JP7836064B2 - Pore-improving agent - Google Patents

Description

This invention relates to a naturally derived, highly safe oral pore-reducing agent that can shrink pores in humans and other organisms, and is suitable for continuous oral intake.

In recent years, concerns about visible pores have increased, particularly among young women, and there is a growing demand for topical skin treatments to improve this appearance. Common methods for improving visible pores include using astringent lotions and removing blackheads. Alternatively, foundation is often used to improve the appearance. However, astringent lotions, for example, aim to tighten the skin by temporarily lowering the skin surface temperature with alcohol or coagulating proteins with organic acids. Therefore, they place a significant burden on the skin and do not provide a fundamental solution to visible pores, nor are their effects sufficient.

For these reasons, there is a need for a naturally derived, highly safe oral pore-reducing agent that can be continuously ingested by humans (Patent Document 1).

Japanese Patent Publication No. 2011-184356 Japanese Patent Publication No. 2020-45308 Patent No. 4108069 Japanese Patent Publication No. 2002-030093 Japanese Patent Publication No. 2006-232699 Japanese Patent Publication No. 2014-94929

The present invention aims to provide a naturally derived, highly safe oral pore-reducing agent (material) that can shrink pores in humans and other organisms, and is suitable for continuous oral intake.

This invention was made to solve the above-mentioned problems. The inventors explored the effects of an extract (containing ceramide) obtained from rice seeds with ethanol, and as a result, invented this invention.

The present invention includes the following embodiments.
(1) An orally administered pore-reducing agent containing ceramide (for example, ceramide derived from rice).
(2) A method for producing an orally ingestible pore-reducing agent, comprising the step of extracting rice seeds with ethanol.
(3) An oral composition containing the agent described in (1) or the agent manufactured by the manufacturing method of (2).

The agents of the present invention can, for example, be used orally to reduce pore size in humans.

The present invention will be described with reference to embodiments.

(Originating from)
In the specification of this application, the phrase "derived from" is used with the intention of encompassing (1) to (3) below.
(1) It is purified,
(2) being isolated, and/or (3) being modified [this includes depolymerization and polymerization (polymerization)] or otherwise altered.

(Ceramide)
Ceramides have a structure in which a fatty acid is bound to sphingosine, a long-chain base. Keratinocytes in the later stages of differentiation (granular layer) synthesize various ceramides, and the diversity of these molecules is due to the diversity of hydroxylation (non-hydroxy, 2-hydroxy, and terminal ω-hydroxy) of the fatty acid and sphingosine base that constitute ceramide. In addition to the diversity of hydroxylation, there is also diversity in the chain length of the fatty acid and sphingosine base. These ceramides are found in living organisms in addition to the skin, in the blood, brain, spinal cord, and nerve tissue, and in plants they are found in pineapple, peach, konjac, wheat, rice, soybean, millet, spinach, mushrooms, etc. (Patent Document 2). In the present invention, ceramide includes, for example, glucosylceramide (a type of sphingoglycolipid in which ceramide is bound to glucose).

Methods for extracting ceramides from plant-based materials include, for example, extraction using an alcohol-based solvent (e.g., ethanol) from plant-based materials such as seeds of pineapple, peach, konjac, yuzu, grapes, and cherries, as well as wheat, rice, and soybeans (Patent Document 3); and extraction using a mixed solvent of hexane, acetone, and water after hydrolysis of plant-based materials such as wheat, soybeans, corn, and rice bran with an alkaline ethanol solvent (e.g., Patent Documents 4 and 5). Plant-derived ceramides, being plant-based, are gentle on the body and less likely to cause irritation when incorporated into cosmetics and supplements. However, because they are plant-derived components, their structure differs slightly from that of ceramides found in human skin.

Methods for extracting glucosylceramide from plant materials include, for example, the method described in Japanese Patent Publication No. 2001-097983, or the use of commercially available rice-derived glucosylceramide (e.g., from Nagara Science Co., Ltd.).

(Rice and rice-derived extracts)
Rice refers to the annual plant Oryza sativa (Oryza sativa LINNE), Oryza glaverrima, and their hybrids, which are cultivated varieties of the genus Oryza. The rice used in this invention may be Japonica, Javanica, or Indica, and may be non-glutinous rice, glutinous rice, sake rice, or feed rice. The rice variety used in this invention is not particularly limited and is not limited to any variety that is commonly cultivated as a crop. The rice used in this invention may also be rice bred using hybrid technology. Rice bred using hybrid technology is a first-generation hybrid obtained by crossing two different strains of rice varieties, and generally possesses hybrid vigor (generally resulting in increased yield potential, improved resistance to biological and abiotic stressors, etc.) which is superior to either of the parents. In order to produce ceramide (a ceramide-containing agent) according to the present invention, rice seeds can preferably be used, taking into consideration the ceramide content.

For obtaining rice-derived extracts, organic solvents such as water, alcohols (e.g., anhydrous ethanol, ethanol, propylene glycol, 1,3-butylene glycol, etc.), ketones such as acetone, and esters such as diethyl ether, dioxane, and ethyl acetate can be used individually or in combination of two or more solvents. The solvent extracts can also be used in their combined state. However, the use of hexane as a solvent is undesirable because it may result in the inclusion of other lipid-soluble components such as ceramides in the extract. Ethanol is preferably used. The amount of solvent used is 1 to 100 parts by weight, preferably 10 to 100 parts by weight, per 1 part by weight of the plant material for extraction.

Furthermore, alkaline organic solvents can be used by adding potassium hydroxide, sodium hydroxide, or the like to these alcohol-based solvents to make them alkaline. The lower limit of the alkali concentration is preferably 0.01 N, more preferably 0.1 N. The upper limit of the alkali concentration is preferably 1 N, more preferably 0.5 N, and even more preferably 0.4 N.

There are no particular restrictions on the extraction method, but generally, any method within the boiling point range of the solvent at room temperature and atmospheric pressure is acceptable, and filtration after extraction is sufficient. Any commonly applied extraction method may be selected and used as appropriate.

The rice-derived extract used in this invention can be prepared, for example, by the manufacturing method described in Production Example 1 below. The rice-derived extracts described in the following examples are those prepared by Production Example 1.

(Manufacturing Example 1) Method for producing rice-derived extract 881 g of rice Oryza sativa Linne (Gramineae) seeds were extracted with 0.2 N potassium hydroxide-ethanol. The extract was purified by silica gel column, neutralized, and desalted to obtain 20 g of rice extract from the concentrated purified solution. 800 g of excipient (dextrin) was added to 200 g of rice extract and dried to obtain 1000 g of a white to pale yellow powder.

(Recommended intake)
The daily intake of the rice-derived extract used in this invention (when taken as an oral composition) can be appropriately adjusted depending on the form of intake, purpose of use, age, body weight, etc. However, in order to exert the desired effect (such as pore reduction), the daily intake of the rice-derived extract per adult human is preferably 20 mg/day or more, more preferably 40 mg/day or more, and even more preferably 60 mg/day or more, when converted to dry matter. From the viewpoint of safety in humans, etc., when such intake is performed, it is preferably 480 mg/day or less, more preferably 360 mg/day or less, and even more preferably 180 mg/day or less.

(Form of pore-tightening agent for oral intake)
The form of the agent (material for shrinking pores) according to the present invention is not particularly limited, but examples include liquid form, solid form, powder form, etc.

(Oral composition)
The oral compositions according to the present invention include, for example, foods and beverages (including functional foods, foods for specified health uses, supplements, etc.), pharmaceuticals, and the like.

For example, if the oral composition is a food or beverage, the form of the food or beverage may include various foods and beverages such as bread, cakes, noodles, confectionery, jellies, frozen foods, ice cream, dairy products, and beverages, as well as forms similar to those of the oral administration preparations described above (tablets, capsules, syrups, etc.). Foods in various forms can be prepared using the active ingredient of the present invention alone, or in appropriate combinations with other food materials, solvents, softeners, oils, emulsifiers, preservatives, flavorings, stabilizers, colorants, antioxidants, humectants, thickeners, etc.

For example, if the oral composition is a pharmaceutical, it is generally easy to assemble a convenient daily dosing regimen that can be adjusted according to the degree of discomfort, but the form of the pharmaceutical may be, for example, a solid or a liquid. Examples of solid forms include powders, tablets, pills, capsules, cachets, lozenges, suppositories, and dispersible granules. For example, in the case of a powder, the carrier is generally a finely ground solid that is a mixture with the finely ground active ingredient. For example, in the case of a tablet, the active ingredient is generally mixed in an appropriate proportion with a carrier having the necessary binding ability and molded into the desired shape and size. Suitable carriers may, but are not limited to, magnesium carbonate, magnesium stearate, talc, sugars, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low-melting-point waxes, cocoa butter, etc. The pharmaceutical product may contain, as necessary, excipients, stabilizers, preservatives, binders, disintegrants, hydrocarbons, fatty acids, alcohols, esters, pH adjusters, antiseptics, etc., to the extent that it does not impair the desired effect.

(pores)
Pores that widen their openings on the skin surface due to aging, etc., are openings that have a reduced convex edge on the skin surface's uneven structure, and exhibit a mortar-like slope from the edge of the opening to the bottom center. There is no specific age at which this occurs; rather, individuals may become aware that their pores have become more noticeable with age. Pores vary from person to person, and in particular, aging can cause the opening on the skin surface to widen, resulting in a mortar-like shape, with a longer slope and a wider bottom (Patent Document 6).

While everyone has pores on their face, the way they appear, and whether or not someone is concerned about them, varies greatly from person to person. However, for women, for example, visible pores are often perceived negatively rather than positively, and there is a demand for effective makeup techniques that minimize the appearance of pores (Patent Document 6).

As mentioned above, the visibility of pores varies from person to person, but one of the contributing factors is aging. Generally, with age, the opening of the pore on the skin surface tends to widen morphologically, and this is one of the reasons why pores become more noticeable with age. In younger people, the pore morphology is thought to consist of relatively cylindrical depressions that occur independently, but with age, the opening of the opening is due to a reduction in the edges of the convex structure of the uneven structure of the skin surface, resulting in the depressions becoming more noticeable. Morphologically comparing the pores of both age groups, in younger people, the skin surface is characterized by a "fine texture," with pores being small and inconspicuous, or if present, exhibiting a vertical cylindrical shape. In contrast, with age, the opening of pores on the skin surface widens, and from there, it is thought to exhibit a slope towards the bottom of the central part, like the slope of a mortar. Thus, since the morphology of pores differs with age, there is no single method for simply concealing pores, and suitable makeup methods for this purpose also differ (Patent Document 6).

The present invention will now be described in more detail with reference to examples, but the present invention is not limited in any way to these examples. In the following examples, the unit % indicating the content of components contained in the agent of the present invention means mass %.

The following describes embodiments of the present invention.

[Test 1: Confirmation of the components of the agent used in Test 2 (containing rice-derived extract)]
The content of a predetermined glucosylceramide in a preparation containing rice-derived extract prepared according to the above-described manufacturing example 1 was measured. The composition of the preparation (powder) is 20% rice-derived extract and 80% dextrin.

Approximately 50 mg of the agent was accurately weighed, dissolved in 3 mL of water, and then 17 mL of methanol was gradually added while stirring. Chloroform was added to this solution to make exactly 50 mL, and the solution was filtered through a membrane filter (pore size 0.45 μm) to obtain the filtrate as the test solution.
Separately, 6 mg of rice-derived glucosylceramide (Nagara Science) was precisely weighed, dissolved in a chloroform/methanol mixture (2:1), and the total volume was made exactly 50 mL to prepare the standard solution.
Three μL of the test solution and one, two, three, four, and five μL of the standard solutions were measured, and liquid chromatography was performed under the following conditions. Next, the peak area of glucosylceramide in each standard solution was measured, and a calibration curve was created. The concentration of glucosylceramide in the test solution was determined from the calibration curve, and the glucosylceramide content in the product was measured.

Measurements taken under the following conditions confirmed that the agent contains 10.0% or more glucosylceramide.

Operating conditions:
• Detector: Light scattering detector • Column packing material: 2.2 μm silica gel for liquid chromatography • Column tube: Stainless steel tube with an inner diameter of 3.0 mm and a length of 75 mm • Column temperature: Constant temperature around 35°C • Mobile phase: 0 min → 5 min Chloroform/95 vol% methanol solution mixture (99:1) → (75:25)
5 minutes → 6.5 minutes Chloroform/95 vol% methanol solution mixture (75:25) → (10:90)
6.5 min → 8 min Chloroform/95 vol% methanol solution mixture (10:90) → (99:1)
・Flow rate: 0.8mL/min

[Test 2: Human Monitor Test]
The study was conducted between April 5, 2021 and April 20, 2021, with 10 healthy male and female subjects aged 30 to 50.

An oral composition (capsule) was prepared for use in this experiment 2. The daily intake of this capsule had the composition shown in Table 1 below.

The subjects took the capsules listed in Table 1 once a day between meals. On day 0 (before ingestion), day 3 (3 days after ingestion), day 7 (7 days after ingestion), and day 14 (14 days after ingestion), the following parameters (total volume of pore openings, total pore area, and deepest pore depth) were measured on the face (both cheeks) using the ANTERA3D ^™ skin analyzer. The measurement results (numerical values) are listed in Table 2. The total volume of pore openings (cubic millimeters) is the total volume of rough areas related to pores in the selected area. The total pore area (square millimeters) is the sum of the areas measured. The deepest pore depth (millimeters) is the maximum pore depth in the area selected for measurement.

The values listed in Table 2 were calculated as follows: First, measurements were taken of the relevant item for 10 individuals (both cheeks). After these measurements, for each of the 10 individuals, the value on day 0 was set to 100, and the values on days 3, 7, and 14 were calculated as relative values. After calculating these relative values, the average of the values on days 3, 7, and 14 was calculated. These average values are listed in Table 2.
Table 2 shows the significant difference for each measurement item compared to the mean value on day 0 (significant difference according to Dunnett's test; * indicates p < 0.01, ** indicates p < 0.05).

The results shown in Table 2 (where a decrease in values over time was observed for each measurement item) indicate that pore reduction was confirmed by taking the capsules listed in Table 1.

The embodiments of the present invention (including examples) have been described above with reference to the drawings. However, the specific configuration of the present invention is not limited thereto, and any design changes, etc., that do not depart from the spirit of the invention are still included in the present invention.

This invention provides a naturally derived, highly safe oral pore-reducing agent (material) that can shrink pores in humans and other organisms, and is suitable for continuous oral intake.

Claims (3)

A method for producing an oral composition for pore reduction containing ceramide,
The oral composition comprises an extract derived from rice and dextrin.
The method for producing the rice-derived extract is as follows:
The process includes extracting ceramide from the seeds of rice Oryza Sativa Linne (Gramineae) using a solvent.
The solvent is ethanol containing 0.01 N to 1 N potassium hydroxide.
A method for producing the oral composition for pore reduction. The manufacturing method according to claim 1, wherein the solvent is solely ethanol containing 0.1 N to 0.5 N potassium hydroxide. The manufacturing method according to claim 1 or 2, wherein the amount of solvent used is 1 to 100 parts by weight per 1 part by weight of the rice seeds.