JP2020117550A - Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof - Google Patents
Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof Download PDFInfo
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- JP2020117550A JP2020117550A JP2020085557A JP2020085557A JP2020117550A JP 2020117550 A JP2020117550 A JP 2020117550A JP 2020085557 A JP2020085557 A JP 2020085557A JP 2020085557 A JP2020085557 A JP 2020085557A JP 2020117550 A JP2020117550 A JP 2020117550A
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- Prior art keywords
- salt
- composition
- external use
- heparin
- ascorbic acid
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Links
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- 238000002845 discoloration Methods 0.000 title claims abstract description 44
- 235000010323 ascorbic acid Nutrition 0.000 title claims abstract description 40
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- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 title abstract 3
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Abstract
Description
本発明は、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物の経時的な変色を抑制する方法に関する。 The present invention relates to a method of suppressing discoloration over time of an external composition containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof.
ジフェンヒドラミン又はその塩は、強い抗ヒスタミン作用を有することから、止痒・鎮痒効果を期待して、医薬品・医薬部外品の薬理活性成分として汎用されている。アスコルビン酸又はその塩は、抗炎症効果、ニキビ改善効果、美白効果、老化防止効果、抗酸化効果などを期待して、医薬品、医薬部外品、化粧品など幅広い用途に汎用されている。ところが、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する製剤は、熱や光によって経時的に変色が生じる場合があることが知られている。このような変色が生じると商品価値が低下して好ましくないため、その解決手段もこれまでに検討されている。 Since diphenhydramine or its salt has a strong antihistamine action, it is widely used as a pharmacologically active ingredient of medicines and quasi drugs in expectation of antipruritic and antipruritic effects. Ascorbic acid or a salt thereof is widely used in a wide range of applications such as pharmaceuticals, quasi-drugs, and cosmetics in anticipation of anti-inflammatory effect, acne improving effect, whitening effect, anti-aging effect, antioxidant effect and the like. However, it is known that a preparation containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof may be discolored with time due to heat or light. If such discoloration occurs, the commercial value is lowered, which is not preferable, and therefore a means for solving the problem has been studied so far.
例えば、ジフェンヒドラミン又はその塩の熱による変色に対しては、ジフェンヒドラミン類を含有する油脂性軟膏剤に、ジブチルヒドロキシトルエンを単独で、又はジブチルヒドロキシトルエン及びメントールを組み合わせて添加することにより、当該油脂性軟膏剤の変色が防止できることが開示されている（特許文献１）。 For example, with respect to discoloration due to heat of diphenhydramine or a salt thereof, an oily ointment containing diphenhydramines, dibutylhydroxytoluene alone or by adding dibutylhydroxytoluene and menthol in combination, It is disclosed that discoloration of an ointment can be prevented (Patent Document 1).
さらに、ジフェンヒドラミン又はその塩の光による変色に対しては、ジフェンヒドラミン又はその塩を含有する製剤を遮光性を有する箱や包装容器内に保管する他、固形製剤の場合は、遮光剤を有するコーティング剤でジフェンヒドラミンを含有する製剤を被覆すること（特許文献２、３）、ジフェンヒドラミン塩を油液中に分散させる（特許文献４）、特定の高分子化合物（特許文献５：カルボキシメチルセルロースカルシウム、特許文献６：低膨潤性高分子及び高膨潤性高分子）を添加して製剤化するなどの手段により、ジフェンヒドラミン又はその塩を含有する製剤の変色が防止できることが開示されている。 Further, for discoloration of diphenhydramine or a salt thereof due to light, in addition to storing the formulation containing diphenhydramine or a salt in a box or a packaging container having a light shielding property, in the case of a solid formulation, a coating agent having a light shielding agent With a formulation containing diphenhydramine (Patent Documents 2 and 3), a diphenhydramine salt is dispersed in an oil liquid (Patent Document 4), and a specific polymer compound (Patent Document 5: carboxymethylcellulose calcium, Patent Document 6). : Low swelling polymer and high swelling polymer) are added to prepare a formulation to prevent discoloration of a formulation containing diphenhydramine or a salt thereof.
アスコルビン酸又はその塩の光による変色に対しては、ポリメタクロイルオキシエトキシホスホリルコリンと組み合わせて添加することにより、変色が防止できることが開示されている（特許文献７）。さらに、アスコルビン酸又はその塩の熱による変色に対しては、合成スチブンサイトと組み合わせて添加することにより、高温時の経時的な変色が抑えられることが開示されている（特許文献８）。 Regarding discoloration of ascorbic acid or a salt thereof due to light, it is disclosed that discoloration can be prevented by adding it in combination with polymethacryloyloxyethoxyphosphorylcholine (Patent Document 7). Further, regarding the discoloration of ascorbic acid or a salt thereof due to heat, it is disclosed that discoloration with time at high temperature can be suppressed by adding it in combination with synthetic stevensite (Patent Document 8).
また、アスコルビン酸又はその塩の経時的に変色する問題については、このアスコルビン酸又はその塩の変色に対して、オキシレスベラトロールと組み合わせてレシチンを用いてゲル化すること（特許文献９）、ショ糖脂肪酸エステルと組み合わせて多価アルコールを含有しない皮膚外用剤（特許文献１０）とすることで変色が防止できることが開示されている。 Regarding the problem of discoloration of ascorbic acid or a salt thereof over time, gelation using lecithin in combination with oxyresveratrol against discoloration of this ascorbic acid or a salt thereof (Patent Document 9), It is disclosed that discoloration can be prevented by combining the sucrose fatty acid ester with a sucrose fatty acid ester to prepare a skin external preparation containing no polyhydric alcohol (Patent Document 10).
しかしながら、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する製剤の、経時的な変色、特に熱及び／又は光による経時的な変色を抑制する手段としてムコ多糖類が有効であることはこれまでに知られていなかった。
さらに、特許文献１〜１０に開示された方法は、光又は熱の一方による変色を抑制するものであり、光及び熱の両方による変色に対して有効な方法もこれまでに知られていない。
However, it has been known that mucopolysaccharide is effective as a means for suppressing discoloration with time of a preparation containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof, particularly due to heat and/or light. Was not known to.
Further, the methods disclosed in Patent Documents 1 to 10 suppress discoloration due to either light or heat, and no method effective against discoloration due to both light and heat has been known so far.
本発明は、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物における経時的な変色、特に熱及び／又は光による経時的な変色を抑制することを目的とする。 An object of the present invention is to suppress discoloration over time in an external composition containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof, particularly discoloration with time due to heat and/or light.
本発明者らは、上記課題を解決するために鋭意研究した結果、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物に、ムコ多糖類（好ましくは、ヘパリン類似物質、コンドロイチン硫酸又はその塩、ヒアルロン酸又はその塩、ヒアルロン酸誘導体又はその塩、及びデルマタン硫酸又はその塩；特に好ましくはヘパリン類似物質）を共存させることにより、当該外用組成物の経時的な変色を抑制し得ることを見出し、本発明を完成するに至った。 The present inventors, as a result of earnest research to solve the above problems, diphenhydramine or a salt thereof and an external composition containing ascorbic acid or a salt thereof, a mucopolysaccharide (preferably a heparin-like substance, chondroitin sulfate or The presence of a salt thereof, hyaluronic acid or a salt thereof, a hyaluronic acid derivative or a salt thereof, and dermatan sulfate or a salt thereof; particularly preferably a heparin-like substance) can suppress discoloration of the external composition over time. The present invention has been completed and the present invention has been completed.
従って、本発明は以下を提供する。
〔１〕ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物において、ムコ多糖類の１種又は２種以上を共存させる、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物の変色抑制方法。
〔２〕ムコ多糖類が、ヘパリン類似物質、コンドロイチン硫酸又はその塩、ヒアルロン酸又はその塩、ヒアルロン酸誘導体又はその塩、及びデルマタン硫酸又はその塩からなる群から選択される１種又は２種以上である、〔１〕に記載の方法。
〔３〕ムコ多糖類が、ヘパリン類似物質及びコンドロイチン硫酸又はその塩からなる群から選択される１種又は２種以上である、〔１〕に記載の方法。
〔４〕ジフェンヒドラミン又はその塩を含有する外用組成物が、乳化物である、〔１〕〜〔３〕のいずれかに記載の方法。
〔５〕アスコルビン酸又はその塩を含有する外用組成物が、液剤である、〔１〕〜〔３〕のいずれかに記載の方法。
〔６〕ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩１重量部に対して、ムコ多糖類の１種又は２種以上を０．００３〜１０重量部共存させる、〔１〕〜〔５〕のいずれかに記載の方法。
〔７〕変色が、熱及び／又は光によるものである、〔１〕〜〔６〕のいずれかに記載の方法。
Accordingly, the present invention provides the following:
[1] A composition for external use containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof, in which one or more mucopolysaccharides are allowed to coexist, and an external composition containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof Discoloration suppression method for objects.
[2] The mucopolysaccharide is one or more selected from the group consisting of a heparin-like substance, chondroitin sulfate or a salt thereof, hyaluronic acid or a salt thereof, a hyaluronic acid derivative or a salt thereof, and dermatan sulfate or a salt thereof. The method according to [1].
[3] The method according to [1], wherein the mucopolysaccharide is one or more selected from the group consisting of a heparin-like substance and chondroitin sulfate or a salt thereof.
[4] The method according to any one of [1] to [3], wherein the composition for external use containing diphenhydramine or a salt thereof is an emulsion.
[5] The method according to any one of [1] to [3], wherein the external composition containing ascorbic acid or a salt thereof is a liquid agent.
[6] One or two or more kinds of mucopolysaccharides are allowed to coexist with 0.003 to 10 parts by weight per 1 part by weight of diphenhydramine or a salt thereof and ascorbic acid or a salt thereof, any of [1] to [5] The method described in crab.
[7] The method according to any one of [1] to [6], wherein the discoloration is due to heat and/or light.
〔８〕ムコ多糖類の１種又は２種以上を有効成分とする、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物の変色抑制剤。
〔９〕ムコ多糖類が、ヘパリン類似物質、コンドロイチン硫酸又はその塩、ヒアルロン酸又はその塩、ヒアルロン酸誘導体又はその塩、及びデルマタン硫酸又はその塩からなる群から選択される１種又は２種以上である、〔８〕に記載の変色抑制剤。
〔１０〕ムコ多糖類が、ヘパリン類似物質及びコンドロイチン硫酸又はその塩からなる群から選択される１種又は２種以上である、〔８〕に記載の変色抑制剤。
〔１１〕ジフェンヒドラミン又はその塩を含有する外用組成物が、乳化物である、〔８〕〜〔１０〕のいずれかに記載の変色抑制剤。
〔１２〕アスコルビン酸又はその塩を含有する外用組成物が、液剤である、〔８〕〜〔１０〕のいずれかに記載の変色抑制剤。
〔１３〕ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩１重量部に対して、ムコ多糖類の１種又は２種以上を０．００３〜１０重量部共存させる、〔８〕〜〔１２〕のいずれかに記載の変色抑制剤。
〔１４〕変色が、熱及び／又は光によるものである、〔８〕〜〔１３〕のいずれかに記載の変色抑制剤。
[8] A discoloration inhibitor for an external composition containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof, which contains one or more kinds of mucopolysaccharides as an active ingredient.
[9] The mucopolysaccharide is one or more selected from the group consisting of a heparin-like substance, chondroitin sulfate or a salt thereof, hyaluronic acid or a salt thereof, a hyaluronic acid derivative or a salt thereof, and dermatan sulfate or a salt thereof. The discoloration inhibitor according to [8], which is
[10] The discoloration inhibitor according to [8], wherein the mucopolysaccharide is one or more selected from the group consisting of a heparin-like substance and chondroitin sulfate or a salt thereof.
[11] The discoloration inhibitor according to any of [8] to [10], wherein the external composition containing diphenhydramine or a salt thereof is an emulsion.
[12] The discoloration inhibitor according to any of [8] to [10], wherein the external composition containing ascorbic acid or a salt thereof is a liquid agent.
[13] Any one of [8] to [12], wherein 0.003 to 10 parts by weight of one or more kinds of mucopolysaccharides coexist with 1 part by weight of diphenhydramine or a salt thereof and ascorbic acid or a salt thereof. The discoloration inhibitor of Crab.
[14] The discoloration inhibitor according to any of [8] to [13], wherein the discoloration is due to heat and/or light.
本発明の方法によれば、ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物の経時的な変色、特に熱及び／又は光による経時的な変色を抑制することができる。 According to the method of the present invention, discoloration with time of an external composition containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof, particularly, discoloration with heat and/or light can be suppressed.
以下、本発明を詳細に説明する。なお、本明細書中において使用される用語は、特に他に言及しない限り、当該分野で通常用いられる意味で用いられていることが理解されるべきである。 Hereinafter, the present invention will be described in detail. It should be understood that the terms used in the present specification have the meanings commonly used in the art, unless otherwise specified.
本発明の外用組成物に含有されるジフェンヒドラミンは公知の化合物であり、ジフェンヒドラミンの塩としては、薬学的に許容されるものであれば、特に制限されず使用できる。ジフェンヒドラミン又はその塩は水和物の形態であってもよい。
ジフェンヒドラミンの塩の具体例としては、有機酸塩（例えば、酢酸塩、トリフルオロ酢酸塩、酪酸塩、パルミチン酸塩、ステアリン酸塩等のモノカルボン酸塩；フマル酸塩、マレイン酸塩、コハク酸塩、マロン酸塩等の多価カルボン酸塩；乳酸塩、酒石酸塩、クエン酸塩等のオキシカルボン酸塩；ラウリル硫酸塩、メタンスルホン酸塩、トルエンスルホン酸塩等の有機スルホン酸塩；等）、無機酸塩（例えば、塩酸塩、硫酸塩、硝酸塩、臭化水素酸塩、リン酸塩等）、有機塩基との塩（例えば、メチルアミン、トリエチルアミン、トリエタノールアミン、モルホリン、ピペラジン、ピロリジン、トリピリジン、ピコリン等の有機アミンとの塩等）、金属との塩（例えば、ナトリウム、カリウム等のアルカリ金属；カルシウム、マグネシウム等のアルカリ土類金属；アルミニウム；等の金属との塩等）、アンモニウム塩等が挙げられる。
Diphenhydramine contained in the composition for external use of the present invention is a known compound, and the salt of diphenhydramine can be used without particular limitation as long as it is pharmaceutically acceptable. Diphenhydramine or a salt thereof may be in the form of a hydrate.
Specific examples of the salt of diphenhydramine include organic acid salts (for example, monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, stearate; fumarate, maleate, succinic acid). Salts, polyvalent carboxylic acid salts such as malonate; oxycarboxylic acid salts such as lactate, tartrate, citrate; organic sulfonic acid salts such as lauryl sulfate, methane sulfonate, toluene sulfonate; etc. ), inorganic acid salts (eg, hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc.), salts with organic bases (eg, methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine) , Salts with organic amines such as tripyridine and picoline), salts with metals (for example, alkali metals such as sodium and potassium; alkaline earth metals such as calcium and magnesium; aluminum; salts with metals such as aluminum), Examples thereof include ammonium salts.
本発明の外用組成物に配合するジフェンヒドラミン又はその塩の配合量は、所望の薬理作用を奏し得る限り特に制限されないが、外用組成物全体に対して、通常は０．１重量％以上、好ましくは０．５重量％以上、さらに好ましくは１重量％以上であり、配合上限は、通常１０重量％以下、好ましくは５重量％以下、さらに好ましくは２重量％以下とするのがよい。 The amount of diphenhydramine or a salt thereof to be added to the composition for external use of the present invention is not particularly limited as long as it can exert a desired pharmacological action, but is usually 0.1% by weight or more, preferably, to the entire composition for external use. It is 0.5% by weight or more, more preferably 1% by weight or more, and the upper limit of the compounding amount is usually 10% by weight or less, preferably 5% by weight or less, more preferably 2% by weight or less.
本発明の外用組成物に含有されるアスコルビン酸は公知の化合物であり、アスコルビン酸の塩としては、薬学的に許容されるものであれば、特に制限されず使用できる。アスコルビン酸又はその塩は水和物の形態であってもよい。
アスコルビン酸の塩の具体例としては、有機塩基との塩（例えば、トリメチルアミン塩、トリエチルアミン塩、モノエタノールアミン塩、トリエタノールアミン塩、ピリジン塩などの第３級アミンとの塩、アルギニンなどの塩基性アンモニウム塩など）、無機塩基との塩（例えば、アンモニウム塩、ナトリウム塩、カリウム塩などのアルカリ金属塩、カルシウム塩、マグネシウム塩などのアルカリ土類金属塩、アルミニウム塩など）などが挙げられ、特に好ましい塩は、ナトリウム塩、カリウム塩である。具体的には、アスコルビン酸ナトリウム、アスコルビン酸モノリン酸エステルナトリウム、アスコルビン酸ジリン酸
エステルナトリウム、アスコルビン酸トリリン酸エステルナトリウム、アスコルビン酸−２−硫酸エステルナトリウム等が挙げられる。
Ascorbic acid contained in the composition for external use of the present invention is a known compound, and the salt of ascorbic acid can be used without particular limitation as long as it is pharmaceutically acceptable. Ascorbic acid or its salt may be in the form of a hydrate.
Specific examples of the salt of ascorbic acid include salts with organic bases (for example, salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, and bases such as arginine). Ammonium salts), salts with inorganic bases (for example, alkali metal salts such as ammonium salts, sodium salts, potassium salts, alkaline earth metal salts such as calcium salts, magnesium salts, aluminum salts, etc.), and the like. Particularly preferred salts are sodium salts and potassium salts. Specific examples include sodium ascorbate, sodium ascorbyl monophosphate, sodium ascorbyl diphosphate, sodium ascorbyl triphosphate, and sodium ascorbate-2-sulfate.
本発明の外用組成物に含有されるアスコルビン酸又はその塩は医薬品、医薬部外品または化粧品分野において皮膚外用剤の成分として市販されているアスコルビン酸又はその塩を用いることができる。本発明で用いるアスコルビン酸又はその塩の配合量は、本発明の効果を奏し得る限り特に制限されないが、皮膚外用剤全体に対して、通常は０．１重量％以上、好ましくは０．５重量％以上、さらに好ましくは１重量％以上であり、配合上限は、通常３０重量％以下、好ましくは１０重量％以下、さらに好ましくは５重量％以下とするのがよい。 Ascorbic acid or a salt thereof contained in the composition for external use of the present invention may be ascorbic acid or a salt thereof which is commercially available as a component of a skin external preparation in the fields of medicines, quasi drugs or cosmetics. The amount of ascorbic acid or a salt thereof used in the present invention is not particularly limited as long as the effects of the present invention can be exhibited, but is usually 0.1% by weight or more, preferably 0.5% by weight, based on the whole external preparation for skin. % Or more, more preferably 1% by weight or more, and the upper limit of compounding is usually 30% by weight or less, preferably 10% by weight or less, and more preferably 5% by weight or less.
ジフェンヒドラミン又はその塩並びにアスコルビン酸又はその塩を含有する外用組成物は、経時的に変色、特に熱及び／又は光によって経時的に変色するが、本発明の変色抑制方法は、ムコ多糖類を有効成分とする点を特徴とする。 The composition for external use containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof is discolored with time, particularly discolored with heat and/or light, but the discoloration suppressing method of the present invention is effective for mucopolysaccharides. It is characterized by the point as an ingredient.
ムコ多糖類は、皮膚の天然保湿因子として知られ、優れた保湿効果を有していることから、本発明の変色抑制方法の有効成分としてムコ多糖類を共存させることにより、本発明の外用組成物は優れた保湿効果を奏することも期待される。 Mucopolysaccharide is known as a natural moisturizing factor for skin and has an excellent moisturizing effect. Therefore, by coexisting mucopolysaccharide as an active ingredient of the discoloration suppressing method of the present invention, the external composition of the present invention is used. It is also expected that the product will have an excellent moisturizing effect.
ムコ多糖類は、その基本骨格にアミノ糖とウロン酸とを含有する多糖類であって、動物の組織から得られる。ムコ多糖類の具体例としては、ヘパリン類似物質、コンドロイチン硫酸、デルマタン硫酸、ヒアルロン酸、ヘパラン硫酸、ヘパリン、ケラタン硫酸Ｉ及びＩＩ等、及びこれらの誘導体、並びにこれらの塩が挙げられる。 Mucopolysaccharide is a polysaccharide containing an amino sugar and uronic acid in its basic skeleton, and is obtained from animal tissues. Specific examples of the mucopolysaccharides include heparin analogs, chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparan sulfate, heparin, keratan sulfate I and II, and their derivatives, and salts thereof.
ヘパリン類似物質、コンドロイチン硫酸、デルマタン硫酸、ヒアルロン酸、ヘパラン硫酸、ヘパリン、ケラタン硫酸Ｉ及びＩＩ等及びこれらの誘導体の塩としては、薬学的・生学的に許容される塩が好ましい。例えば、ナトリウム、カリウム等のアルカリ金属塩；マグネシウム、カルシウム等のアルカリ土類金属塩；アンモニウム塩；モノエタノールアミン等のアルカノールアミン塩；等を挙げることができ、好ましくはナトリウム塩等のアルカリ金属塩である。 As salts of heparin-like substances, chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparan sulfate, heparin, keratan sulfate I and II and the derivatives thereof, pharmaceutically and biologically acceptable salts are preferable. Examples thereof include alkali metal salts such as sodium and potassium; alkaline earth metal salts such as magnesium and calcium; ammonium salts; alkanolamine salts such as monoethanolamine; and the like, preferably alkali metal salts such as sodium salt. Is.
本発明に用いるムコ多糖類の由来は特に制限されず、医薬品、医薬部外品、又は化粧品の分野において通常用いられ得るものを特に限定されず用いることができる。
本発明において、ムコ多糖類は、１種単独で使用しても、また２種以上を任意に組み合わせて使用してもよい。また、ムコ多糖類は、市販品がある場合、市販品をそのまま使用してもよい。
The origin of the mucopolysaccharide used in the present invention is not particularly limited, and those commonly used in the fields of pharmaceuticals, quasi drugs, or cosmetics can be used without particular limitation.
In the present invention, the mucopolysaccharides may be used alone or in any combination of two or more. If a mucopolysaccharide is commercially available, the commercially available mucopolysaccharide may be used as it is.
本発明の組成物において、ムコ多糖類の平均分子量は特に制限されないが、通常は１０００〜４００万、好ましくは１０００〜１２０万であり、より好ましくは５０００〜１００万、特に好ましくは５０００〜４０万である。 In the composition of the present invention, the average molecular weight of the mucopolysaccharide is not particularly limited, but is usually 1000 to 4,000,000, preferably 1000 to 1.2 million, more preferably 5000 to 1,000,000, and particularly preferably 5000 to 400,000. Is.
本発明に用いられるムコ多糖類としては、具体的には、ヘパリン類似物質；コンドロイチン硫酸、コンドロイチン硫酸ナトリウム等のコンドロイチン硫酸又はその塩；デルマタン硫酸、デルマタン硫酸ナトリウム等のデルマタン硫酸またはその塩；ヒアルロン酸、ヒアルロン酸ナトリウム、ヒアルロン酸カリウム、ヒアルロン酸マグネシウム、ヒアルロン酸カルシウム等のヒアルロン酸又はその塩；アセチルヒアルロン酸、アセチルヒアルロン酸ナトリウム、アセチルヒアルロン酸カリウム、アセチルヒアルロン酸マグネシウム、アセチルヒアルロン酸カルシウム等のヒアルロン酸誘導体又はその塩；ヘパラン硫酸；ヘパリン；ケラタン硫酸Ｉ及びＩＩ；等や、これらの混合物等が挙げられる。 Specific examples of the mucopolysaccharides used in the present invention include heparin-like substances; chondroitin sulfates, chondroitin sulfates such as sodium chondroitin sulfate or salts thereof; dermatan sulfates such as dermatan sulfate and sodium dermatan sulfate or salts thereof; hyaluronic acid. , Sodium hyaluronate, potassium hyaluronate, hyaluronic acid magnesium, calcium hyaluronate, or a salt thereof; acetyl hyaluronic acid, sodium acetyl hyaluronate, potassium acetyl hyaluronate, magnesium acetyl hyaluronate, hyaluronic acid such as calcium acetyl hyaluronate Acid derivatives or salts thereof; heparan sulfate; heparin; keratan sulfates I and II; and the like, and mixtures thereof.
本発明に用いられるムコ多糖類としては、本発明の効果の発揮の観点から、好ましくはヘパリン類似物質；コンドロイチン硫酸、コンドロイチン硫酸ナトリウム等のコンドロイチン硫酸又はその塩；ヒアルロン酸、ヒアルロン酸ナトリウム等のヒアルロン酸又はその塩；アセチルヒアルロン酸、アセチルヒアルロン酸ナトリウム等のヒアルロン酸誘導体又はその塩；デルマタン硫酸、デルマタン硫酸ナトリウム等のデルマタン硫酸またはその塩；等が、より好ましくはヘパリン類似物質や、コンドロイチン硫酸、コンドロイチン硫酸ナトリウム等のコンドロイチン硫酸又はその塩等が、特に好ましくはヘパリン類似物質が挙げられる。 From the viewpoint of exhibiting the effects of the present invention, the mucopolysaccharide used in the present invention is preferably a heparin-like substance; chondroitin sulfate, chondroitin sulfate such as sodium chondroitin sulfate or a salt thereof; hyaluronic acid, hyaluronic acid such as sodium hyaluronate. An acid or a salt thereof; a hyaluronic acid derivative such as acetyl hyaluronic acid or sodium acetyl hyaluronate or a salt thereof; a dermatan sulfate such as dermatan sulfate or sodium dermatan sulfate or a salt thereof; and the like, more preferably a heparin analogue or chondroitin sulfate, Chondroitin sulphate such as sodium chondroitin sulphate or a salt thereof, particularly preferably a heparin-like substance.
ここで、ヘパリン類似物質とは、コンドロイチン多硫酸等の多硫酸化ムコ多糖の総称を意味し、ムコ多糖を構成する単糖１分子当たり平均０．５〜５分子、好ましくは平均０．６〜３分子の硫酸基を有するのが好ましい。より具体的には、ヘパリン類似物質は、ヘパリン、コンドロイチンポリ硫酸と呼ばれるコンドロイチン硫酸Ｄやコンドロイチン硫酸Ｅ等を含有する。
ヘパリン類似物質は、ムコ多糖を硫酸化することにより得ることもできるし、ウシ、ブタ等の動物の気管支を含む内臓より水性担体を用いて抽出・精製したり、その後必要に応じて硫酸化することによっても得ることもできる。このようなヘパリン類似物質は、医薬化粧品原料として開発されているため、このような市販品を利用することもできる。
本発明の外用組成物において、ヘパリン類似物質としては、日本薬局方外医薬品規格に収戴されているものが好適に使用される。
Here, the heparin-like substance means a general term for polysulfated mucopolysaccharides such as chondroitin polysulfate, and the average of 0.5 to 5 molecules, preferably the average of 0.6 to 1 molecule per monosaccharide constituting the mucopolysaccharide. It preferably has 3 molecules of sulfate groups. More specifically, the heparin-like substance contains heparin, chondroitin sulfate D called chondroitin polysulfate, chondroitin sulfate E, and the like.
The heparin-like substance can be obtained by sulfating a mucopolysaccharide, or can be extracted and purified from an internal organ including bronchi of an animal such as bovine or pig using an aqueous carrier, and then sulfated if necessary. It can also be obtained. Since such a heparin-like substance has been developed as a raw material for pharmaceuticals and cosmetics, such commercially available products can also be used.
In the composition for external use of the present invention, as the heparin-like substance, those contained in the Japanese Pharmacopoeia standard are preferably used.
本発明の外用組成物に配合するムコ多糖類の配合量は、本願効果を奏し得る限り特に制限されないが、外用組成物全体に対して、通常は０．００５重量％以上、好ましくは０．０１重量％以上、さらに好ましくは０．０５重量％以上、特に好ましくは０．１重量％以上であり、配合上限は、通常１０重量％以下、好ましくは５重量％以下、さらに好ましくは１重量％以下、特に好ましくは０．５重量％以下とするのがよい。 The amount of the mucopolysaccharide to be added to the composition for external use of the present invention is not particularly limited as long as the effect of the present invention can be obtained, but is usually 0.005% by weight or more, preferably 0.01% to the entire composition for external use. % Or more, more preferably 0.05% by weight or more, particularly preferably 0.1% by weight or more, and the upper limit of compounding is usually 10% by weight or less, preferably 5% by weight or less, more preferably 1% by weight or less. It is particularly preferable that the amount is 0.5% by weight or less.
本発明の外用組成物におけるジフェンヒドラミン又はその塩とムコ多糖類との重量比は、本願効果を奏し得る限り特に制限されないが、ジフェンヒドラミン又はその塩１重量部に対して、ムコ多糖類が通常は０．００５〜１０重量部、好ましくは０．０１〜５重量部、さらに好ましくは０．０５〜２重量部、特に好ましくは０．１〜１重量部の範囲内とするのがよい。 The weight ratio of diphenhydramine or a salt thereof and mucopolysaccharide in the composition for external use of the present invention is not particularly limited as long as the effect of the present application can be exerted, but the mucopolysaccharide is usually 0 with respect to 1 part by weight of diphenhydramine or a salt thereof. 0.005 to 10 parts by weight, preferably 0.01 to 5 parts by weight, more preferably 0.05 to 2 parts by weight, and particularly preferably 0.1 to 1 part by weight.
本発明の外用組成物におけるアスコルビン酸又はその塩とムコ多糖類との重量比は、本願効果を奏し得る限り特に制限されないが、アスコルビン酸又はその塩１重量部に対して、ムコ多糖類が通常は０．００３〜１０重量部、好ましくは０．００５〜１重量部、さらに好ましくは０．０１〜０．３重量部の範囲内とするのがよい。 The weight ratio of ascorbic acid or a salt thereof and mucopolysaccharide in the composition for external use of the present invention is not particularly limited as long as the effect of the present invention can be exerted, but 1 part by weight of ascorbic acid or a salt thereof is usually mucopolysaccharide. Is 0.003 to 10 parts by weight, preferably 0.005 to 1 part by weight, and more preferably 0.01 to 0.3 part by weight.
本発明の外用組成物は、その用途に応じて、種々の形態に調製することができ、例えば、クリーム、乳液、ゲル乳液、ローション、美容液、化粧水、軟膏剤、固形剤等の形態が挙げられる。なかでも、広範囲に塗布しやすいことから、本発明の実施形態としてはクリーム、乳液、ゲル乳液等の乳化物、ローション、美容液、化粧水等の液剤が好ましい。 The composition for external use of the present invention can be prepared in various forms depending on its use, and examples thereof include creams, emulsions, gel emulsions, lotions, beauty essences, lotions, ointments, and solid formulations. Can be mentioned. Among them, emulsions such as creams, emulsions, gel emulsions, liquids such as lotions, beauty essences, and lotions are preferable because they can be easily applied over a wide range.
本発明の外用組成物には、保存安定性や粘度等の品質を損なわず、また本発明の効果を損なわない量的及び質的範囲内で、必要に応じて医薬品、医薬部外品または化粧品分野において一般的に用いられる各種の成分、例えば水、油性成分（例えば、炭化水素、植物油、エステル油、高級アルコール、シリコーン油、脂肪酸等）、多価アルコール、増粘剤、低級アルコール、界面活性剤、保存剤、ｐＨ調整剤、安定化剤、刺激軽減剤、防腐剤、着色剤、分散剤、香料等を配合することができる。なお、これらの成分は１種単独で、または２種以上を任意に組み合わせて配合することができる。またこれらの成分の配合量は、本発明の効果を奏すれば特に制限されないが、望ましくは薬学上許容される上限配合量を限度に適宜選択される。 The composition for external use of the present invention contains a drug, a quasi drug or a cosmetic as needed, within a quantitative and qualitative range that does not impair the quality such as storage stability and viscosity, and does not impair the effects of the present invention. Various components commonly used in the field, such as water, oily components (eg, hydrocarbons, vegetable oils, ester oils, higher alcohols, silicone oils, fatty acids, etc.), polyhydric alcohols, thickeners, lower alcohols, surfactants Agents, preservatives, pH adjusters, stabilizers, stimulants, preservatives, colorants, dispersants, fragrances and the like can be added. In addition, these components can be blended individually by 1 type or in arbitrary combination of 2 or more types. Further, the blending amount of these components is not particularly limited as long as the effects of the present invention are exhibited, but is preferably selected appropriately within the upper limit of the pharmaceutically acceptable blending amount.
本発明の外用組成物には、該組成物に所望の効果を持たせるため、さらに有効成分を配合することができる。本発明において有効成分とは、薬理活性成分や生理活性成分等の皮膚に対して有用な効果を有する成分で、特に制限されないが、例えば、非ステロイド性抗炎症剤、ビタミン類、美白剤、抗シワ剤、消炎鎮痛剤、抗真菌剤、ステロイド剤、育毛剤、痩身剤、局所麻酔剤、鎮痒剤、抗菌剤、抗ウイルス剤、角質軟化剤、保湿剤、収斂剤、抗酸化剤、発毛抑制剤、紫外線吸収剤、紫外線散乱剤等が挙げられる。これらの成分は１種単独でまたは２種以上を組み合わせて用いることができる。またこれらの成分の配合量は、本発明の効果を奏すれば特に制限されないが、望ましくは薬学上許容される上限配合量を限度に適宜選択される。 The external composition of the present invention may further contain an active ingredient in order to give the composition a desired effect. In the present invention, the active ingredient is an ingredient having a useful effect on the skin, such as a pharmacologically active ingredient or a physiologically active ingredient, and is not particularly limited, and examples thereof include nonsteroidal anti-inflammatory agents, vitamins, whitening agents, and Wrinkles, anti-inflammatory analgesics, antifungals, steroids, hair growth agents, slimming agents, local anesthetics, antipruritics, antibacterial agents, antiviral agents, keratin softeners, moisturizers, astringents, antioxidants, hair growth. Inhibitors, UV absorbers, UV scatterers and the like can be mentioned. These components may be used alone or in combination of two or more. In addition, the blending amount of these components is not particularly limited as long as the effects of the present invention are exhibited, but is preferably selected appropriately within the upper limit of the pharmaceutically acceptable blending amount.
本発明の外用組成物は、通常、容器に充填されて使用される。このような容器としては、使用目的・用途に応じ、適宜選択した形状、材質の容器に収容し、使用することができ、当該技術分野において通常使用されるものであれば、特に制限されず使用できる。
容器（本体、キャップ、吐出部材、中栓、シール部材等）の材質としては、最内層が外用組成物の保存安定性等や、容器の耐薬品性、強度、柔軟性、耐候性等を考慮して適宜選択すればよく、例えば、ポリエチレン、ポリプロピレン、ポリエチレンテレフタレート、ポリスチレン、アルミ、ポリ塩化ビニル、ＡＢＳ樹脂、エチレン−ビニルアルコール樹脂、アクリロニトリル・スチレン樹脂、エポキシ樹脂、ポリアミド・イミド樹脂及びガラス等が挙げられる。好ましくは、容器材質として最内層がポリエチレン、ポリプロピレン、ポリエチレンテレフタレート、アルミ、エポキシ樹脂、ポリアミド・イミド樹脂及びガラスの容器が挙げられる。また、これらの容器樹脂を使用した積層体を用いてもよい。
The composition for external use of the present invention is usually used by filling it in a container. As such a container, it can be contained and used in a container having an appropriately selected shape and material depending on the intended purpose and application, and is not particularly limited as long as it is a container normally used in the technical field. it can.
Regarding the material of the container (main body, cap, discharge member, inner plug, seal member, etc.), the innermost layer is the storage stability of the composition for external use, and the chemical resistance, strength, flexibility and weather resistance of the container are taken into consideration. And polyethylene, polypropylene, polyethylene terephthalate, polystyrene, aluminum, polyvinyl chloride, ABS resin, ethylene-vinyl alcohol resin, acrylonitrile/styrene resin, epoxy resin, polyamide/imide resin, glass and the like. Can be mentioned. Preferred examples of the container material include containers whose innermost layer is polyethylene, polypropylene, polyethylene terephthalate, aluminum, epoxy resin, polyamide-imide resin, and glass. Moreover, you may use the laminated body which uses these container resins.
本発明の外用組成物は、様々な症状や疾患の治療、予防又は改善用の組成物として用いることができる。本発明の外用組成物の外皮への適用量や用法は特に制限されず、該組成物は通常、一日数回、適量を皮膚等の外皮に塗布する等して用いることができる。 The composition for external use of the present invention can be used as a composition for treating, preventing or ameliorating various symptoms and diseases. The amount of the externally applied composition of the present invention to be applied to the outer skin and the usage thereof are not particularly limited, and the composition can be usually used several times a day by applying an appropriate amount to the outer skin such as skin.
本発明の外用組成物は、ジフェンヒドラミン又はその塩及びムコ多糖類が、治療、予防又は改善効果を奏する症状や疾患に対して用いるのが特に好ましい。このような症状、疾患としては、例えば、痒み症状；皮膚の乾燥に起因する症状；痒み症状や皮膚の乾燥に起因する症状を示す疾患；等が挙げられる。
皮膚の乾燥に起因する症状の具体例としては、皮膚表面の落屑、粉ふき、けばだち、かさつき、ひび、あかぎれ、ひじ・ひざ・かかと・くるぶし等の角化、顔の小じわ、皮膚柔軟性の低下、手指のあれ、痒み、乾燥肌（ドライスキン）、敏感肌、皮膚のかぶれ、紅斑、アトピー肌、肌荒れ等がある。
痒み症状や皮膚の乾燥に起因する症状を示す疾患の具体例としては、乾皮症、老人性乾皮症、小児乾燥性皮膚、尋常性鱗癬（鮫肌）、アトピー性皮膚炎、アレルギー性皮膚炎、皮脂減少性湿疹、敏感肌、季節性乾皮症、水性掻痒症、主婦湿疹、皮膚炎、かぶれ、じんましん、虫さされ、湿疹、ただれ、あせも、しもやけ等が挙げられる。
本発明の外用組成物は、痒みを伴う、皮膚の乾燥に起因する症状を示す疾患（例えば、乾皮症、老人性乾皮症、小児乾燥性皮膚等）に対して、特に有効である。
In the composition for external use of the present invention, it is particularly preferable to use diphenhydramine or a salt thereof and mucopolysaccharide for a symptom or disease having a therapeutic, preventive or ameliorating effect. Examples of such symptoms and diseases include itching symptoms; symptoms caused by dry skin; diseases showing itching symptoms and symptoms caused by dry skin; and the like.
Specific examples of symptoms caused by dry skin include scaling of the skin surface, dusting, fluff, lumps, cracks, cracks, keratinization of elbows, knees, heels and ankles, fine lines on the face, skin Decreased flexibility, finger rash, itching, dry skin (dry skin), sensitive skin, skin irritation, erythema, atopic skin, and rough skin.
Specific examples of diseases that cause itching and dry skin include xeroderma, senile xerosis, dry childhood, ichthyosis vulgaris (shark skin), atopic dermatitis, and allergic skin. Inflammation, sebum-decreasing eczema, sensitive skin, seasonal xerosis, pruritus vulgaris, housewife eczema, dermatitis, rash, urticaria, insect bites, eczema, sores, heat rashes, and burns.
The composition for external use of the present invention is particularly effective against diseases accompanied by itching and symptoms caused by dry skin (for example, xerosis, senile xerosis, pediatric dry skin, etc.).
本発明の外用組成物は、アスコルビン酸又はその塩及びムコ多糖類が、治療、予防又は改善効果を奏する症状や疾患に対して用いるのが特に好ましい。このような症状、疾患としては、例えば炎症症状；皮膚の炎症に起因する症状；肌あれ症状や皮膚の炎症に起因する症状を示す疾患；にきび等が挙げられる。皮膚の炎症に起因する症状の具体例としては、ひび、あかぎれ、手指のあれ、痒み、乾燥肌（ドライスキン）、敏感肌、皮膚のかぶれ、紅斑、アトピー肌、肌荒れ、日焼けによるしみ、そばかす等がある。
本発明の外用組成物は、皮膚の炎症に起因する症状を示す疾患（例えば、にきび、日焼けによるしみ、そばかす）に対して、特に有効である。
In the composition for external use of the present invention, it is particularly preferable to use ascorbic acid or a salt thereof and mucopolysaccharide for a symptom or disease for which a therapeutic, preventive or ameliorating effect is exhibited. Examples of such symptoms and diseases include inflammatory symptoms; symptoms caused by inflammation of the skin; diseases exhibiting skin roughness symptoms and symptoms caused by inflammation of the skin; acne and the like. Specific examples of the symptoms caused by skin inflammation include cracks, cracks, finger rash, itching, dry skin (dry skin), sensitive skin, skin irritation, erythema, atopic skin, rough skin, sunburn stains, freckles, etc. There is.
The composition for external use of the present invention is particularly effective against diseases (for example, acne, sunburn spots, freckles) that exhibit symptoms caused by skin inflammation.
以下に、実施例に基づいて本発明を詳細に説明するが、本発明はこれらの実施例によって限定されるものではない。なお、下記の各実施例において％とは特に言及しない限り、質量（Ｗ／Ｗ）％を意味するものとする。 Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to these examples. In each of the following examples,% means mass (W/W)% unless otherwise specified.
試験例１ ジフェンヒドラミン含有クリームの熱安定性及び光安定性試験
油相（パルミチン酸イソプロピル、流動パラフィン、セトマクロゴール、モノステアリン酸グリセリン、セタノール、白色ワセリンを混合溶解したもの）にジフェンヒドラミンを加え、７０℃まで加熱した。同様に水相（精製水、濃グリセリン、パラオキシ安息香酸メチル、カルボキシビニルポリマー、エデト酸ナトリウムを混合攪拌したもの）にヘパリン類似物質を加え、７０℃に加熱した。２相（油相、水相）を高温で攪拌・乳化し、室温まで冷却して、表１に示す組成の実施例１のクリームを得た。
比較例１のクリームは、ヘパリン類似物質を加えない以外は実施例１のクリームと同様にして、製造した。
Test Example 1 Thermal and Light Stability Test of Diphenhydramine-Containing Cream Diphenhydramine was added to an oil phase (mixture of isopropyl palmitate, liquid paraffin, cetomacrogol, glyceryl monostearate, cetanol and white petrolatum), and 70 Heated to °C. Similarly, a heparin-like substance was added to the aqueous phase (purified water, concentrated glycerin, methyl paraoxybenzoate, carboxyvinyl polymer, and sodium edetate mixed and stirred), and the mixture was heated to 70°C. The two phases (oil phase and water phase) were stirred and emulsified at high temperature and cooled to room temperature to obtain the cream of Example 1 having the composition shown in Table 1.
The cream of Comparative Example 1 was produced in the same manner as the cream of Example 1 except that the heparin-like substance was not added.
熱安定性試験
５０ｍｌの透明なねじ口ビンに、実施例１及び比較例１の外用組成物をそれぞれ約４０ｇ入れ、６０℃にて３日間保存し、目視にて色の変化を観察した。結果を表１に示す。
光安定性試験
５０ｍｌの透明なねじ口ビンに、実施例１及び比較例１の組成物をそれぞれ約４０ｇ入れ、２０〜２５℃にて光照射を行い（総照度１２０万ｌｕｘ・ｈｒ）、目視にて色の変化を観察した。結果を表１に示す。
Thermal Stability Test Approximately 40 g of each of the compositions for external use of Example 1 and Comparative Example 1 was placed in a transparent screw cap bottle of 50 ml, stored at 60° C. for 3 days, and the color change was visually observed. The results are shown in Table 1.
Light Stability Test Approximately 40 g of the composition of each of Example 1 and Comparative Example 1 was placed in a transparent screw cap bottle of 50 ml, and light irradiation was performed at 20 to 25° C. (total illuminance: 1,200,000 lux·hr), and visually observed. The change in color was observed at. The results are shown in Table 1.
表１に示した通り、熱及び光安定性試験のいずれにおいても、ヘパリン類似物質を含有する実施例１は、ヘパリン類似物質を含有しない比較例１と比較して、外用組成物の経時的な変色が抑制されていることが認められた。 As shown in Table 1, in both the heat and photostability tests, Example 1 containing the heparin-like substance was compared with Comparative Example 1 containing no heparin-like substance, and It was confirmed that discoloration was suppressed.
試験例２ ジフェンヒドラミン含有乳液の熱安定性及び光安定性試験
油相（パルミチン酸イソプロピル、フィトステロール、ポリオキシエチレン硬化ヒマシ油、白色ワセリンを混合溶解したもの）にジフェンヒドラミンを加え、７０℃まで加熱した。同様に水相（精製水、濃グリセリン、パラオキシ安息香酸メチル、クエン酸ナトリウム、クエン酸を混合溶解したもの）にヘパリン類似物質を加え、７０℃に加熱した。２相（油相、水相）を高温で攪拌・乳化し、キサンタンガムを加え攪拌し、室温まで冷却して、表２に示す組成の実施例２の乳液を得た。
比較例２の乳液は、ヘパリン類似物質を加えない以外は実施例２の乳液と同様にして、製造した。
Test Example 2 Thermal Stability and Light Stability Test of Diphenhydramine-Containing Emulsion Diphenhydramine was added to an oil phase (mixture of isopropyl palmitate, phytosterol, polyoxyethylene hydrogenated castor oil, and white vaseline), and heated to 70°C. Similarly, a heparin-like substance was added to the aqueous phase (purified water, concentrated glycerin, methyl paraoxybenzoate, sodium citrate, and citric acid mixed and dissolved), and the mixture was heated to 70°C. The two phases (oil phase and water phase) were stirred and emulsified at high temperature, xanthan gum was added and stirred, and the mixture was cooled to room temperature to obtain an emulsion of Example 2 having the composition shown in Table 2.
The emulsion of Comparative Example 2 was produced in the same manner as the emulsion of Example 2 except that the heparin-like substance was not added.
熱安定性試験
５０ｍｌの透明なねじ口ビンに、実施例１及び比較例１の外用組成物をそれぞれ約４０ｇ入れ、６０℃にて１日間保存し、目視にて色の変化を観察した。結果を表２に示す。
Thermal Stability Test Approximately 40 g of each of the compositions for external use of Example 1 and Comparative Example 1 was placed in a transparent screw cap bottle of 50 ml and stored at 60° C. for 1 day, and the color change was visually observed. The results are shown in Table 2.
表２に示した通り、熱安定性試験において、ヘパリン類似物質を含有する実施例２は、ヘパリン類似物質を含有しない比較例２と比較して、外用組成物の経時的な変色が抑制されていることが認められた。なお、熱安定性と同様に、試験例２の外用組成物の光安定性についても試験例1と同様の傾向が認められる。 As shown in Table 2, in the heat stability test, Example 2 containing the heparin-like substance showed suppressed discoloration with time of the external composition as compared with Comparative Example 2 containing no heparin-like substance. It was recognized that Similar to the thermal stability, the same tendency as in Test Example 1 is observed in the light stability of the external composition of Test Example 2.
試験例３ アスコルビン酸含有ローション剤（美容液）の熱安定性及び光安定性試験
精製水、濃グリセリン、１．３−ブチレングリコール、プロピレングリコール、パラオキシ安息香酸メチル、エデト酸ナトリウム、アスコルビン酸、ヘパリン類似物質を４０℃で混合溶解し、室温まで冷却して、表１に示す組成の実施例３のローション剤（美容液）を得た。
比較例３のローション剤（美容液）は、ヘパリン類似物質を加えない以外は実施例３のローション剤（美容液）と同様にして、製造した。
Test Example 3 Thermal stability and photostability test of ascorbic acid-containing lotion (beauty essence) Purified water, concentrated glycerin, 1.3-butylene glycol, propylene glycol, methyl paraoxybenzoate, sodium edetate, ascorbic acid, heparin Similar substances were mixed and dissolved at 40° C. and cooled to room temperature to obtain a lotion (cosmetic liquid) of Example 3 having the composition shown in Table 1.
The lotion agent (beauty essence) of Comparative Example 3 was produced in the same manner as the lotion agent (beauty essence) of Example 3 except that the heparin-like substance was not added.
熱安定性試験
５０ｍｌの透明なねじ口ビンに、実施例３及び比較例３の外用組成物をそれぞれ約４０ｇ入れ、６０℃にて３日間保存し、目視にて色の変化を観察した。結果を表３に示す。
光安定性試験
５０ｍｌの透明なねじ口ビンに、実施例１及び比較例１の組成物をそれぞれ約４０ｇ入れ、２０〜２５℃にて光照射を行い（総照度１２０万ｌｕｘ・ｈｒ）、目視にて色の変化を観察した。結果を表３に示す。
Thermal Stability Test Approximately 40 g of each of the compositions for external use of Example 3 and Comparative Example 3 was placed in a transparent screw cap bottle of 50 ml, stored at 60° C. for 3 days, and the color change was visually observed. The results are shown in Table 3.
Light Stability Test Approximately 40 g of the composition of each of Example 1 and Comparative Example 1 was placed in a transparent screw cap bottle of 50 ml, and light irradiation was performed at 20 to 25° C. (total illuminance: 1,200,000 lux·hr), and visually observed. The change in color was observed at. The results are shown in Table 3.
表３に示した通り、熱及び光安定性試験のいずれにおいても、ヘパリン類似物質を含有する実施例３は、ヘパリン類似物質を含有しない比較例３と比較して、外用組成物の経時的な変色が抑制されていることが認められた。 As shown in Table 3, in both the heat and photostability tests, Example 3 containing the heparin-like substance was compared with Comparative Example 3 containing no heparin-like substance, and It was confirmed that discoloration was suppressed.
以下に製剤実施例を挙げるが、本発明はこれらの実施例に限られるものではない。製剤実施例を収容する容器素材としては、最内層が、ポリエチレン、ポリプロピレン、ポリエチレンテレフタレート、アルミ、エポキシ樹脂、ポリアミド・イミド樹脂及びガラスの容器を用いることができる。なお、各配合成分の単位は重量（Ｗ／Ｗ）％を意味するものとする。 Formulation examples are given below, but the present invention is not limited to these examples. As the container material for accommodating the formulation examples, containers whose innermost layer is polyethylene, polypropylene, polyethylene terephthalate, aluminum, epoxy resin, polyamide-imide resin, and glass can be used. In addition, the unit of each compounding component shall mean weight (W/W)%.
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| JP2015075704A Pending JP2015120766A (en) | 2009-01-09 | 2015-04-02 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2016130714A Active JP6152202B2 (en) | 2009-01-09 | 2016-06-30 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2017104388A Pending JP2017141304A (en) | 2009-01-09 | 2017-05-26 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2018138913A Withdrawn JP2018162322A (en) | 2009-01-09 | 2018-07-24 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2020085557A Active JP7096285B2 (en) | 2009-01-09 | 2020-05-14 | A method for suppressing discoloration of an external composition containing diphenhydramine or a salt thereof and ascorbic acid or a salt thereof. |
| JP2021186727A Active JP7320581B2 (en) | 2009-01-09 | 2021-11-17 | Method for suppressing discoloration of topical composition containing diphenhydramine or its salt and ascorbic acid or its salt |
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| JP2010003318A Active JP5951173B2 (en) | 2009-01-09 | 2010-01-08 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2015075704A Pending JP2015120766A (en) | 2009-01-09 | 2015-04-02 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2016130714A Active JP6152202B2 (en) | 2009-01-09 | 2016-06-30 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2017104388A Pending JP2017141304A (en) | 2009-01-09 | 2017-05-26 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
| JP2018138913A Withdrawn JP2018162322A (en) | 2009-01-09 | 2018-07-24 | Method for inhibiting discoloration of composition for external use containing diphenhydramine or salt thereof and ascorbic acid or salt thereof |
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|---|---|---|---|---|
| JP6495706B2 (en) * | 2014-03-31 | 2019-04-03 | 小林製薬株式会社 | Skin external composition |
| JP6646390B2 (en) * | 2015-09-14 | 2020-02-14 | 小林製薬株式会社 | External composition |
| JP2018203672A (en) * | 2017-06-06 | 2018-12-27 | 小林製薬株式会社 | Sebum secretion promoter |
| JP2018203673A (en) * | 2017-06-06 | 2018-12-27 | 小林製薬株式会社 | Sebum secretion promoter |
| JP7313111B2 (en) * | 2017-06-06 | 2023-07-24 | 小林製薬株式会社 | Sebum secretion stimulator and composition for external use |
| JP7153429B2 (en) * | 2017-06-22 | 2022-10-14 | 小林製薬株式会社 | Active oxygen scavenging agent |
| WO2019131892A1 (en) * | 2017-12-27 | 2019-07-04 | ロート製薬株式会社 | External composition containing ascorbic acid and/or salt thereof |
| JP7321680B2 (en) * | 2018-06-28 | 2023-08-07 | 小林製薬株式会社 | external composition |
| WO2020067132A1 (en) * | 2018-09-25 | 2020-04-02 | ロート製薬株式会社 | Topical composition containing ascorbic acid and/or salt thereof |
| JP7464243B2 (en) * | 2019-09-17 | 2024-04-09 | ジャパンメディック株式会社 | Treatment for dry, itchy skin |
| JP2022094515A (en) * | 2020-12-15 | 2022-06-27 | 小林製薬株式会社 | Topical composition |
| JP7265278B2 (en) * | 2021-05-31 | 2023-04-26 | ホーユー株式会社 | COMPOSITION FOR IMPROVING SKIN BARRIER FUNCTION OR REPAIR |
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2016
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2017
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2018
- 2018-07-24 JP JP2018138913A patent/JP2018162322A/en not_active Withdrawn
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|---|---|
| JP2022010339A (en) | 2022-01-14 |
| JP2015120766A (en) | 2015-07-02 |
| JP2018162322A (en) | 2018-10-18 |
| JP6152202B2 (en) | 2017-06-21 |
| JP7096285B2 (en) | 2022-07-05 |
| JP2016169240A (en) | 2016-09-23 |
| JP7320581B2 (en) | 2023-08-03 |
| JP2017141304A (en) | 2017-08-17 |
| JP2010180206A (en) | 2010-08-19 |
| JP5951173B2 (en) | 2016-07-13 |
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