CN1300593A - Medical application of pseudo-paraquilon F11 - Google Patents
Medical application of pseudo-paraquilon F11 Download PDFInfo
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- CN1300593A CN1300593A CN 99122651 CN99122651A CN1300593A CN 1300593 A CN1300593 A CN 1300593A CN 99122651 CN99122651 CN 99122651 CN 99122651 A CN99122651 A CN 99122651A CN 1300593 A CN1300593 A CN 1300593A
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Abstract
The application of pseudo-panaquilon F11 in medicine field is disclosed, which includes obviously inhibiting the dysmnesia caused by morphine and the position-preferable hehaviour and autonomous motion increasement caused by morphine, antagonism to antalgic action of morphine, stronger promotion to intelligence, and antioxidizing action for protecting organs.
Description
The present invention relates to medical technical field, exactly it is a kind of pseudo-ginsenoside F of following structure
11Medical usage.
The opioid drug abuse is one of social effects of pollution in the world today.The main cause that body and mind dependency that opioid drug causes and toleration are its abuse.At present, dependency and the toleration to opioid drug still do not have the very ideal method of preventing and treating.The medicine that research can effectively suppress opiates dependency and toleration also is one of present new drug development focus.
At present, the medicine that drug rehabilitation is used clinically mainly is divided into two big classes from the Therapeutic Method: the one, and alternative medicine, or by decrement gradually, or alternative by application class like medicine, but this kind method often causes the dependence of new a kind of medicine.The 2nd, symptomatic treatment adopts composite treatment to alleviate drug rehabilitation patient's withdrawal symptom more.Using the Chinese medicine drug rehabilitation in recent years also has some reports, but uses compound medicine more, and curative effect is medium, and is unfavorable for that dissection mechanism instructs further raising curative effect.Though physical dependence can be partly removed in above-mentioned treatment, most medicines can not be removed the psychologic dependence problem, promptly so-called " reverting to take drugs " phenomenon.
Report abroad that in recent years the saponin constituent of Radix Ginseng can resist the addiction and the tolerance effect of opium.Proper deficient syndrome with tcm clinical practice of drug abuse patient is close.Thereby in numerous drug rehabilitation sides medicine, also use Radix Ginseng with invigorating primordial QI more.Report that also the ocotillol type saponin in the Panax vietnamensis Ha et Grushv. has the effect of anti-morphine sample abroad.
The objective of the invention is to clearly propose pseudo-ginsenoside F
11New medical usage, it is characterized in that: have effect of anti-morphine sample and nootropic effect (comprising that the learning memory injury and the early stage senile dementia disease people that improve due to the disordered brain function improve learning and memory etc.).The present invention makes pseudo-ginsenoside F
11Can expect to become new anti-additive medicament and nootropics, and provide new approach for developing the Radix Panacis Quinquefolii resource.
The present invention finds through a large amount of screening active ingredients, separates the monomer pseudo-ginsenoside F that obtains from natural drug Radix Panacis Quinquefolii (Panaxquinquefolium L.) stem and leaf
11(pseudo-ginsenoside F
11) anti-morphine addiction and the effect of anti-morphine toleration and nootropic effect (comprising that the learning memory injury and the early stage senile dementia disease people that improve due to the disordered brain function improve learning and memory etc.) arranged.The pharmacodynamic experiment of system studies show that:
1, pseudo-ginsenoside F
11Can suppress the dysmnesia that morphine causes significantly; The autonomic activities that caused position preference behavior of remarkable antagonism morphine and morphine bring out increases; Significantly the analgesic activity of antagonism morphine and the pain that gives for a long time due to the morphine tolerate.
2, pseudo-ginsenoside F
11Stronger nootropic effect is arranged, can obviously improve the animal learning dysmnesia of intact animal and drug-induced; Pseudo-ginsenoside F
11Also have stronger antioxidation, can protect body, especially central nervous system's normal physiological function.
The present invention has provided ginseng saponin F
11New medical usage is characterized in that the effect of anti-morphine sample, nootropic effect, can expect to become novel medicine for stopping narcotic taking.Nootropic effect can comprise the learning and memory that promotes the normal person and the learning memory injury and the early stage alzheimer disease people that improve due to the disordered brain function improve learning and memory etc.The effect of anti-morphine sample mainly is to improve the dysmnesia that morphine causes; The autonomic activities that caused position preference behavior of antagonism morphine and morphine bring out increases; The analgesic activity of antagonism morphine and give the tolerance of the pain due to the morphine for a long time.Nootropic effect is pseudo-ginsenoside F
11Antioxidation, it protects body, especially central nervous system's normal physiological function effect.
Advantage of the present invention is: the present invention finds the pseudo-ginsenoside F in the stem and leaf of Radix Panacis Quinquefolii
11Have stronger anti-morphine sample effect, especially find pseudo-ginsenoside F
11Can suppress the position preference behavior that morphine causes, point out it to have therapeutical effect to psychological dependence, this is one of characteristic of the present invention.Recent research also proves pseudo-ginsenoside F
11Do not combine with opiate receptor and may disturb the signal transducting system of opiate receptor, this may constitute the new role mechanism of drug treatment function, and this is two of a characteristic of the present invention.The domestic people of having uses the scopolamine drug rehabilitation, but scopolamine can cause serious dysmnesia, is discovering pseudo-ginsenoside F
11Also have the stronger effect of kind intelligence, antioxidation, help protecting body, central nervous system's normal physiological function especially, this is three of a characteristic of the present invention.
In addition, this product toxicity is lower, in application dose and drug metabolism study process, does not see the toxic reaction that produces animal, is suitable for medical usage.
Following examples are represented practicality of the present invention, and the present invention is not limited.
Embodiment 1, morphine caused the influence of mouse memory obstacle
Adopt Morris water maze method.Every mice is trained four times every day, trains continuously 5 days.The 1st, 2 day, oral distilled water 60min behind the subcutaneous injection normal saline 30min, put into the Morris water maze with mice and trained every day; The 3rd, 4,5 days, every day oral PF
1160min behind the subcutaneous injection morphine 30min, puts into the Morris water maze with mice and trains, and record mice every day is found the time of platform, calculates the average latency of every day.(experimental result sees Table 1)
Table 1 PF
11Morphine is caused the influence of mouse memory obstacle
Group | Dosage (mg/kg) | Incubation period | ||||
The 1st day | The 2nd day | The 3rd day | The 4th day | The 5th day | ||
Blank morphine PF 11+ morphine | - 10 4+10 8+10 | 41.1±8.4 49.9±10.4 45.7±6.9 42.6±10.0 | 25.7±10.6 22.9±15.9 18.1±7.4 12.4±4.3 | 11.9±3.2 33.0±13.4 △△△20.7±8.3 18.3±9.7 * | 11.2±5.6 41.7±16.8 △△△22.9±4.5 *20.5±12.2 * | 9.2±4.5 34.2±23.0 △△△22.0±8.8 16.0±7.6 |
Δ Δ ΔCompare with blank P<0.001,
*Compare with the morphine group p<0.05
The result shows, PF
11Can suppress the dysmnesia that morphine causes significantly,
Embodiment 2, morphine caused the influence of mice position preference
The box that the place preference device is equated fully by two sizes forms that (15 * 15 * 13cm), there is a closable hole centre.Two boxes are respectively white, smooth earth and black, grid ground.Behind the matched group subcutaneous injection normal saline, put into flight data recorder immediately, the oral PF of administration group
11Behind the 60min, the subcutaneous injection morphine is put into clear box.Experiment was carried out 12 days.The 1st, 2 day, mice was free movable between two boxes, adapts to two days, the time of mice in clear box in the 3rd day record 15min.The 4th, 6,8,10 days, close the hole, put into clear box 60min after the injected in mice morphine, the 5th, 7,9,11 days, close the hole, put into black box 60min behind the injected in mice saline.The 12nd day, open the hole, make mice free movable, the time of mice in clear box in the record 15min.(experimental result sees Table 2)
Table 2 PF
11Morphine is caused the influence of mice position preference
Group | Dosage (mg/kg) | Number of animals | Base value (min) | Time (min) |
Blank morphine PF 11+ morphine | - 5 4+5 8+5 | 14 13 16 16 | 5.11±2.4 4.84±3.1 5.38±2.4 5.42±2.8 | 5.08±1.7 8.40±3.0 △△5.64±3.9 *8.40±3.6 |
The Δ ΔCompare with blank p<0.01,
*Compare with the morphine group p<0.05
Place preference reflection animal is to the psychological dependence situation of set factor, and this experiment shows that morphine can cause the behavior of visibility point preference, and this effect can be by PF
11Institute's antagonism.
Embodiment 3, morphine caused the influence of analgesic activity
Adopt the tail method of pressing.With metal holder folder mice root of the tail 1cm place, later biting with animal is index, chooses that folder tail tenderness is reacted is that animal about 1 second experimentizes.For avoiding tissue injury, it was deadline with 6 seconds.PF
11Continuous oral 5 days, subcutaneous injection morphine behind the last administration 60min measures 30,60,90 respectively, the incubation period of folder tail tenderness reaction during 120min.(experimental result sees Table 3)
Table 3 PF
11Morphine is caused the influence of analgesic activity
Group | Dosage (mg/kg) | Response latency (min) | |||
30min | 60min | 90min | 120min | ||
Blank morphine PF 11+ morphine | - 5 4+5 8+5 | 1.05±0.56 2.85±2.23 △1.95±1.84 1.06±1.02 * | 1.18±0.56 3.46±1.99 △△1.48±1.22 *1.26±1.00 ** | 1.19±0.44 2.48±1.78 △1.41±0.95 2.15±2.06 | 1.39±1.36 2.11±1.22 1.54±0.91 2.26±1.92 |
The Δ ΔP<0.01,
ΔCompare with blank p<0.05,
*P<0.01,
*Compare with the morphine group p<0.05
This experiment shows, PF
11Analgesic activity that also can the antagonism morphine.
Embodiment 4, morphine is caused the enhanced influence of mice autonomic activities
Adopt toy autonomic activities analyzer to measure.The experiment carried out 7 days, every day the subcutaneous injection morphine once, the injection before the oral PF of 60min
11Put into analyzer immediately after injecting morphine every day, behind the adaptation 5min, measure the autonomic activities number of every mice 30min, METHOD FOR CONTINUOUS DETERMINATION 7 days.(experimental result sees Table 4)
Table 4 PF
11Morphine causes the enhanced influence of mice autonomic activities
Group | Dosage (mg/kg) | The 1st day | The 2nd day | The 3rd day | The 4th day | The 5th day | The 6th day | The 7th day |
Blank morphine PF 11+ morphine | - 10 4+10 8+10 | 795.1±837.4 1011.6±751.5 406.0±326 *479.6±543.6 | 667.2±706.2 1214.5±20.8 △655.4±629.6 *652.5±772.6 * | 594.4±526.5 1243.3742.8 △550.8608.0 *665.0693.7 | 596.8604.8 1153.9472.5 △632.9469.0 *708.0754.6 | 559.3639.5 1118.2719.4 △702.5726.5 86605685.2 | 579.6479.2 1137.9407.2 △750.7700.3 807.1650.5 | 677.8675.9 1177.9555.4 779.0502.9 782.8448.4 |
ΔCompare with blank p<0.05,
*Compare with the morphine group p<0.05
This experiment shows, PF
11The autonomic activities that energy antagonism morphine brings out increases.
Embodiment 5, morphine caused the influence of mice tenderness tolerance
Adopt the tail method of pressing.The experiment carried out 9 days, every day the subcutaneous injection morphine once, the injection before the oral PF of 60min
11After the last injection morphine 24 hours, give every mouse subcutaneous injection morphine 5mg/kg, measure 30,60,90 respectively, the incubation period of folder tail tenderness reaction during 120min.(experimental result sees Table 5)
Table 5 PF
11Morphine is caused the influence of mice tenderness tolerance
Group | Dosage (mg/kg) | Response latency (second) | |||
30min | 60min | 90min | 120min | ||
Blank morphine PF 11+ morphine | - 10 4+10 8+10 | 3.06±1.87 1.69±1.21 △2.04±1.71 1.27±0.67 | 4.36±2.06 2.11±1.08 △△△3.64±2.26 *2.67±2.22 | 2.72±1.70 1.07±0.44 △△△3.17±2.15 2.79±2.42 | 2.63±2.23 1.70±1.79 3.69±2.38 *2.87±2.53 |
The Δ ΔP<0.001,
ΔCompare with blank p<0.05,
*Compare with the morphine group p<0.05
Give morphine for a long time and can produce tolerance effect, PF
11The obviously tolerance effect of antagonism morphine.
Embodiment 6, scopolamine caused the influence of mouse memory acquired disturbance
In the diving tower experiment, scopolamine (Scop) 2mg/kg significantly increases mouse wrong times, F
112mg/kg significantly reduces errors number.(the results are shown in Table 6)
Keep away in the dark experiment PQS and F
11Each dosage all makes error latence significant prolongation, F
114g/kg significantly reduces errors number, and obviously reduces wrong percentage rate.F is described
11Can significantly improve scopolamine and cause the mouse memory acquired disturbance.(the results are shown in Table 7)
Table 6, scopolamine caused the influence (diving tower method) of mouse memory acquired disturbance
Group | Dose(mg/kg) | Number(n) of mice | Number of errors |
Control Scop F 11+Scop F 11+Scop NIM | 2 2 4 0.2 | 12 23 19 20 23 | 0.25±0.62 2.18±0.80 △△△1.44±0.71 **1.75±0.72 1.43±0.73 ** |
ΔΔΔP<0.001??compared?with?Control
*p<0.05?
**p<0.01?compared?with?Scop
Table 7, scopolamine caused the influence (darkness avoidance test) of mouse memory acquired disturbance
Group | Dose (mg/kg) | Number (n) | Latencies (s) | Number of errors | Erroneous Percent |
Control Scop F 11+Scop F 11+Scop NIM | 2 2 4 0.2 | 11 11 11 11 11 | 290.55±30.38 85.55±65.86 △△△219.73±84.95 ***251.09±94.22 ***189.55±117.65 * | 0.18±0.41 1.36±0.51 △△△0.82±0.75 0.45±0.69 **1.00±0.89 | 18.18 100 72.72 36.36 63.64 |
ΔΔΔP<0.001?????compared?with?Control
*p<0.05?
**p<0.01?compared?with?Scop
Embodiment 7, chloromycetin is caused the influence that mouse memory is consolidated obstacle
The diving tower experimental result shows: chloromycetin (Chlo) 200mg/kg significantly increases mouse wrong times, and significantly shorten incubation period, F
112mg/kg all makes errors number obviously reduce, and obviously prolong incubation period.F is described
11Can obviously improve chloromycetin causes mouse memory and consolidates obstacle.(as table 8)
Table 8, chloromycetin is caused the influence that mouse memory is consolidated obstacle
Group | Dose (mg/kg) | Number (n) | Latencies (s) | Number of errors |
Control Chol F 11+Chol F 11+Chol | 200 2 4 | 12 11 12 12 | 168.38±27.58 65.64±71.32 △△△132.25±79.01 *93.75±90.20 | 0.18±0.39 1.27±1.10 △△△0.33±0.49 *0.67±0.78 |
ΔΔΔP<0.001?????compared?with?Control
*p<0.05?
**p<0.01?compared?with?Chlo
Embodiment 8, ethanol is caused the influence that mouse memory reproduces obstacle
The result shows: in the diving tower experiment, and F
112mg/kg reduces the errors number increase that ethanol causes.Keep away in the dark experiment F
112mg/kg, 4mg/kg all can make significant prolongation incubation period, and errors number obviously reduces, and show F
11Can significantly improve ethanol and cause mouse memory reproduction obstacle.(the results are shown in Table 9, table 10)
Table 9, ethanol is caused the influence (diving tower method) that mouse memory reproduces obstacle
Group | Dose(mg/kg) | Number(n) | Number of errors |
Control Ethanol F 11+Ethanol F 11+Ethanol NIM | 10(ml/kg) 2 4 0.2 | 22 23 23 23 22 | 0.27±0.65 2.22±1.65 △△△1.23±1.05 *1.39±1.23 1.18±1.18 * |
ΔΔΔP<0.001????compared?with?Control
*p<0.05??????????compared?with?Ethanol
Table 10, ethanol is caused the influence (darkness avoidance test) that mouse memory reproduces obstacle
Group | Dose (mg/kg) | Number (n) | Latencies (s) | Number of errors |
Control Ethanol F 11+Ethanol F 11+Ethanol NIM | 10(ml/kg) 2 4 0.2 | 11 11 11 11 11 | 273.72±57.64 56.18±85.78 △△△186.64±110.56 **159.91±108.32 *139.09±114.19 | 0.27±0.47 3.09±1.21 △△△1.36±1.21 *1.36+1.29 *2.18±1.72 |
ΔΔΔp<0.001?????compared?with?Control
*p<0.05?
**p<0.01?compared?with?Ethanol
Above embodiment has proved absolutely effect of the present invention.
Claims (4)
1, pseudo-ginsenoside F
11Medical usage, it is characterized in that: following structure pseudo-ginsenoside F
11The effect of anti-morphine sample, nootropic effect, can expect to become novel medicine for stopping narcotic taking.
2, pseudo-ginsenoside F according to claim 1
11Medical usage, it is characterized in that: nootropic effect can comprise the learning and memory that promotes the normal person and the learning memory injury and the early stage alzheimer disease people that improve due to the disordered brain function improve learning and memory etc.
3, pseudo-ginsenoside F according to claim 1
11Medical usage, it is characterized in that: improve the dysmnesia that morphine causes; The autonomic activities that caused position preference behavior of antagonism morphine and morphine bring out increases; The analgesic activity of antagonism morphine and give the tolerance of the pain due to the morphine for a long time.
4, pseudo-ginsenoside F according to claim 2
11Medical usage, it is characterized in that: pseudo-ginsenoside F
11Antioxidation, it protects body, especially central nervous system's normal physiological function effect.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101948498A (en) * | 2010-09-03 | 2011-01-19 | 吉林圣亚医药科技有限公司 | Pseudo-ginsenoside G2, extraction method and drug application thereof |
CN112089772A (en) * | 2020-09-15 | 2020-12-18 | 汉济生物科技(武汉)有限公司 | A pharmaceutical composition and its application in preparing drug-relief medicine |
-
1999
- 1999-12-21 CN CN 99122651 patent/CN1300593A/en active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101948498A (en) * | 2010-09-03 | 2011-01-19 | 吉林圣亚医药科技有限公司 | Pseudo-ginsenoside G2, extraction method and drug application thereof |
CN101948498B (en) * | 2010-09-03 | 2012-09-26 | 吉林圣亚医药科技有限公司 | Pseudo-ginsenoside G2, extraction method and drug application thereof |
CN112089772A (en) * | 2020-09-15 | 2020-12-18 | 汉济生物科技(武汉)有限公司 | A pharmaceutical composition and its application in preparing drug-relief medicine |
CN112089772B (en) * | 2020-09-15 | 2022-02-18 | 汉济生物科技(武汉)有限公司 | A pharmaceutical composition and its application in preparing drug-relief medicine |
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