TWI551301B - Containing hyaluronic acid decomposition inhibitor with rosemary extract and retinyl acetate - Google Patents
Containing hyaluronic acid decomposition inhibitor with rosemary extract and retinyl acetate Download PDFInfo
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本發明係關於一種具有優異之玻尿酸酶抑制作用之玻尿酸酶抑制劑。 The present invention relates to a hyaluronic acid inhibitor having excellent hyaluronic acid inhibitory action.
近年來，正在進行有關老化之研究。關於皮膚老化之原因，從宏觀來看年齡增加為重要之因素，除此之外，亦可列舉乾燥、氧化、太陽光(紫外線)等之影響作為關係到皮膚老化之直接因素。作為皮膚老化之具體現象，已知有以玻尿酸為首之黏多糖類之減少、膠原蛋白之交聯反應、紫外線引起之細胞損傷等。 In recent years, research on aging is underway. Regarding the cause of skin aging, the increase in age is an important factor from the macroscopic point of view. In addition, effects such as drying, oxidation, and sunlight (ultraviolet rays) may be cited as a direct factor related to skin aging. As a specific phenomenon of skin aging, reduction of mucopolysaccharide including hyaluronic acid, cross-linking reaction of collagen, and cell damage by ultraviolet rays are known.
其中，以β-D-N-乙醯胺基葡糖與β-D-葡糖醛酸交替鍵結而成之直鏈狀高分子多糖之形式與硫酸軟骨素等一同廣泛存在於哺乳動物之結締組織中之糖胺聚多糖之一種即玻尿酸，其具有以下多種功能：向細胞間隙保持水分，基於在組織內形成啫喱狀之基質而保持細胞，保持組織之潤滑性及柔軟性，抵抗機械損傷等外力，及防止細菌感染等(參照非專利文獻1)。又，一般認為，皮膚之玻尿酸量隨著年齡增加而減少，伴隨於此而出現細紋或乾燥等皮膚老化。因此，提出有大量調配有玻尿酸之化妝料作為此種老化皮膚之改善劑。然而，該等先前之化妝料僅發揮皮膚表面之保濕效果，無法本質上改善老化肌膚。又，最近亦逐漸提出大量調配有增加皮膚中之玻尿酸量之藥劑的化妝料(參照專利文獻1)，但現狀為該等亦無法達到可明顯改善、治 療老化肌膚之程度。一般認為，藉由玻尿酸之外用或玻尿酸產生促進劑之外用而未必可明顯改善老化肌膚的原因在於：皮膚中之玻尿酸之分解速度較快。有報告稱，由於皮膚中之玻尿酸於生物體內合成之同時受到其分解酶即玻尿酸酶之酶分解，故而分解速度較快，皮膚中玻尿酸之半生期大約為1天(參照非專利文獻2)。玻尿酸酶係廣泛分佈於生物體中且亦存在於皮膚中之酶，如名稱所示般會分解玻尿酸。因此，一般認為，抑制促進玻尿酸分解之玻尿酸酶之活性有助於製劑所使用之玻尿酸之安定性，或塗佈於皮膚後之製劑之玻尿酸及存在於皮膚中之玻尿酸的安定性。又，已知，玻尿酸酶亦作為炎症酶而為人所知，抑制其活性會抑制炎症，又亦對過敏有抑制作用。由於上述原因，為了維持皮膚之彈性及保濕性，防止皺紋、細紋、乾燥，維持濕潤之年輕肌膚之狀態，而要求開發玻尿酸分解酶即玻尿酸酶之有效抑制劑。 Among them, a form of a linear polymer polysaccharide in which β-DN-acetamidose glucose and β-D-glucuronic acid are alternately bonded together with chondroitin sulfate and the like are widely present in mammalian connective tissue. Hyaluronic acid, a kind of glycosaminoglycan, has the following functions: maintaining moisture in the intercellular space, maintaining cells based on the formation of a gel-like matrix in the tissue, maintaining the lubricity and flexibility of the tissue, and resisting external forces such as mechanical damage. And prevention of bacterial infection, etc. (refer to Non-Patent Document 1). Further, it is considered that the amount of hyaluronic acid in the skin decreases with age, and skin aging such as fine lines or dryness occurs. Therefore, a large amount of cosmetic formulated with hyaluronic acid has been proposed as an improvement agent for such aged skin. However, these prior cosmetics only exert a moisturizing effect on the surface of the skin and do not substantially improve the aged skin. Further, recently, a large amount of cosmetics having a drug for increasing the amount of hyaluronic acid in the skin has been proposed (see Patent Document 1). However, the current situation is that such a treatment cannot be improved. The degree of aging skin. It is generally believed that the use of hyaluronic acid or hyaluronic acid to produce an accelerator may not significantly improve the aged skin because the hyaluronic acid in the skin decomposes faster. It has been reported that hyaluronic acid in the skin is decomposed by the enzyme of hyaluronidase, which is a decomposition enzyme, and the decomposition rate is fast, and the half-life of hyaluronic acid in the skin is about one day (refer to Non-Patent Document 2). Hyaluronic acid enzymes, which are widely distributed in living organisms and are also present in the skin, decompose hyaluronic acid as indicated by the name. Therefore, it is considered that the activity of inhibiting hyaluronic acid which promotes hyaluronic acid decomposition contributes to the stability of hyaluronic acid used in the preparation, or the hyaluronic acid of the preparation applied to the skin and the stability of hyaluronic acid present in the skin. Further, it is known that hyaluronic acid is also known as an inflammatory enzyme, and inhibition of its activity inhibits inflammation and also has an inhibitory effect on allergy. For the above reasons, in order to maintain the elasticity and moisturization of the skin, prevent wrinkles, fine lines, and dryness, and maintain the state of moist young skin, it is required to develop an effective inhibitor of hyaluronic acid, a hyaluronic acid decomposing enzyme.
迷迭香、百里香以及檸檬薄荷等唇形花科植物之萃取物顯示玻尿酸酶之抑制活性或血小板凝集抑制作用、以及己糖胺酶釋放抑制作用，顯示具有消炎作用(專利文獻2)。於該文獻中，關於自迷迭香、百里香或檸檬薄荷中任一者萃取之玻尿酸酶抑制物質、該等之混合物、進而與其他抗過敏劑之混合物有記載，但關於發揮超過累加效果之相乘效果之混合物並無任何記載。 The extract of the Labiatae plant such as rosemary, thyme, and lemon mint exhibits hyaluronic acid inhibitory activity, platelet aggregation inhibitory action, and hexosaminidase release inhibitory action, and exhibits an anti-inflammatory action (Patent Document 2). In this document, a hyaluronic acid inhibitory substance extracted from any of rosemary, thyme or lemon mint, a mixture thereof, and a mixture with other antiallergic agents are described, but the phase which exerts an effect exceeding the cumulative effect is described. There is no record of the mixture of effects.
[專利文獻1]日本專利特開平11-209261號公報 [Patent Document 1] Japanese Patent Laid-Open No. Hei 11-209261
[專利文獻2]日本專利特開平8-333267號公報 [Patent Document 2] Japanese Patent Laid-Open No. Hei 8-333267
[非專利文獻1] "BioIndustry", vol. 8, p. 346(1991) [Non-Patent Document 1] "BioIndustry", vol. 8, p. 346 (1991)
[非專利文獻2] TammiR. etal,. J. Invest. Dermatol., 97, 126~130 (1991) [Non-Patent Document 2] TammiR. etal, J. Invest. Dermatol., 97, 126~130 (1991)
本發明係鑒於上述情況而完成者，其目的在於提供一種安全且可簡便地使用之具有人體中之玻尿酸酶抑制作用之玻尿酸酶抑制劑。 The present invention has been made in view of the above circumstances, and an object thereof is to provide a hyaluronic acid inhibitor having a hyaluronic acid inhibitory action in a human body which is safe and easy to use.
本發明者等人為解決上述課題，廣泛地對多種物質關於玻尿酸酶抑制作用進行潛心研究，結果驚訝地發現，於將已知有玻尿酸酶抑制作用之迷迭香之萃取物與尚未知有玻尿酸酶抑制作用之維生素A類併用之情形時，玻尿酸酶抑制作用大幅增強，基於此而完成了本發明。 In order to solve the above problems, the inventors of the present invention have extensively studied a variety of substances on the inhibition of hyaluronic acid, and as a result, have surprisingly found that an extract of rosemary which is known to have a hyaluronic acid inhibitory effect and a hyaluronic acid are not known. When the vitamin A of the inhibitory action is used in combination, the hyaluronic acid inhibitory action is greatly enhanced, and the present invention has been completed based on this.
因此，本發明係關於以下發明： Accordingly, the present invention is directed to the following inventions:
[1]一種玻尿酸酶抑制劑，其包含迷迭香萃取物及維生素A類。 [1] A hyaluronic acid inhibitor comprising rosemary extract and vitamin A.
[2]如[1]之玻尿酸酶抑制劑，其中上述維生素A類係選自由視黃醇、乙酸視黃酯、棕櫚酸視黃酯所組成之群。 [2] The hyaluronic acid inhibitor according to [1], wherein the vitamin A is selected from the group consisting of retinol, retinyl acetate, and retinyl palmitate.
[3]如[1]或[2]之玻尿酸酶抑制劑，其中上述維生素A類為乙酸視黃酯。 [3] The hyaluronic acid inhibitor of [1] or [2], wherein the vitamin A is a retinyl acetate.
[4]一種皮膚外用劑，其包含如[1]至[3]中任一項之玻尿酸酶抑制劑，係用以改善或預防選自由皮膚老化、皺紋、皮膚粗糙、乾性皮膚、乾燥、粉刺及異位性皮膚炎所組成之群中之皮膚問題。 [4] A skin external preparation comprising the hyaluronidase inhibitor according to any one of [1] to [3], which is for improving or preventing a skin exfoliation, wrinkles, rough skin, dry skin, dryness, acne And skin problems in a group of atopic dermatitis.
[5]一種皮膚外用劑，其包含如[1]至[3]中任一項之玻尿酸酶抑制劑，係用以治療選自由異位性皮膚炎、乾性皮膚、關節炎、牙齦炎、風濕病、變形性關節病、及燙傷所組成之群中之玻尿酸減少相關疾病。 [5] A skin external preparation comprising the hyaluronic acid inhibitor according to any one of [1] to [3], which is for use in the treatment selected from the group consisting of atopic dermatitis, dry skin, arthritis, gingivitis, rheumatism Hyaluronic acid-related diseases in a group consisting of disease, deformed joint disease, and scald.
[6]一種迷迭香萃取物及維生素A類之用途，其係用以改善或預防玻尿酸之減少。 [6] A use of rosemary extract and vitamin A for improving or preventing hyaluronic acid reduction.
[7]一種迷迭香萃取物及維生素A類之用途，其係用以預防或改善皮膚老化、皺紋、皮膚粗糙、乾性皮膚、乾燥、粉刺或異位性皮膚炎等皮膚問題，或用以治療乾性皮膚、關節炎、牙齦炎、風濕病、變形性關節病、燙傷等玻尿酸減少相關疾病。 [7] A use of rosemary extract and vitamin A for preventing or improving skin problems such as skin aging, wrinkles, rough skin, dry skin, dryness, acne or atopic dermatitis, or Treatment of dry skin, arthritis, gingivitis, rheumatism, osteoarthritis, scald and other diseases related to hyaluronic acid reduction.
[8]一種玻尿酸酶抑制方法，其包括於患玻尿酸減少之對象中投予迷迭香萃取物及維生素A類。 [8] A method for inhibiting hyaluronic acid, which comprises administering rosemary extract and vitamin A in a subject suffering from hyaluronic acid reduction.
[9]一種美容方法或治療方法，其包括於玻尿酸減少之對象中投予迷迭香萃取物及維生素A類，用以改善或預防玻尿酸減少。 [9] A cosmetic method or treatment method comprising administering rosemary extract and vitamin A to a subject having reduced hyaluronic acid for improving or preventing hyaluronic acid reduction.
[10]如[9]之美容方法或治療方法，其係用以改善或預防皺紋、皮膚粗糙、乾性皮膚、乾燥、粉刺或異位性皮膚炎等皮膚問題。 [10] The cosmetic method or treatment method according to [9], which is for improving or preventing skin problems such as wrinkles, rough skin, dry skin, dryness, acne or atopic dermatitis.
[11]一種治療方法，其包括於患玻尿酸減少之對象中投 予迷迭香萃取物及維生素A類，治療異位性皮膚炎、乾性皮膚、關節炎、牙齦炎、風濕病、變形性關節病、燙傷等玻尿酸減少相關疾病。 [11] A method of treatment comprising administering to a subject suffering from hypouricemia For rosemary extract and vitamin A, for the treatment of atopic dermatitis, dry skin, arthritis, gingivitis, rheumatism, osteoarthritis, scald and other diseases related to hyaluronic acid reduction.
[12]一種迷迭香萃取物及維生素A類之用途，其係用以製造玻尿酸酶抑制劑。 [12] A use of rosemary extract and vitamin A for the manufacture of a hyaluronic acid inhibitor.
[13]一種迷迭香萃取物及維生素A類之用途，其係用於製造用以改善或預防老化、皺紋、皮膚粗糙、乾性皮膚、乾燥、粉刺或異位性皮膚炎等皮膚問題之化妝料或醫藥品。 [13] A use of rosemary extract and vitamin A for the manufacture of a cosmetic for improving or preventing skin problems such as aging, wrinkles, rough skin, dry skin, dryness, acne or atopic dermatitis Materials or pharmaceuticals.
[14]一種迷迭香萃取物及維生素A類之用途，其係用於製造用以治療異位性皮膚炎、乾性皮膚、關節炎、牙齦炎、風濕病、變形性關節病、燙傷等玻尿酸減少相關疾病之醫藥品。 [14] A use of rosemary extract and vitamin A for the manufacture of hyaluronic acid for treating atopic dermatitis, dry skin, arthritis, gingivitis, rheumatism, osteoarthritis, scald, etc. Reduce the amount of medicines related to the disease.
本發明之玻尿酸酶抑制劑所包含之維生素A類於單獨使用之情形時，不發揮或幾乎不發揮玻尿酸酶抑制作用，但於與迷迭香萃取物一併使用之情形時，可顯著增強迷迭香萃取物所具有之玻尿酸酶抑制作用，而發揮人體皮膚老化、皺紋、皮膚粗糙、乾性皮膚、乾燥、粉刺或異位性皮膚炎等皮膚問題，或關節炎、牙齦炎、風濕病及變形性關節病、燙傷等玻尿酸減少相關疾病之改善或預防中之任一效果。 The vitamin A contained in the hyaluronic acid inhibitor of the present invention does not exert or hardly exerts hyaluronic acid inhibition when used alone, but can significantly enhance the fan when used together with the rosemary extract. The hyaluronic acid inhibitor of the rosemary extract exerts skin problems such as skin aging, wrinkles, rough skin, dry skin, dryness, acne or atopic dermatitis, or arthritis, gingivitis, rheumatism and deformation. Any of the effects of improvement or prevention of hyaluronic acid-related diseases such as arthrosis and scald.
於本發明中，玻尿酸酶係藉由切割糖苷鍵而分解玻尿酸之酶之總稱。玻尿酸酶廣泛分佈於動物組織中，期望藉由 抑制其活性而提高體內尤其皮膚或關節液等中之玻尿酸含量。經切割之糖苷鍵存在葡糖醛酸苷鍵或N-乙醯胺基葡糖苷鍵之情形。 In the present invention, hyaluronic acid is a general term for an enzyme which decomposes hyaluronic acid by cleavage of a glycosidic bond. Hyaluronicase is widely distributed in animal tissues, and is expected to It inhibits its activity and increases the hyaluronic acid content in the body, especially in skin or joint fluids. The case where the cleaved glycosidic bond is present with a glucuronide bond or an N-acetamidoglucoside bond.
於本發明中，玻尿酸酶抑制劑係指抑制玻尿酸酶之玻尿酸分解活性之藥劑，藉此，可增加體內尤其關節液或皮膚中之玻尿酸含量。本發明之較佳樣態中，玻尿酸酶抑制劑特別包含迷迭香萃取物及維生素A類。 In the present invention, the hyaluronic acid inhibitor refers to an agent which inhibits the hyaluronic acid decomposition activity of hyaluronic acid, thereby increasing the hyaluronic acid content in the body, especially in the joint fluid or skin. In a preferred aspect of the invention, the hyaluronanase inhibitor comprises in particular rosemary extract and vitamin A.
已知，玻尿酸與體內之彈性、保濕性及潤滑性相關，隨著老化玻尿酸含量降低，並且由於皮膚中之玻尿酸降低而引起皺紋、皮膚粗糙、乾性皮膚或乾燥等症狀。又，已知玻尿酸酶與炎症相關，亦已知玻尿酸酶之活化與異位性皮膚炎或粉刺有關。因此，藉由本發明之玻尿酸酶抑制劑，可治療、改善或預防老化、皺紋、皮膚粗糙、乾性皮膚、乾燥、粉刺或異位性皮膚炎等皮膚問題，以及玻尿酸減少相關疾病，例如乾性皮膚、關節炎、牙齦炎、風濕病及變形性關節病、燙傷。 It is known that hyaluronic acid is associated with elasticity, moisturizing and lubricity in the body, and the hyaluronic acid content decreases with aging, and wrinkles, rough skin, dry skin or dryness are caused by a decrease in hyaluronic acid in the skin. Further, it is known that hyaluronic acid is associated with inflammation, and activation of hyaluronan is also known to be associated with atopic dermatitis or acne. Therefore, the hyaluronic acid inhibitor of the present invention can treat, ameliorate or prevent skin problems such as aging, wrinkles, rough skin, dry skin, dryness, acne or atopic dermatitis, and diseases related to hyaluronic acid reduction, such as dry skin, Arthritis, gingivitis, rheumatism and deformed joint disease, burns.
於本發明中，迷迭香萃取物係來自原產於地中海沿岸地區之唇形花科迷迭香屬之迷迭香(Rosmarinus officinalis)的萃取物，該植物之植物全株，尤其全草、葉及花用作原材料。已知，迷迭香萃取物具有抗菌性、抗氧化效果、消炎效果，報告稱其可用作皮膚改善劑等抗衰老劑、免疫活化劑、抗糖尿病劑、抗骨質疏鬆症劑、抗肥胖劑、睡眠促進劑、抗中樞神經劑等醫藥品。 In the present invention, the rosemary extract is an extract of Rosmarinus officinalis which is native to the Mediterranean coastal region, and the whole plant of the plant, especially whole grass, Leaves and flowers are used as raw materials. It is known that rosemary extract has antibacterial, anti-oxidative and anti-inflammatory effects, and it is reported to be used as an anti-aging agent such as a skin improving agent, an immune activator, an anti-diabetic agent, an anti-osteoporosis agent, an anti-obesity agent. , sleep accelerators, anti-central nerve agents and other pharmaceutical products.
本發明之迷迭香萃取物可藉由常用方法而獲得，例如， 可於將植物與萃取溶劑一併浸漬或加熱回流之後進行過濾、濃縮而獲得。作為萃取溶劑，只要為通常萃取所使用之溶劑則可任意使用，例如可分別單獨或組合使用水，甲醇、乙醇、丙二醇、1,3-丁二醇、甘油等醇類，含水醇類，氯仿，二氯乙烷，四氯化碳，丙酮，乙酸乙酯，己烷等有機溶劑等。可直接使用利用上述溶劑萃取所得之萃取液，或亦可使用將經濃縮之萃取物利用吸附法，例如使用離子交換樹脂除去雜質者，或利用多孔性聚合物(例如Amberlite XAD-2)之管柱吸附後利用甲醇或乙醇進行溶出並經濃縮而得者。進而，亦可使用經乾燥者。又，亦可使用以分配法，例如以水/乙酸乙酯萃取而得之萃取物等。 The rosemary extract of the present invention can be obtained by a usual method, for example, It can be obtained by immersing the plant together with the extraction solvent or heating and refluxing, followed by filtration and concentration. The extraction solvent can be used arbitrarily as long as it is a solvent used for usual extraction. For example, water, methanol, ethanol, propylene glycol, 1,3-butylene glycol, or glycerin, alcohol, and alcohol can be used singly or in combination. , an organic solvent such as dichloroethane, carbon tetrachloride, acetone, ethyl acetate or hexane. The extract obtained by the above solvent extraction may be used as it is, or the concentrated extract may be removed by adsorption, for example, using an ion exchange resin, or a tube using a porous polymer (for example, Amberlite XAD-2). After the column is adsorbed, it is eluted with methanol or ethanol and concentrated. Further, a dried person can also be used. Further, an extract obtained by a distribution method such as extraction with water/ethyl acetate or the like can also be used.
以上述方式而獲得之上述植物或其萃取物均具有優異之玻尿酸酶抑制作用。就用於直接用於皮膚之化妝料或醫藥品例如皮膚外用劑等中之觀點而言，較佳為使用低刺激性溶劑例如水、1,3-丁二醇、甘油等萃取而得之萃取物，例如較佳為使用1,3-丁二醇之50質量%水溶液。 The above plants or their extracts obtained in the above manner all have excellent hyaluronic acid inhibitory action. From the viewpoint of being used for cosmetics for direct application to the skin or pharmaceuticals such as external preparations for skin, etc., extraction by extraction with a low irritant solvent such as water, 1,3-butanediol, glycerin or the like is preferred. For example, a 50% by mass aqueous solution of 1,3-butanediol is preferably used.
於將上述植物或其萃取物調配於化妝料或醫藥品中而使用之情形時，較佳為於化妝料或醫藥品全部重量中以乾重0.00001~0.1質量%進行調配，更佳為0.00005~0.01質量%、進而較佳為以0.0001~0.001質量%進行調配。 When the plant or the extract thereof is used in a cosmetic or a pharmaceutical product, it is preferably formulated in a dry weight of 0.00001 to 0.1% by mass based on the total weight of the cosmetic or the pharmaceutical product, more preferably 0.00005~ 0.01% by mass, and more preferably 0.0001 to 0.001% by mass.
已知，若缺乏維生素A類則發生夜盲症或佝僂病，又已知，皮膚中若缺乏維生素A類則發生皮膚或黏膜之角質化、皮膚之異常乾燥及色素沈積等，為了治療粉刺、促進皮膚更新而對皮膚使用維生素A類，但關於可增強玻尿酸 酶抑制作用並無任何記載及暗示。作為維生素A類，可設為含有視黃醇、視黃醛、視黃酸等維生素A群及該等之前驅物或衍生物，例如乙酸視黃酯、棕櫚酸視黃酯、維A酸、視黃酸甲酯、視黃酸乙酯、視黃酸視黃酯等中之1種或2種以上之成分者。就適用於皮膚之觀點而言，較佳為視黃醇、乙酸視黃酯、棕櫚酸視黃酯，尤佳為乙酸視黃酯。 It is known that night blindness or rickets occur in the absence of vitamin A. It is also known that if there is a lack of vitamin A in the skin, skin or mucosal keratinization, abnormal skin drying and pigmentation occur, in order to treat acne and promote skin renewal. And use vitamin A for the skin, but about the enhanced hyaluronic acid There is no record or suggestion for enzyme inhibition. The vitamin A may be a vitamin A group such as retinol, retinal or retinoic acid, and such precursors or derivatives, such as retinyl acetate, retinyl palmitate, retinoic acid, One or more components of methyl retinoic acid, ethyl retinoic acid, and retinyl retinoic acid ester. From the viewpoint of application to the skin, retinol, retinyl acetate, retinyl palmitate, and preferably retinyl acetate are preferred.
本發明所使用之維生素A類之調配量只要可增強迷迭香萃取物之玻尿酸酶抑制效果，則無特別限定，例如以化妝料或醫藥品整體計算，通常為0.000001~0.01質量%，較佳為0.000005~0.001質量%、尤佳為0.00001~0.0001質量%即可。 The amount of the vitamin A to be used in the present invention is not particularly limited as long as it can enhance the hyaluronic acid inhibitory effect of the rosemary extract, and is usually 0.000001 to 0.01% by mass, preferably 0.000001 to 0.01% by mass, preferably, based on the total amount of the cosmetic or the pharmaceutical product. It is 0.000005 to 0.001% by mass, and particularly preferably 0.00001 to 0.0001% by mass.
迷迭香萃取物與維生素A類之調配比只要為於可增強迷迭香萃取物之玻尿酸酶抑制效果之範圍內即可，例如，相對於迷迭香萃取物1質量份而可以0.01質量份~5質量份使用維生素A類，更佳為可以0.05~1質量份、進而較佳為可以0.1~0.5質量份使用。 The blending ratio of the rosemary extract to the vitamin A may be within a range that can enhance the hyaluronic acid inhibitory effect of the rosemary extract, for example, 0.01 parts by mass relative to 1 part by mass of the rosemary extract. The amount of the vitamin A to be used is preferably from 0.05 to 1 part by mass, more preferably from 0.1 to 0.5 part by mass.
維生素A類通常不具有玻尿酸酶抑制作用，因此於與迷迭香萃取物併用之情形時，若使迷迭香萃取物所具有之玻尿酸酶抑制作用增強，則認為發揮了超過相加之相乘效果。例如，維生素A類即便具有玻尿酸酶抑制作用，該作用亦較弱，另一方面，於與迷迭香萃取物併用之情形時，大大增強迷迭香萃取物所具有之玻尿酸酶抑制作用，因此發揮了超過相加之相乘效果。 Vitamin A usually does not have hyaluronic acid inhibition, so when combined with rosemary extract, if the hyaluronic acid inhibition of rosemary extract is enhanced, it is considered to be more than additive addition. effect. For example, vitamin A has a weaker effect even if it has hyaluronic acid inhibition. On the other hand, when used in combination with rosemary extract, it greatly enhances the hyaluronan inhibition of rosemary extract. Played a multiplication effect that is more than additive.
本發明之玻尿酸酶抑制劑進而亦可調配於化妝料或醫藥品中。因此，除迷迭香萃取物與維生素A類之外，可進而根據需要，於不損害本發明效果之範圍內，視需要適當調配通常化妝品或醫藥品等所使用之有效成分及/或賦形劑，例如保濕劑、抗氧化劑、油分、紫外線防禦劑、界面活性劑、增黏劑、醇類、甘油、玻尿酸等基劑，及pH值調整劑粉末成分、紫外線吸收劑、穩定劑、抗菌劑、香料、色料、水、各種皮膚營養劑等。 The hyaluronic acid inhibitor of the present invention can be further formulated into a cosmetic or a pharmaceutical product. Therefore, in addition to the rosemary extract and the vitamin A, it is possible to appropriately mix the active ingredients and/or shapes used in usual cosmetics or pharmaceuticals, as needed, without damaging the effects of the present invention as needed. Agents, such as moisturizers, antioxidants, oils, ultraviolet defense agents, surfactants, tackifiers, alcohols, glycerin, hyaluronic acid, and the like, and pH adjuster powder components, ultraviolet absorbers, stabilizers, antibacterial agents , spices, colorants, water, various skin nutrients, etc.
進而，亦可適當調配依地酸二鈉、依地酸三鈉、檸檬酸鈉、聚磷酸鈉、偏磷酸鈉、葡萄糖酸等金屬離子封阻劑，對羥基苯甲酸甲酯、對羥基苯甲酸乙酯、對羥基苯甲酸丁酯等防腐劑，咖啡因、鞣酸、維拉帕米、傳明酸及其衍生物、甘草萃取物、光甘草啶、木瓜果實之熱水萃取物、各種天然藥、乙酸維生素E酯、甘草酸及其衍生物或其鹽等藥劑，維生素C、抗壞血酸磷酸鎂、抗壞血酸葡糖苷、熊果苷、曲酸等美白劑，葡萄糖、果糖、甘露糖、蔗糖、海藻糖等糖類等。 Further, a metal ion blocking agent such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate or gluconic acid, methylparaben or p-hydroxybenzoic acid may be appropriately formulated. Preservatives such as ethyl ester and butyl paraben, caffeine, citric acid, verapamil, tranexamic acid and its derivatives, licorice extract, licorice, papaya fruit hot water extract, various natural Medicine, acetic acid vitamin E ester, glycyrrhizic acid and its derivatives or its salts, vitamin C, magnesium ascorbyl phosphate, ascorbyl glucoside, arbutin, kojic acid and other whitening agents, glucose, fructose, mannose, sucrose, seaweed Sugars such as sugar.
又，調配有本發明之玻尿酸酶抑制劑之化妝料或醫藥品亦可為適用於外皮之化妝料、準藥品等皮膚外用劑，適用溶液系、可溶化系、乳化系、粉末分散系、水-油雙層系、水-油-粉末三層系、軟膏、化妝水、凝膠、噴霧等任意劑型。 In addition, the cosmetic or pharmaceutical preparation containing the hyaluronic acid inhibitor of the present invention may be a skin external preparation such as a cosmetic or a quasi-drug suitable for the outer skin, and is suitable for a solution system, a solubilization system, an emulsification system, a powder dispersion system, and water. - Any of various forms such as oil double layer, water-oil-powder three-layer system, ointment, lotion, gel, spray, and the like.
作為調配有本發明之玻尿酸酶抑制劑之化妝料，例如可列舉：化妝水、乳液、乳霜、美容液、面膜等面部化妝 料，或粉底、口紅、眼影等彩妝化妝料，防曬劑、芳香化妝料、毛髮用化妝料、沐浴露等，但並不限定於此。 Examples of the cosmetic containing the hyaluronic acid inhibitor of the present invention include facial makeup such as lotion, lotion, cream, beauty lotion, and facial mask. Materials, or foundations, lipsticks, eye shadows and other make-up cosmetics, sunscreens, aromatic cosmetics, hair cosmetics, shower gel, etc., but are not limited thereto.
又，本發明之玻尿酸酶抑制劑除經皮投予之外，亦可藉由經口投予及其他非經口投予(例如經黏膜、舌下、肌內、關節內或皮下投予)而投予。因此，本發明之玻尿酸酶抑制劑除了調配於用以防止由玻尿酸量降低而產生之皺紋、皮膚粗糙、乾性皮膚、乾燥、粉刺或異位性皮膚炎等皮膚問題之皮膚外用的化妝料或醫藥品之外，亦可調配於防止由老化而產生之人體玻尿酸量下降之食品中，及針對玻尿酸分解異常亢進之症狀，尤其牙齦炎、風濕病及變形性關節症或關節炎之預防治療、燙傷之初期治療等玻尿酸異常分解疾病治療劑等醫藥組合物中。將本發明之玻尿酸酶抑制劑用作醫藥組合物之情形時，其劑型無特別限定，可根據投予途徑等而適當選擇。例如，作為適於經口投予之製劑，可列舉錠劑、膠囊劑、散劑、細粒劑、顆粒劑、液劑、糖漿劑等，作為適於非經口投予之製劑，可列舉注射劑、點滴劑、栓劑、吸入劑、經皮吸收劑、經黏膜吸收劑、貼劑等。注射劑可用於關節內注射、靜脈注射、肌肉注射、皮下注射、點滴等任一者。 Further, the hyaluronan inhibitor of the present invention may be administered by oral administration or other non-oral administration (for example, transmucosal, sublingual, intramuscular, intra-articular or subcutaneous administration) in addition to transdermal administration. And vote. Therefore, the hyaluronic acid inhibitor of the present invention is formulated in addition to a cosmetic or medicine for external use of the skin for preventing skin problems such as wrinkles, rough skin, dry skin, dryness, acne or atopic dermatitis caused by a decrease in the amount of hyaluronic acid. In addition to the product, it can also be formulated in foods that prevent the decrease of the amount of hyaluronic acid in the human body caused by aging, and the symptoms of abnormal hyperthermia decomposition, especially gingivitis, rheumatism and osteoarthritis or arthritis. In the pharmaceutical composition such as a therapeutic agent for hyaluronic acid abnormal decomposition diseases such as initial treatment. When the hyaluronic acid inhibitor of the present invention is used as a pharmaceutical composition, the dosage form thereof is not particularly limited, and may be appropriately selected depending on the administration route or the like. For example, as a preparation suitable for oral administration, a tablet, a capsule, a powder, a fine granule, a granule, a liquid, a syrup, or the like can be mentioned, and as a preparation suitable for parenteral administration, an injection can be cited. , drip, suppository, inhalation, percutaneous absorption, transmucosal absorbent, patch, and the like. The injection can be used for any of intra-articular injection, intravenous injection, intramuscular injection, subcutaneous injection, drip, and the like.
本發明亦關於一種美容方法或治療方法，其包括於玻尿酸減少之對象中塗佈迷迭香萃取物及維生素A類，用以改善或預防玻尿酸減少。於本發明之美容方法或治療方法中，迷迭香萃取物與維生素A類可同時塗佈，亦可隔開時間分別塗佈。關於美容方法，不僅為個人進行之方法，亦 於提供美容相關商品時，作為適合顧客之化妝料之處方而提供，由除醫生外之化妝料售貨員或美容師提供。 The invention also relates to a cosmetic or therapeutic method comprising coating a rosemary extract and a vitamin A in a subject having reduced hyaluronic acid for improving or preventing hyaluronic acid reduction. In the cosmetic method or treatment method of the present invention, the rosemary extract and the vitamin A may be simultaneously coated, or may be separately coated at intervals. About the beauty method, not only for the individual, but also When providing beauty-related products, it is provided as a cosmetic material suitable for the customer, and is provided by a cosmetic salesperson or a beautician other than a doctor.
玻尿酸減少之對象除了隨著年齡增加而玻尿酸減少之對象外，亦指患有異位性皮膚炎、乾性皮膚、關節炎、牙齦炎、風濕病、變形性關節症、或燙傷等玻尿酸減少相關疾病之對象。 In addition to the decrease in hyaluronic acid with increasing age, the subject of hyaluronic acid reduction also refers to hyaluronic acid-related diseases such as atopic dermatitis, dry skin, arthritis, gingivitis, rheumatism, osteoarthritis, or burns. Object.
繼而，列舉實施例對本發明進行進一步詳細說明，但本發明之技術範圍並不受此任何限定。再者，調配量全部為質量%。 Then, the present invention will be further described in detail by way of examples, but the technical scope of the present invention is not limited thereto. Furthermore, the blending amounts are all in mass%.
對將10 kg迷迭香葉切細而得者添加50質量%之1,3-丁二醇水溶液，於室溫下浸漬7~10天。浸漬後過濾去除雜質，將濾液進而於低溫場所中保溫7~10天。保溫後過濾去除雜質，而獲得迷迭香萃取物BG。 A 50% by mass aqueous solution of 1,3-butanediol was added to the 10 kg rosemary leaves, and immersed at room temperature for 7 to 10 days. After immersion, the impurities are removed by filtration, and the filtrate is further incubated in a low temperature place for 7 to 10 days. After the heat preservation, the impurities were removed by filtration to obtain the rosemary extract BG.
將50 μL之玻尿酸酶溶液(1 mg/mL)(Sigma-Aldrich Japan股份有限公司)倒入微型管內，添加50 μL評價藥劑並於37℃下保溫10分鐘。作為評價藥劑，使用迷迭香萃取物BG(丸善製藥(股))、乙酸視黃酯(BASF JAPAN(股))、迷迭香萃取物BG及乙酸視黃酯，對照則添加水代替評價藥劑。迷迭香萃取物BG係以添加玻尿酸鈉水溶液後之最終濃度以乾重計為0.000165質量%之方式進行添加，乙酸視黃酯係以相同情況下最終濃度為0.0000516質量%之方式進 行添加。保溫後，添加400 μL之1 mg/mL玻尿酸鈉溶液(資生堂股份有限公司，分子量110~160萬)，進而於37℃下保溫10分鐘後，添加50 μl氫氧化鈉水溶液(0.2 M)而使反應停止。將該溶液煮沸3分鐘後，用水流冷卻，添加300 μL之10% p-DMAB(二甲胺基苯甲醛)溶液(Nacalai Tesque股份有限公司)並於37℃下保溫20分鐘。於恢復至室溫後，每100 μL地轉移至96孔板中，使用POWER SCAN HT(DS Pharma Biomedical股份有限公司)測定OD585 nm。將把對照之吸光度設為100之結果示於圖1。圖1顯示，迷迭香萃取物單獨地具有玻尿酸酶抑制作用，另一方面，乙酸視黃酯不發揮玻尿酸酶抑制作用，但於將迷迭香萃取物與乙酸視黃酯併用之情形時，可增強迷迭香萃取物所具有之玻尿酸酶抑制作用。 50 μL of hyaluronic acid solution (1 mg/mL) (Sigma-Aldrich Japan Co., Ltd.) was poured into a microtube, and 50 μL of the evaluation agent was added and incubated at 37 ° C for 10 minutes. As an evaluation agent, rosemary extract BG (Maruzen Pharmaceutical Co., Ltd.), retinyl acetate (BASF JAPAN), rosemary extract BG and retinyl acetate were used, and water was added instead of the evaluation agent. . The rosemary extract BG was added in such a manner that the final concentration after the addition of the aqueous sodium hyaluronate solution was 0.0001665% by dry weight, and the retinyl acetate was added in the same manner as the final concentration of 0.0000516% by mass. Line added. After incubation, add 400 μL of 1 mg/mL sodium hyaluronate solution (Shiseido Co., Ltd., molecular weight 110-1.6 million), and then incubate at 37 ° C for 10 minutes, then add 50 μl of sodium hydroxide solution (0.2 M) to make The reaction stopped. After boiling the solution for 3 minutes, it was cooled with a water stream, and 300 μL of a 10% p-DMAB (dimethylaminobenzaldehyde) solution (Nacalai Tesque Co., Ltd.) was added and incubated at 37 ° C for 20 minutes. After returning to room temperature, it was transferred to a 96-well plate every 100 μL, and OD585 nm was measured using POWER SCAN HT (DS Pharma Biomedical Co., Ltd.). The result of setting the absorbance of the control to 100 is shown in Fig. 1. Figure 1 shows that the rosemary extract alone has hyaluronan inhibition. On the other hand, retinyl acetate does not exert hyaluronic acid inhibition, but when the rosemary extract is used in combination with retinyl acetate, It can enhance the hyaluronan inhibition of rosemary extract.
圖1係表示迷迭香萃取物具有玻尿酸酶抑制作用但乙酸視黃酯不具有玻尿酸酶抑制作用，另一方面藉由併用迷迭香萃取物與乙酸視黃酯而迷迭香萃取物之玻尿酸酶抑制作用明顯增強的圖。 Figure 1 is a diagram showing that the rosemary extract has hyaluronic acid inhibitory action but the retinyl acetate does not have hyaluronic acid inhibition, and on the other hand, the hyaluronic acid extract of the rosemary extract by using the rosemary extract and the retinyl acetate together. A diagram showing a marked increase in enzyme inhibition.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08333267A (en) * | 1995-06-02 | 1996-12-17 | Maruzen Pharmaceut Co Ltd | Antiallergic agent |
| JP2002080338A (en) * | 2000-06-20 | 2002-03-19 | Shiseido Co Ltd | Antiaging skin care preparation |
| JP2010270062A (en) * | 2009-05-21 | 2010-12-02 | Pias Arise Kk | Skin hyaluronic acid degradation enzyme inhibitor, skin hyaluronic acid-reinforcing composition, and external preparation for skin and cosmetic compounded with the hyaluronic acid degradation enzyme inhibitor or the hyaluronic acid-reinforcing composition |
-
2012
- 2012-06-29 TW TW101123677A patent/TWI551301B/en not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08333267A (en) * | 1995-06-02 | 1996-12-17 | Maruzen Pharmaceut Co Ltd | Antiallergic agent |
| JP2002080338A (en) * | 2000-06-20 | 2002-03-19 | Shiseido Co Ltd | Antiaging skin care preparation |
| JP2010270062A (en) * | 2009-05-21 | 2010-12-02 | Pias Arise Kk | Skin hyaluronic acid degradation enzyme inhibitor, skin hyaluronic acid-reinforcing composition, and external preparation for skin and cosmetic compounded with the hyaluronic acid degradation enzyme inhibitor or the hyaluronic acid-reinforcing composition |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201400135A (en) | 2014-01-01 |
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| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |