CN106580963A - Pharmaceutical composition for alzheimer's disease - Google Patents
Pharmaceutical composition for alzheimer's disease Download PDFInfo
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- CN106580963A CN106580963A CN201611248816.1A CN201611248816A CN106580963A CN 106580963 A CN106580963 A CN 106580963A CN 201611248816 A CN201611248816 A CN 201611248816A CN 106580963 A CN106580963 A CN 106580963A
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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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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a pharmaceutical composition for an alzheimer's disease. The pharmaceutical composition is prepared from oleracein E and piracetam according to the mass ratio of (20-28):1. APP/PS1 double transgenic mice are selected as an animal model of the alzheimer's disease, the time of a passive avoidance incubation period of the mice is detected through passive avoidance test ethology to serve as the index for measuring the learning and memory ability of the mice, the distinguishing index of the mice is detected through a new object recognition test to serve as the cognitive ability of the mice. The result shows that the pharmaceutical composition can significantly shorten the time of the passive avoidance incubation period of the APP/PS1 double transgenic mice, the distinguishing index of the APP/PS1 double transgenic mice is increased, and a good therapeutic effect on the alzheimer's disease of the APP/PS1 double transgenic mice is achieved.
Description
Technical field
The present invention relates to technical field of western medicines, specifically a kind of pharmaceutical composition for senile dementia.
Background technology
Alzheimer（Alzheimer ' sdisease, AD）That is senile dementia, is common a kind of multiple of old people
Chronic progressive external neurodegenerative disease, clinical signs are dysmnesia, 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 sickness rate of AD is in what is risen year by year
Trend.Due to lacking effective treatment meanss, AD has become the 4th harm mankind after Cardial or cerebral vascular diseases and tumor 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 sciences.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition for senile dementia evident in efficacy.
For achieving the above object, the present invention provides following technical scheme：
A kind of pharmaceutical composition for senile dementia, is made up of oleracein E and piracetam, wherein, Herba Portulacae acyl
Amine E is 20-28 with the mass ratio of piracetam：1.
As further scheme of the invention：Described oleracein E is 23-26 with the mass ratio of piracetam：1.
As further scheme of the invention：Described oleracein E 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 pharmaceutical composition is 3.5-4.5mg/kg/
Day.
As further scheme of the invention：Adult's dosage of described pharmaceutical composition is 4.0mg/kg/ days.
Compared with prior art, the invention has the beneficial effects as follows：
The present invention selects the animal model that APP/PS1 bi-transgenic mices are senile dementia, to keep away the detection of dark test behavioristicss
APP/PS1 bi-transgenic mices keep away dark latency as the learning memory of measurement APP/PS1 bi-transgenic mices
Index.As a result prove, pharmaceutical composition of the present invention extremely can significantly shorten when keeping away dark incubation period of APP/PS1 bi-transgenic mices
Between, the learning memory of APP/PS1 bi-transgenic mices is greatly improved, the senile dementia to APP/PS1 bi-transgenic mices
With preferable therapeutic effect.
In addition, the present invention detects the resolving index of APP/PS1 bi-transgenic mices as measurement using new object recognition test
The cognitive competence of APP/PS1 bi-transgenic mices.As a result find, pharmaceutical composition of the present invention can improve APP/PS1 pair and turn base
Because of the resolving index of mice, the cognitive competence 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 the embodiment of whole.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, by oleracein E and piracetam group
Into, wherein, oleracein E 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, by oleracein E and piracetam group
Into, wherein, oleracein E 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, by oleracein E and piracetam group
Into, wherein, oleracein E 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, by oleracein E and piracetam group
Into, wherein, oleracein E 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, by oleracein E and piracetam group
Into, wherein, oleracein E 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：With Herba Portulacae acyl
Amine E and piracetam are effective ingredient, using acceptable technique and adjuvant on pharmaceuticss, make and be subjected on various pharmaceuticss
Peroral dosage form.
Test example 1
Impact test of the pharmaceutical composition of the present invention to the memory 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, test packet
Take 100 APP/PS1 bi-transgenic mices and be randomly divided into 10 groups, 10 per group, respectively model group, 1 group of test, test
2 groups, test 3 groups, test 4 groups, test 5 groups, contrast 1 group, contrast 2 groups, test 5 subtract dosage group, test 5 increase dosage groups.Each group
The administering mode of rat is rear tail vein injection, and once a day, continuous 4 weeks, each packet dosage was as follows：
Model group：Inject isopyknic normal saline；
Test 1 group：The pharmaceutical composition of the embodiment 1 of 4.0mg/kg is given, injection injection is configured to；
Test 2 groups：The pharmaceutical composition of the embodiment 2 of 4.0mg/kg is given, injection injection is configured to；
Test 3 groups：The pharmaceutical composition of the embodiment 3 of 4.0mg/kg is given, injection injection is configured to；
Test 4 groups：The pharmaceutical composition of the embodiment 4 of 4.0mg/kg is given, injection injection is configured to；
Test 5 groups：The pharmaceutical composition of the embodiment 5 of 4.0mg/kg is given, injection injection is configured to；
Contrast 1 group：The oleracein E of 3.84mg/kg is given, injection injection is configured to；
Contrast 2 groups：The piracetam of 0.16mg/kg is given, injection injection is configured to；
Test 5 subtracts dosage group：The pharmaceutical composition of the embodiment 5 of 2.0mg/kg is given, injection injection is configured to；
Test 5 increases dosage group：The pharmaceutical composition of the embodiment 5 of 8.0mg/kg is given, injection injection is configured to.
3rd, test method
Detected using dark auto testing instrument is kept away, kept away clearly demarcated dark two Room of active box of dark auto testing instrument, had one between two Room
Hole, bottom passes to copper grid.Each group APP/PS1 bi-transgenic mice is trained before formal test, by APP/PS1 pair base is turned
Carry hole because of mice head and be put into bright room, first adapt to environment 2min, then give darkroom copper grid logical 36V electric currents, APP/PS1 is double to turn base
Shocked by electricity into after darkroom because of mice and run away to bright room, copper grid are persistently powered 5min, as training process.Carry out after 24h
The test of memory of APP/PS1 bi-transgenic mices, records the time that APP/PS1 bi-transgenic mices enter for the first time darkroom（Keep 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.
The each administration group of table 1 keeps away APP/PS1 bi-transgenic mices dark preclinical impact（±SD）
| Project | n | Keep away dark incubation period（s） |
| Model group | 10 | 103.58±17.65 |
| Test 1 group | 10 | 40.36±7.26** |
| Test 2 groups | 10 | 39.89±6.48** |
| Test 3 groups | 10 | 36.05±5.31** |
| Test 4 groups | 10 | 34.74±4.78** |
| Test 5 groups | 10 | 31.20±3.96** |
| Contrast 1 group | 10 | 84.32±15.26 |
| Contrast 2 groups | 10 | 97.84±16.94 |
| Test 5 subtracts dosage group | 10 | 52.06±10.78* |
| Test 5 increases dosage group | 10 | 30.69±3.54** |
Compared with model group, * P ＜ 0.05, * * P ＜ 0.01.
As can be seen from Table 1：
（1）Compare for 2 groups with contrast with model group, 1 group of contrast, testing the pharmaceutical composition of 1-5 groups can significantly shorten APP/PS1
Bi-transgenic mice keeps away dark latency, especially tests 5 groups of pharmaceutical composition to APP/PS1 bi-transgenic mices
Keep away dark latency to shorten with extremely significant difference（P ＜ 0.01）；
（2）Compare with 2 groups of 1 group of contrast and contrast, testing 5 groups of pharmaceutical composition extremely can significantly shorten double turns of APP/PS1
DNA murine keeps away dark latency, illustrates oleracein E and piracetam in the APP/PS1 bi-transgenic mices for shortening
Dark latency aspect of keeping away there is significant synergism, can significantly recover the memory of APP/PS1 bi-transgenic mices
Ability；
（3）Compared with test 5 subtracts dosage group, testing the pharmaceutical composition of 5 groups and the increasing dosage group of test 5 can significantly shorten APP/
PS1 bi-transgenic mices keep away dark latency, but test 5 groups and test 5 increases between dosage groups to APP/PS1 double transgenics
The dark latency of keeping away of mice shortens not with significant difference.
Test example 2
Impact test of the pharmaceutical composition of the present invention to the cognitive competence 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, test packet
Take 100 APP/PS1 bi-transgenic mices and be randomly divided into 10 groups, 10 per group, respectively model group, 1 group of test, test
2 groups, test 3 groups, test 4 groups, test 5 groups, contrast 1 group, contrast 2 groups, test 5 subtract dosage group, test 5 increase dosage groups.Each group
The administering mode of rat is rear tail vein injection, and once a day, continuous 4 weeks, each packet dosage was as follows：
Model group：Inject isopyknic normal saline；
Test 1 group：The pharmaceutical composition of the embodiment 1 of 4.0mg/kg is given, injection injection is configured to；
Test 2 groups：The pharmaceutical composition of the embodiment 2 of 4.0mg/kg is given, injection injection is configured to；
Test 3 groups：The pharmaceutical composition of the embodiment 3 of 4.0mg/kg is given, injection injection is configured to；
Test 4 groups：The pharmaceutical composition of the embodiment 4 of 4.0mg/kg is given, injection injection is configured to；
Test 5 groups：The pharmaceutical composition of the embodiment 5 of 4.0mg/kg is given, injection injection is configured to；
Contrast 1 group：The oleracein E of 3.84mg/kg is given, injection injection is configured to；
Contrast 2 groups：The piracetam of 0.16mg/kg is given, injection injection is configured to；
Test 5 subtracts dosage group：The pharmaceutical composition of the embodiment 5 of 2.0mg/kg is given, injection injection is configured to；
Test 5 increases dosage group：The pharmaceutical composition of the embodiment 5 of 8.0mg/kg is given, injection injection is configured to.
3rd, test method
Tested using new object identification method, test is carried out in a homemade white plastic behavior case, behavior case
Length, width and height are respectively 500mm × 500mm × 300mm, and 3 stages of whole test point complete.
First stage：With one day as laundering period, mice is put in behavior case and allows it freely to explore 5 minutes, in this single order
Section, without data collection.
Second stage：With one day as training period, two identical object A and object B are put in behavior case, object distance
Behavior case about 5cm, two objects are put into mice and allow it freely to explore 5 minutes at a distance of 20cm；Wherein exploratory behaviour is defined as：
The nose of mice touches object apart from object less than 2cm or with nose, walks about around object or lies prone in its near vicinity not
Can be used as exploratory behaviour；In this stage, the time that mice explores each object is recorded, after terminating, mice puts back at once cage.
Phase III：With one day to test the phase, mice is placed on object A is changed into the behavior case after a new object C
Freely explore 5 minutes.
The cognitive function of mice is weighed using resolving index, time of the new object of resolving index=exploration/（Explore new object
Time+exploration past heritage body time）, i.e., the time of the resolving index of training period=exploration object A/（The time of exploration object A+
Explore the time of object B）, test the phase resolving index=exploration object C time/（Explore the time+exploration object B of object C
Time）.
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, for the time that training period each group mice explores two same objects counts, find each
Group mice explores the resolving index no difference of science of statistics of two same objects；For test phase each group mice explores two not jljls
The time of body is counted, and is found：
（1）Compare for 2 groups with contrast with model group, 1 group of contrast, testing the pharmaceutical composition of 1-5 groups can significantly improve APP/PS1
Bi-transgenic mice resolving index, especially tests 5 groups of pharmaceutical composition to APP/PS1 bi-transgenic mice resolving indexs
Improve and there is extremely significant difference（P ＜ 0.01）；
（2）Compare with 2 groups of 1 group of contrast and contrast, testing 5 groups of pharmaceutical composition extremely can significantly improve double turns of APP/PS1
The resolving index of DNA murine, illustrates that oleracein E and piracetam refer in the resolution for improving APP/PS1 bi-transgenic mices
Number aspect has significant synergism, can significantly improve the cognitive competence of APP/PS1 bi-transgenic mices；
（3）Compared with test 5 subtracts dosage group, testing the pharmaceutical composition of 5 groups and the increasing dosage group of test 5 can significantly improve APP/
The resolving index of PS1 bi-transgenic mices, but test between 5 groups and the increasing dosage group of test 5 to APP/PS1 bi-transgenic mices point
The raising for distinguishing 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 spirit or essential attributes without departing substantially from the present 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 is required rather than described above is limited, 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 this specification is been described by according to embodiment, not each embodiment is only wrapped
Containing an independent technical scheme, this narrating mode of description is only that for clarity those skilled in the art should
Using description as an entirety, the technical scheme in each embodiment can also Jing it is appropriately combined, form those skilled in the art
Understandable other embodiment.
Claims (6)
1. a kind of pharmaceutical composition for senile dementia, it is characterised in that be made up of oleracein E and piracetam,
Wherein, oleracein E and the mass ratio of piracetam are 20-28：1.
2. the pharmaceutical composition for senile dementia according to claim 1, it is characterised in that described Herba Portulacae acyl
Amine E 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 Herba Portulacae acyl
Amine E is 24 with the mass ratio of piracetam：1.
4. treatment senile dementia is being prepared according to the arbitrary described pharmaceutical composition 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 pharmaceutical composition 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 pharmaceutical composition be 4.0mg/kg/ days.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611248816.1A CN106580963A (en) | 2016-12-29 | 2016-12-29 | Pharmaceutical composition for alzheimer's disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611248816.1A CN106580963A (en) | 2016-12-29 | 2016-12-29 | Pharmaceutical composition for alzheimer's disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106580963A true CN106580963A (en) | 2017-04-26 |
Family
ID=58604087
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611248816.1A Pending CN106580963A (en) | 2016-12-29 | 2016-12-29 | Pharmaceutical composition for alzheimer's disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106580963A (en) |
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2016
- 2016-12-29 CN CN201611248816.1A patent/CN106580963A/en active Pending
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Application publication date: 20170426 |