JP6159382B2 - Oral UV resistance improver - Google Patents
Oral UV resistance improver Download PDFInfo
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- JP6159382B2 JP6159382B2 JP2015251658A JP2015251658A JP6159382B2 JP 6159382 B2 JP6159382 B2 JP 6159382B2 JP 2015251658 A JP2015251658 A JP 2015251658A JP 2015251658 A JP2015251658 A JP 2015251658A JP 6159382 B2 JP6159382 B2 JP 6159382B2
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- skin
- erythema
- oral
- salt
- acetyltryptophan
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、経口摂取により、皮膚の紫外線抵抗性を向上させる経口紫外線抵抗性向上剤に関する。 The present invention relates to an oral ultraviolet resistance improver that improves the ultraviolet resistance of skin by oral ingestion.
近年、オゾン層の減少が一要因となり、紫外線による皮膚障害が問題になっている。例えば、慢性的な紫外線の暴露により、皮膚の紅斑や浮腫が発生したり、しわやたるみ、しみやそばかすの形成が顕著となったり、皮膚の弾力性の低下、皮膚の黒化、黄ばみの増加、角質水分量の減少等が誘導される。 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 significantly, skin elasticity decreases, skin darkening, yellowing increases A decrease in the amount of keratin water is induced.
従来、紫外線による皮膚へのダメージを改善する手段としては、紫外線散乱剤や紫外線吸収剤を配合したいわゆる日焼け止めを用いることや、メラニン産生抑制作用等を有する美白剤を用いることが主に行われているが、これらのほとんどは皮膚外用剤として使用した際に得られる作用を期待したものである。 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.
しかしながら、近年、ホリスティック皮膚制御に基づくアプローチから、紫外線に強い身体をつくることが理想的であるとされ、経口摂取によって、皮膚の紫外線に対する抵抗力を向上させることが試みられている。例えば、ラクトバチルス属菌を経口摂取した場合に紫外線照射による皮膚バリア機能の損傷を抑制すること(特許文献1)、カロチノイドにエラスチンやセラミドを配合した組成物を経口摂取した場合に、紫外線に誘発される皮膚の紅斑を効果的に抑制し得ること(特許文献2)が報告されている。 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).
一方、セバシン酸ジイソプロピルは、難溶性物質の溶解性や浸透性を高める浸透促進剤として、化粧品、シャンプー、リンス等に配合される物質として知られている。アセチルトリプトファンは、主として、アルブミン製剤の安定化剤として使用されている。また、低蛋白血症、低栄養状態、手術前後におけるアミノ酸(トリプトファン)補給を目的として点滴静脈内注射、静脈内注射の形態で使用されている物質でもあり、皮膚に塗布した場合に皮膚引き締め効果があることも報告されている(特許文献3)。また、アゼライン酸は、アクネ菌に対して抗菌作用を有することからニキビ治療のために外用で使用されている他、5αリダクターゼ抑制作用を有し、男性ホルモン型脱毛症に有効であることが報告されている。また、美白作用があることも知られ、当該目的で美白化粧料(特許文献4)や皮膚外用剤(特許文献5)に配合されることが報告されている。 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.
しかしながら、セバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩又はアゼライン酸若しくはその塩を経口摂取した場合に、皮膚の紫外線に対する抵抗性を向上する作用があることはこれまで知られていない。 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.
本発明は、経口摂取により、皮膚の紫外線に対する抵抗力を高め、紫外線の暴露により生じる皮膚のダメージを軽減又は抑制できる、紫外線抵抗性向上剤を提供することに関する。 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.
本発明者らは、皮膚の紫外線抵抗性を向上させる経口摂取可能な素材について検討したところ、セバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩又はアゼライン酸若しくはその塩を経口摂取した場合に、紫外線暴露による皮膚紅斑の発症が有意に抑制でき、これが紫外線抵抗性向上剤として有用であることを見出した。 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.
すなわち本発明は、以下の1)〜3)に係るものである。
1)セバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩又はアゼライン酸若しくはその塩を有効成分とする経口紫外線抵抗性向上剤。
2)紫外線暴露により誘発される皮膚障害を軽減又は抑制する上記1)の経口紫外線抵抗性向上剤。
3)紫外線暴露により誘発される皮膚障害が、皮膚の炎症又は皮膚老化である上記2)の経口紫外線抵抗性向上剤。
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.
本発明の紫外線抵抗性向上剤は、例えば、皮膚への紫外線の暴露によって生じる、紅斑や浮腫等の皮膚の炎症、しわやたるみの形成、しみやそばかすの形成、皮膚の弾力性の低下、色素沈着、皮膚の黒化、黄ばみの増加、皮膚バリア機能の低下、角層機能の低下といった、いわゆる皮膚老化又は皮膚劣化等の種々の皮膚のダメージの軽減又は抑制に有効である。 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.
本発明において用いられるセバシン酸ジイソプロピルは、例えばセバシン酸とイソプロピルアルコールとのエステル化反応により容易に製造でき、また市販品を購入して使用することもできる。 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.
本発明において用いられるアセチルトリプトファン(N−アセチルトリプトファン)は、D−、L−またはDL−体であってよく、好ましくはL−体である。
アセチルトリプトファンの塩としては、ナトリウム塩、カリウム塩等の塩基付加塩や、塩酸塩等の酸付加塩が挙げられる。
アセチルトリプトファン又はその塩は、例えばL-トリプトファンをアルカリ金属水酸化物水溶液中で無水酢酸に加えることにより容易に製造でき、また市販品を購入して使用することもできる。
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.
本発明において用いられるアゼライン酸は、ノナン二酸若しくは1,7−へプタンジカルボン酸とも表される。アゼライン酸の塩としては、例えば、ジナトリウム塩、ジリチウム塩、ジカリウム塩等が挙げられる。
アゼライン酸又はその塩は、小麦、ライ麦、大麦等の穀物から抽出精製することもできるが、オレイン酸をオゾン分解することによっても得られる。また、市販品を購入して使用することもできる。
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.
後記実施例に示すように、セバシン酸ジイソプロピル、アセチルトリプトファン又はアゼライン酸をマウスに経口摂取した後に紫外線照射した場合、当該紫外線による皮膚紅斑の発症が有意に抑制された。すなわち、セバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩、又はアゼライン酸若しくはその塩は、皮膚の紫外線に対する抵抗力を高める紫外線抵抗性向上剤として使用することができ、また、当該紫外線抵抗性向上剤を製造するために使用することができる。
従って、本発明の経口紫外線抵抗性向上剤は、紫外線暴露によって誘発される、皮膚の紅斑や浮腫等の皮膚の炎症、しわやたるみの形成、しみやそばかすの形成、皮膚の弾力性の低下、色素沈着、皮膚の黒化、黄ばみの増加、皮膚バリア機能の低下、角層機能の低下といった、皮膚老化又は皮膚劣化等の皮膚障害を軽減又は抑制するための経口医薬品、医薬部外品、サプリメント又は食品として、或いはこれらへ配合するための素材又は製剤として有用である。
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.
上記医薬品、医薬部外品或いはサプリメントの剤型は、固形製剤又は液体製剤の何れでもよく、具体的には、錠剤、被覆錠剤、カプセル剤、顆粒剤、散剤、粉剤、徐放性製剤、懸濁液、エマルジョン剤、内服液、糖衣錠、丸剤、細粒剤、シロップ剤、エリキシル剤等が挙げられる。 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.
上記製剤には、セバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩、又はアゼライン酸若しくはその塩に、薬学的に許容される担体を配合することができる。斯かる担体としては、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、希釈剤、浸透圧調整剤、流動性促進剤、吸収助剤、pH調整剤、乳化剤、防腐剤、安定化剤、酸化防止剤、着色剤、紫外線吸収剤、湿潤剤、増粘剤、光沢剤、活性増強剤、抗炎症剤、殺菌剤、矯味剤、矯臭剤、増量剤、界面活性剤、分散剤、緩衝剤、保存剤、固着剤、香料、被膜剤等が挙げられる。また、当該製剤には公知の薬効成分を適宜配合することもできる。斯かる成分としては、例えば、各種ビタミン類、アミノ酸やペプチドおよびその誘導体、核酸およびその誘導体、糖類及びその誘導体、その他、カロチノイド、大豆イソフラボン、カテキン類、クロロゲン酸等の抗酸化剤等が挙げられる。 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. .
上記製剤におけるセバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩、又はアゼライン酸若しくはその塩の含有量は、通常、製剤全質量の0.001〜90質量%であり、0.01〜60質量%が好ましい。 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.
上記各種食品には、一般飲食品のほか、紫外線によって生じる、皮膚の紅斑や浮腫、しわやたるみの形成、しみやそばかすの形成、皮膚の弾力性の低下、色素沈着、皮膚の黒化、黄ばみの増加、皮膚バリア機能の低下、角層機能の低下等の皮膚のダメージを軽減又は抑制することをコンセプトとし、必要に応じてその旨を表示した美容食品、病者用食品、栄養機能食品又は特定保健用食品等の機能性食品が包含される。 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.
食品の形態は、固形、半固形または液状であり得る。食品の例としては、パン類、麺類、クッキー等の菓子類、ゼリー類、乳製品、冷凍食品、インスタント食品、でんぷん加工製品、加工肉製品、その他加工食品、コーヒー飲料等の飲料、スープ類、調味料、栄養補助食品等、及びそれらの原料が挙げられる。また、上記の経口投与製剤と同様、錠剤形態、丸剤形態、カプセル形態、液剤形態、シロップ形態、粉末形態、顆粒形態等であってもよい。 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.
斯かる食品は、セバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩、又はアゼライン酸若しくはその塩の他、他の飲食品材料や、溶剤、軟化剤、油、乳化剤、防腐剤、香科、安定剤、着色剤、紫外線吸収剤、酸化防止剤、保湿剤、増粘剤、固着剤、分散剤、湿潤剤等を適宜組み合わせて配合し、調製することができる。
また、各種ビタミン類、アミノ酸やペプチドおよびその誘導体、核酸およびその誘導体、糖類及びその誘導体、その他、カロチノイド、大豆イソフラボン、カテキン類、クロロゲン酸等の抗酸化成分等も適宜配合することができる。
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.
また、飲食品中におけるセバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩、又はアゼライン酸若しくはその塩の含有量は、その使用形態により異なるが、通常、0.0001〜50質量%であり、0.001〜10質量%が好ましい。 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.
本発明のセバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩、又はアゼライン酸若しくはその塩を医薬品として、或いは医薬品に配合して使用する場合の投与量は、患者の状態、体重、性別、年齢又はその他の要因に従って変動し得るが、経口投与の場合の成人1人当たりの1日の投与量は、通常、セバシン酸ジイソプロピル、アセチルトリプトファン若しくはその塩、又はアゼライン酸若しくはその塩として0.001〜100gが好ましい。また、上記製剤は、任意の投与計画に従って投与され得るが、1日1回〜数回に分け、数週間〜数ヶ月間継続して投与することが好ましい。 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.
実施例1 セバシン酸ジイソプロピル経口摂取のUVB照射による紅斑抑制効果
1)方法
ヘアレスマウスHR-1(雌性、7週齢)(日本SLC)を1週間予備飼育後、コントロール群、セバシン酸ジイソプロピル投与群とに分けた(各n=4)。試験期間中、飼料および水は自由摂取させ、温度23±1℃、湿度50±1%、照明時間7:00−19:00の条件下で飼育した。セバシン酸ジイソプロピル投与群は、「セバシン酸ジイソプロピル」(和光純薬工業(株))100mg/kg体重 を、投与量が0.1mL/10g体重 になるように調製し、エマルジョン形態で、1日1回2週間、胃ゾンデを用いて強制経口投与した。コントロール群は、セバシン酸ジイソプロピルを除いたものでエマルジョンとし、同様に経口投与した。経口投与2週後に、ペントバルビタール麻酔下にて、マウス背部に0.6cm×1.0cmの部位を近接して2列×3行=6ヶ所設定し、1mW/cm2のUVB照射線量で、0秒間(0mJ)と40秒間(40mJ)照射した(各3ヶ所)。
照射48時間後の紅斑の程度を、目視による5段階評価(−;反応なし、±(最小紅斑);軽度または部分的紅斑、+;明らかな全面紅斑、++;紅斑と浮腫、+++;紅斑と浮腫と水疱)と、分光式色差計SE-6000(日本電色工業)を用いて皮膚色(a*値)測定を行った。a*値は皮膚色の赤味を表す指標であり、a*値が大きいほど皮膚が赤色に変化、すなわち紅斑が生じていることを示している。
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)結果
結果を表1(目視による評価)、表2(a*値)に示した。コントロール群と比較してセバシン酸ジイソプロピル投与群において、UVB照射によるa*値の上昇を抑制する効果が見出され、目視による評価によっても紅斑を抑制することが明らかにされた。
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.
実施例2 アセチルトリプトファン経口摂取のUVB照射による紅斑抑制効果
1)方法
ヘアレスマウスHR-1(雌性、7週齢)(日本SLC)を1週間予備飼育後、コントロール群、アセチルトリプトファン投与群とに分けた(各n=4)。試験期間中、飼料および水は自由摂取させ、温度23±1℃、湿度50±1%、照明時間7:00−19:00の条件下で飼育した。アセチルトリプトファン投与群は、「N-アセチル-L-トリプトファン」(Sigma-Aldrich Co. LLC.)100mg/kg体重 を、投与量が0.1mL/10g体重 になるように調製し、エマルジョン形態で、1日1回2週間、胃ゾンデを用いて強制経口投与した。コントロール群は、アセチルトリプトファンを除いたものでエマルジョンとし、同様に経口投与した。経口投与2週後に、ペントバルビタール麻酔下にて、マウス背部に0.6cm×1.0cmの部位を近接して2列×3行=6ヶ所設定し、1mW/cm2のUVB照射線量で、0秒間(0mJ)と40秒間(40mJ)照射した(各3ヶ所)。
照射48時間後の紅斑の程度を、目視による5段階評価(−;反応なし、±(最小紅斑);軽度または部分的紅斑、+;明らかな全面紅斑、++;紅斑と浮腫、+++;紅斑と浮腫と水疱)と、分光式色差計SE-6000(日本電色工業)を用いて皮膚色(a*値)測定を行った。a*値は皮膚色の赤味を表す指標であり、a*値が大きいほど皮膚が赤色に変化、すなわち紅斑が生じていることを示している。
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)結果
結果を表3(目視による評価)、表4(a*値)に示した。
コントロール群と比較してアセチルトリプトファン投与群において、UVB照射によるa*値の上昇を抑制する効果が見出され、目視による評価によっても紅斑を抑制することが明らかにされた。
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.
実施例3 アゼライン酸経口摂取のUVB照射による紅斑抑制効果
1)方法
ヘアレスマウスHR-1(雌性、6週齢)(日本SLC)を1週間以上予備飼育後、コントロール群、アゼライン酸投与群とに分けた(各n=4)。試験期間中、飼料および水は自由摂取させ、温度23±1℃、湿度50±1%、照明時間7:00−19:00の条件下で飼育した。アゼライン酸投与群は、「アゼライン酸」(和光純薬工業(株))100mg/kg体重 を、投与量が0.1mL/10g体重 になるように調製し、エマルジョン形態で、1日1回2週間、胃ゾンデを用いて強制経口投与した。コントロール群は、アゼライン酸を除いたものでエマルジョンとし、同様に経口投与した。経口投与2週後に、ペントバルビタール麻酔下にて、マウス背部に0.6cm×1.0cmの部位を近接して2列×3行=6ヶ所設定し、1mW/cm2のUVB照射線量で、0秒間(0mJ)と40秒間(40mJ)照射した(各3ヶ所)。
照射48時間後の紅斑の程度を、目視による5段階評価(−;反応なし、±(最小紅斑);軽度または部分的紅斑、+;明らかな全面紅斑、++;紅斑と浮腫、+++;紅斑と浮腫と水疱)と、分光式色差計SE-6000(日本電色工業)を用いて皮膚色(a*値)測定を行った。a*値は皮膚色の赤味を表す指標であり、a*値が大きいほど皮膚が赤色に変化、すなわち紅斑が生じていることを示している。
2)結果
結果を表5(目視による評価)、表6(a*値)に示した。
コントロール群と比較してアゼライン酸投与群において、UVB照射によるa*値の上昇を抑制する効果が見出され、目視による評価によっても紅斑を抑制することが明らかにされた。
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 the control group and 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.
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