CN106389740A - Composition for preventing and/or delaying old people with mild cognitive impairment and use method thereof - Google Patents
Composition for preventing and/or delaying old people with mild cognitive impairment and use method thereof Download PDFInfo
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- CN106389740A CN106389740A CN201610823216.7A CN201610823216A CN106389740A CN 106389740 A CN106389740 A CN 106389740A CN 201610823216 A CN201610823216 A CN 201610823216A CN 106389740 A CN106389740 A CN 106389740A
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Classifications
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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)
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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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)
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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)
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention discloses a composition for preventing and/or delaying old people with mild cognitive impairment and a use method thereof; the composition comprises the following components in parts by weight: 3000-6000 parts of a coffee powder, 0.2-0.4 part of folic acid, 15000-30000 parts of coconut oil, 15000-30000 parts of semen cannabis, and 3-5 parts of melatonin, wherein the coffee powder contains 3.6-4.2 wt% of caffeine. The composition can improve the antioxidant capacity of brain tissues and prevents the brain tissues from being damaged by free radicals. Animal experiments indicate that the composition can effectively improve learning and memory impairment in Alzheimer's disease model mice; human body test-meal experiments indicate that the old people with mild cognitive impairment take the composition at a specific point in time, and have a significant improving effect on memory improvement. With regular effective taking of the composition, the old people with mild cognitive impairment can be prevented from suffering from Alzheimer's disease, or the incidence time can be delayed.
Description
Technical field
The present invention relates to food, health product technology field, prevent and/or delay old mild cognitive barrier particularly to one kind
Hinder composition and its using method of (MCI).
Background technology
Alzheimer disease (Alzheimer's Disease, AD) is a kind of lethal neurological carrying out sexual development
Property disease, clinical manifestation is cognitive and memory function constantly deteriorates, and activity of daily living progressive goes down, and has various nerve essences
Refreshing symptom and behavior disorder.Clinically with memory disorders, aphasia, appraxia, agnosia, the infringement of visual space technical ability, perform function obstacle
And the performance of the generalized dementia such as personality and behavior change is characterized.
AD is one of senescence phase modal disease, and the World Health Organization (WHO) estimates global over-65s elderly population
The illness rate of AD is 4%～7%.AD illness rate is closely related with the age, and the age averagely often increases by 6.1 years old, and illness rate raises 1
Times；In elderly population more than 85 years old, AD illness rate may be up to 20%～30%.Calendar year 2001 the whole world AD patient more than 20,000,000,
Estimate the year two thousand forty, global AD patient will exceed 80,000,000.The population of Aged in China crowd AD illness at present alreadys exceed 6,000,000,
Expect the year two thousand fifty illness population and will exceed 20,000,000, be the area that AD illness is most populous in the world, growth rate is the fastest.AD
It is the most common disease causing the elderly to lose activity of daily living, be also the 5th cause of disease leading to the elderly dead.AD is not only
Bring huge misery to patient, return family and society brings heavy stress and medical treatment, Burden of care.2010
Year, the expense that the whole world is used for AD is estimated as 604,000,000,000 dollars.Therefore, AD has become impact global public health and society can hold
The significant problem of supervention exhibition.
Although the upstream mechanism now resulting in AD generation is not clear, downstream pathomechanism is clear and definite, characteristic
Pathological change deposits, for amyloid beta, the nerve cell that the extracellular senile plaque expelling being formed and Protein tau Hyperphosphorylationof are formed
Interior neurofibrillary tangles, and neuron loss is with glial cells hyperplasia etc..When a series of paathogenic factors lead to beta-amyloyd egg
During white formation oligomer, just toxic action is produced to cell, promote neurofibrillary tangles to be formed, cause the cognition such as memory region thin
, clinically dementia symptom in born of the same parents' atrophy.Until amyloid beta oligomer is discharged to extracellular and forms senile plaque expelling, cell
Also atrophy, therapeutic effect is also and inconspicuous, here it is the reason many AD medicines do not have successful in the world.Therefore, exist
Cell function still exists, and when also not having severely damaged, i.e. the mild cognitive impairment stage, carries out active prevention very crucial.
There is no medicine can effectively treatment AD it may be said that at present clinic used by treatment medicine also can not be how to this disease
What.Common drug is as follows at this stage for Alzheimer disease：Anticholinesterase, suppresses acetylcholine to degrade with this and improves it
Activity, reaches the purpose improving neurotransmitter transmission function.Galanthamine as first generation reversible anticholinesterase depressant,
Increase the content of acetylcholine by suppressing cholinesterase, both can suppress the cholinesterase in blood plasma, brain tissue can be suppressed again
In cholinesterase, but to include the symptoms such as hepatotoxicity wind agitation and digestive tract reaction very common due to the bad reaction that this medicine causes,
Then occur in that " donepezil " i.e. existing frequently-used " Aricept " again.As second generation anticholinesterase, " how how piperazine
The cholinesterase in brain tissue can substantially be suppressed together ", and will not patient's cardiac muscle and small intestine be caused to bear, Central nervous toxicity
More much smaller than " Tacrine ".But still the symptoms such as diarrhoea, nausea and insomnia can be produced, or even occur producing easily after patient medication
Enrage and attack, glutamatergic neurotransmission dysfunction, especially NMA function of receptors in dementia patients
During infringement." memantine " is NMA receptor antagonist, and also approved is used for Alzheimer disease at present
Treatment." Memantine " be used for treatment in severe to severe DAT, after medication small number of patients also occur illusion,
Misunderstanding, dizziness, headache and the bad reaction such as tired.Using the dull-witted essence of antipsychotic medications Alzheimer characteristic of disease
Refreshing behavior symptom, easily induces epilepsy simultaneously, and epilepsy is also likely to be one of performance of Alzheimer disease temporal atrophy, some medicines
Product even can affect the cognitive function of dementia, thereby produces this drug therapy and the awkward situation increasing the state of an illness.
The pre- tetrandra root of AD is increasingly turned to AD preliminary stage-mild cognitive impairment (MCI) at present.MCI is normally to silly from cognition
In one interstage of slow-witted morbidity, patient has mild memory power to damage, but activity of daily living retains substantially, does not reach dementia and examines
Disconnected standard.With aggravation, patient engenders that cognitive and activity of daily living declines further, relies on other people and takes care of, turns
Turn to dementia patients.At present, academia unanimously thinks that MCI is the important transition stage of AD pre-dementia, and MCI patient is AD morbidity
People at highest risk, carry out prevention and treatment for delaying dull-witted morbidity, improve patients ' life quality there is important work for MCI
With.
Dementia symptom occur before, even mild cognition impairment (MCI) diagnosis before 10～20 years intracerebrals just
Appearance significantly changes, and when memory function and other cognition dysfunctions, intracerebral may have occurred that irreversibility
Serious infringement, now start to treat, late, this is also the key point of many AD clinical drug trial failures at present.
Therefore, just people at highest risk should be intervened as early as possible before symptom appearance.MCI, as the commitment of senile dementia, draws
The concrete reason sending out MCI is unknown, is difficult to diagnosis, there is presently no effective prevention or the preparation for the treatment of MCI or method.
Content of the invention
In view of problem, the purpose of the present invention present in the above-mentioned prevention and treatment in old mild cognition impairment
Be to provide one kind is used for preventing and (or) delay senile mild cognitive impairment (MCI) can be used as the group of long-term dietotherapy preparation
Compound and its using method, said composition can improve memory dysfunction, improves the Sleep efficiency of MCI patient, MMSE comments
Point, word at once and Delay recall achievement, effectively prevent mild cognitive impairment (MCI) patients' Alzheimer disease, or push away
Disease time late, for preventing and (or) delaying Alzheimer disease.
The purpose of the present invention employs the following technical solutions realization：
A kind of composition preventing and/or delay senile mild cognitive impairment, described composition includes as follows by weight
Component：3000～6000 parts of ground coffee, 0.2～0.4 part of folic acid, 15000～30000 parts of coconut oil, fructus cannabis 15000～
30000 parts, 3～5 parts of epiphysin；Wherein, described ground coffee contains the caffeine of 3.6～4.2wt%.
In preferred technical scheme, described composition includes following component：3000 parts of ground coffee, 0.4 part of folic acid, coconut
30000 parts of oil, 30000 parts of fructus cannabis, 3 parts of epiphysin.
In preferred technical scheme, described coconut oil is obtained from squeezing coconut meat at normal temperatures.Described coconut
Oil is specifically adopted and is prepared with the following method：Choose the ripe coconut more containing coconut meat, cocoanut husk peelled off by machine, and polishes off
Brown duricrust, derives Coconut Juice, and coconut meat pulverized by machine, and the coconut meat after pulverizing is dried, and with mechanical expression, does not heat, does not add
Plus any additive, coconut oil is filtered, finally carries out ultraviolet ray sterilization bactericidal, packing.
In technical scheme, coffee bean grinding is become fine powder and is dried to obtain by described ground coffee, wherein contains
There is the caffeine of 3.6～4.2wt%.Described ground coffee can also be carried with conventional method using becoming coffee bean grinding after fine powder
Powdered coffee extract that is pure, being dried to obtain, the wherein caffeine containing 3.6～4.2wt%.
In technical scheme, described folic acid can be with the vegetables containing suitable content folic acid, meat or commercially available
B race multivitamin tablet containing folic acid replaces.
The present invention also provides composition described above in preparation prevention and/or to delay senile mild cognitive impairment illness medicine
Application in thing.Said composition can be controlled with other preventions or treatment senile mild cognitive impairment illness or Alzheimer disease
Treat medicine, or improve the supplement medicine of immunity of organisms, dietary supplements etc. and use cooperatively.
The present invention also provides the using method of composition of the present invention.The present composition is eaten as food or health care
Product, can adopt and use with the following method：Eat ground coffee 3～6g that content of caffeine is 3.6～4.2wt% daily, folic acid 200～
400 μ g, coconut oil 15～30mL, fructus cannabis 15～30g, epiphysin 3～5mg；Preferably eat described ground coffee 3g, folic acid daily
400 μ g, epiphysin 3mg, coconut oil 30mL and fructus cannabis 30g.Can with the food component of dosage described in disposable food it is also possible to
Edible by several times, edible preferably 1～2 time by several times.It is highly preferred that described composition time segment eats, specially：Early 10：00 1
Secondary property eats ground coffee, folic acid and fructus cannabis, and coconut oil, as edible oil, eats corresponding dosage, evening 22 daily:00 take take off black
Element.
The present invention carries out preparing Alzheimer disease mouse model under zoopery, aseptic condition using kunming mice.Adopt
With ground coffee (content of caffeine 3.6%～4.2%), folic acid, epiphysin, coconut oil, fructus cannabis composition recipe, carry out to Ah
The experimental study of Alzheimer's disease prevention, includes space learning energy by the content of Morris water maze main detection and test
Power and space exploration ability, hippocampal tissue aβ protein, IL-6 and IL-12 protein content.Result shows, the composition energy of the present invention
Improve the learning and memory function of AD model mice, in the prevention of MCI and prolonged with other inflammatory factor albumen by suppressing aβ protein
Play a role in slow.
The ground coffee of high-load caffeine, folic acid, epiphysin, fructus cannabis and coconut oil are combined by the present invention, are made for one
Plant and be used for preventing and (or) delay the food therapeutic composition of senile mild cognitive impairment (MCI), edible time is：22：00 takes and takes off
Melanocyte, 10：00 takes other components；Before and after taking, monitor PSG respectively, and carry out multiple neuropsychological, sleep scale test,
Observe sleep, the situation of cognitive change.Result shows, early 10：00 drinks high coffee coffee dietotherapy combination, cooperation evening 22:00 takes
After epiphysin is intervened, the Sleep efficiency of MCI patient, MMSE score, at once and Delay recall achievement carries, with other word
The group difference that time takes dietotherapy combination has statistical significance (P<0.05).
Beneficial effects of the present invention：
1. the present invention provide a kind of have prevention and/delay the composition of mild cognition impairment, said composition conduct
Food rather than medicine, carry out early intervention and have security and the feasibility that medicine does not have.Up to the present, domestic also do not go out
Now with high-load caffeine coffee, folic acid, epiphysin, fructus cannabis and coconut oil for combine recipe, prevention and/delay mild cognitive
Dysfunction (MCI), thus intervene the report that MCI develops into AD.
2. the composition of the present invention, can preferably prevent and (or) delay than alone a certain component therein the generation of MCI,
Thus delaying the morbidity of AD, the contrast test by using method shows, the method that the present invention provides can make curative effect reach maximum
Effect.
3. the present invention passes through to design precisian's body test-meal test, has carried out effect pair to the Time of Administration of each component
According to this is first Time of Administration to be done so accurate, rigorous analysis, assesses using method in terms of sleep-disorder, memory etc.
Improvement to MCI Patients ' Cognitive, specify that the Time of Administration of the compositions such as high-load caffeine coffee, for the first time to make food
The curative effect treating combination maximizes.
4. the composition of the present invention can improve the oxidation resistance of brain tissue, it is to avoid it is damaged by free radical.Dynamic
Thing experiment shows, the present invention can be effectively improved the learning memory injury of Alzheimer disease model mouse；Human feeding trial
Prove, the elderly of mild cognitive impairment, said composition significantly improves the memory capability of senile mild cognitive impairment patient, especially
Take in particular point in time, more preferable to the improvement of memory.Test confirms, rule takes the present composition effectively can be pre-
Anti- senile mild cognitive impairment (MCI) suffers from Alzheimer disease, or postpones disease time.
Specific embodiment
Subordinate's non-limiting example can make those of ordinary skill in the art that the present invention is more fully understood, but not with
Any mode limits the present invention.In addition, in following embodiments, if no special instructions, the experimental technique being used is routine side
Method, material therefor, reagent etc. all can be bought from biological or chemical Reagent Company.
The material that following embodiments adopt：
Composition component：High coffee coffee (containing 4% caffeine, lot number 20151102), coconut oil (lot number 20150915),
Fructus cannabis (lot number 20151012) is purchased from Dalian A Mo Science and Technology Ltd.；Aβ1-42Purchased from the silent Cbio Ltd. in Shanghai.
Key instrument and equipment：Thermo company of U.S. VARIOSKANFLASH 3001 all-wave length readout instrument, FDAC
Company 20PR-5 type high speed freezing centrifuge, HH-S type constant water bath box, OPTIZEN2120UV ultraviolet-uisible spectrophotometer,
Northern Huaihe River Anhui Zheng Hua biological Instrument and equipments Co., Ltd Morris water maze, plum Teller-support benefit Instrument Ltd. PLZOZ-S
Electronic balance etc..
Embodiment 1
1. animal used as test：Kunming kind Alzheimer disease modeling success mouse 70, SPF level, male and female half and half, body weight (20
± 2) g, is provided by Dalian Medical Univ's animal center.Modeling obtains this Alzheimer disease mouse model according to a conventional method, tool
Body is：Observe the general state of kunming mice, capture kunming mice, using 10% chloraldurate, kunming mice is anaesthetized,
Fixing mouse, under aseptic condition, micro sample adding appliance is in the bilateral ventricles of the brain disposable the injection 5 μ l, condensed state A β of mouse1-42
(80pmol/ μ l), syringe needle stays 2 minutes, wraps up mouse, allows mouse fully to rest, and prevents from infecting.Control group is using same simultaneously
The bilateral intracerebroventricular equivalent in mouse for the method physiological saline.
2. animal used as test packet and administration：Alzheimer disease mouse is randomly divided into 6 groups by body weight, sex, respectively
Be model group, coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, group charge-coupled.The normal elder brother of no Alzheimer disease
Bright kind of mouse is set to control group.Every group of 10 mouse, after point cage adaptability is fed 1 week, gastric infusion as follows, daily one
Secondary administration.
Control group, model group, fructus cannabis+coconut oil group：9：00 uses physiological saline gavage；
Coffee group：9：00 high coffee coffee gavage liquid gavage, gavage amount is 382mg high coffee coffee/kg；
Folic acid group：9：00 uses folic acid gavage liquid, and gavage amount is 26 μ g folic acid/kg；
Epiphysin group：20：00 uses epiphysin gavage liquid, and gavage amount is 382 μ g epiphysins/kg；
Group is charge-coupled：9：00 mixes gavage liquid gavage with high coffee coffee and folic acid, and gavage amount is 382mg high coffee coffee/kg+26
μ g folic acid/kg)；20：00 uses epiphysin gavage liquid gavage, and gavage amount is 382 μ g epiphysins/kg.
Wherein, the charge-coupled gavage liquid of described coffee group, folic acid group, epiphysin group, group is that corresponding component is dissolved in physiology
After salt solution, configuration obtains.
The test of Y labyrinth is carried out to mouse according to described dosage continuous gavage after 20 days.Gavage experiment during, group charge-coupled and
Fructus cannabis+coconut oil group fructus cannabis+coconut oil forage feed, remaining group normal diet is fed.
The configuration of fructus cannabis+coconut oil feed：Fructus cannabis is finely ground, according to every mouse daily eat 1.8g fructus cannabis/
The amount of kg is added in normal diet powder, then coconut oil is melted, and eats 1.8mL coconut oil/kg daily according to every mouse
Amount be sprinkled upon among feed powder mix.After mixed, spray suitable quantity of water is binder, is added in granulator and makes bar-shaped feed.
3. test position fix operational capabilities and space exploration ability：
The capital equipment of Morris water maze test includes：Morris water maze, computer camera system and software analysis system
System.Each group mouse orientation navigation ability and space exploration ability, i.e. of each group mouse are detected using Morris water maze instrument
Habit ability and memory capability.This Morris water maze instrument is circular pond, is contained within a transportable platform, platform
On have band, mouse can be facilitated to stop, the shooting instrument above pond is connected with computer, the movement locus to mouse at any time
It is tracked, the corresponding experimental data of analysis mouse.Need to keep the object of reference of indoor and outdoor consistent when test, reduce extraneous
Interference.Morris water maze instrument depth of water 20cm, temperature control, in (23 ± 2) DEG C, is put prepared Chinese ink and is formed muddy black in water
Background, because mouse is white, needs to manufacture black background, is easy to carry out experiment.
Determine four quadrants by imaging instrument.Wherein Morris water maze platform is put in the fourth quadrant of water maze, separately
Outer 3 quadrants are as the quadrant of test.Test the 1st, 2,3,4 days for the training time, be trained for every time 60 seconds, will when test
First, second and third quadrant that mouse head is put in Morris water maze instrument respectively towards outside carries out experimental study, records each mouse
Swimming track and its corresponding experiment number Ju.Test the 5th day test mouse reach the underwater platform position time be denoted as incubation period
Time, the orientation navigation ability of mouse is weighed with this.In addition remove Morris water maze instrument when testing the 5th day to put down
Platform, detection mouse in 60 seconds finds the swimming distance of platform as weighing mouse space exploration ability, to weigh mouse with this
Memory capability.
The impact to Alzheimer disease mouse orientation navigation ability for the 3.1 each experimental group
Mouse orientation navigation ability was represented with incubation period.Shown by table 1 result, compare with control group, model group mouse is dived
The volt phase is obviously prolonged (P<0.05)；Compare with model group, coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group
(26.35 ± 5.32 seconds), group charge-coupled mouse incubation period substantially shorten (P<0.05)；With coffee group, folic acid group, epiphysin group, fire
Numb benevolence+coconut oil group compares, and group charge-coupled mouse incubation period substantially shortens (P<0.05).
The impact to Alzheimer disease mouse space exploration ability for the 3.2 each experimental group
Mouse space exploration ability swimming distance represents.Shown by table 1 result, compare with control group, model group mouse
Swimming distance is obvious to increase (P<0.05)；Compare with model group, coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group,
Organize charge-coupled mouse swimming distance and significantly reduce (P<0.05)；With coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group ratio
Relatively, group charge-coupled mouse swimming distance significantly reduces (P<0.05).
The impact to Alzheimer disease mouse orientation navigation ability and space exploration ability for each experimental group of table 1
| Group | Incubation period (second) | Swimming distance (cm) |
| Control group | 17.06±7.59 | 569.66±69.46 |
| Model group | 35.8±9.48 | 987.64±86.23a |
| Coffee group | 27.06±7.12 | 759.23±86.35b |
| Folic acid group | 25.06±6.35 | 773.56±68.63b |
| Epiphysin group | 26.06±7.86 | 776.85±75.65b |
| Fructus cannabis+coconut oil group | 26.35±5.32 | 768.35±65.32b |
| Group is charge-coupled | 20.06±5.23 | 617.89±54.23c |
Note：Statistical procedures are carried out using SPSS 19.0 software, experimental data adoptsRepresent, multigroup is compared employing
One-way analysis of variance experimental data.P<0.05 thinks that difference is statistically significant.In table 1, a. is compared with control group, P<
0.05；B. compare with model group, P<0.05；C. coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group compare, P<
0.05.
The result of table 1 shows, the ability of learning and memory of model group mouse is decreased obviously, model stability, suitably carries out experiment
Research.Coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, the ability of learning and memory of the charge-coupled mouse of group are obviously improved,
Prompting coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, the charge-coupled symptom that can substantially delay model mice of group,
And organize charge-coupled improvement and be substantially better than other one pack system nursing groups.
Embodiment 2
Measure Hippocampus of Mice A β, IL-6 and IL-12 protein content：
After Morris water maze test experiments in embodiment 1 terminate 2 hours, each group mouse breaks end on superclean bench
Put to death, remove brain tissue skin, open cranium, take out complete mouse brain tissue and be placed on ice platform, remove brain stem and cerebellum, rapidly
Take the hippocampal tissue of each group mouse, be homogenized Hippocampus of Mice, 4 DEG C of refrigerator standings, 5000rpm is centrifuged 10 minutes, draws hippocampus
Tissue supernatant, packing, -20 DEG C of preservations.Operated by enzyme linked immunological kit specification, measure each hole absorbance, try to achieve
The content of mouse brain hippocampal tissue A β, IL-6 and IL-12 albumen, result such as table 2.
From table 2 interpretation of result, compare with control group, model group mouse hippocampus of rats with Alzheimer disease tissue aβ protein,
IL-6 albumen, the significantly raised (P of IL-12 protein content<0.05)；Compare with model group, coffee group, folic acid group, epiphysin group, fire
Numb benevolence+coconut oil group, group charge-coupled mouse hippocampus of rats with Alzheimer disease tissue aβ protein, IL-6 albumen, IL-12 protein content are obvious
Reduce (P<0.05)；Compare with coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, organize charge-coupled mouse alzheimer '
Silent disease hippocampal tissue aβ protein, IL-6 albumen, IL-12 protein content substantially reduce (P<0.05).
Table 2 each experimental group organizes aβ protein, IL-6 albumen, IL-12 protein content to mouse hippocampus of rats with Alzheimer disease
Impact
| Group | Aβ protein (ng/L) | IL-6 albumen (ng/ml) | IL-12 albumen (pg/ml) |
| Control group | 259.23±23.36 | 6.78±1.03 | 289.45±66.23a |
| Model group | 359.48±31.25 | 8.86±1.45 | 413.56±69.45b |
| Coffee group | 295.14±24.35 | 7.16±1.23 | 346.13±68.24b |
| Folic acid group | 294.23±30.14 | 7.32±0.89 | 352.12±56.75b |
| Epiphysin group | 295.46±26.89 | 7.45±1.03 | 362.46±63.12b |
| Fructus cannabis+coconut oil group | 295.34±30.12 | 7.56±1.09 | 352.03±51.07b |
| Group is charge-coupled | 280.12±23.16 | 7.02±0.86 | 302.79±65.12c |
Note：Statistical procedures are carried out using SPSS 19.0 software, experimental data adoptsRepresent, multigroup is compared employing
One-way analysis of variance experimental data.P<0.05 thinks that difference is statistically significant.In table 2, a. is compared with control group, P<
0.05；B. compare with model group, P<0.05；C. coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group compare, P<
0.05
IL-6 albumen, IL-12 protein content are significantly raised, model group inflammatory reaction are described substantially, substantial amounts of inflammatory factor
Take part in Alzheimer disease to develop.Compare with model group, coffee group, folic acid group, epiphysin group, fructus cannabis+coconut
Oily group, the charge-coupled IL-6 albumen of group, IL-12 protein content substantially reduce, illustrate high coffee coffee, folic acid, epiphysin, coconut oil,
Fructus cannabis can be obviously improved the inflammatory reaction of Hippocampus of Mice, and to affect the process of Alzheimer disease with this, and
Organize charge-coupled effect especially notable.
Embodiment 3
1. animal used as test and animal used as test packet and administration：See embodiment 1.
Control group, model group, fructus cannabis+coconut oil group：9：00 uses physiological saline gavage；
Coffee group：9：00 high coffee coffee gavage liquid gavage, gavage amount is 764mg high coffee coffee/kg；
Folic acid group：9：00 uses folic acid gavage liquid, and gavage amount is 52 μ g folic acid/kg；
Epiphysin group：20：00 uses epiphysin gavage liquid, and gavage amount is 637 μ g epiphysins/kg；
Group is charge-coupled：9：00 uses coffee and folic acid to mix gavage liquid gavage, and gavage amount is 764mg coffee/kg, 52 μ g folic acid/
kg)；20：00 uses epiphysin gavage liquid gavage, and gavage amount is 637 μ g epiphysins/kg.
Wherein, the charge-coupled gavage liquid of described coffee group, folic acid group, epiphysin group, group is that corresponding component is dissolved in physiology
After salt solution, configuration obtains.
The test of Y labyrinth is carried out to mouse according to described dosage continuous gavage after 20 days.Gavage experiment during, group charge-coupled and
Fructus cannabis+coconut oil group fructus cannabis+coconut oil forage feed, remaining group normal diet is fed.
The configuration of fructus cannabis+coconut oil feed：Fructus cannabis is finely ground, according to every mouse daily eat 3.6g fructus cannabis/
Kg, amount be added in normal diet powder, then coconut oil is melted, eats 3.6mL coconut oil/kg daily according to every mouse
Amount be sprinkled upon among feed powder mix.After mixed, spray suitable quantity of water is binder, is added in granulator and makes bar-shaped feed.
2. test position fix operational capabilities and space exploration ability：Method is shown in embodiment 1.
The impact to Alzheimer disease mouse orientation navigation ability for the 2.1 each experimental group
Mouse orientation navigation ability was represented with incubation period.Shown by table 3 result, compare with control group, model group mouse is dived
The volt phase is obviously prolonged (P<0.05)；Compare with model group, coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, combination
Group mouse incubation period substantially shortens (P<0.05)；Compare with coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, group
Charge-coupled mouse incubation period substantially shortens (P<0.05).
The impact to Alzheimer disease mouse space exploration ability for the 2.2 each experimental group
Mouse space exploration ability swimming distance represents.Shown by table 3 result, compare with control group, model group mouse
Swimming distance is obvious to increase (P<0.05)；Compare with model group, coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group,
Organize charge-coupled mouse swimming distance and significantly reduce (P<0.05)；With coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group ratio
Relatively, group charge-coupled mouse swimming distance significantly reduces (P<0.05).
The impact to Alzheimer disease mouse orientation navigation ability and space exploration ability for each experimental group of table 3
| Group | Incubation period (second) | Swimming distance (cm) |
| Control group | 16.08±7.45 | 534.64±65.73 |
| Model group | 34.3±9.65 | 934.62±85.03a |
| Coffee group | 28.03±6.10 | 736.13±85.32b |
| Folic acid group | 24.05±6.32 | 745.57±67.36b |
| Epiphysin group | 25.18±7.96 | 768.05±70.35b |
| Fructus cannabis+coconut oil group | 27.32±5.28 | 752.30±62.42b |
| Group is charge-coupled | 21.04±5.03 | 615.84±53.22c |
Note：Statistical procedures are carried out using SPSS 19.0 software, experimental data adoptsRepresent, multigroup is compared employing
One-way analysis of variance experimental data.P<0.05 thinks that difference is statistically significant.In table 3, a. is compared with control group, P<
0.05；B. compare with model group, P<0.05；C. coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group compare, P<
0.05.
The result of table 3 shows, the ability of learning and memory of model group mouse is decreased obviously, model stability, suitably carries out experiment
Research.Coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, the ability of learning and memory of the charge-coupled mouse of group are obviously improved,
Prompting coffee group, folic acid group, epiphysin group, fructus cannabis+coconut oil group, the charge-coupled symptom that can substantially delay model mice of group,
And organize charge-coupled improvement and be substantially better than other one pack system nursing groups.After changing amount, the experiment of effect and embodiment 1
Result is approximate, shows, in the dosage of claims statement, can produce a desired effect.
Embodiment 4
1. determine MCI group and control group crowd as follows：
MCI group crowd：Experimenter is conditions in community retired old man, proposes with reference to U.S. Mayo neurology research center
MCI diagnostic criteria, and reference《Americanism obstacle diagnosis and statistic handbook》4th edition with regard to mild neurocognitive infringement diagnosis mark
Standard, formulates inclusion criteria：1. the age was more than 60 years old.2. private prosecution has memory or other cognitive decline, or has in insider's report
State situation.3. the course of disease was more than 6 months.4. comprehensive cognitive function is normal：Brief mental state inspection (MMSE) >=24 point.5. clinical
Dementia scale (CDR) is 0.5 point.6. ADL scale (ADL) score≤18 point.7. Huggins's base blood index<4 points.
8. Cognitive function damage not yet reaches dull-witted standard.9. exclusion can cause the nervous system disease and the serious medical of brain disorder
Disease, exclusion depression, head injury history, special medication history etc..Meet above-mentioned standard person 44, wherein man 21, female 23,
Averagely (73.95 ± 4.74) year, year of school (9.32 ± 3.7) year.
Control group crowd：1. the age was more than 60 years old.2. only private prosecution has slight hypomnesia and (or) sleep-disorder.3. overall
Cognitive function is normal：Many 24 points of MMSE.4. CDR is 0 point.5. ADL score is at 18 points.Meet above-mentioned condition person 23, wherein man
11, female 12, average (71.54 ± 5.31) year, year of school (11.02 ± 3.41) year.
2. detecting method
(1) application MMSE, word immediate memory, word 2 minutes delay memories, words postpone conservation rate (%), symbol for 2 minutes
The test of number word checks cognitive function；Sleep-disorder inspection sprinkles Butterworth scale with Pittsburgh Sleep Quality Index (PSQI) and love
(ESS), part experimenter accepts polysomnogram (PSG) sleep monitor.
(2) MCI randomized double-blind is grouped
44 MCI aged subjects of dietotherapy group are randomly divided into two groups, MCI-A group 22：00 takes epiphysin, and 10：00 takes
High coffee coffee, folic acid and fructus cannabis, coconut oil is as the daily ingestion of 30mL of unique edible oil；MCI-B group 22：00 take take off black
Element, 14：00 takes high coffee coffee, folic acid and fructus cannabis, and coconut oil is as the daily ingestion of 30mL of unique edible oil；Control group 23
The elderly, 22：00 takes placebo, and 10：00 placebo taking other components, replaces high coffee coffee with caffeinless coffee.
Instructions of taking：According to the time setting, once a day, it is administered orally, takes 90 days altogether.During taking, forbid taking hypnotic and other
Nootropic.Before and after taking, inspection Chinese edition Wechsler Memory Scale (WMS-RC) respectively, monitor PSG, and carry out repeatedly the neural heart
Reason, sleep scale test, observe sleep, the situation of cognitive change.
The daily amount of each component is：Epiphysin 3mg；High coffee coffee 3g, folic acid 400 μ g, coconut oil 30mL, fructus cannabis
30g.
3. result such as table 4.
Table 4 different time edible composition compares to the sleep of MCI the elderly and cognitive function
Note：* compare before eating with this group, P ＜ 0.05；#Compare after eating with MCI-A group, P ＜ 0.05.
After being intervened with dietotherapy combination, MCI group Sleep efficiency, MMSE achievement, word are at once and Delay recall achievement carries
, group difference has statistical significance (P<0.05), refer to table 4, illustrate that dietotherapy combination has improvement to memory and cognition.
MCI-A group is compared with MCI-B group, the PQSI of the latter, ESS, Sleep efficiency, the improvement of Sleep latency all not as the former, between group
Difference has statistical significance (P<0.05) 14, are illustrated：00 coffee for drinking has harmful effect to sleep, so, 10 should be selected：00
Coffee for drinking simultaneously takes other components except coconut oil and epiphysin, and coconut oil is as the daily ingestion of 30mL of unique edible oil.
Human feeding trial shows, eats high coffee coffee (content of caffeine 3.6%～4.2%) 3g, folic acid 400 μ daily
G, epiphysin 3mg, coconut oil 30ml, fructus cannabis 30g to hypomnesia be cardinal symptom MCI patient Sleep efficiency,
MMSE achievement, word are at once and the raising of Delay recall achievement is significantly improved, and are favorably improved its cognitive function, as clothes
With method 22：00 takes epiphysin, and 10：00 takes the other components except coconut oil and epiphysin, and coconut oil is as uniquely eating
Oil is daily ingestion of.
The foregoing is only the preferred embodiment of the present invention, be merely illustrative for the purpose of the present invention, and nonrestrictive；This
The those of ordinary skill in field can carry out many modifications in the spirit and scope that claim is limited to it, falls within this
In the protection domain of invention.
Claims (4)
1. a kind of composition preventing and/or delay senile mild cognitive impairment it is characterised in that described composition by weight
Including following component：3000～6000 parts of ground coffee, 0.2～0.4 part of folic acid, 15000～30000 parts of coconut oil, fructus cannabis
15000～30000 parts, 3～5 parts of epiphysin；
Wherein, described ground coffee contains the caffeine of 3.6～4.2wt%.
2. composition according to claim 1 is it is characterised in that described composition includes following component：
3000 parts of ground coffee, 0.4 part of folic acid, 30000 parts of coconut oil, 30000 parts of fructus cannabis, 3 parts of epiphysin.
3. composition according to claim 1 it is characterised in that described coconut oil be that coconut meat is squeezed at normal temperatures and
Obtain.
4. the composition as described in any one of claims 1 to 3 in preparation prevention and/or delays senile mild cognitive impairment medicine
Application in thing.
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| CN114305457A (en) * | 2021-12-28 | 2022-04-12 | 上海仪器仪表研究所 | Senile dementia judging system |
| CN115737820A (en) * | 2022-11-15 | 2023-03-07 | 河北医科大学第二医院 | Medicine for improving cognitive impairment after epilepsy |
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| CN115737820A (en) * | 2022-11-15 | 2023-03-07 | 河北医科大学第二医院 | Medicine for improving cognitive impairment after epilepsy |
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