Stimulus-responsive micellar carrier

Patent metadata

Field	Value
Publication number	US-11045552-B2
Application number	US-201715479071-A
Country	US
Kind code	B2
Filing date	Apr 4, 2017
Priority date	Apr 4, 2017
Publication date	Jun 29, 2021
Grant date	Jun 29, 2021

Abstract

A stimulus-responsive micellar carrier, methods that may be associated with making a stimulus-responsive micellar carrier, and methods that may be associated with using a stimulus-responsive micellar carrier are disclosed. The stimulus-responsive micellar carrier comprises a cargo molecule, and a linear block copolymer having a hydrophilic block connected to a hydrophobic block by a stimulus-responsive junction moiety. The micellar carrier can be supplied to a patient body for therapeutic purposes, such as the treatment of cancerous tissue. A method of preparing or obtaining a stimulus-responsive micellar carrier may include preparing a polyethylene glycol material having an acetal end group and then preparing a block copolymer by forming a reaction mixture including the polyethylene glycol material, a cyclic carbonate monomer, and a base.

First claim

What is claimed is:

1. A method of using a micellar carrier, comprising:
preparing a micellar carrier, the micellar carrier comprising:
a cargo molecule, and
a linear block copolymer consisting of a hydrophilic block comprising a polyethylene glycol, a hydrophobic block having a structure comprising a carbonate group, and a stimulus-responsive junction moiety having the structure

wherein one wavy bond represents a bond directly connected to the polyethylene glycol of the hydrophilic block and the other wavy bond represents a bond directly connected to the carbonate group of the hydrophobic block; and

supplying the micellar carrier to a patient body.

2. The method of claim 1 , wherein the cargo molecule is a therapeutic agent.

3. The method of claim 1 , wherein supplying the micellar carrier is performed via intravenous injection.

4. The method of claim 1 , wherein the cargo molecule is an anti-cancer compound.

5. The method of claim 1 , wherein the micellar carrier has a diameter between 20 nm and 200 nm.

6. The method of claim 1 , wherein preparing the micellar carrier comprises:
preparing the hydrophilic block having an acetal end group; and
preparing the linear block copolymer by forming a reaction mixture including the hydrophilic block, a cyclic carbonate monomer, and a base.

7. A method of using a micellar carrier, comprising:
preparing a micellar carrier, wherein the micellar carrier is a nanoscale (10 −9 m) to microscale (10 −6 m) particle, the micellar carrier comprising:
a therapeutic agent, and
a linear block copolymer consisting of a hydrophilic block connected to a hydrophobic block by a stimulus-responsive junction moiety having the structure

wherein:
the hydrophilic block comprises a polyethylene glycol,
the hydrophobic block comprises a carbonate group,
one wavy bond represents a bond directly connected to the polyethylene glycol of the hydrophilic block and the other wavy bond represents a bond directly connected to the carbonate group of the hydrophobic block; and

supplying the micellar carrier to a patient body.

8. The method of claim 7 , wherein supplying the micellar carrier is performed via intravenous injection.

9. The method of claim 7 , wherein the therapeutic agent is an anti-cancer compound.

10. The method of claim 7 , wherein the micellar carrier has a diameter between 20 nm and 200 nm.

11. The method of claim 7 , wherein preparing a micellar carrier comprises:
preparing a polyethylene glycol material having an acetal end group; and
preparing the linear block copolymer by forming a reaction mixture including the polyethylene glycol material, a cyclic carbonate monomer, and a base.

12. A method of using a micellar carrier, comprising:
preparing a micellar carrier comprising preparing a polyethylene glycol material having an acetal end group, and preparing a linear block copolymer by forming a reaction mixture including a polyethylene glycol material, a cyclic carbonate monomer, and a base, wherein the micellar carrier is a nanoscale (10 −9 m) to microscale (10 −6 m) particle, the micellar carrier comprising:
a cargo molecule, and
a linear block copolymer consisting of a hydrophilic block connected to a hydrophobic block by a stimulus-responsive junction moiety having the structure

wherein:
the hydrophilic block comprises a polyethylene glycol,
the hydrophobic block comprises a carbonate group,
one wavy bond represents a bond directly connected to the polyethylene glycol of the hydrophilic block and the other wavy bond represents a bond directly connected to the carbonate group of the hydrophobic block; and

supplying the micellar carrier to a patient body.

13. The method of claim 12 , wherein the cargo molecule is a therapeutic agent.

14. The method of claim 12 , wherein supplying the micellar carrier is performed via intravenous injection.

15. The method of claim 12 , wherein the cargo molecule is an anti-cancer compound.

16. The method of claim 12 , wherein the micellar carrier has a diameter between 20 nm and 200 nm.

17. The method of claim 1 , wherein the structure of the hydrophobic block further comprises an R group, wherein the R group is one of a methyl group, a benzyl group, a derivate of a benzyl group, a linear alkyl group having 2 to 20 carbon atoms, a branched alkyl group having 2 to 20 carbon atoms, a carbamide group having the chemical formula (R 1 R 2 N)CO(NR 3 R 4 ), or a thiourea group having the chemical formula (R 1 R 2 N)CS(NR 3 R 4 ), wherein each of R 1 , R 2 , R 3 , and R 4 is independently a hydrogen or a group that includes at least one carbon atom.

18. The method of claim 1 , wherein the structure of the hydrophobic block further comprises an R group, wherein the R group includes a boronic acid functional group, a carbamide group having the chemical formula (R 1 R 2 N)CO(NR 3 R 4 ), a thiourea group having the chemical formula (R 1 R 2 N)CS(NR 3 R 4 ), one or more unsaturated groups, one or more cyclic groups, or one or more heterocyclic groups, wherein each of R 1 , R 2 , R 3 , and R 4 is independently a hydrogen or a group that includes at least one carbon atom.

19. The method of claim 1 , wherein the structure of the hydrophobic block further comprises an R group, wherein the R group is one of a methyl group or a benzyl group.

20. The method of claim 7 , wherein the structure of the hydrophobic block further comprises an R group, wherein the R group is one of a methyl group or a benzyl group.

Assignees

• IBM
• Agency For Science Tech And Research Astar

Inventors

• Boday Dylan J
• Garcia Jeannette M
• Hedrick James L
• Park Nathaniel H
• Wojtecki Rudy J
• Chuan Yang
• Lee Ashlynn
• Liang zhen chang
• Liu Shaoqiong
• Yang Yi Yan

Classifications

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K47/34 Primary

  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

• C08G64/183

  containing polyether sequences · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title