Drug delivery compositions and applications thereof

Patent metadata

Field	Value
Publication number	US-12448475-B2
Application number	US-202017620800-A
Country	US
Kind code	B2
Filing date	Jun 19, 2020
Priority date	Jun 21, 2019
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

In one aspect, amphiphilic block copolymers are described herein comprising a first block and a second block, the second block including monomer having a side chain comprising a heteroaryl moiety, wherein the second block is more hydrophobic than the first block. In some embodiments, the heteroaryl moiety is a five-membered ring or six membered ring. Amphiphilic block copolymers described herein, in some embodiments, can be used to form micellar compositions for solubilizing and delivering water insoluble pharmaceutical and/or therapeutic agents.

First claim

The invention claimed is:

1. An amphiphilic block copolymer comprising:
a first block and a second block, the second block including oxazoline monomer having a side chain comprising a heteroaryl moiety, wherein the second block is more hydrophobic than the first block, and the heteroaryl moiety is of the formula:

wherein X, Y and Z are heteroatoms independently selected from the group consisting of N, O, and S, and R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, amine, —SH, hydroxyl, halo, carboxyl, and —CONR 3 wherein R 3 is alkyl and represents a point of attachment of the heteroaryl moiety to the monomer.

2. The amphiphilic block copolymer of claim 1 , wherein the heteroaryl moiety comprises two or more heteroatoms.

3. The amphiphilic block copolymer of claim 2 , wherein the heteroatoms are selected from the group consisting of nitrogen, oxygen, and sulfur.

4. The amphiphilic block copolymer of claim 1 , wherein the heteroaryl moiety is a five-membered ring or six membered ring.

5. The amphiphilic block copolymer of claim 2 , wherein the heteroaryl moiety comprises an azine.

6. The amphiphilic block copolymer of claim 1 , wherein the second block comprises poly (2-N,N-dimethyl-1,3,5-triazine-2,4-diamine-6-ethyl-2-oxazoline).

7. The amphiphilic copolymer of claim 1 , wherein the first block comprises a poly (2-oxazoline) or derivative thereof.

8. The amphiphilic block copolymer of claim 1 , wherein the first block comprises polymer of the formula:

wherein R 4 is selected from the group consisting of alkyl, cycloalkyl and alkenyl, each optionally substituted with hydroxyl, —SH, —COOR 5 , —NR 6 2 , —CONR 7 or —CHO, wherein R 5 -R 7 are independently selected from the group consisting of hydrogen and alkyl and wherein p is at least 5.

9. The amphiphilic block copolymer of claim 1 having a diblock structure.

10. The amphiphilic block copolymer of claim 1 , wherein the first block is represented by A and the second block is represented by B, and having an ABA triblock structure.

11. An amphiphilic block copolymer comprising:
a first block and a second block, the second block including monomer having a side chain comprising a heteroaryl moiety, wherein the second block is more hydrophobic than the first block comprises poly (2-N,N-dimethyl-1,3,5-triazine-2,4-diamine-6-ethyl-2-oxazoline).

12. The amphiphilic block copolymer of claim 11 , wherein the heteroaryl moiety comprises two or more heteroatoms.

13. The amphiphilic block copolymer of claim 12 , wherein the heteroatoms are selected from the group consisting of nitrogen, oxygen, and sulfur.

14. The amphiphilic block copolymer of claim 11 , wherein the heteroaryl moiety is a five-membered ring or six membered ring.

15. The amphiphilic block copolymer of claim 12 , wherein the heteroaryl moiety comprises an azine.

16. The amphiphilic block copolymer of claim 11 , wherein the heteroaryl moiety is of the formula:

wherein X, Y and Z are heteroatoms independently selected from the group consisting of N, O, and S, and R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, amine, —SH, hydroxyl, halo, carboxyl, and —CONR 3 , wherein R 3 is alkyl and represents a point of attachment of the heteroaryl moiety to the monomer.

17. The amphiphilic copolymer of claim 11 , wherein the first block comprises a poly (2-oxazoline) or derivative thereof.

18. The amphiphilic block copolymer of claim 11 , wherein the first block comprises polymer of the formula:

wherein R 4 is selected from the group consisting of alkyl, cycloalkyl and alkenyl, each optionally substituted with hydroxyl, —SH, —COOR 5 , —NR 6 2 , —CONR 7 or —CHO, wherein R 5 -R 7 are independently selected from the group consisting of hydrogen and alkyl and wherein p is at least 5.

19. The amphiphilic block copolymer of claim 11 having a diblock structure.

20. The amphiphilic block copolymer of claim 11 , wherein the first block is represented by A and the second block is represented by B, and having an ABA triblock structure.

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Kabanov Alexander
• Hwang Duhyeong
• Sokolsky Marina

Classifications

• C08F20/54

  Amides {, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide} · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title