CN1395933A - Medicine for treating cardiovascular and cerebrovascular diseases - Google Patents
Medicine for treating cardiovascular and cerebrovascular diseases Download PDFInfo
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- CN1395933A CN1395933A CN 02125648 CN02125648A CN1395933A CN 1395933 A CN1395933 A CN 1395933A CN 02125648 CN02125648 CN 02125648 CN 02125648 A CN02125648 A CN 02125648A CN 1395933 A CN1395933 A CN 1395933A
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- semen ginkgo
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Abstract
A medicine for treating cardiovascular and cerebrovascular diseases such as angina pectories, cerebral thrombus, apoplexy sequela, etc. is prepared from puerarflavone and high-purity ginkgolide. Its advantage is high preventive and curative effects.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of cardiovascular and cerebrovascular disease, specifically it is the medicament that is composited with Radix Puerariae flavone and Semen Ginkgo lactone B, belongs to field of medicaments.
Background technology
Folium Ginkgo extract is as medicinal treatment cardiovascular and cerebrovascular disease, have a lot of products both at home and abroad, Ginaton as import, home-made Jin Keluo, but these medicines all are crude extracts of Folium Ginkgo, Folium Ginkgo extract as medicinal mainly be to utilize ginkgetin contained in the Folium Ginkgo and bilobalide as active component, ginkgetin mainly is made up of Quercetin (qucrcctin) kaempferol (laemoferol) and isorhamnetin (isorhamnetin), three's proportionate relationship is roughly about 0.35: 0.35: 0.2, but present extraction process particularly the suitability for industrialized production basic controlling not the ratio between the three, if, have a strong impact on medical value according to the relevant ratio that to control between the three of reporting; The main pharmacological of ginkgetin can be expanded coronary vasodilator, increase cerebral blood flow, and Radix Puerariae flavone has similar effect, and the extraction process of Radix Puerariae flavone is simple, stable components, and therefore low price can utilize Radix Puerariae flavone to replace ginkgetin; Ginkalide B is the active composition of tool among ginkalide A, B, C, G, the M, it is hematoblastic antagonist, formation to pre-preventing thrombosis is the composition that has medical value, present industrial dna purity can reach more than 90%, but be not reported as pharmaceutical formulation with the ginkalide B of purity more than 90% at present, therefore utilize Radix Puerariae flavone and ginkgetin to have similar drug effect, form the medicine of a treatment cardiovascular and cerebrovascular disease with easy acquisition Radix Puerariae flavone band for ginkgetin that is difficult for obtaining and ginkalide B.
Summary of the invention
Purpose of the present invention utilizes Radix Puerariae flavone and ginkgetin to have similar pharmacological action just.A kind of medicine for the treatment of cardiovascular and cerebrovascular disease that can organically combine with Semen Ginkgo lactone B, thus the extraction difficulty of Folium Ginkgo can be simplified, can reach ideal therapeutic effect again, can reduce cost again simultaneously.
The objective of the invention is to realize by following technical proposal:
The medicine of treatment cardiovascular and cerebrovascular disease is characterized in that it by the medicament that the Semen Ginkgo lactone B of the Radix Puerariae flavone of 90% above purity and 90% above purity forms, and its weight proportion is
Radix Puerariae flavone 20-100 part,
Semen Ginkgo lactone B 1-20 part.
Described medicament is injection, pill, powder, electuary, drop, the tablet on any pharmaceutics.
The used Semen Ginkgo lactone B of medicine of the present invention is the product that adopts the low temperature critical method for extraction to make; it slightly carries the critical abstraction purification of low temperature with Folium Ginkgo again; it can make the effective ingredient medical value in the Folium Ginkgo improve; proved that by effect experiment Semen Ginkgo lactone B is that hematoblastic antagonist can prevent thrombosis; can remove free radical; brain cell there is oxygen lack resistant function; to acute; the brain insufficiency that chronic cerebral ischemia causes; apoplexy sequela has the excellent treatment effect; Radix Puerariae flavone is sophisticated product; it is to cerebrovascular and cardiovascular expansion; blood flow increasing has good effect; can improve hemodynamics and protection cerebral tissue and myocardial ischemia, spasmolysis is arranged again simultaneously.
Medicine of the present invention has carried out zoopery, and division is as follows as a result for it:
One, the experimental result of Semen Ginkgo lactone B treatment myocardial ischemia:
Adopt Semen Ginkgo lactone B injection, include lactone B 1mg/ml, oral agents is test group for the muddy liquid of water is provided by Chinese People's Liberation Army General Hospital, matched group is a nitroglycerin injection, content is 5mg/ml, is produced by Beijing Yimin Pharmaceutical Factory, and experimental animal is the SD rat, male and female half and half, body weight 250-300g is provided by 301 Hospital of the Chinese People's Liberation Army, and the test group injected dose is 8.0mg/kg, 6.0mg/kg, four dosage of 4.0mg/kg, 2.0mg/kg.Oral dose is 10mg/kg, 14mg/kg.
Result of the test:
With medicine of the present invention lobus posterior hypophyseos is brought out rat angina pectoris model and observe its therapeutical effect, result of the test X
2The method check moves the ST section, and the T ripple is inverted, and T method of inspection statistics is taked in effects such as decreased heart rate.
1, Semen Ginkgo lactone B intravenous fluid brings out the Electrocardiographic influence of angina pectoris to pituitrin and sees Table 1,2,3,
Table 1 BN-52021 brings out the influence of rat heart muscle ischemia to pituitrin
| Group | Dosage mg/kg | Effective routine number (effectively %) | Invalid routine number (effectively %) | Add up to | ???X 2Value | The P value |
| Matched group | ???- | ?1(7.14) | ?13(92.86) | ?14 | ||
| Nitroglycerin | ???0.5 | ?8(80.00) | ?2(20.00) | ?10 | ???39.6343 | ??＜0.001 |
| The Semen Ginkgo lactone | ???8.0 | ?11(68.75) | ?5(31.25) | ?16 | ???11.8080 | ??＜0.001 |
| The Semen Ginkgo lactone | ???6.0 | ?2(50.00) | ?2(50.00) | ?4 | ???4.1143 | ??＜0.05 |
| Semen Ginkgo lactone B | ???4.0 | ?5(35.71) | ?9(64.29) | ?14 | ???3.3938 | ??＞0.05 |
| Semen Ginkgo lactone B | ???2.0 | ?0(0.00) | ?6(100.0) | ?6 | ???0.4511 | ??＞0.05 |
| Add up to | ?27 | ?37 | ?64 |
Annotate: degree of freedom=1, marginal value are 3.841
Table 2 Semen Ginkgo lactone B brings out rat heart muscle sum of ischemia ST section to pituitrin and moves influence
| Group | Number of elements | Dosage mg/kg | Before the iv Pit | ∑ ST section moves (mv) back 1 ' | Back 2 ' | Back 5 ' |
| Matched group | 14 | ?- | ?0.049±0.043 | 0.242±0.272# | ?0.200±0.181# | 0.173±0.135# |
| Nitroglycerin | 10 | 0.5 | ?0.035±0.035 | 0.054±0.031* | ?0.060±0.046* | 0.052±0.043* |
| Semen Ginkgo lactone B | 16 | 8.0 | ?0.054±0.031 | 0.054±0.021* | ?0.062±0.023* | 0.064±0.044* |
| Semen Ginkgo lactone B | 14 | 4.0 | ?0.069±0.056 | 0.063±0.039* | ?0.075±0.039* | 0.066±0.040* |
| Semen Ginkgo lactone B | ?6 | 2.0 | ?0.083±0.041 | 0.117±0.041 | ?0.100±0.632 | 0.112±0.068 |
Annotate: * name group P value all compares * P＜0.05 with matched group
Compare #P＜0.05 before # P value and the iv Pit
Table 3 BN-52021 brings out the influence of heart rate behind the rat heart muscle ischemia to pituitrin
| Group | Number of elements | Dosage mg/kg | Before the iv Pit | ∑ ST section moves (mv) back 1 ' | Back 2 ' | Back 5 ' |
| Matched group | 14 | ?- | ?344.6±105.9 | 243.3±82.34# | 247.2±65.69# | 237.5±41.98# |
| Nitroglycerin | 10 | 0.5 | ?350.1±49.71 | 375.0±60.55*** | 339.5±31.92*** | 334.5±25.65*** |
| Semen Ginkgo lactone B | 16 | ?8.0 | ?346.6±35.01 | 280.6±68.95 | 283.3±52.52 | 287.9±47.33** |
| Semen Ginkgo lactone B | 14 | 4.0 | ?351.4±42.20 | 310.9±79.86* | 276.7±60.35 | 280.7±54.73* |
| Semen Ginkgo lactone B | ?6 | 2.0 | ?354.7±49.40 | 252.0±43.84 | 288.0±64.64 | 274.3±58.83 |
Annotate:
*Each is organized the P value and all compares with matched group
*P＜0.05
*P＜0.01
* *P＜0.001
Compare # P＜0.05 before #P value and the iv Pit
2, Semen Ginkgo lactone B intravenous fluid to coronary artery ligation after the Electrocardiographic influence of rat
See Table 4,5
Table 4 BN-52021 to coronary ligation after influence (the mv) (X ± SD) of Mus ∑ ST section voltage
After the preceding ligation of group ligation
15 days heavy dose of 0.02 ± 0.02 0.27 ± 0.19 0.17 ± 0.15 0.13 ± 0.12 0.056 ± 0.089 (n=11) tables 5 of (medicine 12 days) model group 0.02 ± 0.01 0.27 ± 0.13 0.25 ± 0.13 0.15 ± 0.19 0.139 ± 0.122 (n=10) of 3 days 7 days (medicine 4 days) 11 days (medicine 8 days), BN-52021 to coronary ligation after rat T ripple be inverted impact that % occurs (before the group ligation of X ± SD) after the ligation
3 days 7 days (medicine 4 days) 11 days (medicine 8 days) 15 days heavy dose of 0 81.82 27.27 54.55 30.00 (n=11) of (medicine 12 days) model group 0 90.0 80.00 40.00 37.50 (n=10)
3, the BN-52021 oral formulations sees Table 6 to the influence that pituitrin brings out angina pectoris rat kinetocardiogram
The oral BN-52021 of table 6 brings out the influence of rat heart muscle ischemia to pituitrin
| Group | Dosage mg/kg | Effective routine number (effectively %) | Invalid routine number (invalid %) | Add up to | ??X 2Value | The P value |
| Matched group | ?-- | ?1(7.14) | ?13(92.86) | 14 | ||
| The Semen Ginkgo lactone | ?10 | ?2(33.33) | ?4(66.67) | 6 | ??2.2596 | ＞0.05 |
| The Semen Ginkgo lactone | ?14 | ?3(50.00) | ?3(50.00) | 6 | ??4.8214 | ＜0.01 |
| Add up to | ?6 | ?20 | ?26 |
Annotate: degree of freedom=1, marginal value are 3.841
Show by above-mentioned result of the test, BN-52021 brings out the angina pectoris model to pituitrin the therapeutical effect that improves myocardial ischemia, notable therapeutic effect is arranged, and the dose-effect positive correlation arranged, the intravenous fluid effective dose is 6.0mg/kg, more remarkable with the 8.0mg/kg effect, the oral formulations effective dose is 14mg/kg.
Two, Semen Ginkgo lactone B injection is to the experimental result of the protective effect of experimental rat cerebral ischemia, experimental animal SD rat, male and female half and half, body weight 230-300g, two groups of matched group injecting normal salines of matched group and administration group, administration group injection 8mg/kg.
Result of the test:
1, Semen Ginkgo lactone B is to the influence of brain water content and cerebral index
See Table 7
Table 7 Semen Ginkgo lactone B is to the influence of brain water content and cerebral index
| Group | Number of elements | Dosage mg/kg | Cerebral index % | Brain water content % |
| Model group | 22 | ?-- | ?0.79±0.057 | ?79.06±2.027 |
| The administration group | 22 | ?8 | ?0.73±0.115* | ?77.37±3.202* |
Annotate: compare * P＜0.05 with model group
Result of the test shows that relatively there were significant differences for the brain water content of cerebral ischemic model group and cerebral index and normal control group, and brain water content and cerebral index increase the generation of explanation cerebral ischemia animal brain edema.
2, Semen Ginkgo lactone B is to the influence of brain capillary permeability
See Table 8
Table 8 Semen Ginkgo lactone B is to the influence of brain capillary permeability
| Group | Dosage (mg/kg) | Number of elements | The content (ug/g) of ivens orchid in the brain | The P value |
| Model group | ????-- | ??17 | ??10.072±1.889 | |
| The administration group | ????8 | ??17 | ??5.809±0.801 | ＜0.01 |
The result shows cerebral ischemic model and administration group relatively, P＞0.05, and Semen Ginkgo lactone B can reduce the cerebrovascular transparency, thereby the cerebral ischemia brain is played a protective role.
3, tectology is observed:
Normal control group neurocyte is normal, and nuclear membrane is clear, and kernel is obvious, and the neurogliocyte kernel is clear, bright or light the dying of endochylema, and cell membrane and nuclear membrane are clear.Blood capillary and little vessel lumen are narrower, and neurocyte, blood capillary are with all producing the space around the little blood vessel.
The endochylema of model group cerebral tissue neurocyte and karyon concentrate, and dyeing is dark, and whole cell space diminishes, aixs cylinder and dendron all are acute angle shape, neurocyte and blood capillary, little circumvascular space broadening, and a matter is loose, neurogliocyte swelling, its endochylema lucent area strengthens.
Heavy dose of group cerebral tissue neurocyte concentrates and engrain has the trend of alleviating than model group.The matter porousness also alleviated to some extent than model group between neurogliocyte swelling reached.
Three, the experimental result of Radix Puerariae flavone and Semen Ginkgo lactone B combination therapy angina pectoris rat model,
Radix Puerariae flavone is made into the muddy liquid of 10mg/kg with distilled water, and Semen Ginkgo lactone B is made into the suspension of 1mg/kg with distilled water.
Experimental animal: the SD rat, 30, male, body weight 220-280g, one group, two groups of separating tests, matched group, 10 every group.
Result of the test:
1, pituitrin brings out the electrocardiogram influence of Acute Myocardial Ischemia in Rats (angina pectoris), sees Table 9
Table 9 pituitrin brings out the influence of rat heart muscle ischemia
| Group | Effective routine number (effectively %) | Invalid routine number (invalid %) | Add up to | The X2 value | The P value |
| Matched group | ????0(0) | ????10(100) | ????10 | ||
| Be subjected to 1 group of reagent | ????7(70) | ????3(30) | ????10 | ??11.7121 | ????＜0.01 |
| Add up to | ????7 | ????13 | ????20 |
Annotate: degree of freedom=1, marginal value are 3.841
Table 10 pair pituitrin brings out the influence of rat heart muscle ischemia
| Group | Effective routine number (effectively %) | Invalid routine number (invalid %) | Add up to | ????X 2Value | The P value |
| Matched group | ????0(0) | ????10(100) | ????10 | ||
| Be subjected to 2 groups of reagents | ????1(10) | ????9(90) | ????10 | ????1.0526 | ????＞0.05 |
| Add up to | ????1 | ????19 | ????20 |
Annotate: degree of freedom=1, marginal value are 3.841
Result of the test shows the have clear improvement effect of myocardial ischemia of medicine of the present invention, can suppress that first-phase T section ripple behind the intravenous injection pituitrin is raised and low flat inversion of T ripple of the second phase.ST is displacement, variations such as decreased heart rate.
Owing to take technique scheme to make the technology of the present invention compared with the prior art have following advantage and effect:
A) by animal model test being proved this medicine has the curative effect of highly significant to cardiovascular and cerebrovascular disease, particularly to crown A blood supply insufficiency, angina pectoris, cerebral embolism, acute and chronic brain insufficiency, apoplexy sequela etc. have obvious treatment and preventive effect;
B) the clinical scope of application is extensive, and drug effect is fast, has no side effect;
The specific embodiment
Embodiment 1
Get the Radix Puerariae flavone 20g of 90% purity and the Semen Ginkgo lactone B20g of 94% purity, mix routinely formulation method and make injection or drop.
Embodiment 2
Get the Radix Puerariae flavone 60g of 92% purity and the Semen Ginkgo lactone B15g of 94% purity, mix routinely formulation method and make powder or tablet.
Embodiment 3
Get the Radix Puerariae flavone 100g of 94% purity and the Semen Ginkgo lactone B1g of 94% purity, mix routinely formulation method and make electuary or pill.
Claims (2)
1, the medicine of treatment cardiovascular and cerebrovascular disease is characterized in that it by the medicament that the Semen Ginkgo lactone B of the Radix Puerariae flavone of 90% above purity and 90% above purity forms, and its weight proportion is
Radix Puerariae flavone 20-100 part,
Semen Ginkgo lactone B 1-20 part.
2, the medicine of treatment cardiovascular and cerebrovascular disease according to claim 1 is characterized in that described medicament is injection, pill, powder, electuary, drop, the tablet on any pharmaceutics.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02125648 CN1395933A (en) | 2002-07-26 | 2002-07-26 | Medicine for treating cardiovascular and cerebrovascular diseases |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02125648 CN1395933A (en) | 2002-07-26 | 2002-07-26 | Medicine for treating cardiovascular and cerebrovascular diseases |
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| CN1395933A true CN1395933A (en) | 2003-02-12 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104415044A (en) * | 2013-08-30 | 2015-03-18 | 陈震 | Pharmaceutical composition and preparation thereof for treating stroke and sequelae thereof |
| CN105287499A (en) * | 2015-10-09 | 2016-02-03 | 成都普瑞法科技开发有限公司 | Natural pharmaceutical composition for preventing and treating cardiovascular and cerebrovascular diseases and application of pharmaceutical composition |
-
2002
- 2002-07-26 CN CN 02125648 patent/CN1395933A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104415044A (en) * | 2013-08-30 | 2015-03-18 | 陈震 | Pharmaceutical composition and preparation thereof for treating stroke and sequelae thereof |
| CN104415044B (en) * | 2013-08-30 | 2018-10-16 | 陈震 | A kind of pharmaceutical composition and its preparation for treating apoplexy and its sequelae |
| CN105287499A (en) * | 2015-10-09 | 2016-02-03 | 成都普瑞法科技开发有限公司 | Natural pharmaceutical composition for preventing and treating cardiovascular and cerebrovascular diseases and application of pharmaceutical composition |
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