WO2006067866A1

WO2006067866A1 - Proanthocyanidin-containing composition

Info

Publication number: WO2006067866A1
Application number: PCT/JP2004/019791
Authority: WO
Inventors: Kinya Takagaki; Takeshi Mitsui
Original assignee: Toyo Shinyaku Co., Ltd.
Priority date: 2004-12-24
Filing date: 2004-12-24
Publication date: 2006-06-29

Abstract

A composition comprising a proanthocyanidin and a xanthine derivative. This composition realizes striking enhancement of the various physiological activities of proanthocyanidin.

Description

Proanthocyanidin-containing composition

Technical field

The present invention relates to a composition for enhancing the bioactive action of proanthocyanidins.

Background art

book

Proanthocyanidins are condensed or polymerized tannins (hereinafter referred to as polycondensation) present in various plants, and are a group of compounds obtained by polycondensation with flavan_3_ol or flavan-3,4-diol as structural units. is there. These are given their names because they produce anthocyanidins such as cyanidin, delphiyudin and pelargonidin by acid treatment. Among proanthocyanidins, a polycondensation polymer having a polymerization degree of 2 to 4 is called oligomeric proanthocyanidin (hereinafter referred to as OPC).

Proanthocyanidins are a kind of polyphenols and have a strong antioxidant action (Patent No. 3 0 40 9 92 2). Furthermore, they suppress bacterial growth in the oral cavity and prevent plaque (teeth It is known that it has the effect of reducing the elasticity of the blood vessels (the effect of protecting the blood vessels) (the effect of protecting the blood vessels); the effect of increasing the utilization efficiency of vitamin C; and the effect of improving the fluidity of blood.

In recent years, in order to effectively utilize various bioactive effects of such proanthocyanidins, combinations with other components have been studied, and the bioactive actions of proanthocyanidins are enhanced and synergistic with other diseases and diseases. Have been found (Japanese Patent No. 2 5 0 3 1 0 7 specification, Japanese Patent Application Laid-Open No. 5-1 1 2 4 4 1, 1 1-8 0 0 0 9 and JP 2 0 2-2 3 8 4 9 7). For example, the combination of proanthocyanidins and ascorbic acid is known to effectively improve the skin. However, there is a demand for means capable of enhancing not only such actions but also various physiologically active actions possessed by oral anthocyanidins. Disclosure of the invention

An object of the present invention is to provide a novel composition that can further enhance various physiologically active actions of proanthocyanidins.

The present inventors have made extensive studies on the above problems, and surprisingly, the combination of proanthocyanidins and xanthine derivatives surprisingly improves the lipid metabolism of proanthocyanidins, improves lipids in blood, and improves exercise capacity. It is possible to remarkably enhance the effects on the living body such as effects, blood flow improvement effect, diet effect, slimming effect, etc., and it was found that these effects are excellent effects that cannot be obtained by single administration. It came to complete.

The composition of the present invention contains proanthocyanidins and xanthine derivatives.

In a preferred embodiment, the xanthine derivative is caffeine.

In a preferred embodiment, the proanthocyanidins are derived from pine bark. Brief Description of Drawings

Fig. 1 shows the swimming of rats when a sample solution containing a pine bark extract and caffeine, a sample solution containing only a pine bark extract, and a sample solution containing only caffeine are taken. It is a graph which shows time. BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the composition of the present invention will be described. The configurations described below are not intended to limit the present invention, and it will be apparent to those skilled in the art that various modifications can be made within the spirit of the present invention.

The composition of the present invention contains a proanthocyanidin and a xanthine derivative, and contains other components as necessary. Hereinafter, each component will be described.

(Proanthocyanidins)

As the proanthocyanidins used in the present invention, those containing a large amount of a condensation polymer having a low polymerization degree are suitable. As the condensation polymer having a low degree of polymerization, a condensation polymer having a degree of polymerization of 2 to 30 (2 to 30 mer) is preferable, and a condensation polymer having a degree of polymerization of 2 to 10 (2 to 10 mer) ) Is more preferred, and a condensation polymer having a degree of polymerization of 2 to 4 (2 to 4 mer: more preferably 0 to 0. Proanthocyanidins are concentrated in plant leaves, bark, fruit peels or seed parts. Proanthocyanidins, especially OPCs, are specifically the bark of plants such as pine, cocoons and wild peaches; buds, blueberries, strawberries, apogados, black acacias, berries and seeds; Included in barley, wheat, soybeans, black soybeans, cacao, red beans, tochi husks, peanut skins, gypsophila leaves, etc. In addition, West African cola nuts, Peruvian latania roots, Japanese green tea Are also known to contain OPC. OPC is a substance that cannot be produced in the human body.

In particular, use of proanthocyanidins with high OPC content or extracts containing proanthocyanidins with high OPC content compared to the case of using proanthocyanidins with a high degree of polymerization (low OPC content). As a result, an excellent blood flow improvement effect and an improvement effect of exercise ability such as an improvement of muscle strength can be obtained. further Improving muscular strength is effective in improving basal metabolism and may contribute to dietary effects. As the proanthocyanidins used in the composition of the present invention, materials such as the bark of the above-mentioned plant, pulverized fruits or seeds, or extracts thereof can be used. Among these, it is preferable to use a plant-derived extract, and it is particularly preferable to use a pine bark-derived extract. Extracts derived from pine bark show a particularly high physiological activity among plant-derived extracts. This is thought to be because, among the plants containing proanthocyanidins, pine bark is rich in OPC, or contains active ingredients in addition to proanthocyanidins. Therefore, pine bark is preferably used as a raw material for proanthocyanidins. The extract is preferably one from which impurities have been removed.

Hereinafter, an example of using pine bark rich in OPC as a raw material plant will be described with reference to a method for preparing an extract containing puffer anthocyanidin as a main component.

Pine bark extract includes French coastal pine (Pinus Martima), larch, black pine, akamatsu, himekomatsu, pine pine, pine pine, wild pine, eucalyx pine, pine pine, pine pine, white pine, Canadian quebec An extract of a bark of a plant belonging to the order of pine is preferably used. Among them, the bark extract of French maritime pine (Pinus Martima) is preferred.

French coastal pine is a marine pine that grows on the Atlantic coast of southern France. This French coastal pine bark contains proanthocyanidins, organic acids, and other physiologically active ingredients, and its main component, broanthocyanidins, has a strong antioxidant action to remove active oxygen. It has been known. The pine bark extract is obtained by extracting the pine bark with water or an organic solvent. When water is used, it is preferable to use warm water or hot water. In order to improve the extraction efficiency, it is preferable to add a salt such as sodium chloride to these waters. Organic solvents used for extraction are used in the production of food or drugs. Acceptable organic solvents are used, such as methanol, ethanol, 1-propanol, 2_propanol, 1-butanol, 2-butanol, acetone, hexane, cyclohexane, propylene glycol, hydrous ethanol, Hydrous propylene glycol, methyl ethyl ketone, glycerin, methyl acetate, ethyl acetate, jetyl ether, dichloromethane, edible oils and fats, 1, 1, 1, 2-tetrafluoroethane, and 1, 1, 2-trichloroethene Are listed. These water and organic solvents may be used alone or in combination. In particular, water, hot water, ethanol, water-containing ethanol, and water-containing propylene glycol are preferable, and water, hot water, ethanol, and water-containing ethanol are more preferable from the viewpoint of safety when used in foods and pharmaceuticals.

The method for extracting proanthocyanidins from pine bark is not particularly limited. For example, by extracting 1 to 100 parts by weight of hot water of 50 to 120 ° C, preferably 70 to 100 ° C with respect to 1 part by weight of the dry weight of pine bark. A pine bark extract having high bioactivity and high water solubility can be obtained. A warm extraction method, a supercritical fluid extraction method, or the like may be used.

Alternatively, supercritical fluid extraction may be performed by an entrainer addition method. In this method, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to a supercritical fluid. By adding about 20 WZV% and performing supercritical fluid extraction with the extracted fluid, the solubility of the target extract such as OPC and catechins (described later) in the extraction solvent is dramatically increased. Alternatively, it is a method for enhancing the selectivity of separation, and a method for efficiently obtaining a pine bark extract.

For extraction from pine bark, a plurality of extraction methods may be combined. By combining multiple extraction methods, it is possible to obtain pine husk extract of various compositions. The pine bark extract obtained by the above extraction may be purified for the purpose of increasing the proanthocyanidin content. For purification, a solvent such as ethyl acetate is usually used, but from the viewpoint of safety as a food or pharmaceutical, a method that does not use a solvent, such as ultrafiltration or Diaion HP-2O, Sephadex It is preferable to purify by a column method or a batch method using an adsorbent carrier such as LH 20 or chitin.

In the present invention, the pine bark extract containing proanthocyanidin as a main component is specifically prepared by the following method, but this is an example and is not limited to this method.

1 kg of French coastal pine bark is placed in 3 L of saturated sodium chloride solution and extracted at 100 ° C for 30 minutes to obtain an extract (extraction process). Thereafter, the extract is filtered, and the resulting insoluble matter is washed with 50 O mL of a saturated solution of sodium chloride to obtain a washing solution (washing step). Combine this extract with the cleaning solution to obtain a crude extract of pine husk.

Next, 25 mL of ethyl acetate is added to the crude extract and the phases are separated to recover the ethyl acetate layer 5 times. Combine the recovered ethyl acetate solution and add directly to 200 g of anhydrous sodium sulfate for dehydration. Then, the ethyl acetate solution is filtered, and the filtrate is concentrated under reduced pressure until the original volume is reduced to one-fifth. The concentrated ethyl acetate solution is poured into 2 L of chloroform, and the resulting precipitate is collected by filtration. Then, after the precipitate is dissolved in 10 mL of ethyl acetate, the washing step is repeated twice, in which the precipitate is added again to 1 L of chloroform and precipitated. By this method, for example, about 5 g of pine peel extract containing 20% by weight or more of OPC and 5% by weight or more of strong techins can be obtained.

The extract derived from the raw material plant such as pine husk preferably contains 40% by weight or more of proanthocyanidins. In addition, this source plant derived The extract preferably contains 20% by weight or more of OPC, more preferably 30% by weight or more. As described above, a pine bark extract is preferably used as a raw material containing proanthocyanidins in a high proportion.

Since OPC is an antioxidant, it has the effect of reducing the risk rate of adult diseases such as cancer, heart disease, and cerebral thrombosis, and has the effect of improving the allergy in nature such as arthritis, atopic dermatitis, and hay fever. In addition, it suppresses bacterial growth in the oral cavity and reduces plaque (dental glands); restores the elasticity of blood vessels; prevents lipoproteins in the blood from being damaged by active oxygen; It also has the effect of preventing cholesterol from adhering to the inner wall of blood vessels and adhering cholesterol; the effect of regenerating vitamin E decomposed by active oxygen; and the effect of enhancing vitamin E.

The plant extract such as the pine bark extract preferably contains catechins together with proanthocyanidins, particularly OPC. Catechin is a general term for polyhydroxyflavan 1-3-ol. The catechins are (+)-force techin (referred to as catechin in the narrow sense), (1) one epi force tekin, (+)-gallocatechin, (1) one epicarocatechin, epicarocatechin gallate, epicatechin gallate, Afzerekin is known. From the above-mentioned extracts derived from raw materials such as pine bark, in addition to the above (+)-power techin, gallocatechin, afuzerekin, (+)-catechin 3-galloyl derivative, and 3-galloyl derivative of gallocatechin It has been isolated. Catechins are poorly water-soluble by themselves and have low physiological activity. However, catechins have the property of being activated at the same time as water solubility increases in the presence of OPC, and they act effectively when ingested with OPC. .

Catechins are preferably contained in the raw material plant extract in an amount of 5% by weight or more, preferably 10% by weight or more. More preferably, the extract contains 20% by weight or more and 20% by weight or more of catechins. Example For example, if the catechin content of the extract is less than 5% by weight, force techins may be added to adjust the final content to 5% by weight or more. It is most preferable to use a pine husk extract containing 20% by weight or more of the same and 5% by weight or more of the strength techins.

(Xanthine derivative)

Typical xanthine derivatives used in the present invention include caffeine, theofylline, theobromine and the like. Caffeine is preferable. These are contained in palatable food materials such as tea, coffee beans, cacao, kola, guarana, mate tea and cola. As the xanthine derivative, a commercially available synthetic product or purified product may be used. However, when the composition of the present invention is orally administered (taken), the above-mentioned palatability food material or its extraction is used from the viewpoint of safety. It is preferable to use a product. These materials can contain a relatively large amount of caffeine.

The above xanthine derivative, together with proanthocyanidins, can remarkably enhance various physiologically active actions possessed by proanthocyanidins. Thus, the inventors found for the first time that a xanthine derivative is a material that efficiently enhances a plurality of bioactive actions of proanthocyanidins. Xanthine derivatives, alone, are known to cause central nervous system excitement, and are contained in pharmaceuticals and foods for the purpose of awakening sleepiness and relieving fatigue. In addition, it has smooth muscle relaxation and anti-inflammatory effects, and is used as a medicine for colds and asthma. In addition, it has a diuretic effect, an increase in heart rate, and a slight basal metabolism improving effect due to fatty acid degradation, and a diet effect. (Other ingredients)

The composition of the present invention contains the above proanthocyanidins and xanthine derivatives. If necessary, it can contain various components. For example, ingredients that can be added as normal foods and pharmaceuticals (excipients, bulking agents, binders, thickeners, emulsifiers, colorants, fragrances, nutritional ingredients, food additives, etc.); and cosmetics, quasi drugs Ingredients commonly used as external preparations for skin (whitening agents, moisturizers, antioxidants, UV absorbers, UV scattering agents, antiseptics, fragrances, gelling agents, polymer polymers, oily ingredients, surfactants, Thickeners, alcohols, powder ingredients, colorants, aqueous ingredients, various skin nutrients, etc.).

Nutritional ingredients include, for example, vitamins such as ascorbic acid, tocopherol, riboflavin, / 3-carotene, folic acid and piotin; minerals such as calcium, magnesium, selenium, iron; and taurine and garlic. Sulfur compounds; Flavanoids such as hesperidin and quercetin; Flavonoids; Dietary fibers such as indigestible dextrin, alginic acid, chitin, chitosan and guagam; Proteins such as soy protein and collagen; Peptide; Amino acid; Animal fats and oils such as milk fat, lard, beef tallow and fish oil; vegetable oils such as soybean oil and rapeseed oil; fruits such as orange, lemon, grapefruit and strawberry and their juices; royal jelly, propolis and the like. Examples of food-added calories include honey, reduced maltose, lactose, sugar alcohol, liquid sugar, and seasonings. (Proanthocyanidin-containing composition)

As described above, the composition of the present invention contains a proanthocyanidin and a xanthine derivative, and, if necessary, contains other components. As described above, the proanthocyanidins and xanthine derivatives may be any of isolated compounds, food materials containing them, and extracts of the food materials. For example, a plant extract containing a xanthine derivative is added to a plant extract containing proanthocyanidins. Specifically, blowers such as pine bark and grape seeds A plant extract containing a xanthine derivative is added to a plant extract containing toxanidine and not containing a xanthine derivative or purified to contain a high concentration of proanthocyanidins. If the plant extract contains both proanthocyanidins and xanthine derivatives, depending on the purpose, the necessary ingredients (for example, pine bark extract containing proanthocyanidins) can be added to the composition. The amount ratio of each component can be adjusted as appropriate.

The content ratio of proanthocyanidins and xanthine derivatives in the composition of the present invention is arbitrary. Preferably, the ratio of proanthocyanidins to xanthine derivatives is from 1: 0.001 to 1000 by weight, more preferably from 1: 0.01 to 1: 500, more preferably from 1: 0.02 to 1: 200, most preferably 1: 0.0.02 :: 1: 50.

There is no restriction | limiting in particular in content of proanthocyanidin in the composition of this invention. Preferably, it is preferably contained so that the daily intake per adult is 1 to 1000 mg, more preferably 2 to 500 mg as proanthocyanidins. In the case of transdermal administration, since it is a topical administration, it is preferable to have a predetermined concentration. Specifically, proanthocyanidins are preferably contained in the composition in an amount of 0.0001% to 20% by weight. / ₀ , more preferably 0.0001 wt% to 10 wt%, and even more preferably 0.001 wt% to 10 wt%.

There is no restriction | limiting in particular in content of the xanthine derivative in the composition of this invention. Preferably, adults should contain 10 mg to 10000 mg, more preferably 20 mg to 500 Omg per day. In particular, among xanthine derivatives, caffeine is preferred to be within the above range because it may cause side effects such as convulsions if taken too much at once. In the case of transdermal administration, since it is a topical administration in the same manner as proanthocyanidins, a predetermined concentration is preferable. Specifically, a xanthine derivative is a composition. Among them, preferably 0.0 0 0 0 1% by weight to 20% by weight, more preferably 0.0 0 0 1%. /. -10% by weight, more preferably 0.01% by weight to 10% by weight, and most preferably 0.1% by weight to 10% by weight. The composition of the present invention can be prepared in various forms depending on the purpose, for example, as a food, a pharmaceutical, a quasi-drug, or a cosmetic.

Among the above-mentioned uses, when the composition of the present invention is orally ingested (administered) as food, pharmaceuticals, quasi drugs, etc., there is no particular limitation on the form. For example, capsules such as hard capsules and soft capsules, tablets, pills, powder (powder), granules, tea bags, bowl-like viscous liquids, liquids, pastes, etc. are used in a form commonly used by those skilled in the art. . These can be taken as they are, or they can be taken in water, hot water, milk, etc., depending on the shape or taste, or you can take the brewed ingredients.

Even when the composition of the present invention is applied to the skin as a quasi-drug, cosmetic, etc., these forms are not particularly limited, such as ointments, creams, emulsions, lotions, packs, poultices, bath preparations, etc. Any form can be used as long as it is conventionally used for an external preparation for skin.

The composition of the present invention can be administered orally (taken) or transdermally (applied) to improve the lipid metabolism of proanthocyanidins, improve blood lipids, improve exercise capacity, improve blood flow. Physiological activity such as diet effect and slimming effect can be remarkably enhanced. These effects are excellent effects that cannot be obtained when proanthocyanidins and xanthine derivatives are administered alone. The composition of the present invention can be used for foods, pharmaceuticals, quasi drugs, cosmetics and the like. Example

Hereinafter, the present invention will be described with reference to examples. However, the present invention is not limited to these examples. It goes without saying that it is not limited.

In this example, a pine bark extract (trade name: Frapangenol, Toyo Shinyaku Co., Ltd.) containing 40% by weight of proanthocyanidins as a material containing proanthocyanidins (containing 20% by weight of OPC as material). Caffeine derived from coffee (caffeine content: 98.5% by weight) (trade name: Chanomoto, Shiratori Pharmaceutical Co., Ltd.) was used as the xanthine derivative.

(Example 1: Preparation of feed)

By mixing the following materials, a purified diet was prepared: corn starch 29.49 by weight ^_0/0, milk casein 20 wt ^_0/0, Alf alpha meal 1 0 wt ^_0/0, alpha-potato starch 10 weight ^_0/0 , cellulose powder 10 weight ^_0/0, Shiyukuro scan 10 weight ^_0/0, soybean oil 6% by weight, mineral mixture (AIN- 76) 3. 5 by weight ^_0/0, vitamin mixture (AIN-76) 1 wt ⁰ / ₀ , and ascorbic acid 0.01% by weight. These were mixed with the refined feed so that the pine bark extract was 0.5% by weight of the whole and the power fuin was 0.01% by weight of the whole, and the solid feed was prepared by molding (prepared as feed 1). )

(Comparative Example 1)

A solid feed was prepared in the same manner as in Example 1 except that caffeine was not mixed (referred to as feed 2).

(Comparative Example 2)

Solid feeds were prepared in the same manner as in Example 1 except that the pine bark extract was not mixed (referred to as feed 3).

(Example 2: Evaluation of blood lipid metabolism improvement effect) Three-week-old male guinea pigs (Japan SLC Co., Ltd.) were given a commercial solid feed (RC4, Oriental Yeast Co., Ltd.) for one week to acclimatize. The guinea pigs were divided into groups of 7 by a total randomization method. Each group of guinea pigs was allowed free intake of the above feeds 1-3 for 28 days. In addition, as a target group, a group that freely consumed purified feed was established. After the intake period, the total cholesterol level, LD L cholesterol level, HDL cholesterol level, triglyceride level, and phospholipid level in each group of guinea pigs were measured. The results are shown in Table 1. The measurement method is as follows.

Total cholesterol _(m g / d L) is, using the "Serotec" TCHO- L (manufactured by stock company Serotec), it was measured by the enzymatic method.

LDL cholesterol (mg / d L) was measured by enzyme method using Collestest LDL (Daiichi Chemical Co., Ltd.).

HDL cholesterol ( _{mg /} d L) was measured by enzyme method using Cholestest HDL (Daiichi Chemical Co., Ltd.).

Triglyceride (mgZdL) was measured by an enzymatic method using “Cellotech” TG-L (Seguchi Tech Co., Ltd.).

Phospholipid (mgZdL) was measured by an enzymatic method using “Serotech” PL-L (manufactured by Serotech Co., Ltd.). table 1

Average soil standard deviation From the results shown in Table 1, the group ingested the feed containing the pine bark extract of Example and caffeine (Feed 1) showed that the feed containing either the pine bark extract of Comparative Example or caffeine was used. Compared to the group ingested (Feed 2 and 3), the total blood cholesterol, triglycerides, and phospholipids were low, and among the cholesterol, the blood concentration of HDL cholesterol, which is said to be good, was high. I understand that This indicates that a composition containing proanthocyanidins and a xanthine derivative has excellent blood lipid improvement effect and lipid metabolism improvement effect that cannot be obtained when each is taken alone.

(Example 3: Preparation of sample solution)

Sample solution 1 was prepared by dissolving in water such that the pine bark extract was 0.05% by weight and caffeine was 0.05% by weight.

(Comparative Example 3)

Sample solution 2 was prepared by dissolving pine bark extract in water to 0.1% by weight.

(Comparative Example 4)

Sample solution 3 was prepared by dissolving in water such that caffeine was 0.1% by weight.

(Example 4: Evaluation of athletic performance improvement effect)

Three 3-week-old SD male rats (Kudo Co., Ltd.) were divided into 7 groups, and each group was fed with a basic diet (MF feed: Oriental Yeast Co., Ltd.) and acclimatized for 7 days. One group of rats was orally administered by gavage using a sonde at a rate of lm L per day. For sample solutions 2 and 3 as well, Each group of rats was orally administered. This administration was performed for 28 days. During the administration period, basic feed and water were ad libitum.

2 A test was conducted to measure exercise capacity 1 hour after administration on the 8th day. The motor ability test was conducted by a swimming test according to the method of Tanaka et al. (Research on Physical Education, 33 (2), 155, 1988). Specifically, from the first day of administration, the rats were habituated to water by swimming for 10 minutes per day from the first day. Then, on the second day after the start of the test, a weight corresponding to 4% by weight of the body weight was placed on the tail of the rat to perform swimming exercise, and the time when it submerged for 10 seconds under the surface of the water was regarded as an all-out. By measuring time (swimming time), motor ability was determined. The results are shown in Figure 1.

From the results shown in FIG. 1, the group to which the sample solution containing the pine bark extract of the example and the force fuin (sample solution 1) was administered showed either one of the pine bark extract or caffeine of the comparative example. It can be seen that the swimming time is longer than that of the group ingesting the sample solutions (sample solutions 2 and 3). This indicates that the composition containing proanthocyanidins and xanthine derivatives has an excellent effect of improving athletic ability that cannot be obtained when each is taken alone.

(Example 5: Manufacture of tablets)

Pine bark extract, caffeine, and excipients were mixed in the proportions (% by weight) shown in Table 2 to produce tablets (about 2500 mg per tablet). .

(Comparative Examples 5 and 6)

In the same manner as in Example 5, the ingredients listed in Table 2 were mixed to produce tablets (about 2500 mg per tablet), which were designated as Foods 2 and 3. Table 2

Unit is% by weight

(Example 6: Evaluation of blood flow improvement effect)

Twenty-four healthy men and women aged 22 to 63 (12 men and 12 women) were randomly assigned to 3 groups except for equal gender. First, the blood flow of each subject was measured before food intake. Next, one group of subjects took the food 1 (1 tablet) together with 10 OmL of water. After ingestion, the patient was rested for 1 hour, and then blood flow was measured again. The blood flow rate was measured using the blood flow meter (laser blood flow imaging device PIM II; Swedish Digital Ltd.) with the subcutaneous blood flow of three fingers (index finger, middle finger, and ring finger). Measurements were made and the average of these values was determined. For foods 2 and 3, blood flow was measured before and after food intake in the same manner as above. The results are shown in Table 3. The values in the table are the average soil standard error. The larger the value, the greater the blood flow. Table 3

Mean value ± standard deviation

From the results in Table 3, the group that ingested the food (food 1) containing the pine bark extract of the example and caffeine was the food containing either the pine bark extract of the comparative example or caffeine. It can be seen that the blood flow is greatly increased compared to the group ingesting (foods 2 and 3). This indicates that the composition containing proanthocyanidins and xanthine derivatives has an excellent blood flow improvement effect that cannot be obtained when each is taken alone.

(Example 7: Evaluation of lipid metabolism improvement effect and diet effect)

2 With 4 female subjects, the diet effect was evaluated by randomly assigning them to 3 groups, except for adjusting the average weight. First, the weight and body fat percentage of each subject were measured using a health meter with a body fat meter (Koyo Sangyo Co., Ltd.). After the measurement, the food 1 obtained in Example 7 was ingested at a rate of 1 tablet per day for 28 days. On the 28th day after the start of intake, body weight and body fat percentage were measured again, and the decrease rate of body weight and body fat percentage was calculated from the following formula. The same was done for foods 2 and 3, and the rate of decrease in body weight and body fat percentage was calculated. In addition, during the study, we told them that no dietary restrictions were required other than strictly observing food intake. The results are shown in Table 4. {(Food intake

Weight loss rate (%): imperial weight)-(weight after food intake)}

X 1 00

(Weight before food intake)

Decrease rate of body fat percentage (%) = ¹ (body fat percentage before food intake) one (body fat percentage after food intake)}

(Percentage of body fat before food intake)

Table 4

Average soil standard deviation From the results in Table 4, the group that ingested the food containing pine husk extract and caffeine of Example (Food 1) showed that the pine bark extract and caffeine of Comparative Example It can be seen that body weight and body fat are reduced compared to the group that ingested foods containing either one (foods 2 and 3). This indicates that a composition containing proanthocyanidins and a xanthine derivative has excellent lipid metabolism improving effects and diet effects that cannot be obtained when taken alone.

(Example 8: Preparation of lotion 1)

A lotion 1 was prepared by mixing pine bark extract, caffeine, alcohol, glycerin, and 1,3-butylene glycol in the proportions shown in Table 5.

(Comparative Examples 7 and 8) In the same manner as in Example 8, the ingredients shown in Table 5 were mixed to prepare lotions 2 and 3, respectively. Table 5

Unit is% by weight

The balance is purified water

(Example 9: Evaluation of blood flow improvement effect and slimming effect)

First, using 24 women as subjects, blood flow was measured using a laser Doppler (Sweden Permied), and the thickness of the upper arm was measured using a measure. The thickness of the upper arm was measured at four locations on the upper arm, and the value with the longest circumference was adopted. The above subjects were divided into 3 groups randomly, except that the average thickness of the upper arm was adjusted. Next, 3 mL of lotion 1 was applied to the entire upper arm of one group of subjects. This application was performed once a day for 28 days. After the application period, the blood flow volume and the upper arm thickness were measured again, and the blood flow increase rate and the outer arm decrease rate were calculated from the following equations, and the average value was calculated. For lotions 2 and 3, the same procedure as above was performed, and the rate of increase in blood flow and the rate of decrease in the outer circumference of the upper arm were determined. The results are shown in Table 6.

_{vi nn} x ^{1 00}

Table 6

From the results shown in Table 6, the group to which the skin lotion containing the pine bark extract of the example and caffeine (skin lotion 1) was applied contained either the pine bark extract of the comparative example or caffeine. It can be seen that the blood flow increased and the outer circumference of the upper arm decreased as compared to the group applied with lotion (lotion 2 and 3). This indicates that by applying a composition containing proanthocyanidins and a xanthine derivative, excellent blood flow improving effects and slimming effects that cannot be obtained when each of them is applied alone are obtained. Industrial applicability

As described above, the composition containing proanthocyanidins and xanthine derivatives can be administered orally or transdermally to improve lipid metabolism, blood lipids, and exercise capacity of proanthocyanidins. Physiological activity such as improvement effect, blood flow improvement effect, diet effect, slimming effect (local slimming effect by application) can be remarkably enhanced. These effects are superior to proanthocyanidins and xanthine derivatives, which cannot be obtained by single administration. It is an effect. The composition of the present invention can be effectively used for foods, pharmaceuticals, quasi drugs, cosmetics, and the like.

Claims

22 Claim

1. A composition comprising proanthocyanidins and a xanthine derivative.

2. The composition according to claim 1, wherein the xanthine derivative is caffeine.

3. The composition according to claim 1 or 2, wherein the proanthocyanidins are derived from pine bark.