JP2012020994A - Composition for external use - Google Patents
Composition for external use Download PDFInfo
- Publication number
- JP2012020994A JP2012020994A JP2011134400A JP2011134400A JP2012020994A JP 2012020994 A JP2012020994 A JP 2012020994A JP 2011134400 A JP2011134400 A JP 2011134400A JP 2011134400 A JP2011134400 A JP 2011134400A JP 2012020994 A JP2012020994 A JP 2012020994A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- amino acid
- external use
- use according
- acid
- 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.)
- Granted
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Landscapes
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Abstract
Description
本発明は、アミノ酸を含有する外用組成物に関し、その経皮吸収性を向上させた外用組成物に関する。 The present invention relates to an external composition containing an amino acid, and relates to an external composition with improved transdermal absorbability.
アミノ酸は、食品,化粧品及び医薬品に幅広く利用されている機能性成分である。アミノ酸は一般的にタンパク質の構成成分として人体に多く存在しているが、皮膚の最外層である角層には遊離アミノ酸が多く存在し、天然保湿成分として皮膚の潤いに影響している。実際に、ヒト角層中の遊離アミノ酸組成において、グリシンは13.27%、アラニンは9.87%、セリンは20.13%、グルタミン酸及びグルタミンは3.88%、アルギニンは9.18%、プロリンは6.09%含まれる(非特許文献1参照)。 Amino acids are functional ingredients widely used in foods, cosmetics and pharmaceuticals. Amino acids are generally present in the human body as a protein component, but a large amount of free amino acids are present in the stratum corneum, which is the outermost layer of the skin, affecting the moisture of the skin as a natural moisturizing component. In fact, in the free amino acid composition in the human stratum corneum, glycine is 13.27%, alanine is 9.87%, serine is 20.31%, glutamic acid and glutamine are 3.88%, arginine is 9.18%, Proline is included in 6.09% (see Non-Patent Document 1).
また、タウリンには恒常性維持機能が知られている(非特許文献2参照)が、近年皮膚や毛髪にとっても重要な役割を担っていることが分かってきた。具体的には、あれ肌改善効果(非特許文献3参照)、保湿への影響(非特許文献4参照)、マウスにおける損傷皮膚の治癒促進効果(非特許文献5参照)、毛包成長への影響(非特許文献6参照)などが知られている。さらに、タウリンから誘導されるチオタウリンには皮脂酸化防止効果(非特許文献7、8、9参照)が、塩化タウリン及び臭化タウリンには黄色ブドウ球菌やアクネ菌に対する抗菌効果(非特許文献10参照)が知られている。 Taurine is known to have a homeostatic function (see Non-Patent Document 2), but recently it has been found that it plays an important role for skin and hair. Specifically, that skin improvement effect (see non-patent document 3), influence on moisture retention (see non-patent document 4), healing promotion effect of damaged skin in mice (see non-patent document 5), hair follicle growth The influence (refer nonpatent literature 6) etc. are known. Further, thiotaurine derived from taurine has a sebum oxidation-preventing effect (see Non-Patent Documents 7, 8, and 9), and taurine chloride and bromide have antibacterial effects against Staphylococcus aureus and acne bacteria (see Non-Patent Document 10). )It has been known.
ところで、アミノ酸は一般的に水溶性であるため、皮膚の最外層であり、脂溶的性質を有する角層への浸透が低く、それらが有する効果を十分に発揮できないといった課題があった。そこで、アミノ酸と脂肪酸とでイオンペアを形成させ、脂溶性を上げることで皮膚への吸収を増大させる方法(非特許文献11参照)、オレイン酸やazone(登録商標)を用いて経皮吸収促進させる方法(非特許文献12参照)、炭素原子数4〜8の1,2−アルカンジオール類の混合物により吸収促進させる方法(特許文献1参照)が知られている。 By the way, since amino acids are generally water-soluble, there is a problem that the outermost layer of the skin, the penetration into the stratum corneum having fat-soluble properties is low, and the effects they have cannot be fully exhibited. Thus, an ion pair is formed with an amino acid and a fatty acid, and the absorption to the skin is increased by increasing fat solubility (see Non-Patent Document 11), and transdermal absorption is promoted using oleic acid or azone (registered trademark). A method (see Non-Patent Document 12) and a method of promoting absorption by a mixture of 1,2-alkanediols having 4 to 8 carbon atoms (see Patent Document 1) are known.
また、経皮吸収促進剤に関しては多くの成分が知られ、例えば、乳酸(特許文献2参照)といった有機酸、乳酸オクチルドデシル(特許文献3参照)といった有機酸エステル、エチルヘキサン酸2−エチルヘキシル(特許文献4参照)、ジエチレングリコールモノエチルエーテル(特許文献5参照)等が知られている。しかしながら、これらは皮膚に対して刺激性を有したり、促進効果が充分でないものであった。 Moreover, many components are known regarding the percutaneous absorption enhancer, for example, organic acids such as lactic acid (see Patent Document 2), organic acid esters such as octyldodecyl lactate (see Patent Document 3), 2-ethylhexyl ethylhexanoate ( Patent Document 4), diethylene glycol monoethyl ether (see Patent Document 5), and the like are known. However, these are irritating to the skin and have insufficient promoting effects.
一方、ジラウロイルグルタミン酸リシンナトリウムは、ジェミニ型界面活性剤であり、あれ肌改善効果など優れたスキンケア効果やヘアケア効果を有すること、さらに皮膚に対して低刺激性であることが知られている。また、特許文献6にはジラウロイルグルタミン酸リシンナトリウムが美白化合物の経皮吸収を上げることが記載されているが、この美白化合物は脂溶性物質であり、水溶性物質であるアミノ酸の経皮吸収効果については記載も示唆もされていない。 On the other hand, dilauroylglutamate ricin sodium is a gemini-type surfactant, and is known to have excellent skin care and hair care effects such as skin improvement effects, and to be hypoallergenic to the skin. Patent Document 6 describes that lysine sodium dilauroylglutamate increases the transdermal absorption of a whitening compound. This whitening compound is a fat-soluble substance, and the transdermal absorption effect of an amino acid which is a water-soluble substance. Is not described or suggested.
アミノ酸は水溶性であるため、単に外用組成物に配合してもそれらが有する効果を発揮できるほど経皮吸収されないといった課題があった。本発明は、アミノ酸の経皮吸収性を増大させた外用組成物を提供することを課題とする。 Since amino acids are water-soluble, there is a problem in that they are not absorbed percutaneously enough to exert their effects even if they are simply blended into an external composition. This invention makes it a subject to provide the composition for external use which increased the percutaneous absorbability of the amino acid.
本発明者らは、前記課題を解決すべく鋭意検討を重ねた結果、ジラウロイルグルタミン酸リシンナトリウムにアミノ酸の経皮吸収性増大効果を見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that ricin sodium dilauroyl glutamate has an effect of increasing the transdermal absorbability of amino acids, and have completed the present invention.
すなわち、本発明は、
(1)アミノ酸、及びジラウロイルグルタミン酸リシンナトリウムを含有することを特徴とする外用組成物、
(2)アミノ酸が含硫アミノ酸である(1)に記載の外用組成物、
(3)含硫アミノ酸がタウリン又はメチオニンである(2)に記載の外用組成物、
(4)含硫アミノ酸がタウリンである(2)に記載の外用組成物、
(5)アミノ酸が脂肪族アミノ酸である(1)に記載の外用組成物、
(6)アミノ酸がヒドロキシアミノ酸である(1)に記載の外用組成物、
(7)アミノ酸が塩基性アミノ酸である(1)に記載の外用組成物、
(8)アミノ酸が複素乾式アミノ酸である(1)に記載の外用組成物、
(9)アミノ酸がイミノ酸である(1)に記載の外用組成物、
(10)脂肪族アミノ酸がアラニンである(5)に記載の外用組成物、
(11)ヒドロキシアミノ酸がセリンである(6)に記載の外用組成物、
(12)塩基性アミノ酸がアルギニンである(7)に記載の外用組成物、
(13)複素乾式アミノ酸がヒスチジンである(8)に記載の外用組成物、
(14)イミノ酸がプロリンである(9)に記載の外用組成物、
である。
That is, the present invention
(1) An external composition comprising an amino acid and lysine sodium dilauroyl glutamate,
(2) The composition for external use according to (1), wherein the amino acid is a sulfur-containing amino acid,
(3) The composition for external use according to (2), wherein the sulfur-containing amino acid is taurine or methionine,
(4) The composition for external use according to (2), wherein the sulfur-containing amino acid is taurine,
(5) The composition for external use according to (1), wherein the amino acid is an aliphatic amino acid,
(6) The composition for external use according to (1), wherein the amino acid is a hydroxyamino acid,
(7) The composition for external use according to (1), wherein the amino acid is a basic amino acid,
(8) The composition for external use according to (1), wherein the amino acid is a complex dry amino acid,
(9) The composition for external use according to (1), wherein the amino acid is imino acid,
(10) The composition for external use according to (5), wherein the aliphatic amino acid is alanine,
(11) The composition for external use according to (6), wherein the hydroxyamino acid is serine,
(12) The composition for external use according to (7), wherein the basic amino acid is arginine,
(13) The composition for external use according to (8), wherein the complex dry amino acid is histidine,
(14) The composition for external use according to (9), wherein the imino acid is proline,
It is.
本発明により、アミノ酸の経皮吸収性を増大させることが可能となった。 According to the present invention, it is possible to increase the transdermal absorbability of amino acids.
本発明におけるアミノ酸には、グリシン、アラニンといった脂肪族アミノ酸、バリン、ロイシン、イソロイシンといった分岐アミノ酸、セリン、トレオニンといったヒドロキシアミノ酸、アスパラギン酸、グルタミン酸といった酸性アミノ酸、アスパラギン、グルタミンといったアミド、リシン、アルギニンといった塩基性アミノ酸、システイン、シスチン、メチオニン、タウリンといった含硫アミノ酸、フェニルアラニン、チロシンといった芳香族アミノ酸、トリプトファン、ヒスチジンといった複素環式アミノ酸、プロリン、ヒドロキシプロリンといったイミノ酸や、それらの塩類、及びそれらの代謝物(グルタミン酸代謝物であるピロリドンカルボン酸など)等が含まれるが、特に皮膚に対して天然保湿成分として働いているグリシン、アラニン、バリン、ロイシン、イソロイシン、セリン、トレオニン、アスパラギン酸、アスパラギン、グルタミン酸、グルタミン、ピロリドンカルボン酸、リシン,アルギニン、メチオニン、フェニルアラニン、チロシン、ヒスチジン、プロリン、及び皮膚や毛髪に有用性が示されているタウリン、チオタウリン、ヒポタウリン、並びにこれらの塩類を好ましく使用できる。さらにグリシン、アラニン、セリン、グルタミン酸、グルタミン、ピロリドンカルボン酸、アルギニン、プロリン、タウリンを使用することがより好ましい。また、アミノ酸は1種でも、2種以上でも構わない。アミノ酸の配合量は外用組成物中、通常0.1質量%〜10質量%であり、好ましくは0.5質量%〜5.0質量%である。0.1質量%以下では効果が期待できない場合があり、10質量%以上では製剤化が困難となる場合があるためである。 The amino acids in the present invention include aliphatic amino acids such as glycine and alanine, branched amino acids such as valine, leucine and isoleucine, hydroxy amino acids such as serine and threonine, acidic amino acids such as aspartic acid and glutamic acid, amides such as asparagine and glutamine, bases such as lysine and arginine. Amino acids, sulfur-containing amino acids such as cysteine, cystine, methionine and taurine, aromatic amino acids such as phenylalanine and tyrosine, heterocyclic amino acids such as tryptophan and histidine, imino acids such as proline and hydroxyproline, their salts, and their metabolites (Such as pyrrolidone carboxylic acid, which is a metabolite of glutamic acid), etc., but especially glycine that works as a natural moisturizing ingredient for the skin Alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, pyrrolidonecarboxylic acid, lysine, arginine, methionine, phenylalanine, tyrosine, histidine, proline, and skin and hair are shown to be useful Taurine, thiotaurine, hypotaurine, and salts thereof can be preferably used. Furthermore, it is more preferable to use glycine, alanine, serine, glutamic acid, glutamine, pyrrolidone carboxylic acid, arginine, proline and taurine. Further, the amino acid may be one type or two or more types. The amount of amino acid in the composition for external use is usually 0.1% by mass to 10% by mass, preferably 0.5% by mass to 5.0% by mass. This is because if 0.1% by mass or less, the effect may not be expected, and if it is 10% by mass or more, formulation may be difficult.
本発明におけるジラウロイルグルタミン酸リシンナトリウムの配合量は外用組成物中、通常0.03〜10質量%であり、好ましくは0.5〜5.0質量%であり、より好ましくは0.15〜3.0質量%である。0.03質量%以下であると、経皮吸収促進効果が低いことがあり、10質量%以上であると粘度増加など製剤化が困難となる場合があるためである。また、アミノ酸1質量部に対して、0.03質量部以上のジラウロイルグルタミン酸リシンナトリウムを配合することが好ましく、0.1質量部以上配合することがより好ましい。 The compounding quantity of dilauroyl glutamic acid sodium lysine in this invention is 0.03-10 mass% normally in an external composition, Preferably it is 0.5-5.0 mass%, More preferably, it is 0.15-3. 0.0% by mass. When the content is 0.03% by mass or less, the effect of promoting percutaneous absorption may be low. When the content is 10% by mass or more, formulation may be difficult due to increase in viscosity. Moreover, it is preferable to mix | blend 0.03 mass part or more of dilauroyl glutamate ricin sodium with respect to 1 mass part of amino acids, and it is more preferable to mix | blend 0.1 mass part or more.
本発明の外用組成物では、ベシクルを形成させる必要は無い。従って、特開2009−1500号公報に記載された様に、ベシクルを形成させるためのセラミドまたはその類縁体と、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル及びピログルタミン酸グリセリン脂肪酸エステルを配合する必要は無い。 In the composition for external use of the present invention, it is not necessary to form vesicles. Therefore, as described in JP-A-2009-1500, it is not necessary to blend ceramide for forming a vesicle or an analog thereof, glycerin fatty acid ester, polyglycerin fatty acid ester, and pyroglutamic acid glycerin fatty acid ester.
本発明の外用組成物は、液剤、ローション剤、ゲル剤、エアゾール剤、クリーム剤等の各種外用剤として使用できる。 The composition for external use of this invention can be used as various external preparations, such as a liquid agent, a lotion agent, a gel agent, an aerosol agent, and a cream agent.
液剤は、アミノ酸とジラウロイルグルタミン酸リシンナトリウムを、水、低級アルコール、多価アルコール又はこれらの混液に溶解・分散させて調製することができる。また、このような液剤と適当な液化ガス(液化石油ガス、ジメチルエーテルなど)をアルミ製耐圧容器に入れてエアゾール剤を調製することもできる。さらに、このような液剤に適当なゲル化剤を配合してゲル剤を調製することも可能である。 The liquid preparation can be prepared by dissolving and dispersing amino acid and dilauroyl glutamic acid sodium lysine in water, lower alcohol, polyhydric alcohol or a mixture thereof. Further, an aerosol agent can be prepared by putting such a liquid agent and an appropriate liquefied gas (liquefied petroleum gas, dimethyl ether, etc.) into an aluminum pressure vessel. Furthermore, it is also possible to prepare a gel agent by blending such a liquid agent with an appropriate gelling agent.
ローション剤、及びクリーム剤も常法により調製が可能である。 Lotions and creams can also be prepared by conventional methods.
本発明の外用組成物には、抗菌剤、抗炎症剤、鎮痛剤、抗ヒスタミン剤、組織修復剤、鎮痒剤、保湿剤、血管収縮剤、抗アレルギー剤、局所麻酔剤、酸素除去剤、清涼化剤、ビタミン、紫外線吸収剤、紫外線散乱剤などを本発明の効果を損なわない範囲で適宜に配合することができる。なお、上記成分が油溶性で外用組成物に完全に溶解できない場合には、可溶化するのに必要な界面活性剤を適宜配合すればよい。 The composition for external use of the present invention includes antibacterial agents, anti-inflammatory agents, analgesics, antihistamines, tissue repair agents, antipruritic agents, moisturizers, vasoconstrictors, antiallergic agents, local anesthetics, oxygen scavengers, and refreshing agents. In addition, vitamins, ultraviolet absorbers, ultraviolet scattering agents and the like can be appropriately blended within a range not impairing the effects of the present invention. In addition, what is necessary is just to mix | blend surfactant required for solubilizing suitably, when the said component is oil-soluble and cannot melt | dissolve completely in an external composition.
本発明の外用組成物には、医薬品、医薬部外品、化粧品に配合可能な種々の基剤成分を本発明の効果を損なわない範囲で適宜に含有させることができる。このような基剤成分としては、精製水、低級アルコールや多価アルコール等の溶解補助剤、炭化水素、グリセリン脂肪酸エステル、ワックス成分、界面活性剤、抗酸化剤、乳化安定剤、ゲル化剤、粘着剤等、各種動植物からの抽出物、pH調整剤、防腐剤、キレート剤、香料、色素、液化ガスなどが挙げられる。 In the composition for external use of the present invention, various base components that can be blended in pharmaceuticals, quasi drugs, and cosmetics can be appropriately contained within a range not impairing the effects of the present invention. Examples of such base components include purified water, solubilizing agents such as lower alcohols and polyhydric alcohols, hydrocarbons, glycerin fatty acid esters, wax components, surfactants, antioxidants, emulsion stabilizers, gelling agents, Examples include extracts from various animals and plants such as pressure-sensitive adhesives, pH adjusters, preservatives, chelating agents, fragrances, pigments, and liquefied gases.
次に、実施例、比較例及び試験例を挙げて、本発明を更に詳細に説明する。表1〜6に実施例1〜11、及び比較例1〜14の処方を示した。表中の数値の単位は「g」である。 Next, the present invention will be described in more detail with reference to examples, comparative examples, and test examples. Tables 1 to 6 show the formulations of Examples 1 to 11 and Comparative Examples 1 to 14. The unit of numerical values in the table is “g”.
実施例1〜4は、タウリン、及びジラウロイルグルタミン酸リシンナトリウムを表記載の処方量に従い秤量し、pH調整剤として0.1N塩酸および0.1N水酸化ナトリウム水溶液適量と共に、精製水にて全量100gになるよう加え、攪拌、溶解し、外用組成物を調製した。 In Examples 1 to 4, taurine and lysine sodium dilauroyl glutamate were weighed in accordance with the prescription amounts shown in the table, and 100 g of purified water was used together with appropriate amounts of 0.1N hydrochloric acid and 0.1N sodium hydroxide aqueous solution as pH adjusters. The mixture was stirred and dissolved to prepare a composition for external use.
比較例1、3及び6はタウリン、及び比較例3と6にはそれぞれ経皮吸収促進剤として、乳酸、ジエチレングリコールモノエチルエーテルを表記載の処方量に従い秤量し、精製水にて全量100gになるよう加え、攪拌、溶解し、外用組成物を調製した。なお、比較例3に関してはpH調整剤として0.1N塩酸および0.1N水酸化ナトリウム水溶液を適量配合し、pH5.4とした。 Comparative Examples 1, 3 and 6 are taurine, and Comparative Examples 3 and 6 are weighed with lactic acid and diethylene glycol monoethyl ether as percutaneous absorption promoters according to the prescription amounts shown in the table, and the total amount is 100 g with purified water. The mixture was stirred and dissolved to prepare a composition for external use. For Comparative Example 3, appropriate amounts of 0.1N hydrochloric acid and 0.1N sodium hydroxide aqueous solution were added as pH adjusters to adjust the pH to 5.4.
比較例2、4、5、及び7はタウリン、ポリオキシエチレン硬化ヒマシ油60、及び比較例4、5、及び7にはそれぞれ経皮吸収促進剤として、乳酸2−オクチルドデシル、ヒドロキシステアリン酸2−エチルヘキシル、1,2−ヘキサンジオール/カプリリルグリコールを表記載の処方量に従い秤量し、60℃にて攪拌、溶解させた後、60℃に温めておいた精製水を少量ずつ添加、攪拌した後、全量100gになるよう加え、外用組成物を調製した。 Comparative Examples 2, 4, 5, and 7 were taurine, polyoxyethylene hydrogenated castor oil 60, and Comparative Examples 4, 5, and 7 were transdermal absorption promoters, such as 2-octyldodecyl lactate and hydroxystearic acid 2, respectively. -Ethylhexyl and 1,2-hexanediol / caprylyl glycol were weighed in accordance with the prescribed amounts in the table, stirred and dissolved at 60 ° C, and then purified water warmed to 60 ° C was added little by little and stirred. Then, it added so that the whole quantity might be 100g, and prepared the composition for external use.
実施例5〜10は、アラニン、アルギニン、ヒスチジン、メチオニン、プロリン、セリン、及びジラウロイルグルタミン酸リシンナトリウムを表記載の処方量に従い秤量し、精製水にて全量100gになるように加え、攪拌、溶解し、外用組成物を調製した。 In Examples 5 to 10, alanine, arginine, histidine, methionine, proline, serine, and dilauroylglutamate sodium lysine were weighed according to the prescribed amounts in the table, added to purified water to a total amount of 100 g, stirred, dissolved Then, a composition for external use was prepared.
比較例8〜13は、アラニン、アルギニン、ヒスチジン、メチオニン、プロリン、及びセリンを表記載の処方量に従い秤量し、pH調整剤として0.1N塩酸および0.1N水酸化ナトリウム水溶液適量と共に、精製水にて全量100gになるよう加え、攪拌、溶解し、外用組成物を調製した。 In Comparative Examples 8 to 13, alanine, arginine, histidine, methionine, proline, and serine were weighed according to the prescription amounts shown in the table, and purified water was added together with appropriate amounts of 0.1N hydrochloric acid and 0.1N sodium hydroxide aqueous solution as a pH adjuster. Was added to a total amount of 100 g, stirred and dissolved to prepare an external composition.
実施例11は、表記載の処方量の1,3−ブチレングリコール、ジプロピレングリコール、グリセリン、マクロゴール、防腐剤を加温しながら溶解させ、キサンタンガムを分散させたマクロゴールを加え、攪拌、溶解させた。そこに、タウリン、ジラウロイルグルタミン酸リシンナトリウム、pH調整剤(0.1N塩酸および0.1N水酸化ナトリウム水溶液)を溶解させた水溶液を添加し、化粧水を調製した。比較例14は、ジラウロイルグルタミン酸リシンナトリウム配合しないで,調製した。 In Example 11, 1,3-butylene glycol, dipropylene glycol, glycerin, macrogol and preservatives in the prescribed amounts shown in the table were dissolved while heating, and macrogol in which xanthan gum was dispersed was added, stirred, and dissolved. I let you. An aqueous solution in which taurine, sodium dilauroylglutamate, and a pH adjuster (0.1N hydrochloric acid and 0.1N aqueous sodium hydroxide) were dissolved was added to prepare a lotion. Comparative Example 14 was prepared without blending dilauroyl glutamic acid ricin sodium.
試験例 in vitroヘアレスラット摘出皮膚透過性試験
電気シェーバーで腹部を剃毛したヘアレスラット(雄、9週齢)の腹部剃毛部より皮膚を摘出した。摘出した皮膚を平均有効面積0.98cm2の横型拡散セルに装着した後、ドナー側のセル内に表1〜6に示した各検体3mLを加え、レシーバー側のセルにpH7.4リン酸緩衝液3mLを加えた。拡散セルの外層には37℃の恒温水を還流し、レシーバー液は撹拌子により撹拌した。
Test Example In Vitro Hairless Rat Extraction Skin Permeability Test Skin was extracted from the abdominal shaved part of a hairless rat (male, 9 weeks old) shaved with an electric shaver. After the extracted skin was attached to a horizontal diffusion cell having an average effective area of 0.98 cm 2 , 3 mL of each specimen shown in Tables 1 to 6 was added to the donor side cell, and pH 7.4 phosphate buffer was added to the receiver side cell. 3 mL of liquid was added. Constant temperature water at 37 ° C. was refluxed to the outer layer of the diffusion cell, and the receiver liquid was stirred with a stirring bar.
経時的にレシーバー液を一定量採取し、常法に従い液体クロマトグラフによりタウリン、アラニン、アルギニン、ヒスチジン、メチオニン、プロリン、セリン量を測定した。なお、タウリン、アラニン、アルギニン、ヒスチジン、メチオニン、プロリン、セリンは元々皮膚中に存在するため、検体を塗布しなくても経時的に僅かにレシーバー液に流出してくる。そこで、比較例1と比較例2について予備試験を行い、両者に差が無いこと(ポリオキシエチレン硬化ヒマシ油60にタウリンの経皮吸収促進効果はない)及び再現性があることを確認した後、各実施例及び比較例で試験を実施した。 A certain amount of receiver solution was collected over time, and taurine, alanine, arginine, histidine, methionine, proline and serine were measured by liquid chromatography according to a conventional method. Since taurine, alanine, arginine, histidine, methionine, proline, and serine are originally present in the skin, they slightly flow out to the receiver solution over time without applying a sample. Therefore, after conducting a preliminary test on Comparative Example 1 and Comparative Example 2 and confirming that there is no difference between them (polyoxyethylene hydrogenated castor oil 60 has no effect of promoting percutaneous absorption of taurine) and reproducibility. The test was carried out in each example and comparative example.
そして、各々の結果は、以下の通り算出し、経皮吸収促進倍率とした。実施例1〜4、並びに比較例3及び6の24時間後の累積透過量を比較例1の24時間後の累積透過量に対して(24時間後の比較例1を1.0とする)、比較例5、及び7の24時間後の累積透過量を比較例2の24時間後の累積透過量に対して(24時間後の比較例2を1.0とする)算出し、それぞれ表7及び表8に結果を纏めた。また、比較例4の8時間後の累積透過量を比較例2の8時間後の累積透過量に対して(8時間後の比較例2を1.0とする)算出したところ結果は0.6倍であり、実施例5の24時間後の累積透過量を比較例8の24時間後の累積透過量に対して(比較例8を1.0とする)算出したところ結果は6.1倍であり、実施例6の24時間後の累積透過量を比較例9の24時間後の累積透過量に対して(比較例9を1.0とする)算出したところ結果は2.4倍であり、実施例7の24時間後の累積透過量を比較例10の24時間後の累積透過量に対して(比較例10を1.0とする)算出したところ結果は8.1倍であり、実施例8の24時間後の累積透過量を比較例11の24時間後の累積透過量に対して(比較例11を1.0とする)算出したところ結果は4.5倍であり、実施例9の24時間後の累積透過量を比較例12の24時間後の累積透過量に対して(比較例12を1.0とする)算出したところ結果は2.6倍であり、実施例10の24時間後の累積透過量を比較例13の24時間後の累積透過量に対して(比較例13を1.0とする)算出したところ結果は3.4倍であり、実施例11の24時間後の累積透過量を比較例14の24時間後の累積透過量に対して(比較例14を1.0とする)算出したところ結果は12.3倍であった。 And each result was computed as follows and was set as the percutaneous absorption promotion magnification. The cumulative permeation amount after 24 hours of Examples 1 to 4 and Comparative Examples 3 and 6 was compared with the cumulative permeation amount after 24 hours of Comparative Example 1 (Comparative Example 1 after 24 hours is assumed to be 1.0). The cumulative permeation amount after 24 hours of Comparative Examples 5 and 7 is calculated with respect to the cumulative permeation amount after 24 hours of Comparative Example 2 (Comparative Example 2 after 24 hours is assumed to be 1.0). 7 and Table 8 summarize the results. Further, the cumulative permeation amount after 8 hours of Comparative Example 4 was calculated with respect to the cumulative permeation amount after 8 hours of Comparative Example 2 (Comparative Example 2 after 8 hours was set to 1.0). The cumulative permeation amount after 24 hours of Example 5 was calculated with respect to the cumulative permeation amount after 24 hours of Comparative Example 8 (Comparative Example 8 was set to 1.0), and the result was 6.1. The cumulative transmission amount after 24 hours of Example 6 was calculated with respect to the cumulative transmission amount after 24 hours of Comparative Example 9 (Comparative Example 9 was set to 1.0), and the result was 2.4 times. The cumulative transmission amount after 24 hours of Example 7 was calculated with respect to the cumulative transmission amount after 24 hours of Comparative Example 10 (Comparative Example 10 was set to 1.0), and the result was 8.1 times. Yes, the cumulative permeation amount after 24 hours of Example 8 is calculated with respect to the cumulative permeation amount after 24 hours of Comparative Example 11 (Comparative Example 11 is set to 1.0). The result was 4.5 times, and the cumulative permeation amount after 24 hours of Example 9 was calculated with respect to the cumulative permeation amount after 24 hours of Comparative Example 12 (Comparative Example 12 was set to 1.0). However, the result was 2.6 times, and the cumulative permeation amount after 24 hours of Example 10 was calculated with respect to the cumulative permeation amount after 24 hours of Comparative Example 13 (Comparative Example 13 was set to 1.0). The result is 3.4 times, and the cumulative permeation amount after 24 hours of Example 11 is calculated with respect to the cumulative permeation amount after 24 hours of Comparative Example 14 (Comparative Example 14 is set to 1.0). Was 12.3 times.
ジラウロイルグルタミン酸リシンナトリウムは、0.06%以上の配合で濃度依存的に経皮吸収性が増大した。また、実施例11の結果からわかるように、ジラウロイルグルタミン酸リシンナトリウムは化粧水処方に配合してもその高い経皮吸収促進効果を発揮した。なお、ウサギを用いた皮膚一次刺激性試験を実施した結果、ジラウロイルグルタミン酸リシンナトリウム10%水溶液の皮膚刺激スコアは0.17と非常に低値で安全な成分である事が示された。 Dilauroyl glutamate ricin sodium increased in transdermal absorbability in a concentration-dependent manner at a content of 0.06% or more. In addition, as can be seen from the results of Example 11, dilauroyl glutamate ricin sodium exhibited a high transdermal absorption promoting effect even when blended in a lotion formulation. In addition, as a result of conducting a skin primary irritation test using rabbits, it was shown that the skin irritation score of 10% aqueous solution of dilauroyl glutamate ricin sodium was 0.17, which is a very low value and a safe component.
一方、一般的に経皮吸収促進剤と言われているそれ以外の成分は、経皮吸収促進効果が低かった。 On the other hand, other components generally referred to as transdermal absorption enhancers have a low transdermal absorption promoting effect.
本発明により、アミノ酸の経皮吸収性を増大させ、アミノ酸の有用性を十分に果たすことが可能な外用組成物を提供することが期待される。 According to the present invention, it is expected to provide an external composition capable of increasing the transdermal absorbability of amino acids and sufficiently fulfilling the usefulness of amino acids.
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