JP5690150B2 - External preparation or internal preparation - Google Patents
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- JP5690150B2 JP5690150B2 JP2011007413A JP2011007413A JP5690150B2 JP 5690150 B2 JP5690150 B2 JP 5690150B2 JP 2011007413 A JP2011007413 A JP 2011007413A JP 2011007413 A JP2011007413 A JP 2011007413A JP 5690150 B2 JP5690150 B2 JP 5690150B2
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- extract
- mmp
- skin
- formulation
- ryukyu
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Description
本発明は、活性酸素消去、MMP産生抑制、メラニン生成抑制及び細胞増殖促進作用に優れた新規な外用剤又は内用剤に関する。 The present invention relates to a novel external or internal preparation excellent in active oxygen elimination, MMP production inhibition, melanin production inhibition and cell growth promoting action.
皮膚は生体の最外層に位置し、紫外線等の影響により活性酸素が発生しやすい臓器であり、絶えずその酸素ストレスに曝されている。一方、皮膚細胞内には活性酸素消去酵素が存在しており、その能力を超える活性酸素が発生しないかぎり活性酸素の傷害から皮膚細胞を防衛している。ところが、皮膚細胞内の活性酸素消去酵素の活性は加齢とともに低下することが知られており、活性酸素による傷害がその防御反応を凌駕したとき、皮膚は酸化され、細胞機能が劣化して老化してゆくと考えられる。また、皮膚以外の臓器においても、その活性酸素消去能を越える活性酸素に曝されたとき、機能低下が起こり老化してゆくと考えられる。そこで、活性酸素による傷害からの防御を目的として活性酸素消去剤や抗酸化剤が検討され、SODやカタラーゼ等の活性酸素消去酵素、SOD様活性物質などの活性酸素消去剤や抗酸化剤を配合した食品、化粧品、医薬部外品及び医薬品等が開発されている(特許文献1,2参照)。 The skin is located in the outermost layer of the living body, is an organ in which active oxygen is easily generated due to the influence of ultraviolet rays and the like, and is constantly exposed to the oxygen stress. On the other hand, active oxygen scavenging enzymes exist in the skin cells, and protect the skin cells from injury of active oxygen unless active oxygen exceeding that capacity is generated. However, it is known that the activity of the active oxygen scavenging enzyme in skin cells decreases with age, and when the injury due to active oxygen surpasses its protective reaction, the skin is oxidized and the cell function deteriorates and ages. It is thought that it will do. Also, in organs other than the skin, when exposed to active oxygen exceeding its active oxygen scavenging ability, it is considered that functional deterioration occurs and aging occurs. Therefore, active oxygen scavengers and antioxidants have been studied for the purpose of protecting against active oxygen injury, and active oxygen scavengers such as SOD and catalase, and active oxygen scavengers and antioxidants such as SOD-like active substances are included. Foods, cosmetics, quasi-drugs and pharmaceuticals have been developed (see Patent Documents 1 and 2).
皮膚の老化に伴う変化を誘導する因子として、マトリックスメタロプロテアーゼ(MMPs;Matrix Metalloproteinases)の関与が指摘されている。このMMPsの中でも、マトリックスメタロプロテアーゼ−1(MMP−1)は、皮膚の真皮細胞外マトリックスの主要構成成分であるコラーゲンを分解する酵素として知られているが、その発現は紫外線の照射により大きく増加し、コラーゲンの減少・変性の一因となり、皮膚のしわの形成、弾力性の低下等の大きな要因となると考えられている。このようなMMP−1活性阻害作用を有するものとしては、例えば、マツ科マツ属二葉松類の樹皮の抽出物等が知られている(特許文献3参照)。 Involvement of matrix metalloproteinases (MMPs) is pointed out as factors that induce changes associated with skin aging. Among these MMPs, matrix metalloproteinase-1 (MMP-1) is known as an enzyme that degrades collagen, which is a major component of the dermal extracellular matrix of skin, but its expression is greatly increased by irradiation with ultraviolet rays. However, it is thought to contribute to the decrease / denaturation of collagen, and to become a major factor such as the formation of wrinkles on the skin and the decrease in elasticity. For example, an extract of a bark of a pine genus Pinaceae is known as one having such an MMP-1 activity inhibitory effect (see Patent Document 3).
ゼラチナーゼ群に属する酵素であるマトリックスメタロプロテアーゼ−2(MMP−2)は、基底膜の主要構成成分であるIV型コラーゲンやラミニン5を分解する酵素として知られているが、その発現及び活性は紫外線の照射により大きく増加し、紫外線による基底膜成分の減少、基底膜の構造変化の原因となり、皮膚におけるシワやたるみの形成等の大きな要因となることが明らかとなっている(非特許文献1参照)。 Matrix metalloproteinase-2 (MMP-2), an enzyme belonging to the gelatinase group, is known as an enzyme that degrades type IV collagen and laminin 5, which are the main components of the basement membrane. Is significantly increased by UV irradiation, causes a decrease in basement membrane components due to ultraviolet rays, changes in the structure of the basement membrane, and is a major factor in the formation of wrinkles and sagging in the skin (see Non-Patent Document 1). ).
さらに、MMP−2は、血管内皮細胞下に存在する基底膜を構成するIV型コラーゲン等を分解し、分解された血管内皮細胞は間質へ遊走していき、間質中で増殖し、管腔を形成し、新生血管を構築していく。そして、この新生された血管が腫瘍細胞に到達して、栄養源と酸素とを腫瘍細胞に供給し、腫瘍が大きくなっていくことが知られている(非特許文献2参照)。また、MMP−2のノックアウトマウスにおいて、血管新生の未発達やガンの増殖抑制が認められるなど、MMP−2は、ガンの増殖や血管新生において重要な役割を果たしている(非特許文献3参照)。 Furthermore, MMP-2 degrades type IV collagen and the like constituting the basement membrane existing under the vascular endothelial cells, and the decomposed vascular endothelial cells migrate to the stroma, proliferate in the stroma, and tube A cavity is formed and new blood vessels are constructed. Then, it is known that the newly formed blood vessels reach the tumor cells, supply nutrient sources and oxygen to the tumor cells, and the tumor grows (see Non-Patent Document 2). In addition, MMP-2 plays an important role in cancer growth and angiogenesis, such as angiogenesis underdevelopment and cancer growth inhibition in MMP-2 knockout mice (see Non-Patent Document 3). .
一般に、シミ、ソバカス、日焼け等に見られる皮膚の色素沈着は、ホルモンの異常や紫外線の刺激により、皮膚内に存在するメラニン色素生成細胞がメラニン色素を過剰に生成し、これが皮膚内に沈着することが原因と考えられている。このような色素沈着を防ぐ方法の一つに、メラニンの過剰な生成を抑制する方法が知られている。従来、色素沈着の治療には、内用や外用などにおいて、アスコルビン酸(ビタミンC)等が用いられてきた。 In general, pigmentation of the skin seen in spots, buckwheat, sunburn, etc. is caused by excessive melanin pigment formation in the skin by melanin pigment-producing cells present in the skin due to hormonal abnormalities and stimulation of ultraviolet rays. It is thought to be the cause. As one method for preventing such pigmentation, a method for suppressing excessive production of melanin is known. Conventionally, ascorbic acid (vitamin C) or the like has been used for treatment of pigmentation in internal use or external use.
加齢とともに表皮細胞の増殖・分裂能は低下し、表皮層自体は薄くなる(非特許文献4参照)。生体因子であるEpidermal Growth Factor(EGF/上皮細胞成長因子)や女性ホルモン(エストロゲン)は皮膚の表皮細胞増殖に働きかけるが、加齢と共にその分泌は低下する。このような加齢による表皮細胞代謝機能の低下は、皮膚のターンオーバー速度を遅らせ、肌荒れや皮膚の老化の原因となる。また、角層表面から剥がれ落ちる角層細胞が滞留することで、表皮内メラニンの排泄がスムーズに行われなくなり、色素沈着や肌のくすみの原因となる。さらに表皮の創傷治癒が遅くなることなども知られている。これらの現象の進行を防止あるいは改善するために、表皮細胞の増殖を促進させる成分の探索や、多くの皮膚外用剤の提案がなされてきた。 The proliferation / division ability of epidermal cells decreases with aging, and the epidermal layer itself becomes thin (see Non-Patent Document 4). Epidermal Growth Factor (EGF / epidermal growth factor) and female hormones (estrogens), which are biological factors, act on the proliferation of epidermal cells in the skin, but their secretion decreases with age. Such a decrease in epidermal cell metabolic function due to aging delays the turnover speed of the skin, causing rough skin and aging of the skin. In addition, the horny layer cells that fall off from the stratum corneum surface stay, and the melanin in the epidermis is not excreted smoothly, causing pigmentation and dull skin. It is also known that epidermal wound healing is delayed. In order to prevent or improve the progression of these phenomena, search for components that promote the proliferation of epidermal cells and proposals for many external preparations for skin have been made.
しかしながら、これらの活性酸素消去効果、MMP産生抑制効果、メラニン生成抑制効果及び細胞増殖促進効果を有する植物由来の天然原料として、本発明に用いたリュウキュウバライチゴは検討されていなかった。 However, the Ryukyu rose strawberry used in the present invention has not been studied as a plant-derived natural raw material having these active oxygen scavenging effects, MMP production inhibitory effects, melanin production inhibitory effects, and cell growth promoting effects.
安全で安定性に優れ、活性酸素消去作用、MMP産生抑制作用、メラニン生成抑制作用及び細胞増殖促進作用に優れた素材が望まれているが、未だ十分満足し得るものが提供されていないのが現状である。 A material that is safe and excellent in stability, excellent in active oxygen scavenging action, MMP production inhibitory action, melanin production inhibitory action, and cell growth promoting action is desired, but a material that is still satisfactory is not provided. Currently.
このような事情により、本発明者らは鋭意検討した結果、リュウキュウバライチゴの抽出物が優れた活性酸素消去作用、MMP産生抑制作用、メラニン生成抑制作用及び細胞増殖促進作用を持ち、安定性においても優れていることを見出した。さらに、その抽出物を含有する外用剤又は内用剤が、安全で安定であり、活性酸素消去作用、MMP産生抑制作用、メラニン生成抑制作用及び細胞増殖促進作用に優れており、多機能性美容・健康用素材と成り得ることを見いだし、本発明を完成するに至った。 Under these circumstances, the present inventors have intensively studied. As a result, the extract of Ryukyu rose strawberry has excellent active oxygen scavenging action, MMP production inhibitory action, melanin production inhibitory action, and cell growth promoting action, and in stability. Also found it to be excellent. Furthermore, the external preparation or internal preparation containing the extract is safe and stable, and has excellent active oxygen scavenging action, MMP production inhibitory action, melanin production inhibitory action, and cell growth promoting action, and has a multifunctional beauty.・ It was found that it could be a health material, and the present invention was completed.
本発明に用いるリュウキュウバライチゴの抽出物とは、バラ科キイチゴ属リュウキュウバライチゴ(学名:Rubus croceacanthus)(別名:オオバライチゴ)の花、茎、葉、枝、枝葉、根、種子等の植物体の一部又は全草から抽出したものである。その抽出方法は特に限定されず、例えば、加熱抽出したものであっても良いし、常温抽出したものであっても良い。 The extract of Ryukyu rose strawberry used in the present invention refers to plants such as flowers, stems, leaves, branches, branches, leaves, roots, seeds, etc. It is extracted from a part of the whole or whole grass. The extraction method is not particularly limited, and for example, it may be a heat extraction or a room temperature extraction.
抽出する溶媒としては、例えば、水、低級アルコール類(メタノール、エタノール、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(1,3−ブチレングリコール、プロピレングリコール、グリセリン等)、ケトン類(アセトン、メチルエチルケトン等)、アセトニトリル、エステル類(酢酸エチル、酢酸ブチル等)、炭化水素類(ヘキサン、ヘプタン、流動パラフィン等)、エーテル類(エチルエーテル、テトラヒドロフラン、プロピルエーテル等)が挙げられる。好ましくは、水、低級アルコール及び液状多価アルコール等の極性溶媒が良く、特に好ましくは、水、エタノール、1,3−ブチレングリコール及びプロピレングリコールが良い。これらの溶媒は一種でも二種以上を混合して用いても良い。 Examples of the solvent to be extracted include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol). , Glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether) Etc.). Preferred are polar solvents such as water, lower alcohols and liquid polyhydric alcohols, and particularly preferred are water, ethanol, 1,3-butylene glycol and propylene glycol. These solvents may be used alone or in combination of two or more.
上記抽出物は、抽出した溶液のまま用いても良く、必要に応じて、濃縮、希釈及び濾過処理、活性炭等による脱色、脱臭処理等をして用いても良い。更には、抽出した溶液を濃縮乾固、噴霧乾燥、凍結乾燥等の処理を行い、乾燥物として用いても良い。 The extract may be used as it is, or may be used after concentration, dilution and filtration treatment, decolorization with activated carbon, deodorization treatment, or the like, if necessary. Further, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.
本発明の外用剤又は内用剤には、上記抽出物をそのまま使用しても良く、抽出物の効果を損なわない範囲内で、化粧品、医薬部外品、医薬品又は食品等に用いられる成分である油脂類、ロウ類、炭化水素類、脂肪酸類、アルコール類、エステル類、界面活性剤、金属石鹸、pH調整剤、防腐剤、香料、保湿剤、粉体、紫外線吸収剤、増粘剤、色素、酸化防止剤、美白剤、キレート剤、賦形剤、皮膜剤、甘味料、酸味料等の成分を配合することもできる。 In the external preparation or internal preparation of the present invention, the above-mentioned extract may be used as it is, and it is a component used in cosmetics, quasi drugs, pharmaceuticals, foods, etc. within the range not impairing the effect of the extract. Certain fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, Components such as a dye, an antioxidant, a whitening agent, a chelating agent, an excipient, a film agent, a sweetener, and a sour agent can also be blended.
本発明の剤型としては、例えば、化粧水、クリーム、マッサージクリーム、乳液、ゲル剤、エアゾール剤、パック、洗浄剤、浴用剤、ファンデーション、打粉、口紅、軟膏、パップ剤、ペースト剤、プラスター剤、エッセンス、散剤、丸剤、錠剤、注射剤、坐剤、乳剤、カプセル剤、顆粒剤、液剤(チンキ剤、流エキス剤、酒精剤、懸濁剤、リモナーデ剤等を含む)、錠菓、飲料等が挙げられる。 Examples of the dosage form of the present invention include lotions, creams, massage creams, emulsions, gels, aerosols, packs, cleaning agents, bath preparations, foundations, powders, lipsticks, ointments, poultices, pastes, plasters. Essences, powders, pills, tablets, injections, suppositories, emulsions, capsules, granules, liquids (including tinctures, fluid extracts, spirits, suspensions, limonades, etc.), tablets, A drink etc. are mentioned.
本発明に用いる上記抽出物の配合量は、外用の場合、全量に対し、固形物に換算して0.0001重量%以上が好ましく、0.001〜10重量%がより好ましい。さらに、0.01〜5重量%が最も好ましい。0.0001重量%未満では十分な効果は望みにくい。10重量%を越えて配合した場合、効果の増強は認められにくく不経済である。一方、内用の場合、投与量は年齢、体重、症状、治療効果、投与方法、処理時間等により異なるが、通常、成人1人当たりの1日の量としては、5mg以上が好ましく、10mg〜0.5gがより好ましい。さらに、20mg〜0.2gが最も好ましい。 In the case of external use, the amount of the extract used in the present invention is preferably 0.0001% by weight or more, more preferably 0.001 to 10% by weight, in terms of solid matter, based on the total amount. Furthermore, 0.01 to 5% by weight is most preferable. If it is less than 0.0001% by weight, a sufficient effect is hardly expected. When the blending amount exceeds 10% by weight, the effect is hardly recognized and it is uneconomical. On the other hand, for internal use, the dose varies depending on age, weight, symptoms, therapeutic effect, administration method, treatment time, etc., but the daily dose per adult is usually preferably 5 mg or more, and 10 mg to 0 0.5 g is more preferable. Furthermore, 20 mg to 0.2 g is most preferable.
次に本発明を詳細に説明するため、実施例として本発明に用いる抽出物の製造例、処方例及び実験例を挙げるが、本発明はこれに限定されるものではない。実施例に示す配合量の部とは重量部を、%とは重量%を示す。 Next, in order to describe the present invention in detail, examples of production of the extract used in the present invention, formulation examples and experimental examples will be given as examples, but the present invention is not limited thereto. In the examples, the part of the amount is part by weight, and% is% by weight.
製造例1 リュウキュウバライチゴの熱水抽出物
リュウキュウバライチゴの全草の乾燥物20gに精製水400mLを加え、95〜100℃で2時間抽出した後、濾過し、その濾液を濃縮し、凍結乾燥してリュウキュウバライチゴの熱水抽出物を2.5g得た。
Production Example 1 Ryukyu rose strawberry hot water extract 400 g of purified water was added to 20 g of dried dried ryukyuba strawberry whole plant, extracted at 95-100 ° C. for 2 hours, filtered, and the filtrate was concentrated and lyophilized. As a result, 2.5 g of a hot water extract of Ryukyu rose strawberry was obtained.
製造例2 リュウキュウバライチゴの50%エタノール抽出物
リュウキュウバライチゴの全草の乾燥物100gに50%エタノール水溶液1Lを加え、常温で7日間抽出した後、濾過し、その濾液を濃縮乾固して、リュウキュウバライチゴの50%エタノール抽出物を3.8g得た。
Production Example 2 50% ethanol extract of Ryukyu rose strawberry 1 L of 50% ethanol aqueous solution was added to 100 g of dry product of whole plant of Ryukyu rose strawberry, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness. 3.8 g of 50% ethanol extract of Ryukyu rose strawberry was obtained.
製造例3 リュウキュウバライチゴのエタノール抽出物
リュウキュウバライチゴの葉の乾燥物100gにエタノール1Lを加え、常温で7日間抽出した後、濾過し、その濾液を濃縮乾固して、リュウキュウバライチゴのエタノール抽出物を4.1g得た。
Production Example 3 Ethanol extract of Ryukyu rose strawberry Add 1 L of ethanol to 100 g of dried Ryukyu rose strawberry leaves, extract at room temperature for 7 days, filter, concentrate the filtrate to dryness, and ethanol of Ryukyu rose strawberry. 4.1 g of extract was obtained.
製造例4 リュウキュウバライチゴの50%1,3−ブチレングリコール抽出物
リュウキュウバライチゴの地上部の乾燥物20gに50%1,3−ブチレングリコール水溶液400mLを加え、常温で7日間抽出した後、濾過し、リュウキュウバライチゴの50%1,3−ブチレングリコール抽出物を370g得た。
Production Example 4 50% 1,3-butylene glycol extract of Ryukyu rose strawberry 400 mL of 50% 1,3-butylene glycol aqueous solution was added to 20 g of the dried product of the above-ground portion of Ryukyu rose strawberry, extracted at room temperature for 7 days, and then filtered. 370 g of 50% 1,3-butylene glycol extract of Ryukyu rose strawberry was obtained.
処方例1 化粧水
処方 配合量(部)
1.リュウキュウバライチゴの熱水抽出物(製造例1) 1.0
2.1,3−ブチレングリコール 8.0
3.グリセリン 2.0
4.キサンタンガム 0.02
5.クエン酸 0.01
6.クエン酸ナトリウム 0.1
7.エタノール 5.0
8.パラオキシ安息香酸メチル 0.1
9.ポリオキシエチレン硬化ヒマシ油(40E.O.) 0.1
10.香料 適量
11.精製水にて全量を100とする
[製造方法]成分1〜6及び11と、成分7〜10をそれぞれ均一に溶解し、両者を混合し濾過して製品とする。
Formulation Example 1 Lotion Prescription Formulation Amount (parts)
1. Ryukyu rose strawberry hot water extract (Production Example 1) 1.0
2. 1,3-butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Perfume proper amount11. [Manufacturing method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved in purified water, and both are mixed and filtered to obtain a product.
比較例1 従来の化粧水
処方例1において、リュウキュウバライチゴの熱水抽出物を精製水に置き換えたものを従来の化粧水とした。
Comparative Example 1 Conventional lotion In Formulation Example 1, the hot water extract of Ryukyu rose strawberry was replaced with purified water to obtain a conventional lotion.
処方例2 クリーム
処方 配合量(部)
1.リュウキュウバライチゴの50%エタノール抽出物(製造例2) 0.5
2.スクワラン 5.5
3.オリーブ油 3.0
4.ステアリン酸 2.0
5.ミツロウ 2.0
6.ミリスチン酸オクチルドデシル 3.5
7.ポリオキシエチレンセチルエーテル(20E.O.) 3.0
8.ベヘニルアルコール 1.5
9.モノステアリン酸グリセリン 2.5
10.香料 0.1
11.パラオキシ安息香酸メチル 0.2
12.パラオキシ安息香酸エチル 0.05
13.1,3−ブチレングリコール 8.5
14.精製水にて全量を100とする
[製造方法]成分2〜9を加熱溶解して混合し、70℃に保ち油相とする。成分1及び11〜14を加熱溶解して混合し、75℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら冷却し、45℃で成分10を加え、更に30℃まで冷却して製品とする。
Formulation Example 2 Cream Formulation Amount (parts)
1. 50% ethanol extract of Ryukyu rose strawberry (Production Example 2) 0.5
2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.1
11. Methyl paraoxybenzoate 0.2
12 Ethyl paraoxybenzoate 0.05
13.1,3-Butylene glycol 8.5
14 [Manufacturing method] Components 2 to 9 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 11 to 14 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.
処方例3 乳液
処方 配合量(部)
1.リュウキュウバライチゴの熱水抽出物(製造例1) 0.01
2.スクワラン 5.0
3.オリーブ油 5.0
4.ホホバ油 5.0
5.セタノール 1.5
6.モノステアリン酸グリセリン 2.0
7.ポリオキシエチレンセチルエーテル(20E.O.) 3.0
8.ポリオキシエチレンソルビタンモノオレエート(20E.O.) 2.0
9.香料 0.1
10.プロピレングリコール 1.0
11.グリセリン 2.0
12.パラオキシ安息香酸メチル 0.2
13.精製水にて全量を100とする
[製造方法]成分2〜8を加熱溶解して混合し、70℃に保ち油相とする。成分1及び10〜13を加熱溶解して混合し、75℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら冷却し、45℃で成分9を加え、更に30℃まで冷却して製品とする。
Formulation Example 3 Latex Formulation Formulation amount (parts)
1. Ryukyu rose strawberry hot water extract (Production Example 1) 0.01
2. Squalane 5.0
3. Olive oil 5.0
4). Jojoba oil 5.0
5. Cetanol 1.5
6). Glycerol monostearate 2.0
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Polyoxyethylene sorbitan monooleate (20E.O.) 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12 Methyl paraoxybenzoate 0.2
13. [Manufacturing method] Components 2 to 8 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 10-13 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring.
処方例4 ゲル剤
処方 配合量(部)
1.リュウキュウバライチゴのエタノール抽出物(製造例3) 1.0
2.エタノール 5.0
3.パラオキシ安息香酸メチル 0.1
4.ポリオキシエチレン硬化ヒマシ油(60E.O.) 0.1
5.香料 適量
6.1,3−ブチレングリコール 5.0
7.グリセリン 5.0
8.キサンタンガム 0.1
9.カルボキシビニルポリマー 0.2
10.水酸化カリウム 0.2
11.精製水にて全量を100とする
[製造方法]成分2〜5と、成分1及び6〜11をそれぞれ均一に溶解し、両者を混合して製品とする。
Formulation Example 4 Gel formulation Formulation Amount (parts)
1. Ethanol extract of Ryukyu rose strawberry (Production Example 3) 1.0
2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Perfume appropriate amount 6.1,3-butylene glycol 5.0
7). Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. [Production method] Ingredients 2 to 5 and ingredients 1 and 6 to 11 are uniformly dissolved in purified water, and the two are mixed to obtain a product.
処方例5 パック
処方 配合量(部)
1.リュウキュウバライチゴの熱水抽出物(製造例1) 1.0
2.リュウキュウバライチゴの
50%1,3−ブチレングリコール抽出物(製造例4) 5.0
3.ポリビニルアルコール 12.0
4.エタノール 5.0
5.1,3−ブチレングリコール 8.0
6.パラオキシ安息香酸メチル 0.2
7.ポリオキシエチレン硬化ヒマシ油(20E.O.) 0.5
8.クエン酸 0.1
9.クエン酸ナトリウム 0.3
10.香料 適量
11.精製水にて全量を100とする
[製造方法]成分1〜11を均一に溶解し製品とする。
Formulation Example 5 Pack Formulation Amount (part)
1. Ryukyu rose strawberry hot water extract (Production Example 1) 1.0
2. 50% 1,3-butylene glycol extract of Ryukyu rose strawberry (Production Example 4) 5.0
3. Polyvinyl alcohol 12.0
4). Ethanol 5.0
5.1,3-Butylene glycol 8.0
6). Methyl paraoxybenzoate 0.2
7). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
8). Citric acid 0.1
9. Sodium citrate 0.3
10. Perfume proper amount11. [Production Method] Components 1 to 11 are uniformly dissolved in purified water to make a total amount of 100 to obtain a product.
処方例6 ファンデーション
処方 配合量(部)
1.リュウキュウバライチゴの50%エタノール抽出物(製造例2) 1.0
2.ステアリン酸 2.4
3.ポリオキシエチレンソルビタンモノステアレート(20E.O.) 1.0
4.ポリオキシエチレンセチルエーテル(20E.O.) 2.0
5.セタノール 1.0
6.液状ラノリン 2.0
7.流動パラフィン 3.0
8.ミリスチン酸イソプロピル 6.5
9.カルボキシメチルセルロースナトリウム 0.1
10.ベントナイト 0.5
11.プロピレングリコール 4.0
12.トリエタノールアミン 1.1
13.パラオキシ安息香酸メチル 0.2
14.二酸化チタン 8.0
15.タルク 4.0
16.ベンガラ 1.0
17.黄酸化鉄 2.0
18.香料 適量
19.精製水にて全量を100とする
[製造方法]成分2〜8を加熱溶解し、80℃に保ち油相とする。成分19に成分9をよく膨潤させ、続いて、成分1及び10〜13を加えて均一に混合する。これに粉砕機で粉砕混合した成分14〜17を加え、ホモミキサーで撹拌し75℃に保ち水相とする。この水相に油相をかき混ぜながら加え、冷却し、45℃で成分18を加え、かき混ぜながら30℃まで冷却して製品とする。
Formulation Example 6 Foundation Formulation Amount (parts)
1. 50% ethanol extract of Ryukyu rose strawberry (Production Example 2) 1.0
2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Sodium carboxymethylcellulose 0.1
10. Bentonite 0.5
11. Propylene glycol 4.0
12 Triethanolamine 1.1
13. Methyl paraoxybenzoate 0.2
14 Titanium dioxide 8.0
15. Talc 4.0
16. Bengala 1.0
17. Yellow iron oxide 2.0
18. Perfume proper amount19. [Manufacturing method] Components 2 to 8 are heated and dissolved in purified water to a total amount of 100, and kept at 80 ° C to obtain an oil phase. Swell component 9 well in component 19, then add components 1 and 10-13 and mix uniformly. To this, components 14 to 17 pulverized and mixed with a pulverizer are added, and the mixture is stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The oil phase is added to this aqueous phase with stirring, cooled, component 18 is added at 45 ° C., and cooled to 30 ° C. with stirring to give a product.
処方例7 浴用剤
処方 配合量(部)
1.リュウキュウバライチゴの熱水抽出物(製造例1) 1.0
2.炭酸水素ナトリウム 50.0
3.黄色202号(1) 適量
4.香料 適量
5.硫酸ナトリウムにて全量を100とする
[製造方法]成分1〜5を均一に混合し製品とする。
Formulation Example 7 Bath preparation Formulation Formulation amount (parts)
1. Ryukyu rose strawberry hot water extract (Production Example 1) 1.0
2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume appropriate amount 5. [Manufacturing method] Ingredients 1 to 5 are mixed uniformly with sodium sulfate to make a product.
処方例8 軟膏
処方 配合量(部)
1.リュウキュウバライチゴの熱水抽出物(製造例1) 1.0
2.リュウキュウバライチゴの
50%1,3−ブチレングリコール抽出物(製造例4) 5.0
3.ポリオキシエチレンセチルエーテル(30E.O.) 2.0
4.モノステアリン酸グリセリン 10.0
5.流動パラフィン 5.0
6.セタノール 6.0
7.パラオキシ安息香酸メチル 0.1
8.プロピレングリコール 10.0
9.精製水にて全量を100とする
[製造方法]成分3〜6を加熱溶解して混合し、70℃に保ち油相とする。成分1、2及び7〜9を加熱溶解して混合し、75℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら30℃まで冷却して製品とする。
Formulation Example 8 Ointment Formulation Formulation amount (parts)
1. Ryukyu rose strawberry hot water extract (Production Example 1) 1.0
2. 50% 1,3-butylene glycol extract of Ryukyu rose strawberry (Production Example 4) 5.0
3. Polyoxyethylene cetyl ether (30E.O.) 2.0
4). Glycerol monostearate 10.0
5. Liquid paraffin 5.0
6). Cetanol 6.0
7). Methyl paraoxybenzoate 0.1
8). Propylene glycol 10.0
9. [Production Method] Components 3 to 6 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C. to obtain an oil phase. Ingredients 1, 2, and 7-9 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled to 30 ° C. with stirring to obtain a product.
処方例9 散剤1
処方 配合量(部)
1.リュウキュウバライチゴの熱水抽出物(製造例1) 1.0
2.乾燥コーンスターチ 39.0
3.微結晶セルロース 60.0
[製造方法]成分1〜3を混合し、散剤とする。
Formulation Example 9 Powder 1
Formulation Amount (parts)
1. Ryukyu rose strawberry hot water extract (Production Example 1) 1.0
2. Dried corn starch 39.0
3. Microcrystalline cellulose 60.0
[Production method] Components 1 to 3 are mixed to obtain a powder.
処方例10 散剤2
処方例9において、リュウキュウバライチゴの熱水抽出物をエタノール抽出物(製造例3)に置き換えたものを散剤2とした。
Formulation Example 10 Powder 2
In Formulation Example 9, Powder 2 was prepared by replacing the hot water extract of Ryukyu rose strawberry with an ethanol extract (Production Example 3).
処方例11 錠剤
処方 配合量(部)
1.リュウキュウバライチゴのエタノール抽出物(製造例3) 5.0
2.乾燥コーンスターチ 25.0
3.カルボキシメチルセルロースカルシウム 20.0
4.微結晶セルロース 40.0
5.ポリビニルピロリドン 7.0
6.タルク 3.0
[製造方法]成分1〜4を混合し、次いで成分5の水溶液を結合剤として加えて顆粒成型する。成型した顆粒に成分6を加えて打錠する。1錠0.52gとする。
Formulation Example 11 Tablet Formulation Blending amount (parts)
1. Ethanol extract of Ryukyu rose strawberry (Production Example 3) 5.0
2. Dried corn starch 25.0
3. Carboxymethylcellulose calcium 20.0
4). Microcrystalline cellulose 40.0
5. Polyvinylpyrrolidone 7.0
6). Talc 3.0
[Production method] Components 1 to 4 are mixed, and then an aqueous solution of component 5 is added as a binder to form granules. Ingredient 6 is added to the molded granules and compressed. One tablet is 0.52 g.
処方例12 錠菓
処方 配合量(部)
1.リュウキュウバライチゴのエタノール抽出物(製造例3) 2.0
2.乾燥コーンスターチ 49.8
3.エリスリトール 40.0
4.クエン酸 5.0
5.ショ糖脂肪酸エステル 3.0
6.香料 0.1
7.精製水 0.1
[製造方法]成分1〜4及び7を混合し、顆粒成型する。成型した顆粒に成分5及び6を加えて打錠する。1粒1.0gとする。
Formulation Example 12 Tablet Confection Formulation Amount (parts)
1. Ethanol extract of Ryukyu rose strawberry (Production Example 3) 2.0
2. Dried corn starch 49.8
3. Erythritol 40.0
4). Citric acid 5.0
5. Sucrose fatty acid ester 3.0
6). Fragrance 0.1
7). Purified water 0.1
[Production method] Components 1 to 4 and 7 are mixed and granulated. Ingredients 5 and 6 are added to the molded granules and tableted. One tablet is 1.0 g.
処方例12 飲料
処方 配合量(部)
1.リュウキュウバライチゴの熱水抽出物(製造例1) 0.05
2.ステビア 0.05
3.リンゴ酸 5.0
4.香料 0.1
5.精製水 94.8
[製造方法]成分2及び3を少量の水に溶解する。次いで、成分1、4及び5を加えて混合する。
Formulation Example 12 Beverage Formulation Blending amount (parts)
1. Ryukyu rose strawberry hot water extract (Production Example 1) 0.05
2. Stevia 0.05
3. Malic acid 5.0
4). Fragrance 0.1
5. Purified water 94.8
[Production Method] Components 2 and 3 are dissolved in a small amount of water. Components 1, 4 and 5 are then added and mixed.
次に、本発明の効果を詳細に説明するため、実験例を挙げる。 Next, experimental examples will be given to explain the effects of the present invention in detail.
実験例1 活性酸素消去作用
フリーラジカル捕捉除去作用の評価を行った。陽性対照としてはアスコルビン酸を用いた。フリーラジカルのモデルとしては、安定なフリーラジカルであるα,α−ジフェニル−β−ピクリルヒドラジル(以下DPPHとする)を用い、試料と一定の割合で一定時間反応させ、減少するラジカルの量を波長517nmの吸光度の減少量から測定した。
Experimental Example 1 Active oxygen scavenging action Free radical scavenging and removing action was evaluated. Ascorbic acid was used as a positive control. As a free radical model, α, α-diphenyl-β-picrylhydrazyl (hereinafter referred to as DPPH), which is a stable free radical, is used and reacted with a sample at a certain rate for a certain period of time. Was measured from the decrease in absorbance at a wavelength of 517 nm.
フリーラジカル捕捉除去作用の測定方法
各試料を、最終濃度0.01mg/mL(アスコルビン酸は0.01mg/mL)となるように加えた0.1M酢酸緩衝液(pH5.5)2mLに無水エタノール2mL及び0.5mM DPPH無水エタノール溶液1mLを加えて反応液とした。また、油溶性の試料の場合は無水エタノール2mLに試料を加えて反応液とした。その後、37℃で30分間反応させ、水を対照として波長517nmの吸光度(A)を測定した。また、ブランクとして試料の代わりに精製水を用いて吸光度(B)を測定した。フリーラジカル捕捉除去率は、以下に示す式より算出した。
フリーラジカル捕捉除去率(%)=(1−A/B)×100
Measurement method of free radical scavenging and removing action Each sample was added to absolute ethanol in 2 mL of 0.1 M acetate buffer (pH 5.5) added to a final concentration of 0.01 mg / mL (ascorbic acid was 0.01 mg / mL). 2 mL and 1 mL of 0.5 mM DPPH absolute ethanol solution were added to prepare a reaction solution. In the case of an oil-soluble sample, the sample was added to 2 mL of absolute ethanol to prepare a reaction solution. Then, it was made to react at 37 degreeC for 30 minute (s), and the light absorbency (A) of wavelength 517nm was measured by using water as a control. Moreover, the light absorbency (B) was measured using the purified water instead of the sample as a blank. The free radical scavenging removal rate was calculated from the following equation.
Free radical scavenging removal rate (%) = (1−A / B) × 100
これらの試験結果を表1に示した。本発明のリュウキュウバライチゴの熱水及び50%エタノール抽出物は、安定で優れたフリーラジカル捕捉除去作用を有していることが認められた。また、その他の抽出物についても効果が認められた。なお、アスコルビン酸は、100℃、1時間の熱処理で失活するが、本発明のリュウキュウバライチゴの抽出物は、活性に変化はなかった。
The test results are shown in Table 1. It was confirmed that the hot water and 50% ethanol extract of Ryukyu rose strawberry of the present invention have a stable and excellent free radical scavenging and removing action. Moreover, the effect was recognized also about the other extract. Ascorbic acid was inactivated by heat treatment at 100 ° C. for 1 hour, but the activity of the Ryukyu rose strawberry extract of the present invention was not changed.
実験例2 MMP産生抑制作用
MMP産生抑制作用をMMP−1及びMMP−2のmRNA発現量を指標として評価した。
Experimental Example 2 MMP Production Inhibitory Action MMP production inhibitory action was evaluated using MMP-1 and MMP-2 mRNA expression levels as indices.
MMP−1及びMMP−2のmRNA発現量の測定方法
正常ヒト皮膚線維芽細胞を10%FCS含有DMEM培地にて37℃、5%CO2条件下で培養し、コンフルエントな状態になったところで試料(終濃度10μg/mL)を添加したDMEM培地にてさらに24時間培養した後、総RNAの抽出を行った。総RNAの抽出にはISOGEN(ニッポンジーン)を用いた。線維芽細胞から抽出した総RNAを基にリアルタイムRT−PCR法によりMMP−1及びMMP−2mRNA発現量の測定を行った。リアルタイムRT−PCR法にはTaKaRa SYBR ExScript RT−PCR Kitを用い、MMP−1用のprimerとしては5’GGGAGATCATCGGGACAACTC3’(配列番号1)及び5’TGAGCATCCCCTCCAATACC3’(配列番号2)を用いた。MMP−2用のprimerとしては5’CCGTCGCCCATCATCAA3’(配列番号3)及び5’CTTCTGCATCTTCTTTAGTGTGTCCTT3’(配列番号4)を用いた。また、内部標準としてはGAPDHを用い、GAPDH用のprimerとしては5’TGCACCACCAACTGCTTAGC3’(配列番号5)及び5’TCTTCTGGGTGGCAGTGATG3’(配列番号6)を用いた。その他の操作は定められた方法に従い、MMP−1及びMMP−2のmRNA発現量を内部標準であるGAPDHのmRNA発現量に対する割合として求めた。
Method for measuring MMP-1 and MMP-2 mRNA expression levels Normal human skin fibroblasts were cultured in DMEM medium containing 10% FCS under conditions of 37 ° C. and 5% CO 2. After further culturing in DMEM medium supplemented with (final concentration 10 μg / mL), total RNA was extracted. ISOGEN (Nippon Gene) was used for extraction of total RNA. MMP-1 and MMP-2 mRNA expression levels were measured by real-time RT-PCR based on total RNA extracted from fibroblasts. TaKaRa SYBR ExScript RT-PCR Kit was used for the real-time RT-PCR method, and 5'GGGAGATCCATGGGACAACTC3 '(SEQ ID NO: 1) and 5'TGAGCATCCCCCTCCATAACC3' (SEQ ID NO: 2) were used as primers for MMP-1. As a primer for MMP-2, 5′CCGTCGCCCATCATCAA3 ′ (SEQ ID NO: 3) and 5′CTTCTGCCATCTTCTTTAGTGGTCCTT3 ′ (SEQ ID NO: 4) were used. In addition, GAPDH was used as an internal standard, and 5′TGCACCACCAACTGCTTTAGC3 ′ (SEQ ID NO: 5) and 5′TCTCTGGGTGGCAGGTGATG3 ′ (SEQ ID NO: 6) were used as primers for GAPDH. For other operations, the mRNA expression levels of MMP-1 and MMP-2 were determined as a ratio to the mRNA expression level of GAPDH, which is an internal standard, in accordance with a predetermined method.
これらの試験結果を表2に示した。本発明のリュウキュウバライチゴの50%エタノール抽出物は、優れたMMP産生抑制作用を有していることが認められた。また、その他の抽出物についても効果が認められた。
The test results are shown in Table 2. It was confirmed that the 50% ethanol extract of Ryukyu rose strawberry of the present invention has an excellent MMP production inhibitory action. Moreover, the effect was recognized also about the other extract.
実験例3 B16マウスメラノーマを用いたメラニン生成抑制試験
対数増殖期にあるB16マウスメラノーマをφ60mmdishに3×104個の細胞を播種し、各試料(最終濃度1μg/mL)を含むEagles’MEM(10%牛胎児血清含有)培地を加え、37℃、5%CO2の条件下にて培養した。培養5日後に細胞をdishから剥離し、細胞を超音波破砕した後、4NNaOHを加え60℃で2時間の処理を行い、分光光度計でO.D.475nmを測定した。尚、超音波処理後の細胞破砕液をLowryの方法(J.Biol.Chem.,193,265−275,1951)でタンパク定量し、タンパク量当りのメラニン量を比較することによって、メラニン生成抑制効果の指標とした。
Experimental Example 3 Inhibition test of melanin production using B16 mouse melanoma B16 mouse melanoma in the logarithmic growth phase was seeded at 3 × 10 4 cells in φ60 mm dish, and Eagles'MEM (final concentration 1 μg / mL) containing each sample (final concentration 1 μg / mL). 10% fetal calf serum-containing medium was added, and the cells were cultured at 37 ° C. and 5% CO 2 . After 5 days of culture, the cells were detached from the dish, and the cells were sonicated, and then treated with 4N NaOH for 2 hours at 60 ° C. D. 475 nm was measured. In addition, the protein quantification is performed for the cell lysate after sonication by Lowry's method (J. Biol. Chem., 193, 265-275, 1951), and the amount of melanin per amount of protein is compared to suppress melanin production. It was used as an effect index.
これらの試験結果を表3に示した。本発明のリュウキュウバライチゴの熱水抽出物は、優れたメラニン生成抑制作用を有していることが認められた。また、その他の抽出物についても効果が認められた。
These test results are shown in Table 3. It was recognized that the hot water extract of Ryukyu rose strawberry of the present invention has an excellent melanin production inhibitory action. Moreover, the effect was recognized also about the other extract.
実験例4 細胞増殖促進試験
HaCaT細胞を0.1%FBSを含むDMEM培養液にて、96wellプレートに1wellあたり5,000個播種し、各試料を添加した後、37℃、5%CO2条件下にて3日間培養した。細胞数の測定は、MTT法により行った。すなわち、培養終了後、培養液を除き、500μg/mLの濃度にて、MTTを溶解させたDMEMに培地を入れ替え、2時間培養した後、150μLのDMEMに細胞を溶解させ、マイクロプレートリーダーをもちいて590及び650nmにおける吸光度を測定した。細胞数は、590nmの吸光度値から、650nmの吸光度値を引いた値にて算出し、試料を添加しない細胞群(未添加細胞群)を100%とした換算値として示した。
Experimental Example 4 Cell Growth Promotion Test HaCaT cells were seeded in a 96-well plate at 5,000 cells per well in a DMEM culture solution containing 0.1% FBS, and after adding each sample, conditions of 37 ° C., 5% CO 2 The cells were cultured for 3 days. The number of cells was measured by the MTT method. That is, after completion of the culture, the culture medium is removed, the medium is replaced with DMEM in which MTT is dissolved at a concentration of 500 μg / mL, the cells are cultured for 2 hours, cells are dissolved in 150 μL of DMEM, and a microplate reader is used. The absorbance at 590 and 650 nm was measured. The number of cells was calculated by subtracting the absorbance value at 650 nm from the absorbance value at 590 nm, and was shown as a conversion value with the cell group to which no sample was added (unadded cell group) as 100%.
これらの実験結果を表4に示した。その結果、本発明のリュウキュウバライチゴの50%エタノール抽出物は、優れた細胞増殖促進作用を示した。また、その他の抽出物についても効果が認められた。
The results of these experiments are shown in Table 4. As a result, the 50% ethanol extract of Ryukyu rose strawberry of the present invention showed an excellent cell growth promoting action. Moreover, the effect was recognized also about the other extract.
実験例5 使用試験1
処方例1の化粧水及び比較例1の従来の化粧水を用いて、シミ、ソバカスに悩む女性10人(23〜50才)を対象に1ヶ月間の使用試験を行った。使用後、シミ、ソバカスの改善効果をアンケートにより判定した。
Experiment 5 Use test 1
Using the skin lotion of Formulation Example 1 and the conventional skin lotion of Comparative Example 1, a use test for 1 month was conducted on 10 women (23 to 50 years old) who suffer from spots and freckles. After use, the effect of improving spots and freckles was judged by a questionnaire.
その結果、本発明の抽出物を含有する皮膚外用剤は、優れたシミ、ソバカスの改善作用を示した。なお、試験期間中、皮膚トラブルは一人もなく、安全性においても問題なかった。また、処方成分の劣化についても問題なかった。 As a result, the external preparation for skin containing the extract of the present invention showed an excellent effect of improving spots and freckles. During the test period, there was no skin problem and there was no problem with safety. There was also no problem with the deterioration of the prescription ingredients.
以上のことから、本発明のリュウキュウバライチゴの抽出物は、優れた活性酸素消去作用、MMP産生抑制作用、メラニン生成抑制作用及び細胞増殖促進作用を有し、安定性にも優れていた。よって、本発明のリュウキュウバライチゴの抽出物は、皮膚の老化や美白といった美容分野だけでなく、老化による機能低下の抑制、ガンの予防、治療や創傷治癒などといった医療分野にも利用ででき、食品、化粧品、医薬部外品及び医薬品等への応用が期待される。 From the above, the extract of Ryukyu rose strawberry of the present invention had excellent active oxygen scavenging action, MMP production inhibitory action, melanin production inhibitory action and cell growth promoting action, and was also excellent in stability. Therefore, the extract of Ryukyu rose strawberry of the present invention can be used not only in the beauty field such as skin aging and whitening, but also in the medical field such as suppression of functional deterioration due to aging, prevention of cancer, treatment and wound healing, Expected to be applied to food, cosmetics, quasi-drugs and pharmaceuticals.
Claims (1)
A melanin production inhibitor comprising an extract of Ryukyu rose strawberry.
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