CN1569008A - Medicine for preventing and treating cerebral infarction - Google Patents
Medicine for preventing and treating cerebral infarction Download PDFInfo
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- CN1569008A CN1569008A CN 200410026150 CN200410026150A CN1569008A CN 1569008 A CN1569008 A CN 1569008A CN 200410026150 CN200410026150 CN 200410026150 CN 200410026150 A CN200410026150 A CN 200410026150A CN 1569008 A CN1569008 A CN 1569008A
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- cerebral infarction
- verbascoside
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- medicine
- puerarin
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Abstract
The invention discloses a medicine for preventing and treating cerebral infarction, i.e. Verproside, related experiment has proved that Verproside has good effect in treating cerebral infarction, especially strong capacity for improving antioxidant capability.
Description
Technical field
The present invention relates to a kind of medicine that is used to prevent and treat cerebral infarction, say from another angle to the present invention relates to a kind of existing novel application of compound.
Background technology
Because cerebrum ischemia causes cerebral infarction can cause the obstacle of aspects such as patient's action, behavior and intelligence.For treating this class disease, now existing part medicine is in clinical use, for example puerarin etc.But existing treatment cerebral infarction medicine generally all has certain toxic and side effects, though can improve patient status in clinical use, also can make patient produce some negative effects.
Summary of the invention
The invention provides a kind of better therapeutic effect that has, low toxic and side effects, be used to prevent and treat the medicine of cerebral infarction.
The present invention is the medicine with Verbascoside preparation control cerebral infarction.
The present inventor once disclosed the relevant situation of extracting Verbascoside from goatweed in Chinese invention patent application 99123015.9, and provided the location parameter and the relevant molecular structure of Verbascoside in detail.
Through studies show that of inventor, Verbascoside can be plugged with the better prevention effect to cerebral infarction, and shows than existing medicine, as puerarin, better effect all has the improvement effect to the various indexs of cerebral ischemic injury, and especially outstanding is the Total antioxidant capacity that can obviously improve body.
Show at the completed animal model test of the present invention, rat for cerebral infarction, can significantly reduce the volume that infraction takes place lesion portion after using Verbascoside, improve the symptom of being tried the rat neurologic defect, reduce the activity of being tried the rat plasma lactic acid dehydrogenase, make superoxide dismutase and glutathion peroxidase return to normal level, reduce MDA content in plasma nitric oxide and the serum, improve Total antioxidant capacity.
The correlation test that carried out also shows, as disclosed content in the Chinese invention patent application 03114454.3, the Verbascoside using dosage does not have toxic and side effects during up to 2g/kg (ip) basically, and the half lethal dose of known puerarin be 0.735g/kg (iv).
Description of drawings
Fig. 1 is the influence of Verbascoside to the cerebral infarction rat behavior, and wherein vertical coordinate is tried rat behavior scoring index.
Fig. 2 for Verbascoside to being tried the influence of rat cerebral infarction volume, wherein vertical coordinate is an infarct volume percentage ratio.
Fig. 3 to Fig. 6 is for being tried the rat brain slice photo.Wherein Fig. 3 is a sham operated rats, Fig. 4 is for being tried Mus cerebral infarction group, Fig. 5 is every Mus brain section photo behind the Verbascoside that is tried interim lumbar injection 10mg/kg (body weight), and Fig. 6 is every Mus brain section photo behind the Verbascoside that is tried interim lumbar injection 50mg/kg (body weight).
Fig. 7 for Verbascoside to being tried the influence of rat plasma lactic acid dehydrogenase activity, wherein vertical coordinate is a lactic acid dehydrogenase activity, unit is U/l.
Fig. 8 for Verbascoside to being tried the influence of rat plasma nitric oxide level, wherein vertical coordinate is a concentration, unit is μ mol/L.
Fig. 9 for Verbascoside to being tried the influence of rat plasma Total antioxidant capacity, wherein vertical coordinate is a Total antioxidant capacity, unit is U/ml.
Figure 10 for Verbascoside to being tried the influence of rat blood serum malonaldehyde, wherein vertical coordinate is the serum concentration of malondialdehyde, unit is nmol/ml.
The rat blood serum superoxide dismutase is active to be influenced Figure 11 to being tried for Verbascoside, and wherein vertical coordinate is a superoxide dismutase activity, and unit is nU/ml.
Figure 12 for Verbascoside to being tried the influence of rat blood serum activity of glutathione peroxidase, wherein vertical coordinate is the serum activity of glutathione peroxidase, unit is U/ml.
PPG10 is Verbascoside 10 (mg/kg) among the above-mentioned figure, and PPG50 is Verbascoside (50mg/kg).
The specific embodiment
The present invention explains orally below in conjunction with related experiment, and the treatment cerebral infarction medicine Pueraria Mirifica element that has adopted existing use in following experiment is as positive control.
Laboratory animal: the used laboratory animal of the present invention is the Wistar rat, and body weight 200～280g is provided by Lanzhou medical college Experimental Animal Center.
Experiment is that the U.S. produces the blue sub-thread surgery of 4-0 nylon yarn, about 0.2 millimeter of diameter with vascular peg stay plug silk thread.Earlier the silk thread head is scalded glomeration before using.
To be tried rat and be divided five groups at random, every group of 7 rats, each group is respectively: sham operated rats, cerebral infarction group, puerarin group, 2 groups of 1 group of administration and administrations.The puerarin group is at art lumbar injection every day first three day puerarin in test, and injection volume is 50mg/kg (a Mus body weight).The administration animal is at art lumbar injection every day first three day Verbascoside, and wherein administration is injected Verbascoside 10mg/kg (Mus body weight) for 1 group, 2 groups of injections of administration Verbascoside 50mg/kg (Mus body weight).The cerebral infarction group is injected the normal saline of equivalent every day first three day in art.Cerebral infarction model is set up: with reference to Zea longa bolt collimation method, carried out intraperitoneal anesthesia (35mg/kg) with 10% chloral hydrate to trying Mus.Through internal carotid artery, insert the bolt line prepare along right common carotid artery, the power that is hampered is ended, and insertion depth is 23 ± 0.5mm, is tried the blood flow of Mus middle cerebral artery with blocking-up, causes focal cerebral ischemia.Bolt line outer ends is placed subcutaneous, realize that gently carry the bolt line when pouring into gets final product again.Cerebral ischemia was gently carried the bolt line in 4 hours then, and blood is passed through again, made cerebral ischemia in this way---and perfusion property damage again reaches the target of cerebral infarction.Sham operated rats is handled with above-mentioned operation process, but the bolt line only inserts 5mm, and this length can not cause cerebral ischemia.
After being tried the Mus ischemia, poured into again after 2 hours in 4 hours and carry out neurological deficits score.Standards of grading: 1) carry the Mus tail, receive in the left fore, left side shoulder inward turning person 1-4 branch; 2) rat is put smooth flat, push away right shoulder and move resistance reduction person 1-3 branch to the left; 3) the left fore muscular tension reduces the 1-3 branch.Scoring totally 10 minutes, mark is high more, and the animal subject behavior disorder is remarkable more.
After neurological deficits score is finished, the rat sacrificed by decapitation, take out the Mus brain rapidly, placed frozen water 10 minutes, get coronalplane and evenly be cut into the thick brain sheet of 2mm, put into 2% TTC solution (37 ℃) dyeing 30 minutes rapidly, measure every brain sheet infarct size and the gross area calculates the percentage rate that cerebral infarct volume accounts for full brain volume with micro-image analyzer.
From standing ischemia---the Mus carotid artery blood sampling of reperfusion injury, measure the ability of plasma lactic dehydrogenase activity, nitric oxide level and total antioxidation, and measure serum malonaldehyde, superoxide dismutase and activity of glutathione peroxidase.
Above measurement result is all represented with x ± SD, with t check analysis result.
Experimental result:
1, Verbascoside is to the influence of function of nervous system
Except that sham operated rats, tried respectively to organize rat and in various degree neurologic defect symptom all occurred, show as in the left fore and receive; To laterally inclined, thrust drag descends body to the left to focus; The oriented paralysis side phenomenon of spinning during the part activities in rats.As seen compare with sham operated rats, serious neurologic defect symptom appears in the cerebral infarction group.And two administration groups of injection puerarin or Verbascoside all can obviously be improved the symptom of rat neurologic defect.Experiment finds that also when dosage was identical, the effect of Verbascoside was suitable with the puerarin effect.About Verbascoside accompanying drawing 1 is seen in cerebral infarction rat behavior influence.N=7 wherein, x ± SD. and sham operated rats relatively, ##P＜0.01; Compare with the cerebral infarction group
*P＜0.01.
2, Herba Verbasci Thapsi is to the influence of rat cerebral infarction volume
Serious cerebral infarction appears in the cerebral infarction group, and cerebral infarction does not appear in sham operated rats, proves that cerebral infarction model sets up successfully.And the puerarin group makes infarct volume reduce by 22.5% (P＜0.05).1 group of administration and administration make infarct volume reduce by 17.8% and 35.6% (P＜0.01) respectively for 2 groups, referring to accompanying drawing 2.N=7 wherein, x ± SD. and sham operated rats relatively, ##P＜0.01; Compare with the cerebral infarction group
*P＜0.05,
*P＜0.01.
Brain section shows, referring to accompanying drawing 3 to accompanying drawing 6, the section of sham operated rats does not have the low contrast zone that ischemia forms, and the low contrast zone that has tangible ischemia to cause in the section of cerebral infarction group, Verbascoside administration group obviously reduces because of the low contrast zone that ischemia forms, and Verbascoside dosage is the essentially no low contrast of the brain section zone of 50mg/kg.When using drug dose identical, the effect of Verbascoside is than puerarin slightly good (P＞0.05).
3, Verbascoside is to the active influence of plasma lactic dehydrogenase (LDH)
Compare with sham operated rats, cerebral infarction group LDH is active to increase by 1.3 times.Puerarin makes active 13.7% (P＜0.05) that reduces of LDH, and Verbascoside 10mg/kg group and 50mg/kg group make LDH reduce by 15.8% and 21.2% respectively.When dosage was identical, the effect of Verbascoside was than puerarin slightly good (P＞0.05), referring to accompanying drawing 7.N=7 wherein, x ± SD. and sham operated rats relatively, ##P＜0.01; Compare with the cerebral infarction group
*P＜0.05.
4, Verbascoside is to the influence of blood plasma nitric oxide (NO) content
Compare with sham operated rats, cerebral infarction group content of nitric oxide has increased by 1.5 times.Make content of nitric oxide reduce by 39.2% (P＜0.01) with cerebral infarction group comparison puerarin, and Verbascoside 10mg/kg group and 50mg/kg group can make content of nitric oxide reduce by 34.5% and 38.6% (P＜0.05) respectively, Verbascoside and puerarin do not have significant difference (P＞0.05) to effect of nitric oxide when dosage is identical, referring to accompanying drawing 8.N=7 wherein, x ± SD. and sham operated rats relatively, ##P＜0.01; Compare with the cerebral infarction group
*P＜0.01.
5, Verbascoside is to the influence of blood plasma Total antioxidant capacity
Cerebral infarction group blood plasma Total antioxidant capacity reduces by 32.8% (P＜0.05), puerarin can not improve blood plasma Total antioxidant capacity (P＞0.05), and Verbascoside 10mg/kg and 50mg/kg can make Total antioxidant capacity increase by 1.3 and 1.4 times respectively, the effect that increases the blood plasma Total antioxidant capacity significantly is better than puerarin, referring to accompanying drawing 9.N=7 wherein, x ± SD. and sham operated rats relatively, #P＜0.01; Compare with the cerebral infarction group
*P＜0.05.
6, Verbascoside is to the influence of serum malonaldehyde (MDA)
2.3 times (P＜0.01) of cerebral infarction group Content of MDA rising, puerarin can make MDA reduce by 39.7%, and Verbascoside 10mg/kg and 50mg/kg can make MDA content reduce by 47.2% and 48.9% (P＜0.01) respectively, and when dosage was identical, the effect of Verbascoside was slightly better than puerarin.Referring to accompanying drawing 10.N=7 wherein, x ± SD. and sham operated rats relatively, ##P＜0.01; Compare with the cerebral infarction group
*P＜0.01.
7, Verbascoside is to the influence of serum superoxide dismutases (SOD)
The cerebral infarction group, activity of SOD in serum reduces by 10.2%.And puerarin group, administration 1 given and administration all can make activity of SOD in serum return to normal level for 2 groups.Referring to accompanying drawing 11.N=7 wherein, x ± SD. and sham operated rats relatively, ##P＜0.01; Compare with the cerebral infarction group
*P＜0.05,
*P＜0.01.
8, Verbascoside is to the active influence of serum glutathion peroxidase (GSH-Px)
Cerebral infarction group serum GSH-Px is active to reduce (P＜0.01), and puerarin and Verbascoside all can make serum GSH-Px activation recovering to normal level, referring to accompanying drawing 12.N=7 wherein, x ± SD. and sham operated rats relatively, ##P＜0.01; Compare with the cerebral infarction group
*P＜0.01.
By above experiment as seen, Verbascoside is plugged with better therapeutic effect to cerebral infarction, and its effect is better than existing medicine puerarin, and is especially more outstanding on the raising oxidation resistance.On the other hand, show by the toxicity test that Verbascoside is carried out, its half lethal dose LD50＞2,000mg/kg belongs to a kind of nontoxic basically medicine, can be referring to Chinese invention patent application 99123015.9 disclosed relevant contents about this point.And the LD50=750mg/kg of existing medicine puerarin, the toxicity of visible puerarin is bigger more than three times than Verbascoside.Therefore Verbascoside is a kind of very valuable, and effect is better than the medicine of the control cerebral infarction of prior art.
Claims (1)
1, the purposes of Verbascoside is characterized in that being used to prepare the medicine of preventing and treating cerebral infarction.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100261506A CN100341514C (en) | 2004-05-14 | 2004-05-14 | Medicine for preventing and treating cerebral infarction |
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| CNB2004100261506A CN100341514C (en) | 2004-05-14 | 2004-05-14 | Medicine for preventing and treating cerebral infarction |
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| CN1569008A true CN1569008A (en) | 2005-01-26 |
| CN100341514C CN100341514C (en) | 2007-10-10 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008542363A (en) * | 2005-05-30 | 2008-11-27 | コリア リサーチインスティテュート オブ バイオサイエンス アンド バイオテクノロジー | Pharmaceutical composition containing a Pseudosimachion longifolium extract having anti-inflammatory, anti-allergic and anti-asthmatic activity and a catarpol derivative isolated therefrom |
| CN102119934B (en) * | 2010-01-11 | 2012-07-11 | 北京天衡药物研究院 | Application of verbascoside in preparation of medicaments for treating chronic prostatitis |
-
2004
- 2004-05-14 CN CNB2004100261506A patent/CN100341514C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008542363A (en) * | 2005-05-30 | 2008-11-27 | コリア リサーチインスティテュート オブ バイオサイエンス アンド バイオテクノロジー | Pharmaceutical composition containing a Pseudosimachion longifolium extract having anti-inflammatory, anti-allergic and anti-asthmatic activity and a catarpol derivative isolated therefrom |
| CN102119934B (en) * | 2010-01-11 | 2012-07-11 | 北京天衡药物研究院 | Application of verbascoside in preparation of medicaments for treating chronic prostatitis |
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| Publication number | Publication date |
|---|---|
| CN100341514C (en) | 2007-10-10 |
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Granted publication date: 20071010 Termination date: 20100514 |