Active Targeting Polymer Micelle Encapsulating Drug, and Pharmaceutical Composition

• US 20100221320A1
• Filed: 07/29/2009
• Published: 09/02/2010
• Est. Priority Date: 07/29/2008
• Status: Active Grant

• Current Assignee: NanoCarrier Co., Ltd.
• Original Assignee: NanoCarrier Co., Ltd.
• Inventors: Saito, Hiroyuki, Kato, Yasuki, Harada, Mitsunori, Hayashi, Tatsuyuki
• Granted Patent: US 8,741,339 B2
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/642 the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
• CPC Class Codes: A61K 47/644 Transferrin, e.g. a lactoferrin or ovotransferrin
• CPC Class Codes: A61K 47/6845 the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6905 the form being a colloid or an emulsion
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention provides an active targeting polymer micelle encapsulating a drug, preventing an inappropriate release of a drug which may damage a normal cell. A polymer micelle 100 includes a backbone polymer unit 10 that has a target binding site 11 and a backbone polymer unit 20 that has a drug 14 and is free from the target binding site 11, such polymer units 10 and 20 being disposed in a radial arrangement in a state where the target binding site 11 is directed outward and the drug 14 is directed inward, in which: i) when the micelle is bound to a target 40 while maintaining the radial arrangement, the micelle is taken up into a cell 50 supplying the target 40 through endocytosis, and the drug 14 is released into the cell 50 by collapse of the radial arrangement in the cell 50; and ii) when the radial arrangement collapses in blood 60 before the micelle is bound to a target 40, the unit 20 is excreted through metabolism, to thereby prevent a normal cell from being damaged by the drug 14.

Claims

1. An active targeting polymer micelle encapsulating a drug, comprising a backbone polymer unit α

that has a target binding site and a backbone polymer unit β

that has a drug and is free from the target binding site, the backbone polymer unit α and

the backbone polymer unit β

being disposed in a radial arrangement in a state where the target binding site is directed outward and the drug is directed inward, wherein;

i) when the micelle is bound to a target while maintaining the radial arrangement, the micelle is taken up into a cell supplying the target through endocytosis, and the drug is released into the cell by collapse of the radial arrangement in the cell; and

ii) when the radial arrangement collapses in blood before the micelle is bound to a target, the backbone polymer unit β

is excreted through metabolism, to thereby prevent a normal cell from being damaged by the drug.

2. The polymer micelle according to claim 1, wherein:

the backbone polymer unit α

is made up of a compound having a target binding site and a block copolymer and is represented by the general formula I;

Z-A₁-B₁ 

 

(I); and

the backbone polymer unit β

is made up of a drug and a block copolymer and is represented by the general formula II;

A₂-B₂(-D) 

 

(II)

where;

Z represents a residue of the compound having a target binding site;

A₁ and A₂ each independently represent a polyethylene glycol chain segment;

B₁ and B₂ each independently represent a polyamino acid chain segment; and

D represents the drug.

3. The polymer micelle according to claim 2, wherein the backbone polymer unit α

is represented by the following general formula I-a or I-b, and the backbone polymer unit β

is represented by the following general formula II-a or II-b;

4. A pharmaceutical composition, comprising the polymer micelle according to claim 1 and a pharmaceutically acceptable carrier.