CN103153322B - Containing oenanthe javanica extract as the learning capacity of effective ingredient or memory disorder prevention or therapeutic composition and manufacture method thereof - Google Patents
Containing oenanthe javanica extract as the learning capacity of effective ingredient or memory disorder prevention or therapeutic composition and manufacture method thereof Download PDFInfo
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Abstract
The present invention relates to containing oenanthe javanica extract as the learning disorder of effective ingredient or memory disorder prevention or therapeutic composition and manufacture method thereof, relate in more detail to extract from a kind of Herba Apii be used as edible condiment vegetable can the activity of acetylcholine esterase inhibition (AChE), prevention or treatment learning capacity or memory disorder effective ingredient, as pharmaceutical composition or healthy functions food.
Description
Technical field
The present invention relates to containing oenanthe javanica extract as the learning capacity of effective ingredient or memory disorder prevention or therapeutic composition and manufacture method thereof, relate to a kind of Herba Apii from being used as edible condiment vegetable in more detail, especially extract from kind of dry land Herba Apii can the activity of acetylcholine esterase inhibition (AChE), prevention or treatment learning capacity or memory disorder effective ingredient be used as pharmaceutical composition or healthy functions food.
Background technology
Herba Apii is also called Herba Apii graveolentis, Herba Oenanthes Javanicae, water English, is at the whole regional self-sow of Korea S, in Sakhalin, China's Mainland, Japan, Southeast Asia, Oceania etc. from subfrigid zone, the condiment vegetable that extensively distributes to the torrid zone of temperate zone.
Herba Apii is divided into paddy field Herba Apii and dry land Herba Apii according to planting type, paddy field Herba Apii be to results time, the Herba Apii of cultivating at Tanaka's irrigation water, can see after being blocked by stem that stem is empty, organize softness to be thus called Herba Apii, dry land Herba Apii starts with paddy field Herba Apii similarly by hydroponic culture, finally water is put dry cultivation, carry out management and cultivation with dry land state, be therefore called dry land Herba Apii, not empty in stem, be full of content.
What be commonly referred to Herba Apii is paddy field Herba Apii, Herba Apii is recited as jaundice in Dong-eui-bo-gam, gynaecopathia, headache after drinking or vomiting are effectively, containing flavonoid (flavonods) in recent various research display Herba Apiis, choline (cholin) quintessence oil, as bright in it (rutamin) also containing the alkaloid (alkaloid) being as quinoline (quinoline), r-Pa Jialin (r-pagarin), coumarin (cumarin) etc., not only there is hepatoprotective effect by these compositions, mutation and antioxidation, hypertension therapeutic effect, also being still drank after a night after drinking is eliminated and there is remarkable effect.
In addition, dull-witted (dementia) occurs that the general disturbance of the brain function such as brain cell death and hypomnesis is the degenerative disease of feature, accounts for 10%, account for more than 50% in the old people of more than 80 years old in the crowd of prediction over-65s.Come in along with the increase of aging populations, estimate that its onset speed increases more hastily, therefore dull-witted become that modern society faces serious society, economic problems.
Dull-witted reason has multiple, is divided into Alzheimer (Alzheimer ' s disease), dementia that vascular dementia, other alcoholism, wound, Parkinsonian sequela cause.All there is Alzheimer in the over half of dementia patients, therefore to attach most importance to Alzheimer to the research of dementia and carry out.
Although the pathogenesis of Alzheimer is also indefinite, but up to the present knownly to reduce with the acetylcholine function in central nervous system, have close association with calm in the brain cell of amyloid-beta (amyloid beta, the A β) senile plaque (senile plaque) that is main constituent or outside with the appearance etc. of the Tau albumen of the peroxophosphoric acid neurofibrillary tangles (Neurofibrillarytangle) that is main constituent.
Had the result of study of mutual relation between the hypofunction of a lot of Cholinergic nerveous system disclosed in above-mentioned reason and memory impairments, therefore people make great efforts to carry out supplementing and improving to choline nerveous system always, treat dementia thus in the past.
Therefore, dementia treatment agent major part is in the past the material such as acetylcholine synthesis precursor and acetyl choline receptor agonists (Receptor agonist) etc. that the acetylcholine decomposing inhibitor of the activity of the acetylcholinesterase (AchE) as acetylcholine catabolic enzyme can be suppressed in brain maybe the concentration of acetylcholine can be maintained certain level.
As object lesson, acetylcholine decomposing inhibitor has and obtains FDA and to admit and at the tacrine of Korea S also in commercially available use (tacrine), aricept (aricept) and galantamine (galantamine); Acetylcholine synthesis precursor has lecithin (lecitin); In addition acetyl choline receptor agonists has RS-86, nicotine (nicotine) etc.
But, along with the carrying out of dementia, be not only acetyl cholinergic neurocyte, the glutamic acid neurocyte occupying the neurocyte overwhelming majority also can be degenerated, and the said method that the activity therefore focusing on acetylcholine is promoted can only obtain temporary faint dull-witted Prevention and Curation effect.In addition, most of medicine of such as tacrine has serious liver toxicity, vomiting, feel sick or the side effect such as diarrhoea, and whether the use therefore for them also exists a lot of dispute.
In addition, modern society becomes complicated and specialized gradually, also needs a large amount of quantity of information and quantity of study thereupon, therefore needs effective cerebral activity.But a lot of people is subject to the puzzlement of hypomnesis due to aging, disease, medicine or pressure, the life along with the mankind needs the ergasia of height.In order to tackle this situation well, people are making great efforts brain is regained consciousness, and improve one's memory, and to meet the demand etc. of ergasia, need exploitation effectively can promote the medicine, functional food etc. of these functions in this field simultaneously.
Therefore, extensive use in among the people or South Korea and the little natural goods of extra side effect can effectively promote for object carries out having learning capacity and memory, prevention or treatment learning disorder or memory disorder, acetylcholine esterase inhibition (AChE) activity natural goods screening process in, confirm oenanthe javanica extract, especially obviously demonstrate above-mentioned activity during dry land oenanthe javanica extract oral administration, this completes the present invention.
Summary of the invention
The object of the present invention is to provide obtained by natural goods almost there is no Side effect, there is powerful anticholinergic effect, can prevent or treat the pharmaceutical composition of learning capacity or memory disorder.
In addition, the present invention also aims to the method that the extract by Herba Apii manufacture with best anticholinergic effect is provided.
In addition, another object of the present invention be to provide obtain from natural goods almost there is no Side effect, there is powerful anticholinergic effect, promote the healthy functions food of learning capacity or memory.
Feature of the present invention is learning disorder using oenanthe javanica extract as effective ingredient or memory disorder prevention or medicine for treatment compositions.
The feature of learning disorder of the present invention or memory disorder prevention or medicine for treatment compositions is described Herba Apii is dry land Herba Apii.
The feature of learning disorder of the present invention or memory disorder prevention or medicine for treatment compositions is oral administration.
Learning disorder of the present invention or memory disorder prevent or medicine for treatment compositions, and wherein, described extract is the extract of the solvent be dissolvable in water in the aqueous solution being selected from carbon number 1 ~ 4 lower alcohol or described lower alcohol.
Learning disorder of the present invention or memory disorder prevention or medicine for treatment compositions, wherein, described alcohol-water solution is the mixing ratio of lower alcohol is 10 ~ 95(v/v) alcohol-water solution of %.
In addition, according to learning disorder of the present invention or memory disorder prevention or the manufacture method for the treatment of oenanthe javanica extract, the aqueous lower alcoholic solutions of drying water Herba Apii graveolentis with the carbon number 1 ~ 4 of 20 ~ 200 times of its weight is mixed, extracts 4 ~ 20 hours at 50 ~ 90 DEG C.
According to learning disorder of the present invention or memory disorder prevention or the manufacture method for the treatment of oenanthe javanica extract, wherein, described aqueous lower alcoholic solutions is 50 ~ 80(v/v) ethanol water of %, after extracting with described ethanol water, its extract ethyl acetate or butyl alcohol extraction.
In addition, the present invention also provides learning capacity using oenanthe javanica extract as effective ingredient or memory enhancement healthy functions food.
According to learning capacity of the present invention or memory enhancement healthy functions food, wherein, described Herba Apii is dry land Herba Apii.
According to learning capacity of the present invention or memory enhancement healthy functions food, wherein, the form of described healthy functions food is powder, granule, tablet, capsule or beverage form.
Oenanthe javanica extract according to the present invention be almost be free from side effects or toxicity natural goods source extract, can the activity of remarkable acetylcholine esterase inhibition (AChE), the effect of the memory injury that the use with the medicine scopolamine of prevention induction dementia or hypomnesis causes, also shows therapeutic effect to the memory disorder that ethanol maybe stress cause.
Accompanying drawing explanation
Fig. 1 is the collection of illustrative plates of the maximum inhibition of the acetylcholinesterase (AChE) comparing with Herba Apii the various natural goodses being representative.
Fig. 2 compares again to extract Herba Apii ethanol extraction with different solvents and the subfraction obtained
the collection of illustrative plates of the acetylcholine esterase active suppression ratio of extract.
Fig. 3 is the collection of illustrative plates of the acetylcholine esterase active suppression ratio comparing paddy field oenanthe javanica extract and dry land oenanthe javanica extract.
Detailed description of the invention
The present invention extracts to have acetylcholinesterase (AChE) activity and to suppress and learning capacity or memory promote the compositions of effect from Herba Apii, and is applied to learning disorder or memory disorder prevention or medicine for treatment compositions or learning capacity or memory enhancement healthy functions food.
In the present invention, Herba Apii belongs to Ostericum coreanum, the Oenanthe stonilifera, Oenanthe javanica etc. of the Oenanthe of Carrot family (Umbelliferaceae); Preferred Korea S produces Herba Apii.
Herba Apii can use the paddy field Herba Apii being called Herba Oenanthes Javanicae of hydroponic culture and the dry land Herba Apii being called fiery celery at culture of dry land in paddy field usually, but dry land Herba Apii is compared with the Herba Apii of paddy field, the inhibit activities of acetylcholinesterase (AChE) is excellent, excellent to the preventive effect of drug-induced memory injury, therefore preferably.
Solvent for oenanthe javanica extract manufacture of the present invention can use the lower alcohol of carbon number 1 ~ 4, or the aqueous solution of above-mentioned lower alcohol.The lower alcohol of carbon number 1 ~ 4 can use such as methanol, ethanol, butanols, propanol, isopropyl alcohol etc.; Preferred use ethanol.
In addition, as the manufacture for oenanthe javanica extract solvent and use alcohol-water solution time, the mixed proportion being used in alcohol in the alcohol-water solution of water and alcohol mixing is 10 ~ 95(v/v) alcohol-water solution of %; Preferred use 20 ~ 90(v/v) alcohol-water solution of %; More preferably 50 ~ 80(v/v is used) alcohol-water solution of %.
Most preferably use 50 ~ 80(v/v) after the alcohol-water solution extract of %, when the fraction this extract ethyl acetate or butyl alcohol extraction obtained is as extract, acetylcholinesterase (AChE) inhibit activities excellence in favourable.
Oenanthe javanica extract of the present invention can carry out the extracting method manufactures such as stirring extraction, reflux cooling extraction, merceration extraction, ultrasound extraction or supercritical extraction by using above-mentioned solvent, particularly, in order to effectively extract the effective ingredient of high concentration from Herba Apii, 20 ~ 200 times of the weight of preferred combination drying Herba Apii, the aqueous lower alcoholic solutions that is preferably the carbon number 1 ~ 4 of 50 ~ 150 times, extract 4 ~ 20 hours at 50 ~ 90 DEG C.
Of the present inventionly comprise oenanthe javanica extract may be used for Alzheimer, vascular dementia, other alcoholism, wound, dementia that Parkinsonian sequela causes or cognitive dysfunction Prevention and Curation as the compositions of effective ingredient, be particularly applicable to the treatment of Alzheimer.
Compositions of the present invention, relative to composition total weight, take solid constituent as benchmark, containing oenanthe javanica extract 0.1 ~ 50 % by weight.
But above-mentioned composition is not limited to this, according to the state of patient and the kind of disease and carry out degree and can change.
Of the present inventionly can also comprise normally used applicable carrier, excipient and diluent in the manufacture of pharmaceutical composition containing oenanthe javanica extract as the compositions of effective ingredient.
The compositions of oenanthe javanica extract as effective ingredient is comprised according to of the present invention, powder is can be made into according to usual way, granule, tablet, capsule, suspension, emulsion, syrup, the oral type dosage forms such as aerosol, external preparation, the form of suppository and sterilizing injecting solution uses, can be included in containing extract as the carrier in the compositions of effective ingredient, excipient and diluent can enumerate lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltose alcohol, starch, Radix Acaciae senegalis, alginate, gelatin, calcium phosphate, calcium silicates, cellulose, methylcellulose, microcrystalline Cellulose, PVP, water, methyl hydroxybenzoate, nipasol, Talcum, magnesium stearate and mineral oil.Diluent or the excipient manufactures such as normally used filler, extender, bonding agent, wetting agent, disintegrating agent, surfactant is used time formulation.
Solid preparation for oral administration comprises tablet, pill, powder, granule, capsule etc., these solid preparations add at least more than one excipient in said extracted thing, the manufactures such as such as starch, calcium carbonate (calcium carbonate), sucrose (sucrose) or lactose (lactose), gelatin.In addition, except simple excipient, the such as lubricant such as magnesium stearate, Talcum is also used.Aqueous preparation for oral administration has suspension, interior liquor, Emulsion, syrup etc., except normally used simple diluent water, liquid paraffin, can also comprise various excipient, such as wetting agent, flavouring agent, aromatic, preservative agent etc.Preparation for non-oral administration comprises sterile water solution, nonaqueous solvent, suspensoid, Emulsion, freeze-dried dose, suppository.Nonaqueous solvent, suspensoid can use the injectable esters etc. such as vegetable oil, ethyl oleate of propylene glycol (propylene glycol), Polyethylene Glycol, olive oil and so on.The substrate of suppository can use witepsol, polidocanol
tween (tween) 61, cocoa butter
laurate
glycerin gelatine etc.
The preferred dosage of compositions of the present invention is different according to the degree of the state of patient and body weight, disease, drug form, route of administration and period, but those skilled in the art can suitably select.But in order to desirable effect, compositions of the present invention with the solid constituent of oenanthe javanica extract for benchmark, administration 0.01mg/kg ~ 10g/kg on the 1st; Preferred 1mg/kg ~ 1g/kg.Administration can once a day, also can administration several times.Thus which no matter above-mentioned dosage do not limit scope of the present invention from the viewpoint of.
Compositions of the present invention carries out administration by number of ways to rat, mice, domestic animal, the mankind.All modes of administration all can use, such as, and the administration by (intracerebroventricular) injection in oral, rectum or vein, muscle, subcutaneous, intrauterine dura mater or cerebrovascular.Intraperitoneal administration is compared excellent to memory injury preventive effect during oenanthe javanica extract oral administration especially of the present invention.
The present invention goes back providing package promotes admissible food auxiliary additive in the oenanthe javanica extract of effect and bromatology healthy functions food containing display learning capacity or memory.
The oenanthe javanica extract that comprises of the present invention such as has various foodstuff, beverage, chewing gum, tea, compound vitamin, healthy accesary foods class etc. as the compositions of effective ingredient as food, can use with the form of powder, granule, tablet, capsule or beverage.
Oenanthe javanica extract of the present invention itself does not almost have toxicity and side effect, can the medicament of relieved use when being the object long-term taking as prevention yet.
When above-mentioned oenanthe javanica extract of the present invention is added in healthy functions food in order to learning capacity or memory enhancement effect, the amount of described extract take solid constituent as benchmark, when being generally used for the healthy functions food of the forms such as powder of the present invention, granule, tablet, capsule, be added to 0.01 ~ 15 % by weight of total food weight; During the healthy functions food of beverage form, with beverage 100ml for benchmark, add 0.02 ~ 10g, preferably add 0.3 ~ 1g.
The healthy functions food of beverage form of the present invention, using above-mentioned ratio as containing outside extract by composition, has no particular limits for liquid component, can add composition as common beverage containing the conduct such as various flavouring agent and natural carbon hydras.The example of above-mentioned natural carbon hydras has monosaccharide, such as glucose; The disaccharide such as fructose; The such as polysaccharide such as maltose, sucrose; The sugar that such as dextrin, cyclodextrin etc. are common, and the sugar alcohol such as xylitol, sorbitol, erythritol.Flavouring agent in addition to that mentioned above can also use natural flavours (Talin, Folium Chrysanthemi extract (such as Lay bud enlightening glycosides A, glycyrrhizin) and synthesis flavouring agent (glucide, aspartame etc.).The ratio of described natural carbon hydras with compositions 100ml of the present invention for benchmark is containing the 1 ~ 20g that has an appointment, preferably about 5 ~ 12g.
Outside above-mentioned compositions of the present invention can also contain various nutrient, vitamin, mineral (electrolyte), synthesis flavoring agent and the flavoring agent such as natural flavour mountaineous dose, coloring agent and filler (
) (cheese, chocolate etc.), pectic acid and salt, alginic acid and salt thereof, organic acid, protective colloid viscosifier, pH adjusting agent, stabilization agent, antiseptic, glycerol, alcohol, the carbonating agent etc. that uses in soda pop.In addition, compositions of the present invention can also sarcocarp containing the manufacture for natural fruit juice and fruit drink and vegetable beverage.These compositions can be used alone or in combination.Although the ratio of these additives is not very important, with compositions 100 weight portion benchmark of the present invention, generally select in the scope of 0 to about 20 weight portion.
Embodiment
Describe the present invention in detail according to embodiment and experimental example below.
But the following example and experimental example just illustrate the present invention, scope of the present invention does not limit thus.
Experimental example 1: the inhibit activities of the acetylcholinesterase (AChE) of various natural goods compares (Ellman ' s method)
Manufacture the 70(v/v of Radix et Caulis Opuntiae Dillenii fruit, Punica granatum L., Fructus Citri grandis, Fructus Fici, angelica keiskei koidzumi (Angelica utilismakino), Fructus Jujubae and paddy field Herba Apii respectively) ethanol water solution extract of %, compare the inhibit activities of acetylcholinesterase.
Each ethanol water solution extract is to add ethanol (ethanol content 70(v/v) % in dry test portion 10g) 600ml, extract 8 hours when not refluxing at 60 DEG C, cross and filter residue, evaporation and concentration under 50 ~ 60mmHg and 30 ~ 40 DEG C condition, carries out hot air drying by the concentrated solution obtained thus and obtains ethanol extraction powder.
Each ethanol extraction powder dissolution above-mentioned in dimethyl sulfoxide (DMSO) after, with the concentration dilution of 1000 μ g/ml (during DMSO dilution for ultimate density 10%) in 100mM phosphate (pH8.0 is called " buffer I ").The acetylthiocholine iodide solution 20 μ l of extract powder 1.5ml, 100mM phosphate (pH7.0 is called " buffer II ") 1.5ml, 75mM of mixed diluting and buffering Ellman ' s reagent [Buffered Ellman ' sreagent in above-mentioned buffer I; Two (2-nitrobenzoic acid) 10mM, the NaHCO of 5,5-bis-sulfur
317.85mM] 100 μ l, at 25 DEG C, leave standstill 10 minutes.Then, add AChE enzyme (20 μ l) and shake up, then with 30 seconds for measuring space absorbance 5 minutes, be confirmed to be linear response (linear reaction).
Add saline solution (saline) in blank group (blank) and replace enzyme.In addition, do not add acetylthiocholine iodide measured in solution absorbance, when confirming ethanol extraction powder and enzyme assay, whether occur nonspecific reaction slightly.
In addition, do not add extract as negative control group, using AChE activity degree now as 100% time, the AChE inhibit activities degree of the ethanol extraction (500 μ g/ml) relative to each plant is expressed as " % suppression " and shown in Figure 1.AChE activity experiment carries out 5 times repeatedly, and the significance one-way ANOVA experiment of result is tested.
According to Fig. 1, Radix et Caulis Opuntiae Dillenii fruit, Punica granatum L. and grapefruit abstract demonstrate the acetylcholine esterase active suppression ratio of 8 ~ 11%, but paddy field oenanthe javanica extract demonstrates the maximum inhibition of more than 2 times 23.5%, the inhibition of enzyme activity rate of Fructus Fici, angelica keiskei koidzumi and Fructus Jujubae extract, less than 5%, has little effect.
Experimental example 2: the inhibit activities according to the acetylcholinesterase (AChE) of Herba Apii extracting method compares
Purified water 600ml is added in drying water water in field Herba Apii graveolentis 10g, hot water extraction 8 hours at 100 DEG C, cross after filtering residue, evaporation and concentration under the condition of 50 ~ 60mmHg and 30 ~ 40 DEG C, obtains hot water extract's powder by the concentrated solution hot air drying obtained thus.
In addition, ethanol (ethanol content 75(v/v) % is added in drying water water in field Herba Apii graveolentis 10g) 600ml, extract 8 hours when not carrying out refluxing at 60 DEG C, cross after filtering residue, evaporation and concentration under the condition of 50 ~ 60mmHg and 30 ~ 40 DEG C, obtains alcohol extract powder by the concentrated solution hot air drying obtained thus.
Measure the acetylcholine esterase active suppression ratio of above-mentioned paddy field Herba Apii hot water extract powder and alcohol extract powder according to the method for experimental example 1, add DHED37.8 μM as positive controls and compare, and its result is illustrated in Table 1.AChE activity experiment carries out 5 times repeatedly, and the significance one-way ANOVA experiment of result is tested.
Table 1
[table 1]
| Distinguish | Concentration | AChE inhibit activities degree (%) |
| Positive controls (DHED) | 37.8μM | 45.2±5.2 |
| Hot water extract's powder | 500μg/ml | 2.4±0.4 |
| Alcohol extract powder | 500μg/ml | 31.5±9.6 |
Experimental example 3: the inhibit activities according to the acetylcholinesterase (AChE) of oenanthe javanica extract fraction method compares
Ethanol (ethanol content 75(v/v) % is added in the drying water water in field Herba Apii graveolentis 10g of experimental example 2) 600ml, extract 8 hours when not carrying out refluxing at 60 DEG C, cross after filtering residue, respective fraction extract is obtained respectively with hexane, chloroform, ethyl acetate, butanols and water extraction, by they evaporation and concentration under the condition of 50 ~ 60mmHg and 30 ~ 40 DEG C respectively, the concentrated solution hot air drying obtained thus is obtained extract powder.
The method of the acetylcholine esterase active suppression ratio of respective fraction extract (500 μ g/ml) example 1 by experiment measures, and shown in Figure 2.In each fraction extract, the inhibition of enzyme activity rate of ethyl acetate and butanol extract is maximum, therefore judges that the effective ingredient of the acetylcholine esterase inhibition activity of the oenanthe javanica extract of alcohol extraction is present in ethyl acetate layer or butanols layer.
Experimental example 4: the inhibit activities of the acetylcholinesterase (AChE) of dry land Herba Apii and paddy field Herba Apii compares
The drying water water in field Herba Apii graveolentis of experimental example 2 replaces with dry land Herba Apii 10g, add ethanol (ethanol content 75(v/v) %) 600ml, extract 8 hours when not carrying out refluxing at 60 DEG C, cross after filtering residue, evaporation and concentration under the condition of 50 ~ 60mmHg and 30 ~ 40 DEG C, obtains extract powder by the concentrated solution hot air drying obtained thus.
Paddy field oenanthe javanica extract powder and dry land oenanthe javanica extract powder are respectively with 500 μ g/ml concentration, DHED is added with the concentration of 100 μMs as positive controls, the maximum inhibition of acetylcholinesterase is measured according to the method for experimental example 1, and by shown in Figure 3 for its result.
Although dry land oenanthe javanica extract is manufactured by same procedure and the identical concentration used, but can confirm to improve more than 2 times compared with the inhibition of enzyme activity rate of paddy field oenanthe javanica extract, demonstrate the inhibition of enzyme activity rate with the DHED peer-level of 50 μMs of concentration.
Experimental example 5: according to learning disorder and the confirmation of memory disorder preventive effect of passive avoidance response
Experimental apparatus uses shuttle box (Shtuule box) (50 × 15 × 40cm), and base plate is electrical network floor (electric grid floor).Chest is divided into the room of 25 × 15cm by partition door.This experiment is less than 60dB at noise, throws light in dim room, and whether the learning and memory power damage that observation rat causes because of scopolamine (scopolamine) can be obtained medical treatment by the paddy field Herba Apii of experimental example 4 and the administration of dry land oenanthe javanica extract.
Experiment first day, all animals becoming experimental subject all implement following experiment.Rat is put into the room of the light in 2 rooms split by partition door, carry out throwing light on and opening partition door with 1500lux.Rat enters the room of the darkness on the bright opposite of without a licence after observing surrounding, now partition door can be closed automatically.Measure from turning on light and open partition door to the waiting time (latency) of partition door down periods, this test (trial) carries out 3 ~ 4 times repeatedly, within 20 seconds, almost can move to dark room from the 4th bar none from the room of light.
Test second day, to paddy field oenanthe javanica extract powder and each 10mg/kg of dry land oenanthe javanica extract powder of the Oral Administration in Rats administration experimental example 4 of body weight 200 ~ 250g, positive controls tacrine oral administration 1mg/kg.
Extract and tacrine administration are after 1 hour, and intraperitoneal administration is dissolved in the scopolamine 4.5mg/kg of normal saline, after 1 hour, in shuttle box (shuttle box), give foot impacts (foot-shock) by the following method.Rat moves to dark room from the room of light, under the state of turning off the light, just connected electric current 3 second of 0.3mA by the rustless steel electrical network (stainless grid) at the bottom of room, thus gives rat foot impacts.Rat can remember the relation between dark room and foot impacts, puts into bright room after 20 hours, even if irradiate, throwing light on also can hesitate enters into dark room.Now compare the waiting time according to group, and illustrate in table 2.
Table 2
[table 2]
| Distinguish | Waiting time (second) |
| Matched group (scopolamine non-administration group) | 260±39.6 |
| Scopolamine administration group | 17±5.4 |
| The group of the bright choline in administration east after tacrine administration | 32±13.4 |
| The group of administration scopolamine after the Herba Apii administration of paddy field | 17±5.1 |
| The group of administration scopolamine after the administration of dry land Herba Apii | 44±7.2 |
Compare matched group, the hypomnesis of scopolamine administration group is remarkable.The memory declined by scopolamine is by anticholinergic and recovered as the tacrine of dementia treatment medicine in the past.In addition, the effect of the recovery of the memory declined by scopolamine, dry land Herba Apii is better than paddy field Herba Apii, and the memory recovery effects of dry land Herba Apii is better than tacrine.
In order to confirm the effect that the memory of this dry land Herba Apii is recovered, when intraperitoneal administration whether also with show identical effect during oral administration, mutually commensurability dry land oenanthe javanica extract powder is diluted with same concentrations, only change route of administration in the above-mentioned methods again to test, and result is illustrated in table 3.
Table 3
[table 3]
For the recovery of the hypomnesis that scopolamine administration causes, during dry land oenanthe javanica extract oral administration compared with scopolamine administration group, waiting time, (Latency time) enhanced 2.6 times, but did not see the recovery effects of hypomnesis when intraperitoneal administration.
Experimental example 6: the therapeutic effect of the hypomnesis caused by alcohol confirms
The therapeutic effect of the hypomnesis caused by alcohol is implemented through 4 time-of-weeks.Alcohol is with 2.5g/kg consumption intraperitoneal administration every day.The dosage of dry land oenanthe javanica extract with 10mg/kg and positive controls linoleic acid with 10mg/kg oral administration 4 weeks.Y maze experiment has been carried out after administration surrounding.
Y-maze experiment is the method for testing of clarifying space consciousness, and the black plastic be made up of the arm that three sizes are identical is got lost.Each arm is made up of 80 × 35 × 15cm, and each arm maintains identical angle.End rat being placed on arm makes its free activity 10 minutes.Record rat enters the order of each arm.Marking is given during different three arms of Continuous Selection.Their mark (% replaced) (% of alternation) is illustrated in table 4 according to group.
Table 4
[table 4]
| Distinguish | % alternately |
| Matched group | 66.8±3.5 |
| Matched group oral administration dry land oenanthe javanica extract | 62.0±5.7 |
| Alcohol intraperitoneal administration | 42.9±5.2 |
| Alcohol intraperitoneal administration and linoleic acid oral administration | 62.3±2.8 |
| Alcohol intraperitoneal administration and dry land oenanthe javanica extract oral administration | 62.2±4.6 |
Matched group intraperitoneal administration alcohol, after 4 weeks, is compared matched group and has been occurred significant hypomnesis.The memory declined by alcohol is like this had the linoleic administration that memory improves effect replied by the past known, during oral administration dry land oenanthe javanica extract of the present invention, demonstrate the recovery effects with the memory injury caused by alcohol of linoleic acid peer-level.
Experimental example 7: confirmed by the therapeutic effect of the memory injury that stress cause
Implemented through 4 time-of-weeks by the Experiment on therapy of the hypomnesis that stress cause.In order to stress tests, rat is kept in detention 6 hours every day in plastics box, give thus fixing stress.The dosage of dry land oenanthe javanica extract is 10mg/kg and positive controls linoleic acid is 10mg/kg oral administration 4 weeks.Administration carried out Y-maze experiment according to the method identical with experimental example 6 after 4 weeks, and its result was illustrated in table 5.
Table 5
[table 5]
| Distinguish | % alternately |
| Matched group | 68.24±4.32 |
| Matched group oral administration dry land oenanthe javanica extract group | 72.54±6.21 |
| Stress group | 60.13±5.17 |
| Linoleic group of stress group oral administration | 67.53±4.94 |
| The group of stress group oral administration dry land oenanthe javanica extract | 69.09±4.52 |
Compare matched group to stress in rats and occur significant hypomnesis.By this hypomnesis that stress cause, by in the past known have memory improve linoleic administration and be restored, during oral administration dry land oenanthe javanica extract of the present invention, demonstrate the recovery effects to the memory injury that alcohol causes with linoleic acid peer-level.
Below the formulation example of the compositions containing extract of the present invention is described, but just in order to illustrate the present invention, not delimit the scope of the invention.
The manufacture of formulation example 1. powder
The dry land oenanthe javanica extract powder 20mg obtained in experimental example 4
Lactose 100mg
Talcum 10mg
Be filled in airtight bag after mentioned component is mixed and manufacture powder.
The manufacture of formulation example 2. tablet
The dry land oenanthe javanica extract powder 10mg obtained in experimental example 4
Corn starch 100mg
Lactose 100mg
Magnesium stearate 2mg
Beat sheet by the manufacture method of common tablet after being mixed by mentioned component and manufacture tablet.
The manufacture of formulation example 3. capsule
The dry land oenanthe javanica extract powder 10mg obtained in experimental example 4
Crystalline cellulose 3mg
Lactose 14.8mg
Magnesium stearate 0.2mg
According to the manufacture method of common capsule, mentioned component is mixed, be filled in gelatine capsule and manufactured capsule.
The manufacture of formulation example 4. injection
The dry land oenanthe javanica extract powder 10mg that experimental example 4 obtains
Mannitol 180mg
Injection sterile purified water 2974mg
Na
2HPO
4·12H
2O 26mg
According to the manufacture method of common injection, manufacture with per ampoule (2ml) mentioned component content.
The manufacture of formulation example 5. liquor
The dry land oenanthe javanica extract powder 20mg obtained in experimental example 4
Isomerized sugar 10g
Mannitol 5g
Purified Water q. s
According to common liquor manufacture method, in purified water, add each component dissolves, after adding appropriate NINGMENGXIANG, mentioned component is mixed, then adding purified water, being adjusted to 100ml by adding the cumulative volume after purified water, be filled in brown bottle and carry out sterilizing manufacture liquor.
The manufacture of formulation example 6. healthy functions food
The dry land oenanthe javanica extract powder 1000mg that experimental example 4 obtains
Vitamin mixtures is appropriate
Vitamin A acetate 70 μ g
Vitamin E 1.0mg
Vitamin B1 0.13mg
Vitamin B2 0.15mg
Vitamin B6 0.5mg
Vitamin B12 0.2 μ g
Vitamin C 10mg
Biotin 10 μ g
Nicotiamide 1.7mg
Folic acid 50 μ g
Calcium pantothenate 0.5mg
Inanimate matter mixture is appropriate
The ferrous 1.75mg of sulfonic acid
Zinc oxide 0.82mg
Magnesium carbonate 25.3mg
Potassium dihydrogen phosphate 15mg
Calcium hydrogen phosphate 55mg
Citric acid calcium 90mg
Calcium carbonate 100mg
Magnesium chloride 24.8mg
The ratio of components of the mixture of said vitamin and mineral is that the composition being relatively applicable to health food is mixed composition according to the preferred embodiment, but it is also harmless that its proportioning carries out random variation, after mentioned component being mixed according to common healthy functions process for preparation of food product, manufacture granule, be used for the manufacture of healthy functions food compositions according to usual way.
The manufacture of formulation example 7. healthy beverage
The dry land oenanthe javanica extract powder 1000mg that experimental example 4 obtains
Citric acid 1000mg
Oligosaccharide 100g
Prunus mume (sieb.) sieb.et zucc. concentrated solution 2g
Taurine 1g
Add purified water to 900ml
After being mixed by mentioned component according to the manufacture method of common healthy beverage, at 85 DEG C, stir about is after 1 hour, is filtered the solution that obtains, is contained in sealing in the 2L container of sterilizing and carries out cold preservation after sterilizing, then for the manufacture of healthy beverage compositions of the present invention.
Industrial utilization
The composition being relatively applicable to hobby beverage is carried out mixing and forms by above-mentioned ratio of components according to the preferred embodiment, but as required stratum, need the region such as country, use, nationality preference degree, it is also harmless its proportioning to be carried out random variation.
Claims (6)
1. learning disorder or memory disorder prevent or a medicine for treatment compositions, it is characterized in that, using oenanthe javanica extract as effective ingredient,
Wherein said Herba Apii is dry land Herba Apii;
The manufacture method of described oenanthe javanica extract is, is mixed by the aqueous lower alcoholic solutions of drying water Herba Apii graveolentis with the carbon number 1 ~ 4 of 20 ~ 200 times of its weight, extracts 4 ~ 20 hours at 50 ~ 90 DEG C;
Described aqueous lower alcoholic solutions is the ethanol water of 50 ~ 80 (v/v) %, after extracting with described alcoholic solution, by extract ethyl acetate or butyl alcohol extraction.
2. learning disorder according to claim 1 or memory disorder prevent or medicine for treatment compositions, and it is characterized in that, said composition is Compositions for oral delivery.
3. learning disorder according to claim 1 or memory disorder prevent or medicine for treatment compositions, and it is characterized in that, described extract is the extract of the solvent be dissolvable in water in the aqueous solution of lower alcohol or the described lower alcohol being selected from carbon number 1 ~ 4.
4. learning disorder according to claim 3 or memory disorder prevention or medicine for treatment compositions, is characterized in that, the alcohol-water solution of the aqueous solution of described lower alcohol to be the mixing ratio of lower alcohol be 10 ~ 95 (v/v) %.
5. a healthy functions food is used in learning capacity or memory enhancement, it is characterized in that, using oenanthe javanica extract as effective ingredient,
Wherein said Herba Apii is dry land Herba Apii;
The manufacture method of described oenanthe javanica extract is, is mixed by the aqueous lower alcoholic solutions of drying water Herba Apii graveolentis with the carbon number 1 ~ 4 of 20 ~ 200 times of its weight, extracts 4 ~ 20 hours at 50 ~ 90 DEG C;
Described aqueous lower alcoholic solutions is the ethanol water of 50 ~ 80 (v/v) %, after extracting with described alcoholic solution, by extract ethyl acetate or butyl alcohol extraction.
6. learning capacity according to claim 5 or memory enhancement healthy functions food, is characterized in that, the form of described healthy functions food is powder, granule, tablet, capsule or beverage form.
Applications Claiming Priority (3)
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| KR10-2010-0087923 | 2010-09-08 | ||
| KR20100087923 | 2010-09-08 | ||
| PCT/KR2011/006591 WO2012033329A2 (en) | 2010-09-08 | 2011-09-07 | Composition containing oenanthe javanica extract as an active ingredient for preventing or treating learning disabilities or memory disorders, and method for preparing same |
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| KR102296347B1 (en) * | 2019-11-27 | 2021-09-01 | 강원대학교산학협력단 | Composition for preventing the ischemic stroke disease containing natural complex extract |
| KR20210147707A (en) | 2020-05-29 | 2021-12-07 | 좋은영농조합법인 | Composition for relieving and preventing hangover comprising Oenanthe javanica extracts |
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| 张桂等.从芹菜中提取黄酮类物质的研究.《食品科学》.2002,第23卷(第8期),第121-125页. * |
| 芹菜中黄酮类物质的提取研究;吉欣等;《现代食品科技》;20060131;第22卷(第1期);摘要 * |
| 芹菜提取液对中老年小鼠学习记忆的影响;李静等;《中草药》;19960229(第2期);第104页第一段、最后一段 * |
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| WO2012033329A3 (en) | 2012-06-28 |
| KR101280421B1 (en) | 2013-07-01 |
| WO2012033329A2 (en) | 2012-03-15 |
| KR20120026010A (en) | 2012-03-16 |
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