200808717 九、發明說明 【發明所屬之技術領域】 本發明係關於皮膚的美白劑，以及含其之化妝料組成 物。 【先前技術】 關於皮膚的美白劑，已知有雄果素、鞣花酸、麹酸、 維他命c衍生物及各種香草萃取物等，但目前仍尋求對皮 膚溫和且容易與化妝料搭配之成份。 另一方面對於鋅，已有報告指出氧化鋅可抑制尿布紅 疹（例如 FEBS Letters，384 期，92-96 頁，1996 年）。然 而，該化合物難溶於水或油性成份，難以使用爲化妝品及 皮膚外用劑之成份。另外，針對爲一種有機鋅鹽之甘胺酸 鋅鹽，已知係具有金屬硫蛋白之誘發促進作用（特開 2005-2 47 729號公報）。其係經由抗氧化效果及自由基清 除活性等路徑，而對黑色素合成障礙及細胞毒性障礙等因 UV引起的皮膚損傷具有抑制作用。同樣的針對爲一種有 機鋅之吡咯烷酮羧酸鋅鹽及醯胺酸鋅鹽，已知可抑制因 UV弓丨起的 AP-1及NF· /cB等發炎因子（特開 2006-022090號公報，國際公開W02005/123062號手冊）。 另外，針對有機鋅鹽及無機鋅鹽，已知可以收斂作用 、消炎作用、白色顏料、紫外線防止劑、消臭•殺菌劑之 用途而與化妝料組成物搭配使用，但因使用接近於可期待 效果之濃度區域時會對皮膚會產生刺激性，而難以利用爲 -4- 200808717 化妝品。而於低濃度之使用，對皮膚無法出現如前述之有 效性，而使鋅化合物與化妝料之搭配無所進展。 【發明內容】 本發明之發明者們，爲達成上述目的重複專心檢討後 ，發現藉由將鋅導入人類色素細胞（黑色素產生細胞（黑 色素細胞）），會具有促進抗壞血酸轉運體表現效果，而 發現伴隨其之可得之美白效果。 抗壞血酸轉運體係促進細胞導入抗壞血酸之膜蛋白質 (請參照 Hiroyasu Tsukaguchi etc ( 1 9 9 9 ) Nature 399, 70-75 )。藉由抗壞血酸轉運體的表現增強，於人類色素 細胞（黑色素產生細胞（黑色素細胞）），引起促進抗壞 血酸對細胞內之導入，而使黑色素產生被抑制。 本發明之目的，係基於上述之知識，而獲得具優異美 白作用之美白劑，以及含其之化妝料組成物。 亦即，本發明係有關特徵係含鋅爲有效成份之美白用 組成物。 自皮膚刺激性及對細胞內之導入效率等觀點，做爲實 際可實施之導入鋅方法’係必須使鋅以鋅鹽形式，以一定 的濃度塗佈於皮膚上’具體係包含以下之發明。 (1 ) 一種美白劑，其係含鋅爲有效成份。 (2 )如（1 )項之美白劑’其中鋅係選自吡咯烷酮羧 酸鋅鹽、葡萄糖酸鋅鹽、苯酚磺酸鋅鹽、乳酸鋅鹽、各種 胺基酸鋅鹽、醯胺酸鋅鹽、硫酸鋅、氯化鋅及氧化鋅所成 -5- 200808717 群之化合物。 (3 )如（1 )項之美白劑，其中鋅係吡咯烷酮羧酸鋅 鹽。 (4 )如前述（1 )〜（3 )項中任一項之美白劑，其 中美白係介由使人類色素細胞（黑色素產生細胞（黑色素 細胞））之抗壞血酸轉運體的表現增強而達成。 (5 ) —種美白用組成物，其係搭配鋅做爲有效成份 〇 (6 )如（5 )項之美白用組成物，其中鋅係選自吡咯 烷酮羧酸鋅鹽、葡萄糖酸鋅鹽、苯酚磺酸鋅鹽、乳酸鋅鹽 、各種胺基酸鋅鹽、醯胺酸鋅鹽、硫酸鋅、氯化鋅及氧化 鋅所成群之化合物。 (7 )如（5 )項之美白用組成物，其中鋅係吡咯烷酮 羧酸鋅鹽。 (8 )如前述（5 )〜（7 )項中任一項之美白用組成 物，其中係搭配鋅使以1 // Μ〜100mM之濃度存在於組成 物中。 (9 )如前述（5 )〜（8 )項中任一項之美白用組成 物，其中進而搭配抗壞血酸。 (10)如則述（5)〜（9)項中任一*項之美白用組成 物，其係搭配濃度爲1 // Μ〜lOOmM之鋅，以及濃度爲 5mM〜600mM之抗壞血酸。 (11 )如前述（5 )〜（1 0 )項中任一項之美白用組 成物，其中進而搭配N -醯基酸性胺基酸酯、胺基酸或胺 -6 - 200808717 基酸衍生物。 (12 )如前述（5 )〜（1 1 )項中任一項之美白用組 成物，其係軟膏、化妝水、洗劑、乳霜、乳液、美容液、 面膜、粉底霜或液狀洗手乳。 (13) —種爲美白肌膚之鋅之使用。 (1 4 ) 一種爲美白肌膚之選自吡咯烷酮羧酸鋅鹽、葡 萄糖酸鋅鹽、苯酚磺酸鋅鹽、乳酸鋅鹽、各種胺基酸鋅鹽 、醯胺酸鋅鹽、硫酸鋅、氯化鋅及氧化鋅所成群之鋅鹽之 使用。 (1 5 ) —種爲美白肌膚之吡咯烷酮羧酸鋅鹽之使用。 (16) —種美白方法，其特徵係將前述（5)〜（11 )項之組成物塗佈於皮膚上。 以下，詳細說明本發明。 於本發明中，美白係指所謂使肌膚漂亮地變白的槪念 ’而美白劑則指具治療目的者，以及具預防目的者任一種 均包含於其中。 於本發明所使用之鋅，自皮膚刺激性及對細胞內之導 入效率等觀點，實際上必須使鋅以鋅鹽形式，以一定的濃 度塗佈於皮膚上。此時可使用有機鋅鹽及無機鋅鹽任何一 種。有機鋅鹽包含吡咯烷酮羧酸鋅鹽、葡萄糖酸鋅鹽、苯 酣磺酸鋅鹽、乳酸鋅鹽、各種胺基酸鋅鹽、醯胺酸鋅鹽等 °無機鋅包含硫酸鋅、氯化鋅及氧化鋅等。 胺基酸鋅鹽可舉出甘胺酸鋅鹽、丙胺酸鋅鹽、纈胺酸 鋅鹽、白胺酸鋅鹽、異白胺酸鋅鹽、苯丙胺酸鋅鹽、甲基 200808717 胺酸鋅鹽、色胺酸鋅鹽、天冬醯胺酸鋅鹽、麩醯胺酸鋅鹽 '絲胺酸鋅鹽、穌胺酸鋅鹽、半胱胺酸鋅鹽、酪胺酸鋅鹽 、天冬胺酸鋅鹽、麩胺酸鋅鹽、離胺酸鋅鹽、精胺酸鋅鹽 或組胺酸鋅鹽等各種胺基酸鋅鹽。 醯胺酸鋅鹽爲胺基酸之胺基與醯基鍵結後之化合物之 鋅鹽’醯胺酸爲例如可舉出具有下述構造式之化合物。 R 3200808717 IX. Description of the Invention [Technical Field of the Invention] The present invention relates to a skin whitening agent, and a cosmetic composition containing the same. [Prior Art] About the skin whitening agent, androgen, ellagic acid, citric acid, vitamin C derivatives and various vanilla extracts are known, but currently, ingredients which are mild to the skin and easy to mix with cosmetics are sought. . On the other hand, for zinc, zinc oxide has been reported to inhibit diaper red rash (e.g., FEBS Letters, No. 384, pp. 92-96, 1996). However, the compound is hardly soluble in water or oily ingredients and is difficult to use as a cosmetic and skin external preparation. Further, the zinc glycinate which is an organic zinc salt is known to have an induction promoting action of metallothionein (JP-A-2005-2 47 729). It has an inhibitory effect on skin damage caused by UV, such as melanin synthesis disorder and cytotoxicity disorder, through a route such as an antioxidant effect and a radical scavenging activity. Similarly, it is known that zinc salt of pyrrolidone carboxylic acid and zinc amide of an organic zinc can suppress inflammatory factors such as AP-1 and NF·/cB which are caused by UV rays (JP-A-2006-022090, International publication WO2005/123062 manual). In addition, it is known that the organic zinc salt and the inorganic zinc salt can be used in combination with a cosmetic composition for astringent action, anti-inflammatory action, white pigment, ultraviolet light preventive agent, deodorant/bactericide, but it is expected to be used close to When the concentration region of the effect is irritating to the skin, it is difficult to use as a -4- 200808717 cosmetic. However, at low concentrations, the skin is not as effective as described above, and the combination of the zinc compound and the cosmetic material is not progressing. SUMMARY OF THE INVENTION In order to achieve the above object, the inventors of the present invention have found that by introducing zinc into human pigment cells (melanocyte-producing cells (melanocytes)), it is found that the effect of promoting ascorbate transporter is promoted. With its whitening effect. The ascorbic acid transport system promotes the introduction of membrane proteins of ascorbic acid into cells (see Hiroyasu Tsukaguchi etc (1 9 9 9 ) Nature 399, 70-75). By the enhanced expression of the ascorbate transporter, in human pigment cells (melanin-producing cells (melanocytes)), the introduction of ascorbic acid into the cells is promoted, and melanin production is inhibited. The object of the present invention is to obtain a whitening agent having an excellent whitening effect, and a cosmetic composition containing the same based on the above knowledge. That is, the present invention relates to a whitening composition containing zinc as an active ingredient. From the viewpoints of skin irritation and introduction efficiency in cells, it is necessary to introduce a zinc method which is practically carried out, and it is necessary to apply zinc to the skin at a constant concentration in the form of a zinc salt. Specifically, the following invention is included. (1) A whitening agent which contains zinc as an active ingredient. (2) The whitening agent of item (1) wherein the zinc is selected from the group consisting of zinc pyrrolidone carboxylate, zinc gluconate, zinc phenolsulfonate, zinc lactate, various zinc aminates, zinc phthalate , zinc sulfate, zinc chloride and zinc oxide are formed into compounds of the group -5 - 200808717. (3) A whitening agent according to (1), wherein the zinc-based pyrrolidone carboxylic acid zinc salt. (4) The whitening agent according to any one of the above (1) to (3), wherein the whitening system is achieved by enhancing the expression of an ascorbic acid transporter of human pigment cells (melanogenic cells (melanocytes)). (5) A composition for whitening, which is formulated with zinc as an active ingredient, (6) a whitening composition according to item (5), wherein the zinc is selected from the group consisting of zinc pyrrolidone carboxylate, zinc gluconate, and phenol. A compound of a group of zinc sulfonate, zinc lactate, various zinc amide salts, zinc phthalate salts, zinc sulfate, zinc chloride and zinc oxide. (7) A whitening composition according to (5), wherein the zinc-based pyrrolidone carboxylic acid zinc salt. (8) A whitening composition according to any one of the above items (5) to (7), wherein the composition is present in the composition at a concentration of from 1 // Μ to 100 mM in combination with zinc. (9) A whitening composition according to any one of the items (5) to (8) above, which further comprises ascorbic acid. (10) A whitening composition according to any one of items (5) to (9), which is a zinc having a concentration of 1 // Μ to 100 mM, and ascorbic acid having a concentration of 5 mM to 600 mM. (11) A whitening composition according to any one of the above items (5) to (10), which further comprises an N-mercapto acid amino acid ester, an amino acid or an amine-6 - 200808717 acid derivative . (12) A whitening composition according to any one of the above items (5) to (1 1), which is an ointment, lotion, lotion, cream, lotion, beauty lotion, mask, foundation cream or liquid hand washing milk. (13) - The use of zinc for whitening skin. (1 4 ) A zinc pyrrolidone carboxylate, zinc gluconate, zinc phenolsulfonate, zinc lactate, various zinc amide salts, zinc phthalate, zinc sulfate, chlorinated for whitening skin The use of zinc salts in groups of zinc and zinc oxide. (1 5 ) - The use of zinc pyrrolidone carboxylate for whitening skin. (16) A whitening method characterized in that the composition of the above items (5) to (11) is applied to the skin. Hereinafter, the present invention will be described in detail. In the present invention, whitening refers to a so-called "whitening effect" which is beautifully whitened, and a whitening agent refers to a therapeutic object, and any one of those having a preventive purpose is included therein. In the zinc used in the present invention, it is necessary to apply zinc to the skin at a certain concentration in the form of a zinc salt from the viewpoints of skin irritation and efficiency in introduction into cells. Any of an organic zinc salt and an inorganic zinc salt can be used at this time. The organic zinc salt comprises a zinc pyrrolidone carboxylic acid salt, a zinc gluconate salt, a zinc benzoate sulfonate, a zinc lactate salt, various zinc amide salts, a zinc phthalate salt, etc. The inorganic zinc comprises zinc sulfate, zinc chloride and Zinc oxide, etc. The zinc amide salt may, for example, be a zinc glycinate, a zinc alaninate, a zinc phthalate, a zinc methinate, a zinc isoleate, a zinc amphetamine or a methyl zinc 200808717. , zinc tryptinate, zinc aspartate, zinc glutamate, zinc salt of serine, zinc salt of zinc amide, zinc cysteate, zinc tyrosinate, aspartame Various zinc amide salts such as zinc acid salt, zinc glutamate, zinc lysate, zinc nitrite or zinc histate. The zinc phthalate salt is a zinc salt of a compound in which an amine group of an amino acid and a thiol group are bonded. The valine acid is, for example, a compound having the following structural formula. R 3
COOHCOOH
R 1 -N-CH (CH2)R 1 -N-CH (CH2)
I R 2 式1 (上述一般式（I )中，R1係碳原子數2〜22之醯基， R2係氫原子或碳原子數1〜6之直鏈或具支鏈之烷基，R3 係表示爲胺基酸之纈胺酸、白胺酸、異白胺酸、苯丙胺酸 、甲基胺酸、色胺酸、天冬醯胺酸、麩醯胺酸、絲胺酸、 酥胺酸、半胱胺酸、酪胺酸、天冬胺酸、麩胺酸、離胺酸 、精胺酸、組胺酸、丙胺酸之側鏈或氫原子，η係表示0 或1之整數。） 於提高美白效果此一觀點，具有促進血流效果之吡咯 烷酮羧酸之鋅鹽，係因期望血管內之抗壞血酸等有用物質 集中於塗佈之部位，而藉由抗壞血酸轉運體之促進表現效 果，而可反映出顯著的美白效果之一種鋅鹽。 吡咯烷酮羧酸鋅鹽，係2-吡咯烷酮-5-羧酸之鋅鹽， 亦可爲各種的水和物。以下，簡稱爲「PCA鋅鹽」、「 PCAZn鹽」。並且，於實施例中所使用之吡咯烷酮羧酸鋅 -8 - 200808717 鹽係2水和物，具有下述之構造。IR 2 Formula 1 (In the above general formula (I), R1 is a fluorenyl group having 2 to 22 carbon atoms, and R2 is a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms, and R3 represents Amino acid, leucine, leucine, isoleucine, phenylalanine, methylamine, tryptophan, aspartic acid, glutamic acid, serine, leucine, half a side chain or a hydrogen atom of cystine, tyrosine, aspartic acid, glutamic acid, lysine, arginine, histidine, or alanine, and η means an integer of 0 or 1. The whitening effect has a zinc salt of pyrrolidone carboxylic acid which promotes blood flow effect, and it is expected that the useful substance such as ascorbic acid in the blood vessel concentrates on the applied portion, and the effect of promoting the expression by the ascorbate transporter can be reflected. A zinc salt that has a remarkable whitening effect. The zinc pyrrolidone carboxylic acid salt is a zinc salt of 2-pyrrolidone-5-carboxylic acid, and may be various waters and substances. Hereinafter, it is simply referred to as "PCA zinc salt" and "PCAZn salt". Further, the pyrrolidone carboxylate -8 - 200808717 salt system 2 water and the compound used in the examples have the following structures.
•2H20 式2 吡咯烷酮羧酸鋅鹽使用D體、L體或DL體（D體與 L體之混合物）之任一種均可。例如可使用L-PCA鋅鹽及 DL-PCA鋅鹽。可單獨或將其混合後使用，使用DL體時 ，並未特別限定D體與L體之比例。 本發明之美白劑，可搭配化妝料及皮膚外用劑等之組 合物而加以使用。此時，其搭配量以搭配1 // Μ〜1 0 OmM (PCA鋅鹽爲0.000035重量％〜3.5重量％)爲佳，1//M 〜50mM(PCA鋅鹽爲 0.000035重量％〜0.35重量％)更 佳，1//M 〜10mM(PCA 鋅鹽爲 0.000035 重量％ 〜0.035 重量％ )最佳。更多鋅鹽時，搭配3 . 5重量％以上時會對 皮膚產生刺激感，或發生有粗澀感等問題，另外，根據使 用培養皮膚細胞之檢討，使用高濃度並無法獲得目標的效 果而不佳。 搭配鋅與化妝料及皮膚外用劑時，除這些成份外，亦 可於不阻礙本發明效果之範圍內，添加一般做爲化妝料或 皮膚外用劑所使用之成份。 本發明更進一步之型態，係有關同時搭配鋅與1種或 2種以上選自抗壞血酸、N -醯基酸性胺基酸酯、胺基酸 -9 - 200808717 或胺基酸衍生物所成群之物質而構成之組成物。 其中，自美白效果之觀點，抗壞血酸以5〜600mM程 度爲佳，5〜3 00mM程度更佳地同時與鋅搭配爲佳。此時 ，抗壞血酸若爲可與化妝料搭配之形態，可使用各種類的 衍生物。亦即可使用除抗壞血酸之游離體及各種鹽類（抗 壞血酸鈉、抗壞血酸-2 -磷酸鈉、抗壞血酸-2 -磷酸鎂、抗 壞血酸-2-硫酸鈉等）之外，還可使用各種配糖體（抗壞 血酸-2-葡萄糖苷等）及抗壞血酸酯（6-維生素C硬脂酸 酯、6 -維生素C棕櫚酸酯、2,6 -維生素C二棕櫚酸酯、 2，3,5，6-四己基癸酸葡萄糖苷、生育酚抗壞血酸等）等之 各種衍生物。 本發明中所使用之N -醯基酸性胺基酸酯係以下述構 造所表不者。 Ο 〇 II Π• 2H20 Formula 2 The pyrrolidone carboxylic acid zinc salt may be any of D, L or DL (a mixture of D and L). For example, L-PCA zinc salt and DL-PCA zinc salt can be used. It can be used singly or in combination, and when the DL body is used, the ratio of the D body to the L body is not particularly limited. The whitening agent of the present invention can be used in combination with a composition such as a cosmetic or an external preparation for skin. At this time, the amount is preferably 1 / Μ ~ 1 0 OmM (PCA zinc salt is 0.000035% by weight to 3.5% by weight), 1 / / M ~ 50mM (PCA zinc salt is 0.000035% by weight ~ 0.35 wt% More preferably, 1/M to 10 mM (PCA zinc salt is 0.000035 wt% to 0.035 wt%) is optimal. When more zinc salt is used, it may cause irritation to the skin when it is combined with 3.5% by weight or more, or may cause problems such as rough feeling. In addition, according to the review using cultured skin cells, the use of high concentration does not achieve the target effect. Not good. In addition to these ingredients, in addition to these ingredients, in addition to these ingredients, it is also possible to add a component which is generally used as a cosmetic or external preparation for skin, without impairing the effects of the present invention. A further aspect of the present invention relates to a group of zinc and one or more selected from the group consisting of ascorbic acid, N-mercapto acid amino acid ester, amino acid-9 - 200808717 or amino acid derivative. a composition of matter. Among them, from the viewpoint of whitening effect, ascorbic acid is preferably in the range of 5 to 600 mM, and preferably 5 to 300 mM is preferably combined with zinc at the same time. In this case, if ascorbic acid is in a form compatible with the cosmetic, various types of derivatives can be used. It is also possible to use a free form of ascorbic acid and various salts (sodium ascorbate, sodium ascorbate-2-phosphate, ascorbyl-2-phosphate, sodium ascorbyl-2-sulfate, etc.), and various glycosides can also be used ( Ascorbate-2-glucoside, etc. and ascorbate (6-vitamin C stearate, 6-vitamin C palmitate, 2,6-vitamin C dipalmitate, 2,3,5,6-tetrahexyl Various derivatives such as gluconic acid citrate, tocopherol ascorbic acid, and the like. The N-mercapto acid amino acid ester used in the present invention is represented by the following constitution. Ο 〇 II Π
X-(OCH2CH2)a- 〇C-(CH2)n-CH-CO-(CH2CH2〇)b-YX-(OCH2CH2)a- 〇C-(CH2)n-CH-CO-(CH2CH2〇)b-Y
NHCOR 式3 (式中，X及Y二者爲相同或相異者均可，X及Y係 至少一種選自固醇之酯生成殘基，碳原子數8〜30之直鏈 或具支鏈之液狀高級烷基醇或烯基醇，或碳原子數1 2〜 38之固狀直鏈或具支鏈之高級醇之酯生成殘基。且與氮 原子結合之COR係碳原子數8〜22之直鏈醯基。η爲1 或2°a、b爲0〜10，b爲0〜10。） 以N-醯基酸性二酯爲佳，其適合之具體例可舉出例 -10- 200808717 如N -月桂基麩胺酸二（膽固醇基脂肪酸基辛基十二烷醇 )、N-月桂基麩胺酸二（膽固醇基辛基十二烷醇）、N 一月桂基麩胺酸二（植物固醇2-辛基十二烷醇）、N—月 桂基麩胺酸二（辛基十二烷醇植物固醇脂肪酸基）等，而 這些物質，係分別爲自味之素股份有限公司以商品名「 Eldew CL-301」、「 Eldew CL-202」、「 Eldew PS-203」、 「EldewPS-3 04」於市面上所販售者。 於本發明中之該N _醯基酸性胺基酸酯，係可倚賴其 提升保濕力及整肌性，另外，亦可藉其來增加安定性，但 爲使其效果可適切地表現，其搭配量以〇.〇1重量％以上爲 佳，0.1重量％以上更佳，0.5重量％以上進而爲佳，而使 用超過必須的N -醯基酸性胺基酸酯之搭配量時，因有可 能造成黏腻感，故而以20重量％以下爲佳，10重量％以 下更佳，5重量％以下最佳。 胺基酸或胺基酸衍生物，因倚賴其提升保濕效果而搭 配於組成物中，該胺基酸可舉出例如丙胺酸、精胺酸、天 冬醯胺酸、天冬胺酸、瓜胺酸、半胱胺酸、胱胺酸、麩醯 胺酸、麩胺酸、甘胺酸、組胺酸、羥脯胺酸、異白胺酸、 白胺酸、離胺酸、甲基胺酸、鳥胺酸、苯丙胺酸、脯胺酸 、絲胺酸、酥胺酸、色胺酸、酪胺酸、纈胺酸等，可使用 這些胺基酸之L體、D體或DL體之任一種，或是這些胺 基酸之鹽類亦可。鹽類可舉出例如鈉鹽、鉀鹽、三乙醇胺 鹽等。 胺基酸衍生物可爲將前述之胺基酸進行環化、醯化或 -11 - 200808717 酯化後者 半胱胺酸 酸鹽、醯 基酯鹽等 於這 ，添加一 做爲化妝 抗發炎劑 合劑、油 物質、色 等。 前述 、膏狀、 本發明之 、洗髮精 、面膜、 、古龍水 使用於皮 用劑、養 光_麻瘆 劑、光免 等而引起 蟲劑、驅 防止改善 ，例如可舉出乙醯麩胺酸、乙醯甲基胺酸、乙醯 、N，N-二乙醯基-L-胱胺酸二甲基酯、醯基麩胺 基甘胺酸鹽、醯基丙胺酸鹽、醯基天冬醯胺酸乙 。但未包含N -醯基酸性胺基酸酯。 些成份之外，亦可於不阻礙本發明效果之範圍內 般做爲化妝料或皮膚外用劑所使用之成份。一般 料或皮膚外用劑所使用之成份可舉出抗氧化劑、 、紫外線吸收劑、細胞復活劑、保濕劑、金屬螯 性原料、界面活性劑、溶劑、高分子物質、粉體 素類劑、香料、促進經皮吸收劑及膽固醇荷爾蒙 之含鋅組成物之形態並無特別限制，可爲溶液狀 凝膠狀、固體狀、粉末狀等任意的形態。另外， 組成物亦可使用於油、塗劑、乳霜、乳液、凝膠 、潤絲精、護髮乳、指甲油、粉底、脣膏、蜜粉 軟膏、錠劑、注射液、顆粒、膠囊、香水、粉末 、牙膏、肥官、氣霧劑、洗顏泡沬等之外，亦可 膚老化防止改善劑、皮膚發炎防止改善劑、沐浴 髮劑、皮膚美容液、防曬劑、色素性乾皮症•日 等光線過敏症之防止改善劑、光過敏之防止改善 疫抑制之防止改善劑’或外傷、皮膚龜裂、裂傷 之皮膚粗糙之防止改善劑、消毒劑、抗菌劑、殺 除害蟲劑、角質溶解劑、表皮剝離劑、青春痘之 劑、角化症•乾皮症·魚鱗癬•乾癬等各種皮膚 -12- 200808717 疾病之防止改善劑。 進而於組成物中，將其他的常用成份以不阻礙本發明 效果之範圍內，添加於含鋅之組成物中。於組成物中其他 的常用成份係可舉出防腐劑、防褪色劑、緩衝劑、青春痘 用藥劑、防止皮屑·搔癢劑、制汗防臭劑、燙傷用藥劑、 防蹣•虱劑、角質軟化劑、乾皮症用藥劑、抗病毒劑、荷 爾蒙類、維他命類、胺基酸·胜肽類、蛋白質類、收斂劑 、清涼•刺激劑、來自動植物成份、抗生物質、抗真菌劑 、育毛劑等。 【實施方式】 實施例 以下，藉由實施例（合成例、試驗例及搭配例）將本 發明更具體地說明，但本發明並未限定於這些實施例，且 於這些實施例中，搭配量以重量％來表示。 實施例1 合成例 吡咯烷酮羧酸鋅鹽之合成 DL-PCA鋅鹽係根據特開平3-168240號公報記載之方 法，係藉由使DL-PCA與氧化鋅於l〇〇°C水中反應2小時 後，再於室溫下持續攪拌5小時，將所析出之結晶過濾後 而合成。L-PCA鋅鹽係以下述之方法進行合成。於滅菌器 中，將L-麩胺酸鈉1水和物（6i.ig)之水溶液於180°C 下進行加熱2小時，而得50wt%之吡咯烷酮羧酸鈉鹽溶液 。再於lOO.Og之50wt%之吡咯烷酮羧酸鈉鹽溶液（0.33 -13- 200808717 mol，pH7.7，光學純度爲84%，L/D比例=92/8 )中添加 2.7g之硝酸（純度60wt%)，調整pH至5.2。再將47.6g 之硫酸鋅7水和物（0.17mol)溶解於34.2g水中後之水 溶液，添加至吡咯烷酮羧酸鈉鹽溶液（pH4.1 )。將該溶 液於室溫下（PH3.7)進行混合30分鐘至獲得結晶爲止， 並進行過濾。將所得之結晶以水（2 1 .9g )洗淨，而得 32.0 g ( 0.09mol，回收率爲55% )之吡咯烷酮羧酸鋅二水 和物。其光學純度爲99.8% ( L/D比例= 99.9/0.1 )。 試驗例1 吡咯烷酮羧酸鋅鹽之抗壞血酸轉運體mRNA 的表現增強效果 將正常人類色素細胞置於培養皿中，植於正常人類色 素細胞增殖用培養液（KURABO製）上。並培養於 5%C02，飽和水蒸氣之37°C下之培養箱中1天。試樣係 自正常人類色素細胞增殖用培養液中，去除所添加之增殖 因子後而調製者。以將試樣（PCΑΖη鹽等）調製爲10 // Μ之濃度之培養液取代培養皿中之培養液後，再於培養箱 中進行培養24小時。完成培養後，吸除培養液，以PBS 進行洗滌。細胞之處理係依循RNeasy Mini Kit ( Quiagen 製）之步驟流程，進行萃取細胞內之RNA。再自所得之 RNA，依循常用方法成c-Dna，再以已知文獻（Christopher Ρ· Corpe etc ( 2005 ) J. Biol. Chem. 280，52 1 1 -5220 )之方 法，對抗壞血酸轉運體SVCT進行RT-PCR (引子：正股 弓[子；5’-CTGAGCTCATGGCGATCTAC-3’（序歹[J編號 3 )，反 -14- 200808717 股弓丨子；5，-CATGTCAGGTAGTGCTGTAGCCCCA-3’（序歹！]編號 4 ) )。將所得之DNA進行電泳，根據試樣之有無評價SVCT 之RNA表現量。電泳亮帶之評價係使用lumino1 · image analyzer ( LAS-3 000/富士底片製）’以G3PDH規格化後 之數値。 如圖1所示，藉由添加1 〇 // Μ之吡咯烷酮羧酸鋅鹽 ，與未添加之控制組相比’確認由於添加1 0 V Μ而使 SVCT增力□ 140%之RNA表現量。因此，於NHEM細胞中 抗壞血酸轉運體增加，細胞內之抗壞血酸濃度增加，伴隨 著於ΝΗΕΜ細胞之黑色素體之氧化反應被抑制，而引起 抑制黑色素產生效果。 試驗例2 PC ΑΖη鹽之促進血流效果 PCAZn鹽與其他Zn鹽之差異係已自促進血流效果（ 血液量增加）而確認。調製各試樣之Zn鹽，塗佈於人類 手腕以目視評價促進血流效果。試樣係使用①PCAZn鹽 ，②PCANa鹽，③葡萄糖酸Zll鹽，④葡萄糖酸Na鹽， ⑤硫酸Zn鹽，⑥硫酸Na2鹽。調製濃度爲5 wt%，pH爲 5.5〜6.5之間。將8 0 // 1的上述試樣於手腕以半封閉方式 貼上貼片’ 3 0分鐘後除去貼片，以目視進行評價。再於 經過3 0分鐘後、5 0分鐘後進行目視觀察。依循表21給 予評點。結果示於表2 2。結果係所得評點之平均値。 -15- 200808717 表2 1 評點 0 無變化 1 於塗佈部位之一部分有微弱的血流促進 2 於塗佈部位之一部分有弱的血流促進 3 於塗佈部位有弱的血流促進 4 於塗佈部位有血流促進 表22 試樣 除去貼片 後◦分鐘 除去貼片 後30分鐘 除去貼片 後50分鐘 5 wt% PCAZn 鹽 2.5 2 1 5 wt% PCANa 鹽 2.5 2.5 1 5 wt%葡萄糖酸Zn鹽 0 0 0 5 wt%葡萄糖酸Na鹽 0 0 0 5 wt%硫酸Zn鹽 0 0 0 5wt%硫酸Na2鹽 0 0 0 確認試樣①以及②具臨時性之促進血流效果。但其他 試樣中，於各種評價時間帶均未發現促進血流效果。由此 結果可明確得知PCΑΖη鹽與其他Zn鹽相比，藉由塗佈於 皮膚上而具有誘導暫時性的促進血流效果。 因此，由於可將血管內抗壞血酸等有用物質集中於塗 佈部位，PC ΑΖη鹽與其他Zn鹽相比，被期待可更提高美 白效果。 以下，各種製劑之搭配例示於下述之1〜1 6。這些製 劑可依循常用方法進行調製。且，搭配量以重量％來表示 200808717 搭配例1 軟膏 L-PCA鋅鹽 0.001% 氯化.苯二甲烴銨 0.1% 尿素 2 0.0% 白色凡士林 15.0% 輕質流動石蠟 6.0% 鯨蠟醇 3.0% 硬脂醇 3.0% 硬脂酸甘油酯 5.0% 香料 適量 防腐劑 適量 緩衝劑 1.0% 純水 殘餘量 搭配例2 軟膏 葡萄糖酸鋅鹽 0.002% 氯化苯二甲烴銨 0.1% 尿素 2 0.0% 白色凡士林 15.0% 輕質流動石蠟 6.0% 鯨蠟醇 3.0% 硬脂醇 3.0% 硬脂酸甘油酯 5.0% -17- 200808717 香料 適量 防腐劑 適量 緩衝劑 1.0% 純水 殘餘量 搭配例3 化妝水 L-PCA鋅鹽 0.03% 甘醇酸 5.0% 甘油 3.0% 山梨糖醇 2.0% 聚氧乙烯（20)油基醚 1.0% 乙醇 15.0% 對苯酚磺酸鋅 0.2% 緩衝劑 0.1% 香料 0.2% 防腐劑 適量 純水 殘餘量 搭配例4 化妝水 D L - P C A鋅鹽 0.005% 檸檬酸 1.0% 尿素 4.0% 水楊酸 2.0% 乳酸 2.0% -18- 200808717 甘油 2.0% 甜菜鹼 2.0% 玻尿酸 0.1% 乙醇 15.0% 緩衝劑 0.1% 香料 0.2% 防腐劑 適量 純水 殘餘量 搭配例5 化妝水 DL-PCA鋅鹽 0.005% 抗壞血酸 1.0% 尿素 4.0% 乳酸 2.0% 甘油 2.0% 甜菜鹼 2.0% 玻尿酸 0.1% 乙醇 15.0% 緩衝劑 0.1% 香料 0.2% 防腐劑 適量 純水 殘餘量 搭配例6 化妝水 -19- 200808717 甘胺酸鋅鹽 0.005% 檸檬酸 1.0% 尿素 4.0% 水楊酸 2.0% 乳酸 2.0% 甘油 2.0% 甜菜鹼 2.0% 玻尿酸 0.1% 乙醇 15.0% 緩衝劑 0.1% 香料 0.2% 防腐劑 適量 純水 殘餘量 搭配例7 塗劑 L-PCA鋅鹽 0.01% 乳酸 0.1% 果酸 0.1% 甘油 4.0% 高嶺土 1.0% 菱鋅礦 0.7% 樟腦 0.2% 乙醇 14.0% 香料 適量 -20- 200808717 純水 殘餘量 搭配例8 塗劑 L-PCA鋅鹽 0.01% 抗壞血酸 0.1% 果酸 0.1% 甘油 4.0% 高嶺土 1.0% 菱鋅礦 0.7% 樟腦 0.2% 乙醇 14.0% 香料 適量 純水 殘餘量 搭配例9 塗劑 氯化鋅鹽 0.005% 乳酸 0.1% 果酸 0.1% 甘油 4.0% 高嶺土 1.0% 菱鋅礦 0.7% 樟腦 0.2% 乙醇 14.0% 香料 適量 -21 - 200808717 純水 殘餘量 搭配例10 乳霜 L-PCA鋅鹽 0.01% 間-苯二酚 0.1% 麴酸 1.0% 硬脂酸 2.0% 聚氧乙烯（25)十六烷基醚 3.0% 硬脂酸甘油酯 2.0% 辛基十二烷醇 10.0% 鯨蠟醇 6.0% 還原羊毛脂 4.0% 蛟鯊烯 9.0% 1，3-丁二醇 6.0% 聚乙二醇（1 5 0 0 ) 4.0% 防腐劑 適量 香料 適量 純水 殘餘量 搭配例η 乳霜 葡萄糖酸鋅鹽 0.02% 間-苯二酚 0.1% 麴酸 1.0% 硬脂酸 2.0% -22- 200808717 聚氧乙烯（25 )十六烷基醚 3.0% 硬脂酸甘油酯 2.0% 辛基十二烷醇 10.0% 鯨蠟醇 6.0% 還原羊毛脂 4.0% 蛟鯊烯 9.0% 1，3 -丁 —^醇 6.0% 聚乙二醇（1 500 ) 4.0% 防腐劑 適量 香料 適量 純水 殘餘量 搭配例12 乳霜 葡萄糖酸鋅鹽 0.02% 間-苯二酣 0.1% 抗壞血酸 5.0% 硬脂酸 2.0% 聚氧乙烯（25 )十六烷基醚 3.0% 硬脂酸甘油酯 2.0% 辛基十二烷醇 10.0% 鯨蠟醇 6.0% 還原羊毛脂 4.0% 蛟鯊烯 9.0% 1，3 - 丁二醇 6.0% -23- 200808717 聚乙二醇（1 500 ) 4.0% 防腐劑 適量 香料 適量 純水 殘餘量 搭配例13 乳霜 DL-PCA 鋅鹽 0.01% 甘醇酸 2.0% 固形石蠟 5.0% 蜜蠟 10.0% 凡士林 15.0% 流動石蠟 41.0% 1，3 - 丁二醇 4.0% 硬脂酸甘油酯 2.0% 聚氧乙烯山梨醇酐單月桂酸酯（2 0 ) 2.0% 硼砂 0.2% 防腐劑 適量 香料 適量 氧化防止劑 適量 純水 殘餘量 搭配例14 乳液 L-PCA 鋅鹽 0.02% 乳酸 2.0% -24- 200808717 硬 脂 醇 0.5% 硬 化 掠 櫚 油 3.0% 流 動 石 蠟 3 5.0% 二 丙 二 醇 6.0% 聚 乙 二 醇 ( 400 ) 4.0% 倍 半 油 酸 山 梨醇酯 1.6% 聚 氧 乙 烯 ( 20 )油基醚 2.4% 羧 基 乙 烯 基 聚合物 1.5% 氫 氧 化 鉀 0.1% 螯 合 劑 適量 防 腐 劑 適量 香 料 適量 純 水 殘餘量 搭配例 15 乳液 硫 酸 鋅 鹽 0.01% 乳 酸 2.0% 硬 脂 醇 0.5% 硬 化 掠 櫚 油 3.0% 流 動 石 蠟 3 5.0% 二 丙 二 醇 6.0% 聚 乙 二 醇 ( 400 ) 4.0% 倍 半 油 酸 山 梨醇酯 1.6% 聚 氧 乙 烯 ( 20 )油基醚 2.4% -25- 200808717 羧基乙烯基聚合物 1.5% 氫氧化鉀 0.1% 螯合劑 適量 防腐劑 適量 香料 適量 純水 殘餘量 搭配例16 美容液 L-PCA鋅鹽 0.05% 果酸 0.5% 二丙二醇 5.0% 聚乙二醇（400 ) 5.0% 乙醇 10.0% 羧基乙烯基聚合物 0.5% 海藻酸鈉 0.5% 氫氧化鉀 0.2% 聚氧乙烯山梨醇酐單硬脂酸酯（20 ) 1.0% 單油酸山梨醇 0.5% 油基醇 0.5% 胎盤萃取 0.2% 醋酸d 1 - α -生育酚 0.2% 香料 適量 防腐劑 適量 褪色防止劑 適量 -26- 200808717 純水 殘餘量 搭配例1 7 美容液 L-PCA鋅鹽 0.05% 抗壞血酸 2.0% 二丙二醇 5.0% 聚乙二醇（400 ) 5.0% 乙醇 10.0% 羧基乙烯基聚合物 0.5% 海藻酸鈉 0.5% 氫氧化鉀 0.2% 聚氧乙烯山梨醇酐單硬脂酸酯（20 ) 1.0% 單油酸山梨醇 0.5% 油基醇 0.5% 胎盤萃取 0.2% 醋酸dl- α -生育酚 0.2% 香料 適量 防腐劑 適量 褪色防止劑 適量 純水 殘餘量 搭配例1 8 美容液 乳酸鋅鹽 0.005% 果酸 0.5% -27- 200808717 二丙二醇 5.0% 聚乙二醇（4 0 0 ) 5.0% 乙醇 10.0% 羧基乙烯基聚合物 0.5% 海藻酸鈉 0.5% 氫氧化鉀 0.2% 聚氧乙烯山梨醇酐單硬脂酸酯（20 ) 1.0% 單油酸山梨醇 0.5% 油基醇 0.5% 胎盤萃取 0.2% 醋酸d 1 - α -生育酚 0.2% 香料 適量 防腐劑 適量 褪色防止劑 適量 純水 殘餘量 搭配例19 面膜 D L - P C Α 鋅鹽 0.03% 異丙醇 2.0% 聚乙烯醇 15.0% 羧基甲基纖維素 5.0% 1，3 - 丁二醇 5.0% 乙醇 12.0% 聚氧乙烯（20 )油基醚 0.5% -28- 200808717 香料 適量 防腐劑 適量 緩衝劑 適量 純水 殘餘量 搭配例20 面膜 葡萄糖酸鋅鹽 0.03% 異丙醇 2.0% 聚乙烯醇 15.0% 羧基甲基纖維素 5.0% 1，3-丁二醇 5.0% 乙醇 12.0% 聚氧乙烯（20 )油基醚 0.5% 香料 適量 防腐劑 適量 緩衝劑 適量 純水 殘餘量 搭配例2 1 粉底 DL-PCA鋅鹽 0.1% 水楊酸 0.5% 流動石蠟 10.0% 聚氧乙烯山梨醇酐單油酸酯（20 ) 3.5% 丙二醇 3.0% -29- 200808717 氧化鈦 9.0% 高嶺土 2 4.0% 滑石 4 2.0% 著色顏料 3.0% 香料 適量 防腐劑 適量 氧化防止劑 適量 搭配例22 液體洗手乳 L-PCA鋅鹽 0.1% 十六烷基硫酸鈉 3 0.0% 甜菜鹼 3.0% 脂肪酸甘油酯 1.0% 苯氧基乙醇 1.0% EDTA 0.1% 純水 殘餘量 本發明係可利用於化妝品領域。 【圖式簡單說明】 圖1係確認因吡咯烷酮羧酸鋅鹽，所引起之於黑色素 細胞中，抗壞血酸轉運體mRNA的表現增強效果之圖。 -30 -NHCOR Formula 3 (wherein, X and Y are the same or different, X and Y are at least one ester residue selected from sterols, and linear or branched with 8 to 30 carbon atoms a liquid-like higher alkyl alcohol or alkenyl alcohol, or an ester of a solid linear or branched higher alcohol having a carbon number of 12 to 38, and a COR-based carbon atom bonded to a nitrogen atom a linear thiol group of ～22. η is 1 or 2°a, b is 0-10, b is 0-10.) An N-fluorenyl acid diester is preferred, and specific examples thereof are exemplified - 10- 200808717 Such as N-lauryl glutamic acid bis(cholesteryl fatty acid octyldodecanol), N-lauryl glutamic acid bis(cholesteryloctyldodecanol), N-lauryl glutamine Acid bis (phytosterol 2-octyldodecanol), N-lauryl glutamic acid bis(octyldodecanol phytosterol fatty acid group), etc., and these substances are respectively The company is sold on the market under the trade names "Eldew CL-301", "Eldew CL-202", "Eldew PS-203", and "EldewPS-3 04". The N-mercapto acid amino acid ester in the present invention can rely on it to enhance moisturizing power and whole muscle properties, and can also be used to increase stability, but in order to make its effect properly manifest, The amount of the collocation is preferably 重量. 〇 1% by weight or more, more preferably 0.1% by weight or more, more preferably 0.5% by weight or more, and when using a combination of more than necessary N-fluorenyl acid urethane, it is possible Since it is sticky, it is preferably 20% by weight or less, more preferably 10% by weight or less, and most preferably 5% by weight or less. The amino acid or amino acid derivative is blended in the composition by relying on it to enhance the moisturizing effect, and examples of the amino acid include alanine, arginine, aspartic acid, aspartic acid, and melon. Aminic acid, cysteine, cysteine, glutamic acid, glutamic acid, glycine, histidine, hydroxyproline, isoleucine, leucine, lysine, methylamine Acid, ornithine, phenylalanine, valine, serine, leucine, tryptophan, tyrosine, valine, etc., L, D or DL of these amino acids can be used. Any of them, or a salt of these amino acids, may also be used. The salt may, for example, be a sodium salt, a potassium salt or a triethanolamine salt. The amino acid derivative may be obtained by cyclizing, deuterating or -11 - 200808717 esterification of the aforementioned amino acid. The latter cysteine, decyl ester salt is equal to this, and adding one as a cosmetic anti-inflammatory agent mixture , oil substances, colors, etc. The above-mentioned paste, the present invention, the shampoo, the mask, the cologne are used for the skin agent, the lightening agent, the sputum agent, the light-free agent, etc., and the insecticide is prevented from being improved, for example, the bran bran is mentioned. Amine acid, acetamidine methylamine, acetamidine, N,N-diethylindenyl-L-cystine dimethyl ester, decyl glutamine-glycinate, mercapto propylamine, sulfhydryl Aspartate B. However, N-decyl acid amino acid ester was not included. In addition to these ingredients, it may be used as a cosmetic or an external preparation for skin, without departing from the effects of the present invention. The ingredients used in general materials or external preparations for skin include antioxidants, ultraviolet absorbers, cell revitalizers, humectants, metal chelating materials, surfactants, solvents, high molecular substances, powders, and perfumes. The form of the zinc-containing composition for promoting the percutaneous absorption agent and the cholesterol hormone is not particularly limited, and may be any form such as a solution gel, a solid or a powder. In addition, the composition can also be used in oils, paints, creams, lotions, gels, conditioners, hair lotions, nail varnishes, foundations, lipsticks, honey ointments, lozenges, injections, granules, capsules, Perfume, powder, toothpaste, fat official, aerosol, facial cleansing, etc., can also be used for skin aging prevention improver, skin inflammation prevention improver, bath hair lotion, skin beauty lotion, sunscreen, pigmented dry skin Diseases, daily light and other allergy prevention agents, photoallergic prevention, anti-inhibition prevention agents, or skin damage prevention agents, disinfectants, antibacterial agents, insecticides for trauma, skin cracking, and laceration , keratinolytic agent, epidermal stripping agent, acne agent, keratosis, dry skin disease, ichthyosis, dryness, etc. -12- 200808717 Disease prevention and improvement agent. Further, in the composition, other usual components are added to the zinc-containing composition within a range not inhibiting the effects of the present invention. Other commonly used ingredients in the composition include preservatives, anti-fading agents, buffers, acne medications, anti-dandruff and itch inhibitors, sweating and deodorizing agents, scalding agents, anti-mite agents, tinctures, and keratin. Softeners, dry skin medications, antiviral agents, hormones, vitamins, amino acids, peptides, proteins, astringents, cooling and irritants, automatic plant ingredients, antibiotics, antifungals, hair growth Agents, etc. EXAMPLES Hereinafter, the present invention will be specifically described by way of examples (synthesis examples, test examples, and collocation examples), but the present invention is not limited to these examples, and in these examples, the amount of collocation Expressed in % by weight. Example 1 Synthesis of a pyrrolidone carboxylic acid zinc salt DL-PCA zinc salt was prepared by reacting DL-PCA with zinc oxide in 10 ° C water for 2 hours according to the method described in JP-A-3-168840. Thereafter, stirring was continued for 5 hours at room temperature, and the precipitated crystals were filtered and synthesized. The L-PCA zinc salt was synthesized in the following manner. In an sterilizer, an aqueous solution of L-glutamic acid 1 water and (6 i.ig) was heated at 180 ° C for 2 hours to obtain 50% by weight of a sodium pyrrolidone carboxylic acid salt solution. Adding 2.7 g of nitric acid (purity) to a 50 wt% sodium pyrrolidone carboxylate solution (0.33 -13 - 200808717 mol, pH 7.7, optical purity 84%, L/D ratio = 92/8) of 100.Og 60 wt%), adjust the pH to 5.2. Further, 47.6 g of zinc sulfate 7 water and (0.17 mol) were dissolved in 34.2 g of water and the aqueous solution was added to a pyrrolidone carboxylic acid sodium salt solution (pH 4.1). The solution was mixed at room temperature (pH 3.7) for 30 minutes until crystallization was obtained, and filtration was carried out. The obtained crystal was washed with water (2 1. 9 g) to obtain 32.0 g (0.09 mol, 55% yield) of the crude pyrrolidonecarboxylate dihydrate. Its optical purity was 99.8% (L/D ratio = 99.9/0.1). Test Example 1 Enhancement of the performance of the ascorbate transporter mRNA of the pyrrolidone carboxylic acid zinc salt The normal human pigment cells were placed in a culture dish and cultured on a culture medium for normal human color cell proliferation (manufactured by KURABO). It was cultured in an incubator at 5% CO 2 and saturated steam at 37 ° C for 1 day. The sample was prepared by removing the added proliferation factor from the culture medium for normal human pigment cell proliferation. The culture solution in the culture dish was replaced with a culture solution in which a sample (PCΑΖη salt or the like) was prepared to have a concentration of 10 // Μ, and then cultured in an incubator for 24 hours. After the completion of the culture, the culture solution was aspirated and washed with PBS. Cell processing is performed by following the procedure of the RNeasy Mini Kit (manufactured by Quiagen) to extract RNA from cells. Further, from the obtained RNA, c-Dna is obtained according to a usual method, and the ascorbic acid transporter SVCT is further known by a method known in the literature (Christopher Ρ Corp. et al. (2005) J. Biol. Chem. 280, 52 1 1 - 5220 ). Perform RT-PCR (introduction: positive femoral arch [sub; 5'-CTGAGCTCATGGCGATCTAC-3' (preface 歹 [J number 3], anti-14-200808717 strand bow scorpion; 5,-CATGTCAGGTAGTGCTGTAGCCCCA-3' (preface! ] No. 4)). The obtained DNA was subjected to electrophoresis, and the amount of RNA expression of SVCT was evaluated based on the presence or absence of the sample. The evaluation of the electrophoretic bright band was carried out by using GMOPD standard image after lumino1 · image analyzer (made by LAS-3 000/Fuji film). As shown in Fig. 1, by adding 1 〇 // 吡 pyrrolidone carboxylic acid zinc salt, it was confirmed that the SVCT was increased by 140% of the RNA expression amount by adding 10 V Μ compared with the unadded control group. Therefore, ascorbic acid transporter increases in NHEM cells, and the concentration of ascorbic acid in the cells increases, and the oxidation reaction of melanosomes in the sputum cells is suppressed, thereby causing the effect of inhibiting melanin production. Test Example 2 Effect of PC ΑΖη salt on promoting blood flow The difference between PCAZn salt and other Zn salts has been confirmed by promoting blood flow effect (increased blood volume). The Zn salt of each sample was prepared and applied to a human wrist to visually evaluate the effect of promoting blood flow. The sample used was 1PCAZn salt, 2PCANa salt, 3 gluconic acid Zll salt, 4 gluconic acid Na salt, 5 sulphate Zn salt, and 6 sulphate Na2 salt. The modulation concentration is 5 wt% and the pH is between 5.5 and 6.5. The above sample of 80 // 1 was attached to the wrist in a semi-closed manner for 30 minutes, and the patch was removed and visually evaluated. The visual observation was carried out after 30 minutes and after 50 minutes. Follow the list to give a comment. The results are shown in Table 22. The result is the average 値 of the points evaluated. -15- 200808717 Table 2 1 Comment 0 No change 1 There is weak blood flow promotion in one part of the coating site 2 Weak blood flow promotion in one part of the coating site 3 Weak blood flow promotion in the coating site 4 The application site has blood flow promotion table. 22 After the sample is removed from the patch, the patch is removed 30 minutes after the patch is removed. 50 minutes after the patch is removed. 5 wt% PCAZn salt 2.5 2 1 5 wt% PCANa salt 2.5 2.5 1 5 wt% gluconic acid Zn salt 0 0 0 5 wt% gluconic acid Na salt 0 0 0 5 wt% sulphate sulphate 0 0 0 5 wt% sulphate Na2 salt 0 0 0 Samples 1 and 2 were confirmed to have a temporary effect of promoting blood flow. However, in other samples, no effect of promoting blood flow was observed in various evaluation time zones. From this result, it was confirmed that the PCΑΖη salt has a temporally promoting blood flow promoting effect by being applied to the skin as compared with other Zn salts. Therefore, since a useful substance such as intravascular ascorbic acid can be concentrated on the coated portion, the PCΑΖη salt is expected to have a more whitening effect than other Zn salts. Hereinafter, the combination of various preparations is exemplified in the following 1 to 16. These formulations can be prepared according to common methods. And, the matching amount is expressed by weight% 200808717. Matching example 1 Ointment L-PCA zinc salt 0.001% Chlorination. Dimethylammonium phosphate 0.1% Urea 2 0.0% White petrolatum 15.0% Light mobile paraffin 6.0% Cetyl alcohol 3.0% Stearyl alcohol 3.0% Stearic acid glyceride 5.0% Perfume amount Preservative appropriate amount Buffer 1.0% Pure water residual amount Example 2 Ointment zinc gluconate 0.002% Chlorophthalate ammonium 0.1% Urea 2 0.0% White Vaseline 15.0% Light mobile paraffin 6.0% Cetyl alcohol 3.0% Stearyl alcohol 3.0% Stearic acid glyceride 5.0% -17- 200808717 Perfume amount Preservative appropriate buffer 1.0% Pure water residue matching example 3 Lotion PC L-PCA Zinc salt 0.03% Glycolic acid 5.0% Glycerin 3.0% Sorbitol 2.0% Polyoxyethylene (20) oleyl ether 1.0% Ethanol 15.0% Phenol sulfonate 0.2% Buffer 0.1% Perfume 0.2% Preservatives Appropriate amount of pure water Residual amount matching example 4 lotion DL - PCA zinc salt 0.005% citric acid 1.0% urea 4.0% salicylic acid 2.0% lactic acid 2.0% -18- 200808717 glycerin 2.0% betaine 2.0% hyaluronic acid 0.1% ethanol 15.0% buffer 0. 1% Perfume 0.2% Preservatives Appropriate amount of pure water Residues Example 5 Lotion DL-PCA zinc salt 0.005% Ascorbic acid 1.0% Urea 4.0% Lactic acid 2.0% Glycerin 2.0% Betaine 2.0% Hyaluronic acid 0.1% Ethanol 15.0% Buffer 0.1% Perfume 0.2% Preservatives Appropriate amount of pure water Residues Example 6 Lotion -19- 200808717 Zinc glycinate 0.005% Citric acid 1.0% Urea 4.0% Salicylic acid 2.0% Lactic acid 2.0% Glycerin 2.0% Betaine 2.0% Hyaluronic acid 0.1 % Ethanol 15.0% Buffer 0.1% Perfume 0.2% Preservatives Appropriate amount of pure water Residues Example 7 Coating agent L-PCA zinc salt 0.01% Lactic acid 0.1% Fruit acid 0.1% Glycerin 4.0% Kaolin 1.0% Polygonite 0.7% Camphor 0.2 % Ethanol 14.0% Perfume amount -20- 200808717 Pure water residue mix example 8 Paint agent L-PCA zinc salt 0.01% Ascorbic acid 0.1% Fruit acid 0.1% Glycerin 4.0% Kaolin 1.0% Sphalerite 0.7% Camphor 0.2% Ethanol 14.0% Perfume amount of pure water residue mix Example 9 Coating agent Zinc chloride salt 0.005% Lactic acid 0.1% Fruit acid 0.1% Glycerin 4.0% Kaolin 1.0% Sphalerite 0.7% Camphor 0. 2% ethanol 14.0% flavor amount-21 - 200808717 pure water residual amount matching example 10 cream L-PCA zinc salt 0.01% m-catechol 0.1% citric acid 1.0% stearic acid 2.0% polyoxyethylene (25) ten Hexyl ether 3.0% stearic acid glyceride 2.0% octyldodecanol 10.0% cetyl alcohol 6.0% reduced lanolin 4.0% squalene 9.0% 1,3-butanediol 6.0% polyethylene glycol ( 1 5 0 0 ) 4.0% Preservatives Proper amount of flavoured pure water Residues η Cream gluconate zinc salt 0.02% m-catechol 0.1% citric acid 1.0% stearic acid 2.0% -22- 200808717 polyoxyethylene (25) cetyl ether 3.0% glyceryl stearate 2.0% octyldodecanol 10.0% cetyl alcohol 6.0% reduced lanolin 4.0% squalene 9.0% 1,3 - butyl- ketone 6.0% Polyethylene glycol (1 500 ) 4.0% Preservatives Proper amount of flavouring amount of pure water Residues Example 12 Cream gluconate zinc salt 0.02% m-benzoquinone 0.1% ascorbic acid 5.0% stearic acid 2.0% polyoxyethylene (25 Cetyl ether 3.0% glyceryl stearate 2.0% octyldodecanol 10.0% cetyl alcohol 6.0% reduced lanolin 4.0% squalene 9.0% 1,3 - Alcohol 6.0% -23- 200808717 Polyethylene glycol (1 500 ) 4.0% Preservatives Proper amount of flavouring amount of pure water Residues Example 13 Cream DL-PCA Zinc salt 0.01% Glycolic acid 2.0% Solid paraffin 5.0% Beeswax 10.0 % Vaseline 15.0% Mobile paraffin 41.0% 1,3 - Butanediol 4.0% Stearic acid glyceride 2.0% Polyoxyethylene sorbitan monolaurate (20) 2.0% Borax 0.2% Preservatives Proper amount of spices to prevent oxidation Formulation amount of pure water residue Example 14 Emulsion L-PCA Zinc salt 0.02% Lactic acid 2.0% -24- 200808717 Stearyl alcohol 0.5% Hardened palm oil 3.0% Mobile paraffin 3 5.0% Dipropylene glycol 6.0% Polyethylene glycol (400 ) 4.0% sorbitan oleate 1.6% Polyoxyethylene ( 20 ) oleyl ether 2.4% Carboxyvinyl polymer 1.5% Potassium hydroxide 0.1% Chelating agent appropriate amount of preservatives appropriate amount of spices appropriate amount of pure water residue matching example 15 Emulsion zinc sulfate salt 0.01% lactic acid 2.0% stearyl alcohol 0.5% hardened palm oil 3.0% mobile paraffin 3 5.0% dipropylene glycol 6.0% polyethylene glycol ( 400 ) 4.0% sorbitan oleate 1.6% Polyoxyethylene ( 20 ) oleyl ether 2.4% -25- 200808717 Carboxyvinyl polymer 1.5% Potassium hydroxide 0.1% Chelating agent Appropriate amount of preservatives Water Residue Matching Example 16 Beauty Liquid L-PCA Zinc Salt 0.05% Fruit Acid 0.5% Dipropylene Glycol 5.0% Polyethylene Glycol (400) 5.0% Ethanol 10.0% Carboxyvinyl Polymer 0.5% Sodium Alginate 0.5% Potassium Hydroxide 0.2% polyoxyethylene sorbitan monostearate (20 ) 1.0% monooleic acid sorbitol 0.5% oleyl alcohol 0.5% placenta extraction 0.2% acetic acid d 1 - α - tocopherol 0.2% perfume amount of preservatives amount fading Proper amount -26- 200808717 Pure water residue matching example 1 7 Beauty liquid L-PCA zinc salt 0.05% Ascorbic acid 2.0% Dipropylene glycol 5.0% Polyethylene glycol (400) 5.0% Ethanol 10.0% Carboxy vinyl polymer 0.5% Sodium alginate 0.5% Potassium hydroxide 0.2% Polyoxyethylene sorbitan monostearate (20 ) 1.0% Monooleate sorbitol 0.5% Olefin 0.5% Placenta extraction 0.2% Acetate dl-α - Tocopherol 0.2 % Proper amount of preservative Amount of fading agent appropriate amount of pure water residue matching example 1 8 beauty liquid zinc lactate 0.005% fruit acid 0.5% -27- 200808717 dipropylene glycol 5.0% polyethylene glycol (400) 5.0% ethanol 10.0% carboxy vinyl polymerization 0.5% sodium alginate 0.5% potassium hydroxide 0.2% polyoxyethylene sorbitan monostearate (20 ) 1.0% oleic acid sorbitol 0.5% oleyl alcohol 0.5% placenta extraction 0.2% acetic acid d 1 - α - Tocopherol 0.2% Perfume amount Preservatives Suitable amount of fading inhibitor Suitable amount of pure water Residues Example 19 Mask DL - PC Α Zinc salt 0.03% Isopropyl alcohol 2.0% Polyvinyl alcohol 15.0% Carboxymethyl cellulose 5.0% 1,3 - Butanediol 5.0% Ethanol 12.0% Polyoxyethylene (20) Olefin Ether 0.5% -28- 200808717 Perfume amount Preservatives Suitable amount of buffer Suitable amount of pure water Residues Example 20 Mask zinc gluconate 0.03% Isopropanol 2.0 % polyvinyl alcohol 15.0% carboxymethyl cellulose 5.0% 1,3-butanediol 5.0% ethanol 12.0% polyoxyethylene (20) oleyl ether 0.5% perfume appropriate amount of preservative appropriate amount of buffer appropriate amount of pure water residual amount 2 1 Foundation DL-PCA zinc salt 0.1% salicylic acid 0.5% mobile paraffin 10.0% polyoxyethylene sorbitan monooleate (20 ) 3.5% propylene glycol 3.0% -29- 200808717 titanium oxide 9.0% kaolin 2 4.0% talc 4 2.0% coloring pigment 3.0% perfume Appropriate amount of preservative appropriate amount of oxidation inhibitor appropriate amount of example 22 liquid hand lotion L-PCA zinc salt 0.1% sodium cetyl sulfate 3 0.0% betaine 3.0% fatty acid glyceride 1.0% phenoxyethanol 1.0% EDTA 0.1% pure water Residual amount The present invention is useful in the field of cosmetics. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a graph showing the effect of enhancing the performance of ascorbate transporter mRNA in melanocytes caused by a zinc salt of pyrrolidone carboxylic acid. -30 -