JPH08231370A - Skin cosmetic - Google Patents
Skin cosmeticInfo
- Publication number
- JPH08231370A JPH08231370A JP7062025A JP6202595A JPH08231370A JP H08231370 A JPH08231370 A JP H08231370A JP 7062025 A JP7062025 A JP 7062025A JP 6202595 A JP6202595 A JP 6202595A JP H08231370 A JPH08231370 A JP H08231370A
- Authority
- JP
- Japan
- Prior art keywords
- collagen synthesis
- placenta
- acid
- alcohol
- skin
- 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
Landscapes
- Cosmetics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は胎盤由来の成分を含有す
ることを特徴とするコラーゲン合成促進剤，その製造法
及びそれを含有することを特徴とする皮膚化粧料（医薬
部外品たる薬用化粧品を含む。以下同じ）に関する。FIELD OF THE INVENTION The present invention relates to a collagen synthesis promoter characterized by containing a placenta-derived component, a method for producing the same, and a skin cosmetic (containing quasi-drug medicinal product) characterized by containing the same. Including cosmetics. The same shall apply hereinafter).
【０００２】[0002]
【従来の技術】老齢化社会を迎えつつあるわが国におい
て、老化（エージング）に対する医学的関心が高まるな
か、皮膚科領域においても皮膚の老化メカニズム等に関
する研究が進められ、特に細胞賦活剤の投与による老化
制御に内外の注目が集まっている。従来、いくつかの動
植物及び菌類の抽出物に組織賦活能が認められ、医薬品
や化粧品に用いられてきた。しかしこれらのものの中
で、細胞レベルにおいて生理活性を有する物質として評
価されたものは少なく、例えば、組織切片に対するこれ
らの抽出物の添加による酸素の消費量の増加をワールブ
ルグ検圧計等を用いて測定する方法、また、ＡＴＰ等の
酸化的リン酸化を触媒するような酵素を用いた定量法が
試みられている。しかしながら、これらの手段では、例
えば、組織切片を用いた酸素消費量試験法によれば、水
も賦活能を有し、極端なことを言えば炭素や窒素源を持
った多くのものは適量の濃度にあって酸素の消費量の増
加を示す。少なくとも栄養剤としての評価にはこれらの
手段は有効であるが、細胞レベルで皮膚の機能を捉え検
体の評価を行うとき、これらの手段により細胞賦活能を
捉えることは無理な点が多かった。2. Description of the Related Art In Japan, which is facing an aging society, with increasing medical interest in aging, research on skin aging mechanism has been promoted in the field of dermatology. Aging control is attracting a lot of attention both inside and outside. Conventionally, some plant and animal extracts and fungal extracts have been found to have a tissue-activating ability, and have been used in pharmaceuticals and cosmetics. However, among these, few have been evaluated as substances having physiological activity at the cellular level, and for example, the increase in oxygen consumption due to the addition of these extracts to tissue sections was measured using a Warburg pressure gauge. In addition, a quantitative method using an enzyme that catalyzes oxidative phosphorylation of ATP and the like has been attempted. However, in these means, for example, according to the oxygen consumption test method using a tissue section, water also has an activating ability, and in extreme cases, many having a carbon or nitrogen source have an appropriate amount. It shows an increase in oxygen consumption depending on the concentration. At least, these means are effective for evaluation as a nutritional supplement, but when assessing the function of the skin at the cell level and evaluating the sample, it is often impossible to determine the cell activation ability by these means.
【０００３】皮膚は、組織化学的に大別すると、表皮，
真皮，皮下組織に分けられるが、特に真皮は皮膚の支持
組織として、皮膚の恒常性維持のために重要な役割を果
たしている。真皮の主な構成細胞は線維芽細胞であり、
コラーゲン等の蛋白質やヒアルロン酸などのグリコサミ
ノグリカンを産生し、これらの結合組織の中で構築構造
を形成している。コラーゲンはすべての多細胞動物にみ
られる特有な繊維蛋白質であり、皮膚真皮組織に存在す
る主要蛋白質である。コラーゲン分子は堅固な三本鎖ら
せん構造をした高分子化合物であり、長いコラーゲン分
子は皮膚真皮組織を強固にしてその形態を保ち、皮膚に
弾力性を与えていることから、生理的に皮膚の弾力性も
この物質にかかる機能と密接に結び付いていると考えら
れる。近年、老化に関する様々な研究が行われるように
なり、特に、コラーゲンが皮膚の機能に重要な役割をも
つことが解明されてきた。従来より、コラーゲンの皮膚
保湿効果などの優れた機能から、コラーゲンが種々の化
粧品に配合されているが、これら化粧品はコラーゲンを
皮膚表面に塗布するだけのものであり、コラーゲンは高
分子であるため表皮のバリアーに阻まれ吸収されないた
め、皮膚表面上にとどまり、その吸水性に起因する保湿
作用を示すのみである。従って、洗い落とせば効果が消
え、本質から皮膚機能を改善するものではなかった。The skin is roughly classified into histochemical epidermis,
The dermis is divided into the dermis and the subcutaneous tissue. Particularly, the dermis plays an important role in maintaining the homeostasis of the skin as a supporting tissue of the skin. The main constituent cells of the dermis are fibroblasts,
It produces proteins such as collagen and glycosaminoglycans such as hyaluronic acid, and forms a structured structure in these connective tissues. Collagen is a unique fibrous protein found in all multicellular animals and is a major protein present in cutaneous dermal tissue. Collagen molecules are high-molecular compounds with a solid triple-stranded helix structure, and long collagen molecules strengthen the dermal tissue of the dermis and maintain its shape, giving it elasticity to the skin, and thus physiologically Elasticity is also thought to be closely linked to the function of this substance. In recent years, various studies on aging have been conducted, and in particular, it has been clarified that collagen plays an important role in skin function. From the past, collagen has been blended in various cosmetics because of its excellent functions such as skin moisturizing effect, but these cosmetics only apply collagen to the skin surface, and collagen is a high molecule. Since it is not absorbed by the barrier of the epidermis and is not absorbed, it stays on the surface of the skin and only exhibits a moisturizing action due to its water absorption. Therefore, the effect disappears when washed off, and the skin function is not essentially improved.
【０００４】[0004]
【発明が解決しようとする問題点】皮膚機能に重要な役
割持つコラーゲンは、老化に伴い減少することが報告さ
れている。Shuster らは、ヒト正常皮膚中におけるコラ
ーゲン量を測定した結果、皮膚コラーゲン量は２０歳か
ら８０歳までの間に６５％減少し、真皮の厚さは薄くな
ることを示した（Brith Journal of Dermatology, 93,
639, 1975）。一方、Legrand らによると、コラーゲン
の代謝回転率も加齢により低下し、生体内に長時間存在
するため、コラーゲン繊維中に無秩序な架橋やメイラー
ド反応が進行し、非可溶性コラーゲンが増加し細胞外マ
トリックスの硬化の原因となる（Pathological Biolog
y, 17, 991, 1969）。これらの研究結果より、皮膚線維
芽細胞のコラーゲン合成を促進することができれば、真
皮のコラーゲン含量が増加し真皮の厚さを増し、それに
伴って代謝回転も活性化され、可溶性コラーゲンが増加
することにより皮膚に柔軟性，伸展性を与え、その結
果、皺に代表される老化皮膚の形態的変化を抑制できる
可能性がある。即ち、本発明は真皮の線維芽細胞のコラ
ーゲン合成を促進し、老化制御機能を有する胎盤由来の
コラーゲン合成促進剤及びその製造法及びそれを含有す
る新規皮膚化粧料を提供することを目的とする。[Problems to be Solved by the Invention] It has been reported that collagen, which plays an important role in skin function, decreases with aging. As a result of measuring the amount of collagen in normal human skin, Shuster et al. Showed that the amount of skin collagen was reduced by 65% between the ages of 20 and 80, and the thickness of the dermis was reduced (Brith Journal of Dermatology). , 93,
639, 1975). On the other hand, according to Legrand et al., The turnover rate of collagen also decreases with aging and stays in the body for a long time, which leads to disordered cross-linking and Maillard reaction in the collagen fiber, resulting in increased insoluble collagen and extracellular extracellular matrix. Causes matrix hardening (Pathological Biolog
y, 17, 991, 1969). From the results of these studies, if it is possible to promote the collagen synthesis of skin fibroblasts, the collagen content of the dermis increases, the dermis thickness increases, the turnover is also activated, and the soluble collagen increases. This may give the skin flexibility and extensibility, and as a result, it may be possible to suppress the morphological changes of aged skin represented by wrinkles. That is, an object of the present invention is to provide a placenta-derived collagen synthesis promoter having a function of controlling senescence, which promotes collagen synthesis of dermal fibroblasts, a method for producing the same, and a novel skin cosmetic containing the same. .
【０００５】[0005]
【問題を解決するための手段】本発明者らは、まず細胞
レベルで検体の評価を行うため、Peterkofsky らの方法
（Arch. Biochem. Biophys., 152, 318 ，1972）に準
じ、培養線維芽細胞を用いたコラーゲン合成能を試験し
た。即ち、本試験法は、細胞培養系に検体を添加後3Ｈ
ラベルしたプロリンを取り込ませることにより、細胞の
コラーゲン合成量を定量するものである。本発明者ら
は、動植物及び菌類より任意に選んだ種々の物質につい
て、そのコラーゲン合成促進作用を上述の試験法にてス
クリーニングした結果、胎盤の分画成分に高いコラーゲ
ン合成促進活性を認めるに至った。即ち、胎盤のコラー
ゲン合成促進作用成分は、胎盤の酸・アルコール可溶画
分に移行することが明らかとなり、コラーゲン合成促進
作用成分を豊富に含有する本発明のコラーゲン合成促進
剤を完成するにいたった。更に、本発明者らは本発明の
コラーゲン合成促進剤を配合した皮膚化粧品を調製し皮
膚に塗布したところ、皮膚機能を亢進し肌の皺を防止
し、きめ細かな、かつしっとりした皮膚にすることを発
見し、更にその高い安全性を確認したため、本発明の皮
膚化粧料を完成するにいたった。なお本発明のコラーゲ
ン合成促進剤を配合した皮膚化粧料は真皮線維芽細胞の
コラーゲン合成を促進することによりその効果を現すも
のと考えられた。[Means for Solving the Problem] In order to evaluate the sample at the cell level, the present inventors have followed the method of Peterkofsky et al. (Arch. Biochem. Biophys., 152, 318, 1972) for culturing fibroblasts. Collagen synthesis ability using cells was tested. That is, this test method uses 3 H after adding the sample to the cell culture system.
By incorporating labeled proline, the amount of collagen synthesis of cells is quantified. The present inventors screened various substances arbitrarily selected from animals and plants and fungi for their collagen synthesis promoting action by the above-mentioned test method, and as a result, they found that the fractional components of the placenta had high collagen synthesis promoting activity. It was That is, it became clear that the placental collagen synthesis-promoting component is transferred to the placenta acid / alcohol-soluble fraction, and thus the collagen synthesis-promoting agent of the present invention containing abundant collagen synthesis-promoting component was completed. It was Furthermore, when the present inventors prepared a skin cosmetic containing the collagen synthesis promoter of the present invention and applied it to the skin, the skin function was enhanced to prevent wrinkles on the skin, and to make the skin delicate and moist. Was found and its high safety was confirmed, so that the skin cosmetic of the present invention was completed. The skin cosmetic containing the collagen synthesis promoter of the present invention was considered to exhibit its effect by promoting collagen synthesis of dermal fibroblasts.
【０００６】一方、従来よりコラーゲン合成促進作用を
有する物質として細胞成長因子ＴＧＦ（発癌増殖因子）
の一つであるＴＧＦ−βがWrana らにより報告されてい
る（Eur. J. Biochem., 159, 69-76, 1986）。これは、
分子量23,000〜25,000のペプチドであり（Biochemistr
y, 22, 5692-5698, 1983 、J. Biol. Chem., 259, 9756
-9761, 1984) 、ＴＧＦ−αとともに多くの腫瘍細胞で
産生される主な増殖因子である。ＴＧＦ（昔はＳＧＦと
も呼ばれいた（組織培養，８，39-45 ，1982））には、
いくつかの分子種が報告されているが、現段階でのＴＧ
Ｆの普遍的な性質は、正常細胞を軟寒天培地中でコロニ
ーを形成させうることと考えられている。Todaroらによ
るとMolony肉腫ウイルス（ＭＳＶ）で形質転換したマウ
ス３Ｔ３細胞が、その培養無血清培地中に正常細胞を悪
性細胞様に転換させる作用をもつ因子（ＳＧＦ）を産生
していることを報告している（Federation Proc., 41,
2996-3003, 1982）。このようなＴＧＦ活性を有するＴ
ＧＦ−βをもって、コラーゲン合成促進作用を期待しヒ
トに塗布することは、非常に危険であるといわざるを得
ず、化粧品に配合する場合においても、安全性において
好ましくなく、イメージ的にもマイナスである。本発明
者らはこのような点に鑑み、安全性が高く、かつ安定性
の良いコラーゲン合成促進剤の研究を行い、本発明を完
成した。また、これまで胎盤抽出液のコラーゲン合成促
進作用、または皮膚化粧料へ配合した場合の本作用に起
因する有用性に関し全く研究されておらず、本発明者ら
により初めて明らかにされたものである。On the other hand, cell growth factor TGF (carcinogenic growth factor) has been conventionally used as a substance having a collagen synthesis promoting action.
One of them, TGF-β, has been reported by Wrana et al. (Eur. J. Biochem., 159, 69-76, 1986). this is,
It is a peptide with a molecular weight of 23,000 to 25,000 (Biochemistr
y, 22, 5692-5698, 1983, J. Biol. Chem., 259, 9756.
-9761, 1984), together with TGF-α, is a major growth factor produced in many tumor cells. TGF (formerly known as SGF (tissue culture, 8, 39-45, 1982))
Although several molecular species have been reported, TG at this stage
The universal nature of F is believed to allow normal cells to colonize in soft agar. According to Todaro et al., Molony sarcoma virus (MSV) -transformed mouse 3T3 cells produce a factor (SGF), which has the effect of converting normal cells into malignant cells, in its serum-free medium. (Federation Proc., 41,
2996-3003, 1982). T having such TGF activity
It cannot be said that applying GF-β to humans in the expectation of a collagen synthesis promoting action is extremely dangerous, and it is unfavorable in terms of safety when incorporated into cosmetics, and it is also negative in terms of image. Is. In view of these points, the present inventors have conducted research on a collagen synthesis promoter having high safety and good stability, and completed the present invention. In addition, until now, no research has been conducted on the collagen synthesis promoting action of the placenta extract, or the usefulness resulting from this action when incorporated into a skin cosmetic, and it was first revealed by the present inventors. .
【０００７】また本発明のコラーゲン合成促進剤及び皮
膚化粧料は組織損傷時、創傷部に遊走した線維芽細胞に
より形成される肉芽組織に作用し、そのコラーゲン合成
を促進し真皮の再構築を促すことにより創傷治癒効果を
有することも期待される。即ち、本発明は真皮の線維芽
細胞のコラーゲン合成を促進し、老化制御機能を有する
胎盤由来のコラーゲン合成促進剤及びその製造法及びそ
れを含有する新規皮膚化粧料を提供することを目的とす
る。以下、本発明につき詳述する。本発明に至る過程で
用いた先述のコラーゲン合成促進能試験法は本発明のコ
ラーゲン合成促進作用を制限するものではなく、細胞レ
ベルでコラーゲン合成能を検出し得る他の試験法、例え
ば、放射性同位元素で標識したヒドロキシプロリンを用
いる免疫学的方法，コラーゲンの抗体を用いる免疫学的
方法，コラーゲンのｍＲＮＡを核酸プローブとハイブリ
ダイズさせ検出する方法等をin vitro，in vivo ，in s
itu で利用することができる。Further, the collagen synthesis promoter and the skin cosmetic of the present invention act on the granulation tissue formed by fibroblasts that have migrated to the wound at the time of tissue damage, promote the collagen synthesis and promote the reconstruction of the dermis. Therefore, it is also expected to have a wound healing effect. That is, an object of the present invention is to provide a placenta-derived collagen synthesis promoter having a function of controlling senescence, which promotes collagen synthesis of dermal fibroblasts, a method for producing the same, and a novel skin cosmetic containing the same. . Hereinafter, the present invention will be described in detail. The above-mentioned collagen synthesis promoting ability test method used in the process leading to the present invention does not limit the collagen synthesis promoting action of the present invention, and other test methods capable of detecting collagen synthesis ability at the cellular level, for example, radioisotope Immunological methods using hydroxyproline labeled with elements, immunological methods using collagen antibodies, methods for detecting collagen mRNA by hybridizing it with a nucleic acid probe, etc. in vitro, in vivo, in s
It can be used in situ.
【０００８】本発明に使用する胎盤は、ヒト，ウシ，ヤ
ギ，ヒツジ，ブタ等の哺乳動物から採取された新鮮な胎
盤、あるいはその胎盤をミンチ状にしたものが用いられ
る。なお、懐胎中のウシ，ヤギ，ヒツジ，ブタの胎盤の
分画成分には、コラーゲン合成促進作用が特に高いこと
が明らかとなり、生理学上重要な意味を持つものと考え
られる。本発明のコラーゲン合成促進剤の調製に当たっ
ては、胎盤に水を加えた後、酸及びアルコールを別々に
加えるかまたは酸・アルコール混液として加え最終ｐＨ
１〜６に調整するか、又はアルコール濃度１０〜５０％
（Ｖ／Ｖ）に調整し、好ましくはｐＨ２〜５．５に調整
するか、又はアルコール濃度２０〜４０％（Ｖ／Ｖ）に
調整する。更に好ましくはｐＨ１〜６かつアルコール濃
度１０〜５０％（Ｖ／Ｖ）に調整し、もっとも好ましく
はｐＨ２〜５．５かつアルコール濃度２０〜４０％（Ｖ
／Ｖ）に調製する。ｐＨ１未満またはアルコール濃度５
０％（Ｖ／Ｖ）以上ではコラーゲン合成促進作用の作用
成分が失活あるいは不溶化を起こす。またｐＨ６以上ま
たはアルコール濃度１０％（Ｖ／Ｖ）以下、あるいは酸
もしくはアルコールのどちらか一方だけの処理では不必
要な画分を除去し得ず、分画効率は著しく低下する。The placenta used in the present invention is a fresh placenta collected from mammals such as humans, cows, goats, sheep and pigs, or a minced placenta. In addition, it was revealed that the fractional components of the placenta of bovine, goat, ovine, and porcine pregnant women have a particularly high collagen synthesis promoting action, which is considered to have important physiological significance. In the preparation of the collagen synthesis promoter of the present invention, water is added to the placenta, and then acid and alcohol are added separately or as an acid / alcohol mixture to give a final pH.
Adjust to 1-6 or alcohol concentration 10-50%
(V / V), preferably pH 2 to 5.5 or alcohol concentration 20 to 40% (V / V). More preferably, the pH is adjusted to 1 to 6 and the alcohol concentration is 10 to 50% (V / V), and most preferably, the pH is 2 to 5.5 and the alcohol concentration is 20 to 40% (V).
/ V). pH less than 1 or alcohol concentration 5
At 0% (V / V) or more, the active ingredient for promoting collagen synthesis is inactivated or insolubilized. Further, unnecessary fractions cannot be removed by treatment with a pH of 6 or more or an alcohol concentration of 10% (V / V) or less, or treatment with either acid or alcohol, and the fractionation efficiency is markedly reduced.
【０００９】なお、使用するアルコールはメタノール，
エタノール，イソプロパノール，ｎ−ブタノールなど任
意のものが用いられるが好ましくはエタノールが用いら
れる。また、使用する酸も塩酸，酢酸，乳酸，硫酸，ク
エン酸，リン酸など任意のものが用いられるが好ましく
は塩酸が用いられ、またその濃度も任意であるが、操作
性，安全性の面からも０．５〜５Ｎが好ましい。このよ
うに酸・アルコール処理して生じる不溶物は、ろ過，遠
心分離又はデカンテーション等により除去し、目的とす
るコラーゲン合成促進作用成分を豊富に含有するコラー
ゲン合成促進剤が得られる。なお、酸・アルコール処理
して生じる不溶物を除去する際の工程としてはろ過、遠
心分離またはデカンテーションがあげられるが、好まし
くはろ過または遠心分離が良い。工程の具体例を示すと
次のとおりである。ろ過としては、自然ろ過，吸引ろ
過，加圧ろ過，圧搾ろ過などがあげられるが、好ましく
は吸引ろ過，加圧ろ過，圧搾ろ過、更に好ましくは加圧
ろ過があげられる。またろ過の際にケイソウ土などのろ
過助剤を加えてろ過すると効率的であり、添加量も任意
であるが、液重量当たり０．５〜１０％（Ｗ／Ｗ）の範
囲の添加が好ましく、更に好ましくは１〜５％（Ｗ／
Ｗ）である。遠心分離の場合、機種により違いがある
が、不溶物が沈殿する条件であれば問題はなく、通常２
０００ｒｐｍ以上の回転数が好ましく、時間節約の面か
らも更に好ましくは回転数５０００ｒｐｍ以上、もっと
も好ましくは回転数８０００ｒｐｍ以上である。また、
遠心ろ過機などの連続遠心機も利用できる。デカンテー
ションとしては、傾しゃ法の他、サイホン，フィルター
ステッキも利用できる。The alcohol used is methanol,
Any of ethanol, isopropanol, n-butanol and the like can be used, but ethanol is preferably used. The acid used may be any of hydrochloric acid, acetic acid, lactic acid, sulfuric acid, citric acid, phosphoric acid, etc., but hydrochloric acid is preferably used, and its concentration is also arbitrary, but in terms of operability and safety. Also, 0.5 to 5 N is preferable. The insoluble matter generated by the acid / alcohol treatment in this way is removed by filtration, centrifugation, decantation, or the like to obtain a target collagen synthesis-promoting agent rich in the collagen synthesis-promoting action component. The process for removing the insoluble matter generated by the acid / alcohol treatment may be filtration, centrifugation or decantation, preferably filtration or centrifugation. A specific example of the process is as follows. Examples of the filtration include natural filtration, suction filtration, pressure filtration, compression filtration, etc., preferably suction filtration, pressure filtration, compression filtration, and more preferably pressure filtration. Further, it is efficient to add a filter aid such as diatomaceous earth at the time of filtration, and the addition amount is optional, but addition in the range of 0.5 to 10% (W / W) per liquid weight is preferable. , And more preferably 1 to 5% (W /
W). In the case of centrifugation, there is a difference depending on the model, but there is no problem as long as the insoluble matter precipitates.
The rotation speed is preferably 000 rpm or more, more preferably 5000 rpm or more, and most preferably 8000 rpm or more from the viewpoint of time saving. Also,
A continuous centrifuge such as a centrifugal filter can also be used. As a decantation, a siphon or a filter stick can be used in addition to the tilting method.
【００１０】更に、コラーゲン合成促進剤は必要に応じ
てｐＨを調整し、ゲルろ過又は限外ろ過にて分子量１万
以上の高分子を除去しても活性は失われることはなく、
更に、活性炭，活性白土，合成吸着剤などの吸着剤や陰
イオン及び陽イオン交換樹脂により分画してもよく、カ
ラム法，バッチ法いずれでも構わない。なお、化粧品へ
の配合上、分子量１万以上の高分子を除去した方が好ま
しい。また、このコラーゲン合成促進剤は減圧濃縮，限
外ろ過又は凍結濃縮等の方法により濃縮してもよく、ま
た、凍結乾燥，噴霧乾燥又は平板乾燥などの方法により
乾燥粉末化することも可能である。Furthermore, the activity of the collagen synthesis promoter is not lost even if the pH is adjusted as necessary and the polymer having a molecular weight of 10,000 or more is removed by gel filtration or ultrafiltration.
Further, it may be fractionated by an adsorbent such as activated carbon, activated clay, a synthetic adsorbent or the like, an anion and cation exchange resin, and either a column method or a batch method may be used. In addition, it is preferable to remove a polymer having a molecular weight of 10,000 or more from the viewpoint of blending into cosmetics. Further, this collagen synthesis promoter may be concentrated by a method such as vacuum concentration, ultrafiltration or freeze concentration, or may be dried and powdered by a method such as freeze drying, spray drying or flat plate drying. .
【００１１】本発明の皮膚化粧料には上記したコラーゲ
ン合成促進剤のほか、化粧料一般に用いられる界面活性
剤，油脂類，多価アルコール，低級アルコール，増粘
剤，紫外線吸収剤・散乱剤，防腐剤，酸化防止剤，キレ
ート剤，ｐＨ調整剤，香料，色素，水等を適宜配合する
ことができる。これらの添加成分の具体例を示すと次の
とおりである。界面活性剤としてはポリオキシエチレン
（以下ＰＯＥ−と略す）オクチルドデシルアルコール、
ＰＯＥ−２−デシルテトラデシルアルコール等のＰＯＥ
−分岐アルキルエーテル、ＰＯＥ−オレイルアルコール
エーテル、ＰＯＥ−セチルアルコールエーテル等のＰＯ
Ｅ−アルキルエーテル、ソルビタンモノオレエート、ソ
ルビタンモノイソステアレート、ソルビタンモノラウレ
ート等のソルビタンエステル、ＰＯＥ−ソルビタンモノ
オレエート、ＰＯＥ−ソルビタンモノイソステアレー
ト、ＰＯＥ−ソルビタンモノラウレート等のＰＯＥ−ソ
ルビタンエステル、グリセリルモノオレエート、グリセ
リルモノステアレート、グリセリルモノミリステート等
のグリセリン脂肪酸エステル、ＰＯＥ−グリセリルモノ
オレエート、ＰＯＥ−グリセリルモノステアレート、Ｐ
ＯＥ−グリセリルモノミリステート等のＰＯＥ−グリセ
リン脂肪酸エステル、ＰＯＥ−ジヒドロコレステロール
エステル、ＰＯＥ−硬化ヒマシ油、ＰＯＥ−硬化ヒマシ
油イソステアレート等のＰＯＥ−硬化ヒマシ油脂肪酸エ
ステル、ＰＯＥ−オクチルフェノールエーテル等のＰＯ
Ｅ−アルキルアリールエーテル、グリセロールモノイソ
ステアレート、グリセロールモノミリステート等のグリ
セロールエステル、ＰＯＥ−グリセロールモノイソステ
アレート、ＰＯＥ−グリセロールモノミリステート等の
ＰＯＥ−グリセロールエーテル、ジグリセリルモノステ
アレート、デカグリセリルデカステアレート、デカグリ
セリルデカイソステアレート、ジグリセリルジイソステ
アレート等のポリグリセリン脂肪酸エステル等の非イオ
ン界面活性剤、ミリスチン酸、ステアリン酸、パルミチ
ン酸、ベヘニン酸、イソステアリン酸、オレイン酸等の
高級脂肪酸のカリウム、ナトリウム、ジエタノールアミ
ン、トリエタノールアミン、アミノ酸等の塩、エーテル
カルボン酸の上記アルカリ塩、Ｎ−アシルアミノ酸の
塩、Ｎ−アシルサルコン酸塩、高級アルキルスルホン酸
塩等の陰イオン界面活性剤、アルキルアミン塩、ポリア
ミン、アミノアルコール脂肪酸有機シリコーン樹脂、ア
ルキル４級アンモニウム塩等の陽イオン界面活性剤ある
いはレシチン、ベタイン誘導体等の両性界面活性剤等。
油脂類としては、ヒマシ油、オリーブ油、カカオ油、椿
油、ヤシ油、木ロウ、ホホバ油、グレープシード油、ア
ボガド油等の植物油脂類、ミンク油、卵黄油等の動物油
脂類、ミツロウ、鯨ロウ、ラノリン、カルナウバロウ、
キャンデリラロウ等のロウ類、流動パラフィン、スクワ
レン、マイクロクリスタリンワックス、セレシンワック
ス、パラフィンワックス、ワセリン等の炭化水素類、ラ
ウリン酸、ミリスチン酸、ステアリン酸、オレイン酸、
イソステアリン酸、ベヘニン酸等の天然及び合成脂肪酸
類、セタノール、ステアリルアルコール、ヘキシルデカ
ノール、オクチルデカノール、ラウリルアルコール等の
天然及び高級アルコール類、ミリスチン酸イソプロピ
ル、パルミチン酸イソプロピル、ミリスチン酸オクチル
ドデシル、オレイン酸オクチルドデシル、コレステロー
ルオレート等のエステル類。多価アルコールとしてはエ
チレングリコール、ポリエチレングリコール、プロピレ
ングリコール、１，３−ブチレングリコール、１，４−
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、ジグリセリン、トリグリセリン、テトラグリセリ
ン等のポリグリセリン、グルコース、マルトース、マル
チトース、ショ糖、フルクトース、キシリトース、ソル
ビトール、マルトトリオース、スレイトール、エリスリ
トール等。増粘剤としては、アルギン酸ナトリウム、キ
サンタンガム、硅酸アルミニウム、マルメロ種子抽出
物、トラガントガム、デンプン、コラーゲン、ヒアルロ
ン酸ナトリウム等の天然高分子物質、メチルセルロー
ス、ヒドロキシエチルセルロース、カルボキシメチルセ
ルロース、可溶性デンプン、カチオン化セルロース等の
半合成高分子物質、カルボキシビニルポリマー、ポリビ
ニルアルコール等の合成高分子物質等。紫外線吸収剤と
しては、パラアミノ安息香酸、パラメトキシケイ皮酸イ
ソプロピル、ブチルメトキシベンゾイルメタン、グリセ
リル−モノ−２−エチルヘキサノイル−ジ−パラメトキ
シベンゾフェノン、ジガロイルトリオレエート、２−
２’−ジヒドキシ−４−メトキシベンゾフェノン、エチ
ル−４−ビスヒドロキシプロピルアミノベンゾエート、
２−エチルヘキシル−２−シアノ−３，３’−ジフェニ
ルアクリレート、パラメトキシケイ皮酸エチルヘキシ
ル、サリチル酸−２−エチルヘキシル、グリセリルパラ
アミノベンゾエート、サリチル酸ホモメチル、オルトア
ミノ安息香酸メチル、２−ヒドロキシ−４−メトキシベ
ンゾフェノン、アミル−パラ−ジメチルアミノベンゾエ
ート、２−フェニルベンゾイミダゾール−５−スルフォ
ン酸、２−ヒドロキシ−４−メトキシベンゾフェノン−
５−スルフォン酸等。防腐剤としては、安息香酸塩、サ
リチル酸塩、ソルビン酸塩、デヒドロ酢酸塩、パラオキ
シ安息香酸エステル、２，４，４’−トリクロロ−２’
−ヒドロキシジフェニルエーテル、３，４，４’−トリ
クロロカルバニリド、塩化ベンザルコニウム、ヒノキチ
オール、レゾルシン、エタノール等。酸化防止剤として
は、トコフェロール、アスコルビン酸、ブチルヒドロキ
シアニソール、ジブチルヒドロキシトルエン、ノルジヒ
ドログアヤレチン酸、没食子酸プロピル等。キレート剤
としては、エデト酸ナトリウム、クエン酸ナトリウム
等。これらの添加成分の中には、本発明の必須成分の安
定性または経皮吸収性を高めることにより、本発明の皮
膚化粧料の有効性をより向上させる働きをもつものもあ
る。また、その剤型も任意であり、更に可溶系，乳化
系，粉末分散系等何れでもよく、用途も化粧水，乳液，
クリーム，パック等の基礎化粧料はもちろんファンデー
ション等のメーキャップ化粧料など幅広く利用できる。In addition to the above-mentioned collagen synthesis promoter, the skin cosmetics of the present invention include surfactants, oils and fats, polyhydric alcohols, lower alcohols, thickeners, ultraviolet absorbers / scattering agents, which are commonly used in cosmetics. Preservatives, antioxidants, chelating agents, pH adjusters, fragrances, dyes, water and the like can be added as appropriate. Specific examples of these additive components are as follows. As the surfactant, polyoxyethylene (hereinafter abbreviated as POE-) octyldodecyl alcohol,
POE-2-POC such as decyl tetradecyl alcohol
-PO such as branched alkyl ether, POE-oleyl alcohol ether, POE-cetyl alcohol ether
POE- such as E-alkyl ether, sorbitan monooleate, sorbitan monoisostearate and sorbitan monolaurate, POE-sorbitan monooleate, POE-sorbitan monoisostearate and POE-sorbitan monolaurate Glycerin fatty acid esters such as sorbitan ester, glyceryl monooleate, glyceryl monostearate, glyceryl monomyristate, POE-glyceryl monooleate, POE-glyceryl monostearate, P
POE-glycerin fatty acid ester such as OE-glyceryl monomyristate, POE-dihydrocholesterol ester, POE-hardened castor oil, POE-hardened castor oil, POE-hardened castor oil fatty acid ester such as isostearate, POE-octylphenol ether, etc. PO
E-alkyl aryl ether, glycerol monoisostearate, glycerol ester such as glycerol monomyristate, POE-glycerol monoisostearate, POE-glycerol ether such as POE-glycerol monomyristate, diglyceryl monostearate, decaglyceryl Non-ionic surfactants such as deglycerate, decaglyceryl decaisostearate, polyglycerin fatty acid esters such as diglyceryl diisostearate, myristic acid, stearic acid, palmitic acid, behenic acid, isostearic acid, oleic acid, etc. Salts of higher fatty acids such as potassium, sodium, diethanolamine, triethanolamine, amino acids, the above-mentioned alkali salts of ether carboxylic acids, salts of N-acyl amino acids, N-acyl monkeys. Anionic surfactants such as phosphates and higher alkyl sulfonates, cationic amines such as alkylamine salts, polyamines, amino alcohol fatty acid organic silicone resins, alkyl quaternary ammonium salts, and amphoteric amphoteric compounds such as lecithin and betaine derivatives. Surfactants, etc.
Examples of oils and fats include castor oil, olive oil, cocoa oil, camellia oil, coconut oil, wood wax, jojoba oil, grape seed oil, vegetable oils such as avocado oil, animal oils such as mink oil and egg yolk oil, beeswax, whale. Wax, lanolin, carnauba wax,
Waxes such as candelilla wax, liquid paraffin, squalene, microcrystalline wax, ceresin wax, paraffin wax, hydrocarbons such as petrolatum, lauric acid, myristic acid, stearic acid, oleic acid,
Natural and synthetic fatty acids such as isostearic acid and behenic acid, natural and higher alcohols such as cetanol, stearyl alcohol, hexyldecanol, octyldecanol and lauryl alcohol, isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, octyl oleate. Esters such as dodecyl and cholesterol oleate. As the polyhydric alcohol, ethylene glycol, polyethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-
Polyglycerin such as butylene glycol, dipropylene glycol, glycerin, diglycerin, triglycerin and tetraglycerin, glucose, maltose, maltose, sucrose, fructose, xylitolose, sorbitol, maltotriose, threitol, erythritol and the like. As the thickener, sodium alginate, xanthan gum, aluminum silicate, quince seed extract, tragacanth gum, starch, collagen, natural polymer substances such as sodium hyaluronate, methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, soluble starch, cationized cellulose. Semi-synthetic polymer substances such as, carboxyvinyl polymer, synthetic polymer substances such as polyvinyl alcohol, etc. As the ultraviolet absorber, paraaminobenzoic acid, isopropyl paramethoxycinnamate, butylmethoxybenzoylmethane, glyceryl-mono-2-ethylhexanoyl-di-paramethoxybenzophenone, digaroyltrioleate, 2-
2'-dihydroxy-4-methoxybenzophenone, ethyl-4-bishydroxypropylaminobenzoate,
2-ethylhexyl-2-cyano-3,3'-diphenyl acrylate, ethyl hexyl paramethoxycinnamate, 2-ethylhexyl salicylate, glyceryl paraaminobenzoate, homomethyl salicylate, methyl orthoaminobenzoate, 2-hydroxy-4-methoxybenzophenone, Amyl-para-dimethylaminobenzoate, 2-phenylbenzimidazole-5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone-
5-sulfonic acid and the like. Preservatives include benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, 2,4,4'-trichloro-2 '.
-Hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, benzalkonium chloride, hinokitiol, resorcin, ethanol and the like. Examples of antioxidants include tocopherol, ascorbic acid, butylhydroxyanisole, dibutylhydroxytoluene, nordihydroguaiaretic acid, propyl gallate and the like. Examples of chelating agents include sodium edetate and sodium citrate. Some of these added components have a function of further improving the effectiveness of the skin cosmetic of the present invention by increasing the stability or transdermal absorbability of the essential components of the present invention. Further, its dosage form is also arbitrary, and may be any soluble system, emulsion system, powder dispersion system, etc.
Not only basic cosmetics such as creams and packs but also makeup cosmetics such as foundations can be widely used.
【００１２】[0012]
【実施例】以下に本発明の実施例を示すが、これらによ
って本発明を制限するものではない。コラーゲン合成促
進剤の調製法と培地への添加量について述べる。なお、
コラーゲン合成促進剤の調製は培養細胞に直接添加する
ことを考慮して、限外濾過や減圧濃縮にてアルコールを
除去し、かつｐＨを中性（ｐＨ６．５〜７．５）に調整
したが、これによって本発明のコラーゲン合成促進剤を
制限するものではない。また、本発明の特色は、酸・ア
ルコール処理可溶画分に豊富なコラーゲン合成促進作用
成分が含有されることにあり、コラーゲン合成促進剤の
調製法に示したように、更に活性成分の濃度を上げ、熱
安定性を良くし、脱色・脱臭するために、濃縮，加熱処
理，活性炭等を用いた吸着剤処理などの種々の工程を行
うことは化粧料への配合上有利であるが、これらによっ
て本発明のコラーゲン合成促進剤を制限するものではな
い。EXAMPLES Examples of the present invention will be shown below, but the present invention is not limited thereto. The method for preparing the collagen synthesis promoter and the amount added to the medium will be described. In addition,
In preparation of the collagen synthesis promoter, alcohol was removed by ultrafiltration or vacuum concentration and the pH was adjusted to neutral (pH 6.5 to 7.5) in consideration of direct addition to cultured cells. However, this does not limit the collagen synthesis promoter of the present invention. Further, the feature of the present invention is that the soluble fraction treated with acid / alcohol contains abundant components for promoting collagen synthesis, and as described in the method for preparing a collagen synthesis accelerator, the concentration of the active ingredient is further increased. In order to improve the heat stability, improve the heat stability, and decolorize and deodorize, various steps such as concentration, heat treatment, adsorbent treatment using activated carbon, etc. are advantageous in blending into cosmetics, These do not limit the collagen synthesis promoter of the present invention.
【００１３】試料Ａ ウシ胎盤由来のコラーゲン合成促
進剤 ウシの胎盤３００ｇを水１ｌに懸濁し、１Ｎ塩酸でｐＨ
４．０に調整し、エタノール３００ｍｌを加え、２時間
撹拌した。その後生じた沈殿物を遠心分離によって除去
し、その上清を分画分子量１０００の限外ろ過膜にて５
００ｇまで濃縮し、ｐＨ７．０に調整し、７０℃，１時
間加熱処理を行った後、生成した不溶物を吸引ろ過によ
り取り除き、清澄な胎盤分画成分を得た。Sample A Collagen synthesis promoter derived from bovine placenta 300 g of bovine placenta was suspended in 1 liter of water, and the pH was adjusted with 1N hydrochloric acid.
The mixture was adjusted to 4.0, 300 ml of ethanol was added, and the mixture was stirred for 2 hours. The resulting precipitate was removed by centrifugation, and the supernatant was filtered with an ultrafiltration membrane having a molecular weight cut off of 1000.
The solution was concentrated to 00 g, adjusted to pH 7.0, heat-treated at 70 ° C. for 1 hour, and the insoluble matter formed was removed by suction filtration to obtain a clear placental fraction component.
【００１４】試料Ｂ ウシ胎盤由来のコラーゲン合成促
進剤 ウシの胎盤３００ｇを水１ｌに懸濁し、５Ｎ酢酸でｐＨ
３．０に調整し、メタノール４００ｍｌを加え、２時間
撹拌した。その後デカンテーションにより上清を分取
し、その液をｐＨ７．５に調整し、減圧下５００ｇまで
濃縮後吸引ろ過し、清澄な胎盤分画成分を得た。Sample B Collagen synthesis promoter derived from bovine placenta 300 g of bovine placenta was suspended in 1 liter of water, and the pH was adjusted with 5N acetic acid.
The mixture was adjusted to 3.0, 400 ml of methanol was added, and the mixture was stirred for 2 hours. Then, the supernatant was separated by decantation, the pH of the solution was adjusted to 7.5, and the solution was concentrated to 500 g under reduced pressure and suction filtered to obtain a clear placental fraction component.
【００１５】試料Ｃ ヤギ胎盤由来のコラーゲン合成促
進剤 ヤギの胎盤３００ｇを水１ｌに懸濁し、２Ｎ乳酸でｐＨ
４．５に調整し、ｎ−ブタノール５００ｍｌを加え、２
時間撹拌した。その後遠心分離し、その上清を減圧下５
００ｇまで濃縮し、ｐＨ６．５に調整し、吸引ろ過し清
澄な液を得た。Sample C Collagen synthesis promoter derived from goat placenta 300 g of goat placenta was suspended in 1 liter of water, and the pH was adjusted with 2N lactic acid.
Adjust to 4.5, add 500 ml of n-butanol and add 2
Stirred for hours. After that, centrifuge, and the supernatant is decompressed.
The solution was concentrated to 00 g, adjusted to pH 6.5, and suction filtered to obtain a clear liquid.
【００１６】試料Ｄ ブタ胎盤由来のコラーゲン合成促
進剤 ブタの胎盤３００ｇを水１ｌに懸濁し、３Ｎクエン酸で
ｐＨ５．５に調整し、イソプロパノール４００ｍｌを加
え、２時間撹拌した。その後セライトろ過し、その液を
ｐＨ７．５に調整し、減圧下５００ｇまで濃縮し、凍結
乾燥にて乾燥粉末化させ、得られた乾燥粉末を１００ｇ
の水に溶解した。Sample D Pig Placenta-Derived Collagen Synthesis Promoter 300 g of pig placenta was suspended in 1 liter of water, the pH was adjusted to 5.5 with 3N citric acid, 400 ml of isopropanol was added, and the mixture was stirred for 2 hours. After that, the mixture is filtered through Celite, the pH is adjusted to 7.5, concentrated to 500 g under reduced pressure, freeze-dried to give a dry powder, and 100 g of the obtained dry powder is obtained.
Dissolved in water.
【００１７】試料Ｅ ヒト胎盤由来のコラーゲン合成促
進剤 ヒトの胎盤３００ｇを水１ｌに懸濁し、６Ｎ塩酸でｐＨ
４．０に調整し、エタノール３００ｍｌを加え、２時間
撹拌した。その後セライトろ過し、その液を減圧下５０
０ｇまで濃縮し、ｐＨ７．５に調整し、８０℃，１０分
間加熱処理を行った後、生成した不溶物を吸引ろ過によ
り取り除き、清澄な胎盤分画成分を得た。Sample E Collagen synthesis promoter derived from human placenta 300 g of human placenta was suspended in 1 liter of water, and the pH was adjusted with 6N hydrochloric acid.
The mixture was adjusted to 4.0, 300 ml of ethanol was added, and the mixture was stirred for 2 hours. After that, it is filtered through Celite, and the liquid is reduced to 50
After concentrating to 0 g, adjusting the pH to 7.5 and performing heat treatment at 80 ° C. for 10 minutes, the generated insoluble matter was removed by suction filtration to obtain a clear placental fraction component.
【００１８】試料Ｆ ウシ胎盤由来のコラーゲン合成促
進剤 試料ＡをｐＨ８．５，０．０１Ｍ燐酸緩衝液にて平衡化
したＤＥＡＥセルロファインに吸着させ、ｐＨ８．５，
０．８ＭＮａＣｌ，０．０１Ｍ燐酸緩衝液にて溶出さ
せ、その溶出液を４℃，１２時間透析を行った。Sample F Collagen synthesis promoter derived from bovine placenta Sample A was adsorbed on DEAE cellulofine equilibrated with pH 8.5, 0.01 M phosphate buffer, and pH 8.5 was obtained.
Elution was performed with 0.8 M NaCl and 0.01 M phosphate buffer, and the eluate was dialyzed at 4 ° C. for 12 hours.
【００１９】試料Ｇ ウシ胎盤由来のコラーゲン合成促
進剤 試料Ｂにヤシガラ炭（武田薬品製）を２％添加し、よく
撹拌後吸引ろ過により清澄な液を得た。この液を分画分
子量１万の限外ろ過膜にて高分子を除去し、凍結乾燥に
て乾燥粉末化後、得られた乾燥粉末を１００ｇの水に溶
解した。 添加量（Ｖ／Ｖ培養液％） 試料Ａ ： ２％ 試料Ｂ ： ２％ 試料Ｃ ： ２％ 試料Ｄ ： １％ 試料Ｅ ： ２％ 試料Ｆ ： ２％ 試料Ｇ ： １％ 表１より明らかなように本発明のコラーゲン合成促進剤
は、線維芽細胞のコラーゲン合成を促進することが明ら
かとなった。かくして得られる本発明のコラーゲン合成
促進剤及びそれを含有する皮膚化粧料の有効性及び安全
性について試験した結果は、次の通りである。Sample G Collagen synthesis promoter derived from bovine placenta To sample B, 2% of coconut husk charcoal (manufactured by Takeda Pharmaceutical Co., Ltd.) was added, and after thorough stirring, a clear liquid was obtained by suction filtration. The polymer was removed from this liquid by an ultrafiltration membrane having a molecular weight cut off of 10,000, and the powder was freeze-dried to give a dry powder. The obtained dry powder was dissolved in 100 g of water. Addition amount (V / V culture solution%) Sample A: 2% Sample B: 2% Sample C: 2% Sample D: 1% Sample E: 2% Sample F: 2% Sample G: 1% Table 1 Thus, it was revealed that the collagen synthesis promoter of the present invention promotes collagen synthesis of fibroblasts. The results of testing the efficacy and safety of the thus-obtained collagen synthesis promoter of the present invention and the skin cosmetics containing the same are as follows.
【００２０】試験例１．培養線維芽細胞のコラーゲン合
成促進能試験 継代培養してきたＷＩ−３８細胞（ヒト胎児肺正常２倍
体細胞）に、ＭＥＭ培地（０．５％牛胎児血清含有）の
低血清培養条件下で本発明のコラーゲン合成促進剤を試
料として添加後、５％ＣＯ2 ＋９５％Ａｉｒにて３７
℃，４日間培養し、培地５ｍｌ中に3Ｈ-プロリン（200
μＣｉ／ｍｌ）を５０μｌ添加して、５％ＣＯ2＋Ａｉ
ｒにて３７℃，６時間培養した。なお、試料無添加区を
対照とした。その後培養上清を取り除き、細胞画分にコ
ラゲナーゼタイプIII(Worthing ton社製）５units ／ｍ
ｌを３７℃，１８時間作用させ、トリクロロ酢酸溶液で
除蛋白を行い、その可溶画分をハイオニックフローと混
合し放射線量を測定した。その結果を表１に示す。Test Example 1. Collagen synthesis promoting ability test of cultured fibroblasts WI-38 cells (human fetal lung normal diploid cells) that have been subcultured are cultured under low serum culture conditions of MEM medium (containing 0.5% fetal bovine serum). After adding the collagen synthesis promoter of the present invention as a sample, the mixture was added with 5% CO 2 + 95% Air to 37
Cultivate at 4 ℃ for 4 days and add 3 H-proline (200
(50 μCi / ml) and added 5% CO 2 + Ai
Incubated at 37 ° C for 6 hours at r. The sample-free area was used as a control. After that, the culture supernatant was removed, and collagenase type III (Worthing ton) 5 units / m was added to the cell fraction.
1 was allowed to act at 37 ° C. for 18 hours, deproteinization was carried out with a trichloroacetic acid solution, and the soluble fraction was mixed with Hyonic Flow to measure the radiation dose. Table 1 shows the results.
【００２１】[0021]
【表１】 [Table 1]
【００２２】試験例２．パネルテスト 小皺の悩みを有する３２〜５１歳（平均年齢４０．５
歳）の女性５０名を対象にして、下記の本発明皮膚化粧
料及び対照皮膚化粧料を、１日２回（朝，夕）連続３ヶ
月塗布、使用せしめた結果の官能評価を表２に示した。Test Example 2. Panel test 32-51 years old with wrinkles (average age 40.5
Table 2 shows the sensory evaluation of the results obtained by applying the following skin cosmetics and control skin cosmetics twice a day (morning and evening) for 3 consecutive months to 50 women aged 50 years. Indicated.
【００２３】[0023]
【表２】 [Table 2]
【００２４】 〈本発明皮膚化粧料〉 試験例１の試料Ａ（対照皮膚化粧料は精製水） ２０％ グリセリン ５％ エタノール ５％ メチルパラベン ０．２％ 精製水 ６９．８％ 表２より明らかなように、本発明の皮膚化粧料は高い有
効性を示すことが明らかとなった。<Inventive Skin Cosmetic> Sample A of Test Example 1 (control skin cosmetic is purified water) 20% Glycerin 5% Ethanol 5% Methylparaben 0.2% Purified water 69.8% As is clear from Table 2. Moreover, it was revealed that the skin cosmetic composition of the present invention exhibits high effectiveness.
【００２５】試験例３．パッチテスト 年齢２１から５５歳までの男性１６名，女性１４名、計
３０名からなる被検者の上腕屈側部に、クローズドパッ
チテストを実施した。試料として試験例１の試料Ａを用
いた。 判定の基準 −：全く無反応，±：軽微な紅斑，＋：明
らかな紅斑，＋＋：紅斑及び腫脹、丘疹 その結果、全被検者において、−（全く無反応）であ
り、刺激反応及びアレルギー反応を惹起する可能性は非
常に少なく、本発明のコラーゲン合成促進剤の安全性が
高く、皮膚化粧料に配合し得るものであることは明らか
となった。Test Example 3. Patch test A closed patch test was performed on the upper arm flexion region of 30 subjects, 16 males and 14 females aged 21 to 55 years old in total. The sample A of Test Example 1 was used as the sample. Criteria for judgment −: No reaction, ±: Minor erythema, +: Clear erythema, ++: Erythema and swelling, papules As a result, in all subjects, − (no reaction), irritation reaction and allergy. It was revealed that the possibility of causing a reaction is very low, the collagen synthesis promoter of the present invention is highly safe, and that it can be incorporated into a skin cosmetic.
【００２６】実施例１ 〈化粧水〉 グリセリン ５％ プロピレングリコール ４％ オレイルアルコール ０．１％ ポリオキシエチレンソルビタンモノラウリン酸エステル １．５％ ポリオキシエチレンラウリルエーテル ０．５％ エタノール １０％ 試験例１の試料Ａ １０％ 香料，染料，防腐剤，紫外線吸収剤 適量 精製水 ６８．９％Example 1 <Lotion> Glycerin 5% Propylene glycol 4% Oleyl alcohol 0.1% Polyoxyethylene sorbitan monolaurate 1.5% Polyoxyethylene lauryl ether 0.5% Ethanol 10% Test Example 1 Sample A 10% Fragrance, dye, preservative, UV absorber Appropriate amount Purified water 68.9%
【００２７】実施例２ 〈クリーム〉 ステアリルアルコール ７％ ステアリン酸 ２％ 還元ラノリン ５％ スクワラン ６％ オクチドデカノール ３％ ポリオキシエチレンセチルエーテル ２％ 親油型モノステアリン酸グリセリン ５％ プロピレングリコール ５％ 試験例１の試料Ｂ １０％ 香料，防腐剤，酸化防止剤 適量 精製水 ５８％Example 2 <Cream> Stearyl alcohol 7% Stearic acid 2% Reduced lanolin 5% Squalane 6% Octidodecanol 3% Polyoxyethylene cetyl ether 2% Lipophilic glyceryl monostearate 5% Propylene glycol 5% Test Sample B of Example 1 10% Fragrance, preservative, antioxidant Proper amount Purified water 58%
【００２８】実施例３ 〈乳液〉 ステアリン酸 ０．２％ セタノール １．５％ ワセリン ３％ ラノリンアルコール ２％ 流動パラフィン １０％ ポリオキシエチレンモノオレイン酸エステル ２％ グリセリン ３％ プロピレングリコール ５％ トリエタノールアミン １％ 試験例１の試料Ｃ １５％ 香料，防腐剤，酸化防止剤 適量 精製水 ５７．３％Example 3 Emulsion Stearic acid 0.2% Cetanol 1.5% Vaseline 3% Lanolin alcohol 2% Liquid paraffin 10% Polyoxyethylene monooleate 2% Glycerin 3% Propylene glycol 5% Triethanolamine 1% Sample C of Test Example 1 15% Fragrance, preservative, antioxidant Proper amount Purified water 57.3%
【００２９】実施例４ 〈パック〉 ポリビニルアルコール １５％ カルボキシメチルセルロースナトリウム ５％ プロピレングリコール ３％ エタノール １０％ 試験例１の試料Ｄ ５％ 香料，防腐剤，酸化剤 適量 精製水 ６２％Example 4 <Pack> Polyvinyl alcohol 15% Sodium carboxymethylcellulose 5% Propylene glycol 3% Ethanol 10% Sample D of Test Example 1 5% Fragrance, preservative, oxidizer Suitable amount Purified water 62%
【００３０】本発明の実施態様ならびに目的生成物を挙
げれば以下のとおりである。 （１）胎盤由来の成分を含有することを特徴とするコラ
ーゲン合成促進剤。 （２）胎盤がヒト，ウシ，ヤギ，ヒツジ，ブタの胎盤よ
り選ばれる１種又は２種以上である前記（１）記載のコ
ラーゲン合成促進剤。 （３）胎盤がヒト，ウシ，ブタの胎盤より選ばれる１種
又は２種以上である前記（１）記載のコラーゲン合成促
進剤。 （４）胎盤がヒトの胎盤である前記（１）記載のコラー
ゲン合成促進剤。 （５）胎盤がウシの胎盤である前記（１）記載のコラー
ゲン合成促進剤。 （６）胎盤がブタの胎盤である前記（１）記載のコラー
ゲン合成促進剤。The embodiments of the present invention and the desired products are as follows. (1) A collagen synthesis promoter comprising a placenta-derived component. (2) The collagen synthesis promoter according to (1), wherein the placenta is one or more selected from human, bovine, goat, sheep, and porcine placenta. (3) The collagen synthesis promoter according to (1), wherein the placenta is one or more selected from human, bovine, and porcine placenta. (4) The collagen synthesis promoter according to (1) above, wherein the placenta is a human placenta. (5) The collagen synthesis promoter according to (1) above, wherein the placenta is a bovine placenta. (6) The collagen synthesis promoter according to (1) above, wherein the placenta is a pig placenta.
【００３１】（７）胎盤由来の成分が、コラーゲン合成
促進作用成分を豊富に含有する胎盤の分画成分である前
記（１）記載のコラーゲン合成促進剤。 （８）胎盤の分画成分が、分子量１万以下の画分である
前記（７）記載のコラーゲン合成促進剤。 （９）胎盤由来の成分が、酸・アルコール処理によって
得られる前記（１）、（７）記載のコラーゲン合成促進
剤。 （１０）胎盤の分画成分が、酸・アルコール処理によっ
て得られる前記（７）記載のコラーゲン合成促進剤。 （１１）分子量１万以下の画分が酸・アルコール処理に
よって得られる前記（８）記載のコラーゲン合成促進
剤。 （１２）酸・アルコール処理がｐＨ１〜６の条件下で不
溶物を除去する処理である前記（９）〜（１１）記載の
コラーゲン合成促進剤。 （１３）酸・アルコール処理がｐＨ２〜５．５の条件下
で不溶物を除去する処理である前記（９）〜（１１）記
載のコラーゲン合成促進剤。 （１４）酸・アルコール処理がアルコール濃度１０〜５
０％（Ｖ／Ｖ）の条件下で不溶物を除去する処理である
前記（９）〜（１１）記載のコラーゲン合成促進剤。 （１５）酸・アルコール処理がアルコール濃度２０〜４
０％（Ｖ／Ｖ）の条件下で不溶物を除去する処理である
前記（９）〜（１１）記載のコラーゲン合成促進剤。(7) The collagen synthesis promoter according to (1) above, wherein the placenta-derived component is a fractionated component of the placenta, which is rich in collagen synthesis promoting components. (8) The collagen synthesis promoter according to (7) above, wherein the fractionated component of placenta is a fraction having a molecular weight of 10,000 or less. (9) The collagen synthesis promoter according to the above (1) or (7), wherein the placenta-derived component is obtained by acid / alcohol treatment. (10) The collagen synthesis promoter according to (7) above, wherein the fractionated component of the placenta is obtained by acid / alcohol treatment. (11) The collagen synthesis promoter according to the above (8), wherein a fraction having a molecular weight of 10,000 or less is obtained by treatment with an acid / alcohol. (12) The collagen synthesis promoter according to the above (9) to (11), wherein the acid / alcohol treatment is a treatment for removing insoluble matter under conditions of pH 1 to 6. (13) The collagen synthesis promoter according to the above (9) to (11), wherein the acid / alcohol treatment is a treatment for removing insoluble matter under the condition of pH 2 to 5.5. (14) Acid / alcohol treatment causes alcohol concentration of 10-5
The collagen synthesis promoter according to the above (9) to (11), which is a treatment for removing insolubles under the condition of 0% (V / V). (15) Acid / alcohol treatment causes alcohol concentration of 20-4
The collagen synthesis promoter according to the above (9) to (11), which is a treatment for removing insolubles under the condition of 0% (V / V).
【００３２】（１６）酸・アルコール処理がｐＨ１〜
６，アルコール濃度１０〜５０％（Ｖ／Ｖ）の条件下で
不溶物を除去する処理である前記（９）〜（１１）記載
のコラーゲン合成促進剤。 （１７）酸・アルコール処理がｐＨ２〜５．５，アルコ
ール濃度１０〜５０％（Ｖ／Ｖ）の条件下で不溶物を除
去する処理である前記（９）〜（１１）記載のコラーゲ
ン合成促進剤。 （１８）酸・アルコール処理がｐＨ１〜６，アルコール
濃度２０〜４０％（Ｖ／Ｖ）の条件下で不溶物を除去す
る処理である前記（９）〜（１１）記載のコラーゲン合
成促進剤。 （１９）酸・アルコール処理がｐＨ２〜５．５，アルコ
ール濃度２０〜４０％（Ｖ／Ｖ）の条件下で不溶物を除
去する処理である前記（９）〜（１１）記載のコラーゲ
ン合成促進剤。(16) Acid / alcohol treatment has a pH of 1 to
6, The collagen synthesis promoter according to the above (9) to (11), which is a treatment for removing insoluble matter under the condition of an alcohol concentration of 10 to 50% (V / V). (17) The collagen synthesis promotion according to the above (9) to (11), wherein the acid / alcohol treatment is a treatment for removing insoluble matter under conditions of pH 2 to 5.5 and alcohol concentration 10 to 50% (V / V). Agent. (18) The collagen synthesis promoter according to the above (9) to (11), wherein the acid / alcohol treatment is a treatment for removing insoluble matter under the conditions of pH 1-6 and alcohol concentration 20-40% (V / V). (19) Acceleration of collagen synthesis according to the above (9) to (11), wherein the acid / alcohol treatment is a treatment for removing insoluble matter under conditions of pH 2 to 5.5 and alcohol concentration 20 to 40% (V / V). Agent.
【００３３】（２０）アルコールがメタノール，エタノ
ール，イソプロパノール，ｎ−ブタノールより選ばれる
１種又は２種以上である前記（９）〜（１９）記載のコ
ラーゲン合成促進剤。 （２１）アルコールがメタノール，エタノール，イソプ
ロパノールより選ばれる１種又は２種以上である前記
（９）〜（１９）記載のコラーゲン合成促進剤。 （２２）アルコールがメタノールである前記（９）〜
（１９）記載のコラーゲン合成促進剤。 （２３）アルコールがエタノールである前記（９）〜
（１９）記載のコラーゲン合成促進剤。 （２４）アルコールがイソプロパノールである前記
（９）〜（１９）記載のコラーゲン合成促進剤。 （２５）酸が塩酸，酢酸，乳酸，硫酸，クエン酸，リン
酸より選ばれる１種又は２種以上である前記（９）〜
（１９）記載のコラーゲン合成促進剤。 （２６）酸が塩酸である前記（９）〜（１９）記載のコ
ラーゲン合成促進剤。 （２７）酸が乳酸である前記（９）〜（１９）記載のコ
ラーゲン合成促進剤。 （２８）酸がクエン酸である前記（９）〜（１９）記載
のコラーゲン合成促進剤。 （２９）前記（１）〜（２８）記載のコラーゲン合成促
進剤の製造法。 （３０）前記（１）〜（２８）記載のコラーゲン合成促
進剤を含有することを特徴とする皮膚化粧料。 （３１）前記（３０）記載の皮膚化粧料の製造法。(20) The collagen synthesis promoter according to the above (9) to (19), wherein the alcohol is one or more selected from methanol, ethanol, isopropanol and n-butanol. (21) The collagen synthesis promoter according to the above (9) to (19), wherein the alcohol is one kind or two or more kinds selected from methanol, ethanol and isopropanol. (22) The above (9), wherein the alcohol is methanol.
The collagen synthesis promoter according to (19). (23) The above (9), wherein the alcohol is ethanol.
The collagen synthesis promoter according to (19). (24) The collagen synthesis promoter according to the above (9) to (19), wherein the alcohol is isopropanol. (25) The above-mentioned (9) to which the acid is one or more selected from hydrochloric acid, acetic acid, lactic acid, sulfuric acid, citric acid and phosphoric acid.
The collagen synthesis promoter according to (19). (26) The collagen synthesis promoter according to the above (9) to (19), wherein the acid is hydrochloric acid. (27) The collagen synthesis promoter according to the above (9) to (19), wherein the acid is lactic acid. (28) The collagen synthesis promoter according to the above (9) to (19), wherein the acid is citric acid. (29) The method for producing the collagen synthesis promoter according to the above (1) to (28). (30) A skin cosmetic containing the collagen synthesis promoter according to any one of (1) to (28). (31) The method for producing a skin cosmetic according to (30) above.
【００３４】[0034]
【発明の効果】以上詳述した如く本願発明のコラーゲン
合成促進剤は優れたコラーゲン合成促進作用を有し、こ
の合成促進剤が添加された皮膚化粧料は、皮膚機能を促
進し、秦の皺を防止し、きめ細やかな、しっとりした皮
膚を与える効果を有する。従って本発明の産業上の意義
は非常に大きい。Industrial Applicability As described in detail above, the collagen synthesis promoter of the present invention has an excellent collagen synthesis promoting action, and the skin cosmetics to which this synthesis promoter is added promotes the skin function and causes the wrinkle of the Qin. And has the effect of giving a delicate, moist skin. Therefore, the industrial significance of the present invention is very great.
Claims (5)
するコラーゲン合成促進剤。1. A collagen synthesis promoter comprising a placenta-derived component.
の胎盤より選ばれる１種又は２種以上である請求項１記
載のコラーゲン合成促進剤。2. The collagen synthesis promoter according to claim 1, wherein the placenta is one or more selected from human, bovine, goat, sheep and porcine placenta.
進剤を含有することを特徴とする皮膚化粧料。3. A skin cosmetic comprising the collagen synthesis promoter according to claim 1 or 2.
て得られる分画物である請求項１記載のコラーゲン合成
促進剤の製造法。4. The method for producing a collagen synthesis promoter according to claim 1, wherein the placenta component is a fraction obtained by acid / alcohol treatment.
コール濃度１０〜５０％（Ｖ／Ｖ）の条件下で不溶物を
除去する処理である請求項４記載のコラーゲン合成促進
剤の製造法。5. The method for producing a collagen synthesis promoter according to claim 4, wherein the acid / alcohol treatment is a treatment for removing insoluble matter under conditions of pH 1-6 and alcohol concentration 10-50% (V / V).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7062025A JPH08231370A (en) | 1995-02-23 | 1995-02-23 | Skin cosmetic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7062025A JPH08231370A (en) | 1995-02-23 | 1995-02-23 | Skin cosmetic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH08231370A true JPH08231370A (en) | 1996-09-10 |
Family
ID=13188228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7062025A Pending JPH08231370A (en) | 1995-02-23 | 1995-02-23 | Skin cosmetic |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH08231370A (en) |
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| JP2001072567A (en) * | 1999-09-07 | 2001-03-21 | Sunstar Inc | Skin cosmetic |
| JP2002097113A (en) * | 2000-09-22 | 2002-04-02 | Japan Natural Laboratory Co Ltd | Pack material |
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| EP2153814A1 (en) | 2008-08-05 | 2010-02-17 | Isdin S.A. | Use of compositions comprising urea |
| JP2010143885A (en) * | 2008-12-22 | 2010-07-01 | Asahi Breweries Ltd | Lactobacillus and food and drink preparations or cosmetic using the same |
| JP2011177156A (en) * | 2010-03-04 | 2011-09-15 | Shigeta Hakko Kagaku Kenkyusho:Kk | Beverage containing rosemary-fermented extract and presenting collagen-increasing effect |
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| WO2014092325A1 (en) | 2012-12-13 | 2014-06-19 | 한국한의학연구원 | Skin-moisturising or wrinkle-improving external composition and cosmetic composition |
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