JP7634252B2 - Oral composition for reducing or inhibiting skin damage induced by ultraviolet exposure - Google Patents

Description

The present invention relates to an oral composition containing rice extract that has excellent effects of reducing and inhibiting skin damage induced by exposure to ultraviolet rays.

As a means of suppressing or reducing skin damage caused by ultraviolet rays, many topical skin preparations such as sunscreens containing ultraviolet scattering agents or ultraviolet absorbing agents have been proposed. Since the condition of the skin is also affected by oral intake such as food, it is considered important to prevent skin damage induced by ultraviolet exposure using foods that can be safely ingested for a long time, and attempts have been made to develop foods that have the effect of suppressing or reducing skin damage induced by ultraviolet exposure. For example, it is known that oral intake of a composition containing methylhesperidin has the effect of suppressing erythema and reduced keratin function caused by ultraviolet exposure (Patent Document 1), and oral intake of a composition containing taurine has the effect of improving wrinkles caused by ultraviolet rays (Patent Document 2). However, the compositions developed so far are not necessarily sufficiently effective, and there is a need to develop a new oral composition that is safe and can be used to suppress or reduce skin damage induced by ultraviolet exposure.

On the other hand, rice extract is known to have anti-fatigue effects (Patent Document 3), but its effect on skin disorders induced by exposure to ultraviolet light is unknown.

JP 2016-104806 A JP 2017-025097 A JP 2007-230881 A

The objective of the present invention is to provide an oral composition that has excellent effects of reducing and suppressing skin damage induced by exposure to ultraviolet rays.

The applicant has conducted extensive research to solve the above problems and has surprisingly found that by including rice extract, an oral composition can be obtained that is excellent in reducing and inhibiting skin damage induced by exposure to ultraviolet light. The present invention was completed based on this finding.

The outline of the present invention is as follows:

[1] An oral composition for reducing or suppressing skin damage induced by exposure to ultraviolet rays, comprising a rice extract.
[2] An oral composition for reducing or inhibiting skin erythema induced by exposure to ultraviolet light, comprising a rice extract.
[3] An oral composition for suppressing the expression of erythema induction-related genes interleukin-1β, interleukin-6, or cyclooxygenase-2 induced by ultraviolet exposure, characterized by containing a rice extract.
[4] The composition according to any one of [1] to [3], wherein the rice extract contains ceramide.
[5] The composition according to [4], wherein the ceramide is glucosylceramide.
[6] The composition according to [5], wherein the glucosylceramide is a glucosylceramide represented by the following general formula (1):

The oral composition of the present invention effectively suppresses the expression of interleukin-1β (hereinafter also referred to as "IL-1β"), interleukin-6 (hereinafter also referred to as "IL-6"), or cyclooxygenase-2 (hereinafter also referred to as "COX-2"), which are genes related to erythema induction induced by ultraviolet exposure, and is therefore excellent in reducing or suppressing skin erythema induced by ultraviolet exposure, and exerts an excellent effect of reducing or suppressing skin disorders induced by ultraviolet exposure.

FIG. 1 shows the expression levels of the erythema induction-related gene IL-1β in Example 1 and Comparative Examples 1 and 2. FIG. 2 is a diagram showing the expression levels of the erythema induction-related gene IL-6 in Example 1 and Comparative Examples 1 and 2. FIG. 3 is a diagram showing the expression levels of the erythema induction-related gene COX-2 in Example 1 and Comparative Examples 1 and 2.

The present invention will be described in detail below. Note that the present invention is not limited to the following embodiments.

The present invention uses rice extract as an essential ingredient. In this specification, rice means seeds and nuts of the genus Oryza. The rice used in the present invention is not particularly limited as long as it belongs to the genus Oryza, but rice (Oryza sativa) is preferred from the viewpoint of reducing or inhibiting skin disorders induced by ultraviolet exposure. There are no limitations on the variety or type, and japonica rice, indica rice, non-glutinous rice, glutinous rice, etc. can be used, but in the present invention, non-glutinous rice (Oryza sativa Linne (Gramineae)) is preferred from the viewpoint of reducing or inhibiting skin disorders induced by ultraviolet exposure. Furthermore, raw or dried rice can be used in the present invention.

The processed form of rice used in the present invention is not particularly limited, and examples include white rice, brown rice, rice bran, and the like. In the present invention, from the viewpoint of reducing or inhibiting skin disorders induced by exposure to ultraviolet light, brown rice and rice bran are preferred, and rice bran is more preferred.

The method for extracting rice extract is not particularly limited and can be appropriately selected depending on the purpose. Examples of extraction methods include adding an extraction solvent commonly used by those skilled in the art, such as ethanol, water, or aqueous ethanol, and extracting by heating as necessary. In the present invention, extraction with ethanol is preferred from the viewpoint of reducing or suppressing skin damage induced by exposure to ultraviolet light.

The content of rice extract to be blended in the composition of the present invention is not particularly limited, and the content can be appropriately set within a wide range depending on various conditions such as the purpose, shape, and subject of use. For example, when the composition of the present invention is a solid preparation (powder, granules, tablet, capsule, chewable, etc.), the content is preferably 0.001 to 80 mass%, more preferably 0.01 to 50 mass%, and particularly preferably 0.1 to 30 mass%. Also, for example, when the composition of the present invention is a liquid preparation (liquid, gel, jelly, paste, etc.), the content is preferably 0.0001 to 30 mass%, more preferably 0.001 to 20 mass%, and particularly preferably 0.01 to 10 mass%.

The rice extract used in the present invention preferably contains ceramide. Ceramide is a general term for a group of compounds in which sphingosine and a fatty acid are bonded by an amide bond. In this specification, ceramide means sphingolipids, sphingoglycolipids, which are compounds in which sugars are bonded to sphingolipids via glycosidic bonds, or mixtures of these.

The type of ceramide contained in the rice extract is not limited, but from the viewpoint of reducing or inhibiting skin damage induced by exposure to ultraviolet light, it is preferably a sphingoglycolipid, more preferably glucosylceramide, which is a type of sphingoglycolipid, and particularly preferably glucosylceramide represented by the following general formula (1).

The content of ceramide in the rice extract used in the present invention is not particularly limited, but is preferably 1 to 80% by mass, more preferably 4 to 50% by mass, and particularly preferably 8 to 15% by mass.
The amount of ceramide in the composition of the present invention can be analyzed by liquid chromatography. For example, it can be measured by a high performance liquid chromatograph equipped with a light scattering detector (HPLC-ELSD), and the analytical column is Inertsil Sil 100-5 (4.6×150 mm) manufactured by GL Sciences, Inc., and the mobile phase is chloroform (mobile phase A) and 95% by volume methanol solution (mobile phase B), the column temperature is 35° C., and the flow rate is 1 mL/min. The gradient conditions can be as follows:

The content of ceramide in the composition of the present invention is not particularly limited, and the content can be appropriately set within a wide range depending on various conditions such as the purpose, shape, and subject of use. For example, when the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the content is preferably 0.001 to 50 mass%, more preferably 0.01 to 40 mass%, and particularly preferably 0.1 to 30 mass%. Furthermore, when the composition of the present invention is a liquid preparation (liquid, gel, jelly, paste, etc.), the content is preferably 0.0001 to 30 mass%, more preferably 0.001 to 20 mass%, and particularly preferably 0.01 to 10 mass%.

The daily intake amount of the oral composition of the present invention is not particularly limited and can be appropriately set depending on the mode of use and the content of use by the user. For example, when the composition of the present invention is a solid formulation (powder, granules, tablets, capsules, chewables, etc.), the daily intake amount is preferably 2 to 2000 mg/kg, more preferably 4 to 1000 mg/kg, based on the weight of the user, and particularly preferably 30 to 400 mg/kg, from the viewpoint of the reduction or suppression of skin disorders induced by ultraviolet exposure. For example, when the composition of the present invention is a liquid formulation (liquid, gel, jelly, paste, etc.), the daily intake amount is preferably 100 to 40,000 mg/kg, more preferably 300 to 30,000 mg/kg, based on the weight of the user, and particularly preferably 500 to 20,000 mg/kg, from the viewpoint of the reduction or suppression of skin disorders induced by ultraviolet exposure.

Similarly, the amount of the composition of the present invention taken at one time is not particularly limited. For example, when the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the amount is preferably 1 to 2000 mg/kg, more preferably 2.5 to 1000 mg/kg, based on the body weight of the user, and particularly preferably 10 to 400 mg/kg, from the viewpoint of the effect of reducing or suppressing skin disorders induced by ultraviolet exposure. Also, for example, when the composition of the present invention is a liquid preparation (liquid, gel, jelly, paste, etc.), the amount is preferably 50 to 40000 mg/kg, more preferably 100 to 30000 mg/kg, based on the body weight of the user, and particularly preferably 300 to 20000 mg/kg, from the viewpoint of the effect of reducing or suppressing skin disorders induced by ultraviolet exposure.

The daily intake of the composition of the present invention is not particularly limited, and for example, when the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the daily intake is preferably 0.2 to 50 g, more preferably 0.4 to 25 g, and particularly preferably 3 to 10 g from the viewpoint of reducing or suppressing skin disorders induced by ultraviolet exposure. The daily intake of the composition of the present invention is preferably 10 to 1000 g, more preferably 30 to 750 g, and particularly preferably 50 to 500 g from the viewpoint of reducing or suppressing skin disorders induced by ultraviolet exposure.

The amount of the composition of the present invention taken at one time is preferably 0.1 to 50 g, more preferably 0.2 to 25 g, when the composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), and particularly preferably 1 to 10 g from the viewpoint of reducing or suppressing skin disorders induced by ultraviolet exposure. Also, for example, when the sleep improving composition of the present invention is a liquid preparation (liquid, gel, jelly, paste, etc.), the amount is preferably 5 to 1000 g, more preferably 10 to 750 g, and particularly preferably 30 to 500 g from the viewpoint of reducing or suppressing skin disorders induced by ultraviolet exposure.

The composition of the present invention may contain only rice extract, or may contain other ingredients in addition to the rice extract. Examples of the other ingredients include proteins, dietary fibers such as soluble dietary fiber and insoluble dietary fiber, minerals, plants other than rice or processed plants, algae, lactic acid bacteria, yeast, and other microorganisms. If necessary, the composition may further include sugars such as dextrin and starch, oligosaccharides, sweeteners, acidulants, colorants, thickeners, gloss agents, excipients, vitamins, nutritional supplements, binders, lubricants, stabilizers, diluents, bulking agents, emulsifiers, food additives, seasonings, and the like that are commonly used in the food industry. The content of these other ingredients may be appropriately selected depending on the form of the composition of the present invention.

The oral composition of the present invention can be utilized in various forms for the purpose of reducing or inhibiting skin damage induced by exposure to ultraviolet light.

The composition of the present invention is not particularly limited as long as it can be distinguished from other products in terms of its use in reducing or suppressing skin disorders induced by UV exposure. For example, the scope of the present invention includes products that display on the main body, packaging, instructions, or advertising materials of the product of the present invention that it has a function of reducing or suppressing skin disorders induced by UV exposure or a function of reducing or suppressing skin erythema induced by UV exposure. Examples of the product include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods such as specified health foods, nutritional functional foods, and functional food with functional claims that have been approved by a designated organization for efficacy, and feed. Examples of so-called health foods include those that display the following: "helps protect the skin from UV irritation," "suppresses redness of skin exposed to UV," "suppresses erythema of skin exposed to UV," and "suppresses erythema of skin caused by UV."

The form of the oral composition of the present invention is not particularly limited and can be any form. For example, forms suitable for oral use, specifically, powder, granules, tablets, liquid, gel, paste, capsules such as hard capsules and soft capsules, caplets, tablets, gels, jellies, gummies, wafers, biscuits, cookies, cakes, chewable, syrups, sticks, etc., can be included, and various excipients, binders, lubricants, stabilizers, diluents, bulking agents, thickeners, gelling agents, emulsifiers, colorants, flavors, sweeteners, additives, etc. can be blended according to the form used. From the viewpoint of the effect of reducing or suppressing skin disorders induced by ultraviolet exposure, the oral composition of the present invention is preferably in the form of granules, tablets, capsules, or jelly, and more preferably in the form of granules, tablets, or capsules. Here, granules refer to a composition obtained by granulating powder, and may be directly consumed or dissolved in a liquid such as water and consumed. Additionally, gel refers to a composition that contains water and a gelling agent and has viscosity or elasticity.

The packaging form of the composition of the present invention is not particularly limited and can be appropriately selected depending on the dosage form, etc., but examples include blister packs such as PTPs, strip packaging, heat seals, aluminum pouches, film packaging using plastics or synthetic resins, glass containers such as vials, and plastic containers such as ampoules.

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples, and the present invention can take various forms as long as the object of the present invention can be solved.

<Test: Evaluation of the effect of reducing or inhibiting skin erythema induced by UV exposure>
In order to confirm that ingestion of the composition of the present invention reduces or inhibits skin erythema induced by exposure to ultraviolet light, the following test was carried out.

[Test substance]
The test substance was a powdered rice extract obtained by adding an excipient (dextrin) to the extract obtained by extracting rice bran with ethanol and drying it. The ratio of glucosylceramide in the rice extract analyzed by liquid chromatography was 10.6%. The glucosylceramide contained in the rice extract contains the compound of the general formula (1) as the main component of ceramide. In this test, the rice extract was mixed with mouse feed (MF powder feed, manufactured by Oriental Yeast Co., Ltd.) at a ratio of 5% by mass to prepare a mixed diet, which was then given to the mice ad libitum.

[Test animals]
After acclimatizing female hairless mice (HOS:HR-1), healthy 9-week-old mice were selected and divided into groups based on their body weights.

[Test group composition]
The three groups were as shown in Table 1 below.

[UV irradiation]
On day 7 after the start of the test, the back of the mouse was irradiated with UVB (40 mJ/cm ² ) using a low-pressure ultraviolet mercury lamp TL/12 series (manufactured by Philips) under isoflurane anesthesia.

[Measurement of expression levels of erythema induction-related genes (IL-1β, IL-6, COX-2)]
On the 8th day after the start of the test (24 hours after UVB irradiation), the mice were dissected under isoflurane anesthesia, and the back skin of the mice was collected using a biopsy trephine (Kai Industries). RNA was extracted from the collected skin, and the expression levels of erythema induction-related genes (IL-1β, IL-6, COX-2) were measured using real-time PCR. The gene expression levels of IL-1β, IL-6, or COX-2 in each test group were corrected by the gene expression level of GAPDH as an endogenous control, and the relative expression levels of the erythema induction-related genes were calculated when the expression level of Comparative Example 2 was set to 1.0. IL-1β and IL-6 are inflammatory cytokines induced by ultraviolet irradiation. UV irradiation of the skin promotes the production of these inflammatory cytokines, causing an inflammatory reaction in the skin and causing skin disorders such as erythema. COX-2 is a synthetic enzyme of prostaglandins involved in inflammation, and its expression is increased by ultraviolet irradiation. UV irradiation promotes the production of COX-2 in the skin, which increases inflammation-inducing prostaglandins in blood vessels, causing skin disorders such as erythema. Therefore, by evaluating the expression levels of erythema induction-related genes (IL-1β, IL-6, COX-2), it is possible to evaluate the effect of reducing or suppressing UV-induced skin erythema and the effect of reducing or suppressing UV-induced skin disorders.

[Results (inhibitory effect on expression of erythema induction-related gene IL-1β)]
The results of IL-1β expression are shown in FIG. 1 (values are average values). Compared to the group not administered with the test substance and not irradiated with UV rays (Comparative Example 1), the group not administered with the test substance and irradiated with UV rays (Comparative Example 2) had a higher expression level of IL-1β. This result confirmed that UV irradiation enhances the expression of the erythema induction-related gene IL-1β. Furthermore, the group administered with the rice extract and irradiated with UV rays (Example 1) had a 65% decrease in the expression level of IL-1β compared to the group not administered with the test substance and irradiated with UV rays (Comparative Example 2). From the above results, it was revealed that the composition of the present invention exhibits an excellent effect in suppressing the expression of the erythema induction-related gene IL-1β induced by UV exposure.

[Results (inhibition of expression of erythema induction-related gene IL-6)]
The results of IL-6 expression are shown in FIG. 2 (values are average values). Compared to the group not administered with the test substance and not irradiated with UV rays (Comparative Example 1), the group not administered with the test substance and irradiated with UV rays (Comparative Example 2) had a higher expression level of IL-6. This result confirmed that UV irradiation enhances the expression of the erythema induction-related gene IL-6. Furthermore, the group administered with the rice extract and irradiated with UV rays (Example 1) had a 47% decrease in the expression level of IL-6 compared to the group not administered with the test substance and irradiated with UV rays (Comparative Example 2). These results demonstrated that the composition of the present invention exhibits an excellent effect in suppressing the expression of the erythema induction-related gene IL-6 induced by UV exposure.

[Results (inhibition of expression of COX-2, an erythema induction-related gene)]
The results of COX-2 expression are shown in FIG. 3 (values are average values). Compared with the group not administered with the test substance and not irradiated with ultraviolet light (Comparative Example 1), the group not administered with the test substance and irradiated with ultraviolet light (Comparative Example 2) had a higher expression level of COX-2. This result confirmed that ultraviolet light irradiation enhances the expression of the erythema induction-related gene COX-2. In addition, the group administered with the rice extract and irradiated with ultraviolet light (Example 1) had a 31% decrease in the expression level of COX-2 compared with the group not administered with the test substance and irradiated with ultraviolet light (Comparative Example 2). From the above results, it was revealed that the composition of the present invention exhibits an excellent effect in suppressing the expression of the erythema induction-related gene COX-2 induced by ultraviolet light exposure.

As shown in Figures 1 to 3, oral ingestion of rice extract effectively suppresses the expression of erythema induction-related genes IL-1β, IL-6, and COX-2 induced by UV exposure, so the composition of the present invention is excellent in reducing or suppressing skin erythema induced by UV exposure, and exerts an excellent effect of reducing or suppressing skin disorders induced by UV exposure.

(Production example)
Based on the results of the Examples, Production Examples of the present invention are given below.

[Production Example 1-4: Granules]
According to the formulation in Table 2, the rice extract and other raw materials were mixed, and then fluidized bed granulation was performed using a granulator, and the mixture was filled into individual sachets to produce the granules described in Production Example 1-4. The granules were produced in a quantity of 3 g per sachet. The granules described in Production Example 1-4 may be taken in 1 to 3 sachets per day, and may be dissolved in 100 ml of water or other solvent before consumption, or may be taken as is without dissolving. All of the granules in Production Examples 1-4 are effective in reducing or suppressing skin disorders induced by exposure to ultraviolet light, and reducing or suppressing skin erythema induced by exposure to ultraviolet light.

[Production Example 5-8: Tablets]
According to the formulation in Table 3, the rice extract and other raw materials were mixed, and then tableted using a rotary tablet press to produce tablets of Production Example 5-8. The tablets were produced to have a tablet diameter of 8 mmφ, a tablet thickness of 4.5 mm, a weight of 300 mg, and a hardness of 5 kgf or more. One to two tablets of the tablets described in Production Example 5-8 may be taken per day, and can be taken with 100 ml of water or the like. All of the tablets of Production Examples 5-8 are effective in reducing or suppressing skin disorders induced by exposure to ultraviolet light, and reducing or suppressing skin erythema induced by exposure to ultraviolet light.

[Production Example 9-12: Soft Capsule]
According to the formulation in Table 4, the rice extract and other raw materials were mixed, and then encapsulated with a coating containing gelatin and glycerin to produce soft capsules of Production Examples 9-12. The soft capsules were produced with a content liquid weight of 300 mg. The soft capsules described in Production Examples 9-12 can be taken at 1 to 2 capsules per day, and can be taken with 100 ml of water or the like. All of the soft capsules of Production Examples 9-12 are effective in reducing or suppressing skin disorders induced by exposure to ultraviolet light, and reducing or suppressing skin erythema induced by exposure to ultraviolet light.

[Manufacture example 13-16: PET beverage]
According to the formulation in Table 5, a liquid preparation obtained by mixing rice extract with other raw materials was packed in a PET container to produce the PET beverages of Production Examples 13-16. The PET beverages were produced in a volume of 500 ml each. One bottle of the PET beverage described in Production Examples 13-16 may be consumed per day. All of the PET beverages of Production Examples 13-16 are effective in reducing or suppressing skin disorders induced by exposure to ultraviolet light, and reducing or suppressing skin erythema induced by exposure to ultraviolet light.

[Production Example 17-20: Jelly]
According to the formulation in Table 6, the rice extract and other raw materials were mixed, and the heated liquid was filled into a pouch to produce the jellies of Production Examples 17-20. The jellies were produced in a quantity of 200 g each. One jellies of Production Examples 17-20 may be taken per day. All of the jellies of Production Examples 17-20 are effective in reducing or suppressing skin disorders induced by exposure to ultraviolet light, and reducing or suppressing skin erythema induced by exposure to ultraviolet light.

The oral composition of the present invention has a high industrial utility because it reduces or inhibits skin erythema induced by UV exposure and has an excellent effect of reducing or inhibiting skin disorders induced by UV exposure by suppressing the expression of erythema induction-related genes IL-1β, IL-6, or COX-2 induced by UV exposure.

Claims (1)

An oral composition for suppressing expression of erythema induction-related genes induced by ultraviolet exposure, characterized by comprising an ethanol extract of rice.