CN101366720B - Pharmaceutical uses of polyene phosphatidyl choline for treating cognitive impairment - Google Patents
Pharmaceutical uses of polyene phosphatidyl choline for treating cognitive impairment Download PDFInfo
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- CN101366720B CN101366720B CN2008102317330A CN200810231733A CN101366720B CN 101366720 B CN101366720 B CN 101366720B CN 2008102317330 A CN2008102317330 A CN 2008102317330A CN 200810231733 A CN200810231733 A CN 200810231733A CN 101366720 B CN101366720 B CN 101366720B
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Abstract
The invention provides medicinal application of polyene phosphatidylcholine in treating cognitive functional disorder, which adopts a clinically commonly used medicine for protecting the liver - the polyene phosphatidylcholine to be a novel medicine for treating the cognitive functional disorder. As proved by clinical application and animal experiments, the polyene phosphatidylcholine has influence on improving the cognitive functional disorder and the memory function and has good effect of treating the cognitive functional disorder. Due to introduction of 'polyene' radicals which are more fat-soluble, the polyene phosphatidylcholine is more favorable to pass through blood-brain barriers and can be completely taken by neurons; and choline products produced by decomposition of the polyene phosphatidylcholine by the neurons can be further synthesized into acetylcholine in the neurons, thereby compensating for choline exhausted by synaptic clefts. The polyene phosphatidylcholine can generate the choline, DHA and an arachidonic acid during the process of metabolism, is a medicine for treating the cognitive functional disorder which has moderate price and small toxic and side effect, and is safe and reliable, and can also become a medicine for improving intelligence.
Description
Technical field
The invention belongs to the medical biotechnology field, relate to a kind of new drug effect of marketed drug, promptly this marketed drug can be used as the active drug of cognitive dysfunction, specifically be a kind of medicinal usage of polyene phosphatidyl choline for treating cognitive impairment.
Background technology
(1) cognitive function and cognitive disorder
Cognitive function be meant human under wakefulness various conscious sophisticated maincenters movable, comprise from simply to the confirming of own and environment, perception, understanding, to memory, calculating, judgement and fill order, accomplish complex task etc.Cognitive dysfunction is meant that then cognitive function receives infringement in various degree, and weight person is dull-witted like all kinds, the lighter such as mild cognitive dysfunction.Be worth because the latter has early intervention, become the focus of international and domestic research in recent years.
(2) neurobiological mechanism of cognitive disorder
In all neurotransmitteies, the relation of acetylcholine and cognitive function is the closest.Acetylcholine is generated under the effect of choline acetyltransterase by S-acetyl-coenzyme-A and choline.Neurocyte acetylcholine synthetic and that discharge is brought into play regulating action through M-receptor (M-AchR, M-ChR) and N-receptor (N-AchR, nicotine receptor), and M-AchR is the G-protein coupling receptor, and N-AchR is the ligand-gated ion channel receptor.Cholinergic neuron in the brain is divided into two types, i.e. local circuit neuron and projection neuron, and the cholinergic fiber that sends from the Meynert basal nuclei is projected to frontal lobe, top, temporal lobe and the visual cortex of cortex, and this path and learning and memory function are closely related.Alzheimer (Alzheimer ' sdisease; AD) patient just has Meynert basal area cholinergic neuron to reduce in early days; Causing cortex choline acetyl transfers enzyme activity and acetyl choline content significantly to reduce, is one of amnemonic important mechanisms of AD patient; The degree of schizophrenia person's cognitive disorder and cortex choline acetyl transfers enzyme activity are negative correlation; Use cholinesterase inhibitor or m receptor agonist can improve its memory defects for AD and schizophrenic.Therefore improve the focus that the content of acetylcholine in brain just becomes the treatment of present cognitive dysfunction field
(3) the Drug therapy present situation of cognitive dysfunction
Because cognitive dysfunction and acetylcholine neuronal degeneration, levels of acetylcholine reduces that substantial connection is arranged, therefore at present to the treatment of cognitive dysfunction mainly around replenishing and the content of raising central nervous system acetylcholine, mainly want three kinds of approach:
1. cholinergic agonist:, still be in the clinic trial stage at present like new drug ENS163, LY246078, the DUP996 of selectively acting in the M1 receptor;
2. acetylcholine prodrug: once attempted with Ach prerequisite medicine replacement therapies such as lecithin and choline, and increased synthesizing and release of Ach, and can act on but fail to improve maincenter Ach;
3. acetylcholinesteraseinhibitors inhibitors:
Be widely used at present clinical improvements intelligence multiple medicine, be cholinesterase inhibitor, the degraded through suppressing Ach also improves activity and plays a role.Comprise:
(1) physostigmine: be the non-selective reversibility acetylcholinesteraseinhibitors inhibitors that uses the earliest, but untoward reaction is more, does not obtain the FDA approval, at present clinical superseded;
(2) his Kelin: first the non-selective reversibility acetylcholinesteraseinhibitors inhibitors that is the FDA approval; Cognitive function and viability are improved more obvious; But side effect is big, shows as the silent serum transaminase and increases and cholinergic symptoms, at present clinical seldom application;
(3) donepezil: second the non-selective reversibility acetylcholinesteraseinhibitors inhibitors that is the FDA approval; But its effective selectivity suppresses the degraded of Ach among the central nervous system; Increase the concentration of neurocyte synaptic space Ach, improve the nerve conduction function in memory brain district.A little less than the effect of periphery anticholinergic, longer plasma half-life, once a day, toleration and compliance are good.Be widely used in clinical treatment at present.
Except that said medicine, the at present clinical medicine that is usually used in treating cognitive dysfunction also comprises antioxidant, Folium Ginkgo extract, compound Chinese medicinal preparation etc., so far, and equal short of reliable treatment foundation of these medicines and clinical effectiveness.
Because many factors such as environment for human survival especially exist the ratio of the disease of cognitive dysfunction to increase year by year among the old people among the crowd, senile dementia is exactly wherein a kind of.People's cognitive dysfunction has a strong impact on people's quality of life, brings burden and difficulty for society and family.Medicine about cognitive dysfunction does not have effectively medicine for a long time, and the present invention has positive meaning for the drug research of cognitive dysfunction for Spirit of Man and physical and mental health.
Research of the present invention is to go deep into more on the basis of theoretical research in the medical biotechnology field; Further, aim to provide the existing Drug therapy cognitive dysfunction of a kind of usefulness and new medicine use that benefit Spirit of Man health from the actual discussion targetedly of theory and combining.
Retrieve in Internet search with to domestic and international patent documentation and the journal article of publishing through project team of the present invention; Do not see the medicine report that adopts polyene phosphatidylcholine to be used for cognitive dysfunction as yet, do not find same report or the document relevant yet with the present invention.
Summary of the invention
The objective of the invention is provides a kind of new medicinal usage about hepatic-polyene phosphatidylcholine commonly used, and promptly the new medicine use of polyene phosphatidyl choline for treating cognitive impairment provides polyene phosphatidylcholine a kind of new treatment indication in other words.
Below the present invention will be described
Polyene phosphatidylcholine is a kind of medication that protects the liver commonly used clinically; Moderate; Toxic and side effects is little, and the present invention is used to treat cognitive dysfunction with this listing patent medicine, and clinical experiment is observed polyene phosphatidylcholine to mild cognitive dysfunction (mild cognitive impairment; MCI) influence of patient's cognitive function is used behind the rat psychological stress cognitive disorder model testing polyene phosphatidylcholine then to the influence of rat memory function.Still be that zoopery all proves from clinical practice no matter: polyene phosphatidylcholine has good effect for the treatment cognitive dysfunction.
The present invention uses polyene phosphatidylcholine to have to improve the effect of cognitive dysfunction.
Application of the present invention proof polyene phosphatidylcholine is for around the content that replenishes and improve central nervous system's acetylcholine, to four target spots: 1. choline: replenish synthesis material; 2.DHA: neurocyte and synaptic vesicle are repaired in nutrition; 3.AA: the antiplatelet aggregation blood viscosity lowering.
Through the present invention about polyene phosphatidylcholine for the treatment cognitive dysfunction mechanism research
The mechanism of polyene phosphatidyl choline for treating cognitive disorder
Polyene phosphatidylcholine (Polyene Phosphatidyl choline) is the strong phosphatidylcholine that contains arachidonic acid (AA) and docosahexenoic acid (DHA) of unsaturated fatty acid on the triglyceride skeleton of lecithin.Polyene phosphatidylcholine is compared with common lecithin, its outstanding feature: (1) phosphatidylcholine content is high, and arachidonic acid (AA) and (3) docosahexenoic acid (DHA) are contained in (2).So it is also different at physiological active functions and Application and Development thereof.Therefore, polyene phosphatidylcholine has the important physiological active function especially aspect lipid metabolism except that having the general physiologically active of ovum fat.And, study it in recent years as polyunsaturated acid sources of supply such as choline and arachidonic acid and DHA.DHA has the learning and memory of raising, brain-strengthening, reduces lipid and blood pressure in the blood, reaches functions such as cholesterol, inhibition arteriosclerosis and thrombosis generation, AFL, reinforcement neurotransmission system activity, antitumor.In addition,, thereby help seeing through blood brain barrier more because polyene phosphatidylcholine introduced and have more fat-soluble " polyenoid " group, can be complete absorbed by neuron.And the further synthesis of acetyl choline in neuron of the product choline that neuron decomposes polyene phosphatidylcholine is exhausted the choline that falls thereby remedy synaptic space.Therefore we can find that polyene phosphatidylcholine can generate in metabolic process: choline (can replenish the acetylcholine synthesis material), DHA (neurocyte and synaptic vesicle are repaired in nutrition) and arachidonic acid (antiplatelet aggregation viscosity reduction).
Therefore, the present invention draws polyene phosphatidylcholine and can treat cognitive dysfunction.Use this medicine; Can replenish and improve the content of central nervous system's acetylcholine, the main improvement is embodied in: the MMSE (immediate memory, attention and computing power, short term memory and total points) that takes the polyene phosphatidylcholine patient obviously improves before marking and all going into group; In stress back cognitive disorder rat model, the polyene phosphatidylcholine group stress the 7 and 14 days reference memory errors number in back obviously descend than matched group stress obviously descending than matched group by back work in 1,3,7,14 days paramnesia number of times.
The invention provides a kind of new medicinal usage of listing medicine polyene phosphatidylcholine, promptly can be used for treating the drug effect of cognitive dysfunction, and analyze and explanation from enterprising having gone of mechanism.Polyene phosphatidylcholine is easy to use, moderate as the drug effect of treatment cognitive dysfunction, and the more important thing is provides a kind of effective, few, safe and reliable medication of toxic and side effects in the cognitive dysfunction medicine.It can be used as a line medication of cognitive dysfunction of new generation.Solved the problem that the cognitive dysfunction medicine exists.For ensureing and promoting that human beings'health has positive effect.
Description of drawings:
Fig. 1 is the molecular structure simulation drawing of polyene phosphatidylcholine.
The specific embodiment:
Below in conjunction with accompanying drawing the present invention is elaborated
Embodiment 1:
(1) polyene phosphatidylcholine improves the clinical observation of cognitive dysfunction
Seminar of the present invention in the past few years be devoted to the mild cognitive dysfunction (mild cognitive impairment, MCI) and the basis of dull-witted diagnosis and treatment and clinical research.In to the early intervention research of MCI, find through laboratory observation and statistical induction: the polyene phosphatidylcholine that is widely used in liver protecting therapy at present has the effect that improves cognitive function.Concrete result of study is following.
Collect the MCI patient that in March, 2007 to 2008, year July, outpatient service was accepted for medical treatment of Xijing hospital of The Fourth Military Medical University; Go into group intervene before the cognitive function evaluation of object of study: 24 minutes≤simple and easy mental state scale (MMSE)≤26 minute; Adult's Webster test of memory memory quotient (MQ) is the 55-79 branch; Go into group objects and have cerebrovascular disease risk factors such as hyperlipidemia, hypertension, arteriosclerosis mostly, take Statins, antihypertensive drugs etc. for a long time.For preventing untoward reaction such as potential abnormal liver function, part patient goes into to begin to take after the group polyene phosphatidylcholine (456mg, oral, every day 3 times).Treating 16 all post analysis finds: the MMSE (immediate memory, attention and computing power, short term memory and total points) that takes the polyene phosphatidylcholine patient obviously improves (seeing table 1) before marking and all going into group.
Each inferior of MMSE compares before and after table 1 polyene phosphatidyl choline for treating
Annotate: relatively, p < 0.05 before * treatment back and the treatment
Embodiment 2
Polyene phosphatidylcholine improves the zoopery of cognitive disorder afterwards
On the basis of clinical observation, change zoopery over to, whether the checking polyene phosphatidylcholine has the effect of collaborative improvement cognitive disorder afterwards equally.Preliminary experiment adopts the radial labyrinth of eight arms trained rat (continuous 8 weeks) to learning and memory to form, again with Communication Box psychological stress model through looking on the process that other rat gets shocked, produce psychological stress through approach such as vision, auditions.Rat carries out the psychological stress of continuous 14d, 30min/d, and experiment beginning per os is irritated stomach and given normal saline respectively, polyene phosphatidylcholine (142.5mg/kg/d).Observe the 1st, 3,7,14 days working memory mistake and reference memory mistake.Getting into an arm of having eaten food is the working memory mistake, and getting into no food arm is the reference memory mistake.The result finds: compare with matched group, the polyene phosphatidylcholine group stress obviously descend than matched group by back work in 1,3,7,14 days paramnesia number of times; Compare with matched group, the polyene phosphatidylcholine group obviously is less than polyene phosphatidylcholine group (seeing table 2,3) stress the 7 and 14 days reference memory errors number in back obviously descending than matched group.Preliminary zoopery further specifies polyene phosphatidylcholine and has the improvement effect of cognitive function afterwards.
The working memory errors number relatively after table 2 was respectively organized stress in rats
Annotate: * and matched group be p < 0.05 relatively
The reference memory errors number relatively after table 3 was respectively organized stress in rats
Annotate: * and matched group be p < 0.05 relatively
The present invention mainly centers on the content that replenishes and improve central nervous system's acetylcholine to the treatment of cognitive dysfunction at present; Mainly want three kinds of approach: 1. cholinergic agonist:, still be in the clinic trial stage at present like new drug ENS163, LY246078, the DUP996 of selectively acting in the M1 receptor; 2. acetylcholine prodrug: once attempted with Ach prerequisite medicine replacement therapies such as lecithin and choline, and increased synthesizing and release of Ach, and can act on but fail to improve maincenter Ach; 3. acetylcholinesteraseinhibitors inhibitors: be widely used at present clinical improvements intelligence multiple medicine, be cholinesterase inhibitor, the degraded through suppressing Ach also improves activity and plays a role.
Referring to Fig. 1 because polyene phosphatidylcholine introduced and have more fat-soluble " polyenoid " group, thereby help seeing through blood brain barrier more, can be complete absorbed by neuron.And the further synthesis of acetyl choline in neuron of the product choline that neuron decomposes polyene phosphatidylcholine is exhausted the neurotransmitter acetylcholine fallen thereby remedy synaptic space.Clinical experiment of the present invention simultaneously and zoopery conclusion also all prove polyene phosphatidyl choline for treating cognitive impairment, and its reference memory errors number obviously descends.Therefore polyene phosphatidylcholine also can become the medicine that improves intelligence.
Claims (1)
1. the purposes of polyene phosphatidylcholine in the medicine of preparation treatment cognitive dysfunction.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008102317330A CN101366720B (en) | 2008-10-14 | 2008-10-14 | Pharmaceutical uses of polyene phosphatidyl choline for treating cognitive impairment |
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| CN2008102317330A CN101366720B (en) | 2008-10-14 | 2008-10-14 | Pharmaceutical uses of polyene phosphatidyl choline for treating cognitive impairment |
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| CN101366720A CN101366720A (en) | 2009-02-18 |
| CN101366720B true CN101366720B (en) | 2012-05-23 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103202849A (en) * | 2012-01-12 | 2013-07-17 | 苏州九龙医院有限公司 | New use of polyene phosphatidyl choline medicine in treatment of obesity and insulin resistance syndromes (metabolic syndromes) |
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Non-Patent Citations (2)
| Title |
|---|
| 曹栋等.多烯磷脂的生物学功能.中国粮油学会第二届学术年会论文选集（综合卷）.2002,384. * |
| 薛飞等.多烯磷脂酰胆碱对大鼠脑缺血再灌注损伤的保护作用.中华中医药学会中药实验药理分会第七届学术会议论文摘要汇编.2007,第9-10页. * |
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