Preparation of robust polythioaminal carriers

Patent metadata

Field	Value
Publication number	US-10457772-B2
Application number	US-201715699416-A
Country	US
Kind code	B2
Filing date	Sep 8, 2017
Priority date	Sep 8, 2017
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

The present disclosure relates to polythioaminals with applications as carriers or delivery vehicles for therapeutic agents or other small molecule cargo. Polythioaminal block copolymer coupled to a therapeutic agent is a polymer-therapeutic conjugate that exhibits higher stability and longer life time in aqueous environments. The polythioaminal block copolymer coupled to a therapeutic agent can be synthesized by reacting hexahydrotriazines with a hydrophobic block precursor, a hydrophilic block precursor, a particle stabilizing segment precursor, and a cargo, such as a therapeutic agent, in a one pot synthesis. The ease of synthesizing the resulting polythioaminal block copolymer coupled to the therapeutic agent while offering the extended stability and polymer life time in aqueous environments make the polythioaminal block copolymer particularly attractive for therapeutic carriers.

First claim

What is claimed is:

1. A method, comprising:
forming a polythioaminal block copolymer by polymerizing a reaction mixture including a hexahydrotriazine, a hydrophobic block precursor, a hydrophilic block precursor, and a particle stabilizing segment precursor.

2. The method of claim 1 , wherein the polythioaminal block copolymer is formed in a two-step one pot synthesis.

3. The method of claim 2 , wherein a first step of the two-step one pot synthesis comprises forming oligomers by reacting the hexahydrotriazine, the hydrophobic block precursor, the hydrophilic block precursor, and the particle stabilizing segment precursor in a reactor at a temperature ranging from about 85 degrees Celsius to about 120 degrees Celsius.

4. The method of claim 3 , wherein a second step of the two-step one pot synthesis comprises placing the oligomers under vacuum condition to remove volatile byproducts at a temperature ranging from about 85 degrees Celsius to about 120 degrees Celsius.

5. The method of claim 1 , wherein the hydrophobic block precursor includes a main component and one or more thiol groups attached to the main component.

6. The method of claim 1 , wherein the hydrophilic block precursor includes a main component and one or more thiol groups attached to the main component.

7. The method of claim 1 , wherein the particle stabilizing segment precursor includes a main component and one or more thiol groups attached to the main component.

8. A method, comprising:
forming a polythioaminal block copolymer particle by polymerizing a reaction mixture including hexahydrotriazine, a hydrophobic block precursor, a hydrophilic block precursor, and a particle stabilizing segment precursor.

9. The method of claim 1 , wherein the polythioaminal block copolymer particle is formed by forming a polythioaminal block copolymer by polymerizing the reaction mixture and placing the polythioaminal block copolymer in aqueous solution.

10. The method of claim 9 , wherein the polythioaminal block copolymer is formed in a two-step one pot synthesis.

11. The method of claim 10 , wherein a first step of the two-step one pot synthesis comprises forming oligomers by reacting the hexahydrotriazine, the hydrophobic block precursor, the hydrophilic block precursor, and the particle stabilizing segment precursor in a reactor at a temperature ranging from about 85 degrees Celsius to about 120 degrees Celsius.

12. The method of claim 11 , wherein a second step of the two-step one pot synthesis comprises placing the oligomers under vacuum condition to remove volatile byproducts at a temperature ranging from about 85 degrees Celsius to about 120 degrees Celsius.

13. The method of claim 8 , wherein the hydrophobic block precursor includes a main component and one or more thiol groups attached to the main component.

14. The method of claim 8 , wherein the hydrophilic block precursor includes a main component and one or more thiol groups attached to the main component.

15. The method of claim 8 , wherein the particle stabilizing segment precursor includes a main component and one or more thiol groups attached to the main component.

16. A polythioaminal block copolymer, comprising:
a hydrophobic block joined to a hydrophilic block by a particle stabilizing segment, wherein the particle stabilizing segment is linked to the hydrophobic block and the hydrophilic block by a thioaminal linkage.

17. The polythioaminal block copolymer of claim 16 , wherein the hydrophobic block includes a main component, and the main component is a compound selected from the group consisting of: polylactone, polyacrylate, polylactic acid, poly(trimethylene carbonate), poly(lactic-co-glycolic acid), and poly(propylene oxide).

18. The polythioaminal block copolymer of claim 16 , wherein the particle stabilizing segment includes a main component, and the main component is a compound selected from the group consisting of: polyurea, polyurethane, and polyamide.

19. The polythioaminal block copolymer of claim 16 , wherein the hydrophilic block includes a main component, and the main component is poly(ethylene glycol).

20. The polythioaminal block copolymer of claim 16 , wherein the polythioaminal block copolymer is a particle, wherein the hydrophobic block is a hydrophobic core, and the hydrophilic block is a hydrophilic shell, and the particle stabilizing segment is between the hydrophobic core and the hydrophilic shell.

Assignees

• IBM
• Agency For Science Tech And Research Astar

Inventors

• Boday Dylan J
• Chin Willy
• Garcia Jeannette M
• Hedrick James L
• Jiayu Eunice Leong
• Venkataraman Shrinivas
• Voo Zhi Xiang
• Wojtecki Rudy J
• Yang Yi Yan

Classifications

• C08G64/406

  Purifying; Drying · 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

• C08G64/18

  Block or graft polymers · CPC title

• C08G64/183 Primary

  containing polyether sequences · CPC title

• C08G63/64 Primary

  Polyesters containing both carboxylic ester groups and carbonate groups · CPC title