JP2008222643A - Liposome for cosmetic use - Google Patents

Liposome for cosmetic use Download PDF

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JP2008222643A
JP2008222643A JP2007064150A JP2007064150A JP2008222643A JP 2008222643 A JP2008222643 A JP 2008222643A JP 2007064150 A JP2007064150 A JP 2007064150A JP 2007064150 A JP2007064150 A JP 2007064150A JP 2008222643 A JP2008222643 A JP 2008222643A
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liposome
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JP5326216B2 (en
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Asako Mizoguchi
亜紗子 溝口
Shinji Tanaka
信治 田中
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NOF Corp
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a liposome for cosmetics better than conventional ones. <P>SOLUTION: The liposome for cosmetic use is characterized in that a cyclic phosphatidic acid represented by formula [I] [wherein, R is a 10-22C acyl; and M is H, an alkali metal atom, alkaline earth metal atom or a (substituted) ammonium group] is compounded as a constituent of the liposome. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

本発明は、特定の構造を有する環状ホスファチジン酸がリポソームの構成成分として配合されている化粧料用リポソーム及び当該化粧料用リポソームを含有する化粧料に関する。   The present invention relates to a cosmetic liposome in which cyclic phosphatidic acid having a specific structure is blended as a component of the liposome, and a cosmetic containing the cosmetic liposome.

紫外線やストレス、あるいは加齢などによって皮膚が老化すると、肌のハリが失われ、乾燥してなめらかさを失ったり、肌がざらついた感触となったりするなどの現象が生じ、やがて、しわ、たるみ、シミなどが生じることとなる。さらに、加齢とともに毛穴の開きが目立ち、肌のきめの細かさが失われるようになる。
皮膚のハリや瑞々しさには、細胞間の水分保持や柔軟性を保つ機能を有するヒアルロン酸が寄与していることから、上記したような皮膚の老化現象には、表皮や真皮中のヒアルロン酸の減少が影響しているとされている。そのため、皮膚の老化対策として、体外からのヒアルロン酸の補給や、ヒアルロン酸の産生能を向上させるための物質の補給などの試みがなされている。
そのうち、特許文献1には、環状ホスファチジン酸が老化した肌のヒアルロン酸産生を促進し、肌のハリを改善する効果を奏することが記載されている。しかし、環状ホスファチジン酸は、水への溶解性が低いため、少量でも水系ではオーロラが生じ、水の多い系へ多量に配合することは困難であった。
If the skin ages due to ultraviolet rays, stress, or aging, the skin will lose its firmness, dry and lose its smoothness, and the skin may become rough and wrinkled. , Spots and the like will occur. In addition, the opening of pores becomes conspicuous with aging and the fineness of the skin is lost.
Hyaluronic acid, which has the function of maintaining moisture and flexibility between cells, contributes to the firmness and freshness of the skin. Therefore, the hyaluronic acid in the epidermis and dermis is responsible for the above-mentioned skin aging phenomenon. The decrease in acid is said to be affected. For this reason, attempts have been made to replenish hyaluronic acid from outside the body and supplement substances to improve hyaluronic acid production as measures against skin aging.
Among them, Patent Document 1 describes that cyclic phosphatidic acid has an effect of promoting hyaluronic acid production in aged skin and improving skin firmness. However, since cyclic phosphatidic acid has low solubility in water, an aurora is produced even in a small amount in an aqueous system, and it has been difficult to incorporate a large amount in a system with a large amount of water.

特許文献2及びその分割出願である特許文献3には、肌に対する抗しわなどの改善効果を期待して、1−O−アシルリゾホスファチジン酸や環状ホスファチジン酸エステルなどを皮膚に外用する技術が開示されている。しかしながら、これらの文献においては、1−O−アシルリゾホスファチジン酸及び環状ホスファチジン酸エステルは、リポソーム化されていないため、さらさらとした感触が得られていない。
特開2002−363081号公報 米国特許第5238965号明細書 米国特許第5521223号明細書
Patent Document 2 and Patent Document 3 which is a divisional application thereof disclose a technique for externally applying 1-O-acyl lysophosphatidic acid or cyclic phosphatidic acid ester to the skin in anticipation of an improvement effect such as anti-wrinkle on the skin. Has been. However, in these documents, since 1-O-acyl lysophosphatidic acid and cyclic phosphatidic acid ester are not made into liposomes, a smooth feel is not obtained.
JP 2002-363081 A US Pat. No. 5,238,965 US Pat. No. 5,512,223

環状ホスファチジン酸は、水への溶解性が低く、水の多い系から構成される化粧料には多量に配合することが困難であった。また、従来の環状ホスファチジン酸を使用した化粧料は、環状ホスファチジン酸が有する特性であるさらさらとした感触が生かされておらず、使用時の感触の点で改良の余地があった。   Cyclic phosphatidic acid has low solubility in water, and it has been difficult to add a large amount to cosmetics composed of a water-rich system. Moreover, the cosmetics using the conventional cyclic phosphatidic acid do not make use of the smooth touch that is a characteristic of the cyclic phosphatidic acid, and there is room for improvement in terms of the touch when used.

本発明者らは、化粧料としての使用感に優れかつ安定な環状ホスファチジン酸含有化粧料を得るべく鋭意研究した結果、特定の構造を有する環状ホスファチジン酸をリポソームの構成成分として配合してリポソームを作製し、これを化粧料に配合したところ、使用感に優れかつ安定な化粧料が得られることを見出し、本発明を完成するに至った。   As a result of earnest research to obtain a cosmetic material containing cyclic phosphatidic acid that is excellent and stable in use as a cosmetic, the present inventors have formulated a liposome by blending a cyclic phosphatidic acid having a specific structure as a component of the liposome. When produced and blended with cosmetics, it was found that a cosmetic having excellent usability and stability was obtained, and the present invention was completed.

すなわち、本発明の要旨は以下のとおりである。
(1) 以下の式[I]で表される環状ホスファチジン酸がリポソームの構成成分として配合されていることを特徴とする化粧料用リポソーム:
That is, the gist of the present invention is as follows.
(1) A liposome for cosmetics, wherein a cyclic phosphatidic acid represented by the following formula [I] is blended as a constituent of the liposome:

Figure 2008222643
Figure 2008222643

(式中、
Rは、炭素数10〜22のアシル基を示し、
Mは、水素原子、アルカリ金属原子、アルカリ土類金属原子、置換又は無置換のアンモニウム基を示す。)。
(2) さらに、リン脂質がリポソームの構成成分として配合されていることを特徴とする、上記(1)に記載の化粧料用リポソーム。
(3) さらに、ステロール類がリポソームの構成成分として配合されていることを特徴とする、上記(1)又は(2)に記載の化粧料用リポソーム。
(4) 上記(1)〜(3)のいずれかに記載の化粧料用リポソームを含有する化粧料。
(Where
R represents an acyl group having 10 to 22 carbon atoms;
M represents a hydrogen atom, an alkali metal atom, an alkaline earth metal atom, or a substituted or unsubstituted ammonium group. ).
(2) The liposome for cosmetics according to (1) above, further comprising phospholipids as a component of the liposome.
(3) The liposome for cosmetics according to (1) or (2) above, wherein sterols are further blended as a component of the liposome.
(4) A cosmetic comprising the cosmetic liposome according to any one of (1) to (3) above.

本発明の化粧料用リポソームは、特定の構造を有する環状ホスファチジン酸がリポソームの構成成分として配合されていることにより、化粧料として使用した場合、肌あれを改善し、ふっくらとした潤いのあるなめらかな肌へと導くことができるだけでなく、従来品に比べ、経時安定性が良く(オーロラが生じない)、べたつき感がないさらさらとした使用感を有する化粧料を得ることができる。また、本発明の化粧料用リポソームを含有する化粧料は、肌のハリ改善効果及び毛穴の引き締め効果があり、保湿性が高く、使用感のよい化粧料である。   The liposome for cosmetics according to the present invention is characterized by the fact that cyclic phosphatidic acid having a specific structure is blended as a constituent component of the liposome, so that when used as a cosmetic, it improves skin roughness and has a plump and moisturized smoothness. In addition to being able to lead to smooth skin, it is possible to obtain a cosmetic having a smooth use feeling that is more stable with time (no aurora) than conventional products and has no stickiness. Moreover, the cosmetic containing the liposome for cosmetics of the present invention has an effect of improving skin firmness and an effect of tightening pores, has a high moisturizing property, and has a good feeling of use.

本発明の化粧料用リポソームは、下記の式[I]で表される環状ホスファチジン酸がリポソームの構成成分として配合されていることを特徴とする。   The liposome for cosmetics of the present invention is characterized in that cyclic phosphatidic acid represented by the following formula [I] is blended as a component of the liposome.

Figure 2008222643
Figure 2008222643

(式中、
Rは、炭素数10〜22のアシル基を示し、
Mは、水素原子、アルカリ金属原子、アルカリ土類金属原子、置換又は無置換のアンモニウム基を示す。)
(Where
R represents an acyl group having 10 to 22 carbon atoms;
M represents a hydrogen atom, an alkali metal atom, an alkaline earth metal atom, or a substituted or unsubstituted ammonium group. )

本発明の化粧料用リポソームは、式[I]の環状ホスファチジン酸が、リポソーム製造時の原料全体の0.000001〜5%配合されていることが好ましく、0.00001〜3%配合されていることがさらに好ましい。式[I]の環状ホスファチジン酸の配合割合が全体の5%を超えると、式[I]の環状ホスファチジン酸が直鎖型の界面活性剤としての性質を有するため、リポソームの構造を壊してしまう可能性がある。また、この配合割合が全体の0.000001%未満であると、式[I]の環状ホスファチジン酸が有する特性であるさらさらとした感触が、その他の成分の影響により弱まってしまう可能性がある。   In the cosmetic liposome of the present invention, the cyclic phosphatidic acid of the formula [I] is preferably blended in an amount of 0.000001 to 5% of the total raw material at the time of producing the liposome, and is blended in a range of 0.00001 to 3%. More preferably. When the blending ratio of the cyclic phosphatidic acid of the formula [I] exceeds 5% of the total, the cyclic phosphatidic acid of the formula [I] has a property as a linear surfactant, so that the structure of the liposome is broken. there is a possibility. Further, if the blending ratio is less than 0.000001% of the total, the smooth feel that is a characteristic of the cyclic phosphatidic acid of the formula [I] may be weakened due to the influence of other components.

式[I]におけるアシル基としては、炭素数10〜22の飽和アシル基、及び、炭素数10〜22で1〜6個の不飽和結合を有するアシル基が挙げられ、炭素数10〜22の飽和アシル基が好ましく、炭素数14〜18の飽和アシル基がさらに好ましい。酸化などの劣化が生じにくく、色やにおいなどの経時変化も起こりにくいため、飽和アシル基が好ましい。
炭素数10〜22の飽和アシル基としては、カプリン酸(C10:0)、ラウリン酸(C12:0)、ミリスチン酸(C14:0)、ペンタデカン酸(C15:0)、パルミチン酸(C16:0)、マルガリン酸(C17:0)、ステアリン酸(C18:0)、ノナデカン酸(C19:0)、アラキジン酸(C20:0)、ヘネイコサン酸(C21:0)、ベヘニン酸(C22:0)等に由来する残基が挙げられる。なかでも、取扱いのしやすさ、および活性の強さなどの点からミリスチン酸(C14:0)、ペンタデカン酸(C15:0)、パルミチン酸(C16:0)、ステアリン酸(C18:0)に由来する残基などの炭素数14〜18の飽和アシル基が好ましい。
炭素数10〜22で1〜6個の不飽和結合を有するアシル基としては、ミリストレイン酸(C14:1)、パルミトレイン酸(C16:1)、オレイン酸(C18:1)、エライジン酸(C18:1)、バクセン酸(C18:1)、リノール酸(C18:2)、リノレン酸(C18:3)、アラキドン酸(C20:4)、エイコサペンタエン酸(C20:5)、エルカ酸(C22:1)、ドコサヘキサエン酸(C22:6)等に由来する残基が挙げられる。なかでも、ミリストレイン酸(C14:1)、パルミトレイン酸(C16:1)、オレイン酸(C18:1)、エライジン酸(C18:1)、リノール酸(C18:2)、リノレン酸(C18:3)に由来する残基が好ましい。
Examples of the acyl group in the formula [I] include a saturated acyl group having 10 to 22 carbon atoms and an acyl group having 10 to 22 carbon atoms and 1 to 6 unsaturated bonds. A saturated acyl group is preferable, and a saturated acyl group having 14 to 18 carbon atoms is more preferable. Saturated acyl groups are preferred because deterioration such as oxidation is unlikely to occur and changes over time such as color and odor are unlikely to occur.
Examples of the saturated acyl group having 10 to 22 carbon atoms include capric acid (C10: 0), lauric acid (C12: 0), myristic acid (C14: 0), pentadecanoic acid (C15: 0), and palmitic acid (C16: 0). ), Margaric acid (C17: 0), stearic acid (C18: 0), nonadecanoic acid (C19: 0), arachidic acid (C20: 0), heneicosanoic acid (C21: 0), behenic acid (C22: 0), etc. The residue derived from is mentioned. Among these, myristic acid (C14: 0), pentadecanoic acid (C15: 0), palmitic acid (C16: 0), and stearic acid (C18: 0) are considered in terms of ease of handling and strength of activity. A saturated acyl group having 14 to 18 carbon atoms such as a residue derived therefrom is preferred.
Examples of the acyl group having 10 to 22 carbon atoms and 1 to 6 unsaturated bonds include myristoleic acid (C14: 1), palmitoleic acid (C16: 1), oleic acid (C18: 1), and elaidic acid (C18 1), vaccenic acid (C18: 1), linoleic acid (C18: 2), linolenic acid (C18: 3), arachidonic acid (C20: 4), eicosapentaenoic acid (C20: 5), erucic acid (C22: 1), residues derived from docosahexaenoic acid (C22: 6) and the like. Among them, myristoleic acid (C14: 1), palmitoleic acid (C16: 1), oleic acid (C18: 1), elaidic acid (C18: 1), linoleic acid (C18: 2), linolenic acid (C18: 3) ) Is preferred.

式[I]におけるアルカリ金属原子としては、ナトリウム、カリウム等が挙げられる。
式[I]におけるアルカリ土類金属原子としてはマグネシウム、カルシウム等が挙げられる。
式[I]におけるアンモニウム基とは、NHで表される原子団であり、置換基を有するものであっても無置換のものであってもよい。
上記アンモニウム基の置換基の例としては、トリエタノールアミン塩が挙げられる。
式[I]におけるMとしては、式[I]で表される環状ホスファチジン酸のリン酸エステル誘導体としての入手のし易さなどの点から、ナトリウム、カリウムが最も好ましい。
Examples of the alkali metal atom in the formula [I] include sodium and potassium.
Examples of the alkaline earth metal atom in the formula [I] include magnesium and calcium.
The ammonium group in the formula [I] is an atomic group represented by NH 4 and may have a substituent or may be unsubstituted.
Examples of the substituent of the ammonium group include triethanolamine salt.
M in the formula [I] is most preferably sodium or potassium from the viewpoint of easy availability as a phosphoric ester derivative of the cyclic phosphatidic acid represented by the formula [I].

本発明に用いられる式[I]の環状ホスファチジン酸は、公知の製造方法で合成することができる。例えば、−O−アシルグリセロールをリン酸化剤と反応させ、加水分解させる全合成で得ることができる(特開平6−2281691号公報参照)。また、特許第3195833号公報に記載のような酵素反応により得たものを使用することもできる。   The cyclic phosphatidic acid of the formula [I] used in the present invention can be synthesized by a known production method. For example, it can be obtained by total synthesis in which —O-acylglycerol is reacted with a phosphorylating agent and hydrolyzed (see JP-A-6-2281691). Moreover, what was obtained by the enzyme reaction as described in patent 3195833 can also be used.

具体的には、例えば、水素添加大豆リン脂質由来のリゾホスファチジルコリンと酵素ホスホリパーゼDを、酢酸緩衝液(pH5〜6程度)中で1〜20時間程度反応させることによって、水素添加大豆由来の式[I]の環状ホスファチジン酸を得ることができる。また、生成した式[I]の環状ホスファチジン酸は、常法に準じて、抽出、カラムクロマトグラフィー、薄層クロマトグラフィー(TLC)などにより精製することができる。   Specifically, for example, by reacting lysophosphatidylcholine derived from hydrogenated soybean phospholipid and enzyme phospholipase D in an acetic acid buffer (pH of about 5 to 6) for about 1 to 20 hours, a formula derived from hydrogenated soybean [ I] cyclic phosphatidic acid can be obtained. In addition, the produced cyclic phosphatidic acid of the formula [I] can be purified by extraction, column chromatography, thin layer chromatography (TLC) and the like according to a conventional method.

本発明における化粧料用リポソームが、リン脂質を含む場合、大豆リン脂質、卵黄リン脂質、水素添加大豆リン脂質、水素添加卵黄リン脂質などの天然由来のリン脂質や、その他ホスファチジルコリン、ホスファチジルエタノールアミン、ホスファチジルグリセロール、ホスファチジルイノシトール、ホスファチジルセリン、スフィンゴミエリンなどを用いることができる。天然由来のリン脂質の場合、なかでも、ホスファチジルコリン含量が60重量%以上である水素添加大豆リン脂質が好ましく、ホスファチジルコリン含量が80重量%以上である水素添加大豆リン脂質がさらに好ましい。   When the liposome for cosmetics in the present invention contains phospholipid, naturally-derived phospholipids such as soybean phospholipid, egg yolk phospholipid, hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid, phosphatidylcholine, phosphatidylethanolamine, Phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, sphingomyelin and the like can be used. In the case of naturally derived phospholipids, hydrogenated soybean phospholipids having a phosphatidylcholine content of 60% by weight or more are preferable, and hydrogenated soybean phospholipids having a phosphatidylcholine content of 80% by weight or more are more preferable.

上記水素添加大豆リン脂質は、例えば、水とヘキサンやアルコールなどとの2相分配により大豆リン脂質を抽出精製し、その後、水素添加をすることにより得ることができる。また、水素添加された大豆リン脂質を、アセトンやアルコールなどの溶媒を用いて晶析精製して得てもよいし、液体クロマトグラフィーなどにより分離精製して得てもよい。   The hydrogenated soybean phospholipid can be obtained, for example, by extracting and purifying soybean phospholipid by two-phase partitioning between water and hexane, alcohol, and the like, and then hydrogenating it. Further, the hydrogenated soybean phospholipid may be obtained by crystallization purification using a solvent such as acetone or alcohol, or may be obtained by separation and purification by liquid chromatography or the like.

本発明の化粧料用リポソームは、リポソームの構成成分としてリン脂質を配合することが好ましい。配合量としては、リポソーム製造時の原料全体の0.001〜20重量%配合するのが好ましく、0.005〜10重量%配合するのがより好ましく、0.01〜5重量%配合するのがさらに好ましい。リン脂質を0.001重量%以上含有させることでリポソーム特有の感触と保湿効果を得ることができ、また、20重量%含有させれば十分な保湿効果を保有することができるので、これを超えての配合はコスト面で不利になる。   The liposome for cosmetics of the present invention preferably contains a phospholipid as a component of the liposome. As a compounding quantity, it is preferable to mix | blend 0.001-20 weight% of the whole raw material at the time of liposome manufacture, It is more preferable to mix | blend 0.005-10 weight%, It is compounding 0.01-5 weight%. Further preferred. By adding 0.001% by weight or more of phospholipid, it is possible to obtain a touch and moisturizing effect peculiar to liposomes, and when it is contained by 20% by weight, a sufficient moisturizing effect can be retained. All blends are costly.

本発明の化粧料用リポソームは、膜の流動性を抑制し、経時安定性を高めることができるので、リポソームの構成成分としてステロール類を配合することが好ましい。ステロール類としては、例えば、コレステロール、フィトステロール、ジヒドロコレステロール、ステアリン酸コレステリル、オレイン酸コレステリル、ノナン酸コレステリル、ヒドロキシステアリン酸コレステリル、オレイン酸ジヒドロコレステリル等が挙げられ、なかでも、コレステロール、フィトステロール、オレイン酸コレステリル、ステアリン酸コレステリルが好ましい。本発明の化粧料用リポソームは、ステロール類をリン脂質に対して1〜50重量%の量で配合することがより好ましい。   Since the liposome for cosmetics of this invention can suppress the fluidity | liquidity of a film | membrane and can improve stability with time, it is preferable to mix | blend sterols as a structural component of a liposome. Examples of sterols include cholesterol, phytosterol, dihydrocholesterol, cholesteryl stearate, cholesteryl oleate, cholesteryl nonanoate, cholesteryl hydroxystearate, dihydrocholesteryl oleate, among others, cholesterol, phytosterol, cholesteryl oleate Cholesteryl stearate is preferred. The cosmetic liposome of the present invention more preferably contains sterols in an amount of 1 to 50% by weight based on the phospholipid.

本発明の化粧料用リポソームが、式[I]の環状ホスファチジン酸、リン脂質、ステロール類から構成されるとき、リン脂質とステロール類との比率は、重量比で5/5〜9.9/0.1であるのが好ましく、6/4〜9/1であるのがより好ましく、7/3〜8/2であるのがさらに好ましい。   When the cosmetic liposome of the present invention is composed of cyclic phosphatidic acid of formula [I], phospholipid, and sterols, the ratio of phospholipid to sterols is 5/5 to 9.9 / by weight. 0.1 is preferable, 6/4 to 9/1 is more preferable, and 7/3 to 8/2 is still more preferable.

本発明の化粧料用リポソームには、本発明が奏する効果を妨げない限り、これまでに特記した構成成分の他に、化粧料への配合が認可されているような成分、例えば、水性成分(例えば、水など)、アルコール(例えば、エタノール、グリセリンなど)、油剤、界面活性剤、水溶性高分子、動植物由来の天然エキス、各種栄養成分、保湿剤、細胞賦活剤、紫外線吸収剤、酸化防止剤、防腐剤、香料、無機塩、目的に応じた各種薬剤など、を配合してもよい。その製造方法は、化粧料を製造するのに通常用いられる方法を使用すればよく、特に限定されない。
上記特記した構成成分及びこれらの追加成分は、リポソームの内水相でも外水相でも、またその両側に存在してもよいし、リポソーム膜の一部となっていてもよい。
In the liposome for cosmetics of the present invention, in addition to the components specially mentioned so far, components that are approved for incorporation into cosmetics, for example, aqueous components (as long as the effects of the present invention are not hindered) For example, water, etc.), alcohol (eg, ethanol, glycerin, etc.), oil agent, surfactant, water-soluble polymer, natural extracts derived from animals and plants, various nutrients, moisturizer, cell activator, UV absorber, antioxidant You may mix | blend an agent, antiseptic | preservative, a fragrance | flavor, an inorganic salt, various chemicals according to the objective, etc. The production method is not particularly limited as long as a method usually used for producing cosmetics may be used.
The specially mentioned constituents and these additional components may be present in the inner aqueous phase or the outer aqueous phase of the liposome, on both sides thereof, or may be part of the liposome membrane.

本発明の化粧料用リポソームは、例えば、式[I]の環状ホスファチジン酸と、脂質(例えば、リン脂質)及びその他配合成分を、リポソームを作製するための公知の技術により混合し、超音波処理法、フレンチプレス法、逆相蒸発法、界面活性剤法、エクストルージョン法、カルシウム−EDTAキレート法、凍結融解法などの方法や、真空乳化機、高圧ホモミキサー、マイクロフルイダイザー、マントンゴーリンなどの乳化機で処理することにより、製造することができる。また、これらのリポソームをフィルターやゲルろ過などのサイジング操作を行うことにより、粒子径のそろったリポソームを選択的に得ることができ、それによりリポソームの安定性をさらに高めることもできる。   The cosmetic liposome of the present invention is prepared by, for example, mixing a cyclic phosphatidic acid of the formula [I] with a lipid (for example, phospholipid) and other compounding ingredients by a known technique for preparing a liposome, and subjecting it to ultrasonic treatment. Method, French press method, reverse phase evaporation method, surfactant method, extrusion method, calcium-EDTA chelate method, freeze-thaw method, vacuum emulsifier, high-pressure homomixer, microfluidizer, manton gorin, etc. It can manufacture by processing with an emulsifier. In addition, by performing sizing operations such as filtering and gel filtration on these liposomes, it is possible to selectively obtain liposomes having a uniform particle diameter, thereby further improving the stability of the liposomes.

リポソームの粒径は安定性や感触にも影響を与えるため、本発明の化粧料用リポソームは、粒径をそろえることが望ましい。リポソームの粒子径の表示方法には、重量平均粒子径と個数平均粒子径が一般に用いられるが、リポソームの保持容量の観点からは重量平均粒子径で表わすことが望ましい。本発明の化粧料用リポソームの重量平均粒子径は一般に20nm〜800nm、好ましくは50〜500nm、より好ましくは100nm〜400nmである。上記の所望の粒径を得るためには、予め決められたポアサイズを有するフィルターを通して大きい粒径のリポソームを濾過する押出濾過法などを使用すればよい。   Since the liposome particle size also affects the stability and feel, the cosmetic liposome of the present invention desirably has the same particle size. As a method for displaying the particle diameter of liposomes, a weight average particle diameter and a number average particle diameter are generally used. From the viewpoint of the retention capacity of liposomes, it is desirable to represent the weight average particle diameter. The weight average particle diameter of the liposome for cosmetics of the present invention is generally 20 nm to 800 nm, preferably 50 to 500 nm, more preferably 100 nm to 400 nm. In order to obtain the desired particle size, an extrusion filtration method or the like that filters liposomes having a large particle size through a filter having a predetermined pore size may be used.

本発明の化粧料用リポソームは、化粧水などの低粘性のものから、クリームなどの高粘性のものまで、化粧料の原料として広範に使用することができる。本発明の化粧料用リポソームは安定性が良好であるため、低粘性の化粧水に配合しても問題がない。   The liposome for cosmetics of the present invention can be widely used as a raw material for cosmetics from low viscosity such as lotion to high viscosity such as cream. Since the liposome for cosmetics of the present invention has good stability, there is no problem even if it is blended in a low viscosity lotion.

本発明の化粧料用リポソームは、化粧料の形態によっても異なるため一概に規定することはできないが、化粧料全体の0.001〜20重量%配合するのが好ましく、0.005〜10重量%配合するのがより好ましく、0.01〜5重量%配合するのがさらに好ましい。0.001重量%未満である場合、本発明の化粧料用リポソームが有する肌のなめらかさ改善や保湿性の効果が化粧料に反映されにくい。また、20重量%配合させればこれらの効果を十分に発揮することができるので、20重量%を超えての配合は費用対効果の面から不利である。
本発明の化粧料用リポソームは様々な種類の化粧料に含有させることができ、化粧料の形態は特に限定されない。
The liposome for cosmetics of the present invention cannot be defined unconditionally because it varies depending on the form of the cosmetic, but it is preferable to blend 0.001 to 20% by weight of the entire cosmetic, 0.005 to 10% by weight More preferably, it is more preferably 0.01 to 5% by weight. When the amount is less than 0.001% by weight, the effect of improving the smoothness of the skin and the moisturizing property of the liposome for cosmetics of the present invention is hardly reflected in the cosmetics. Further, if 20% by weight is incorporated, these effects can be sufficiently exerted, and therefore the blending exceeding 20% by weight is disadvantageous from the viewpoint of cost effectiveness.
The liposome for cosmetics of the present invention can be contained in various types of cosmetics, and the form of the cosmetics is not particularly limited.

本発明の化粧料用リポソームを含有する化粧料は、さらさらとした使用感であり、あれ肌を改善し、ふっくらとした潤いのあるなめらかな肌へと導くことができる。   The cosmetic containing the cosmetic liposome of the present invention has a smooth use feeling, can improve that skin, and can lead to a smooth, moist and smooth skin.

以下、実施例を記載して本発明を具体的に説明するが、本発明はこれらに限定されるものではない。なお、各実施例及び比較例におけるそれぞれの成分の配合量は、特に記載がない場合すべて重量%である。   EXAMPLES Hereinafter, although an Example is described and this invention is demonstrated concretely, this invention is not limited to these. In addition, unless otherwise indicated, the compounding quantity of each component in each Example and a comparative example is weight%.

合成例
リゾホスファチジルコリンの合成
水素添加大豆由来リン脂質(ホスファチジルコリン含量96%、脂肪酸組成:パルミチン酸11.5%、マルガリン酸0.2%、ステアリン酸87.8%、リノール酸0.3%、その他微量成分0.2%;比較例4においても使用)20gにクロロホルム300gを加え十分に溶解させた。pH8.5の1M Tris−HCl緩衝液120g、2M塩化カルシウム10mL、ホスホリパーゼA2(レシターゼ、ノボザイムズ社製)2gを添加し、50℃で加温した。24時間後にメタノール600gを添加し、激しく混合した。混合後、静置し下層を回収し溶媒を留去し、固体15gを得た。この固体15gを酢酸エチル200gに添加し、45℃で1時間撹拌した後、ろ過を行い、固体14gを得た。さらにこの操作を繰り返して行い、固体11g(水素添加大豆由来リゾホスファチジルコリン)を得た。
得られた水素添加大豆由来リゾホスファチジルコリンの脂肪酸組成:パルミチン酸19.3%、ステアリン酸80%、マルガリン酸0.2%、リノール酸0.3%、その他0.2%
Synthesis example
Synthesis of lysophosphatidylcholine Phospholipids derived from hydrogenated soybeans (phosphatidylcholine content 96%, fatty acid composition: palmitic acid 11.5%, margaric acid 0.2%, stearic acid 87.8%, linoleic acid 0.3%, other minor components 0.2%; also used in Comparative Example 4) 300 g of chloroform was added to 20 g and sufficiently dissolved. 120 g of 1M Tris-HCl buffer at pH 8.5, 10 mL of 2M calcium chloride and 2 g of phospholipase A2 (lecitase, manufactured by Novozymes) were added and heated at 50 ° C. After 24 hours, 600 g of methanol was added and mixed vigorously. After mixing, the mixture was allowed to stand to recover the lower layer, and the solvent was distilled off to obtain 15 g of a solid. 15 g of this solid was added to 200 g of ethyl acetate and stirred at 45 ° C. for 1 hour, followed by filtration to obtain 14 g of a solid. Further, this operation was repeated to obtain 11 g of solid (hydrogenated soybean-derived lysophosphatidylcholine).
Fatty acid composition of the obtained hydrogenated soybean-derived lysophosphatidylcholine: palmitic acid 19.3%, stearic acid 80%, margaric acid 0.2%, linoleic acid 0.3%, others 0.2%

環状ホスファチジン酸ナトリウムの合成
上記で得られた水素添加大豆由来リゾホスファチジルコリン(LPC)10gに水250gを加え十分に溶解させた。pH5.5の1M酢酸ナトリウム緩衝液100g、2M塩化ナトリウム10mL、ホスホリパーゼD(PL−D、名糖産業)100mgを添加し、55℃で加温した。18時間後に、10M水酸化ナトリウム水溶液でpH6.5まで中和した後、クロロホルム650gとメタノール700gを添加し、激しく混合した。さらにクロロホルム650gを加えて混合後、静置し下層を回収し溶媒を留去し、環状ホスファチジン酸ナトリウム8gを得た。この環状ホスファチジン酸ナトリウムを以下の実施例及び比較例において使用した。
得られた環状ホスファチジン酸ナトリウムの脂肪酸組成:パルミチン酸19.3%、ステアリン酸80%、マルガリン酸0.2%、リノール酸0.3%、その他0.2%
Synthesis of cyclic sodium phosphatidic acid 250 g of water was sufficiently dissolved in 10 g of hydrogenated soybean-derived lysophosphatidylcholine (LPC) obtained above. 100 g of 1M sodium acetate buffer solution at pH 5.5, 10 mL of 2M sodium chloride, and 100 mg of phospholipase D (PL-D, Meisei Sangyo) were added and heated at 55 ° C. After 18 hours, the solution was neutralized with 10M aqueous sodium hydroxide solution to pH 6.5, and then 650 g of chloroform and 700 g of methanol were added and mixed vigorously. Further, 650 g of chloroform was added and mixed, and then allowed to stand. The lower layer was recovered and the solvent was distilled off to obtain 8 g of cyclic sodium phosphatidate. This cyclic sodium phosphatidate was used in the following examples and comparative examples.
Fatty acid composition of the obtained cyclic sodium phosphatidate: 19.3% palmitic acid, 80% stearic acid, 0.2% margaric acid, 0.3% linoleic acid, other 0.2%

実施例1
表1に示す量の配合成分1〜7を混合し、60℃で加熱融解した後、成分8(精製水)を添加し、60℃で30分間撹拌を行った。得られた分散液に孔径0.4μmのポリカーボネートフィルターによるエクストルージョンを行い、実施例1のリポソーム液を得た。
Example 1
After mixing the components 1-7 of the quantity shown in Table 1 and heat-melting at 60 degreeC, the component 8 (purified water) was added and it stirred at 60 degreeC for 30 minutes. The obtained dispersion was subjected to extrusion using a polycarbonate filter having a pore size of 0.4 μm to obtain the liposome solution of Example 1.

実施例2〜4
表1に示す実施例2〜4のリポソーム液を実施例1と同様にして製造したが、エクストルージョンについては、実施例2及び3においては0.3μm、実施例4においては0.2μmの孔径のポリカーボネートフィルターを使用した。
Examples 2-4
The liposome solutions of Examples 2 to 4 shown in Table 1 were produced in the same manner as in Example 1. However, regarding the extrusion, the pore diameter was 0.3 μm in Examples 2 and 3, and 0.2 μm in Example 4. Polycarbonate filters were used.

実施例5及び6
表1に示す量の配合成分1〜7を混合し、60℃で加熱融解した後、成分8(精製水)を添加し、60℃で30分間ホモジナイズを行い、実施例5及び6のリポソーム液を得た。
Examples 5 and 6
After mixing the components 1-7 of the quantity shown in Table 1, and heat-melting at 60 degreeC, the component 8 (purified water) is added, homogenization is performed for 30 minutes at 60 degreeC, and the liposome liquid of Examples 5 and 6 Got.

比較例1
表2に示す量の配合成分1〜10を混合し、60℃で加熱融解した後、成分11(精製水)を添加し、60℃で10分間ホモジナイズを行い、比較例1の環状ホスファチジン酸水溶液を得た。
Comparative Example 1
After mixing the components 1 to 10 in the amounts shown in Table 2 and heating and melting at 60 ° C., component 11 (purified water) is added, homogenized at 60 ° C. for 10 minutes, and the cyclic phosphatidic acid aqueous solution of Comparative Example 1 Got.

比較例2及び3
表2に示す量の配合成分1〜10を混合し、60℃で加熱融解した後、成分11(精製水)を添加し、高圧乳化機により乳化し、比較例2及び3の環状ホスファチジン酸乳液を得た。
比較例4
表2に示す量の配合成分1〜10を混合し、60℃で加熱融解した後、成分11(精製水)を添加し、60℃で30分間撹拌を行った。得られた分散液に孔径0.4μmのポリカーボネートフィルターによるエクストルージョンを行い、比較例4のリポソーム液を得た。
Comparative Examples 2 and 3
After mixing the components 1 to 10 in the amounts shown in Table 2 and heating and melting at 60 ° C., component 11 (purified water) is added, emulsified with a high-pressure emulsifier, and the cyclic phosphatidic acid emulsions of Comparative Examples 2 and 3 Got.
Comparative Example 4
After mixing the components 1-10 of the quantity shown in Table 2 and heat-melting at 60 degreeC, the component 11 (purified water) was added and it stirred at 60 degreeC for 30 minutes. The obtained dispersion was subjected to extrusion using a polycarbonate filter having a pore size of 0.4 μm to obtain a liposome solution of Comparative Example 4.

実施例及び比較例で得られたサンプル液について以下の評価を行い、結果も表1及び2に併記した。なお、表1の成分1〜3はリポソームを構成する成分となる物質である。また、表2の成分5及び6はリポソームの構成成分として主要なものであり、脂質二分子膜を形成する。表2において、成分1〜6はリポソームの構成成分となりうる成分であるが、成分5及び6がなければ、成分1〜4は脂質二分子膜を形成しないため、比較例4以外はリポソーム形態をとっていない。   The following evaluations were performed on the sample solutions obtained in the examples and comparative examples, and the results are also shown in Tables 1 and 2. In addition, the components 1-3 of Table 1 are substances which become a component which comprises a liposome. In addition, components 5 and 6 in Table 2 are main components of the liposome, and form a lipid bilayer. In Table 2, components 1 to 6 are components that can be constituents of liposomes, but if components 5 and 6 are not present, components 1 to 4 do not form a lipid bilayer. Not taken.

〔安定性〕
実施例1〜6又は比較例1〜4のサンプル液を透明なガラスバイアルへ入れ密封し、遮光して40℃の恒温槽に静置した。40℃での保存における溶液のオーロラの有無について調べた。それぞれの評価は以下の基準に従って行った。
<基準A>
○:1カ月以上オーロラが認められない。
△:2週間までは、変化が認められないが、その後オーロラが見られた。
×:2週間でオーロラが認められた。
〔Stability〕
The sample solutions of Examples 1 to 6 or Comparative Examples 1 to 4 were placed in a transparent glass vial, sealed, and left in a constant temperature bath at 40 ° C. with light shielding. The presence or absence of aurora in the solution during storage at 40 ° C. was examined. Each evaluation was performed according to the following criteria.
<Criteria A>
○: Aurora is not recognized for more than 1 month.
Δ: No change was observed until 2 weeks, but aurora was observed thereafter.
X: Aurora was recognized in 2 weeks.

〔使用感の評価〕
実施例1〜6又は比較例1〜4のサンプル液を皮膚に塗布した際の使用感(べたつき感のなさ、しっとり感)について、女性10名により下記の5段階にて評価し、その平均点を基準Bに従い判定した。◎又は○を効果があると判定した。
<評価>
5点:非常に良好
4点:良好
3点:普通
2点:不良
1点:非常に不良
<基準B>
◎:平均点4.5点以上
○:平均点3.5点以上4.5点未満
△:平均点2.5点以上3.5点未満
×:平均点2.5点未満
[Evaluation of feeling of use]
About the feeling of use (no stickiness, moist feeling) when the sample liquids of Examples 1 to 6 or Comparative Examples 1 to 4 were applied to the skin, the average score was evaluated by 10 women. Was determined according to criteria B. ◎ or ○ was determined to be effective.
<Evaluation>
5 points: very good 4 points: good 3 points: normal 2 points: defective 1 point: very bad <reference B>
◎: Average point 4.5 points or more ○: Average point 3.5 points or more and less than 4.5 points △: Average point 2.5 points or more and less than 3.5 points ×: Average point less than 2.5 points

〔効果感〕
荒れ肌、乾燥を気にしている女性(25〜55才)5名ずつに1日2回(朝、夕)、左右の頬に実施例1と比較例1、実施例2と比較例1、実施例3と比較例2、実施例4と比較例2、実施例5と比較例3、実施例6と比較例4の組み合わせでそれぞれを片頬ずつ塗布し、左右の肌の改善効果について評価した。塗布後1ヵ月後の肌の状態の「肌のなめらかさ」、「肌のハリ」について改善効果を下記評価基準により評価し、その平均点を基準Cに従い判定した。◎又は○を効果があると判定した。
<評価>
3点:非常に効果が感じられた
2点:効果が感じられた
1点:どちらともいえない
0点:効果を感じられなかった
<基準C>
◎:平均点2.5点以上
○:平均点1.5点以上2.5点未満
△:平均点0.5点以上1.5点未満
×:平均点0.5点未満
[Effect]
Example 1 and Comparative Example 1, Example 2 and Comparative Example 1 on the left and right cheeks twice a day (morning and evening) for five women (25 to 55 years old) who care about rough skin and dryness Example 3 and Comparative Example 2, Example 4 and Comparative Example 2, Example 5 and Comparative Example 3, Example 6 and Comparative Example 4 were each applied in one cheek, and the improvement effect on the left and right skin was evaluated. . The improvement effect was evaluated according to the following evaluation criteria for “smoothness of skin” and “skinness” of the skin state one month after application, and the average score was determined according to criteria C. ◎ or ○ was determined to be effective.
<Evaluation>
3 points: 2 points where the effect was felt 2 points: 1 point where the effect was felt: 0 points which cannot be said to be 0: No effect was felt <Criteria C>
◎: Average point 2.5 points or more ○: Average point 1.5 points or more and less than 2.5 points △: Average point 0.5 points or more and less than 1.5 points ×: Average point less than 0.5 points

Figure 2008222643
Figure 2008222643

Figure 2008222643
Figure 2008222643

実施例1〜6のリポソーム液は、安定性、使用感、効果感すべての性能を満足するものであった。
比較例1の水溶液は、調製後放冷した時点で、オーロラが生じた。また、比較例2及び3の乳液並びに比較例4のリポソーム液は、実施例のリポソーム液に比べ、使用感及び/又は効果感が劣っていた。
The liposome solutions of Examples 1 to 6 satisfied all the performances of stability, feeling of use and effect.
When the aqueous solution of Comparative Example 1 was allowed to cool after preparation, aurora was produced. In addition, the emulsions of Comparative Examples 2 and 3 and the liposome solution of Comparative Example 4 were inferior in usability and / or effect compared to the liposome solution of Examples.

〔肌のハリ及び毛穴の引き締め効果の比較〕
毛穴の開きを気にしている女性5名に対し、実施例又は比較例のサンプル液の1日2回(朝、夕)の顔全体への塗布を、2ヵ月間行った。
被験者5名の2ヵ月後の肌状態を、肌の写真及びマイクロスコープ画像を3名の評価者が肉眼で観察することにより評価した。肌のハリについては、肌の写真を使用して、頬丘の位置が高くなった場合の改善効果を下記評価基準により評価し、さらにその平均点を求め表3に示した。毛穴の引き締めについては、マイクロスコープ画像を使用して、毛穴の形状、凹凸、表面のなめらかさに着目し、連用前と比較して、その改善効果を下記評価基準により評価し、その平均点を求め表3に示した。
<評価>
5点:非常に効果が感じられた
3点:効果が感じられた
1点:どちらともいえない
0点:効果を感じられなかった
[Comparison of skin firmness and pore tightening effect]
For five women who care about the opening of pores, the sample solution of Example or Comparative Example was applied to the entire face twice a day (morning and evening) for 2 months.
The skin condition after 2 months of 5 subjects was evaluated by observing a photograph of the skin and a microscope image with the naked eye by 3 evaluators. As for skin firmness, a photograph of the skin was used to evaluate the improvement effect when the position of the cheek cone increased, and the average score was obtained and shown in Table 3. Regarding tightening of pores, using a microscope image, paying attention to the shape of the pores, unevenness, and smoothness of the surface, compared with before continuous use, the improvement effect was evaluated according to the following evaluation criteria, and the average score was calculated. The results are shown in Table 3.
<Evaluation>
5 points: 3 points where the effect was felt very much: 1 point where the effect was felt: 0 points that cannot be said to be 0: No effect was felt

Figure 2008222643
Figure 2008222643

実施例のリポソーム液が、肌のハリ及び毛穴の引き締めの点でも優れた改善効果を有することが分かった。   It was found that the liposome solutions of the examples had an excellent improvement effect in terms of skin firmness and pore tightening.

実施例7〜10、比較例5〜8
上記実施例又は比較例のサンプル液を用いて、表4に示す化粧水(実施例7及び8、比較例5及び6)及び表5に示すクリーム(実施例9及び10、比較例7及び8)を作製した。
〔化粧水の製造法〕
1) 表4に示す成分8(精製水)に成分1、2及び6を室温にて溶解した。
2) 1)の混合物に、成分3〜5及び7を混合し可溶化した。
Examples 7-10, Comparative Examples 5-8
Using the sample liquids of the above Examples or Comparative Examples, the lotions shown in Table 4 (Examples 7 and 8, Comparative Examples 5 and 6) and the creams shown in Table 5 (Examples 9 and 10, Comparative Examples 7 and 8) ) Was produced.
[Manufacturing method of lotion]
1) Components 1, 2 and 6 were dissolved in component 8 (purified water) shown in Table 4 at room temperature.
2) Components 3 to 5 and 7 were mixed and solubilized in the mixture of 1).

Figure 2008222643
Figure 2008222643

〔クリームの製造法〕
1)表5に示す成分1〜8を80℃に加温し、よく混練りした。
2)成分9〜19も80℃に加温し、よく混練りした。
3) 1)と2)を混合分散させ、室温まで冷却してクリームを得た。
[Production method of cream]
1) Components 1 to 8 shown in Table 5 were heated to 80 ° C. and kneaded well.
2) Components 9 to 19 were also heated to 80 ° C. and kneaded well.
3) 1) and 2) were mixed and dispersed, and cooled to room temperature to obtain a cream.

Figure 2008222643
Figure 2008222643

上記化粧水及びクリームについて、使用感及び肌の状態の改善効果をそれぞれ評価した。結果をそれぞれ表6及び7に示す。   About the said skin lotion and cream, the feeling of use and the improvement effect of the skin state were evaluated, respectively. The results are shown in Tables 6 and 7, respectively.

〔使用感の評価〕
実施例7〜10、比較例5〜8の化粧料を皮膚に塗布した際の使用感(べたつき感のなさ・肌のなめらかさ)について、パネル10名により下記の5段階にて評価し、その平均点を基準Dに従い判定した。◎又は○を効果があると判定した。
<評価>
5点:非常に良好
4点:良好
3点:普通
2点:不良
1点:非常に不良
[Evaluation of feeling of use]
The feeling of use (no stickiness / smoothness of skin) when the cosmetics of Examples 7 to 10 and Comparative Examples 5 to 8 were applied to the skin was evaluated by the 10 panelists in the following 5 levels. Average points were determined according to criteria D. ◎ or ○ was determined to be effective.
<Evaluation>
5 points: very good 4 points: good 3 points: normal 2 points: bad 1 point: very bad

〔肌の状態の改善効果感〕
荒れ肌及び乾燥を気にしている女性(25〜55才)5名ずつに1日2回(朝、夕)、左右の頬に実施例7と比較例4、実施例8と比較例5、実施例9と比較例6といった組み合わせでそれぞれを片頬ずつ塗布し、左右の肌の改善効果について評価した。塗布後1ヵ月後の「肌のなめらかさ」及び「肌のハリ」の点での改善効果を下記評価基準により評価し、その平均点を基準Dに従い判定した。◎又は○を効果があると判定した。
<評価>
3点:非常に効果が感じられた
2点:効果が感じられた
1点:どちらともいえない
0点:効果を感じられなかった
<基準D>
◎:平均点2.5点以上
○:平均点1.5点以上2.5点未満
△:平均点0.5点以上1.5点未満
×:平均点0.5点未満
[Improvement effect on skin condition]
Example 7 and Comparative Example 4, Example 8 and Comparative Example 5 on the left and right cheeks twice a day (morning and evening) for five women (25 to 55 years old) who care about rough skin and dryness Each combination of Example 9 and Comparative Example 6 was applied on one cheek, and the left and right skin improvement effects were evaluated. The improvement effect in terms of “smoothness of skin” and “skin elasticity” one month after application was evaluated according to the following evaluation criteria, and the average score was determined according to criteria D. ◎ or ○ was determined to be effective.
<Evaluation>
3 points: 2 points where the effect was felt 2 points: 1 point where the effect was felt: 0 points that cannot be said to be 0: No effect was felt <Criteria D>
◎: Average point 2.5 points or more ○: Average point 1.5 points or more and less than 2.5 points △: Average point 0.5 points or more and less than 1.5 points ×: Average point less than 0.5 points

Figure 2008222643
Figure 2008222643

実施例のサンプル液を使用して作製した化粧水は使用感及び効果感すべての性能を満足するものであった。
一方、比較例のサンプル液を使用して作製した化粧水は使用感及び/又は肌への効果感が劣っていた。
The skin lotion produced using the sample liquid of the example satisfied all the feelings of use and effects.
On the other hand, the lotion produced using the sample liquid of the comparative example was inferior in the feeling of use and / or the effect on the skin.

Figure 2008222643
Figure 2008222643

実施例のサンプル液を使用して作製したクリームは使用感及び効果感すべての性能を満足するものであった。
比較例のサンプル液を使用して作製したクリームはべたつきが強く感じられ、また肌への効果感も劣っていた。
The cream produced using the sample solution of the example satisfied all the feelings of use and effects.
The cream produced using the sample solution of the comparative example felt strongly sticky and had a poor effect on the skin.

Claims (4)

以下の式[I]で表される環状ホスファチジン酸がリポソームの構成成分として配合されていることを特徴とする化粧料用リポソーム:
Figure 2008222643

(式中、
Rは、炭素数10〜22のアシル基を示し、
Mは、水素原子、アルカリ金属原子、アルカリ土類金属原子、置換又は無置換のアンモニウム基を示す。)。
A liposome for cosmetics characterized in that a cyclic phosphatidic acid represented by the following formula [I] is blended as a component of the liposome:
Figure 2008222643

(Where
R represents an acyl group having 10 to 22 carbon atoms;
M represents a hydrogen atom, an alkali metal atom, an alkaline earth metal atom, or a substituted or unsubstituted ammonium group. ).
さらに、リン脂質がリポソームの構成成分として配合されていることを特徴とする、請求項1に記載の化粧料用リポソーム。   Furthermore, the lipolipid is mix | blended as a structural component of a liposome, The liposome for cosmetics of Claim 1 characterized by the above-mentioned. さらに、ステロール類がリポソームの構成成分として配合されていることを特徴とする、請求項1又は2に記載の化粧料用リポソーム。   Furthermore, sterols are mix | blended as a structural component of a liposome, The liposome for cosmetics of Claim 1 or 2 characterized by the above-mentioned. 請求項1〜3のいずれか1項に記載の化粧料用リポソームを含有する化粧料。   Cosmetics containing the liposome for cosmetics of any one of Claims 1-3.
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JP2013203667A (en) * 2012-03-27 2013-10-07 Nof Corp Matrix metalloprotease-2 inhibitor and skin care preparation for external use containing the same
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