JP5932783B2 - Wrinkle improving composition containing placenta-derived component - Google Patents

Wrinkle improving composition containing placenta-derived component Download PDF

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JP5932783B2
JP5932783B2 JP2013515211A JP2013515211A JP5932783B2 JP 5932783 B2 JP5932783 B2 JP 5932783B2 JP 2013515211 A JP2013515211 A JP 2013515211A JP 2013515211 A JP2013515211 A JP 2013515211A JP 5932783 B2 JP5932783 B2 JP 5932783B2
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JPWO2012157734A1 (en
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英矢 田邊
英矢 田邊
賢一 永峰
賢一 永峰
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Nichirei Biosciences Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728Hyaluronic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48Reproductive organs
    • A61K35/50Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00Make-up preparations; Body powders; Preparations for removing make-up
    • A61Q1/02Preparations containing skin colorants, e.g. pigments
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/10Washing or bathing preparations

Description

本発明はブタ等の胎盤に由来する成分(特に、胎盤の高圧処理物の液状画分)を有効成分として含有するシワ改善用組成物に関する。   The present invention relates to a composition for improving wrinkles comprising a component derived from a placenta such as a pig (particularly, a liquid fraction of a high-pressure treated product of placenta) as an active ingredient.

シワは加齢によって増加する老化現象のひとつである。しかし、シワの発生の原因としては老化によるもの以外にも皮膚水分量の低下や紫外線による皮膚組織の損傷など多くの事象がある。これらの原因によるシワは、美容の上では大きな課題である。   Wrinkles are one of the aging phenomena that increase with aging. However, wrinkles are caused by many events other than those caused by aging, such as a decrease in skin water content and skin tissue damage caused by ultraviolet rays. Wrinkles due to these causes are a major issue in beauty.

そのため、シワを改善させる組成物については多く検討されている。例えば、皮膚外用剤と経口用組成物を同時に作用させることによりシワ改善用の美容セットを提供する方法(特許文献1)やアスタキサンチンと真皮マトリックス成分安定作用を有する化合物または抽出物を含むことを特徴とするシワ改善組成物(特許文献2)など、複数の成分組成からなる抗シワ作用を有する組成物が報告されている。複数の成分を含有する組成物に、プラセンタエキス(胎盤エキス)を配合する技術も多く報告されているが、プラセンタエキスは、美白作用、代謝活性化作用、細胞賦活作用、活性酸素除去作用、創傷修復作用などを有する有効成分として配合されており、プラセンタエキスを、シワを改善するための有効成分として用いられているわけではない。   Therefore, many studies have been made on compositions that improve wrinkles. For example, a method for providing a cosmetic set for improving wrinkles by simultaneously acting an external preparation for skin and an oral composition (Patent Document 1), and a compound or extract having an astaxanthin and dermal matrix component stabilizing action A composition having an anti-wrinkle action comprising a plurality of component compositions such as a wrinkle improving composition (Patent Document 2) has been reported. Many techniques for combining placenta extract (placenta extract) with a composition containing multiple components have been reported. However, placenta extract is used for whitening, metabolic activation, cell activation, active oxygen removal, wounds, etc. It is formulated as an active ingredient having a restorative action and the placenta extract is not used as an active ingredient for improving wrinkles.

また、ブタ若しくはウマの胎盤を酵素などで加水分解して得られる水溶性成分とポリフェノールを配合した組成物で、紫外線を照射したモデル動物のシワを軽減化する方法(特許文献3)、ヒト胎盤エキスを紙状にすることを特徴とするシワ・シミ改善紙(特許文献4)、細胞・組織・増殖因子にノイラミン酸類及び/又はプラセンタエキス成分を配合することを特徴とする美容組成物をシワやたるみの改善目的に使用する方法(特許文献5)などが報告されているが、さらに効果が明確なシワの改善方法が望まれている。   In addition, a method for reducing wrinkles in a model animal irradiated with ultraviolet rays using a composition comprising a water-soluble component obtained by hydrolyzing pig or horse placenta with an enzyme and polyphenol (Patent Document 3), human placenta A wrinkle / wrinkle improving paper characterized by making the extract into a paper form (Patent Document 4), and a beauty composition characterized by blending neuraminic acids and / or placenta extract components into cells / tissues / growth factors. Although a method (patent document 5) used for the purpose of improving slackness has been reported, a wrinkle improving method with a clearer effect is desired.

一方、食品組成物等を製造するための技術として原料を高圧処理する技術が知られている。特許文献6には蛋白質分解酵素を含む食品素材に対して、40〜60℃の温度域で50〜100 MPaの圧力を負荷して保持することにより微生物の増殖を抑制しながら酵素の作用を促進することを含む、酵素分解法による調味料の製造方法が開示されている。   On the other hand, as a technique for producing a food composition or the like, a technique for processing a raw material under high pressure is known. Patent Document 6 discloses that food materials containing proteolytic enzymes promote the action of enzymes while suppressing the growth of microorganisms by holding a pressure of 50 to 100 MPa in a temperature range of 40 to 60 ° C. A method for producing a seasoning by an enzymatic decomposition method is disclosed.

特許第4666537号公報Japanese Patent No. 4666537 特開2011-63563号公報JP 2011-63563 A 特開2002-212046号公報JP 2002-212046 A 特開2004-182706号公報JP 2004-182706 A 特開2009-234980号公報JP 2009-234980 特許第3475328号公報Japanese Patent No. 3475328

本発明の課題は、保湿作用を有し優れたシワ改善効果を有するシワ改善用組成物を提供することにある。   The subject of this invention is providing the composition for wrinkle improvement which has a moisturizing effect and has the outstanding wrinkle improvement effect.

本発明者らは上記課題を解決するために鋭意研究した結果、胎盤を高圧処理することにより保湿成分であるヒアルロン酸を含有する液状画分(プラセンタエキス)が得られること、そして、該液状画分が保湿作用を有し優れたシワ改善効果を有することを見出し、本発明を完成させるに至った。   As a result of intensive studies to solve the above problems, the present inventors have obtained a liquid fraction (placenta extract) containing hyaluronic acid, which is a moisturizing component, by high-pressure treatment of the placenta, and the liquid fraction It has been found that the minute has a moisturizing action and has an excellent wrinkle improving effect, and has led to the completion of the present invention.

本発明は以下の発明を包含する。   The present invention includes the following inventions.

(1) 胎盤の高圧処理物の液状画分又は該画分の処理物を含有する、シワ改善用組成物。 (1) A wrinkle improving composition containing a liquid fraction of a high-pressure treated placenta or a treated product of the fraction.

(2) 前記胎盤の高圧処理物の液状画分又は該画分の処理物に由来するヒアルロン酸を0.02w/w%以上含有する、(1)に記載の組成物。 (2) The composition according to (1), containing 0.02 w / w% or more of a liquid fraction of the high-pressure treated placenta or hyaluronic acid derived from the treated fraction.

(3) 前記高圧処理の圧力が50〜150MPaである、(1)または(2)に記載の組成物。 (3) The composition according to (1) or (2), wherein the pressure of the high-pressure treatment is 50 to 150 MPa.

(4) 胎盤由来成分を含有する、シワ改善用組成物であって、
前記成分が、固形分重量1に対して窒素重量が0.08以上である成分であり、かつ、前記組成物の全量に対して、前記成分に由来するヒアルロン酸を0.02w/w%以上、前記成分の固形分を0.5w/w%以上含有する、前記組成物。
(4) A wrinkle improving composition containing a placenta-derived component,
The component is a component having a nitrogen weight of 0.08 or more with respect to a solid content weight of 1, and 0.02 w / w% or more of the hyaluronic acid derived from the component with respect to the total amount of the composition. The above-mentioned composition containing a solid content of 0.5 w / w% or more.

(5) 前記胎盤由来成分が、胎盤の高圧処理物の液状画分又は該画分の処理物である、(4)に記載の組成物。 (5) The composition according to (4), wherein the placenta-derived component is a liquid fraction of a high-pressure treated product of placenta or a treated product of the fraction.

(6) 前記高圧処理の圧力が50〜150MPaである、(5)に記載の組成物。 (6) The composition according to (5), wherein the pressure of the high-pressure treatment is 50 to 150 MPa.

(7) 皮膚にうるおいを与え、乾燥によるシワを目立たなくするためのシワ改善用組成物である、(1)〜(6)のいずれかの組成物。 (7) The composition according to any one of (1) to (6), which is a composition for improving wrinkles for imparting moisture to skin and making wrinkles due to drying inconspicuous.

(8) (1)〜(6)のいずれかに記載の組成物を含む、化粧品または医薬品(医薬部外品を含む)。 (8) Cosmetics or pharmaceuticals (including quasi drugs) comprising the composition according to any one of (1) to (6).

(9) シワ改善用組成物の製造のための、胎盤の高圧処理物の液状画分又は該画分の処理物の使用。 (9) Use of the liquid fraction of the high-pressure treated placenta or the treated product of the fraction for the production of a composition for improving wrinkles.

(10) 胎盤の高圧処理物の液状画分又は該画分の処理物の、シワ改善のための使用。 (10) Use of the liquid fraction of the high-pressure treated placenta or the treated product of the fraction for wrinkle improvement.

(11) 胎盤の高圧処理物の液状画分又は該画分の処理物を美容のために皮膚に適用し、シワを改善する方法。 (11) A method for improving wrinkles by applying a liquid fraction of a placental high-pressure treated product or a treated product of the fraction to the skin for cosmetic purposes.

本願は、2011年5月18日に出願された日本国特許出願2011−111299号の優先権を主張するものであり、該特許出願の明細書に記載される内容を包含する。   This application claims the priority of the Japan patent application 2011-111299 for which it applied on May 18, 2011, and includes the content described in the specification of this patent application.

本発明のシワ改善用組成物は、保湿作用により顔面のシワを目立たなくする効果があり、美容上において有用である。   The composition for improving wrinkles of the present invention has an effect of making facial wrinkles inconspicuous by a moisturizing action, and is useful in cosmetics.

図1は本発明のシワ改善用組成物(高圧抽出プラセンタエキス)を塗布した群(n=21)及び無塗布群(n=21)の目尻部位の角質水分量の経時変化を示す。FIG. 1 shows changes with time in the amount of horny water in the eye corners of the group (n = 21) to which the composition for improving wrinkles (high-pressure extraction placenta extract) of the present invention is applied and the non-application group (n = 21). 図2は本発明のシワ改善用組成物(高圧抽出プラセンタエキス)を塗布した群(n=21)及び無塗布群(n=21)の目視評価によるシワグレードの経時変化を示す。FIG. 2 shows changes over time in the wrinkle grade by visual evaluation of the group (n = 21) to which the composition for improving wrinkles (high-pressure extraction placenta extract) of the present invention was applied and the non-application group (n = 21).

本発明において原料として利用できる胎盤としてはブタ、ウマ等の胎盤が挙げられ、好適にはブタの胎盤である。ブタの品種は特に限定されない。胎盤は高圧処理等の処理の前に適宜、洗浄及び粉砕される。   Examples of the placenta that can be used as a raw material in the present invention include placenta such as pigs and horses, with pig placenta being preferred. The breed of pig is not particularly limited. The placenta is appropriately washed and pulverized prior to processing such as high pressure processing.

高圧処理の圧力は特に限定されないが、典型的には50〜150MPa、好ましくは50〜100MPa、より好ましくは100MPaである。高圧処理時の温度は特に限定されず胎盤の状態等により適宜選択すればよいが、典型的には45〜65℃の範囲である。高圧処理の時間は特に限定されないが、典型的には1〜24時間の範囲である。高圧処理を実施する装置は特に限定されず、例えば特許文献6に記載された装置等を用いることができる。   The pressure of the high-pressure treatment is not particularly limited, but is typically 50 to 150 MPa, preferably 50 to 100 MPa, more preferably 100 MPa. The temperature during the high-pressure treatment is not particularly limited and may be appropriately selected depending on the condition of the placenta and the like, but typically ranges from 45 to 65 ° C. The time for the high pressure treatment is not particularly limited, but is typically in the range of 1 to 24 hours. An apparatus for performing the high-pressure treatment is not particularly limited, and for example, an apparatus described in Patent Document 6 can be used.

胎盤の高圧処理物から、遠心分離、ろ過、圧搾等の通常の固液分離手段により固形状画分を分離除去し、液状画分(エキス)を取得する。液状画分は必要に応じてステロイドホルモン除去処理等の処理を施してもよい。液状画分はそれ自体がプラセンタエキスとして利用可能であるため、本明細書では胎盤の高圧処理物から分離された液状画分を「プラセンタエキス」、「エキス」又は「高圧抽出プラセンタエキス」と称する場合がある。原料として用いられる胎盤の70〜90%量を液状画分として回収することができる。   A solid fraction is separated and removed from a high-pressure treated product of the placenta by ordinary solid-liquid separation means such as centrifugation, filtration, and pressing to obtain a liquid fraction (extract). The liquid fraction may be subjected to treatment such as steroid hormone removal treatment as necessary. Since the liquid fraction itself can be used as a placenta extract, in this specification, the liquid fraction separated from the high-pressure treated placenta is referred to as “placenta extract”, “extract” or “high-pressure extraction placenta extract”. There is a case. 70-90% of the placenta used as a raw material can be recovered as a liquid fraction.

本発明において「液状画分の処理物」とは、液状画分の減圧蒸留等により濃縮した濃縮物、凍結乾燥法等により乾燥した乾燥物(粉末化された乾燥物も含む)や、液状画分、濃縮物又は乾燥物を水等の溶媒で希釈した希釈物が挙げられる。液状画分を更に水や有機溶媒等の溶媒により抽出処理して得られた抽出物も該画分の処理物に包含される。   In the present invention, “processed product of liquid fraction” means a concentrate concentrated by vacuum distillation or the like of a liquid fraction, a dried product (including powdered dried product) dried by a freeze-drying method, etc. And a diluted product obtained by diluting a concentrated product or a dried product with a solvent such as water. An extract obtained by further extracting the liquid fraction with a solvent such as water or an organic solvent is also included in the processed product of the fraction.

胎盤の高圧処理物の液状画分又は該画分の処理物は、精製水により抽出された抽出物よりも窒素含量、遊離アミノ酸含量が高く、ヒアルロン酸を含有する。このことは、高圧処理により微生物の増殖が抑制されるとともに細胞が圧力により破砕され、通常は水に溶解しにくい成分が可溶化されるためであると考えられる。上記手順による胎盤の高圧処理物の液状画分又は該画分の処理物の製造方法は、ペプシン等のタンパク質分解酵素添加による酵素分解や、熱、酸、アルカリ等による加水分解が含まれないため、有用な成分(例えば有用なポリペプチド(タンパク質よりも分子量の小さなアミノ酸が複数結合した成分))が分解又は変性される可能性が低いため好ましい。上記手順による胎盤の高圧処理物の液状画分又は該画分の処理物の製造方法は、胎盤を凍結し、融解させる凍結融解法による抽出法と異なり、抽出効率が高い点、臭気を低減できる点、及び、抽出物中に微生物などが繁殖する可能性が低い点において有利である。   The liquid fraction of the high-pressure treated placenta or the treated product thereof has a higher nitrogen content and free amino acid content than the extract extracted with purified water, and contains hyaluronic acid. This is considered to be because the growth of microorganisms is suppressed by high-pressure treatment, the cells are crushed by pressure, and the components that are usually difficult to dissolve in water are solubilized. The liquid fraction of the high-pressure treated placenta by the above procedure or the method for producing the treated fraction does not include enzymatic degradation by addition of proteolytic enzymes such as pepsin or hydrolysis by heat, acid, alkali, etc. It is preferable because a useful component (for example, a useful polypeptide (a component in which a plurality of amino acids having a molecular weight smaller than that of a protein is bound)) is less likely to be degraded or denatured. The liquid fraction of the placenta high-pressure treated product by the above procedure or the method of producing the treated product of the fraction is different from the extraction method by the freeze-thaw method in which the placenta is frozen and thawed. This is advantageous in that the microorganisms and the like are less likely to propagate in the extract.

本発明のシワ改善用組成物は、胎盤の高圧処理物の液状画分又は該画分の処理物を有効成分として含有し、かつ、保湿作用及びシワ改善作用を奏する種々の形態で提供されることができる。胎盤の高圧処理物の液状画分又は該画分の処理物自体をシワ改善用組成物として用いることもできる。本発明のシワ改善用組成物は皮膚外用剤として用いることが好ましく、化粧品、医薬部外品、医薬品等の形態で提供することができる。   The composition for improving wrinkles of the present invention contains a liquid fraction of a high-pressure treated placenta or a treated product of the fraction as an active ingredient, and is provided in various forms that exhibit a moisturizing action and a wrinkle improving action. be able to. The liquid fraction of the placental high-pressure treated product or the treated product itself of the fraction can also be used as a wrinkle-improving composition. The composition for improving wrinkles of the present invention is preferably used as an external preparation for skin, and can be provided in the form of cosmetics, quasi drugs, pharmaceuticals and the like.

皮膚外用剤は、化粧品、医薬部外品及び医薬品の製剤化のために通常使用される成分を用いて製剤化することが可能である。本発明のシワ改善用組成物には、他の有効成分が更に含まれてもよい。製剤化用成分及び他の有効成分としては、例えば、精製水、アルコール類、油性物質、保湿剤、増粘剤、防腐剤、乳化剤、生薬成分、紫外線吸収剤、色素、美白剤、香料、乳化安定剤、pH調製剤等が挙げられる。皮膚外用剤の剤型は限定されるものではなく、液状、クリーム状、軟膏状、ローション状、ゲル状、パック状、スティック状など、どのような形態でもよいが、好ましくは液状である。また、皮膚外用剤の種類としては、例えば、化粧水、乳液、ジェル、美容液、一般クリーム、パック、マスク、洗顔料、化粧石鹸、ファンデーション、ボディローション等が挙げられるが、これらに限定はされない。また、上記の種々の形態の製品における本発明のシワ改善用組成物の配合量は、シワ改善効果を発揮できる量であればよく、対象製品の一般的な使用量、製品の形態、効能・効果、及びコストなどを考慮して適宜設定すればよい。 The external preparation for skin can be formulated using ingredients usually used for the preparation of cosmetics, quasi drugs and pharmaceuticals. The wrinkle improving composition of the present invention may further contain other active ingredients. Examples of ingredients for formulation and other active ingredients include purified water, alcohols, oily substances, moisturizers, thickeners, preservatives, emulsifiers, herbal medicine ingredients, ultraviolet absorbers, dyes, whitening agents, perfumes, and emulsifiers. Stabilizers, pH adjusters and the like can be mentioned. The dosage form of the external preparation for skin is not limited, and may be any form such as liquid, cream, ointment, lotion, gel, pack or stick, but is preferably liquid. Examples of the external skin preparation include, but are not limited to, lotion, milky lotion, gel, cosmetic liquid, general cream, pack, mask, facial cleanser, cosmetic soap, foundation, body lotion and the like. . In addition, the blending amount of the composition for improving wrinkles of the present invention in the above-mentioned various forms of products may be an amount that can exhibit the effect of improving wrinkles. What is necessary is just to set suitably in consideration of an effect, cost, etc.

また、本発明のシワ改善用組成物は、皮膚外用剤のみならず、経口製剤として用いてもよく、飲食品、好ましくは、シワ改善を目的とした美容ドリンク、美容用健康食品に配合することもできる。   In addition, the composition for improving wrinkles of the present invention may be used not only as an external preparation for skin but also as an oral preparation, and is incorporated into foods and drinks, preferably beauty drinks and beauty health foods for the purpose of improving wrinkles. You can also.

本発明のシワ改善用組成物では、有効成分として用いられる胎盤の高圧処理物の液状画分又は該画分の処理物が、固形分(蒸発残留物)重量1に対する窒素重量が0.08以上、好ましくは0.10〜0.15の成分であることが好ましい。また本発明のシワ改善用組成物は、組成物の全量に対して、前記有効成分に由来するヒアルロン酸を0.02w/w%以上、好ましくは0.03〜0.12w/w%、前記有効成分に由来する固形分を0.5w/w%以上、好ましくは0.55〜1.0w/w%、より好ましくは0.60〜0.65w/w%含有することが好ましい。   In the composition for improving wrinkles of the present invention, the liquid fraction of the high-pressure treated placenta used as an active ingredient or the treated product of this fraction has a nitrogen weight of 0.08 or more, preferably 1 solid content (evaporation residue). Is preferably a component of 0.10 to 0.15. In addition, the composition for improving wrinkles of the present invention has a hyaluronic acid derived from the active ingredient of 0.02 w / w% or more, preferably 0.03-0.12 w / w%, derived from the active ingredient, based on the total amount of the composition. The solid content is preferably 0.5 w / w% or more, preferably 0.55 to 1.0 w / w%, more preferably 0.60 to 0.65 w / w%.

更に、胎盤の高圧処理物の液状画分又は該画分の処理物を有効成分として用いる実施形態には限定されず、上記と同様の組成を有する、胎盤由来成分を有効成分として含有するシワ改善用組成物もまた本発明の範囲に包含される。「胎盤由来成分」とは胎盤を処理して得られる組成物(胎盤処理物)を指し、複数種の物質を含み得る。すなわち本発明は、固形分(蒸発残留物)重量1に対する窒素重量が0.08以上、好ましくは0.10〜0.15である胎盤由来成分を、組成物の全量に対して前記成分に由来するヒアルロン酸を0.02w/w%以上、好ましくは0.03〜0.12w/w%、前記成分に由来する固形分を0.5w/w%以上、好ましくは0.55〜1.0w/w%、より好ましくは0.60〜0.65w/w%となるように含有するシワ改善用組成物を提供する。   Furthermore, it is not limited to the embodiment using the liquid fraction of the high-pressure treated product of placenta or the treated product of the fraction as an active ingredient, and it has a composition similar to that described above and contains a placenta-derived component as an active ingredient. Compositions are also included within the scope of the present invention. The “placenta-derived component” refers to a composition (placenta processed product) obtained by treating the placenta, and may contain a plurality of types of substances. That is, the present invention relates to a placenta-derived component having a nitrogen weight of 0.08 or more, preferably 0.10 to 0.15 relative to the solid content (evaporation residue) weight of 1, and 0.02 w of hyaluronic acid derived from the component with respect to the total amount of the composition. / w% or more, preferably 0.03 to 0.12 w / w%, solid content derived from the above components is 0.5 w / w% or more, preferably 0.55 to 1.0 w / w%, more preferably 0.60 to 0.65 w / w% A composition for improving wrinkles is provided.

本発明のシワ改善用組成物は、シワ改善作用のなかでも特に皮膚にうるおいを与え、乾燥によるシワを目立たなくする作用を有する。   The wrinkle-improving composition of the present invention has an effect of imparting moisture to the skin, and making wrinkles due to drying inconspicuous among the wrinkle-improving effects.

以下、実施例に基づき本発明を説明するが、本発明の範囲は実施例には限定されない。   EXAMPLES Hereinafter, although this invention is demonstrated based on an Example, the scope of the present invention is not limited to an Example.

(実施例1)高圧抽出プラセンタエキスの製造および成分分析ならびに評価試験
実験1: 高圧抽出プラセンタエキスの製造法(本発明品)
健常な妊娠3〜4ヶ月の種豚から得られた胎盤2770gを解凍し、低温の精製水により血液等を十分に洗浄除去する。洗浄された胎盤は、ワーリングブレンダーにより粉砕する。粉砕された胎盤をポリエチレン製袋に入れ、高圧処理装置(東洋高圧社製)により100MPa、16時間、50℃で処理する。
(Example 1) Production and component analysis of high-pressure extraction placenta extract and evaluation test experiment 1: Production method of high-pressure extraction placenta extract (product of the present invention)
Thaw 2770 g of placenta obtained from a healthy pig of 3-4 months of gestation and thoroughly wash and remove blood etc. with low temperature purified water. The washed placenta is crushed with a Waring blender. The crushed placenta is placed in a polyethylene bag and processed at 100 MPa for 16 hours at 50 ° C. using a high-pressure processing device (manufactured by Toyo Koatsu Co., Ltd.).

高圧処理豚胎盤を、5000回転/分、30分、5℃で遠心分離処理し、固形分を分離し、上清2210gを回収した。この上清を0.2μmのフィルター(日本ポール社製)でろ過し、ステロイドホルモン除去処理を行い、高圧抽出プラセンタエキスとして1760gを回収した。   The high-pressure treated porcine placenta was centrifuged at 5000 rpm for 30 minutes at 5 ° C. to separate the solid content, and 2210 g of the supernatant was recovered. This supernatant was filtered through a 0.2 μm filter (manufactured by Nippon Pole Co., Ltd.) and subjected to steroid hormone removal treatment to recover 1760 g as a high-pressure extraction placenta extract.

実験2: 水溶性プラセンタエキスの製造法(比較品)
健常な妊娠3〜4ヶ月の種豚から得られた胎盤100Kgを解凍し、低温の精製水により血液等を十分に洗浄除去する。洗浄された胎盤は、ワーリングブレンダーにより粉砕する。粉砕された胎盤に精製水10Kgを加え、低温下で攪拌抽出する。
Experiment 2: Manufacturing method of water-soluble placenta extract (comparative product)
Thaw 100 kg of placenta obtained from a healthy pig of 3 to 4 months of gestation, and thoroughly wash and remove blood and the like with low-temperature purified water. The washed placenta is crushed with a Waring blender. Add 10 kg of purified water to the ground placenta, and stir and extract under low temperature.

攪拌抽出処理された豚胎盤を、5000回転/分、30分、5℃で遠心分離処理し、固形分を分離し、上清を回収した。この上清を精製精密ろ過フィルター等で臭気が低減するまで精製し、その後にステロイドホルモン除去処理を行い、水溶性プラセンタエキスとしておよそ80Kgを回収した。   The porcine placenta that had been subjected to the stirring and extraction treatment was centrifuged at 5000 rpm for 30 minutes at 5 ° C. to separate the solids, and the supernatant was collected. The supernatant was purified with a purification microfiltration filter or the like until the odor was reduced, and then steroid hormone removal treatment was performed to recover approximately 80 kg as a water-soluble placenta extract.

評価試験1: 高圧抽出プラセンタエキスと水溶性プラセンタエキスの成分比較試験
高圧抽出プラセンタエキスと水溶性プラセンタエキスの成分として、蒸発残留物(固形分量)、総窒素量(日本薬局方一般試験法 窒素定量法)、ヒアルロン酸量(ELISA法、ヒアルロン酸測定キット・生化学バイオビジネス株式会社)の定量分析を行い、表1に示した。また、遊離アミノ酸の分析も行い、表2に示した。
Evaluation test 1: Component comparison test of high-pressure extraction placenta extract and water-soluble placenta extract As components of high-pressure extraction placenta extract and water-soluble placenta extract, evaporation residue (solid content), total nitrogen amount (Japanese Pharmacopoeia General Test Method Nitrogen Determination Method) and the amount of hyaluronic acid (ELISA method, hyaluronic acid measurement kit, Seikagaku Biobusiness Co., Ltd.) were quantitatively analyzed and are shown in Table 1. Free amino acids were also analyzed and are shown in Table 2.

これらの分析の結果、高圧抽出プラセンタエキスは固形分中の窒素量比率が多く、また遊離アミノ酸比率も高いことが判明した。また、胎盤由来のヒアルロン酸は、高圧抽出プラセンタエキスに多く検出された。これらのことから、高圧抽出プラセンタエキスは、アミノ酸を豊富に含有し、ヒアルロン酸も含有し、皮膚の保湿作用がより期待できるプラセンタエキスであると考えられる。   As a result of these analyses, it was found that the high-pressure extraction placenta extract has a high nitrogen content ratio and a high free amino acid ratio in the solid content. A large amount of placenta-derived hyaluronic acid was detected in the high-pressure placenta extract. From these facts, the high-pressure extraction placenta extract is considered to be a placenta extract that contains abundant amino acids and also contains hyaluronic acid and can be expected to have a moisturizing action on the skin.

Figure 0005932783
Figure 0005932783

Figure 0005932783
Figure 0005932783

評価試験2: ヒトに対する保湿性及び抗シワ試験
シワのグレード標準写真(シワグレード0〜7の8段階)(日本香粧品学会の抗シワ製品評価ガイドライン 日本香粧品学会誌 Vol.30, No.4,pp.316-332(2006))により目視評価を行い、シワグレードが2〜3に該当する被験者21名の健常女性パネルを用いた。
Evaluation test 2: Human moisturizing and anti-wrinkle test Wrinkle grade standard photos (8 levels of wrinkle grade 0-7) (Japan Cosmetics Society anti-wrinkle product evaluation guidelines Vol.30, No.4 , pp.316-332 (2006)), and a healthy female panel of 21 subjects with wrinkle grades 2 to 3 was used.

試験は、日本香粧品学会の抗シワ製品評価ガイドラインに準じて実施した。被験者の目尻周辺に検体である本発明品の高圧抽出プラセンタエキスを、半顔に1日3回(1回、約220mg)塗布し8週間継続した。もう半顔は検体を無塗布とした。0、4、8週目に目視評価、目尻の部位の角質水分量の測定を実施した。   The test was conducted in accordance with the anti-wrinkle product evaluation guidelines of the Japanese Cosmetic Society. The high-pressure extraction placenta extract of the present invention, which is a specimen, was applied to the periphery of the subject's eye corners three times a day (once, about 220 mg) and continued for 8 weeks. The other half face did not apply the sample. Visual evaluation was performed at 0, 4, and 8 weeks, and the amount of horny water in the area of the corner of the eye was measured.

<シワの評価>
試験開始日、試験開始4週間後及び8週間後(試験終了日)にシワの目視評価を実施した。シワのグレード評価は、各グレードの間を0.5として判定した。
<Evaluation of wrinkles>
Visual evaluation of wrinkles was performed on the test start date, 4 weeks and 8 weeks after the test start (the test end date). Wrinkle grade evaluation was determined with 0.5 between each grade.

シワのグレード
グレード0:シワは無い
グレード1:不明瞭な浅いシワが僅かに認められる
グレード2:明瞭な浅いシワが僅かに認められる
グレード3:明瞭な浅いシワが認められる
グレード4:明瞭な浅いシワの中に、やや深いシワが僅かに認められる
グレード5:やや深いシワが認められる
グレード6:明瞭な深いシワが認められる
グレード7:著しく深いシワが認められる
<保湿性の評価>
試験開始日、試験開始4週間後及び8週間後(試験終了日)に検体の塗布部位及び無塗布部位の角質水分量を Corneometer CM825 (Courage-Khazaka, Germany) により測定し、検体の保湿性について検証した。結果は、塗布部位と無塗布部位の差で表した。数値が大きいほど保湿性があることを意味している。
Wrinkle grade Grade 0: No wrinkle grade 1: Slightly unclear shallow wrinkles are observed Grade 2: Clear shallow wrinkles are slightly observed Grade 3: Clear shallow wrinkles are observed Grade 4: Clear shallow Slightly deep wrinkles are observed in grade 5: Slightly deep wrinkles are observed Grade 6: Clear deep wrinkles are observed Grade 7: Extremely deep wrinkles are observed <Evaluation of moisture retention>
Moisture retention of the specimens was measured by Corneometer CM825 (Courage-Khazaka, Germany) on the test start date, 4 weeks and 8 weeks after the test start (study end date) using the Corneometer CM825 (Courage-Khazaka, Germany). Verified. The result was expressed by the difference between the coated part and the non-coated part. It means that there is moisture retention, so that a numerical value is large.

<評価結果>
表3、図1及び図2に評価結果を記載した。図1及び図2のグラフにおいてエラーバーは標準誤差を示す。試験開始4週間後に角質水分量は21名中18名で無塗布より多く、目尻周辺のシワグレードは21名中12名で改善が認められた。この結果は、Wilcoxon検定ではp<0.01である。本発明品の高圧抽出プラセンタエキスは、保湿作用を有し、有意に抗シワ改善作用を有することが判明した。通常、4週間では抗シワ効果は有意に認められないことから、本発明品は非常に高い効果を有していると考えられる。さらに8週目では明確な効果が確認できた。
<Evaluation results>
The evaluation results are shown in Table 3, FIG. 1 and FIG. In the graphs of FIGS. 1 and 2, error bars indicate standard errors. Four weeks after the start of the test, the keratin water content was higher in 18 of 21 subjects than in the case of no application, and the wrinkle grade around the eye corners was improved in 12 of 21 subjects. This result is p <0.01 in the Wilcoxon test. It was found that the high-pressure extraction placenta extract of the present invention has a moisturizing action and has a significant anti-wrinkle improving action. Usually, since the anti-wrinkle effect is not significantly observed in 4 weeks, the product of the present invention is considered to have a very high effect. Furthermore, a clear effect was confirmed in the 8th week.

Figure 0005932783
Figure 0005932783

(実施例2)高圧抽出処理条件の検討
(1) 圧力条件の検討
実施例1と同様にして調製した胎盤を用い、抽出温度を50℃、抽出時間を16時間として、25〜600 MPaの範囲の各圧力で抽出を行った。得られた各抽出液(プラセンタエキス)の蒸発残留物(以下「固形分濃度」という)の定量分析を行ない、結果を表4に示した。また、各抽出液のヒアルロン酸量、総窒素量の定量分析も同時に行い、結果を表4に合わせて示した。結果は、抽出圧力100Mpa、抽出温度50℃、抽出時間16時間での抽出液の固形分濃度、ヒアルロン酸量、総窒素量の値を1として相対値で示した。
(Example 2) Examination of high-pressure extraction treatment conditions
(1) Examination of pressure conditions
Using a placenta prepared in the same manner as in Example 1, the extraction temperature was 50 ° C., the extraction time was 16 hours, and extraction was performed at each pressure in the range of 25 to 600 MPa. Quantitative analysis of the evaporation residue (hereinafter referred to as “solid content concentration”) of each extract (placenta extract) obtained was performed, and the results are shown in Table 4. In addition, quantitative analysis of hyaluronic acid amount and total nitrogen amount of each extract was also performed, and the results are shown in Table 4. The results were expressed as relative values, with the solid content concentration, hyaluronic acid amount, and total nitrogen amount of the extract at an extraction pressure of 100 MPa, an extraction temperature of 50 ° C., and an extraction time of 16 hours.

Figure 0005932783
Figure 0005932783

抽出液中の固形分濃度は100MPaで最も高く、50〜300 MPaでは大きな差は認められなかった。ヒアルロン酸、窒素はいずれの抽出液中にも含有されることが確認できた。   The solid content concentration in the extract was highest at 100 MPa, and no significant difference was observed between 50 and 300 MPa. It was confirmed that hyaluronic acid and nitrogen were contained in any of the extracts.

また、得られた各抽出プラセンタエキスのpHを表5に示した。   In addition, Table 5 shows the pH of each obtained placenta extract.

Figure 0005932783
Figure 0005932783

抽出液のpHは、25〜150 MPaでは大きな変化が認められないが、300 MPa以上では上昇していた。   The pH of the extract did not change significantly at 25 to 150 MPa, but increased at 300 MPa or more.

以上の抽出液の各分析結果と高圧処理に用いる装置を総合的に考慮すると、プラセンタエキスの高圧処理の圧力条件は、50〜150 MPaが適切である。   Considering each analysis result of the above extract and the apparatus used for high pressure treatment, the pressure condition for the high pressure treatment of placenta extract is appropriately 50 to 150 MPa.

(2) 温度条件の検討
実施例1と同様にして調製した胎盤を用い、抽出圧力を100MPa、抽出時間を16時間として、40〜75℃の範囲の各温度で抽出を行った。得られた各抽出液の固形分濃度を表6に示した。また、各抽出液のヒアルロン酸量、総窒素量を表6に合わせて示した。結果は、抽出圧力100Mpa、抽出温度50℃、抽出時間16時間での抽出液の固形分濃度、ヒアルロン酸量、総窒素量の値を1として相対値で示した。
(2) Examination of temperature conditions
Using a placenta prepared in the same manner as in Example 1, the extraction pressure was 100 MPa, the extraction time was 16 hours, and extraction was performed at each temperature in the range of 40 to 75 ° C. Table 6 shows the solid concentration of each of the obtained extracts. In addition, Table 6 shows the hyaluronic acid amount and total nitrogen amount of each extract. The results were expressed as relative values, with the solid content concentration, hyaluronic acid amount, and total nitrogen amount of the extract at an extraction pressure of 100 MPa, an extraction temperature of 50 ° C., and an extraction time of 16 hours.

Figure 0005932783
Figure 0005932783

ヒアルロン酸、窒素はいずれの抽出液中にも含有されることが確認できた。抽出液中の固形分濃度は60℃で最も高く、プラセンタエキスの高圧処理の温度条件は、45℃〜65℃の範囲が適切と考えられた。   It was confirmed that hyaluronic acid and nitrogen were contained in any of the extracts. The solid content concentration in the extract was the highest at 60 ° C, and it was considered that the range of 45 ° C to 65 ° C was appropriate as the temperature condition for the high-pressure treatment of placenta extract.

(3) 時間条件の検討
実施例1と同様にして調製した胎盤を用い、抽出圧力を100MPa、抽出温度50℃として、2〜48時間の範囲の各時間で抽出を行った。得られた各抽出液の固形分濃度を表7に示した。また、各抽出液のヒアルロン酸量、総窒素量を表7に合わせて示した。結果は、抽出圧力100Mpa、抽出温度50℃、抽出時間16時間での抽出液の固形分濃度、ヒアルロン酸量、総窒素量の値を1として相対値で示した。
(3) Examination of time conditions
Using a placenta prepared in the same manner as in Example 1, the extraction pressure was 100 MPa, the extraction temperature was 50 ° C., and extraction was performed in each time range of 2 to 48 hours. Table 7 shows the solid content concentration of each extract obtained. In addition, Table 7 shows the hyaluronic acid amount and total nitrogen amount of each extract. The results were expressed as relative values, with the solid content concentration, hyaluronic acid amount, and total nitrogen amount of the extract at an extraction pressure of 100 MPa, an extraction temperature of 50 ° C., and an extraction time of 16 hours.

Figure 0005932783
Figure 0005932783

ヒアルロン酸、窒素はいずれの抽出液中にも含有されることが確認できた。高圧抽出における処理時間は、長いほど抽出液中の固形分濃度が増加することが確認された。しかしながら、時間単位の抽出効率は処理時間が長くなると低下するため、作業効率と稼動時間を考慮すると、24時間以内が好ましいと考えられる。   It was confirmed that hyaluronic acid and nitrogen were contained in any of the extracts. It was confirmed that the solid content concentration in the extract increased as the treatment time in high-pressure extraction increased. However, since the extraction efficiency in units of time decreases as the processing time becomes longer, it is considered that 24 hours or less is preferable in consideration of work efficiency and operation time.


産業上の利用可能性
本発明は、シワ改善を目的とした化粧品、医薬品、医薬部外品の製造分野において利用できる。

INDUSTRIAL APPLICABILITY The present invention can be used in the field of manufacturing cosmetics, pharmaceuticals, and quasi drugs intended to improve wrinkles.

本明細書で引用した全ての刊行物、特許及び特許出願をそのまま参考として本明細書に組み入れるものとする。   All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.

Claims (4)

胎盤を25〜150MPaの圧力で高圧処理し、胎盤の高圧処理物を得る工程と、該胎盤の高圧処理物を固液分離して固形状画分を分離除去し、液状画分を得る工程とを含み、酵素添加、熱、酸、またはアルカリによる胎盤の加水分解処理工程は含まないことを特徴とする、シワ改善用高圧抽出プラセンタエキスの製造方法。   A high-pressure treatment of the placenta at a pressure of 25 to 150 MPa to obtain a high-pressure treated product of the placenta; a step of separating the solid fraction from the high-pressure treated product of the placenta to separate and remove a solid fraction; A method for producing a high-pressure extraction placenta extract for wrinkle improvement, which does not include a placenta hydrolysis treatment step with enzyme addition, heat, acid, or alkali. 前記高圧処理が、45〜65℃の範囲内で行われる、請求項1に記載の製造方法。   The manufacturing method according to claim 1, wherein the high-pressure treatment is performed within a range of 45 to 65 ° C. 前記液状画分に対し、濃縮、乾燥、および希釈から選ばれる少なくとも1種の処理をさらに行う、請求項1または2に記載の製造方法。   The production method according to claim 1, wherein the liquid fraction is further subjected to at least one treatment selected from concentration, drying, and dilution. 前記シワ改善が、皮膚にうるおいを与え、乾燥によるシワを目立たなくするものである、請求項1〜3のいずれかに記載の製造方法。   The manufacturing method according to any one of claims 1 to 3, wherein the wrinkle improvement gives moisture to skin and makes wrinkles due to drying inconspicuous.
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