CN104771501A - Traditional Chinese medicine composition used for preventing and treating alzheimer's disease - Google Patents
Traditional Chinese medicine composition used for preventing and treating alzheimer's disease Download PDFInfo
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- CN104771501A CN104771501A CN201410009309.7A CN201410009309A CN104771501A CN 104771501 A CN104771501 A CN 104771501A CN 201410009309 A CN201410009309 A CN 201410009309A CN 104771501 A CN104771501 A CN 104771501A
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Abstract
The invention discloses a traditional Chinese medicine composition used for preventing and treating alzheimer's disease. The traditional Chinese medicine composition is prepared by mixing radix astragali, ginseng, honey-fried licorice root, radix puerariae, rhizoma cimicifugae, chastetree fruit, radix paeoniae alba, and cortex phellodendri at a ratio of 5:5:5:3:3:1.5:1:1.
Description
Technical field
This case is a kind of prevention and the Chinese medicine composition for the treatment of Alzheimer disease, espespecially utilizes a plurality of Chinese medicine to carry out the Chinese medicine composition of a kind of prevention and the treatment Alzheimer disease mixed with specific ratio.
Background technology
Along with the progressive old man of the promotion mouth of sanitary condition increases.According to the statistics of Department of Health, the ratio of China old people population has the trend risen year by year, and has marched toward the standard of the United Nations's " aging society ".So various Senile disease produces gradually, as cancer, apoplexy, cardiovascular disease, Parkinson's disease and old dementia etc. all belong to this type of, and the impact that old dementia (senile dementia) causes family is maximum.The cranial nerve degenerative disease that old dementia is a kind of growth with the age and causes, sick man memory, behavior, emotion, personality etc. all have damage.In old dementia, Alzheimer disease (Alzheimer ' s disease) patient accounts for about over half.Alzheimer disease patient much Cerebral cortex and hippocampal gyrus in postmortem have many senile plaques (senileplaque) and the neural pathological characters such as (neurofibrillary tangles) that tangles, and are mainly kind of starch sample proteinosis on inspection.
As for the development of " kind of starch sample albumen hypothesis " (amyloid β peptide hypothesis), be that visible cerebral cortex has many specklees on Alzheimer disease patient becomes celestial, purification is learnt as kind of starch sample albumen (amyloid β peptide hypothesis) in addition, and is studied this type of amyloid.Kind of starch sample albumen is made up of A β, and A β is the first body albumen of kind of starch (the amyloid precursorproteion in organism; APP) 40-43 the amino acid decomposed.Mostly being in normal condition hypencephalon that fibrillar A β 40 is decomposed through α and beta-secretase (secretase) by APP, is originally nontoxic, but not knowing that why APP decomposes through r-catabolic enzyme obtains many A β 42, and is piled up in cell and makes cell death.
Because old dementia has caused the no small danger of society, medical system and families of patients and burden, so medical profession there's no one who doesn't or isn't drops into a large amount of mental and physical efforts research therapy.Current medicine has acetylcholine enzyme inhibitor, nmda antagonist, brain cell promoting agent, anti-inflammatory drug (NSAID), anticholesteremic agent, still there is Amyloid β-peptide vaccine in the future, Secretase inhibitors (secretase inhibitors) though etc. have improvement in various degree, but the course of disease still can not be stoped to worsen, and have gastrointestinal upset, central nerve inhibition, headache and drowsiness side effect.Therefore, find from Chinese medicine and develop and there is intelligence promote effect and the lower medicine of side effect is still the topmost object of development this case.
Summary of the invention
This case is a kind of prevention and the Chinese medicine composition for the treatment of Alzheimer disease, its Chinese medicine composition includes: a Radix Astragali, a Radix Ginseng, a Radix Glycyrrhizae Preparata, a Radix Puerariae, a Rhizoma Cimicifugae, a Fructus Viticis, a Radix Paeoniae Alba and a Cortex Phellodendri, and this Chinese medicine composition uses this Radix Astragali above-mentioned, this Radix Ginseng, this Radix Glycyrrhizae Preparata, this Radix Puerariae, this Rhizoma Cimicifugae, this Fructus Viticis, this Radix Paeoniae Alba and this Cortex Phellodendri to mix with mixed proportion 5:5:5:3:3:1.5:1:1.
According to above-mentioned conception, the Chinese medicine composition of the prevention described in this case and treatment Alzheimer disease, it can be one Powdered.
According to above-mentioned conception, the prevention described in this case and the Chinese medicine composition for the treatment of Alzheimer disease, it can be an ingot shape.
According to above-mentioned conception, the Chinese medicine composition of the prevention described in this case and treatment Alzheimer disease, it can be one liquid.
Accompanying drawing explanation
This case must by following graphic and illustrate, in order to do a more deep understanding:
Fig. 1, rat after 24h training is accounted for whole ratio in 300 seconds holdup times of bright room in passive avoidance response experiment by it.
Fig. 2, it is carry out the water maze laboratory result of 1-3 days.
Fig. 3, it is for after carrying out water maze laboratory the 3rd day training, remove platform assay mouse 60 seconds, sham operated rats (sham) is p<0.01 relative to (vs.) A β input group, and high dose group (high dose) is relative to (vs.) A β input group p<0.01.
Fig. 4, it is carry out the water maze laboratory result of the 5th day.
Fig. 5, it is comparative experiments group (basic, normal, high dosage group), matched group (sham operated rats) and A β input group, the formation degree of kind of starch speckle in brain, measures the immunohistochemical staining result of the activity of NMDA acceptor (N-methyl-D-aspartate receptor) in brain further.
fig. 6, it is water maze device and subregion schematic diagram.
[primary clustering symbol description]
The each assembly column comprised in this case icon is as follows:
(20) water maze
(21) swimming pool
Detailed description of the invention
This case is a kind of prevention and the Chinese medicine composition for the treatment of Alzheimer disease, the composition that this Chinese medicine composition mainly comprises has: a Radix Astragali, a Radix Ginseng, a Radix Glycyrrhizae Preparata, a Radix Puerariae, a Rhizoma Cimicifugae, a Fructus Viticis, a Radix Paeoniae Alba and a Cortex Phellodendri, and this Chinese medicine composition uses this Radix Astragali above-mentioned, this Radix Ginseng, this Radix Glycyrrhizae Preparata, this Radix Puerariae, this Rhizoma Cimicifugae, this Fructus Viticis, this Radix Paeoniae Alba and this Cortex Phellodendri to be that 5:5:5:3:3:1.5:1:1 is obtained by mixing with mixed proportion.
And each composition comprised in prevention described in this case and the Chinese medicine composition for the treatment of Alzheimer disease, its pharmacological action is described below:
(1) Radix Astragali: 1. have cardiotonic.2. there is the effect of moderate diuresis and blood pressure lowering.3. have and strengthen capillary resistance effect.4. have anti-hidropoiesis, the secretory pit of the inaccessible skin of energy, suppresses inducing sweat excessively.5. to quench one's thirst effect, Radix Astragali energy QI invigorating, to promote the production of body fluid, the diabetes (being commonly called as diabetes) of gas Tianjin treatment.
(2) Radix Ginseng: 1. pair Cardiovascular System: Radix Ginseng is vasodilation.2. substance metabolism is affected: Radix Ginseng and Radix saponariae composition thereof have facilitation to the RNA of each tissue and protein synthesis.3. the effect of central nervous system: Radix Ginseng is to the acquisition of different task learning and memory, and memory retains to reproduce invigoration effect in various degree.4. blood system effect: Radix Ginseng soap can adenyl cyclase on excited platelet membrane suppress the activity of phosphodiesterase, and cAMP level in platelet is significantly improved.5. anti-aging effects; The lipid peroxidation of the tissue such as animal liver, brain, lung that Folium Ginseng saponin and Radix Ginseng polysaccharides can suppress many factors to bring out, eliminates free free radical.6. antitumor action.
(3) Radix Glycyrrhizae: 1. on the impact of adrenal cortex and hormone thereof: the biosynthesis of the ACTH that candy corticosteroids causes is suppressed and secretion suppressions, atrophy of thymus gland, anti-granuloma, the former accumulation of glycogen, short near liver cholesterol synthesis, promotes that tryptophan ratio is coughed up enzyme etc. and acted on and all can resist.2. affect 3. impacts on phagocytic function on immunologic function: to engulf and digestive function all has short early work to use white mice is monocytic in body.4. on the impact of inflammatory effect 5. on digestive system: stimulate the gastric secretion increase caused to have certain inhibitory action to histamine, acetylcholine, Gastrin (Gastrin).Wherein glycyrrhizic acid is to the inhibitory action of gastric secretion, is to be increased cAMP content in gastric mucosa by the suppression to phosphodiesterase.
(4) Radix Puerariae: 1. pair Cardiovascular System: Radix Puerariae flavone can make the reduction of ischemic region oxygen content increase lactic acid content improve ischemia infarcted myocardium cardiotonic.2., on the impact of blood pressure: puerarin can make the of short duration reduction of the blood pressure of anesthesia Canis familiaris L., reduce renin activity.3. anti-arrhythmia effect.4. reducing blood sugar and blood fat.5. anticoagulant effect.6. beta receptor blocking effect.7. improve learning and memory.8. neurocyte protection.
(5) Rhizoma Cimicifugae: 1. have antibacterial action.2. there is antiinflammatory action.3. couple central nervous system has inhibitory action: Rhizoma Cimicifugae extract can resist the convulsions that Camphora or strychnine cause.Effect is had: the visamminol in Rhizoma Cimicifugae has obvious mitigation to Cavia porcellus jejunum to smooth muscle.5. there is liver protection effect.
(6) Fructus Viticis: 1. analgesic activity.2. antiinflammatory action.3. phlegm-dispelling functions.4. antiasthmatic effect.5. hypotensive effect.
(7) Radix Paeoniae Alba: 1. immune system effect: Radix Paeoniae Alba total glucosides produces leukocyte circle element-1 to the rat peritoneal macrophages that ester polysaccharide is induced and has low concentration promotion and high concentration inhibitory action.2. the impact of cellular immunization: the Radix Paeoniae Alba can make the cellular immune function being in low state recover.3., on the impact of humoral immunization: the Radix Paeoniae Alba can promote the generation of splenocyte antibody, specificity strengthens.4. blood system effect: Radix Paeoniae Alba extract has and alleviates platelet thrombus, inhibition thrombosis.5. hepatoprotective effect.
(8) Cortex Phellodendri: 1. anti-disease microbial effect.2. pair Cardiovascular System.3. pair digestion systemic effect.4. antitussive, phlegm-dispelling functions.5. other effect: phellodendrine has certain myorelaxant effects.
Via the above-mentioned description to each Chinese medicine ingredients pharmacological action, mix through the partition ratio 5:5:5:3:3:1.5:1:1 described in this case again, just the prevention described in this case and the Chinese medicine composition for the treatment of Alzheimer disease can be produced, described Chinese medicine composition finds that in zoopery Norepinephrine (NE) and the striatal dopamine (DA) of its hypothalamus obviously increase continuously to mice dispensing 7 to 9 days; In aging resistance effect, described Chinese medicine composition can extend life span of drosophila melanogaster, repair genetic defect and scavenging free radicals; In addition, described Chinese medicine formula still obviously can reduce T-CHOL in serum, triglyceride and heart and brain tissues peroxide (SOD), improves HDL in blood, alleviates tremulous pulse atherosclerotic Mottling formation degree.Meanwhile, described Chinese medicine composition is also satisfactory for the treatment achievement of vascular mistake intelligence.Below be further described with regard to various method of carrying out testing for the prevention described in this case and the Chinese medicine composition for the treatment of Alzheimer disease again.
Prevention described in this case is observe described Chinese medicine composition to the curative effect losing intelligence rat with " animal behavior " with the Chinese medicine composition for the treatment of Alzheimer disease, and by the change of NMDAR in Shu Naozuo histopathologic slide and the west point method of the use of ink and water, SDS-PAGE, PCR observation brain.The research method of its " animal behavior " is as following:
(1) laboratory animal: the animal that this institute adopts is provided Sprague's-Du Le (Sprague-Dawley) to be male rat by China Medical University's animal center, body weight is 250 ~ 300kg about, raise in the room of air-conditioning, temperature maintains 23 DEG C of positive and negative scopes of 1 DEG C, light takes 12 hours bright 12 hours secretly, and food and water will not limit.
(2) experimental apparatus: 1.Alzet pump: by osmotic pressure help Pu (mini-osmotic pump, Model2002,0.5 μ l/hr, inner capacities 200 μ l,
), flexible pipe (being about 4-5cm, inner capacities about 80 μ l) and infusion syringe needle formed.2. passive avoidance instrument.3.Morris water maze.
(3) experimental procedure:
(1) induction like A Zihaimo rat is intended:
1. A β (1-40) is won peptide (peptide) pour into Alzet osmotic pumps connect brain perfusion external member.Be placed on stereotaxic instrument, carry out the location of tricorn.
2. brain is poured into external member and be set up tricorn, Alzet osmotic pumps is placed in rim surface zone after neck.
3. sew up, put into rearging cage.
4. matched group (sham) then fills 35% acetonitrile (acetonitrile)/0.1% trifluoroacetic acid (trifluoacetic acid) in Alzet-osmotic pump.
5. treatment group is after embedding completing, and continues every day fixed time next day and gives A β (1-40) and win peptide, until 14 days terminate.
(2) passive avoidance response (passive avoidance learning)
Rat is inserted bright room simultaneously starting gate, enter behind darkroom until rat, closed shutter, pass to electric current (1mA, 2 seconds) in base plate simultaneously, after electricity irritation 5 seconds, take out rat from darkroom, take back rearging cage; As rat never enters darkroom, after 90 seconds, rat is pushed into darkroom, closed shutter, passes to electric current in base plate simultaneously, then take back rearging cage.Test period: in latter 24 hours of training, then rat is inserted bright room, simultaneously starting gate, record rat is at bright room holdup time (step-through latency STL).When being greater than 5 minutes (300sec) in the delay of bright room, then claim the ability of learning and memory of rat normal.
(3) Morris water maze
Rat was through continuous three days, and each training of upper and lower noon, every has 4 exerciser meetings, and each exercise rat has 60 second time to exist for finding position " southwest " platform of quadrant.If rat cannot find platform within the time, then will be directed to this platform.All animals, after arrival platform, can have a rest 30 seconds.When whole process comprises swimming path and flees from latent, all taken by computerization tracing system and record with computer software analysis.General forecast asymptotic latent time reached at 4th ~ 6 days, the 4th and and test for the 6th day.Removed by platform during test, in adding up one minute, rat appears at the time that region originally put by platform, compares with other zone times, within the 7th day, carries out negative testing, platform is moved to diagonal angle (northeast) quadrant.
(4) statistical method:
(1) by avoidance response the data that obtain with without adding up with Kruskal-Wallis nonparametric one-way analysis (Kruskal-Wallis nonparametic one wayanalysis) between each group of female number analytical method (Mann-Whitney U test) and analyzing the significance of difference therebetween; Think there is statistical significance during p<0.05.
(2) water maze space learning operation, reference memory and working memory, glutamate receptor NMADR(N-Methyl-D-aspartic acid or N-Methyl-D-aspartate receptor) concentration etc. detects the data obtained, analyze with single-factor analysis of variance (one way ANOVA), add up with Dennett many-one manner of comparison (Dunnet ' s test) and the calibrating of snow expense (Scheffe ' s test) and analyze significance therebetween between each group; P<0.05, then think there is statistical significance.
(3) the RT-PCR representation of data of NR1, NR2A, NR2B is with gap between variance analysis group, and p<0.05 is for there being significance.
Via above-mentioned experimental technique, we can obtain following result:
(1) refer to Fig. 1, rat after 24h training is accounted for whole ratio in 300 seconds holdup times of bright room in passive avoidance response experiment by it.From figure, we can know and learn, sham operated rats (sham) is 0% relative to the ratio of 300 seconds in (vs.) A β input group, represent that the mouse learning capacity of A β input group is not good, the group of the Chinese medicine composition of the prevention described in feeding this case and treatment Alzheimer disease, as low dose group (low dose), middle dosage group (medium dose), high dose group (high dose) are all p<0.001 relative to (vs.) A β input group.
(2) refer to Fig. 2, it is carry out the water maze laboratory result of 1-3 days.From figure, we can know and learn, first day sham operated rats (sham), low dose group (low dose), middle dosage group (medium dose), high dose group (high dose) vs.A β input group are all p<0.05; Within second day, be then that middle dosage group (mediumdose) is relative to (vs.) A β input group p<0.05; Within 3rd day, be then all p<0.01 relative to (vs.) A β input group p<0.05, middle dosage group (medium dose), high dose group (high dose) relative to (vs.) A β input group relative to (vs.) A β input group p<0.01, low dose group (low dose) for sham operated rats (sham).Within 1-3 days, be mainly and observe the ability of learning and memory of rat, from figure, we can learn that the learning effect of each group all has clear improvement situation.
(3) Fig. 3 is referred to, it is for after carrying out water maze laboratory the 3rd day training, remove platform assay mouse 60 seconds, sham operated rats (sham) is p<0.01 relative to (vs.) A β input group, high dose group (high dose) is relative to (vs.) A β input group p<0.01, this test main detection rat is after removing platform, whether have and remember position of platform, from figure, we can know and learn, all comparatively A β input group is excellent in the performance for the treatment of group, but high dose group and A β input group are compared, there is obvious significant difference (p<0.001).
(4) refer to Fig. 4, it is carry out the water maze laboratory result of the 5th day.From figure, we can know and find out, sham operated rats (sham) is p<0.01 relative to (vs.) A β input group; Administration group is all p<0.001 relative to (vs.) A β input group, the working memory being mainly the working memory mouse observing mouse on the 5th day with how remember the ability that access, from result, we learn the experimental result that gives administration group all there were significant differences property existence (p<0.001).
(5) Fig. 5 is referred to, it is comparative experiments group (basic, normal, high dosage group), matched group (sham operated rats) and amyloid beta albumen (Beta-amyloid) input group, the formation degree of kind of starch speckle in brain, measures the immunohistochemical staining result of the activity of NMDA acceptor (N-methyl-D-aspartate receptor) in brain further.From figure, we can know and find out, the colour generation block of amyloid beta albumen input group comes few compared with other groups (basic, normal, high dosage group), the obvious comparatively amyloid beta albumen input group of other groups (basic, normal, high dosage group) colour generation block is come many, its main cause is that nmda receptor and many nervous system disease are closely bound up, and normal mouse should be able to detect the existence of nmda receptor.On the contrary, the probability generation that amyloid beta albumen can cause nmda receptor content to reduce is inputted.
separately refer to shown in Fig. 6, be another assay device of this creation, it is a water maze (20),
the diameter of its circular swimming pool (21) is 140cm, height 45cm, moveable containing one in swimming pool
half space P1 (or claiming escape platform (escape platform)).The diameter of platform is 12cm, is highly 25cm.
the liquid level that front swimming pool (21) need add water to 27cm is carried out in experiment.Circular swimming pool (21) district
be divided into four quadrants (I, II, III and IV district), and arrange 5 starting points, half space P1 is positioned over and appoints
the central point of one quadrant.Duration of test also sets up camera to record experiment directly over swimming pool central point
the swimming path of animal.
Comprehensive above technology explanation, we can be well understood to, the Chinese medicine composition of the prevention described in this case and treatment Alzheimer disease is in the experiment of " animal behavior ", really obviously change the learning behavior of animal and promote the memory ability of animal, and then complete the topmost object of development this case, in addition, the Chinese medicine composition described in this case can be one Powdered, an ingot shape or liquid.And the present invention must be thought by the personage Ren Shi craftsman haveing the knack of this skill and modify as all, so neither de-if attached claim institute is for protector.
Claims (4)
1. a prevention and the Chinese medicine composition for the treatment of Alzheimer disease, it is characterized in that, described Chinese medicine composition includes: a Radix Astragali, a Radix Ginseng, a Radix Glycyrrhizae Preparata, a Radix Puerariae, a Rhizoma Cimicifugae, a Fructus Viticis, a Radix Paeoniae Alba and a Cortex Phellodendri, and this Chinese medicine composition uses this Radix Astragali above-mentioned, this Radix Ginseng, this Radix Glycyrrhizae Preparata, this Radix Puerariae, this Rhizoma Cimicifugae, this Fructus Viticis, this Radix Paeoniae Alba and this Cortex Phellodendri to mix with mixed proportion 5:5:5:3:3:1.5:1:1.
2. prevention as claimed in claim 1 and the Chinese medicine composition for the treatment of Alzheimer disease, is characterized in that, can be one Powdered.
3. prevention as claimed in claim 1 and the Chinese medicine composition for the treatment of Alzheimer disease, is characterized in that, can be an ingot shape.
4. prevention as claimed in claim 1 and the Chinese medicine composition for the treatment of Alzheimer disease, is characterized in that, can be one liquid.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090105262A1 (en) * | 2007-08-10 | 2009-04-23 | Whiteford Jeffery A | Bridged polycyclic compound based compositions for coating oral surfaces in humans |
| CN101991716A (en) * | 2009-08-26 | 2011-03-30 | 王新祥 | New application of pharmaceutical composition of vital energy benefiting and smart decoction and the like in prevention and cure of osteoporosis |
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2014
- 2014-01-09 CN CN201410009309.7A patent/CN104771501A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090105262A1 (en) * | 2007-08-10 | 2009-04-23 | Whiteford Jeffery A | Bridged polycyclic compound based compositions for coating oral surfaces in humans |
| CN101991716A (en) * | 2009-08-26 | 2011-03-30 | 王新祥 | New application of pharmaceutical composition of vital energy benefiting and smart decoction and the like in prevention and cure of osteoporosis |
Non-Patent Citations (3)
| Title |
|---|
| 丁安伟等: "《现代中药临床手册》", 31 August 2000 * |
| 冯泳等: "《临床常用方剂手册》", 31 January 2001 * |
| 张汤敏等: "《中医健脑法》", 31 May 2001 * |
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Application publication date: 20150715 |