JP7048249B2 - Foot skin indigenous bacterial plexus improving agent - Google Patents

Description

The present invention relates to a foot skin indigenous bacterial flora improving agent that improves the indigenous bacterial flora of the foot skin.

Symbiotic microorganisms called skin flora form a group on human skin, and these microorganisms live at the point of contact with the outside world and have a protective function to prevent the invasion of pathogenic bacteria from the outside of the host skin. are doing.
Indigenous skin flora is generally site-specific, but generally aerobic Staphylococcus epidermidis (eg, Staphylococcus epidermidis, Staphylococcus aureus) on the surface of the skin and anaerobic P. acnes on hair follicles and fat glands. (Propionibacterium acnes) inhabits as an indigenous bacterium (Non-Patent Documents 1 to 4).
Staphylococcus epidermidis is less pathogenic on the surface of the skin and is superior to Staphylococcus aureus, which is the same staphylococcus and highly pathogenic. Staphylococcus epidermidis produces fatty acids from sebum and sweat, keeps the skin surface weakly acidic along with the fatty acids produced by P. acnes, and suppresses the growth of Staphylococcus aureus and fungi (molds) that prefer weak alkalinity.

However, there are some changes on the skin due to poor general condition due to trauma, illness, mental stress, cold, dryness, improper cleaning and improper application (cosmetics, drugs, etc.), and appropriate bacteria. When the flora is out of balance, overgrowth of indigenous bacteria and invasion and proliferation of other pathogens can occur, resulting in various skin symptoms. For example, when body fluid elutes in the affected area due to trauma or the like and the skin pH rises, pathogenic bacteria such as Staphylococcus aureus can easily grow, which may cause purulent inflammation such as pyoderma and jumps. In addition, it has been reported that an abnormal condition in which Staphylococcus aureus proliferates may cause atopic dermatitis (Non-Patent Document 5).
Therefore, in order to keep the skin in a healthy condition and to make the poor skin condition healthy, it is important to control the balance of the indigenous bacterial flora of the skin, especially the genus Staphylococcus. Be done.

On the other hand, chlorogenic acids are one of the polyphenols found in green coffee beans and the like. It has been reported that chlorogenic acids have various physiological functions such as antioxidant action, blood pressure lowering action, and lipid burning promoting action (Patent Document 1).
However, no effect has been reported on the effects of chlorogenic acids on the indigenous bacterial flora of the skin of the feet.

Japanese Unexamined Patent Publication No. 2010-241800

Noble, J. Med. Microbol., 17, p1-12 (1984) Tomida S. et al., MBio., Vol.4, Issue 3, e00003-13 (2013) Oh J. et al., Cell, Vol.165, p854-866 (2016) Takeda, Cosmetics Society Magazine, Vol.27, No.1, p29-32 (2003) Hirata et al., Nikkikai Journal, Vol.104 (11), p1353-1359 (1994)

The present invention relates to providing a foot skin indigenous bacterial plexus improving agent that can be used for pharmaceuticals, foods and the like.

As a result of investigating the action of chlorogenic acids on the indigenous bacterial flora of the skin of the foot, the present inventor selectively suppresses pathogenic bacteria such as Staphylococcus aureus without adversely affecting Staphylococcus epidermidis when ingesting chlorogenic acids. It was found that chlorogenic acids are effective in improving the indigenous bacterial flora of the skin of the feet.

That is, the present invention provides an agent for improving the indigenous bacterial flora of the foot, which contains chlorogenic acids as an active ingredient.
The present invention also provides a food composition for improving the indigenous bacterial flora of the foot, which contains chlorogenic acids as an active ingredient.

According to the present invention, the indigenous bacterial flora of the skin of the foot can be improved.

The figure which shows the result of the bacterial count measurement before and after ingestion of a test drink.

The active ingredient for improving the indigenous bacterial flora of the skin of the foot used in the present invention is chlorogenic acids.
Examples of chlorogenic acids include 3-cafe oil quinic acid, 4-cafe oil quinic acid and 5-cafe oil quinic acid-containing monocafe oil quinic acid; 3-ferloyl quinic acid, 4-ferloyl quinic acid and 5 -Monopherroylquinic acid containing ferroylquinic acid can be mentioned.
Chlorogenic acids can be any one or a combination of two or more of the compounds listed above. The chlorogenic acids preferably include the above 6 types. In the present specification, the content of chlorogenic acids is defined based on the total amount of the above six kinds.

Chlorogenic acids can be extracted from natural products containing them, particularly plants, and can also be industrially produced by chemical synthesis. There are steric isomers in chlorogenic acids, and in the present invention, pure steric isomers thereof or mixtures of steric isomers thereof can be used.

Chlorogenic acids can preferably be extracted from the plants containing them. Examples of plants containing chlorogenic acids include coffee, cabbage, lettuce, arch choke, tomatoes, eggplants, potatoes, carrots, apples, pears, plums, peaches, apricots, cherries, sunflowers, moroheiya, kansho, and southern leaves. Examples include blueberries and wheat.

More preferably, chlorogenic acids can be extracted from green coffee beans, lightly roasted coffee beans, Nanten leaves, immature apple fruits, sunflower seeds and the like. For example, chlorogenic acids are extracted from the seeds of Coffee arabica LINNE with warm ascorbic acid, acidic aqueous solution of citric acid or hot water, and then filtered, activated charcoal and ion exchange resin treatment as necessary to obtain chlorogenic acids. Raw coffee bean extract containing can be prepared. Alternatively, an extract containing chlorogenic acids may be prepared from lightly roasted coffee beans. The L value of the lightly roasted coffee beans is preferably 27 or more, more preferably 35 or more, further preferably 40 or more, and preferably less than 62, preferably 60 or less, from the viewpoint of chlorogenic acid content and the like. Is more preferable, and 55 or less is further preferable. Here, in the present specification, the "L value" is obtained by measuring the brightness of roasted coffee beans with a color difference meter, where black is L value 0 and white is L value 100. Alternatively, in the present invention, commercially available green coffee bean extract, apple extract, and sunflower seed extract can be used as chlorogenic acids.

Chlorogenic acids may be in free form or in salt form. By making it a salt, water solubility can be improved and physiological effectiveness can be increased. The salt of chlorogenic acids used in the present invention may be any pharmaceutically acceptable salt. Examples of the basic substance for forming such a salt include hydroxides of alkali metals such as lithium hydroxide, sodium hydroxide and potassium hydroxide; and hydroxylation of alkaline earth metals such as magnesium hydroxide and calcium hydroxide. Substances; Inorganic bases such as ammonium hydroxide; Basic amino acids such as arginine, lysine, histidine, ornithine; Organic bases such as monoethanolamine, diethanolamine and triethanolamine are used, of which alkali metals or alkaline earths are used. Metal hydroxides are preferred.

As shown in the examples below, when chlorogenic acids were orally ingested, the total number of bacteria on the foot skin decreased as compared with that before ingestion. Looking at the bacterial species, especially Staphylococcus aureus species, there was no effect on the habitat of Staphylococcus epidermidis, which is a skin beneficial bacterium, while Staphylococcus aureus, which is a skin pathogenic bacterium, was suppressed. In addition, the pH of the skin surface of the foot decreased.
Therefore, chlorogenic acids are effective in improving the indigenous bacterial flora of the skin of the foot, and chlorogenic acids can be an agent for improving the indigenous bacterial flora of the skin of the foot, in order to improve the indigenous bacterial flora of the skin of the foot. Can be used. It can also be used to produce an agent for improving the indigenous bacterial plexus of the skin of the foot.
Here, in the present invention, "improvement of the indigenous bacterial flora on the skin of the foot" means that the imbalance of the indigenous bacterial flora on the foot skin is prevented or normalized by ingesting chlorogenic acids. Preferably, the balance of the resident bacterial flora is the balance of Staphylococcus aureus, and prevention or normalization of the imbalance of Staphylococcus aureus does not suppress Staphylococcus epidermidis, which is a skin beneficial bacterium, but is a skin pathogen. Certain Staphylococcus aureus is suppressed. Suppression includes sterilization and sterilization that kills bacteria, bacteriostatic and bacteriostatic control that suppresses the development, growth and proliferation of bacteria. Skin pathogens include Staphylococcus saprophyticus and Staphylococcus saprophyticus subsp. In addition to Staphylococcus aureus. , Streptococcus and the like.
The foot refers to the part from the ankle to the tip of the ankle, and includes parts such as the instep (sole), sole (sole), heel, and toe (toe). The improvement of the resident bacterial flora of the skin of the foot is preferably the improvement of the resident bacterial flora of the sole (sole), heel, and toe (toe).
By suppressing Staphylococcus epidermidis, which is a beneficial skin bacterium, but by suppressing Staphylococcus aureus, which is a skin pathogenic bacterium, the skin environment of the foot can be normalized, the skin of the foot can be kept in a healthy condition, and the skin of the foot can be kept in a healthy condition. Poor skin condition can be made healthy.
Thus, chlorogenic acids can be used to improve the indigenous flora of the skin of the foot, yet the skin of the foot is healthy through the improvement of the indigenous flora of the skin of the foot. It can be used to keep the condition and to make the poor skin condition healthy.
"Use" can be administration or ingestion to animals, including humans, and may be therapeutic or non-therapeutic use. "Non-therapeutic" is a concept that does not include medical practice, that is, a concept that does not include a method of surgery, treatment or diagnosis of humans, more specifically, surgery on humans by a doctor or a person who has been instructed by a doctor. , A concept that does not include a method of performing treatment or diagnosis.

The foot skin indigenous bacterial flora improving agent of the present invention is a drug, a non-medicinal product or a food that exerts an effect of improving the foot skin indigenous bacterial flora when administered or ingested to animals including humans, and the foot. The skin indigenous bacterial flora improving agent can be a material or a preparation used in combination with the drug, non-pharmaceutical product or food.

The foods include foods (foods for specified health use, foods with functional claims) that appeal to improve the indigenous bacterial flora of the skin of the feet and are permitted to be labeled to that effect as necessary. As a display example, there is "for those who are worried about germs on the feet". Foods that have been approved for functional labeling can be distinguished from ordinary foods.

The administration form of the above-mentioned pharmaceutical products (including non-pharmaceutical products) may be solid, semi-solid or liquid, and is orally administered by, for example, tablets, capsules, granules, powders, troches, liquids, syrups, drinks and the like. Administration: Parenteral administration with injections, suppositories, inhalants, transdermal absorbents, external preparations and the like can be mentioned. Oral administration is preferred.
Formulations of such various dosage forms are optionally pharmaceutically acceptable carriers such as excipients, binders, bulking agents, disintegrants, surfactants, lubricants, dispersants, etc. Buffering agents, osmotic pressure regulators, pH regulators, emulsifiers, preservatives, stabilizers, preservatives, thickeners, fluidity improvers, flavoring agents, foaming agents, fragrances, coating agents, diluents, etc. It can be prepared by appropriately combining medicinal ingredients other than acids.
The content of chlorogenic acids in pharmaceuticals or quasi-drugs varies depending on the mode of use, but in the form of liquid preparations such as drinks, it is preferably 0.01 to 90% by mass, more preferably 0.05 to 70% by mass. %, More preferably 0.1 to 50% by mass. In the form of a solid preparation such as a tablet or a parenteral administration agent, it is generally 1% by mass or more, preferably 50% by mass or less.

The form of the above food may be solid, semi-solid or liquid, and various food compositions (breads, cakes, noodles, confectionery, jellies, frozen foods, ice creams, dairy products, beverages, etc.), Further, a nutritional supplement composition having the same form as the above-mentioned orally administered preparation (solid preparation such as tablets, capsules and troches) can be mentioned. Beverages, preferably beverages, include soft drinks, tea-based beverages, coffee beverages, fruit juice beverages, carbonated beverages and the like.
Various forms of foods may include other food materials, such as solvents, softeners, oils, emulsifiers, preservatives, acidulants, sweeteners, bitterness agents, pH regulators, stabilizers, colorants, as needed. It can be prepared by appropriately combining active ingredients other than chlorogenic acids, such as antioxidants, moisturizers, thickeners, fluidity improvers, foaming agents, fragrances, and seasonings.
The content of chlorogenic acids in foods varies depending on the form of use thereof, but in the form of beverages, it is preferably 0.01 to 90% by mass, more preferably 0.05 to 70% by mass, and further preferably 0.1 to 50% by mass. It is mass%.

In the form of solid foods such as tablets and processed foods, the content of chlorogenic acids is 1% by mass or more, preferably 50% by mass or less.

The dose or ingestion of the indigenous skin plexus improving agent for the feet of the present invention may vary depending on the body weight, gender, age, condition or other factors of the subject to be administered or ingested. The dose, route, interval, and amount and interval of ingestion may be appropriately determined by those skilled in the art, but usually 10 to 10000 mg of chlorogenic acids per day per adult (60 kg), preferably 10 to 10,000 mg. It is more preferably 50 to 5000 mg, still more preferably 100 to 1000 mg.
In the present invention, it is preferable to administer or ingest such an amount once to a plurality of times, preferably once a day.

The above-mentioned preparation can be administered or ingested according to an arbitrary plan.
The administration or ingestion period is not particularly limited, but it is preferable to administer or ingest repeatedly and continuously, and it is preferable to administer or ingest continuously for 2 weeks or more, further 4 weeks or more, and further 8 weeks or more.
The subject to be administered or ingested is not particularly limited as long as it is a human or non-human animal that needs or desires it. A preferred example of the subject is human.

[Test drink]
A raw coffee bean extract was obtained by extracting a crushed raw coffee bean with hot water and then treating it with concentrated activated carbon.
A beverage containing chlorogenic acids (hereinafter referred to as a test beverage) was prepared by blending the raw coffee bean extract with an acidulant, a sweetener and other materials.
HPLC (manufactured by Hitachi, Ltd.) was used for quantification of chlorogenic acids in the prepared beverage. In HPLC, 1 g of the sample was precisely weighed, then scalpelped to 10 mL with an eluent, filtered through a membrane filter (GL chromatodisc 25A, pore size 0.45 μm, GL Sciences Co., Ltd.), and then subjected to analysis. Using 5-cafe oil quinic acid as a standard substance, 3-cafe oil quinic acid, 4-cafe oil quinic acid, 5-cafe oil quinic acid, 3-ferloyl quinic acid, 4-ferloyl quinic acid and 5-ferroy Lukinic acid was quantified.
Of chlorogenic acids (3-cafe oil quinic acid, 4-cafe oil quinic acid, 5-cafe oil quinic acid, 3-ferloyl quinic acid, 4-ferloyl quinic acid and 5-ferloyl quinic acid) in 100 mL of the test beverage. The total amount was 270 mg.

Test Example 1
[Test outline]
(1) Subjects and methods The test was conducted on 4 healthy men and women aged 20 to 63 years, 8 in total (samples were managed by combining alphabets and numbers as subject identifiers). In the test, the subjects were allowed to take the test drink once a day (100 mL) for 8 weeks at free time. Before ingesting the test beverage, 4 weeks after ingestion, and 8 weeks after ingestion, the pH of the sole of the subject was measured with a pH meter (HI99181N manufactured by Hannah Instruments). In addition, non-antibacterial cotton socks were supplied to the subjects, and those worn on their feet during daytime activities from morning to night were collected before ingestion of the test drink, 4 weeks after ingestion, and 8 weeks after ingestion. Bacterial test was performed.
About 2 g of the toe portion was cut out from the collected socks, adjusted to 10% w / w with physiological saline, and extracted with a stamaker for 4 minutes. After adjusting the concentration of each sample 3 by the stock solution, 10-fold dilution, and 100-fold dilution, the extract was applied to a standard medium, and then cultured at 36 ° C. for 2 days, and colonies were counted. In addition, some samples were collected for each bacterial species, and the bacterial species were identified by rDNA request analysis by PCR analysis at Technosuruga Co., Ltd.

(2) Results Figure 1 shows the results of bacterial count measurement by gender. In addition, Table 1 shows the results of bacterial species identification analysis using subject B3, in which many skin pathogens were detected before ingestion of the test beverage, as the subject of analysis, and measured the pH of the sole of the foot of subject B3 before and after ingestion of the test beverage. The results are shown in Table 2.

As shown in FIG. 1, the total number of bacteria on the foot skin decreased in both men and women by ingesting the test drink.
Looking at the species of Staphylococcus spp., As shown in Table 1, ingestion of the test beverage did not affect the habitat of Staphylococcus epidermidis, which is a skin beneficial bacterium, but many skin pathogens detected before ingestion of the test beverage were found. It was suppressed. A decrease in the pH of the sole of the foot was also observed.

Claims (6)

An agent for improving the indigenous bacterial plexus of foot skin, which contains a hot water extract of green coffee beans containing chlorogenic acids as an active ingredient. The agent for improving the indigenous plexus of the skin of the foot according to claim 1, which is ingested as chlorogenic acids in an amount of 10 to 10000 mg per day. The agent for improving the indigenous bacterial flora of the foot skin according to claim 1 or 2, which does not suppress Staphylococcus epidermidis but suppresses Staphylococcus aureus in the skin of the foot. A food composition for improving the indigenous bacterial flora of foot skin containing a hot water extract of green coffee beans containing chlorogenic acids as an active ingredient. The food composition for improving the indigenous bacterial flora of the foot skin according to claim 4, which is ingested as chlorogenic acids in an amount of 10 to 10000 mg per day. The food composition for improving the indigenous bacterial flora of foot skin according to claim 4 or 5, which does not suppress Staphylococcus epidermidis but suppresses Staphylococcus aureus in the skin of the foot.

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