices turns to APP/PS1 pairs
The dark latency of keeping away of DNA murine shortens without significant difference.
Test example 2
Influence experiment of the Western medicine compound of the present invention to the cognitive ability of APP/PS1 bi-transgenic mices
1st, subjects
100 APP/PS1 bi-transgenic mices are chosen, is provided by Ze Sheng Bioisystech Co., Ltd of BeiJing ZhongKe.
2nd, experiment packet
Take 100 APP/PS1 bi-transgenic mices and be randomly divided into 10 groups, every group 10, respectively model group, 1 group of experiment,
Test 2 groups, experiment 3 groups, experiment 4 groups, experiment 5 groups, contrast 1 group, contrast 2 groups, experiment 5 subtract dosage group, experiment 5 increase dosage groups.
The administering mode of each group rat is rear tail vein injection, and once a day, continuous 4 weeks, each packet dosage was as follows：
Model group：The isometric physiological saline of injection；
Test 1 group：The Western medicine compound of the embodiment 1 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 2 groups：The Western medicine compound of the embodiment 2 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 3 groups：The Western medicine compound of the embodiment 3 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 4 groups：The Western medicine compound of the embodiment 4 of 4.0mg/kg is given, parenteral solution injection is configured to；
Test 5 groups：The Western medicine compound of the embodiment 5 of 4.0mg/kg is given, parenteral solution injection is configured to；
Contrast 1 group：The levamisole hydrochloride bolt of 3.84mg/kg is given, parenteral solution injection is configured to；
Contrast 2 groups：The Piracetam of 0.16mg/kg is given, parenteral solution injection is configured to；
Experiment 5 subtracts dosage group：The Western medicine compound of the embodiment 5 of 2.0mg/kg is given, parenteral solution injection is configured to；
Experiment 5 increases dosage group：The Western medicine compound of the embodiment 5 of 8.0mg/kg is given, parenteral solution injection is configured to.
3rd, test method
Tested using new object identification method, experiment is carried out in a homemade white plastic behavior case, behavior
The length, width and height of case are respectively 500mm × 500mm × 300mm, and 3 stages of whole experiment point complete.
First stage：It was the laundering period with one day, mouse is put into behavior case and allows it freely to explore 5 minutes, in this single order
Section, does not have Data Collection.
Second stage：It was training period with one day, two identical object A and object B is put into behavior case, object distance
Behavior case about 5cm, two objects are put into mouse and allow it freely to explore 5 minutes at a distance of 20cm；Wherein exploratory behaviour is defined as：
The nose of mouse touches object apart from object less than 2cm or with nose, is walked about around object or lain prone in its near vicinity not
Can be used as exploratory behaviour；In this stage, record mouse explores the time of each object, and after terminating, mouse puts back to cage at once.
Phase III：With one day for the test phase, mouse is placed on object A is changed into the behavior case after a new object C
Freely explore 5 minutes.
The cognitive function of mouse, time/(the new object of exploration of the new object of resolving index=exploration are weighed using resolving index
Time+exploration past heritage body time), i.e. time of the resolving index of training period=exploration object A/(explore the time of object A
The time of+exploration object B), test the time/(time+exploration object of exploration object C of the resolving index=exploration object C of phase
The time of B).
4th, result of the test
Result of the test is as shown in table 2.
The APP/PS1 bi-transgenic mice training periods of table 2 and the resolving index of test phase
Compared with model group, * P ＜ 0.05, * * P ＜ 0.01.
As can be seen from Table 2, counted for the time that training period each group mouse explores two same objects, found each
Group mouse explores two resolving index no difference of science of statistics of same object；Two not jljls are explored for test phase each group mouse
The time of body is counted, and is found：
(1) compared with 2 groups of model group, 1 group of contrast and contrast, the Western medicine compound for testing 1-5 groups can be significantly improved
APP/PS1 bi-transgenic mice resolving indexs, especially test 5 groups of Western medicine compound to APP/PS1 bi-transgenic mices point
Distinguishing the raising of index has extremely significant difference (p ＜ 0.01)；
(2) compared with 2 groups of 1 group of contrast and contrast, the Western medicine compound of 5 groups of experiment extremely can significantly improve APP/PS1
The resolving index of bi-transgenic mice, illustrates that levamisole hydrochloride bolt and Piracetam are improving APP/PS1 bi-transgenic mices
Resolving index aspect there is significant synergy, can significantly improve the cognitive ability of APP/PS1 bi-transgenic mices；
(3) compared with experiment 5 subtracts dosage group, the Western medicine compound of 5 groups of experiment and the increasing dosage group of experiment 5 can be significantly improved
It is small to APP/PS1 double transgenics between the resolving index of APP/PS1 bi-transgenic mices, but 5 groups of experiment and the increasing dosage group of experiment 5
The raising of mouse resolving index does not have significant difference.
It is obvious to a person skilled in the art that the invention is not restricted to the details of above-mentioned one exemplary embodiment, Er Qie
In the case of without departing substantially from spirit or essential attributes of the invention, the present invention can be in other specific forms realized.Therefore, no matter
From the point of view of which point, embodiment all should be regarded as exemplary, and be nonrestrictive, the scope of the present invention is by appended power
Profit requires to be limited rather than described above, it is intended that all in the implication and scope of the equivalency of claim by falling
Change is included in the present invention.
Moreover, it will be appreciated that although the present specification is described in terms of embodiments, not each implementation method is only wrapped
Containing an independent technical scheme, this narrating mode of specification is only that for clarity, those skilled in the art should
Specification an as entirety, the technical scheme in each embodiment can also be formed into those skilled in the art through appropriately combined
May be appreciated other embodiment.
Claims (6)
1. a kind of pharmaceutical composition for senile dementia, it is characterised in that by levamisole hydrochloride bolt and Piracetam group
Into, wherein, levamisole hydrochloride bolt is 20-28 with the mass ratio of Piracetam：1.
2. the pharmaceutical composition for senile dementia according to claim 1, it is characterised in that described hydrochloric acid is left-handed
Imidazoles bolt is 23-26 with the mass ratio of Piracetam：1.
3. the pharmaceutical composition for senile dementia according to claim 2, it is characterised in that described hydrochloric acid is left-handed
Imidazoles bolt is 24 with the mass ratio of Piracetam：1.
4. treatment senile dementia is being prepared according to any described pharmaceutical compositions for senile dementia of claim 1-3
Application in medicine.
5. the pharmaceutical composition for senile dementia according to claim 4 is in treatment senile dementia is prepared
Application, it is characterised in that adult's dosage of described Western medicine compound be 3.5-4.5mg/kg/ days.
6. the pharmaceutical composition for senile dementia according to claim 5 is in treatment senile dementia is prepared
Application, it is characterised in that adult's dosage of described Western medicine compound be 4.0mg/kg/ days.
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| CN201611093832.8A CN106727537A (en) | 2016-12-02 | 2016-12-02 | A kind of pharmaceutical composition and its application for senile dementia |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389429A (en) * | 2016-12-02 | 2017-02-15 | 郑州莉迪亚医药科技有限公司 | Western medicine composition for treating senile dementia and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994027603A1 (en) * | 1993-06-01 | 1994-12-08 | Cortex Pharmaceuticals, Inc. | Alkaline and acid phosphatase inhibitors in treatment of neurological disorders |
| CN102188471A (en) * | 2011-04-20 | 2011-09-21 | 长春中医药大学 | Pharmaceutical composition for treating Alzheimer disease symptom and its preparation method |
-
2016
- 2016-12-02 CN CN201611093832.8A patent/CN106727537A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994027603A1 (en) * | 1993-06-01 | 1994-12-08 | Cortex Pharmaceuticals, Inc. | Alkaline and acid phosphatase inhibitors in treatment of neurological disorders |
| CN102188471A (en) * | 2011-04-20 | 2011-09-21 | 长春中医药大学 | Pharmaceutical composition for treating Alzheimer disease symptom and its preparation method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389429A (en) * | 2016-12-02 | 2017-02-15 | 郑州莉迪亚医药科技有限公司 | Western medicine composition for treating senile dementia and application thereof |
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