JP7570095B2 - Ginkgo leaf extract composition and oral composition - Google Patents

Description

The present invention relates to a ginkgo leaf extract composition and an oral composition containing the ginkgo leaf extract composition.

Ginkgo leaves are used in medicines, cosmetics, health foods, etc. in Europe, and in Japan they are used in health foods (granules, tablets, beverages, etc.), cosmetics, luxury items, etc. Active ingredients in ginkgo leaves include about 20 kinds of flavonoid glycosides such as quercetin, isorhamnetin, kaempferol, and terpene lactones such as ginkgolides and bilobalide. These active ingredients are known to have various useful functions such as improving circulatory function, promoting and improving blood flow (preventing neuralgia, stiff shoulders, poor circulation, and improving headaches and migraines), preventing aging, strengthening the stomach, healthy eyes, healthy brain, preventing senile dementia (especially preventing dementia caused by cerebrovascular disorders such as cerebral infarction and cerebral thrombosis), preventing heart disease (lowering blood pressure and cholesterol, preventing arteriosclerosis), and improving allergy symptoms (improving the symptoms of atopic dermatitis and asthma).

In the production of ginkgo leaf extract, extraction is mainly performed using aqueous ethanol in order to efficiently extract the active ingredients and from the viewpoint of safety. Therefore, when ginkgo leaf extract is used in foods and beverages, health foods, cosmetics, medicines, etc., there is a problem that it is very difficult to dissolve in aqueous solutions and is difficult to work with.

In addition, when ginkgo leaf extract is used in soft drinks and the like that contain fruit juice or acidulants and have a low pH, the solubility stability of the ginkgo leaf extract is significantly reduced, and even at extremely low concentrations of about 0.01% by mass, precipitation occurs, causing problems such as impairing the appearance of the product. Furthermore, there is also the problem that the flavonoid glycoside, one of the active ingredients of ginkgo leaf extract, is easily decomposed under acidic conditions.

In response to these problems, a liquid water-dispersible or water-soluble ginkgo leaf extract composition has been proposed that contains ginkgo leaf extract, quillaja saponin, enzymatically hydrolyzed lecithin, dextrin, cyclodextrin, or a mixture thereof, and has excellent dispersibility and solubility in water, and can prevent the formation of precipitates for a long period of time when added to foods and beverages, health foods, cosmetics, medicines, etc. (see Patent Document 1).

However, the ginkgo leaf extract composition proposed above does not have fully satisfactory solubility in acidic solvents, and furthermore has the problem of being prone to foaming due to saponin.

Therefore, there is currently a strong demand for the prompt provision of a ginkgo leaf extract composition that has excellent dispersibility and solubility in water or acidic solvents, can prevent the formation of precipitates over a long period of time, and can suppress foaming.

Patent No. 4502549

The present invention aims to solve the above-mentioned problems in the past and to achieve the following objectives. That is, the present invention aims to provide a ginkgo leaf extract composition that has excellent dispersibility and solubility in water or an acidic solvent, can prevent the formation of precipitation over a long period of time, and can suppress foaming, and an oral composition containing the ginkgo leaf extract composition.

The means for solving the above problems are as follows.
<1> A composition comprising (A) ginkgo leaf extract, (B) enzymatically decomposed lecithin containing lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), (C) saponin, and (D) glycerin;
The ginkgo leaf extract composition (B) is characterized in that the mass ratio [LPA/LPC] of the content (mass) of the lysophosphatidylcholine to the content (mass) of the lysophosphatidic acid in the enzymatically hydrolyzed lecithin is 150 or more.
<2> A composition for oral administration, comprising the ginkgo leaf extract composition according to <1>.

The present invention can solve the above-mentioned problems of the prior art and achieve the above-mentioned objectives, and can provide a ginkgo leaf extract composition that has excellent dispersibility and solubility in water or an acidic solvent, can prevent the formation of precipitates over a long period of time, and can suppress foaming, and an oral composition containing the ginkgo leaf extract composition.

(Ginkgo Leaf Extract Composition)
The ginkgo leaf extract composition of the present invention contains (A) ginkgo leaf extract, (B) enzymatically hydrolyzed lecithin containing lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), (C) saponin, and (D) glycerin, and further contains other ingredients as necessary.

<(A) Ginkgo Leaf Extract>
Ginkgo (scientific name: Ginkgo biloba ) used as the raw material for extracting ginkgo leaf extract as component (A) is a deciduous tall tree belonging to the genus Ginkgo in the family Ginkgoaceae . Ginkgo is distributed throughout the world by artificial transplantation and is easily available from these regions. The height of the stem of ginkgo is 20 to 30 m, and it is a type of gymnosperm.
The method for obtaining the ginkgo leaves is not particularly limited and can be appropriately selected depending on the purpose. The leaves may be collected from nature or may be commercially available.

The ginkgo leaf extract can be easily obtained by a method generally used for plant extraction. For example, the ginkgo leaf used as the extraction raw material is immersed in a treatment tank filled with an extraction solvent, and soluble components are dissolved while stirring as necessary, and then the extract is filtered to remove the extraction residue to obtain the ginkgo leaf extract. It is preferable that the ginkgo leaf extract is a crude or purified product.

There are no particular limitations on the size of the ginkgo leaves used as the extraction raw material, and they can be appropriately selected depending on the purpose. For example, the size of the leaves as they are when harvested, the size of the leaves cut to the desired size, or the size of the leaves pulverized (powdered) can be mentioned.

The state of the ginkgo leaves used as the extraction raw material is not particularly limited and can be appropriately selected depending on the purpose. For example, the leaves may be in the state as they are harvested, dried, crushed, or juiced. Among these, the dried state is preferred.

The method for drying the ginkgo leaves is not particularly limited and can be appropriately selected depending on the purpose. For example, the method includes drying in the sun and drying using a commonly used dryer.

The method for crushing the ginkgo leaves is not particularly limited and can be appropriately selected depending on the purpose. Examples of the method include crushing the ginkgo leaves using a mixer, sugar mill, power mill, jet mill, impact crusher, etc.

There are no particular limitations on the method for making the ginkgo leaves into the juice state, and it can be appropriately selected depending on the purpose, and examples include squeezing.

The extraction solvent for the ginkgo leaf extract is not particularly limited and can be appropriately selected depending on the purpose. Examples of the solvent include water, a hydrophilic solvent, or a mixture thereof.

The water is not particularly limited and can be appropriately selected depending on the purpose. Examples of the water include pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, ion-exchanged water, saline solution, phosphate buffer, and phosphate buffered saline solution. These may be used alone or in combination of two or more.

The hydrophilic solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples of the hydrophilic solvent include lower alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones, such as acetone and methyl ethyl ketone; and polyhydric alcohols having 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin. These may be used alone or in combination of two or more.

The mixed solvent of water and the hydrophilic solvent is not particularly limited and can be appropriately selected depending on the purpose. When the lower alcohol is used as the hydrophilic solvent, it is preferable to use 1 to 90 parts by mass of the hydrophilic solvent per 10 parts by mass of the water. When the lower aliphatic ketone is used as the hydrophilic solvent, it is preferable to use 1 to 40 parts by mass of the hydrophilic solvent per 10 parts by mass of the water. When a polyhydric alcohol is used as the hydrophilic solvent, it is preferable to use 1 to 90 parts by mass of the hydrophilic solvent per 10 parts by mass of the water. These may be used alone or in combination of two or more.

Among these, the extraction solvent for the ginkgo leaf extract is preferably a mixed solvent of water and ethanol (hydrous ethanol) from the viewpoints of safety and ease of handling.
When the aqueous ethanol is used as the extraction solvent, the concentration of ethanol is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 50% by mass or more, and more preferably 70% by mass or more.

There are no particular limitations on the amount of the extraction solvent used and it can be selected appropriately depending on the purpose, but it is preferable to use an amount (mass ratio) of 5 to 15 times the amount of ginkgo leaves used as the extraction raw material.

The extraction conditions for the ginkgo leaf extract (extraction time, extraction temperature, atmospheric conditions such as pressure, etc.) are not particularly limited and can be appropriately selected from known methods depending on the purpose.
The extraction time for dissolving the soluble components of the ginkgo leaf extract is usually about 30 minutes to 2 hours.
The temperature of the extraction solvent is preferably room temperature or a temperature not higher than the boiling point of the solvent used.
When a mixed solvent of water and ethanol is used as the extraction solvent, it is preferable to carry out the extraction at 40° C. to 80° C. for 30 minutes to 4 hours.

The state of the ginkgo leaf extract is not particularly limited and can be appropriately selected depending on the purpose. For example, it may be the ginkgo leaf extract itself, a crude or purified product of the ginkgo leaf extract, a concentrate of the ginkgo leaf extract, a diluted product of the ginkgo leaf extract, or a dried product of the ginkgo leaf extract. The ginkgo leaf extract may also be obtained by mixing or dissolving the dried product of the ginkgo leaf extract again in a solvent such as water, a hydrophilic solvent, or a mixture thereof.

The purification method of the ginkgo leaf extract is not particularly limited and can be appropriately selected depending on the purpose. Examples of the purification method include chromatography such as partition chromatography, adsorption chromatography, ion exchange chromatography, and size exclusion chromatography, liquid-liquid partition extraction, and membrane separation. These purification methods may be performed alone or in combination of two or more. Among these, it is preferable that the ginkgo leaf extract is purified using the adsorption resin.

The adsorption resin is not particularly limited and can be appropriately selected depending on the purpose, but aromatic or aromatic modified adsorption resins are preferred.
Specific examples of the adsorption resin include Diaion HP20, Diaion HP21, Sepabeads SP825L, Sepabeads SP850, Sepabeads SP207 (all manufactured by Mitsubishi Chemical Corporation), Amberlite XAD-2, Amberlite XAD4, Amberlite XAD7 (all manufactured by Organo Corporation), and the like.

Commercially available products of this type of ginkgo leaf extract include Ginkgo Leaf Extract C (manufactured by Maruzen Pharmaceutical Co., Ltd.).

The ginkgo leaf extract contains active ingredients such as flavonoid glycosides, such as quercetin, isorhamnetin, and kaempferol, and terpene lactones, such as ginkgolides and bilobalide.

The content of the ginkgo leaf extract in the ginkgo leaf extract composition is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 0.01% by mass to 50% by mass, and more preferably 0.1% by mass to 30% by mass, of the entire ginkgo leaf extract composition. If the content of the ginkgo leaf extract is 0.01% by mass or more, it is advantageous in that the desired effect of the active ingredient ginkgo leaf extract can be obtained, and if it is 50% by mass or less, it is advantageous in that the dispersibility and solubility in water or acidic solvents are good and the formation of precipitation can be prevented for a long period of time.

<(B) Enzymatically Decomposed Lecithin>
The enzymatically decomposed lecithin as component (B) contains lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), and the mass ratio [LPA/LPC] of the content (mass) of the lysophosphatidylcholine in the enzymatically decomposed lecithin to the content (mass) of the lysophosphatidic acid is 150 or more, preferably 170 or more. When the mass ratio [LPA/LPC] is 150 or more, the ginkgo leaf extract composition has excellent dispersibility and solubility in water or an acidic solvent, can prevent the formation of precipitation for a long period of time, and is advantageous in that foaming can be suppressed.
The contents of the LPC and the LPA in the enzymatically decomposed lecithin can be measured by supercritical fluid chromatography.

The raw material for the enzymatically decomposed lecithin is not particularly limited and can be appropriately selected depending on the purpose. For example, it is preferable to use phospholipids extracted from poultry egg yolks such as chicken, quail, and duck eggs, soybeans, rapeseed, and other animals and plants, which are treated with enzymes derived from microorganisms, etc., and soybean-derived enzymatically decomposed lecithin is more preferable.

The mass ratio [LPA/LPC] varies depending on the state of the raw material of the enzymatically decomposed lecithin. In the case of soybean-derived lecithin, it is known that the phospholipid composition and fatty acid composition in the lecithin vary depending on the climate change such as temperature and drought during soybean cultivation, and the maturity of soybeans at harvest time (see D. L. Dornbos et al., Journal of the American Oil Chemists' Society, 01 Sep 1989, Vol. 66, Issue 9, p. 1371-1373).
Therefore, the upper limit of the mass ratio [LPA/LPC] is not particularly limited and can be appropriately selected depending on the state of the raw material of the enzymatically decomposed lecithin, but is preferably not more than 3,000, more preferably not more than 1,500, and even more preferably not more than 1,200. When the mass ratio [LPA/LPC] is not more than 3,000, the ginkgo leaf extract composition has excellent dispersibility and solubility in water or an acidic solvent, and is advantageous in that the formation of precipitation can be prevented for a long period of time and foaming can be suppressed.
The lower limit and upper limit of the mass ratio [LPA/LPC] can be appropriately combined, and the range of the mass ratio [LPA/LPC] is preferably 150 to 3,000, more preferably 170 to 3,000, even more preferably 170 to 1,500, and particularly preferably 170 to 1,200.

The type of the enzymatically decomposed lecithin is not particularly limited as long as the mass ratio [LPA/LPC] is 150 or more, and can be appropriately selected depending on the purpose.
The LPC and the LPA are lysophospholipids in which one fatty acid of the phospholipid is cleaved to form a lyso form.
The lysophospholipids, depending on the structure of the phosphate ester, include, in addition to the LPC and LPA, for example, lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS), lysophosphatidylglycerol (LPG), and the like.
The enzymatically decomposed lecithin as component (B) contains the LPC and the LPA, and may contain one or more of the other lysophospholipids as long as the mass ratio [LPA/LPC] is 150 or more.

The method for obtaining the enzymatically decomposed lecithin is not particularly limited and can be appropriately selected depending on the purpose. The enzymatically decomposed lecithin may be appropriately produced by a known production method, or a commercially available product may be used.
As a commercially available enzymatically decomposed lecithin having a mass ratio [LPA/LPC] of 150 or more, Lysophospholipid Nagase L (manufactured by Nagase ChemteX Corporation, an enzymatically treated product of soybean-derived lecithin) can be suitably used.

The content of the enzymatically decomposed lecithin in the ginkgo leaf extract composition is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 0.3% to 4% by mass, and more preferably 0.3% to 2% by mass, of the entire ginkgo leaf extract composition. If the content of the enzymatically decomposed lecithin is 0.3% by mass or more, it is advantageous in that it has good dispersibility and solubility in water or acidic solvents and can suppress foaming, and if it is 4% by mass or less, it is advantageous in that it has good dispersibility and solubility in water or acidic solvents.

<(C) Saponin>
The saponin used as component (C) is not particularly limited and may be appropriately selected depending on the purpose. However, taking into consideration today's health-consciousness, from the standpoint of safety, it is preferable for the saponin to be derived from a natural product, and it is more preferable for the saponin to be derived from a plant.

The plant-derived saponin is not particularly limited and can be appropriately selected according to the purpose, and examples thereof include Quillaja saponin, soybean saponin, yucca saponin, soybean saponin, tea seed saponin, beet saponin, carrot saponin, and licorice saponin (glycyrrhizic acid). These may be used alone or in combination of two or more. Among these, Quillaja saponin is preferred because it has excellent surface activity and is easily available.
The method for obtaining the saponin is not particularly limited and can be appropriately selected depending on the purpose. The saponin may be obtained from a plant collected from nature, or a commercially available product may be used.

The Quillaja saponaria used as the raw material for the Quillaja saponin is an evergreen small tree of the Quillaja genus of the Quillaja family. The Quillaja grows naturally in Chile, Bolivia, and Peru in South America, and is easily available from these regions. The bark of the Quillaja contains tannins and triterpene saponins. The Quillaja saponin ( Quillaja saponin) is a triterpene saponin with quillajaic acid as the aglycone, and is known to have excellent surface activity and homogeneity compared to saponins obtained from other plants, and is widely used in industrial fields such as food emulsifiers, vitamin E, solubilization of flavors, foaming agents for toothpaste and beverages, toiletry products, and photographic films.

The plant-derived saponin can be easily obtained by a method commonly used for plant extraction. For example, the plant-derived raw material is immersed in a treatment tank filled with an extraction solvent, and the soluble components are dissolved while stirring as necessary, and then the extraction residue is removed by filtration to obtain saponin. It is preferable that the saponin is crudely purified or purified.

There are no particular limitations on the part of the plant used as the extraction raw material, and it can be appropriately selected depending on the type of plant used as the extraction raw material, and examples include leaves, branches, trunks, bark, flowers, fruits, and roots. When Quillaja quilla is used as the extraction raw material, the bark is preferred.

There are no particular limitations on the size of each part of the plant used as the extraction raw material, and it can be appropriately selected depending on the purpose. For example, it can be the size as it is when harvested, the desired size after cutting, or the size after pulverization (powder).

The state of each part of the plant used as the extraction raw material is not particularly limited and can be appropriately selected depending on the purpose. For example, the part may be in the state as it is when it is collected, in a dried state, in a crushed state, or in a juice-squeezed state. Among these, the dried state is preferred.

There are no particular limitations on the method for drying each of the extracted parts of the plant used as the extraction raw material, and it can be appropriately selected depending on the purpose. For example, it can be dried in the sun or using a commonly used dryer.

There are no particular limitations on the method for pulverizing each part of the plant used as the extraction raw material, and it can be appropriately selected depending on the purpose. For example, it can be pulverized using a mixer, sugar mill, power mill, jet mill, impact grinder, etc.

There are no particular limitations on the method for making each part of the plant used as the extraction raw material into the juice, and it can be appropriately selected depending on the purpose, such as squeezing.

The extraction solvent for extracting saponin from the plant is not particularly limited and can be appropriately selected depending on the purpose. Examples of the extraction solvent include water, a hydrophilic solvent, and a mixed solvent thereof.
The water and the hydrophilic solvent are not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include those similar to those described for the ginkgo leaf extract as component (A).

The mixed solvent of water and the hydrophilic solvent is not particularly limited and can be appropriately selected depending on the purpose. When the lower alcohol is used as the hydrophilic solvent, it is preferable to use 1 to 90 parts by mass of the hydrophilic solvent per 10 parts by mass of the water. When the lower aliphatic ketone is used as the hydrophilic solvent, it is preferable to use 1 to 40 parts by mass of the hydrophilic solvent per 10 parts by mass of the water. When a polyhydric alcohol is used as the hydrophilic solvent, it is preferable to use 1 to 90 parts by mass of the hydrophilic solvent per 10 parts by mass of the water. These may be used alone or in combination of two or more.

Among these, the extraction solvent is preferably a mixed solvent of water and ethanol (hydrous ethanol) from the viewpoints of safety and ease of handling.
When the aqueous ethanol is used as the extraction solvent, the concentration of ethanol is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 50% by mass or more, and more preferably 70% by mass or more.

There are no particular limitations on the amount of the extraction solvent used and it can be selected appropriately depending on the purpose, but it is preferable to use an amount (mass ratio) of 5 to 15 times the amount of each part of the plant used as the extraction raw material.

The extraction conditions (extraction time, extraction temperature, atmospheric conditions such as pressure, etc.) for extracting saponin from the plant are not particularly limited, and can be appropriately selected from known methods depending on the purpose.
The extraction time for eluting saponin from each of the extracted parts of the plant is usually about 30 minutes to 2 hours.
The temperature of the extraction solvent is preferably room temperature or a temperature not higher than the boiling point of the solvent used.
When a mixed solvent of water and ethanol is used as the extraction solvent, it is preferable to carry out the extraction at 40° C. to 80° C. for 30 minutes to 4 hours.

The state of the saponin is not particularly limited and can be appropriately selected depending on the purpose. For example, it may be the extracted saponin itself, a crude or purified product of the saponin, a concentrate of the saponin, a diluted product of the saponin, or a dried product of the saponin. The saponin may also be the dried product of the saponin that has been mixed or dissolved again in a solvent such as water, a hydrophilic solvent, or a mixture thereof.

The purification method of the saponin is not particularly limited and can be appropriately selected depending on the purpose. Examples of the purification method include chromatography such as partition chromatography, adsorption chromatography, ion exchange chromatography, and size exclusion chromatography, liquid-liquid partition extraction, and membrane separation. These purification methods may be performed alone or in combination of two or more.

Commercially available Quillaja saponins include Quillajanin C-100, Quillajanin P-20, and Quillajanin S-100 (all manufactured by Maruzen Pharmaceutical Co., Ltd.).

The purity of the saponin is not particularly limited and can be selected appropriately depending on the purpose, but taking into account the unique taste of saponin, a higher purity is preferable.

The saponin content in the plant extract can be measured by diluting the plant extract containing the saponin appropriately with water, adding an alkaline solution to the dilution, and then adding at least one of an organic solvent, an organic acid, and water, and performing liquid chromatography.

The content of the saponin in the ginkgo leaf extract composition is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 0.01% to 30% by mass, more preferably 0.1% to 10% by mass, and even more preferably 0.1% to 0.5% by mass of the entire ginkgo leaf extract composition. If the content of the saponin is 0.01% by mass or more or 30% by mass or less, the dispersibility and solubility in water or acidic solvents are good, and it is advantageous in that the formation of precipitation can be prevented for a long period of time.

<(D) Glycerin>
The glycerin used as the component (D) is not particularly limited and may be appropriately selected depending on the purpose, but it is preferable that the glycerin be food-grade and highly safe.
The glycerin used may be one that has been appropriately synthesized by a known method, or a commercially available product.

The content of the glycerin in the ginkgo leaf extract composition is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 40% to 90% by mass, and more preferably 60% to 90% by mass, of the entire ginkgo leaf extract composition. If the content of the glycerin is 40% by mass or more, it is advantageous in that the dispersibility and solubility in water or acidic solvents are good and the formation of precipitation can be prevented for a long period of time, and if the content is 90% by mass or less, it is advantageous in that the desired effect of the active ingredient ginkgo leaf extract can be easily obtained.

<Other ingredients>
The ginkgo leaf extract composition may contain other components in addition to the components (A), (B), (C), and (D). The other components are not particularly limited as long as they do not impair the effects of the present invention, and examples thereof include fatty acid esters (hereinafter sometimes referred to as component (E)).

The fatty acid ester is not particularly limited and can be appropriately selected depending on the purpose. Examples of the fatty acid ester include glycerin fatty acid ester and sucrose fatty acid ester. These may be used alone or in combination of two or more. Among these, glycerin fatty acid ester is preferred, and polyglycerin fatty acid ester is more preferred.

The polyglycerol fatty acid ester contains polyglycerol, which is a polymer of glycerol, and fatty acids as constituent components, and these components are formed by ester bonds via the hydroxyl groups of the polyglycerol and the carboxylic acids of the fatty acids.
The polyglycerol fatty acid ester may be an appropriately synthesized product or a commercially available product.

The number of carbon atoms in the fatty acid portion of the fatty acid ester is not particularly limited and can be selected appropriately depending on the purpose, but 12 to 18 is preferable.

The degree of polymerization of glycerin in the polyglycerol fatty acid ester is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 5 to 10.

Specific examples of the polyglycerol fatty acid ester include polyglyceryl-10 laurate, polyglyceryl-10 myristate, polyglyceryl-5 laurate, polyglyceryl-5 myristate, polyglyceryl-5 oleate, polyglyceryl-10 oleate, etc. These may be used alone or in combination of two or more.

Specific examples of commercially available fatty acid esters include SANSOFT Q-12S (polyglyceryl-10 laurate), SANSOFT Q-14S (polyglyceryl-10 myristate), SANSOFT A-121E (polyglyceryl-5 laurate), SANSOFT A-141E (polyglyceryl-5 myristate), SANSOFT A-171E (polyglyceryl-5 oleate) (all manufactured by Taiyo Kagaku Co., Ltd.), and NIKKOL DECAGLYN 1-OVEX (polyglyceryl-10 oleate) (manufactured by Nikko Chemicals Co., Ltd.).

The content of the fatty acid ester in the ginkgo leaf extract composition is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 0.1% to 50% by mass, and more preferably 0.1% to 10% by mass, of the entire ginkgo leaf extract composition. If the content of the fatty acid ester is 0.1% by mass or more or 50% by mass or less, it is advantageous in that the dispersibility and solubility in water or an acidic solvent are good and the ginkgo leaf extract composition has a viscosity that makes it easy to handle.

The state of the ginkgo leaf extract composition is not particularly limited and can be appropriately selected depending on the purpose. For example, the composition may be in a paste form or liquid form.
These conditions can be appropriately adjusted by the method for producing the ginkgo leaf extract composition.

- Manufacturing method -
A method for producing a paste or liquid of a ginkgo leaf extract composition will now be described.
The method for producing the paste or liquid of the ginkgo leaf extract composition is not particularly limited and can be appropriately selected depending on the purpose. For example, the composition can be produced by adding and mixing the ginkgo leaf extract (A), the enzymatically hydrolyzed lecithin (B), the saponin (C), the glycerin (D), and, if necessary, other components such as the fatty acid ester (E) of the component, and concentrating the mixture under reduced pressure using an apparatus such as a rotary evaporator.

--Applications--
The ginkgo leaf extract composition of the present invention has excellent dispersibility and solubility in water or acidic solvents, can prevent precipitation for a long period of time, and can suppress foaming, so it can be widely used in a wide range of fields, including cosmetics, foods and beverages, and pharmaceuticals. It can also be suitably used in the oral composition of the present invention described below.

The ginkgo leaf extract composition of the present invention is suitable for use in humans, but can also be used in animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as the respective functional effects are achieved.

(Oral Composition)
The oral composition of the present invention contains the ginkgo leaf extract composition of the present invention, and further contains other ingredients such as an acidic pH adjuster, if necessary.

The oral composition of the present invention contains the ginkgo leaf extract composition, and therefore, due to the action of the ginkgo leaf extract, which is the active ingredient of the ginkgo leaf extract composition, it can be used to improve circulatory function, promote blood flow (prevent neuralgia, stiff shoulders, poor circulation, and improve headaches or migraines), prevent aging, improve stomach, eyes, and brain, prevent senile dementia (particularly, prevent dementia due to cerebrovascular disorders such as cerebral infarction and cerebral thrombosis), prevent heart disease (reduce blood pressure and cholesterol, prevent arteriosclerosis), and improve allergy symptoms (improve symptoms of atopic dermatitis and asthma).

The oral composition refers to a composition that is unlikely to be harmful to human health and is taken orally or by administration through the digestive tract in normal social life, and is not limited to administrative classifications such as food, medicine, and quasi-drugs. Therefore, the oral composition refers to a wide range of foods and beverages that are taken orally, including general foods, health foods (functional food and beverages), health functional foods (foods for specified health uses, foods with nutrient functions, and foods with functional claims), quasi-drugs, and medicines.

The type of the oral composition is not particularly limited and can be appropriately selected depending on the purpose, and examples of the composition include beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks; cold desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, harusame, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; sweets such as candy, candy, gum, chocolate, tablet candy, snacks, biscuits, jelly, jam, cream, baked goods, and bread; seafood such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oysters, pacific saury, squid, ark shells, scallops, abalone, sea urchin, salmon roe, and tokobushi; processed seafood and livestock foods such as kamaboko, ham, and sausage; processed foods Dairy products such as milk and fermented milk; oils and fats and processed oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; seasonings such as sauces and sauces; retort pouch foods such as curry, stew, oyakodon, porridge, porridge, Chinese rice bowl, katsudon, tempura bowl, eel bowl, hayashi rice, oden, mabo dolph, beef bowl, meat sauce, egg soup, omelet rice, gyoza, shumai, hamburger, and meatballs; side dishes such as salads and pickles; various forms of health, beauty, or nutritional supplement foods; medicines and quasi-drugs such as tablets, granules, capsules, drinks, lozenges, and mouthwash; oral fresheners used in the oral cavity such as mouth fresheners and breath fresheners, and toothpastes.

Among these, the type of oral composition is preferably a beverage with a pH of 2 to 7.

<Ginkgo Leaf Extract Composition>
The ginkgo leaf extract composition contained in the oral composition is the ginkgo leaf extract composition of the present invention described above.
The content of the ginkgo leaf extract composition in the oral composition is not particularly limited and can be appropriately adjusted taking into consideration the purpose of use, symptoms, gender, etc. When the oral composition is a beverage, the content of the ginkgo leaf extract composition in the beverage is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 0.01% by mass to 50% by mass.

<Other ingredients>
The other components in the oral composition are not particularly limited and can be appropriately selected according to the purpose from auxiliary raw materials, additives, or other components used in the production of ordinary oral compositions, and examples thereof include various additives such as acidic pH adjusters, glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, corn syrup, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, fatty acid esters other than the component (E), gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin B, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorants, flavorings, preservatives, solvents, stabilizers, and antioxidants. These may be used alone or in combination of two or more.

The content of the other components in the oral composition is not particularly limited as long as it does not impair the effects of the present invention, and can be appropriately selected depending on the purpose.

The acidic pH adjuster is not particularly limited and can be appropriately selected from known pH adjusters depending on the purpose, and examples thereof include phosphoric acid, ascorbic acid, citric acid, tartaric acid, malic acid, lactic acid, phytic acid, gluconic acid, succinic acid, fumaric acid, etc. These may be used alone or in combination of two or more.
The content of the acidic pH adjuster is not particularly limited and can be appropriately selected depending on the target pH.

The present invention will be specifically explained below with reference to test examples, examples, comparative examples, preparation examples, and formulation examples, but the present invention is not limited to these test examples, examples, preparation examples, and formulation examples.

(Test Example 1)
The following enzymatically decomposed lecithins 1 to 5 were used as test samples, and the mass ratios [LPA/LPC] of the enzymatically decomposed lecithins 1 to 5 were determined by the following method. For the enzymatically decomposed lecithin 1, three different lots were used as test samples.
Enzymatically decomposed lecithin 1: Lysophospholipid Nagase L (manufactured by Nagase ChemteX Corporation, content as enzymatically decomposed lecithin: 18% by mass)
Enzymatically decomposed lecithin 2: SLP-LPC70 (Tsuji Oil Mills, content as phospholipid: 90% to 94% by mass)
Enzymatically decomposed lecithin 3: SLP White Lyso (Tsuji Oil Mills, content as phospholipid: 96% to 98% by mass)
Enzymatically decomposed lecithin 4: Elmizer A (Kyowa Hakko Kogyo Co., Ltd., content as enzymatically decomposed lecithin: 100% by mass)
Enzymatically decomposed lecithin 5: Sunlecithin A1 (manufactured by Taiyo Kagaku Co., Ltd., content as enzymatically decomposed lecithin: 33% by mass)

<Preparation of sample solution for LPA analysis or standard solution for LPA analysis>
LPA has a strong metal coordination property, and it is difficult to analyze it in normal HPLC or SFC using metal piping because it is adsorbed to the column and piping. Therefore, methylation was performed according to the method of Izumi Motoyasu et al. (Oleoscience, 14, 2014, p.329-335) to prepare a sample for LPA analysis.
Each test sample was prepared in methanol so that the content as enzymatically decomposed lecithin was 4 mg/mL. In addition, an LPA standard (1-oleoyl lysophosphatidic acid (sodium salt) manufactured by Cayman Chemical Co.) was prepared in methanol so that the content was 10 μg/mL. 0.5 mL of trimethylsilyldiazomethane (TMS-diazomethane) was added to 1 mL of a methanol solution containing each test sample or an LPA standard at 0° C., and the mixture was reacted at room temperature (25±5° C.) for 10 minutes. The reaction solution was concentrated to dryness, and then prepared in methanol so that the content as enzymatically decomposed lecithin was 100 μg/mL. This solution was filtered through a membrane filter (pore size 0.2 μm) to prepare a sample solution for LPA analysis or a standard solution for LPA analysis.

<Preparation of sample solution for LPC analysis or standard solution for LPC analysis>
Each of the test samples was prepared in methanol so that the content of enzymatically decomposed lecithin was 100 μg/mL, and the solution was filtered through a membrane filter (pore size: 0.2 μm) to prepare a sample solution for LPC analysis.
Furthermore, an LPC standard (L-α-lysophosphatidylcholine, derived from egg yolk, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was prepared with methanol to give concentrations of 1 μg/mL, 5 μg/mL, or 10 μg/mL, and each solution was filtered through a membrane filter (pore size: 0.2 μm) to prepare a standard solution for LPC analysis.

Analysis
It has been revealed that phospholipids have similar retention times in supercritical fluid chromatography, regardless of the type of fatty acid chain (see Waters application 'Lipid Class Separation Using UPC ² /MS'). As shown in Table 1, since the molecular weight of each type of phospholipid is determined, mass chromatograms were prepared within the range of masses that can be detected for methylated LPA and LPC, and quantification was performed under the analytical conditions described below. Since soybean lecithin contains almost no fatty acids with 14 or less carbon atoms or 20 or more carbon atoms, these were excluded from the mass spectrum to be quantified (see Matsumoto Yoshinobu et al., Kawasaki Medical Welfare Society Journal, 15, 2005, pp. 209-216).
The peaks of the LPA analysis sample solution were identified by comparing with the retention time of the LPA analysis standard solution, and the area of all peaks between 3.5 and 4.0 minutes was calculated by adding up the peaks. The peaks of the LPC analysis sample solution were identified by comparing with the retention time of the LPC analysis standard solution, and the area of all peaks between 6.9 and 7.6 minutes was calculated by adding up the peaks.
The peak area of methylated LPA or LPC in each analytical sample solution was substituted into the calibration curve of the standard solution to calculate the respective quantitative values, and the mass ratio [LPA/LPC] was calculated. The results are shown in Table 2 below.
[Analysis conditions]
SFC device: ACQUITY UPC ² (manufactured by Waters)
MS device: Xevo G2 Tof (Waters)
Column: Viridis BEH (1.7 μm, 100 × 3.0 mm i.d., Waters)
Column temperature: 40°C
Mobile phase: A = _CO2 , B = 0.1% _NH3 /methanol Gradient program: 0 min (A:B = 99:1) → 7.0 min (A:B = 50:50) → 7.5 min (A:B = 50:50)
Flow rate: 1.6 mL/min Injection volume: 1.0 μL
Detector: MS
- MS conditions for LPA -
Polarity: Negative mode ( ^ES- )
Capillary voltage: 2.0 kV
Extraction cone voltage: 4.0 kV
Cone Voltage: 10V
Source temperature: 120° C.
Desolvation temperature: 450° C.
Cone gas flow: 50 L/hr Desolvation gas flow: 800 L/hr Mass scan range: 50 Da to 1,500 Da
Scan time: 0.2 ^sec
- MS conditions for LPC -
Polarity: Positive (ES ⁺ )
Capillary voltage: 3.0 kV
Extraction cone voltage: 4.0 kV
Cone Voltage: 30V
Source temperature: 120° C.
Desolvation temperature: 450° C.
Cone gas flow: 50 L/hr Desolvation gas flow: 800 L/hr Mass scan range: 50 Da to 1,500 Da
Scan time: 0.2 ^sec

なお、表１において、「脂肪酸鎖」は、脂肪酸を炭素数と二重結合との数み合わせ（炭素数：二重結合数）で示した数値表現である。

In Table 1, "fatty acid chain" is a numerical expression showing a fatty acid by combining the number of carbon atoms and the number of double bonds (number of carbon atoms: number of double bonds).

Example 1
8 mL of 50% by volume ethanol was added to 2.00 g of ginkgo leaf extract (product name: Ginkgo Leaf Extract C, manufactured by Maruzen Pharmaceutical Co., Ltd.), and dissolved under heating at 60° C. to obtain 10 mL of a solution.
A mixture of 7.50 g of glycerin and 0.09 g of enzymatically decomposed lecithin 1 (product name: Lysophospholipid Nagase L (Lot No. 1 of Test Example 1), manufactured by Nagase ChemteX Corporation) was added with 10 mL of the ginkgo leaf extract solution and 0.041 g of Quillaja extract (product name: Quillayanin C-100, manufactured by Maruzen Pharmaceutical Co., Ltd.) equivalent to partially hydrolyzed saponin to obtain a mixed solution. The mixed solution was concentrated to 10 g under reduced pressure at 60° C. using a rotary evaporator N-1100 (manufactured by Tokyo Rikakikai Co., Ltd.), to obtain the ginkgo leaf extract composition of Example 1 in liquid form.

Example 2
8 mL of 50% by volume ethanol was added to 2.00 g of ginkgo leaf extract (product name: Ginkgo Leaf Extract C, manufactured by Maruzen Pharmaceutical Co., Ltd.), and dissolved under heating at 60° C. to obtain 10 mL of a solution.
Also, 4 mL of 50% by volume ethanol was added to 0.10 g of fatty acid ester 1 (product name: Sunsoft Q-12S, manufactured by Taiyo Kagaku Co., Ltd.) and dissolved under heating at 60° C. to obtain 4 mL of a solution.
A mixture of 7.50 g of glycerin and 0.09 g of enzymatically decomposed lecithin 1 (product name: Lysophospholipid Nagase L, manufactured by Nagase Chemtex Corporation) was mixed, and 10 mL of the solution of the ginkgo leaf extract, an amount of Quillaja extract (product name: Quillayanin C-100, manufactured by Maruzen Pharmaceutical Co., Ltd.) equivalent to 0.041 g of partially hydrolyzed saponin, and 4 mL of the solution of the fatty acid ester were added to the mixture to obtain a mixed solution. The mixed solution was concentrated to 10 g under reduced pressure at 60° C. using a rotary evaporator N-1100 (manufactured by Tokyo Rikakikai Co., Ltd.), to obtain the ginkgo leaf extract composition of Example 2 in liquid form.

Example 3
10 g of the ginkgo leaf extract composition of Example 3 was obtained in the same manner as in Example 2, except that the type of fatty acid ester in Example 2 was changed from Fatty Acid Ester 1 (product name: Sunsoft Q-12S, manufactured by Taiyo Kagaku Co., Ltd.) to Fatty Acid Ester 2 (product name: Sunsoft Q-14S, manufactured by Taiyo Kagaku Co., Ltd.).

Example 4
10 g of the ginkgo leaf extract composition of Example 4 was obtained in the same manner as in Example 2, except that the type of fatty acid ester in Example 2 was changed from Fatty Acid Ester 1 (product name: Sunsoft Q-12S, manufactured by Taiyo Kagaku Co., Ltd.) to Fatty Acid Ester 3 (product name: Sunsoft A-121E, manufactured by Taiyo Kagaku Co., Ltd.).

Example 5
10 g of the ginkgo leaf extract composition of Example 5 was obtained in the same manner as in Example 2, except that the type of fatty acid ester in Example 2 was changed from Fatty Acid Ester 1 (product name: Sunsoft Q-12S, manufactured by Taiyo Kagaku Co., Ltd.) to Fatty Acid Ester 4 (product name: Sunsoft A-141E, manufactured by Taiyo Kagaku Co., Ltd.).

Example 6
10 g of the ginkgo leaf extract composition of Example 6 was obtained in the same manner as in Example 2, except that the type of fatty acid ester in Example 2 was changed from Fatty Acid Ester 1 (product name: Sunsoft Q-12S, manufactured by Taiyo Kagaku Co., Ltd.) to Fatty Acid Ester 5 (product name: Sunsoft A-171E, manufactured by Taiyo Kagaku Co., Ltd.).

(Example 7)
10 g of the ginkgo leaf extract composition of Example 7 was obtained in the same manner as in Example 2, except that the type of fatty acid ester in Example 2 was changed from Fatty Acid Ester 1 (product name: Sunsoft Q-12S, manufactured by Taiyo Kagaku Co., Ltd.) to Fatty Acid Ester 6 (product name: NIKKOLDECAGLYN1-OVEX, manufactured by Nikko Chemicals Co., Ltd.).

(Example 8)
In Example 3, the amount of fatty acid ester added was changed from 0.10 g to 1.00 g of fatty acid ester 2 (product name: Sunsoft Q-14S, manufactured by Taiyo Kagaku Co., Ltd.), and the amount of glycerin added was changed from 7.50 g to 6.60 g. Except for this, 10 g of the ginkgo leaf extract composition of Example 8 was obtained in the same manner as in Example 3.

(Example 9)
Example 9, 10 g of ginkgo leaf extract composition was obtained in the same manner as in Example 4, except that the amount of fatty acid ester added was changed from 0.10 g to 0.50 g of fatty acid ester 3 (product name: Sunsoft A-121E, manufactured by Taiyo Kagaku Co., Ltd.) in Example 4 and the amount of glycerin added was changed from 7.50 g to 7.10 g.

(Example 10)
In Example 1, the amount of ginkgo leaf extract added was changed from 2.00 g to 1.00 g, the amount of enzymatically decomposed lecithin 1 (Lot No. 2 in Test Example 1) added was changed from an amount equivalent to 0.09 g of enzymatically decomposed lecithin to an amount equivalent to 0.018 g of enzymatically decomposed lecithin, and the amount of glycerin added was changed from 7.50 g to 8.57 g, but the same method as that described in Example 1 was used to obtain 10 g of ginkgo leaf extract composition of Example 10.

Example 11
In Example 1, the amount of ginkgo leaf extract added was changed from 2.00 g to 1.00 g, the amount of enzymatically decomposed lecithin 1 (Lot No. 3 in Test Example 1) added was changed from an amount equivalent to 0.09 g of enzymatically decomposed lecithin to an amount equivalent to 0.18 g of enzymatically decomposed lecithin, and the amount of glycerin added was changed from 7.50 g to 8.41 g, but the same method as that described in Example 1 was used to obtain 10 g of ginkgo leaf extract composition of Example 11.

(Comparative Example 1)
8 mL of 50% by volume ethanol was added to 2.00 g of ginkgo leaf extract (product name: Ginkgo Leaf Extract C, manufactured by Maruzen Pharmaceutical Co., Ltd.), and dissolved under heating at 60° C. to obtain 10 mL of a solution.
A mixture of 7.50 g of water and 0.09 g of enzymatically decomposed lecithin 1 (product name: Lysophospholipid Nagase L, manufactured by Nagase Chemtex Corporation) was mixed with 10 mL of the ginkgo leaf extract solution and 0.041 g of Quillaja extract (product name: Quillayanin C-100, manufactured by Maruzen Pharmaceutical Co., Ltd.) equivalent to partially hydrolyzed saponin to obtain a mixed solution. The mixed solution was concentrated to 10 g under reduced pressure at 60° C. using a rotary evaporator N-1100 (manufactured by Tokyo Rikakikai Co., Ltd.) to obtain a liquid ginkgo leaf extract composition of Comparative Example 1.

(Comparative Example 2)
10 g of a ginkgo leaf extract composition of Comparative Example 2 was obtained in the same manner as in Example 1, except that Quillaja saponin was not added.

(Comparative Example 3)
10 g of a ginkgo leaf extract composition of Comparative Example 3 was obtained in the same manner as in Example 1, except that the enzymatically decomposed lecithin 1 in Example 1 was not added.

(Comparative Example 4)
8 mL of 50% by volume ethanol was added to 2.00 g of ginkgo leaf extract (product name: Ginkgo Leaf Extract C, manufactured by Maruzen Pharmaceutical Co., Ltd.), and dissolved under heating at 60° C. to obtain 10 mL of a solution.
In addition, 0.09 g of enzymatically decomposed lecithin 2 (product name: SLP-LPC70, manufactured by Tsuji Oil Mills) was dispersed in 4 mL of distilled water to obtain 4 mL of a dispersion.
10 mL of the ginkgo leaf extract solution and 0.041 g of Quillaja extract (product name: Quillayanin C-100, manufactured by Maruzen Pharmaceutical Co., Ltd.) equivalent to partially hydrolyzed saponin were added to 7.50 g of glycerin, and the mixture was concentrated under reduced pressure at 60° C. using a rotary evaporator N-1100 (manufactured by Tokyo Rikakikai Co., Ltd.). After ethanol was evaporated from the solvent by the reduced pressure concentration, 4 mL of the enzymatically decomposed lecithin 2 dispersion was added, and the mixture was further concentrated to 10 g under reduced pressure at 60° C. to obtain 10 g of a liquid ginkgo leaf extract composition of Comparative Example 4.

(Comparative Example 5)
In Comparative Example 4, the type of enzymatically decomposed lecithin was changed from Enzymatically Decomposed Lecithin 2 (product name: SLP-LPC70, manufactured by Tsuji Oil Mills) to Enzymatically Decomposed Lecithin 3 (product name: SLP-White Lyso, manufactured by Tsuji Oil Mills) to obtain 10 g of a ginkgo leaf extract composition of Comparative Example 5 in the same manner as in Comparative Example 4.

(Comparative Example 6)
Ginkgo leaf extract composition 10 of Comparative Example 6 was obtained in the same manner as in Example 1, except that the type of enzymatically decomposed lecithin in Example 1 was changed from Enzymatically Decomposed Lecithin 1 (product name: Lysophospholipid Nagase L, manufactured by Nagase ChemteX Corporation) to Enzymatically Decomposed Lecithin 4 (product name: Elmeizer A, manufactured by Kyowa Hakko Co., Ltd.).

(Comparative Example 7)
10 g of the ginkgo leaf extract composition of Comparative Example 7 was obtained in the same manner as in Comparative Example 4, except that the type of enzymatically decomposed lecithin in Comparative Example 4 was changed from Enzymatically Decomposed Lecithin 2 (product name: SLP-LPC70, manufactured by Tsuji Oil Mills) to Enzymatically Decomposed Lecithin 5 (product name: Sunlecithin A1, manufactured by Taiyo Kagaku Co., Ltd.).

The ginkgo leaf extract compositions of Examples 1 to 11 and Comparative Examples 2, 3, and 5 to 7 were evaluated for "transmittance," "storage stability (turbidity)," "storage stability (precipitation)," and "foamability" using the methods described below. The results are shown in Tables 3 to 6 below. The blending amount of each component described in the Examples and Comparative Examples in Tables 3 to 6 is shown in "mass (g)." Note that the ginkgo leaf extract compositions of Comparative Examples 1 and 4 were separated or precipitated during preparation, and the above evaluations could not be performed, so they are shown as "N.D." in Table 5.

- Preparation of test samples -
Each of the ginkgo leaf extract compositions of Examples 1 to 11 and Comparative Examples 2, 3, and 5 to 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract, and diluted with 20 mM sodium citrate buffer at pH 3.5 to give a diluted solution of 100 mL (ginkgo leaf extract concentration: 0.16% by mass).
These diluted solutions were exposed to 90° C. for 10 minutes and then left to stand at 5° C. for one week to prepare test samples.

<Transmittance>
Using an ultraviolet-visible spectrophotometer (model: UV-1800, manufactured by Shimadzu Corporation), the test samples of Examples 1 to 11 and Comparative Examples 2, 3, and 5 to 7 were placed in a glass cell with an optical path length of 10 mm, and the transmittance (% T) at 600 nm was measured.

<Storage stability (turbidity)>
The turbidity of each of the test samples of Examples 1 to 11 and Comparative Examples 2, 3, and 5 to 7 was visually confirmed and evaluated according to the following evaluation criteria.
[Evaluation criteria for storage stability (turbidity)]
-: Transparent, no turbidity observed +: Slight turbidity observed ++: Turbidity observed +++: Significant turbidity observed +++++: Even more turbidity observed ++++++: Significantly more turbidity observed

<Storage stability (precipitation)>
The precipitation of each test sample of Examples 1 to 11 and Comparative Examples 2, 3, and 5 to 7 was visually confirmed and evaluated according to the following evaluation criteria.
[Evaluation criteria for storage stability (precipitation)]
-: No precipitation observed +: Slight precipitation observed ++: Precipitation observed +++: Much precipitation observed ++++: Even more precipitation observed ++++++: Significantly more precipitation observed

<Foaming properties>
Each of the ginkgo leaf extract compositions of Examples 1 to 11 and Comparative Examples 2, 3, and 5 to 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract, and diluted with 20 mM potassium phosphate buffer at pH 6.0 to prepare 100 mL of diluted solution (ginkgo leaf extract concentration: 0.16% by mass).
15 mL of the diluted solution was placed in a 50 mL Nessler tube (diameter: 2 cm), plugged and shaken 40 times, and the height (mm) from the liquid surface to the foam surface was measured as the foam height, which was used to evaluate foamability.

(Preparation Examples 1 to 4)
Ascorbic acid was added to distilled water to adjust the pH to 3.5 to obtain an ascorbic acid solution.
Each of the ginkgo leaf extract compositions of Examples 1, 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract, and dissolved in 100 mL of the ascorbic acid solution to prepare organic acid solutions containing the ginkgo leaf extract compositions of Preparation Examples 1 to 4 (ginkgo leaf extract concentration: 0.16% by mass).

(Preparation Examples 5 to 8)
Citric acid was added to distilled water to adjust the pH to 3.5 to obtain a citric acid solution.
Each of the ginkgo leaf extract compositions of Examples 1, 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract and dissolved in 100 mL of the citric acid solution to prepare organic acid solutions containing the ginkgo leaf extract compositions of Preparation Examples 5 to 8 (ginkgo leaf extract concentration: 0.16% by mass).

(Preparation Examples 9 to 12)
Tartaric acid was added to distilled water to adjust the pH to 3.5 to obtain a tartaric acid solution.
Each of the ginkgo leaf extract compositions of Examples 1, 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract, and dissolved in 100 mL of the tartaric acid solution to prepare organic acid solutions containing the ginkgo leaf extract compositions of Preparation Examples 9 to 12 (ginkgo leaf extract concentration: 0.16% by mass).

(Preparation Examples 13 to 16)
Malic acid was added to distilled water to adjust the pH to 3.5 to obtain a malic acid solution.
Each of the ginkgo leaf extract compositions of Examples 1, 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract, and dissolved in 100 mL of the malic acid solution to prepare organic acid solutions containing the ginkgo leaf extract compositions of Preparation Examples 13 to 16 (ginkgo leaf extract concentration: 0.16% by mass).

(Preparation Examples 17 to 20)
Phosphoric acid was added to distilled water to adjust the pH to 3.5 to obtain a phosphoric acid solution.
Each of the ginkgo leaf extract compositions of Examples 1, 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract and dissolved in 100 mL of the phosphoric acid solution to prepare organic acid solutions containing the ginkgo leaf extract compositions of Preparation Examples 17 to 20 (ginkgo leaf extract concentration: 0.16% by mass).

For each of the ginkgo leaf extract composition-containing organic acid solutions of Preparation Examples 1 to 20, the "transmittance,""storage stability (turbidity),""storage stability (precipitation)," and "foamability" were evaluated by the methods shown below.
The results are shown in the following Tables 6 to 8. The blending amount of the pH adjuster (organic acid solution) described in the preparation examples in Tables 6 to 8 is shown in "volume (mL)".

- Preparation of test samples -
Each of the organic acid solutions containing the ginkgo leaf extract composition of Preparation Examples 1 to 20 was exposed to 90° C. for 10 minutes, and then left to stand at 5° C. for one week to prepare a test sample.

<Transmittance>
Using an ultraviolet-visible spectrophotometer (model: UV-1800, manufactured by Shimadzu Corporation), each test sample of Preparation Examples 1 to 20 was placed in a glass cell having an optical path length of 10 mm, and the transmittance (% T) at 600 nm was measured.

<Storage stability (turbidity)>
The turbidity of each test sample of Preparation Examples 1 to 20 was visually confirmed and evaluated according to the following evaluation criteria.
[Evaluation criteria for storage stability (turbidity)]
-: Transparent, no turbidity observed +: Slight turbidity observed ++: Turbidity observed

<Storage stability (precipitation)>
The precipitation of each test sample of Preparation Examples 1 to 20 was visually confirmed and evaluated according to the following evaluation criteria.
[Evaluation criteria for storage stability (precipitation)]
-: No precipitation observed +: Slight precipitation observed ++: Precipitation observed

<Foaming properties>
15 mL of each test sample of Preparation Examples 1 to 20 was placed in a 50 mL Nessler tube (diameter: 2 cm), stoppered and shaken 40 times, and then the height (mm) from the liquid surface to the foam surface was measured as the foam height, and this was used to evaluate the foamability.

(Formulation Examples 1 to 3)
1.5 L of hot water at 100°C was added to 8 g of domestically produced barley, and extracted for 5 minutes over medium heat. After that, the heat was turned off and the barley was left to stand for 1 hour to obtain barley tea.
Each of the ginkgo leaf extract compositions of Examples 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract and dissolved in 100 mL of the barley tea to prepare the barley teas of Formulation Examples 1 to 3 (ginkgo leaf extract concentration: 0.16% by mass).

(Formulation Examples 4 to 6)
600 mL of hot water at 100° C. was added to 8 g of black tea and extracted for 1 minute to obtain black tea.
Each of the ginkgo leaf extract compositions of Examples 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract and dissolved in 100 mL of the black tea to prepare black teas of Formulation Examples 4 to 6 (ginkgo leaf extract concentration: 0.16% by mass).

(Formulation Examples 7 to 9)
720 mL of hot water at 98° C. was added to 40 g of ground coffee beans, and the mixture was extracted and filtered to obtain coffee.
Each of the ginkgo leaf extract compositions of Examples 3, 5, and 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract, and dissolved in 100 mL of the coffee to prepare the coffees of Formulation Examples 7 to 9 (ginkgo leaf extract concentration: 0.16% by mass).

(Formulation Examples 10 to 12)
To 50 mL of 100% grapefruit juice, 25 g of sugar, 0.5 g of sodium citrate, and 0.5 g of vitamin C were added, and water was added to make up to 500 mL. This was thoroughly mixed to obtain a fruit juice beverage.
Each ginkgo leaf extract composition of Examples 3, 5, or 7 was weighed out in an amount equivalent to 16 mg of ginkgo leaf extract and dissolved in 100 mL of the fruit juice beverage to prepare the fruit juice beverages of Formulation Examples 10 to 12 (ginkgo leaf extract concentration: 0.16% by mass).

For each beverage of Formulation Examples 1 to 12, test samples were prepared in the manner described below, and the "transmittance," "storage stability (turbidity)," "storage stability (precipitation)," and "foamability" were evaluated in the same manner as in Examples 12 to 23. The results are shown in Tables 9 and 10 below.

- Preparation of test samples -
Each of the beverages of Formulation Examples 1 to 12 was exposed to 90° C. for 10 minutes and then stored at 5° C. for one week to prepare a test sample.

Details of each component used in the above examples and comparative examples are shown in Table 11 below.

Examples of aspects of the present invention include the following.
<1> A composition comprising (A) ginkgo leaf extract, (B) enzymatically decomposed lecithin containing lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), (C) saponin, and (D) glycerin;
The ginkgo leaf extract composition (B) is characterized in that the mass ratio [LPA/LPC] of the content (mass) of the lysophosphatidylcholine to the content (mass) of the lysophosphatidic acid in the enzymatically hydrolyzed lecithin is 150 or more.
<2> A composition for oral administration, comprising the ginkgo leaf extract composition according to <1>.
<3> The composition for oral administration according to <2>, which is a beverage having a pH of 2 to 7.

The ginkgo leaf extract composition of the present invention has excellent dispersibility and solubility in water or acidic solvents, can prevent the formation of precipitation for a long period of time, and can suppress foaming, and therefore can be widely used in a variety of fields, including cosmetics, foods and beverages, and pharmaceuticals.
In addition, since the oral composition of the present invention contains the ginkgo leaf extract composition, it can be suitably used for improving circulatory function, promoting blood flow (preventing neuralgia, stiff shoulders, poor circulation, and improving headaches or migraines), preventing aging, strengthening the stomach, healthy eyes, and healthy brain, preventing senile dementia (particularly, preventing dementia caused by cerebrovascular disorders such as cerebral infarction and cerebral thrombosis), preventing heart disease (reducing blood pressure and cholesterol, preventing arteriosclerosis), and improving allergic symptoms (improving the symptoms of atopic dermatitis and asthma).

Claims (4)

(A) ginkgo leaf extract, (B) enzymatically decomposed lecithin containing lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), (C) saponin, and (D) glycerin;
A ginkgo leaf extract composition characterized in that the mass ratio [LPA/LPC] of the content (mass) of lysophosphatidylcholine to the content (mass) of lysophosphatidic acid in the enzymatically hydrolyzed lecithin (B) is 150 or more. The ginkgo leaf extract composition according to claim 1, further comprising (E) a fatty acid ester, the fatty acid moiety of which has 12 to 18 carbon atoms. 3. A composition for oral administration, comprising the ginkgo leaf extract composition according to claim 1 or 2. The composition for oral administration according to claim 3, which is a beverage having a pH of 2 to 7.