CAPSULE PROTEIN AND MULTIMERIC COMPLEX COMPOSITION THEREOF, AND PHARMACEUTICAL COMPOSITION USING SAME
| Foreign code | F210010291 |
|---|---|
| File No. | (S2019-0482-N0) |
| Posted date | Jan 28, 2021 |
| Country | WIPO |
| International application number | 2020JP019827 |
| International publication number | WO 2020235570 |
| Date of international filing | May 19, 2020 |
| Date of international publication | Nov 26, 2020 |
| Priority data |
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| Title | CAPSULE PROTEIN AND MULTIMERIC COMPLEX COMPOSITION THEREOF, AND PHARMACEUTICAL COMPOSITION USING SAME |
| Abstract | There has been an idea to pack a pharmaceutical agent in a lipocalin-type prostagladin H synthase having a barrel structure, and seal the pharmaceutical agent in the barrel structure by introducing a disulfide bond between α-helix H2 and E-F loop. However, in some cases the pharmaceutical agent is released through a gap in an opening of the barrel structure. This capsule protein is characterized in that: a cysteine, which is the active center of a human lipocalin-type prostagladin D synthetase, has been substituted with alanine; and at least one amino acid of a β strand D has been substituted with a barrier amino acid. The capsule protein has a barrier amino acid provided to the β strand D constituting the opening of the barrel structure, and as a result, the release of the pharmaceutical agent that has been packed is suppressed. |
| Outline of related art and contending technology |
BACKGROUND ART In DDS, the development of drug carriers is a key technique. Liposomes, microparticles, nano-related substances, drug-polymer conjugates, and the like have been investigated. Among these, polymer micelles have been focused on as favored carriers for the transmission of poorly water-soluble drugs. For example, Patent Document 1) discloses a micelle-forming composition comprising a hydrophobic core surrounded by a hydrophilic shell, wherein the hydrophilic shell comprises PVP (N-vinyl-2-pyrrolidone). Patent Document 2 discloses lipocalin type prostaglandin d synthase ((hereinafter referred to as "L-PGDS"), which is a biological product. a capsule protein modified with) discloses that the effect of a drug can be exhibited by dissolving a poorly water-soluble drug in water and administering the drug. Because the capsule protein modified with L-PGDS is an organism in vivo, it is not an antigen and is not toxic to humans, so it can be said to be a safe and reliable drug delivery device. Patent Document 3 discloses a protein in which a capsule protein modified with L-PGDS is labeled to recognize affected cells. For example, it is thought that a capsule protein modified with L-PGDS, which is labeled peptide that specifically binds to cancer cells, collects in affected cancer cells and improves the therapeutic effect. Patent Document 4 discloses a protein in which 34 th and 92 th tryptophan from the N-terminal of a capsule protein modified with L-PGDS are replaced with cysteine, and a lid made of a disulfide bond that opens and closes in an oxidation-reduction atmosphere is provided. The purpose of the present invention is to enhance the ability to retain the drug by opening and closing disulfide bonds. |
| Scope of claims |
(In Japanese)[請求項1] ヒト型リポカリン型プロスタグランジンD合成酵素の活性中心のシステインがアラニンに置換され、βストランドDの少なくとも1つのアミノ酸を障壁アミノ酸に置換されたことを特徴とするカプセルタンパク質。 [請求項2] E－FループとαヘリックスH2との間にジスルフィド結合を導入したことを特徴とする請求項1に記載されたカプセルタンパク質。 [請求項3] 前記カプセルタンパク質のN末端若しくはC末端に標識ペプチドが結合されたことを特徴とする請求項1または2に記載されたカプセルタンパク質。 [請求項4] 前記障壁アミノ酸が、リシン（K）、ヒスチジン（H）、トリプトファン（W）、チロシン（Y）、フェニルアラニン（F）の内から選択された少なくとも1つのアミノ酸であることを特徴とする請求項1乃至3の何れか一の請求項に記載されたカプセルタンパク質。 [請求項5] 前記カプセルタンパク質を複数個結合させたことを特徴とするカプセルタンパク質の多量体組成物。 [請求項6] 前記多量体組成物が4量体若しくは8量体であることを特徴とする請求項5に記載されたカプセルタンパク質の多量体組成物。 [請求項7] 前記多量体組成物が、ストレプトアビジンの4量体にビオチンを介して前記カプセルタンパク質が結合されたことを特徴とする請求項6に記載されたカプセルタンパク質の多量体組成物。 [請求項8] 請求項1乃至7の何れか一の請求項に記載された前記カプセルタンパク質に薬剤を含ませた医薬組成物。 [請求項9] 凍結乾燥されたことを特徴とする請求項8に記載された医薬組成物。 [請求項10] 請求項1乃至7の何れか一の請求項に記載された前記カプセルタンパク質に薬剤以外の化合物を含ませた複合体を含有する加工食品。 |
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| Specified countries |
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN WS ZA ZM ZW ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL ST SZ TZ UG ZM ZW EAPO: AM AZ BY KG KZ RU TJ TM EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN TD TG |
Contact Information for " CAPSULE PROTEIN AND MULTIMERIC COMPLEX COMPOSITION THEREOF, AND PHARMACEUTICAL COMPOSITION USING SAME "
- Osaka Prefecture University (In Japanese)研究推進本部URAセンター
- URL: http://www.osakafu-u.ac.jp/en/
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E-mail:
- Address: 1-2 Gakuen-cho, Naka-ku, Sakai-shi, Osaka , 599-8570
- Phone: 81-72-254-9128
- Fax: 81-72-254-7475
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