JP7530200B2 - Skin redness relief agent - Google Patents

Description

The present invention relates to an agent for improving redness and dullness in the skin.

A red face is a permanent redness of the facial protrusions (nose, cheeks, forehead, chin, etc.) in which a few blood vessels may be visible to the naked eye. There are various causes of a red face, but a typical chronic disease with these symptoms is rosacea.
Rosacea refers to the external signs of a worsening red face, such as rashes, patches, irritation and redness of the eyes.

Another cause of red face is hyperkeratosis of the skin.
Here, hyperkeratosis refers to a condition in which the keratin (dead skin) that is supposed to naturally fall off on the surface of the skin remains on the skin for a long time due to the effects of weak ultraviolet rays, etc., causing the skin to thicken and harden. When the skin becomes hyperkeratotic, it loses its transparency and dullness, especially red dullness, becomes more noticeable. It has been reported that Western women tend to have more uneven redness as they age compared to Japanese women.

Under these circumstances, the present inventors have discovered that maqui berry extract has the effect of improving facial redness, and further has the effect of improving the radiance of facial skin and improving dullness, particularly red dullness, and have thus completed the present invention.
That is, the present invention aims to provide an agent for improving redness in the skin, which has the effect of improving facial redness and further has the effect of improving the color saturation of the facial skin and improving dullness, particularly red dullness.

The features of the present invention for solving the above problems are as follows.
1. A skin redness improving agent containing maqui berry (Aristotelia Chilensis) extract as an active ingredient.
2. A skin radiance enhancer containing maqui berry (Aristotelia Chilensis) extract as an active ingredient.
3. A skin dullness improving agent that contains maqui berry (Aristotelia Chilensis) extract as an active ingredient.
4. The dullness improving agent according to the above 3., wherein the dullness is red dullness.

The redness-reducing agent of the present invention has an effect of reducing redness in the skin by ingesting an extract of maqui berry (Aristotelia Chilensis), thereby reducing facial redness.
Furthermore, the color enhancement agent of the present invention has a color enhancement effect by ingesting maqui berry (Aristotelia Chilensis) extract.
Here, the above-mentioned "colorfulness" is a value between 0 and 100 evaluated by the Robo Skin Analyzer, and indicates blood circulation and dullness. A low value (20 or less) indicates a dull state caused by a thickened stratum corneum (i.e., hyperkeratosis) that makes it difficult to see the blood circulation of the skin. A high value (75 or more) indicates clear, undull skin.
Furthermore, the skin dullness improving agent of the present invention has the effect of improving skin dullness, particularly dullness caused by keratinocyte hyperplasia, since the above-mentioned color brilliance is improved.
Furthermore, the skin dullness improving agent of the present invention has effects of improving redness and dullness, and is therefore particularly effective in improving red dullness.

The present invention will be described in detail below.
The present invention is characterized in that it contains maqui berry (Aristotelia Chilensis) extract as an active ingredient.
Maqui berry (Aristotelia Chilensis) is a berry plant native to southern Chile in South America and is known to have extremely high antioxidant properties.
It is also known to contain delphinidin derivatives, delphinidin 3,5-O-diglucoside and delphinidin 3-sambubioside-5-glucoside, although these components have not been confirmed to be present in other berries, such as bilberry and blackcurrant.
Furthermore, the contents of these compounds are not particularly limited, but when the plant extract is taken as 100 wt %, it is preferable that the plant extract contains 6 to 25 wt %, preferably 10 to 20 wt %, of delphinidin 3,5-O-diglucoside, and further contains 1 to 10 wt %, preferably 4 to 8 wt %, of delphinidin 3-sambubioside-5-glucoside.

When using maqui berry to extract active ingredients in the present invention, there are no particular limitations on the part of the plant that can be used, and for example, the fruit, seeds, flowers, leaves, roots, stems, etc. can be used, with the fruit being particularly preferred, as this allows the active ingredients to be extracted in high concentrations.

As the extraction solvent, a polar solvent such as water, methanol, ethanol, isopropyl alcohol, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, ethyl acetate, etc. Two or more of these solvents may be mixed.
Preferably, water-ethanol or a mixture thereof, that is, water-containing ethanol, is used as the extraction solvent, which allows the effective ingredients to be extracted efficiently.

When water is used as the extraction solvent, the type of water is not particularly limited, and tap water, distilled water, mineral water, alkaline ionized water, deep sea water, etc. can be used.

When using hydrous ethanol as the extraction solvent, the concentration of ethanol is not particularly limited, but it is preferable that the ethanol concentration is 10 to 90% (wt/wt), and preferably 20 to 80% (wt/wt). The reason for setting the ethanol concentration at 90% (wt/wt) or less is that if the ethanol concentration is too high, the oil in the maqui berry will easily dissolve in the hydrous ethanol.

The extraction temperature should be between 20 and 80°C, preferably around 40 to 50°C. If the extraction temperature is too low, it will be difficult to extract the active ingredients, and if the extraction temperature is too high, the active ingredients will decompose, reducing their physiological activity (health functionality).

As an extraction method, any method can be used, such as stirring extraction, continuous extraction, immersion extraction, countercurrent extraction, and supercritical extraction, and any device can be used at room temperature or under reflux heating.

Specific extraction methods include placing the raw material (maqui berry fruit, etc.) in a processing tank filled with an extraction solvent, and stirring to dissolve the active ingredients. For example, when using aqueous ethanol as the extraction solvent, about 2 to 100 times (by weight) the amount of extraction solvent as the extraction raw material is used, and extraction is carried out for about 30 minutes to 2 hours. After the active ingredients have been dissolved into the solvent, the extract is obtained by filtering to remove the extraction residue.

Thereafter, the extract is subjected to treatments such as dilution, concentration, purification, drying, etc. according to conventional methods to obtain the skin redness improving agent according to the present invention.
The purification method may involve passing the extract through a synthetic adsorption resin, gel filtration resin, or the like to adsorb the active ingredient, and then eluting it with methanol, ethanol, or the like to concentrate it.

The skin redness improving agent of the present invention can be used as an ingredient in various foods and beverages. Examples of foods and beverages include general foods such as confectioneries (gum, candy, caramel, chocolate, cookies, snacks, jellies, gummies, candy tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, green tea, carbonated drinks, sports drinks, etc.), health foods (tablets, capsules, etc.), and nutritional supplements (nutritional drinks, etc.). The skin redness improving agent of the present invention can be appropriately blended into these foods and beverages.

These foods and beverages can contain various ingredients depending on the type, for example, the following food ingredients can be used: glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorings, flavorings, and preservatives.

As a specific manufacturing method, the skin redness improving agent is spray-dried or freeze-dried together with powdered cellulose, and then made into a powder, granules, tablets, or solution, which can be easily incorporated into food and beverages (instant foods, etc.). The skin redness improving agent can also be dissolved in, for example, fats and oils, ethanol, glycerin, or a mixture of these to make a liquid, which can be added to beverages or solid foods. If necessary, it can also be mixed with a binder such as gum arabic or dextrin to make a powder or granules, which can be added to beverages or solid foods.

When the skin redness improving agent of the present invention is applied to food and beverages, the amount of active ingredient added is preferably 1 to 20 wt% in total, since the main purpose is disease prevention and health maintenance.

The skin redness improving agent of the present invention may be used as a material for medicines (including pharmaceuticals and quasi-drugs). The medicines can be produced by appropriately mixing the skin redness improving agent of the present invention with raw materials for pharmaceutical preparations. Examples of pharmaceutical raw materials that can be incorporated into the skin redness improving agent of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hardened vegetable oil, kaolin, talc, etc.), binders (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, agar, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearate monoglyceride, starch, lactose, powdered gum arabic, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cacao butter, hydrogenated oil, etc.), absorption enhancers (quaternary ammonium base, sodium lauryl sulfate, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, etc.), etc.

The method of administration of the skin redness improving agent of the present invention is generally oral administration in the form of tablets, pills, soft/hard capsules, fine granules, powders, granules, liquids, etc., but it may also be parenterally administered. When administered parenterally, it may be administered in the form of a solution or with the addition of a dispersing agent, suspending agent, stabilizer, etc., by local tissue administration, intradermal, subcutaneous, intramuscular, or intravenous injection. It may also be in the form of a suppository, etc. Furthermore, it may be administered as an eye drop.

The dosage may vary depending on the method of administration, the condition, the age of the patient, etc., but typically, an adult may be administered 0.5 to 5,000 mg of the active ingredient per day, and a child may be administered 0.5 to 3,000 mg.
The compounding ratio of the redness improving agent in the skin can be appropriately changed depending on the dosage form, but it is usually about 0.3 to 15.0 wt% when administered orally or via mucosal absorption, and about 0.01 to 10 wt% when administered parenterally. Note that the dosage varies depending on various conditions, so in some cases a smaller dosage than the above-mentioned dosage is sufficient, and in other cases it is necessary to administer an amount exceeding the range.

The following are examples of the present invention. Note that the examples shown below are provided to confirm the various actions and effects of the skin redness relief agent obtained by the present invention, and the scope of the present invention is not limited to these products and manufacturing methods.

Example: Preparation of Maqui Berry Extract Maqui berry (Aristotelia Chilensis) fruit was extracted with distilled water at 50°C by stirring. The extract was then filtered and passed through a synthetic adsorbent column, and the maqui berry extract containing the active ingredient was eluted with 80% ethanol aqueous solution. It was then dried to obtain a maqui berry extract (Example). The maqui berry extract of Example 1 was analyzed by HPLC and found to contain 12.26% delphinidin 3,5-diglucoside and 7.76% delphinidin 3-sambubioside-5-glucoside.

Test materials and test method 1. Test design This test was a placebo-controlled comparative study on 16 healthy female subjects, who were given either the above maqui berry extract or a placebo for 8 weeks. Facial color (colorfulness), number of red spots (Level 1, 2, 3), and area (Level 1, 2, 3) were evaluated before, 4 weeks after, and 8 weeks after intake. Allocation was performed before the start of the test, and 8 subjects were assigned to each group as described in 3. Subjects below.

The test products were hard capsules containing 60 mg of the above-mentioned maqui berry extract or hard capsules filled with excipients alone as a placebo. Subjects were asked to take one capsule per day for an 8-week intake period.

3. Subjects The subjects were healthy adult women, excluding those who (1) suffered from a serious illness, (2) suffered from a chronic illness including asthma, (3) showed an allergic reaction to the test product, and (4) suffered from atopic dermatitis. The subjects were 16 healthy women aged 27 to 57 years old, sorted by age, and assigned to two groups based on age. It was confirmed that there was no difference in the average age between the groups. The average age of each group was 37.3 ± 8.9 years for the maqui berry extract intake group and 38.5 ± 10.5 years for the placebo group.

4. Measurement items Using Robo Skin Analyzer (Inforward, Inc.), the number of rednesses (Levels 1, 2, 3) and the color tone (saturation) of the face were measured. Here, redness is defined as two groups in the three-dimensional space of the color image (RGB): "skin-colored areas containing redness" and "skin areas without redness or pigmentation." The vector connecting these groups is used as a reference to define the redness based on the shade of the image in which the color information of the image is converted into one dimension (monochrome). The redness evaluated by Robo Skin Analyzer can be detected from Level 1 to Level 2 to Level 3 as the degree of redness increases. Since Level 1 includes light to dark redness, it can be said that Level 1 has high detection sensitivity and Level 3 has low detection sensitivity.
Furthermore, "colorfulness" is a number between 0 and 100 that is evaluated by the Robo Skin Analyzer, and indicates blood circulation and dullness. A low number (20 or less) indicates a dull state caused by a thickened stratum corneum (i.e., hyperkeratosis) that makes it difficult to see the blood circulation in the skin. A high number (75 or more) indicates clear, unblemished skin.
Measurements were taken three times: before intake, after 4 weeks, and after 8 weeks. The subjects were asked to remove their facial makeup 15 minutes before entering the measurement room, and were allowed to acclimate for 15 minutes in a room with a temperature of 25±1°C and humidity of 50%±5% before the measurements were taken.

5. Statistical analysis The measured values for each item are shown as the mean ± standard deviation. Significant differences were tested by analysis of variance followed by intergroup comparison (Welch's t test) of the difference before and after intake. All tests were two-tailed.
The results are shown in Table 1 (redness) and Table 2 (color (saturation)).

Measurement results and effects of the embodiment Table 1 above shows the number (Level 1, 2, 3) and area (Level 1, 2, 3) of redness before and after intake, as well as the amount of change before and after intake. Significant improvement was observed between the placebo group and the maqui berry extract group in the amount of change in the area (Level 1) and number (Level 2) of redness after 4 weeks of intake. Significant improvement was observed between the placebo group and the maqui berry extract group.

In Table 2, saturation is expressed on a scale of 0 to 100, with the higher the value, the more toned the skin is. Therefore, since saturation was significantly higher in the maqui berry extract group after ingestion, it was confirmed that the skin tone was improved, and this confirmed that the maqui berry extract has an effect of improving skin sagging. This confirmed that maqui berry extract is useful as a saturation enhancer and a dullness improver.
In addition, the number and area of redness were significantly reduced (Table 1), and dullness was improved (Table 2), confirming that red dullness was improved. This confirmed that maqui berry extract is useful as an agent for improving red dullness.

The following are examples of the formulation of the skin redness improving agent (maqui berry extract) according to the present invention. Note that the following formulation examples do not limit the present invention.
Formulation example 1: Chewing gum
Sugar 53.0wt%
Gum base 20.0
Glucose 10.0
Syrup 16.0
Fragrance 0.5
Skin redness relief agent 0.5
100.0wt%

Mixture Example 2: Gummies
Reduced starch syrup 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Yuzu juice 4.0
Yuzu flavor 0.6
Pigment 0.02
Skin redness relief agent 1.0
100.0wt%

Mixture example 3: Candy
Sugar 50.0wt%
Syrup 33.0
Water 14.4
Organic acids 2.0
Fragrance 0.2
Skin redness relief agent 0.4
100.0wt%

Mixture example 4: Yogurt (hard/soft)
Milk 41.5wt%
Skim milk powder 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Skin redness relief agent 0.4
Fragrance: Trace
Water Residual
100.0wt%

Mixture example 5: Soft drinks
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Skin redness relief agent 0.3
Fragrance (appropriate amount)
Purified water Residual
100.0wt%

Mixture Example 6: Tablets
Sugar 76.4wt%
Glucose 19.0
Sucrose fatty acid ester 0.2
Skin redness relief agent 0.5
Purified water 3.9
100.0wt%

Formulation Example 7: Soft Capsule
Brown rice germ oil 47.0wt%
Yuzu seed oil 40.0
Emulsifier 12.0
Skin redness relief agent 1.0
100.0wt%

Formulation Example 8: Tablets
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch hydrolysate 10.0
Glycerin fatty acid ester 5.0
Skin redness relief agent 1.0
100.0wt%

Formulation Example 9: Eye drops Ketotifen fumarate 0.7 wt%
Sodium azulene sulfonate 0.2
Sodium cromoglycate 9.8
Potassium L-aspartate 8.5
Allantoin 3.0
Tetrahydrozoline hydrochloride 0.5
Neostigmine methylsulfate 0.05
Benzalkonium chloride solution 0.1
Glycerin 25.0
Skin redness relief agent 1.0
pH adjuster (appropriate amount)
Purified water Remainder
100.0wt%

As described above, the present invention can provide a skin redness improving agent that has the effect of improving facial redness, and further has the effect of improving the color of facial skin and improving dullness, particularly red dullness.

Claims (2)

An oral skin redness improving agent containing maqui berry (Aristotelia Chilensis) extract as an active ingredient. An oral skin dullness improving agent containing maqui berry (Aristotelia Chilensis) extract as an active ingredient,
The above-mentioned dullness refers to red dullness, and is an oral dullness-improving agent.