CN101317867B - Application of standard extract of pseudo-ginseng in preparing medicament for preventing and controlling senile dementia - Google Patents

Application of standard extract of pseudo-ginseng in preparing medicament for preventing and controlling senile dementia Download PDF

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CN101317867B
CN101317867B CN2008100586489A CN200810058648A CN101317867B CN 101317867 B CN101317867 B CN 101317867B CN 2008100586489 A CN2008100586489 A CN 2008100586489A CN 200810058648 A CN200810058648 A CN 200810058648A CN 101317867 B CN101317867 B CN 101317867B
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panax notoginseng
standard extract
notoginseng
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ethanol
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CN101317867A (en
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张伟
杨兆祥
刘国光
刘一丹
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Kun Yao Group Plc
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Kunming Pharmaceutical Corp
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Abstract

The present invention relates to application of notoginseng standard extraction to preparation of senile dementia prevention medicine. In weight percentage content, the notoginseng standard extraction of the present invention mainly contains 10 to 20 percent of panaxadiol saponins Rb1(C54H92O23), 10 to 20 percent of panaxatriol saponins Rg1(C42H72O14), 2 to 3.5 percent of notoginseng saponin R1 (C47H80O18), 0.03 to 0.2 percent of notoginseng flavone and 10 to 20 percent of micromolecule notoginseng polyose. Improvement function of notoginseng standard extraction on cognition obstruction of AD model space is observed with Morris water maze experiment and the function mechanism is discussed. In addition, further demonstration is performed on mouse dysmnesia caused by NaNO2. Results prove that the notoginseng standard extraction has obvious improvement effect on learning memory descent caused by senile dementia and cerebral ischemia, and obvious improvement effect on mouse dysmnesia caused by NaNO2. Therefore, the extraction can be used for preventing or curing senile dementia.

Description

The application of Panax notoginseng standard extract in preparation control medicine for senile dementia
Technical field
The present invention relates to medical technical field, specifically the new purposes of Panax notoginseng standard extract in preparation control medicine for senile dementia.
Background technology
Senile dementia be occur in the senilism phase and senile be the intelligence infringement syndrome that the disordered brain function of feature produces with the progressive dementia.Comprise alzheimer disease, be Alzheimer's disease (Alzheimer disease is called for short AD) and vascular dementia (Vascular dementia is called for short VD) two classes again.Wherein AD is a kind of constitutional central nervous system regression disease that betides middle-aged and elderly people; VD is the dementia that cerebral lesion caused that causes because of cerebrovascular disease.The cause of disease of VD relates to two aspects, i.e. cerebrovascular and risk factor.Risk factor comprises that risk factor (hypertension, hyperlipidemia, heart disease, diabetes, universality arteriosclerosis, smoking), apoplexy, ischemic leukodystrophy, advanced age and the schooling of cerebrovascular is low etc.
Alzheimer disease often shows as the decline of memory aspect at first, progressively occurs the behavioral competence obstacle afterwards, and emotion is easily gone to extremes, anxiety, dejected, and dystropy loses normal shame sense and moral sense, handles simple financial problem and has any problem.If do not give suitable treatment in time, the patient completely loses activity of daily living the most at last.
According to incompletely statistics, the ratio of suffering from the severe alzheimer disease in the over-65s crowd is 5%~8%, and by 80 years old, this ratio just rose to 15%~20%.China alzheimer disease patient has 6,000,000 people at present, account for 1/3 of global patient's sum, about 1,800,000 people of annual neopathy, extremely forget 105.6 ten thousand people, the morbidity situation is very severe, having become modern society and caused the main cause that the old people is disabled and can not live on one's own life, is one of four big diseases of serious threat senior health and fitness.
Regrettably, treat alzheimer disease up to now and still do not have good plan, if the drug main cholinergic drug that has or be about to appear on the market on the present domestic and international market, common mainly is cholinesterase inhibitor.Tacrine (trade name group can cause) is first kind of medicine that is approved for senile dementia treatment, but the hepatotoxicity of this medicine is bigger, now gradually not by clinical use.Donepezil (trade name aricept) compare with tacrine safer effectively, general recommendations preceding clothes of sleeping at night, but the patient of insomnia is then advised taking medicine daytime.Rivastigmine-hydrogentartrate (trade name Exelon) also is the critical treatment medicine of old people's cognitive disorder.Clinical experiment both at home and abroad also points out cognitive symptom and the ADL tool of this medicine to dementia patients to have some improvement, and few side effects.Huperzine A (trade name huperzine A) is a kind of alkaloid that institute of materia medica, Chinese Academy of Sciences Shanghai extracts from Herba Lycopodii serrati (Huperzia serrata.), is a kind of high selectivity cholinesterase inhibitor, tool the have some improvement memory and the effect of cognitive function.
The traditional Chinese medical science is from organic conception, and dialectical opinion is controlled, and senile dementia is divided into five pattern of syndrome: the marrow of 1. suffering from a deficiency of the kidney subtracts card; 2. syndrome of qi stagnation and blood stasis; 8. turbid phlegm blocking the clear orifices is demonstrate,proved; 4. deficiency of YIN of both the heart and liver is demonstrate,proved; 5. syndrome of deficiency of both heart and spleen.Each syndrome has symptom grouping quantization table again respectively, can be divided into light, in, heavy Three Estate, and assessed in conjunction with lab index such as brain electrical activity mapping, rheoencephalogram, head CT scanning, gait test, cerebrospinal fluid acetylcholinesterase and Protein tau content.
At present, the etiology and pathology of the whole world relevant senile dementia in the neuroscience field is unclear as yet, and the animal model foundation and the drug research method of senile dementia are still not mature enough.Laboratory animal mice commonly used or rat, method is optional: 1. naturally-aged animal model; 2. mice sucks ozone with high concentration for a long time and causes the brain aging animal model; Cause aging model 3. for mice long term injections D-galactose; 4. accelerated ageing mouse model (SAMP series) is damaged the experimental AD animal model of cholinergic nerve of centrum unit; 5. the chemicals overall applicability causes dysmnesia model; 7. transgenic mice is simulated SDAT type Model of Dementia etc.Observational technique is optional: darkness avoidance test, the method for shuttling back and forth, diving tower method, water maze method, electric maze method etc. are learning and memory and the space exploration ability of evaluation experimental animal preferably.Wherein, keeping away the experiment purpose of secretly shuttling back and forth is test rat ability of learning and memory recent and at a specified future date.Morris water maze laboratory purpose is test AD rat model ability of learning and memory and space exploration ability.
Panax notoginseng standard extract is diol type and triol type arasaponin, Radix Notoginseng polysaccharide and a spot of Radix Notoginseng flavones ingredient that mainly contains appropriate ratio.A large amount of bibliographical informations arasaponin have protective effect and anti-aging effects to nervous system ischemic lesions and traumatic infringement.Be main effective ingredient with the dammarane type four-ring triterpenoid saponins in the arasaponin, 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 arasaponin to the animal learning memory, the result show arasaponin to the memory acquisition disturbance of animal, obstacle is consolidated in memory, the memory represents obstacle all has improvement effect 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.
The Radix Notoginseng flavone has antioxidation and neuroprotective function.Radix Notoginseng flavone and arasaponin share, and physiologically active is the strongest, and separately using proves that then the Radix Notoginseng flavone can significantly increase myocardium coronary flow.
Senile dementia does not still have good prophylactico-therapeutic measures at present.For this reason, we further expand Panax notoginseng standard extract carry out about the control senile dementia the test of pesticide effectiveness, invent its new purposes in pharmaceutical field.
Summary of the invention
The purpose of this invention is to provide the application of a kind of Panax notoginseng standard extract in preparation control medicine for senile dementia.
The definition of Panax notoginseng standard extract (code name SPNS): the Panax notoginseng standard extract of indication of the present invention is meant the common Radix Notoginseng extract of forming of the notoginseng glycol saponins, notoginseng triol saponins, Radix Notoginseng flavone and the micromolecular polysaccharide that contain appropriate ratio, the effective ingredient of for many years Panax notoginseng standard extract (key is given birth to peaceful sheet), i.e. Radix Notoginseng extract had been produced already as Kunming pharmacy group.
The definition of person in middle and old age's dementia of the present invention: comprise alzheimer disease, be Alzheimer's disease (Alzheimerdisease is called for short AD) and vascular dementia (Vascular dementia is called for short VD) two classes again.Wherein AD is a kind of constitutional central nervous system regression disease that betides middle-aged and elderly people; VD is the dementia that cerebral lesion caused that causes because of cerebrovascular disease.The westerner more is AD, and the Asians more is VD.
Though existing a large amount of documents confirms the effect of ginsenoside on alzheimer disease, also has some reports to confirm the effect of plant flavone on senile dementia.Be used for senile dementia but not studying combines both, more do not study the control that the ginsenoside of proper proportion, flavone, Radix Notoginseng polysaccharide combination is used for senile dementia, provided by the invention is exactly that standard extract with the notoginseng glycol saponins that contains proper proportion, notoginseng triol saponins, Radix Notoginseng flavone, micromolecule Radix Notoginseng polysaccharide is used for the more excellent technical scheme of the prevention and the treatment of senile dementia.Wherein notoginseng glycol saponins improves acquired disturbance, anti-peroxidation effect etc. to memory good action, and the notoginseng triol saponins has tangible effect to albumen facilitation, memory improvement, and notoginseng glycol saponins and Radix Notoginseng flavone all are the A beta inhibitors.The Radix Notoginseng flavone also has mitigation to the dysmnesia due to the scopolamine.The pointed senile dementia to due to the non-single factors of several composition cooperations has many targets synergism.Thereby it is single to solve existing medicine for senile dementia effect, the problem that can not effectively work.
Of the present invention being used to prepares the Panax notoginseng standard extract of preventing and treating medicine for senile dementia, contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage should be the ginsenoside Rg of 10%-20%, triol group 1(C 42H 72O 14) should be at 10%-20%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 2~3.5%, Radix Notoginseng flavone 0.03%-0.2%, micromolecule Radix Notoginseng polysaccharide 10%-20%.
Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) preferable weight percentage should be the ginsenoside Rg of 11%-15%, triol group 1(C 42H 72O 14) should be at 11%-15%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 2~3%, Radix Notoginseng flavone 0.05%-0.2%, micromolecule Radix Notoginseng polysaccharide 10%-20%.
The product of this standard extract preparation can prevent or treat alzheimer disease.The form of product is that the acceptable pharmaceutical preparation is gone up in medical treatment, or the Kunming pharmacy group peaceful sheet of the strong god (authentication code: the accurate word B20050010 of traditional Chinese medicines) of having produced.
Described Panax notoginseng standard extract preparation technology: get the Radix Notoginseng clip, with 25%-45% ethanol after softening 24 hours, pulverize, measured the 70%-95% soak with ethanol 96 hours with 7 times for the first time, measured the 50%-65% soak with ethanol 72 hours with 6 times for the second time, measured the 50%-65% soak with ethanol 48 hours with 6 times for the third time, merge extractive liquid, filters, filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.24~1.26 (80 ℃), adds the water of 2 times of amounts of clear paste, heating for dissolving, add an amount of ZTC1+1 (II type) natural clarifying agent and (add the A part earlier, 50~60 ℃ of insulations are warming up to 80 ℃ after 1 hour and add the B part again), place more than 10 hours, filter, it is 1.24~1.28 (80 ℃) that filtrate is concentrated into relative density, 80 ℃ of drying under reduced pressure are pulverized, promptly.
(1) Panax notoginseng standard extract is inquired into the experimentation and the mechanism of the preventive and therapeutic effect of experimental AD
1. experiment material
1.1 laboratory animal: SD rat, body weight 160~200g, male and female are regardless of, the cleaning level, provide by unming Medical College's Experimental Animal Center, laboratory animal is produced and occupancy permit number: laboratory animal production and occupancy permit number are respectively: SCXK (Yunnan) 2005-0009 number, SYXK (Yunnan) 2005-0006 number.
1.2 medicine and reagent: Panax notoginseng standard extract, Kunming Medicine Group Stock Co., Ltd, lot number: 20060621, assay: contain ginsenoside Rb 1(C 54H 92O 23) 12.04%, the ginsenoside Rg 1(C 42H 72O 14) 11.91%, Panax Notoginseng saponin R 1(C 47H 80O 18) 3.02%.And ginsenoside Rb 1, the ginsenoside Rg 1, Panax Notoginseng saponin R 1Total amount be 26.97%.Pulverize before the experiment, cross 100 mesh sieves, be dissolved in the water recently distilled, be made into concentration and be 5% aqueous solution and be stored in 4 ℃ of refrigerators standby; The D-galactose, the packing of AMRSCO company; The deep propylhomoserin of goose cream (Ibotenic acid is called for short IBO), Sigma company purchases; Huperzine A sheet (huperzine A), 50 μ g/ sheets, ShangHai Fudan Fuhua Pharmaceutical Co., Ltd, lot number: 060506.
1.3 experimental apparatus: rat founds position finder, the SN-2 type, and Japan produces; The dentistry drill carriage, 307-6 type, Shanghai medical analytical instrument factory; Agilent1100 series HPLC instrument, U.S. Agilent company.High speed refrigerated centrifuge, Shanghai medical analytical instrument factory; LS-6500 type liquid scintillation counter, U.S. Beckmen company.Keep away camera bellows: self-control, the long 60cm of case, wide 25cm, high 30cm divides light and shade two Room, and it is the circular hole of 8cm size that a diameter is arranged between two Room.Be evenly equipped with the copper grid at the bottom of the chamber, the copper grid in darkroom can be switched on, and select 40V voltage for use.The bulb of 2 25W is equipped with in top, bright chamber.Morris water maze (Morris Watermaze, be called for short MWM) is a rustless steel round pool, diameter 200cm, and high 50cm, depth of water 30cm, water temperature is controlled at (26 ± 1) ℃.Pool wall is indicated 4 place of entry, thus the pond is divided into 4 quadrants, represents platform quadrant, offside quadrant, right side quadrant and left side quadrant with respect to the platform quadrant respectively with P, O, R, L, and a diameter 11cm, the platform of high 29cm are placed in the center.
Experimental data is all handled with the SPSS11.5 statistical package.
2. experimental technique and result
2.1 the influence (experiment of Morris water maze behavioristics) that Panax notoginseng standard extract improves alzheimer disease animal model spatial cognition barrier
Adopt IBO to activate thing alzheimer disease model, modeling method is with reference to relevant document chief editors such as (, pharmacological experimental methodology, the third edition, People's Health Publisher) Xu Shuyun.After model builds up, surviving animals is divided into 5 groups at random: 1. operative control group; 2. model control group; 3. huperzine A group; 4. Panax notoginseng standard extract 100mg dosage group (be equivalent to be grown up clinical dosage half); 5. the Panax notoginseng standard extract 200mg dosage group dose,equivalent of clinical dosage (be equivalent to be grown up).Each organizes continuous irrigation stomach 2 months.After this carry out the experiment of Morris water maze behavioristics, continuous 6 days, experiment was divided into two stages: (1) 1~5 day trained rat; Carry out the experiment of relevant behavioristics in (2) the 6th days, the results are shown in following table.
Table 1: the influence that Panax notoginseng standard extract improves alzheimer disease animal model spatial cognition obstacle (x ± s)
Figure S2008100586489D00051
Annotate: compare with model group, * p<0.05, * * p<0.01, SPNS is a Panax notoginseng standard extract
The result shows that Panax notoginseng standard extract improves significantly to the spatial cognition obstacle of AD rat, and 200mg and 100mg group more all have significant difference with model group.
2.2 the influence that Panax notoginseng standard extract improves alzheimer disease animal memory dysfunction (rat is kept away the camera bellows experiment: chief editors such as Xu Shuyun, pharmacological experimental methodology, the third edition, People's Health Publisher).
Above-mentioned laboratory animal in administration after 2 months, will be tested earlier to place with rat and kept away in the camera bellows camera-lucida, after rat enters camera bellows, shocked by electricity 1 second, and took out animal then, repeated experiments after 1 week, the record rat enters time of camera bellows and number of times, number, result such as following table by camera-lucida.
Table 2: the influence that Panax notoginseng standard extract improves senile dementia animal memory dysfunction (x ± s)
Figure S2008100586489D00052
Annotate: compare with model group, * p<0.05, * * p<0.01, SPNS is a Panax notoginseng standard extract
The result shows that Panax notoginseng standard extract improves significantly to the memory dysfunction of AD rat, and 100,200 dosage groups and model group more all have significant difference, and the positive drug huperzine A also has certain effect.
2.3 Panax notoginseng standard extract is to the influence of alzheimer disease rat cerebral cortex tissue homogenate amino acid neurotransmitter
Experiment is got the ultrasonic homogenate of rat cerebral cortex after finishing, and measures the influence of amino acid neurotransmitter with the HPLC method.
Table 3: Panax notoginseng standard extract is to the influence of alzheimer disease rat cerebral cortex tissue homogenate amino acid neurotransmitter (x ± s)
Figure S2008100586489D00061
Annotate: compare * p<0.05, * * p<0.01 with model group; Compare with the huperzine A group, #p<0.05, ##p<0.01, SPNS is a Panax notoginseng standard extract.
The result shows that Panax notoginseng standard extract has the obvious suppression effect to experimental AD rat cerebral cortex glutamic acid and rising, can increase the content of AD rat cerebral cortex inhibitory aminoacid and γ-An Jidingsuan, and more all there were significant differences with model group.
2.4 Panax notoginseng standard extract is to (the influence of β-AP) of alzheimer disease rat brain hippocampal tissue homogenate 4 amyloid
Experiment is got the ultrasonic homogenate of rat brain Hippocampus after finishing, and with the content of ria-determination β-AP, the result is as follows.
Table 4: Panax notoginseng standard extract is to the alzheimer disease rat brain hippocampal tissue homogenate 4 amyloid (influence of β-AP) (x ± s)
Annotate: compare with model group, * p<0.05, * * p<0.01, SPNS is a Panax notoginseng standard extract.
The result shows that Panax notoginseng standard extract 100,200mg dosage group have the obvious suppression effect to the rising of β-AP in the experimental AD rat brain tissue, with model group significant difference are arranged relatively.
(2) Panax notoginseng standard extract is to the influence of experimental vascular dementia (VD) learning and memory function
1. experiment material
1.1 laboratory animal: male Wistar rat, body weight 450-550g, the cleaning level is provided by unming Medical College's Experimental Animal Center, laboratory animal is produced and occupancy permit number: laboratory animal production and occupancy permit number: SCXK (Yunnan) 2005-0009 number, SYXK (Yunnan) 2005-0006 number.
1.2 medicine and reagent: Panax notoginseng standard extract, Kunming Medicine Group Stock Co., Ltd, lot number: 20060621, content is the same, pulverizes before the experiment, crosses 100 mesh sieves, is dissolved in the water recently distilled, is made into concentration and is 5% aqueous solution and be stored in 4 ℃ of refrigerators standby; Ginaton tablets contains Folium Ginkgo extract 40mg/ sheet, production company of Dr Willmar Schwabe, lot number 2006A0423.
1.3 experimental apparatus: keep away camera bellows: self-control, the long 60cm of case, wide 25cm, high 30cm divides light and shade two Room, and it is the circular hole of 8cm size that a diameter is arranged between two Room.Be evenly equipped with the copper grid at the bottom of the chamber, the copper grid in darkroom can be switched on, and select 40V voltage for use.The bulb of 2 25W is equipped with in top, bright chamber.
Experimental data is all handled with the SPSS11.5 statistical package.
2. method and result
Male Wistar rat places and keeps away in the camera bellows camera-lucida, after rat enters camera bellows, shocks by electricity 1 second, takes out animal then.The intraperitoneal anesthesia of inferior daily 10% chloral hydrate (0.3ml/100g) body weight is fixed on the operation plate, prior to the head opening, exposes atlas transverse process wing aperture, burns the bilateral vertebral artery with electric cautery, causes the permanent occlusion, skin suture.Climb over rat, expose and free bilateral common carotid arteries, close bilateral common carotid arteries 5 minutes with arteriole folder folder, poured into 3 times repeatedly again 1 hour, ischemia is irritated again, cause serious learning memory disorder, postoperative suture muscles, skin, 2 days infection (Zhu Yu chief editors of intramuscular injection penicillin, the disease model of laboratory animal, Tianjin Scientific English Translation publishing house).Experiment is divided into 5 groups at random with 40 rats: 1. Sham-operated control group; 2. model control group; 3. Ginaton matched group; 4. strong refreshing peaceful 100mg dosage group (be equivalent to be grown up clinical dosage half); 5. strong refreshing peaceful 200mg dosage group (being equivalent to the clinical dose,equivalent of being grown up), 8 every group.Second day after operation begins medication, successive administration 10 days, and after the last administration 1 hour, rat put into successively keep away the camera bellows camera-lucida, each one, write down the number of times, number of elements and the incubation period that enter camera bellows in 5 minutes, the result is as follows.
Table 5: the influence that Panax notoginseng standard extract improves the vascular dementia rats memory dysfunction (x ± s)
Figure S2008100586489D00081
Annotate: compare with model group, * p<0.05, * * p<0.01, SPNS is a Panax notoginseng standard extract.
The result shows, the learning and memory function decline effect of having clear improvement that Panax notoginseng standard extract causes cerebral ischemia.
(3) Panax notoginseng standard extract NaNO 2The amnemonic influence of induced mice
1. experiment material
1.1 laboratory animal: ICR mice, body weight 18-20g, cleaning level, Kunming pharmacy group Experimental Animal Center, laboratory animal production and occupancy permit number: SCXK (Yunnan) 2005-0006 number, SYXK (Yunnan) 2005-0006 number.
1.2 medicine and reagent: Panax notoginseng standard extract, Kunming Medicine Group Stock Co., Ltd, lot number: 20060621, content is the same, pulverizes before the experiment, crosses 100 mesh sieves, is dissolved in the water recently distilled, is made into concentration and is 5% aqueous solution and be stored in 4 ℃ of refrigerators standby; Ginaton tablets contains Folium Ginkgo extract 40mg/ sheet, production company of Dr Willmar Schwabe, lot number 2006A0423.
2. method and result
72 of Kunming mouses are divided into 6 groups at random, and each organized gastric infusion after 7 days, respectively organize subcutaneous injection NaNO immediately after training except that normal group 2120mg/kg, each is organized in training last administration in back 24 hours, and carries out step down test after administration in 1 hour, incubation period and errors number that the record animal is made mistakes.The result is as follows.
Table 6: Panax notoginseng standard extract NaNO 2The amnemonic influence of induced mice (x ± s)
Figure S2008100586489D00082
Annotate: compare with model group, * p<0.05, * * p<0.01, SPNS is a Panax notoginseng standard extract.
The result shows that Panax notoginseng standard extract 100,200,300mg dosage group are to NaNO 2The induced mice dysmnesia all improve significantly, and can obviously reduce the number of times that mice is made mistakes, and prolong the incubation period that mice is made mistakes.
By above-mentioned experiment, proved spatial cognition obstacle that Panax notoginseng standard extract causes senile dementia and cerebral ischemia and the learning and memory function effect that improves significantly that descends.Can increase the content of alzheimer disease rat cerebral cortex inhibitory aminoacid, glycine and γ-An Jidingsuan, reduce the toxicity of irritability glutamic acid, and can reduce the generation of β-AP in the AD rat hippocampus tissue, the learning and memory function that cerebral ischemia is caused descends and also improves significantly; Can also obviously improve NaNO 2The induced mice dysmnesia.
Clinical 30 examples of strong refreshing peaceful sheet treatment senile dementia are observed
Data and method:
Physical data: treatment group: 30 examples, male's 20 examples, women's 10 examples, age 60-80 year, average 70 years old, the course of disease 0.5 month~4 years, wherein cerebral arteriosclerosis and cerebral infarction 20 examples, multiple infarct 10 examples, this group patient all meets " practical neurological " diagnostic criteria, clinical symptoms all increases the weight of, 9 routine apathetic expressions wherein, bradykinesia, insight, the obvious obstacle of orientation force, wilfulness, the forced smile of crying by force.CT scan is that brain atrophy changes, and 11 examples are slow for reaction, hypomnesis, and it is unstable to walk, and clumsy in one's movement, CT scan is a multiple infarct, and wherein 4 examples and brain atrophy change.Matched group 10 examples, male's 7 examples, women's 3 examples, 56~86 years old age.
Diagnostic criteria: fixed: 1. recent memory power by following clinical symptoms improvement situation; 2. orientation force; 3. computing power; 4. judgment; 5. personality; 6. personality; 7. gait; 8. urinary incontinence.Produce effects: more than 5 improvement is arranged; Effectively: 1~4 has improvement; Invalid: the symptom no change.
Therapeutic Method: the two groups of equal dead point brain cell of patient nutrients, treatment group add strong refreshing peaceful sheet, one time 2,3 times on the one, 15 days is a course of treatment.
The result: through 3~6 courses of treatment, produce effects 15 examples, effective 12 examples, invalid 3 examples, total effective rate 90.0%.Matched group 10 examples, produce effects 1 example, effective 2 examples, invalid 7 examples, total effective rate 70.0%.Learn by statistics and handle, p<0.01, treatment group curative effect is better than matched group.
The specific embodiment
Embodiment 1: strong refreshing peaceful sheet:
Prescription (1000):
Panax notoginseng standard extract 100g
Medical starch 160g
Magnesium stearate 2g
Wherein, Panax notoginseng standard extract contains ginsenoside Rb 1(C 54H 92O 23) percentage by weight is 12.04%, the ginsenoside Rg 1(C 42H 72O 14) be 11.91%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 3.02%, the Radix Notoginseng flavone is 0.05%.
Method for making: material is crossed 100 mesh sieves respectively, take by weighing material by recipe quantity, mix homogeneously stirs the system soft material, and the 18-24 mesh sieve is granulated, 70 ℃ of following aeration-dryings, and tabletting, sugar coating, promptly.
Embodiment 2: the Panax notoginseng standard extract Film coated tablets;
Prescription (1000):
Panax notoginseng standard extract 100g
Medical starch 160g
Magnesium stearate 2g
Wherein, Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage is 11%, the ginsenoside Rg of triol group 1(C 42H 72O 14) be 11%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 3%, the Radix Notoginseng flavone is 0.05%, the micromolecule Radix Notoginseng polysaccharide is 12%.
Method for making: material is crossed 100 mesh sieves respectively, take by weighing material by recipe quantity, mix homogeneously stirs the system soft material, and the 18-24 mesh sieve is granulated, 70 ℃ of following aeration-dryings, and tabletting, the bag film-coat, promptly.
Embodiment 3: the Panax notoginseng standard extract dispersible tablet;
Prescription (1000):
Panax notoginseng standard extract 100g
Microcrystalline Cellulose 70g
Lactose 80g
In add crospolyvinylpyrrolidone 25g
Add crospolyvinylpyrrolidone 25g
Micropowder silica gel 4g
Aspartame 4g
Magnesium stearate 2g
Low-substituted hydroxypropyl cellulose 12.5g
Wherein, Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage is 11%, the ginsenoside Rg of triol group 1(C 42H 72O 14) be 13%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 3%, the Radix Notoginseng flavone is 0.1%, the micromolecule Radix Notoginseng polysaccharide is 18%.
Method for making: material is crossed 100 mesh sieves respectively, take by weighing material by recipe quantity, mix homogeneously.Make wetting agent with 95% ethanol, the 18-24 mesh sieve is granulated, mix, and tabletting, Opadry II film coating, promptly.
Embodiment 4: the Panax notoginseng standard extract drop pill;
Prescription:
Panax notoginseng standard extract 100g
Polyethylene glycol 6000 500g
Wherein, Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage is 20%, the ginsenoside Rg of triol group 1(C 42H 72O 14) be 15%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 2%, the Radix Notoginseng flavone is 0.2%, the micromolecule Radix Notoginseng polysaccharide is 20%.
Method for making: the ormal weight polyethylene glycol 6000 is heated to whole fusions in water-bath after, add the Panax notoginseng standard extract of ormal weight through 100 mesh sieves, be transferred to rapidly after stirring in the reservoir, airtight and insulation is at 80 ℃, drip system from top to bottom with dosing pump drop pill machine, coolant is a dimethicone, drips fast 30 balls/minute kind, and liquid coolant is use up and wiped to the drop pill drop that forms, pour in the dish of absorbent paper, back fill to be dried, packing, promptly.
Embodiment 5: the Panax notoginseng standard extract granule;
Prescription (1000 bags): Panax notoginseng standard extract 100g
Sucrose 70g
Micropowder silica gel 70g
Wherein, Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage is 18%, the ginsenoside Rg of triol group 1(C 42H 72O 14) be 18%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 3%, the Radix Notoginseng flavone is 0.15%, the micromolecule Radix Notoginseng polysaccharide is 18%.
Method for making: Panax notoginseng standard extract, sucrose and the micropowder silica gel of recipe quantity are made soft material in right amount with 70% ethanol, cross 18 mesh sieves and granulate, 60 ℃ of forced air dryings 30 minutes, 14 mesh sieve granulate, again in 60 ℃ of dryings, packing, promptly.
Embodiment 6: the Panax notoginseng standard extract capsule;
Prescription (1000): Panax notoginseng standard extract 100g
Starch 60g
Microcrystalline Cellulose 35g
Low-substituted hydroxypropyl cellulose 14g
Calcium sulphate dihydrate 10g
Wherein, Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage is 10%, the ginsenoside Rg of triol group 1(C 42H 72O 14) be 10%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 3%, the Radix Notoginseng flavone is 0.03%, the micromolecule Radix Notoginseng polysaccharide is 10%.
Method for making: above-mentioned Panax notoginseng standard extract and adjuvant mix homogeneously is encapsulated, make 1000, promptly.
Embodiment 7: the Panax notoginseng standard extract soft capsule
Prescription (1000):
Content: Panax notoginseng standard extract 100g
PEG400 200g
Propylene glycol 30g
Softgel shell: gelatin 60.2g
Glycerol 19.8g
Water is an amount of
Ethyl hydroxybenzoate (ethyl hydroxybenzoate) 0.12g
Wherein, Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage is 16%, the ginsenoside Rg of triol group 1(C 42H 72O 14) be 16%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 3.02%, the Radix Notoginseng flavone is 0.16%, the micromolecule Radix Notoginseng polysaccharide is 16%.
Method for making: get Panax notoginseng standard extract, add in the PEG400, stir and make its dissolving, add the propylene glycol mixing, the compacting soft capsule, drying is made 1000, promptly.
More than used Panax notoginseng standard extract can prepare by the following method:
Get the Radix Notoginseng clip, with 25%-45% ethanol after softening 24 hours, pulverize, measured the 70%-95% soak with ethanol 96 hours with 7 times for the first time, measured the 50%-65% soak with ethanol 72 hours with 6 times for the second time, measured the 50%-65% soak with ethanol 48 hours with 6 times for the third time, merge extractive liquid, filters, filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.24~1.26 (80 ℃), adds the water of 2 times of amounts of clear paste, heating for dissolving, add an amount of ZTC1+1 (II type) natural clarifying agent and (add the A part earlier, 50~60 ℃ of insulations are warming up to 80 ℃ after 1 hour and add the B part again), place more than 10 hours, filter, it is 1.24~1.2880 ℃ that filtrate is concentrated into relative density, 80 ℃ of drying under reduced pressure are pulverized, promptly.
The instructions of taking of the control medicine for senile dementia of Panax notoginseng standard extract of the present invention preparation is: oral, and two minimum preparation unit (being equivalent to Panax notoginseng standard extract 200mg) once, twice, 30 day on the one is a course of treatment.

Claims (5)

1. the application of Panax notoginseng standard extract in preparation control medicine for senile dementia is characterized in that described Panax notoginseng standard extract mainly contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage is the ginsenoside Rg of 10%-20%, triol group 1(C 42H 72O 14) be 10%-20%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 2~3.5%, the Radix Notoginseng flavone is 0.03%-0.2%, the micromolecule Radix Notoginseng polysaccharide is 10%-20%; The preparation technology of Panax notoginseng standard extract is: get the Radix Notoginseng clip, with 25%-45% ethanol after softening 24 hours, pulverize, measured the 70%-95% soak with ethanol 96 hours with 7 times for the first time, measure the 50%-65% soak with ethanol 72 hours with 6 times for the second time, measured the 50%-65% soak with ethanol 48 hours, merge extractive liquid, with 6 times for the third time, filter, filtrate recycling ethanol is concentrated into 80 ℃ of following relative densities and is 1.24~1.26 clear paste, adds the water of 2 times of amounts of clear paste, heating for dissolving, add an amount of II type ZTC1+1 natural clarifying agent, add the A part earlier, 50~60 ℃ of insulations are warming up to 80 ℃ after 1 hour and add the B part again, place more than 10 hours, filter, it is 1.24~1.28,80 ℃ of drying under reduced pressure that filtrate is concentrated into 80 ℃ of following relative densities, pulverize, promptly.
2. the application of Panax notoginseng standard extract according to claim 1 in preparation control medicine for senile dementia is characterized in that described Panax notoginseng standard extract contains the ginsenoside Rb of glycol group 1(C 54H 92O 23) weight percentage be the ginsenoside Rg of 11-15%, triol group 1(C 42H 72O 14) be 11-15%, Panax Notoginseng saponin R 1(C 47H 80O 18) be 2~3%, the Radix Notoginseng flavone is 0.05%-0.2%, the micromolecule Radix Notoginseng polysaccharide is 12%-18%.
3. the application of Panax notoginseng standard extract according to claim 1 in preparation control medicine for senile dementia is characterized in that preventing or to treat alzheimer disease.
4. the application in the medicine of Panax notoginseng standard extract according to claim 1 preparation control senile dementia, the dosage form that it is characterized in that being prepared on the pharmaceutics and comprised.
5. the preparation technology of the described Panax notoginseng standard extract of claim 1, it is characterized in that: get the Radix Notoginseng clip, with 25%-45% ethanol after softening 24 hours, pulverize, measured the 70%-95% soak with ethanol 96 hours with 7 times for the first time, measured the 50%-65% soak with ethanol 72 hours with 6 times for the second time, measured the 50%-65% soak with ethanol 48 hours with 6 times for the third time, merge extractive liquid, filters filtrate recycling ethanol, be concentrated into 80 ℃ of following relative densities and be 1.24~1.26 clear paste, add the water of 2 times of amounts of clear paste, heating for dissolving adds an amount of II type ZTC1+1 natural clarifying agent, add the A part earlier, 50~60 ℃ of insulations are warming up to 80 ℃ after 1 hour and add the B part again, place more than 10 hours, filter, it is 1.24~1.28 that filtrate is concentrated into 80 ℃ of following relative densities, 80 ℃ of drying under reduced pressure are pulverized, promptly.
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