CN104435025A - Novel use of broadleaf holly leaf in preparation of drugs for Alzheimer's disease - Google Patents

Novel use of broadleaf holly leaf in preparation of drugs for Alzheimer's disease Download PDF

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CN104435025A
CN104435025A CN201410833147.9A CN201410833147A CN104435025A CN 104435025 A CN104435025 A CN 104435025A CN 201410833147 A CN201410833147 A CN 201410833147A CN 104435025 A CN104435025 A CN 104435025A
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total flavone
ilicis
ethanol
concentrated
concentration
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刘冠萍
贤明华
陈瑛
张栩颜
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Guangxi Wuzhou Pharmaceutical Group Co Ltd
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Guangxi Wuzhou Pharmaceutical Group Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps

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Abstract

The invention relates to a novel use of broadleaf holly leaf, i.e., novel use of broadleaf holly leaf in preparation of drugs for Alzheimer's disease, and specifically novel use of broadleaf holly leaf extractant and broadleaf holly leaf general flavone in preparation of drugs for Alzheimer's disease.

Description

The novelty teabag of Folium Ilicis in preparation treatment alzheimer medicine
Technical field
The present invention relates to the novelty teabag of the novelty teabag of Folium Ilicis, particularly Folum Ilicis extract and ilexlutifolia thumb total flavone, the novelty teabag namely in preparation treatment alzheimer medicine.
Background technology
Alzheimer (AD) and vascular dementia (VD) are modal types in senile dementia.The progress of inflammatory reaction " in the onset of Alzheimer disease mechanism " that " Aged in China magazine " records, discloses AD and accounts for 50% ~ 60%, VD of dementia sum and account for 15% ~ 20%.Its characteristic pathological change is neurofibrillary tangles (NFT) under cerebral cortex and cortex, a large amount of senile plaque in extracellular (SP) is formed and neuron loss.Large quantity research thinks that amyloid beta (β amyloidprotein, A β) plays main shaft effect in AD morbidity, and the neurotoxicity of A β is the co-channel that many factors causes AD to fall ill.Prophylactico-therapeutic measures at present for the neurotoxicity of A β mainly contains following several respects: reduce the precursor of A β and the amount of amyloid beta-protein precursor (β amyloidprecursorprotein, APP); Regulate the cracking of APP, reduce the generation of A β; Promote degraded and the removing of A β; Prevent gathering and the deposition of A β; Block (" in Alzheimer amyloid beta neurotoxic effect progress ", " Chinese neuropsychiatric disease magazines ") such as the key links of A β mechanism of action.
Record in Compendium of Material Medica that Folium Ilicis boils that drink can quench the thirst, improving eyesight, relieving restlessness, make us not saliva, expectorant diuretic, logical small intestinal, control pouring, dysphoria with smothery sensation of only having a headache, holds in the mouth or the eyes pharynx, clear postcibal vomiting, throat." Chinese medicine voluminous dictionary " record Folium Ilicis " loose liver-wind, refresh oneself, control ear toot, deaf, Ting discharging ear, arteries and veins of invigorating blood circulation, cool uterus.”
Containing 200 Multiple components such as Herba Lactucae formosanae Saponin, aminoacid, vitamin C, Polyphenols, flavonoid, caffeine, protein in Folium Ilicis.Chemical composition in Folium Ilicis is mainly flavonoid and triterpene and saponins.From Cortex Ilicis Rotundae and Ilex kudincha C. J. Tseng plant, isolation identification goes out 8 kinds of flavones ingredients at present, mostly is flavone and flavonol, flavanone, flavanone kind composition and Kaempferol, Isorhamnetin, Nicotiflorin, Quercetin.
According to existing Folium Ilicis result of study, think that Folium Ilicis has hypoglycemic, blood pressure lowering, antibacterial, antioxidation, immunity moderation, fat-reducing fat eliminating, improves the multiple effect such as cerebullar and cardiac system and antifertility.
" the cardiovascu-lar effects research of Folium Ilicis " " Chinese crude drug " is openly shown by rat experiment: Folium Ilicis aqueous extract is useful for preventing and treating coronary heart disease allevating angina pectoris.
The hypotensive effect of the Ilex kudincha C. J. Tseng leaf " research " " medical education explorations " discloses Ilex kudincha C. J. Tseng leaf extract all can produce obvious hypotensive effect to 2K1CH rat and the important indispensable animal model of research human essential hypertension pathogeny of SHR these two kinds.
" experiment of Folium Ilicis blood fat reducing and clinical research " " Nursing graduate education " molten two kind compositions insoluble with alcohol have carried out experiment and clinical research to Folium Ilicis alcohol, and the molten two kind compositions insoluble with alcohol of result Folium Ilicis alcohol all have the effect reducing rat triacylglycerol significantly; Be 78.57% to the blood fat reducing total effective rate of people, to dyslipidemia person, TC, TG reduce, and HDL-C raises.
" research of Folum Ilicis extract antioxidation " " Guangxi University for Nationalities's journal ", open Folum Ilicis extract all has certain inhibitory action to the external lipid peroxidation of rats'liver.And Leaf of Ilex latifolia decocting liquid has obvious inhibitory action to adult rat adrenal tissue disposition hyperglycemia, Clinical practice significantly can regulate indices and the clinical symptoms of patient, and curative effect is obvious.
" Folium Ilicis is on the impact of guinea-pig isolated tracheal smooth muscle contractile function " " Chinese medicine will " shows that Folium Ilicis can the bronchial smooth muscle contraction that causes of antagonism medium, may have non-specific tracheal smooth muscle Ca 2+antagonism.
" Folium Ilicis is on the impact of immune function of mice " " Mudanjiang Medical College's journal " finds that Folium Ilicis decocting liquid has the conclusion of enhancing and the effect of conditioner body immunity function.
" the routine observation of curative effect of Herba Lactucae formosanae soup treatment chronic prostate 80 " " Guangxi Chinese medicine " finds to have good improvement result from intending the cardinal symptom of Herba Lactucae formosanae millet paste to chronic prostatitis, does not wherein accommodate urethral symptom to local pain and improves particularly evident.
" Folum Ilicis extract is on the impact of D-galactose Aging mice learning and memory " " Aged in China magazine " finds that the learning memory of Folum Ilicis extract to D-galactose Aging mice has facilitation.
In addition, certain references disclose Ilex kudincha C. J. Tseng in addition and there is raising mice anoxia enduring, low temperature resistant, increase the effect of motor capacity; , sclerosis of blood vessels scorching to patients with gastric cancer chemotherapy posterior vein has certain therapeutical effect; Have certain anti-tumor activity, and wherein Lao Ye ethanol extraction and fresh leaf volatile oil anti-tumor activity the highest.
From Aquifoliaceae Folium Ilicis, isolation identification goes out 8 kinds of flavones ingredients at present, mostly be flavone and flavonol, flavanone, flavanone kind composition and Kaempferol (kaempferol), Isorhamnetin (isorhamnetin), Nicotiflorin, Quercetin (Quercetin).The research relevant to ilexlutifolia thumb total flavone is as follows:
" Folium Ilicis antioxidant content and antioxygenic property research " " GUIHAIA " disclose be separated from Cortex Ilicis Rotundae polyphenol, polysaccharide, alkaloid, Flavonoid substances at different oils and fats, under different temperatures, all there is obvious antioxygenic property.
" the some Biochemical Indexes of Leaf of Ilex latifolia and antibacterial activity research " " Yangzhou University's journal (agricultural and life sciences version) " discloses total flavone glucoside unit, total flavone glucoside total alkaloids etc. in Cortex Ilicis Rotundae microwave drying leaf and has certain antibacterial activity.
Do not have documents and materials to mention Aquifoliaceae Folium Ilicis or ilexlutifolia thumb total flavone at present to can be used for treating alzheimer disease.
Summary of the invention
The object of this invention is to provide the novelty teabag of Folium Ilicis in preparation treatment alzheimer medicine;
Another object of the present invention is to provide the novelty teabag of Folum Ilicis extract in preparation treatment alzheimer medicine;
Another object of the present invention is to provide the novelty teabag of ilexlutifolia thumb total flavone in preparation treatment alzheimer medicine;
Another object of the present invention is to provide the preparation method of Folum Ilicis extract;
Another object of the present invention is to provide the preparation method of ilexlutifolia thumb total flavone.
The object of the invention is by following technical scheme realize:
Raw material sources of the present invention:
Folium Ilicis: the dried leaves of holly plant Folium Ilicis IlexkudingchaC.J.Tseng.Record " Guangxi Chinese crude drug standard " nineteen ninety version the 63rd page.[nature and flavor] are bitter, sweet, cool.[function with cure mainly] loose wind heat, refresh oneself, relieving thirst and restlessness.For headache, toothache, conjunctival congestion, tinnitus, suppurates in ear, calentura excessive thirst, dysentery.
Inventor finds in the therapeutic process of research alzheimer disease; holly plant Folium Ilicis particularly total flavones contained by Folium Ilicis shows the gathering that can reduce beta-amyloid polypeptide 1-in neurocyte; also there is neuroprotective simultaneously; achieve the remarkable improvement of intervention to alzheimer's disease pathogenesis and pathological symptom, thus effectively treat alzheimer disease.
The ofneurodegenerative diseases pathogeny such as AD are complicated, and the peroxide injury that wherein oxygen-derived free radicals causes is the key factor of the infirmities of age morbidities such as AD.SOD is the important enzyme of body scavenging free radicals, and it acts on mainly catalysis biological oxidation and produces superoxide radical, removes and stops the free radical chain reactions caused by oxygen-derived free radicals.MDA is the main metabolites of radical pair biological cell membrane damage, can make biomembrane degeneration, necrosis, DNA is undergone mutation, interlinkage, makes SOD activity reduce simultaneously, and causes the vicious cycle of free radical chain reactions.In brain aging process, the a large amount of free radical of the oxidized generation of neuron membrane unsaturated fatty acid, damaging cells film, organelle, produce inflammatory reaction, finally cause apoptosis, degeneration, ability of learning and memory to decline, finally cause the generation of numerous senile disease such as AD.Find under study for action, the increase considerably reducing rat cerebral tissue MDA content of Folium Ilicis and ilexlutifolia thumb total flavone, and the SOD of rat cerebral tissue can be provided active simultaneously, these data show that the removing tool of ilexlutifolia thumb total flavone to AD rat cerebral tissue oxygen-derived free radicals improves significantly.
Existing large quantifier elimination confirms the important function of free radical resisting at treatment AD at present.Ilexlutifolia thumb total flavone as anti-radical action mechanism may be: for lipid peroxide, interrupt chain lock reactor, suppresses unsaturated fatty acid peroxidating, inhibition of phospholipase A 2 and esterified enzymatic activity, reduces free radical and is formed.Certainly, ilexlutifolia thumb total flavone may be a complicated mechanism to the protective effect of AD rat, and its concrete mechanism also needs to make further research.Although also not exclusively clear to its concrete mechanism of action at present; but ilexlutifolia thumb total flavone all has treatment and protective effect preferably to animal pattern brain injury, neuronal degenerations such as AD; it provides another kind of enlightenment to the control of the neuronal degeneration diseases such as AD: namely free radical resisting may play key player in the ofneurodegenerative diseases such as AD, and may obtain good curative effect by the use of free radical resisting to ofneurodegenerative diseases.
The safety of patent clinical practice of the present invention is higher, to can yet be regarded as a kind of good medicine in the Drug therapy for the treatment of alzheimer disease, it has widened the new method for the treatment of alzheimer disease, the untoward reaction simultaneously for occurring when patient solves prior art treatment alzheimer disease.
Therefore, applicant provides Folium Ilicis, Folum Ilicis extract, ilexlutifolia thumb total flavone to can be used in treating the novelty teabag of alzheimer medicine aspect.
The invention also discloses the application of Folum Ilicis extract at preparation treatment alzheimer medicine, the preparation of described Folum Ilicis extract comprises the following steps:
Folium Ilicis is pulverized, and adding concentration is that the alcohol heating reflux of 40-80% extracts three times, and each ethanol consumption is medical material gross weight 10-20 times amount, each extraction time is 30-60 minute, and Extracting temperature is 60-80 DEG C, merge extractive liquid, concentrated, filter, obtain Folum Ilicis extract.
The invention also discloses the application of ilexlutifolia thumb total flavone at preparation treatment alzheimer medicine, the preparation of described ilexlutifolia thumb total flavone comprises the following steps:
After Folium Ilicis is pulverized, add the ethanol microwave extraction three times that concentration is 40-80%, each ethanol consumption is medical material gross weight 10-20 times amount, each extraction time is 3-10 minute, Extracting temperature is 50-90 DEG C, merge extractive liquid, concentrated, filter, crossing weak-acid cation-exchange resin absorption, is the ethanol elution of 70-90% by concentration, collects eluent, concentrated, dry, obtain ilexlutifolia thumb total flavone.
Ilexlutifolia thumb total flavone disclosed by the invention is in the application of preparation treatment alzheimer medicine, and the preparation of described ilexlutifolia thumb total flavone can also pass through following steps:
Folium Ilicis is pulverized, and crosses 80 orders and sieves, and adds the ethanol 780W microwave extraction three times that concentration is 70%, each ethanol consumption is medical material gross weight 15 times amount, and each extraction time is 5 minutes, and Extracting temperature is 80 DEG C, merge extractive liquid, concentrated, add diatomite filtration, cross ADS-17 resin absorption, be the ethanol elution of 90% by concentration, collect eluent, concentrated, dry, obtain ilexlutifolia thumb total flavone.
The novelty teabag that Folium Ilicis provided by the invention, Folum Ilicis extract, ilexlutifolia thumb total flavone are used for the treatment of alzheimer medicine aspect has the following advantages:
1, Folium Ilicis, Folum Ilicis extract, ilexlutifolia thumb total flavone obtain, safety non-toxic from holly plant Folium Ilicis, can long-term taking.
2, Spatial memory ability measures display, Folum Ilicis extract and ilexlutifolia thumb total flavone group rat seek platform incubation period what decrease rat in varying degrees respectively, and these data show that Folium Ilicis, Folum Ilicis extract, ilexlutifolia thumb total flavone improve significantly to Rats With Memory power tool.
3, find in " impact on AD Rats With Memory ability " experiment, Folum Ilicis extract and ilexlutifolia thumb total flavone considerably reduce the increase of rat cerebral tissue MDA content, and the SOD that can improve rat cerebral tissue is active simultaneously, these data show that Folium Ilicis, Folum Ilicis extract, the ilexlutifolia thumb total flavone removing tool to AD rat cerebral tissue oxygen-derived free radicals improves significantly.
Detailed description of the invention
The present invention is further illustrated below by embodiment.It should be understood that embodiments of the invention are for illustration of the present invention instead of limitation of the present invention.Essence according to the present invention all belongs to the scope of protection of present invention to the simple modifications that the present invention carries out.Except as otherwise noted, the percent of the amount of alcohol in the present invention is percentage by volume, and v/v represents the volume ratio of solution.
Embodiment 1:
Get 10kg Folium Ilicis to pulverize, add concentration be 40% alcohol heating reflux extract three times, each ethanol consumption is medical material gross weight 10 times amount, and each extraction time is 60 minutes, and Extracting temperature is 60 DEG C, merge extractive liquid, concentrated, filters, obtains Folum Ilicis extract.
Embodiment 2:
Get 10kg Folium Ilicis to pulverize, add the ethanol microwave extraction three times that concentration is 40%, each ethanol consumption is medical material gross weight 10 times amount, each extraction time is 10 minutes, Extracting temperature is 50 DEG C, merge extractive liquid, concentrated, filter, crossing ADS-17 resin absorption, is the ethanol elution of 90% by concentration, collects eluent, concentrated, dry, obtain ilexlutifolia thumb total flavone.
Compare product with rutin, surveying ilexlutifolia thumb total flavone yield is 2.91%.
Embodiment 3:
Get 10kg Folium Ilicis to pulverize, cross 80 orders and sieve, add the ethanol 780W microwave extraction three times that concentration is 70%, each ethanol consumption is medical material gross weight 15 times amount, and each extraction time is 5 minutes, and Extracting temperature is 80 DEG C, merge extractive liquid, concentrated, add diatomite filtration, cross ADS-17 resin absorption, be the ethanol elution of 90% by concentration, collect eluent, concentrated, dry, obtain ilexlutifolia thumb total flavone.
Product are compared with rutin.Surveying ilexlutifolia thumb total flavone yield is 3.67%.
Embodiment 4:
Get 10kg Folium Ilicis to pulverize, add concentration be 80% alcohol heating reflux extract three times, each ethanol consumption is medical material gross weight 20 times amount, and each extraction time is 30 minutes, and Extracting temperature is 60 DEG C, merge extractive liquid, concentrated, filters, obtains Folum Ilicis extract.
Embodiment 5:
Get after 10kg Folium Ilicis pulverizes, add the ethanol microwave extraction three times that concentration is 80%, each ethanol consumption is medical material gross weight 20 times amount, each extraction time is 3 minutes, Extracting temperature is 90 DEG C, merge extractive liquid, concentrated, filter, crossing ADS-17 resin absorption, is the ethanol elution of 70% by concentration, collects eluent, concentrated, dry, obtain ilexlutifolia thumb total flavone.
Compare product with rutin, surveying ilexlutifolia thumb total flavone yield is 3.26%.
Effect experiment: on the impact of AD Rats With Memory ability
1 experiment material
1.1 animal
SD rat cleaning grade, at 2 monthly ages, ♂, quality 180 ~ 220g, buy from Guangxi Medical University's Experimental Animal Center (production licence number: SCXK osmanthus 2009-0002).
1.2 instrument
Morris water maze XR-XM (aze) and BI2000 image analysis system (the glad Soft Inform ation Science and Technology Ltd. in Shanghai).
1.3 reagent
AlCl 36H 2o (domestic analytical pure), sodium carboxymethyl cellulose (domestic analytical pure), superoxide dismutase (SOD), malonaldehyde (MDA) test kit, building up Bioengineering Research Institute by Nanjing provides.
2. method
2.1 solution preparation
AlCl 36H 2o and sodium carboxymethyl cellulose are prepared with distilled water before use; Folum Ilicis extract and ilexlutifolia thumb total flavone are being that to be mixed with concentration be 15mg/ml to 0.2% sodium carboxymethyl cellulose by mass concentration before use.
The foundation (chronic aluminum overload sets up senile dementia (AD) rat model) of 2.2AD animal model
Rat is divided into 5 groups at random by quality, often organizes 12, that is:
Blank: 0.2% sodium carboxymethyl cellulose
Model group: AlCl 3solution 200mg/kg;
Embodiment 1 group: after modeling, rat gives embodiment 1 Folum Ilicis extract, and dosage is by crude drug amount 100mg/kg;
Embodiment 2 groups: give embodiment 2 ilexlutifolia thumb total flavone, dosage is by crude drug amount 100mg/kg;
Embodiment 3 groups: give embodiment 3 ilexlutifolia thumb total flavone, dosage is by crude drug amount 100mg/kg;
Embodiment 1,2,3 groups of administrations after gavage aluminum 1h, gavage volume calculates according to 1ml/100g rat body weight, 5d weekly, continuous 20 weeks.
2.3 Spatial memory aptitude tests
Use Morris water maze to test rat Spatial memory ability, water temperature controls at 24 ~ 25 DEG C.Test is divided into 2 stages: the 1st stage, during first time training, rat is put on platform and adapts to 60s, then allow its free swimming to platform, the person that do not find platform in 3min, experimenter assists to be caused platform, from the 2nd day, train 4 every day, select 1 place of entry during each training, rat is put into water towards pool wall, rat is allowed to carry out constant-bearing navigation, continuous training 4d; 2nd stage, namely tested the 5th day time, remove platform, and arbitrarily rat is put into from the water orientation that enters during last training, computer record rat first time crosses over time of original platform and namely seeks platform incubation period, to seek platform incubation period as the spatial orientation ability achievement of rat, calculate with 180s more than 180s.
2.4 cerebral tissue SOD and MDA assay
After Spatial memory aptitude tests, put to death whole rat, get rat cerebral tissue and isolate hippocampal tissue, become mass concentration to be the homogenate of 100g/L with normal saline, measure SOD activity and rat cerebral tissue MDA content, concrete assay method and step are carried out according to corresponding reagent box description.
2.5 statistical procedures
Experimental data x ± s represents, adopt SPSS 16.0 statistical package to carry out variance analysis, P<0.05 is for there being significant difference, and P<0.01 is for there being pole significant difference.
3. experimental result
3.1 impacts on AD rat model Spatial memory ability
Spatial memory ability measures display, and the time that AD model group rats finds platform obviously extended (P<0.01) than blank group respectively at the 1st, 2,3,4 day, and this shows that the learning capacity of AD model group rats obviously reduces.And embodiment 2,3 groups of rats sought platform compares AD model group rats incubation period obviously shorten (P<0.01 at the 1st, 2,3,4 day, P<0.05), embodiment 1 group of rat also has shortening in various degree than AD model group rats in the platform incubation period of seeking of front 4d, but shorten degree obviously not as embodiment 2,3 groups, the results are shown in Table 1.
Table 1 is on the impact (n=12, x ± s) of AD rat Spatial learning ability
Note: compare with blank group, * is p < 0.01; Compare with model group, & is p < 0.05, # is p < 0.01.
Water maze the 5th day test result then shows, and AD model group rats is compared blank group rat and sought platform and rise appreciably (P<0.01) incubation period, illustrates that AD rat model memory re-production capabilities is affected.Rats in test groups of the present invention seeks platform (P<0.01 incubation period what decrease rat in varying degrees respectively, P<0.05), and ilexlutifolia thumb total flavone group will significantly better than Folum Ilicis extract group to the improvement of Rats With Memory power, in table 2.
Table 2 is on the impact (n=12, x ± s) of AD rat spatial memory capacity
Note: compare with blank group, * is p < 0.01; Compare with AD model group, & is p < 0.05, # is p < 0.01.
The Spatial memory ability that AD rat model Spatial memory ability test result points out the present invention can significantly improve rat, and the effect of ilexlutifolia thumb total flavone is better than Folum Ilicis extract.
3.2 impacts on AD rat cerebral tissue SOD activity
Compared with Normal group, AD model group rats SOD activity presents the trend of reduction, and medicine of the present invention can improve the trend of AD model group rats SOD activity, and the improvement effect of ilexlutifolia thumb total flavone is better than Folum Ilicis extract, the results are shown in Table 3.
Table 3 is on the impact (n=12, x ± s) of AD rat cerebral tissue SOD activity
Note: compare with blank group, * is p < 0.01; Compare with AD model group, & is p < 0.05, # is p < 0.01.
3.3 impacts on AD rat cerebral tissue MDA content
Compared with normal rat, the MDA content of AD model group rats cerebral tissue significantly raises, and ilexlutifolia thumb total flavone group and Folum Ilicis extract group rat cerebral tissue MDA content obviously reduce compared with the rat of AD model group, and the improvement of ilexlutifolia thumb total flavone group to MDA activity particularly evident (p < 0.01), in table 4.
Table 4 is on the impact (n=12, x ± s) of AD rat cerebral tissue MDA
Note: compare with blank group, * p < 0.01; Compare with AD model group, & p < 0.05, #p < 0.01.
4 discuss
This test adopts chronic aluminum overload method establishment rat AD animal model, and experimental data shows, AD rat model ability of learning and memory obviously goes down, and reduction trend appears in AD rat model cerebral tissue SOD activity simultaneously, and MDA content then obviously raises.These data show that the modeling method that this test adopts is believable, the neuronal degeneration animal models such as the AD set up by intracerebro-ventricular injection neurotoxin than ever mutually, this test model more can represent the pathological process of AD actual clinical, and result of study also has more practical significance.
Find under study for action, the increase considerably reducing rat cerebral tissue MDA content of ilexlutifolia thumb total flavone, and the SOD of rat cerebral tissue can be provided active simultaneously, these data show that the removing tool of ilexlutifolia thumb total flavone to AD rat cerebral tissue oxygen-derived free radicals improves significantly, and effectively can improve rat study and memory.Prompting the present invention has preferably therapeutic effect to ofneurodegenerative diseases, all has reference significance for the developmental research of the Senile disease medicines such as clinical treatment alzheimer disease and clinical treatment.
Overall experiment effect display, the present invention effectively can treat alzheimer disease, and therapeutic effect optimum is ilexlutifolia thumb total flavone, and Folum Ilicis extract takes second place, but both all demonstrate significant therapeutic effect.
Although above with general explanation, detailed description of the invention and test, the present invention is described in detail, and on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.

Claims (8)

1. the novelty teabag of Folium Ilicis in preparation treatment alzheimer medicine.
2. the novelty teabag of Folum Ilicis extract in preparation treatment alzheimer medicine.
3. purposes according to claim 2, it is characterized in that described Folum Ilicis extract is prepared by following steps and obtains: Folium Ilicis is pulverized, adding concentration is that the alcohol heating reflux of 40-80% extracts three times, each ethanol consumption is medical material gross weight 10-20 times amount, and each extraction time is 30-60 minute, and Extracting temperature is 60-80 DEG C, merge extractive liquid, concentrated, filter, obtain Folum Ilicis extract.
4. the novelty teabag of ilexlutifolia thumb total flavone in preparation treatment alzheimer disease.
5. purposes according to claim 4, it is characterized in that described ilexlutifolia thumb total flavone is prepared by following steps and obtains: after Folium Ilicis is pulverized, add the ethanol microwave extraction three times that concentration is 40-80%, each ethanol consumption is medical material gross weight 10-20 times amount, each extraction time is 3-10 minute, Extracting temperature is 50-90 DEG C, merge extractive liquid, concentrated, filter, cross weak-acid cation-exchange resin absorption, be the ethanol elution of 70-90% by concentration, collect eluent, concentrated, dry, obtain ilexlutifolia thumb total flavone.
6. purposes according to claim 4, it is characterized in that described ilexlutifolia thumb total flavone is prepared by following steps and obtains: Folium Ilicis is pulverized, cross 80 orders to sieve, add the ethanol 780W microwave extraction three times that concentration is 70%, each ethanol consumption is medical material gross weight 15 times amount, each extraction time is 5 minutes, Extracting temperature is 80 DEG C, merge extractive liquid, concentrated, add diatomite filtration, crossing ADS-17 resin absorption, is the ethanol elution of 90% by concentration, collects eluent, concentrated, dry, obtain ilexlutifolia thumb total flavone.
7. Folum Ilicis extract becomes with pharmaceutically acceptable carrier combination preparing the novelty teabag for the treatment of in alzheimer medicine.
8. ilexlutifolia thumb total flavone becomes with pharmaceutically acceptable carrier combination preparing the novelty teabag for the treatment of in alzheimer medicine.
CN201410833147.9A 2014-12-29 2014-12-29 Novel use of broadleaf holly leaf in preparation of drugs for Alzheimer's disease Pending CN104435025A (en)

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Application publication date: 20150325