CN101007035B - Application of notoginseng glycol saponins for treating memory deterioration - Google Patents
Application of notoginseng glycol saponins for treating memory deterioration Download PDFInfo
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- CN101007035B CN101007035B CN2007100368047A CN200710036804A CN101007035B CN 101007035 B CN101007035 B CN 101007035B CN 2007100368047 A CN2007100368047 A CN 2007100368047A CN 200710036804 A CN200710036804 A CN 200710036804A CN 101007035 B CN101007035 B CN 101007035B
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Abstract
The invention relates to the diol group saponin of notoginseng,radix, the content of panaxsaponin Rb1 and Rd is more than 50%. The invention also relates to the application of the product in medicine that can treat memory impairment and medicine that can prevent and treat senile dementia. According to the pharmacological results, the group saponin has good function of improving the memory obtaining handicap, the effects of which is far more better than the panaxsaponin Rb1 of the same dosage.
Description
Technical field
The present invention relates to field of medicaments, specifically, relate to the application in panasadiol saponio and the application in preparation treatment hypomnesis medicine thereof and prevention, the treatment medicine for senile dementia.
Background technology
Memory is a human brain to the reflection of the things that lives through.People that we met or thing, the sound of listening, the abnormal smells from the patient of smelling, the taste of tasting, the thing that touched, the problem of thinking deeply, the emotion of experiencing and emotion etc. all can be left a trace in brains, and present memory that Here it is under certain condition.In the daily life, as find that own recent memory power is much worse than in the past, often do not remember thing, forgetful, forget the thing just done etc., Here it is our hypomnesis of often saying medically, is called " forgetful ".
Chinese medicine is thought " the brain being the house of mentality ", brain is the place that marrow and gods height converge, people's vision, audition, olfactory sensation, sensation, thinking memory etc., all be because the effect of brain, this explanation brain is the extremely important organ of human body, be the place at life key, health preserving is valued for brain-strengthening, and brain-strengthening is the key of body-building.
The main cause that causes hypomnesis is brain fag and cerebral anoxia.Brain works overloadingly for a long time, and synthetic, the secretion of neurotransmitter all reduce, and have influence on speed and quality that information is transmitted, cause dysmnesia; On the other hand, because big cerebral anoxia, can cause that the brain micro-circulation speed slows down, nutrient substance just can not be by complete oxidation, metabolism rubbish accumulation such as the free radical that produces in the metabolism, make neurocyte be in the hypoxic-ischemic state, cause the acute or chronic injury of neurocyte, thereby influence the activity and the response speed of cerebral neuron, cause the memory path not smooth, thinking is obstructed, and the knowledge that is accumulated in the human brain can't be extracted and be used at short notice.As wire short-circuiting, whole memory path paralysis.Modern society strives fierceness unexpectedly, makes people's a large amount of muscle power and mental of overdrawing, and brain overwork has seriously injured people's health level; Simultaneously the old people with advancing age cerebrum metabolism slow down, blood supply oxygen supply deficiency, hypomnesis is obvious, as not prevented, also might develop into senile dementia, therefore, needs very vigilant and is paid attention to.
Radix Notoginseng is araliaceae ginseng plant Radix Notoginseng Panax notoginseng (Burk.) F.H.Chen, has another name called ginseng Radix Notoginseng, Tienchi-Ginseng, Radix Stephaniae Sinicae (Radix Stephaniae Dielsianae). be the high traditional rare medicinal herbs of medical value.Radix Notoginseng and Radix Ginseng are equal, congener, sibship is nearer, show from recent studies: Radix Notoginseng and Radix Ginseng be plesiomorphism not only, and its chemical constituent and pharmacological action have many similarities until aspects such as clinical practices, and is main effective ingredient with the dammarane type ginsenoside all.Proved that now Radix Ginseng, Radix Notoginseng have certain facilitation to learning and memory, its active ingredient be dammarane type four-ring triterpenoid saponin (Zhang Lei, Zhang Juntian. Radix Ginseng and Radix Notoginseng are to the facilitation of mice. combination of Chinese and Western medicine magazine, 1987.7 (1): 610～612.Zhang Juntian. Radix Ginseng, Radix Notoginseng enhancement learning and memory of little mouse reach the two-way conciliation effect [A] to body temperature. Japanese natural drug water Si lecture main idea [c]. Tokyo .1986 :).Radix Notoginseng is almost consistent with the tonic compositions such as tetracyclic triterpene saponin that Radix Ginseng contains, and total amount than Radix Ginseng also high (Zhou Jiaming, Ke Jinhu. the discussion that Radix Notoginseng and Radix Ginseng are used. Chinese herbal medicine, 2000,30 (12)).
As the active substance basis of Radix Ginseng and Radix Notoginseng, tetracyclic triterpenes has central nervous system's pharmacological action widely, as central excitation, improve the anti-stress ability of learning and memory, resisting fatigue, defying age and enhancing body etc.In recent years Chinese scholars by chemical drugs, cerebral ischemia, galvanic shock, stress wait method to set up various learning memory disorder models, observe the improvement effect of ginsenoside to the animal learning memory, the result show the ginsenoside to the memory acquisition disturbance of animal, obstacle is consolidated in memory, the memory represents obstacle hinders the improvement effect that all has in various degree.Intact animal and geriatric animals learning and memory function also all there are obvious facilitation, can promote acquisition, consolidation and the reproduction remembered, can improve the behavioral activity function of geriatric animals decline.At present inquire into the two and lay equal stress on research the sixth of the twelve Earthly Branches of ginsenoside's nootropic effect moving towards behavior observation and mechanism from the research of single behavioristics gradually, affirmed ginsenoside's constituents good improve the learning and memory effect.
The inventor selects for use first-class Radix Notoginseng as raw material, has optionally concentrated improving the effective saponin of learning and memory through the purifying process process.The inventor utilizes the gained sample to carry out the animal experiment study that mice is improved learning and memory, results sample is consolidated the incubation period that has all obviously prolonged the mice diving tower in bad and the experiment of memory represents obstacle and entered the darkroom at mouse memory, and efficacy strength is better than known ginsenoside Rb
1, result of the test demonstrates panasadiol saponio and has the tangible effect of improving learning and memory, truly has certain effect to improving memory disorder, thereby has finished the present invention.
Summary of the invention
The purpose of this invention is to provide a kind of panasadiol saponio.
The present invention also aims to provide the application of panasadiol saponio in preparation treatment hypomnesis medicine.
The present invention also aims to provide the application of panasadiol saponio in preparation prevention and treatment medicine for senile dementia.
In order to realize purpose of the present invention, the invention provides panasadiol saponio, wherein ginsenoside Rb
1With Rd content sum greater than 50%, be preferably 50～60%.Wherein, ginsenoside Rb
1With the ratio of Rd content be 4～7: 1, preferred 4: 1.Above content is the quality percentage composition.
Described panasadiol saponio becomes tablet, capsule, oral liquid, drop pill or injection with receivable preparing carriers medically.
The present invention also provides the application of described panasadiol saponio in preparation treatment hypomnesis medicine.
The present invention also provides the application of described panasadiol saponio in preparation prevention and treatment medicine for senile dementia.
Pharmacological evaluation proves that panasadiol saponio has the good effect that improves the mouse memory acquired disturbance, and the dosage with 30mg/kg is good especially, and its effect of improving memory is better than the ginsenoside Rb of same dose far away
1
The specific embodiment
Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
Pseudo-ginseng is ground into coarse powder, and 70% soak with ethanol is extracted secondary, each 18 hours, merge extractive liquid,, being evaporated to does not have alcohol flavor, standing over night, the elimination precipitation, supernatant is crossed the type macroporous adsorptive resins, and deionized water is eluted to colourless, again with 40% ethanol elution impurity (triol saponins), use 70% ethanol elution at last, collect 70% ethanol elution, concentrating under reduced pressure, vacuum drying promptly gets panasadiol saponio.Record wherein ginsenoside Rb
1With Rd content sum 55%, wherein, ginsenoside Rb
1Be respectively 4: 1 with Rd content.
Below strengthen learning and memory by this area proof the type testing model study the pharmacology pharmacodynamic situation of embodiment 1 described panasadiol saponio:
Experiment purpose: observe ginsenoside Rb
1, protoparaxotriol saporlirs and embodiment 1 described panasadiol saponio be to there being not improvement effect by the memory acquisition disturbance due to the scopolamine.
1 animal
Strain: Kunming kind white mice
Sex: male
Body weight: 18-20g
The source: Shanghai Si Laike laboratory animal responsibility company limited provides
The quality certification number: SCXK (Shanghai) 2003-0003
Raise: animal feeding in positive pressure purification ventilation Animal House, 25 ± 2 ℃ of temperature, ad lib and drinking-water
2 medicines
2.1 test specimen
Sample I
Title: ginsenoside Rb
1
Character: white powder, water-soluble
Source: Nat'l Pharmaceutical ﹠ Biological Products Control Institute
Lot number: 110704-200420
Sample II
Title: protoparaxotriol saporlirs
Character: brown dry extract, water-soluble
The source: Shanghai Chinese Medicine Creation Research Center provides
Lot number: 061220
Sample III
Title: panasadiol saponio
Character: the dark-brown dry extract, water-soluble
Source: embodiment 1 described panasadiol saponio
2.2 control sample
Sample I
Title: brain is light
Character: capsule
Specification: 200mg/ grain
Source: available from Hong Kong Kangfulai International Enterprise Co., Ltd.
Lot number: 061020
Sample II
Title: huperzine A (huperzine A)
Character: white tablet
Specification: 50ug/ sheet
Source: available from ShangHai Fudan Fuhua Pharmaceutical Co., Ltd
Lot number: 060506
2.3 other reagent
Title: scopolamine hydrobromide
Character: water white transparency injection
Specification: 0.3mg/ml
Source: available from Shanghai Hefeng Pharmaceutical Co., Ltd.
Lot number: 4AL8002
The preparation of 3 medicinal liquids
3.1 test specimen
Three test specimens are all established 30mg/kg and two dosage groups of 15mg/kg, and compound method is identical.
30mg/kg：
15mg/kg：
3.2 control sample
Sample I: brain is light
Dosage: 200mg/kg
Preparation:
Sample II: huperzine A
Dosage: 66.7 μ g/kg
Preparation:
4 instruments
Title: mice is kept away dark monitor
Model: YLS-1A type
Source: Shandong Academy of Medical Sciences equipment station
5 experimental techniques
5.1 animal grouping and dosage
100 mices are divided into 10 groups by the random digit method, every group of 10 animals.
Organize 1. blank group N.S
Organize 2. model group N.S
Organize the light 200mg/kg of 3. brains
Organize 4. huperzine As, 66.7 μ g/kg
Organize 5. ginsenoside Rb
115mg/kg
Organize 6. ginsenoside Rb
130mg/kg
Organize 7. protoparaxotriol saporlirs 15mg/kg
Organize 8. protoparaxotriol saporlirs 30mg/kg
Organize 9. panasadiol saponio 15mg/kg
Organize 10. panasadiol saponio 30mg/kg
5.2 test method
The 1st, 2 group oral (po) gives normal saline, and the 3rd, 4,5,6,7,8,9 and 10 groups animal per os filling stomach (ig) respectively gives corresponding medicinal liquid, and the administration volume is the 0.2mL/10g body weight, and 1 time/day, successive administration 14 days.After the last administration 1 hour, lumbar injection scopolamine 2mg/kg behind the 30min put into mice and keeps away dark instrument training once.Method is: mice is put into keep away camera bellows, the back of the body is put into bright chamber towards the hole, starts timer simultaneously, and animal passes the hole and enters the darkroom and shocked by electricity, and timing stops automatically.Take out mice, monitor writes down every Mus automatically and causes and enter the darkroom and run into the required time of electric shock from putting into bright chamber, and this is incubation period.Test after 24 hours, method is the same, and record enters the interior number of shocks (errors number) of number of animals, incubation period and 5min in darkroom.
6 results
Model group has significantly shortened mice and has entered incubation period in darkroom by bright chamber, and the number of animals that enters the darkroom increases, and errors number increases, and illustrate that scopolamine has obviously destroyed the memory acquisition function of mice.The positive control drug brain easily (200mg/kg) to scopolamine memory acquisition disturbance extremely do not have tangible improvement effect; Positive control drug huperzine A (66.7 μ g/kg) has then obviously prolonged the memory acquisition disturbance mice and has entered incubation period in darkroom by bright chamber, compares with model group, and P＜0.01, errors number reduces, and has shown the good animal learning memory impairments of improving.Ginsenoside Rb
1Also shown certain function of improving memory acquisition disturbance with protoparaxotriol saporlirs, and presented certain dose-effect relationship, but compared, statistical significant difference all do not occurred with model group.Ginsenoside Rb
1Effect be better than protoparaxotriol saporlirs.Panasadiol saponio has shown the dosage of the good effect that improves the animal memory acquisition disturbance, especially 30mg/kg, its efficacy strength and 66.7 μ g/kg huperzine As suitable (comparing P＜0.01 with model group).
Data are with mean+SD
Expression, the data difference statistics adopts one factor analysis of variance (ANOVA) or X 2 test, and group difference is judged with P＜0.05.The results are shown in Table 1.
Table 1. medicine oral administration to be measured to mouse memory reproduce obstacle influence (n=10,
)
*P＜0.01 is compared with model group
7. preliminary conclusion and analysis
Panasadiol saponio has the good effect that improves the mouse memory acquired disturbance, and the dosage with 30mg/kg is good especially, and its effect of improving memory is better than the Radix Ginseng total saponins and the ginsenoside Rb of same dose far away
1This point also is that the inventor is serendipitous in experimentation, ginsenoside Rb in its principle estimation and the panasadiol saponio
1With other component, particularly to bring into play synergism with the ginsenoside Rd relevant, in addition, also may be owing to removed the composition that drug effect disappears mutually in technology, makes it have the better memory impairments of improving than mixing saponin.In addition, ginsenoside Rb
1Certain function of improving memory acquisition disturbance is also arranged, and present good dose-effect relationship.This effect of protoparaxotriol saporlirs is not obvious.
Claims (2)
1. the application of panasadiol saponio in preparation treatment hypomnesis medicine, ginsenoside Rb in the described panasadiol saponio
1With Rd content sum be 50～60%, ginsenoside Rb in the described panasadiol saponio
1With the ratio of Rd content be 4～7: 1.
2. application as claimed in claim 1 is characterized in that, ginsenoside Rb in the described panasadiol saponio
1With Rd content sum be 55%, ginsenoside Rb in the described panasadiol saponio
1With the ratio of Rd content be 4: 1.
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| CN101007035B true CN101007035B (en) | 2010-12-01 |
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| CN101463061B (en) * | 2007-12-21 | 2013-09-18 | 中国医学科学院药物研究所 | Ginseng saponin Rg1 and Rb1 in pseudo-ginseng and preparation of total saponin thereof |
| CN104173358B (en) * | 2014-08-27 | 2017-01-11 | 哈尔滨珍宝制药有限公司 | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases |
| CN109619582A (en) * | 2019-01-04 | 2019-04-16 | 云南七丹药业股份有限公司 | A kind of folk prescription improves the health care product of memory |
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| CN1699396A (en) * | 2004-08-04 | 2005-11-23 | 李明劲 | Process for preparing notoginseng diol saponin |
| CN1706396A (en) * | 2004-08-04 | 2005-12-14 | 李明劲 | Orally taken Bi-dredging prepn containing notoginseng glycol saponin and its prepn process and application |
| WO2005120536A1 (en) * | 2004-06-11 | 2005-12-22 | Unigen, Inc. | Ginseng composition for preventing or improving the lowering of concentration and memory capability |
| CN1771977A (en) * | 2004-11-09 | 2006-05-17 | 成都华神集团股份有限公司制药厂 | Notoginseng glycol-saponin composition and its prepn and use |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005120536A1 (en) * | 2004-06-11 | 2005-12-22 | Unigen, Inc. | Ginseng composition for preventing or improving the lowering of concentration and memory capability |
| CN1699396A (en) * | 2004-08-04 | 2005-11-23 | 李明劲 | Process for preparing notoginseng diol saponin |
| CN1706396A (en) * | 2004-08-04 | 2005-12-14 | 李明劲 | Orally taken Bi-dredging prepn containing notoginseng glycol saponin and its prepn process and application |
| CN1628684A (en) * | 2004-09-07 | 2005-06-22 | 张平 | Medicine combination containing panax pseudo-ginseng saponin triol and preparation method thereof |
| CN1771977A (en) * | 2004-11-09 | 2006-05-17 | 成都华神集团股份有限公司制药厂 | Notoginseng glycol-saponin composition and its prepn and use |
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