CN106728570A - A kind of pharmaceutical composition for preventing and treating diabetes cognitive disorder and preparation method thereof - Google Patents
A kind of pharmaceutical composition for preventing and treating diabetes cognitive disorder and preparation method thereof Download PDFInfo
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Abstract
本发明公开了一种防治糖尿病认知障碍的药物组合物，其特征在于：所述药物组合物为西洋参和石菖蒲，且西洋参和石菖蒲两种药材的重量比1‑4:1‑3。本发明提供的一种防治糖尿病认知障碍的药物组合物及其制备方法，该药物组合物能够促进西洋参在体内吸收，同时相对在治疗糖尿病认知障碍中活性更好。The invention discloses a pharmaceutical composition for preventing and treating cognitive impairment of diabetes, which is characterized in that: the pharmaceutical composition is American ginseng and Shichangpu, and the weight ratio of the two medicinal materials is 1-4:1-3. The invention provides a pharmaceutical composition for preventing and treating diabetic cognitive impairment and a preparation method thereof. The pharmaceutical composition can promote the absorption of American ginseng in the body, and meanwhile has better activity in treating diabetic cognitive impairment.
Description
Technical field
The invention belongs to biomedicine technical field, more specifically to a kind of medicine for preventing and treating diabetes cognitive disorder
Compositions.Meanwhile, the invention further relates to a kind of preparation method of the pharmaceutical composition for preventing and treating diabetes cognitive disorder.
Background technology
There is diabetes (DM) patient 4.14 hundred million in the current whole world, it is contemplated that will reach 6.42 hundred million to the year two thousand forty, according to another《Cure in the U.S.
Association's magazine》Report, Chinese adult has nearly 12% with DM, and the illness rate of forerunner DM is about 50%.China has become
Suffer from DM numbers highest country in the world.Influence about DM Central nervous systems causes the extensive attention of people already.It is early
In the twenties in 20th century, MileS and Root first reported DM influence cognitive functions.Nineteen sixty-five proposes the concept of " DM encephalopathics ".
Mijnhout is proposed " DM related cognitive disorder (DACD) " within 2006.Afterwards many studies have shown that DM patient exist it is a series of
The change of Neuropsychology and neuroethology, while having the DM patient of 60-70% with light, moderate cognitive dysfunction, portion
Divide Patients ' Cognitive to damage constantly to aggravate, finally develop into dementia, dull-witted once to be formed, therapeutic effect is little.At present, treat cognitive
The medicine of obstacle has the medicines such as acetylcholinesteraseinhibitors inhibitors, glutamate receptor (NMDA) adjusting control agent, polypeptide, treats diabetes
Medicine have a medicines such as biguanides, sulfonylureas, but cause the cognitive disorder medicine there is no clear and definite finished medicines for diabetes.
American Ginseng is the root of Araliaceae American Ginseng (PanaxquinquefoliusL.), and American Ginseng is cold in nature, with benefit
Gas yin-nourishing, clearing heat and promoting fluid, the effect of nourishing Yin and falling fire.Short Term Clinical research finds that diabetic individually takes American Ginseng, can carry
Immunity of organisms high, helps to repair islet function, eliminates insulin resistance, improves serum insulin.While reducing blood lipid and blood
Platelet PAR, hence it is evident that improve diabetic symptom.Meanwhile, main component ginsenoside can be obviously improved study note in American Ginseng
Recall ability.
Grass-leaved sweetflag is the drying of Araeceae herbaceos perennial grass-leaved sweetflag (Acorus tatarinowii Schott)
Root, taste is pungent is warm in nature, and the gas for having fragrance, the scattered power of row is stronger, is the sensible good merchantable brand of a surname's gas.Can remove dampness by means of aromatics, activating spleen and strengthening stomach, and
Can inducing resuscitation intelligence development.
Research display American Ginseng can improve abnormal carbohydrate metabolism and the cognitive disorder caused by diabetes or other reasonses or
It is dull-witted.To improve bioavilability, reducing adverse drug reaction and improving the targeting of central nervous system, the present invention is with the West
Ginseng, grass-leaved sweetflag medicine pair, are intervened DM cognitive disorders, and on the one hand compatibility grass-leaved sweetflag is that ginseng and calamus are one in using for reference ancient prescription
Classical medicine pair, another aspect grass-leaved sweetflag has promotion drug absorption, improves blood-brain barrier permeability, the effect of consciousness regaining, matches somebody with somebody
5 medicinal applications become apparent in treatment brain diseases advantage, therefore the present invention proposes that a kind of diabetes of preventing and treating cause cognitive disorder
Pharmaceutical composition and preparation method.
The content of the invention
The invention aims to solve shortcoming present in prior art, and the one kind for proposing prevents and treats diabetes cognition
Pharmaceutical composition of obstacle and preparation method thereof.
To achieve the above object, the present invention provides following technical scheme：
A kind of pharmaceutical composition for preventing and treating diabetes cognitive disorder, it is characterised in that：Described pharmaceutical composition is American Ginseng
And grass-leaved sweetflag, and two kinds of weight of medicinal material of American Ginseng and grass-leaved sweetflag compare 1-4:1-3.
Preferably, two kinds of optimum weight ratios of medicinal material 3 of the American Ginseng and grass-leaved sweetflag:2.
The present invention also provides a kind of application of the pharmaceutical composition for preventing and treating diabetes cognitive disorder, described American Ginseng stone Chang
Pu pharmaceutical composition is applied in treatment diabetes cognitive disorder.
The present invention also provides a kind of preparation method of the pharmaceutical composition for preventing and treating diabetes cognitive disorder, including following step
Suddenly：
S1, the dried root of American Ginseng is milled to fine powder, adds 8 times of 70% ethanol of volume, 78-82 DEG C of water-bath backflow
3h is extracted, is extracted 2 times；
S2, filtering：Filtrate is collected, 56-62 DEG C of recycling design is to without alcohol taste；
S3 and then use 0.5gmL-1Filtrate by D101 macroreticular resins, 5 times of column volumes washings, 3 times of column volumes 20%
Ethanol elution, 6 times of ethanol elutions of column volume 70% collect 70% ethanol eluate, flow velocity 5mLmin-1；
S4,70% ethanol eluate of collection, flow velocity 1mLmin-1, collect pregnant solution, 58-62 DEG C of recycling design of pregnant solution
To without alcohol taste, American ginseng extract is obtained；
S5, dry of grass-leaved sweetflag is ground into fine powder, crosses 38-42 mesh sieves, add 12 times of distilled waters, returned after immersion 2h
Stream extracts 9h, and period collects the volatile oil for extracting, with 1% Tween 80 aqueous dissolution, that is, obtains Essential Oil of Acorus tatarinowii extract solution；
Essential Oil of Acorus tatarinowii extract solution in S6, the American ginseng extract and S5 that will be obtained in S4 is mixed by motor stirrer
Close uniform, you can obtain pharmaceutical composition.
Preferably, the American ginseng extract at least includes ginsenoside.
Technique effect of the invention and advantage：A kind of pharmaceutical composition for preventing and treating diabetes cognitive disorder that the present invention is provided
And preparation method thereof, the pharmaceutical composition can promote American Ginseng to absorb in vivo, while relative in the cognitive barrier for the treatment of diabetes
Hinder middle activity more preferably.
Specific embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, below in conjunction with specific embodiment, to this
Invention is further elaborated.It should be appreciated that specific embodiment described herein is only used to explain the present invention, and without
It is of the invention in limiting.Based on the embodiment in the present invention, those of ordinary skill in the art are not making creative work premise
Lower obtained every other embodiment, belongs to the scope of protection of the invention.
Embodiment 1：Pharmaceutical composition (American Ginseng-grass-leaved sweetflag) main chemical compositions analysis in rat blood and cerebrospinal fluid
The current incidence of disease of diabetes is very high, while six or seven ten percent can occur cognitive disorder, in heat more than diabetic duration
The development process of dry inclined Sheng-deficiency of both qi and yin-yin-yang deficiency, it is dry to it for syndrome of deficiency of both qi and yin American Ginseng, grass-leaved sweetflag medicine pair
In advance, American Ginseng has functions that supplementing qi and nourishing yin tonifying Qi is promoted the production of body fluid, while with phlegm is held under the arm in diabetic duration, grass-leaved sweetflag is then had one's ideas straightened out open-minded
Phlegm, and by blood-brain barrier, to determine whether grass-leaved sweetflag has facilitation to American Ginseng, investigate American Ginseng and American Ginseng,
After grass-leaved sweetflag medicine is to gastric infusion, ginsenoside is determined in rat in-vivo content.Because disease model metabolism of rat factor is a lot,
Therefore selection normal rat is used as experimental animal.
American Ginseng 100g is taken, 8 times of 70% ethanol of volume are added, 80 DEG C of water-bath refluxing extraction 3h are extracted 2 times, and filtering is received
Collection filtrate, 60 DEG C of recycling designs to without alcohol taste, afterwards with 0.5 times of column volume sample solution (0.5gmL-1) by D101 macroreticular resins,
5 times of column volume washings, 3 times of ethanol elutions of column volume 20%, 6 times of ethanol elutions of column volume 70% collect 70% ethanol eluate,
Flow velocity 1mLmin-1.60 DEG C of recycling designs of pregnant solution are settled to 100mL to without alcohol taste；Grass-leaved sweetflag 100g is taken simultaneously, adds 12
Times distilled water, refluxing extraction 9h after immersion 2h, period collects the volatile oil for extracting, is settled to the 1% Tween 80 aqueous solution
100mL。
Wistar rats 20, are randomly divided into American Ginseng group, pharmaceutical composition group, every group 10, male and female half and half.American Ginseng
Group gavage gives American ginseng extract (6g crude drugs kg-1·d-1), pharmaceutical composition group is the American Ginseng extract solution that will be obtained
(volume ratio is 3 with Essential Oil of Acorus tatarinowii extract solution：2) well mixed by motor stirrer, gavage gives pharmaceutical composition (west
American ginseng extract 6g crude drugs kg-1·d-1, Essential Oil of Acorus tatarinowii extract solution 4g crude drugs kg-1·d-1) be administered 3 days, daily 2 times.
Whole free water, the fasting 12h before last time is administered, the 1.5h after last dose, the anesthesia of 3% yellow Jackets, neck
Venous blood collection 3mL, 3500rpm centrifugation 10min, draw upper serum 1.5ml serum, in putting tool plug centrifuge tube.By blood serum sample
Preprocess method is operated, and the residue μ L of methyl alcohol 60 dissolve (concentrate 25 times equivalent to blood serum sample)；Taken out in cisterna magna simultaneously
Cerebrospinal fluid is taken, 3500rpm centrifugation 10min draw the μ L of upper strata cerebrospinal fluid 200, in putting tool plug centrifuge tube.By cerebrospinal fluid pretreatment side
Method is operated, and the residue μ L of methyl alcohol 60 dissolve (concentrate 3.3 times equivalent to spinal fluid samples), ultrasound 1min after vortex 3min,
(4 DEG C) centrifugation 15min of 13000rmp, take supernatant, UPLC-MS/MS difference sample introduction 10uL analyses.Obtain American Ginseng group and medicine
Composition group effective constituents mesarcs composition ginsenoside in rat body enters blood, enters brain content and is shown in Table 1, table 2.
In the rat body of table 1 effective constituents mesarcs composition ginsenoside enter blood content (N=10) unit：ng/mL
Compare with American Ginseng group, * P<0.05 has significant difference, * * P<0.01 has significant differences
In the rat body of table 2 effective constituents mesarcs composition ginsenoside enter brain content (N=10) unit：ng/mL
Compare with American Ginseng group, * P<0.05 has significant difference, * * P<0.01 has significant differences
Result shows that main component Ginsenosides are in blood during grass-leaved sweetflag can promote American Ginseng in pharmaceutical composition group
And the absorption in cerebrospinal fluid.Therefore, for treatment diabetes cause cognitive disorder medicine to provide theoretical foundation.Embodiment 2Morris water
Labyrinth determines pharmaceutical composition (American Ginseng-grass-leaved sweetflag) to the intervention effect of diabetes rat cognitive disorder
American Ginseng 1000g is taken, 8 times of 70% ethanol of volume are added, 80 DEG C of water-bath refluxing extraction 3h is extracted 2 times, filtering,
Collect filtrate, 60 DEG C of recycling designs to without alcohol taste, afterwards with 0.5 times of column volume sample solution (0.5gmL-1) by D101 macropore trees
Fat, 5 times of column volume washings, 3 times of ethanol elutions of column volume 20%, 6 times of ethanol elutions of column volume 70% collect 70% ethanol elution
Liquid, flow velocity 1mLmin-1.60 DEG C of recycling designs of pregnant solution are settled to 1000mL to without alcohol taste；Grass-leaved sweetflag 1000g is taken simultaneously, plus
Enter 12 times of distilled waters, refluxing extraction 9h after immersion 2h, period collects the volatile oil for extracting, 1000ML is settled to 1% Tween 80.
Wistar rats, cleaning grade, female, weight 180-220g, totally 100, rat is randomly divided into 5 groups, respectively：
Blank control group；Diabetic model group；American Ginseng grass-leaved sweetflag group；American Ginseng group；Positive drug group；Every group of experimental animal in two batches,
Every group 20, it is administered 12 weeks.Dosage gives American ginseng extract (1.08g crude drugs kg for American Ginseng group gavage-1·d-1), pharmaceutical composition group is that (volume ratio is 1 for the American Ginseng extract solution that will obtain and Essential Oil of Acorus tatarinowii extract solution：1) by electricity
Power agitator is well mixed, and gavage gives pharmaceutical composition (American ginseng extract 1.08g crude drugs kg-1·d-1, grass-leaved sweetflag waves
Hair oil extract solution 0.72g crude drugs kg-1·d-1), positive drug group gavage gives donepezil (2mgkg-1·d-1), blank pair
According to group, model group gives isometric physiological saline, daily gastric infusion 2 times.
The general status such as stabilization 3d before above-mentioned rat experiment, observation the ingesting of rat, excrement, activity.Respectively at experiment point
Group carries out Morris water maze tests on the 80th, and Morris water mazes are diameter 150cm, the round pool of 50cm high, in pond
It is black that wall is painted, and pond is divided into 4 quadrants, sticks not isolabeling at the center of 4 quadrant pool walls respectively by 4 equidistant points
Thing, is triangle, square, the circular and five-pointed star white scraps of paper.Platform is put into the center of one of quadrant, less than the water surface
2cm, control water temperature is at 23.0 ± 2.0 DEG C.Morris water maze learning trainings are carried out to rat, by rat except target during experiment
Three quadrants outside quadrant (quadrant where platform) are put into water in face of pool wall at random, (the escape of going up on the stage the time of record rat
Incubation period, hereinafter referred to as incubation period) used as the index for evaluating school grade, incubation period decline is that school grade is improved.Before experiment
Rat is put into platform station 10s, allows rat that 10s is stopped on platform after finding platform, incubation period finds platform for rat
Time；If rat does not find platform in 90s, incubation period is designated as 90s, then by rat guiding climb up platform allow its
10s is stopped on platform, allows it to carry out Spatial memory according to four objects of reference of quadrant, and it is nervous to reduce rat.Instruct every time
Rat is taken out after the completion of white silk is dried, stress with prevent hypothermia from causing.Every Rat Septal 20min repeats above-mentioned experiment
Journey.The double rat for finding platform in training process, it is believed that remember position of platform, does not still remember platform position the 6th time
The rat put is then the rat of learning ability exception.
Morris water mazes determine diabetes rat learning and memory level.Result shown, 80d is set up in diabetes model,
Model group compares with control group, and diabetes model incubation period is more long, there is significant difference, illustrates that diabetes rat is present cognitive
Obstacle；American Ginseng group, pharmaceutical composition group compare with model group, American Ginseng group and pharmaceutical composition (American Ginseng-grass-leaved sweetflag) group
Latency is short, there is significant difference.American Ginseng and pharmaceutical composition have certain to diabetes cognitive disorder during explanation
Therapeutic action, American Ginseng-grass-leaved sweetflag medicine is more notable to therapeutic effect.Morris water mazes measure diabetes rat incubation period is shown in Table
3。
The Morris water mazes of table 3 determine diabetes rat incubation period
Compared with control group, * p ＜ 0.05 have significant difference, and * * p ＜ 0.01 have significant differences
Compared with model group,▲P<0.05 has significant difference,▲▲P ＜ 0.01 have significant differences
The experiment of the Social behaviors of embodiment 3 determines pharmaceutical composition (American Ginseng-grass-leaved sweetflag) to diabetes rat human communication disorders
Intervention effect
American Ginseng 1000g is taken, 8 times of 70% ethanol of volume are added, 80 DEG C of water-bath refluxing extraction 3h is extracted 2 times, filtering,
Collect filtrate, 60 DEG C of recycling designs to without alcohol taste, afterwards with 0.5 times of column volume sample solution (0.5gmL-1) by D101 macropore trees
Fat, 5 times of column volume washings, 3 times of ethanol elutions of column volume 20%, 6 times of ethanol elutions of column volume 70% collect 70% ethanol elution
Liquid, flow velocity 1mLmin-1.60 DEG C of recycling designs of pregnant solution are settled to 1000mL to without alcohol taste；Grass-leaved sweetflag 1000g is taken simultaneously, plus
Enter 12 times of distilled waters, refluxing extraction 9h after immersion 2h, period collects the volatile oil for extracting, 1000mL is settled to 1% Tween 80.
Wistar rats, cleaning grade, female, weight 180-220g, totally 100, rat is randomly divided into 5 groups, respectively：
Blank control group；Diabetic model group；American Ginseng grass-leaved sweetflag group；American Ginseng group；Positive drug group；Every group of experimental animal in two batches,
Every group 20, it is administered 12 weeks.Dosage gives American ginseng extract (1.08g crude drugs kg for American Ginseng group gavage-1·d-1), pharmaceutical composition group is that (volume ratio is 2 for the American ginseng extract that will obtain and Essential Oil of Acorus tatarinowii extract solution：1) by electricity
Power agitator is well mixed, and gavage gives pharmaceutical composition (American ginseng extract 1.08g crude drugs kg-1·d-1, grass-leaved sweetflag waves
Hair oil extract solution 0.72g crude drugs kg-1·d-1), positive drug group gavage gives donepezil (2mgkg-1·d-1), blank pair
According to group, model group gives isometric physiological saline, daily gastric infusion 2 times.
Social behaviors test is carried out to each group rat in modeling 80d, test is 100cm × 100cm × 40cm in specification
Carried out in spacious field case, mouse device is put in the self-control that a diameter 14cm is put in spacious field case, the exchange between this device without prejudice to rat.
All of rat is individually placed in spacious field case freely activity 5min, daily 2 times, continuous 2d, to mitigate rat pair by 2d before experiment
The anxiety of new environment.1h isolates tested mouse single cage before experiment.Put the centre that mouse device is placed on spacious field case, the inside be put into one and
Normal social rat of the mouse with batch is tested, all tested mouse carry out Social behaviors test, testing time with this mouse
It is 5min.The indexs such as distance, the frequency of exposure of average speed and device mouse, time of contact using the tested rat of software records.
Using the frequency of exposure with device mouse less than or equal to 1 time as the standard for evaluating diabetes human communication disorders.
Refer to table 4, table 5.Model group rats are substantially less than control group (p with the frequency of exposure of device mouse and time of contact
＜ 0.01), therefore the sociability substantially less than control group of model group can be illustrated.Compare with model group, American Ginseng group, medicine group
Compound (American Ginseng-grass-leaved sweetflag group) although sociability is not significantly higher than model group, the human communication disorders of model group occurs
Rate is 83.33%, and the human communication disorders of American Ginseng group occurs 66.66%, and pharmaceutical composition group 56.25% shows, pharmaceutical composition
The incidence of diabetes rat human communication disorders can be obviously improved.
Result shows that American Ginseng group and pharmaceutical composition (American Ginseng-grass-leaved sweetflag) can improve rat sociability.
The frequency of exposure of 4 two groups of rat Social behaviors of table and time of contact
Compared with control group, * p ＜ 0.05 have significant difference, and * * p ＜ 0.01 have significant differences
Compared with model group,▲P<0.05 has significant difference,▲▲P ＜ 0.01 have significant differences
The static number of times of 5 two groups of rat Social behaviors of table and quiescent time
Compared with control group, * p ＜ 0.05 have significant difference, and * * p ＜ 0.01 have significant differences
Compared with model group,▲P<0.05 has significant difference,▲▲P ＜ 0.01 have very significant poor
Finally it should be noted that：The preferred embodiments of the present invention are the foregoing is only, are not intended to limit the invention,
Although being described in detail to the present invention with reference to the foregoing embodiments, for a person skilled in the art, it still may be used
Modified with to the technical scheme described in foregoing embodiments, or equivalent carried out to which part technical characteristic,
All any modification, equivalent substitution and improvements within the spirit and principles in the present invention, made etc., should be included in of the invention
Within protection domain.
Claims (5)
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|---|---|---|---|---|
| CN111393534A (en) * | 2020-02-21 | 2020-07-10 | 广东药科大学 | Acorus gramineus sugar polymer and preparation method and application thereof |
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