CN1293191A

CN1293191A - Process for extracting ginkgolic total flavone

Info

Publication number: CN1293191A
Application number: CN 00129807
Authority: CN
Inventors: 巴伟松
Original assignee: Individual
Current assignee: Individual
Priority date: 2000-10-24
Filing date: 2000-10-24
Publication date: 2001-05-02
Anticipated expiration: 2020-10-24
Also published as: CN1102147C

Abstract

A process for extracting ginkgo total flavone includes such steps as defatting, preparing the deposit of flavonoid, displacing flavone, recovering alcohol and drying. Its advantages are high purity up to 49.8% of flavone glycoside content, simple operation, and high safety and speed.

Description

A kind of method of extracting Ginkgo total flavones

The present invention relates to a kind of technology of from Semen Ginkgo extrac, purifying again.

The pharmaceutical use of Ginkgo Leaf has obtained countries in the world medical science worker's confirmation and clinical sure, and contained main effective constituent is flavonoid glycosides in the Ginkgo Leaf, reaches 33 kinds more than, accounts for 6% of dry weight; Secondly be bilobalide, totally 5 kinds, account for 0.8% of dry weight; 1 kind of bilobalide accounts for 0.7% of dry weight.At present, be raw material with the Ginkgo Leaf, technology and the method for therefrom extracting main pharmacological component Ginkgo total flavones, terpene lactones are a lot, and the standard code of relevant product contains flavones 〉=24%, lactone 〉=6%.The sky wave of producing as Germany peaceful (TEBONIN), the Tan Nakang (TANAKAN) that France produces wait and all carry out above the regulation.Chinese Shanghai institute of Chinese materia medica disclosed " high content ginko leaves flavone lactone extract and preparation method thereof " middle medicinal extract in 1997 contains flavones 〉=44% (wherein flavonoid glycoside 〉=24%), lactone 〉=6%, control ginkgoic acid≤10ppm.Though above-mentioned these methods and parameter meet general international standard, the per-cent of the contained effective constituent flavonoid glycosides of product is lower.

The purpose of this invention is to provide a kind of processing method of from Semen Ginkgo extrac, separating high-content ginkgolic flavone glycoside glucoside.

The objective of the invention is to realize by following technical scheme:

A kind of method of extracting Ginkgo total flavones, it is a raw material with the Semen Ginkgo extrac, comprises following operation,

1. grease removal

Get the some weight unit of Semen Ginkgo extrac, add 5 times of amount waters for injection in separating funnel, add 2-3 again and doubly measure ether, after shake well extracts, divide water-yielding stratum, discard the ether layer.

Then, in the above-mentioned aqueous solution, add 5 times of water gagings again, heat while stirring to dissolving fully.

2. produce the throw out of flavonoid compound

Add freshly prepd 25% milk of lime to pH value more than 12, be stirred well to and react completely, decompress filter is washed to colourlessly, and filtrate discards.

3. displacement flavones

Add ethanol, precipitation is suspended in 95% ethanol, fully stir;

Add sulfuric acid, in above-mentioned solution, add 40%H2SO4, adjust pH value to 5, fully stir, leave standstill filtration;

Hydro-oxidation sodium adds 40%NaOH in above-mentioned filtrate, adjust pH value to 7, filters.

4. recovery ethanol

With filtrate decompression, reclaim ethanol, be concentrated into no ethanol after, add an amount of water for injection again, heating for dissolving.

5. dry

Add a little gac, be heated to and boil, leave standstill 5 minutes suction filtrations, filtrate gets finished product at freeze-day with constant temperature below 80 ℃.

The method of said extracted Ginkgo total flavones, the add-on of described gac are the 3-5% of liquor capacity.

The method of said extracted Ginkgo total flavones, in the described displacement flavones operation, when finish transfer pH value after, filter before, precipitate fully for making impurity, can under 5-8 ℃ of temperature, refrigerate and leave standstill 12 hours.

The method of said extracted Ginkgo total flavones, in the described recovery ethanol operation, the decompression pressure of filtrate is 0.5-0.7 normal atmosphere,

This purifying technique is according to basic constructional feature of the molecule of ginkgolic flavone glycoside class and the solvability that shown, physico-chemical properties such as slightly acidic are taken all factors into consideration, the method of utilizing physical chemistry to combine is carried out, its advantage is to isolate high-load Ginkgo total flavones from Semen Ginkgo extrac, its flavonoid glycosides is (with quercetin glycoside, the kaempferol glucoside, Isorhamnetol glucoside meter) content can reach 49.8%, and detrimental impurity ginkgoic acid content is equalled zero, other impurity such as tannin, protein etc. are also eliminated, this technological operation is easy, safety, fast, the productive rate height, economic benefit is good, is fit to large-scale commercial production.

The principle analysis of this purifying technique is as follows:

Main bio-pharmacology activeconstituents is flavonoid glycosides and terpene lactones in the known Ginkgo Leaf alcohol extract, also contains other composition, as protein and enzyme, monose, oligose, polysaccharide, pigment, inorganic salt, tannin, ginkgolic acid etc.When this purifying technique of design, consider that injection is an aqueous solution preparation, and terpene lactone is a fat-soluble component, water insoluble, have to remove, and some water soluble components such as tannin, protein, ginkgolic acid, enzyme, monose, polysaccharide, oligose, pigment, inorganic salt etc., although when the Ginkgo Leaf alcohol extract is produced, also rejected a part, but when the preparation injection, must reject totally, particularly detrimental impurity such as tannin, protein, ginkgolic acid.

In flavonoid compounds water soluble, ethanol, methyl alcohol, the ethyl acetate, solubleness increases in hot water, is insoluble in organic solvents such as ether, benzene, chloroform.Owing to contain a plurality of phenolic hydroxyl groups in its structure, so show certain acidity, can be dissolved in the alkali lye, separate out precipitation again after adding acid, therefore can utilize this character to extract flavonoid compound.

In purifying technique, add ether fat-soluble component dissolving back separation is removed, as lactone, glucoside unit etc.Adding milk of lime Ca (OH) 2 makes calcium ion generate insoluble calcium salt or inner complex with flavonoid compound under certain pH value, in water, precipitate and separate out, compositions such as the organic acid that may contain simultaneously, tonka bean camphor, phenolic compound, acid saponin, tannin, polyphenol, partial protein, some polysaccharide, acidic resins also all combine with calcium ion and precipitate, but since flavonoid compound acidity a little less than, formed calcium salt and inner complex instability, just dissociating out again behind the adding H2SO4 goes in the ethanolic soln.Experimental results show that, the compound that major part is considered to effective constituent all dissolves when pH value 4-6 basically, and acid stronger compound, more stable as organic acid, acidic resins, acid saponin, tannic acid etc. with the salt that calcium ion forms, when this pH value, can not dissolve substantially, in addition, not producing sedimentary protein during most pH value 12 also all precipitates when pH value 4-6 and separates out.Adjusting pH value with NaOH again is 7, can further remove calcium sulfate, sodium sulfate, tannin, sodium salt etc.Behind the underpressure distillation ethanol, reduction along with alcohol concn, some pure dissolubilities, the fat-soluble but proximate insoluble impurities of chemical property and flavones can be separated out gradually, at this moment can reject the pyrogen (bacterial endotoxin) in the also adsorbable purification thing of gac with charcoal absorption.Because flavonoid glycosides easily decomposes when temperature is too high, easily caramelize, temperature is unsuitable too high when therefore dry, is advisable to be controlled at below 100 ℃.

The invention will be further described below in conjunction with embodiment:

Get ginkgo leaf powder (commercial goods, demarcation contains total flavones and is not less than 24%) 40g, add 200ml water for injection, put in the 1000ml volume separating funnel, add the 80ml ether again, after shake well extracts, divide water-yielding stratum, discard the ether layer.Add 200ml water again in the aqueous solution, heat while stirring to dissolving fully, 25% milk of lime that adds prepared fresh is to pH value more than 12, be stirred well to and react completely, decompress filter is washed to colourless, filtrate discards, and precipitation is suspended in 95% ethanol, stirs, add the H2SO4 that concentration is 35-40% then, fully stirring and transferring pH value is 5, filters, and filtrate adds concentration 40%NaOH and transfers pH value to 7,5-8 ℃, refrigeration was left standstill 12 hours, filtered decompression filtrate recycling ethanol, decompression pressure is 0.5-0.7 normal atmosphere, boiling point is reduced to 60 ℃, adds 50ml water for injection again, heating for dissolving after being concentrated into no ethanol, add the long-pending 3-5% gac of solution body, be heated to and boil, leave standstill 5 minutes suction filtrations, 80 ℃ of freeze-day with constant temperature of filtrate, promptly get the Ginkgo total flavones crystallization, weight is about 10 grams.

Claims

1. method of extracting Ginkgo total flavones, it is a raw material with the Semen Ginkgo extrac, it is characterized in that, it comprises following operation,

A. grease removal

B. produce the throw out of flavonoid compound

C. replace flavones

Add ethanol, precipitation is suspended in 95% ethanol, fully stir;

D. reclaim ethanol

E. dry

Add gac, be heated to and boil, leave standstill 5 minutes suction filtrations, filtrate gets finished product at freeze-day with constant temperature below 80 ℃.

2. the method for extraction Ginkgo total flavones according to claim 1 is characterized in that, described Semen Ginkgo extrac is a ginkgo leaf powder, and its demarcation contains total flavones and is not less than 24%.

3. the method for extraction Ginkgo total flavones according to claim 2 is characterized in that, the add-on of described gac is the 3-5% of liquor capacity.

4. the method for extraction Ginkgo total flavones according to claim 3 is characterized in that, in the described displacement flavones operation, when finish transfer pH value after, filter before, can under 5-8 ℃ of temperature, refrigerate and leave standstill 12 hours.

5. the method for extraction Ginkgo total flavones according to claim 4 is characterized in that, in described recovery ethanol operation, the decompression pressure of filtrate is 0.5-0.7 normal atmosphere.