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JP4880233B2 - Anti-dermatological agent and external preparation for skin containing the same - Google Patents
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JP4880233B2 - Anti-dermatological agent and external preparation for skin containing the same - Google Patents

Anti-dermatological agent and external preparation for skin containing the same Download PDF

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JP4880233B2
JP4880233B2 JP2005049828A JP2005049828A JP4880233B2 JP 4880233 B2 JP4880233 B2 JP 4880233B2 JP 2005049828 A JP2005049828 A JP 2005049828A JP 2005049828 A JP2005049828 A JP 2005049828A JP 4880233 B2 JP4880233 B2 JP 4880233B2
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chrysanthemum
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紘明 三谷
明美 高山
久美 亀山
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Kose Corp
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Description

本発明は、紫外線曝露に起因する皮膚障害を抑制又は改善する抗皮膚障害剤、及びこれを含有する皮膚外用剤に関する。更に詳細には、キク科キク属植物抽出物を有効成分とする抗皮膚障害剤、及び前記キク科キク属植物抽出物の抗皮膚障害剤を含有し、紫外線曝露に起因する皮膚細胞外マトリックス成分の異常蓄積、コラーゲン架橋形成、シワ形成、皮膚肥厚、及び皮膚硬化等の少なくとも一つ以上を抑制又は改善する化粧品や医薬品として有用な皮膚外用剤に関する。   The present invention relates to an anti-dermatological agent that suppresses or ameliorates skin damage caused by exposure to ultraviolet rays, and an external preparation for skin containing the same. More specifically, an anti-dermatological agent comprising a Compositae Chrysanthemum genus plant extract as an active ingredient, and a skin extracellular matrix component resulting from exposure to ultraviolet rays, comprising the anti-dermatological agent of the Asteraceae Chrysanthemum genus plant extract. The present invention relates to a skin external preparation useful as a cosmetic or pharmaceutical agent that suppresses or improves at least one of abnormal accumulation, collagen cross-linking formation, wrinkle formation, skin thickening, and skin hardening.

紫外線(例えば、太陽光)の連続的な長期間曝露は皮膚にケミカルメディエーター、サイトカイン等による炎症を生じせしめ、シワ、タルミ、皮膚肥厚、皮膚硬化、皮膚癌、日光性弾性線維症等の皮膚障害が生じる(非特許文献1参照)。特に表皮及び真皮が肥厚することにより、皮膚の弾性、保湿性が低下し、これが皮膚老化の要因の一つとなっていると考えられている。そこで、従来からこれらの障害を防ぐために、紫外線吸収剤(特許文献1、非特許文献2参照)、紫外線散乱剤(非特許文献3参照)が配合された外用剤、すなわち乳液、クリーム、ローション、美容液、ファンデーション、軟膏、パップ剤、貼付剤等が使用されている。
又、加齢、紫外線曝露等により生じる皮膚のシワやタルミ、ハリや弾力性の低下を予防、あるいは改善するために、レチノイン酸(非特許文献4参照)、抗炎症薬(非特許文献5参照)やオウバクエキス、シラカバエキス、セージエキス、ローマカミツレエキス等(特許文献2参照)、メリッサ抽出物(特許文献3参照)、更に細胞外マトリックス成分の異常蓄積、皮膚肥厚、シワ等の抑制に活性型ビタミンD(非特許文献6参照)の配合が報告されている。
Long-term exposure to ultraviolet rays (e.g. sunlight) causes skin to become irritated by chemical mediators, cytokines, etc., and skin disorders such as wrinkles, talmi, skin thickening, skin sclerosis, skin cancer, solar elastic fibrosis, etc. (See Non-Patent Document 1). In particular, thickening of the epidermis and dermis results in a decrease in skin elasticity and moisture retention, which is considered to be one of the causes of skin aging. Therefore, in order to prevent these obstacles conventionally, an external preparation containing an ultraviolet absorber (see Patent Document 1 and Non-Patent Document 2) and an ultraviolet scattering agent (see Non-Patent Document 3), that is, an emulsion, cream, lotion, Cosmetic liquids, foundations, ointments, cataplasms, patches, etc. are used.
In addition, retinoic acid (see Non-Patent Document 4), anti-inflammatory drug (see Non-Patent Document 5) in order to prevent or improve skin wrinkles, tarmi, elasticity and reduced elasticity caused by exposure to ultraviolet rays, etc. ), Buckwheat extract, birch extract, sage extract, roman chamomile extract, etc. (see Patent Document 2), Melissa extract (see Patent Document 3), and also active in inhibiting abnormal accumulation of extracellular matrix components, skin thickening, wrinkles, etc. Formulation of type vitamin D 3 (see Non-Patent Document 6) has been reported.

しかしながら、例えば、レチノイン酸を配合した皮膚外用剤は、真皮上層にコラーゲンを増殖させ、シワを改善する効果は有するが、シワの発生を抑制する効果は認められず、塗布を中止すると元に戻ってしまい、また、塗布部位が紫外線に曝露されると却って皮膚癌を誘発する等の問題がある。又、活性型ビタミンDはカルシウム代謝等の副作用の問題がある。他の紫外線吸収剤、紫外線散乱剤、抗炎症薬、植物抽出物等を配合した皮膚外用剤においても、シワ形成、皮膚肥厚等の抑制、改善効果が十分ではなかったり、効果を高めるためにこれらの添加物を高濃度に配合すると製剤の使用感が損なわれたり、高温時や経時で変質する等の問題が生じる場合があった。 However, for example, a topical skin preparation containing retinoic acid has the effect of improving the wrinkle by proliferating collagen in the upper layer of the dermis, but is not effective in suppressing the generation of wrinkles. In addition, when the application site is exposed to ultraviolet rays, there are problems such as inducing skin cancer. The active vitamin D 3 have a side effect problems such as calcium metabolism. Even in the topical skin preparations containing other UV absorbers, UV scattering agents, anti-inflammatory agents, plant extracts, etc., these are not effective in suppressing or improving wrinkle formation, skin thickening, etc. When these additives are blended at a high concentration, the usability of the preparation may be impaired, and problems such as deterioration at high temperatures and over time may occur.

特開平09−268194号公報JP 09-268194 A 特開平08−109122号公報Japanese Patent Application Laid-Open No. 08-109122 特開平09−241148号公報JP 09-241148 A 菅原努、野津敬一著「太陽紫外線と健康」裳華房(1998) P.2〜100Tsutomu Sugawara and Keiichi Nozu, “Solar UV and Health,” Yukabo (1998) p. 2-100 ニコラス・J・ローウ/ナディム・A・ジャーム編「サンスクリーン剤と皮膚科学」フレグランスジャーナル社、1993年5月20日発行、P.195〜262Nicholas J. Rowe / Nadim A. Germ, “Sunscreens and Dermatology”, Fragrance Journal, published May 20, 1993, p. 195-262 「フレグランスジャーナル」フレグランスジャーナル社編 2002年7月号 P.16〜27、33〜38“Fragrance Journal”, Fragrance Journal, July 2002 16-27, 33-38 Lorraine H.Kligman著,“Effects of all−trans−retinoic acid on the dermis of hairless mice”,Journal of the American Academy of Dermatology,1986年,vol.15,No.4,Part.2,October,P.779〜785Lorraine H. Kligman, “Effects of all-trans-retinoic acid on the dermis of hairless rice,” Journal of the American Academy of Dermatology, 1988. 15, no. 4, Part. 2, October, P.M. 779-785 Bissett DL,et al.著,“Photoprotective effect of topical anti−inflammatory agents against ultraviolet radiation−induced chronic skin damage in the hairless mouse”,1990年,vol.7,P.153〜158Bissett DL, et al. Author, “Photoprotective effect of topical anti-inflammatory agents against ultraradiation radiation-induced chronic skin damage in the hair 90.” 7, p. 153-158 Koshiishi I,et al.著,“1,25−dihydroxyvitamin D3 prevents the conversion of adipose tissue into fibrous tissue in skin exposed to chronic UV irradiation.”,Toxicology and Applied Pharmacology,2001年,vol.173,P.99〜104Koshiishi I, et al. "1,25-dihydroxyvitamin D3 presents the conversion of adipose tissue into fibrosstic in inspired toporic UV iradiation.", Toxol. 173, P.I. 99-104

従って、紫外線曝露に起因する細胞外マトリックス成分の異常蓄積、コラーゲン架橋形成、シワ形成、皮膚肥厚、及び皮膚硬化等の少なくとも一つ以上の皮膚障害を有効に抑制又は改善する抗皮膚障害剤、及び使用感や剤型に悪影響を及ぼすことなくこれを含有した皮膚外用剤の開発が望まれていた。   Accordingly, an anti-dermatological agent that effectively suppresses or ameliorates at least one skin disorder such as abnormal accumulation of extracellular matrix components, collagen cross-linking formation, wrinkle formation, skin thickening, and skin hardening caused by ultraviolet exposure, and There has been a demand for the development of an external preparation for skin containing this without adversely affecting the feeling of use and dosage form.

本発明者らは、上記目的を達成するために、すでに安全性が確認されている医薬品、化粧品原料、及び民間薬等で使用されている植物に着目し、鋭意研究を重ねた結果、キク科キク属植物抽出物が、紫外線曝露に起因する細胞外マトリックス成分の異常蓄積、コラーゲンやエラスチンの架橋、さらにはシワ形成、皮膚肥厚、皮膚硬化等の少なくとも一つ以上の皮膚障害の発現を抑制又は改善する効果に優れるとの新知見を得、本発明を完成した。   In order to achieve the above object, the present inventors have focused on plants already used in pharmaceuticals, cosmetic raw materials, folk medicines, etc., which have already been confirmed to be safe, and as a result of intensive research, Chrysanthemum plant extract suppresses the abnormal accumulation of extracellular matrix components caused by UV exposure, cross-linking of collagen and elastin, and further the development of at least one skin disorder such as wrinkle formation, skin thickening, skin hardening, etc. The present invention was completed by obtaining new knowledge that the effect of improvement was excellent.

すなわち、本発明は、キク科キク属植物抽出物を有効成分とする紫外線曝露に起因する皮膚障害を抑制改善する抗皮膚障害剤に関するものであり、キク科キク属植物がリュウノウギク(Chrysanthemum Makino Matsum.etNakai)、キクタニギク(Chrysanthemum boreale Makino)、シマカンギク(Chrysanthemum indicum L.)、イソギク(Chrysanthemum pacificum)、シュンギク(Chrysanthemum coronarium)、フランスギク(Chrysanthemum Leucanthemum L.)、及びナツシロギク(Chrysanthemum parthenium Peres.)(以下、各植物の学名のラテン語表記は省略とする)からなる群から選ばれる少なくとも一種以上である前記抗皮膚障害剤に関するものである。また、紫外線暴露に起因する皮膚障害が、皮膚細胞外マトリックス成分の異常蓄積、コラーゲン架橋形成、シワ形成、皮膚肥厚、及び皮膚硬化の少なくとも一つ以上である抗皮膚障害剤に関するものである。また更には、該抗皮膚障害剤を有効成分として含有し、前記皮膚障害を抑制又は改善する皮膚外用剤、特に老化防止用の皮膚外用剤に関するものである。   That is, the present invention relates to an anti-dermatological agent that suppresses and improves skin damage caused by exposure to ultraviolet rays, comprising an extract of Asteraceae plant extract as an active ingredient, and the Asteraceae plant belongs to Chrysantheum Makino Matsum. etNakai), Kikutanigiku (chrysanthemum boreale Makino), Shimakangiku (chrysanthemum indicum L.), chrysanthemum pacificum (chrysanthemum pacificum), garland chrysanthemum (chrysanthemum coronarium), France chrysanthemum (chrysanthemum Leucanthemum L.), and feverfew (chrysanthemum parthenium Peres.) (hereinafter, Each plant Latin notation scientific name is related to the anti-skin-disorder agent is at least one or more selected from the group consisting of a drawing). Further, the present invention relates to an anti-dermatological agent in which the skin damage caused by ultraviolet exposure is at least one of abnormal accumulation of skin extracellular matrix components, collagen cross-linking formation, wrinkle formation, skin thickening, and skin hardening. Still further, the present invention relates to an external preparation for skin containing the anti-dermatological agent as an active ingredient and suppressing or improving the above-mentioned skin damage, particularly to an external preparation for preventing aging.

本発明に係わるキク科キク属植物抽出物は、紫外線曝露に起因する皮膚細胞外マトリックス成分の異常蓄積やコラーゲン架橋形成、シワ形成、皮膚肥厚、及び皮膚硬化の少なくとも一つ以上の皮膚障害の抑制又は改善に効果の高い抗皮膚障害剤である。また、前記抗皮膚障害剤を有効成分として含有する皮膚外用剤は、紫外線曝露に起因する前記皮膚障害を有効に抑制又は改善するものであり、従って、皮膚老化を防止する化粧品や医薬部外品等として有利に利用することができるものである。   The Asteraceae plant extract according to the present invention suppresses abnormal accumulation of skin extracellular matrix components and collagen cross-linking formation, wrinkle formation, skin thickening, and skin hardening caused by ultraviolet exposure. Or it is an anti-dermatological agent highly effective in improvement. The topical skin preparation containing the anti-dermatological agent as an active ingredient effectively suppresses or ameliorates the skin disorder caused by exposure to ultraviolet rays. Therefore, a cosmetic or quasi-drug that prevents skin aging. Etc., which can be used advantageously.

以下、本発明を詳細に説明する。
本発明に用いられるキク科キク属植物抽出物は、紫外線曝露に起因する細胞外マトリックス成分の異常蓄積特にコラーゲンの異常産生や、コラーゲンの架橋形成、さらにはシワ形成、皮膚肥厚、皮膚硬化等の少なくとも一つ以上の皮膚障害を抑制又は改善するものである。本発明に用いられるキク科キク属植物抽出物としては、特に制限はないが、中でもリュウノウギク、キクタニギク、シマカンギク、イソギク、シュンギク、フランスギク、及びナツシロギクが効果の点から好ましい。
Hereinafter, the present invention will be described in detail.
The Asteraceae plant extract used in the present invention is an abnormal accumulation of extracellular matrix components caused by exposure to ultraviolet rays, particularly abnormal production of collagen, collagen cross-linking, wrinkle formation, skin thickening, skin hardening, etc. It suppresses or improves at least one skin disorder. There are no particular limitations on the Asteraceae genus plant extract used in the present invention, but among these, Ryunogi, Kikutaniku, Shimakangi, Rhizome, Sungiku, French Giku, and Feverfew are preferred from the viewpoint of effects.

本発明に用いられるキク属植物抽出物はその調製法についても、特に限定されるものではなく、全草、又は根、茎、幹、樹皮、幼芽、葉、花、果実、種子等のいずれか1ヶ所以上から抽出することができ、これらを乾燥、細切、圧搾、或いは発酵等、適宜処理を施した後、低温もしくは室温〜加温下で溶媒により抽出する方法を挙げることができる。   The Chrysanthemum plant extract used in the present invention is not particularly limited in its preparation method, and any of whole plant or root, stem, stem, bark, bud, leaf, flower, fruit, seed, etc. It is possible to extract from one or more places, and after subjecting these to appropriate treatment such as drying, chopping, pressing, or fermentation, extraction with a solvent at low temperature or room temperature to warming can be mentioned.

抽出溶媒としては、例えば水、低級1価アルコール(メチルアルコール、エチルアルコール、1−プロパノール、2−プロパノール、1−ブタノール、2−ブタノール等)、液状多価アルコール(グリセリン、プロピレングリコール、1,3−ブチレングリコール等)、低級アルキルエステル(酢酸エチル等)、炭化水素(ベンゼン、ヘキサン、ペンタン等)、ケトン類(アセトン、メチルエチルケトン等)、エーテル類(ジエチルエーテル、テトラヒドロフラン、ジプロピルエーテル等)、アセトニトリル等が挙げられ、一種又は二種以上を用いることができる。特に好ましい抽出溶媒としては、水又は、水−エチルアルコール系の混合溶媒が挙げられる。   Examples of the extraction solvent include water, lower monohydric alcohols (methyl alcohol, ethyl alcohol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1, 3 -Butylene glycol, etc.), lower alkyl esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile 1 type, or 2 or more types can be used. Particularly preferred extraction solvents include water or water-ethyl alcohol mixed solvents.

更に抽出物は、分子量分画、溶媒分画、各種の樹脂処理(イオン交換樹脂、吸着剤等)等によって精製されたもの、凍結乾燥されたもの等いずれのものでも用いることができる。   Further, the extract may be any of a molecular weight fraction, a solvent fraction, a product purified by various resin treatments (ion exchange resin, adsorbent, etc.), and a freeze-dried product.

具体的な製法としては、例えば植物の乾燥物を粉砕し、約10倍質量の濃度0〜100vol%の含水エチルアルコール又は1,3−ブチレングリコールを用い、室温で1〜5日間抽出又は還流抽出を2時間行った後、又は熱水抽出1時間を行なった後、ろ過し、更に抽出液を分子量分画、溶媒分画、各種の樹脂処理(イオン交換樹脂、吸着剤等)等によって精製し、凍結乾燥し、固形物を得る方法等がある。また、水−エチルアルコール系の溶媒においてはエチルアルコールを留去後、凍結乾燥し、固形分を得る。   As a specific production method, for example, a dried plant product is pulverized, and about 10-fold mass concentration of hydrous ethyl alcohol or 1,3-butylene glycol is used for extraction or reflux extraction at room temperature for 1 to 5 days. After 2 hours or after 1 hour of hot water extraction, it is filtered and the extract is further purified by molecular weight fractionation, solvent fractionation, various resin treatments (ion exchange resin, adsorbent, etc.), etc. There are methods such as lyophilization to obtain a solid. In a water-ethyl alcohol solvent, ethyl alcohol is distilled off and then lyophilized to obtain a solid content.

本発明の抗皮膚障害剤のその形態については、キク属植物抽出物として含む限り、特に制限はなく、液状、ペースト状、クリーム状、ゲル状等いずれの形態で用いることもでき、更にスプレードライ等により乾燥させて粉末として用いることもできる。   The form of the anti-dermatological agent of the present invention is not particularly limited as long as it is contained as a Chrysanthemum plant extract, and can be used in any form such as liquid, paste, cream, gel, and spray drying. It is also possible to use it as a powder after being dried by, for example.

本発明の皮膚外用剤は、キク科キク属植物抽出物の抗皮膚障害剤を含有することを特徴とする。本発明の皮膚外用剤における抗皮膚障害剤の含有量は、特に限定されるものではないが、皮膚外用剤中、乾燥固形分として0.0001〜10質量%(以下、単に「%」と記す)であり、好ましくは0.001〜5%である。この範囲であれば、紫外線曝露に起因する細胞外マトリックス成分の異常蓄積、特にコラーゲンの異常産生やコラーゲン架橋形成、さらにはシワ形成、皮膚肥厚、皮膚硬化等の少なくとも一つ以上の皮膚障害の発現を抑制又はその症状を改善する効果に優れ、経時安定性の面からも良好なものが得られる。   The external preparation for skin of the present invention is characterized by containing an anti-dermatopathic agent of the Asteraceae plant extract. The content of the anti-dermatological agent in the external preparation for skin of the present invention is not particularly limited, but is 0.0001 to 10% by mass (hereinafter, simply referred to as “%”) as a dry solid content in the external preparation for skin. And preferably 0.001 to 5%. Within this range, abnormal accumulation of extracellular matrix components due to UV exposure, especially abnormal production of collagen and collagen cross-linking, as well as the development of at least one skin disorder such as wrinkle formation, skin thickening, skin hardening, etc. It is excellent in the effect of suppressing or improving the symptom thereof, and good in terms of stability over time can be obtained.

本発明の抗皮膚障害剤を含有する皮膚外用剤には上記必須成分の他、化粧料や医薬部外品、外用医薬品等に通常使用される各種の成分、即ち、水、アルコール、油剤、界面活性剤、増粘剤、粉体、キレート剤、pH調整剤、美白剤、抗炎症剤、抗酸化剤、保湿剤、殺菌剤、血行促進剤等の各種薬効剤、動植物・微生物由来の抽出物、紫外線吸収剤、紫外線散乱剤、香料等を、本発明の効果を損なわない範囲で目的に応じて適宜加えることができる。   In addition to the above essential components, the external preparation for skin containing the anti-dermatological agent of the present invention includes various components usually used in cosmetics, quasi-drugs, external medicines, that is, water, alcohols, oils, interfaces. Active agents, thickeners, powders, chelating agents, pH adjusters, whitening agents, anti-inflammatory agents, antioxidants, moisturizers, bactericides, blood circulation promoters and other medicinal agents, extracts derived from animals, plants and microorganisms In addition, an ultraviolet absorber, an ultraviolet scattering agent, a fragrance and the like can be appropriately added depending on the purpose within a range not impairing the effects of the present invention.

また、本発明の抗皮膚障害剤を含有する皮膚外用剤としては、化粧料、医薬部外品、医薬品等が挙げられ、剤型も水性剤型、油性剤型、乳化剤型、粉末剤型、固形剤型等いずれの剤型にも配合することができる。例えば、化粧料としては、化粧水、乳液、クリーム、美容液、パック、バスソルト軟膏、ゲル剤、ファンデーション、パウダー、リップクリーム、口紅、日焼け止め製品等に用いることができる。   Examples of the external preparation for skin containing the anti-dermatological agent of the present invention include cosmetics, quasi-drugs, pharmaceuticals, etc., and the dosage form is an aqueous dosage form, an oil-based dosage form, an emulsifier type, a powder dosage form, It can mix | blend with any dosage forms, such as a solid dosage form. For example, as cosmetics, it can be used in lotions, milky lotions, creams, cosmetic liquids, packs, bath salt ointments, gels, foundations, powders, lip balms, lipsticks, sunscreen products, and the like.

次に植物抽出物の製造例、及び実施例を挙げて本発明を更に詳細に説明するが、本発明はこれらに何ら制約されるものではない。   Next, although the manufacture example of a plant extract and an Example are given and this invention is demonstrated further in detail, this invention is not restrict | limited at all.

キク科キク属植物抽出物の製造例を製造例1〜11に、また、比較例用試料として既に抗シワ作用、抗老化作用が報告されているシラカバ樹皮抽出物の製造例を製造例12に示した。
[製造例1]
リュウノウギク花の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液600mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として7.4gを得た。
Production examples 1 to 11 of the Asteraceae genus plant extract, and production examples 12 of birch bark extract whose anti-wrinkle action and anti-aging action have already been reported as samples for comparative examples Indicated.
[Production Example 1]
1,000 mL of a 25 vol% aqueous ethanol solution was added to 100 g of a crushed dried product of Ryunogi flower, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a sample having a molecular weight of 5,000 or less to obtain 600 mL of an extract, which was concentrated under reduced pressure using an evaporator. After distilling off ethanol, this solution was freeze-dried. 7.4 g was obtained as a solid.

[製造例2]
キクタニギク花の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液650mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として6.9gを得た。
[Production Example 2]
1,000 mL of a 25 vol% aqueous ethanol solution was added to 100 g of the crushed dry matter of Kikutaniku flowers, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a product having a molecular weight of 5,000 or less, and 650 mL of an extract was obtained and concentrated under reduced pressure using an evaporator. After distilling off ethanol, this solution was freeze-dried. 6.9 g was obtained as a solid.

[製造例3]
シマカンギク花の乾燥物の破砕物100gに対して、精製水1,000mLを加え、熱水抽出を1時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液620mLを得、エバポレーターで減圧濃縮後、この液を凍結乾燥し、固形物として9.3gを得た。
[Production Example 3]
Purified water (1,000 mL) was added to 100 g of crushed dried citrus flowers, and hot water extraction was performed for 1 hour. Centrifugation, pressure filtration, and membrane separation were used to collect one having a molecular weight of 5,000 or less to obtain 620 mL of an extract. After concentration under reduced pressure using an evaporator, this solution was lyophilized to obtain a solid as 9. 3 g was obtained.

[製造例4]
イソギク葉の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液700mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として5.7gを得た。
[Production Example 4]
1,000 mL of 25 vol% ethanol aqueous solution was added to 100 g of a dried product of dried sea oyster leaves, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a sample having a molecular weight of 5,000 or less, 700 mL of an extract was obtained, concentrated under reduced pressure using an evaporator, ethanol was distilled off, and this solution was freeze-dried. 5.7 g was obtained as a solid.

[製造例5]
シュンギク花の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液610mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として7.4gを得た。
[Production Example 5]
1,000 mL of a 25 vol% ethanol aqueous solution was added to 100 g of a crushed dried syringa flower, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a product having a molecular weight of 5,000 or less, to obtain 610 mL of an extract, which was concentrated under reduced pressure with an evaporator, ethanol was distilled off, and this solution was freeze-dried. 7.4 g was obtained as a solid.

[製造例6]
フランスギク花の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液700mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として5.4gを得た。
[Production Example 6]
1,000 mL of a 25 vol% aqueous ethanol solution was added to 100 g of a crushed dried dried daisy flower, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a sample having a molecular weight of 5,000 or less, 700 mL of an extract was obtained, concentrated under reduced pressure using an evaporator, ethanol was distilled off, and this solution was freeze-dried. 5.4 g was obtained as a solid.

[製造例7]
ナツシロギク全草の乾燥物の破砕物100gに対して、精製水1,000mLを加え、熱水抽出を1時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液670mLを得、この液を凍結乾燥し、固形物として7.5gを得た。
[Production Example 7]
Purified water (1,000 mL) was added to 100 g of dried fractured feverfew, and hot water extraction was performed for 1 hour. This was subjected to centrifugal separation and pressure filtration, and membrane separation was used to collect one having a molecular weight of 5,000 or less to obtain 670 mL of an extract, which was freeze-dried to obtain 7.5 g as a solid.

[製造例8]
シュンギク葉の乾燥物の破砕物100gに対して、精製水1,000mLを加え、熱水抽出を1時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液760mLを得、エバポレーターで減圧濃縮し、この液を凍結乾燥し、固形物として7.9gを得た。
[Production Example 8]
Purified water (1,000 mL) was added to 100 g of crushed dried synghi leaf, and hot water extraction was performed for 1 hour. Centrifugation, pressure filtration, and membrane separation were used to collect a product having a molecular weight of 5,000 or less to obtain 760 mL of an extract, which was concentrated under reduced pressure using an evaporator. 9 g was obtained.

[製造例9]
ナツシロギク全草の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液660mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として6.6gを得た。
[Production Example 9]
1,000 mL of a 25 vol% aqueous ethanol solution was added to 100 g of a crushed dried product of feverfew, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a sample having a molecular weight of 5,000 or less, and 660 mL of an extract was obtained and concentrated under reduced pressure using an evaporator. After distilling off ethanol, this solution was freeze-dried. 6.6 g was obtained as a solid.

[製造例10]
シマカンギク葉の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液580mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として5.5gを得た。
[Production Example 10]
1,000 mL of a 25 vol% ethanol aqueous solution was added to 100 g of the crushed dried citrus leaves, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a sample having a molecular weight of 5,000 or less, and 580 mL of an extract was obtained and concentrated under reduced pressure using an evaporator. After distilling off ethanol, this solution was freeze-dried. 5.5 g was obtained as a solid.

[製造例11]
イソギク全草の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液660mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として8.2gを得た。
[Production Example 11]
1,000 mL of a 25 vol% aqueous ethanol solution was added to 100 g of a crushed dry matter of whole sea anemone, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a sample having a molecular weight of 5,000 or less, and 660 mL of an extract was obtained and concentrated under reduced pressure using an evaporator. After distilling off ethanol, this solution was freeze-dried. 8.2 g were obtained as a solid.

[製造例12]
シラカバ樹皮の乾燥物の破砕物100gに対して、25vol%エタノール水溶液1,000mLを加え、還流抽出を2時間行なった。これを遠心分離、加圧ろ過し、膜分離を用い、分子量5,000以下のものを採取し、抽出液660mLを得、エバポレーターで減圧濃縮し、エタノールを留去後、この液を凍結乾燥し、固形物として7.4gを得た。
[Production Example 12]
1,000 mL of 25 vol% ethanol aqueous solution was added to 100 g of a crushed dried birch bark, and reflux extraction was performed for 2 hours. Centrifugation, pressure filtration, and membrane separation were used to collect a sample having a molecular weight of 5,000 or less, and 660 mL of an extract was obtained and concentrated under reduced pressure using an evaporator. After distilling off ethanol, this solution was freeze-dried. 7.4 g was obtained as a solid.

実施例1:ヘアレスマウス紫外線照射による皮膚障害試験
下記調製方法により抗皮膚障害製剤を調製し、紫外線照射による皮膚肥厚、シワ形成、皮膚硬化、皮膚細胞外マトリックス成分の異常蓄積(総ヒドロキシプロリン量、デルマタン硫酸量)、コラーゲン架橋(ペプシン耐性ヒドロキシプロリン)について評価した。
Example 1: Skin damage test by hairless mouse UV irradiation Anti-skin damage preparation was prepared by the following preparation method, skin thickening by UV irradiation, wrinkle formation, skin hardening, abnormal accumulation of skin extracellular matrix components (total hydroxyproline amount Dermatan sulfate amount) and collagen crosslinking (pepsin resistant hydroxyproline) were evaluated.

[試料(抗皮膚障害製剤)の調製]
製造例1〜11のキク属植物抽出物及び製造例12のシラカバ樹皮抽出物を基剤(ポリエチレングリコール1000:エチルアルコール=1:1)に溶解し、固形分濃度5%に試料を調製し、ヘアレスマスウス紫外線照射による皮膚評価試験に用いた。
[Preparation of sample (anti-dermatological preparation)]
A chrysanthemum plant extract of Production Examples 1 to 11 and a birch bark extract of Production Example 12 were dissolved in a base (polyethylene glycol 1000: ethyl alcohol = 1: 1), and a sample was prepared to a solid content concentration of 5%. It was used for the skin evaluation test by hairless Mousus ultraviolet irradiation.

[試料塗布法と紫外線照射法]
1群8匹とし、紫外線照射90分前に上述の試料をヘアレスマウス(10週齢)背中に0.1g塗布し、一定量の紫外線(東芝FL20S・BLBランプ)を1日2時間(5回/週)20週間照射し(総照射量:720J/cm)、皮膚肥厚、シワ形成、及び皮膚硬化、皮膚細胞外マトリックス成分の異常蓄積、コラーゲン架橋形成の抑制効果を調べた。
尚、これらの試料の紫外線吸収スペクトルを測定し、これらは評価試験に影響を与えないことを確認した。
[Sample application method and UV irradiation method]
One group consists of 8 animals, and 0.1 g of the above sample is applied to the back of hairless mice (10 weeks old) 90 minutes before UV irradiation, and a certain amount of UV light (Toshiba FL20S / BLB lamp) is applied for 2 hours a day (5 times). / Week) Irradiation was performed for 20 weeks (total irradiation amount: 720 J / cm 2 ), and skin thickening, wrinkle formation, skin hardening, abnormal accumulation of skin extracellular matrix components, and inhibition of collagen cross-linking formation were examined.
In addition, the ultraviolet absorption spectrum of these samples was measured, and it was confirmed that these did not affect the evaluation test.

[評価法]
(皮膚肥厚抑制効果)
紫外線照射前と紫外線照射20週後の皮膚の厚みをダイアル厚みゲージ(OZAK.MFG.CO.LTD.)を用い測定した。結果は、8匹の皮膚厚みの平均値、及びその20週間後の増加率で評価した。
[Evaluation method]
(Skin thickening suppression effect)
The thickness of the skin before ultraviolet irradiation and 20 weeks after ultraviolet irradiation was measured using a dial thickness gauge (OZAK.MFG.CO.LTD.). The results were evaluated by the average value of the skin thickness of 8 animals and the rate of increase after 20 weeks.

(シワ形成抑制効果)
紫外線照射20週後のシワ形成について、下記表4に示す「光皮膚老化グレード」に基づいてシワグレードを判定した。なお、結果は、8匹の評点の平均値で表し評価した。
(Wrinkle formation inhibitory effect)
About wrinkle formation 20 weeks after ultraviolet irradiation, the wrinkle grade was determined based on the “photoskin aging grade” shown in Table 4 below. In addition, the result was expressed and evaluated as an average value of 8 scores.

(皮膚硬化抑制効果)
ヘアレスマウス皮膚背部中央部位を摘み、復元に5秒以上を要する皮膚を皮膚硬化とし、マウス8匹中の発現率で評価した。
(Skin hardening inhibitory effect)
The central part of the back of the hairless mouse skin was picked, and the skin requiring 5 seconds or more for restoration was regarded as skin hardening, and the expression rate in 8 mice was evaluated.

[細胞外マトリックス成分の異常蓄積;総ヒドロキシプロリン量、デルマタン硫酸量]
(総ヒドロキシプロリン;コラーゲン定量法)
皮膚中のヒドロキシプロリンを測定し、コラーゲン異常蓄積量を評価した。
ヒドロキシプロリンの定量は先ず、ヘアレスマウス背部皮膚の凍結切片(20ミクロン)を作製し、スライドガラス上で皮膚切片を加熱処理後、0.05%アルカリ性プロテアーゼ(アクチナーゼE;科研製薬製)(500チロシナーゼ単位/mL)で酵素分解(40℃−2時間)し、可溶化した。その後、真空封印し、6N塩酸を用い加水分解後(145℃−4時間)、Woessener法にてヒドロシキプロリンを発色させ、測定した。
[Abnormal accumulation of extracellular matrix components; total hydroxyproline content, dermatan sulfate content]
(Total hydroxyproline; collagen determination method)
Hydroxyproline in the skin was measured and the amount of abnormal collagen accumulation was evaluated.
For the determination of hydroxyproline, first, a frozen section (20 microns) of hairless mouse dorsal skin was prepared, and the skin section was heat-treated on a slide glass, and then 0.05% alkaline protease (actinase E; manufactured by Kaken Pharmaceutical) (500 tyrosinase) (Unit / mL) was enzymatically decomposed (40 ° C.-2 hours) and solubilized. Thereafter, the sample was vacuum-sealed, hydrolyzed with 6N hydrochloric acid (145 ° C. for 4 hours), and then hydroxyproline was colored by the Woessner method and measured.

(デルマタン硫酸定量法)
コラーゲン同様、細胞外マトリックス成分であるデルマタン硫酸の異常蓄積は紫外線照射による皮膚老化指標の一つで、この成分を測定することにより皮膚老化度を評価した。ヘアレスマウス背部皮膚をホルマリン固定後、6ミクロンの皮膚切片を作製し、スライドガラス上で該皮膚切片をコンドロイチナーゼABC(0.5単位/mL)及びコラーゲナーゼ(500マンデル単位/mL)で酵素分解(37℃−2時間)し、可溶化後、下記の条件のポストカラム法にてHPLC装置を用いて試料を分離し、反応試薬1及び反応試薬2と混合後、110℃−2分間チューブ内で反応させ、蛍光誘導体とし、蛍光検出器で測定した。
(Dermatan sulfate determination method)
Like collagen, abnormal accumulation of dermatan sulfate, an extracellular matrix component, is one of the indicators of skin aging caused by ultraviolet irradiation, and the degree of skin aging was evaluated by measuring this component. After formalin fixation of the hairless mouse dorsal skin, a 6-micron skin section was prepared, and the skin section was enzyme-enzymed with chondroitinase ABC (0.5 units / mL) and collagenase (500 mandel units / mL) on a slide glass. After decomposition (37 ° C-2 hours) and solubilization, the sample is separated using an HPLC apparatus by the post-column method under the following conditions, mixed with the reaction reagent 1 and the reaction reagent 2, and then at 110 ° C-2 minutes The reaction was carried out in the interior to obtain a fluorescent derivative, which was measured with a fluorescence detector.

(HPLC条件)
HPLCカラム:DOCOSIL(4.6i.d.×150mm:センシュー科学社製)
蛍光検出:Ex.346nm、Em.410nm
移動相:8.5%アセトニトリル−1mMテトラn−ブチルアンモニウム水素硫酸
流速:1.5mL/分
カラム温度:60℃
反応試薬1:0.3M NaOH(0.25mL/分)
反応試薬2:0.25%2−シアノアセトアミド
(HPLC conditions)
HPLC column: DOCOSIL (4.6id × 150mm: manufactured by Senshu Scientific Co., Ltd.)
Fluorescence detection: Ex. 346 nm, Em. 410nm
Mobile phase: 8.5% acetonitrile-1 mM tetra n-butylammonium hydrogensulfate Flow rate: 1.5 mL / min Column temperature: 60 ° C.
Reaction reagent 1: 0.3 M NaOH (0.25 mL / min)
Reaction reagent 2: 0.25% 2-cyanoacetamide

(コラーゲン架橋:ペプシン耐性ヒドロキシプロリン定量法)
酸性プロテアーゼ(ペプシン;ナカライテスク社製)による分解の難易により、皮膚中のコラーゲン架橋度を評価した。
先ず、上記コラーゲン定量法で作製したヘアレスマウス背部皮膚の凍結切片(20ミクロン)をスライドガラス上で0.01%ペプシン(366単位/mL)で酵素分解(5℃−64時間)し、ペプシン可溶のコラーゲンを水にて洗浄し、除去した。その後、上述した同様な方法にてペプシン耐性のコラーゲンを加熱後、アクチナーゼEを用い酵素分解し、可溶化した。次に溶液を真空封印し、6N塩酸を用い加水分解後(145℃−4時間)、Woessener法にてヒドロシキプロリンを発色させ、ペプシン耐性ヒドロキシプロリンを測定した。
(Collagen cross-linking: Pepsin resistant hydroxyproline quantitative method)
The degree of collagen cross-linking in the skin was evaluated based on the difficulty of degradation by acid protease (pepsin; manufactured by Nacalai Tesque).
First, a frozen section (20 microns) of the hairless mouse dorsal skin prepared by the above-described collagen quantification method was enzymatically degraded with 0.01% pepsin (366 units / mL) on a slide glass (5 ° C.-64 hours) to allow pepsin. The dissolved collagen was washed with water and removed. Thereafter, pepsin-resistant collagen was heated by the same method as described above, and then enzymatically decomposed using actinase E and solubilized. Next, the solution was sealed in a vacuum, hydrolyzed with 6N hydrochloric acid (145 ° C. for 4 hours), and then developed with hydroxyproline by Woessener method to measure pepsin resistant hydroxyproline.

(ペプシン耐性ヒドロキシプロリン(%)算出法)
皮膚中の総ヒドロキシプロリンに対するペプシン耐性ヒドロキシプロリンの含有率を算出し、コラーゲン架橋形成の指標とした。
ペプシン耐性ヒドロキシプロリン含有率(%)=(ペプシン耐性ヒドロキシプロリン/総ヒドロキシプロリン)×100
(Pepsin resistant hydroxyproline (%) calculation method)
The content of pepsin resistant hydroxyproline relative to total hydroxyproline in the skin was calculated and used as an index for collagen cross-linking formation.
Pepsin resistant hydroxyproline content (%) = (pepsin resistant hydroxyproline / total hydroxyproline) × 100

皮膚肥厚、シワ形成、皮膚硬化、細胞外マトリックス成分の異常蓄積(総ヒドロキシプロリン量、デルマタン硫酸量)、コラーゲン架橋(ペプシン耐性ヒドロキシプロリン量、含有率)の評価結果をそれぞれ表1〜3に併せて示す。 Tables 1 to 3 show the evaluation results of skin thickening, wrinkle formation, skin hardening, abnormal accumulation of extracellular matrix components (total hydroxyproline amount, dermatan sulfate amount), and collagen cross-linking (pepsin resistant hydroxyproline amount, content), respectively. Show.

(シワグレード(光皮膚老化グレード)判定基準)
(Wrinkle grade (light skin aging grade) criteria)

表1〜3から明らかなように、本発明品製造例1〜11のキク属植物抽出物は比較例であるシラカバ樹皮抽出物と比較し、いずれも顕著な皮膚肥厚、皮膚硬化、シワ形成、細胞外マトリックス成分異常蓄積、コラーゲン架橋を抑制する効果に極めて優れたものであった。 As is clear from Tables 1 to 3, the Chrysanthemum plant extracts of Production Examples 1 to 11 of the present invention are compared with the birch bark extract that is a comparative example, all of which are marked skin thickening, skin hardening, wrinkle formation, It was extremely excellent in the effect of suppressing abnormal accumulation of extracellular matrix components and collagen crosslinking.

実施例2 クリーム
(成分) (%)
(1)モノステアリン酸
ポリエチレングリコール(40E.O.) 2.0
(2)自己乳化型モノステアリン酸グリセリン 5.0
(3)ステアリン酸 5.0
(4)ベヘニルアルコール 1.0
(5)流動パラフィン 10.0
(6)トリオクタン酸グリセリル 10.0
(7)リュウノウギク花抽出物*1 0.5
(8)キクタニギク花抽出物*2 2.0
(9)グリセリン 5.0
(10)防腐剤 適量
(11)香料 適量
(12)精製水 残量
*1 製造例1
*2 製造例2
Example 2 Cream (ingredient) (%)
(1) Monostearic acid polyethylene glycol (40E.O.) 2.0
(2) Self-emulsifying glyceryl monostearate 5.0
(3) Stearic acid 5.0
(4) Behenyl alcohol 1.0
(5) Liquid paraffin 10.0
(6) Glyceryl trioctanoate 10.0
(7) Ryunogi flower extract * 1 0.5
(8) Kikutaniku flower extract * 2 2.0
(9) Glycerin 5.0
(10) Preservative appropriate amount (11) perfume appropriate amount (12) remaining amount of purified water * 1 Production Example 1
* 2 Production Example 2

(製法)
A.成分(1)〜(6)を混合し、加熱して70℃に保つ。
B.成分(9)、(10)及び(12)を混合し、加熱して70℃に保つ。
C.AにBを加えて乳化する。
D.Cに成分(7)、(8)、(11)を加えた後、冷却してクリームを得た。
(Manufacturing method)
A. Ingredients (1)-(6) are mixed and heated to keep at 70 ° C.
B. Ingredients (9), (10) and (12) are mixed and heated to keep at 70 ° C.
C. B is added to A and emulsified.
D. Components (7), (8) and (11) were added to C, and then cooled to obtain a cream.

実施例2は、変色変臭などがなく安定であり、肌に適用すると、滑らかなエモリエント効果が高く、連続的に適用することによりシワ形成、皮膚肥厚、皮膚硬化など皮膚障害を抑制又は改善する効果に優れるものであった。   Example 2 is stable without discoloration and odor and has a high smooth emollient effect when applied to the skin, and continuously applied to suppress or improve skin disorders such as wrinkle formation, skin thickening, and skin hardening. It was excellent in effect.

実施例3 化粧水
(成分) (%)
(1)グリセリン 10.0
(2)1,3−ブチレングリコール 6.0
(3)クエン酸 0.1
(4)クエン酸ナトリウム 0.3
(5)シマカンギク花抽出物*1 0.5
(6)イソギク花抽出物*2 0.5
(7)精製水 残量
(8)ポリオキシエチレン(60E.O.)硬化ヒマシ油 0.5
(9)エチルアルコール 8.0
(10)防腐剤 適量
(11)香料 適量
*1 製造例3
*2 製造例4
Example 3 lotion (ingredient) (%)
(1) Glycerin 10.0
(2) 1,3-butylene glycol 6.0
(3) Citric acid 0.1
(4) Sodium citrate 0.3
(5) Shimakangi Flower Extract * 1 0.5
(6) Sea anemone flower extract * 2 0.5
(7) Purified water remaining amount (8) polyoxyethylene (60E.O.) hydrogenated castor oil 0.5
(9) Ethyl alcohol 8.0
(10) Preservative appropriate amount (11) Fragrance appropriate amount * 1 Production Example 3
* 2 Production Example 4

(製法)
A.成分(1)〜(7)を混合溶解する。
B.成分(8)〜(11)を混合溶解する。
C.AとBを混合して、均一にし、化粧水を得た。
(Manufacturing method)
A. Components (1) to (7) are mixed and dissolved.
B. Components (8) to (11) are mixed and dissolved.
C. A and B were mixed and made uniform to obtain a skin lotion.

実施例3は、変色変臭、沈殿などがなく安定であり、肌に適用すると、みずみずしい保湿感があり、連続的に適用することによりシワ形成、皮膚肥厚、皮膚硬化などの皮膚障害を抑制又は改善する効果のあるものであった。   Example 3 is stable without discoloration, odor, precipitation, and the like, and has a fresh moisturizing feeling when applied to the skin. By applying continuously, skin damage such as wrinkle formation, skin thickening, and skin hardening is suppressed or It was effective in improving.

実施例4 乳液
(成分) (%)
(1)モノステアリン酸ソルビタン 0.3
(2)モノオレイン酸ポリオキシエチレン(20E.O.)
ソルビタン 0.1
(3)親油型モノステアリン酸グリセリル 0.2
(4)ステアリン酸 0.5
(5)セタノール 0.5
(6)スクワラン 3.0
(7)流動パラフィン 4.0
(8)トリ2−エチルヘキサン酸グリセリル 2.0
(9)ジメチルポリシロキサン 1.0
(10)水素添加大豆リン脂質 0.1
(11)カルボキシビニルポリマー水溶液(1.0%) 10.0
(12)水酸化ナトリウム 0.05
(13)グリセリン 5.0
(14)1,3−ブチレングリコール 7.0
(15)精製水 残量
(16)シュンギク花抽出物:*1 0.1
(17)エチルアルコール 5.0
(18)無水ケイ酸 1.0
(19)防腐剤 適量
(20)香料 適量
*1 製造例5
Example 4 Latex (component) (%)
(1) Sorbitan monostearate 0.3
(2) Polyoxyethylene monooleate (20E.O.)
Sorbitan 0.1
(3) Lipophilic glyceryl monostearate 0.2
(4) Stearic acid 0.5
(5) Cetanol 0.5
(6) Squalane 3.0
(7) Liquid paraffin 4.0
(8) Glyceryl tri-2-ethylhexanoate 2.0
(9) Dimethylpolysiloxane 1.0
(10) Hydrogenated soybean phospholipid 0.1
(11) Carboxyvinyl polymer aqueous solution (1.0%) 10.0
(12) Sodium hydroxide 0.05
(13) Glycerin 5.0
(14) 1,3-butylene glycol 7.0
(15) Purified water remaining amount (16) sengoku flower extract: * 1 0.1
(17) Ethyl alcohol 5.0
(18) Silicic anhydride 1.0
(19) Preservative appropriate amount (20) Fragrance appropriate amount * 1 Production Example 5

(製法)
A.成分(1)〜(10)を加熱混合し、70℃に保つ。
B.成分(11)〜(15)を加熱混合し、70℃に保つ。
C.AにBを加えて混合し、均一に乳化する。
D.Cを冷却後(16)、(17)〜(20)を加え、均一に混合して乳液を得た。
(Manufacturing method)
A. Ingredients (1) to (10) are heated and mixed and maintained at 70 ° C.
B. Ingredients (11) to (15) are heated and mixed and maintained at 70 ° C.
C. Add B to A, mix and uniformly emulsify.
D. After cooling C, (16) and (17) to (20) were added and mixed uniformly to obtain an emulsion.

実施例4は、変色変臭、分離などがなく安定であり、肌に適用すると、滑らかな保湿感があり、連続的に適用することによりシワ形成、皮膚肥厚、皮膚硬化などの皮膚障害を抑制又は改善する効果のあるものであった。   Example 4 is stable without discoloration, odor, separation, etc., and has a smooth moisturizing feeling when applied to the skin, and continuously applied to suppress skin disorders such as wrinkle formation, skin thickening, and skin hardening. Or it had the effect of improving.

実施例5 パック
(成分) (%)
(1)ポリビニルアルコール 15.0
(2)無水ケイ酸 0.5
(3)ポリエチレングリコール 0.5
(4)ポリオキシプロピレンメチルグルコシド 5.0
(5)グリセリン 5.0
(6)精製水 残量
(7)エチルアルコール 10.0
(8)防腐剤 適量
(9)フランスギク花抽出物*1 0.05
(10)香料 適量
*1 製造例6
Example 5 Pack (ingredient) (%)
(1) Polyvinyl alcohol 15.0
(2) Silicic anhydride 0.5
(3) Polyethylene glycol 0.5
(4) Polyoxypropylene methyl glucoside 5.0
(5) Glycerin 5.0
(6) Purified water remaining amount (7) Ethyl alcohol 10.0
(8) Preservative Appropriate amount (9) French chrysanthemum flower extract * 1 0.05
(10) Perfume appropriate amount * 1 Production Example 6

(製法)
A.成分(1)〜(6)を混合し、70℃に加熱して溶解する。
B.成分(7)〜(8)を混合して溶解する。
C.Bを先のAに加え、混合した後、冷却して(9)、(10)を均一に分散してパックを得た。
(Manufacturing method)
A. Components (1) to (6) are mixed and heated to 70 ° C. to dissolve.
B. Components (7) to (8) are mixed and dissolved.
C. B was added to the previous A, mixed, and then cooled to uniformly disperse (9) and (10) to obtain a pack.

実施例5は、変色変臭、分離などがなく安定であり、肌に適用すると、適度な緊張感があり、パックを剥がしたが後の肌は潤い感が高く、シワ形成、皮膚肥厚、皮膚硬化など皮膚障害を抑制又は軽減する効果に優れるものであった。   Example 5 is stable without discoloration, odor, separation, etc. When applied to the skin, it has a moderate tension, and after peeling off the pack, the skin has a high moist feeling, wrinkle formation, skin thickening, skin It was excellent in the effect of suppressing or reducing skin disorders such as curing.

実施例6 リキッドファンデーション
(成分) (%)
(1)ジペンタエリトリットテトラ12−ヒドロキシステアリン酸
セスキステアリン酸ヘミロジンエステル 2.0
(2)流動パラフィン 5.0
(3)ステアリン酸 2.0
(4)セタノール 1.0
(5)自己乳化型モノステアリン酸グリセリル 1.0
(6)パラメトキシケイ皮酸−2−エチルヘキシル 8.0
(7)ナツシロギク全草抽出物*1 0.01
(8)防腐剤 適量
(9)グリセリン 5.0
(10)トリエタノールアミン 1.0
(11)カルボキシメチルセルロース 0.2
(12)ベントナイト 0.5
(13)精製水 残量
(14)酸化チタン 6.0
(15)微粒子酸化チタン 2.0
(16)微粒子酸化亜鉛 5.0
(17)マイカ 2.0
(18)タルク 4.0
(19)着色顔料 4.0
(20)香料 適量
*1 製造例9
Example 6 Liquid foundation (component) (%)
(1) Dipentaerythritol tetra 12-hydroxystearic acid sesquistearic acid hemirosin ester 2.0
(2) Liquid paraffin 5.0
(3) Stearic acid 2.0
(4) Cetanol 1.0
(5) Self-emulsifying glyceryl monostearate 1.0
(6) Paramethoxycinnamic acid-2-ethylhexyl 8.0
(7) Feverfew whole plant extract * 1 0.01
(8) Preservative appropriate amount (9) Glycerin 5.0
(10) Triethanolamine 1.0
(11) Carboxymethylcellulose 0.2
(12) Bentonite 0.5
(13) Purified water remaining amount (14) Titanium oxide 6.0
(15) Fine particle titanium oxide 2.0
(16) Fine zinc oxide 5.0
(17) Mica 2.0
(18) Talc 4.0
(19) Color pigment 4.0
(20) Perfume appropriate amount * 1 Production Example 9

(製法)
A.成分(1)〜(6)を加熱し混合溶解する。
B.Aに成分(14)〜(19)を加え、均一に混合し、70℃に保つ。
C.成分(8)〜(13)を均一に溶解し、70℃に保つ。
D.CにBを添加して、均一に乳化する。
E.Dを冷却後、成分(7)、(20)を添加してリキッドファンデーションを得た。
(Manufacturing method)
A. Components (1) to (6) are heated and mixed and dissolved.
B. Ingredients (14) to (19) are added to A, mixed uniformly, and kept at 70 ° C.
C. Ingredients (8) to (13) are uniformly dissolved and kept at 70 ° C.
D. B is added to C and emulsified uniformly.
E. After cooling D, components (7) and (20) were added to obtain a liquid foundation.

実施例6は、変臭、分離などがなく安定であり、肌に適用すると、潤い感のあるメイク効果に優れ、日中の紫外線からも適度に肌を守り、シワ、皮膚肥厚、皮膚硬化など皮膚障害を抑制又は軽減する効果に優れるものであった。   Example 6 is stable with no odor, separation, etc., and when applied to the skin, is excellent in a moisturizing makeup effect, moderately protects the skin from ultraviolet rays during the day, wrinkles, skin thickening, skin hardening, etc. It was excellent in the effect of suppressing or reducing skin damage.

実施例7 日焼け止め乳液
(成分) (%)
(1)ポリオキシアルキレン変性オルガノポリシロキサン 1.0
(2)ジメチルポリシロキサン 5.0
(3)オクタメチルシクロテトラシロキサン 20.0
(4)イソノナン酸イソトリデシル 5.0
(5)パラメトキシケイ皮酸−2−エチルヘキシル 5.0
(6)微粒子酸化チタン 10.0
(7)微粒子酸化亜鉛 10.0
(8)酸化ジルコニウム 5.0
(9)ポリスチレン末 3.0
(10)トリメチルシロキシケイ酸 0.5
(11)防腐剤 適量
(12)ジプロピレングリコール 3.0
(13)エチルアルコール 10.0
(14)精製水 残量
(15)食塩 0.2
(16)シュンギク葉抽出物*1 0.2
(17)香料 適量
*1 製造例8
Example 7 Sunscreen Latex (Component) (%)
(1) Polyoxyalkylene-modified organopolysiloxane 1.0
(2) Dimethylpolysiloxane 5.0
(3) Octamethylcyclotetrasiloxane 20.0
(4) Isotridecyl isononanoate 5.0
(5) Paramethoxycinnamic acid-2-ethylhexyl 5.0
(6) Fine particle titanium oxide 10.0
(7) Fine zinc oxide 10.0
(8) Zirconium oxide 5.0
(9) Polystyrene powder 3.0
(10) Trimethylsiloxysilicate 0.5
(11) Preservative appropriate amount (12) Dipropylene glycol 3.0
(13) Ethyl alcohol 10.0
(14) Purified water remaining amount (15) Salt 0.2
(16) Chrysanthemum leaf extract * 1 0.2
(17) Perfume appropriate amount * 1 Production Example 8

(製法)
A.成分(1)〜(10)を混合分散する。
B.成分(11)〜(15)を混合溶解する。
C.AにBを添加して、均一に乳化する。
D.Cに成分(16)、(17)を添加して日焼け止め乳液を得た。
(Manufacturing method)
A. Components (1) to (10) are mixed and dispersed.
B. Components (11) to (15) are mixed and dissolved.
C. Add B to A and emulsify uniformly.
D. Components (16) and (17) were added to C to obtain a sunscreen emulsion.

実施例7は、変臭、分離などがなく安定であり、肌に適用すると、さっぱりとしたエモリエント効果があり、日中の紫外線から肌を守り、シワ形成、皮膚肥厚、皮膚硬化など皮膚障害を抑制又は軽減する効果に優れるものであった。   Example 7 is stable with no odor, separation, etc., and when applied to the skin, has a refreshing emollient effect, protects the skin from ultraviolet rays during the day, and prevents skin disorders such as wrinkle formation, skin thickening, and skin hardening. It was excellent in the effect of suppressing or reducing.

Claims (1)

リュウノウギク(Chrysanthemum Makino Matsum.etNakai)、キクタニギク(Chrysanthemum boreale Makino)、シマカンギク(Chrysanthemum indicum L.)、イソギク(Chrysanthemum pacificum)、シュンギク(Chrysanthemum coronarium)、及びフランスギク(Chrysanthemum Leucanthemum L.)からなる群から選ばれる少なくとも一種以上を有効成分とする、紫外線曝露に起因する皮膚細胞外マトリックス成分異常蓄積抑制作用、又は紫外線曝露に起因する皮膚肥厚抑制作用を示す老化防止用皮膚外用剤。 Ryuunougiku (Chrysanthemum Makino Matsum.etNakai), Kikutanigiku (Chrysanthemum boreale Makino), Shimakangiku (Chrysanthemum indicum L.), chrysanthemum pacificum (Chrysanthemum pacificum), garland chrysanthemum (Chrysanthemum coronarium), and selected from the group consisting of French Chrysanthemum (Chrysanthemum Leucanthemum L.) A skin external preparation for anti-aging which exhibits an action to suppress abnormal accumulation of skin extracellular matrix components caused by exposure to ultraviolet rays, or an action to suppress skin thickening caused by exposure to ultraviolet rays, comprising at least one selected from the above as an active ingredient.
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