CN101310715A - Tanshinol for preparing the medicine for preventing and treating depression and sodium salt thereof - Google Patents
Tanshinol for preparing the medicine for preventing and treating depression and sodium salt thereof Download PDFInfo
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- CN101310715A CN101310715A CNA200710109322XA CN200710109322A CN101310715A CN 101310715 A CN101310715 A CN 101310715A CN A200710109322X A CNA200710109322X A CN A200710109322XA CN 200710109322 A CN200710109322 A CN 200710109322A CN 101310715 A CN101310715 A CN 101310715A
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Abstract
Salvianic acid A with the chemical name of D - (plus) Beta-(3, 4-dihydroxyphenyl) lactic acid is an unstable free acid and commonly uses the sodium salt thereof which is salvianic acid A sodium. The salvianic acid A sodium can significantly shorten the immobility time in the swimming test of rats and mice and the immobility time in the tail suspension test of mice, and the function of the salvianic acid A sodium is better than fluoxetine hydrochloride. The times of spontaneous motor activity of mice induced by the monosodium glutamate inverted by salvianic acid A sodium are increased, and the duration of sleep of the mice is prolonged. The salvianic acid A sodium does not resist the body temperature reduction, drooping eyelids and movement disorder caused by reserpine, does not inhibit the reuptake of 5-serotonine and does not enhance the toxicity of norepinephrine. The salvianic acid A sodium has strong protective effects of glucocorticoid-induced rat pheochromocytoma PC12 cellular injury (including the leakage of lactic dehydrogenase) and glutamate-induced brain injury of adult mice. The salvianic acid A sodium can play the antidepressant role by protecting nerve cells.
Description
Background of invention
Danshensu (danshensu), chemical name D-(+) β-(3, the 4-dihydroxyphenyl) lactic acid, D-(+) β-(3,4-dihydoxyphenyl) lactic acid is the active component that extracts from Chinese medicine Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bge).Because danshensu is a kind of unsettled free acid, so its sodium salt danshensu sodium (Sodiun danshensu, sodium β-3,4-dihydroxyphenyl lactate) commonly used.The structural formula of danshensu and sodium salt thereof such as Fig. 1.Hydroxyl on the danshensu phenyl ring is a functional group, can remove free radical, inhibited oxidation reaction and radical reaction.
The characteristic symptom of depression (depression) is: pessimistic mental state, self feel very bad; Sleep disorder, insomnia or early awakening; Appetite is very poor, is short of power; Lack cordiality, interest and happy sense disappear; Self-accusation is from crime, and passiveness is wanted to die; Weight loss; Libido reduces.Depression often has the complaint of constipation and various pain, anxiety, terror, feels uncertain or forces symptom very general, and the preemption idea of depressibility is particularly common.Depression can be divided into PDI (two-phase or unipolar depression) and secondary depression (being secondary to other mental sickness or physical disease).
The classical antidepressant of present three classes; comprise tricyclic antidepressants desipramine, 5-hydroxy tryptamine reuptake inhibitor fluoxetine (Prozac) and monoamine oxidase A inhibitor horse clofibride; rat pheochromocytoma PC12 cell to the corticosterone damage has significant protective effect, and psychosis chlorpromazine and antianxiety drugs diazepam then do not have this effect.Desipramine or fluoxetine significantly weaken corticosterone and handle Ca in the born of the same parents of PC12 cell induction
2+Overload, significantly improve the expression of nerve growth factor (NGF) informational RNA.Therefore, although all kinds of antidepressant structure is totally different, cytoprotection may be its effect co-channel, and weakens Ca in the born of the same parents
2+The expression of neurotrophic factors such as overload and raising NGF then may be one of cytoprotection mechanism of antidepressants.
Depression is just becoming global the fifth-largest disease, expects the year two thousand twenty, will rise to be second largest disease, and will become fatal disease.World Health Organization (WHO) has been listed as depression, cancer and acquired immune deficiency syndrome (AIDS) three big disease and the work of health education key preventive of 21 century.Tranquilizer or sleeping pill, side effect is big, causes drug dependence easily, and therapeutic effect is also bad, is not suitable for depression.Present popular anti-depression drug comprises famous fluoxetine, western Pulan (Celexa) and Efexor XR (Effexor), all begins to take effect taking several Zhou Houcai, and side effect such as the sexual function of reduction is arranged.In addition, these medicines are also invalid to about 1/3rd patient.Serotonin modulating agent belongs to antidepressants of new generation, and effect is better and side effect is little, but domestic production as yet.Off the beaten track from motherland's medicine, perhaps can find the new drug of preventing and treating depression.
Brief summary of the invention
The present invention relates to danshensu and sodium salt thereof as the pharmaceutical composition that is used to prepare prevention and treatment depression, this pharmaceutical composition comprises danshensu and sodium salt and pharmaceutically useful carrier.
The present invention relates to require defined preparation of drug combination method as right 1, this method is meant that danshensu and sodium salt thereof mix with pharmaceutically useful carrier or dissolve.
Danshensu and sodium salt thereof can mix with any pharmaceutically useful carrier or dissolve, as in skin, mucosa, gastrointestinal and pharmaceutically suitable carrier of parenteral.This medicine uses with the form of conventional pharmaceutical formulation, as tablet, granule, powder, capsule and the cachet etc. of solid form, or the injection of crystalline powder shape injection and liquid form, suspending agent, syrup and Emulsion etc.Use pharmaceutically useful excipient and additive in this medicine, these pharmaceutically useful excipient and additive comprise nontoxic compatible filler, binding agent, disintegrating agent, buffer agent, antiseptic, antioxidant, lubricant, correctives, thickening agent, coloring agent, emulsifying agent, stabilizing agent etc., as lactose, citric acid, stearic acid, magnesium stearate Gypsum Fibrosum powder, sucrose, corn starch, agar, pectin, Oleum Arachidis hypogaeae semen, cocoa butter, ethylene glycol, glucose, procaine hydrochloride, lidocaine hydrochloride and ascorbic acid etc.This medicine can be by the common process preparation of various preparations.
The present invention relates to danshensu and sodium salt thereof medicine, can be used as food additive and join in the food as the prevention depression.The present invention relates to danshensu and sodium salt thereof medicine as the treatment depression.The dosage of danshensu sodium is the about 0.1-100mg of every kg body weight every day in the made various oral drugs, preferably about 0.05-50mg, more excellent about 0.1-20mg, best about 1-5mg.Divide every day and take for 2-4 time, 10-30 days is a course of treatment, and general medication 3-10 course of treatment, each, the interval was 5-30 days course of treatment.Made injectable drug can supply muscle, intravenous injection and intravenous drip, and wherein the dosage of danshensu sodium is every kg body weight 0.01-50mg every day, preferably about 0.05-25mg/kg, more excellent about 0.1-10mg, best about 0.5-5mg.Divide 1-3 use every day, 10-30 days is a course of treatment, and general medication 3-30 course of treatment, each, the interval was 5-30 days course of treatment.Yet accurate dose and persistent period should be determined by the doctor, depend on patient's age, body weight, the state of an illness and reaction etc.
Enumerate experiment content and result thereof below, can be used for preparing the evidence that prevents and treat the depression medicine as danshensu and sodium salt thereof.
Material
Animal: NIH mice, 8 ages in week, SPF level; The SD rat, 200-230g, SPF level.
Danshensu sodium, purity＞98%; Monosodium glutamate is available from Sigma company.
One, rat forced swimming experiment
Method: the rat random packet, 10 every group, male and female half and half are respectively contrast, positive control and danshensu sodium group.Experiment every rats'swimming training the previous day 15min.Positive controls fluoxetine Hydrochloride (20mg/kg) is irritated stomach twice (test preceding 17,7h) before the experiment, danshensu sodium group lumbar injection danshensu sodium (5,10,20mg/kg) 2 times (experiment preceding 17h, 7min), and matched group is synchronously to normal saline.Behind the last administration 7min, put Plastic Drum (the high 40cm of rat in 25 ℃ of water temperatures, depth of water 23cm, diameter 30cm) in, observes and measures simultaneously administration group and control rats accumulative total dead time in the 5min (be extremity motionless fully or only have foot to pat arm stroke).Data statistics is handled and is adopted Student ' s t check, result (x ± s) expression.
Result: the desperate behavior of the motionless state reflection animal that occurs in the rat forced swimming model.Danshensu sodium (10,20mg/kg * 2) highly significant shortens the rats'swimming dead time (table 1) (p＜0.01), and effect is better than fluoxetine Hydrochloride (table 1) slightly.
Table 1 danshensu sodium is to the rat forced swimming influence of model dead time (x ± s)
Compare with matched group,
*P＜0.05;
*P＜0.01.
Two, mice forced swimming experiment
Method: the mice random packet, 10 every group, male and female half and half are respectively matched group, positive controls and danshensu sodium group.Experiment every mice swimming instruction the previous day 15min.Positive group fluoxetine Hydrochloride (20mg/kg) is irritated stomach twice (test preceding 17,7h) before the experiment, danshensu sodium group lumbar injection danshensu sodium (10,20,40mg/kg) 2 times (17h, 7min before the experiment), and contrast and experimental group are synchronously to normal saline.Behind the mice last administration 7min, place in the graduated cylinder (high 20cm, diameter 14cm) of 25 ℃ of water temperatures, depth of water 10cm, put an opaque dividing plate between the graduated cylinder, in case mice is seen each other.Observe 6min, measure administration group and the control group mice accumulative total dead time in the 4min of back simultaneously.Judge motionless standard: stop to struggle, vertical position, motionless floating, the activity of only doing some necessity makes its head above water.Data statistics is handled and is adopted Student ' s t check, result (x ± s) expression.
Result: the desperate behavior of the motionless state reflection animal that mice occurs in the forced swimming model.The danshensu sodium group significantly shortens mice non-swimming time (table 2).
Table 2 danshensu sodium is to the mice forced swimming influence of model dead time (x ± s)
Compare with matched group,
*P＜0.05.
Three, mouse tail suspension experiment
Method: grouping and the same swimming test of medication, behind the mice last administration 7min, the position of its tail end 2cm is attached on the horizontal waddy, make animal become reversal of the natural order of things state, the about 5cm of head destage face.Separate the sight line of facing animal mutually with plate, observe 6min, measure administration group and the control group mice accumulative total dead time in the 4min of back simultaneously.Data statistics is handled and is adopted Student ' s t check, result (x ± s) expression.
Result: the desperate behavior of the motionless state reflection animal that mice occurs in outstanding tail model.Three dosage groups of danshensu sodium all can reduce the mouse tail suspension dead time, and 20,40mg/kg group effect highly significant.
Table 3 danshensu sodium is to the influence of mouse tail suspension dead time (x ± s)
Compare with matched group
*P＜0.05,
*P＜0.01.
Four, reserpine causes body temperature decline experiment
Method: the mice random packet, is respectively model, positive control and danshensu sodium group by 10 every group.Measure every mice anus temperature before the experiment earlier, survey altogether 3 times, ask its meansigma methods as basal body temperature.Positive controls fluoxetine Hydrochloride (40mg/kg) is irritated stomach 2 times (giving reserpine preceding 17,7h), danshensu sodium group lumbar injection danshensu sodium (10,20,40mg/kg) 2 times (giving reserpine front and back 30min).Each organizes mice behind lumbar injection reserpine (5mg/kg) 2h, measures mice anus temperature.
Result: compare with basal body temperature, reserpine can significantly reduce mouse temperature (p＜0.01), fluoxetine Hydrochloride can reverse reserpine induced mice body temperature decline (p＜0.01), and danshensu sodium descends to animal heat due to the reserpine and does not have obviously effect, and promptly danshensu sodium can not reverse reserpine induced mice body temperature and descends.
Five, strengthen 5-hydroxy tryptamine effect experiment
Experiment according to a conventional method, grouping and medication are the same.The result shows that danshensu sodium does not suppress the reuptake of 5-hydroxy tryptamine.
Six, strengthen the norepinephrine toxicity test
Experiment according to a conventional method, grouping and medication are the same.The result shows that danshensu sodium does not strengthen the toxicity of norepinephrine.
Seven, danshensu sodium is to the influence of mice autonomic activities
Method: male NIH mice is divided into 4 groups, 10 every group at random.Matched group gives normal saline, and experimental group gives monosodium glutamate (2.0g/kg/d, irritate stomach) or/and danshensu sodium (20mg/kg/d, lumbar injection), once a day, and continuous 5 days.30min after the last administration places the autonomic activities instrument with mice, movable number of times in the record mice 5min behind the adaptation 3min.
The result: danshensu sodium does not have obvious influence to normal mouse autonomic activities number of times, increases (table 4) but reverse the inductive mice autonomic activities of monosodium glutamate number of times.
Table 4 danshensu sodium is to the influence of mice autonomic activities
Compare with matched group,
*P＜0.05.
Eight, danshensu sodium is induced down the influence of mice sleep to the threshold dose pentobarbital sodium
Method: the NIH mice is divided into 4 groups at random, and 10 every group, male and female half and half.Matched group gives normal saline, and the administration group is lumbar injection danshensu sodium 10,20,40mg/kg/d respectively, once a day, and continuous 10 days.30min mouse peritoneal injection pentobarbital sodium (40mg/kg/d) is a time for falling asleep with the mice righting reflex loss after the last administration, is sleep time from righting reflex loss to recovery time.Time for falling asleep and the sleep time of record mice.
The result: danshensu sodium induces down the mice time for falling asleep not have obvious influence to pentobarbital sodium, but prolongs the persistent period of mice sleep.Danshensu sodium (20,40mg/kg/d * 10) the group significant prolongation mice sleep persistent period (P＜0.05) (table 5).
Table 5 danshensu sodium is induced down the influence of mice sleep to pentobarbital sodium
Compare with matched group,
*P＜0.05.
Nine, danshensu sodium is to the protective effect of the rat pheochromocytoma PC12 cell injury of glucocorticoid inducible
Method:
1, the cultivation of rat adrenal gland pheochromocytoma strain PC12 cell
The PC12 cell inoculation is in culture bottle, and culture fluid is for containing 7.5% calf serum, 7.5% hyclone, 1 * 10
5The DMEM culture medium of U/L penicillin, 100mg/L streptomycin, pH7.4 places 37 ℃, 5%CO
2, humidity 98% CO
2Cultivate in the incubator, went down to posterity once in 3～4 days.
2, dexamethasone is to the inhibitory action of PC12 cell growth
After at the bottom of cell covers with bottle, blow and beat gently for several times, cell is disperseed fully with suction pipe.Regulating cell density is 2 * 10
5Cell/mL is inoculated in 0.01% poly-D-lysine bag by 96 orifice plates of crossing, every hole 100 μ L.Treat that cell covers with to 70%～80%, inhale and go culture fluid, D-hanks to wash 1 time.Matched group adds serum-free DMEM culture fluid 100 μ L, and the damage group adds and contains variable concentrations dexamethasone (10,1,0.1,10
-2, 10
-3, 10
-4μ mol/L) serum-free DMEM culture fluid 100 μ L establish 6 multiple holes for every group.Continue cultivation 24,48,72h, inhale and remove culture fluid, wash 2 times with D-hanks.Every hole adds the MTT liquid of 20 μ L 5g/mL, cultivates 4h.Every hole adds 100 μ L, three liquid, treat blue particle dissolve fully (12～16h), read absorbance (OD) value at wavelength 570nm place with enzyme-linked immunosorbent assay instrument, adopt the Bliss method to calculate median lethal concentration LD
50Cell survival rate=experimental group OD value/matched group OD value * 100%
3, danshensu sodium is to the influence of the inductive PC12 cell injury of dexamethasone
With the PC12 cell suspension inoculation in 96 orifice plates that 0.01% poly-D-lysine bag is crossed, every hole 100 μ L.Treat that cell covers with after 70%～80%, inhale and go culture fluid, D-hanks to wash 1 time.Matched group adds serum-free DMEM culture fluid 100 μ L; the damage group adds the serum-free DMEM culture fluid 100 μ L that contain dexamethasone 10 μ mol/L; protection group (danshensu sodium+dexamethasone) adds danshensu sodium (25,50,100,200,400,800 μ mol/L) the serum-free DMEM culture fluid 50 μ L pretreatment 1h that contain various dose; add the dexamethasone serum-free DMEM culture fluid 50 μ L that contain 20 μ mol/L again, continue to cultivate 24h.Cell culture fluid is removed in suction, washes 2 times with D-hanks, and every hole adds the MTT liquid of 20 μ L 5g/mL, cultivates 4h.Every hole adds 100 μ L, three liquid, treat blue particle dissolve fully (12～16h), read absorbance (OD) value at wavelength 570nm place with enzyme-linked immunosorbent assay instrument, establish 8 multiple holes for every group.
4, danshensu sodium spills the influence of rate to the inductive PC12 cell of dexamethasone lactic acid dehydrogenase
With the PC12 cell inoculation in 96 orifice plates that 0.01% poly-D-lysine bag is crossed, every hole 100 μ L.Treat that cell covers with to 70%～80%, inhale and go original fluid, D-hanks to wash 1 time.Matched group adds serum-free DMEM culture fluid 100 μ L; the damage group adds the serum-free DMEM culture fluid 100 μ L that contain dexamethasone 10 μ mol/L; protection group (danshensu sodium+dexamethasone) adds danshensu sodium (25,50,100,200,400,800 μ mol/L) the serum-free DMEM culture fluid 50 μ L pretreatment 1h that contain various dose; add the dexamethasone serum-free DMEM culture fluid 50 μ L that contain 20 μ mol/L again, continue to cultivate 24h.Draw cell culture fluid, measure PC12 cells and supernatant lactic dehydrogenase enzyme activity in night, establish 5 multiple holes for every group according to the explanation of lactic dehydrogenase enzyme reagent kit.The order and the amount that add each reagent are undertaken by the test kit explanation.
Lactic dehydrogenase enzyme activity (U/L)=(measuring pipe OD value-mensuration control tube OD value)/(standard pipe OD value-standard control pipe OD value) * standard pipe concentration (2 μ mol/ml) * 1000ml * diluted sample multiple
The result:
1, dexamethasone is to the influence of PC12 cell growth
The result shows, 10
-4Dexamethasone suppresses the growth of PC12 cell in～10 μ mol/L dosage ranges, and becomes positive correlation with dosage.The most obvious to the inhibition of PC12 cell growth when dexamethasone concentration is 10 μ mol/L, effect 24h survival rate is 59.6%.24～48h period, the survival rate of PC12 cell descends slow.48～72h period survival rate descends greatly, has not belonged to the retardance course of damage.The IC of dexamethasone when the Bliss method calculates 24h
50Be about 16.3 μ mol/L.Select 10 μ mol/L dexamethasone to do following experiment.
2, danshensu sodium is to the protective effect of the inductive PC12 cell injury of dexamethasone
Danshensu sodium obviously influences PC12 cell growth nothing, but can resist the inhibitory action of dexamethasone to the growth of PC12 cell, and becomes positive correlation with dosage.When danshensu sodium concentration was 400 μ mol/L, the survival rate of PC12 cell was 98.6%, had almost completely offset the inhibitory action of dexamethasone to the growth of PC12 cell.
3, danshensu sodium protective effect that the inductive PC12 cell of dexamethasone lactic acid dehydrogenase is spilt
The result shows that the rate that spills of dexamethasone damage group lactic acid dehydrogenase sharply raises, up to 2 times of matched group; Danshensu sodium can reduce induced by dexamethasone PC12 cell and discharge lactic acid dehydrogenase, and its effect becomes positive correlation with dosage.When danshensu sodium concentration was 400 μ mol/L, its effect was the most obvious, and suppression ratio reaches 60.4% (P＜0.01).
Ten, danshensu sodium is to the protective effect of the inductive adult mice brain injury of glutamate, Glu
Method: 8 the week age mice, male and female have concurrently, random packet.Except that matched group, mice is accepted monosodium glutamate (1.0,2.0,4.0g/kg/d, irritate stomach) and/or danshensu sodium (10,20,40mg/kg/d, lumbar injection), continuous 10 days.Carry out behavioristics's experiment and histopathologic examination then.
1, the ability of learning and memory experiment is differentiated in the Y-labyrinth: the learning and memory experiment is differentiated in the 1st day beginning Y-labyrinth of adult mice after monosodium glutamate and/or danshensu sodium processing, and continuous 6 days, the 30th day repeated once again.
2, open wild experiment: opening wild experiment is to be used for detecting the reaction of animal to new environment.The 7th day after monosodium glutamate and/or danshensu sodium processing begins experiment, and the movable number of times in the record mice 3min was surveyed once in per 5 days, up to end in the 27th day.
3, histopathological examination: accept monosodium glutamate and/or danshensu sodium and handled the back the 4th day, mouse peritoneal injection pentobarbital sodium (60mg/kg) anesthesia, make cardiac perfusion with 10% formalin solution and sacrifice animal, get brain, put in 10% formalin solution and fix a week.Carry out the section of 10 μ m thickness by hippocampus, conventional H E dyeing.Light microscopic checks that down cerebral hippocampal district histopathology changes.
4, statistical analysis: Y labyrinth and open wild experimental data and adopt the analysis of Repeated Measurement Data analytic process.
The result:
1, danshensu sodium is differentiated the influence of ability of learning and memory damage to the inductive mice Y-of monosodium glutamate labyrinth
The result shows, adult mice gives monosodium glutamate (1.0,2.0,4.0g/kg/d * 10, irritate stomach) and ability of learning and memory differentiated in the Y-labyrinth obvious impairment is arranged.Handle back 1-6 day and the 85th day at monosodium glutamate, the Y-labyrinth of monosodium glutamate group mice is differentiated ability of learning and memory and is starkly lower than matched group (P＜0.001).Yet, danshensu sodium (20mg/kg/d * 10, lumbar injection) or ability of learning and memory is differentiated in the Y-labyrinth of monosodium glutamate (2.0g/kg/d * 10, irritate stomach)+danshensu sodium (20mg/kg/d * 10, lumbar injection) group mice and matched group does not have significant difference (P＞0.05).The danshensu sodium decapacitation reverses monosodium glutamate and mice Y-labyrinth is differentiated outside the damage of ability of learning and memory, and itself differentiates ability of learning and memory to the Y-labyrinth of adult mice and there is no obvious influence.
2, the protective effect that increases of danshensu sodium autonomic activities that monosodium glutamate is caused
Adult mice increases its autonomic activities after giving monosodium glutamate (2.0,4.0g/kg/d * 10, irritate stomach) to a certain extent, but not statistically significant (0.1＞P＞0.05).(stomach is irritated in 2.0g/kg/d * 10)+danshensu sodium (20mg/kg/d * 10, lumbar injection) group is compared then very close with matched group for danshensu sodium (20mg/kg/d * 10, lumbar injection) and monosodium glutamate.The result shows that the danshensu sodium decapacitation reverses outside the influence of monosodium glutamate to autonomic activities, and itself there is no obvious influence to the autonomic activities of adult mice.
3, danshensu sodium is to the protective effect of the inductive encephalopathy reason of monosodium glutamate tissue injury
In the cerebral tissue to the damage the most responsive zone be Hippocampus, Hippocampus plays an important role in learning and memory.The result shows that adult mice causes hippocampus neurons in mice degeneration and necrosis (Fig. 2 B) after giving monosodium glutamate (stomach is irritated in 2.0g/kg/d * 10).Yet danshensu sodium group and monosodium glutamate+danshensu sodium group mice hippocampus is not found tangible neuronal damage (Fig. 2 C).
Embodiment
Embodiment 1: tablet
NO amounts of components (mg/ grain)
1 danshensu sodium 50 100
2 lactose USP 122 123
3 corn starchs, food stage 30 40
Be 10% pure water slurry)
4 corn starchs, food stage 95 130
5 magnesium stearate NF 37
Add up to 300 400
Manufacture method
In suitable mixer, mixed the 1st, 2 components 15 minutes, the 3rd component and mixture granulation.If desired, grind moist granule, and make it dry.If desired, dried granules is sieved, and mixed 10-15 minute with the 4th component by a primary dcreening operation.Adding the 5th component mixed 1-3 minute.In suitable tablet machine, mixture is pressed into suitable size and weight.
Embodiment 2: capsule
NO amounts of components (mg/ grain)
1 danshensu sodium 50 100
2 lactose USP 106 120
3 corn starchs, food stage 40 73
4 magnesium stearate NF 47
Add up to 200 300
Manufacture method
The 1st, 2,3 components were mixed 10-15 minute in suitable mixer, add the 4th component and mixed 1-3 minute.On suitable encapsulation machine with in the capsule that it is suitable that this mixture is packed into.
Embodiment 3: injection
Danshensu sodium 100g or 500g, glucose 400g or 250g add the injection water to 10000ml.
Description of drawings
The chemical constitution of Fig. 1, Radix Salviae Miltiorrhizae acid (A) and danshensu sodium (B)
Fig. 2, danshensu sodium are to the protective effect of the inductive adult mice brain injury of glutamate, Glu
Except that matched group, mice is accepted monosodium glutamate (2.0g/kg/d irritates stomach) and/or danshensu sodium (40mg/kg/d, lumbar injection), continuous 10 days, checks that thereafter the histopathology of mice hippocampus changes.
A, contrast, * 200;
B, monosodium glutamate (stomach is irritated in 2.0g/kg/d * 10), * 200, a. neuronal degeneration and necrosis;
C, monosodium glutamate (stomach is irritated in 2.0g/kg/d * 10)+danshensu sodium (40mg/kg/d * 10, lumbar injection), * 200.
Claims (1)
1. danshensu and sodium salt thereof are used to prepare the medicine of prevention and treatment depression.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102342909A (en) * | 2010-07-30 | 2012-02-08 | 湖南康普医药研究院 | Preparation method of salvianic acid A sodium injection |
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2007
- 2007-05-23 CN CNA200710109322XA patent/CN101310715A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102342909A (en) * | 2010-07-30 | 2012-02-08 | 湖南康普医药研究院 | Preparation method of salvianic acid A sodium injection |
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