Production method for poly(amino acid)

Patent metadata

Field	Value
Publication number	US-9815938-B2
Application number	US-201414392185-A
Country	US
Kind code	B2
Filing date	Jun 25, 2014
Priority date	Jun 26, 2013
Publication date	Nov 14, 2017
Grant date	Nov 14, 2017

Abstract

The present invention relates to a graft copolymer of a poly(amino acid) or a salt thereof and a hydrophobic primary amine compound or a salt thereof (e.g., a graft copolymer (γ-PGA-PAE) of poly(γ-glutamic acid) (γ-PGA) and phenylalanine ethyl ester (PAE)), an ionized graft copolymer of a poly(amino acid) or a salt thereof and a hydrophobic primary amine compound or a salt thereof, nanoparticles containing the ionized graft copolymer, and a production method thereof. The nanoparticles acquired in this way are useful as an adjuvant for producing a vaccine.

First claim

The invention claimed is:

1. A production method of a graft copolymer of a poly(amino acid) selected from the group consisting of poly(α-glutamic acid) or a salt thereof, and poly(aspartic acid) or a salt thereof, and a hydrophobic primary amine compound represented by Formula (I): A-NH 2 or a salt thereof, wherein A denotes a hydrophobic moiety, the method comprising the steps of:
(1) acquiring a graft copolymer by condensation of the poly(amino acid) or a salt thereof with the hydrophobic primary amine compound represented by Formula (I) or a salt thereof; and
(2) isolating the graft copolymer by allowing an acid to act on the graft copolymer acquired at step (1) at a temperature of 40 to 70° C.

2. The production method according to claim 1 , wherein the hydrophobic primary amine compound is an α-amino acid derivative.

3. The production method according to claim 2 , wherein the α-amino acid derivative is a phenylalanine derivative.

4. The production method according to claim 3 , wherein the phenylalanine derivative is phenylalanine ethyl ester.

5. A production method of a graft copolymer of poly(γ-glutamic acid) or a salt thereof, and a hydrophobic primary amine compound represented by Formula (I): A-NH 2 or a salt thereof, wherein A denotes a hydrophobic moiety, the method comprising the steps of:
(1) acquiring a graft copolymer by condensation of the poly(γ-glutamic acid) or salt thereof with the hydrophobic primary amine compound represented by Formula (I) or salt thereof, and
(2) isolating the graft copolymer by allowing an acid to act on the graft copolymer acquired at step (1).

6. The production method according to claim 5 , wherein at step (2), the acid is allowed to act on the graft copolymer at a temperature of 0 to 80° C.

7. A production method of nanoparticles containing an ionized graft copolymer of a poly(amino acid) selected from the group consisting of poly(γ-glutamic acid), poly(α-glutamic acid), and poly(aspartic acid) or a salt thereof and a hydrophobic primary amine compound represented by Formula (I): A-NH 2 or a salt there, wherein A denotes a hydrophobic moiety, the method comprising the steps of
(1) condensing a poly(amino acid) selected from the group consisting of poly(γ-glutamic acid), poly(α-glutamic acid), and poly(aspartic acid) or a salt thereof and a hydrophobic primary amine compound represented by Formula (I): A-NH 2 or a salt thereof, wherein A denotes a hydrophobic moiety;
(2) isolating a graft copolymer by allowing an acid to act on a condensate acquired at step (1);
(3) ionizing the graft copolymer by allowing a hydroxide of alkali metal, a carbonate of alkali metal, a hydrogencarbonate of alkali metal, a phosphate of alkali metal, a monohydrogen phosphate of alkali metal, a dihydrogen phosphate of alkali metal, an organic acid salt of alkali metal, or an acidic amino-acid salt of alkali metal to act on the graft copolymer isolated at step (2); and
(4) forming nanoparticles of the ionized graft copolymer acquired at step (3).

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Yamano Mitsuhisa
• Nagata Toshiaki
• Saitoh Hideki

Classifications

• C08L77/04

  Polyamides derived from alpha-amino carboxylic acids (C08L77/10 takes precedence) · CPC title

• C08G69/48 Primary

  Polymers modified by chemical after-treatment · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K47/42

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• C08G69/08

  derived from amino-carboxylic acids · CPC title