CN103784448A - Preparation method of natural 6-hydroxykynurenic acid extract and application thereof - Google Patents
Preparation method of natural 6-hydroxykynurenic acid extract and application thereof Download PDFInfo
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- CN103784448A CN103784448A CN201410007590.0A CN201410007590A CN103784448A CN 103784448 A CN103784448 A CN 103784448A CN 201410007590 A CN201410007590 A CN 201410007590A CN 103784448 A CN103784448 A CN 103784448A
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Abstract
The invention discloses a preparation method of a natural 6-hydroxykynurenic acid extract by separation from production waste water of a ginkgo biloba extract. The 6-hydroxykynurenic acid (6-HKA) extract is prepared through separation from the production waste water of the ginkgo biloba extract as a raw material. The preparation method comprises the steps: directly performing adsorption separation on the production waste water by using polyamide resin, and regulating a pH of an eluting concentrated solution and the like to prepare the 6-HKA extract. According to the preparation method, by fully utilizing folium ginkgo resources, the content of the 6-hydroxykynurenic acid in the extract is 50-90 percent, and the natural 6-hydroxykynurenic acid extract can be used for preparing foods, health foods or medicines for preventing or treating the nervous system disease, resisting the cardiovascular and cerebrovascular diseases or resisting depression.
Description
(1) technical field: the present invention relates to natural plant extracts, be specifically related to separate method and the application thereof of the natural 6-HKA extract of preparation from Folium Ginkgo extract factory effluent.
(2) background technology: contain the organic acid of rich content in Folium Ginkgo and extract thereof, its content in Semen Ginkgo standard extract EGb761 reaches 13%.Semen Ginkgo organic acid composition can be divided into two large classes, non-phenolic acid and phenolic acid, and the former comprises ascorbic acid, maltonic acid, quinic acid and shikimic acid; The latter comprises protocatechuic acid, P-hydroxybenzoic acid, vanillic acid, caffeic acid, P-coumaric acid, ferulic acid and chlorogenic acid.Except above-mentioned these common phenolic acid, also have a kind of rare nitrogenous phenolic acid, be called 6-HKA (6-hydroxykynurenic acid, 6-HKA).6-HKA is the derivant of kynurenic acid, the same with kynurenic acid, is all glutamate receptor antagonists, has the effect of fine neuroprotective cell.So far, 6-HKA is not also put into the quality standard of Folium Ginkgo and preparation thereof.
But along with the development of Semen Ginkgo industry and scientific and technical progress, in Folium Ginkgo and preparation thereof, the separation and purification of each composition and pharmacological effect research thereof are more and more, separate the effective ingredient of formulating in Folium Ginkgo extract efficiently and become the separation and Extraction of main flow direction, the especially ginkgetin of current research and development, bilobalide, gingkolic acid.Current most of document mainly concentrates on synthetic, isolation identification about the report of 6-HKA, but the synthetic ratio of 6-HKA is very low, and two step synthesis rate is only also 8.2%.Therefore, from plant, extracting the 6-HKA for preparing high-load becomes the main source of 6-HKA, but it is less to extract the report of preparation about 6-HKA at present.By P.K.MACNICOL has measured the 6-HKA content of the each plant parts of Nicotiana tabacum L., and result shows that in tobacco leaf, 6-HKA content is the highest; Grasel etc. separate 6-HKA from Folium Ginkgo with Folium Ginkgo extract, and it successively adopts dichloromethane defat, 70% methanol extraction, and the solution after concentrating under reduced pressure adsorbs with strong cation-exchanging resin, with the first remove impurity of 70% methanol, then use 10% NH
4oH eluting, recrystallization, finally obtains 6-HKA extract by activated carbon decolorizing; The thick product of 6-HKA prepared by this technique and the rate of transform of pure substance are respectively 82%, 49.5%.Above-mentioned technique has been used the toxic solvents such as dichloromethane, methanol, ammonia, no matter be safety in preparation process or the processing of the follow-up three wastes, all has larger problem; The more important thing is, this technique directly adopts Folium Ginkgo to extract 6-HKA, and the compositions such as its ginkgetin, bilobalide all lose in preparation process.CN102133243A discloses a kind of technique of preparing Folium Ginkgo extract, contains the 6-HKA of 3-4.5% in this Folium Ginkgo extract.
In Chinese Pharmacopoeia, the preparation method of Folium Ginkgo extract is, after Diluted Alcohol extracts, carry out purification with macroporous resin, but 6-HKA to be the micromolecular compound that a kind of polarity is very large, in the Folium Ginkgo extract production process of Chinese Pharmacopoeia, runs off in a large number.Through technical staff, to process for preparing gingko leaf extract process monitoring, result overwhelming majority 6-HK is lost in resin water-washing process, and 6-HKA is present in factory effluent.Therefore, find a kind of from Folium Ginkgo extract factory effluent the method for separate and prepare high-content 6-HKA extract, significant for further developing of the comprehensive utilization of Folium Ginkgo resource and Semen Ginkgo industry.
(3) summary of the invention: the natural 6-HKA extract that the object of the present invention is to provide a kind of high-load, and in the waste water producing, separate the method for the natural 6-HKA extract of preparation (6-HKA) from Folium Ginkgo extract production process, also provide prepared natural 6-HKA extract in the application of preparing food, health food or medicine.
Wherein, in 6-HKA extract, contain 50～90%(w/w) natural 6-HKA.The waste water producing take Folium Ginkgo extract is as raw material, and upper polyamide, alcoholic solution eluting, the concentrated rear recrystallization of eluent, obtain 6-HKA extract, and wherein the weight percent content of natural 6-HKA is 50～90%, and concrete preparation process is as follows:
1) by the macroporous resin water lotion waste water producing in the Folium Ginkgo extract production process of preparing according to Chinese Pharmacopoeia (being Folium Ginkgo extract factory effluent), upper polyamide, with containing 0～0.2%(v/v) 30～90%(v/v of hydrochloric acid) concentration ethanol solution carries out eluting separation, obtains eluent;
2) eluent reclaims ethanol, concentrates to obtain concentrated solution, and concentrated solution relative density is at normal temperatures 1.05～1.25;
3) concentrated solution adjusts pH to acid with acid, filters to obtain crystallization;
4) after gained crystallizing and drying, obtain 6-HKA extract, its purity is weight ratio 50～90%.
Folium Ginkgo extract factory effluent of the present invention is for preparing the factory effluent of Folium Ginkgo extract according to " Chinese Pharmacopoeia ", main component is the large polar substances such as monosaccharide and disaccharide, polysaccharide, aminoacid, and the content of 6-HKA is 0.1～0.3%(w/w).
In the composite Folium Ginkgo extract to preparing according to " Chinese Pharmacopoeia " of the prepared 6-HKA extract of the present invention, improve the content of 6-HKA in Folium Ginkgo extract, strengthen activating blood circulation to dissipate blood stasis and dredge the collateral effect of Folium Ginkgo extract.
In preparation method of the present invention:
In step 1), polyamide on macroporous resin water lotion waste water, first with containing 0～0.02%(v/v) remove impurity of salt aqueous acid, then with containing 0～0.2%(v/v) the alcoholic solution eluting separation of hydrochloric acid, wherein, the concentration of alcoholic solution is 30～90%(v/v).
In step 1) of the present invention, elution step optimised process preferably certainly, polyamide on macroporous resin water lotion waste water, first with containing 0.01%(v/v) salt aqueous acid carries out eluting remove impurity, then with containing 0.1%(v/v) 70% alcoholic solution of hydrochloric acid carries out eluting separation.
Step 2) in, the relative density the best under concentrated solution room temperature is preferably 1.15.
In step 3), concentrated solution adjusts pH to acid with acid, and the acid that regulates pH value can be the one of hydrochloric acid, sulphuric acid, phosphoric acid or any two kinds, and the pH value of concentrated solution is 0～2.0; Optimised process is preferably from hydrochloric acid adjust pH to 1.0 for, concentrated solution.
Inventor's discovery, 6-HKA extract can improve the function of nervous system of ischemia-reperfusion mice, reduces the infarct size of cerebral tissue, reduces the content of the glutamic acid of cerebral tissue, reduces the irritability loss of cerebral tissue, and apoplexy is had to protective effect; In addition, 6-HKA extract can improve the concentration of neurotransmitter norepinephrine (NE) in depression Rat hippocampus, dopamine (DA) and 5-hydroxy tryptamine (5-HT), and it has a better role to depression.Therefore, 6-HKA extract prepared by the present invention, can be used as food, health food or medicine for the preparation of prevention or treatment nervous system disease, especially prepares resisting cardiovascular disease, antidepressant food, health food or medicine.
The present invention is take Folium Ginkgo extract factory effluent as raw material, utilize low sour remove impurity, and with alcoholic solution from polyamide eluting separate targets product, then according to the characteristic Crystallization Separation of 6-HKA different solubility under different pH condition, obtain highly purified 6-HKA product.The present invention obtains following beneficial effect:
1, the invention provides a kind of weight ratio content is 50～90%(w/w) natural 6-HKA extract and preparation method thereof, efficiently solve the source problem that comes of high-purity 6-HKA; And it,, to have extracted Folium Ginkgo extract factory effluent after ginkgetin, bilobalide as raw material, takes full advantage of Folium Ginkgo resource, turns waste into wealth, and has produced great economic worth.
2, the present invention is with containing 0.01%(v/v) salt aqueous acid rinses polyamide for the first time, and this step can be got off the water-soluble substances of low acid from resin elution, improved the purity of next step 6-HKA; And with containing 0.1%(v/v) the 70% alcoholic solution eluting polyamide again of hydrochloric acid, can farthest 6-HKA be eluted from resin.It is the highest that this stepwise elution step makes the rate of transform of 6-HKA exceed the purity of 98%, 6-HKA; And it is follow-up only needs simply to regulate pH value just can obtain highly purified 6-HKA extract by recrystallization.This preparation method has obtained beyond thought effect.
3, extraction preparation method of the present invention, except ethanol, is not introduced organic solvent again, and compared to existing technology, this preparation method is easy and simple to handle, safe, to instrument and equipment require low, cost is low, be applicable to suitability for industrialized production; And the follow-up three wastes are processed only needs to reclaim ethanol and a small amount of alkali neutralization.
4, the natural 6-HKA extract of preparing by preparation method of the present invention has the effect for the treatment of cardiovascular and cerebrovascular disease or depression, can be used for preparing resisting cardiovascular disease or antidepressant food, health food or medicine.
(4) accompanying drawing explanation
Fig. 1 is 6-HKA reference substance chromatogram, the appearance time that wherein 10.633min is reference substance;
Fig. 2 is 6-HKA extract chromatogram, and wherein 10.633min is the appearance time of 6-HKA in 6-HKA extract.
(5) specific embodiments:
The following examples, for further illustrating and describe the present invention, but and do not mean that the present invention only limits to this.The arbitrary concrete numerical value that in embodiment, value is scope of the present invention, is and can implements.
Folium Ginkgo extract waste water used in following examples is for preparing the factory effluent of Folium Ginkgo extract according to " Chinese Pharmacopoeia 2010 editions ".
Embodiment 1:6-HKA is the research of the rate of transform in process of production
Get 20kg Folium Ginkgo, be crushed to particle diameter and be less than 1cm, add the ethanol water of 200L50%, reflux, extract, 3 times, each 2h, merge extractive liquid; Reclaim ethanol, to extractum density 1.2g/ml, filter, by macroporous resin adsorption, after washing, with 70% ethanol water eluting, collect elute soln and water lotion; Elute soln reclaims ethanol, and vacuum drying is pulverized, and obtains Folium Ginkgo extract.
In Folium Ginkgo, macroporous resin water lotion, Folium Ginkgo extract, the method for 6-HKA content is as follows:
Instrument: Agilent HPLC1260;
Immobile phase: Agilent XDB-C8 post 250mm × 4.6mm, 5 μ m
Mobile phase and gradient list
Flow velocity: 1.0ml/min; Detect wavelength: 350nm; Sample size: 10 μ L.
Result is as follows:
(1) in Folium Ginkgo, 6-HKA content is that in 0.036%, 20kg Folium Ginkgo, 6-HKA total amount is 7.2g;
(2) Folium Ginkgo extract yield is that 2.09%, 6-HKA content is 0.161%, and in Folium Ginkgo extract, 6-HKA total amount is 0.673g, and the 6-HKA rate of transform is 9.35%;
(3) macroporous resin water lotion 60L, content is 0.108mg/ml, in macroporous resin water lotion, 6-HKA total amount is 6.48g, accounts for 90% of Folium Ginkgo 6-HKA total amount.Fig. 1 is shown in by the HPLC collection of illustrative plates of 6-HKA, and reference substance HPLC is shown in Fig. 2.
Embodiment 2: the screening of remove impurity solvent
Get Folium Ginkgo extract factory effluent (macroporous resin water lotion) 1L, use polyamide adsorbing separation, the aqueous solution of aqueous solution/0.02%HCl of aqueous solution/0.01%HCl of water/0.005%HCl carries out eluting remove impurity respectively, collect each remove impurity position, measure 6-HKA loss rate prepared by each eluent.Concrete outcome is in table 1, and when front 3 kinds of solution carry out eluting remove impurity, 6-HKA does not lose; In the time that HCl volumetric concentration brings up to 0.02%, 6-HKA starts to run off with eluent, therefore uses containing the aqueous solution of HCl0.01% and following concentration and carries out good impurity removing effect.
The impact of table 1 remove impurity position on 6-HKA loss rate
| Remove impurity position | 6-HKA loss rate (%) |
| Water | 0% |
| Containing the aqueous solution of 0.005%HCl | 0% |
| Containing the aqueous solution of 0.01%HCl | 0% |
| Containing the aqueous solution of 0.02%HCl | 3.7% |
Embodiment 3: the screening of concentration of hydrochloric acid in eluting solvent
Folium Ginkgo extract factory effluent (macroporous resin water lotion) is used polyamide adsorbing separation, with carrying out eluting remove impurity containing the aqueous solution of 0.01%HCl, carry out eluting with volume ratio 70% concentration ethanol aqueous solution or containing 70% ethanol water of 0.05%HCl or containing 70% ethanol water of 0.1%HCl or containing 70% ethanol water of 0.2%HCl again, obtain eluent, after concentrate drying, measure the rate of transform and the purity of 6-HKA.Concrete outcome is in table 2, carries out eluting, best results with 70% ethanol water of 0.1%HCl.
The impact of the different eluting of table 2 position on the 6-HKA rate of transform, purity
| Eluting position | The 6-HKA rate of transform (%) | 6-HKA purity (%) |
| 70% ethanol water | 9.67 | 0.88% |
| 70% ethanol water of 0.05%HCl | 78.31 | 7.73% |
| 70% ethanol water of 0.1%HCl | 98.20 | 12.38% |
| 70% ethanol water of 0.2%HCl | 97.35 | 12.15% |
?embodiment 4: the screening of concentration of alcohol in eluting solvent
Folium Ginkgo extract factory effluent (macroporous resin water lotion) is used polyamide adsorbing separation, with carrying out eluting remove impurity containing the aqueous solution of volume ratio 0.01%HCl, use again the ethanol water gradient elution successively containing 30%, 50%, 70%, 90% volumetric concentration of volume ratio 0.1%HCl, obtain eluent, after concentrate drying, measure the eluting rate of 6-HKA.Concrete outcome is in table 3, with the 70% ethanol water eluting 6-HKA substantially completely containing 0.1%HCl.
The impact of the different gradient elutions of table 3 position on 6-HKA eluting rate
| Eluting position | 6-HKA eluting rate (%) | The 6-HKA accumulation rate of transform (%) |
| 30% ethanol water of 0.1%HCl | 2.32% | 2.32% |
| 50% ethanol water of 0.1%HCl | 37.76% | 39.08% |
| 70% ethanol water of 0.1%HCl | 60.33% | 99.41% |
| 90% ethanol water of 0.1%HCl | 0% | 99.41% |
Embodiment 5: the screening of concentrated solution density
Folium Ginkgo extract factory effluent (macroporous resin water lotion) is used polyamide adsorbing separation, with carrying out eluting remove impurity containing the aqueous solution of 0.01%HCl, then carries out eluting, acquisition eluent with 70% ethanol water containing 0.1%HCl; Eluent reclaims ethanol, is concentrated into the concentrated solution of relative density 1.05,1.10,1.15,1.20,1.25g/ml; Adjust pH to 1.0 with HCl again, filter to obtain crystallization; After crystallizing and drying, measure the rate of transform and the purity of 6-HKA.Concrete outcome is in table 4, the purity of gained 6-HKA extract between 79.86% to 89.61%, take concentrated solution density as 1.15g/ml effect best.
The impact of the different concentrated solution densities of table 4 on the 6-HKA rate of transform
| Concentrated solution density (g/ml) | The 6-HKA rate of transform (%) | 6-HKA purity (%) |
| 1.05 | 73.14% | 79.86% |
| 1.10 | 78.27% | 84.27% |
| 1.15 | 84.36% | 89.61% |
| 1.20 | 82.33% | 88.48% |
| 1.25 | 80.17% | 88.25% |
Embodiment 6: the screening of recrystallization solution pH value
Folium Ginkgo extract factory effluent (macroporous resin water lotion) is used polyamide adsorbing separation, with carrying out eluting remove impurity containing the aqueous solution of 0.01%HCl, then carries out eluting, acquisition eluent with 70% ethanol water containing 0.1%HCl; Eluent reclaims ethanol, is concentrated into the concentrated solution of relative density 1.15g/ml; Adjust pH to 0,1.0,2.0 with HCl again, filter to obtain crystallization; After crystallizing and drying, measure the rate of transform and the purity of 6-HKA.Concrete outcome is in table 5, and the content of gained 6-HKA extract is 51.86%～81.37%, and concentrated solution adjusts pH to 1.0 effect best.
The impact of the different pH value of table 5 on the 6-HKA rate of transform, purity
| PH value | The 6-HKA rate of transform (%) | 6-HKA purity (%) |
| 0 | 83.25% | 51.86% |
| 1.0 | 84.36% | 89.61% |
| 2.0 | 64.42% | 81.37% |
Embodiment 7: regulate sour screening for pH value
Folium Ginkgo extract factory effluent (macroporous resin water lotion) is used polyamide adsorbing separation, with carrying out eluting remove impurity containing the aqueous solution of 0.01%HCl, then carries out eluting, acquisition eluent with 70% ethanol water containing 0.1%HCl; Eluent reclaims ethanol, is concentrated into the concentrated solution of relative density 1.15g/ml; Adjust pH to 1.0 with HCl, sulphuric acid, phosphoric acid again, filter to obtain crystallization; After crystallizing and drying, measure the rate of transform and the purity of 6-HKA.Concrete outcome is in table 6, and the content of gained 6-HKA extract is 78.23%～89.61%, best by HCl tune pH effect.
The impact of the different acid of table 6 on the 6-HKA rate of transform
| PH value | The 6-HKA rate of transform (%) | 6-HKA purity (%) |
| Hydrochloric acid | 84.36% | 89.61% |
| Phosphoric acid | 83.32% | 81.04% |
| Sulphuric acid | 82.55% | 78.23% |
Embodiment 8:6-HKA extract preparation technology checking
Get the upper polyamide of 3 batches of Folium Ginkgo extract factory effluents (macroporous resin water lotion), with containing 0.01%(v/v) aqueous solution of HCl carries out eluting remove impurity, again with containing 0.1%(v/v) 70%(v/v of HCl) ethanol water carries out eluting separation, obtains eluent; Eluent reclaims ethanol, is concentrated into the concentrated solution of relative density 1.15g/ml; Adjust pH to 1.0 with HCl again, filter to obtain crystallization; After crystallizing and drying, measure the rate of transform and the purity of 6-HKA.Concrete outcome is in table 7, and the rate of transform of 3 batches of 6-HKA extracts and purity are all basic identical, and this process stabilizing is described.
Table 76-HKA extract stable preparation process is investigated
| Factory effluent batch | The 6-HKA rate of transform (%) | 6-HKA purity (%) |
| 1 | 84.13% | 90.11% |
| 2 | 85.67% | 89.25% |
| 3 | 84.48% | 89.87% |
| On average | 84.76% | 89.74% |
| RSD（%） | 0.95% | 0.49% |
The impact of embodiment 9:6-HKA extract on apoplexy mice
Get 6-HKA extract prepared by the embodiment of the present invention 8, purity 90.10%.
Male ICR mouse is divided into 5 groups at random, model group, sham operated rats, 6-HKA extract group (purity 90.10%, 3mg/kg), bilobalide group (purity 95.13%, 3mg/kg), ginkalide B group (purity 95.32%, 3mg/kg).Test and carry out gastric infusion in first 3 days, model group and sham operated rats give the distilled water of same volume.
After mice is weighed, by 400mg/kg lumbar injection 4% chloral hydrate anesthesia, the sterilization of skin of neck unhairing, median incision, separates left carotid and external carotid artery.Ligation external carotid artery, on common carotid artery, cut off an osculum, by a head end with burning to the diameter of the globulate fishing line that is 0.11mm along common carotid artery, be inserted to middle cerebral artery crotch through internal carotid artery to intracranial, insertion depth is 12～13mm approximately, ligation internal carotid artery and common carotid artery, fixing fishing line, skin suture.Ischemia pulls out fishing line gently to aortic bifurcation place inside and outside neck after 2 hours, realize and pouring into.Sham operated rats only separates common carotid artery and external carotid artery, does not insert fishing line.After reviving, mice occurs that the operation contralateral limbs dyskinesia is model and is successfully prepared.Function of nervous system's defect scoring is carried out function of nervous system's defect scoring with reference to 5 points of standards of grading processed of Longa.0 is divided into normally, impassivity damage symptom; L is divided into can not full extension offside fore paw; 2 are divided into and carry the backward outside of tail and turn-take; 3 are divided into walking time topples over to offside; 4 be divided into can not spontaneous walking or loss of consciousness.Perform the operation latter 24 hours by mice sacrificed by decapitation, get brain, calculate brain infarction area percentage ratio, and measure the Glu content in brain tissue homogenate.Concrete outcome is in table 8.
6-HKA extract prepared by presentation of results the present invention has good protective effect to apoplexy mice, the just energy onset of the dosage of 3mg/kg, but bilobalide and ginkalide B are in the time of the dosage of 3mg/kg, and apoplexy mice is not had to protective effect.
The impact of table 86-HKA extract on apoplexy mice
With sham operated rats ratio: ##:P<0.01; With model group ratio: * *: P<0.01;
The impact of embodiment 10:6-HKA extract on chronic stress depression model rat
Get 6-HKA extract prepared by the embodiment of the present invention 8, purity 90.10%.
Male SD rat is divided into 5 groups at random, model group, normal group, 6-HKA extract high and low group of (purity 90.10%, 3,1mg/kg), positive drug group (fluoxetine 3.5mg/kg).
Normal group does not stimulate, other treated animal is raised separately, accepts the chronic stress processing of continuous 28 days, comprising: water 24h is prohibited in fasting, 4 ℃ of frozen water swimming 5min, 40 ℃ of hot environment 5min, electric shock vola 5min, puts upside down round the clock, folder tail 1min etc., a kind of stimulation every day, the discontinuous appearance of same stimulation, causes chronic stress depression model.Animal is put to death after experiment finishes, and gets brain bilateral hippocampus tissue, measures the concentration of neurotransmitter norepinephrine (NE), dopamine (DA) and 5-hydroxy tryptamine (5-HT) in hippocampal tissue.Concrete outcome is in table 9.
6-HKA extract prepared by presentation of results the present invention has good curative effect to depression.
The impact of table 96-HKA extract on chronic stress depression model rat
Note: with normal group comparison
#p<0.05,
##p<0.01; With model group comparison
*p<0.05,
*p<0.01.
Claims (8)
1. one kind separates the method for the natural 6-HKA extract of preparation from Folium Ginkgo extract factory effluent, the waste water producing take Folium Ginkgo extract is as raw material, with polyamide separation, adjustment eluting concentrated solution pH value recrystallization, obtain 6-HKA extract, the weight percent content of 6-HKA is 50%～90%; Concrete preparation process is as follows: 1) by polyamide on the macroporous resin water lotion waste water producing in Folium Ginkgo extract production process, carry out eluting separation, acquisition eluent with 30～90% volumetric concentration alcoholic solution of volume ratio 0～0.2% hydrochloric acid; 2) eluent reclaims ethanol, concentrates to obtain concentrated solution, concentrated solution relative density 1.05～1.25 at normal temperatures; 3) concentrated solution adjusts pH to acid with acid, filters and obtains crystallization; 4) after crystallizing and drying, obtain 6-HKA extract.
2. preparation method according to claim 1, it is characterized in that in step 1) polyamide on macroporous resin water lotion waste water, first carry out eluting remove impurity with volume ratio 0～0.02% salt aqueous acid, carry out eluting separation by volume ratio containing 30～90% volumetric concentration alcoholic solution of 0～0.2% hydrochloric acid again, obtain eluent.
3. preparation method according to claim 1 and 2, it is characterized in that in step 1) polyamide on macroporous resin water lotion waste water, first carry out eluting remove impurity by volume ratio containing 0.01% salt aqueous acid, carry out eluting separation by volume ratio containing 70% alcoholic solution of 0.1% hydrochloric acid again, obtain eluent.
4. preparation method according to claim 1, is characterized in that acid used in step 3) can be any in hydrochloric acid, sulphuric acid or phosphoric acid, and the pH value of adjusting concentrated solution is 0～2.0.
5. according to the preparation method described in claim 1 or 4, it is characterized in that acid used in step 3) is hydrochloric acid, adjust the pH value to 1.0 of concentrated solution.
6. the 6-HKA extract that prepared by preparation method claimed in claim 1, it is for the preparation of health food or the medicine of prevention or treatment nervous system disease.
7. the 6-HKA extract that prepared by preparation method claimed in claim 1, it is for the preparation of resisting cardiovascular disease or antidepressant food, health food or medicine.
8. the 6-HKA extract that prepared by preparation method claimed in claim 1, it is for the preparation for the treatment of apoplexy or antidepressant food, health food or medicine.
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| CN115006435A (en) * | 2022-06-21 | 2022-09-06 | 浙江康恩贝制药股份有限公司 | Ginkgo leaf organic acid extract and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1965870A (en) * | 2005-11-18 | 2007-05-23 | 北京天新园医药科技开发有限公司 | Pharmaceutical composition containing ligustrazine and effective component of ginkgo leaf and formulation thereof |
| CN102133243A (en) * | 2011-03-09 | 2011-07-27 | 上海诺德生物实业有限公司 | Folium ginkgo extract containing 6-hydroxykynurenic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1965870A (en) * | 2005-11-18 | 2007-05-23 | 北京天新园医药科技开发有限公司 | Pharmaceutical composition containing ligustrazine and effective component of ginkgo leaf and formulation thereof |
| CN102133243A (en) * | 2011-03-09 | 2011-07-27 | 上海诺德生物实业有限公司 | Folium ginkgo extract containing 6-hydroxykynurenic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115006435A (en) * | 2022-06-21 | 2022-09-06 | 浙江康恩贝制药股份有限公司 | Ginkgo leaf organic acid extract and preparation method and application thereof |
| CN115006435B (en) * | 2022-06-21 | 2023-11-28 | 浙江康恩贝制药股份有限公司 | Ginkgo leaf organic acid extract and preparation method and application thereof |
| WO2023246355A1 (en) * | 2022-06-21 | 2023-12-28 | 浙江康恩贝制药股份有限公司 | Ginkgo leaf organic acid extract, method for prearing same and use thereof |
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