Summary of the invention
The purpose of this invention is to provide the Chinese medicine extract that a kind of purity of extracting higher good effect, consumption are low, have no side effect substantially from Radix Scrophulariae.
Another object of the present invention provides the pharmaceutical composition that contains this extract.
A further object of the present invention provides the preparation technology of this extract.
A further object of the invention provides this extract or contains the application of pharmaceutical composition in preparation treatment ischemia apoplexy medicine of this extract.
Purpose of the present invention can realize by following measures:
A kind of Radix Scrophulariae total glucosides extract, wherein the content of Radix Scrophulariae total phenylpropyl glycosides class is greater than 40%, and the content of Radix Scrophulariae total iridoid glycosides class is greater than 10%.
Described Radix Scrophulariae total glucosides extract, this extract prepares through the following step:
(1) get the Radix Scrophulariae medical material, with 40~90% ethanol extraction of 5~20 times of crude drug amounts 1~3 time, each 1~3 hour, extracting liquid filtering concentrated;
(2) concentrated solution adds ethanol to containing alcohol amount 40~80%, staticly settles, and supernatant liquid filtering concentrates;
(3) concentrated solution is with nonpolar or low pole macroporous adsorbent resin column chromatography, the water eluting, do not have reducing sugar reaction to effluent after, the concentration of 3~20 times of crude drug amounts of reuse is 20~90% ethanol elution, collects ethanol elution;
(4) eluent concentrates, and drying promptly gets Radix Scrophulariae total glucosides extract.
Described Radix Scrophulariae total glucosides extract, model wherein nonpolar or the low pole macroporous adsorptive resins is HPD-100, HPD-400, AB-8, D-101, D-301, NKA-9.
The pharmaceutical composition that contains above-mentioned Radix Scrophulariae total glucosides extract.This pharmaceutical composition is made up of described Radix Scrophulariae total glucosides extract and pharmaceutically acceptable carrier; Can also add other active component and form pharmaceutical composition.Pharmaceutically acceptable carrier is meant one or more inert, atoxic solids or liquid filler material, diluent, cosolvent etc., and they are not reverse has an effect with reactive compound or patient.
Described pharmaceutical composition, its dosage form are dosage form commonly used on the pharmaceuticss such as tablet, capsule, soft capsule, pill, drop pill, suppository, oral liquid, suspension, injection or injection lyophilized powder.
The preparation method of described Radix Scrophulariae total glucosides extract, the process following steps:
(1) get the Radix Scrophulariae medical material, with 40~90% ethanol extraction of 5~20 times of crude drug amounts 1~3 time, each 1~3 hour, extracting liquid filtering concentrated;
(2) concentrated solution adds ethanol to containing alcohol amount 40~80%, staticly settles, and supernatant liquid filtering concentrates;
(3) concentrated solution is with nonpolar or low pole macroporous adsorbent resin column chromatography, the water eluting, do not have reducing sugar reaction to effluent after, the concentration of 3~20 times of crude drug amounts of reuse is 20~90% ethanol elution, collects ethanol elution;
(4) eluent concentrates, and drying promptly gets Radix Scrophulariae total glucosides extract.
The preparation method of described Radix Scrophulariae total glucosides extract, model wherein nonpolar or the low pole macroporous adsorptive resins is HPD-100, HPD-400, AB-8, D-101, D-301, NKA-9.
Described Radix Scrophulariae total glucosides extract or pharmaceutical composition treat and/or prevent application in the medicine of ischemia apoplexy in preparation.
Contain the plain glycoside of phenylpropyl alcohol, iridoid glycosides and other materials in the extract of the present invention, usually, the content of Radix Scrophulariae total phenylpropyl glycosides class is greater than 40% in the extract, the content of Radix Scrophulariae total iridoid glycosides class is greater than 10%, therefore can be with the content of the content of total phenylpropanoid glycoside and total iridoid glycoside as quality index in quality control.
Beneficial effect of the present invention:
Extract good effect of the present invention, consumption be low, have no side effect substantially, and its preparation technology is simple, dna purity is high.
Below be part pharmacodynamic experiment and data:
One, to the influence of clotting time of mice
Experiment purpose: distinguish of the influence of Radix Scrophulariae total glycosides to clotting time of mice by slide method.
Experiment material: animal: healthy ICR mice (18-22 gram, half and half, 60 of male and female are provided by Nanjing military medicine institute, animal credit number: SCXK (Soviet Union) 2002-0025).Equipment: microscope slide, pin, stopwatch.Medicine and reagent: the Radix Scrophulariae total glycosides (lot number is provided by the Kaierteng Science and Technology Co., Ltd., Shenzhen City: 040819, by the embodiment of the invention 1 preparation, down together), XUESAITONG PIAN (manufacturer: Yunnan Jintaide Notoginseng Industry Co., Ltd; Batch number: 040511); Use the fresh preparation of normal saline (table 1) every day
Table 1 dosage conversion table (mice administration volume is 0.2ml/10g, the back administration of weighing in every day)
Be subjected to the reagent thing | Clinical people's dosage | Be converted into the mice dosage |
XUESAITONG PIAN | ????0.3g/70kg/day | ??39mg/kg/day |
The Radix Scrophulariae total glycosides | (0.15g/70kg/day dose,equivalent) | (19.5mg/kg/day low) |
Experimental technique:
1, get 60 of 18~22g mices, male and female half and half, being divided at random is 5 groups (seeing the experiment packet design), weighs.
I, negative control normal saline
II, positive control XUESAITONG PIAN (1.95mg/ml)
III, test group 1 Radix Scrophulariae total glycosides (0.975mg/ml) dose,equivalent group
IV, 2 times of dose,equivalent groups of test group 2 Radix Scrophulariae total glycosides (1.95mg/ml)
V, 4 times of dose,equivalent groups of test group 3 Radix Scrophulariae total glycosides (3.9mg/ml)
2, press above-mentioned dosage filling stomach (0.2ml/10g/day) for every group, irritate stomach and continue 7 days.
3, got the hematometry clotting time with slide method on the 8th day.
Slide method: pluck a branch hole ball rapidly with the curved tweezer of ophthalmology, promptly have blood to flow out.Each one is bled in the microscope slide two ends, and the drop of blood diameter is about 5mm, uses manual time-keeping immediately.Provoked once gently inwards from the drop of blood edge with the cleaning pin every 5 seconds, and observation has or not the blood streak to provoke.End to provoking the blood streak from the blood sampling beginning, be the blood clotting time between institute lasts.Another is bled and reviews for last.The record clotting time is done the mean test of significance.
Experimental result sees Table 2:
Table 2 Radix Scrophulariae total glycosides to the influence (slide method) of clotting time of mice (X ± SD, n=10)
Group | Dosage (mg/kg) | Number of animals (only) | Clotting time (s) | The t value |
Negative control group | Normal saline | ????10 | ??60.15±28.42 | |
Positive controls | ????39 | ????10 | ??107.8±45.00
* | ??2.831 |
Tried Radix Scrophulariae total glycosides 1 | ????19.5 | ????10 | ??118.55±55.01
** | ??2.982 |
Tried Radix Scrophulariae total glycosides 2 | ????39 | ????10 | ??130.62±53.33
** | ??3.688 |
Tried Radix Scrophulariae total glycosides 3 | ????78 | ????10 | ??141.03±58.2
** | ??3.949 |
(
*P<0.05,
*Compare with negative control p<0.01.)
Experiment conclusion: judge the influence of three various dose of Radix Scrophulariae total glycosides and XUESAITONG PIAN to clotting time of mice by slide method, the result shows that the Radix Scrophulariae total glycosides has good blood coagulation resisting function, with negative control group significant differences is arranged relatively, and obviously being better than positive controls, its oral effect dosage is 19.5mg/kg.
Two, collagen protein-epinephrine is brought out the inhibitory action that the mice thrombus in vivo forms
Experiment purpose: measure the Radix Scrophulariae total glycosides collagen protein-epinephrine is brought out the inhibitory action that the mice thrombus in vivo forms
Experiment material: animal: healthy ICR male mice (25~34g, is provided animal credit number: SCXK (Soviet Union) 2002-0025 by 60 by Nanjing military medicine institute).Instrument and equipment: mouse tail vein injection liquid device, irrigation stomach device.Medicine and reagent: the Radix Scrophulariae total glycosides (lot number is provided by the Kaierteng Science and Technology Co., Ltd., Shenzhen City: 040819), Aspirin Enteric-coated Tablets (manufacturer: Baijingyu Pharmaceutical Co., Ltd., Nanjing; Batch number: 040901), collagen protein (Nanjing great order bio tech ltd), epinephrine (Tianjin gold credit aminoacid company limited, batch number: 0306051), normal saline.
Table 3 dosage conversion table (mice administration volume is 0.2ml/10g, the back administration of weighing in every day)
Be subjected to the reagent thing | Clinical people's dosage | Be converted into the mice dosage |
Aspirin Enteric-coated Tablets | ????0.154g/70kg/day | 20mg/kg/day |
The Radix Scrophulariae total glycosides | (0.15g/70kg/day dose,equivalent) | (19.5mg/kg/day low) |
Experimental technique
Get 60 mices, be divided into 5 groups at random, weigh.
I, negative control normal saline
II, positive control Aspirin Enteric-coated Tablets (1mg/ml)
III, test group 1 Radix Scrophulariae total glycosides (0.975mg/ml) dose,equivalent group
IV, 2 times of dose,equivalent groups of test group 2 Radix Scrophulariae total glycosides (1.95mg/ml)
V, 4 times of dose,equivalent groups of test group 3 Radix Scrophulariae total glycosides (3.9mg/ml)
The isometric normal saline of matched group, experimental group are given Radix Scrophulariae total glycosides (0.975mg/ml, 1.95mg/ml respectively, 3.9mg/ml three dosage groups), Aspirin Enteric-coated Tablets (1mg/ml), all gastric infusion (every group by above-mentioned dosage filling stomach 0.2ml/10g/day) is irritated stomach and is continued 8 days.
Administration in the 9th day tail vein injection collagen protein after 1 hour (225ug/ only) and epinephrine (9ug/) mix derivant (volume: 0.09ml/10g).
Promptly observe the not recovery number of dead mouse number within 5 minutes or 15 minutes mice hemiplegias after the injection.
Calculate the protective rate of medicine, the x2 check to the mouse brain thrombosis.
Experimental result sees Table 4:
Table 4 Radix Scrophulariae total glycosides brings out the influence that the mice thrombus in vivo forms to collagen protein-epinephrine
Group | Drug dose (mg/kg) | Number of animals | Recover number (only) in the 15min | Recovery rate (%) | The P value |
Negative control group | Normal saline | ????12 | ????4 | ????33.33 | |
Positive controls | ????20 | ????12 | ????9 | ????75.00 | 0.0436 |
Tried Radix Scrophulariae total glycosides 1 | ????19.5 | ????12 | ????9 | ????75.00 | 0.0436 |
Tried Radix Scrophulariae total glycosides 2 | ????39 | ????11 | ????9 | ????81.82
* | 0.0238 |
Tried Radix Scrophulariae total glycosides 3 | ????78 | ????9 | ????8 | ????88.89
* | 0.0152 |
(
*Compare with negative control p<0.05.)
Experiment conclusion: compared three various dose of Radix Scrophulariae total glycosides and Aspirin Enteric-coated Tablets and suppressed the drug effect that collagen protein-epinephrine brings out the formation of mice thrombus in vivo, the result shows that the Radix Scrophulariae total glycosides has the thrombotic effect of good inhibition, wherein, high dose group and negative control group relatively have significant difference, its oral effect dosage is 39mg/kg, obviously is better than Aspirin Enteric-coated Tablets.
Three, to the protective effect of middle cerebral artery thromboembolism rat model
1. experiment material
1.1 animal: the SD rat, male, 250-350g, available from Nanjing University of Traditional Chinese Medicine's animal center, the quality certification number: SCXK (Soviet Union) 2002-0015.
1.2 medicine: the Radix Scrophulariae total glycosides (is provided lot number: 040819) by the Kaierteng Science and Technology Co., Ltd., Shenzhen City; XUESAITONG PIAN (manufacturer: Yunnan Jintaide Notoginseng Industry Co., Ltd; Batch number: 040511).
1.3 dosage and grouping: Radix Scrophulariae total glycosides high dose group (54mg/kgd), dosage group (27mg/kgd) in the Radix Scrophulariae total glycosides, Radix Scrophulariae total glycosides low dose group (13.5mg/kgd), positive drug group (XUESAITONG PIAN) is (27mg/kgd).
1.4 reagent: chloral hydrate, produce lot number: 20000218 by China Medicine (Group) Shanghai Chemical Reagent Co.,
2,4,5-triphenyltetrazolium chloride (TTC) is produced lot number: F20030102 by China Medicine (Group) Shanghai Chemical Reagent Co..
Benzylpenicillin sodium for injection Lukang Medical Co., Ltd., Shandong produces, lot number: S021202.
Glacial acetic acid, chemical reagent factory in Nanjing provides lot number: 20001103.
Pentobarbital sodium is produced (advancing to divide), lot number: F20020405 by China Medicine (Group) Shanghai Chemical Reagent Co..
1.5 instrument: AF-1 electrically heated drying cabinet, East Platform electrical apparatus factory; GS-15R type desk type high speed refrigerated centrifuger, U.S. Beckman company; DK-8D type constant temperature water bath, the grand experimental facilities company limited of last Nereid; MS1 type vortex agitator, German IKA company; The Sartorius electronic balance, German Sartorius company; The T25basic refiner, German IKA company.
1.6 the preparation of nylon embolus: the reference literature method, with a long 50mm, the heating of an end of the nylon wire of diameter 0.24mm is melt into slick sphere, and at 18.0mm place, distance pommel labelling, standby after the alcohol wipe.
2. test method
2.1 experimental program: adopt the method for Longa, and improved, prepare this model with internal carotid artery line bolt method.Get 72 of rats, be divided into 6 groups, be i.e. sham operated rats, XUESAITONG PIAN group, model group, the high, medium and low dosage group of Radix Scrophulariae total glycosides.Every group 12, gastric infusion, after half an hour with 10% chloral hydrate anesthesia (350mg/kg, ip), facing upward the position is fixed on the operating-table, the cervical region median incision, after cutting skin, passivity is separated, find out common carotid artery (CCA), continue to separate downwards and ligation external carotid artery (ECA) and each branch's (occipital artery of external carotid artery, superior thyroid artery, lingual artery and facial artery), peel off vagus nerve gently, isolate internal carotid artery (ICA) and arteria pterygopalatina, the ECA proximal part is equipped with line, closes ICA and CCA with the bulldog clamp folder, cuts an osculum at ECA apart from the ICA2mm place, one nylon wire (diameter 0.24mm) is inserted ECA and enters CCA, the light bundle is equipped with line, prevents hemorrhagely, cuts off ECA, unclamp the bulldog clamp of ICA, traction ECA makes itself and ICA approximately in line, gently the pumpback nylon wire, make it along going into ICA, (the nylon wire insertion depth is about 18mm, shows that nylon wire has passed middle cerebral artery (MCA) The initial segment, arrives anterior cerebral artery (ACA) near-end to continue propelling downwards, all blood of having blocked MCA comprise the blood supply from ICA and ACA and posterior cerebral artery for the source.Unclamp the CCA bulldog clamp, tighten line fully, stay the long the end of a thread of 1cm outward, skin suture steams again and raises.
Nylon wire is gently drawn in perfusion again behind the ischemia 3h when pouring into again, and nylon wire is extracted outside the cranium, and blood flow is logical again, prunes nylon wire, and skin suture steams again nature and feeds.Above process is all carried out under room temperature constant (24~25 ℃) situation, is beneficial to estimate the cerebral ischemia situation.Observation is to the influence of focal cerebral ischemia in rats behavior scoring and cerebral infarct size.
2.2 rat experiment cerebral ischemia behavior scoring method: with reference to the method for Bederson etc. the behavioral deficiency of postoperative animal is carried out rank scores, grade scale is as follows:
The animal symptom | Grade |
Carry tail when unsettled, two forelimbs of animal all stretch to the floor direction and do not have other behavioral deficiencies | 0 grade |
Carry tail when unsettled, the operation offside forelimb of animal shows as wrist elbow flexing, shoulder inward turning, elbow abduction, is close to thoracic wall | 1 grade |
Animal is placed on the smooth flat, and pushing hands art side shoulder resistance to side shifting the time reduces | 2 grades |
During the animal walking freely, to performing the operation to the side ring commentaries on classics or turn-taking | 3 grades |
(rating fraction is high more, shows that the behavioral deficiency of animal is serious more)
2.3 the measurement of cerebral infarct size: 2,4, cerebral infarct size is measured in 5-triphenyltetrazolium chloride (TTC) dyeing: back 24 hours broken ends of rat medium-sized artery line bolt (MCAO) are got brain, brain is put (2~3 ℃) 10min in the ice-cold normal saline, after removing olfactory bulb, cerebellum and low brain stem, make not stagnant blood dirt of surface with the normal saline flushing brain, blot on every side moisture after, along the crown four blade of cutting, be cut into five.First cutter is before brain in the middle of the utmost point and the optic chiasma line; Second cutter is at the optic chiasma position; The 3rd cutter is at the infundibular stalk position; Four blade is between the infundibular stalk and the posterior lobe tail utmost point.Rapidly the brain sheet is put then in the phosphate buffer solution that 5ml contains 1%TTC, the lucifuge temperature was incubated 30 minutes, wherein stirred once every 7~8 minutes, dyed after, normal cerebral tissue is rose, and blocking tissue is white in color, and boundary is clearly demarcated.After temperature is incubated and finished the brain sheet is taken a picture, cut the calculating of weighing of red white colour district.Then according to the weight area method, calculate five brain sheets area of totally 10 planar gross areas and infarct area respectively, obtain the percentage ratio that the infarct area accounts for the hemisphere gross area, i.e. the infraction rate.
2.4 the mensuration of brain water content: behind the sacrifice of animal, take out brain and claim to place 115 ℃ of electrically heated drying cabinets to dry to constant weight cerebral tissue after the weight in wet base, claim dry weight, calculate brain water content by following formula:
Water content (%)=[(weight in wet base-dry weight)/weight in wet base] * 100%
Cerebral index=(cutaneous horn weight/body weight) * 100
2.5 pathological tissue inspection: repeat 2.1 tests, behind the sacrifice of animal, get its cerebral tissue and place 10% formalin internal fixation, routine is drawn materials, paraffin embedding, slice thick 4~5 μ m, HE dyeing, the pathology professional reads sheet, and according to the pathological changes light and heavy degree, sxemiquantitative is "+" successively, " ++ ", " +++", " ++ ++ ", no pathological changes normal structure is labeled as "-", keeping the score respectively again is 1 minute, 2 minutes, and 3 minutes, 4 minutes, 0 minute, all marks that add up drew total points, calculate (X ± SD) the dividing equally of every treated animal, the high more prompting of score value damage is serious more, otherwise then illustrates damage after drug treating and alleviate, and treatment is effective.
2.6 date processing: use Microsoft Excel software to carry out date processing to all data, and through t inspection statistics analysis result.
3. result
3.1 the influence that the Radix Scrophulariae total glycosides is marked to the behavioristics of Focal Cerebral Ischemia Reperfusion rat: the results are shown in Table 5
Table 5 Radix Scrophulariae total glycosides is to the influence of behavioristics's scoring of Focal Cerebral Ischemia Reperfusion rat
Group | The example number | Dosage | Behavioristics's scoring |
??4h | ??24h |
Model group | ????10 | ?-- | ??2.6±0.53
ΔΔ | ??2.5±0.53
ΔΔ |
Sham operated rats | ????11 | ?-- | ??0 | ??0 |
The positive drug group | ????10 | ?27mg/kg·d | ??2.56±0.53 | ??1.67±0.50
* |
Low dose group | ????12 | ?13.5mg/kg·d | ??2.63±0.52 | ??1.88±0.64 |
Middle dosage group | ????11 | ?27mg/kg·d | ??2.57±0.5 | ??1.67±0.71
* |
High dose group | ????11 | ?54mg/kg·d | ??2.5±0.53 | ??1.5±0.93
** |
Compare with model group,
*P<0.05,
*P<0.01.Compare Δ P<0.05, Δ Δ P<0.01 with sham operated rats.
As can be seen from the above table, when 4h and 24h, delayed ischemic neurological deficits has in various degree all appearred in all experimental animals.During 4h, behavioristics's score of each administration treated animal and model group be there was no significant difference relatively, behind 24h, behavioristics's scoring of each dosage treated animal of Radix Scrophulariae total glycosides is all on a declining curve, and significantly be lower than model group, learn by statistics and handle, significant difference is arranged, prompting Radix Scrophulariae total glycosides can improve behavioristics's obstacle of animal pattern.
3.2 the influence to cerebral infarct size and infraction rate: see Table 6.
The influence of table 6 pair Focal Cerebral Ischemia Reperfusion rat cerebral infarction area and infraction rate (X ± SD)
Group | The example number | Dosage | Infarct size (cm
2)
| Infraction rate (%) | Suppression ratio (%) |
Model group | ??10 | ?-- | ?3.35±0.44
ΔΔ | ??21.65±3.3
ΔΔ | |
Sham operated rats | ??11 | ?-- | ?0 | ??0 | |
The positive drug group | ??10 | ?27mg/kg·d | ?2.35±1.05
** | ??13.13±5.69
** | ??39.35 |
Low dose group | ??12 | ?13.5mg/kg·d | ?2.84±1.03 | ??16.56±5.19
* | ??23.51 |
Middle dosage group | ??11 | ?27mg/kg·d | ?1.46±0.85
** | ??8.94±4.88
** | ??58.71 |
High dose group | ??11 | ?54mg/kg·d | ?1.26±0.4
** | ??7.52±2.78
** | ??65.27 |
Annotate: compare with model group,
*P<0.05,
*P<0.01.Compare Δ P<0.05, Δ Δ P<0.01 with sham operated rats.
Show that by table 2 result cerebral infarct size and the infraction rate of each administration group rat all are starkly lower than model group, learn by statistics and handle that significant difference is arranged, prompting Radix Scrophulariae total glycosides can obviously dwindle the cerebral infarct size of rat model, reduces the infraction rate.
3.3 the influence to brain water content and cerebral index: see Table 7.
The influence of table 7 pair Focal Cerebral Ischemia Reperfusion rat brain index and brain water content (X ± S)
Group | The example number | Dosage | Cerebral index | Water content (%) |
Model group | ????10 | ?-- | ??0.54±0.06
ΔΔ | ??83.54±2.47
ΔΔ |
Sham operated rats | ????11 | ?-- | ??0.48±0.05 | ??81.09±1.73 |
The positive drug group | ????10 | ?27mg/kg·d | ??0.52±0.05 | ??81.74±2.68 |
Low dose group | ????12 | ?13.5mg/kg.d | ??0.52±0.04 | ??82.12±1.7 |
Middle dosage group | ????11 | ?27mg/kg·d | ??0.49±0.02
* | ??81.02±2.39
* |
High dose group | ????11 | ?54mg/kg·d | ??0.49±0.03
* | ??81.1±1.52
* |
Annotate: compare with model group,
*P<0.05,
*P<0.01.Compare Δ P<0.05, Δ Δ P<0.01 with sham operated rats.
Show that by table 3 result rat model cerebral index and water content all are higher than sham operated rats, Radix Scrophulariae total glycosides high dose, middle dosage can reduce the cerebral index and the brain water content of rat model, with model group significant difference are arranged more all.Prompting Radix Scrophulariae total glycosides can alleviate cerebral edema.
3.4 the influence to the ischemia apoplexy histopathology: see Table 8.
Table 8 Radix Scrophulariae total glycosides is to the influence of ischemia apoplexy rat brain histopathology
Group | Brain number (n) | The degree score value of brain damaged |
Model group | ????8 | ????5.00±1.6
ΔΔ |
Sham operated rats | ????8 | ????0.88±1.25 |
The positive drug group | ????6 | ????3.5±0.75
* |
Low dose group | ????5 | ????4.2±1.30 |
Middle dosage group | ????8 | ????3.33±1.63
* |
High dose group | ????6 | ????1.67±1.36
** |
Annotate: compare with model group,
* P<0.05,
*P<0.01.Compare Δ P<0.05, Δ Δ P<0.01 with sham operated rats.
Histopathology is observed, and line bolt method copies the cerebral infarction rat model, shows as cerebral tissue grey matter and/or white matter edema in various degree, the slight degeneration of neurocyte, necrosis.Positive drug and Radix Scrophulariae total glycosides are having the brain tissue impairment of alleviating effect in varying degrees to the apoplexy model, and its effect is followed successively by Radix Scrophulariae total glycosides high dose group by descending order, middle dosage group, positive drug group, low dose group.
4. conclusion
Show that from above result the Radix Scrophulariae total glycosides can improve behavioristics's obstacle of animal pattern, can obviously dwindle the cerebral infarct size of rat model, reduce the infraction rate; Reduce the water content of ischemic tissue of brain, alleviate cerebral edema.