CN106832037A - A kind of notoginseng polysaccharide extracting method rapidly and efficiently - Google Patents

A kind of notoginseng polysaccharide extracting method rapidly and efficiently Download PDF

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Publication number
CN106832037A
CN106832037A CN201710199806.1A CN201710199806A CN106832037A CN 106832037 A CN106832037 A CN 106832037A CN 201710199806 A CN201710199806 A CN 201710199806A CN 106832037 A CN106832037 A CN 106832037A
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notoginseng polysaccharide
purified water
concentration
ethanol
extracting method
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李继国
李继民
刘瑾
李吉莉
李腾飞
张春力
林飞
杨凯
黄刚国
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Yunnan Run Jia Pharmaceutical Co Ltd
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Yunnan Run Jia Pharmaceutical Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0003General processes for their isolation or fractionation, e.g. purification or extraction from biomass

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

The present invention relates to pharmaceutical formulating art, a kind of method that notoginseng polysaccharide is extracted is disclosed, be characterized in that:After the pseudo-ginseng dregs of a decoction containing ethanol are reclaimed into ethanol, directly add and purify after water is mixed with flash extracter extraction, then filter and collect filtrate;The filtrate of collection is separated by centrifuge, and centrifugate is obtained;By centrifuge dripping after the concentration of prepared centrifugate, precipitated crystal, purified water is added to be washed after crossing cationic resin column, feed liquid with purifying water dissolves, and eluent is obtained;Ethanol is added after prepared eluent is concentrated, is stood, centrifugation separates out sediment, sediment is added to the water and is dissolved, spraying feed liquid is obtained;Feed liquid is directly vacuum dried prepared notoginseng polysaccharide by being spray-dried or separating out sediment.Solve during existing notoginseng polysaccharide preparation method has final extract that notoginseng polysaccharide content is relatively low, ash grades, and impurity content is too high, and quality is unstable, and the production cycle is long, recovery rate lowly has pollution to environment.

Description

A kind of notoginseng polysaccharide extracting method rapidly and efficiently
Technical field
Concretely it is a kind of notoginseng polysaccharide extracting method rapidly and efficiently the present invention relates to pharmaceutical formulating art.
Background technology
Chinese medicine pseudo-ginseng is the dry root and root of panax araliaceae plant Panax notoginseng (Burk.) F.H.Chen Stem, main product is in the ground such as Yunnan, Guangxi, wild or cultivation.Its sweet, slight bitter, warm in nature, main enter liver, stomach, large intestine channel, with nourishing, It is strong, enrich blood, Repercusion analgesia, styptic powder addiction, strengthen immunity the effects such as.20 end of the centurys, domestic and foreign scholars are carried out to pseudo-ginseng Extensive pharmacological research and clinical trial, achieve substantial amounts of new results, the field of medical applications of pseudo-ginseng is expanded.
Pseudo-ginseng main component is arasaponin, polysaccharide, dencichine, flavones, volatile oil, amino acid and various micro units Element etc..The research of pseudo-ginseng for many years is concentrated mainly on the chemistry and pharmacological action of saponin(e, is studied it has proven convenient that arasaponin has Myocardium protecting action;Pre- preventing thrombosis and anti thrombotic action;Analgesic activity;Protection liver;Anti-inflammatory effect;Radiation resistance;Increase Plus superoxide dismutase activity etc., the research of other compositions is then less.With the reach of science, the bioactivity of higher plant Composition polysaccharide is increasingly aroused people's interest, and the Effect study of polysaccharide also gradually gos deep into.
At present, in pseudo-ginseng chemical composition using it is more be arasaponin, during arasaponin is extracted, lose The residue for leaving generally all is taken as Solid state fermentation.In fact, in these waste residues also containing more in addition to arasaponin Other active materials, as Solid state fermentation, suitable waste is caused to pseudo-ginseng resource, be unfavorable for the comprehensive profit of pseudo-ginseng resource With.Therefore, develop it is a kind of turn waste into wealth, the method that can comprehensively utilize pseudo-ginseng raw material is very important.
Existing, the preparation method of notoginseng polysaccharide carries out polysaccharide purification using ultrafiltration membrance filter more, due to extracting notoginseng polysaccharide Raw material be almost the pseudo-ginseng dregs of a decoction containing ethanol, wherein rich in having protein, inorganic impurity and heavy metal, in ultrafiltration Membrane cleaning In easily cause the problem of filter membrane blocking, investment is big, high cost, and notoginseng polysaccharide is carried from other sorbing materials such as activated carbon It is pure, still there is notoginseng polysaccharide and be adsorbed and cause the notoginseng polysaccharide yield for extracting too low (yield reduction is 10% or so), place In high cost production, it is impossible to reach medicine, food and cosmetics quality acceptable material low cost technological requirement, while final obtain Contain ash content higher in thing (concentration is 30% or so).Notoginseng polysaccharide extracting method is typically extracted using solvent reflux extraction Prepare, cause the production cycle to extend the method, the increased problem of energy consumption cost, additionally due to carrying out under the high temperature conditions more Extract, have also been introduced more impurity.
Homogenate extraction (also referred to as dodge and carry) is a kind of new process for extracting developed in recent years, and it is according to historrhexis The principle of extraction, using appropriate solvent in flash extracter by material quick crashing to appropriate granularity, while having high-speed stirring Mix, superpower vibration, the function such as negative pressure diafiltration reach extraction purpose.Due to once extracting typically within the several seconds to a few minutes i.e. Can complete, its extraction rate is more than hundred times of conventional method.
Therefore needing one kind can improve final obtained notoginseng polysaccharide content, and any additive or fining agent are not used, The control extracted and concentrated by simple homogenate extraction technique and automation, the use of new type resin reaches reduction and finally carries Take a kind of notoginseng polysaccharide extracting method rapidly and efficiently of heavy metal and content of ashes in thing.
The content of the invention
Notoginseng polysaccharide content is relatively low during the present invention has final extract for existing notoginseng polysaccharide preparation method, and ash grades Impurity content is too high, and quality is unstable, and the production cycle is long, and recovery rate is low, there is a problem of pollution to environment, there is provided a kind of fast Fast efficient notoginseng polysaccharide extracting method.
The present invention solves above-mentioned technical problem, and the technical scheme of use is, a kind of notoginseng polysaccharide extraction side rapidly and efficiently Method, comprises the following steps:
The first step, extracts, and after the pseudo-ginseng dregs of a decoction containing ethanol are reclaimed into ethanol, is directly added into purified water and is mixed, and uses Flash extracter is extracted, and then filters and collect filtrate;
Second step, centrifugation, the filtrate of collection is separated by centrifuge, and centrifugate is obtained;
3rd step, automatic economic benefits and social benefits concentration, automatic concentration device retraction volume is passed through by centrifugate;
4th step, crude crystalline precipitation, the extract solution that will have been concentrated is precipitated with alcohol crystal;
The notoginseng polysaccharide crude product of crystalline deposit is filtered in 5th step, centrifugal filtration with flat centrifuge;
6th step, is refined, and prepared centrifugation thing is added into purifying water dissolves, and upper novel cation resin column is carried out with purified water Washing, and merge eluent;
7th step, re-refines, and by the concentration of prepared eluent, adds ethanol, stands, centrifugation, obtains final product notoginseng polysaccharide crystallization heavy Starch;
8th step, is dried, and sediment purified water tone pitch is vacuum dried by hig h-speed centrifugal spray drying or directly, is obtained Notoginseng polysaccharide.
Further, the pseudo-ginseng dregs of a decoction reclaim Yi Chun≤30% in the first step, and water is 2~5 with the volume ratio of the dregs of a decoction:1, with sudden strain of a muscle Formula extractor is extracted 1 time at being 20 DEG C~50 DEG C in temperature, and extraction time is 5~20min.
Further, there is step between the first step and second step, circulation is extracted secondary, extract solution is filtered, and filtrate is complete Add purified water again afterwards, volume is extracted 2 times as the first time at being 20 DEG C~50 DEG C in temperature with flash extracter, is carried The time is taken for 3~10min, is then filtered again and is collected filtrate, extraction terminates.
The purpose of this method is, can be with notoginseng polysaccharide in of short duration raising mixed solution by being extracted with flash extracter Dissolution rate, in follow-up preparation technology, improve the concentration of notoginseng polysaccharide under same volume, while by Automated condtrol, Reach parameter to be precisely controlled, it is to avoid artificial factor, influence quality fluctuation.
Further, in second step, disk centrifugation, centrifuge speed is 3000~6400r/min, by centrifugation big portion Divide Impurity removal, reduce the content of ashes in final extract.
Further, in the 3rd step, automatic economic benefits and social benefits concentration, precise control of temperature ≤70 DEG C, Zhen Kong Du≤- 0.08mpa, Material liquid volume is than 0.5~1 times for inventory after concentration.Accurately control each parameter, it is ensured that material will not be pasted in concentration process Material, runs material, the final content for improving notoginseng polysaccharide.
Further, in fourth, fifth step, before resin cation is added, alcohol crystal precipitation is 95% using ethanol, Ethanol consumption is 3~5 times of inventory, stands material concentration 65%~80%, stands Shi Jian≤12h.Flat centrifuge from The heart is filtered, centrifuge speed 2000r/min, mesh~600 mesh of filter bag 400.By the albumen of the step operation handlebar notoginseng polysaccharide of four step five Matter, heavy metal and ash content and the overwhelming majority removal of other impurity, the high content of notoginseng polysaccharide is improved to reach.
Further, in the 6th step, centrifugation thing adds purified water meltage for 10~30 times, novel cation resin with feed intake Amount amount ratio 0.8~2.5:1, it is 2~8 times of resin amounts to be carried out washing with purified water, and the flow velocity for being passed through water is 200~400L/ H, is isolated and purified by resin cation, protein, heavy metal and ash content and other Impurity removals final residual.
Optionally, novel cation resin is that D001 macropore strong acid styrene cationic ion-exchange resin, D113 macropores are weak Acidic acrylate's cationic ion-exchange resin, 732 strongly acidic styrene type cation exchange resins and 724,001 × 16,001 × 7, One or more in LX-207 acidulous acrylic acid's cation exchanger resins.
The beneficial effect of the inventive method at least includes one below,
1st, the dregs of a decoction after extracting arasaponin are for raw material is extracted, concentrates, refine, re-refining, drying steps are obtained Arrive, wherein notoginseng polysaccharide content (in terms of DEXTROSE ANHYDROUS), be not less than 400.0mg/g.
2nd, notoginseng polysaccharide ash content can be greatly reduced by exchanging the method being combined using alcohol precipitation and novel cation Content, advantageously reduce ash content and content of beary metal, improve the quality of product.
3rd, by the crystalline deposit by first time alcohol precipitation, can greatly reduce the content of the ash contents such as heavy metal, prevent from Sub-exchange resin is poisoned, and reduces the pressure of ion exchange resin, improves the efficiency of ion exchange resin.
4th, it is simple to operate, be suitable to industrialized production, and low cost, turn waste into wealth, reach it is energy-saving, realize China it is rare The comprehensive exploitation of Chinese medicine pseudo-ginseng, the purpose of sustainable use.
5th, extracting method is simple, and manufacturing cycle shortens, and saves heating and energy consumption needed for cooling, reduces production cost.
6th, extract and complete at room temperature, reduce the introducing of impurity, be conducive to follow-up purifying.
Specific embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments to the present invention It is described in further detail.It should be appreciated that specific embodiment described herein is used only for explaining the present invention, limit is not used to The fixed present invention.
Embodiment 1
The dregs of a decoction 3000g for taking extracted complete notoginsenoside determines its pseudo-ginseng polyoses content, content of beary metal and ash content and contains Amount, is made initial data, is then uniformly divided into three parts and is respectively labeled as A, B, C, every part of 1000g.
Embodiment 2
Based on embodiment 1, the material for being marked as A is taken, the 1000g pseudo-ginseng dregs of a decoction and purified water mix being carried Take, the addition of purified water is 5000ml, extracted 1 time at being 20 DEG C in temperature with flash extracter, extraction time is 5min, so After filter and collect filtrate.The filtrate 9500ml of collection is concentrated, control Wen Du ≤70 DEG C, Zhen Kong Du≤- 0.08mpa, material liquid volume 1000ml after concentration, alcohol crystal precipitation, is 95% using ethanol, and ethanol consumption is 5000ml, quiet Put material concentration 80%, during standing between≤12h.Flat centrifuge filtering, centrifuge speed 2000r/min, filter bag 400 Mesh.Centrifugation thing adds purifying water dissolves, and purifying water is 3000ml, new 732 strongly acidic styrene type cation exchange resin 1000g carries out de-ash, when complete under feed liquid, carried out washing with purified water be resin 3000ml, the flow velocity for being passed through water is 200ml/h, and eluent 5850ml is obtained;Prepared 5850ml eluents are concentrated, effluent volume is after concentration 800ml, adds 95% ethanol, and consumption is 3000ml, stands material concentration 77%, stands Shi Jian≤12h, centrifuge speed 2000r/min, the mesh of filter bag 800 obtains final product notoginseng polysaccharide crystalline deposit thing;Spray drying:Carried out during sediment is added into purified water Dissolving, density is obtained feed liquid, spray drying 1.03;Or be directly vacuum dried sediment, do dry Wen Du≤80 DEG C, vacuum Du≤- 0.08mpa, is obtained notoginseng polysaccharide, determines wherein notoginseng polysaccharide content, content of beary metal and content of ashes, and is made the One group of data.
Embodiment 3
Based on embodiment 1, the material for being marked as B is taken, the 1000g pseudo-ginseng dregs of a decoction and purified water mix being carried Take, the addition of purified water is 3000ml, extracted 1 time at being 30 DEG C in temperature with flash extracter, extraction time is 13min, Then filter and collect filtrate.The filtrate of collection is separated by disk plate centrifuge, wherein centrifuge speed is 3000r/ Min, and centrifugate 5500ml is obtained;By prepared 5500ml centrifugates, exchanged with new 732 strongly acidic styrene cation and set Fat 1000g carries out de-ash, when complete under feed liquid, carried out washing with purified water be resin 3000ml, the flow velocity for being passed through water is 200ml/h, and eluent 8500ml is obtained;Prepared 8500ml eluents are concentrated, effluent volume is after concentration 800ml, adds 95% ethanol, and consumption is 3000ml, stands material concentration 77%, stands Shi Jian≤12h, centrifuge speed 2000r/min, the mesh of filter bag 800 obtains final product notoginseng polysaccharide crystalline deposit thing;Spray drying:Carried out during sediment is added into purified water Dissolving, density is obtained feed liquid, spray drying 1.03;Or be directly vacuum dried sediment, do dry Wen Du≤80 DEG C, vacuum Du≤- 0.08mpa, is obtained notoginseng polysaccharide, determines wherein notoginseng polysaccharide content, content of beary metal and content of ashes, and is made the Two groups of data.
Embodiment 4
Based on embodiment 1, the material for being marked as C is taken, the 1000g pseudo-ginseng dregs of a decoction and purified water mix being carried Take, the addition of purified water is 2000ml, extracted 1 time at being 30 DEG C in temperature with flash extracter, extraction time is 20min, Then filter and collect filtrate.The filtrate of collection is separated by disk plate centrifuge, wherein centrifuge speed is 6000r/ Min, and centrifugate 3500ml is obtained;Prepared 3500ml centrifugates are concentrated, control Wen Du ≤70 DEG C, Zhen Kong Du≤- 0.08mpa, material liquid volume 600ml after concentration, alcohol crystal precipitation, is 95% using ethanol, and ethanol consumption is 3000ml, is stood Material concentration 80%, stands Shi Jian≤12h.Flat centrifuge filtering, centrifuge speed 2000r/min, filter bag 400 Mesh.Centrifugation thing adds purifying water dissolves, and purifying water is 2000ml, new 732 strongly acidic styrene type cation exchange resin 1000g carries out de-ash, when complete under feed liquid, carried out washing with purified water be resin 2000ml, the flow velocity for being passed through water is 200ml/h, and eluent 3850ml is obtained;Prepared 3850ml eluents are concentrated, effluent volume is after concentration 500ml, adds 95% ethanol, and consumption is 1500ml, stands material concentration 75%, stands Shi Jian≤12h, centrifuge speed 2000r/min, the mesh of filter bag 800 obtains final product notoginseng polysaccharide crystalline deposit thing;Spray drying:Carried out during sediment is added into purified water Dissolving, density is obtained feed liquid, spray drying 1.03;Or be directly vacuum dried sediment, do dry Wen Du≤80 DEG C, vacuum Du≤- 0.08mpa, is obtained notoginseng polysaccharide, determines wherein notoginseng polysaccharide content, content of beary metal and content of ashes, and is made the Three groups of data.
The preprocess method of resin is:Resin is soaked in water, loads chromatographic column, with equivalent to 1.5~3 times of resin volume Mass concentration be 2.5-4% HCl treatments, wash with water to neutrality, be with the mass concentration equivalent to 1.5~3 times of resin volume 3~5% naoh treatments, wash with water to neutrality, then with 95% ethanol saturation, after standing 12~24h, with alcohol flushing to second The water dilution mixing of the alcohol liquid amount of doubling is haze-free, is rinsed to without ethanol with water, both may be used without organic substance residual to HPLC detections To use.
Embodiment 5
Five groups of data on notoginseng polysaccharide, ash content, lead and total arsenic accounting are obtained in comparative example 1~4 and obtains as follows Table:
Contrast initial data, first group of data, second group of data and the 3rd group of data can draw, be provided using the present invention Method can greatly improve and produce species notoginseng polysaccharide content, while contrast first group and second group of data, by repeatedly carrying Taking can reduce a certain amount of ash levels, improve a certain amount of notoginseng polysaccharide concentration, contrast first group and the 3rd group of data, pass through The method being combined using alcohol precipitation cation exchange can greatly reduce the content of notoginseng polysaccharide ash content, advantageously reduce ash content And content of beary metal, improve the quality of product.Decontamination is carried out first with alcohol precipitation by by before cationic ion-exchange resin, can be with Greatly reduce the content of the ash content such as heavy metal, prevent ion exchange resin to be poisoned, reduce the pressure of ion exchange resin, improve from The efficiency of sub-exchange resin.

Claims (10)

1. a kind of notoginseng polysaccharide extracting method rapidly and efficiently, it is characterised in that comprise the following steps:
The first step, extracts, and after the pseudo-ginseng dregs of a decoction containing ethanol are reclaimed into ethanol, is directly added into purified water and is mixed, with flash Extractor is extracted, and then filters and collect filtrate;
Second step, centrifugation, the filtrate of collection is separated by centrifuge, and centrifugate is obtained;
3rd step, automatic economic benefits and social benefits concentration, by centrifugate by automatic concentration device retraction volume, is obtained extract solution;
4th step, crude crystalline precipitation, the extract solution that will have been concentrated alcohol crystal is precipitated, and crystalline deposit is obtained;
The notoginseng polysaccharide crude product of crystalline deposit is filtered in 5th step, centrifugal filtration with centrifuge, and centrifugation thing is obtained;
6th step, is refined, and purifying water dissolves are added in centrifugation thing is obtained, and adds resin cation, is washed with purified water, and Combination system obtains eluent;
7th step, re-refines, and by the concentration of prepared eluent, adds ethanol, stands, and centrifugation is obtained notoginseng polysaccharide crystalline deposit thing;
8th step, is dried, and purified water is added in sediment, density is adjusted, by hig h-speed centrifugal spray drying or direct vacuum Dry, notoginseng polysaccharide is obtained.
2. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:The first step The middle pseudo-ginseng dregs of a decoction reclaim Yi Chun≤30%, and purified water is 2~5 with the volume ratio of the dregs of a decoction:1, with flash extracter temperature be 20 DEG C~50 DEG C at extract 1 time, extraction time be 5~20min.
3. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 2, it is characterised in that:The first step There is step between second step, extract solution is filtered in second extraction, adds purified water, purified water to add after having filtered again Dosage and first time, extracted 2 times at being 20 DEG C~50 DEG C in temperature with flash extracter, extraction time is 3~10min, Then filtrate is filtered and collected again.
4. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:The second step In, centrifuge is disk plate centrifuge, and centrifuge speed is 3000~6400r/min.
5. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:3rd step In, automatic economic benefits and social benefits concentration, accurate control Wen Du≤70 DEG C processed, very sky degree≤- 0.08mpa, material liquid volume ratio is 0.5~1 after concentration: 1。
6. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:4th step In, crude crystalline precipitation is 95% using ethanol, and ethanol is 3~5 with the volume ratio of concentrate:1, material concentration after standing 65%~80%, stand Shi Jian≤12h.
7. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:5th step In, centrifugal filtration, centrifuge is plate centrifuge, centrifuge speed 2000r/min, mesh~600 mesh of filter bag 400.
8. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:6th step In, refine, purifying water dissolves are added in centrifugation thing, purified water is 10~30 with centrifugation amount of substance ratio:1, resin cation with centrifugation Amount of substance ratio is 0.8~2.5:1, when being washed with purified water, purified water is 2~8 with the volume ratio of resin cation:1, lead to The flow velocity for entering purified water is 200~400L/h.
9. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:7th step In, to re-refine, effluent volume and the preceding effluent volume ratio of concentration are 0.3~0.8 after concentration:1, add 95% ethanol, ethanol It is 2~5 with effluent volume ratio after concentration:1, material concentration 60%~80% after standing stands Shi Jian≤12h, centrifugal basket Fast 2000r/min, mesh~800 mesh of filter bag 600, obtains final product notoginseng polysaccharide crystalline deposit thing.
10. a kind of notoginseng polysaccharide extracting method rapidly and efficiently according to claim 1, it is characterised in that:Described 8th In step, dry, it is 1.02~1.15 that purified water adjustment density is added in sediment, spray drying;Or be directly vacuum dried, do Dry Wen Du≤80 DEG C, very sky degree≤- 0.08mpa.
CN201710199806.1A 2017-03-30 2017-03-30 A kind of notoginseng polysaccharide extracting method rapidly and efficiently Pending CN106832037A (en)

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CN110105459A (en) * 2019-05-27 2019-08-09 云南绿戎生物产业开发股份有限公司 A kind of extracting method of notoginseng polysaccharide
CN111533820A (en) * 2020-05-11 2020-08-14 昆明理工大学 A kind of Panax notoginseng polysaccharide and its preparation method and application
CN114031694A (en) * 2021-12-23 2022-02-11 云南三七科技有限公司 Extraction method of pseudo-ginseng polysaccharide
CN115812892A (en) * 2021-09-18 2023-03-21 天津市尖峰天然产物研究开发有限公司 Method for reducing ash content of ginseng extract

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CN110105459A (en) * 2019-05-27 2019-08-09 云南绿戎生物产业开发股份有限公司 A kind of extracting method of notoginseng polysaccharide
CN111533820A (en) * 2020-05-11 2020-08-14 昆明理工大学 A kind of Panax notoginseng polysaccharide and its preparation method and application
CN115812892A (en) * 2021-09-18 2023-03-21 天津市尖峰天然产物研究开发有限公司 Method for reducing ash content of ginseng extract
CN114031694A (en) * 2021-12-23 2022-02-11 云南三七科技有限公司 Extraction method of pseudo-ginseng polysaccharide

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