JP2006500341A - プレプチン機能を有する化合物の使用方法 - Google Patents
プレプチン機能を有する化合物の使用方法 Download PDFInfo
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- JP2006500341A JP2006500341A JP2004525887A JP2004525887A JP2006500341A JP 2006500341 A JP2006500341 A JP 2006500341A JP 2004525887 A JP2004525887 A JP 2004525887A JP 2004525887 A JP2004525887 A JP 2004525887A JP 2006500341 A JP2006500341 A JP 2006500341A
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- preptin
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Abstract
Description
本明細書中使用する「プレプチン」とは、その配列が以下の式(I):
Asp Val Ser Thr R1 R2 R3 Val Leu Pro Asp R4 Phe Pro Arg Tyr Pro Val Gly Lys Phe
25 30
Phe R5 R6 Asp Thr Trp R7 Gln Ser R8 R9 Arg Leu 式(I)
1 5 10 15 20
Asp Val Ser Thr Pro Pro Thr Val Leu Pro Asp Asn Phe Pro Arg Tyr Pro Val Gly Lys
25 30
Phe Phe Gln Tyr Asp Thr Trp Lys Gln Ser Thr Gln Arg Leu
1 5 10 15 20
Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys
25 30
Phe Phe Lys Phe Asp Thr Trp Arg Gln Ser Ala Gly Arg Leu
1 5 10 15 20
Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys
25 30
Phe Phe Gln Tyr Asp Thr Trp Arg Gln Ser Ala Gly Arg Leu。
遺伝子治療に対するex vivo生体外アプローチもまた本発明で企図されており、患者自身の細胞の除去、遺伝子修飾、拡張および再投与を包含する。例として、糖尿病治療のためのβ細胞移植または前駆細胞の遺伝的修飾がある。
「β細胞質量」という語はβ細胞の質量および/または重量を指す。
「β細胞増殖」という語は、β細胞数の増加を指す。
「β細胞またはβ細胞質量の減少または無防備状態」とは、全体として、または部分的に、正常または望ましい身体機能にとって正常以下のまたは不充分なβ細胞および/またはβ細胞質量を特徴とする状態を包含する。
本明細書中使用する「精製された」とは、完全に純粋である必要はなく、当該蛋白またはその他の物質が、細胞内の天然環境またはその他の環境、例えば製造環境にあるよりも純粋である場合の相対的用語であることを意図している。実際に当該材料を典型的には例えば分画に付して種々のその他の成分を除去したところ、得られた材料は、その望ましい生物活性または生物活性群を実質的に保持していた。
「β細胞仲介疾患」とは、その疾患の病理において、全体または何らかの部分にβ細胞が関わっている任意の疾患である。β細胞仲介疾患は、例えば1型または2型糖尿病を包含する。
好適な担体は、鉱油(mineral oil)、モノステアリン酸ソルビタン、ポリソルベート60、セチルエステルロウ、セテアリールアルコール、2-オクチルドデカノール、ベンジルアルコールおよび水を包含するが、これらに限定される訳ではない。
<NIH-3T3細胞の増殖の刺激>
NIH-3T3細胞は、有糸分裂促進性の調査に関する研究を包含する様々な目的のために使用できる。例えば、Buergisser et al. (1990). BiochemBiophys Res Comm 169(3):832-839;Burgisser et al. (1991). J Biol Chem 266(2):1029-33;Yang et al. (1996). Endocrinol 137(7):2766-2773;Geddes et al. (2001). Prot Engin 14(1):61-65を参照されたい。
<INS-1E β細胞の増殖の刺激>
INS-1E細胞を2 x 105細胞/ウェルの密度で24ウェルプレートに蒔いた。細胞を、改良RPMI-1640(GIBCO R-1383 Lot108H83032;23.8mM 炭酸水素ナトリウム、2mM L-グルタミン、10mM HEPES、50μM β-メルカプトエタノール、1mM ピルビン酸ナトリウム、105 IU/lペニシリン、0.01% 硫酸ストレプトマイシンを添加)および10% 牛胎児血清中で37℃で24時間成長させ、その後これらを改良RPMI-1640中で24時間血清枯渇させた。次にこの無血清培地を、0% 牛胎児血清(負の対照)、10% 牛胎児血清(正の対照)、10nM ラットプレプチン(rPreptin 10nM)、10nM ヒトGLP-1(hGLP-1 10nM)、10nM ヒトIGF-II(hIGF-II 10nM)を含有するRPMI-1640 500μlに交換し、細胞をさらに18時間インキュベートし、その後各ウェルに5μCiの3H-チミジンを添加した。さらに6時間インキュベートした後、培地を吸引し、細胞を、冷PBSで2回、冷5%TCAで1回、そして冷100%エタノールで2回洗浄した。次いでプレートを30分間風乾し、細胞を0.5M NaOH 400μlで可溶化した。次にこのアルカリ性細胞溶解液を0.5M HCl 400μlで中和し、その後500μlアリコートをStarscintシンチレーション液2mlと混合し、シンチレーションカウンターで計数した。シンチレーションカウンターから得られる1分あたりのカウント(cpm)の増加が3H-チミジン取り込みの増加を示し、結果として細胞増殖の増大を示す。細胞増殖の結果を図2に示す。
Claims (65)
- 対象において減少したβ細胞質量および/または減少したβ細胞数を特徴とする、もしくはそれらを含む、またはそれらを改善することによりある程度緩和できる症状の治療方法であって、プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を該対象に投与することを含む、前記方法。
- 前記プレプチンが、アミノ酸配列Asp Val Ser Thr Pro Pro Thr Val Leu Pro Asp Asn Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Lys Gln Ser Thr Gln Arg Leu(配列番号1)を含むヒトプレプチン、アミノ酸配列Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Lys Phe Asp Thr Trp Arg Gln Ser Ala Gly Arg Leu(配列番号2)を含むラットプレプチン、およびアミノ酸配列 Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Arg Gln Ser Ala Gly Arg Leu(配列番号3)を含むマウスプレプチンよりなる群から選ばれる、請求項1に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2もしくは3のアミノ酸配列のフラグメントまたは全体を含む、請求項1に記載の方法。
- 前記フラグメントが、配列番号1、2または3の残基17-34を含む、請求項3に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2または3と少なくとも約60%一致するアミノ酸配列を含む、請求項1に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2または3と少なくとも約80%一致するアミノ酸配列を含む、請求項5に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2または3と少なくとも約90%一致するアミノ酸配列を含む、請求項5に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2または3と少なくとも約95%一致するアミノ酸配列を含む、請求項5に記載の方法。
- 前記プレプチンアゴニストが、約14までの保存的その他のアミノ酸置換を有する配列番号1、2または3を含む、請求項1に記載の方法。
- 前記プレプチンアゴニストが、約10〜13までの保存的その他のアミノ酸置換を有する配列番号1、2または3を含む、請求項9に記載の方法。
- 前記プレプチンアゴニストが、約6〜9までの保存的その他のアミノ酸置換を有する配列番号1、2または3を含む、請求項9に記載の方法。
- 前記プレプチンアゴニストが、約2〜5までの保存的その他のアミノ酸置換を有する配列番号1、2または3を含む、請求項9に記載の方法。
- プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を、それを必要とする対象に投与することを含む、β細胞質量および/またはβ細胞数を増加または維持する方法。
- 前記プレプチンが、アミノ酸配列Asp Val Ser Thr Pro Pro Thr Val Leu Pro Asp Asn Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Lys Gln Ser Thr Gln Arg Leu(配列番号1)を含むヒトプレプチン、アミノ酸配列Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Lys Phe Asp Thr Trp Arg Gln Ser Ala Gly Arg Leu(配列番号2)を含むラットプレプチン、およびアミノ酸配列 Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Arg Gln Ser Ala Gly Arg Leu(配列番号3)を含むマウスプレプチンよりなる群から選ばれる、請求項13に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2もしくは3のアミノ酸配列のフラグメントまたは全体を含む、請求項13に記載の方法。
- 前記フラグメントが、配列番号1、2または3の残基17-34を含む、請求項15に記載の方法。
- 前記プレプチンアゴニストが、(1) 配列番号1、2または3と少なくとも約60%一致するアミノ酸配列、(2) 配列番号1、2または3と少なくとも約80%一致するアミノ酸配列、(3) 配列番号1、2または3と少なくとも約90%一致するアミノ酸配列、および(4) 配列番号1、2または3と少なくとも95%一致するアミノ酸配列、よりなる群から選ばれるペプチドを含む、請求項13に記載の方法。
- 前記プレプチンアゴニストが、(1) 約14までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(2) 約10〜13までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(3) 約6〜9までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(4) 約2〜5までの保存的その他のアミノ酸置換を有する配列番号1、2または3、を含むペプチドよりなる群から選ばれる、請求項13に記載の方法。
- プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を、それを必要とする対象に投与することを含む、β細胞増殖の成長および/またはβ細胞質量の増加を刺激する方法。
- 前記プレプチンが、アミノ酸配列Asp Val Ser Thr Pro Pro Thr Val Leu Pro Asp Asn Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Lys Gln Ser Thr Gln Arg Leuを含むヒトプレプチン、アミノ酸配列Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Lys Phe Asp Thr Trp Arg Gln Ser Ala Gly Arg Leuを含むラットプレプチン、およびアミノ酸配列 Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Arg Gln Ser Ala Gly Arg Leuを含むマウスプレプチンよりなる群から選ばれる、請求項19に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2もしくはは3のアミノ酸配列のフラグメントまたは全体を含む、請求項19に記載の方法。
- 前記フラグメントが、配列番号1、2または3のアミノ酸残基17-34を含む、請求項21に記載の方法。
- 前記プレプチンアゴニストが、(1) 配列番号1、2または3と少なくとも約60%一致するアミノ酸配列、(2) 配列番号1、2または3と少なくとも約80%一致するアミノ酸配列、(3) 配列番号1、2または3と少なくとも約90%一致するアミノ酸配列、および(4) 配列番号1、2または3と少なくとも約95%一致するアミノ酸配列、よりなる群から選ばれるペプチドを含む、請求項19に記載の方法。
- 前記プレプチンアゴニストが、(1) 約14までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(2) 約10〜13の保存的その他のアミノ酸置換を有する配列番号1、2または3、(3) 約6〜9までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(4) 約2〜5までの保存的その他のアミノ酸置換を有する配列番号1、2または3、を含むペプチドよりなる群から選ばれる、請求項19に記載の方法。
- 前記プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を対象に投与することを含む、該対象における、β細胞又はβ細胞機能不全によって全体もしくは一部が仲介される仲介疾患、症状の異常を治療する方法。
- 前記プレプチンが、アミノ酸配列Asp Val Ser Thr Pro Pro Thr Val Leu Pro Asp Asn Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Lys Gln Ser Thr Gln Arg Leuを含むヒトプレプチン、アミノ酸配列Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Lys Phe Asp Thr Trp Arg Gln Ser Ala Gly Arg Leuを含むラットプレプチン、およびアミノ酸配列 Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Arg Gln Ser Ala Gly Arg Leuを含むマウスプレプチンよりなる群から選ばれる、請求項25に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2もしくは3のアミノ酸配列のフラグメントまたは全体を含む、請求項25に記載の方法。
- 前記疾患が、1型糖尿病または2型糖尿病である、請求項25に記載の方法。
- プレプチン、プレプチン類縁体、および/またはプレプチンアゴニストの有効量を対象に投与することを含む、該対象におけるインスリン分泌を増大させる方法。
- 前記プレプチンが、アミノ酸配列Asp Val Ser Thr Pro Pro Thr Val Leu Pro Asp Asn Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Lys Gln Ser Thr Gln Arg Leuを含むヒトプレプチン、アミノ酸配列Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Lys Phe Asp Thr Trp Arg Gln Ser Ala Gly Arg Leuを含むラットプレプチン、およびアミノ酸配列 Asp Val Ser Thr Ser Gln Ala Val Leu Pro Asp Asp Phe Pro Arg Tyr Pro Val Gly Lys Phe Phe Gln Tyr Asp Thr Trp Arg Gln Ser Ala Gly Arg Leuを含むマウスプレプチンよりなる群から選ばれる、請求項29に記載の方法。
- 前記プレプチンアゴニストが、配列番号1、2もしくは3のアミノ酸配列のフラグメントまたは全体を含む、請求項29に記載の方法。
- プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の量を、疾患、症状もしくは異常、またはそれらの1以上の症候を治療あるいは改善する有効量で含む容器;ならびに、
対象への投与を含む、損傷、創傷、β細胞質量減少、β細胞数減少、もしくはβ細胞機能低下を含む疾患、症状もしくは異常、またはそれらの1以上の症候の治療あるいは改善のための、当該容器の内容物の使用についての説明書、
を含む製造品。 - 包装材料;ならびに、
疾患、症状もしくは異常、またはそれらの1以上の症候の治療あるいは改善に有効な量で、該包装材料に内包された、プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物;
を含む製造品であって、
当該包装材料が、対象における損傷、創傷、またはβ細胞喪失もしくはβ細胞機能不全によって全体または一部が仲介される症状を治療するための、プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる前記1またはそれ以上の化合物の使用を記載しあるいはそれに言及する、前記製造品。 - i) 内部損傷;
ii) 外部損傷;
iii) 内部創傷;
iv) 外部創傷;
v) 全体または一部がβ細胞質量減少によって特徴付けられる症状;
vi) 全体または一部がβ細胞数減少によって特徴付けられる症状;
vii) β細胞質量の増大または維持;
viii) β細胞数の増大または維持;
ix) 細胞分化または新生を介したβ細胞増殖の刺激;
x) 細胞分化または新生を介したβ細胞質量の増大;
xi) β細胞仲介疾患;
xii) 全体または一部が、望ましくない低インスリン分泌によって特徴付けられる症状;および、
xiii) 全体または一部がインスリン耐性によって特徴付けられる症状;
xiv) 全体または一部が高血糖によって特徴付けられる症状;および、
xv) 全体または一部が食後高血糖によって特徴付けられる症状、
のうちのいずれか1つまたはそれ以上にある対象の治療のための医薬製造における、プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の使用。 - 前記プレプチンが、ヒト、ラットまたはマウスのプレプチンである、請求項34に記載の使用。
- 前記プレプチンアゴニストが、配列番号1、2もしくは3のアミノ酸配列のフラグメントまたは全体を含む、請求項34に記載の使用。
- 前記フラグメントが、配列番号1、2または3のアミノ酸残基17-34を含む、請求項36に記載の使用。
- 前記プレプチンアゴニストが、(1) 配列番号1、2または3と少なくとも約60%一致するアミノ酸配列、(2) 配列番号1、2または3と少なくとも約80%一致するアミノ酸配列、(3) 配列番号1、2または3と少なくとも約90%一致するアミノ酸配列、および (4) 配列番号1、2または3と少なくとも95%一致するアミノ酸配列、よりなる群から選ばれるペプチドを含む、請求項34に記載の使用。
- 前記プレプチンアゴニストが、(1) 約14までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(2) 約10〜13までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(3) 約6〜9までの保存的その他のアミノ酸置換を有する配列番号1、2または3、(4) 約2〜5までの保存的その他のアミノ酸置換を有する配列番号1、2または3、を含むペプチドよりなる群から選ばれる、請求項34に記載の使用。
- 前記β細胞仲介疾患が、1型糖尿病または2型糖尿病のいずれかである、請求項34に記載の使用。
- 薬学的に許容されるカプセルまたはマトリックス、薬学的に許容される担体、薬学的に許容される好適な共同物質(co-active)、薬学的に許容される緩衝剤、薬学的に許容される塩、薬学的に許容される浸透圧剤、および/または薬学的に許容される希釈剤のうち1またはそれ以上を用いて投与または自己投与されるべく調合された、プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物を含む、請求項1〜40のいずれか1項に記載の方法において有用な、あるいは該方法における使用に好適な投薬単位。
- 前記のプレプチン、プレプチン類縁体、プレプチンアゴニスト、その塩、およびその誘導体よりなる群から選ばれる1またはそれ以上の化合物の量が、対象の体重当たり約10〜約40μg/Kgから対象の体重当たり約200〜約500μg/Kgから対象の体重当たり約600〜約1000μg/Kgの範囲内である、請求項41に記載の投薬単位。
- プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を含む組成物を損傷または創傷に適用することを含む、対象におけるまたは対象上の損傷あるいは創傷を治療するための方法。
- 前記対象がヒトである、請求項43に記載の方法。
- 前記対象がヒト以外である、請求項43に記載の方法。
- 前記創傷が、皮膚もしくはその他の外表面が裂け、穴があき、切断され、またはその他の態様で破壊されている創傷である、請求項43〜45のいずれか1項に記載の方法。
- 前記創傷が、肉は貫通しているが下部の骨または生存臓器は実質的に損傷されていない創傷である、請求項43〜45のいずれか1項に記載の方法。
- 前記創傷が皮膚表面の損傷である、請求項43〜45のいずれか1項に記載の方法。
- 前記創傷が内出血である、請求項43〜45のいずれか1項に記載の方法。
- 前記組成物が軟膏、クリームまたはゲルである、請求項43〜45のいずれか1項に記載の方法。
- 前記創傷が、化学的熱傷、熱傷、皮膚移植ドナー部位、皮膚移植の移植部位、皮膚潰瘍、外科的創傷、創傷離開、角膜外傷、角膜移植部位、抜歯部位、口腔手術創傷、粘膜崩壊、皮膚崩壊、および結合組織の崩壊よりなる群から選ばれる、請求項43〜45のいずれか1項に記載の方法。
- 前記の皮膚潰瘍が、褥瘡性潰瘍、糖尿病性潰瘍、鬱血性潰瘍、およびリポイド類壊死症性潰瘍よりなる群から選ばれる、請求項51に記載の方法。
- 前記の粘膜崩壊が、胃腸管内部の粘膜崩壊、および膀胱内部の粘膜崩壊よりなる群から選ばれる、請求項51に記載の方法。
- 前記の胃腸管内の粘膜崩壊が潰瘍性大腸炎を含む、請求項53に記載の方法。
- 前記の胃腸管内の粘膜崩壊がクローン病を含む、請求項53に記載の方法。
- 前記の皮膚崩壊が擦過傷を含む、請求項51に記載の方法。
- 前記の結合組織崩壊が擦過傷を含む、請求項51に記載の方法。
- プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を創傷に局所適用することを含む、創傷治癒を亢進するための方法。
- 間葉由来細胞および/または細胞質量の増殖を促進する化合物の適用あるいは投与によって対象の症状を治療する方法において、プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を該対象に投与することを含むことを特徴とする、前記方法。
- 前記間葉由来細胞が線維芽細胞を含む、請求項59に記載の方法。
- 末梢神経系損傷を治療および/または防止し、運動ニューロンの細胞死を減少させ、筋終板を増加させ、損傷した坐骨神経の機能回復を促進し、化学療法中のまたはその結果としての末梢運動麻痺を防止し、アルツハイマー病を治療および/または防止し、卒中を治療および/または防止し、筋萎縮性側索硬化症を治療および/または防止し、パーキンソン病を治療および/または防止し、筋ジストロフィーを治療および/または防止し、糖尿病性神経障害を治療および/または防止し、心筋機能を改善し、心筋炎および心筋梗塞を包含する心筋症を治療および/または防止し、心臓病および急性発作を治療および/または防止し、そして虚血により惹起される急性腎不全を治療および/または防止するための、プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を含む組成物の投与。
- プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を対象に適用または投与することを含む、組織の成長を促進する化合物の適用または投与によって該対象の組織の成長を促進する方法。
- 前記組織が結合組織および上皮組織よりなる群から選ばれる、請求項62に記載の方法。
- プレプチン、プレプチン類縁体、プレプチンアゴニスト、それらの塩、およびそれらの誘導体よりなる群から選ばれる1またはそれ以上の化合物の有効量を対象に適用または投与することを含む、免疫機能を改善する化合物の適用または投与によって該対象の免疫機能を改善する方法。
- 前記の免疫機能の改善がリンパ球増殖の改善を含む、請求項64に記載の方法。
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US40044502P | 2002-08-01 | 2002-08-01 | |
NZ52053602 | 2002-08-01 | ||
PCT/NZ2003/000171 WO2004012761A1 (en) | 2002-08-01 | 2003-08-01 | Methods of use of compounds with preptin function |
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JP2006500341A true JP2006500341A (ja) | 2006-01-05 |
JP2006500341A5 JP2006500341A5 (ja) | 2006-08-31 |
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EP (1) | EP1534321A1 (ja) |
JP (1) | JP2006500341A (ja) |
CN (1) | CN1684705A (ja) |
AU (1) | AU2003258895A1 (ja) |
CA (1) | CA2494308A1 (ja) |
WO (1) | WO2004012761A1 (ja) |
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WO2000018392A1 (en) | 1998-09-25 | 2000-04-06 | Glycox Corporation Limited | Fructosamine oxidase: antagonists and inhibitors |
EP2500018B1 (en) | 2002-03-08 | 2017-07-19 | PhilERA New Zealand Limited | Preventing and/or Treating Cardiovascular Disease and/or Associated Heart Failure |
US20060100278A1 (en) | 2002-08-20 | 2006-05-11 | Cooper Garth J S | Dosage forms and related therapies |
CA2875095C (en) | 2004-07-19 | 2019-09-03 | Philera New Zealand Limited | Synthesis of triethylenetetramines |
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2003
- 2003-08-01 EP EP03766791A patent/EP1534321A1/en not_active Withdrawn
- 2003-08-01 CA CA002494308A patent/CA2494308A1/en not_active Abandoned
- 2003-08-01 WO PCT/NZ2003/000171 patent/WO2004012761A1/en active Application Filing
- 2003-08-01 CN CNA03823520XA patent/CN1684705A/zh active Pending
- 2003-08-01 AU AU2003258895A patent/AU2003258895A1/en not_active Abandoned
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CN1684705A (zh) | 2005-10-19 |
WO2004012761A1 (en) | 2004-02-12 |
AU2003258895A1 (en) | 2004-02-23 |
EP1534321A1 (en) | 2005-06-01 |
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