JP2004217629A - Bleaching agent and vitamin-mixed composition - Google Patents
Bleaching agent and vitamin-mixed composition Download PDFInfo
- Publication number
- JP2004217629A JP2004217629A JP2003420438A JP2003420438A JP2004217629A JP 2004217629 A JP2004217629 A JP 2004217629A JP 2003420438 A JP2003420438 A JP 2003420438A JP 2003420438 A JP2003420438 A JP 2003420438A JP 2004217629 A JP2004217629 A JP 2004217629A
- Authority
- JP
- Japan
- Prior art keywords
- group
- riboflavin
- calcium pantothenate
- nicotinamide
- vitamin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
Description
本発明は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物に関する。 The present invention is characterized in that it contains at least one active ingredient selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as a whitening agent and at least three active ingredients selected from the group consisting of these. Vitamin composition.
美容上の観点から、シミやソバカスに悩んでいる人が多い。シミやソバカスあるいはクスミやシワといった肌の老化は、紫外線照射、酸化的刺激、ホルモン異常、遺伝的要素などに大きく影響を受けていると言われており、その中でも紫外線照射の影響が最も大きいと考えられている。皮膚表面上で紫外線を受けると、組織内でフリーラジカル（活性酸素）が発生し、この活性酸素によって、細胞損傷や炎症が惹起されると、炎症系のケミカル・メディエーターを介して、色素沈着を惹起すると言われている。 From a cosmetic point of view, many people are worried about spots and freckles. It is said that aging of skin such as spots and freckles or wrinkles and wrinkles is greatly affected by ultraviolet irradiation, oxidative stimulation, hormonal abnormalities, genetic factors, etc. It is considered. When exposed to ultraviolet light on the surface of the skin, free radicals (active oxygen) are generated in the tissue, and when this active oxygen causes cell damage or inflammation, pigmentation occurs via chemical mediators of the inflammatory system. It is said to cause.
また紫外線照射などの影響により、メラノサイト刺激ホルモン（α−ＭＳＨ）や副腎皮質刺激ホルモン（ＡＣＴＨ）など複数のメラノサイト活性化因子の分泌が促進され、色素沈着を誘発することも知られている。 It is also known that the influence of ultraviolet irradiation or the like promotes secretion of a plurality of melanocyte activating factors such as melanocyte stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH), and induces pigmentation.
また、現代社会で増え続けるストレスによってもメラノサイト刺激ホルモン（α−ＭＳＨ）や副腎皮質刺激ホルモン（ＡＣＴＨ）など複数のメラノサイト活性化因子の分泌が促進され、色素沈着を誘発することも知られており、ストレス環境下で紫外線を浴びることは、色素沈着が顕著に強くなり、難治性のシミやソバカスが生じやすくなる。 It is also known that stress that continues to increase in modern society promotes secretion of multiple melanocyte activating factors such as melanocyte stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH), and induces pigmentation. Exposure to ultraviolet light in a stressed environment significantly increases pigmentation, and causes intractable spots and freckles.
一方、色素沈着の生成は本来、生体防御反応の一つと考えられている。すなわち、皮膚表面細胞上で遺伝情報であるＤＮＡを紫外線照射などから防御するために、表皮細胞に存在する色素細胞（メラノサイト）内のメラノソームと呼ばれるメラニン生成顆粒においてメラニン色素が産生される。このようにして生成したメラニン色素が隣接する細胞に拡散し、表皮細胞のケラチノサイトに蓄積され、皮膚の新陳代謝によりケラチノサイトは通常角質層となり、やがて皮膚から剥がれ落ちると考えられているが、必要以上に過剰にメラニン色素が産生された場合には、表皮内や真皮層に沈着して、その結果、シミとなって残存すると考えられている。 On the other hand, the formation of pigmentation is considered to be one of the biological defense reactions. That is, melanin pigment is produced in melanin-producing granules called melanosomes in pigment cells (melanocytes) present in epidermal cells in order to protect DNA, which is genetic information, from ultraviolet irradiation on skin surface cells. It is believed that the melanin pigment thus generated diffuses into adjacent cells, accumulates in keratinocytes of epidermal cells, and keratinocytes usually become a stratum corneum by metabolism of the skin and eventually peel off from the skin, but more than necessary. When the melanin pigment is produced excessively, it is considered that the melanin pigment is deposited in the epidermis and the dermis layer, and as a result, remains as a stain.
そして上記のメラニン色素は大きく分けて色の濃いユウメラニンと淡色のフェオメラニンの２種類があり、いずれも紫外線の防御に寄与すること、また紫外線照射時にはユウメラニン合成が活性化されることも知られている。 The above-mentioned melanin pigments are broadly divided into two types, dark melanin and pale pheomelanin, both of which contribute to the protection against ultraviolet rays. It is also known that the synthesis of eumelanin is activated when irradiated with ultraviolet rays. Have been.
一方、シワはシミとともに皮膚老化の代表的な変化である。加齢に伴う皮膚の組織学的変化は日光暴露部と被覆部とでは大きく異なり、それぞれ、光老化及び生理的老化と区別されている。特に、顔面のシワが美容上問題となり、ここでは、生理的老化に加えて光老化の関与が大きい。この光老化には紫外線などにより生じる活性酸素などのフリーラジカルが主な原因と考えられており、紫外線による酸化障害として、脂質の過酸化、ＤＮＡ損傷、蛋白変性、代謝異常などが生じる。それらが、急性・慢性炎症、真皮細胞外マトリックスの変性を引き起こし、光老化につながると考えられている。 Wrinkles, on the other hand, are a typical change in skin aging along with spots. The histological changes of the skin with aging are significantly different between the sun-exposed area and the covered area, and are distinguished from photoaging and physiological aging, respectively. In particular, wrinkles on the face pose a cosmetic problem, and here, photoaging is significantly involved in addition to physiological aging. This photoaging is considered to be mainly caused by free radicals such as active oxygen generated by ultraviolet rays and the like, and oxidative damage caused by ultraviolet rays causes lipid peroxidation, DNA damage, protein denaturation, metabolic abnormality and the like. They are thought to cause acute and chronic inflammation and degeneration of the extracellular matrix of the dermis, leading to photoaging.
真皮細胞外マトリックスの変性は主に、活性酸素・フリーラジカルの繊維構造の分解・断片化作用によるものであり、また、活性酸素によりコラーゲン繊維の老化架橋が促進される。このようにして弾力繊維の変性が起こり、シワの原因になると考えられている。 The denaturation of the extracellular matrix of the dermis is mainly due to the decomposition and fragmentation of the fiber structure of active oxygen and free radicals, and the active oxygen promotes aging crosslinking of collagen fibers. It is believed that the elastic fibers are denatured in this way and cause wrinkles.
従来より、このようなシミやシワの生成を防止することを目的として種々の方法が検討されてきた。 Conventionally, various methods have been studied for the purpose of preventing the generation of such spots and wrinkles.
その一つとしては、紫外線照射などにより生じたフリーラジカルを消去し、またメラニン色素産生に関与する酵素のチロシナーゼを阻害することでメラニン色素産生自体を抑制する方法が挙げられる。 As one of the methods, there is a method of eliminating free radicals generated by ultraviolet irradiation or the like and inhibiting melanin pigment production itself by inhibiting tyrosinase, an enzyme involved in melanin pigment production.
上記作用を有する化合物としては、抗酸化作用のあるビタミンＣやビタミンＥが挙げられ、ビタミンＣが唯一の医薬品成分として古くから主に経口投与で用いられてきた。また、上記以外のビタミンと色素沈着に関連する事項としては以下の内容が知られている。 Examples of the compound having the above action include vitamin C and vitamin E having an antioxidant action, and vitamin C has been mainly used orally as a sole pharmaceutical ingredient since ancient times. In addition, the following contents are known as matters related to vitamins and pigmentation other than the above.
すなわち、リボフラビンはグルタチオン還元酵素の補酵素として重要であり、過酸化脂質の生成を抑制すること、またフリーラジカル捕捉剤として作用する可能性があること（例えば、非特許文献１参照。）、さらにリボフラビンを局所注射後に紫外線照射することが青色母斑の治療に有効であることが知られている（例えば、非特許文献２参照。）。 That is, riboflavin is important as a coenzyme of glutathione reductase, which suppresses the production of lipid peroxide, and may act as a free radical scavenger (for example, see Non-Patent Document 1). It is known that irradiating ultraviolet light after local injection of riboflavin is effective for treating blue nevus (for example, see Non-Patent Document 2).
ニコチン酸アミドは、色素細胞から表皮細胞へのメラニンの転送を阻害することにより色素沈着を防止することが知られている（例えば、非特許文献３参照。）。 Nicotinamide is known to prevent pigmentation by inhibiting the transfer of melanin from pigment cells to epidermal cells (for example, see Non-Patent Document 3).
パントテン酸カルシウムは、単独では紫外線照射後の色素沈着に対して効果がないが、ビタミンＣとの併用で色素沈着防止効果があることが知られている（例えば、非特許文献４参照。）。 It is known that calcium pantothenate alone has no effect on pigmentation after ultraviolet irradiation, but has an effect of preventing pigmentation when used in combination with vitamin C (for example, see Non-Patent Document 4).
上記以外では外用の美白剤が主に用いられている。具体的には、メラニン色素産生自体を抑制するハイドロキノン誘導体（例えば、特許文献１参照。）、チロシナーゼ阻害による美白効果を期待したエラグ酸（例えば、非特許文献５参照。）、コウジ酸（例えば、特許文献２、３参照。）、アルブチン（例えば、特許文献４参照。）などが既に提案されているが、前述のとおり、メラニン色素は紫外線防御における重要な物質であり、これらの成分はメラニン色素産生自体を抑制するので必ずしも好ましいことではない。 Other than the above, an external whitening agent is mainly used. Specifically, hydroquinone derivatives that suppress melanin pigment production itself (for example, see Patent Document 1), ellagic acid (for example, see Non-Patent Document 5) that is expected to have a whitening effect by inhibiting tyrosinase, kojic acid (for example, Patent Documents 2 and 3) and arbutin (for example, see Patent Document 4) have already been proposed. However, as described above, melanin is an important substance in ultraviolet protection, and these components are melanin pigments. This is not always desirable because it suppresses the production itself.
しかしながら、上記公報及び文献のいずれにも、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上が効率的にメラノサイトの活性化を抑制し美白作用を有することについては何ら開示も示唆もされていない。また、それらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物がより効果的に美白作用を有することも何ら開示も示唆もされていない。 However, in any of the above publications and documents, it is described that at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate effectively suppresses activation of melanocytes and has a whitening effect. No disclosure or suggestion is made. Moreover, there is no disclosure or suggestion that a vitamin mixture composition characterized by containing three or more selected from the group consisting of them has a more effective whitening effect.
本発明の目的は、優れた美白作用を有する、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物を提供することにある。 An object of the present invention is to provide a whitening agent having at least one active ingredient selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate having an excellent whitening action, and a whitening agent selected from the group consisting of these. An object of the present invention is to provide a vitamin mixture composition characterized by containing at least one species.
本発明者らの研究によれば、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上が意外にも優れた美白作用を見出し、それらからなる群から選ばれる３種以上を組合せたビタミン混合組成物がさらに優れた美白作用を有することを見出し本発明を完成させた。 According to the study of the present inventors, at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate has found an unexpectedly excellent whitening effect, and 3 or more selected from the group consisting of these. The present inventors have found that a vitamin mixture composition comprising a combination of more than one kind has a more excellent whitening effect, and completed the present invention.
すなわち、本発明は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物である。
好ましくは、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる２種以上を有効成分とする美白剤であり、さらに好ましくはリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる３種以上を有効成分とする美白剤であり、最も好ましくはリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムを有効成分とする美白剤である。
また、本発明は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物に関する。
That is, the present invention comprises a whitening agent containing at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as an active ingredient, and containing three or more selected from the group consisting of them. It is a characteristic vitamin mixed composition.
Preferably, riboflavin, pyridoxine hydrochloride, a whitening agent containing two or more active ingredients selected from the group consisting of nicotinamide and calcium pantothenate as active ingredients, more preferably from riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate A whitening agent containing at least three selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as active ingredients.
The present invention also relates to a vitamin mixture composition comprising three or more members selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate.
本発明のリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤は、優れた美白作用を示し、それらからなる群から選ばれる３種以上を組合せたビタミン混合組成物がさらに優れた美白作用を示し、色素沈着が悪化するストレス環境下においても優れた美白効果を示した。従って、本発明の美白剤及びビタミン混合組成物が色素沈着を予防し、シミやソバカスの紫外線による悪化を抑制することが示唆され、美白剤として有用である。 The whitening agent containing one or more active ingredients selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as the active ingredient of the present invention exhibits excellent whitening action, and three or more selected from the group consisting of them. The vitamin-mixed composition obtained by combining the above showed a more excellent whitening effect, and also showed an excellent whitening effect even in a stress environment where pigmentation was deteriorated. Therefore, it is suggested that the whitening agent and vitamin mixture composition of the present invention prevents pigmentation and suppresses deterioration of spots and freckles due to ultraviolet rays, and is useful as a whitening agent.
以下、本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明に用いられるリボフラビンは、第十四改正日本薬局方、（株式会社じほう発行、２００１年、以下局方と略記する）、７４９−７５０頁に記載のものが挙げられる。 Examples of the riboflavin used in the present invention include those described in the Japanese Pharmacopoeia, 14th Edition, published by Jiho Co., Ltd., 2001, hereinafter abbreviated as Pharmacopoeia, pp. 749-750.
本発明に用いられる塩酸ピリドキシンは、局方、３６１頁に記載のものが挙げられる。 The pyridoxine hydrochloride used in the present invention includes those described on p. 361 of the Pharmacopoeia.
本発明に用いられるニコチン酸アミドは、局方、５８８頁に記載のものが挙げられる。 The nicotinamide used in the present invention includes those described on page 588 of the Pharmacopoeia.
本発明に用いられるパントテン酸カルシウムは、局方、６１５−６１６頁に記載のものが挙げられる。 The calcium pantothenate used in the present invention includes those described in Pharmacopoeia, pp. 615-616.
本発明の美白剤及びビタミン混合組成物としては、固形剤、半固形剤、液剤等特に制限されるものではなく、具体的には錠剤、細粒剤、顆粒剤、散剤、カプセル剤、チュアブル剤、発泡剤、ドライシロップ剤、ゼリー剤、ゼリードロップ剤、液剤等の形態をした食品及び医薬品などが挙げられる。 The whitening agent and the vitamin mixture composition of the present invention are not particularly limited, such as solid preparations, semi-solid preparations, and liquid preparations. Specifically, tablets, fine granules, granules, powders, capsules, chewables Foods and pharmaceuticals in the form of foaming agents, dry syrups, jellies, jelly drops, liquids and the like.
本発明の美白剤及びビタミン混合組成物は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を混合したものをそのままの形で使用することもできるが、その他の成分として、通常の食品及び医薬品に用いられるものを使用することができる。例えば結晶セルロース、ショ糖脂肪酸エステル、白糖等の賦形剤を加え、例えば乾式顆粒打錠法あるいは湿式顆粒打錠法により造粒して製造することができる。 The whitening agent and the vitamin mixture composition of the present invention may be used in the form of a mixture of one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide, and calcium pantothenate as they are. As the components of, those used for ordinary foods and pharmaceuticals can be used. For example, it can be produced by adding excipients such as crystalline cellulose, sucrose fatty acid ester and sucrose, and granulating by, for example, dry granulation or wet granulation.
また、通常、液状の食品及び医薬品に使用される浸潤剤、乳化剤、分散助剤、界面活性剤、甘味料、酸味料、糖アルコール、フレーバー、芳香物質等賦形剤を加えて溶解し、液体の状態として製造することもできる。 In addition, infiltrating agents, emulsifiers, dispersing aids, surfactants, sweeteners, sour agents, sugar alcohols, flavors, aromatic substances, and other excipients usually used in liquid foods and pharmaceuticals are added and dissolved, It can also be manufactured as a state.
本発明のリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴ビタミン混合組成物における、各有効成分の配合割合は用いられる種類によっても若干異なるが、全組成物１０００重量部当たり、リボフラビンは０．４〜３０重量部、好ましくは２〜３０重量部、塩酸ピリドキシンは０．５〜１００重量部、好ましくは５〜１００重量部、ニコチン酸アミドは２〜６０重量部、好ましくは１２〜６０重量部及びパントテン酸カルシウムは５〜３０重量部、好ましくは５〜１５重量部である。当該範囲内の使用であれば、優れた美白効果を示し、コスト的にも有効である。 A lipoflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate according to the present invention, comprising at least one active ingredient selected from the group consisting of a whitening agent and three or more active ingredients selected from the group consisting of vitamins. In the composition, the mixing ratio of each active ingredient is slightly different depending on the kind used, but riboflavin is 0.4 to 30 parts by weight, preferably 2 to 30 parts by weight, and pyridoxine hydrochloride is 0 per 1000 parts by weight of the total composition. 0.5 to 100 parts by weight, preferably 5 to 100 parts by weight, nicotinamide is 2 to 60 parts by weight, preferably 12 to 60 parts by weight, and calcium pantothenate is 5 to 30 parts by weight, preferably 5 to 15 parts by weight. It is. When used within the above range, an excellent whitening effect is exhibited and the cost is effective.
さらに具体的には、一日の投与量が、リボフラビン０．４〜３０ｍｇ、塩酸ピリドキシン０．５〜１００ｍｇ、ニコチン酸アミド２〜６０ｍｇ及びパントテン酸カルシウム５〜３０ｍｇとなるよう適宜混合する。 More specifically, they are appropriately mixed so that the daily dose is 0.4 to 30 mg of riboflavin, 0.5 to 100 mg of pyridoxine hydrochloride, 2 to 60 mg of nicotinamide and 5 to 30 mg of calcium pantothenate.
本発明の美白剤及びビタミン混合組成物は、必須成分である上記化合物の他に通常の医薬品及び飲食品において使用されるアスコルビン酸、コウジ酸、アルブチン、胎盤抽出物、ビタミンＥ、システイン、グルタチオン等の公知の美白剤、ビタミンＢ１、ビタミンＤ、アミノ酸、ペプチド、蛋白質等を配合することができる。 The whitening agent and the vitamin-mixed composition of the present invention include ascorbic acid, kojic acid, arbutin, placental extract, vitamin E, cysteine, glutathione, etc., which are used in ordinary pharmaceuticals and foods and drinks in addition to the above-mentioned compounds as essential components Known whitening agents, vitamin B 1 , vitamin D, amino acids, peptides, proteins and the like.
本発明の美白剤及びビタミン混合組成物は、美白剤として、通常成人１日当たり１〜３回に分けて経口投与する。 The whitening agent and the vitamin mixture composition of the present invention are orally administered as a whitening agent usually in 1 to 3 times per day for an adult.
以下に試験例を挙げて本発明を詳細に説明する。リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムは市販のものを用いた。 Hereinafter, the present invention will be described in detail with reference to test examples. Riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate were commercially available.
[試験例]
試験例１（紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
ＤＢＡ／２ＮＣｒｊマウス（雄性、６週齢）６匹を１群として用いた。体重を測定し、
表１に示す被験物質を１％レシチンに溶解させて用いた。５群のＤＢＡ／２ＮＣｒｊマウスにそれぞれ試験試料１ａ〜１ｄ、対照試料１をゾンデで直接胃の中に投与した。その後、投与１時間後に医療用紫外線照射装置デルマレー（クリニカル・サプライ社製）を用いて、中波長紫外線を５分間０．０９Ｊ／ｃｍ２照射した。被験試料投与と照射を１日１回、９日間行った。次ぎに１０日目にＤＢＡ／２ＮＣｒｊマウスの両耳を採取し、外側の皮膚が上になるように置き、左右の耳から１箇所ずつ６ｍｍのトレパンで皮膚を採取した。その後、外側の皮膚を採取し、定法に従ってメラニン色素を産生しているメラノサイトの指標であるド−パ陽性メラノサイトの染色を行い、顕微鏡下でメラノサイト数を数え、１ｍｍ２当たりのメラノサイト数を計測した。なお、１群のＤＢＡ／２ＮＣｒｊマウスは中波長紫外線を照射せず、同様に実験を行った（非照射投与群という）。
[Test example]
Test Example 1 (Melanocyte proliferation activation suppression test after ultraviolet irradiation)
(1) Test method Six DBA / 2NCrj mice (male, 6 weeks old) were used as one group. Measure your weight,
The test substances shown in Table 1 were dissolved in 1% lecithin before use. Five groups of DBA / 2NCrj mice were administered test samples 1a to 1d and control sample 1 directly into the stomach by sonde. Then, one hour after the administration, 0.09 J / cm 2 of medium-wavelength ultraviolet rays was irradiated for 5 minutes using a medical ultraviolet irradiation apparatus Dermalai (manufactured by Clinical Supply Co., Ltd.). Test sample administration and irradiation were performed once a day for 9 days. Next, on the 10th day, both ears of the DBA / 2NCrj mouse were collected, placed so that the outer skin was on top, and the skin was collected from the left and right ears one by one with a 6 mm trepan. Thereafter, the outer skin was collected, stained for dopa-positive melanocytes, which are indicators of melanocytes producing melanin pigment, according to a standard method, the number of melanocytes was counted under a microscope, and the number of melanocytes per 1 mm 2 was measured. . One group of DBA / 2NCrj mice was similarly exposed to medium-wavelength ultraviolet light, and the same experiment was performed (referred to as a non-irradiated administration group).
（２）検定方法
結果の判定は、対照試料投与群１と本発明の試験試料投与群１ａ〜１ｄのそれぞれのドーパ陽性メラノサイト数を比較して行った。また、有意差検定はダネット（ｄｕｎｎｅｔｔ）検定を用いた。
（３）試験結果
結果を表２に示す。表２から明らかなようにリボフラビン、塩酸ピリドキシン、パントテン酸カルシウム及びニコチン酸アミドは有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制し、本発明の美白剤が色素沈着防止に有効であることが示された。
(2) Assay Method The results were determined by comparing the number of dopa-positive melanocytes in each of the control sample administration group 1 and the test sample administration groups 1a to 1d of the present invention. The Dunnett test was used as a significant difference test.
(3) Test results The results are shown in Table 2. As is clear from Table 2, riboflavin, pyridoxine hydrochloride, calcium pantothenate and nicotinamide significantly suppress the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation, and the whitening agent of the present invention is effective in preventing pigmentation. It was shown.
試験例２（紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
表３に示す被験物質を用いる以外は試験例１と同様に試験を行った。
Test Example 2 (Melanocyte proliferation activation suppression test after ultraviolet irradiation)
(1) Test method A test was performed in the same manner as in Test Example 1 except that the test substances shown in Table 3 were used.
（２）検定方法
試験例１と同様の方法を用いた。
(2) Test method The same method as in Test example 1 was used.
（３）試験結果
結果を表４に示す。表４から明らかなように本発明のビタミン混合組成物は有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制した。また、参考試料２ａ〜２ｃのビタミンＣ、ビタミンＥに比べて本発明のビタミン混合組成物は有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制した。
(3) Test results The results are shown in Table 4. As is clear from Table 4, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation. In addition, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation as compared with the vitamin C and vitamin E of Reference Samples 2a to 2c.
試験例３（紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
表５に示す被験物質を用いる以外は試験例１と同様に試験を行った
Test Example 3 (Melanocyte proliferation activation suppression test after ultraviolet irradiation)
(1) Test method The test was performed in the same manner as in Test Example 1 except that the test substances shown in Table 5 were used.
（２）検定方法
試験例１と同様の方法を用いた。
（３）試験結果
結果を表６に示す。表６から明らかなように本発明のビタミン混合組成物は有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制した。
(2) Test method The same method as in Test example 1 was used.
(3) Test results The results are shown in Table 6. As is clear from Table 6, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation.
尚、抑制率は下記式より求めた。
抑制率（％）＝｛（対照群−ストレス群）−（各試料群−ストレス群）｝／（対照群−ストレス群）×１００
The suppression rate was determined by the following equation.
Inhibition rate (%) = {(control group−stress group) − (each sample group−stress group)} / (control group−stress group) × 100
試験例３（ストレス環境飼育下での紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
ＤＢＡ／２ＮＣｒｊマウス（雄性、６週齢）６匹を１群として用い、通常環境下と過密ストレス環境下で飼育を行った。すなわち、非照射投与群（紫外線非照射）と紫外線照射群（紫外線照射のみ）は、飼育を通常ケージ（３０×２０×１２ｃｍ）で行い、ストレス群（過密ストレス環境飼育のみ）とストレス下紫外線照射群（対象群；過密ストレス環境飼育で紫外線照射）及び試験試料投与群は、飼育を過密ストレスケージ（１４×７×８ｃｍ）で行った。試験には、表７に示す被験物質を０．５％カルメロースナトリウムに溶解させて用いた。８群のＤＢＡ／２ＮＣｒｊマウスにそれぞれ試験試料４ａと４ｂ、参考試料４及び対照試料４をゾンデで直接胃の中に投与した。その後、投与１時間後に医療用紫外線照射装置デルマレー（クリニカル・サプライ社製）を用いて、中波長紫外線を５分間０．０４５Ｊ／ｃｍ２照射した。過密ストレス環境飼育したＤＢＡ／２ＮＣｒｊマウスは紫外線照射の際には通常ケージを用いて行った。被験試料投与と照射を１日１回、９日間行った。９日目の照射５〜３０分の間にＤＢＡ／２ＮＣｒｊマウスをジエチルエーテル麻酔をし採血後、両耳を採取し、外側の皮膚が上になるように置き、左右の耳から１箇所ずつ６ｍｍのトレパンで皮膚を採取した。その後、外側の皮膚を採取し、定法に従ってメラニン色素を産生しているメラノサイトの指標であるド−パ陽性メラノサイトの染色を行い、顕微鏡下でメラノサイト数を数え、１ｍｍ２当たりのメラノサイト数を計測した。なお、１群のＤＢＡ／２ＮＣｒｊマウスは中波長紫外線を照射せず、同様に実験を行った。また、採血した血清については、血清中のＡＣＴＨ濃度を、ＭＤ Ｂｉｏｓｃｉｅｎｃｅ社キットのＥＬＩＳＡ法により測定した。
Test Example 3 (Melanocyte proliferation activation suppression test after irradiation with ultraviolet light under stress environment rearing)
(1) Test method Six DBA / 2NCrj mice (male, 6 weeks old) were used as one group, and bred under a normal environment and an overcrowded stress environment. That is, the non-irradiated administration group (non-ultraviolet irradiation) and the ultraviolet irradiation group (ultraviolet irradiation only) are reared in a normal cage (30 × 20 × 12 cm), and the stress group (only breeding in an overstressed environment) and the ultraviolet irradiation under stress. The group (subject group; irradiation with ultraviolet rays in an overstressed environment) and the test sample administration group were bred in overstressed cages (14 × 7 × 8 cm). In the test, the test substances shown in Table 7 were used by dissolving them in 0.5% carmellose sodium. Eight groups of DBA / 2NCrj mice were each administered test samples 4a and 4b, reference sample 4 and control sample 4 directly into the stomach by sonde. Then, one hour after the administration, medium wavelength ultraviolet rays were irradiated at 0.045 J / cm 2 for 5 minutes using a medical ultraviolet irradiation apparatus Dermalet (manufactured by Clinical Supply Co., Ltd.). DBA / 2NCrj mice reared in an overcrowded stress environment were usually irradiated with ultraviolet light using a cage. Test sample administration and irradiation were performed once a day for 9 days. DBA / 2NCrj mice were anesthetized with diethyl ether for 5 to 30 minutes on the ninth day of irradiation, and blood was collected. Then, both ears were collected and placed so that the outer skin was on top, and 6 mm each from the left and right ears. The skin was collected with a trepan. Thereafter, the outer skin was collected, stained for dopa-positive melanocytes, which are indicators of melanocytes producing melanin pigment, according to a standard method, the number of melanocytes was counted under a microscope, and the number of melanocytes per 1 mm 2 was measured. . In addition, one group of DBA / 2NCrj mice was similarly irradiated without irradiation with medium-wavelength ultraviolet rays. For the collected serum, the ACTH concentration in the serum was measured by an ELISA method using a kit from MD Bioscience.
（２）検定方法
結果の判定は、対照群と本発明の試験試料４ａ、４ｂ投与群及び参考試料４投与群のそれぞれのドーパ陽性メラノサイト数を比較して行った。また、有意差検定はダネット（ｄｕｎｎｅｔｔ）検定を用いた。
(2) Assay Method The results were determined by comparing the numbers of dopa-positive melanocytes in the control group, the test sample 4a, 4b administration group of the present invention, and the reference sample 4 administration group. The Dunnett test was used as a significant difference test.
（３）試験結果
ドーパ陽性メラノサイト数の結果を表８に、ＡＣＴＨ濃度を表９に示す。表８から明らかなように本発明のビタミン混合組成物はストレス環境下の紫外線照射によるド−パ陽性メラノサイト数の増加を有意に抑制した。また、参考試料のビタミンＣに比べて本発明の組成物は低用量で有効で、紫外線照射によるド−パ陽性メラノサイト数の増加を有意に抑制した。また、表９から明らかなように、ストレス環境下の紫外線照射により顕著に増加するＡＣＴＨに対して、本発明の組成物は有意に抑制することが明らかになり、本発明の組成物が色素沈着を予防し、シミやソバカスの紫外線による悪化を抑制する可能性があることが示唆された。
(3) Test results Table 8 shows the results of the number of dopa-positive melanocytes, and Table 9 shows the ACTH concentrations. As is clear from Table 8, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation in a stress environment. In addition, the composition of the present invention was effective at a lower dose than the reference sample of vitamin C, and significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation. Further, as is clear from Table 9, the composition of the present invention was found to significantly suppress ACTH, which is significantly increased by ultraviolet irradiation in a stress environment. It is suggested that there is a possibility of preventing blemishes and freckles caused by ultraviolet rays.
以下に、実施例を挙げて本発明をさらに具体的に説明する。 Hereinafter, the present invention will be described more specifically with reference to examples.
実施例１（錠剤）
（処方）
リボフラビン ０．８ｇ
塩酸ピリドキシン １．０ｇ
ニコチン酸アミド ２．０ｇ
結晶セルロース ８０．０ｇ
二酸化ケイ素 ６．０ｇ
ソルビトール １９８．２ｇ
ショ糖脂肪酸エステル １２．０ｇ
――――――――――――――――――――――――――――――
合計 ３００．０ｇ
Example 1 (tablet)
(Prescription)
Riboflavin 0.8g
Pyridoxine hydrochloride 1.0g
Nicotinamide 2.0g
80.0 g of crystalline cellulose
6.0 g of silicon dioxide
Sorbitol 198.2g
12.0 g sucrose fatty acid ester
――――――――――――――――――――――――――――――
300.0g in total
（製造方法）
上記の各成分を混合し、その混合物を打錠機で１錠３００ｍｇに打錠して１錠中にリボフラビン０．８ｍｇ、塩酸ピリドキシン１．０ｍｇ、ニコチン酸アミド２．０ｍｇ含む実施例１の錠剤を得る。
(Production method)
The above components are mixed, and the mixture is compressed into 300 mg / tablet using a tableting machine. Each tablet contains 0.8 mg of riboflavin, 1.0 mg of pyridoxine hydrochloride, and 2.0 mg of nicotinamide in each tablet. Get.
実施例２（錠剤）
リボフラビン０．８ｇ及びソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９５．８ｇに代えた以外は実施例１と同様にして調製し、実施例２の錠剤を得る。
Example 2 (tablet)
The tablet of Example 2 is obtained in the same manner as in Example 1 except that 0.8 g of riboflavin and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 195.8 g of sorbitol.
実施例３（錠剤）
塩酸ピリドキシン１．０ｇ及びソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９６．０ｇに代えた以外は実施例１と同様にして調製し、実施例３の錠剤を得る。
Example 3 (tablet)
The tablet of Example 3 is obtained in the same manner as in Example 1, except that 1.0 g of pyridoxine hydrochloride and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 196.0 g of sorbitol.
実施例４（錠剤）
ニコチン酸アミド２．０ｇ及びソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９７．０ｇに代えた以外は実施例１と同様にして調製し、実施例４の錠剤を得る。
Example 4 (tablet)
The tablet of Example 4 is obtained in the same manner as in Example 1 except that 2.0 g of nicotinamide and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 197.0 g of sorbitol.
実施例５（錠剤）
ソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９５．０ｇに代えた以外は実施例１と同様にして調製し、実施例５の錠剤を得る。
Example 5 (tablet)
Except that 198.2 g of sorbitol was replaced by 3.2 g of calcium pantothenate and 195.0 g of sorbitol, it was prepared in the same manner as in Example 1 to obtain a tablet of Example 5.
実施例６（液剤）
（処方）
リボフラビン １ｇ
塩酸ピリドキシン ５ｇ
ニコチン酸アミド ５ｇ
クエン酸 ２８ｇ
リンゴ酸 ２０ｇ
スクラロース ５ｇ
香料 １０ｇ
精製水 適 量
――――――――――――――――――――――――――――――
全量 １５ｋｇ
Example 6 (solution)
(Prescription)
1 g of riboflavin
Pyridoxine hydrochloride 5g
Nicotinamide 5g
28 g of citric acid
20 g of malic acid
5g sucralose
Perfume 10g
Appropriate amount of purified water ――――――――――――――――――――――――――――――
15kg
（製造方法）
上記のリボフラビンからスクラロースまでの各成分を加えて加熱溶解し、冷後、香料及び精製水を加えて全量１５ｋｇとする。この液を１００ｍＬずつ容器に分注し、実施例６の液剤を得る。
(Production method)
The components from riboflavin to sucralose are added and dissolved by heating. After cooling, a perfume and purified water are added to bring the total amount to 15 kg. This solution is dispensed into the container 100 mL at a time to obtain the liquid preparation of Example 6.
実施例７（液剤）
リボフラビン１ｇをパントテン酸カルシウム５ｇに代えた以外は実施例６と同様にして調製し、実施例７の液剤を得る。
Example 7 (solution)
A liquid preparation of Example 7 is obtained in the same manner as in Example 6, except that 1 g of riboflavin is replaced by 5 g of calcium pantothenate.
実施例８（液剤）
塩酸ピリドキシン５ｇをパントテン酸カルシウム５ｇに代えた以外は実施例６と同様にして調製し、実施例８の液剤を得る。
Example 8 (solution)
The liquid preparation of Example 8 is obtained in the same manner as in Example 6, except that 5 g of pyridoxine hydrochloride is replaced with 5 g of calcium pantothenate.
実施例９（液剤）
ニコチン酸アミド５ｇをパントテン酸カルシウム５ｇに代えた以外は実施例６と同様にして調製し、実施例９の液剤を得る。
Example 9 (solution)
A liquid preparation of Example 9 is obtained in the same manner as in Example 6, except that 5 g of nicotinamide is replaced by 5 g of calcium pantothenate.
実施例１０（液剤）
パントテン酸カルシウム５ｇを加える以外は実施例６と同様にして調製し、実施例１０の液剤を得る。
Example 10 (solution)
Except that 5 g of calcium pantothenate is added, the preparation is carried out in the same manner as in Example 6 to obtain the liquid preparation of Example 10.
実施例１１（錠剤）
ソルビトール１９８．２ｇをバラの花びらエキス１０．０ｇ及びソルビトール１８８．２ｇに代えた以外は実施例１と同様にして調製し、実施例１１の錠剤を得る。
Example 11 (tablet)
Except that 198.2 g of sorbitol was replaced by 10.0 g of rose petal extract and 188.2 g of sorbitol, it was prepared in the same manner as in Example 1 to obtain the tablet of Example 11.
実施例１２（液剤）
バラの花びらエキス５ｇを追加した以外は実施例６と同様にして調製し、実施例１２の液剤を得る。
Example 12 (solution)
A liquid preparation of Example 12 is obtained in the same manner as in Example 6, except that 5 g of rose petal extract is added.
本発明に係る、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上からなる美白剤は、優れた美白作用を示す。それらからなる群より選ばれる３種以上からなることを特徴とするビタミン混合組成物は
、さらに優れた美白作用を示す。さらに本発明のビタミン混合組成物は、ストレスで増加するＡＣＴＨの分泌を抑える作用が明らかであり、日常生活で受ける様々なストレスで悪化する色素沈着に対しても優れた効果を発揮することで、頑固なシミ・ソバカスなどの治療効果も期待できる。
The whitening agent according to the present invention, which comprises at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate, exhibits an excellent whitening effect. A vitamin mixture composition comprising three or more selected from the group consisting of them exhibits a more excellent whitening effect. Furthermore, the vitamin mixture composition of the present invention is clearly effective in suppressing the secretion of ACTH that increases due to stress, and exhibits an excellent effect on pigmentation that worsens due to various stresses received in daily life, It can also be used to treat stubborn spots and freckles.
Claims (5)
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009256326A (en) * | 2008-03-21 | 2009-11-05 | Kose Corp | Skin whitening preparation, and skincare preparation |
| JP2010159252A (en) * | 2008-12-12 | 2010-07-22 | Daiichi Sankyo Healthcare Co Ltd | Melanosome traffick inhibitor, and method for the same |
| JP2018080128A (en) * | 2016-11-16 | 2018-05-24 | 株式会社ファンケル | Il-1 receptor antagonist (il-1ra) production promoting composition |
| WO2018147385A1 (en) * | 2017-02-08 | 2018-08-16 | オリエンタル酵母工業株式会社 | Skin pigmentation inhibitor |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009256326A (en) * | 2008-03-21 | 2009-11-05 | Kose Corp | Skin whitening preparation, and skincare preparation |
| JP2010159252A (en) * | 2008-12-12 | 2010-07-22 | Daiichi Sankyo Healthcare Co Ltd | Melanosome traffick inhibitor, and method for the same |
| JP2018080128A (en) * | 2016-11-16 | 2018-05-24 | 株式会社ファンケル | Il-1 receptor antagonist (il-1ra) production promoting composition |
| WO2018147385A1 (en) * | 2017-02-08 | 2018-08-16 | オリエンタル酵母工業株式会社 | Skin pigmentation inhibitor |
| KR20190112117A (en) * | 2017-02-08 | 2019-10-02 | 오리엔탈고우보고오교가부시끼가이샤 | Skin pigmentation inhibitors |
| CN110461339A (en) * | 2017-02-08 | 2019-11-15 | 东方酵母工业株式会社 | Cutaneous pigmentation inhibitor |
| JPWO2018147385A1 (en) * | 2017-02-08 | 2019-12-12 | オリエンタル酵母工業株式会社 | Skin pigmentation inhibitor |
| US11219632B2 (en) | 2017-02-08 | 2022-01-11 | Oriental Yeast Co., Ltd. | Skin pigmentation inhibitor |
| JP2022180453A (en) * | 2017-02-08 | 2022-12-06 | オリエンタル酵母工業株式会社 | skin pigmentation inhibitor |
| KR102566670B1 (en) | 2017-02-08 | 2023-08-11 | 오리엔탈고우보고오교가부시끼가이샤 | skin pigmentation inhibitor |
| JP7374585B2 (en) | 2017-02-08 | 2023-11-07 | オリエンタル酵母工業株式会社 | skin pigmentation inhibitor |
| JP7428767B2 (en) | 2017-02-08 | 2024-02-06 | オリエンタル酵母工業株式会社 | skin pigmentation inhibitor |
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