JP2008013442A - Rough skin improving agent - Google Patents

Rough skin improving agent Download PDF

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JP2008013442A
JP2008013442A JP2006183235A JP2006183235A JP2008013442A JP 2008013442 A JP2008013442 A JP 2008013442A JP 2006183235 A JP2006183235 A JP 2006183235A JP 2006183235 A JP2006183235 A JP 2006183235A JP 2008013442 A JP2008013442 A JP 2008013442A
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improving agent
rough skin
ovarian
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JP3899116B1 (en
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Tadashi Eto
忠士 江藤
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Nippon Barrier Free Co Ltd
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Nippon Barrier Free Co Ltd
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a new use of component extracted from the ovarian film of fishes. <P>SOLUTION: This rough skin improving agent contains components extracted from the ovarian film of fishes. The ovarian film is the ovarian film of salmon, for example, and the components extracted from the ovarian film are extracted by processing the ovarian film with a proteolytic enzyme. The rough skin improving agent is formulated into a tablet, for example, and when it is taken as food such as health food, various cases of rough skin can be relaxed and improved. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

本発明は、肌荒れ改良剤に関するものである。   The present invention relates to a rough skin improving agent.

従来、魚類の卵巣膜(魚卵外皮)を予めオゾン水で処理した後、その構成タンパク質である筋原線維タンパク質を酵素分解してアミノ酸及びペプチドを抽出する方法が知られている(例えば特許文献1参照)。   Conventionally, a method of extracting amino acids and peptides by treating the ovarian membrane (fish egg rind) of fish with ozone water in advance and then enzymatically degrading myofibrillar protein, which is a constituent protein thereof, is known (for example, patent document). 1).

前記アミノ酸及びペプチドは、生理活性物質として、あるいは食品強化剤として用いることができるとされており、さらに詳しくは、ACE阻害活性を備え、血圧上昇抑制剤(降圧剤)として作用するとされている。   The amino acids and peptides can be used as physiologically active substances or as food fortifiers. More specifically, the amino acids and peptides have ACE inhibitory activity and act as blood pressure increase inhibitors (hypertensive agents).

しかしながら、魚類の卵巣膜から抽出された成分には、さらに多くの用途の開発が望まれる。
特開2004−73186号公報
However, it is desired to develop more applications for components extracted from the ovarian membrane of fish.
JP 2004-73186 A

本発明は、かかる事情に鑑み、魚類の卵巣膜から抽出された成分の新たな用途を提供することを目的とする。   In view of such circumstances, an object of the present invention is to provide a new use of a component extracted from the ovarian membrane of fish.

かかる目的を達成するために、本発明の肌荒れ改良剤は、魚類の卵巣膜から抽出された成分を含むことを特徴とする。   In order to achieve this object, the rough skin improving agent of the present invention is characterized by containing a component extracted from the ovarian membrane of fish.

生体においては、成年期を過ぎると加齢に伴って、肌の肌理が粗くなる、つややはりが無くなる、シワが深くなる等の肌荒れの諸症状が現れてくる。また、若年層においても、水分不足やストレス等によって肌のかさつき、吹き出物ができる等の肌荒れの諸症状を訴える人が多い。   In the living body, after the adulthood, with the aging, various symptoms of rough skin such as rough skin, loss of gloss, and deep wrinkles appear. In addition, many young people complain of various symptoms of rough skin, such as skin irritation and pimples due to lack of moisture or stress.

ところが、本発明の肌荒れ改良剤によれば、肌荒れの諸症状を緩和、改善することができる。   However, the rough skin improving agent of the present invention can alleviate and improve various symptoms of rough skin.

本発明の肌荒れ改良剤において、前記卵巣膜から抽出された成分は、該卵巣膜をタンパク分解酵素で処理することにより抽出された成分であることが好ましい。また、前記卵巣膜としては、例えば鮭の卵巣膜を挙げることができる。   In the rough skin improving agent of the present invention, the component extracted from the ovarian membrane is preferably a component extracted by treating the ovarian membrane with a proteolytic enzyme. Examples of the ovarian membrane include a spider ovarian membrane.

次に、添付の図面を参照しながら本発明の実施の形態についてさらに詳しく説明する。図1は本実施形態の肌荒れ改良剤を8週間摂取した後の肌状態と摂取中止から2週間後の肌状態との比較を示すグラフ、図2は本実施形態の肌荒れ改良剤を摂取した場合とプラセボ(偽薬)を摂取した場合とのシワ係数の経時的変化を示すグラフ、図3は本実施形態の肌荒れ改良剤を摂取した場合とプラセボを摂取した場合とのシワ係数の変化量を示すグラフ、図4は本実施形態の肌荒れ改良剤を摂取した場合とプラセボを摂取した場合とのIGF−1値の経時的変化を示すグラフ、図5は本実施形態の肌荒れ改良剤を摂取した場合とプラセボを摂取した場合とのIGF−1値の変化量を示すグラフである。   Next, embodiments of the present invention will be described in more detail with reference to the accompanying drawings. FIG. 1 is a graph showing a comparison between the skin condition after ingesting the skin roughness improving agent of this embodiment for 8 weeks and the skin condition after 2 weeks of ingestion, and FIG. 2 is the case of ingesting the skin roughness improving agent of this embodiment. And FIG. 3 shows the amount of change in the wrinkle coefficient between the case of taking the rough skin improving agent of this embodiment and the case of taking placebo. Graph, FIG. 4 is a graph showing changes over time in IGF-1 values when ingesting the rough skin improving agent of the present embodiment, and when ingesting placebo, FIG. 5 is a case of ingesting the rough skin improving agent of the present embodiment It is a graph which shows the variation | change_quantity of the IGF-1 value at the time of ingesting a placebo.

本実施形態の肌荒れ改良剤は、例えば鮭等の魚類の卵巣膜から抽出された成分(以下、卵巣膜抽出成分と略記する)を含む。前記卵巣膜抽出成分は、例えば、魚卵から分離された前記卵巣膜を酵素処理してタンパク質を抽出した溶液を濾過し、得られた濾液を乾燥させる方法等により得ることができる。   The skin roughness improving agent of the present embodiment includes, for example, a component extracted from the ovarian membrane of fish such as salmon (hereinafter abbreviated as ovarian membrane extracted component). The ovarian membrane extract component can be obtained by, for example, a method of filtering a solution obtained by extracting the protein by enzymatic treatment of the ovarian membrane separated from fish eggs and drying the obtained filtrate.

前記方法では、具体的には、まず、鮭の卵巣膜を原料とし、該卵巣膜に対して水を卵巣膜:水=1:1〜1:3の重量比で加えて撹拌、混合し、さらにタンパク分解酵素を卵巣膜の全量に対して1〜3重量%の範囲で添加し、45〜55℃の温度で30分間〜5時間、好ましくは2時間加熱する。このようにすると、前記卵巣膜の成分のうち、前記タンパク分解酵素で分解された成分が水中に溶出し、該成分の水溶液が得られる。   Specifically, in the method, first, the ovarian membrane of the pupa is used as a raw material, and water is added to the ovarian membrane in a weight ratio of ovarian membrane: water = 1: 1 to 1: 3, and the mixture is stirred and mixed. Furthermore, proteolytic enzyme is added in the range of 1 to 3% by weight with respect to the total amount of the ovarian membrane, and heated at a temperature of 45 to 55 ° C. for 30 minutes to 5 hours, preferably 2 hours. If it does in this way, the component decomposed | disassembled with the said proteolytic enzyme will elute in water among the components of the said ovary membrane, and the aqueous solution of this component will be obtained.

次に、前記水溶液に含まれている前記タンパク分解酵素を失活する。前記失活は、例えば、前記水溶液を90℃の温度で5分間加熱することにより行うことができる。   Next, the proteolytic enzyme contained in the aqueous solution is inactivated. The deactivation can be performed, for example, by heating the aqueous solution at a temperature of 90 ° C. for 5 minutes.

次に、前記水溶液を30メッシュ程度の金網で簡易濾過し、未分解の卵巣膜等の粗大物を除去する。そして、得られた濾液に活性炭を添加して、該濾液の脱臭、脱色、脱脂を行う。前記濾液の脱臭、脱色、脱脂は、前記原料としての卵巣膜の全量に対して2〜4重量%の範囲の活性炭を該濾液に添加し、例えば60℃の温度で30分間加熱することにより行うことができる。   Next, the aqueous solution is simply filtered through a wire mesh of about 30 mesh to remove coarse materials such as undecomposed ovarian membranes. Then, activated carbon is added to the obtained filtrate to deodorize, decolorize, and degrease the filtrate. The deodorization, decolorization, and degreasing of the filtrate is performed by adding activated carbon in the range of 2 to 4% by weight to the total amount of the ovarian membrane as the raw material and heating the filtrate at a temperature of 60 ° C. for 30 minutes, for example. be able to.

前記活性炭による脱臭、脱色、脱脂処理後、前記濾液を例えばフィルタープレスにより濾過し、得られた濾液を、減圧下、例えば60℃の温度で濃縮した後、例えば80℃の温度に10分間維持して滅菌する。そして、滅菌後の前記濾液をスプレードライにて乾燥させることにより、前記卵巣膜抽出成分を得ることができる。前記卵巣膜抽出成分は、アミノ酸、ペプチド、ビタミン、ミネラル、糖類、酵素、核酸及びその代謝物、各種成長因子、サイトカイン等を含んでいる。   After the deodorization, decolorization, and degreasing treatment with the activated carbon, the filtrate is filtered by, for example, a filter press, and the obtained filtrate is concentrated at a temperature of 60 ° C. under reduced pressure, for example, and then maintained at a temperature of 80 ° C. for 10 minutes, for example. And sterilize. Then, the ovarian membrane extract component can be obtained by drying the sterilized filtrate by spray drying. The ovarian membrane extract component contains amino acids, peptides, vitamins, minerals, sugars, enzymes, nucleic acids and their metabolites, various growth factors, cytokines, and the like.

本実施形態の肌荒れ改良剤は、前記卵巣膜抽出成分を、例えば錠剤等の形に製剤したものであり、例えば健康食品等の食品として摂取することにより、肌荒れの諸症状を緩和、改善することができる。   The rough skin improving agent of the present embodiment is prepared by formulating the ovarian membrane extract component in the form of, for example, a tablet. By taking it as a food such as a health food, various symptoms of rough skin are alleviated and improved. Can do.

次に、本発明の実施例と比較例とを示す。   Next, examples of the present invention and comparative examples will be described.

本実施例では、まず、鮭の卵巣膜抽出成分を錠剤の形に製剤して、肌荒れ改良剤を製造した。前記錠剤は、前記卵巣膜抽出物245mg、賦形剤(ラブリワックス(登録商標))5mgからなり、8mmの直径を備えている。   In this example, first, the ovarian membrane extract component of salmon was formulated in the form of tablets to produce a rough skin improving agent. The tablet consists of 245 mg of the ovarian membrane extract and 5 mg of excipient (Loveli wax (registered trademark)) and has a diameter of 8 mm.

次に、38〜42歳の健康な女性モニター10名に、前記錠剤を健康食品として1日当たり4錠、8週間に亘って摂取させた。なお、各モニターは、1ヶ月前からサプリメント、薬品(漢方薬を含む)の摂取を行っていない。   Next, 10 healthy female monitors aged 38 to 42 years old took 4 tablets per day for 8 weeks as a health food. Each monitor has not taken supplements or medicines (including herbal medicines) since one month ago.

そして、各モニターの自己申告による肌状態について、摂取開始前と、摂取開始から8週間目と、摂取中止から2週間後との状態を比較した。結果を図1に示す。   And about the skin state by self-report of each monitor, the state before the start of ingestion, the 8th week after the start of ingestion, and the state after 2 weeks after the ingestion were compared. The results are shown in FIG.

また、摂取開始前、摂取開始から4週間目、摂取開始から8週間目に、次のようにして目尻のシワの目立ち度を測定した。まず、日本電気株式会社製のダイレクトスキンアナライザー(以下「DSA」と記載する)を用いて、目尻にDSAのセンサー部を接触させる。このとき、DSAは、目尻の画像を取り込み、センサー部に内蔵された光源(UVストロボ)から320〜400nmの紫外線を皮膚に照射し、CCDカメラで表面画像を撮影した後に、画像全体の輝度分布(0〜63段階)を求め、2値化画像を作成する。次に、得られた2値化画像を9×9のメッシュに分割し、1メッシュ中の黒画素比率が60%以上であるメッシュの数(以下、「シワ係数」という)を求める。シワ係数は、シワの目立ち度を示しており、シワ係数が大きいほどシワが目立つことを意味している。   In addition, before the start of ingestion, 4 weeks after the start of ingestion and 8 weeks after the start of ingestion, the degree of wrinkle conspicuousness was measured as follows. First, using a direct skin analyzer (hereinafter referred to as “DSA”) manufactured by NEC Corporation, the sensor portion of the DSA is brought into contact with the corner of the eye. At this time, the DSA captures an image of the corner of the eye, irradiates the skin with ultraviolet light of 320 to 400 nm from a light source (UV strobe) built in the sensor unit, and takes a surface image with a CCD camera. (0 to 63 steps) is obtained and a binarized image is created. Next, the obtained binarized image is divided into 9 × 9 meshes, and the number of meshes (hereinafter referred to as “wrinkle coefficient”) having a black pixel ratio of 60% or more in one mesh is obtained. The wrinkle coefficient indicates the degree of wrinkle conspicuous, and the larger the wrinkle coefficient, the more noticeable the wrinkle is.

前記モニター10人のシワ係数の平均値を図2に、摂取開始から4週間目まで、摂取開始から8週間目までのシワ係数の平均値の変化量を図3に、それぞれ示す。なお、図2中、摂取開始前を「0週」、摂取開始から4週間目を「4週」、摂取開始から8週間目を「8週」と記載し、図3中、摂取開始から4週間目までを「0−4週」、摂取開始から8週間目までを「0−8週」と記載する。   The average value of the wrinkle coefficient of the 10 monitors is shown in FIG. 2, and the amount of change in the average value of the wrinkle coefficient from the start of intake to the 4th week is shown in FIG. In FIG. 2, “0 week” before the start of intake, “4 weeks” after 4 weeks from the start of intake, and “8 weeks” after 8 weeks from the start of intake are shown in FIG. The week up to the week 0 is described as “0-4 weeks”, and the period from the start of intake to the 8th week is described as “0-8 weeks”.

さらに、摂取開始前、摂取開始から4週間目、摂取開始から8週間目に、血液検査を行い、インシュリン成長因子−1(IGF−1:Insulin−like Growth Factor−1)値を測定した。なお、IGF−1とは、インシュリンに非常に似た構造を持つポリペプチドである。IGF−1値は加齢に伴って低下し、一旦下降したIGF−1値が再度上昇することはないといわれている。   Further, before the start of ingestion, 4 weeks after the start of ingestion and 8 weeks after the start of ingestion, blood tests were performed to measure insulin growth factor-1 (IGF-1: Insulin-like Growth Factor-1) values. IGF-1 is a polypeptide having a structure very similar to insulin. It is said that the IGF-1 value decreases with aging, and the once lowered IGF-1 value does not increase again.

前記モニター10人のIGF−1値の平均値を図4に、摂取開始から4週間目まで、摂取開始から8週間目までのIGF−1値の平均値の変化量を図5に、それぞれ示す。
〔比較例〕
本比較例では、まず、前記実施例の肌荒れ改良剤に代えて、コーンスターチ125mg、乳糖125mgからなるプラセボ(偽薬)を、直径8mmの錠剤の形に製剤した。
The average value of the IGF-1 values of the 10 monitors is shown in FIG. 4, and the amount of change in the average value of the IGF-1 value from the start of intake to the fourth week is shown in FIG. .
[Comparative example]
In this comparative example, first, a placebo (placebo) consisting of 125 mg of corn starch and 125 mg of lactose was formulated in the form of a tablet having a diameter of 8 mm instead of the rough skin improving agent of the above-mentioned example.

次に、前記実施例とは異なる38〜42歳の健康な女性モニター10名に、前記偽薬のカプセル剤を1日当たり4錠、8週間に亘って投与した。なお、各モニターは、1ヶ月前からサプリメント、薬品(漢方薬を含む)の摂取を行っていない。   Next, the placebo capsules were administered 4 times a day for 8 weeks to 10 healthy female monitors aged 38 to 42 years different from the Examples. Each monitor has not taken supplements or medicines (including herbal medicines) since one month ago.

そして、前記実施例と全く同一にして、目尻のシワの目立ち度とIGF−1値とを測定した。前記モニター10人のシワ係数の平均値を図2に、摂取開始から4週間目、摂取開始から8週間目のシワ係数の平均値の変化量を図3に、前記モニター10人のIGF−1値の平均値を図4に、摂取開始から4週間目、摂取開始から8週間目のIGF−1値の平均値の変化量を図5に、それぞれ示す。   Then, the degree of wrinkle conspicuousness and the IGF-1 value were measured in exactly the same manner as in the previous example. The average value of the wrinkle coefficient of the 10 monitors is shown in FIG. 2, the amount of change in the average value of the wrinkle coefficient at the 4th week from the start of intake and the 8th week from the start of intake is shown in FIG. The average value is shown in FIG. 4, and the amount of change in the average value of the IGF-1 value after 4 weeks from the start of intake and 8 weeks from the start of intake is shown in FIG.

図1から、本実施形態の肌荒れ改良剤(実施例)によれば、摂取開始前の肌状態よりも摂取開始から8週間目の肌状態の方が優れているとともに、摂取開始から8週間目の肌状態よりも摂取中止から2週間後の肌状態の方がさらに優れていることが明らかである。   From FIG. 1, according to the rough skin improving agent (Example) of this embodiment, the skin state at the 8th week from the start of intake is superior to the skin state before the start of intake, and the 8th week from the start of intake. It is clear that the skin condition after 2 weeks from the discontinuation of intake is even better than the skin condition.

従って、本実施形態の肌荒れ改良剤を摂取したことによって、肌荒れの諸症状が緩和、改善したと考えられる。さらに、本実施形態の肌荒れ改良剤には、効果の持続性があると考えられる。   Therefore, it is considered that various symptoms of rough skin were alleviated and improved by taking the rough skin improving agent of this embodiment. Furthermore, the rough skin improving agent of the present embodiment is considered to have a sustained effect.

また、図2から、本実施形態の肌荒れ改良剤によれば、摂取開始から4週間目には摂取開始前に比較してシワ係数が低下しており、摂取開始から8週間目には摂取開始から4週間目よりもさらに低下しており、単調に低下していることが明らかである。これに対して、プラセボ(比較例)によれば、摂取開始から4週間目には摂取開始前に比較してシワ係数が低下しているものの、摂取開始から8週間目には摂取開始前と同程度であり、単調な低下ではないことが明らかである。   Further, from FIG. 2, according to the rough skin improving agent of the present embodiment, the wrinkle coefficient is lower than that before the start of intake at 4 weeks from the start of intake, and the start of intake at 8 weeks after the start of intake. From the 4th week, it is further lower than the 4th week, and it is clear that it is decreasing monotonously. On the other hand, according to the placebo (comparative example), although the wrinkle coefficient is lower at 4 weeks after the start of intake than before the start of intake, It is clear that it is similar and not a monotonous decline.

また、図3から、本実施形態の肌荒れ改良剤によれば、シワ係数の低下量がプラセボよりも大きいことが明らかである。   Moreover, it is clear from FIG. 3 that according to the rough skin improving agent of the present embodiment, the amount of decrease in the wrinkle coefficient is larger than that of the placebo.

従って、本実施形態の肌荒れ改良剤を摂取したことによって、皮膚表面内側の新陳代謝が促進され、真皮部分の線維芽細胞の構造とヒアルロン酸等を含む細胞外マトリックス(ECM)とが整えられたことにより、シワの深さが浅くなったと考えられる。   Therefore, by taking the skin roughness improving agent of this embodiment, the metabolism inside the skin surface was promoted, and the structure of the dermal fibroblasts and the extracellular matrix (ECM) containing hyaluronic acid and the like were prepared. It is thought that the depth of wrinkles became shallow.

さらに、図4から、本実施形態の肌荒れ改良剤によれば、摂取開始から4週間目には摂取開始前に比較してIGF−1値が増加しており、摂取開始から8週間目には摂取開始から4週間目よりもさらに増加しており、単調に増加していることが明らかである。これに対して、プラセボによれば、摂取開始から8週間目には摂取開始前に比較してIGF−1値が増加しているものの、摂取開始から4週間目には摂取開始前に比較して一旦IGF−1値が減少しており、単調な増加ではないことが明らかである。   Furthermore, from FIG. 4, according to the rough skin improving agent of the present embodiment, the IGF-1 value increased compared to before the start of intake at 4 weeks from the start of intake, and after 8 weeks from the start of intake. It is further increased than the 4th week from the start of ingestion, and it is clear that the increase is monotonous. On the other hand, according to the placebo, although the IGF-1 value increased in the 8th week from the start of the intake compared to before the start of the intake, it was compared in the 4th week after the start of the intake before the start of the intake. It is clear that the IGF-1 value has once decreased and is not a monotonous increase.

また、図5から、本実施形態の肌荒れ改良剤によれば、IGF−1値の増加量がプラセボよりも大きいことが明らかである。   Moreover, it is clear from FIG. 5 that according to the rough skin improving agent of this embodiment, the increase amount of IGF-1 value is larger than the placebo.

従って、本実施形態の肌荒れ改良剤を摂取したことによって、IGF−1値が上昇したと考えられる。また、前述の肌荒れの諸症状の緩和、改善は、IGF−1値の上昇も一因であると考えられる。   Therefore, it is considered that the IGF-1 value increased by taking the rough skin improving agent of the present embodiment. In addition, the above-described alleviation and improvement of various symptoms of rough skin are considered to be caused by an increase in IGF-1 value.

本発明に係る肌荒れ改良剤を8週間摂取した後の体調と摂取中止から2週間後の肌状態との比較を示すグラフ。The graph which shows the comparison with the physical condition after ingesting the rough skin improving agent which concerns on this invention for 8 weeks, and the skin state after 2 weeks from ingestion. 本発明に係る肌荒れ改良剤を摂取した場合とプラセボ(偽薬)を摂取した場合とのシワ係数の経時的変化を示すグラフ。The graph which shows the time-dependent change of the wrinkle coefficient when the skin roughness improving agent according to the present invention is ingested and when the placebo (placebo) is ingested. 本発明に係る肌荒れ改良剤を摂取した場合とプラセボを摂取した場合とのシワ係数の変化量を示すグラフ。The graph which shows the variation | change_quantity of the wrinkle coefficient when the skin roughness improving agent which concerns on this invention is ingested, and the case where a placebo is ingested. 本発明に係る肌荒れ改良剤を摂取した場合とプラセボを摂取した場合とのIGF−1値の経時的変化を示すグラフ。The graph which shows the time-dependent change of the IGF-1 value when the skin roughness improving agent according to the present invention is ingested and when the placebo is ingested. 本発明に係る肌荒れ改良剤を摂取した場合とプラセボを摂取した場合とのIGF−1値の変化量を示すグラフ。The graph which shows the variation | change_quantity of the IGF-1 value when the skin roughness improving agent which concerns on this invention is ingested, and the case where a placebo is ingested.

符号の説明Explanation of symbols

符号なし。   No sign.

Claims (3)

魚類の卵巣膜から抽出された成分を含むことを特徴とする肌荒れ改良剤。   A rough skin improving agent comprising a component extracted from a ovarian membrane of fish. 請求項1記載の肌荒れ改良剤において、前記卵巣膜から抽出された成分は、該卵巣膜をタンパク分解酵素で処理することにより抽出された成分であることを特徴とする肌荒れ改良剤。   The rough skin improving agent according to claim 1, wherein the component extracted from the ovarian membrane is a component extracted by treating the ovarian membrane with a proteolytic enzyme. 請求項1または請求項2記載の肌荒れ改良剤において、前記卵巣膜は、鮭の卵巣膜であることを特徴とする肌荒れ改良剤。   The rough skin improving agent according to claim 1 or 2, wherein the ovarian membrane is a ovarian membrane of a pupa.
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JP2010083762A (en) * 2008-09-29 2010-04-15 Kyowa Yakuhin Kk Climacteric disorders-improving agent and dietary supplement

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EP1938866B1 (en) * 2006-12-22 2011-09-21 Nippon Barrier Free Co. Ltd. Cosmetic product comprising a component extracted from a Salmonidae fish ovarian membrane
JP5171752B2 (en) * 2009-07-23 2013-03-27 株式会社ノエビア Topical skin preparation
JP6085137B2 (en) * 2012-10-02 2017-02-22 株式会社日本バリアフリー Anti-aging agent

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010083762A (en) * 2008-09-29 2010-04-15 Kyowa Yakuhin Kk Climacteric disorders-improving agent and dietary supplement

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