JP6166544B2 - Preventive or therapeutic agent for pigmentation disease - Google Patents
Preventive or therapeutic agent for pigmentation disease Download PDFInfo
- Publication number
- JP6166544B2 JP6166544B2 JP2013025662A JP2013025662A JP6166544B2 JP 6166544 B2 JP6166544 B2 JP 6166544B2 JP 2013025662 A JP2013025662 A JP 2013025662A JP 2013025662 A JP2013025662 A JP 2013025662A JP 6166544 B2 JP6166544 B2 JP 6166544B2
- Authority
- JP
- Japan
- Prior art keywords
- pigmentation
- composition
- loxoprofen
- tranexamic acid
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は新規な色素沈着症の予防又は治療用組成物に関する。 The present invention relates to a novel composition for preventing or treating pigmentation.
シミ（肝斑、老人性色素斑等を含む）、そばかす、日やけ、色黒やステロイド等の薬物による皮膚の黒化症等の色素沈着症は、皮膚にメラニン色素が過剰に沈着して生じるものである。このように、皮膚にメラニン色素が過剰に沈着して生じる色素沈着症は、特に女性にとって美容上好ましくないものである。 Pigmentation such as skin spots (including liver spots, senile pigment spots, etc.), freckles, sunburn, skin darkening, and melanin pigmentation caused by drugs such as steroids is caused by excessive deposition of melanin pigment on the skin. Is. Thus, pigmentation caused by excessive deposition of melanin on the skin is particularly cosmetically unfavorable for women.
トラネキサム酸は、メラニンの産生を抑制し、色素沈着症の予防・治療効果や美白効果を有することが知られており、トラネキサム酸を配合した美白用の薬用化粧品（医薬部外品）が市販されている。 Tranexamic acid is known to suppress the production of melanin, and to prevent and treat pigmentation, and to have a whitening effect. Whitening medicinal cosmetics (quasi-drugs) containing tranexamic acid are commercially available. ing.
ロキソプロフェンは、シクロオキシゲナーゼ（ＣＯＸ）を阻害し、プロスタグランジンの産生を抑制することによる抗炎症作用、解熱作用、鎮痛作用が知られており（非特許文献１参照）、非ステロイド性解熱鎮痛薬として広く用いられている。
また、ロキソプロフェンが、ジクロフェナクナトリウム等と同様に、皮膚の沈着色素の排出を促進することが知られている。（特許文献１参照）
Loxoprofen is known to have anti-inflammatory action, antipyretic action, and analgesic action by inhibiting cyclooxygenase (COX) and suppressing the production of prostaglandins (see Non-Patent Document 1), and as a nonsteroidal antipyretic analgesic. Widely used.
In addition, loxoprofen is known to promote the discharge of deposited pigment in the skin, like diclofenac sodium and the like. (See Patent Document 1)
トラネキサム酸とロキソプロフェンを配合した組成物は、消化管障害抑制や配合変化の防止用途として知られているが（特許文献２、３参照）、色素沈着症の予防又は治療用途や美白用途は知られておらず、また、皮膚外用剤として、両成分を配合したものは知られていない。 Compositions containing tranexamic acid and loxoprofen are known for use in inhibiting gastrointestinal disorders and preventing changes in the composition (see Patent Documents 2 and 3), but are known for use in prevention or treatment of pigmentation and whitening use. Moreover, the thing which mix | blended both components as a skin external preparation is not known.
本発明は、効果に優れた色素沈着症の予防又は治療用組成物を提供するのが課題である。 An object of the present invention is to provide a composition for preventing or treating hyperpigmentation that is excellent in effect.
本発明者らは、鋭意研究を行った結果、ロキソプロフェン又はその塩が色素沈着抑制作用を有することを見出した。さらに、色素沈着症に対する効果が知られている成分であるトラネキサム酸と、従来、色素沈着症に対する効果の知られていないロキソプロフェン又はその塩とを併用した場合、各々の単独の効果よりもさらに優れた色素沈着症の予防又は治療効果が得られることを新たに見出し、本発明を完成した。
すなわち、本発明は以下の（１）〜（７）に関する。
（１）ロキソプロフェン又はその塩、及びトラネキサム酸又はその塩を含有する、色素沈着症の予防又は治療用組成物。
（２）ロキソプロフェン又はその塩が、ロキソプロフェンナトリウム２水和物である、（１）に記載の色素沈着症の予防又は治療用組成物。
（３）トラネキサム酸又はその塩が、トラネキサム酸である、（１）又は（２）に記載の色素沈着症の予防又は治療用組成物。
（４） ロキソプロフェン又はその塩の配合量が、製剤全体の０．１〜１５重量％である、（１）〜（３）のいずれか１に記載の色素沈着症の予防又は治療用組成物。
（５）トラネキサム酸又はその塩の配合量が、製剤全体の１〜５重量％である、（１）〜（４）のいずれか１に記載の色素沈着症の予防又は治療用組成物。
（６）外用剤である、（１）〜（５）のいずれか１に記載の色素沈着症の予防又は治療用組成物。
（７）剤形が、軟膏、クリーム又はローションである、（１）〜（６）のいずれか１に記載の色素沈着症の予防又は治療用組成物。
As a result of intensive studies, the present inventors have found that loxoprofen or a salt thereof has a pigmentation inhibitory action. Furthermore, when tranexamic acid, which is a known component for pigmentation, is used in combination with loxoprofen or a salt thereof, which has not been known for its effect on pigmentation, it is even better than each individual effect. The present inventors have newly found that the effect of preventing or treating pigmentation can be obtained.
That is, the present invention relates to the following (1) to (7).
(1) A composition for preventing or treating pigmentation, comprising loxoprofen or a salt thereof and tranexamic acid or a salt thereof.
(2) The composition for preventing or treating pigmentation according to (1), wherein the loxoprofen or a salt thereof is loxoprofen sodium dihydrate.
(3) The composition for prevention or treatment of pigmentation disease according to (1) or (2), wherein tranexamic acid or a salt thereof is tranexamic acid.
(4) The composition for prevention or treatment of pigmentation disease according to any one of (1) to (3), wherein the amount of loxoprofen or a salt thereof is 0.1 to 15% by weight of the whole preparation.
(5) The composition for prevention or treatment of pigmentation disease according to any one of (1) to (4), wherein the amount of tranexamic acid or a salt thereof is 1 to 5% by weight of the whole preparation.
(6) The composition for prevention or treatment of pigmentation disease according to any one of (1) to (5), which is an external preparation.
(7) The composition for prevention or treatment of pigmentation disease according to any one of (1) to (6), wherein the dosage form is an ointment, cream or lotion.
本発明は、実施例に記載したように優れた色素沈着抑制効果を示した。したがって、本発明は、特に、シミ（肝斑を含む）、そばかす、日やけ、色黒やステロイド等の薬物による皮膚の黒化症等の色素沈着症の予防又は治療剤や、肌色をさらに白くしたいと希望する者に対する美白剤として有用なものである。 The present invention showed an excellent pigmentation inhibitory effect as described in the examples. Therefore, the present invention particularly prevents or treats pigmentation such as skin melanosis by drugs such as stains (including measles), freckles, sunburn, dark skin and steroids, and makes the skin color even whiter. It is useful as a whitening agent for those who want to do it.
本発明にかかるロキソプロフェン又はその塩はロキソプロフェンのみならず、ロキソプロフェンの薬学上許容される塩、さらには水やアルコール等との溶媒和物が含まれる。これらは公知の化合物であり、公知の方法により製造できるほか、市販のものを用いることができる。本発明において、ロキソプロフェン又はその塩としては、ロキソプロフェンナトリウム２水和物が好ましい。 Loxoprofen or a salt thereof according to the present invention includes not only loxoprofen but also a pharmaceutically acceptable salt of loxoprofen, and further a solvate with water or alcohol. These are known compounds, and can be produced by known methods, or commercially available products can be used. In the present invention, loxoprofen or a salt thereof is preferably loxoprofen sodium dihydrate.
本発明におけるトラネキサム酸塩は、公知の化合物であり、その入手方法としては、市販品を用いてもよく、また公知の方法に基づき製造することもできる。本発明におけるトラネキサム酸又はその塩としては、トラネキサム酸が好ましい。 The tranexamic acid salt in the present invention is a known compound, and as a method for obtaining it, a commercial product may be used, or it can be produced based on a known method. In the present invention, tranexamic acid or a salt thereof is preferably tranexamic acid.
本発明の組成物におけるロキソプロフェン又はその塩の配合量は、通常、ロキソプロフェン又はその塩の無水物換算で製剤全体の０．１〜２０重量％であり、０．５〜１５重量％が好ましく、１〜１０重量％がより好ましい。
本発明におけるトラネキサム酸又はその塩の配合量は、通常、製剤全体の０．１〜１０重量％であり、０．５〜５重量％が好ましく、１〜３重量％がより好ましい。
また、本発明の組成物における、ロキソプロフェン又はその塩と、トラネキサム酸又はその塩との配合比は、適宜検討を行い、適当な配合比を決めればよいが、重量比として、１：０．０１〜１５が好ましく、１：０．１〜５がさらに好ましく、１：０．１〜２が特に好ましい。
The blending amount of loxoprofen or a salt thereof in the composition of the present invention is usually 0.1 to 20% by weight, preferably 0.5 to 15% by weight, based on the anhydrous form of loxoprofen or a salt thereof. 10 to 10% by weight is more preferable.
The compounding amount of tranexamic acid or a salt thereof in the present invention is usually 0.1 to 10% by weight of the whole preparation, preferably 0.5 to 5% by weight, and more preferably 1 to 3% by weight.
In addition, the mixing ratio of loxoprofen or a salt thereof and tranexamic acid or a salt thereof in the composition of the present invention may be appropriately determined and an appropriate mixing ratio may be determined. To 15 is preferable, 1: 0.1 to 5 is more preferable, and 1: 0.1 to 2 is particularly preferable.
本発明の色素沈着症の予防又は治療用組成物は、経口的又は非経口的に投与（服用）すればよい。経口的に投与する製剤（経口投与製剤）としては、錠剤、カプセル剤、散剤、細粒剤、液剤、トローチ剤、ゼリー剤等の剤形を挙げることができる。非経口的に投与する製剤（非経口投与製剤）としては、エキス剤、硬膏剤、酒精剤、坐剤、懸濁剤、チンキ剤、軟膏剤、パップ剤、リニメント剤、ローション剤、エアゾール剤、点眼剤、注射剤等の医薬品で使用される剤形のほか、クリーム、化粧水、乳液、フォーム剤、ファンデーション、パック剤、皮膚洗浄剤、シャンプー、リンス、コンディショナー等の化粧料組成物の形態の剤形を挙げることができる。本発明の非経口投与製剤としては、軟膏剤、クリーム、ローションが好ましい。また、本発明の組成物は、非経口的に投与する製剤（外用剤）が好ましく、皮膚に適用する外用剤（皮膚外用剤）がより好ましい。 The composition for preventing or treating pigmentation of the present invention may be administered orally or parenterally. Examples of preparations for oral administration (oral administration preparations) include dosage forms such as tablets, capsules, powders, fine granules, liquids, troches, and jelly. As preparations for parenteral administration (parenteral administration preparations), extracts, plasters, spirits, suppositories, suspensions, tinctures, ointments, poultices, liniments, lotions, aerosols, In addition to the dosage forms used in pharmaceuticals such as eye drops, injections, etc., in the form of cosmetic compositions such as creams, lotions, emulsions, foams, foundations, packs, skin cleansers, shampoos, rinses, conditioners, etc. A dosage form can be mentioned. The parenteral preparation of the present invention is preferably an ointment, cream or lotion. The composition of the present invention is preferably a preparation (external preparation) administered parenterally, more preferably an external preparation (skin external preparation) applied to the skin.
本発明の組成物の製剤化は、公知の製剤技術により行うことができ、製剤中には適当な製剤添加物を加えることができる。製剤添加物としては、賦形剤、結合剤、崩壊剤、滑沢剤、流動化剤、懸濁化剤、乳化剤、安定化剤、保湿（湿潤）剤、保存剤、溶剤、溶解補助剤、防腐剤、矯味剤、甘味剤、色素、香料、噴射剤等を挙げることができ、製剤添加物は、本発明の効果を損なわない範囲で適宜選択して、適当量を加えればよい。 Formulation of the composition of the present invention can be performed by known formulation techniques, and appropriate formulation additives can be added to the formulation. Formulation additives include excipients, binders, disintegrants, lubricants, fluidizers, suspending agents, emulsifiers, stabilizers, moisturizing (wetting) agents, preservatives, solvents, dissolution aids, Preservatives, taste-masking agents, sweeteners, pigments, fragrances, propellants, and the like can be mentioned, and formulation additives may be appropriately selected within a range that does not impair the effects of the present invention, and an appropriate amount may be added.
本発明の色素沈着症の予防又は治療剤は、シミ（肝斑を含む）、そばかす、日やけ、色黒やステロイド等の薬物による皮膚の黒化症等の色素沈着症の予防又は治療を目的としている者や肌色をさらに白くしたいと希望する者に対する美白剤として投与するものである。
以下に、実施例を示して本発明をさらに説明するが、本発明はこれらのみに限定されるべきものではない。
The agent for preventing or treating pigmentation of the present invention is intended to prevent or treat pigmentation such as melanosis of skin caused by drugs such as spots (including melasma), freckles, sunburn, dark black and steroids. It is administered as a whitening agent for those who want to make the skin color whiter.
EXAMPLES The present invention will be further described below with reference to examples, but the present invention should not be limited to these examples.
１．色素沈着抑制効果の評価
１．１ 試験方法
Weiser-Maples系褐色 モルモット（6週齢、オス；東京実験動物）の背部左右2箇所（計4箇所）を電気バリカン及び電気シェーバーで毛刈りを行った。翌日より1日1回週5日間（土日を除く）毛刈り部に検体を塗布した。塗布方法は、媒体又は被験物質溶液40μL［媒体は、エタノール、1,3-ブタンジオール、注射用水（1：1：8）混液］を塗布した後、3％アラキドン酸溶液（媒体はエタノール）40μLをマイクロピペットで塗布した。
塗布した被験物質、アラキドン酸塗布の有無、及び無処置群の６つの実験群［（１）〜（６）］を表１に示した。なお、ロキソプロフェンナトリウムは、第一三共プロファーマ(株)社製のロキソプロフェンナトリウム２水和物を、トラネキサム酸は第一三共プロファーマ(株)社製のものを、アラキドン酸はシグマアルドリッチ社製のものを使用し、表１に記載した被験物質濃度になるように媒体［エタノール、1,3-ブタンジオール、注射用水（1：1：8）混液］で希釈溶解し、当該溶液40μLをモルモットに塗布した。なお、以下の実験、製剤例に記載のロキソプロフェンナトリウムの使用量は、使用したロキソプロフェンナトリウム２水和物を無水物換算したものを示す。
1. Evaluation of pigmentation inhibitory effect 1.1 Test method
Weiser-Maples brown guinea pigs (6 weeks old, male; Tokyo experimental animals) were trimmed with an electric clipper and electric shaver at two places on the left and right sides of the back (total of four places). From the next day, the sample was applied to the shaved portion once a day for 5 days a week (except Saturdays and Sundays). Application method is 40 μL of medium or test substance solution [medium is ethanol, 1,3-butanediol, water for injection (1: 1: 8)], then 3% arachidonic acid solution (medium is ethanol) 40 μL Was applied with a micropipette.
Table 1 shows the test substance applied, the presence or absence of arachidonic acid application, and six experimental groups [(1) to (6)] of the untreated group. Loxoprofen sodium is loxoprofen sodium dihydrate manufactured by Daiichi Sankyo Propharma Co., Ltd., tranexamic acid is manufactured by Daiichi Sankyo Propharma Co., Ltd., and arachidonic acid is Sigma Aldrich. Use the product made by diluting and dissolving in a medium [ethanol, 1,3-butanediol, water for injection (1: 1: 8)] so that the test substance concentration shown in Table 1 is obtained. Applied to guinea pigs. In addition, the usage-amount of the loxoprofen sodium described in the following experiment and formulation example shows what used the loxoprofen sodium dihydrate converted to the anhydride.
１．２ 結果
投与開始日及び投与開始16日目に色彩色差計（CR-400、コニカミノルタ製）を用いて検体塗布部位のL値（明度）を測定し、ΔL値（観察日のL値−投与開始日のL値）を求め、結果を図１に示した。（ΔL値の絶対値が小さいほど、色素沈着を抑制する効果が高いことを示す。）。
また、図２は媒体群に対する抑制率（％）を示した図である。
1.2 Results The L value (lightness) of the specimen application site was measured using a color difference meter (CR-400, manufactured by Konica Minolta) on the administration start day and the administration start day 16, and ΔL value (L value on the observation day) -L value of administration start date) was determined, and the results are shown in FIG. (The smaller the absolute value of the ΔL value, the higher the effect of suppressing pigmentation).
FIG. 2 is a graph showing the suppression rate (%) for the medium group.
図１の（１）、（２）の比較からアラキドン酸溶液の塗布によりΔL値（観察日のL値−投与開始日のL値）が減少しており、色素沈着が起きたことが分かる。また、図１（２）〜（４）及び図２（３）及び（４）の結果からトラネキサム酸塗布により用量依存的なΔL値の減少作用抑制（色素沈着抑制作用）が見られた（3％トラネキサム酸塗布で抑制率10.86％）。一方、図１（２）と（５）の比較及び図２（５）の結果から10％ロキソプロフェンナトリウムの色素沈着抑制効果が確認できた（抑制率34.15%）。図１の（５）と（６）、及び図２の（６）の結果から、10%ロキソプロフェンナトリウムと3％トラネキサム酸の併用による抑制率は58.56％であり、ロキソプロフェンナトリウムとトラネキサム酸を併用することにより色素沈着抑制作用はより強まり、優れた効果を奏することが分かった。 From the comparison of (1) and (2) in FIG. 1, it can be seen that ΔL value (L value on the observation day−L value on the start date of administration) decreased due to the application of the arachidonic acid solution, and pigmentation occurred. In addition, from the results of FIGS. 1 (2) to (4) and FIGS. 2 (3) and (4), a dose-dependent decrease in ΔL value (pigmentation inhibitory effect) was observed by application of tranexamic acid (3). % Tranexamic acid application rate 10.86%). On the other hand, the pigmentation inhibitory effect of 10% loxoprofen sodium was confirmed from the comparison of FIGS. 1 (2) and (5) and the result of FIG. 2 (5) (suppression rate 34.15%). From the results of (5) and (6) of FIG. 1 and (6) of FIG. 2, the inhibition rate by the combined use of 10% loxoprofen sodium and 3% tranexamic acid is 58.56%, and the combination of loxoprofen sodium and tranexamic acid is used. As a result, it was found that the pigmentation-inhibiting action was strengthened and an excellent effect was achieved.
２．製剤例
２．１ ローション剤
（製剤例１）
下記（表２）の組成にて、第１６改正日本薬局方製剤総則に準じてローション剤を製造した。
2. Formulation Example 2.1 Lotion (Formulation Example 1)
A lotion preparation was produced with the composition shown below (Table 2) according to the 16th revised Japanese Pharmacopoeia General Rules for Preparations.
（製剤例２）
下記（表３）の組成にて、第１６改正日本薬局方製剤総則に準じてローション剤を製造した。
(Formulation example 2)
A lotion preparation was produced with the composition shown below (Table 3) according to the 16th revised Japanese Pharmacopoeia Preparation General Rules.
（製剤例３）
下記（表４）の組成にて、第１６改正日本薬局方製剤総則に準じてローション剤を製造した。
(Formulation example 3)
A lotion preparation was produced with the composition shown below (Table 4) according to the 16th revised Japanese Pharmacopoeia General Rules for Preparations.
（製剤例４）
下記（表５）の組成にて、第１６改正日本薬局方製剤総則に準じてローション剤を製造した。
(Formulation example 4)
A lotion preparation was produced with the composition shown below (Table 5) according to the 16th revised Japanese Pharmacopoeia General Rules for Preparations.
２．２ クリーム剤
下記（表６）の組成（重量％）にて、第１６改正日本薬局方製剤総則に準じてクリーム剤を製造した。
2.2 Cream Agent A cream agent was produced according to the 16th revised Japanese Pharmacopoeia General Formulation with the composition (% by weight) shown below (Table 6).
２．３ 化粧水
下記（表７）の組成（重量％）にて、常法に従って化粧水を製造した。
2.3 Lotion Toner lotion was produced according to a conventional method with the composition (% by weight) shown below (Table 7).
２．４ クリーム
下記（表８）の組成（重量％）にて、常法に従ってクリームを製造した。
2.4 Cream A cream was produced according to a conventional method with the composition (% by weight) shown below (Table 8).
本発明の組成物は、優れた色素沈着抑制効果を示した。したがって、本発明の色素沈着症の予防又は治療剤、シミ（肝斑を含む）、そばかす、日やけ、色黒やステロイド等の薬物による皮膚の黒化症等の色素沈着症の予防及び／又は治療剤として、又は美白剤として有用なものである。 The composition of this invention showed the outstanding pigmentation inhibitory effect. Therefore, the preventive or therapeutic agent for pigmentation of the present invention, the prevention of pigmentation such as skin darkening caused by drugs such as stains (including measles), freckles, sunburn, dark skin and steroids, and / or It is useful as a therapeutic agent or a whitening agent.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2013025662A JP6166544B2 (en) | 2013-02-13 | 2013-02-13 | Preventive or therapeutic agent for pigmentation disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2013025662A JP6166544B2 (en) | 2013-02-13 | 2013-02-13 | Preventive or therapeutic agent for pigmentation disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2014152159A JP2014152159A (en) | 2014-08-25 |
| JP6166544B2 true JP6166544B2 (en) | 2017-07-19 |
Family
ID=51574376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013025662A Active JP6166544B2 (en) | 2013-02-13 | 2013-02-13 | Preventive or therapeutic agent for pigmentation disease |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6166544B2 (en) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5093998B2 (en) * | 2004-09-22 | 2012-12-12 | 大塚製薬株式会社 | Pigmentation preventing or improving agent |
| JP5514268B2 (en) * | 2004-09-22 | 2014-06-04 | 大塚製薬株式会社 | Pigmentation preventing or improving agent |
| JP5835865B2 (en) * | 2008-09-04 | 2015-12-24 | 興和株式会社 | Loxoprofen-containing pharmaceutical composition |
| JP5797374B2 (en) * | 2009-09-24 | 2015-10-21 | ポーラ化成工業株式会社 | Phagocytosis inhibitor |
| JP6126780B2 (en) * | 2010-12-13 | 2017-05-10 | 第一三共ヘルスケア株式会社 | Solid formulation containing loxoprofen sodium and tranexamic acid |
| JP5797470B2 (en) * | 2011-06-13 | 2015-10-21 | エスエス製薬株式会社 | Skin deposition pigment elimination promoter |
| JP5789426B2 (en) * | 2011-06-17 | 2015-10-07 | エスエス製薬株式会社 | Epidermis turnover accelerator |
| JP5694271B2 (en) * | 2012-10-24 | 2015-04-01 | 第一三共ヘルスケア株式会社 | Topical skin preparation |
-
2013
- 2013-02-13 JP JP2013025662A patent/JP6166544B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014152159A (en) | 2014-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230277477A1 (en) | Compositions for treating dermatological diseases | |
| WO2000021925A1 (en) | Cysteine derivatives | |
| JP4605774B2 (en) | Whitening agent, whitening skin external preparation and whitening method | |
| KR20150088302A (en) | Dermatitis treatment | |
| AU2010217615B2 (en) | Uses of NK receptor antagonists | |
| JP5425229B2 (en) | Use of NK receptor antagonists | |
| JP6822648B2 (en) | Tryptase inhibitor composition | |
| JP2009221154A (en) | Interleukin-6 production inhibitor | |
| JP6166544B2 (en) | Preventive or therapeutic agent for pigmentation disease | |
| ITBS20120093A1 (en) | COSMETIC AND PHARMACEUTICAL COMPOSITION FOR TREATMENT OF SKIN INFLAMMATION AND RELATED SYNDROMES | |
| JP2009062316A (en) | Skin care preparation for external application containing furan fatty acid or derivative thereof | |
| JP7166397B2 (en) | P. acnes biofilm disrupting composition | |
| JP6255154B2 (en) | Topical skin preparation | |
| JP2012219061A (en) | Moisturizing agent and skin care preparation | |
| JP2013133303A (en) | Advanced glycation end product production inhibitor | |
| JP5462504B2 (en) | Whitening composition | |
| JP2022554390A (en) | ROR gamma T inhibitors and their topical use | |
| JP2016150916A (en) | Sebum secretion inhibitor | |
| JP6177638B2 (en) | Skin external preparation for whitening | |
| JP6209350B2 (en) | Acne control composition, external preparation for skin and cosmetics | |
| JP4813886B2 (en) | Skin preparation for improving skin barrier function | |
| TW200306857A (en) | Skin preparation for external use | |
| JP2009519267A (en) | Diarylureas for treating inflammatory skin, eye and / or ear diseases | |
| JP2022186873A (en) | Acne bacteria biofilm destructive composition | |
| US20220288049A1 (en) | Bioactive phytochemicals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150827 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160527 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160608 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160722 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160801 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160909 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20161215 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170210 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20170605 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170623 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6166544 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |