JP2016041765A - Oral ultraviolet resistance improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ultraviolet resistance improving agent that increases the resistance of skin to ultraviolet light and can alleviate or suppress damage to the skin caused by exposure to the ultraviolet light by oral ingestion.SOLUTION: There is provided an oral ultraviolet resistance improving agent including diisopropyl sebacate, acetyltryptophan or a salt thereof, or azelaic acid or a salt thereof as active ingredients.SELECTED DRAWING: None

Description

  The present invention relates to an oral ultraviolet resistance improver that improves the ultraviolet resistance of skin by oral ingestion.

  In recent years, a decrease in the ozone layer has become a factor, and skin damage due to ultraviolet rays has become a problem. For example, chronic UV exposure may cause erythema and edema of the skin, wrinkles, sagging, spots and freckles appear to be noticeable, skin elasticity decreases, skin darkening, yellowing increases A decrease in the amount of keratin water is induced.

  Conventionally, as means for improving damage to the skin due to ultraviolet rays, so-called sunscreens containing ultraviolet scattering agents and ultraviolet absorbers have been mainly used, and whitening agents having a melanin production inhibitory effect and the like have been mainly used. However, most of these are expected to have an effect obtained when used as a skin external preparation.

  However, in recent years, from an approach based on holistic skin control, it is considered ideal to create a body resistant to ultraviolet rays, and attempts have been made to improve the resistance of skin to ultraviolet rays by ingestion. For example, when Lactobacillus sp is orally ingested, the skin barrier function damage caused by UV irradiation is suppressed (Patent Document 1), and when carotenoids are mixed with elastin or ceramide, they are induced by UV. It has been reported that the erythema of the skin which can be effectively suppressed (patent document 2).

  On the other hand, diisopropyl sebacate is known as a substance blended in cosmetics, shampoos, rinses and the like as a penetration enhancer that enhances the solubility and permeability of hardly soluble substances. Acetyltryptophan is mainly used as a stabilizer for albumin preparations. It is also a substance used in the form of intravenous infusion and intravenous injection for the purpose of hypoproteinemia, undernutrition, amino acid (tryptophan) supplementation before and after surgery, and skin tightening effect when applied to the skin It is also reported that there is (patent document 3). In addition, azelaic acid has antibacterial activity against acne bacteria, so it has been used externally for acne treatment, and has a 5α reductase inhibitory effect, and is reported to be effective for androgenetic alopecia Has been. It is also known that it has a whitening effect, and it has been reported that it is blended into a whitening cosmetic (Patent Document 4) and a skin external preparation (Patent Document 5) for this purpose.

  However, it has not been known so far that when diisopropyl sebacate, acetyltryptophan or a salt thereof, or azelaic acid or a salt thereof is taken orally, there is an action to improve the resistance to ultraviolet rays of the skin.

JP 2008-179601 A JP 2004-229611 A Special Table 2002-534369 JP-A-5-186324 Japanese Patent Laid-Open No. 2005-23042

  The present invention relates to providing an ultraviolet resistance improver that can increase the resistance of skin to ultraviolet rays and reduce or suppress skin damage caused by exposure to ultraviolet rays by ingestion.

  The present inventors examined materials that can be taken orally to improve the ultraviolet resistance of the skin. It has been found that the onset of erythema can be significantly suppressed, which is useful as an ultraviolet resistance improver.

That is, the present invention relates to the following 1) to 3).
1) An oral ultraviolet resistance improver comprising diisopropyl sebacate, acetyltryptophan or a salt thereof or azelaic acid or a salt thereof as an active ingredient.
2) The oral ultraviolet resistance improver of 1) above, which reduces or suppresses skin damage induced by ultraviolet exposure.
3) The oral ultraviolet resistance improver according to 2) above, wherein the skin disorder induced by UV exposure is skin inflammation or skin aging.

  The ultraviolet resistance improver of the present invention is, for example, skin inflammation such as erythema and edema caused by exposure to ultraviolet rays on the skin, formation of wrinkles and sagging, formation of spots and freckles, reduction of skin elasticity, pigment It is effective for reducing or suppressing various skin damages such as so-called skin aging or skin deterioration such as deposition, darkening of the skin, increased yellowing, decreased skin barrier function, and decreased stratum corneum function.

  The diisopropyl sebacate used in the present invention can be easily produced by, for example, an esterification reaction between sebacic acid and isopropyl alcohol, or a commercially available product can be purchased and used.

The acetyltryptophan (N-acetyltryptophan) used in the present invention may be D-, L- or DL-form, preferably L-form.
Examples of the salt of acetyltryptophan include base addition salts such as sodium salt and potassium salt, and acid addition salts such as hydrochloride.
Acetyltryptophan or a salt thereof can be easily produced, for example, by adding L-tryptophan to acetic anhydride in an aqueous alkali metal hydroxide solution, or a commercially available product can be purchased and used.

The azelaic acid used in the present invention is also represented as nonanedioic acid or 1,7-heptanedicarboxylic acid. Examples of azelaic acid salts include disodium salt, dilithium salt, and dipotassium salt.
Azelaic acid or a salt thereof can be extracted and purified from grains such as wheat, rye and barley, but can also be obtained by ozonolysis of oleic acid. Moreover, a commercial item can also be purchased and used.

As shown in Examples below, when diisopropyl sebacate, acetyltryptophan or azelaic acid was orally ingested into mice and then irradiated with ultraviolet rays, the development of skin erythema due to the ultraviolet rays was significantly suppressed. That is, diisopropyl sebacate, acetyltryptophan or a salt thereof, or azelaic acid or a salt thereof can be used as an ultraviolet resistance improver that increases the resistance to ultraviolet rays of the skin, and the ultraviolet resistance improver is produced. Can be used to
Therefore, the oral UV resistance improver of the present invention is induced by UV exposure, skin inflammation such as erythema and edema of the skin, formation of wrinkles and sagging, formation of spots and freckles, reduction of skin elasticity, Oral drugs, quasi-drugs, and supplements to reduce or suppress skin disorders such as skin aging or skin deterioration, such as pigmentation, skin darkening, increased yellowing, decreased skin barrier function, and decreased stratum corneum function Or it is useful as a foodstuff, or as a raw material or a formulation for mix | blending with these.

  The pharmaceutical, quasi-drug or supplement dosage form may be either a solid preparation or a liquid preparation. Specifically, tablets, coated tablets, capsules, granules, powders, powders, sustained-release preparations, suspensions. Suspensions, emulsions, oral liquids, dragees, pills, fine granules, syrups, elixirs and the like can be mentioned.

  In the above preparation, a pharmaceutically acceptable carrier can be added to diisopropyl sebacate, acetyltryptophan or a salt thereof, or azelaic acid or a salt thereof. Such carriers include, for example, excipients, binders, disintegrants, lubricants, diluents, osmotic pressure regulators, fluidity promoters, absorption aids, pH adjusters, emulsifiers, preservatives, stabilization. Agent, antioxidant, colorant, UV absorber, wetting agent, thickener, brightener, activity enhancer, anti-inflammatory agent, bactericidal agent, flavoring agent, flavoring agent, extender, surfactant, dispersant, Buffering agents, preservatives, fixing agents, fragrances, coating agents and the like can be mentioned. Moreover, a well-known medicinal component can also be suitably mix | blended with the said formulation. Examples of such components include various vitamins, amino acids and peptides and derivatives thereof, nucleic acids and derivatives thereof, saccharides and derivatives thereof, carotenoids, soybean isoflavones, catechins, and antioxidants such as chlorogenic acid. .

  The content of diisopropyl sebacate, acetyltryptophan or a salt thereof, or azelaic acid or a salt thereof in the above preparation is usually 0.001 to 90% by mass, preferably 0.01 to 60% by mass, based on the total mass of the preparation.

  In addition to general foods and drinks, the above-mentioned various foods include erythema and edema of the skin caused by ultraviolet rays, formation of wrinkles and sagging, formation of spots and freckles, reduced skin elasticity, pigmentation, skin blackening, yellowing The concept is to reduce or suppress skin damage such as increase in skin barrier function, decrease in stratum corneum function, etc., and if necessary, beauty foods, foods for the sick, nutritional functional foods Functional foods such as foods for specified health use are included.

  The form of the food product can be solid, semi-solid or liquid. Examples of food include confectionery such as breads, noodles, cookies, jelly, dairy products, frozen foods, instant foods, processed starch products, processed meat products, other processed foods, coffee beverages, soups, Examples include seasonings, dietary supplements, and the like, and raw materials thereof. Further, like the above-mentioned preparation for oral administration, it may be in tablet form, pill form, capsule form, liquid form, syrup form, powder form, granule form and the like.

Such foods include diisopropyl sebacate, acetyltryptophan or salts thereof, or azelaic acid or salts thereof, other food and drink materials, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, colorings. An agent, an ultraviolet absorber, an antioxidant, a humectant, a thickener, a sticking agent, a dispersant, a wetting agent, and the like can be mixed and prepared as appropriate.
Various vitamins, amino acids and peptides and derivatives thereof, nucleic acids and derivatives thereof, sugars and derivatives thereof, carotenoids, soybean isoflavones, catechins, antioxidant components such as chlorogenic acid, and the like can be appropriately blended.

  In addition, the content of diisopropyl sebacate, acetyltryptophan or a salt thereof, or azelaic acid or a salt thereof in a food or drink varies depending on the use form, but is usually 0.0001 to 50% by mass, 10 mass% is preferable.

  When the diisopropyl sebacate, acetyltryptophan or salt thereof, or azelaic acid or salt thereof of the present invention is used as a pharmaceutical or in combination with a pharmaceutical, the dose depends on the patient's condition, body weight, sex, age or other factors. In general, the daily dose per adult for oral administration is preferably 0.001 to 100 g as diisopropyl sebacate, acetyltryptophan or a salt thereof, or azelaic acid or a salt thereof. Moreover, although the said formulation can be administered according to arbitrary administration schedules, it is preferable to divide once to several times a day, and to administer continuously for several weeks to several months.

Example 1 Effect of Oral Intake of Diisopropyl Sebacate by UVB Irradiation on Erythema 1) Method Hairless mouse HR-1 (female, 7 weeks old) (Japan SLC) was preliminarily raised for 1 week, then a control group, a diisopropyl sebacate administration group, (N = 4 each). During the test period, food and water were freely consumed, and the animals were raised under conditions of a temperature of 23 ± 1 ° C., a humidity of 50 ± 1%, and a lighting time of 7: 00-19: 00. In the diisopropyl sebacate group, 100 mg / kg body weight of “Diisopropyl sebacate” (Wako Pure Chemical Industries, Ltd.) was prepared so that the dosage would be 0.1 mL / 10 g body weight. For 2 weeks, gavage was administered using a stomach tube. The control group was an emulsion except for diisopropyl sebacate, and was orally administered in the same manner. 2 weeks after oral administration, under pentobarbital anesthesia, 0.6 cm x 1.0 cm site was placed close to the back of the mouse, 2 rows x 3 rows = 6 sites were set, and the UVB irradiation dose of 1 mW / cm ² was used for 0 second. (0 mJ) and 40 seconds (40 mJ) were irradiated (each at 3 locations).
Grade of erythema after 48 hours of irradiation was evaluated on a five-point scale (-; no response, ± (minimal erythema); mild or partial erythema, +; clear erythema, ++; erythema and edema, +++; erythema) Skin color (a * value) was measured using an edema and blisters) and a spectroscopic color difference meter SE-6000 (Nippon Denshoku Industries Co., Ltd.). The a * value is an index representing the redness of the skin color, and the larger the a * value, the more the skin changes to red, that is, erythema occurs.

2) Results The results are shown in Table 1 (visual evaluation) and Table 2 (a * value). Compared to the control group, the diisopropyl sebacate administration group was found to have an effect of suppressing an increase in a * value due to UVB irradiation, and visual evaluation revealed that erythema was also suppressed.

Example 2 Inhibition of erythema by UVB irradiation after ingestion of acetyltryptophan 1) Method Hairless mouse HR-1 (female, 7 weeks old) (Japan SLC) is preliminarily raised for 1 week, and then divided into a control group and an acetyltryptophan administration group. (Each n = 4). During the test period, food and water were freely consumed, and the animals were raised under conditions of a temperature of 23 ± 1 ° C., a humidity of 50 ± 1%, and a lighting time of 7: 00-19: 00. In the acetyltryptophan administration group, “N-acetyl-L-tryptophan” (Sigma-Aldrich Co. LLC.) 100 mg / kg body weight was prepared so that the dosage would be 0.1 mL / 10 g body weight. It was administered by oral gavage once a day for 2 weeks using a stomach tube. In the control group, acetyltryptophan was removed and an emulsion was prepared and administered orally in the same manner. 2 weeks after oral administration, under pentobarbital anesthesia, 0.6 cm x 1.0 cm site was placed close to the back of the mouse, 2 rows x 3 rows = 6 sites were set, and the UVB irradiation dose of 1 mW / cm ² was used for 0 second. (0 mJ) and 40 seconds (40 mJ) were irradiated (each at 3 locations).
Grade of erythema after 48 hours of irradiation was evaluated on a five-point scale (-; no response, ± (minimal erythema); mild or partial erythema, +; clear erythema, ++; erythema and edema, +++; erythema) Skin color (a * value) was measured using an edema and blisters) and a spectroscopic color difference meter SE-6000 (Nippon Denshoku Industries Co., Ltd.). The a * value is an index representing the redness of the skin color, and the larger the a * value, the more the skin changes to red, that is, erythema occurs.

2) Results The results are shown in Table 3 (visual evaluation) and Table 4 (a * value).
Compared with the control group, the acetyltryptophan administration group was found to have an effect of suppressing an increase in a * value due to UVB irradiation, and visual evaluation also revealed that erythema was suppressed.

Example 3 Effect of Oral Azelaic Acid Intake of Erythema by UVB Irradiation 1) Method Hairless mouse HR-1 (female, 6 weeks old) (Japan SLC) was preliminarily raised for 1 week or more, and then divided into a control group and an azelaic acid administration group. Divided (each n = 4). During the test period, food and water were freely consumed, and the animals were raised under conditions of a temperature of 23 ± 1 ° C., a humidity of 50 ± 1%, and a lighting time of 7: 00-19: 00. In the azelaic acid administration group, “Azelaic acid” (Wako Pure Chemical Industries, Ltd.) 100 mg / kg body weight was prepared so that the dosage would be 0.1 mL / 10 g body weight, and in emulsion form, once a day for 2 weeks Forcibly orally using a stomach tube. In the control group, an azelaic acid was removed and an emulsion was prepared and administered orally in the same manner. 2 weeks after oral administration, under pentobarbital anesthesia, 0.6 cm x 1.0 cm site was placed close to the back of the mouse, 2 rows x 3 rows = 6 sites were set, and the UVB irradiation dose of 1 mW / cm ² was used for 0 second. (0 mJ) and 40 seconds (40 mJ) were irradiated (each at 3 locations).
Grade of erythema after 48 hours of irradiation was evaluated on a five-point scale (-; no response, ± (minimal erythema); mild or partial erythema, +; clear erythema, ++; erythema and edema, +++; erythema) Skin color (a * value) was measured using an edema and blisters) and a spectroscopic color difference meter SE-6000 (Nippon Denshoku Industries Co., Ltd.). The a * value is an index representing the redness of the skin color, and the larger the a * value, the more the skin changes to red, that is, erythema occurs.
2) Results The results are shown in Table 5 (visual evaluation) and Table 6 (a * value).
Compared to the control group, the azelaic acid-administered group was found to have an effect of suppressing an increase in a * value due to UVB irradiation, and visual evaluation also revealed that erythema was suppressed.

Claims (3)

  An oral ultraviolet resistance improver comprising acetyltryptophan or a salt thereof as an active ingredient.   The oral ultraviolet resistance improver according to claim 1, which reduces or suppresses skin damage induced by ultraviolet exposure.   The oral ultraviolet resistance enhancer according to claim 2, wherein the skin disorder induced by ultraviolet exposure is skin inflammation or skin aging.