JP2024022901A - Skin external composition - Google Patents
Skin external composition Download PDFInfo
- Publication number
- JP2024022901A JP2024022901A JP2022126346A JP2022126346A JP2024022901A JP 2024022901 A JP2024022901 A JP 2024022901A JP 2022126346 A JP2022126346 A JP 2022126346A JP 2022126346 A JP2022126346 A JP 2022126346A JP 2024022901 A JP2024022901 A JP 2024022901A
- Authority
- JP
- Japan
- Prior art keywords
- skin
- composition
- heparin
- substance
- centella asiatica
- 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.)
- Pending
Links
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 229940098760 steareth-2 Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 150000003611 tocopherol derivatives Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 150000003700 vitamin C derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Abstract
【課題】ヘパリン類似物質を含む皮膚外用組成物であって、従来よりも高い皮膚の保湿作用を有しつつ、好ましくは、敏感肌にも刺激が少ない皮膚外用組成物、好ましくは保湿剤を提供する。【解決手段】ヘパリン類似物質と、ツボクサエキス抽出物と、水と、を含む皮膚外用組成物を提供する。前記ヘパリン類似物質の含有量は、前記皮膚外用組成物に対して、0.005 質量％～5 質量％であることが好ましく、また、前記ツボクサエキス抽出物の含有量は、前記皮膚外用組成物に対して、0.0000001 (1×10-7) ～5 質量％であることが好ましい。【選択図】なし[Problem] To provide a composition for external use on the skin, preferably a moisturizer, which contains a heparin-like substance and has a higher skin moisturizing effect than before and is less irritating to sensitive skin. do. A composition for external use on the skin is provided, which includes a heparin-like substance, an extract of Centella asiatica, and water. The content of the heparin-like substance is preferably 0.005% by mass to 5% by mass based on the composition for external use on the skin, and the content of the Centella asiatica extract is preferably 0.005% by mass to 5% by mass based on the composition for external use on the skin. The amount is preferably 0.0000001 (1×10-7) to 5% by mass. [Selection diagram] None
Description
本発明は、皮膚外用組成物に関する。 The present invention relates to compositions for external use on the skin.
ヘパリン類似物質を含む組成物は、外用剤として皮膚に適用されると、皮膚の保湿作用や、皮膚の抗炎症作用や、血行促進作用などが得られることが知られている（非特許文献１）。そのため、ヘパリン類似物質を含む外用組成物がいくつか提案されており、例えば、特許文献１には、ヘパリン類似物質とアミノ酸成分を含む外用組成物が記載されており、特許文献２には、ヘパリン類似物質と、トコフェロール、抗炎症剤及び鎮痒剤を含む皮膚外用剤が記載されている。 It is known that when a composition containing a heparin-like substance is applied to the skin as an external preparation, it has a moisturizing effect on the skin, an anti-inflammatory effect on the skin, an effect on promoting blood circulation, etc. (Non-patent Document 1) ). Therefore, several external compositions containing heparin-like substances have been proposed. For example, Patent Document 1 describes a topical composition containing a heparin-like substance and an amino acid component, and Patent Document 2 describes heparin-like substances and an amino acid component. Similar substances and topical skin preparations have been described, including tocopherols, anti-inflammatory agents and anti-pruritic agents.
また、シカ (CICA) と称されるツボクサエキス抽出物を含む組成物は、外用剤として皮膚に適用されると、肌荒れ改善効果などを示すことが知られており、例えば、特許文献３には、ツボクサエキス抽出物と、ビタミンとを含む皮膚外用剤が記載されている。 Furthermore, a composition containing an extract of Centella asiatica called CICA is known to have an effect on improving rough skin when applied to the skin as an external preparation. For example, Patent Document 3 describes , an external skin preparation containing Centella asiatica extract and vitamins is described.
前述の通り、ヘパリン類似物質を含む従来の皮膚外用組成物は、皮膚の保湿作用、抗炎症作用、血行促進作用を有しているものの、これらの外用組成物には、さらなる高い作用、とりわけ、さらに高い保湿作用が求められることがあった。そこで本発明は、ヘパリン類似物質を含む皮膚外用組成物であって、高い皮膚の保湿作用を有しつつ、好ましくは、敏感肌にも刺激が少ない皮膚外用組成物を提供する。 As mentioned above, conventional skin compositions containing heparin-like substances have skin moisturizing effects, anti-inflammatory effects, and blood circulation promoting effects, but these topical compositions have even higher effects, especially: There were times when an even higher moisturizing effect was required. Therefore, the present invention provides an external skin composition containing a heparin-like substance, which has a high skin moisturizing effect and is preferably less irritating to sensitive skin.
すなわち、本発明は、以下に示す皮膚外用組成物に関する。
［１］ヘパリン類似物質と、ツボクサエキス抽出物と、液状担体と、を含む皮膚外用組成物。
［２］前記ヘパリン類似物質の含有量は、前記皮膚外用組成物に対して、0.005 質量％～5 質量％である、前記［１］に記載の皮膚外用組成物。
［３］前記ツボクサエキス抽出物の含有量は、前記皮膚外用組成物に対して、0.0000001 (1×10-7) ～5 質量％である、前記［１］又は［２］に記載の皮膚外用組成物。
［４］保湿剤である、前記［１］～［３］のいずれかに記載の皮膚外用組成物。
That is, the present invention relates to the skin external composition shown below.
[1] A skin external composition containing a heparin-like substance, an Centella asiatica extract, and a liquid carrier.
[2] The skin external composition according to [1], wherein the content of the heparin-like substance is 0.005% by mass to 5% by mass based on the skin external composition.
[3] The skin external use according to [1] or [2], wherein the content of the Centella asiatica extract is 0.0000001 (1×10 -7 ) to 5% by mass based on the skin external use composition. Composition.
[4] The skin external composition according to any one of [1] to [3] above, which is a humectant.
さらに、本発明は、以下に示す保湿作用を増強する方法に関する。
［５］ヘパリン類似物質を含む皮膚外用組成物の保湿作用を増強する方法であって、前記皮膚外用組成物に、ツボクサエキス抽出物を配合することを含む、保湿作用増強方法。
Furthermore, the present invention relates to a method for enhancing the moisturizing effect shown below.
[5] A method for enhancing the moisturizing effect of a composition for external use on the skin containing a heparin-like substance, the method comprising blending an extract of Centella asiatica extract into the composition for external use on the skin.
本発明の皮膚外用組成物は、皮膚に適用されることで、従来のヘパリン類似物質含有組成物と比較して、皮膚の保湿性を高めることができる。 When applied to the skin, the external skin composition of the present invention can improve the moisturizing properties of the skin compared to conventional heparin-like substance-containing compositions.
［１.皮膚外用組成物］
本発明の皮膚外用組成物は、１）ヘパリン類似物質と、２）ツボクサエキス抽出物と、液状担体と、を含有し、さらに、他の配合成分を含んでいてもよい。
[1. Skin external composition]
The skin external composition of the present invention contains 1) a heparin-like substance, 2) an Centella asiatica extract, and a liquid carrier, and may further contain other ingredients.
［１-１.ヘパリン類似物質］
ヘパリン類似物質とは、ムコ多糖類の多硫エステル体である。ムコ多糖類とは、動物組織や体液に広く分布するアミノ糖を含む複合多糖であり、例えば、コンドロイチン硫酸などである。ヘパリン類似物質は、ムコ多糖類を多硫酸化することにより得てもよく、食用獣の組織（例えば、ウシの気管軟骨を含む肺臓）から抽出して得てもよい。また、本発明の皮膚外用組成物に含まれるヘパリン類似物質は、日本薬局方外医薬品規格に収戴されているヘパリン類似物質であってもよい。
[1-1. Heparin-like substance]
Heparin-like substances are polysulfur esters of mucopolysaccharides. Mucopolysaccharides are complex polysaccharides containing amino sugars that are widely distributed in animal tissues and body fluids, such as chondroitin sulfate. Heparin-like substances may be obtained by polysulfating mucopolysaccharides, or may be obtained by extracting from tissues of food animals (for example, bovine lungs containing tracheal cartilage). Furthermore, the heparin-like substance contained in the skin external composition of the present invention may be a heparin-like substance that is included in the non-Japanese Pharmacopoeia pharmaceutical standards.
本発明の皮膚外用組成物は、ヘパリン類似物質を、組成物に対して 0.005 質量％以上、好ましくは 0.01 質量％以上、より好ましくは 0.05質量％以上、さらに好ましくは 0.1質量％以上含む。また、本発明の皮膚外用組成物は、ヘパリン類似物質を、組成物に対して 5 質量％以下、好ましくは3 質量％以下、より好ましくは 1質量％以下、さらに好ましくは0.5質量％以下含む。本発明の皮膚外用組成物は、ヘパリン類似物質を、例えば 0.1質量％、又は0.3質量％含む。なお、ヘパリン類似物質の含有量は、皮膚外用組成物が適切な保湿作用を有するように、適宜設定することができる。 The skin external composition of the present invention contains a heparin-like substance in an amount of 0.005% by mass or more, preferably 0.01% by mass or more, more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more. Furthermore, the skin external composition of the present invention contains a heparin-like substance in an amount of 5% by mass or less, preferably 3% by mass or less, more preferably 1% by mass or less, and still more preferably 0.5% by mass or less. The skin external composition of the present invention contains a heparin-like substance, for example, 0.1% by mass or 0.3% by mass. The content of the heparin-like substance can be appropriately set so that the composition for external use on the skin has an appropriate moisturizing effect.
［１-２.ツボクサエキス抽出物］
ツボクサエキス抽出物とは、セリ科の植物であるツボクサ（別名：積雪草）の一部または全草から抽出された生薬エキスでありうる。ツボクサエキス抽出物は、アジアチコサイド、マデカシコサイドなどのトリテルペン誘導体の成分を含みうる。ツボクサの原産国はアジア、アフリカ、インド等であるが、その栽培方法や産地は特に限定されない。
[1-2. Centella asiatica extract]
The Centella asiatica extract may be a crude drug extract extracted from a part or the whole plant of Centella asiatica (also known as snowweed), which is a plant of the Umbelliferae family. Centella asiatica extract may contain components of triterpene derivatives such as asiaticoside, madecascicoside. The countries of origin of centella asiatica are Asia, Africa, India, etc., but there are no particular restrictions on its cultivation method or place of production.
ツボクサエキス抽出物の調製法（抽出法）は特に限定されるものではないが、ツボクサの一部（好ましくは、葉及び茎）や全草をそのまま、あるいは乾燥物を、溶媒等で抽出して得ることができる。抽出に用いる溶媒は、例えば、低級１価アルコール（メチルアルコール、エチルアルコール、１-プロパノール、２-プロパノール、１-ブタノール、２-ブタノール等）、液状多価アルコール（グリセリン、プロピレングリコール、１,３-ブチレングリコール等）、低級エステル（酢酸エチル等）、炭化水素（ベンゼン、ヘキサン、ペンタン等）、ケトン類（アセトン、メチルエチルケトン等）、エーテル類（ジエチルエーテル、テトラヒドロフラン、ジプロピルエーテル等）、アセトニトリル等が挙げられ、それらの一種又は二種以上を用いることができる。好ましい抽出法の例としては、濃度0～100 vol% の含水エチルアルコール、プロピレングリコール又は１,３-ブチレングリコールを用い、室温で、又は加温して１～１０日間抽出を行った後濾過し、得られた濾液を更に１週間程放置して熟成させ、再び濾過を行う。ツボクサエキス抽出物として、抽出液をそのまま用いてもよいし、脱溶媒して乾燥固形物を用いてもよい。 The preparation method (extraction method) for the Centella asiatica extract is not particularly limited, but a part of Centella asiatica (preferably leaves and stems) or the whole plant may be extracted as is, or the dried product may be extracted with a solvent, etc. Obtainable. Solvents used for extraction include, for example, lower monohydric alcohols (methyl alcohol, ethyl alcohol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1,3 -butylene glycol, etc.), lower esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile, etc. are mentioned, and one or more types thereof can be used. Examples of preferred extraction methods include using aqueous ethyl alcohol, propylene glycol, or 1,3-butylene glycol at a concentration of 0 to 100 vol%, extraction at room temperature or heating for 1 to 10 days, and then filtration. The obtained filtrate is left to mature for about one week, and then filtered again. As the Centella asiatica extract, the extract may be used as it is, or the solvent may be removed and a dry solid may be used.
ツボクサエキス抽出物は、医薬部外品添加物として、医薬部外品原料規格2021の成分コード520774として登録されている。また、例えば、セキセツソウ抽出液BG70（丸善製薬）、T.E.C.A（SEPPIC S.A.）、センテリンCG（SAMI-SABINSA GROUP LIMITED）、CENTELLA ASIATICA BT（Bio Component Research）、CICA EX(BG)（Radiant, Inc）、CICAegg (登録商標)（株式会社ナノエッグ）、Neosome NE ダーマファーム（Nexthia USA LLC）、VEGETOL HYDROCOTYL GR 040 HYDRO（Gattefosse S.A.S.）として市場から入手可能である。 Centella asiatica extract is registered as a quasi-drug additive with component code 520774 in the Quasi-drug Ingredient Standards 2021. In addition, for example, CENTELLA ASIATICA BT (Bio Component Research), CICA EX (BG) (Radiant, Inc), CICAegg (registered trademark) (Nano Egg Co., Ltd.), Neosome NE Dermafirm (Nexthia USA LLC), and VEGETOL HYDROCOTYL GR 040 HYDRO (Gattefosse S.A.S.).
本発明の皮膚外用組成物は、組成物全体に対してツボクサエキス抽出物を、乾燥固形分として0.0000001 (1×10-7) 質量％以上、好ましくは0.000001 (1×10-6) 質量％以上、より好ましくは0.00001 (1×10-5) 質量％以上、さらに好ましくは0.0001 (1×10-４) 質量％以上、特に好ましくは0.001 (1×10-３) 質量％以上含む。また、本発明の皮膚外用組成物は、組成物全体に対してツボクサエキス抽出物を、乾燥固形分として5 質量％以下、好ましくは2 質量％以下、より好ましくは1 質量％以下、さらに好ましくは0.5 質量％以下、特に好ましくは0.1 質量％以下含む。ツボクサエキス抽出物として抽出液を用いる場合は、乾燥固形分に換算したときに上記範囲となるように配合すればよい。この範囲内であれば、抽出物を安定に配合することができ、かつ高い効果（ヘパリン類似物質の保湿作用を増強する効果など）を発揮することができる。乾燥固形分としてのツボクサエキス抽出物の含有量が、0.0000001 (1×10-7) 質量%以上であると、ヘパリン類似物質の保湿作用を増強することができ、5 質量％を超えても、それ以上に効果が上がりにくくなる。 The skin external composition of the present invention contains Centella asiatica extract in a dry solid content of 0.0000001 (1×10 -7 ) mass % or more, preferably 0.000001 (1×10 -6 ) mass % or more of the entire composition. , more preferably 0.00001 (1×10 −5 ) mass % or more, still more preferably 0.0001 (1×10 −4 ) mass % or more, particularly preferably 0.001 (1×10 −3 ) mass % or more. In addition, the skin external composition of the present invention contains Centella asiatica extract in a dry solid content of 5% by mass or less, preferably 2% by mass or less, more preferably 1% by mass or less, even more preferably It contains 0.5% by mass or less, particularly preferably 0.1% by mass or less. When using an extract as the Centella asiatica extract, it may be blended so that it falls within the above range when converted to dry solid content. Within this range, the extract can be stably blended and exhibit high effects (such as the effect of enhancing the moisturizing effect of heparin-like substances). When the content of Centella Centella asiatica extract as a dry solid content is 0.0000001 (1×10 -7 )% by mass or more, the moisturizing effect of heparin-like substances can be enhanced, and even if it exceeds 5% by mass, The effect becomes more difficult to increase beyond that.
ツボクサエキス抽出物を含む皮膚外用組成物は、ヘパリン類似物質を共配合されていない場合にも（つまり、単独でも）、保湿作用を示すことがあるが；本発明のように、ヘパリン類似物質とツボクサエキス抽出物とを共配合した皮膚外用組成物は、ツボクサエキス抽出物の濃度が単独では保湿作用を示さない低濃度であっても、ヘパリン類似物質の保湿作用を増強しうる。また、ヘパリン類似物質とツボクサエキス抽出物とを共配合した皮膚外用組成物は、ツボクサエキス抽出物によってヘパリン類似物質の保湿作用を増強するが、その保湿作用の増強は、ツボクサエキス抽出物が単独で示す保湿作用よりも高くなりうる。このように、ヘパリン類似物質は、ツボクサエキス抽出物によって、相乗的に保湿作用を高められ得る。この相乗効果については、本明細書の後述の実施例によっても示される。 A composition for external use on the skin containing Centella asiatica extract may exhibit a moisturizing effect even when it is not co-formulated with a heparin-like substance (that is, even alone); A skin external composition co-blended with Centella asiatica extract can enhance the moisturizing effect of a heparin-like substance even if the concentration of Centella asiatica extract is too low to exhibit a moisturizing effect by itself. In addition, in a skin external composition co-blended with a heparin-like substance and Centella asiatica extract, the moisturizing effect of the heparin-like substance is enhanced by the Centella asiatica extract; It can be higher than the moisturizing effect shown in . Thus, heparin-like substances can have their moisturizing effects synergistically enhanced by Centella asiatica extract. This synergistic effect is also demonstrated by the examples later in this specification.
［1-3.液状担体］
本発明の皮膚外用組成物は、組成物の性状に応じて適切な液状担体を含むことができる。例えば、本発明の皮膚外用組成物が水溶液（例えば、化粧水や美容液）やジェルであれば主な担体を水とすることができるし、乳液であれば水とともに油分（例えば、ワセリンなど）を主な担体とすることができるし、軟膏や油性クリームであれば主な担体を油分とすることができる。
[1-3. Liquid carrier]
The skin external composition of the present invention can contain an appropriate liquid carrier depending on the properties of the composition. For example, if the skin external composition of the present invention is an aqueous solution (e.g., lotion or serum) or gel, the main carrier can be water; if it is an emulsion, water and oil (e.g., petrolatum) can be used as the main carrier. The main carrier can be oil, and in the case of ointments and oil-based creams, the main carrier can be oil.
本発明の皮膚外用組成物は、液状担体として、グリセリン、プロピレングリコール、1,3-ブチレングリコールなどの多価アルコールを含むことができる。さらに、本発明の皮膚外用組成物は、液状担体として、エタノールやプロパノールなどの低級アルコールを含んでもよい。ただし、本発明の皮膚外用組成物を敏感肌に適用したときの皮膚への刺激を少なくすることが望まれる場合には、皮膚外用組成物が低級アルコール、特にエタノールを含まないか、または実質的に含まないことが好ましい。 The skin external composition of the present invention can contain a polyhydric alcohol such as glycerin, propylene glycol, 1,3-butylene glycol, etc. as a liquid carrier. Furthermore, the skin external composition of the present invention may contain a lower alcohol such as ethanol or propanol as a liquid carrier. However, if it is desired to reduce the irritation to the skin when the external skin composition of the present invention is applied to sensitive skin, the skin external composition does not contain lower alcohols, especially ethanol, or substantially It is preferable not to include it.
［1-4.他の配合成分］
本発明の皮膚外用組成物は、ヘパリン類似物質、ツボクサエキス抽出物及び液状担体に加えて、皮膚外用組成物に求められる効果、あるいは、所望とする製剤の剤形に応じて、他の配合成分を含んでいてもよい。
[1-4.Other ingredients]
In addition to the heparin-like substance, Centella asiatica extract, and liquid carrier, the composition for external use on skin of the present invention may contain other ingredients depending on the desired effect of the composition for external use on skin or the desired dosage form of the preparation. May contain.
本発明の皮膚外用組成物は、他の有効成分、例えば、アンチエイジング剤、抗炎症剤、アクネケア剤、抗ヒスタミン剤などを含んでいてもよい。アンチエイジング剤の例には、ナイアシンアミド（ニコチン酸アミドともいう）、アルブチン、トラネキサム酸、ビタミン類（例えば、トコフェロール誘導体、ビタミンC誘導体、パルミチン酸レチノール等）、エラグ酸、リノール酸などが含まれ；抗炎症剤の例には、アラントイン、グリチルリチン酸又はその塩（例えば、グリチルリチン酸ジカリウム）、ε-アミノカプロン酸などが含まれ；アクネケア剤の例には、イソプロピルメチルフェノール、サリチル酸などが含まれ；抗ヒスタミン剤の例には、ジフェンヒドラミンまたはその塩などが含まれる。 The skin external composition of the present invention may contain other active ingredients, such as anti-aging agents, anti-inflammatory agents, acne care agents, antihistamines, and the like. Examples of anti-aging agents include niacinamide (also called nicotinamide), arbutin, tranexamic acid, vitamins (e.g. tocopherol derivatives, vitamin C derivatives, retinol palmitate, etc.), ellagic acid, linoleic acid, etc. Examples of anti-inflammatory agents include allantoin, glycyrrhizic acid or its salts (e.g., dipotassium glycyrrhizinate), ε-aminocaproic acid, etc.; Examples of acne care agents include isopropylmethylphenol, salicylic acid, etc.; Examples of antihistamines include diphenhydramine or its salts.
本発明の皮膚外用組成物は、さらに湿潤剤を含んでいてもよい。前述のツボクサエキス抽出物も湿潤剤として機能し得るが；さらに、１）セラミド又はセラミド類似成分、２）リン脂質ポリマー、３）アロエエキス、４）アミノ酸系湿潤剤、５）スクワラン、または６）多価アルコールなどが含まれうる。これらは、皮膚外用組成物に求められる保湿作用などに応じて、その配合量を設定することができる。 The skin external composition of the present invention may further contain a humectant. The aforementioned Centella asiatica extract may also function as a humectant; in addition, 1) ceramides or ceramide-like components, 2) phospholipid polymers, 3) aloe extract, 4) amino acid-based humectants, 5) squalane, or 6) Polyhydric alcohols and the like may be included. The amount of these ingredients to be added can be determined depending on the moisturizing effect required for the external skin composition.
１）セラミドとはスフィンゴ脂質の一種であり、スフィンゴイドに脂肪酸がアミド結合した化合物である。セラミド類似成分は、グルコシルセラミド、ガラクトシルセラミドのような糖セラミドであっても、ソフケア(登録商標)セラミドSL-E（花王株式会社製、Ｎ-（ヘキサデシロキシヒドロキシプロピル）-Ｎ-（ヒドロキシエチルヘキサデカナミド））、CERACUTE(登録商標)-L（日油株式会社、グリセリル-Ｎ-（２-メタクリロイルオキシエチル）カルバメート・メタクリル酸ステアリル共重合体）のような合成セラミドであってもよい。本発明の皮膚外用組成物におけるセラミド及び／又はセラミド類似成分の含有量は、目的に応じて設定すればよく、特に限定されない。 1) Ceramide is a type of sphingolipid, and is a compound in which a fatty acid is bound to an amide bond to a sphingoid. Ceramide-like components include sugar ceramides such as glucosylceramide and galactosylceramide; Hexadecanamide)), CERACUTE (registered trademark)-L (NOF Corporation, glyceryl-N-(2-methacryloyloxyethyl) carbamate/stearyl methacrylate copolymer) may also be a synthetic ceramide. . The content of ceramide and/or ceramide-like components in the skin external composition of the present invention may be set depending on the purpose and is not particularly limited.
２）リン脂質ポリマーとは、メタクリロイルオキシエチルホスホリルコリン重合体であり、生体膜の主要な構成成分であるリン脂質に類似する生体適合性ポリマーである。リン脂質ポリマーの例には、リピジュア (登録商標)（日油株式会社、２-メタクリロイルオキシエチルホスホリルコリン・メタクリル酸ブチル共重合体）、NIKKOL (登録商標) レシノール S-10（日光ケミカルズ株式会社、水素添加大豆リン脂質）などが含まれる。本発明の皮膚外用組成物におけるリン脂質ポリマーの含有量は、目的に応じて設定すればよく、特に限定されない。 2) The phospholipid polymer is a methacryloyloxyethylphosphorylcholine polymer, which is a biocompatible polymer similar to phospholipids, which are the main constituents of biological membranes. Examples of phospholipid polymers include RIPIDURE® (NOF Corporation, 2-methacryloyloxyethylphosphorylcholine/butyl methacrylate copolymer), NIKKOL® Resinol S-10 (Nikko Chemicals Co., Ltd., hydrogen This includes added soy phospholipids). The content of the phospholipid polymer in the skin external composition of the present invention may be set depending on the purpose and is not particularly limited.
３）アロエエキスとは、ユリ科の薬用植物であるアロエ（ケープアロエ、アロエベラ、キダチアロエなど）の葉肉などからの抽出成分である。アロエエキスには、ウロン酸、脂質、蛋白、アミノ酸、アントラキノン系化合物（アロイン、アロエエモジン等）が含有しているとされている。本発明の皮膚外用組成物におけるアロエエキスの含有量は、目的に応じて設定すればよく、特に限定されない。 3) Aloe extract is a component extracted from the mesophyll of aloe (Cape Aloe, Aloe Vera, Kidachi Aloe, etc.), which is a medicinal plant of the Liliaceae family. Aloe extract is said to contain uronic acid, lipids, proteins, amino acids, and anthraquinone compounds (aloin, aloe emodin, etc.). The content of aloe extract in the skin external composition of the present invention may be set depending on the purpose and is not particularly limited.
４）アミノ酸系湿潤剤とは、グルタミン酸などのアミノ酸から導かれる湿潤剤である。アミノ酸系湿潤剤としては、ピロリドンカルボン酸又はその塩類（例えば、ナトリウム塩）、ピロリジンカルボン酸又はその塩類、アシルピロリジンカルボン酸又はその塩類などが挙げられる。アミノ酸系湿潤剤のアミノ酸は、ラセミ体であってもよいし、光学活性体であってもよい。アミノ酸系湿潤剤は、AJIDEW (登録商標)（味の素株式会社）、PRODEW (登録商標)（味の素株式会社）、アクアデュウ(登録商標) （味の素株式会社）などとして市場から入手可能である。本発明の皮膚外用組成物におけるアミノ酸系湿潤剤の含有量は、目的に応じて設定すればよく、特に限定されない。 4) Amino acid humectants are humectants derived from amino acids such as glutamic acid. Examples of the amino acid wetting agent include pyrrolidone carboxylic acid or its salts (eg, sodium salt), pyrrolidine carboxylic acid or its salts, acylpyrrolidine carboxylic acid or its salts, and the like. The amino acid of the amino acid-based wetting agent may be a racemate or an optically active form. Amino acid-based humectants are commercially available as AJIDEW (registered trademark) (Ajinomoto Co., Inc.), PRODEW (registered trademark) (Ajinomoto Co., Inc.), Aquadew (registered trademark) (Ajinomoto Co., Inc.), and the like. The content of the amino acid humectant in the skin external composition of the present invention may be set depending on the purpose and is not particularly limited.
５）スクワランとは、アイザメなど深海に生息するサメ類の肝油から得られる炭化水素であるスクワレンを還元（水素添加）させて得られる飽和炭化水素であり、無色液体である。本発明の皮膚外用組成物におけるアミノ酸系湿潤剤の含有量は、目的に応じて設定すればよく、特に限定されない。 5) Squalane is a saturated hydrocarbon obtained by reducing (hydrogenating) squalene, a hydrocarbon obtained from the liver oil of sharks that live in the deep sea, such as merganser sharks, and is a colorless liquid. The content of the amino acid humectant in the skin external composition of the present invention may be set depending on the purpose and is not particularly limited.
湿潤剤としての６）多価アルコールの例には、グリセリン、プロピレングリコール、1,3-ブチレングリコール、ポリエチレングリコールなどが含まれる。 6) Examples of polyhydric alcohols as wetting agents include glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, and the like.
本発明の皮膚外用組成物は、粘稠剤を含んでいてもよい。粘稠剤としては、薬学的に許容されることを限度として特に制限されないが、例えば、カルボキシビニルポリマー、ポリビニルピロリドン、ポリエチレングリコール、ポリビニルアルコール、キサンタンガム、コンドロイチン硫酸ナトリウム、ヒアルロン酸ナトリウム等の水溶性高分子；ヒドロキシエチルセルロース、メチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロースナトリウム等のセルロース類等が挙げられる。これらの粘稠剤は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The skin external composition of the present invention may contain a thickening agent. The thickening agent is not particularly limited as long as it is pharmaceutically acceptable, but examples include highly water-soluble thickeners such as carboxyvinyl polymer, polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, xanthan gum, sodium chondroitin sulfate, and sodium hyaluronate. Molecules: Examples include celluloses such as hydroxyethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and sodium carboxymethylcellulose. These thickeners may be used alone or in combination of two or more.
本発明の皮膚外用組成物は、組成物のpHを所望の値に調整するためのpH調整剤を含んでいてもよい。ｐH調整剤の例には、無機酸（リン酸、ピロリン酸、メタリン酸、ポリリン酸、硫酸、硝酸、塩酸など）及びその塩；有機酸（モノカルボン酸（例えば、酢酸、ソルビン酸）、ポリカルボン酸（例えば、シュウ酸、コハク酸、マレイン酸、フマル酸）、オキシカルボン酸［例えば、ヒドロキシモノカルボン酸（例えば、グリコール酸、乳酸、グルコン酸）、ヒドロキシポリカルボン酸（例えば、酒石酸、リンゴ酸、クエン酸等）等］及びその塩；無機塩基（金属水酸化物（例えば、水酸化ナトリウム、水酸化カリウム、水酸化カルシウム等）等）；有機塩基（アミン類［例えば、アルカノールアミン（例えば、モノエタノールアミン、ジエタノールアミン、トリエタノールアミン、ジイソプロパノールアミン、トリイソプロパノールアミン、Ｎ-メチルエタノールアミン、Ｎ-アミノエチルエタノールアミン、Ｎ-メチルジエタノールアミン等）等］、アミノ酸（例えば、グリシン等）等）があげられる。本発明の皮膚外用組成物は、複数種のpH調整剤を組み合わせて含んでいてもよい。 The skin external composition of the present invention may contain a pH adjuster for adjusting the pH of the composition to a desired value. Examples of pH adjusters include inorganic acids (phosphoric acid, pyrophosphoric acid, metaphosphoric acid, polyphosphoric acid, sulfuric acid, nitric acid, hydrochloric acid, etc.) and their salts; organic acids (monocarboxylic acids (e.g., acetic acid, sorbic acid), polyphosphoric acid, Carboxylic acids (e.g. oxalic acid, succinic acid, maleic acid, fumaric acid), oxycarboxylic acids [e.g. hydroxymonocarboxylic acids (e.g. glycolic acid, lactic acid, gluconic acid), hydroxypolycarboxylic acids (e.g. tartaric acid, apple acids, citric acid, etc.] and their salts; inorganic bases (metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), etc.); organic bases (amines [e.g., alkanolamines (e.g., , monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, N-methylethanolamine, N-aminoethylethanolamine, N-methyldiethanolamine, etc.), amino acids (e.g., glycine, etc.) The skin external composition of the present invention may contain a combination of multiple types of pH adjusters.
本発明の皮膚外用組成物は、防腐剤を含んでいてもよい。防腐剤の例には、いわゆる「パラベン」と称されるパラオキシ安息香酸エステルが含まれる。具体的には、メチルパラベン（パラオキシ安息香酸メチル）、エチルパラベン（パラオキシ安息香酸エチル）、プロピルパラベン、イソプロピルパラベン、ブチルパラベン、イソブチルパラベン等、及びそれらの塩が防腐剤として例示される。本発明の皮膚外用組成物は、複数種のパラベンを組み合わせて含んでいてもよく、例えば、メチルパラベンと、エチルパラベンまたはプロピルパラベンとを組み合わせてもよい。本発明の皮膚外用組成物にパラベンが含まれる場合には、組成物に対するパラベンの含有量は、１ｗ/ｖ％以下、好ましくは 0.5 ｗ/ｖ％以下、さらに好ましくは0.25ｗ/ｖ％以下でありうる。 The skin external composition of the present invention may contain a preservative. Examples of preservatives include paraoxybenzoic acid esters, so-called "parabens." Specifically, methylparaben (methyl paraoxybenzoate), ethylparaben (ethyl paraoxybenzoate), propylparaben, isopropylparaben, butylparaben, isobutylparaben, and salts thereof are exemplified as preservatives. The external skin composition of the present invention may contain a combination of multiple types of parabens, for example, methylparaben and ethylparaben or propylparaben. When the skin external composition of the present invention contains parabens, the content of parabens in the composition is 1 w/v% or less, preferably 0.5 w/v% or less, more preferably 0.25 w/v% or less. It's possible.
本発明の皮膚外用組成物は、剤形が乳液である場合には乳化剤を含む。乳化剤は、アニオン性、カチオン性、両性、非イオン性界面活性剤のいずれかでありうる。乳化剤の例には、モノステアリン酸グリセリン、ステアリン酸ポリオキシル、ジステアリン酸グリコール、レシチン、セスキオレイン酸ソルビタン、トリオレイン酸ソルビタン、ステアレス-2、ヤシ油脂肪酸PEG-7グリセリルなどが含まれるが、特に限定されない。 The skin external composition of the present invention contains an emulsifier when the dosage form is an emulsion. Emulsifiers can be anionic, cationic, amphoteric, or nonionic surfactants. Examples of emulsifiers include, but are not particularly limited to, glyceryl monostearate, polyoxyl stearate, glycol distearate, lecithin, sorbitan sesquioleate, sorbitan trioleate, steareth-2, PEG-7 glyceryl coconut fatty acid, etc. Not done.
本発明の皮膚外用組成物は、軟化剤、着色剤や香料などを含有してもよい。 The skin external composition of the present invention may contain an emollient, a coloring agent, a fragrance, and the like.
［1-5. 皮膚外用組成物の剤形］
本発明の皮膚外用組成物は液状製剤であることが好ましいが、水性製剤、油性製剤、エマルション製剤（水中油型エマルション、油中水型エマルションのいずれもよい）、サスペンション製剤、エアゾール製剤、ゲル製剤など、剤形は特に限定されない。また、本発明の皮膚外用組成物は、化粧品の剤形として、固型(ソリッド)、プレスト、オイル(油)、液状(リキッド)、ジェル、練り(バーム)、マッド、クリーム、乳液、ローション、フォーム(バブル)、フィルム、パウダー(粉)、水、ペンシル、スプレー(ミスト)、スティック、シート等であり得る。
[1-5. Dosage form of composition for external use on skin]
The skin external composition of the present invention is preferably a liquid preparation, including an aqueous preparation, an oil-based preparation, an emulsion preparation (either an oil-in-water emulsion or a water-in-oil emulsion), a suspension preparation, an aerosol preparation, or a gel preparation. The dosage form is not particularly limited. In addition, the skin external composition of the present invention can be used as cosmetic dosage forms such as solid, pressed, oil, liquid, gel, balm, mud, cream, milky lotion, lotion, etc. It can be a foam (bubble), film, powder, water, pencil, spray (mist), stick, sheet, etc.
本発明の皮膚外用組成物のpHは５～７の範囲に調整されていることが好ましい。皮膚外用組成物の皮膚への浸透性を高めやすいからである。 The pH of the skin external composition of the present invention is preferably adjusted to a range of 5 to 7. This is because it is easy to increase the permeability of the external skin composition into the skin.
本発明の皮膚外用組成物の粘度は、製剤の剤形、及び組成物を皮膚に適用するときに求められる使用感に応じて、適宜調整されうる。例えば、組成物の粘度が低い方が、皮膚に適用されたときに濡れ広がりやすさを有しやすく；組成物の粘度が高い方が、皮膚に適用されたときに馴染みやすさを有しやすい。例えば目安として、本発明の皮膚外用組成物が水溶液であれば粘度400～1300ｍPa・sの範囲にあり、乳液であれば粘度2000～12000ｍPa・sの範囲にあり得る。粘度は、レオメーター条件：25℃、0.33rpm 90秒後の粘度として測定される。 The viscosity of the skin external composition of the present invention can be adjusted as appropriate depending on the dosage form of the preparation and the desired feel when applying the composition to the skin. For example, the lower the viscosity of the composition, the easier it is to spread when applied to the skin; the higher the viscosity of the composition, the easier it is to spread when applied to the skin. . For example, as a guide, if the skin external composition of the present invention is an aqueous solution, the viscosity may be in the range of 400 to 1,300 mPa·s, and if it is an emulsion, the viscosity may be in the range of 2,000 to 12,000 mPa·s. The viscosity is measured as the viscosity after 90 seconds under rheometer conditions: 25°C, 0.33 rpm.
本発明の皮膚外用組成物は、容器に充填されているが、例えば、遮光容器に充填されている。また、本発明の皮膚外用組成物はポンプ又はスプレータイプの容器に充填されることで、皮膚への適用を簡便にすることができる。 The skin external composition of the present invention is filled in a container, for example, a light-shielding container. Moreover, the skin external composition of the present invention can be easily applied to the skin by being filled in a pump or spray type container.
［2.皮膚外用組成物の用途］
本発明の皮膚外用組成物は、皮膚に適用、例えば、皮膚に塗布されることで使用される。例えば、皮膚外用組成物を直接皮膚にすりこんだり、皮膚外用組成物を染み込ませたガーゼなどを皮膚に貼ったりすることができる。本発明の皮膚外用組成物を適用する患部は、皮膚である限り特に限定されず、例えば、特に保湿が求められる患部、例えば、顔、粉ふきがあるひざやかかと、背中、などが例示されるが、特に限定されない。皮膚に適用する頻度は、特に限定されないが、1日1～数回程度でありうる。
[2. Uses of skin external composition]
The skin external composition of the present invention is used by applying it to the skin, for example, by applying it to the skin. For example, the composition for external use on the skin can be rubbed directly onto the skin, or gauze or the like impregnated with the composition for external use on the skin can be applied to the skin. The affected area to which the skin external composition of the present invention is applied is not particularly limited as long as it is the skin, and examples thereof include affected areas where moisturization is particularly required, such as the face, powdery knees and heels, and the back. However, there is no particular limitation. The frequency of application to the skin is not particularly limited, but may be about once to several times a day.
本発明の皮膚外用組成物は、皮膚に適用されることで、保湿作用、抗炎症作用、血行促進作用などを発揮することが期待され；それにより、肌荒れやあれ性の改善、あせも・しもやけ・ひび・あかぎれ・にきびを防いだり、肌を整えて皮膚をすこやかに保つ、皮膚にうるおいを与える、皮膚を保護する、皮膚の乾燥を防ぐ、などの効果が得られうる。 When applied to the skin, the external skin composition of the present invention is expected to exhibit moisturizing effects, anti-inflammatory effects, blood circulation promoting effects, etc. It can have effects such as preventing cracks, chapped skin, and acne, conditioning the skin to keep it healthy, moisturizing the skin, protecting the skin, and preventing skin dryness.
本発明の皮膚外用組成物は、特に、皮膚への保湿作用が高いため、皮膚の保湿剤として用いられることが好ましい。 The external skin composition of the present invention has a particularly high moisturizing effect on the skin, and is therefore preferably used as a skin moisturizer.
［3.皮膚外用組成物の製造方法］
本発明の皮膚外用組成物の製法は、特に限定されず、剤形に応じて常法にしたがって製造することができる。例えば、所定量の各配合成分（少なくとも、ヘパリン類似物質及びツボクサエキス抽出物を含む）を、液状担体に順次、添加・混合することで得ることができる。各剤形の組成物の製造方法は、例えば、「エマルションの調製技術事例集（出版社：技術情報協会、著者：水野朝子, 寺田千春 企画編集）」に記載がされており、参照することができる。
[3. Method for producing skin external composition]
The method for producing the skin external composition of the present invention is not particularly limited, and can be produced according to conventional methods depending on the dosage form. For example, it can be obtained by sequentially adding and mixing predetermined amounts of each of the ingredients (including at least a heparin-like substance and Centella asiatica extract) to a liquid carrier. The manufacturing method of the composition of each dosage form is described in, for example, "Example Collection of Emulsion Preparation Techniques (Publisher: Technical Information Association, Authors: Planning and Editing: Asako Mizuno, Chiharu Terada)", which you can refer to. can.
以下において、実施例を参照して本発明をより詳細に説明するが、これら実施例によって本発明は限定されない。 The present invention will be explained in more detail below with reference to Examples, but the present invention is not limited by these Examples.
［実施例１］及び［実施例２］：精製水に、表１に示す通りの配合量のヘパリン類似物質（局外規収載品）とツボクサエキス抽出物（セキセツソウ抽出液BG70（丸善製薬）、1%溶液）とを添加して常温で溶解させた。
［比較例１］：精製水に、表１に示す通りの配合量のヘパリン類似物質（局外規収載品）を添加して常温で溶解させた。
［比較例２］及び［比較例３］：精製水に、表１に示す通りの配合量のツボクサエキス抽出物（セキセツソウ抽出液BG70（丸善製薬）、1%溶液）を添加して常温で溶解させた。
[Example 1] and [Example 2]: To purified water, a heparin-like substance (listed as an external regulatory product) and Centella asiatica extract (Cantella asiatica extract BG70 (Maruzen Pharmaceutical), 1% solution) was added and dissolved at room temperature.
[Comparative Example 1]: A heparin-like substance (listed in external regulations) in the amount shown in Table 1 was added to purified water and dissolved at room temperature.
[Comparative Example 2] and [Comparative Example 3]: Add Centella asiatica extract (Centella asiatica extract BG70 (Maruzen Pharmaceutical), 1% solution) in the amount shown in Table 1 to purified water and dissolve at room temperature. I let it happen.
実施例1及び2並びに比較例1～3で調製した検体、及び水（対照検体）について、被験者（ヒト2名）の皮膚における保湿作用を確認した。まず、各検体の塗布前に、被験者の皮膚塗布部位（前腕内側）の皮膚水分量について5回の測定を行い、最大値及び最小値を除いた3回の水分上昇率の平均を塗布前水分量Xとした。そして、当該部位の直径約0.8 cm の円領域に、各検体５μLを塗布した。塗布後30分経過した時点で、皮膚塗布部位の皮膚水分量について5回の測定を行い、最大値及び最小値を除いた3回の水分上昇率の平均を塗布後水分量Yとした。 The moisturizing effect on the skin of test subjects (2 humans) was confirmed for the samples prepared in Examples 1 and 2 and Comparative Examples 1 to 3, and water (control sample). First, before application of each sample, the skin moisture content of the subject's skin application site (inner forearm) was measured five times, and the average of the moisture increase rates of the three measurements, excluding the maximum and minimum values, was calculated as the pre-application moisture content. Let the amount be X. Then, 5 μL of each sample was applied to a circular area of approximately 0.8 cm in diameter at the site. 30 minutes after application, the skin moisture content at the skin application site was measured five times, and the average of the three moisture increase rates excluding the maximum and minimum values was taken as the post-application moisture content Y.
各検体ついて、「（塗布後水分量Y－塗布前水分量X）／塗布前水分量X×100」を算出して水分上昇率Z（％）とした。各検体での水分上昇率Z（％）から、対照検体である水での水分上昇率（％）を差し引いた値を、表1の水分上昇率として示した。 For each specimen, "(moisture content Y after application - moisture content X before application)/moisture content before application X x 100" was calculated to determine the moisture increase rate Z (%). The value obtained by subtracting the moisture increase rate (%) for water, which is a control sample, from the moisture increase rate Z (%) for each sample is shown as the moisture increase rate in Table 1.
皮膚水分量の測定は、皮表角層水分量測定装置 SKICON(登録商標)-200EX (株式会社ヤヨイ)を用いて行った。本装置は、高周波を用いた交流電流に対する伝導度(conductance μS)を測定することで、「表層」の角層の水分量を測定することができる。高周波電流は物の表面を流れやすく、伝導度と水分含有量の間には密接な相関関係があるからである。このように、本実施例では、「表層」の角層の水分量を測定することで、皮膚の柔らかさや滑らかさを適切に評価している。 The skin moisture content was measured using a skin surface stratum corneum moisture content measuring device SKICON (registered trademark)-200EX (Yayoi Co., Ltd.). This device can measure the water content of the "surface layer" of the stratum corneum by measuring the conductance (μS) of alternating current using high frequency waves. This is because high-frequency current easily flows on the surface of objects, and there is a close correlation between conductivity and moisture content. In this way, in this example, the softness and smoothness of the skin is appropriately evaluated by measuring the moisture content of the "surface layer" of the stratum corneum.
表1に示される通り、0.1％のヘパリン類似物質を含有する比較例1の検体では水分量の上昇率が5.0 ％であり、0.000001(1×10-6)％のツボクサエキス抽出物(固形分)を含有する比較例2の検体では水分量の上昇率が見られなかった（-0.5%）。比較例1と比較例2の結果を踏まえると、0.1％のヘパリン類似物質と0.000001(1×10-6)％のツボクサエキス抽出物を含有する検体による水分上昇率は、相加効果として理論値4.5 ％である。ところが、0.1％のヘパリン類似物質と0.000001(1×10-6)％のツボクサエキス抽出物を含有する実施例1の検体では4.5％を大きく上回る上昇率（9.5%）を示しており、ヘパリン類似物質の保湿効果を、ツボクサエキス抽出物が相乗的に増強していることがわかる。 As shown in Table 1, the increase rate of water content in the sample of Comparative Example 1 containing 0.1% heparin-like substance was 5.0%, and the rate of increase in water content was 5.0%, and the increase rate of water content in the sample of Comparative Example 1 containing 0.1 % heparin-like substance was 5.0%. ) No increase in water content was observed in the sample of Comparative Example 2 containing (-0.5%). Based on the results of Comparative Example 1 and Comparative Example 2, the moisture increase rate due to the sample containing 0.1% heparin-like substance and 0.000001(1×10 -6 )% Centella asiatica extract is the theoretical value as an additive effect. 4.5%. However, the sample of Example 1 containing 0.1% heparin-like substance and 0.000001 (1×10 -6 )% centella asiatica extract showed an increase rate (9.5%) that was much higher than 4.5%, indicating that heparin-like substance It can be seen that Centella asiatica extract synergistically enhances the moisturizing effect of the substance.
また、表1に示される通り、0.1％のヘパリン類似物質を含有する比較例1の検体では水分量の上昇率が5.0 % であり、0.001 (1×10-3)％のツボクサエキス抽出物を含有する比較例3の検体では水分量の上昇率が9.5 % であった。比較例1と比較例3の結果を踏まえると、0.1％のヘパリン類似物質と0.001 (1×10-3)％のツボクサエキス抽出物を含有する検体による水分上昇率は、相加効果として理論値14.5 ％である。ところが、0.1％のヘパリン類似物質と0.001 (1×10-3)％のツボクサエキス抽出物を含有する実施例2の検体では14.5％を大きく上回る上昇率（24.0%）を示しており、ヘパリン類似物質の保湿効果を、ツボクサエキス抽出物が相乗的に増強していることがわかる。 Furthermore, as shown in Table 1, the rate of increase in water content in the sample of Comparative Example 1 containing 0.1% heparin-like substance was 5.0%, and the rate of increase in water content was 5.0% when 0.001 (1×10 -3 )% Centella asiatica extract was added. In the sample of Comparative Example 3, the rate of increase in water content was 9.5%. Based on the results of Comparative Example 1 and Comparative Example 3, the rate of moisture increase due to the sample containing 0.1% heparin-like substance and 0.001 (1×10 -3 )% Centella asiatica extract is the theoretical value as an additive effect. It is 14.5%. However, the sample of Example 2 containing 0.1% heparin-like substance and 0.001 (1×10 -3 )% Centella asiatica extract showed an increase rate (24.0%) that was much higher than 14.5%, indicating that heparin-like substance It can be seen that Centella asiatica extract synergistically enhances the moisturizing effect of the substance.
このように、表1に示された結果から、ツボクサエキス抽出物は、その濃度に応じて、ヘパリン類似物質の保湿効果を相乗的に増強していることがわかる。 Thus, from the results shown in Table 1, it can be seen that Centella asiatica extract synergistically enhances the moisturizing effect of heparin-like substances depending on its concentration.
［実施例３］化粧水の調製
表2に記載の水性溶媒に粘稠剤を加えて分散した。当該分散して得られた溶液に、表2に記載の残りの成分（有効成分、pH調整剤、防腐剤、ツボクサエキス抽出物）を全て加え、室温で混合した。その後、70℃まで温度を昇温させながら撹拌した後、30℃まで冷却させながら撹拌した後、室温に戻し、組成物を得た。得られた組成物は、成分が溶解状態にあった。
[Example 3] Preparation of lotion A thickening agent was added to the aqueous solvent shown in Table 2 and dispersed. All remaining components listed in Table 2 (active ingredient, pH adjuster, preservative, Centella asiatica extract) were added to the solution obtained by the dispersion and mixed at room temperature. Thereafter, the mixture was stirred while raising the temperature to 70°C, and then stirred while being cooled to 30°C, and then returned to room temperature to obtain a composition. In the resulting composition, the components were in a dissolved state.
表2において、％は、質量％を示す。また、キサンタンガムとしてはKELTROL (登録商標) CG-SFT（CP Kelco Inc. 社製）を、カルボキシビニルポリマーとしてはNTC-CARBOMER 381（Guangzhou Tinci Materials Technology社製）を、ツボクサエキス抽出物（BG70）としてはセキセツソウ抽出液BG70（丸善製薬社製）を使用した。 In Table 2, % indicates mass %. In addition, KELTROL (registered trademark) CG-SFT (manufactured by CP Kelco Inc.) is used as xanthan gum, NTC-CARBOMER 381 (manufactured by Guangzhou Tinci Materials Technology) as carboxyvinyl polymer, and Centella asiatica extract (BG70). For this purpose, Bulgaria oleracea extract BG70 (manufactured by Maruzen Pharmaceutical Co., Ltd.) was used.
［実施例４］乳液の調製
表3に記載の水性溶媒に粘稠剤を加えて分散した。当該混合して得られた溶液に、有効成分、pH調整剤、ツボクサエキス抽出物を加え80℃まで温度を昇温させた（溶解液A）。別途、油性成分、界面活性剤（乳化剤）、防腐剤を80℃まで温度を昇温させながら撹拌した（溶解液B）。80℃の溶解液Bを撹拌しながら、80℃の溶解液Aと混合した後、30℃まで冷却させながら撹拌した。その後、室温に戻し、組成物を得た。得られた組成物は、成分が乳化状態にあった。
[Example 4] Preparation of emulsion A thickening agent was added to the aqueous solvent shown in Table 3 and dispersed. The active ingredient, pH adjuster, and Centella asiatica extract were added to the solution obtained by mixing, and the temperature was raised to 80°C (dissolved solution A). Separately, an oily component, a surfactant (emulsifier), and a preservative were stirred while raising the temperature to 80°C (solution B). The 80°C solution B was mixed with the 80°C solution A while stirring, and then stirred while being cooled to 30°C. Thereafter, the temperature was returned to room temperature to obtain a composition. The components of the obtained composition were in an emulsified state.
表3において、％は、質量％を示す。また、カルボキシビニルポリマーとしてはNTC-CARBOMER 381（Guangzhou Tinci Materials Technology社製）を、ステアリン酸ポリオキシル40としてはNIKKOL MYS-40MV（日光ケミカルズ株式会社製）を、モノステアリン酸グリセリンとしてはNIKKOL MGS-BMV（日光ケミカルズ株式会社製）を、ツボクサエキス抽出物（BG70）としてはセキセツソウ抽出液BG70（丸善製薬社製）を使用した。 In Table 3, % indicates mass %. In addition, the carboxyvinyl polymer is NTC-CARBOMER 381 (manufactured by Guangzhou Tinci Materials Technology), the polyoxyl stearate 40 is NIKKOL MYS-40MV (manufactured by Nikko Chemicals Co., Ltd.), and the glycerin monostearate is NIKKOL MGS-BMV. (manufactured by Nikko Chemicals Co., Ltd.), and Centella asiatica extract BG70 (manufactured by Maruzen Pharmaceutical Co., Ltd.) was used as Centella asiatica extract (BG70).
実施例3で調製した化粧水、及び比較例４として市場で入手可能な化粧水（NALC(登録商標)薬用モイストローション）、並びに実施例4で調製した乳液、及び比較例５として市場で入手可能な乳液（NALC(登録商標)薬用ミルクローション）について、被験者（ヒト8名）の皮膚における保湿作用を確認した。まず、各検体の塗布前に、被験者の皮膚塗布部位（前腕内側）の皮膚水分量について5回の測定を行い、最大値及び最小値を除いた3回の水分上昇率の平均を塗布前水分量Xとした。そして、当該部位の直径約0.8 cm の円領域に、各検体５μLを塗布した。塗布後1時間、2時間、4時間、及び6時間経過した時点で、皮膚塗布部位の皮膚水分量について5回の測定を行い、最大値及び最小値を除いた3回の水分上昇率の平均を塗布後水分量Yとした。 The lotion prepared in Example 3 and the lotion (NALC® medicated moist lotion) available on the market as Comparative Example 4, and the emulsion prepared in Example 4 and available on the market as Comparative Example 5 The moisturizing effect of a milky lotion (NALC (registered trademark) medicated milk lotion) on the skin of test subjects (8 humans) was confirmed. First, before application of each sample, the skin moisture content of the subject's skin application site (inner forearm) was measured five times, and the average of the three moisture increase rates excluding the maximum and minimum values was calculated as the pre-application moisture content. Let the amount be X. Then, 5 μL of each sample was applied to a circular area of approximately 0.8 cm in diameter at the site. At 1 hour, 2 hours, 4 hours, and 6 hours after application, the skin moisture content at the skin application site was measured five times, and the average of the three moisture increase rates excluding the maximum and minimum values was calculated. was defined as the moisture content Y after application.
各検体ついて、「（塗布後水分量Y－塗布前水分量X）／塗布前水分量X×100」を算出した値を表４（実施例３及び比較例４）及び表５（実施例４及び比較例５）の水分上昇率（％）として示した。なお、皮膚水分量の測定は、皮表角層水分量測定装置 SKICON-200EX (株式会社ヤヨイ)を用いて行った。 For each sample, the calculated value of "(moisture content Y after application - moisture content X before application) / moisture content before application X x 100" is shown in Table 4 (Example 3 and Comparative Example 4) and Table 5 (Example 4) and Comparative Example 5) as the moisture increase rate (%). Note that the skin moisture content was measured using a skin surface stratum corneum moisture content measuring device SKICON-200EX (Yayoi Co., Ltd.).
比較例４で使用したNALC薬用モイストローションは、有効成分としてヘパリン類似物質とグリチルリチン酸ジカリウムを配合された化粧水であり、その他成分として、精製水、2-メタクリロイルオキシエチルホスホリルコリン・メタクリル酸ブチル共重合体液、ヒアルロン酸ナトリウム(2)、リン酸L-アスコルビルマグネシウム、ユズセラミド、1,3-ブチレングリコール、濃グリセリン、グリコシルトレハロース・水添デンプン分解物混合溶液、クエン酸、クエン酸ナトリウム、フェノキシエタノールを含むが、ツボクサエキス抽出物を含有しない。表４に示す通り、実施例３で調製した化粧水は、比較例４の市販品化粧水よりも、皮膚の水分上昇率を高めており、保湿性能が高いことがわかる。 The NALC medicated moist lotion used in Comparative Example 4 is a lotion containing a heparin-like substance and dipotassium glycyrrhizinate as active ingredients, and other ingredients include purified water, 2-methacryloyloxyethylphosphorylcholine/butyl methacrylate copolymer. Contains body fluids, sodium hyaluronate (2), magnesium L-ascorbyl phosphate, yuzu ceramide, 1,3-butylene glycol, concentrated glycerin, mixed solution of glycosyltrehalose/hydrogenated starch decomposition product, citric acid, sodium citrate, and phenoxyethanol. , does not contain centella asiatica extract. As shown in Table 4, it can be seen that the lotion prepared in Example 3 has a higher rate of skin moisture increase than the commercial lotion of Comparative Example 4, and has higher moisturizing performance.
比較例5で使用したNALC薬用ミルクローションは、有効成分としてヘパリン類似物質とグリチルリチン酸ジカリウムを配合された乳液であり、その他成分として、精製水、ジプロピレングリコール、1,3-ブチレングリコール、濃グリセリン、ソルビット液、ヒアルロン酸ナトリウム(2)、2-メタクリロイルオキシエチルホスホリルコリン・メタクリル酸ブチル共重合体液、スクワラン、トリ2-エチルヘキサン酸グリセリル、2-エチルヘキサン酸セチル、メドウフォーム油、軽質流動イソパラフィン、モノステアリン酸ポリオキシエチレンソルビタン(20E.O.)、自己乳化型モノステアリン酸グリセリル、ポリオキシエチレンラウリルエーテル(7E.O.)、ポリアクリ ル酸アミド、アクリル酸・メタクリル酸アルキル共重合体、キサンタンガム、水酸化カリウム、天然ビタミンE、エデト酸二ナトリウム、フェノキシエタノール、パラオキシ安息香酸メチルを含むが、ツボクサエキス抽出物を含有しない。表5に示す通り、実施例４で調製した乳液は、比較例４の市販品乳液よりも、皮膚の水分上昇率を高めており、保湿性能が高いことがわかる。 The NALC medicated milk lotion used in Comparative Example 5 is an emulsion containing a heparin-like substance and dipotassium glycyrrhizinate as active ingredients, and other ingredients include purified water, dipropylene glycol, 1,3-butylene glycol, and concentrated glycerin. , sorbitol liquid, sodium hyaluronate (2), 2-methacryloyloxyethylphosphorylcholine/butyl methacrylate copolymer liquid, squalane, glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, meadowfoam oil, light liquid isoparaffin, Polyoxyethylene sorbitan monostearate (20E.O.), self-emulsifying glyceryl monostearate, polyoxyethylene lauryl ether (7E.O.), polyacrylic acid amide, acrylic acid/alkyl methacrylate copolymer, xanthan gum Contains , potassium hydroxide, natural vitamin E, disodium edetate, phenoxyethanol, methyl paraoxybenzoate, but does not contain centella asiatica extract. As shown in Table 5, it can be seen that the emulsion prepared in Example 4 has a higher rate of skin moisture increase than the commercially available emulsion of Comparative Example 4, and has higher moisturizing performance.
本発明によれば、保湿作用が増強された皮膚外用組成物を提供することができるため、皮膚にうるおいを与えたり、皮膚を保護したり、皮膚の乾燥を防いだりするための化粧料等として本発明を利用することができる。 According to the present invention, it is possible to provide a composition for external use on the skin with enhanced moisturizing effect, so that it can be used as a cosmetic for moisturizing the skin, protecting the skin, and preventing dryness of the skin. The present invention can be used.
Claims (5)
前記皮膚外用組成物に、ツボクサエキス抽出物を配合することを含む、保湿作用増強方法。
A method for enhancing the moisturizing effect of an external skin composition containing a heparin-like substance, the method comprising:
A method for enhancing moisturizing effect, comprising blending Centella Centella asiatica extract into the skin external composition.
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