Polyethylene glycol/polycation block copolymers

• US 20070059271A1
• Filed: 05/07/2004
• Published: 03/15/2007
• Est. Priority Date: 05/08/2003
• Status: Active Grant

• Current Assignee: University of Tokyo
• Original Assignee: Japan Science And Technology Agency
• Inventors: Kataoka, Kazunori, Kanayama, Naoki, Harada, Atsushi, Fukushima, Shigeto, Itaka, Keiji
• Granted Patent: US 7,780,957 B2
• Time in Patent Office: Days
• US Class Current: 424/78.300
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: C08G 69/10 Alpha-amino-carboxylic acids polysuccinimides C08G73/1092
• CPC Class Codes: C08G 69/48 Polymers modified by chemical after-treatment
• CPC Class Codes: C08G 81/00 Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers involving only carbon-to-carbon unsaturated bond reactions C08F299/00 ; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

The invention provides block copolymers formed of poly(ethylene glycol) segments and poly(amino acid derivative) segments having side chains of at least one kind of specific amine residue. The invention also provides polyion complexes of such copolymers with polynucleotides and the like. These block copolymers are useful as carriers for in vivo delivery of active substances such as DNA.

Claims

1. A polyethylene glycol/polycation block copolymer characterized by having segment A formed of polyethylene glycol or a derivative thereof and segment B formed of polyamino acid, a derivative thereof or a salt of the foregoing, the segment B containing bulky amines of pKa value not higher than 7.4 or containing both primary amine and secondary amine, tertiary amine or quaternary ammonium salt;

2. A copolymer as set forth in claim 1, in which the structure of the block copolymer is one represented by a general formula (I) or (II) or a salt thereof,

3. A copolymer as set forth in claim 1, in which the structure of the block copolymer is one represented by a general formula (III) or (IV) or a salt thereof,

4. A copolymer as set forth in claim 2, in which R¹ is methyl.

5. A copolymer as set forth in claim 2, in which R¹ stands for substituted straight or branched chain C_1-12 alkyl, wherein the substituent is acetalized formyl, cyano, formyl, carboxyl, amino, C_1-6 alkoxycarbonyl, C_2-7 acylamide, same or different tri-C_1-6 alkylsiloxy, siloxy or silylamino.

6. A copolymer as set forth claim 2, in which L¹ is —

(CH₂)_b—

NH—

, b being an integer of 1-5.

7. A copolymer as set forth in claim 2, in which L² is —

(CH₂)_c—

CO—

, c being an integer of 1-5.

8. A copolymer as set forth in claim 2, in which R² is methylene.

9. A copolymer as set forth in claim 2, in which X is selected from the group consisting of the following Groups A, B, C, D and E:

10. A copolymer as set forth in claim 2, in which R³ is acetyl, acryloyl or methacryloyl.

11. A copolymer as set forth in claim 2, in which R⁴ is —

NH—

R⁹, R⁹ standing for unsubstituted or substituted, straight or branched chain C_1-20 alkyl.

12. A polyion complex comprising a copolymer as described in claim 1 and nucleic acid or anionic protein.

13. A polyion complex as described in claim 12, which is in the form of a polymer micelle carrying nucleic acid or anionic protein in its core portion with the shell portion composed mainly of polyethylene glycol segment.