JP6866518B2 - 発毛及び/又は育毛促進活性を示すペプチド及びその用途 - Google Patents
発毛及び/又は育毛促進活性を示すペプチド及びその用途 Download PDFInfo
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- JP6866518B2 JP6866518B2 JP2020036395A JP2020036395A JP6866518B2 JP 6866518 B2 JP6866518 B2 JP 6866518B2 JP 2020036395 A JP2020036395 A JP 2020036395A JP 2020036395 A JP2020036395 A JP 2020036395A JP 6866518 B2 JP6866518 B2 JP 6866518B2
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Images
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A61K38/07—Tetrapeptides
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Description
合成例1:ペプチドの合成
クロロトリチルクロライドレジン(Chloro trityl chloride resin; CTL resin, Nova biochem Cat No. 01−64−0021)700mgを反応容器に入れてメチレンクロライド(MC)10mlを加えて3分間撹拌した。溶液を除去し、ジメチルホルムアミド(DMF)10mlを入れて3分間撹拌した後、また溶媒を除去した。反応器に10mlのジクロロメタン溶液を入れてFmoc−Ile−OH(Bachem、Swiss)200mmole及びジイソプロピルエチルアミン(DIEA)400mmoleを入れた後、撹拌してよく溶かして、1時間の間撹拌しながら反応させた。反応後、洗浄し、メタノールとDIEA(2:1)をDCM(dechloromethane)に溶かして10分間反応させ、過量のDCM/DMF(1:1)で洗浄した。溶液を除去し、ジメチルホルムアミド(DMF)を10ml入れて3分間撹拌した後、また溶媒を除去した。脱保護溶液(20%のピペリジン(Piperidine)/DMF)10mlを反応容器に入れて10分間常温で撹拌した後、溶液を除去した。同量の脱保護溶液を入れて、また10分間反応を維持した後、溶液を除去し、各々3分ずつDMFで2回、MCで1回、DMFで1回洗浄してIle−CTL Resinを製造した。新たな反応器に10mlのDMF溶液を入れてFmoc−Lys(Boc)−OH(Bachem、Swiss)200mmole、HoBt 200mmole、及びBop 200mmoleを入れた後、撹拌してよく溶かした。反応器に400mmole DIEAを分画に2回に亘って入れた後、全ての固体が溶けるまで最小限5分間撹拌した。溶かしたアミノ酸混合溶液を脱保護されたレジンがある反応容器に入れて1時間の間常温で撹拌しながら反応させた。反応液を除去し、DMF溶液で3回5分ずつ撹拌した後、除去した。反応レジンを少量取ってカイザーテスト(Nihydrin Test)を用いて反応程度を点検した。脱保護溶液で上記のように同一に2回脱保護反応させてLys(Boc)−Ile−CTL Resinを製造した。DMFとMCで十分に洗浄し、もう一度カイザーテストを遂行した後、前記と同様に以下のアミノ酸付着実験を遂行した。選ばれたアミノ酸配列に基づいてFmoc−Arg(Pbf)−OH及びFmoc−Arg(Pbf)−OHの順に連鎖反応させた。Fmoc−保護基を脱保護溶液で10分ずつ2回反応させた後、よく洗浄して除去した。無水酢酸とDIEA、HoBtを入れて一時間の間アセチル化を遂行した後、製造されたペプチジルレジンをDMF、MC、及びメタノールで各々3回洗浄し、窒素空気をゆっくり流して乾燥した後、P2O5下で真空に減圧して完全に乾燥した後、脱漏溶液[トリフルロ化酢酸(Trifluroacetic acid)95%、蒸留水2.5%、チオアニソール(Thioanisole)2.5%]30mlを入れた後、常温で時々揺らしながら2時間反応を維持した。フィルタリングを行ってレジンを濾して、レジンを少量のTFA溶液で洗浄した後、母液と合せた。減圧を用いて全体ボリュームが半分位残るように蒸留し、50mlの冷たいエーテルを加えて沈殿を誘導した後、遠心分離して沈殿を集めて、もう2回冷たいエーテルで洗浄した。母液を除去し、窒素下で十分に乾燥して精製前の配列番号1のアミノ酸配列Arg−Arg−Lys−Ileからなるペプチド1を0.7g合成した(収率:90.0%)。分子量測定機を用いて測定時、分子量571.7(理論値:571.72)を得ることができた。
ヒト毛乳頭細胞(Human hair follicle dermal papilla cells)を2×103細胞/ウェルの密度で96−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して3日間培養し、4mg/ml MTT溶液を100ulずつウェルに処理して4時間反応させた。生成されたホルマザンをDMSO処理を通じて溶かして出した後、マイクロプレートリーダを使用して560nmでの吸光度を測定して、その結果を図1a乃至図1cに示した。
ヒト毛乳頭細胞を4×105細胞/ウェルの密度で6−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して15、30分培養し、細胞を回収して核と細胞質タンパク質を各々分離した。β−カテニン抗体(santacruz biotechnology、USA)を用いてウェスタンブロッティングを遂行して核でのβ−カテニン発現様相を比較して、その結果を図2a乃至図2cに示した。
ヒト毛乳頭細胞を4×105細胞/ウェルの密度で6−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して24時間の間培養して細胞を回収してRNAを分離した。RNA定量後、cDNA合成キット(Intron、Korea)を用いてcDNAを合成し、PCRプリミックス(Intron、Korea)、及びKGF、bFGF、VEGF各々のプライマーを用いてPCR進行後、5%アガロースゲルに電気泳動して各サンプル処理条件で前記成長因子のmRNA発現程度を比較して、その結果を図3a乃至図3cに示した。
ヒト毛乳頭細胞を4×105細胞/ウェルの密度で6−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して15、30分培養し、細胞を回収して細胞溶解物を準備した。PI3K抗体(santacruz biotechnology、USA)及びphospho−ERK抗体(Cell Signaling Technology、USA)を用いてウェスタンブロッティングを遂行してタンパク質発現様相を比較して、その結果を図4a及び図4bに示した。
ヒト毛乳頭細胞を4×105細胞/ウェルの密度で6−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して24時間の間培養して細胞を回収してRNAを分離した。RNA定量後、cDNA合成キット(Intron、Korea)を用いてcDNAを合成し、PCRプリミックス(Intron、Korea)及びMSX2プライマーを用いてPCR進行後、5%アガロースゲルに電気泳動して各サンプル処理条件でmRNA発現程度を比較して、その結果を図5a及び図5bに示した。
ヒト毛乳頭細胞を4×105細胞/ウェルの密度で6−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して24時間の間培養し、細胞を回収してRNAを分離した。RNA定量後、cDNA合成キット(Intron、Korea)を用いてcDNAを合成し、PCRプリミックス(Intron、Korea)及びTGF−β1プライマーを用いてPCR進行後、5%アガロースゲルに電気泳動して各サンプル処理条件でmRNA発現程度を比較して、その結果を図6a及び図6bに示した。
ヒト毛乳頭細胞を4×105細胞/ウェルの密度で6−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して24時間培養し、細胞を回収して細胞溶解物を準備した。Bcl−2及びBax抗体(santacruz biotechnology、USA)を用いてウェスタンブロットを遂行してタンパク質発現様相を比較して、その結果を図7a及び図7bに示した。
ヒト毛乳頭細胞を5×105細胞/ウェルの密度で6−ウェルプレートにシーディングした後、一晩中培養した。無血清培地に変えた後、ペプチドを処理して24時間の間培養し、細胞を回収してRNAを分離した。RNA定量後、cDNA合成キット(Intron、Korea)を用いてcDNAを合成し、PCRプリミックス(Intron、Korea)及びケラチン−14プライマーを用いてPCR進行後、5%アガロースゲルに電気泳動して各サンプル処理条件でmRNA発現程度を比較して、その結果を図8に示した。
Claims (10)
- 配列番号2のアミノ酸配列からなる発毛促進活性を示す、ペプチド。
- 前記ペプチドは、毛嚢細胞成長を促進することを特徴とする、請求項1に記載のペプチド。
- 前記ペプチドは、β−カテニンの発現を増加させることを特徴とする、請求項1に記載のペプチド。
- 前記ペプチドは、KGF(Keratinocyte Growth Factor)、bFGF(Basic fibroblast growth factor)、及びVEGF(Vascular endothelial growth factor)からなる群から選択される発毛関連成長因子の発現を増加させることを特徴とする、請求項1に記載のペプチド。
- 前記ペプチドは、MSX2(Msh homeobox 2)及びケラチン−14からなる群から選択される発毛関連因子の発現を増加させることを特徴とする、請求項1に記載のペプチド。
- 前記ペプチドは、PI3K(Phosphoinositide 3−kinase)の発現及びERK(Extracellular Signal−regulated Kinase)のリン酸化を増加させることを特徴とする、請求項1に記載のペプチド。
- 前記ペプチドは、TGF−β1(transforming growth factor beta 1)の発現を抑制することを特徴とする、請求項1に記載のペプチド。
- 前記ペプチドは、Bcl−2(B−cell lymphoma 2)の発現を増加させ、Bax(BCL2−associated X protein)の発現を減少させることを特徴とする、請求項1に記載のペプチド。
- 配列番号2のアミノ酸配列からなるペプチドを有効成分として含む、脱毛防止または改善用組成物。
- 配列番号2のアミノ酸配列からなるペプチドを有効成分として含む、発毛または育毛促進用組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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KR10-2016-0019292 | 2016-02-18 | ||
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KR102069184B1 (ko) | 2019-06-28 | 2020-01-22 | (주)미래씨티 | 신경줄기세포 추출물유래 bmp신호전달경로 억제 펩타이드 및 상기 펩타이드를 유효성분으로 포함하는 발모촉진 또는 탈모방지 조성물 |
KR102265431B1 (ko) * | 2019-08-20 | 2021-06-15 | 주식회사 케어젠 | 발모 촉진 활성을 갖는 펩타이드 및 이의 용도 |
JP7485336B2 (ja) | 2020-04-01 | 2024-05-16 | 丸善製薬株式会社 | MSX-2 mRNA発現促進剤、まつ毛の育毛剤、及びまつ毛の育毛用外用剤組成物 |
KR20230047690A (ko) * | 2021-10-01 | 2023-04-10 | (주)케어젠 | 탈모 방지 또는 발모 촉진 활성을 갖는 펩타이드와 이의 용도 |
KR20230047688A (ko) * | 2021-10-01 | 2023-04-10 | (주)케어젠 | 탈모 방지 또는 발모 촉진 활성을 갖는 펩타이드와 이의 용도 |
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Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1226552B (it) * | 1988-07-29 | 1991-01-24 | Ellem Ind Farmaceutica | Peptidi immunostimolanti. |
US5516891A (en) | 1992-06-16 | 1996-05-14 | Kinerton, Ltd. | Liquid phase synthesis of peptides and peptide derivatives |
US6696417B1 (en) | 1997-11-21 | 2004-02-24 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Skin and hair darkening composition |
GB9801191D0 (en) * | 1998-01-20 | 1998-03-18 | Unilever Plc | Skin and hair darkening composition |
ES2146552B1 (es) | 1998-11-24 | 2001-04-16 | Inst Cientifico Tecnol Navarra | Peptidos inhibidores de tgf/31 |
EP1705487A3 (en) * | 2000-07-17 | 2008-03-19 | Diadexus, Inc. | Method of diagnosing, monitoring, staging, imaging and treating colon cancer |
US20030060438A1 (en) * | 2000-08-18 | 2003-03-27 | Henry James L. | Oligonucleotides and other modulators of the NK-1 receptor pathway and therapeutic uses thereof |
DE60115958T2 (de) * | 2000-09-18 | 2006-08-03 | Genencor International, Inc., Palo Alto | Zwillingsarginin translokation in bacillus |
FR2857667B1 (fr) * | 2003-07-18 | 2007-07-13 | Inst Europ Biolog Cellulaire | Nouveaux conjugues peptidiques utiles dans le traitement preventif et curatif de l'alopecie |
JP2005239695A (ja) | 2004-02-27 | 2005-09-08 | Mitsui Chemicals Inc | TGF−β産生抑制ペプチド |
JPWO2005082395A1 (ja) * | 2004-03-02 | 2008-01-17 | 国立大学法人京都大学 | 新規な育毛剤、抗脱毛症剤 |
JP4461261B2 (ja) * | 2004-05-27 | 2010-05-12 | 国立大学法人京都大学 | 新規な育毛剤 |
JP4861686B2 (ja) * | 2005-11-17 | 2012-01-25 | ライオン株式会社 | 神経栄養因子−4(Neurotrophin−4)アンタゴニスト |
JP5048372B2 (ja) * | 2007-03-30 | 2012-10-17 | 日本サプリメント株式会社 | 育毛促進剤 |
KR101163171B1 (ko) * | 2009-01-20 | 2012-07-19 | (주)케어젠 | 노긴?유래 펩타이드 및 그의 용도 |
KR101187871B1 (ko) * | 2009-09-23 | 2012-10-05 | (주)케어젠 | Fgf10-유래 펩타이드 및 그의 용도 |
KR101337767B1 (ko) * | 2011-07-26 | 2013-12-09 | 서울대학교산학협력단 | Vegf 발현을 증가시키는 신규한 펩타이드 및 이를 함유하는 약학적 조성물 |
KR101285263B1 (ko) * | 2011-08-04 | 2013-07-11 | (주)케어젠 | Edar 리간드 유래 펩타이드 및 이의 용도 |
KR101285259B1 (ko) * | 2011-08-04 | 2013-07-11 | (주)케어젠 | Wnt 계열 유래 펩타이드 및 이의 용도 |
KR20140107784A (ko) * | 2013-02-28 | 2014-09-05 | 주식회사 크라운진 | 탈모 방지 및 모발 성장 촉진용 조성물 |
KR20150130616A (ko) * | 2014-05-13 | 2015-11-24 | (주)케어젠 | 피부상태 개선 활성을 갖는 펩타이드 및 이의 용도 |
KR101632948B1 (ko) | 2014-05-13 | 2016-06-27 | (주)케어젠 | 항염증, 골 형성 및 발모 촉진 활성을 갖는 펩타이드 및 이의 용도 |
KR101618335B1 (ko) * | 2015-12-21 | 2016-05-19 | (주)케어젠 | 항염증, 골 형성 및 발모 촉진 활성을 갖는 펩타이드 및 이의 용도 |
KR101618329B1 (ko) | 2015-12-21 | 2016-05-19 | (주)케어젠 | 항염증, 골 형성 및 발모 촉진 활성을 갖는 펩타이드 및 이의 용도 |
KR101841748B1 (ko) * | 2016-02-18 | 2018-05-08 | (주)케어젠 | 멜라닌 생성 촉진 활성을 나타내는 펩타이드 및 이의 용도 |
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