CN108392622A - Cerebrolysin Vial and its preparation are preparing the application in treating vascular dementia drug - Google Patents
Cerebrolysin Vial and its preparation are preparing the application in treating vascular dementia drug Download PDFInfo
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- CN108392622A CN108392622A CN201710714048.2A CN201710714048A CN108392622A CN 108392622 A CN108392622 A CN 108392622A CN 201710714048 A CN201710714048 A CN 201710714048A CN 108392622 A CN108392622 A CN 108392622A
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
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Abstract
The invention discloses Cerebrolysin Vials and its preparation to prepare the application in treating vascular dementia drug, pass through its influence to vascular dementia model learning and memory ability of animal experiment study, and then its effect in promoting Patients with Vascular Dementia brain neuroblastoma member injury repair and growth is determined, the present invention also has studied influence of the Cerebrolysin Vial to IGF in body 1 and neurotransmitter content for the first time, and theoretical foundation is provided for the clinical application of Cerebrolysin Vial.
Description
Technical field
The present invention relates to Cerebrolysin Vials and its preparation to prepare promotion Patients with Vascular Dementia brain neuroblastoma member damage
Repair and grow the application in drug.
Background technology
Vascular dementia（Vascular dementia, VaD）It is being recognized with higher nerve on the basis of being happened at cerebrovascular disease
Know based on dysfunction, is damaged with the acquired intelligent duration of language, visual space technical ability and emotion or personality disorder.
The incidence of VaD is higher and higher, is the most common dementia for occuping the 2nd.In recent years, as aging of population and cerebrovascular disease are sent out
The raising of sick rate, China VaD patient increase year by year, and white elephant is caused to family and society.
Cerebrolysin Vial is a kind of active brain polypeptide through multienzyme enzymolysis and extraction by health, fresh animal cerebral tissue
Substance, the necessary important elements such as amino acid and cephalin, lecithin, peptides nerve growth factor of human brain containing there are many, clinically
It is mainly used for craniocerebral trauma, sequal of cerebrovascular diseases concentrates the symptom of obstacle to improve with hypomnesia and attention.At present
There are no the systemic theoretical researches that vascular dementia is treated about Cerebrolysin Vial.
Invention content
Based on the above state of the art, it is silly in preparation treatment vascular that the object of the present invention is to provide pharmaceutics of hydrolysate of brain protein
Application in slow-witted drug.
The technical solution adopted by the present invention is as follows：
Cerebrolysin Vial and its preparation are preparing the application in treating vascular dementia drug.
Further, the Cerebrolysin Vial and its preparation can mitigate brain edema, reduce cerebral ischemia area and/or raising
Ability of learning and memory.
Meanwhile the Cerebrolysin Vial and its preparation can also promote Patients with Vascular Dementia brain neuroblastoma member injury repair
And growth.
Further, IGF-1 in body, norepinephrine, more can be improved in the Cerebrolysin Vial and its preparation
The content of bar amine, serotonin, L-aminobutanedioic acid and/or γ-aminobutyric acid.
Further, Cerebrolysin Vial of the present invention is the method recorded according to ZL 201210235771.X
Cerebrolysin Vial stoste obtained, the pharmaceutics of hydrolysate of brain protein are that pharmacy and system is added in above-mentioned Cerebrolysin Vial stoste
Preparation made from the auxiliary material that agent allows.
Further, the pharmaceutics of hydrolysate of brain protein is freeze dried powder.
The positive effect of the present invention is：
Cerebrolysin Vial is a kind of by health, a kind of multicomponent activity brain of the fresh animal cerebral tissue through multienzyme enzymolysis and extraction
Polypeptides matter, production technology is sufficiently complex, and the finally composition of the Cerebrolysin Vial of different process production is different, from
And cause different products may be different to the mode of action of nervous system.Report Cerebrolysin Vial for god in existing research
Mechanism of action through system is mainly：（1）Improve adenosine tripho hate production quantity；（2）Ionic pump energy is improved, free radical life is reduced
At；（3）Adjust intracerebral excitatory substance and inhibitory substance balance；（4）Increase utilization of the tissue to oxygen.Research there is no to report at present
Effect of the road Cerebrolysin Vial in neure damage reparation and regeneration, the also not no report in terms of mitigating brain edema.
The present invention determines influence of the Cerebrolysin Vial to the learning and memory ability of vascular dementia model by Behavior Test,
And then effect of the Cerebrolysin Vial in promoting Patients with Vascular Dementia brain neuroblastoma member injury repair and growth is determined, and
Cerebrolysin Vial has been determined to mitigating Patients with Vascular Dementia degree of cerebral edema and reducing brain by pathologyofbraintissue
The effect of ischemic areas.
Numerous studies show acetylcholine（Ach）It is considered as the important neurotransmitter of learning and memory, therefore VaD is ground
Ach levels are mostly used in studying carefully to evaluate learning and memory ability.The present invention is under study for action then it was unexpectedly observed that Cerebrolysin Vial can
Influence type-1 insulin like growth factor in body（IGF-1）Level, and determine IGF-1 levels to VaD model learnings and memory energy
The effect of power.IGF-1 is a kind of neurotrophic factor widely distributed in big intracerebral, can make damage zone neural in some cases
Member missing substantially reduces, and nerve cell is stimulated to regenerate.In addition, it has also been found that Cerebrolysin Vial can influence on first kidney
The content of the neurotransmitters such as parathyrine, dopamine, serotonin, L-aminobutanedioic acid, γ-aminobutyric acid, wherein improving γ-aminobutyric acid
The effect of content is significantly better than similar imported product Cerebrolysin（Cerebrolysin）.The present invention is Cerebrolysin Vial to nerve
The mode of action of system provides new approach, and then treats the clinical application of vascular dementia for it and provide theoretical foundation.
Specific implementation mode
Technical scheme of the present invention is described in detail with specific embodiment below.
The modeling method of 1 vascular dementia rats of embodiment
VaD majorities with multiple larger cerebral artery infraction or lacunar infarction or the low filling of brain, brain blood flow reduce degree with
Severity of dementia is related, chronic progressive cerebral insufficiency, makes it to oxygen and glucose and other required metabolite profits
With decline, it is impaired that result causes neuron oxidative damage and neuron to synthesize, and then shows as patient closely memory and space
Consciousness fails, and learning and memory ability declines.In recent years, researcher is mostly used maze experiment and step-through test to detect rat study
It therefore can be by establishing rat VaD models, to observe neure damage of the drug to the model with memory space position capability
The effect repaired and grown.
The present embodiment modeling method is as follows：
Take SPF grades of Wistar rats（Beijing Vital River Experimental Animals Technology Co., Ltd. provides, production licence number：SCXK
(capital) 2016-0011）, male, weight 180-200g, rat is first through Y labyrinths, superseded learning ability difference or to electro photoluminescence spy
Not sensitive rat.Random to select 20 rats to be used as sham-operation group, remaining rat be operation group, using improveing two blood vessel blockings
Legal system makees VaD rat models.Method is as follows：1% yellow Jackets are injected intraperitoneally in the preoperative 12h fasting of rat（5ml/kg）Anesthesia,
Rat lies on the back fixation, preserved skin, disinfection, neck median incision, blunt separation bilateral common carotid arteries（CCA）, No. 1 silk thread of set is buckled standby
With.Screw thread is tensed, before folder closes bilateral CCA, sodium nitroprussiate is injected intraperitoneally（2.5mg/kg）, press from both sides close bilateral CCA, 20min immediately
Afterwards, then logical 10min, after continuous 3 times, Line 1 ligatures its remote, proximal part, and is cut from centre, sews up the incision, puts back in cage and protect
1% Benzylpenicillin sodium salt 4ml/kg is injected intraperitoneally in temperature raising, postoperative and next day（Dosage is 6.4 ten thousand units/kg）.Rats in sham-operated group point
From sewing up the incision after arteria carotis communis.
It performs the operation latter week, Y tests in labyrinth the operation group learning and memory in rats ability of all survivals, eliminates correct number and is more than
10 rats, remaining is grouped at random, is divided into model group and Cerebrolysin Vial is high, medium and low（20,10,5mg/kg, with
Total nitrogen meter）Dosage group, every group 20, wherein Cerebrolysin Vial is using brain egg made from ZL 201210235771.X embodiments 1
White hydrolysate stoste）.Grouping, which finishes, starts tail vein administration, and sham-operation group and model group are all noted with equivalent sterile saline
It penetrates, once a day, successive administration 2 weeks.
2 maze experiment of embodiment
Rat is first put into the labyrinths ZH-DSX type Y (Anhui Zhenghua Biology Instrument Equipment Co., Ltd.) before experiment, it is allowed freely to live
It is dynamic, 5min is adapted to, training Day rat is shocked by electricity in starting area causes it to escape to safety zone, and light continues 10s, rest of then turning off the light
5s starts next operation, tests 20 times altogether.Next day is test day, is operated with training Day, is recorded correct anti-in 20 tests
Answer number for statistical analysis.Experiment carries out under dark, quiet environment.Regulation rat directly escape from starting area after being shocked by electricity to
The reaction of safety zone is known as " correct response ", is otherwise " wrong reaction ".Using the achievement of training Day as school grade, test day
Achievement as Memory result.It the results are shown in Table 1.
Influence of 1 Cerebrolysin Vial of table to VaD rat Y maze experiments
* P and sham-operation group ratio,***P<0.001；#P and model group ratio,#P<0.05,###P<0.001。
By table 1 as it can be seen that compared with sham-operation group, the correct number of model group rats Y maze learnings and Memory result is extremely aobvious
It writes and declines（P<0.001）, show learning and remembering ability occur obstacle, that is, cause neure damage and neuron biosynthesis by
Resistance.Compared with model group, it is administered 2 weeks, the height of Cerebrolysin Vial, middle dose group are remarkably improved Y maze learnings and memory
The correct number of achievement（P<0.001 or P<0.05）, it is seen that Cerebrolysin Vial has played the reparation of promotion neure damage and life
Long effect.
3 step-through test of embodiment
Rat is put into the shuttle of RD1114-PT rats and keeps away dark instrument by training Day（Shanghai Yishu Information Technology Co., Ltd.）Camera-lucida
In, 3min is adapted to, wicket is opened, rat closes wicket and shock by electricity to rat continuous 6s, be again turned on after camera-lucida enters camera bellows
Wicket, rat escape from camera bellows immediately, and the time that rat escapes from camera bellows to the 1st time needed for camera-lucida is incubation period, records incubation period,
Using the achievement of training Day as school grade；Next day is test day, and rat is put into camera bellows and does not shock by electricity, and records incubation period, test day
Achievement as Memory result.It the results are shown in Table 2.
Influence of 2 Cerebrolysin Vial of table to VaD rat step-through tests
* P and sham-operation group ratio,**P<0.01,***P<0.001；#P and model group ratio,#P<0.05, ##P<0.01.
As can be seen from Table 2, compared with sham-operation group, the latency that model group rats keep away dark learning and memory achievement is notable
Extend（P<0.01 or P<0.001）, show that obstacle occurs for learning and remembering ability, that is, cause neure damage and neuron biology
Biosynthesis block.Compared with model group, it is administered 2 weeks, the high, medium and low dosage group of Cerebrolysin Vial, which can significantly shorten, keeps away dark
Practise the latency with Memory result（P<0.001 or P<0.05）, it is seen that Cerebrolysin Vial has played promotion neuron damage
Wound is repaired and the effect of growth.
Influence of 4 Cerebrolysin Vial of embodiment to IGF-1 contents in VaD rat blood serums
After the behaviouristics of embodiment 2 and embodiment 3 detects, 1% yellow Jackets of rats by intraperitoneal injection（5ml/kg）Anesthesia,
Abdominal aortic blood.3000r/min is centrifuged, and then takes serum, is placed in -20 DEG C of refrigerators after packing and is preserved.Using ELISA method
（Varioskan Flash type microplate reader, U.S. Thermo）Carry out IGF-1 content detections.It the results are shown in Table 3.
Influence of 3 Cerebrolysin Vial of table to IGF-1 contents in VaD rat blood serums
* P and sham-operation group ratio,***P<0.001；#P and model group ratio,#P<0.05,##P<0.01,###P<0.001。
By table 3 as it can be seen that compared with sham-operation group, the content of the IGF-1 in model group rats serum is remarkably decreased（P<
0.001）.Compared with model group, it is administered 2 weeks, the height of Cerebrolysin Vial, middle dose group are remarkably improved VaD rat blood serums
In IGF-1 content（P<0.01 or P<0.001）, and IGF-1 can be such that damage zone neuron loss substantially reduces, and stimulate god
Through cytothesis, show that Cerebrolysin Vial can promote injury repair and the regeneration of brain neuroblastoma member.
Influence of 5 Cerebrolysin Vial of embodiment to GABA levels in VaD rat layers
After Y Y-maze tests, 1% yellow Jackets of rat ip（5 mL/kg）It anaesthetizes, after abdominal aortic blood, quickly breaks end
Brain is taken, meninx is removed on ice pan and blood vessel, selective separating is weighed, add 9 times of physiological saline, be homogenized in ice bath, 5000 r/
Min centrifuges 5 min, then takes supernatant, is placed in -20 DEG C of refrigerators after packing and preserves.GABA level inspections are carried out using ELISA method
It surveys, colorimetric method progress Glu level detections, the results are shown in Table 4.
4 Cerebrolysin Vial of table（Ι）Influence to GABA levels in VaD rat layers
Compared with model group：### P＜ 0.001；Compared with Cerebrolysin groups：$$$ P＜ 0.001
Cerebrolysin groups are to inject Cerebrolysin under equal conditions（Cerebrolysin）Rat.
By table 4 as it can be seen that compared with model group, it is administered 2 weeks, the height of Cerebrolysin Vial, middle dose group are remarkably improved
GABA in VaD rat layers is horizontal（P ＜ 0.001）.GABA levels in Cerebrolysin group rat layers slightly improve.
The effect of Cerebrolysin Vial middle dose group raising GABA levels is significantly stronger than the similar imported medicine Cerebrolysin of equal dosage（P
＜ 0.001）.
In addition, in each dosage group of Cerebrolysin Vial, norepinephrine, dopamine, serotonin in VaD rat layers
It is all remarkably higher than model group with the level of L-aminobutanedioic acid.
It has also been found that, compared with model group, each dosage group cerebral edema degree of Cerebrolysin Vial is notable in experimentation
Mitigate, cerebral ischemia area is substantially reduced.
It these are only the better embodiment of the present invention, rather than to the limitation of its protection domain, utilize ZL
Cerebrolysin Vial stoste made from other conditions in 201210235771.X, and freeze-dried powder made from proper auxiliary materials is added
The dosage forms such as injection, suitable with the function and effect of 1-4 of the embodiment of the present invention, the present invention no longer repeats one by one, this is considered as at this
In the protection domain of invention, those skilled in the art are made any without creativeness under the spirit and principles in the present invention
Improvement, also be regarded as within the scope of the present invention.
Claims (8)
1. Cerebrolysin Vial and its preparation are preparing the application in treating vascular dementia drug.
2. application according to claim 1, it is characterised in that：The Cerebrolysin Vial and its preparation can mitigate brain water
Swollen, reduction cerebral ischemia area and/or raising ability of learning and memory.
3. application according to claim 1 or 2, it is characterised in that：The Cerebrolysin Vial and its preparation can promote blood
Pipe dementia patients brain neuroblastoma member injury repair and growth.
4. application according to claim 3, it is characterised in that：The Cerebrolysin Vial and its preparation can be improved in body
The content of type-1 insulin like growth factor.
5. application according to claim 3, it is characterised in that：Vascular can be improved in the Cerebrolysin Vial and its preparation
The content of norepinephrine, dopamine and/or serotonin in dementia patients body.
6. application according to claim 3, it is characterised in that：Vascular can be improved in the Cerebrolysin Vial and its preparation
The content of L-aminobutanedioic acid and/or γ-aminobutyric acid in dementia patients body.
7. according to claim 1-6 any one of them applications, it is characterised in that：The Cerebrolysin Vial is according to ZL
Cerebrolysin Vial stoste made from the method that 201210235771.X is recorded, the pharmaceutics of hydrolysate of brain protein are above-mentioned brain egg
Preparation obtained after the auxiliary material that pharmacy is added in white hydrolysate stoste and galenic pharmacy allows.
8. application according to claim 7, it is characterised in that：The pharmaceutics of hydrolysate of brain protein is freeze dried powder.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2017105276399 | 2017-06-30 | ||
| CN201710527639 | 2017-06-30 |
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| CN108392622A true CN108392622A (en) | 2018-08-14 |
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Citations (3)
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|---|---|---|---|---|
| CN101002930A (en) * | 2005-12-19 | 2007-07-25 | 黄振华 | Medicine composition containing aniracetam and brain protein hydrolyte |
| CN101732695A (en) * | 2008-11-20 | 2010-06-16 | 深圳四环医药有限公司 | Compound of brain protein hydrolyzate and maleic acid and method for preparing same |
| CN102718857B (en) * | 2012-07-09 | 2013-05-22 | 河北智同医药控股集团有限公司 | Denatured protein powder and brain protein hydrolyzate prepared from same |
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2017
- 2017-08-18 CN CN201710714048.2A patent/CN108392622A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002930A (en) * | 2005-12-19 | 2007-07-25 | 黄振华 | Medicine composition containing aniracetam and brain protein hydrolyte |
| CN101732695A (en) * | 2008-11-20 | 2010-06-16 | 深圳四环医药有限公司 | Compound of brain protein hydrolyzate and maleic acid and method for preparing same |
| CN102718857B (en) * | 2012-07-09 | 2013-05-22 | 河北智同医药控股集团有限公司 | Denatured protein powder and brain protein hydrolyzate prepared from same |
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Application publication date: 20180814 |