CN100423753C - Method of extracting medicamout having memory strengthening function from natural plant compound preparation - Google Patents
Method of extracting medicamout having memory strengthening function from natural plant compound preparation Download PDFInfo
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Abstract
The present invention relates to a method for extracting a medicine for enhancing memory power from a compound preparation, which belongs to pharmacological activity of natural products and a method for separating and purifying the natural products. The prescriptions is 8.57% of grassleaf sweetflag rhizome, 11.35% of rehmanniae, 11.35% of ophiopogon root, 5.67% of fleeceflower root, 5.67% of red sage root, 3.53% of notoginseng, 5.67% of ginseng, 5.67% of tuckahoe, 5.67% of Chinese arborvitae kernel, 2.83% of polygala, 5.67% of Chinese magnolivine fruit, 5.67% of cornel, 5.67% of eucommia bark, 5.67% of ledebouriella root, 5.67% of tendrilleaf fritillary bulb and 5.67% glycyrrhiza. The present invention has the positive effects that the method for extracting a medicine for enhancing memory power from a compound preparation uses advanced macroporous resin for adsorbing effective components and a gas phase finger trace spectrum for fixing quantity, and the stability and the high quality of the medicine are ensured.
Description
(1) technical field
The present invention relates to extract in a kind of compound preparation the method for hypermnesis goods medicine, belong to natural product pharmacologically active and Separation ﹠ Purification natural product method.Its trade name is " black wheat Fructus Alpiniae Oxyphyllae ".
(2) background technology
The piracetam that people use always, ANSHEN JIANNAO YE and SHENRONG WANGJIANG and melatonin etc. all are a kind of health product of supplementing the brain, and people wish that urgently a kind of crude drug of improving memory comes out, the good drug efficacy of crude drug, and the product of producing will improve a level.
(3) summary of the invention
Technical scheme comprises prescription new technology, process chart and various toxicity, pharmacology summary.
Technical solution is:
Purpose of the present invention discloses the method for extracting hypermnesis goods medicine in a kind of compound preparation; Prepare the high-purity raw medicine by this method.
Rhizoma Acori Graminei 8.57%, Radix Rehmanniae 11.35%, Radix Ophiopogonis 11.35%, Radix Polygoni Multiflori 5.67%, Radix Salviae Miltiorrhizae 5.67%, Radix Notoginseng 3.53%, Radix Ginseng 5.67%, Poria 5.67%, Semen Platycladi 5.67%, Radix Polygalae 2.83%, Fructus Schisandrae Chinensis 5.67%, Fructus Corni 5.67%, the Cortex Eucommiae 5.67%, Radix Saposhnikoviae 5.67%, Bulbus Fritillariae Cirrhosae 5.67%, Radix Glycyrrhizae 5.67% compound recipe hypermnesis goods, adopt macroporous resin adsorption, elution technique, strictly separate under the condition in carefulness, purifying natural product, refer to the quantitative assay of trace collection of illustrative plates composition with high performance liquid chromatograph, to guarantee Products Quality stability.The pharmacologically active experiment shows, compound product can strengthen the white mice memory, reduce the wrong reaction number of times that mice occurs in Y type labyrinth, after injection hydrobromic acid east Liang Rong alkali caused the white mice memory impairment, can prevent the degree of memory impairment, reduce the number of times of damaged mice wrong reaction in Y type labyrinth, compound product can strengthen the ability of rat learning and memory, the number of times that occurs mis action behind the minimizing rat learning and memory, pharmacological evaluation shows that compound product not only has facilitation to intact animal's learning and memory, and the memory impairment obstacle of white mice due to the eastern Liang Rong alkali is had the improvement effect, promote learning and memory, improve memory impairment.Compound product can increase the activity of superoxide dismutase in the rat blood plasma (SOD), reduces the generation of the lipid peroxide of brain tissue of rat and liver, significantly improves S0D activity in the blood plasma, and presents certain dose-effect relationship.Compound product has sedation and syngignoscism preferably to white mice, and with pentobarbital sodium collaborative syngignoscism is arranged.
Extract the method for extracting hypermnesis goods medicine in the compound preparation in the compound preparation and adopt advanced macroporous resin adsorption active ingredient and use liquid phase to refer to that trace spectrum is quantitative, guarantee the stability and the high-quality of medicine.
Creativeness of the present invention embodies by clinical toxicity, pharmacology, provides in the lump when examination as to substances.
(4) description of drawings
Fig. 1 is a process chart of the present invention.Its technological process is described below:
(1) the present invention prescription: Rhizoma Acori Graminei 60g, Radix Rehmanniae 80g, Radix Ophiopogonis 80g, Radix Polygoni Multiflori 40g, Radix Salviae Miltiorrhizae 40g, Radix Notoginseng 25g, Radix Ginseng 40g, Poria 40g, Semen Platycladi 40g, Radix Polygalae 20g, Fructus Schisandrae Chinensis 40g, Fructus Corni 40g, Cortex Eucommiae 40g, Radix Saposhnikoviae 40g, Bulbus Fritillariae Cirrhosae 40g, Radix Glycyrrhizae 40g.
(2) solvent: water.
(3) extracting solution: brown aqueous solution.
(4) physical parameter
Water extraction, resin absorption, spray-dired pressure are normal pressure; Wherein, the temperature of water extraction is 100 ℃, and the temperature of resin absorption is a room temperature, and spray-dired temperature is 80-85 ℃.
(5) operating process
1. 16 flavor medical materials add 6 times of water gagings decoctions 3 hours, filter, and get filtrate (1); Medicinal residues add 4 times of water gagings and decocted 2 hours, filter, and get filtrate (2); Medicinal residues add 2 times of water gagings again and decocted 1 hour, filter, and get filtrate (3).
2. leave standstill merging filtrate (1), (2), (3), gets supernatant, gets extracting solution (4).
3. extracting solution (4) adsorbs with macroporous resin.
4. be adsorbed on chemical constituent on the resin in ethanol with 65% ethanol elution, eluent (5).
5. reclaim under reduced pressure eluent (5) gets concentrated solution (6).
6. concentrated solution (6) is carried out spray drying, get medicated powder.
With 16 kind of plant raw materials, every 100kg adds water 600kg, 400kg, 200kg, extracts respectively 3 hours under 100 ℃ of conditions, 2 hours, 1 hour, merge water extraction filtrate, by the pillar of macroporous resin filling, use macroporous resin adsorption, ethanol with 65% at normal temperatures, is eluted to the composition that is adsorbed on the macroporous resin in the ethanol, under 85 ℃ of conditions, spray drying, refer to the quantitative assay of trace collection of illustrative plates composition with the high-performance liquid chromatogram determination instrument after, make the standard raw materials medicine.
(5) specific embodiment
Rhizoma Acori Graminei 60g, Radix Rehmanniae 80g, Radix Ophiopogonis 80g, Radix Polygoni Multiflori 40g, Radix Salviae Miltiorrhizae 40g, Radix Notoginseng 25g, Radix Ginseng 40g, Poria 40g, Semen Platycladi 40g, Radix Polygalae 20g, Fructus Schisandrae Chinensis 40g, Fructus Corni 40g, Cortex Eucommiae 40g, Radix Saposhnikoviae 40g, Bulbus Fritillariae Cirrhosae 40g, Radix Glycyrrhizae 40g.
With Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, the Radix Glycyrrhizae plant material, every 100kg adds water 600kg, 400kg, 200kg, under 100 ℃ of conditions, extracted respectively 3 hours, 2 hours, 1 hour, merge water extraction filtrate, pillar by the macroporous resin filling, use macroporous resin adsorption, ethanol with 65% at normal temperatures, is eluted to the composition that is adsorbed on the macroporous resin in the ethanol, under 85 ℃ of conditions, spray drying, refer to the quantitative assay of trace collection of illustrative plates composition with the high-performance liquid chromatogram determination instrument after, make the standard raw materials medicine.
Creativeness of the present invention by toxicity, pharmacology is clinical embodies, replenishing during substantive examination provides existing brief introduction as follows:
From natural plant compound formulation, extract the method pharmacological action of hypermnesis goods medicine
Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, Radix Glycyrrhizae plant compound recipe hypermnesis goods (are called for short: compound product), have hypermnesis, calmness, calm the nerves, syngignoscism, pharmacodynamics is investigated, and compound product has following pharmacologically active.
Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, Radix Glycyrrhizae plant compound product
Thiobarbituricacid, tetraethoxypropane Flukd, scopolamine hydrobromide Adriok, SOD measures test kit, sodium pentobarbital Union..
Method and result
1. compound product is to the influence of white mice memory
Get the white mice random packet of body weight 18～22g, 10 every group, the administration compound product.After the last administration 30 minutes.Revise slightly by the method for document and white mice to be put into Y type labyrinth train.Earlier white mice is put into and lead to 36V voltage after Y type labyrinth adapts to 5 minutes, with continued stimulus the correct person of 9 secondary responses being arranged for 10 times is qualified white mice.After 24 hours white mice is reentered in the Y type labyrinth, identical voltage stimulates 10 times, writes down the percent that it wrong reaction occurs, the results are shown in Table 1.
Table 1 compound product is to the influence of normal white mice memory
| Medicine | Dosage (ml/kg) | Administration time | n | The wrong reaction number of times (X ± SD) |
| NS | Etc. appearance | Bid×7 | 10 | 0.425±0.114 |
| Compound product | 4 | Bid×7 | 10 | 0.293±0.126 ** |
| Compound product | 8 | Bid×7 | 10 | 0.211±0.093 *** |
Compare with NS * P＜0.05 * * * P＜0.01
2. compound product is to the influence of scopolamine memory impairment white mice
Get body weight 18～20g white mice, random packet, 10 every group.The administration compound product is irritated stomach and is waited the capacity normal saline to do memory impairment pathological model usefulness.After the last administration 60 minutes, except that normal saline blank group, compound product is respectively organized equal subcutaneous injection scopolamine hydrobromide 3mg/kg, experimental technique by 2.9 after 10 minutes is put into Y type labyrinth with mice, write down it and the wrong reaction percentage rate occurs, observe compound product scopolamine is caused the influence that the white mice memory is hindered, the results are shown in Table 2.
Table 2 compound product is to the influence of scopolamine memory impairment mice
| Medicine | Dosage (ml/kg) | Administration time | N | The wrong reaction number of times (X ± SD) |
| NS | Etc. appearance | Bid×7 | 10 | 0.309±0.158 |
| The NS+ scopolamine | 3mg/kg | Bid×7 | 10 | 0.538±0.140TT |
| Compound product+scopolamine | 4 8 | Bid×7 Bid×7 | 10 10 | 0.370±0.144*** 0.300±0.110*** |
TT P＜0.01 model group and NS relatively * * * P＜0.01 compare with model control group
3. compound product influences the rat learning and memory
Get rat, random packet, 10 every group.Experimental group is irritated stomach and is given compound product 4.8ml/kg, and the blank group waits the capacity normal saline with method, once a day, and continuous 7 days.Rat was put into 35 * 45 * 55cm in 1 hour after the last administration
3The trained reflex case in, be bronze medal grid at the bottom of the case, put a valve rubber on the copper grid, the end directly is 5.5cm, high 5.5cm.
Allow rat after case adapts to 5 minutes, rat is placed on the valve rubber, energising 25V, the record rat can be detained the number of times of 3 minutes skip before upper mounting plates on platform, as the study index.Observe same index after 24 hours once more and be the memory index, it the results are shown in Table 3.
Table 3 compound product is to the influence of rat learning and memory
Compare with NS * P＜0.05 * * * P＜0.01
As can be seen from Table 3, compound product not only has facilitation to intact animal's learning and memory, and the memory impairment obstacle of white mice due to the scopolamine is had the improvement effect, promotes learning and memory, improves memory impairment.
4. compound product is to the influence of rat superoxide dismutase
Get male white rat, random packet, 10 every group.Experimental group is irritated stomach and is given compound product 4,8ml/kg, and another group waits the capacity normal saline to make blank with method, every day 1 time, continuous use 15 days.1 hour socket of the eye vein is got blood after the last administration, and anticoagulant heparin prepares serum, measures the activity of rat blood plasma superoxide dismutase (SOD), the results are shown in Table 4.
Table 4 compound product is to the active influence of SOD in the rat blood plasma
| Group | Dosage (ml/kg) | Administration time | n | SOD activity (X ± SD nu/ml) |
| NS | Etc. appearance | qd×15 | 10 | 19.8±3.1 |
| Compound product | 4 | qd×15 | 10 | 24.3±4.1 ** |
| Compound product | 8 | qd×15 | 10 | 27.1±2.9 *** |
Compare with NS * P＜0.05 * * * P＜0.01
5. compound product is to the influence of brain tissue of rat regulating liver-QI lipid peroxide
With experiment 4 animal, get blood after dislocation immediately put to death, take out the brain regulating liver-QI in the ice bath environment rapidly and make 5% the equal serosity of normal saline, measure the lipid peroxide (seeing Table 5) of brain tissue of rat regulating liver-QI.
Table 5 compound product is to the influence of DABAI Hepar Mus and cephalopin peroxide
Compare with NS * P＜0.05 * * * P＜0.01
By table 4,5 as can be seen, compound product can obviously reduce the generation of brain tissue of rat regulating liver-QI inner lipid peroxide, significantly improves the activity of SOD in the blood plasma, and presents certain dose-effect relationship.
6. the sedation of compound product
Get the male white mouse random packet of body weight 18～21g, 10 every group.Experimental group is irritated stomach and is given compound product 0.1,0.2ml/10g, the blank group waits the capacity normal saline with method, after 30 minutes white mice is put into GJ-7902 type three session mice activity inventory instrument, adapts to after 5 minutes, the active number of times of record white mice the results are shown in Table 1.By table 6 as seen, compound product has sedation preferably.
The sedation of table 6 compound product
| Group | Dosage (ml/kg) | n | The movable number of times of mice (X ± SD) |
| NS | - | 10 | 45.6±26.4 |
| Compound product | 0.2 | 10 | 8.4±5.6 ***T |
| Compound product | 0.1 | 10 | 41.7±18.6 * |
Compare with NS * P＞0.05 * * * P＜0.01
7. the syngignoscism of compound product
Get the white mice of body weight 18～22g, random packet, 25 every group.Irritate stomach respectively and give compound product 0.08,0.3,0.4ml/10g, pentobarbital sodium 30mg/kg, give and wait the capacity normal saline to make blank, then white mice is put into 37 ℃ constant temperature baby case, observe the sleep number of white mice, the sleep index is to continue to be as the criterion more than 30 seconds with righting reflex loss.Result such as table 7, by table 7 as seen, compound product high dose group 0.4ml/10g can make most of animal sleep occur, but sleep is more shallow.The 30mg/kg pentobarbital sodium is all sleeping, illustrates that compound product has syngignoscism.
Table 7 compound product is to the influence of white mice syngignoscism
* relatively compare with NS TT P＜0.01 with pentobarbital sodium P＞0.05
Brief summary and discussion
Pharmacodynamic study is the result show, Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, Radix Glycyrrhizae plant compound recipe hypermnesis goods have calmness, syngignoscism, promote the learning and memory of large and small white mouse, obviously improve memory impairment obstacle due to the scopolamine.
Compound product can reduce the generation of the lipid peroxide of liver, brain, improves the activity of body SOD, has the removing free radical, and the protection cell exempts from the infringement of lipid peroxide, plays antidotal effect.
The clinical observation of plant compound recipe hypermnesis goods: people with advancing age, in entering especially, geratic period deterioration or imbalance, often occur forgetful, be insomnia, cardiopalmus, dreaminess, soreness of the waist and knees, dizzy, Hiccough and deaf.Symptoms such as hyposexuality are in having a strong impact on, life of elderly person quality and work efficiency.Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, Radix Glycyrrhizae plant compound recipe hypermnesis goods (are called for short: compound product), pharmacologically active with hypermnesis Cure for insomnia, for verifying its clinical efficacy, 100 routine patients are carried out clinical observation on the therapeutic effect, are reported as follows:
Observation index:
(1) health giving quality observation: the improvement and the situation of change of observing treatment front and back objective indication of clinical symptoms and electroencephalogram, lipid peroxide physical and chemical indexs such as (LPO).
(2) safety observation: the situation of change for the treatment of projects such as front and back routine blood test, routine urinalysis, liver function by observation is to understand the safety of medicine.
Therapeutic outcome:
The comparison of (one) two group of clinical efficacy
As seen from Table 1, compound product and the above percentage rate of matched group produce effects are respectively 45%, 15%, and total effective rate is respectively 89%, 73.3%, through X
2Check, P value difference＜0.01 and 0.05 has highly significant and significant difference.
The comparison of table 1 liang group clinical efficacy
| Group | The example number | Clinical recovery | Produce effects | Effectively | Invalid | The above percentage rate of produce effects | Total effective rate |
| Compound product | 100 | 4 | 41 | 44 | 11 | 45％ | 29％ |
| Matched group | 60 | 0 | 9 | 35 | 16 | 15％ | 73.3％ |
(2) relation of the cardinal symptom and the course of treatment, curative effect
1. the relation of the insomnia and the course of treatment, curative effect
As seen from Table 2,2 week of compound product group medication back symptom integral value decline 138 minutes, rate of descent is to descend 396 fens after 29.9%, 4 week, rate of descent 85.9% is through X
2Check, there is highly significant difference P＜0.01.4 week of treatment, back integration rate of descent was above 2/3.Point out this compound product that insomnia is had tangible curative effect, take the curative effect that compound product 4 all backs curative effects obviously were better than for 2 weeks.
The relation of table 2 insomnia and the course of treatment, curative effect
2. the relation of the soreness of the waist and knees and the course of treatment, curative effect
As seen from Table 3, decline mark and rate of descent were respectively 64 minutes, 17.6% after 2 weeks of compound product group medication, 4 weeks; 219 minutes, 60.2%, through X
2Check, there is highly significant difference P＜0.01, and prompting is taken the curative effect that the curative effect of compound product after 4 weeks was better than for 2 weeks to this symptom, and rate of descent illustrates that greater than 1/3 of total mark the curative effect to this symptom is sure after 4 weeks of medication.
The relation of table 3 soreness of the waist and knees and the course of treatment, curative effect
3. the relation of forgetful and the course of treatment, curative effect
As seen from Table 4, decline mark and rate of descent were respectively 52 minutes, 11% after 2 weeks of compound product group medication, 4 weeks; 125 minutes, 27%, through X
2Check, there is highly significant difference P＜0.01, and prompting is taken the curative effect that the curative effect of compound product after 4 weeks was better than for 2 weeks to this symptom.
The forgetful relation with the course of treatment, curative effect of table 4
(3) variation before and after main physical and chemical index and the routine examination treatment
Compound product group treatment before and after look electroencephalogram is normal electroencephalogram, the serum lipid peroxide detects (LPO), is 18.56 ± 4.43nmol/ml before the treatment, is higher than normal value, drop to 10.47 ± 4.06nmol/ml after taking the compound product treatment, reduce to normal range.Through the T check, there is highly significant difference P＜0.001, and compound product has the effect of LPO in the obvious reduction blood.After taking compound product, routine blood test, routine urinalysis and liver function all do not have change before and after the treatment.Any toxicity does not appear in the treatment phase.
Discuss and brief summary
1. Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, Radix Glycyrrhizae plant compound recipe hypermnesis goods clinical treatment 100 routine patients, the above percentage rate of its total effective rate and produce effects is respectively 89%, 45%, hypermnesis is arranged, alleviate and improve forgetful effect.
The compound product group to be insomnia, primary symptom such as soreness of the waist and knees, common minor symptoms such as cardiopalmus, dreaminess, deafness and tinnitus have significant curative effect.Less important symptoms such as lassitude and weak also there is certain curative effect.
3. the comparison of curative effects after treating for 2 weeks and treated for 4 weeks by forgetful, insomnia, three main symptoms of soreness of the waist and knees, the curative effect of compound product after 4 weeks is better than the curative effect in 2 weeks as can be seen.Certain clinical foundation is provided the course of treatment of taking for compound product.
4. compound product has the effect that reduces lipid peroxide in the blood, points out this medicine that certain antioxidation, free radical resisting and anti-aging effects are arranged.
5. compound product is during observing the course of treatment, and conventional indexs such as blood, urine, liver function are not seen obvious change, also do not find any toxic and side effects.The compound product curative effect is better, and taking convenience, mouthfeel are good.
From natural plant compound formulation, extract the method pharmacodynamics test data of hypermnesis goods medicine
Compound product is made up of tens kinds of Chinese medicines such as Rhizoma Acori Graminei, Semen Platycladi, Radix Ginsengs, effect such as clinic trial has calmness, calms the nerves, hypnosis, hypermnesis, life lengthening.This paper investigates its main pharmacodynamics.
One, experiment material
Compound product: Shenyang FeiLong Health Food Co., Ltd provides, lot number 930228
The multiple health of abdomen: available from Dongbei Pharmaceutical General Factory
SHENRONG WANGJIANG: Tonghua, Jilin Bai Shan pharmacy two factories, lot number: 920421
ANSHEN JIANNAO YE: Chinese medicine refinery of Beijing Tongrentang, lot number: 921231
Thiobarbituricacid: Beijing chemistry two factories
Tetraethoxypropane Flukd, hydrogen Australia acid scopolamine Adrlck
SOD measures test kit, available from hospital general, naval district molecular biosciences laboratory
Pentobarbital sodium Union import packing, Shanghai chemical reagent purchasing and supply station packing factory.
Used other reagent is commercially available analytical pure in the experiment.
Two, method and result
(1) sedation of compound product
The male white mouse of getting body weight 18～21g divides 4 groups at random, 10 every group.Experimental group is irritated stomach and is given compound product 0.1,0.2ml/10g, positive controls gives ANSHEN JIANNAO YE 0.2ml/10g with method, the blank group waits the capacity normal saline with method, after 30 minutes white mice put into GJ-7902 type three session mice activity inventory instrument, adapt to after 5 minutes, the active number of times of record white mice the results are shown in Table 1.By table 1 as seen, compound product has sedation preferably, and sedation effect and ANSHEN JIANNAO YE are suitable.
The sedation of table 1 compound product
* relatively compare with ANSHEN JIANNAO YE T P＞0.05 with NS P＞0.05 * * * P＜0.01
2. the synergism of compound product and pentobarbital sodium
Get the white mice of body weight 18～22g, be divided into 6 groups at random, every group 25, irritate stomach respectively and give compound product and each 0.2mlg/10g of ANSHEN JIANNAO YE for preceding 2 groups, the back is irritated stomach respectively for 4 groups and is given compound product 0.1,0.2ml/10g, ANSHEN JIANNAO YE 0.2ml/10g and equivalent normal saline, after 5 minutes, and equal lumbar injection pentobarbital sodium 15mg/10g, after the administration white mice put into 37 ℃ constant temperature baby case, observe the sleep response number of white mice.The sleep index is to continue to be as the criterion more than 1 minute with the white mice righting reflex loss.The results are shown in Table 2.By table 2 as seen, two medicines and pentobarbital sodium subliminal hypnosis amount 15mg/kg all have synergism, and the reinforcing the heart brain invigorating liquid is rapid-action, the length of holding time, side light the effect of reinforcing the heart brain invigorating liquid fast, effect is strong.
Table 2 compound product and pentobarbital sodium sleep synergism
Relatively compare with ANSHEN JIANNAO YE TT P＜0.05 with NS * P＜0.05 * * P＜0.01
3. the syngignoscism of compound product
Get the white mice of body weight 18～22g, be divided into 7 groups at random, 25 every group.Irritate stomach respectively and give compound product 0.08,0.3,0.4ml/10g, pentobarbital sodium 30mg/kg, giving for the 7th group waits the capacity normal saline to make blank, then white mice is put into 37 ℃ constant temperature baby case, observe the sleep number of white mice, the sleep index is to continue to be as the criterion more than 30 seconds with righting reflex loss.Result such as table 3, by table 3 as seen, compound product high dose group 0.4ml/10g can make most of animal sleep occur, but sleep is more shallow.ANSHEN JIANNAO YE low dose, heavy dose all do not have the sleep animal, and the 30mg/kg pentobarbital sodium is all sleeping.Illustrate that compound product has syngignoscism, and commercially available ANSHEN JIANNAO YE 40ml/kg there is not syngignoscism.
Table 3 compound product is to the influence of white mice syngignoscism
* relatively compare with NS TT P＜0.01 with pentobarbital sodium P＞0.05
4. compound product is to the influence of white mice acute cerebral ischemia
The white mice of getting body weight 18～22g is divided into 5 groups at random, 10 every group.Experimental group is irritated stomach and is given reinforcing the heart brain invigorating liquid 4,8ml/kg, SHENRONG WANGJIANG 8ml/kg, piracetam 300mg/kg, and another group waits the capacity normal saline to compare with method, administration every day 2 times, continuous use 7 days.40 minutes cervical region broken ends behind the white mice ears after the last administration, observe white mice from time that the broken end beginning stops to breathing for the last time as snorting the holding time of broken end, the results are shown in Table 4.By table 4 as seen, compound product can obviously prolong the white mice broken end breathes the time, and dosage strengthens, and prolong action time, presents certain dose-effect relationship.Its effect is equivalent to the SHENRONG WANGJIANG group of clinical equivalent amount, and obviously is better than the piracetam group.
Table 4 compound product is to the breathe influence of time of white mice broken end
Compare with NS * P＞0.05 * * P＜0.05
Compare with the SHENRONG WANGJIANG oral liquid T P＞0.05
Compare with piracetam ZZ P＜0.01
5. compound product is to the influence of mice time-to-live of ligation bilateral common carotid arteries
After the last administration 40 minutes, white mice is used the ether light anaesthesia, separate bilateral common carotid arteries rapidly, together with the vagus nerve ligation, observe the time-to-live of white mice, the results are shown in Table 5.By table 5 as seen; compound product can obviously prolong the time-to-live of ligation bilateral common carotid arteries; high dose group is apparently higher than SHENRONG WANGJIANG group and piracetam group, illustrates that it all has stronger protective effect to cerebral ischemia and cerebral ischemia that blood pressure drops due to the vagal excitation is caused.
Table 5 compound product is to the influence of white mice time-to-live of ligation bilateral common carotid arteries
Compare with NS * P＞0.05 * * P＜0.05 * * * P＜0.01
Compare with piracetam TT P＜0.05
6. compound product is to the influence of white mice normal pressure anoxia enduring
White mice put into the wide mouthed bottle that fills 10g soda lime 250ml in 30 minutes after the last administration, the time-to-live that white mice is observed in the sealing back, result such as table 6.Compound product obviously prolongs the time-to-live under the white mice normobaric hypoxia condition, and it is close with the SHENRONG WANGJIANG group to prolong percentage rate, has prolonged 17.8% than 300mg/kg piracetam group.
Table 6 compound product is to the influence of normobaric hypoxia white mice time-to-live
Compare with NS * P＜0.05 * * * P＜0.01
7. compound product is to the influence of white mice swimming time
After the last administration 30 minutes, every white mice added the 0.5g load by the 20g body weight, then white mice is put into 39 ± 1 ℃ constant temperature water bath, adds an amount of surfactant in the water, and the volume of water is 60 * 65 * 50cm
3White mice is swum in the heat stress environment of higher temperature, observes its swimming time.Swimming time is to sink under water no longer with white mice that the upstream is a swimming time, the results are shown in Table 7.By table 7 as seen, compound product can obviously prolong the swimming time of white mice high temperature in stress environment, and its prolongation effect is similar to SHENRONG WANGJIANG, and is longer than the 300mg/kg piracetam.Illustrate that compound product has stronger resisting fatigue, anti-stress effect.
Table 7 compound product is to the influence of white mice swimming time
* P＞0.05 is compared with NS in * P＜0.05
8. compound product is to the influence of white mice swimming time
Get male white rat, be divided into 5 groups at random, 10 every group.Experimental group is irritated stomach respectively and is given compound product 4,8ml/kg, and positive controls is irritated stomach and given SHENRONG WANGJIANG 8ml/kg, piracetam 200mg/kg.Once a day, continuous 7 days.Every rat adds the 4g load by every 100g after the last administration, puts into 39 ± 1 ℃ water bath with thermostatic control then, and the bath water volume is 60 * 65 * 50cm
3, and add suitable surfactant, amplify 10 of Mus at every turn.By the swimming time of experiment 7 method record rat in high temperature stress environment, the results are shown in Table 8.Compound product obviously prolongs the swimming time of rat in high temperature stress environment, and the high dose group effect is obvious, and its swimming time is the longest, obviously is longer than piracetam group 28.96%.
Table 8 compound product is to the influence of white mice swimming time
* compare with NS P＞0.05 * * P＜0.05 * * * P＜0.01
9. compound product is to the influence of white mice memory
By the method grouping of experiment 4, administration.After the last administration 30 minutes.White mice is put into Y type labyrinth to be trained.Earlier white mice is put into and lead to 36V voltage after Y type labyrinth adapts to 5 minutes, the correct qualified white mice of 9 secondary responses is arranged for 10 times with continued stimulus.After 24 hours white mice is reentered in the Y type labyrinth, identical voltage stimulates 10 times.Write down the percent that it wrong reaction occurs, the results are shown in Table 9.
Table 9 compound product is to the influence of normal white mice memory
Compare with NS * P＜0.05 * * * P＜0.01
10. compound product is to the influence of scopolamine memory impairment white mice
Get body weight 18～22g white mice, be divided into 6 groups at random, 10 every group.The first five group is irritated stomach for the 6th group and is waited the capacity normal saline to do memory impairment pathological model usefulness by the method administration of experiment 4.After the last administration 60 minutes, except that normal saline blank group, all the other respectively organize equal subcutaneous injection scopolamine hydrobromide 3mg/kg, experimental technique by 2g after 10 minutes is put into Y type labyrinth with mice, write down it and the wrong reaction percentage rate occurs, observe medicine scopolamine is caused the influence of white mice memory impairment, the results are shown in Table 10.
Table 10 compound product is to the influence of scopolamine memory impairment mice
TT＜0.01 model group and NS relatively * * * P＜0.01 compare with model control group
11. compound product is to the influence of rat learning and memory
Get rat, be divided into 5 groups at random, 10 every group.Experimental group is irritated stomach respectively and is given compound product 4.8ml/kg, SHENRONG WANGJIANG 8ml/kg, and piracetam 200mg/kg, the blank group waits the capacity normal saline with method, once a day, continuous 7 days.Rat was put into 35 * 45 * 55cm in 1 hour after the last administration
3The trained reflex case in, be bronze medal grid at the bottom of the case, put a valve rubber on the copper grid, the end directly is 5.5cm, high 5.5cm.Allow rat after case adapts to 5 minutes, rat is placed on the valve rubber, energising 25V, the record rat can be detained the number of times of 3 minutes skip before upper mounting plates on platform, as the study index.Observe same index after 24 hours once more and be the memory index, it the results are shown in Table 11.
Table 11 compound product is to the influence of rat learning and memory
Compare with NS * P＜0.05 * * * P＜0.01
As can be seen from Table 11, compound product not only has facilitation to intact animal, learning and memory, and the memory impairment obstacle of white mice due to the scopolamine is had the improvement effect.It promotes learning and memory, it is similar to commercially available SHENRONG WANGJIANG to improve the memory impairment effect, but the promotion memory effect of mice is not so good as piracetam.
12. compound product is to the influence of rat superoxide dismutase
Get male white rat, be divided into 5 groups at random, 10 every group.Experimental group is irritated stomach and is given compound product 4,8ml/kg, and positive controls is irritated stomach and given SHENRONG WANGJIANG and each 8ml/kg of piracetam and 200mg/kg.Another group waits the capacity normal saline to make blank with method, every day 1 time, continuous use 15 days.1 hour socket of the eye vein is got blood after the last administration, and anticoagulant heparin prepares serum, measures the activity of rat blood plasma superoxide dismutase (SOD), the results are shown in Table 12.
Table 12 compound product is to the active influence of SOD in the rat blood plasma
Compare with NS * P＜0.05 * * * P＜0.01
13. compound product is to the influence of brain tissue of rat regulating liver-QI lipid peroxide
Dislocation is immediately put to death after getting blood, takes out the brain regulating liver-QI in the ice bath environment rapidly and makes 5% the equal serosity of normal saline, measures the lipid peroxide of brain tissue of rat regulating liver-QI, the results are shown in Table 12.
Table 13 compound product is to the influence of DABAI Hepar Mus and cephalopin peroxide
Compare with NS * P＜0.05 * * * P＜0.01
By table 12,13 as can be seen, compound product can obviously reduce the generation of brain tissue of rat regulating liver-QI inner lipid peroxide, significantly improves the activity of SOD in the blood plasma, and presents certain dose-effect relationship.It suppresses the generation of lipid peroxide and the effect of enhance SOD activity, obviously is better than commercially available SHENRONG WANGJIANG and piracetam group.
Brief summary and discussion
Pharmacodynamic study is the result show, compound product has calmness, hypnosis reaches and the synergism of pentobarbital sodium, and its effect is better than commercially available ANSHEN JIANNAO YE.Acute cerebral ischemia, anoxia had protective effect; improve body to the anoxybiotic tolerance of whole body; prolong the swimming time of large and small white mouse in high temperature stress environment; the anti-stress ability of enhancing body and the endurance of body; promote the learning and memory of large and small white mouse, obviously improve memory impairment obstacle due to the scopolamine, except that the memory aspect is weaker than the piracetam; all other pharmacological actions or similar to commercially available SHENRONG WANGJIANG, or the multinomial pharmacological action that is better than SHENRONG WANGJIANG all is better than piracetam.
Compound product still can reduce the generation of the lipid peroxide of liver, brain, improves the activity of body SOD, and this two aspects effect all is better than SHENRONG WANGJIANG and piracetam group.Point out this medical instrument that the removing free radical is arranged, the protection cell exempts from the infringement of lipid peroxide, plays antidotal effect.
Claims (2)
1. from natural plant compound formulation, extract the method for hypermnesis goods medicine, it is characterized in that following 16 natural product Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, Radix Glycyrrhizae, adopt advanced macroporous resin adsorption active ingredient, and use gas phase to refer to that trace spectrum is quantitative; Its percentage by weight is Rhizoma Acori Graminei 8.57%, Radix Rehmanniae 11.35%, Radix Ophiopogonis 11.35%, Radix Polygoni Multiflori 5.67%, Radix Salviae Miltiorrhizae 5.67%, Radix Notoginseng 3.53%, Radix Ginseng 5.67%, Poria 5.67%, Semen Platycladi 5.67%, Radix Polygalae 2.83%, Fructus Schisandrae Chinensis 5.67%, Fructus Corni 5.67%, the Cortex Eucommiae 5.67%, Radix Saposhnikoviae 5.67%, Bulbus Fritillariae Cirrhosae 5.67%, Radix Glycyrrhizae 5.67%; With Rhizoma Acori Graminei, Radix Rehmanniae, Radix Ophiopogonis, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Ginseng, Poria, Semen Platycladi, Radix Polygalae, Fructus Schisandrae Chinensis, Fructus Corni, the Cortex Eucommiae, Radix Saposhnikoviae, Bulbus Fritillariae Cirrhosae, the Radix Glycyrrhizae plant material, every 100kg adds water 600kg, 400kg, 200kg, under 100 ℃ of conditions, extracted respectively 3 hours, 2 hours, 1 hour, merge water extraction filtrate, pillar by the macroporous resin filling, use macroporous resin adsorption, ethanol with 65% at normal temperatures, is eluted to the composition that is adsorbed on the macroporous resin in the ethanol, under 85 ℃ of conditions, spray drying, refer to the quantitative assay of trace collection of illustrative plates composition with the high-performance liquid chromatogram determination instrument after, make the standard raw materials medicine.
2. according to the described method of from natural plant compound formulation, extracting hypermnesis goods medicine of claim 1, it is characterized in that described crude drug can be prepared into tablet, pill, capsule, oral liquid, mixture, granule and injection.
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|---|---|---|---|---|
| CN102119986B (en) * | 2011-03-07 | 2013-03-27 | 北京中医药大学 | Traditional Chinese medicine extract with anti-dementia effect and preparation method thereof |
| CN104688973A (en) * | 2015-04-02 | 2015-06-10 | 韩桂莲 | Traditional Chinese medicine preparation for treating insomnia |
| CN105148144A (en) * | 2015-09-22 | 2015-12-16 | 麻翠秋 | Foot bathing liquid capable of promoting brain fitness and intelligence reinforcement |
| CN105250642A (en) * | 2015-10-28 | 2016-01-20 | 雷少华 | Traditional Chinese medicine composition for treating insomnia |
| CN108949677B (en) * | 2018-07-05 | 2021-11-30 | 浙江大学 | Application of rehmannia root glycoside C and salvianolic acid A in promoting proliferation of mesenchymal stem cells cultured in vitro and inhibiting replicative senescence |
| CN111366672B (en) * | 2020-04-24 | 2021-06-22 | 劲牌有限公司 | Detection method of health wine fingerprint |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1153046A (en) * | 1995-12-26 | 1997-07-02 | 沈阳科进工程有限公司 | Brain protection liquid |
-
2004
- 2004-02-02 CN CNB2004100011479A patent/CN100423753C/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1153046A (en) * | 1995-12-26 | 1997-07-02 | 沈阳科进工程有限公司 | Brain protection liquid |
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| CN1650895A (en) | 2005-08-10 |
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