JP3144789B2 - Ginkgo biloba leaf extract-containing composition - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a composition containing a water-containing organic solvent extract (Ginkgo biloba extract) obtained from Ginkgo biloba leaves.

[Conventional technology]

Conventionally, therapeutic agents containing ginkgo biloba extract as an active ingredient have been widely used in France and Germany for the purpose of improving cerebral circulation metabolism. Ginkgo biloba extract extracts pharmacological action to relax smooth muscle of blood vessels contracted by stress and tension, reduce resistance of peripheral arteries and cerebral circulatory system, enhance vasodilation and blood circulation speed, and increase capillary tissue Is known to have a pharmacological action to increase blood flow. In addition, a therapeutic effect on peripheral vascular disease or an antiallergic effect has been observed, and almost no side effects have been observed. For this reason, it is currently marketed not only as a pharmaceutical product but also as a health food, and it is expected that it will become more widely used in the future.

However, the ginkgo biloba extract is difficult to dissolve in water even when dissolved in an organic solvent such as alcohol.
If it is intended to take the drug without using alcohol, the use of the solid extract is limited to filling the extract powder as it is in a hard capsule or compressing it into a tablet. However, elderly people, minors, and sick people are more likely to take liquids than solid preparations, and liquids generally have higher absorption rates in the body. Therefore, ginkgo biloba extract is provided as a liquid that does not contain alcohol. It was desired.

Methods for liquefying ginkgo biloba leaf extract without using an organic solvent such as alcohol include a method in which a monosaccharide alcohol such as sorbitol is added, and a method in which a disaccharide or trisaccharide such as maltitol which the present inventors have previously found. There are a method of adding a sugar alcohol (Japanese Patent Application No. 1-344492) and a method of adding polydextrose (Japanese Patent Application No. 63-295372).

[Problems to be Solved by the Invention] However, the above conventional method of adding an additive such as sugar alcohol or polydextrose and dissolving the extract of Ginkgo biloba in water involves extracting the Ginkgo biloba directly into an aqueous solution containing the above additive at room temperature. The extract cannot be completely dissolved. Therefore, for example, the powder of ginkgo biloba extract extract is dissolved in an organic solvent such as ethanol at a high concentration in advance, and this is diluted with an aqueous solution containing the additive,
Using an aqueous solution of a surfactant in place of an organic solvent such as ethanol, and performing the same treatment as above, using hot water in place of an organic solvent such as ethanol, and performing the same treatment as above, the complicated operation such as Required. It is presumed that this is probably because the components of the extract of Ginkgo biloba leaves do not become a true solution but form a fine dispersion in the conventional method.

In addition, the liquid preparation of the extract of Ginkgo biloba leaf obtained by the above-mentioned conventional method does not always have good storage stability, and the extract may precipitate and precipitate over time depending on the composition and storage conditions. Further improvement in stability is desired.

The present inventor has repeatedly studied the liquefaction of ginkgo biloba leaf extract, and found that an aqueous solution containing a certain organic compound can rapidly dissolve the ginkgo biloba extract at room temperature, and moreover, the ginkgo biloba leaf extract produced using this aqueous solution The extract liquid is found to have extremely good storage stability,
The present invention has been completed.

An object of the present invention is to provide a technique capable of improving the storage stability of a liquid preparation containing a ginkgo leaf extract extract.

Another object of the present invention is to provide a technique capable of easily producing a liquid preparation containing a ginkgo leaf extract by dissolving a ginkgo leaf extract in water at room temperature.

[Means for solving the problem]

The present invention, ginkgo biloba leaf extract, having a basic nitrogen atom in the molecule, and solubility in water at room temperature 10g / 10
A ginkgo biloba leaf extract-containing composition in which 0 ml or more of an organic compound is dissolved in water, and is a medicine or food or drink for internal use.

Organic compounds having a basic nitrogen atom in the molecule and having a solubility in water at room temperature of 10 g / 100 ml or more (hereinafter referred to as the organic compound of the present invention) include, for example, urea, guanidine hydrochloride, ethanolamine, Amines such as ethylenediamine and morpholine and their analogous compounds; amino acids such as glycine, cysteine, threonine, arginine, lysine and histidine and their salts; alkyltrimethylammonium salts, alkylpyridinium salts, betaine alkyl acetates, alkylimidazolium betaines, Pyridoxine hydrochloride (vitamin B ₆ ), carnitine chloride (vitamin B _T ), thiamine hydrochloride (vitamin
B ₁₎ quaternary nitrogen-containing compounds, such as and the like can be exemplified; formamide, dimethylformamide, nicotinic acid amide, calcium pantothenate, acid amides such as pantothenol.

Ginkgo biloba leaf extract is mainly used for pharmaceuticals (including external use) and food and drink, and therefore, among the above-mentioned organic compounds, particularly preferable ones are amino acids, vitamins, urea, and the above-mentioned applications. Surfactants and the like.

In order to prepare the composition containing the ginkgo leaf extract extract of the present invention, it is only necessary to add the ginkgo leaf extract extract to an aqueous solution containing the organic compound of the present invention at room temperature, stir and dissolve, and special operations such as heating are required. And not. In this case, it is a practical and easy method to add and extract a ginkgo biloba leaf extract to a concentrated aqueous solution having a concentration close to the saturation concentration of the organic compound of the present invention, and dilute the aqueous solution with water.

The fact that ginkgo biloba extract, which does not dissolve in water at room temperature, rapidly dissolves in the above-mentioned aqueous solution, which is considered to have poor solubility, is a surprising phenomenon, but it is probably a component of the ginkgo biloba extract. It is considered that some strong interaction occurs between the glycoside of the polyphenols and the basic nitrogen atom in the organic compound of the present invention, such as formation of a molecular compound. It is known that the extract of Ginkgo biloba leaves dissolves in an aqueous solution of a strong alkali (such as caustic alkali), but the dissolution phenomenon found by the present inventor is completely different from the dissolution mechanism. .

As described above, the extract of Ginkgo biloba leaves is dissolved in water by the action of the organic compound of the present invention, so that the aqueous solution of the organic compound of the present invention preferably has a high concentration, and the extract component precipitates and precipitates at a low concentration. easy. Although the minimum concentration of the organic compound of the present invention varies depending on the type, it cannot be unconditionally specified, but is usually about 1% by weight. The ratio of the organic compound of the present invention and the ginkgo biloba leaf extract in the aqueous solution is 10% by weight or more of the latter, preferably
The content is preferably 20% by weight or more.

When the ginkgo biloba leaf extract-containing composition of the present invention is used for beverages and the like, it is desirable to add sugar or sugar alcohol. Since the addition of sugar or sugar alcohol has the effect of improving the storage stability of the composition of the present invention, the addition thereof also has the effect of significantly reducing the amount of the organic compound of the present invention. . For example, 40% by weight
In the case of an aqueous solution to which sucrose is added, the extract of Ginkgo biloba leaf can be rapidly dissolved at room temperature even when the concentration of the organic compound of the present invention is about 0.02 to 0.1% by weight. Preferred sugars to be used are monosaccharides such as glucose and fructose, and oligosaccharides such as sucrose and maltose.
As the sugar alcohol, a monosaccharide alcohol such as sorbitol and an oligosaccharide alcohol such as maltitol are preferable. These sugars and sugar alcohols are preferably added to the composition of the present invention in an amount of 20% by weight or more. In order to prepare the composition of the present invention containing these sugars and sugar alcohols, it is practical to add and extract a ginkgo biloba leaf extract to an aqueous solution of the organic compound of the present invention and dilute the aqueous solution with an aqueous solution of sugar or sugar alcohol. It is a simple and easy-to-implement method. Also in this case, no special operation such as heating is required.

The ginkgo biloba leaf extract-containing composition of the present invention thus obtained may further contain known flavors, coloring agents, fragrances, preservatives, auxiliaries such as penetrants, or other additives used in medicines and foods and beverages. May be added. Further, storage stability may be improved by adding a water-soluble plant gum such as gum arabic or sodium alginate, or a surfactant such as polyglycerin fatty acid ester.

The ginkgo biloba leaf extract-containing composition of the present invention can be used for medicines (for internal use and external use), food and drink, and cosmetics.

 Hereinafter, the present invention will be described in detail with reference to examples.

[Example 1] Dissolution test-1 5 g of various organic compounds (No. 1 to No. 27) and inorganic compounds (No. 28) shown in Table 1 were dissolved in 100 ml of water at 20 ° C to prepare an aqueous solution. Then, 10 g of dry powder of ginkgo biloba leaf extract was added to each aqueous solution, and the solution was observed after shaking for 10 minutes. The solubility in water at 20 ° C is 5 g / 100 ml
In the case of the following organic compounds, a saturated solution was prepared, and a ginkgo biloba leaf extract was added in an amount twice that of the organic compound.

-Test results-As is clear from Table 1, the dry powder of the extract of Ginkgo biloba leaves has a basic nitrogen atom in the molecule, and has a temperature of 20 ° C.
Organic compounds having a solubility in water of 10 g / 100 ml or more (No.
1 to No. 12) completely dissolved in an aqueous solution, but having a basic nitrogen atom in the molecule and a solubility in water at 20 ° C. of 10 g /
Less than 100 ml of an organic compound (No. 13 to No. 19), an organic compound having no basic nitrogen atom in the molecule (No. 20 to No. 27), and having a basic nitrogen atom in the molecule; It was insoluble in any of the inorganic compounds (No. 28) having a solubility in water at 10 ° C. of 10 g / 100 ml or more.

Dissolution test-2 In Table 1, 100 ml of water at 20 ° C.
Was dissolved in 10 g to prepare an aqueous solution, 20 g of dry powder of ginkgo biloba leaf extract was added to each aqueous solution, and the dissolution state was observed after shaking for 10 minutes. Was completely dissolved.

Storage test In Table 1, 5 g of the organic compounds No. 1 to No. 12 in water at 20 ° C.
An aqueous solution was prepared by dissolution, and 10 g of a dry powder of a ginkgo biloba leaf extract was added to each aqueous solution, followed by shaking for 10 minutes to prepare a transparent aqueous solution containing a ginkgo biloba leaf extract. After observing the state after leaving them at room temperature for one month,
All of the aqueous solutions containing the extract of Ginkgo biloba leaves did not precipitate and formed stable aqueous solutions.

Example 2 2 g of lysine hydrochloride was dissolved in 5 g of water at 20 ° C. to prepare an aqueous solution. Dissolve 1 g of Ginkgo biloba leaf extract dry powder in this aqueous solution and add maltitol syrup (maltitol syrup).
After adding 2 kg of a 75% by weight aqueous solution, water was added so that the total amount was 5, to prepare a syrup containing a ginkgo leaf extract extract. The syrup did not form a precipitate when left at room temperature for one month.

Example 3 A syrup containing a ginkgo biloba extract extract was prepared in the same manner as in Example 2 except that calcium pantothenate was used instead of lysine hydrochloride, and sucrose syrup (a 65% by weight aqueous solution of sucrose) was used instead of maltitol syrup. Was prepared. The syrup did not form a precipitate when left at room temperature for one month.

[Example 4] Glycine was used instead of lysine hydrochloride, and 3 g of sodium alginate was used instead of 2 kg of maltitol syrup. An aqueous solution containing a ginkgo leaf extract extract was prepared in the same manner as in Example 2. This aqueous solution did not precipitate when left at room temperature for 15 days.

Example 5 An aqueous solution containing a ginkgo biloba leaf extract was prepared in the same manner as in Example 4, except that 2.5 g of decaglycerin monolaurate was used instead of 3 g of sodium alginate. This aqueous solution did not precipitate when left at room temperature for 15 days.

Example 6 1 g of calcium pantothenate was dissolved in 1 g of water at 20 ° C. to prepare an aqueous solution. 1 g of dry powder of ginkgo leaf extract was dissolved in this aqueous solution, and 13.3 g of maltitol syrup (75% by weight aqueous solution of maltitol) was added. Then, water was added so that the total volume would be 100 ml. A syrup containing was prepared. The syrup did not form a precipitate when left at room temperature for one month.

Example 7 A transparent ginkgo leaf extract-containing aqueous solution was prepared by dissolving 5 g of a dry powder of a ginkgo leaf extract in 10 g of a saturated aqueous solution of urea (20 ° C.). This aqueous solution is 100
No precipitate was formed even when diluted twice.

[Comparative Example 1] After dissolving 1 g of dry powder of ginkgo biloba extract in 100 ml (20 ° C) of a 50 (V / V)% aqueous ethanol solution, the total amount was 5 g.
When water (20 ° C.) was added to the solution, the mixture became cloudy and a precipitate was deposited.

[Comparative Example 2] 1 g of dry powder of ginkgo biloba extract was dissolved in 100 ml (20 ° C) of a 50 (V / V)% aqueous ethanol solution, and 2.5 g of decaglycerin monolaurate was added. Water (20 ° C.) was added to prepare a transparent ginkgo biloba leaf extract-containing aqueous solution. When this aqueous solution was left at room temperature, it became cloudy two days later, and a precipitate was deposited.

[Comparative Example 3] 1 g of a dry powder of a ginkgo biloba extract was dissolved in 100 ml (20 ° C) of a 50 (V / V)% aqueous ethanol solution, and 2 kg of sucrose syrup (a 65% by weight aqueous solution of sucrose) was added. Water (20 ° C.) was added so that the total amount was 5, to prepare a transparent ginkgo leaf extract-containing syrup. When this syrup was left at room temperature, it became cloudy after 5 days, and a precipitate was deposited.

[Comparative Example 4] 1 g of dry powder of ginkgo leaf extract was added to 1 g of water, and
And then uniformly dispersed with a homogenizer. Then, maltitol syrup (75% by weight aqueous solution of maltitol) was added to 13.3%.
g was added and stirred. After cooling, water (20 ° C.) was added so that the total amount was 100 ml, to prepare a slightly turbid ginkgo leaf extract-containing syrup. When this syrup was allowed to stand at room temperature, it became cloudy three days later, and a precipitate was deposited.

〔The invention's effect〕

As described above, ginkgo biloba leaf extract has a basic nitrogen atom in the molecule, and has a solubility in water at room temperature of 10
According to the ginkgo leaf extract-containing composition of the present invention in which g / 100 ml or more of an organic compound is dissolved in water, a liquid preparation containing a ginkgo leaf extract having high storage stability can be obtained.

Further, according to the present invention, the extract of Ginkgo biloba leaf extract can be rapidly dissolved in water at room temperature, so that a liquid preparation containing the extract of Ginkgo biloba leaf extract can be easily produced.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-2-22229 (JP, A) JP-A-2-48512 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A23L 1/30 A61K 35/78 JICST file (JOIS)

Claims (4)

(57) [Claims] 1. A compound having a basic nitrogen atom in the molecule and at 20 ° C.
A ginkgo biloba extract extract is prepared by dissolving an organic compound selected from the group consisting of amino acids, vitamins and urea having a solubility in water of 10 g / 100 ml or more as an organic compound in water at room temperature in an amount of 1% by weight or more. Wherein the organic compound is added to the ginkgo biloba leaf extract in an amount of 10%.
A ginkgo biloba leaf extract-containing composition, which is not more than 10% by weight, contains substantially no surfactant, and is a medicine for internal use. 2. It is selected from the group consisting of dimethylformamide, monoethanolamine, urea, glycine, cysteine hydrochloride, threonine, histidine hydrochloride, lauryltrimethylammonium chloride, pyridoxine hydrochloride, thiamine hydrochloride, nicotinamide, and calcium pantothenate. An organic compound is prepared by adding 1
It is an aqueous solution obtained by adding a ginkgo leaf extract to an aqueous solution in which the extract is extracted by weight.
A ginkgo biloba leaf extract-containing composition, which is not more than 10% by weight, contains substantially no surfactant, and is a medicine for internal use. 3. A compound having a basic nitrogen atom in the molecule and at 20 ° C.
A ginkgo biloba extract extract is prepared by dissolving an organic compound selected from the group consisting of amino acids, vitamins and urea having a solubility in water of 10 g / 100 ml or more as an organic compound in water at room temperature in an amount of 1% by weight or more. Wherein the organic compound is added to the ginkgo biloba leaf extract in an amount of 10%.
A ginkgo biloba leaf extract-containing composition, which is not less than% by weight, is substantially free of a surfactant, and is a food or drink. 4. A compound selected from the group consisting of dimethylformamide, monoethanolamine, urea, glycine, cysteine hydrochloride, threonine, histidine hydrochloride, lauryltrimethylammonium chloride, pyridoxine hydrochloride, thiamine hydrochloride, nicotinamide, and calcium pantothenate. An organic compound is prepared by adding 1
It is an aqueous solution obtained by adding a ginkgo leaf extract to an aqueous solution in which the extract is extracted by weight.
A ginkgo biloba leaf extract-containing composition, which is not less than% by weight, is substantially free of a surfactant, and is a food or drink.