CN107865920A - Application of the Yangxinshi tablets in preparing for medicament for treatment of depression - Google Patents
Application of the Yangxinshi tablets in preparing for medicament for treatment of depression Download PDFInfo
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Abstract
The invention provides purposes of the Yangxinshi tablets in the medicine for preparing treatment depression.The test of pesticide effectiveness shows that Yangxinshi tablets treat depression significant effect.Therefore, Yangxinshi tablets can be used for the medicine for preparing treatment depression, have good exploitation purposes prospect.
Description
Technical field
The present invention relates to field of medicaments, and in particular to by the Radix Astragali, Radix Codonopsis, the red sage root, the root of kudzu vine, barrenwort, hawthorn, glutinous rehmannia, when
Return, the coptis, vinegar corydalis tuber, ganoderma lucidum, ginseng, the taste medicinal material of honey-fried licorice root 13 composition Yangxinshi tablets prepare be used for treat depression
Application in medicine.
Background technology
Depression is a kind of universal phrenoblabia, can cause the injury of spirit and body.The characteristics of depression is main
It is depressed, happy feeling missing, in addition it is pessimistic and worldweary, can there are conamen or behavior, this state is simultaneously with fatigue, note
Meaning power is not concentrated, sleep-disorder and cognition, linguistic function obstacle etc..Depression seriously perplexs daily life and the study work of patient
Make, be one of source of family and social white elephant.Counted according to the World Health Organization, there are about 3.5 hundred million populations with suppression
Strongly fragrant disease, this turns into one of major reason of global disease burden.Because it has a high incidence, high relapse rate, high homicide rate,
Through causing extensive concern.Depression mechanism is not fully aware of, and many factors take part in the morbidity of depression
Journey, biological, psychological, society, environment and hereditary etc. influence is all to cause depressed formation hazards.Should in clinic
In, although the antidepressants of some chemical syntheses can reduction of patient clinical symptoms, it is same secondary with stronger poison
Act on for example drowsiness, hypertension, liver property etc..In addition, effective antidepressants class only can mitigate 2/3 patient at present
Slight illness, these medication effects are not obvious in remaining patient to be embodied, and this is for ideally treating depression disease
Disease is not nearly enough.
Yang Xinshi is by the Radix Astragali, Radix Codonopsis, the red sage root, the root of kudzu vine, barrenwort, hawthorn, glutinous rehmannia, Radix Angelicae Sinensis, the coptis, vinegar corydalis tuber, spirit
Sesame, ginseng, wherein the taste medicinal material of honey-fried licorice root 13 composition, the gas of the help spleen and lung such as ginseng, the Radix Astragali, Radix Codonopsis, honey-fried licorice root, barrenwort temperature
The yang-energy of kidney tonifying, the red sage root, Radix Angelicae Sinensis, hawthorn, vinegar corydalis tuber etc. is promoting blood circulation and removing blood stasis, promoting the circulation of qi coronary circulation-promoting pain-relieving；The enriching yin such as the root of kudzu vine, the dried rhizome of rehmannia are given birth to
Tianjin, nourishing heart；Ginseng, Radix Codonopsis isothermal health Tianjin；The coptis is helped with relieving restlessness that clears away heart-fire；Ganoderma lucidum, Radix Codonopsis, red sage root etc. still have calming heart, nourishing heart peace
The work(of god.Yangxinshi tablets with the help motive, help metaplasia qi and blood with Qi-tonifying drug, the characteristics of highlighting " nourishing heart ".《The red small stream heart
Method six is strongly fragrant》Middle proposition：" qi and blood rush and, ten thousand diseases are not given birth to, and one has looking angry strongly fragrant, and all diease occurrences are here, all diseases of old friend's body, are born in strongly fragrant more." can
See that the regulation of qi and blood can not only treat heart disease, the mental diseases such as depression can also be improved.It is therefore proposed that Yangxinshi tablets
" diplocardia theoretical ", i.e. " nourishing heart is theoretical " of Yangxinshi tablets include heart and psychology, can not only treat the diseases such as chronic heart failure,
And the mental handicape disease such as depression can be improved.At present Yangxinshi tablets clinically be used for coronary heart disease with qi deficiency and blood stasis, angina pectoris,
Miocardial infarction, heart failure and merge high fat of blood, hyperglycaemia etc..And up to now, many documents are all in report Yangxinshi tablets
The clinical observation result of the chronic heart failure of angina pectoris, coronary heart disease etc. is treated, and has no Yangxinshi tablets as antidepressant application
Report.
The content of the invention
It is an object of the invention to the Yangxinshi tablets found in being studied according to Chinese medicine composition to have showing for antidepressant effect
Shape, there is provided its application in preparing for medicament for treatment of depression.
The Yangxinshi tablets tablet that described Yangxinshi tablets produce for Qingdao Guofeng Pharmaceutical Co., Ltd., Chinese medicines quasi-word number
Z37021102, main component be the Radix Astragali, Radix Codonopsis, the red sage root, the root of kudzu vine, barrenwort, hawthorn, glutinous rehmannia, Radix Angelicae Sinensis, the coptis, vinegar corydalis tuber,
Ganoderma lucidum, ginseng, honey-fried licorice root.
Purposes of the Yangxinshi tablets of the present invention in preparing for medicament for treatment of depression belongs to first public.
Beneficial effect：Preclinical validation of the present invention is curative for effect, notable.Pharmacological experiment finds this medicine treatment depression effect
Fruit is notable, safely, effectively, Small side effects.Therefore, Yangxinshi tablets can be used for the medicine for preparing depression, have good open
Hair way prospect.
Embodiment
With reference to specific embodiment, the present invention is further elaborated, but does not limit the present invention.
Yangxinshi tablets (factory：Qingdao Guofeng Pharmaceutical Co., Ltd., lot number 150310)；(Shanghai is enzyme-linked for Prozac
Bio tech ltd, lot number 20150427).Sodium carboxymethylcellulose, chloraldurate and other reagents are domestic point
Analyse pure.
Example 1：The Yangxinshi tablets influence experiment for stimulating depression rat unpredictable to chronic mildness
1 experimental method
1.1 experimental animals and packet
Experimental animal is provided by the western pul-Bi Kai experimental animals Co., Ltd in Shanghai：80 SD male rats, SPF levels, body
Weight is 180~220g, animal productiong licensing number：SCYK (Shanghai) 2013-0016.Before experiment, rat is placed in normal experiment
Environmental suitability is raised, normal to provide food and water, ensures 12 hours periodicity of illuminations, this 80 rats are randomly divided into blank pair
According to group, model group, Prozac group, high dose Yangxinshi tablets group, middle dosage Yangxinshi tablets group, low dosage Yangxinshi tablets group.
1.2 animal models and administration
In model preparation process, model group, Prozac group, high dose Yangxinshi tablets group, middle dosage Yangxinshi tablets group, low dose
The rat of amount Yangxinshi tablets group receives 2 kinds daily according to plan stress sexual stimulus selected from following：Turn off the light 3 hours, it is crowded overnight, 4
DEG C frozen water swims 5 minutes, turn on light overnight, folder tail 10 minutes, tilt 45 spend night, drinking-water deprive overnight, foot shock 5 divides
Clock, the wet cage of pad overnight, tilt that 45 degree (8 hours daytimes), food deprivation be overnight, wet cage (8 hours daytimes), stress sexual stimulus it is continuous
Carry out 35 days, daily last carries out the detection of every Testing index after stimulating.Blank control group, any stimulation is not given.
Positive drug Prozac and Yangxinshi tablets are dissolved with 0.5% sodium carboxymethylcellulose (CMC-Na) or are suspended to required
Administration concentration.The beginning daily administration in modeling first day, the fluoxetine dose of Prozac group is 10mg/kg/d, and high dose is supported
The Yangxinshi tablets dosage of Xin Shi piece groups is 1000mg/kg/d, and the Yangxinshi tablets dosage of middle dosage Yangxinshi tablets group is 500mg/kg/
D, the Yangxinshi tablets dosage of low dosage Yangxinshi tablets group is 250mg/kg/d, and method of administration is gavage, once a day, continues 4 weeks,
Blank control group and model group not drug, normal raising.
1.3 Testing index
1.3.1 sucrose water preference is tested
Experiment before in quiet room, animal training adapt to containing sugar drinking-water, per cage simultaneously place 2 water bottles, first
In 24h, 2 bottles are contained 1% sucrose water (mass fraction is 1% sucrose water), and subsequent 24h a, bottle contains 1% sucrose water, separately
One bottle contains pure water.Again after 24h fasting for solids and liquids, every rat gives fixed measured 2 water bottle in advance：One bottle of 1% sucrose water, one bottle
Pure water, after 1h, 2 water bottles are taken to weigh, the difference of quality consumes for syrup before and after the experiment of 1% sucrose water, quality before and after pure water is tested
Difference be pure water consumption, syrup consumption and pure water consumption sum are total liquid-consumed.Rat syrup is calculated according to the following equation
Preference value：Syrup preference value (%)=syrup consumption/always liquid-consumed × 100%.
1.3.2 forced swim test (FST)
By the single depth of water that is put into of rat for (high 45cm, diameter 30cm) in 25cm plastic cylinder during experiment, 25 DEG C of water temperature,
Gather altogether 6 minutes, be used as within first 2 minutes rat laundering period, the rear time statistics for including motionless state in 4 minutes.
1.3.3 spacious field experiment (OFT)
According to animal travels bottom surface grid block number as horizontal anomalous movement (distance traveled) score, with upright time
Number is used as Vertical movements (standing upright) score, and horizontal and vertical activity score summation is overall score.Spacious case apparatus
For the black chest of each l00cm of length and width (bottom surface is divided into 25 equilateral grids), each finish paints of high 50cm.Rat is put into central square
Interior, observation rat passes through lattice number (grid that four paws enters just counts, and is horizontal movement score), rear time in 3min
Number (two fore paws soar or sought connections with wall, for the score that moves vertically).
1.3.4 serotonin (5-HT), cortisone (CORT) and corticotropin (ACTH) water in serum are detected
It is flat
Every group of selection 8,5-HT, CORT and ACTH water in serum are detected with enzyme linked immunosorbent assay (ELISA) (ELISA) method
It is flat.
2 experimental results
2.1 sucrose water preference test results
After modeling, model group rats syrup consumption is substantially less than blank control group (P<0.01)；Compared with model group, support
The rat syrup consumption of each dosage group of Xin Shi pieces and Prozac group raises, and difference has statistical significance (P<0.05), specifically
It is shown in Table 1.
The result of each group rat syrup of table 1 consumption
Note：Compared with blank control group,##P<0.01；Compared with model group,*P<0.05。
2.2 forced swim test results
After modeling, the model group rats forced swimming dead time is significantly higher than blank control group (P<0.01) modeling, is illustrated
There is depressive symptom in success, rat；Compared with model group, each dosage group of Yangxinshi tablets and Prozac group rat dead time subtract
Few, difference has statistical significance (P<0.05) 2, are specifically shown in Table.
The comparison of each group rats'swimming dead time of table 2
Note：Compared with blank control group,##P<0.01；Compared with model group,*P<0.05。
2.3 spacious field experimental results
After modeling, the level of model group rats passes through lattice number, erects number substantially less than blank control group (P<0.01),
Illustrate that depressive symptom, modeling success occurs in rat；Compared with model group, the water of each dosage group of Yangxinshi tablets and Prozac group rat
Flat to pass through lattice number, erect number and have increase, difference has statistical significance (P<0.05, P<0.01) 3, are specifically shown in Table.
The each group rat spacious field experimental result of table 3
Note：Compared with blank control group,#P ＜ 0.05,##P<0.01；Compared with model group,*P<0.05,**P<0.01
The horizontal result of 5-HT, CORT and ACTH in 2.4 rat blood serums
5-HT, CORT, ACTH are horizontal in model group rats serum is substantially less than blank control group (P<0.001).With model
Group is compared, the horizontal significantly rise (P of 5-HT, CORT, ACTH of Prozac group<0.001, P<0.01, P<0.001)；Yangxinshi tablets
The horizontal significantly rise (P of low dose group 5-HT, ACTH<0.001, P<0.01)；Yangxinshi tablets middle dose group CORT, ACTH is horizontal aobvious
Write rise (P<0.001, P<0.01)；The horizontal significantly rise (P of Yangxinshi tablets high dose group CORT, ACTH<0.001, P<0.01),
Specifically it is shown in Table 4.
The comparison of 5-HT, CORT, ACTH content in each group rat blood serum of table 4
Note：Compared with blank control group,#P<0.05,##P<0.01,###P<0.001；Compared with model group,**P<0.01,***
P<0.001
3 conclusions
Yangxinshi tablets, which can be obviously improved chronic mild unpredictable stress stimulus, stimulates the depressive state of depression rat, has anti-
Depression effect.
Example 2：The influence experiment for the vascular Depression mouse that Yangxinshi tablets are induced cerebral ischemia re-pouring
1 experimental method
1.1 experimental animals and packet
Experimental animal is provided by the western pul-Bi Kai experimental animals Co., Ltd in Shanghai：90 ICR male mices, SPF levels,
Body weight is 18~22g, animal productiong licensing number：SCYK (Shanghai) 2013-0016.Before experiment, mouse is placed in normal experiment
Environmental suitability is raised, normal to provide food and water, ensures 12 hours periodicity of illuminations, this 90 mouse are randomly divided into and are divided into vacation
Operation group, model group, Prozac group, high dose Yangxinshi tablets group, middle dosage Yangxinshi tablets group, low dosage Yangxinshi tablets group.
1.2 animal models and administration
By model group, Prozac group, high dose Yangxinshi tablets group, middle dosage Yangxinshi tablets group, low dosage Yangxinshi tablets group
Mouse adaptability raising after, through be injected intraperitoneally 3% chloraldurate (0.1mL/10g mouse weights), after anaesthetizing successfully, take and face upward
Clinostatism, front tooth and four limbs are fixed, and cut off throat skin and manadesma, respectively are isolated by left and right arteria carotis in tracheae both sides, use is small
After number artery clamp blocks bilateral carotid arteries blood supply 5min, unclamp artery clamp and recover blood supply 10min, moved after blocking blood supply 5min again
Except artery clamp.For the mouse of sham-operation group in addition to arteria carotis blood supply is not blocked, remaining operation technique is identical with other experimental groups.It is postoperative
Start within 8th day behaviouristics detection, detected by Depressive behaviors such as tail-suspention test, spacious field experiments, the mouse of model group is compared with sham-operation
There is obvious Depressive behavior in group, it is determined that animal model success.
Positive drug Prozac and Yangxinshi tablets dissolve or are suspended to required administration concentration with 0.5%CMC-Na.In modeling
Beginning daily administration from first day, the dosage of the Prozac of Prozac group are 15mg/kg/d, the nourishing heart of high dose Yangxinshi tablets group
Family name's tablet amounts are 1500mg/kg/d, and middle dosage Yangxinshi tablets group Yangxinshi tablets dosage is 750mg/kg/d, low dosage Yangxinshi tablets
Group Yangxinshi tablets dosage is 375mg/kg/d, and method of administration is gavage, and dosing interval is 1 time a day.Sham-operation group and model group
Not drug, the daily normal water of sham-operation group, feed；Model group drinking-water, feed daily from modeling first day；Prozac group
The daily administration from modeling first day；The daily administration from modeling first day of Yangxinshi tablets each group.
1.3 Testing index
1.3.1 tail-suspention test (TST)
Using self-control mouse hang tail apparatus, arrange the 8th day after surgery carry out, away from tail point about at 1cm with immobilization with adhesive tape in outstanding tail
On the pintle of system testing case, mouse head observes 6min, adapts to 2min, set 4min after recording altogether away from ground about 7.5cm
The mouse dead time.
1.3.2 spacious field experiment (OFT)
Carried out in postoperative 9th day, mouse is sequentially placed into spacious field test box, mouse is put into start recording after 2min, surveys
Time 15min is tried, record mouse passes through bottom surface grid block number as horizontal anomalous movement (distance traveled) score, with straight
Vertical number is as Vertical movements (standing upright) score.
1.3.3 correlation factor detects in cerebral hippocampus tissue and serum
After experiment terminates, blood is taken, centrifuging and taking serum, takes hippocampal tissue, is stored in -80 DEG C of refrigerators, norepinephrine to be measured
(NA), dopamine (DA), 5-HT, tumor necrosis factor α (TNF-α), interleukin-1 beta (IL-1 β), interleukin-6 (IL-
6) equal size.
2 experimental results
2.1 tail-suspention test results
After modeling, the model group mouse tail suspension dead time is significantly higher than sham-operation group (P<0.01), can determine that to go out for mouse
Existing Depressive behavior；Compared with model group, each dosage group of Yangxinshi tablets and Prozac group mouse tail suspension dead time reduce, difference tool
Statistically significant (P<0.05, P<0.01) 5, are specifically shown in Table.
The comparison of each group mouse tail suspension dead time of table 5
Note：Compared with blank control group,##P<0.01；Compared with model group,*P<0.05,**P<0.01
2.2 open field test results
After modeling, model group mouse level passes through lattice number, setting number is substantially less than sham-operation group (P<0.01), can determine that
There is Depressive behavior for mouse；Compared with model group, each dosage group of Yangxinshi tablets and Prozac group mouse level are passed through lattice number, erected
Vertical number increases, and difference has statistical significance (P<0.01, P<0.05) 6, are specifically shown in Table.
The each group mouse open field test result of table 6
Note：Compared with blank control group,#P<0.05,##P<0.01；Compared with model group,*P<0.05,**P<0.01
Correlation factor result in 2.3 cerebral hippocampus tissues and serum
Compared with blank control group, NA, DA, 5-HT level significantly reduce (P in model group mice serum<0.001), TNF-
α, IL-1 β, IL-6 level significantly rise (P<0.001).Compared with model group, Prozac group and Yangxinshi tablets group mice serum
Middle DA and 5-HT level significantly rise (P<0.05, P<0.001), TNF-α, IL-1 β, IL-6 level significantly reduce (P<
0.05, P<0.01, P<0.001) 7, are specifically shown in Table.
Table 7 each group mouse NA, DA, 5-HT, TNF, IL-1 β, IL-6 content comparison
Note：Compared with blank control group,#P<0.05,##P<0.01,###P<0.001；Compared with model group,*P<0.05,**P
<0.01,***P<0.001.3 conclusions
Mouse vascular Depression model modeling success is found by outstanding tail and spacious field experiment.Detect mice serum in it is related because
The expression of son understands that bilateral carotid occlusion causes mouse to suffer from the angiocardiopathy with depressive symptom, while with inflammation
Phenomenon.Depressive symptom can be improved after gastric infusion Yangxinshi tablets, while mitigation is also played to inflammation.
Above-mentioned experiment can clearly show, the invention discloses the purposes that Yangxinshi tablets have antidepressant effect, can use
In preparing the application in safe and efficient antidepressant, the medical value of Yangxinshi tablets has been opened up, has been the development of traditional Chinese medicine and pharmacy
Make creative contribution.
The foregoing is only a specific embodiment of the invention, but protection scope of the present invention is not limited thereto, any
Those skilled in the art in disclosed technical scope, can without the change that creative work is expected or
Replace, should all be included within the scope of the present invention.
Claims (2)
1. purposes of the Yangxinshi tablets in the medicine for preparing treatment depression.
2. purposes according to claim 1, the main components of the Yangxinshi tablets include the Radix Astragali, Radix Codonopsis, the red sage root, the root of kudzu vine,
Barrenwort, hawthorn, glutinous rehmannia, Radix Angelicae Sinensis, the coptis, vinegar corydalis tuber, ganoderma lucidum, ginseng, honey-fried licorice root.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1824008A (en) * | 2005-12-16 | 2006-08-30 | 江西青春康源制药有限公司 | Heart nourishig capsule and its preparation method |
| CN105943701A (en) * | 2016-06-23 | 2016-09-21 | 上海医药集团青岛国风药业股份有限公司 | Application of medicine with functions of tonifying qi and promoting blood circulation to preparation of medicines for treating insomnia |
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2016
- 2016-09-28 CN CN201610860733.1A patent/CN107865920B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1824008A (en) * | 2005-12-16 | 2006-08-30 | 江西青春康源制药有限公司 | Heart nourishig capsule and its preparation method |
| CN105943701A (en) * | 2016-06-23 | 2016-09-21 | 上海医药集团青岛国风药业股份有限公司 | Application of medicine with functions of tonifying qi and promoting blood circulation to preparation of medicines for treating insomnia |
Non-Patent Citations (2)
| Title |
|---|
| LI YERRUI ET AL.: "Development of a method using high-performance liquid chromatographic fingerprint and multi-ingredients quantitative analysis for the quality control of Yangxinshi Pian", 《JOURNAL OF SEPARATION SCIENCE》 * |
| 郝近大: "《中华人民共和国药典辅助说明•2010年版一部•中成药》", 31 January 2012, 中国中医药出版社 * |
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