JP2019205371A - Oral alleviating agent against ultraviolet skin damage or skin state improving agent - Google Patents

Abstract

To provide an oral alleviating agent against ultraviolet damage or a skin state improving agent capable of increasing resistivity against ultraviolet radiation through daily ingestion, repressing pigmentation or inflammation due to ultraviolet radiation, and improving facial skin color, dullness, stickiness, and oiliness.SOLUTION: This invention relates to an orally ingestible alleviating agent or a skin state improving agent against ultraviolet skin damage, the agent including Lactobacillus gasseri as an active ingredient, and a skin-intended beverage/food product or a skin-intended pharmaceutical including the alleviating agent or a skin state improving agent against ultraviolet skin damage. The lactic acid bacteria are preferably Lactobacillus gasseri N320 strain (NITE BP-02287).SELECTED DRAWING: Figure 1

Description

  The present invention relates to an ultraviolet damage reducing agent or a skin condition improving agent containing, as an active ingredient, an Lactobacillus genus Lactobacillus derived from the intestine of an infant as an active ingredient, and a skin drug containing the ultraviolet damage reducing agent or a skin condition improving agent as an active ingredient And food and drink for skin.

  In recent years, research on the prevention of skin aging has been actively conducted, and it is said that the influence of photoaging by ultraviolet rays rather than aging by aging is dominant in the skin. When the skin is exposed to ultraviolet light, inflammation is induced, causing damage to cells and DNA, as well as the extracellular matrix, causing wrinkles and spots due to skin thickening and pigmentation, so-called photoaging ( Non-patent document 1). Chronic UV exposure cannot completely repair DNA damage and increases the risk of skin cancer (Non-patent Document 2). Therefore, it can be said that how to reduce the influence of ultraviolet rays is important in terms of preventing skin aging.

  An easy-to-understand example of UV damage is sunburn. Sunburn is mainly caused by exposure of the skin to high-energy UVB in the ultraviolet rays that fall on the earth's surface. Many Japanese people undergo sunburn due to inflammation and produce suntan due to pigmentation, but the UV resistance of the skin varies from individual to individual, and it is also known that the response varies among individuals. Therefore, it can be said that increasing the resistance to ultraviolet rays and suppressing inflammation caused by ultraviolet rays are effective in reducing ultraviolet ray damage. Moreover, it is thought that pigmentation is also suppressed by suppressing the inflammation by ultraviolet rays.

  As a means for reducing the influence of ultraviolet rays, methods of applying directly to the skin, such as blocking ultraviolet rays with a sunscreen agent and measures against stains and freckles with cosmetics, are the mainstream. Although the means for reducing the effects of ultraviolet rays by ingesting foods and beverages is increasing, it is still developing.

  On the other hand, although the health effect by ingestion of lactic acid bacteria has been studied for a long time, in recent years, not only the intestinal regulating action but also the effectiveness to the whole body and organs other than the intestinal tract has been clarified one after another (Non-Patent Document 3). . However, there are still few effective reports on the effect on the skin, which can be said to be the largest organ of the human body, compared to other organs, and there is almost no report on the effect on the UV damage to the skin.

John D’ Orazio et al., UV Radiation and the Skin, Int. J. Mol. Sci., 14, 12222-12248, 2013 Skotarczak K et al., Photoprotection: facts and controversies, Eur. Rev. Med. Pharmacol. Sci., 19, 98-112, 2015 Linares DM et al., Lactic Acid Bacteria and Bifidobacteria with Potential to Design Natural Biofunctional Health-Promoting Dairy Foods, Front Microbiol., 8 (846), 1-10, 2017

  The present invention relates to an ultraviolet damage reducing agent or a skin condition improving agent containing, as an active ingredient, an Lactobacillus genus Lactobacillus derived from the intestine of an infant as an active ingredient, and a skin drug containing the ultraviolet damage reducing agent or a skin condition improving agent as an active ingredient And it aims at providing food-drinks for skin.

The present inventors paid attention to the point that hyaluronic acid is indispensable for improving the moisture retention of the skin, and as a result of screening for a large number of lactic acid bacteria, lactic acid bacteria of the Lactobacillus sp. Bacillus gasseri N320 strain (NITE BP-02287) has a high ability to promote hyaluronic acid production. For example, the moisture content of the skin decreases due to dryness, the dryness of the cheeks, back, and neck deteriorates. So far, it has been found to be effective in improving skin conditions, including the reduction of skin gloss.
In addition, new strains of this strain will be searched for, for example, improved UV resistance at exposed sites, reduced redness of skin, reduced skin pigmentation, reduced skin color and dullness, facial It has been found that it is effective in improving the skin condition including stickiness and oiliness improvement, and the present invention has been completed.

  That is, the first invention of the present application is an orally administrable ultraviolet damage reducing agent or skin condition improving agent comprising, as an active ingredient, a lactic acid bacterium of Lactobacillus gasseri species or a fermented product of the lactic acid bacterium. , UV damage reduction including any of the effects of improving UV resistance at the site of UV irradiation, reducing redness of the skin or reducing pigmentation of the skin, improving skin color, dullness, stickiness of the face or oiliness The ultraviolet damage reducing agent or skin condition improving agent according to the first invention of the present application including effects, and the third invention of the present application is that the lactic acid bacterium is Lactobacillus gaselli N320 strain (NITE BP-02287). The ultraviolet damage reducing agent or skin condition improving agent according to one invention or the second invention of the present application. Furthermore, the present applicant also contemplates a skin drug and a skin food or drink for reducing UV damage or improving the skin condition, which contain the Lactobacillus gasseri lactic acid bacteria.

  According to the present invention, an ultraviolet damage reducing agent that can be taken orally on a daily basis to improve skin dryness, a skin condition improving agent, and the skin damage containing the ultraviolet damage reducing agent or skin condition improving agent as an active ingredient. A pharmaceutical product or food or drink for skin is provided.

FIG. 1 is a diagram comparing the skim milk medium growth of the strain of the present invention and the comparative strain. FIG. 2 is a diagram comparing the amount of change in MED before and after intake for the test food group and the placebo group. FIG. 3 is a diagram comparing L * value changes before and after intake for the test food group and the placebo group without irradiation, one day after irradiation, and seven days after irradiation. FIG. 4 is a diagram comparing the change in a * value before and after intake for the test food group and the placebo group, unirradiated, 1 day after irradiation, and 7 days after irradiation. FIG. 5 is a diagram comparing the amount of score change from before the ingestion of “facial skin color / dullness” according to a usability questionnaire for the test food group and the placebo group. FIG. 6 is a diagram comparing the amount of change in score from before the ingestion of “facial stickiness / oiliness” according to a feeling-of-use questionnaire for the test food group and the placebo group.

Hereinafter, the present invention will be described in detail.
1. Lactobacillus gaselli N320 strain (NITE BP-02287)
The lactic acid bacterium used in the present invention is Lactobacillus gasseri. Among the lactic acid bacteria belonging to Lactobacillus gasseri, in particular, Lactobacillus gasseri strain N320 (NITE BP-02287). The symbol N320 referred to in the present invention is a number uniquely assigned to the strain by Nissin Foods Holdings Co., Ltd., and the present Lactobacillus gasseri N320 strain was first isolated by the present inventor.

The Lactobacillus gasseri N320 strain of the present invention is deposited under the following conditions.
(1) Depositary Institution: National Institute of Technology and Technology Patent Microorganisms Deposit Center (2) Contact: Room 2-5-8 Kazusa Kamashi, Kisarazu City, Chiba 292-0818 (3) Deposit Number: NITE BP -02287
(4) Display for identification: N320
(5) Date of original deposit: June 14, 2016 (6) Date of transfer to deposit under the Budapest Treaty: April 10, 2017 The bacteriological properties of the Lactobacillus gasseri N320 strain used in the Japanese invention are as follows: As shown in Tables 1 and 2. This bacteriological property is determined by the method described in Bergey's manual of systematic bacteriology Vol. 2 (1986). Table 1 shows the shape and the like related to this strain, and Table 2 shows the results of the sugar assimilation test using API 50CH and API CHL (manufactured by Biomelieu). In Table 2, “+” indicates fermentability, and “−” indicates no fermentability.

2. Proliferation test on skim milk medium <Skim milk medium growth test>
The preculture was inoculated into a 10% skim milk medium, which was cultured at 37 ° C. for 24 hours, and then the growth in the milk medium was evaluated by the number of living lactic acid bacteria.

3. Ultraviolet ray damage reducing agent In the present invention, an ultraviolet ray damage reducing agent comprising the lactic acid bacteria of the Lactobacillus sp. Here, the term “reducing ultraviolet damage” as used in the present invention refers to a substance that exhibits any of the effects of improving the ultraviolet resistance at the site irradiated with ultraviolet light, reducing redness of the skin, or reducing pigmentation of the skin.
The ultraviolet damage reducing agent may be the lactic acid bacterium itself after fermentation of the lactic acid bacterium, or may be extracted and powdered by concentration, separation, or the like after fermentation. Furthermore, the lactic acid bacterium may contain other components (for example, sugars, proteins, amino acids, lipids, moisture, vitamins, minerals, etc.). Further, it goes without saying that the ultraviolet damage reducing agent may be in a water-containing form or a dry form.

4). Skin condition-improving agent In the present invention, a skin condition-improving agent comprising the lactic acid bacteria of the Lactobacillus sp. Here, the improvement of the skin condition referred to in the present invention means an effect that exhibits any of the following effects: facial skin color, dullness improvement, stickiness of the face, or oiliness improvement.
The skin condition-improving agent may be the lactic acid bacterium itself after fermentation of the lactic acid bacterium, or may be extracted and powdered by concentration, separation, or the like after fermentation. Furthermore, the lactic acid bacterium may contain other components (for example, sugars, proteins, amino acids, lipids, moisture, vitamins, minerals, etc.).
Furthermore, it goes without saying that the skin condition improving agent may be in a water-containing form or a dry form.

5. Food and drink for skin The UV damage reducing agent or skin condition improving agent of the present invention can be used as a food and drink for skin by containing it in a food or drink. The UV damage reducing agent or skin condition improving agent of the present invention can be particularly suitably used for dairy products. For example, fermented milk containing lactic acid bacteria and lactic acid bacteria-containing beverages containing lactic acid bacteria can be considered. The current ministerial ordinance on milk and dairy product component specifications does not specify the number of lactic acid bacteria as a component standard, but fermented milk (non-fat milk solid content of 8.0% or more) and lactic acid bacteria beverage (non-fat milk solids) 1.0 × 10 ⁷ cfu / ml or more if it ’s 3.0% or more), and 1.0 × 10 ⁶ cfu / ml or more if it ’s a lactic acid bacteria beverage (non-fat milk solid content less than 3.0%). The above-mentioned number of bacteria can be realized by growing or growing in the form of a final product.
In addition to fermented milk containing lactic acid bacteria and lactic acid bacteria beverages containing lactic acid bacteria, it can also be used for dairy products such as butter, processed egg products such as mayonnaise, and confectionery breads such as butter cake. Moreover, it can utilize suitably also for processed foods, such as instant noodles and a cookie. In addition to the above, the food of the present invention may be in the form of a formulation (for example, powder, granule, capsule, tablet, etc.) by adding an appropriate carrier and additives as necessary together with the lactic acid bacteria. .

  The lactic acid bacteria used in the present invention are also useful for inclusion in foods for specified health use, dietary supplements, etc. in addition to general beverages and foods.

 The skin food or drink of the present invention only needs to contain the ultraviolet damage reducing agent or skin condition improving agent of the present invention as an active ingredient, and other components (in addition to the ultraviolet damage reducing agent or skin condition improving agent) ( For example, saccharides, proteins, amino acids, lipids, moisture, vitamins, minerals, etc.) may be included.

6). Skin care pharmaceuticals The ultraviolet damage reducing agent or skin condition improving agent of the present invention is prepared by extracting and pulverizing after fermentation by concentration, separation or the like, and then using the ultraviolet damage reducing agent or skin condition improving agent as an active ingredient. It can be used as a medicinal product. For example, it can be provided in the form of a tablet obtained by granulating, encapsulating, or compressing a product obtained by filling an extract into a bottle or using a fermented liquid dry powder with excipients.
In addition, the dermatological drug of the present invention only needs to contain the ultraviolet damage reducing agent or skin condition improving agent of the present invention as an active ingredient, and other components (for example, the ultraviolet damage reducing agent or skin condition improving agent (for example, Of course, saccharides, proteins, amino acids, lipids, moisture, vitamins, minerals, etc.) may be contained.

The lactic acid bacteria (Lactobacillus gasseri N320 strain) used in the present invention can be used as an ultraviolet damage reducing agent or a skin condition improving agent containing the lactic acid bacteria as an active ingredient. In addition, daily ingestion of dermatological drugs or skin foods and drinks containing the UV damage-reducing agent or skin condition-improving agent as an active ingredient, for example, improving UV resistance at UV-exposed sites and reducing skin redness It is possible to reduce UV damage including reduction of skin pigmentation, improve skin color and dullness of the face, and improve skin condition including improvement of stickiness and oiliness of the face.

Test Example 1 Skim Milk Medium Proliferation Test A Lactobacillus gasseri N320 strain of the present invention and three Lactobacillus gasseri comparative strains (N219, N220, N313) owned by the company were subjected to a skim milk medium growth test.

  Each strain was inoculated into a 10% skim milk medium and cultured at 37 ° C. for 24 hours, and then the viability of the lactic acid bacteria was measured to evaluate the growth on the skim milk medium.

  The results are shown in Table 3 and FIG.

The viable count of the strain of the present invention (Lactobacillus gaselli N320 strain) is 22 × 10 ⁷ cfu / ml, which is highly proliferative compared to other comparative strains, producing fermented milk containing lactic acid bacteria and lactic acid bacteria-containing beverages containing lactic acid bacteria It was a level with no problem.

<Test Example 2> Efficacy evaluation test for human subjects
A total of 70 subjects were selected from 35 groups belonging to Fitzpatrick Skin Type II or III who are 30 to 49 years of age and belong to the major Japanese skin types, and an efficacy evaluation test was conducted. When screening, random numbers are used to assign gender, age, minimum erythema amount (MED), skin brightness (L * value), skin redness (a * value) as much as possible between groups. It was.

  In addition, Fitzpatrick skin type refers to the classification of skin color type, especially type II shows a reaction that the skin turns red (sunburn) when exposed to sunlight (ultraviolet rays) and a reaction that turns black after a while. Sometimes referred to as (Santan) skin type. Type III refers to a skin type that exhibits a reaction that makes the skin red when exposed to sunlight (ultraviolet rays) and a reaction that becomes black after a while.

<Preparation of test meal>
A hard capsule containing 20 mg of Lactobacillus gasseri N320 strain per day as a test meal and a hard capsule containing only excipients as a placebo meal were prepared. In addition, this strain contained in the test meal is dead cells.

<Test method>
A placebo-controlled, randomized, double-blind, parallel group comparison study was performed on these subjects. Each subject was ingested once a day for a total of 9 weeks (63 days), including a test week or a placebo diet for 8 weeks, including a test period of 1 week. Subjects were instructed to observe the following restrictions during the study period. The test was conducted after obtaining consent from the ethical considerations.
(1) During the test period, be careful not to be exposed to excessive UV rays beyond daily life. When going out, wear clothing that does not expose the UV irradiation site.
(2) During the test period, maintain lifestyles such as eating, exercising, drinking, and sleeping hours before changing the test. (Limitations)
(3) During the test period, avoid excessive exercise, sleep deprivation, dieting and heavy eating and drinking (banquets, all-you-can-eat, buffet, etc.) that greatly deviate from the daily range. (Limitations)
(4) Do not take medicines during the test period unless it is unavoidable. When taking medicines, record the name of the medicine and the amount taken. (Limitations)
(5) During the test period, it is prohibited to receive aesthetic medicine and special skin care treatments (esthetics, etc.). (Prohibited matter)
(6) Cosmetics (including skin care products) and quasi-drugs (medicinal cosmetics) that have the same or related effects (whitening / skin-beautifying effects) as or related to the efficacy studied in this study. Including) or health foods (especially those containing yogurt, lactic acid bacteria preparations, vitamins, polyphenols, etc.). (Prohibited matter)
(7) Stay up late for 3 days before the test date, and all night and intense exercise (breathing running, swimming, climbing, etc.) are prohibited. (Prohibited matter)
(8) Bath on the day before the test day before going to bed, and on the day of the test, bathing (including a shower) is prohibited from getting up to the end of the test. (Prohibited matter)
(9) Prohibit drinking the day before the test date, sleep well, and maintain physical condition.

 As a general rule, the subject management items described above must be observed, but this does not apply to cases where there is a medical need or other danger to life or physical safety. In the event that a matter that contradicts subject management matters occurs, the subject will immediately contact the study site. The subjects evaluated the MED, L * value, and a * value of the ultraviolet irradiation site before ingestion and 8-9 weeks after ingestion. In addition, a usability questionnaire was conducted at 0 weeks of intake, 4 weeks of intake, and 9 weeks of intake.

  MED was determined to be the smallest amount of energy that caused erythema by irradiating the back of the subject with ultraviolet rays having an energy amount of 1.2 in 6 steps and observing the irradiated site one day later. The larger the MED, the higher the resistance to ultraviolet light.

  The L * value and the a * value were evaluated with a spectrocolorimeter for the irradiated part 1 day after irradiation and 7 days after irradiation with 1.5 times the amount of MED determined in the pre-intake examination. It shows that pigmentation is suppressed as the L * value increases, and inflammation is suppressed as the a * value decreases.

The usability questionnaire is about the subject's skin condition or trouble, 1: very concerned, 2: a little worried, 3: not say either, 4: not much, 5: not at all It was evaluated as a 5-point score.

<Result>
Excluding those who dropped out during the study period, 33 test food groups and 32 placebo groups were used in the analysis.
When analysis was performed on subjects with high sensitivity to ultraviolet rays (the degree of pigmentation due to ultraviolet rays was greater than the average of subjects), as shown in FIG. 2, the amount of change in MED before and after intake of the test meal increased significantly. There was no significant difference in the placebo group.

 In addition, analysis was performed on subjects who were also highly sensitive to ultraviolet rays. As shown in FIGS. 3 and 4, the L * value change amount after 7 days of ultraviolet irradiation was significant in the test food group compared to the placebo group. The tendency increased and the a * value change was significantly suppressed.

  As shown in FIGS. 5 and 6, the usability questionnaire was analyzed. As shown in FIG. 5 and FIG. 6, the amount of change in score in the items of “skin color / dullness” and “stickiness / oiliness” of the face, Significant improvement in scores was observed in the test food group at 4 and 9 weeks of ingestion. There was no significant difference in the placebo group.

 As a result of a placebo-controlled randomized double-blind parallel group comparison test, the UV damage-reducing agent and skin condition-improving composition based on lactic acid bacteria of the Lactobacillus gasseri species are highly sensitive to UV rays, It was confirmed that there was an improvement in UV resistance, suppression of inflammation and pigmentation at the UV-irradiated site, improvement of facial skin color and dullness, improvement of facial stickiness and oiliness.

Claims (5)

An orally administrable skin UV damage-reducing agent or skin condition improving agent comprising a lactobacillus species of Lactobacillus gasseri as an active ingredient.
The UV damage reduction of the skin includes any of the effects of improving the UV resistance of the UV irradiation site, reducing the redness of the skin or reducing the pigmentation of the skin, and improving the skin condition includes improving the skin color of the face, dullness, The ultraviolet damage reducing agent or skin condition improving agent according to claim 1, comprising any effect of improving the stickiness of the face or oiliness.
The said lactic acid bacteria is a Lactobacillus gasseri N320 strain | stump | stock (NITE BP-02287), The ultraviolet damage reduction agent or skin condition improvement agent of Claim 1 or 2.
A skin food or drink comprising the ultraviolet damage reducing agent or the skin condition improving agent according to any one of claims 1 to 3 as an active ingredient.
  A skin medicinal product comprising the ultraviolet damage reducing agent or skin condition improving agent according to any one of claims 1 to 3 as an active ingredient.

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