JP2003012528A - Extract from ginkgo biloba l. and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an extract from Ginkgo biloba L. comprising a flavone glycoside with low contents of a salicylic acid derivative and quercetin and high safety in good yield by simple operation. SOLUTION: This extract from Ginkgo biloba L. is obtained by extracting a leaf of the Ginkgo biloba L. with water, etc., and treating the resultant extract liquid with an adsorbent such as Amberlite XAD-2000 (R). The adsorbent is washed with water, etc., and adsorbed components are then eluted with a <=55 vol.% aqueous solution of a hydrophilic alcohol or an aqueous elution solvent, etc., containing 0-15 vol.% of an alcohol at pH >=9.5. The resultant eluate is concentrated to thereby provide the extract from the Ginkgo biloba L. containing about >=15 wt.% of a flavone glycoside and having <=30 ppm content of the salicylic acid derivative and <=0.02 wt.% content of the quercetin. The contents of the quercetin and/or colored components in the extract from the Ginkgo biloba L. can remarkably be reduced by carrying out concentration of the separated liquid containing the extracted components of the leaf of the Ginkgo biloba L. (a) at <=80 deg.C temperature, (b) at a regulated pH of 6-8 or (c) in an inert gas atmosphere.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a ginkgo biloba extract, which is useful as a medicine, a food additive, and the like, and a method for producing the same.

[0002]

BACKGROUND OF THE INVENTION Ginkgo biloba extract extracted from ginkgo biloba has effects such as vasodilation, increased blood flow, prevention of aging of vascular system, especially improvement of peripheral blood flow in the brain, improvement of mental symptoms, and so on. In Europe, it is used as a drug for treating cerebral arteriosclerosis, senile blur, diabetic vascular disorder, mental disorder and the like. In Japan, etc.,
It is added to foods and used as health foods. Further, it has been recognized that a skin agent containing Ginkgo biloba extract normalizes or promotes the peripheral circulation of the skin and has a remarkable cosmetic effect.

On the other hand, the structure and pharmacological action of some active ingredients have been elucidated from the pharmacological studies on the ingredients contained in ginkgo leaves. For example, flavone glycosides unique to ginkgo biloba show hypotensive effects (Japan Society of Pharmaceutical Sciences,
It is known that ginkgolides have an inhibitory effect on platelet activating factor, at the 107th Annual Meeting Abstracts, p. 345). In addition, bilobalide has been reported to exhibit an anti-convulsive effect. In addition, bilobetin, siadopithicin,
It has been recognized that biflavones such as ginkgetin and isoginkgetin have an anticarcinogenic promoter action (Proceedings of the 108th Annual Meeting of the Pharmaceutical Society of Japan, 331st meeting).
page).

On the other hand, however, the harmful effects of ginkgo biloba components are also known. For example, salicylic acid derivatives such as gingoleic acid have an action of causing allergic dermatitis (Tatsuo Karime, "Latest phytochemistry", 2nd edition, Hirokawa Shoten, 1979). Free flavonols such as quercetin are known to be positive in the Ames test, which is a method for detecting mutagenicity of chemical substances using microorganisms.

As a method for producing a ginkgo biloba extract containing the above-mentioned components having a pharmacological action, a method utilizing partition between liquid phases, a method utilizing fractional precipitation, a method utilizing an adsorbent and the like are known. There is.

As a method utilizing the partition between the liquid phases,
JP-B-46-28091 and JP-B-49-273
No. 23, discloses a method of subjecting a ginkgo biloba extract to an extraction operation with a water-immiscible fat-soluble organic solvent such as carbon tetrachloride, and a method of subsequently extracting with methyl ethyl ketone and treating with a lead compound. There is. But,
Since these methods use highly toxic solvents and metal compounds, they are not preferable as a method for producing food additives or ginkgo extracts for pharmaceuticals.

Japanese Unexamined Patent Publication (Kokai) No. 2-121998 discloses a method for extracting a ginkgo biloba extract with a solvent consisting of an aromatic hydrocarbon having 6 to 8 carbon atoms and a lower alkanol having 3 to 6 carbon atoms. There is. In addition, JP-A-3-26453
Japanese Patent Publication No. 3 discloses a method in which a ginkgo biloba extract is concentrated, subjected to multistage extraction with acetic acid ester and the like, and then subjected to extraction with an alkanol having 4 to 5 carbon atoms. However, in these methods, since a plurality of solvent extraction methods are used, the manufacturing process becomes extremely complicated.

Further, in the method utilizing the partition between the liquid phases, the content of the quercetin or salicylic acid derivative in the obtained ginkgo biloba extract is high.

As a method for producing a ginkgo biloba extract using fractional precipitation, Japanese Unexamined Patent Publication No. 2-193907 discloses
A method for producing a Ginkgo biloba extract is disclosed in which dried Ginkgo biloba leaves are extracted with a 30 to 45% ethanol aqueous solution. But,
With this method, it is difficult to remove free flavonols such as quercetin.

On the other hand, as a method of producing a ginkgo biloba extract using an adsorbent, JP-A-2-73079 discloses a flavonoid in which an extract of ginkgo biloba is treated with activated carbon and the adsorbed flavonoids are desorbed with an alkaline solution. Is disclosed.

Further, in JP-A-3-275629, in order to obtain a ginkgo biloba extract having a high solubility in water, the ginkgo biloba extract is made weakly alkaline and then passed through a non-polar porous resin to remove the resin from water. Alternatively, there is disclosed a method for producing a ginkgo biloba extract, which is washed with an aqueous solution having a low alcohol concentration and then eluted with an aqueous solution having a high alcohol concentration of 50 to 70%. Further, in JP-A-4-182434, in order to obtain a ginkgo biloba extract containing a high concentration of an active ingredient,
An extract of ginkgo biloba leaves with 40-80% ethanol aqueous solution is concentrated, filtered, and adsorbed on a non-substituted group type porous resin, then the resin is washed with water, desorbed with 60% or more ethanol aqueous solution, and concentrated to dryness. A method for producing a ginkgo biloba extract is disclosed. As described above, high-concentration alcohol is considered to be advantageous for increasing the elution efficiency of adsorbed components.

However, even in the method using these adsorbents, the contents of the quercetin and the salicylic acid derivative cannot both be suppressed to extremely low concentrations.

[0013] In general, when a separation liquid containing a Ginkgo biloba extract component such as a Ginkgo biloba leaf extract or an eluate from an adsorbent is concentrated, quercetin and a coloring component are produced by hydrolysis of flavone glycosides. Often. Therefore, the quercetin content in the resulting ginkgo biloba extract is likely to increase, and the degree of coloring is also likely to increase.

Further, conventionally, no Ginkgo biloba extract having a high concentration of flavone glycosides and a low content of quercetin and salicylic acid derivatives has been known.

[0015]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a ginkgo biloba extract having a low content of quercetin and a salicylic acid derivative and having high safety, and a method for producing the same.

[0016] Another object of the present invention is to provide a method for producing a ginkgo biloba extract, which allows a high concentration of flavone glycosides and a highly safe ginkgo biloba extract to be obtained in a high yield with a simple operation. To provide.

Still another object of the present invention is to provide a method for producing a ginkgo biloba extract containing a flavone glycoside and having a low content of quercetin and / or coloring components by a simple operation. Especially.

[0018]

Means for Solving the Problems As a result of intensive studies for achieving the above-mentioned object, the inventors of the present invention have treated an extract of ginkgo biloba with an adsorbent, and
Alcohol aqueous solution of not more than volume% (e.g., an aqueous elution solvent containing 1 to 15 volume% alcohol), (ii) an elution solvent of pH 9.5 or more, or (iii) pH 9.5 containing 0 to 15 volume% alcohol. It was found that ginkgo biloba extract having a low content of quercetin and salicylic acid can be easily obtained by elution with the above aqueous elution solvent and concentration of the obtained eluate.

Further, the inventors of the present invention concentrated the eluate by (a) a temperature of 80 ° C. or lower, (b) a pH of 6 to 8, or (c).
When performed in an inert gas atmosphere, decomposition of flavone glycosides and formation of coloring components are significantly suppressed, and quercetin and / or
It has also been found that a ginkgo biloba extract having a remarkably low content of coloring components can be easily obtained. The present invention has been completed based on these findings.

That is, the present invention is (1) a Ginkgo biloba extract containing 15% by weight or more of flavone glycosides and having a quercetin content of 0.02% by weight or less (for example, 0.
01 wt% or less), and the salicylic acid derivative content is 30
Provide ginkgo biloba extract which is below ppm (eg below 10 ppm, especially below 1 ppm). The present invention relates to a Ginkgo biloba extract containing 15% by weight or more of flavone glycosides, which has a salicylic acid derivative content of less than 1 ppm, and a Ginkgo biloba extract containing 15% by weight or more of flavone glycosides. A ginkgo biloba extract having a quercetin content of 0.01% by weight or less is also provided.
These ginkgo extracts contain 30% by weight of flavone glycosides.
The above may be contained.

The present invention also provides (2) an extraction step of extracting ginkgo biloba leaves with an extraction solvent, an adsorption step of treating the obtained extract with an adsorbent, and a component adsorbed on the adsorbent with an elution solvent. A method for producing a ginkgo biloba extract, which comprises an elution step of eluting and a concentration step of concentrating the eluate to obtain a ginkgo biloba extract, wherein the elution solvent is 55% by volume or less of an aqueous alcohol solution (for example, 0 to 15% by volume). A method for producing a ginkgo biloba extract using a water-based elution solvent containing alcohol (hereinafter sometimes referred to as a low alcohol concentration elution solvent) is provided. The extract may be treated with an adsorbent under acidic conditions. A monohydric alcohol having 1 to 3 carbon atoms may be used as the alcohol.

The present invention further includes (3) an extraction step of extracting ginkgo biloba leaves with an extraction solvent, an adsorption step of treating the obtained extract with a hydrophobic synthetic resin adsorbent, and components adsorbed on the adsorbent. An elution step of eluting with an elution solvent,
A method for producing a Ginkgo biloba extract, which comprises a concentration step of concentrating an eluate to obtain a Ginkgo biloba extract, wherein a method for producing a Ginkgo biloba extract using an elution solvent having a pH of 9.5 or higher (hereinafter sometimes referred to as an alkaline elution solvent) is provided. provide. In this method, as an elution solvent, an aqueous elution solvent having a pH of 9.5 or more containing 0 to 15% by volume of alcohol (hereinafter,
A low alcohol concentration alkaline elution solvent may be used). The pH of the eluting solvent may be 10 or higher.

The present invention further comprises (4) an extraction step of extracting ginkgo biloba leaves with an extraction solvent, an adsorption step of treating the obtained extract with an adsorbent, and an elution solvent for components adsorbed on the adsorbent. A method for producing a ginkgo biloba extract, comprising: an elution step of elution by the step of: and a concentration step of concentrating the eluate to obtain a ginkgo biloba extract, wherein an aqueous elution solvent containing 0 to 15% by volume of alcohol and having a pH of 9.5 or more ( A method for producing a ginkgo biloba extract using the above-mentioned low alcohol concentration alkaline elution solvent) is provided.

The present invention further provides (5) a method for producing a ginkgo biloba extract, wherein a separation liquid (eluate) containing a ginkgo biloba extract component is concentrated at a temperature of 80 ° C. or lower, and (6) a separation containing a ginkgo biloba leaf extract component. Method for producing ginkgo biloba extract by adjusting the liquid (eluate) to pH 6 to 8 and (7) producing ginkgo biloba extract by concentrating the separated liquid (eluate) containing ginkgo biloba extract components under an inert gas atmosphere Provide the law. In this method, an extract obtained by extracting ginkgo biloba leaves with an extraction solvent is treated with an adsorbent, and components adsorbed to the adsorbent are eluted with an aqueous alcohol solution of 55% by volume or less, and the obtained eluate is subjected to the above method. Ginkgo biloba extract can be obtained by concentrating with. As the adsorbent, a hydrophobic synthetic resin adsorbent may be used, and as the elution solvent, an aqueous elution solvent containing 0 to 15% by volume of alcohol (low alcohol concentration elution solvent) may be used.

[0025]

BEST MODE FOR CARRYING OUT THE INVENTION The flavone glycosides include flavone glycosides contained in Ginkgo biloba leaves, such as quercetin glycoside [eg rutin, isoquercitrin, quercetin-3-O-α- (6 ″ ” '-P-Coumaroylglucosyl-β-1,2-rhamnoside), etc.], isoquercetin glycoside, kaempferol glycoside [eg, kaempferol-3-rutinoside, kaempferol-3-rhamnoglucoside, kaempferol-3- O-
α- (6 ″ ″-p-coumaroyl glucosyl-β-1,
2-rhamnoside)], luteolin glycoside and the like.

The content of flavone glycosides is, for example, 15 to
It is about 70% by weight. The preferred flavone glycoside content is 30% by weight or more.

The salicylic acid derivative is a group of salicylic acid derivatives contained in ginkgo biloba, for example, gingoleic acid, in which a long-chain alkyl or alkenyl group having about 13 to 19 carbon atoms is bonded to the 6-position of the benzene ring. Includes salicylic acid derivatives. The salicylic acid derivative content in the ginkgo biloba extract is preferably 10 ppm or less, more preferably less than 1 ppm (detection limit). Since the ginkgo biloba extract of the present invention has a low content of salicylic acid derivative, it does not cause allergic dermatitis.

The quercetin content of the ginkgo biloba extract is
It is preferably 0.01% by weight or less, more preferably 0.
It is 007% by weight or less, particularly preferably 0.003% by weight or less. The ginkgo biloba extract of the present invention has extremely low quercetin content, and therefore has extremely high safety. Preferred ginkgo biloba extract includes ginkgo biloba extract which is negative in the Ames test.

The quantification of the flavone glycoside, salicylic acid derivative and quercetin can be carried out by high performance liquid chromatography (HPLC).

As the Ginkgo biloba extract, Ginkgo biloba extract, which is less colored, is preferable. Among the ginkgo biloba extracts of the present invention, the absorbance at a wavelength of 550 nm [cell: 1 cm quartz cell; solvent: 50% by volume ethanol aqueous solution; concentration: 4 mg / ml] is 0.20 or less, for example, 0.
A ginkgo biloba extract of 01 to 0.20, particularly 0.01 to 0.14 is preferable.

The ginkgo biloba extract of the present invention usually contains other useful ingredients other than flavone glycosides having pharmacological activity, such as ginkgolides, bilobalide, and biflavones.

The production methods (2) to (4) of the present invention will be described below.

In the production methods (2) to (4), the ginkgo leaves to be subjected to the extraction step may be a fresh material or a dry material. Ginkgo leaves can also be crushed before use.

The extraction solvent used in the extraction step may be any solvent which can extract components having pharmacological activity such as flavone glycosides contained in ginkgo leaves, and examples thereof include water, organic solvents and mixed solvents thereof. . The organic solvent includes
Hydrophilic organic solvents such as monohydric lower alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, t-butanol;
Polyhydric alcohols such as ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, 1,3-butanediol, 1,4-butanediol and glycerin; cellosolves such as methyl cellosolve and ethyl cellosolve; dioxane, tetrahydrofuran. Ethers such as; ketones such as acetone and methyl ethyl ketone are included. These organic solvents may be mixed and used. Among these organic solvents, the monohydric lower alcohols and ketones are preferable, and among them, monohydric alcohols having 1 to 4 carbon atoms, particularly monohydric alcohols having 1 to 3 carbon atoms (for example, ethanol and the like) are preferable.

Preferred extraction solvents include water, monohydric lower alcohols and mixed solvents thereof. As the extraction solvent, water and hydrous alcohol such as hydrous ethanol are particularly preferable. The alcohol concentration when using hydrous alcohol as the extraction solvent is, for example, 0 to 80% by volume, preferably about 0 to 30% by volume.

The extraction with the extraction solvent is carried out by allowing the solution to stand still or under stirring.
Although any method such as cold soaking, hot soaking, refluxing, and ultrasonic treatment can be used, hot extraction is preferable in order to enhance extraction efficiency.

The extraction temperature is, for example, 30 ° C. or higher, preferably about 40 ° C. to the reflux temperature. When the extraction temperature is 80 ° C or lower, particularly 70 ° C or lower, the coloration of the ginkgo biloba extract can be reduced. The extraction can be carried out in an air atmosphere, but it is preferable to carry out the extraction in an atmosphere of an inert gas such as nitrogen, helium or argon, especially when the extraction temperature exceeds 80 ° C. When the extraction is performed under an inert gas atmosphere, even if the extraction is performed at a relatively high temperature, almost no coloring component is generated during the extraction.

The amount of the extraction solvent used varies depending on the composition of the extraction solvent and the like, and can be appropriately selected, for example, in the range of 100 to 8000 parts by weight with respect to 100 parts by weight of ginkgo leaves. For example, when water is used as the extraction solvent, it is, for example, 500 to 100 parts by weight of ginkgo leaves.
It is 8000 parts by weight, preferably about 1000 to 5000 parts by weight. The extraction time can be selected according to the extraction temperature,
In the case of cold extraction, for example, 10 hours to 15 days, preferably about 1 to 10 days, and in the case of hot extraction,
For example, it is 30 minutes to 24 hours, preferably about 1 hour to 8 hours. The extraction operation can be performed multiple times.

After the extraction operation, in order to remove impurities, the extract is usually subjected to a filtration step using a filter agent such as Celite. The extract is concentrated, if necessary, and then subjected to the adsorption step. The ginkgo biloba extract usually exhibits weak acidity, for example, a pH of about 3 to 6. The pH of the extract may be adjusted before subjecting the extract to the adsorption step. The liquidity of the extract can be adjusted to neutral or alkaline. In the production method (2) described above, it is preferable that the extract liquid is kept acidic and is subjected to the adsorption step, and the treatment with the adsorbent is performed under acidic conditions.

In the adsorption step, the extract is treated with an adsorbent to adsorb useful components such as flavone glycosides to the adsorbent.

The adsorbents in the production methods (2) and (4) include an inorganic adsorbent and a synthetic resin adsorbent. Examples of the inorganic adsorbent include activated carbon. Examples of the activated carbon include plant-based activated carbon made of wood, sawdust, charcoal, coconut shell, etc .; mineral-based activated carbon made of coal, coke, petroleum, pitch, etc .; phenolic resin, acrylic resin, cellulose, etc. Includes polymer-based activated carbon.

The synthetic resin adsorbent may be either a hydrophilic synthetic resin adsorbent or a hydrophobic synthetic resin adsorbent.
A hydrophobic synthetic resin adsorbent is preferred.

Examples of the resin matrix of the hydrophobic synthetic resin adsorbent include a styrene-divinylbenzene copolymer, a styrene-acrylic acid amide copolymer, and a phenol resin. Preferred resin bases include styrene-divinylbenzene copolymers and styrene-acrylic acid amide copolymers. As the adsorbent, a porous synthetic resin adsorbent having a large surface area is preferable. The specific surface area of the synthetic resin adsorbent is, for example, 100 to 1000 m ^2.
/ G, preferably about 250 to 800 m ² / g.

As the hydrophobic synthetic resin adsorbent, for example, DIAION HP-10 and HP-2 manufactured by Mitsubishi Kasei Co., Ltd.
0, HP-21, HP-30, HP-40, HP-5
0, MCI GEL CHL-20P, Sepa beads SP
-206, SP-207, SP-800, SP-900
Etc; Duolite S from Diamond Shamrock
-761, S-861, S-862, ES-863, E
S-865, ES-866, ES-8610, etc .; Amberlite XAD-2, X from Rohm and Haas
AD-4, XAD-7, XAD-26, XAD-200
0, AXT-204 and the like.

Preferred adsorbents include hydrophobic synthetic resin adsorbents and activated carbon. The adsorbent may be pretreated in advance of the adsorption treatment. For example, when a hydrophobic synthetic resin adsorbent is used as the adsorbent, the pretreatment is, for example, washing the adsorbent with a solvent such as methanol to remove impurities, and then further washing with water to remove a solvent such as methanol. It can be performed by removing.

In the method (3) of the present invention, the hydrophobic synthetic resin adsorbent is used as the adsorbent.

The treatment with the adsorbent may be carried out by either a batch method or a column method, but the column method is preferable because it can be efficiently treated with a relatively small amount of the adsorbent. The treatment with the adsorbent may be performed at least once. The ratio of the adsorbent to the extract can be selected according to the type of adsorbent used.

After the adsorption step, the adsorbent is often washed with a washing liquid in order to remove non-adsorbed components and the like, if necessary. The washing liquid is preferably a solvent that elutes non-adsorbed components and suppresses elution of useful components such as flavone glycosides. The preferred cleaning solution is water,
Alternatively, it contains an aqueous alcohol solution of 30% by volume or less, particularly 25% by volume or less. As the alcohol, the monohydric lower alcohols, particularly monohydric alcohols having 1 to 4 carbon atoms,
Particularly, a monohydric alcohol having 1 to 3 carbon atoms (for example, ethanol) is preferable. Particularly preferred cleaning liquids include
Water, 30% by volume or less aqueous ethanol solution (for example, 5 to
30% by volume aqueous solution of ethanol) and the like. If an alcohol aqueous solution exceeding 30% by volume is used as the cleaning liquid, the flavone glycosides are likely to be eluted and the yield of Ginkgo biloba extract may be reduced.

The amount of the cleaning liquid used can be appropriately selected according to the composition of the cleaning liquid and the like. The washing may be performed multiple times with the same or different washing liquids.

In the elution step, the components adsorbed on the adsorbent are
Elution is carried out with the aforementioned (i) low alcohol concentration elution solvent, (ii) alkaline elution solvent, or (iii) low alcohol concentration elution solvent. Hereinafter, a method using each of the above-mentioned elution solvents will be described.

(I) Low alcohol concentration elution solvent The concentration of alcohol in the low alcohol concentration elution solvent is preferably 30 to 55% by volume, more preferably 35 to 50% by volume, and particularly preferably about 35 to 45% by volume. Is.

When an alcoholic aqueous solution of 55% by volume or less is used as an elution solvent, a fraction having a high concentration of flavone glycosides and an extremely low concentration of harmful flavonols such as quercetin and salicylic acid derivatives can be obtained. it can. Especially, the alcohol concentration of the eluting solvent should be 45
When the content is less than or equal to volume%, a fraction having a significantly low quercetin concentration is obtained. This is probably because the use of the above-mentioned elution solvent suppresses the elution of the harmful components.

Examples of the alcohol include the monovalent lower alcohols exemplified above. Among them, carbon number 1
4 monohydric alcohols, especially monohydric alcohols having 1 to 3 carbon atoms (for example, ethanol) and the like are frequently used. The amount of the elution solvent used can be appropriately selected depending on the composition of the solvent and the like. The elution may be performed by changing the alcohol concentration stepwise or continuously.

(Ii) Alkaline elution solvent The alkaline elution solvent preferably has a pH range of 10 or higher, particularly 10 to 12.5, and particularly 10.5-11.5.
It is a degree.

When an elution solvent having a pH of 9.5 or more is used, the concentration of flavone glycosides is extremely high, and the salicylic acid derivative,
Fractions with low concentrations of free flavonols and other components such as quercetin can be obtained. This is considered to be because the flavone glycoside is easily eluted by setting the elution solvent to pH 9.5 or more.

The preparation of the elution solvent having a pH of 9.5 or more is as follows.
For example, it can be carried out by adding a base to an aqueous solvent such as water. The base includes an inorganic base (for example,
Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; Alkaline earth metal hydroxides such as magnesium hydroxide and barium hydroxide; Alkali metal carbonates such as sodium carbonate and potassium carbonate; Magnesium carbonate, Alkaline earth metal carbonates such as barium carbonate; sodium hydrogen carbonate, potassium hydrogen carbonate and other alkali metal hydrogen carbonates; ammonium carbonate; ammonia, etc., and organic bases (eg, sodium acetate, potassium propionate, etc.) Organic acid salts of metals; organic acid salts of alkaline earth metals such as magnesium formate and magnesium acetate; amines such as trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, butylamine and piperidine; nitrogen-containing heterocyclic compounds such as pyridine It is included. Among these, preferred are ammonia, ammonium carbonate, and low-boiling amines such as methylamine and ethylamine, which can be easily removed from the eluate after elution. Ammonia and the like are particularly preferably used.

The elution solvent having a pH of 9.5 or more may contain a hydrophilic organic solvent in a range that does not reduce the purity of the flavone glycoside in the eluate. Examples of the hydrophilic organic solvent include the organic solvents exemplified above, and among them, alcohols such as the monovalent lower alcohols exemplified above, particularly monohydric alcohols having 1 to 4 carbon atoms, and particularly 1 to 3 carbon atoms. A polyhydric alcohol (eg ethanol) is preferred. The content of the organic solvent is, for example, 0 to 15% by volume, preferably about 0 to 10% by volume. When the content of the organic solvent exceeds 15% by volume, for example, free flavonols, salicylic acid derivatives and other components are easily eluted together with useful components such as flavone glycosides.

A preferred elution solvent is a water-based elution solvent having a pH of 9.5 or higher and containing 0 to 15% by volume of a monovalent lower alcohol, such as water, or 15% by volume or less of a monovalent lower solvent. A lower alcohol aqueous solution and the like are included. In particular, water having a pH of 9.5 or more, or an aqueous solution of 10% by volume or less of a monohydric alcohol having 1 to 3 carbon atoms (eg, ethanol) is preferable.

(Iii) Low Alcohol Concentration Alkaline Elution Solvent The low alcohol concentration alkaline elution solvent has a pH of
It contains water or an aqueous alcohol solution of 9.5 or more and 15% by volume or less. Examples of the alcohol include the above-exemplified monohydric lower alcohols and the like.
Preferred are monohydric alcohols, especially monohydric alcohols having 1 to 3 carbon atoms (eg, ethanol).

The preferred alcohol concentration in the eluting solvent is 0.
It is about 10% by volume. Also, the preferred p of the elution solvent is
H is 10 or more, especially 10 to 12.5, especially 10.5
It is about 11.5. The alcohol concentration is 0 to 15
When an aqueous elution solvent having a volume% and a pH of 9.5 or more is used, the concentration of flavone glycosides is extremely high, and the concentration of free flavonols such as salicylic acid derivatives and quercetin and other components are low. Can be obtained. The pH of the elution solvent can be adjusted in the same manner as in the case of the elution solvent in (ii) above.

The amount of the elution solvent (ii) or (iii) used can be appropriately selected depending on the pH and composition of the solvent. The elution may be performed by changing the pH of the aqueous solution or the concentration of the organic solvent stepwise or continuously.

The eluate obtained in the elution step is concentrated in the concentration step to obtain a ginkgo biloba extract. The above of the present invention
In the methods of (2) to (4), the temperature, pH and atmosphere for concentrating the eluate are not particularly limited, but the concentration of the eluate is (a) at a temperature of 80 ° C. or lower, (b) It is preferable to adjust the pH to 6 to 8 or (c) under an inert gas atmosphere.

The concentration temperature is 80 ° C. or lower, especially 20 to 70 ° C.
When kept at a certain level, by-products of free flavonols such as quercetin due to hydrolysis of flavone glycosides are remarkably suppressed even when the concentration of the eluate to be concentrated is acidic, for example, pH 6 or less, particularly 4 or less. Therefore, a ginkgo biloba extract having a significantly low quercetin content can be obtained. Further, if the concentration temperature is 80 ° C. or lower, the production of coloring components during concentration is significantly suppressed. So, for example,
Absorbance at a wavelength of 550 nm [cell: 1 cm quartz cell; solvent: 50% by volume aqueous ethanol solution; concentration: 4 mg
/ Ml] of 0.20 or less, a ginkgo biloba extract having a very small degree of coloring can be obtained.

If the liquid property of the eluate is adjusted to pH 6 to 8, more preferably pH 6 to 7 prior to the concentration, it can be concentrated even at a relatively high temperature of about 105 ° C., for example. Hydrolysis of flavone glycosides in Ginkgo biloba extract during the process is significantly suppressed. Therefore, a ginkgo biloba extract having an extremely low content of free flavonols such as quercetin can be efficiently obtained. Further, when the liquid property of the eluate is alkaline, the coloring of the ginkgo biloba extract can be reduced by adjusting the liquid property to a neutral region and concentrating.

The adjustment of the liquid property of the eluate is carried out by adding a base when the eluate is acidic, or when the eluate is alkaline, the base in the eluate is distilled off or decomposed, This can be done by adding an acid to the eluate. Examples of the base include the inorganic bases and organic bases exemplified above. Examples of the acid include pharmaceutically acceptable acids, for example, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and boric acid; and acetic acid, propionic acid, oxalic acid, glycolic acid, lactic acid, malic acid, tartaric acid and the like. Examples thereof include organic acids.

Furthermore, if the concentration is carried out in an atmosphere of an inert gas such as nitrogen, helium or argon, most of the coloring components are produced during the concentration even if the concentration is carried out at a relatively high temperature, for example about 105 ° C. do not do. Therefore, for example, it is possible to obtain a ginkgo biloba extract having a very low degree of coloring, the absorbance at a wavelength of 550 nm being 0.14 or less.

The concentration conditions of (a) to (c) above can be used in combination of two or more. For example, the eluate can be concentrated at a temperature of 80 ° C. or lower under an inert gas atmosphere. The eluate can be adjusted to pH 6 to 8 and concentrated under an inert gas atmosphere. Further, the eluate is adjusted to pH 6
It can be adjusted to ˜8 and concentrated at a temperature of 80 ° C. or lower. Furthermore, the eluate can be adjusted to pH 6 to 8 and concentrated at a temperature of 80 ° C. or lower in an inert gas atmosphere. As described above, by using the concentration conditions (a) to (c) in combination, it is possible to obtain an extremely safe ginkgo biloba extract having a significantly low quercetin content and coloring degree.

The ginkgo biloba extract thus obtained may be a liquid concentrated extract or an extract powder. The extract powder can be obtained by drying a liquid extract and crushing it if necessary. Drying
It can be performed by a conventional drying method such as ventilation drying, heat drying, sun drying, reduced pressure drying, spray drying, or a combination thereof. Preferred drying methods include spray drying and the like.

The ginkgo biloba extract may be sterilized if necessary. The sterilization treatment can be performed, for example, by performing the treatment at a temperature of about 80 to 120 ° C. for about 10 minutes to 1 hour.

Thus, by the methods (2) to (4) of the present invention, the flavone glycoside is contained at a concentration of, for example, 15% by weight or more, and the salicylic acid derivative content is 30 ppm or less, preferably 10 ppm or less, Preferably 1p
It is less than pm (detection limit of HPLC) and the quercetin content is 0.02 wt% or less, preferably 0.01 wt% or less, more preferably 0.001 wt% (HPL
Ginkgo biloba extract of less than C detection limit) can be obtained. Particularly, according to the production method of (3) or (4), ginkgo biloba containing an extremely high concentration of flavone glycoside, for example, 30 wt% or more, preferably 35 wt% or more, more preferably 40 wt% or more. The extract can be easily obtained. Further, according to the method of the present invention, the absorbance at 550 nm is, for example, 0.20 or less, preferably 0.14.
Ginkgo biloba extract having the following extremely low degree of coloring can be obtained.

The method of concentrating under the concentrating conditions of (a), (b) or (c) above is not limited to the eluate from the adsorbent, but generally the separation liquid containing ginkgo biloba extract components is used. Applicable for concentration.

It is sufficient that the separated liquid contains a Ginkgo biloba extract component. For example, as the separated liquid, Ginkgo biloba extract and Ginkgo biloba extract are filtered, centrifuged, distilled, extracted, and adsorbed. Examples thereof include a solution or suspension containing a ginkgo biloba extract component obtained by a separation operation such as separation.

The solvent of the separated liquid may be water or a hydrophilic organic solvent exemplified as the extraction solvent, and, for example, an aliphatic hydrocarbon such as pentane, hexane, heptane, octane; cyclohexane, Alicyclic hydrocarbons such as methylcyclohexane; benzene, toluene,
Aromatic hydrocarbons such as xylene and ethylbenzene; Halogenated hydrocarbons such as chloroform, dichloromethane and 1,2-dichloroethane; Esters such as ethyl formate, methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, amyl acetate and ethyl propionate An ether such as diethyl ether or dibutyl ether; a hydrophobic organic solvent such as alcohol such as 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol or 2-ethylhexanol, and a mixed solvent thereof. Good.

By concentrating the separated liquid at (a) a temperature of 80 ° C. or lower, (b) adjusted to pH 6 to 8 or (c) in an inert gas atmosphere, or a combination thereof. ,
Hydrolysis of flavone glycosides and formation of coloring components are significantly suppressed. Therefore, it is possible to obtain a ginkgo biloba extract having an extremely low content of free flavonols such as quercetin and / or coloring components.

Since the ginkgo biloba extract obtained by the method of the present invention contains flavone glycosides and has a low concentration of harmful components and high safety, it is used for sweets such as candy, chocolate and gum, health drinks and foods such as tea. It can be suitably used as an additive or a pharmacologically active ingredient of a pharmaceutical preparation.

[0076]

INDUSTRIAL APPLICABILITY The ginkgo biloba extract of the present invention is highly safe because the salicylic acid derivative and quercetin content are both extremely low.

According to the method of the present invention, the above excellent ginkgo biloba extract can be obtained in a high yield by a simple operation.

According to the method of the present invention, a ginkgo biloba extract containing flavone glycosides and having a low content of quercetin and / or coloring components can be obtained by a simple operation.

[0079]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited by these examples.

In the examples, quantification of flavone glycosides, quercetin and salicylic acid derivatives in Ginkgo biloba extract was carried out by high performance liquid chromatography (HPLC). The content of flavone glycosides in the ginkgo biloba extract is determined by subjecting the ginkgo biloba extract to hydrolysis with hydrochloric acid,
The flavonols released (quercetin, kaempferol and isorhamnetin) were determined by quantifying by HPLC. That is, about 75 ginkgo extract samples
Accurately weigh mg, add 10 ml of methanol to dissolve this, and then add 10 ml of 1.5N HCl to obtain 3
After refluxing for a period of time, the mixture was allowed to cool, adjusted to 50 ml with methanol and subjected to HPLC analysis. The absorbance of Ginkgo biloba extract was measured by an ultraviolet spectrophotometer [U-3300; manufactured by Hitachi, Ltd.]. The analysis conditions are described below.

[Quantification of flavone glycosides] Column: Capsule pack C-18 [manufactured by Shiseido Co., Ltd.] Mobile phase: 0.05 wt% phosphoric acid aqueous solution / methanol = 7
/ 3 (V / V) to 4/6 (V / V) (45-minute linear gradient) Flow rate: 1.0 ml / min Column temperature: Room temperature detection: UV360 nm [quantification of quercetin] Column: TSKgel ODS-80TS [Tosoh Mobile phase: 15 vol% acetonitrile, 0.1 vol% trifluoroacetic acid aqueous solution flow rate: 1.0 ml / min Column temperature: 50 ° C Detection: UV 360 nm [Quantification of salicylic acid derivative] Column: Capsule Pack C-18 [Shiseido Co., Ltd.] Mobile phase: 0.05M phosphoric acid aqueous solution / methanol = 8/9
2 (V / V) Flow rate: 1.0 ml / min Column temperature: Room temperature Detection: UV308 nm [Measurement of absorbance] Cell: 1 cm Quartz cell Wavelength: 550 nm Solvent: 50% by volume ethanol aqueous solution concentration: 20 mg / 5 ml Example 1 Ginkgo biloba 2000 ml of water was added to 150 g, extraction was performed at 90 ° C. for 3 hours, and the residue was filtered off. Furthermore, 10 water is added to the residue.
00 ml was added, the mixture was extracted at 90 ° C. for 1.5 hours, and filtered. The obtained filtrates were combined, 15 g of Celite was added, and the mixture was stirred and then filtered using 5A filter paper.

Hydrophobic synthetic resin adsorbent [ROHM &
Amber Light XAD-2000] 15m
1 was loaded onto the column and equilibrated with water. Of the filtrate obtained by the above Celite filtration, 440 ml was used with a space velocity of 2 hr.
^-1 was passed through the column for adsorption treatment.

Then, the column is charged with 75 ml of water and 20
It was washed successively with 75 ml of a volume% ethanol aqueous solution. 40
75 ml of a volume% ethanol aqueous solution was passed through the column to elute the adsorbed components.

The eluate was concentrated to dryness with a rotary evaporator (bath temperature: 40 to 50 ° C.), and Ginkgo biloba extract 32 was added.
0 mg (1.45 wt.% Per ginkgo leaf) were obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 17.
It was 8% by weight. The quercetin content in the ginkgo biloba extract was less than 0.001% by weight (detection limit), and the salicylic acid derivative content was less than 1 ppm (detection limit).

Example 2 Ginkgo biloba extract 43 was operated in the same manner as in Example 1 except that the adsorbed component was eluted using 75 ml of 45% by volume aqueous ethanol solution instead of 40% by volume aqueous ethanol solution.
8 mg (1.16% by weight per ginkgo leaf) were obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 18.
0% by weight, quercetin content was 0.002% by weight, and salicylic acid derivative content was less than 1 ppm (detection limit).

Example 3 Ginkgo biloba extract 39 was operated in the same manner as in Example 1 except that the adsorbed components were eluted using 75 ml of 50% by volume aqueous ethanol solution instead of 40% by volume aqueous ethanol solution.
0 mg (1.04% by weight to ginkgo biloba) was obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 24.
The content was 1% by weight, the quercetin content was 0.005% by weight, and the salicylic acid derivative content was less than 1 ppm (detection limit).

Example 4 1500 g of water was added to 150 g of ginkgo biloba, and the mixture was extracted at 70 ° C. for 2 hours, and the residue was filtered off. Furthermore, 10 water is added to the residue.
00 ml was added, extraction was performed at 70 ° C. for 0.5 hours, and the residue was filtered off. Furthermore, add 1000 ml of water to the residue,
Extracted at 0 ° C. for 0.5 hours and filtered. The obtained filtrates were combined, 15 g of Celite was added, and the mixture was stirred and then filtered using 5A filter paper.

Hydrophobic synthetic resin adsorbent [ROHM &
Amberlite XAD-2000] 100 manufactured by Hearth
The column was filled with ml and equilibrated with water. The filtrate obtained by the above Celite filtration was passed through the column at a space velocity of 2 hr ⁻¹ for adsorption treatment.

Next, the column was washed successively with 500 ml of water and 500 ml of a 20% by volume aqueous ethanol solution. 45
500 ml of a volume% ethanol aqueous solution was passed through the column to elute the adsorbed components.

Half of the eluate was concentrated to dryness with a rotary evaporator (bath temperature: 40 to 50 ° C.) to obtain 960 mg (1.3% by weight of ginkgo biloba leaf) of ginkgo biloba extract. The content of flavone glycosides in the obtained ginkgo biloba extract was 2
0.9% by weight, quercetin content is 0.001% by weight
Less than (detection limit), salicylic acid derivative content is 1ppm
It was less than (detection limit). The absorbance of the ginkgo biloba extract at a wavelength of 550 nm was 0.11.

Comparative Example 1 Ginkgo biloba extract 56 was operated in the same manner as in Example 1 except that 75 ml of a 60% by volume aqueous ethanol solution was used instead of the 40% by volume aqueous ethanol solution to elute the adsorbed components.
1 mg (1.5% by weight to ginkgo biloba) was obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 25.4.
% By weight. However, the quercetin content in ginkgo biloba extract is 0.05% by weight, and the salicylic acid derivative content is 4%.
6 ppm, which is a high value.

Example 5 To 150 g of ginkgo leaves, 2000 ml of water was added, and the mixture was extracted at 90 ° C. for 2 hours, and the residue was filtered off. Furthermore, 10 water is added to the residue.
00 ml was added, the mixture was extracted at 90 ° C. for 1.5 hours, and filtered. The obtained filtrates were combined, 5 g of Celite was added and stirred, and then filtered using 5A filter paper.

Hydrophobic synthetic resin adsorbent [ROHM &
Made by Hearth, Amberlite XAD-2000] 33m
1 was loaded onto the column and equilibrated with water. Of the filtrate obtained by the above Celite filtration, 1100 ml was filtered at a space velocity of 6 h.
It was passed through the column at r ⁻¹ for adsorption treatment.

Then, the column was washed successively with 166 ml of water, 166 ml of 20% by volume aqueous ethanol, and 166 ml of water. 166 ml of a 5 volume% aqueous ethanol solution (pH about 12) containing 1% by weight of ammonia was passed through the column to elute the adsorbed components.

The eluate was concentrated to dryness with a rotary evaporator (bath temperature: 40 to 50 ° C.), and Ginkgo biloba extract 35
0 mg (0.7 wt.% Per ginkgo leaf) were obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 47.6.
% By weight. The quercetin content in the ginkgo biloba extract was less than 0.001% by weight (detection limit), and the salicylic acid derivative content was less than 1 ppm (detection limit).

Example 6 To 150 g of ginkgo biloba leaves was added 2000 ml of water, the mixture was extracted at 90 ° C. for 2 hours, and the residue was filtered off. In addition, water 15
00 ml was added, the mixture was extracted at 90 ° C. for 1.5 hours, and filtered. The obtained filtrates were combined, 15 g of Celite was added, and the mixture was stirred and then filtered using 5A filter paper.

Hydrophobic synthetic resin adsorbent [ROHM &
Amberlite XAD-2000] 100 manufactured by Hearth
The column was filled with ml and equilibrated with water. 2000 ml of the filtrate obtained by the above Celite filtration was used as a space velocity 6
It was passed through the column at hr ⁻¹ for adsorption treatment.

Then, the column was washed successively with 500 ml of water, 500 ml of 20% by volume aqueous ethanol, and 500 ml of water. 2 wt% ammonia solution (pH about 1
3) 500 ml was passed through the column to elute the adsorbed components.

The eluate was concentrated to dryness with a rotary evaporator (bath temperature: 40 to 50 ° C.), and Ginkgo biloba extract 37 was used.
0 mg (0.42 wt% relative to ginkgo leaves) were obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 35.
It was 4% by weight. The quercetin content in the ginkgo biloba extract was less than 0.001% by weight (detection limit), and the salicylic acid derivative content was less than 1 ppm (detection limit).

Example 7 1500 ml of the filtrate obtained by filtration through Celite was passed through a column for adsorption treatment, and 500 ml of 0.5 wt% ammonia aqueous solution (pH about 11) was passed through the column to elute adsorbed components. Except for the above points, the same operation as in Example 6 was carried out to obtain 270 mg of ginkgo biloba extract (0.4% by weight relative to ginkgo biloba leaves). The content of flavone glycosides in the obtained Ginkgo biloba extract was 38.5% by weight. The quercetin content in ginkgo biloba extract is 0.001% by weight.
Less than (detection limit), salicylic acid derivative content is 1ppm
It was less than (detection limit).

Example 8 1500 g of water was added to 150 g of ginkgo biloba, extraction was carried out at 90 ° C. for 2 hours, and the residue was filtered off. In addition, water 15
00 ml was added, extraction was carried out at 90 ° C. for 1.5 hours, and the residue was filtered off. Furthermore, 1500 ml of water was added to the residue,
Extracted at 0 ° C. for 1.5 hours and filtered. The obtained filtrates were combined, 15 g of Celite was added, and the mixture was stirred and then filtered using 5A filter paper.

Hydrophobic synthetic resin adsorbent [ROHM &
Made by Hearth, Amberlite XAD-2000] 33m
1 was loaded onto the column and equilibrated with water. 1360 ml of the filtrate obtained by the above Celite filtration was used for space velocity 6h.
It was passed through the column at r ⁻¹ for adsorption treatment.

Then, the column was washed successively with 167 ml of water, 167 ml of 20% by volume aqueous ethanol, and 167 ml of water. 167 ml of 0.1 M ammonium carbonate aqueous solution adjusted to pH 11.0 with ammonia was passed through the column to elute the adsorbed components.

The eluate was concentrated to dryness with a rotary evaporator (bath temperature: 40 to 50 ° C.), and Ginkgo biloba extract 69 was added.
mg (0.10% by weight to ginkgo biloba) was obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 41.0.
% By weight. The quercetin content in the ginkgo biloba extract was less than 0.001% by weight (detection limit), and the salicylic acid derivative content was less than 1 ppm (detection limit).

Comparative Example 2 Except that the adsorbed components were eluted by passing a 0.1 M ammonium carbonate aqueous solution (pH 9.2) through the column instead of the 0.1 M ammonium carbonate aqueous solution adjusted to pH 11.0 with ammonia. The same operation as in Example 8 was performed. As a result, the weight of the obtained ginkgo biloba extract was 17 mg (0.0
4% by weight to ginkgo leaves), and the content of flavone glycosides in the ginkgo extract was 2.5% by weight, which was an extremely low value.

Comparative Example 3 According to the method described in Example 2 of JP-A-2-73079, a ginkgo biloba extract was obtained as follows.

100 kg of ginkgo biloba leaves were reflux-extracted with a 60% aqueous ethanol solution, and 20% was added to 27 kg of the obtained extract.
After 200 L of ethanol was added and heated to 50 to 60 ° C, insoluble matter was removed. 10 kg of activated carbon in the obtained solution
And stir for 10 minutes, then filter and add 100 L
It was washed with 20% ethanol aqueous solution. Subsequently, the components adsorbed on the activated carbon were promptly eluted with a 40% ethanol aqueous solution containing 2% ammonia.

The eluate was concentrated to dryness and ginkgo biloba extract 75
0 g was obtained. The content of flavone glycosides in the obtained ginkgo biloba extract was 33% by weight. However, the quercetin content in the ginkgo biloba extract was 0.05% by weight, and the salicylic acid derivative content was 73 ppm, which were both high values.

Examples 9 to 11, Comparative Examples 4 to 5 2000 g of water was added to 150 g of ginkgo biloba, extraction was carried out at 90 ° C. for 3 hours, and the residue was filtered off. Furthermore, 10 water is added to the residue.
00 ml was added, the mixture was extracted at 90 ° C. for 1.5 hours, and filtered. The obtained filtrates were combined, 15 g of Celite was added, and the mixture was stirred and then filtered using 5A filter paper.

Hydrophobic synthetic resin adsorbent [ROHM &
Made by Hearth, Amberlite XAD-2000] 90m
1 was loaded onto the column and equilibrated with water. 2640 ml of the filtrate obtained by the above Celite filtration was used for space velocity 2 h
It was passed through the column at r ⁻¹ for adsorption treatment.

Then, the column was charged with 450 ml of water and 2 times.
It was washed successively with 450 ml of 0% by volume aqueous ethanol.
450 ml of 40% by volume aqueous ethanol was passed through the column to elute the adsorbed components.

From this eluate, ethanol was distilled off under reduced pressure by a rotary evaporator (about 45 ° C., about 2 ° C.).
Time), an aqueous solution containing 1% by weight of ginkgo biloba extract (pH
3.3) was prepared.

An aqueous solution containing the above Ginkgo biloba extract was prepared for each of the experiments, and concentrated and dried at the temperature shown below for the time shown in Table 1.

Example 9 60 ° C. Example 10 70 ° C. Example 11 80 ° C. Comparative Example 4 95 ° C. Comparative Example 5 105 ° C. The quercetin content (% by weight) in the obtained ginkgo biloba extract was measured by HPLC. The results are shown in Table 1 and FIG. The numbers in the table indicate the quercetin content (% by weight) in the ginkgo biloba extract. Further, "-" in the table indicates that there is no data (hereinafter the same).

[0115]

[Table 1] As is clear from Table 1 and FIG. 1, when concentrated at a temperature of 95 ° C. or higher, a ginkgo biloba extract having a very high quercetin content was obtained, whereas when concentrated at 60 ° C. to 80 ° C. , Ginkgo biloba extract with extremely low quercetin content was obtained even when concentrated over a relatively long period of time.

Examples 12 to 13 and Comparative Example 6 From the eluate obtained in the same manner as in Example 4, ethanol was distilled off under reduced pressure by a rotary evaporator (about 45 ° C., about 2 hours), and Ginkgo biloba extract 1 was obtained. An aqueous solution containing wt% was prepared.

An aqueous solution containing the above-mentioned ginkgo biloba extract was prepared for each of the experiments, and concentrated and dried at the temperature shown below in the air atmosphere for the time shown in Table 2.

Example 12 60 ° C. Example 13 70 ° C. Comparative Example 6 90 ° C. The absorbance of the obtained ginkgo biloba extract at a wavelength of 550 nm was measured. The results are shown in Table 2. The numbers in the table indicate the absorbance.

[0119]

[Table 2] As can be seen from Table 2, the absorbance at 60 ° C. and 70 ° C. is about 25 times higher than that at 90 ° C.
%, And the above-mentioned absorbance was 0.20 or less, and the ginkgo biloba extract with extremely little coloration was obtained even after concentration for a relatively long time.

Examples 14 to 15 An aqueous sodium hydroxide solution was added to an aqueous solution containing 1% by weight of ginkgo biloba extract prepared in the same manner as in Examples 9 to 11 to adjust the pH to 6.8. This solution was prepared by the number of experiments, and each solution was concentrated to dryness at the temperature shown below for the time shown in Table 3.

Example 14 95 ° C. Example 15 105 ° C. The quercetin content (% by weight) in the obtained ginkgo biloba extract was measured by HPLC. The results are shown in Table 3. The numbers in the table indicate the quercetin content (% by weight) in the ginkgo biloba extract.

[0122]

[Table 3] As is clear from Tables 1 and 3, when the temperature during concentration was relatively high, a ginkgo biloba extract having a very high quercetin content was obtained when the pH of the aqueous solution containing ginkgo biloba extract was 3.3. On the other hand, when the pH of the aqueous solution containing the Ginkgo biloba extract was adjusted to 6.8 and concentrated, a Ginkgo biloba extract with an extremely low quercetin content was obtained.

Example 16, Comparative Example 1 1% by weight prepared in the same manner as in Examples 12 to 13
Prepare an aqueous solution containing ginkgo biloba extract for the number of experiments,
In the following atmosphere, each was concentrated to dryness at a temperature of 105 ° C. for the time shown in Table 4.

Example 16 Nitrogen atmosphere Comparative example 12 Air atmosphere The absorbance of the obtained ginkgo biloba extract at a wavelength of 550 nm was measured. The results are shown in Table 4. The numbers in the table indicate the absorbance.

[0125]

[Table 4] As shown in Table 4, the absorbance increased with time in the air atmosphere, whereas in the nitrogen atmosphere, the absorbance did not change even after 8 hours.

[Brief description of drawings]

FIG. 1 is a graph showing the results of Examples 9-11 and Comparative Examples 4-5.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 3/10 A61P 3/10 9/00 9/00 9/10 101 9/10 101 25/18 25 / 18 25/28 25/28 (72) Inventor Takeshi Matsumoto 500F term, Kamimayu, Himeji City, Hyogo Prefecture (reference) 4B018 LB01 LB08 MD61 ME04 MF01 4C083 AA111 AC311 AC841 CC02 CC05 EE12 FF01 4C088 AB02 BA08 CA08 MA52 MA63 NA06 ZA16 ZA16 ZA18 ZA36 ZA45 ZC35

Claims (17)

[Claims] 1. A ginkgo biloba extract containing 15% by weight or more of flavone glycosides and having a quercetin content of 0.
02 wt% or less, and salicylic acid derivative content 30p
Ginkgo biloba extract that is pm or less. 2. The content of salicylic acid derivative is 10 ppm.
The ginkgo biloba extract according to claim 1, which is as follows. 3. The ginkgo biloba extract according to claim 1, which has a quercetin content of 0.01% by weight or less and a salicylic acid derivative content of less than 1 ppm. 4. A ginkgo biloba extract containing 15% by weight or more of flavone glycosides and having a salicylic acid derivative content of less than 1 ppm. 5. A ginkgo biloba extract containing 15% by weight or more of flavone glycosides and having a quercetin content of 0.
Ginkgo biloba extract, which is less than or equal to 01% by weight. 6. The ginkgo biloba extract according to claim 1, which contains 30% by weight or more of flavone glycosides. 7. An extraction step of extracting ginkgo biloba leaves with an extraction solvent, an adsorption step of treating the obtained extract with an adsorbent, an elution step of eluting components adsorbed on the adsorbent with an elution solvent, and elution A method for producing a ginkgo biloba extract, comprising the steps of concentrating a liquid to obtain a ginkgo biloba extract,
A method for producing a Ginkgo biloba extract, wherein an aqueous elution solvent containing 0 to 15% by volume of alcohol is used as the elution solvent. 8. The method for producing a ginkgo biloba extract according to claim 7, wherein the extract is treated with an adsorbent under acidic conditions. 9. The method for producing a ginkgo biloba extract according to claim 7, wherein a monohydric alcohol having 1 to 3 carbon atoms is used as the alcohol. 10. An extraction step of extracting ginkgo biloba leaves with an extraction solvent, an adsorption step of treating the obtained extract with a hydrophobic synthetic resin adsorbent, and an elution in which components adsorbed on the adsorbent are eluted with an elution solvent. A method for producing a ginkgo biloba extract, which comprises a step of concentrating an eluate to obtain a ginkgo biloba extract, the method comprising:
A method for producing a ginkgo biloba extract using an aqueous elution solvent of H9.5 or higher. 11. The method for producing a ginkgo biloba extract according to claim 10, wherein an elution solvent having a pH of 10 or more is used. 12. An extraction step of extracting ginkgo biloba leaves with an extraction solvent, an adsorption step of treating the obtained extract with an adsorbent, an elution step of eluting components adsorbed on the adsorbent with an elution solvent, and elution A method for producing a ginkgo biloba extract, comprising the steps of concentrating a liquid to obtain a ginkgo biloba extract, which comprises using an aqueous elution solvent containing 0 to 15% by volume of alcohol and having a pH of 9.5 or more. 13. An extract obtained by extracting ginkgo biloba leaves with an extraction solvent is treated with an adsorbent, components adsorbed on the adsorbent are eluted with an aqueous alcohol solution of 55% by volume or less, and the obtained eluate is concentrated. A method for obtaining ginkgo biloba extract, the eluate containing ginkgo biloba extract components at 80 ° C
A method for producing Ginkgo biloba extract, which is concentrated at the following temperatures. 14. An extract obtained by extracting ginkgo biloba leaves with an extraction solvent is treated with an adsorbent, components adsorbed on the adsorbent are eluted with an aqueous alcohol solution of 55% by volume or less, and the obtained eluate is concentrated. A method for obtaining ginkgo biloba extract, wherein the eluate containing ginkgo biloba extract components is adjusted to pH 6
A method for producing a ginkgo biloba extract, which is adjusted to ~ 8 and concentrated. 15. An extract obtained by extracting ginkgo biloba leaves with an extraction solvent is treated with an adsorbent, components adsorbed on the adsorbent are eluted with an alcohol aqueous solution of 55% by volume or less, and the obtained eluate is concentrated. A method for producing a ginkgo biloba extract, which comprises concentrating an eluate containing a ginkgo biloba extract component in an inert gas atmosphere. 16. The method for producing a ginkgo biloba extract according to any one of claims 13 to 15, wherein the adsorbent is a hydrophobic synthetic resin adsorbent. 17. The method for producing a ginkgo biloba extract according to any one of 13 to 16, which is eluted with an aqueous elution solvent containing 0 to 15% by volume of alcohol.