JP2019513750A - テロメラーゼ活性の増加及びテロメアの延長の効能を有するペプチド、及びこれを含む組成物 - Google Patents
テロメラーゼ活性の増加及びテロメアの延長の効能を有するペプチド、及びこれを含む組成物 Download PDFInfo
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Abstract
Description
配列番号1のペプチドを含有する。適当な濃度の選択は、例えば、好ましい投与量、頻度及び活性成分の送達方法のような因子に依存的である。
配列番号1のペプチド(以下、「PEP1」という)を、従来知られている固相ペプチド合成法(solid phase peptide synthesis, SPPS)に従って製造した。具体的に、ペプチドは、ASP48S(Peptron, Inc., 大韓民国・大田)を用いて、Fmoc固相合成法でC−末端からアミノ酸を一つずつカップリングすることにより合成した。以下のように、ペプチドのC−末端の一番目のアミノ酸が、レジンに付着されたものを用いた。例えば、次の通りである。
NH2−Ala−2−クロロ−トリチルレジン
NH2−Arg(Pbf)−2−クロロ−トリチルレジン
ペプチドの合成に用いた全てのアミノ酸原料は、N−末端がFmocで保護(protection)され、残基は全て酸で除去される、Trt、Boc、t−Bu(t-ブチルエステル)、Pbf(2、2、4、6、7−ペンタメチルジヒドロ−ベンゾフラン−5−スルフォニル)などで保護されたものを用いた。例えば、次の通りである。
NH2−Lys(Boc)−2−クロロ−トリチルレジンに、保護されたアミノ酸(8当量)と、カップリング試薬HBTU(8当量)/HOBt(8当量)/NMM(16当量)とをDMFに溶解して加えた後、常温で2時間反応させ、DMF、MeOH 、DMFの順に洗浄した。
20%のDMF中のピペリジン(piperidine in DMF)を加えて、常温で5分間2回反応させ、DMF、MeOH 、DMFの順に洗浄した。
実施例2−1:実験動物の用意
動物に関する全ての手続きは、ハンヤン大学校(Hanyang University)の実験動物ガイドラインに従って進行した。全ての実験は、動物の個体数と、苦痛とを最小化し、全ての動物は、一度だけ使用した。
2群:0.01mg/kgのPEP1
3群:0.1mg/kgのPEP1
4群:1mg/kgの PEP1
5群:1mg/kgのドネペジル
PEP1、食塩水及びドネペジルは、12ケ月のときから2ケ月の間、1週間に3回ずつ、各濃度別に皮下注射した後、1ケ月後(15ケ月令)に、マウス(各群当りの10匹)を麻酔した後、0.9%食塩水を用いて、マウスの心臓を通した再灌流を行い、全血を除去した。その後、脳を摘出し、海馬部位と、全体の脳部位とに分離して、脳組織を得た後、液体窒素を用いて、急激に凍らせた。
テロメラーゼの活性及びテロメアの長さが、時間が経つにつれ、減少されることを確認するために、アルツハイマー誘導の動物モデルの7ケ月令(AD Tg 7Mとして表示)と、15ケ月令(AD Tg 15Mとして表示)において、実施例2−1の方法で脳組織を得て、テロメラーゼの活性及びテロメアの長さを測定した。
全ての統計的検証において、SPSS21統計プログラムと、統計サイト(http://vassarstats.net)とを用いた。等間尺度や比率尺度で測定したデータは、mean±S.E.M.として示し、母数統計のためには、一元配置分散分析(one-way ANOVA test)又は2元配置分散分析(two-way ANOVA test)の後、チューキー検定(Tukey test)で事後検定を行い、非母数統計のためには、クラスカル−ウォリス検定(Kruskal-Wallis test)、マン・ホイットニーのU検定(Mann-Witney U-test)を用いて分析した。各群間の比較は、チューキー検定法を行った。命名尺度の場合、カイ二乗検定(chi-square test)を用いて、群間の比較を行った。p値が0.05未満の場合に、統計学的に有意であると判定した。
実施例3−1:テロメラーゼ活性の測定結果
PEP1がテロメラーゼ活性を増加するかを確認するために、実施例2−1及び2−2による方法を通じて測定した。その結果、PEP1(0.1mg/kg)投与群(3群)において、食塩水投与群(1群)対比の増加率が266%を示し、 PEP1(1mg/kg)投与群(4群)において、食塩水投与群(1群)対比の増加率が370%を示し、ドネペジル(1mg/kg)投与群(5群)と対比しても、統計的に有意に増加した(図1参照)。また、テロメラーゼ活性が、7ケ月令(AD Tg 7M)に比べて、15ケ月令(AD Tg 15M)において減少されたことも確認した。
PEP1が示したテロメラーゼ活性の増加率が、テロメア長の維持又は増加にも直接的な影響を及ぼすかを確認するために、テロメア長の測定実験を、実施例2−2による方法を通じて実施した。その結果、テロメラーゼ活性の増加の結果と同様に、PEP1の投与濃度に応じて、テロメアの長さが増加する結果が現れた(図2参照)。これは、 PEP1がテロメアの長さもまた増大させ、これにより染色体の安定性の増大及び細胞保護の効果を与えることが分かる。また、テロメアの長さは、7ケ月令(AD Tg 7M)に比べ、15ケ月令(AD Tg 15M)において減少されたことも確認した。
Claims (11)
- 配列番号1のアミノ酸配列を含むペプチド、該アミノ酸配列と80%以上の配列相同性を有するペプチド、及びそのフラグメントであるペプチドからなる群から選ばれる一つ以上を、薬学的に有効な量で含む、テロメラーゼ活性の増加又はテロメア長の延長のための組成物。
- 前記組成物は、テロメラーゼ活性の減少又はテロメア長の減少により誘導される疾患、又は細胞損失及び老化による症状を、予防又は治療することを特徴とする、テロメラーゼ活性の増加又はテロメア長の延長のための、請求項1に記載の組成物。
- 前記疾患は、神経変性疾患、神経系退行性疾患、骨格系の退行性疾患、筋肉系の退行性疾患、ウィルス性感染疾患、加速化された細胞死亡率を誘発する遺伝的疾患から選ばれる一つ以上の疾患であることを特徴とする、テロメラーゼ活性の増加又はテロメア長の延長のための、請求項2に記載の組成物。
- 前記神経系退行性疾患は、脳疾患、脊髄損傷、末梢神経損傷、抹消神経系疾患、筋萎縮性側索硬化症(amyotrophic lateral sclerosis)、痴呆、ハンチントン病、パーキンソン病、アルツハイマー性疾患、脊髄小脳変性症、及び多発性神経病症のうちいずれか一つであることを特徴とする、テロメラーゼ活性の増加又はテロメア長の延長のための、請求項3に記載の組成物。
- 前記細胞損失及び老化による症状は、皮膚の創傷による組織の損失、皮膚のシワ、貧血、皮膚の乾癬、皮膚の癌化から選ばれる一つ以上の症状であることを特徴とする、テロメラーゼ活性の増加又はテロメア長の延長のための、請求項2に記載の組成物。
- 請求項1から請求項5のうちいずれか一つに記載の組成物を活性成分とする、テロメラーゼ活性の増加又はテロメア長の延長のための薬学的組成物。
- 前記薬学的組成物は、配列番号1のペプチドが、0.1μg/kg〜100mg/kgで投与されるようにすることを特徴とする、テロメラーゼ活性の増加又はテロメア長の延長のための、請求項6に記載の薬学的組成物。
- 請求項1から請求項5のうちいずれか一つに記載の組成物を活性成分とする、テロメラーゼ活性の増加又はテロメア長の延長のための健康機能食品用組成物。
- 前記組成物は、粉末、顆粒、丸、錠剤、カプセル、キャンディ、シロップ及び飲料から選ばれたいずれか一つの剤形として製造されることを特徴とする、請求項8に記載の健康機能食品用組成物。
- 請求項1から請求項5のうちいずれか一つに記載の組成物を活性成分とする、テロメラーゼ活性の増加又はテロメア長の延長のための化粧用組成物。
- 前記化粧用組成物は、スキン、ロション、クリーム、ファウンデーション、エッセンス,ジェル、パック、フォームクレンジング、石鹸及び皮膚外用軟膏からなる群より選ばれるいずれか一つの剤形を有することを特徴する、テロメラーゼ活性の増加又はテロメア長の延長のための、請求項10に記載の化粧用組成物。
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KR102413243B1 (ko) | 2014-12-23 | 2022-06-27 | 주식회사 젬백스앤카엘 | 안질환 치료 펩티드 및 이를 포함하는 안질환 치료용 조성물 |
EP3263122B1 (en) | 2015-02-27 | 2020-05-06 | Gemvax & Kael Co., Ltd. | Peptide for preventing hearing loss, and composition comprising same |
US11015179B2 (en) | 2015-07-02 | 2021-05-25 | Gemvax & Kael Co., Ltd. | Peptide having anti-viral effect and composition containing same |
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KR20170054310A (ko) | 2015-11-09 | 2017-05-17 | 주식회사 젬백스앤카엘 | 텔로머라제 유래 펩티드를 포함하는 수지상세포 치료제 및 면역 치료제, 및 이를 사용하는 치료방법 |
EP3441082B1 (en) | 2016-04-07 | 2023-06-21 | Gemvax & Kael Co., Ltd. | Peptide having effects of increasing telomerase activity and extending telomere, and composition containing same |
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2017
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- 2017-04-07 KR KR1020237005976A patent/KR20230028596A/ko not_active Application Discontinuation
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WO2014171792A1 (ko) * | 2013-04-19 | 2014-10-23 | 주식회사 카엘젬백스 | 허혈성 손상 치료 및 예방용 조성물 |
KR20140140396A (ko) * | 2013-05-29 | 2014-12-09 | 주식회사 카엘젬백스 | 피부 주름 개선 및 미백용 조성물 |
WO2015067781A1 (en) * | 2013-11-07 | 2015-05-14 | Centre National De La Recherche Scientifique (Cnrs) | New methods to produce active tert |
KR20150128336A (ko) * | 2014-05-09 | 2015-11-18 | 주식회사 젬백스앤카엘 | 텔로머라제 펩티드를 유효성분으로 포함하는 뇌혈관 질환 예방 또는 치료용 조성물 |
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US10898540B2 (en) | 2021-01-26 |
JP7114481B2 (ja) | 2022-08-08 |
KR20230028596A (ko) | 2023-02-28 |
EP3441082C0 (en) | 2023-06-21 |
CN109328068A (zh) | 2019-02-12 |
EP3441082A4 (en) | 2019-12-25 |
CN117018162A (zh) | 2023-11-10 |
KR20180123512A (ko) | 2018-11-16 |
EP3441082A1 (en) | 2019-02-13 |
ES2949697T3 (es) | 2023-10-02 |
EP4272829A3 (en) | 2024-01-17 |
EP3441082B1 (en) | 2023-06-21 |
US20190142894A1 (en) | 2019-05-16 |
WO2017176087A1 (ko) | 2017-10-12 |
EP4272829A2 (en) | 2023-11-08 |
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