CN105902840B - Cardiovascular disease and the drug of dementia and preparation method thereof caused by a kind of prevention and treatment Apolipoprotein E-deficient - Google Patents
Cardiovascular disease and the drug of dementia and preparation method thereof caused by a kind of prevention and treatment Apolipoprotein E-deficient Download PDFInfo
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- CN105902840B CN105902840B CN201610231956.1A CN201610231956A CN105902840B CN 105902840 B CN105902840 B CN 105902840B CN 201610231956 A CN201610231956 A CN 201610231956A CN 105902840 B CN105902840 B CN 105902840B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
- A61K36/8988—Gastrodia
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
- A23D9/00—Other edible oils or fats, e.g. shortenings, cooking oils
- A23D9/007—Other edible oils or fats, e.g. shortenings, cooking oils characterised by ingredients other than fatty acid triglycerides
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
- A23D9/00—Other edible oils or fats, e.g. shortenings, cooking oils
- A23D9/02—Other edible oils or fats, e.g. shortenings, cooking oils characterised by the production or working-up
- A23D9/04—Working-up
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/52—Juglandaceae (Walnut family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
Abstract
The invention discloses cardiovascular diseases and the drug of dementia and preparation method thereof caused by a kind of prevention and treatment Apolipoprotein E-deficient, and drug includes the component of following mass percent: Rhizoma Gastrodiae liposoluble constituent 5%~10%, Co-Q10 5%~15%, vitamin E 0.1%~1.5%, walnut oil 80%~85%.The present invention passes through special proportion and special preparation method by Rhizoma Gastrodiae liposoluble constituent, Co-Q10, vitamin E and walnut oil, a kind of drug for effectively preventing cardiovascular disease caused by ApoE defect and dementia is made, hyperlipidemia caused by ApoE defect, atherosclerosis and cognition dysfunction can be effectively relieved；The present invention, which passes through mould gesture zooscopy and confirms the pharmaceutical composition, can effectively improve the hyperlipidemia, atherosclerosis and cognition dysfunction of APOE deficient animals.
Description
Technical field
The present invention relates to a kind of pharmaceutical formulations, belong to technical field of pharmaceuticals, refer in particular to a kind of prevention and treatment Apolipoprotein E-deficient
Caused cardiovascular disease and the drug of dementia and preparation method thereof.
Background technique
Cardiovascular disease and senile dementia are to seriously threaten two big fatal killers of the elderly's life and health, wherein high
Pionemia and atherosclerosis are considered as inducing the key factor of above-mentioned illness, and apo E (apolipoprotein
E, ApoE) it is the important link for participating in lipid metabolism and transhipment, it is closely related with the formation of disorders of lipid metabolism and congee artery sclerosis.
Further investigations have shown that having more than 40% coronary heart disease, the allele of myocardial infarction patient its ApoE gene and normal person
There is notable difference, to disturb the normal lipid metaboli transport process of ApoE；Simultaneously research have also discovered dementia patients (including
Vascular dementia and Alzheimer disease) in the allele of about 30%~50% crowd its ApoE also have and significantly change
Become.The change of ApoE allele makes it participate in lipoprotein transhipment as the ligand of LDL receptor and GAP-associated protein GAP
It is impaired with the function of metabolism, lead to intracorporal chylomicron, very low density lipoprotein, intermediate density lipoprotein and high density lipoprotein level
White equal proportional imbalance, causes disorders of lipid metabolism, to induce hyperlipidemia and atherosclerosis.In addition, atheromatous plaque
Energy coup injury blood vessel endothelium is formed, the response to oxidative stress of body is activated, ROS is discharged, further activates the inflammation of body anti-
It answers, accelerates the progress of the state of an illness.Therefore, improve disorders of lipid metabolism, inhibit the response to oxidative stress of body, helping, which improves ApoE, lacks
Cardiovascular disease caused by falling into and dementia.
There is clinical research to point out, omega-3 polyunsaturated fatty acids only to improve ApoE defect caused by senile dementia (Ah
Alzheimer's disease) there is apparent curative effect, and also can effectively adjust intracorporal lipid structures type.Insatiable hunger more than the ω -3 of walnut oil
It is ideal natural tune fat foods with content highest of the fatty acid (linolenic acid) in conventional plant oil；Rhizoma Gastrodiae is traditional medicine
Eat homologous medicinal material, water soluble ingredient Gastrodin has good anti-senile dementia and a neuroprotection, Rhizoma Gastrodiae it is fat-soluble
Ingredient also polyunsaturated fatty acid rich in, while the volatile materials such as limonene are ancillary drugs through blood-brain barrier
Good transdermal enhancer.For this purpose, the present invention exactly using both components be made it is a kind of have can prevent and treat the heart caused by ApoE defect
Vascular diseases can improve the pharmaceutical formulation because of the ApoE dementia induced again.
Summary of the invention
It is an object of the invention to overcome deficiency in the prior art, angiocarpy caused by a kind of prevention and treatment ApoE defect is provided
The drug of disease and dementia, which, which has, adjusts lipid structures, improves disorders of lipid metabolism, is anti-oxidant and protection neuron
Effect can be applied to the drug or health food of cardiovascular disease and dementia caused by preparation prevention and treatment ApoE defect.
Another object of the present invention is to provide the methods of the preparation of said medicine.
In order to realize that first purpose, the present invention are realized according to following technical scheme:
The drug of cardiovascular disease and dementia caused by a kind of prevention and treatment Apolipoprotein E-deficient comprising have following quality
The component of percentage: Rhizoma Gastrodiae liposoluble constituent 5%~10%, Co-Q10 5%~15%, vitamin E 0.1%~1.5%,
Walnut oil 80%~85%.
Further, the Rhizoma Gastrodiae liposoluble constituent Linoleic acid content is 20%-50%, limonene content 1.5%-
5%.
Further, the walnut oil Linoleic acid content is 60%-73%, linolenic acid content 8%-20%.
In order to realize that second purpose, the present invention are realized according to following technical scheme:
A kind of preparation method of the drug of cardiovascular disease caused by prevention and treatment Apolipoprotein E-deficient and dementia comprising
Following steps: Rhizoma Gastrodiae liposoluble constituent 5%~10%, Co-Q10 5%~15% and vitamin E 0.1 are weighed respectively in proportion
~1.5%, it is uniformly mixed, suitable 40 DEG C~45 DEG C hot walnut oils is then added and make it dissolve, and finally make the matter of walnut oil
Amount score reaches 80%~85%, as gained pharmaceutical composition.
Further, the preparation step of the Rhizoma Gastrodiae liposoluble constituent includes: S1, taking sun-dried Rhizoma Gastrodiae, is enucleated, crushes, mistake
40 meshes, obtain Tall Gastrodis Tuber；S2, Tall Gastrodis Tuber is set in volatile oil extractor, using extraction by steam distillation 8h, divides and go
Water layer retains volatile oil；S3, extract is set to 4 DEG C of refrigerator-freezer 12h, divides and removes solid content, retain oil reservoir to get the Rhizoma Gastrodiae liposoluble
Property ingredient.
Further, the preparation step of the walnut oil includes: S1, using gradient freezing freezing method to traditional cold press legal system
Standby walnut oil is refined；S2, thick walnut oil is set in refrigerator-freezer, using programmed cooling method, respectively in 8 DEG C~4 DEG C, 2 DEG C~0
DEG C and 6~12h of minus 1 DEG C~minus 3 DEG C of placement, collect minus 1 DEG C~minus 3 DEG C of grease below, as described in walnut oil.
Further, described pharmaceutical composition is soft capsule or oral solutions.
Compared with prior art, the present invention has the advantages that:
The present invention passes through special proportion and special preparation by Rhizoma Gastrodiae liposoluble constituent, Co-Q10, vitamin E and walnut oil
Method is made a kind of drug for effectively preventing cardiovascular disease caused by ApoE defect and dementia, ApoE can be effectively relieved
Hyperlipidemia caused by defect, atherosclerosis and cognition dysfunction；The present invention passes through mould gesture zooscopy and confirms
The pharmaceutical composition can effectively improve the hyperlipidemia, atherosclerosis and cognition dysfunction of APOE deficient animals.
In order to the clearer understanding present invention, a specific embodiment of the invention described in detail below.
Specific embodiment
Rhizoma Gastrodiae liposoluble constituent is prepared, step includes: S1, taking sun-dried Rhizoma Gastrodiae 1.0kg, be enucleated, crushed, crosses 40 meshes,
Obtain Tall Gastrodis Tuber；S2, Tall Gastrodis Tuber is set in volatile oil extractor, the distilled water of 3 times of medicinal material weight is added, using vapor
The way of distillation extracts 8h, and branch vibration layer retains volatile oil；S3, extract is set to 4 DEG C of refrigerator-freezer 12h, divides and removes solid content, retain yellow
Oil reservoir 78mL to get the Rhizoma Gastrodiae liposoluble constituent.The linoleic acid in 9 batches of Rhizoma Gastrodiae liposoluble constituents measured by GC method contains
Amount is 42%-50%, limonene content 1.5%-5%.
Walnut oil is prepared, step includes: S1, the walnut oil prepared using gradient freezing freezing method to traditional cold-press
1.0L is refined；S2, thick walnut oil is set in refrigerator-freezer, using programmed cooling method, respectively in 8 DEG C of placement 8h, divides and remove coagulum,
Oil content continues in 2 DEG C of placement 8h, then divides coagulum, and oil content is taken to be placed in minus 2 DEG C of placements 8h, divides and removes coagulum, collects oil content,
Obtain flaxen walnut oil 582mL.
The drug of cardiovascular disease and dementia caused by preparation prevention and treatment ApoE defect, step includes: distinguishing in proportion
It weighs Rhizoma Gastrodiae liposoluble constituent 150mL, Co-Q10 100g and vitamin E 5g is mixed, 40 DEG C of -45 DEG C of thermonuclears of 200mL are added
Peach oil makes it dissolve, and the walnut oil for adding 650mL finally makes its mass fraction reach 80%-85%, as gained medicine group
Close object.
Experimental comparison:
One, drug of the present invention is to APOE-/-Model mice Aorta atheromatous plague lesion pathological observation
Atherosclerosis (Atherosclerosis, AS) is the basis disease of the cardiovascular diseases such as coronary heart disease, cerebral apoplexy
Become, determines the prognosis of disease and lapse to.The reason of AS formation, is extremely complex, and wherein the expression regulation of lipid transfer protein is in rouge egg
Key effect has been played in white metabolism and the formation of AS.ApoE is the ligand for removing chylomicron and very low density lipoprotein receptor,
Therefore lacking ApoE will lead to the photosynthetic matter accumulation that cholesterol is rich in blood circulation, and Yi Yinqi AS lesion is formed.Group of the invention
The accumulation of cholesterol and blood lipid caused by conjunction object can be effectively reduced because of ApoE shortage, reduces aorta atheromatous plaque shape to play
At effect.
1.1 experimental method
1.1.1 experimental animal grouping and model foundation
Take 30 8 week old male ApoE-/-Mouse is randomly divided into 3 groups, and every group 10, it is high to be respectively as follows: model group, composition
Dosage group 15mL/kg, low dose group 7.5mL/kg separately take 10 8 week old Male wild-type C with background57BL/6J mouse sky is made
For blank control group.Wherein blank control group gives normal diet nursing, and model group and remaining each group give high lipid food
(78.85% raw grain, 21% lard, 0.15% cholesterol) is fed.Each dosage group of composition 4h gastric infusion before feeding, blank
Control group and model control group are filled with corresponding saline volume, and 1 time/d, continuous 12 weeks.After the last administration, mouse fasting can't help
Anesthesia takes blood after water 24 hours, routinely prepares serum, leaves and takes whole aorta of aortic root to abdominal aorta end, detects
Index of correlation.
1.1.2 the measurement of aorta AS plaque area
Mouse thoracic cavity and abdominal cavity are opened, whole aorta, 10% Fu Er are separated from aortic root to abdominal aorta end
Malin fixes, and next day, routinely dehydration, paraffin embedding and serial section, 5 μm of production paraffin sections of slice thickness, HE dyed simultaneously mirror
It examines, take pictures, using 6.0 image analysis system of Image-Pro Plus, detect atherosclerotic plaque area and active vascular
Cavity area calculates ratio between two, and calculates aortic tunica intima and media thickness ratio.
1.1.3 Serum Indexes detect
Automatic clinical chemistry analyzer detects total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-
C), high-density lipoprotein cholesterol (HDL-C), it is horizontal using MDA, SOD and GSH in spectrophotometry serum, specifically press
Kit illustrates to be operated.
1.1.4 data processing
One-way analysis of variance is carried out to experimental data using SPSS18.0 software, is as a result indicated with x ± s, with P < 0.05
It is statistically significant for difference.
1.2 experimental result
1.2.1 composition is to ApoE-/-The morphologic influence of rat aorta atherosis
Compared with model group, give in each dosage group atherosclerotic plaque area of composition and Lumen Area ratio, aorta
Film and media thickness ratio and lipid content are decreased significantly (P < 0.05).(the results are shown in Table 1).
1. composition of table is to ApoE-/-The morphologic influence (n=10) of rat aorta atherosis
P < 0.01 a, compared with blank control group；P < 0.01 ab P < 0.05, b, the compared with model group
1.2.2 composition is to ApoE-/-The influence of lipid of mice
Compared with model group, give TC, TG, LDL-C content in each dosage group blood lipid of composition decreased significantly (P <
0.05), and the content of LDL-C then significantly rises.(the results are shown in Table 2).
2. composition of table is to ApoE-/-The influence (n=10) of lipid of mice
P < 0.01 a, compared with blank control group；P < 0.01 ab P < 0.05, b, the compared with model group
1.2.3 composition is to ApoE-/-The influence of mice serum lipid peroxide
Compared with model group, the GSH level and SOD vigor of each dosage group of composition are significantly increased (P < 0.05), and
MDA content is then substantially reduced compared with model group, and difference is statistically significant (P < 0.05).(the results are shown in Table 3).
3. composition of table is to APOE-/-The influence (n=10) of lipid peroxide in mice serum
P < 0.01 a, compared with blank control group；P < 0.01 ab P < 0.05, b, the compared with model group
Conclusion: drug energy anti-lipid peroxidation object of the invention adjusts the fat metabolism and turn-over capacity of body, thus
The atherosclerosis for improving model mice is horizontal.
Two, drug of the present invention is to ApoE-/-The improvement result of model mice cognitive ability obstacle
Vascular dementia (vascular dementia, VaD) and Alzheimer disease (Alzheimer disease, AD)
It is considered as the primary two types of senile dementia.Although the morbidity of VaD and AD is the product as caused by more pathogenic factors,
APOE gene pleiomorphism has been considered as the high-risk pathogenic factor being now uniquely determined.ApoE allele can promote solvable extremely
A β formed precipitating, activation cerebrovascular pericyte proinflammatory cyclophilin-A mediate access, lead to the damage of cerebrovascular integrality
The collapse of blood-brain barrier of becoming estranged causes neure damage.ApoE defect causes the accumulation of cholesterol and blood lipid simultaneously, also results in
Cerebrovascular atherosis causes brain tissue groundwater increment to reduce, and neural cell excitability reduces, and causes brain metabolic rate to decline, draws
Play cognition dysfunction.Cognition dysfunction caused by composition of the invention can effectively improve because of ApoE shortage.
2.1 experimental method
2.1.1 experimental animal grouping and model foundation
Take 8 week old C57BL/6J male mice 8 has only reached C57The ApoE of BL/6J genetic background-/-Transgenic mice 24.
With C57BL/6J mouse is blank control group, 24 ApoE mouse is randomly divided into three groups: model group, composition high dose group
15mL/kg, low dose group 7.5mL/kg, wherein blank control group gives normal diet nursing, and model group and remaining each group give height
Rouge feed (78.85% raw grain, 21% lard, 0.15% cholesterol) is fed.The 4h stomach-filling before feeding of each dosage group of composition is given
Medicine, blank control group and model control group are filled with corresponding saline volume, and 1 time/d, continuous gavage 28 weeks.Stomach-filling 5 days weekly,
Rest 2 days.
2.1.2 experimental animal water maze Behavior test
Water maze Spatial memory ability detection, using Morris water maze.Water maze is diameter 150cm, high
The round pool of 50cm.Pond is divided into 4 quadrants with 4 equidistant points, each quadrant posts unlike signal object, target as
It limits (being set as third quadrant) and places escape platform.The video camera of placement connection display system, synchronous recording mouse fortune above labyrinth
Dynamic rail mark.
Behavior Test includes two aspects: (1) orientation navigation experiment (place navigation), and mouse is faced pool wall
It is put into labyrinth, place of entry is respectively the midpoint of II, IV quadrant, fixes place of entry sequence, every mouse at random in experimentation
The continuous training of test 2 times every time, enters water from the relative sector in pond every time, and each 90s records rat in 90s and finds platform simultaneously
Stop the incubation period of 2s；If not found in 90s, incubation period 90s, and guide it to stop 15s in platform by operator.Observation
The situation of change of mouse escape latency.(2) space search experiment (spatial probe test), experimentation last
It, removes platform, and other conditions are constant, carries out space exploration experiment, and by mouse from I, it is primary that III quadrant midpoint respectively enters water,
Continue 90s.Record the situation of change of the indexs such as mouse spanning platform number.Data acquisition and processing (DAP) is by Morris water maze image
Automatic monitoring processing system is completed.
2.1.3 serological index
Automatic clinical chemistry analyzer detects total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-
C), high-density lipoprotein cholesterol (HDL-C), the TNF-α in ELISA method detection blood are horizontal.
2.1.4 the expression of immunohistochemical staining measurement brain tissue tissue GFAP
After mouse anesthesia takes blood, brain is taken in broken end on ice rapidly, the physiological saline being pre-chilled with 4 DEG C washes away blood, blots more
Remaining moisture, left half brain tissue are fixed with 4% paraformaldehyde, and brain tissue paraffin embedding, slice, dimethylbenzene is transparent, and conventional dewaxing is extremely
Water, 3% hydrogen peroxide are incubated for 15min, and PBS is washed 3 times, each 3min, Microwave method 15min；People's Normal Goat Serum is added to close
Then primary antibody (1:100 dilution) is added in liquid, 37 DEG C of incubation 15min, 4 DEG C overnight, and PBS is washed 3 times, each 3min；Secondary antibody is added,
37 DEG C of incubation 15min, PBS are washed 3 times, each 3min；It is eventually adding horseradish peroxidase-labeled strepto- avidin (SABC) work
Make liquid, 37 DEG C of incubation 15min, PBS are washed 3 times, each 3min；DAB develops the color, and developing time is controlled under microscope, and tap water rinses,
Haematoxylin is redyed, neutral gum mounting.Every group is used PBS to replace primary antibody as negative control.GFAP immuning tissue in brain tissue
Chemical staining image carries out image analysis with Image-Pro Plus6.0 analysis software, and every slice takes 5 visual field measurements
Integral optical density (integrated optical density, IOD) value of GFAP protein positive product, is averaged expression
GFAP expression.IOD value is bigger, and the expression of expression destination protein is stronger.
2.1.5 data processing
Experimental data indicates that comparison among groups use one-way analysis of variance with x ± s, and all data are applied
The analysis of SPSS18.0 software is that difference is statistically significant with P < 0.05.
2.2 experimental result
2.2.1 protective effect of the composition to model mice Spatial memory obstacle
To the 28W that experiment terminates since 20w, the escape latency of each group mouse starts to space out, model group
The escape latency of mouse is significantly higher than other each group mouse (P < 0.01), and occur with the increase of feeding time it is extended become
Gesture, the escape latency of each dosage group mouse of composition are substantially less than model group mouse (P < 0.05), and with the increasing of time
Add its Long-term change trend unobvious.From the point of view of the situation of mouse search platform, compared with model group mouse, each dosage group of composition
Mouse can repeatedly, spanning platform number obviously increases for search repeatedly near original platform position, shows to find underwater platform
Purpose, specific aim are very strong (the results are shown in Table 4).
The ApoE of 4. composition pair of table-/-The influence (n=8) of model mice Spatial memory obstacle
P < 0.01 a, compared with blank control group；P < 0.01 ab P < 0.05, b, compared with model group.
2.2.2 composition is to ApoE-/-The influence of lipid of mice and TNF-α level
Compared with model group, give TC, TG, LDL-C content in each dosage group blood lipid of composition decreased significantly (P <
0.05), and the content of LDL-C then significantly rises.Meanwhile TNF-α level composition intervention each and two groups compared with model group
Also there is apparent reduction.(the results are shown in Table 5)
5. composition of table is to ApoE-/-The influence (n=10) of lipid of mice and TNF-α level
P < 0.01 a, compared with blank control group；P < 0.01 ab P < 0.05, b, compared with model group.
2.2.3 composition is to ApoE-/-The influence of astroglia in mouse brain
GFAP immunohistochemistry positive cell (astroglia) has stronger bright green fluorescence signal under light microscopic, shows
Cell is similar to starlike profile.In blank control group mouse hippocampus, GFAP immuning positive cell is distributed sparse, cell number
Few, cell volume is small, and fluorescence signal is weaker.Compared with blank photo group, model group hippocampus of mice region GFAP immuning positive cell
It increased significantly, cell volume is larger, and endochylema is abundant, and branch's thickening of most cells, growth, and cell entirety area coverage is big,
Fluorescence signal is strong, it is believed that the astrocyte in APOE mouse brain largely activates, for repairing possible brain neuron
It is impaired.And the mouse GFAP positive cell number of composition high and low dose group is considerably less than model group, fluorescence signal is weaker.By
Table 5 is as it can be seen that the average optical density value and IOD value of blank control group and composition intervention group hippocampus are significantly less than model group (P
<0.05).Illustrate that composition can mitigate and delay the hypertrophy and hyperplasia degree of the astroglia of APOE mouse brain, reduces
Damage suffered by nerve fibre and cynapse (the results are shown in Table 6).
The result (x ± s) of table 6. each group hippocampus of mice area GFAP average optical density and IOD
P < 0.01 a, compared with blank control group；P < 0.01 ab P < 0.05, b, compared with model group.
Conclusion: drug of the present invention can be obviously improved the Spatial memory obstacle of ApoE transgenic mice, improve memory energy
Power improves the learning efficiency of ApoE transgenic mice.Its mechanism and adjusting fat metabolism and transhipment, astroglia swash
It is living, inflammatory factor TNF-α level is lowered, protection neuron is related.
In conclusion the present invention is damaged by ApoE deficient mice model because simulation ApoE transports fatty function, draw
The lipid metaboli imbalance risen induces the symptoms such as hyperlipidemia, congee artery sclerosis and cognition dysfunction, it was confirmed that the Rhizoma Gastrodiae liposoluble
The lipid metaboli that property ingredient, Co-Q10, vitamin E and walnut fluid composition can correct body is unbalance, reduces lipid peroxide
It generates, reduces the activation of inflammatory factor, the atherosclerosis of aorta generated so as to improve animal pattern and cognition dysfunction.Separately
Outside, the present invention has also opened up the new medicinal usage of composition, can be used for angiocarpy disease caused by preventing or/and treating ApoE defect
The drug or health food of disease and dementia.It is worth mentioning that: prevention prepared by the composition and/or treatment alzheimer '
Piece can be made with pharmaceutically acceptable auxiliary material and conventional preparation method in the drug or health food that silent disease mentions, form of administration
The dosage forms such as agent, granule, capsule or oral solution.
Finally, it should be noted that these are only the preferred embodiment of the present invention, it is not intended to restrict the invention, although
Referring to embodiment, invention is explained in detail, for those skilled in the art, still can be to aforementioned
Technical solution documented by each embodiment is modified or equivalent replacement of some of the technical features, but it is all
Within the spirit and principles in the present invention, any modification, equivalent replacement, improvement and so on should be included in protection of the invention
Within the scope of.
Claims (5)
1. it is a kind of prevention and treatment Apolipoprotein E-deficient caused by cardiovascular disease and dementia drug, it is characterised in that include with
The component of lower mass percent: Rhizoma Gastrodiae liposoluble constituent 5%~10%, Co-Q10 5%~15%, vitamin E 0.1%~
1.5%, walnut oil 80%~85%；Wherein: the Rhizoma Gastrodiae liposoluble constituent Linoleic acid content is 20%-50%, limonene
Content is 1.5%-5%；The walnut oil Linoleic acid content is 60%-73%, linolenic acid content 8%-20%.
2. the preparation side of the drug of cardiovascular disease caused by prevention and treatment Apolipoprotein E-deficient and dementia as described in claim 1
Method, it is characterised in that the following steps are included: weigh respectively in proportion Rhizoma Gastrodiae liposoluble constituent 5%~10%, Co-Q10 5%~
15% and vitamin E 0.1~1.5%, it is uniformly mixed, suitable 40 DEG C~45 DEG C hot walnut oils is then added and make it dissolve, and
Finally the mass fraction of walnut oil is made to reach 80%~85%, as gained pharmaceutical composition.
3. preventing and treating the preparation of the drug of cardiovascular disease caused by Apolipoprotein E-deficient and dementia according to claim 2
Method, it is characterised in that: the preparation step of the Rhizoma Gastrodiae liposoluble constituent includes: S1, taking sun-dried Rhizoma Gastrodiae, is enucleated, and crushes, mistake
40 meshes, obtain Tall Gastrodis Tuber；S2, Tall Gastrodis Tuber is set in volatile oil extractor, using extraction by steam distillation 8h, divides and go
Water layer retains volatile oil；S3, extract is set to 4 DEG C of refrigerator-freezer 12h, divides and removes solid content, retain oil reservoir to get the Rhizoma Gastrodiae liposoluble
Property ingredient.
4. preventing and treating the preparation of the drug of cardiovascular disease caused by Apolipoprotein E-deficient and dementia according to claim 2
Method, it is characterised in that: the preparation step of the walnut oil includes: S1, using gradient freezing freezing method to traditional cold-press
The walnut oil of preparation is refined；S2, thick walnut oil is set in refrigerator-freezer, using programmed cooling method, respectively in 8 DEG C~4 DEG C, 2 DEG C
~0 DEG C and 6~12h of minus 1 DEG C~minus 3 DEG C of placements, minus 1 DEG C of collection~minus 3 DEG C of grease below, the as walnut oil.
5. preventing and treating the preparation of the drug of cardiovascular disease caused by Apolipoprotein E-deficient and dementia according to claim 2
Method, it is characterised in that: described pharmaceutical composition is soft capsule or oral solutions.
Priority Applications (1)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101283796A (en) * | 2008-05-08 | 2008-10-15 | 昆明云大医药开发有限公司 | Health products for osteoporosis and cardio-cerebrovascular disease using walnut oil as matrix |
| CN101732586A (en) * | 2010-01-13 | 2010-06-16 | 云南中医学院 | Medicinal application of ethyl acetate extracts from Gastrodia elata Blume in treating ischemic cerebrovascular disease |
| CN203601807U (en) * | 2013-11-27 | 2014-05-21 | 腾冲高黎贡山生态食品发展有限公司 | Walnut oil storage tank |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101283796A (en) * | 2008-05-08 | 2008-10-15 | 昆明云大医药开发有限公司 | Health products for osteoporosis and cardio-cerebrovascular disease using walnut oil as matrix |
| CN101732586A (en) * | 2010-01-13 | 2010-06-16 | 云南中医学院 | Medicinal application of ethyl acetate extracts from Gastrodia elata Blume in treating ischemic cerebrovascular disease |
| CN203601807U (en) * | 2013-11-27 | 2014-05-21 | 腾冲高黎贡山生态食品发展有限公司 | Walnut oil storage tank |
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