JP5342455B2 - 細胞調整及び免疫調整のための短い生物活性ペプチド - Google Patents
細胞調整及び免疫調整のための短い生物活性ペプチド Download PDFInfo
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Description
本発明は、哺乳類の傷治癒を促進するために効果的な短い生物活性ペプチドに関する。単離されたペプチドにより好ましく目標とされる傷は、皮膚に影響し粘膜表面に関連する傷である。特定のメカニズムに限定するものではないが、最適の治癒過程を損ねる可能性のある炎症の抑制と同様に、発明のペプチドは細胞増殖及び移動の促進により、傷治癒に効果を及ぼすことができる。発明のペプチドは生体内及び生体外の両方において役立ち、角化細胞において上記に述べた活性を誘発することが可能である。
米国特許第5,962,410号と第5,861,478号は、本発明の理解に役立つ開示をもたらし、これらの開示は引用を以て本願に記載加入とする。その発明は短い、生物活性ペプチドに関して教示する、たとえば、ペプチドHB−107(配列番号1)に由来するペプチド及びその使用法に関してである。ペプチドHB−107自体は、セクロピンBの一部分を構成し、それは、蛾の種に存在する抗菌ペプチドである。HB−107はそれが由来するタンパク質の静菌効果を示さないが、表皮の傷治癒特性を示す(Lee at al., 2004)。
さらなる現発明の実施例は、製剤或いは治療剤のように、上述のペプチドの使用について教示する。これらの方法は、一つのペプチドまたは複数のペプチドの使用の組合せに関係するかもしれない。
予め、HB−107(配列番号1)ペプチドフラグメントが、体内にいて創傷治癒を促進することを示すために、HB−107配列中に、創傷治癒及び関連するプロセスを同じように又はより刺激する短いペプチドフラグメントがさらに存在するとの仮説を立てた。この疑問を検証するために、HB−107のペプチドフラグメントの重複セットを標準固相ペプチド化学を用いて生成した。これらのペプチドを次に、濃度0.22、2.15、21.5及び46.4μg/mlで細胞増殖活性のために分析した。ペプチドの多くは、夫々7アミノと6アミノを含有するのみであるペプチドHB−1061(配列番号3)及びHD−1072(配列番号6)を含め、低濃度で表皮角化細胞の増殖が顕著に増大した(表2)。幾つかの他のペプチドは、HB−107の刺激活性とほぼ同等又はそれ以上のレベルの刺激活性を呈した(表2)。結果として、発明のペプチドの多くによって誘発される細胞増殖は、親HB−107ペプチドによって誘発されるレベルを超えていた。重要なのは、これらのフラグメントの内の幾つかは、HB−107よりも極めて短いことである。
試薬:
細胞プレーティング
サンプル調製
投薬
データの分析
EC50計算:各テストサンプルについて、データを対照吸光度対濃度のパーセントでプロットする。EC50は、エクセル5.0グラフでデータを通じて引いた回帰線から推定する。さらに、EC50は、エクセル5.0グラフによって、又は、エクセル5.0マクロを用いることによってもたらされる回帰線に対する方程式を用いて計算する。
細胞増殖だけでは、創傷治癒に役立つには十分ではない。損傷を受けた状態で、創傷に隣接する細胞が増殖する;そのような損傷(又は古い機能異常の組織の慢性病巣)の近くで新たに形成された細胞の移動は、等しく重要である。この問題を対処するために、単一組織培養スクラッチテストに基づいて角化細胞移動分析を用いて、HB−107とそのペプチドフラグメントを観察した。この分析は、HB−1072(配列番号6)やHB−1061(配列番号3)のようなペプチドが親HB−107ペプチドと同様に細胞移動を増大させることができることを示した(表3)。HB−1072とHB−1061ペプチドは、HB−107の一部と重複しており、アナログHB−1062(配列番号4)は、細胞に移動活性を示さないことに気付いたことは興味深いものである。この分析のプロトコルは標準的であり、Shanleyらによって記述されており(2004, Invest. Ophthalmol. Vis. Sci. 45:1088-1094)、この論文の引用を以て全文の記載加入とする。
治癒の割合いの増大に加えて、ペプチドHB−107は、創傷に関連する炎症のレベルを減少させることが示されている。そのような活動を呈する小ペプチドフラグメントを識別するために、HB−107のフラグメントが、主要な炎症性サイトカインIL6を減じる活動を探った。ペプチドフラグメントHB−802(配列番号12)とHB−1076(配列番号8)は、IL6発現のレベルが、HB−107親ペプチドと同程度まで減じられたことがわかった(表4)。この分析のプロトコルは標準的であり、Murakamiらによって記述されており(2004, J.Immunol. 172:3070-3037)、この論文の引用を以て全文の記載加入とする。
ある小ペプチドが、静止細胞中で抗炎症活動を促進することができることを前提として(実施例3参照)、小ペプチドが、UVB放射に曝された細胞中で、そにょうな活動を促進できることは興味深いものである。UVB放射は、肌にダメージを与え、肌のエージングを促進する。ダメージを受けた組織中の炎症は、その組織のエージングの一因であるので、紫外線光により誘発されるダメージに由来する表皮炎症の現象は、そのエージング効果を小さくすることとなる。
Braff MH, Gallo RL (2006). Antimicrobial peptides: an essential component of the skin defensive barrier. Curr. Top. Microbiol. Immunol. 306:91-110.
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Claims (10)
- 単離ペプチドであって、ペプチドは、配列番号2、配列番号3、配列番号5、配列番号6、配列番号7、配列番号8、配列番号9、配列番号10、配列番号11、配列番号12、又は、配列番号15である、単離ペプチド。
- ペプチドは、Lアミノ酸鏡像体及びDアミノ酸鏡像体の何れか又は両方であるか、及び/又は、担体分子に結合されるか、アミド化されるか若しくは脂質化される請求項1に記載のペプチド。
- ペプチドは、配列番号2、配列番号3、配列番号5、配列番号6、配列番号7、配列番号9、配列番号10、配列番号11、又は、配列番号12である請求項1に記載のペプチド。
- ペプチドは、配列番号3、配列番号8、配列番号12、又は、配列番号15である請求項1に記載のペプチド。
- 請求項1乃至4の何れかに記載の少なくとも1のペプチドと薬学的に許容できるキャリアを含む組成物。
- ペプチドは、0.1μg/mLから50μg/mLの濃度範囲又は0.1μg/mLから20μg/mLの濃度範囲で存在する請求項5に記載の組成物。
- 組成物は、エアゾール、エマルジョン、液体、ローション、クリーム、ペースト、軟膏、粉又は泡の形態である請求項5に記載の組成物。
- 治療に効果的な量を、効果的な時間適用することにより、哺乳類の創傷を治癒させるために用いられる薬剤の製造における、請求項5又は6に記載の組成物の使用。
- 創傷は、前記哺乳類の皮膚又は粘膜組織に影響を与える請求項8の使用。
- 創傷は、擦り傷、水膨れ、やけど、裂傷、潰瘍、打撲、発疹、傷跡、又は、エージング若しくは環境曝露による影響に起因する請求項8の使用。
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JPS6360939A (ja) * | 1986-08-29 | 1988-03-17 | Shin Etsu Chem Co Ltd | 抗菌物質 |
WO1989000194A1 (en) | 1987-07-06 | 1989-01-12 | Louisiana State University Agricultural And Mechan | Inhibition of eucaryotic pathogens and neoplasms and stimulation of fibroblasts and lymphocytes with lytic peptides |
US5861478A (en) | 1987-07-06 | 1999-01-19 | Helix Biomedix, Inc. | Lytic peptides |
EP0365655B1 (en) | 1988-04-21 | 1994-09-21 | Uab Research Foundation | Bioelastomeric materials suitable for the protection of wound repair sites from the occurrence of adhesions |
AU647732B2 (en) * | 1989-01-31 | 1994-03-31 | Stuart A. Aaronson | DNA encoding a growth factor specific for epithelial cells |
AU5433190A (en) * | 1989-04-10 | 1990-11-16 | Louisiana State University And Agricultural And Mechanical College | Lytic peptides, use for growth, infection and cancer |
US5561107A (en) | 1993-06-04 | 1996-10-01 | Demeter Biotechnologies, Ltd. | Method of enhancing wound healing by stimulating fibroblast and keratinocyte growth in vivo, utilizing amphipathic peptides |
US5763576A (en) | 1995-10-06 | 1998-06-09 | Georgia Tech Research Corp. | Tetrapeptide α-ketoamides |
EP0858808B1 (en) | 1997-01-17 | 2003-04-02 | Johnson & Johnson Medical Ltd. | Peptides for use in wound treatment |
US6492326B1 (en) | 1999-04-19 | 2002-12-10 | The Procter & Gamble Company | Skin care compositions containing combination of skin care actives |
CA2276542C (en) | 1999-06-28 | 2013-07-30 | Vladislav I. Deigin | Novel peptide, a method for its preparation and a pharmaceutical composition containing the peptide |
KR100385293B1 (ko) * | 2000-05-13 | 2003-05-23 | 주식회사 리젠 바이오텍 | βig-h3의 일부 도메인을 이용한 세포 부착 및 창상치유 방법 |
GB0029777D0 (en) | 2000-12-06 | 2001-01-17 | Regen Therapeutics Plc | Peptides |
JP4310107B2 (ja) * | 2001-03-28 | 2009-08-05 | ヘリックス バイオメディックス,インコーポレイテッド | 生物活性を有する短ペプチド及び該ペプチドの使用方法 |
US6875744B2 (en) * | 2001-03-28 | 2005-04-05 | Helix Biomedix, Inc. | Short bioactive peptides |
US7041506B2 (en) | 2001-11-19 | 2006-05-09 | Becton Dickinson And Company | Peptides promoting cell adherence, growth and secretion |
CA2468187A1 (en) | 2001-11-28 | 2003-06-05 | Becton, Dickinson And Company | Peptides with growth inhibitory action |
US20040009911A1 (en) | 2002-01-31 | 2004-01-15 | Irm, Llc | Hepsin substrates and prodrugs |
US7491691B2 (en) | 2002-05-03 | 2009-02-17 | Sindrey Dennis R | Connective tissue stimulating peptides |
US7541440B2 (en) | 2002-09-30 | 2009-06-02 | Immunomedics, Inc. | Chimeric, human and humanized anti-granulocyte antibodies and methods of use |
EP1686957B1 (en) | 2003-11-17 | 2012-03-07 | Sederma | Compositions containing mixtures of tetrapeptides and tripeptides |
DE102004055541A1 (de) | 2004-11-17 | 2006-05-18 | Henkel Kgaa | Kosmetische und dermatologische Zusammensetzungen zur Behandlung reifer Haut |
DE102005000868A1 (de) | 2004-10-15 | 2006-04-20 | Henkel Kgaa | Zusammensetzungen mit Inhibitoren der Prostaglandin- und/oder Leukotrien-Synthese in Kombination mit Stimulatoren der Freisetzung kutaner Neuromediatoren |
DE202004012807U1 (de) | 2004-08-13 | 2004-10-21 | Henkel Kgaa | Kosmetische und dermatologische Zusammensetzungen mit DNA-Reparaturenzymen und Oligopeptiden |
DE102004050563A1 (de) | 2004-10-15 | 2006-04-20 | Henkel Kgaa | Kosmetische und der dermatologische Zusammensetzungen mit Wirkstoffen für einen verbesserten Hautkomfort |
US20060046271A1 (en) | 2004-09-02 | 2006-03-02 | Vanderbilt University | Assessment of cancer susceptibility to molecular targeted therapy by use of recombinant peptides |
US20070224150A1 (en) | 2005-03-24 | 2007-09-27 | Yongji Chung | Growth factor for hair and skin treatment |
FR2884418B1 (fr) | 2005-04-15 | 2008-11-21 | Soc Extraction Principes Actif | Utilisation d'un peptide comme principe actif amincissant |
WO2007004869A2 (en) | 2005-07-05 | 2007-01-11 | Biotempt B.V. | Treatment of tumors |
DE102005063062A1 (de) | 2005-12-29 | 2007-07-05 | Henkel Kgaa | Synergistische Proteinhydrolysat-Kombinationen zur Behandlung reifer Haut |
US7807625B2 (en) | 2006-01-18 | 2010-10-05 | Grant Industries, Inc | Anti-wrinkle composition |
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- 2007-12-27 CN CN200780051983XA patent/CN101679495B/zh active Active
- 2007-12-27 RU RU2009129950/10A patent/RU2458069C2/ru active
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- 2007-12-27 US US12/005,653 patent/US7696174B2/en active Active
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BRPI0720874A2 (pt) | 2014-03-04 |
PL2125878T3 (pl) | 2013-08-30 |
HK1137463A1 (en) | 2010-07-30 |
SI2125878T1 (sl) | 2013-06-28 |
AU2007342353B2 (en) | 2012-06-28 |
DK2125878T3 (da) | 2013-05-27 |
MX2009007248A (es) | 2009-08-17 |
AU2007342353A1 (en) | 2008-07-17 |
RU2009129950A (ru) | 2011-02-10 |
US20080206160A1 (en) | 2008-08-28 |
EP2125878B1 (en) | 2013-02-20 |
US7696174B2 (en) | 2010-04-13 |
EP2125878A1 (en) | 2009-12-02 |
CY1114002T1 (el) | 2016-07-27 |
RU2458069C2 (ru) | 2012-08-10 |
CA2673791A1 (en) | 2008-07-17 |
CA2673791C (en) | 2014-11-25 |
BRPI0720874C1 (pt) | 2021-05-25 |
CN101679495A (zh) | 2010-03-24 |
JP2010515679A (ja) | 2010-05-13 |
BRPI0720874B1 (pt) | 2018-11-21 |
ES2404669T3 (es) | 2013-05-28 |
CN101679495B (zh) | 2013-07-17 |
WO2008085494A1 (en) | 2008-07-17 |
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