CN103417664B - Application of fructus ziziphi jujubae in preparing medicine or health-care product for treating Alzheimer disease - Google Patents
Application of fructus ziziphi jujubae in preparing medicine or health-care product for treating Alzheimer disease Download PDFInfo
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Abstract
The invention discloses application of fructus ziziphi jujubae in preparing of a medicine or a health-care product for treating Alzheimer disease. An experimental research shows that the fructus ziziphi jujubae and extract thereof can improve the space learning and memory ability of an model mouse with Alzheimer disease, shorten the escape latent period and the search distance of the mouse, meanwhile reduce the oxidative damage degree of the brain tissue of the mouse, inhibit the activity of the acetylcholin esterase in the brain tissue, and achieve a good effect of preventing and treating the Alzheimer disease. The fructus ziziphi jujubae and the extract thereof are expected to be developed to be the new-generation safe and effective medicine or the health-care product for treating the Alzheimer disease.
Description
Technical field
The present invention relates to the novelty teabag of Fructus Jujubae, the particularly application of Fructus Jujubae in preparation treatment Alzheimer disease drugs or health product.
Background technology
Alzheimer, also known as alzheimer disease, be that a kind of central nervous system degeneration is sick, insidious onset, the course of disease is chronic progressive external, is the modal type of senile dementia.Main manifestations is the neuropsychic symptoms such as gradual memory obstacle, cognitive dysfunction, personality changes and aphasis, has a strong impact on social activity, occupation and vital function.The cause of disease and the pathogenesis of Alzheimer are not yet illustrated, characteristic pathological changes into neurofibrillary tangles in the extracellular senile plaque of amyloid beta formation of deposits and the neurocyte of Protein tau Hyperphosphorylationof formation, and neuron loss companion glial cells hyperplasia etc.
Senile dementia is the pertinacious disease affecting senior health and fitness.The data display that U.S.'s " general psychiatry document " provides, about has 10% to suffer from this disease in more than the 60 years old old people in the whole world.According to World Health Organization (WHO) and international senile dementia association statistics, the current whole world has suffers from senile dementia more than 1,800 ten thousand old men.Expect the year two thousand twenty, global patients of senile dementia will reach 3,400 ten thousand people.In China, along with the arrival of aging society, 6,000,000 aging population will be increased newly every year, and the sickness rate of senile dementia is also increasing year by year.According to incompletely statistics, the ratio of suffering from severe senile dementia in over-65s crowd reaches more than 5%, and by 80 years old, this ratio just rose to 15% ~ 20%.And the mean survival time (MST) of senile dementia patients is 5.5 years, make one of this disease main fatal disease becoming modern society old people.Along with the prolongation of human longevity and becoming increasingly conspicuous of social senilization's problem, the quantity of old dementia patients and ratio also will continue to increase.Because the cause of disease of senile dementia and pathogenesis are illustrated not yet completely, there is no the medicine of specific treatment or reverse disease progression at present.Therefore, the active drug finding treatment senile dementia further remains the striving direction of current pharmacology worker.
The dry mature fruit of Fructus Jujubae system Rhamnaceae jujube Fructus Jujubae is conventional Chinese medicine, tool invigorating the spleen and replenishing QI, effect of nourishing blood to tranquillize the mind.Be mainly used in treating insufficiency of the spleen lack of appetite, weak loose stool, the diseases such as woman hysteria, modern pharmacological research and clinical practice prove, Fructus Jujubae has multiple biological activitys such as improving immunity of organisms, antitumor, mutation, and having not yet to see with Fructus Jujubae is mainly form component to be applied to the control medicine of Alzheimer's disease or the report of health food.
Summary of the invention
Goal of the invention: the object of the invention is to overcome the deficiencies in the prior art, on the basis of the original effect of Fructus Jujubae, develop the clinical application that it is new, the application of Fructus Jujubae in treatment Alzheimer is provided, experimental result shows, it has the effect of well control Alzheimer.
Technical scheme: in order to realize above object, the technical scheme that the present invention takes is:
The present invention shows through lot of experiments, and Fructus Jujubae and extract thereof effectively can improve the cognitive function of patients with Alzheimer disease, the development delaying brain in patients atrophy, raising patient memory.Fructus Jujubae can be applicable to preparation treatment Alzheimer disease drugs or health product.
As another preferred version, the application of Fructus Jujubae extract in preparation treatment Alzheimer disease drugs or health product, described Fructus Jujubae extract prepares by the following method: get Fructus Jujubae medical material, by the water heating and refluxing extraction 1 to 3 time of 6 to 12 times amount, merge extractive liquid, concentrated under 60 DEG C to 80 DEG C conditions, adding ethanol to alcohol content is 50% to 85%, leave standstill, solid-liquid separation, obtain supernatant, be evaporated to the water dilution without adding 1 to 5 times of volume after alcohol taste, diluent crosses macroporous adsorbent resin chromatographic column, be the ethanol elution of 30% to 60% by concentration, collect eluent, obtain Fructus Jujubae extract.
Above-described macroreticular resin is D101 type, AB-8 type or HP-20 type.
The application of Fructus Jujubae extract of the present invention in preparation treatment Alzheimer disease drugs or health product, makes the medicine of tablet, injection, capsule, granule, pill, micropill, powder, drop pill, decoction, syrup, mixture, soft extract or extractum dosage form by Fructus Jujubae extract and pharmaceutically acceptable carrier.
Fructus Jujubae extract and carrier lactose or corn starch mix homogeneously when Fructus Jujubae extract provided by the invention makes capsule, granulate, then encapsulatedly makes capsule.
When Fructus Jujubae extract provided by the invention is made tablet, Fructus Jujubae extract and lactose or corn starch, add magnesium stearate lubricant when needing, mix homogeneously, then tablet made by tabletting.
When Fructus Jujubae extract provided by the invention makes granule, Fructus Jujubae extract and diluent lactose or corn starch mix homogeneously, granulate, dry, make granule.
When Fructus Jujubae extract provided by the invention makes injection, get Fructus Jujubae extract to add physiological saline solution and then add activated carbon, stir, 80 DEG C are heated 30 minutes, filter, adjust ph, with sintered glass funnel or other frit to clear and bright, fill, makes injection in 30 minutes 100 to 115 DEG C of sterilizings.
When Fructus Jujubae extract provided by the invention makes other dosage form, can prepare by pharmacy conventional method.
Beneficial effect: the present invention carries out new purposes exploitation on the basis of the original effect of Fructus Jujubae, test proves: through mice orientation navigation and space exploration experiment, Fructus Jujubae group can improve AD(Alzheimer) the Spatial memory ability of model mice, shorten its escape latency and detection range, and original platform place quadrant search time and distance account for the percentage ratio of total time and distance in remarkable increase space exploration experiment, reduce Mice brain tissues oxidative damage degree simultaneously, suppress acetylcholine esterase active in cerebral tissue.Above experimental result shows, Fructus Jujubae can be used for treating senile dementia, especially treats senile dementia early stage (as Alzheimer early stage), improves cognitive function of patients obstacle, delay the development of brain in patients atrophy, improve patient memory.Therefore Fructus Jujubae and Fructus Jujubae extract thereof are expected to exploitation becomes of new generation safe and effective, for preventing and treating medicine or the health product of Alzheimer.
Detailed description of the invention
The present invention is illustrated further below in conjunction with specific embodiment, these embodiments should be understood only be not used in for illustration of the present invention and limit the scope of the invention, after having read the present invention, the amendment of those skilled in the art to the various equivalent form of value of the present invention has all fallen within the application's claims limited range.
The preparation of embodiment 1 Fructus Jujubae extract
Get Fructus Jujubae medical material 1kg, by the water heating and refluxing extraction three times of 6 times amount, merge extractive liquid, under 60 DEG C of conditions, be concentrated into 2kg, adding ethanol to alcohol content is 65%, leaves standstill, solid-liquid separation, obtain supernatant, be evaporated to the water dilution without adding 3 times of volumes after alcohol taste, diluent crosses D101 type macroporous adsorption resin chromatography post, be the ethanol elution of 30% to 60% by concentration, collect eluent, be concentrated into 1L, obtain Fructus Jujubae extract.
The experimentation of embodiment 2 Fructus Jujubae extract anti-Alzheimer disease
One, experiment material and medicine
1. experiment material
SOD, MDA, GSH, AChE, NO and Coomassie brilliant blue protein determination kit, build up Bioengineering Research Institute purchased from Nanjing.
2. experimental apparatus
Morris water maze hardware and video analytic system Xeye, Tian Ming Hongyuan, Beijing development in science and technology company limited; UV-2000 type ultraviolet spectrophotometer, Beijing Lai Baitaike Instrument Ltd..
3. test medicine and processing method
The Fructus Jujubae extract that embodiment 1 prepares, thin up makes desired concn; Positive drug is rapamycin, is mixed with desired concn before administration with 5% dissolve with ethanol.
4. laboratory animal and grouping
6 monthly age SAM mices, male, body weight (28 ± 4) g, is provided by Department Of Medicine, Peking University, the animal quality certification number: SCXK(capital) 2011-0012.
Except 15 normal aging mices (SAMR1) are done except Normal group, the Fructus Jujubae extract low dose group (5g/kg/d), middle dosage group (10g/kg/d) and the high dose group (20g/kg/d) that are divided into model control group, rapamycin positive drug group (0.5mg/kg/d), embodiment 1 to prepare at random 80 Senescence-accelerated Mouse's (SAMP8).Every day gastric infusion 1 time, continuous 60 days.
Two, experimental technique
1. learning and memory performances test
The device of Morris water maze to be connected with computer by video camera by a rustless steel round pool and to form.Pool inner wall is painted as black, diameter 120cm, high 50cm, depth of water 25cm, and water temperature remains on (22 ± 2) DEG C.In target quadrant (being set to third quadrant), be placed with a diameter is 6cm, and the circular black platform of high 23cm, is positioned at underwater 2cm.Adopt the ability of learning and memory of Morris water maze laboratory method testing SA M mice.Orientation navigation experiment, i.e. every day 1 time, last 6d, track record mice swimming track, record mice searches out the time (being called escape latency) of platform in 2min; Space exploration is tested, and namely orientation navigation experiment completes after, (7d) removes platform, select from original platform quadrant be farthest mice place of entry, in record 2min mice former platform quadrant the time of staying with pass through former platform number of times.
2. tissue homogenate preparation and Indexs measure
Experiment carries out the 60th day, and after gavage, 30min sacrificed by decapitation mice, gets cerebral tissue rapidly, is placed in 4 DEG C of pre-cold salines, and after filter paper is wiped and done, weigh, the normal saline adding 9 times of volumes makes 10% brain homogenate liquid.Refrigerated centrifuger 3500rmin
-1centrifugal 15min, gets supernatant and measures SOD, MDA, GSH, AChE, NO by the method for test kit.
3. statistical procedures
All experimental datas all adopt SPSS11.5 statistical processing software to carry out statistical procedures, result with
represent, between group, compare employing variance analysis.
Three, experimental result
1. Fructus Jujubae extract is on the impact of SAMP8 learning and memory of little mouse
1.1 orientation navigation experiment
Each experimental group 6 days average escape latency compare, and test as shown in table 1.
Table 1 Fructus Jujubae extract is on the impact of each experimental group of SAMP8 mice 6 days average escape latency
Show from the experimental result of table 1, the escape latency of SAMR1 Normal group is significantly shorter than SAMP8 model control group, shows that the normal aging ability of learning and memory in mice of same germline is stronger than Senescence-accelerated Mouse's.Through the training of 6 days, the change of Normal group mice school grade relaxed; Model control group mice escape latency curve is steady, illustrates that model control group learning and memory of little mouse behavioral competence is obviously impaired; Each group of incubation period of drug treatment shortens along with the increase of training natural law, illustrates that Fructus Jujubae extract provided by the invention is improved effect to mouse memory behavioral competence.
After Mice water maze achievement tends towards stability, satisfy with the average achievement of 4th ~ 6 days for experimental data is analyzed.Compare with model control group, in Fructus Jujubae, the escape latency of dosage group and high dose group mice obviously shortens, and difference has statistical significance (P<0.05).Orientation navigation experiment result shows, Fructus Jujubae extract has the effect of the ability strengthening SAMP8 learning and memory of little mouse.The results are shown in Table 2.
Table 2 Fructus Jujubae extract is on each experimental group average escape latency of SAMP8 mice and the impact of space exploration time
Note: compare with model group, * P<0.05.
1.2 space exploration experiments
After removing platform, compare with model control group, Normal group, positive drug group, Fructus Jujubae high dose group mice obviously extended in the time of staying of Morris water maze through platform place quadrant, and difference has statistical significance (P<0.05).Space exploration experimental result shows, Fructus Jujubae extract is improved the trend of SAMP8 mice to locus memory ability effect.The results are shown in Table 2.
2. Fructus Jujubae extract is on the impact of SAMP8 Mice brain tissues biochemical indicator
2.1 impacts on SOD
Specific experiment result is as table 3.As shown in Table 3, the middle and high dosage group of positive drug group, Fructus Jujubae extract compares with model control group, and its difference has statistical significance, and after administration, SOD vigor raises all to some extent, show that Fructus Jujubae extract can improve the vigor of SOD in SAMP8 mouse brain, play the effect alleviating oxidative damage.
2.2 impacts on MDA
Specific experiment result is as table 3.As shown in Table 3; the middle and high dosage group of positive drug group, Fructus Jujubae compares with model control group; difference all has statistical significance; after administration, MDA content declines all to some extent; show that Fructus Jujubae extract can reduce MDA content in SAMP8 Mice brain tissues at middle dosage and high dose, play the protective effect for neurocyte.
2.3 impacts on GSH
Specific experiment result is as table 3.As shown in Table 3, the middle and high dosage group of positive drug group, Fructus Jujubae extract compares with model control group, its difference has statistical significance, after administration, GSH content raises all to some extent, show that Fructus Jujubae extract can raise the content of GSH in SAMP8 Mice brain tissues when middle dosage and high dose, play antioxidation.
2.4 impacts on AChE
Specific experiment result is as table 3.As shown in Table 3, the basic, normal, high dosage group of positive drug group, Fructus Jujubae extract compares with model control group, and difference all has statistical significance, and AChE in SAMP8 Mice brain tissues all can be suppressed active, thus Ach content in increase brain, thus improve the cognitive competence of SAMP8 mice.
2.5 impacts on NO
Specific experiment result is as table 3.As shown in Table 3, the basic, normal, high dosage group of positive drug group, Fructus Jujubae extract compares with model control group, and difference all has statistical significance, all can raise NO content in SAMP8 Mice brain tissues, thus increases the anti-oxidative damage ability of SAMP8 Mice brain tissues.
Table 3 Fructus Jujubae extract is on the impact (mean ± SD, n=8) of SOD, MDA, GSH, AChE, NO in SAMP8 Mice brain tissues
Note: compare with model group, * P<0.05.
Above experimental result shows, Fructus Jujubae provided by the invention and Fructus Jujubae extract thereof can effectively improve AD(Alzheimer) the Spatial memory ability of model mice, shorten its escape latency and detection range, and original platform place quadrant search time and distance account for the percentage ratio of total time and distance in remarkable increase space exploration experiment, reduce Mice brain tissues oxidative damage degree simultaneously, suppress acetylcholine esterase active in cerebral tissue.To Alzheimer, there is good preventive and therapeutic effect.And compared with existing medicine, Fructus Jujubae extract is safer, has no adverse reaction.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (1)
1. the application of Fructus Jujubae extract in preparation treatment Alzheimer disease drugs or health product, described Fructus Jujubae extract prepares by the following method: get Fructus Jujubae medical material, by the water heating and refluxing extraction 1 to 3 time of 6 to 12 times amount, merge extractive liquid, concentrated under 60 DEG C to 80 DEG C conditions, adding ethanol to alcohol content is 50% to 85%, leave standstill, solid-liquid separation, obtain supernatant, be evaporated to the water dilution without adding 1 to 5 times of volume after alcohol taste, diluent crosses macroporous adsorbent resin chromatographic column, be the ethanol elution of 30% to 60% by concentration, collect eluent, obtain Fructus Jujubae extract.
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| JP2007230938A (en) * | 2006-03-02 | 2007-09-13 | Toyama Univ | Preventing or improving agent of alzheimer type memory disorder |
| KR20090054228A (en) * | 2007-11-26 | 2009-05-29 | (주)네추럴에프앤피 | An extract of zizyphus jujuba mill. var spinosus and a pharmaceutical composition comprising thereof for promoting neurogenesis |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2007230938A (en) * | 2006-03-02 | 2007-09-13 | Toyama Univ | Preventing or improving agent of alzheimer type memory disorder |
| KR20090054228A (en) * | 2007-11-26 | 2009-05-29 | (주)네추럴에프앤피 | An extract of zizyphus jujuba mill. var spinosus and a pharmaceutical composition comprising thereof for promoting neurogenesis |
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| 德温特摘要数据库.KR20090054228A德温特摘要.《KR20090054228A德温特摘要》.2009,第1页. * |
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