JP2008290975A - 美白剤 - Google Patents
美白剤 Download PDFInfo
- Publication number
- JP2008290975A JP2008290975A JP2007138522A JP2007138522A JP2008290975A JP 2008290975 A JP2008290975 A JP 2008290975A JP 2007138522 A JP2007138522 A JP 2007138522A JP 2007138522 A JP2007138522 A JP 2007138522A JP 2008290975 A JP2008290975 A JP 2008290975A
- Authority
- JP
- Japan
- Prior art keywords
- metal
- whitening agent
- bicarbonate
- complex
- whitening
- 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
- 239000007854 depigmenting agent Substances 0.000 title abstract 4
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- 238000000354 decomposition reaction Methods 0.000 claims abstract description 22
- 239000002537 cosmetic Substances 0.000 claims abstract description 14
- 235000013305 food Nutrition 0.000 claims abstract description 14
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052751 metal Inorganic materials 0.000 claims description 48
- 239000002184 metal Substances 0.000 claims description 48
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- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
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- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 8
- 229910052742 iron Inorganic materials 0.000 claims description 7
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
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Abstract
【解決手段】炭酸及び/又は重炭酸−金属−LF類の複合体、その複合体の分解物及び、炭酸及び/又は重炭酸−金属−LF類分解物の複合体を有効成分とする美白剤及び、これらを配合した飲食品、飼料、化粧品。炭酸及び/又は重炭酸−金属−LF類の複合体、その複合体の分解物及び、炭酸及び/又は重炭酸−金属−LF類分解物の複合体は日常的に摂取しても安全性が高く、また優れた美白効果を有する。
【選択図】なし
Description
以下の溶液を調製した後、混合して重炭酸−金属−LFの複合体を調製した。
(A溶液)1M重炭酸ナトリウムを含む溶液1L
(B1溶液) 各濃度各金属塩を含む溶液0.2L
但し、1種の金属を含む溶液の場合は、金属塩100mMを含む溶液を調整した。2種の金属を含む溶液の場合は、各金属塩を等量混合し、金属塩 200mMを含む溶液を調製した。また、3種の金属を含む溶液の場合は、各金属塩を等量混合し、金属塩300mMを含む溶液を調製した。
(B2溶液)1mM LF類を含む溶液0.8L
まず、A溶液に、B1溶液とB2溶液を混合したB溶液を加えて撹拌し、各金属が結合したLF類を含む溶液を調製した。そして、この溶液300ml を分子量10kDaの透析膜で超純水に対して透析し、結合しなかった金属を除去して完全に脱塩した後、凍結乾燥し、LF類に結合している各金属量を誘導結合プラズマ発光分光分析器(ICP)で測定した。その結果を表1に示す。この結果、重炭酸−金属−LF類の複合体をLFに対し、90%以上の収率で得ることができた。
以下の溶液を調製した後、混合して重炭酸−金属−LF類の複合体分解物を調製した。実施例1で得られた重炭酸−金属−LF類の複合体にトリプシン(TYPEIII、シグマ社製)を1重量%添加し、37℃で24時間加水分解した。その後、さらにトリプシン1重量%を添加し、37℃で24時間加水分解することにより、重炭酸−金属−LF類の複合体を完全に加水分解した。なお、この加水分解反応を行うに際し、反応液を除菌フィルターにより除菌して菌の増殖を抑制し、さらに、トルエン一滴を滴下した状態で反応に供した。次に、分子量 1kDaの透析膜で透析し、凍結乾燥して、分子量が主として55kDa及び30kDa及び10kDaからなり、その他分子量 1kDa以上のペプチドからなる重炭酸−金属−LF類の複合体分解物を得た。重炭酸−金属−LF類の複合体分解物に結合している各金属量をICPで測定した。その結果を表2に示す。
以下の溶液を調製した後、混合して重炭酸−金属−LF類分解物の複合体を調製した。
(A溶液)1M重炭酸ナトリウムを含む溶液1L
(B1溶液) 各濃度各金属塩を含む溶液0.2L
但し、1種の金属を含む溶液の場合は、金属塩100mMを含む溶液を調整した。2種の金属を含む溶液の場合は、各金属塩を等量混合し、金属塩 200mMを含む溶液を調製した。また、3種の金属を含む溶液の場合は、各金属塩を等量混合し、金属塩300mMを含む溶液を調製した。
(B2溶液)LF類換算で13.2μM/L となるようLF類分解物を水に溶解した溶液0.8L
なお、LF類分解物は、特許第3223958号公報の参考例1の方法に従って得られたものを使用した。まず、A溶液に、B1溶液とB2溶液を混合したB溶液を加えて撹拌し、各金属が結合したLF類分解物を含む溶液を調製した。そして、この溶液を4℃で90時間、分子量 1kDaの透析膜で超純水に対して透析し、完全に脱塩した後、凍結乾燥し、LF類分解物に結合している各金属量をICPで測定した。その結果を表3に示す。
(メラニン生成阻害効果の検証)
実験はマウス悪性黒色腫B16-F0細胞(大日本住友製薬社より購入)を使用した。牛胎児血清を10%含むEagle’s MEM培地(Sigama‐Aldrich社)を使用し、CO2インキュベーター(5% CO2、37℃)内で培養した。B16細胞を細胞濃度3×105個/mlの懸濁液とし、この1mlを培地が9ml入っている100mmディッシュに分注した。翌日、0.01〜1%LF、実施例1における重炭酸−金属−LF複合体(FeLF(70)、FeLF(200)、CuLF(32)、CuLF(160)、Fe+CuLF(98+62))及び金属塩とLFまたはLF分解物をそれぞれを含む培地に交換し、4日間培養した。培養終了後、細胞をはがし、各群の細胞数を5×106個にそろえ遠心した。1M NaOHを500ml添加して溶解した後、その溶解液の405nmにおける吸光度を吸光光度計で測定した。無添加群を100%として各群のメラニン生成阻害率を算出した結果を下の表4に示す。
(チロシナーゼ活性阻害作用の検証)
チロシナーゼはチロシンからメラニンを合成する経路に関わる酵素であり、チロシンをドーパに、さらにドーパをドーパキノンへ変換する。そこで、本発明の美白剤によるメラニン合成経路に対する抑制効果を検討するため、チロシナーゼ活性阻害作用について検証した。実験は、チロシナーゼ(Sigama‐Aldrich社、マッシュルーム由来)を用い、LF、実施例1の重炭酸−金属−LFの複合体、実施例2の炭酸−金属−LFの複合体分解物、実施例3の重炭酸−金属−LF分解物の複合体又は金属塩を加え37℃で15分間前処理を行った。基質としてドーパ(Sigama‐Aldrich社)を添加し、さらに37℃で5分間反応させた後、476nmにおける吸光度を測定した。無添加の値を100%として阻害率を算出した。重炭酸−金属−LFの複合体を用いた場合の結果を表5に、重炭酸−金属−LFの複合体分解物を用いた場合の結果を表6に、重炭酸−金属−LF分解物の複合体を用いた場合の結果を表7に示す。
(経口投与によるメラニン分解/排出促進効果の検証)
A-1系雌モルモット、体重約400gの背部を除毛し、背部に紫外線(UVA(max.360nm)30.3kJ/m2、UVB(max.312nm)4.8kJ/m2)照射を1回/日、4日行った。その後、生理食塩水をモルモット体重1kgあたり5ml投与する群(A群)、FeLF(70)(実施例1)をモルモット体重1kgあたり2mg/5ml投与する群(B群)、FeLF(70)をモルモット体重1kgあたり5mg/5ml投与する群(C群)、FeLF(70)をモルモット体重1kgあたり10mg/5ml投与する群(D群)の4試験群(各群10匹ずつ)にわけ、それぞれを毎日1回ゾンデで経口投与して4週間飼育した。試料投与開始時と試料投与終了時にモルモット背部皮膚の色素沈着への影響をそれぞれMINOLTA社製の色差計(CHROMA METER CR-200)で測定した。紫外線照射前の明度と照射後の明度の差から照射前の明度を100%として回復率を算出した。その結果を表8に示す。
(塗布によるメラニン分解/排出促進効果の検証)
A-1系雌モルモット、体重約400gの背部を除毛し、背部に紫外線(UVA(max.360nm)30.3kJ/m2、UVB(max.312nm)4.8kJ/m2)照射を1回/日、4日行った。その後、1日2回、4週間被験部位に試料を連続塗布した。被験試料は水、エタノール、プロピレングリコールを2:2:1の比率で混和したものに溶解してを塗布した。コントロール群)(A群)、0.01%FeLF(70)(実施例1)(B群)、0.1%FeLF(70)(C群)、1%FeLF(70)(D群)の4試験群(各群10匹ずつ)にわけた。試料塗布開始時と試料塗布終了時にモルモット背部皮膚の色素沈着への影響をそれぞれMINOLTA社製の色差計(CHROMA METER CR-200)で測定した。紫外線照射前の明度と照射後の明度の差から、照射前の明度を100%として回復率を算出した。その結果を表9に示す。
実施例1の美白剤を用い、表10の配合で混合して美白クリームを製造した。
実施例1の美白剤を用い、表11の配合で混合し、美白ローションを製造した。
実施例1の美白剤を用い、表12に示す配合で原料を混合後、常法により1gに成型、打錠して本発明の美白錠剤を製造した。なお、この美肌錠剤1g中には、FeLF(70)が100mg含まれていた。
実施例1の美白剤を用い、以下の方法で美白用液状栄養組成物を調製した。実施例1のCuLF(32)50g及びカゼイン1000gを3950gの脱イオン水に溶解し、50℃まで加熱後、TKホモミクサー(TK ROBO MICS;特殊機化工業社製)にて、6000rpmで30分間撹拌混合してCuLF含量50g/5kgのCuLF溶液を得た。このCuLF溶液5.0kgに、カゼイン4.0kg、大豆タンパク質5.0kg、魚油1.0kg、シソ油3.0kg、デキストリン18.0kg、ミネラル混合物6.0kg、ビタミン混合物1.95kg、乳化剤2.0kg、安定剤4.0kg、香料0.05kgを配合し、200mlのレトルトパウチに充填し、レトルト殺菌機 (第1種圧力容器、TYPE: RCS-4CRTGN、日阪製作所製)で121℃、20分間殺菌して、本発明の美白用液状栄養組成物50kgを製造した。なお、この美白用液状栄養組成物には、100gあたり、CuLF(32)が100mg含まれていた。
実施例2の美白剤を用い、以下の方法で美白用ゲル状食品を調製した。実施例2のCuLF(32)分解物2g及びペクチン10g、乳清タンパク質濃縮物10gを978gの脱イオン水に溶解し、ウルトラディスパーサー(ULTRA-TURRAX T-25;IKAジャパン社製)にて、9500rpmで3分間撹拌混合した。その後、上記の溶液に、ソルビトール80g、酸味料4g、香料4g、乳酸カルシウム2g、水910gを添加して、撹拌混合し、本発明の美白用ゲル状食品を調製した。200mlのチアパックに充填し、85℃、20分間殺菌後、密栓し、本発明の美白用ゲル状食品10袋を調製した。なお、この美白用ゲル状食品には、100gあたりCuLF(32)分解物が100mg含まれていた。
実施例3の美白剤を用い、以下の方法で美白用飲料を調製した。
脱脂粉乳 300gを409gの脱イオン水に溶解した後、実施例3のFeLF分解物(201)1gを溶解し、50℃まで加熱後、ウルトラディスパーサー(ULTRA-TURRAX T-25;IKAジャパン社製)にて、9500rpmで30分間撹拌混合した。マルチトール100g、酸味料 2g、還元水飴20g、香料2g、脱イオン水166gを添加した後、100mlのガラス瓶に充填し、90℃、15分間殺菌後、密栓し、本発明の美白用飲料10本(100ml入り)を調製した。なお、この美白用飲料には、100mlあたりFeLF分解物(201)が100mg含まれていた。
実施例1の美白剤を用い、以下の方法で美白用犬用飼料を調整した。実施例1のFeLF(70)0.2kgを99.8kgの脱イオン水に溶解し、50℃まで加熱後、TKホモミクサー(MARK II 160型;特殊機化工業社製)にて、3600rpmで40分間撹拌混合してFeLF含量2g/100gのFeLF溶液を得た。このFeLF溶液10kgに大豆粕12kg、脱脂粉乳14kg、大豆油4kg、コーン油2kg、パーム油23.2kg、トウモロコシ澱粉14kg、小麦粉9kg、ふすま2kg、ビタミン混合物5kg、セルロース2.8kg、ミネラル混合物2kgを配合し、120℃、4分間殺菌して、本発明のイヌ用美肌用飼料100kgを製造した。なお、この美白用イヌ用飼料には、100gあたりFeLF(70)が20mg含まれていた。
Claims (6)
- ラクトフェリン類又はその分解物と金属、炭酸及び/又は重炭酸の複合体を有効成分とする美白剤。
- 複合体が炭酸イオン及び/又は重炭酸イオンを含有する溶液と、単一あるいは複数種の金属を含む溶液と、ラクトフェリン類又はその分解物を含む溶液とを混合することにより得られる請求項1記載の美白剤。
- ラクトフェリン類と金属、炭酸及び/又は重炭酸の複合体を加水分解した分解物を有効成分とする美白剤。
- 複合体がラクトフェリン類又はその分解物1分子当り、単一あるいは複数種の金属が3〜1000分子、炭酸及び/又は重炭酸が15分子以上を含むことを特徴とする複合体である請求項1又は3記載の美白剤。
- 金属が鉄、銅、亜鉛、マンガン、コバルト、ニッケル及びアルミニウムの中から選択される1又は2種以上のミネラルである請求項1〜4記載の美白剤。
- 請求項1〜5のいずれかに記載の美白剤を配合した飲食品、飼料、化粧品、及び医薬。
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JP2007138522A JP5311760B2 (ja) | 2007-05-25 | 2007-05-25 | 美白剤 |
CN200880017515A CN101707906A (zh) | 2007-05-25 | 2008-05-22 | 美白剂 |
NZ581212A NZ581212A (en) | 2007-05-25 | 2008-05-22 | Skin whitening agent comprising lactoferrins, a metal, carbonic acid and bicarbonic acid as active ingredients |
EP08764523A EP2156820B1 (en) | 2007-05-25 | 2008-05-22 | Skin whitening agent |
PCT/JP2008/059462 WO2008146710A1 (ja) | 2007-05-25 | 2008-05-22 | 美白剤 |
CA2688318A CA2688318C (en) | 2007-05-25 | 2008-05-22 | Whitening agent |
AU2008255930A AU2008255930B2 (en) | 2007-05-25 | 2008-05-22 | Skin whitening agent |
US12/601,294 US20100215767A1 (en) | 2007-05-25 | 2008-05-22 | Skin whitening agent |
DK08764523.0T DK2156820T3 (da) | 2007-05-25 | 2008-05-22 | Hudblegemiddel |
KR1020097027070A KR101478383B1 (ko) | 2007-05-25 | 2008-05-22 | 미백제 |
US13/273,834 US20120034177A1 (en) | 2007-05-25 | 2011-10-14 | Method of whitening skin |
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JP2007138522A JP5311760B2 (ja) | 2007-05-25 | 2007-05-25 | 美白剤 |
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US (2) | US20100215767A1 (ja) |
EP (1) | EP2156820B1 (ja) |
JP (1) | JP5311760B2 (ja) |
KR (1) | KR101478383B1 (ja) |
CN (1) | CN101707906A (ja) |
AU (1) | AU2008255930B2 (ja) |
CA (1) | CA2688318C (ja) |
DK (1) | DK2156820T3 (ja) |
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CN102451185A (zh) * | 2010-10-19 | 2012-05-16 | 长春纳米生技公司 | 金属离子纳米簇组合物 |
WO2014146782A1 (en) | 2013-03-18 | 2014-09-25 | Qiagen Gmbh | Stabilization and isolation of extracellular nucleic acids |
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JPH0459714A (ja) * | 1990-06-26 | 1992-02-26 | Morinaga Milk Ind Co Ltd | チロシナーゼ活性阻害剤 |
JPH05320068A (ja) * | 1990-06-26 | 1993-12-03 | Morinaga Milk Ind Co Ltd | ラクトフェリン分解物を有効成分とする抗菌剤、チロシナーゼ活性阻害剤、及びラクトフェリン分解物を用いる物品の処理方法 |
JP2004269372A (ja) * | 2003-03-05 | 2004-09-30 | Toshiko Hori | 人体に塗布、付着させる組成物 |
Family Cites Families (14)
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DE69017921T2 (de) * | 1990-01-23 | 1995-10-12 | Morinaga Milk Industry Co Ltd | Lactoferrinhydrolysat zur Verwendung als tyrosinagehemmendes Mittel. |
JP2835902B2 (ja) * | 1993-02-16 | 1998-12-14 | 雪印乳業株式会社 | 耐熱性ラクトフェリン−鉄結合体及びその製造法 |
JP2572931B2 (ja) * | 1993-04-28 | 1997-01-16 | 雪印乳業株式会社 | 美白剤 |
JP2884045B2 (ja) | 1994-03-18 | 1999-04-19 | 雪印乳業株式会社 | 鉄−ラクトフェリン複合体及びその製造法 |
JP3606665B2 (ja) * | 1995-12-06 | 2005-01-05 | 雪印乳業株式会社 | 亜鉛−ラクトフェリン、その製造法および利用 |
JP3223958B2 (ja) | 1996-12-17 | 2001-10-29 | 雪印乳業株式会社 | 金属結合ラクトフェリン及びその用途 |
JP3439686B2 (ja) * | 1999-03-30 | 2003-08-25 | 雪印乳業株式会社 | 鉄強化飲料 |
JP3887704B2 (ja) * | 1999-03-31 | 2007-02-28 | 雪印乳業株式会社 | 細菌毒素中和剤 |
JP3739589B2 (ja) * | 1999-03-31 | 2006-01-25 | 雪印乳業株式会社 | 骨強化剤 |
JP4014330B2 (ja) * | 1999-03-31 | 2007-11-28 | 雪印乳業株式会社 | ウイルス感染防御剤 |
US6696043B2 (en) * | 2000-09-20 | 2004-02-24 | Scientific Pharmaceuticals, Inc. | Teeth whitening composition in the form of a chewing gum |
US20030129259A1 (en) * | 2001-12-28 | 2003-07-10 | Avon Products, Inc. | Topical lightening compostitions and methods of use |
US20040166069A1 (en) * | 2003-02-21 | 2004-08-26 | Gupta Shyam K. | Boosting Tyrosinase Inhibiting Activity of Skin Whitening and Sunscreen Compositions |
JP4208799B2 (ja) * | 2004-09-06 | 2009-01-14 | 雪印乳業株式会社 | 炎症性サイトカイン産生抑制剤 |
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- 2008-05-22 EP EP08764523A patent/EP2156820B1/en not_active Not-in-force
- 2008-05-22 US US12/601,294 patent/US20100215767A1/en not_active Abandoned
- 2008-05-22 KR KR1020097027070A patent/KR101478383B1/ko active IP Right Grant
- 2008-05-22 CN CN200880017515A patent/CN101707906A/zh active Pending
- 2008-05-22 NZ NZ581212A patent/NZ581212A/xx not_active IP Right Cessation
- 2008-05-22 WO PCT/JP2008/059462 patent/WO2008146710A1/ja active Application Filing
- 2008-05-22 CA CA2688318A patent/CA2688318C/en not_active Expired - Fee Related
- 2008-05-22 DK DK08764523.0T patent/DK2156820T3/da active
- 2008-05-22 AU AU2008255930A patent/AU2008255930B2/en not_active Ceased
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JPH0459714A (ja) * | 1990-06-26 | 1992-02-26 | Morinaga Milk Ind Co Ltd | チロシナーゼ活性阻害剤 |
JPH05320068A (ja) * | 1990-06-26 | 1993-12-03 | Morinaga Milk Ind Co Ltd | ラクトフェリン分解物を有効成分とする抗菌剤、チロシナーゼ活性阻害剤、及びラクトフェリン分解物を用いる物品の処理方法 |
JP2004269372A (ja) * | 2003-03-05 | 2004-09-30 | Toshiko Hori | 人体に塗布、付着させる組成物 |
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KR101478383B1 (ko) | 2014-12-31 |
EP2156820A1 (en) | 2010-02-24 |
JP5311760B2 (ja) | 2013-10-09 |
CA2688318C (en) | 2015-04-28 |
DK2156820T3 (da) | 2012-11-19 |
WO2008146710A1 (ja) | 2008-12-04 |
AU2008255930B2 (en) | 2014-02-27 |
AU2008255930A1 (en) | 2008-12-04 |
US20120034177A1 (en) | 2012-02-09 |
CN101707906A (zh) | 2010-05-12 |
EP2156820A4 (en) | 2010-11-24 |
KR20100030624A (ko) | 2010-03-18 |
CA2688318A1 (en) | 2008-12-04 |
NZ581212A (en) | 2012-08-31 |
US20100215767A1 (en) | 2010-08-26 |
EP2156820B1 (en) | 2012-08-22 |
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