CN101366720A - The medicinal use of polyene phosphatidylcholine in the treatment of cognitive dysfunction - Google Patents
The medicinal use of polyene phosphatidylcholine in the treatment of cognitive dysfunction Download PDFInfo
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- CN101366720A CN101366720A CNA2008102317330A CN200810231733A CN101366720A CN 101366720 A CN101366720 A CN 101366720A CN A2008102317330 A CNA2008102317330 A CN A2008102317330A CN 200810231733 A CN200810231733 A CN 200810231733A CN 101366720 A CN101366720 A CN 101366720A
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Abstract
本发明提供了一种多烯磷脂酰胆碱治疗认知功能障碍的药物用途，采用临床上常用的保肝用药多烯磷脂酰胆碱作为治疗认知功能障碍的新药物，经临床应用以及动物实验均证明：多烯磷脂酰胆碱对于改善认知功能障碍和记忆功能均有影响，治疗认知功能障碍效果良好。由于多烯磷脂酰胆碱引入了更具脂溶性的“多烯”基团，从而更加有利于透过血脑屏障，可以完整的被神经元所摄取。而神经元分解多烯磷脂酰胆碱的产物胆碱可以进一步在神经元内合成乙酰胆碱，从而弥补突触间隙耗竭掉的胆碱。多烯磷脂酰胆碱在代谢过程中可以生成：胆碱，DHA以及花生四烯酸。是一种价格适中，毒副作用小，安全可靠，治疗认知功能障碍的用药，也可成为改善智能的药物。The invention provides a medicinal use of polyene phosphatidylcholine for treating cognitive dysfunction. Polyene phosphatidylcholine, a commonly used hepatoprotective drug in clinical practice, is used as a new drug for treating cognitive dysfunction. Experiments have proved that polyene phosphatidylcholine has an effect on improving cognitive dysfunction and memory function, and the effect of treating cognitive dysfunction is good. Since polyene phosphatidylcholine introduces a more fat-soluble "polyene" group, it is more conducive to passing through the blood-brain barrier and can be completely taken up by neurons. Choline, the product of polyene phosphatidylcholine decomposed by neurons, can further synthesize acetylcholine in neurons, thereby making up for the depleted choline in the synaptic cleft. Polyene phosphatidylcholine can be produced during metabolism: choline, DHA and arachidonic acid. The medicine is moderately priced, has few toxic and side effects, is safe and reliable, and can be used for treating cognitive dysfunction, and can also be used as 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 is meant human various conscious sophisticated maincenter activity under wakefulness, comprise from simply to the determining of own and environment, perception, understanding, to memory, calculating, judgement and fill order, finish complex task etc.Cognitive dysfunction is meant that then cognitive function is subjected to infringement in various degree, and weight person is as all kinds dementia, 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 by 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 classes, 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 as 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 the synthetic of Ach and discharge, 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 by 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., and so far, these medicines all lack reliable treatment foundation and clinical effectiveness.
Because environment for human survival etc. is all multifactor, especially exists 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 and the new medicine use that benefit Spirit of Man health of a kind of usefulness from the discussion targetedly of theory and combining reality.
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 document related to the present invention yet.
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, the present invention is used for the treatment of cognitive dysfunction with this listing patent medicine, 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, at 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 height, (2) contain arachidonic acid (AA) and (3) docosahexenoic acid (DHA).So it is also different at physiological active functions and Application and Development thereof.Therefore, polyene phosphatidylcholine has important physiological activity 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, anti-fatty liver, 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, can be used for the treatment of the drug effect of cognitive dysfunction, and analyze and illustrate from 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:
The present invention is described in detail below in conjunction with accompanying drawing
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.Find through laboratory observation and statistical induction in to the early intervention research of MCI: 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 as follows.
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: compare p＜0.05 before * treats the back and treats
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 by looking on the process that other rat gets shocked, produce psychological stress by 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.Entering an arm of having eaten food is the working memory mistake, and entering no food arm is the reference memory mistake.Found that: 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 as 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 the synthetic of Ach and discharge, 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 by 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 (2)
1. the medicinal usage of polyene phosphatidyl choline for treating cognitive impairment.
2. according to the medicinal usage of the described polyene phosphatidyl choline for treating cognitive impairment of claim 1, it is characterized in that: polyene phosphatidylcholine has the effect that improves cognitive function.
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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 true CN101366720A (en) | 2009-02-18 |
| CN101366720B CN101366720B (en) | 2012-05-23 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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