Block copolymer and micelle compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12528903-B2
Application number	US-202117198006-A
Country	US
Kind code	B2
Filing date	Mar 10, 2021
Priority date	Sep 22, 2010
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises

wherein R′ is —H or —CH 3 , wherein R is —NR 1 R 2 , wherein R 1 and R 2 are alkyl groups, wherein R 1 and R 2 are the same or different, wherein R 1 and R 2 together have from 5 to 16 carbons, wherein R 1 and R 2 may optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.

First claim

The invention claimed is:

1 . A block copolymer capable of forming a pH-sensitive micelle comprising a compound of Formula (I):

wherein R is —NR 1 R 2 , wherein R 1 and R 2 together have from 5 to 16 carbons, and
wherein R 1 and R 2 join to form a ring;
L is a labelling moiety;
R′ is —H or —CH 3 ;
n is 1 to about 10;
x is about 20 to about 200 in total;
m is 1 to about 10;
y is 0 to about 6;
wherein z is such that the PEO is about 2 kD to about 20 kD in size;
wherein R′″ is any suitable moiety; and
wherein the following portion of the structure:

may be arranged in any order.

2 . The block copolymer of claim 1 , wherein the micelles have a pH transition range ΔpH 10-90 % of less than about 1 pH unit.

3 . The block copolymer of claim 1 , wherein R 1 and R 2 join to form a ring having —(CH 2 ) 5 — or —(CH 2 ) 6 —.

4 . The block copolymer of claim 1 , wherein n is 2 and R 1 and R 2 join to form a ring having —(CH 2 ) 5 —.

5 . The block copolymer of claim 4 , wherein the micelles have a pH transition value of about 7.2.

6 . The block copolymer of claim 1 , wherein n is 2 and R 1 and R 2 join to form a ring having —(CH 2 ) 6 —.

7 . The block copolymer of claim 6 , wherein the micelles have a pH transition value about 6.8.

8 . The block copolymer of claim 1 , wherein the block copolymer has a polydispersity index of less than 1.2.

9 . The block copolymer of claim 1 , wherein the block copolymer has a polydispersity index of less than 1.1.

10 . The block copolymer of claim 1 , wherein the micelles have a size of about 10 to about 200 nm.

11 . The block copolymer of claim 1 , wherein the micelles have a size of about 20 to about 100 nm.

12 . The block copolymer of claim 1 , wherein the micelles have a size of about 30 to about 50 nm.

13 . The block copolymer of claim 1 , wherein the fluorescent label is tetramethyl rhodamine (TMR).

14 . The block copolymer of claim 1 , wherein L is a near-infrared (NIR) label.

15 . The block copolymer of claim 14 , wherein the NIR label is cypate or a cypate analog.

16 . The block copolymer of claim 1 , wherein the block copolymer is

Assignees

• Univ Texas

Inventors

• Gao Jinming
• Boothman David
• Zhou Kejin
• Huang Xiaonan
• Wang Yiguang

Classifications

• A61K47/6845

  the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon · CPC title

• A61K47/6811

  the drug being a protein or peptide, e.g. transferrin or bleomycin · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• A61K49/0054

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title