CN100579519C - Use of patchouli alcohol in preparing medicament for preventing and controlling senile dementia - Google Patents
Use of patchouli alcohol in preparing medicament for preventing and controlling senile dementia Download PDFInfo
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- CN100579519C CN100579519C CN200710176344A CN200710176344A CN100579519C CN 100579519 C CN100579519 C CN 100579519C CN 200710176344 A CN200710176344 A CN 200710176344A CN 200710176344 A CN200710176344 A CN 200710176344A CN 100579519 C CN100579519 C CN 100579519C
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- patchouli alcohol
- senile dementia
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Abstract
The invention discloses the usage of patchouli alcohol in the process of preparing medicament for preventing and curing senile dementia, belonging to the medical field. The invention has the advantages that the invention is extensively and deeply researched, patchouli alcohol is unexpectedly found to have the functions of neural protection and nutrition in the process of screening medicament which is anti senile dementia. Further study finds that patchouli alcohol has a promoting effect to the study and memory of a senile dementia mould mouse. Thereby patchouli alcohol can be used to prepare a medicament which can prevent and cure senile dementia. The medicament which utilizes patchouli alcohol to be active component may have significant effects in clinic, thereby bringing out large social and economic benefits.
Description
Technical field
The present invention relates to patchouli alcohol and prevent and treat purposes in the medicine of senile dementia, belong to field of medicaments in preparation.
Background technology
Herba Pogostemonis, Pogostemon cablin (Blanco) Benth is a Labiatae thorn stamen grass platymiscium, perennial herb, herb is medicinal.Its acrid in the mouth, tepor is returned spleen, stomach, lung three warps, has eliminating turbid pathogen with aromatics, the preventing or arresting vomiting that whets the appetite, delivers the function of expelling summer-heat.The medicinal ingredient of Herba Pogostemonis mainly is its volatile oil, claims Herba Pogostemonis oil (patchouli oil), has digestive tract function, gastrointestinal smooth muscle spasmolytic and the antibacterial action of adjusting.Its main component is patchouli alcohol (patchoulialcohol, a patchouli alcohol), has calcium antagonism (Chem Pharm Bull, 1989,37 (2): 345-348).Patchouli alcohol belongs to the tricyclic sesquiterpene compounds, and is crystallizable, fusing point 55～56%, and 140 ℃ of boiling points (1.06kPa), optical rotation-97.4 ° (c=24, chloroform), water insoluble, be dissolved in alcohol, ether and organic solvent commonly used.Molecular formula C15H26O, the CAS registration number is 5986-55-0, molecular weight is 222.37, chemical being called (1R-(1alpha, 4beta, 4-alpha, 6beta, 8-alpha))-Octahydro-4,8a, 9,9-tetramethyl-1
, 6-methano-1 (2H)-naphthol, structural formula is as follows:
Senile dementia be a kind of be the chronic central nervous system degenerative disease of main clinic symptoms with carrying out property cognitive decrease.Its sickness rate with age and sharply rises, and China over-65s old people's prevalence is to reach 20%～40% more than 1%～5%, 85 years old.The pathological change of senile dementia comprises neuron loss, interior countless neurofibrillary tangle (neurofibrillary tangles) and the senile plaque (senile plaque) etc. of occurring of brain widely.The senile dementia medicine such as aricept, the tacrine etc. that have gone on the market at present can improve or alleviate the dementia symptom of patients with mild to a certain extent, but can not stop or reverse further developing of pathological changes.
Summary of the invention
The technical problem to be solved in the present invention provides patchouli alcohol and prevents and treats purposes in the medicine of senile dementia in preparation.
Another technical problem that the present invention will solve provides a kind of pharmaceutical composition of preventing and treating senile dementia.
For achieving the above object, the present invention is by the following technical solutions:
Patchouli alcohol is prevented and treated purposes in the medicine of senile dementia in preparation.
A kind of pharmaceutical composition of preventing and treating senile dementia is made up of the adjuvant that active component patchouli alcohol and pharmacy are accepted.
The adjuvant that described pharmacy is accepted includes but not limited to pharmaceutically acceptable diluent, antiseptic, solvent, emulsifying agent, adjuvant and/or carrier.
The described medicine of preventing and treating senile dementia or pharmaceutical composition be oral formulations, injection, through lung, nose agent, percutaneous or other mode form of administration.
Described peroral dosage form is including but not limited to capsule, tablet, pill, lozenge, granule, liposome etc.
Patchouli alcohol among the present invention is available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute, and purity reaches more than 98%.At cellular level, adopt Flow cytometry patchouli alcohol anti-beta amyloid (A β) to cause the PC12 apoptotic effect and to former generation hippocampal neuron axon growth facilitation.In the animal level, adopt mice step down test and Morris water maze test to observe its facilitation to senile dementia model mice learning and memory due to the scopolamine.The result shows that patchouli alcohol has protection and Nutrition to neurocyte, can improve senile dementia model mice ability of learning and memory.
Advantage of the present invention is: the present invention finds unexpectedly that patchouli alcohol has neuroprotective and Nutrition through extensively and profoundly research in the medicine of the anti-senile dementia disease of screening.Discover that further it has facilitation to senile dementia model mice learning and memory.Therefore, patchouli alcohol can be used to prepare the medicine of preventing and treating senile dementia.The medicine that with the patchouli alcohol is active component may have significant curative effect clinically, thereby has a tremendous social and economic benefits.
Below in conjunction with the specific embodiment the present invention's invention is described further; it is not limitation of the invention; according to prior art well known in the art; embodiments of the present invention are not limited to this; therefore all this areas of having done according to present disclosure be equal to replacement, all belong to protection scope of the present invention.
The specific embodiment
Embodiment 1: the anti-apoptotic effect of patchouli alcohol
One. material
1. patchouli alcohol, available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute, purity reaches more than 98%.
2.A β
25～35, available from Sigma company.
3.Annexin V-FITC, the annexin V of FITC labelling is available from the U.S. biological engineering company limited of crystalline substance.
4.PI solution, propidium iodide solution.
5. the preservation of going down to posterity of rat pheochromocyte oncocyte (PC12) cell strain, this chamber.
Two. method
Adopt Flow cytometry patchouli alcohol antagonism A β
25～35Cause rat pheochromocyte oncocyte (PC12) apoptotic effect.Experiment is grouped as follows: matched group; A β
25～35Processed group; Various dose medicine group.
The cell suspension of getting 100 μ l adds 5 μ l Annexin V-FITC and 10 μ l PI solution (20 μ g/ml) mixings in the streaming pipe, the room temperature lucifuge was hatched 15 minutes, added 400 μ l PBS, flow cytometry analysis.
Three. the result
With normal group ratio, A β
25～35Transaction module group apoptosis rate obviously increases, and statistical significance (P＜0.01) is arranged; Each dosing group apoptosis rate significantly reduces (P＜0.01) with the model group ratio, and patchouli alcohol has anti-A β
25～35Cause the effect of PC12 apoptosis.
Table 1: the anti-A β of patchouli alcohol
25～35Cause the apoptotic effect of PC12 cell
Annotate:
*With matched group than P＜0.01;
*With model group than P＜0.01
Embodiment 2: patchouli alcohol promotes former being commissioned to train to support the effect of hippocampal neuron axon growth
One. material
1. patchouli alcohol, available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute, purity reaches more than 98%.
2. pancreatin, concentration is 0.25%, available from Sigma company
3.DMEM/F-12 culture medium is available from Gibco company.
4. nerve growth factor (NGF) is available from Beijing fiesta medical sci-tech Development Co., Ltd.
5. hyclone is available from Gibco company.
6.N2, available from Gibco company.
7.B27, available from Gibco company.
8. cytosine arabinoside is available from Harbin Bolai Pharmaceutical Co., Ltd..
9.SD the rat neonatal rat, in the birth 12h, ♀ ♂ dual-purpose is divided into matched group and various dose medicine group, available from Military Medical Science Institute's Experimental Animal Center.
Two. method
The rat neonatal rat is after volume fraction is 75% ethanol disinfection, and broken end places and contains the plate of dissecting liquid, isolates full brain, and anatomic microscope separates hippocampal tissue down.Be placed in 0.25% trypsin and and shred with shears.Draw pancreatin to containing in the serum centrifuge tube every 4min, and add fresh pancreatin until no macroscopic piece of tissue.200 order metallic sieves filter the back with 1000rpmmin
-1Centrifugal 10min.Its DMEM/F-12 kind that is resuspended in 10% hyclone is planted liquid, be inoculated in 24 orifice plates that wrap in advance by poly-D-lysine, be changed to 3% hyclone, 1%N2,1%B27 and 3ngmL after the overnight incubation
-1The DMEM/F-12 culture fluid of cytosine arabinoside.Adding the final concentration mass fraction is 0.05,0.5,5 μ gmL
-1Patchouli alcohol adds 2ngmL simultaneously
-1Nerve growth factor (NGF); Matched group only adds 2ngmL
-1NGF.Under fluorescence microscope, take pictures behind the 2d, and statistics aixs cylinder length, method is 10 every group, measures each neuron axon length for every, the summation back is divided by its neuron sum.
Three. the result
Patchouli alcohol itself to former generation the hippocampal neuron axon growth do not have facilitation, but at 2ngmL
-1NGF can obviously promote its axon growth under existing, and its aixs cylinder length obviously is longer than matched group (P＜0.01).The result shows, in the presence of extremely low concentration NGF, and patchouli alcohol 0.05～5 μ gmL
-1Concentration range in to former generation the hippocampal neuron axon growth facilitation (table 2) is arranged.
Table 2: patchouli alcohol is to the facilitation of former generation hippocampal neuron axon growth
Annotate: n=10
*With matched group than P＜0.01
Embodiment 3: patchouli alcohol is to the facilitation of senile dementia model mice learning and memory
One. material
1. patchouli alcohol, available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute, purity reaches more than 98%.
2. scopolamine, Lai En pharmaceutcal corporation, Ltd in Xuzhou produces.
3. kunming mice, body weight 14～16g, female, be divided into normal control, scopolamine group and various dose medicine group, mice is by the isostatic principle randomly assigne grouping of body weight, and 10 every group, available from Military Medical Science Institute's Experimental Animal Center.
Two. method
Adopt the facilitation of mice step down test and Morris water maze test observation patchouli alcohol to senile dementia model mice learning and memory due to the scopolamine.Mice is by the isostatic principle randomly assigne grouping of body weight.Behind the administration 7d, modeling is also tested.
1. mice step down test:
Animal is placed on the platform, and the 3min that conforms passes to 36V voltage then, training 5min.Test behind the 24h, record jumps off for the first time incubation period, the errors number in the 5min of platform and always shocks by electricity the time, with this as the memory achievement.
2.Morris water maze test:
The previous day is put into water maze free swimming 2min to conform with mice earlier in test.15min lumbar injection scopolamine 5mgkg before the training in morning every day
-1, be administered once every day.First day mice training 3 times is put into water with mice towards chamber wall from 3 different place of entry respectively at every turn and is swum, if mice can not be found underwater platform in 90s, then directly places it on platform and stops 30s.Began each training morning and afternoon every day in second day once, climb up used time of platform, road after the entry of record mice, carry out repetition measurement by the step after 24 hours, trained altogether 3 days through the index of conduct detection mices such as track to space and clue study.
Get 4 murine brains for every group and do SABC mensuration cholinergic M1 acceptor levels, every Mus is cooked two sections, and SABC adopts the SABC method, and the DAB colour developing is examined with haematoxylin at last and redyed.Get a section as negative control (one anti-replace) for every group with PBS.During data analysis, every section is chosen 5 visuals field by Hippocampus and cortex same area, and the result handles with MIAS medical image analysis management system 4.0, analyzes average optical and integral optical density.
Three. the result
1. mice step down test:
The diving tower result shows that with the normal group ratio, errors number obviously increases in the model group 5min, and significantly shorten incubation period.With the model group ratio, patchouli alcohol group errors number obviously reduces, but the trend of increase is arranged but no difference of science of statistics (seeing Table 3) incubation period.
Table 3: patchouli alcohol is to the influence of scopolamine memory dysfunction model diving tower achievement
Annotate: compare with normal group,
* *P＜0.001; Compare with model group: #＜0.05, ##P＜0.01.
2.Morris water maze test:
Morris water maze result shows that along with the increase of frequency of training, each is organized mice and finds shorten gradually the incubation period of platform.Compare model group (scopolamine 5mgkg with matched group
-1) each time training achievement all demonstrates significant difference.The patchouli alcohol group demonstrates significant difference from the 5th training beginning with model group.The result is as shown in table 4:
Table 4: patchouli alcohol is to the preclinical influence of appearing on the stage of scopolamine memory dysfunction model water maze
Annotate: compare with normal group:
*P＜0.05,
*P＜0.01,
* *P＜0.001; Compare with model group: #P＜0.05, ##P＜0.01, ###P＜0.001.
The 1-3 time is first day training result, and the 4th, 5 time is second day training result, and the 6th, 7 time is the 3rd day training result.
Average optical result shows that compare with the normal control group, the model control group average optical density value significantly descends, and illustrates that the cell dyeing degree descends, and cholinergic M1 acceptor levels reduces.And patchouli alcohol group average optical density value all increases than model group, illustrates that medicine may make the M1 acceptor levels improve.Integral optical density result also display model group significantly reduces than normal control group, and the patchouli alcohol group is than the remarkable rising of model group.The integral level that medicine group positive cell dyeing level is described raises, and promptly the antigen total amount level raises, and the results are shown in Table 5.
Table 5: patchouli alcohol causes the acquired learning memory disorder model of mice cerebral tissue M to scopolamine
1The influence of acceptor levels
Annotate: compare with normal group,
* *P＜0.001; Compare with model group: #P＜0.05, ##P＜0.01, ###P＜0.001.
Claims (1)
1. patchouli alcohol is prevented and treated purposes in the medicine of senile dementia in preparation.
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| CN101485647B (en) * | 2009-02-27 | 2013-04-24 | 东莞广州中医药大学中医药数理工程研究院 | Use of patchouli alcohol in preparing medicament |
| CN102349884B (en) | 2011-08-26 | 2013-04-03 | 东莞广州中医药大学中医药数理工程研究院 | Application of patchouli alcohol in preparation of helicobacter pylori resistant medicament |
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Non-Patent Citations (4)
| Title |
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| 广藿香精油对植物病原真菌的抑菌活性研究. 莫小路等.中药材，第27卷第11期. 2004 |
| 广藿香精油对植物病原真菌的抑菌活性研究. 莫小路等.中药材，第27卷第11期. 2004 * |
| 广藿香醇及广藿香油中广藿香醇在大鼠体内药代动力学比较. 杨甫传等.药学学报，第24卷第9期. 2004 |
| 广藿香醇及广藿香油中广藿香醇在大鼠体内药代动力学比较. 杨甫传等.药学学报，第24卷第9期. 2004 * |
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