JP2019116441A5 - - Google Patents

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JP2019116441A5
JP2019116441A5 JP2017251049A JP2017251049A JP2019116441A5 JP 2019116441 A5 JP2019116441 A5 JP 2019116441A5 JP 2017251049 A JP2017251049 A JP 2017251049A JP 2017251049 A JP2017251049 A JP 2017251049A JP 2019116441 A5 JP2019116441 A5 JP 2019116441A5
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vesicle
diseases
disease
pharmaceutical composition
selectin
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JP2019116441A (en
JP7253762B2 (en
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Claims (19)

小胞の表面に発現される、またはコンジュゲートされる1つもしくは複数のレクチンまたはそのフラグメントと、必要な場合には薬剤とを含
前記レクチンまたはそのフラグメントが、カチオン依存性マンノース−6−リン酸受容体(M6PR)、P−セレクチン、E−セレクチン、L−セレクチン、P−セレクチン−リガンド−1(PSGL−1)、CD22、CD206、ガレクチン3、アネキシンV、CD31、インテグリンαLβ2、VE−カドヘリン、CD44、CD300a、CD47、トロンボスポンジン1(TSP1)およびCD36、ならびにそれらのフラグメントからなる群から選択される第1のタンパク質を含む、
タンパク質がコンジュゲートされた小胞。
And one or more lectins or fragments thereof are expressed on the surface of the vesicle or conjugate, if necessary viewing contains a drug,
The lectin or fragment thereof is a cation-dependent mannose-6-phosphate receptor (M6PR), P-selectin, E-selectin, L-selectin, P-selectin-ligand-1 (PSGL-1), CD22, CD206. , Galectin 3, anexin V, CD31, integrin αLβ2, VE-cadherin, CD44, CD300a, CD47, thrombospondin 1 (TSP1) and CD36, and a first protein selected from the group consisting of fragments thereof.
Protein-conjugated vesicles.
小胞の表面に発現される、またはコンジュゲートされる1つもしくは複数のレクチンまたはそのフラグメントと、必要な場合には薬剤とを含み、Containing one or more lectins or fragments thereof expressed or conjugated to the surface of the vesicle and, if necessary, a drug.
前記レクチンまたはそのフラグメントが、CD300a、CD47、トロンボスポンジン1(TSP1)、CD36およびToll様受容体4(TLR4)ならびにそれらのフラグメントからなる群から選択される、第2のタンパク質を含む、The lectin or fragment thereof comprises a second protein selected from the group consisting of CD300a, CD47, thrombospondin 1 (TSP1), CD36 and Toll-like receptor 4 (TLR4) and fragments thereof.
タンパク質がコンジュゲートされた小胞。Protein-conjugated vesicles.
前記薬剤が小胞内に封入される、または、小胞の外側表面に付加される、請求項1又は2に記載の小胞。 The vesicle according to claim 1 or 2, wherein the drug is encapsulated in the vesicle or added to the outer surface of the vesicle. リポソームまたはミセルである、請求項1〜3のいずれか一項に記載の小胞。 The vesicle according to any one of claims 1 to 3 , which is a liposome or a micelle. 人為的に改変することができる、または、細胞に由来することができる、請求項1〜4のいずれか一項に記載の小胞。 The vesicle according to any one of claims 1 to 4, which can be artificially modified or derived from a cell. 前記第1のタンパク質の1つまたは複数と、請求項に記載される前記第2のタンパク質の1つまたは複数とを含む、請求項1、3〜5のいずれか一項に記載の小胞。 Wherein one or a plurality of first protein, and said one or more second proteins described in claim 2, vesicle according to any one of claims 1, 3 to 5 .. M6PRを、P−セレクチン、E−セレクチン、PSGL−1またはガレクチン3との組合せで含む、請求項1、3〜5のいずれか一項に記載の小胞。 The vesicle according to any one of claims 1 , 3 to 5 , which comprises M6PR in combination with P-selectin, E-selectin, PSGL-1 or galectin-3. Siglec2を、P−セレクチン、ガレクチン3またはCD31との組合せで含む、請求項1、3〜5のいずれか一項に記載の小胞。 The vesicle according to any one of claims 1 , 3 to 5 , which comprises Sigma2 in combination with P-selectin, galectin-3 or CD31. P−セレクチンまたはM6PRを、TLR4、ガレクチン3、CLEC2、インテグリンαLβ2またはCD31との組合せで含む、請求項1、3〜5のいずれか一項に記載の小胞。 The vesicle according to any one of claims 1 , 3 to 5 , which comprises P-selectin or M6PR in combination with TLR4, galectin-3, CLEC2, integrin αLβ2 or CD31. 前記薬剤が、診断用造影剤、細胞生存強化剤、細胞生存抑制剤、細胞成分、オルガネラ、細胞、細胞傷害性薬剤、抗腫瘍薬物、毒素抗体、脂質、タンパク質、DNA、RNA、治療剤またはナノ材料である、請求項1〜9のいずれか一項に記載の小胞。 The drug is a diagnostic contrast agent, cell survival enhancer, cell survival inhibitor, cell component, organella, cell, cytotoxic drug, antitumor drug, toxin , antibody, lipid, protein, DNA, RNA, therapeutic agent or The vesicle according to any one of claims 1 to 9 , which is a nanomaterial. 溶性形態、対応するリガンド、中和抗体およびブロッキング抗体から選択される、前記第1のタンパク質および前記第2のタンパク質のアンタゴニストが、
オートファジー細胞および/またはアポトーシス細胞、ならびに、オートファジー細胞および/またはアポトーシス細胞を含有する組織への
小胞標的化を低下させるための解毒物として働くことができる、請求項6〜10のいずれか一項に記載の小胞。
The soluble form, corresponding ligand is selected from neutralizing antibodies and blocking antibodies, antagonists of the first protein and the second protein,
To tissues containing autophagy cells and / or apoptotic cells, as well as autophagy cells and / or apoptotic cells
The vesicle according to any one of claims 6 to 10, which can act as a detoxifier for reducing vesicle targeting.
請求項1〜11のいずれか一項に記載小胞と、医薬的に許容され得るキャリアとを含む医薬組成物。 And vesicle according to any one of claims 1 to 11, pharmaceutically and a acceptable carrier, a pharmaceutical composition. オートファジー細胞および/またはアポトーシス細胞、ならびに前記細胞を含有する組織に対して、
薬剤送達するための、請求項12に記載の医薬組成物
Autophagy cells and / or apoptotic cells, as well as for tissue containing said cells,
For delivering a drug, pharmaceutical composition according to claim 12.
前記医薬組成物を投与する前において、別のオートファジー誘導剤および/またはアポトーシス誘導剤が対象に投与される、、請求項12又は13に記載の医薬組成物The pharmaceutical composition according to claim 12 or 13, wherein another autophagy inducer and / or an apoptosis inducer is administered to the subject before administering the pharmaceutical composition . ートファジーの脱調節に伴う疾患の治療用又は診断用である、請求項12〜14のいずれか一項に記載の医薬組成物 A therapeutic or diagnosis of a disease associated with deregulated Oh Tofaji The pharmaceutical composition according to any one of claims 12 to 14. オートファジーの脱調節に伴う前記疾患が、外傷、化学的および物理的な毒性因子への曝露、遺伝性疾患、老化関連疾患、心臓血管疾患、感染性疾患、腫瘍性疾患、神経変性疾患、代謝性疾患、老化、肥満、ガン、β−アミロイドまたはα−シヌクレインまたは毒性により誘発される神経変性、筋変性状態、あるいは、嚢胞性線維症によって引き起こされる慢性の肺炎症である、請求項15に記載の医薬組成物The diseases associated with autophagy deregulation include trauma, exposure to chemical and physical toxic factors, hereditary diseases, aging-related diseases, cardiovascular diseases, infectious diseases, neoplastic diseases, neurodegenerative diseases, metabolism. 15. A sexually transmitted disease, aging, obesity, cancer, β-amyloid or α-synuclein or a toxic-induced neurodegenerative, myopathic state, or chronic lung inflammation caused by cystic fibrosis. Pharmaceutical composition . ポトーシスの変化に伴う疾患の治療用又は診断用である、請求項12〜14のいずれか一項に記載の医薬組成物 A therapeutic or diagnostic of a disease caused by changes in apoptosis, a pharmaceutical composition according to any one of claims 12 to 14. アポトーシスの変化に伴う前記疾患が、外傷、化学的および物理的な毒性因子への曝露、遺伝性疾患、老化関連疾患、老化関連疾患、心臓血管疾患、感染性疾患、腫瘍性疾患、神経変性疾患、代謝性疾患、老化、肥満、ガン、β−アミロイドまたはα−シヌクレインまたは毒性により誘発される神経変性、筋変性状態、あるいは、嚢胞性線維症によって引き起こされる慢性の肺炎症、または自己免疫疾患である、請求項17に記載の医薬組成物The diseases associated with changes in apoptosis include trauma, exposure to chemical and physical toxic factors, hereditary diseases, aging-related diseases, aging-related diseases, cardiovascular diseases, infectious diseases, neoplastic diseases, and neurodegenerative diseases. , Metabolic disease, aging, obesity, cancer, β-amyloid or α-synuclein or toxic-induced neurodegeneration, muscle degeneration, or chronic lung inflammation caused by cystic fibrosis, or autoimmune disease The pharmaceutical composition according to claim 17 . 前記神経変性疾患が、アルツハイマー、パーキンソン、ハンチントン、筋萎縮性側索硬化症または脳卒中であり、前記心臓血管障害が、虚血、心不全または感染性疾患であり、かつ、前記自己免疫疾患が、全身性エリテマトーデス、自己免疫性リンパ増殖症候群、関節リウマチまたは甲状腺炎である、請求項16又は18に記載の医薬組成物The neurodegenerative disease is Alzheimer's disease , Parkinson's disease , Huntington's disease , muscular atrophic lateral sclerosis or stroke, and the cardiovascular disorder is ischemic, heart failure or infectious disease, and the autoimmune disease. The pharmaceutical composition according to claim 16 or 18 , wherein is systemic lupus erythematosus, autoimmune lymphoproliferative syndrome, rheumatoid arthritis or thyroiditis.
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CN111110855B (en) * 2019-12-26 2023-06-23 深圳百纳心致生命科学有限公司 Targeting vesicle medicine prepared from erythrocytes
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