Phosphate-containing copolymers for virulence suppression

Patent metadata

Field	Value
Publication number	US-12448484-B2
Application number	US-202118004910-A
Country	US
Kind code	B2
Filing date	Jun 14, 2021
Priority date	Jul 16, 2020
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

Phosphate-containing copolymers, medical compositions containing the phosphate-containing copolymers, and methods of suppressing microbial virulence are provided. By suppressing virulence, administration and/or application of the medical compositions can be used to prevent, mitigate, or treat a microbial infection. The phosphate-containing copolymers are prepared by phosphorylating either a random copolymer or a random copolymeric block that contains monomeric units of propylene oxide and glycidol.

First claim

What is claimed is:

1. A phosphate-containing copolymer comprising a first copolymeric unit comprising:
(a) monomeric units of Formula (I) and

(b) monomeric units of Formula (II) or a salt thereof and

(c) optional monomeric units of Formula (III)

wherein
R 1 is hydrogen, alkyl, aryl, alkaryl, or aralkyl;
x is mole percent monomeric units of Formula (I) based on total moles of monomeric units in the first copolymeric unit;
y is mole percent monomeric units of Formula (II) based on total moles of monomeric units in the first copolymeric unit;
z is mole percent monomeric units of Formula (III) based on total moles of monomeric units in the first copolymeric unit;
(x+y+2z) is at least 90 mole percent based on total moles of monomeric units in the first copolymeric unit;
100[(y+2z)÷(x+y+2z)] is in a range of 3.5 to 30 percent; and
each asterisk (*) denotes a connection site to another monomeric unit or to a terminal group.

2. The phosphate-containing copolymer of claim 1 , wherein 100[(y+2z)÷(x+y+2z)] is in a range of 5 to 30 mole percent based on total moles of monomeric units in the first copolymeric unit.

3. The phosphate-containing copolymer of claim 1 , wherein the phosphate-containing copolymer is a random copolymer comprising a single first copolymeric unit.

4. The phosphate-containing copolymer of claim 1 , wherein the phosphate-containing copolymer is a block copolymer comprising at least one block that comprises the first copolymeric unit and at least one second block that is free of phosphate groups and that comprises poly(ethylene oxide), poly(propylene oxide), or a combination thereof.

5. The phosphate-containing copolymer of claim 4 , wherein the phosphate-containing copolymer is a triblock copolymer comprising (a) two endblocks that are each the first copolymeric unit and (b) a midblock that is free of phosphate groups and that comprises poly(ethylene oxide), poly(propylene oxide), or a combination thereof.

6. The phosphate-containing copolymer of claim 5 , wherein the midblock is of Formula (IV)
*—(CH 2 CH 2 O) n —(CH 2 CH(CH 3 )O) q —(CH 2 CH 2 O) m —*   (IV)

wherein
n, q, and m are each an integer that is at least 1; and
each asterisk (*) denotes a connection site to another monomeric unit or to a terminal group.

7. The phosphate-containing copolymer of claim 5 , wherein the phosphate-containing copolymer comprises 20 to 70 weight percent midblock based on a total weight of the copolymer.

8. The phosphate-containing copolymer of claim 1 , wherein the phosphate-containing copolymer contains 0.8 to 6.5 mmoles of phosphate per gram of the phosphate-containing copolymer.

9. The phosphate-containing copolymer of claim 8 , wherein the phosphate-containing copolymer contains 1 to 3.5 mmoles of phosphate per gram of the phosphate-containing copolymer.

10. The phosphate-containing copolymer of claim 1 , wherein the phosphate-containing copolymer has a number average molecular weight in a range of 6,000 to 80,000 Daltons.

11. The phosphate-containing copolymer of claim 10 , wherein the number average molecular weight is in a range of 20,000 to 40,000 Daltons.

12. The phosphate-containing copolymer of claim 1 , wherein the phosphate-containing copolymer has a solubility in water that is no greater than 200 milligrams per mL at 30 degrees Celsius.

13. A medical composition comprising a phosphate-containing copolymer, wherein the medical composition is suitable for administration to a mammal and wherein the phosphate-containing copolymer comprises a first copolymeric unit comprising:
(a) monomeric units of Formula (I) and

(b) monomeric units of Formula (II) or a salt thereof and

(c) optional monomeric units of Formula (III)

wherein
R 1 is hydrogen, alkyl, aryl, alkaryl, or aralkyl;
x is mole percent monomeric units of Formula (I) based on total moles of monomeric units in the first copolymeric unit;
y is mole percent monomeric units of Formula (II) based on total moles of monomeric units in the first copolymeric unit;
z is mole percent monomeric units of Formula (III) based on total moles of monomeric units in the first copolymeric unit;
(x+y+2z) is at least 90 mole percent based on total moles of monomeric units in the first copolymeric unit;
100[(y+2z)÷(x+y+2z)] is in a range of 3.5 to 30 percent; and
each asterisk (*) denotes a connection site to another monomeric unit or to a terminal group.

14. The medical composition of claim 13 , wherein the medical composition prevents, mitigates, or treats a microbial infection.

15. The medical composition of claim 13 , wherein the medical composition is a spray, gel, coating, tablet, or capsule.

16. A method of suppressing microbial virulence, the method comprising administering and/or applying a medical composition, the medical composition comprising a phosphate-containing copolymer, the phosphate-containing copolymer comprising a first copolymeric unit comprising:
(a) monomeric units of Formula (I) and

(b) monomeric units of Formula (II) or a salt thereof and

(c) optional monomeric units of Formula (III)

wherein
R 1 is hydrogen, alkyl, aryl, alkaryl, or aralkyl;
x is mole percent monomeric units of Formula (I) based on total moles of monomeric units in the first copolymeric unit;
y is mole percent monomeric units of Formula (II) based on total moles of monomeric units in the first copolymeric unit;
z is mole percent monomeric units of Formula (III) based on total moles of monomeric units in the first copolymeric unit;
(x+y+2z) is at least 90 mole percent based on total moles of monomeric units in the first copolymeric unit;
100[(y+2z)÷(x+y+2z)] is in a range of 3.5 to 30 percent; and
each asterisk (*) denotes a connection site to another monomeric unit or to a terminal group.

17. The method of claim 16 , wherein administering and/or applying the medical composition suppresses at least one type of virulence factor selected from pyocyanin, pyoverdine, collagenase, or biofilm.

18. The method of claim 16 , wherein administering and/or applying the medical composition prevents, mitigates, or treats a microbial infection but does not prevent growth of microbes.

19. The method of claim 16 , wherein administrating and/or applying the medical composition comprises applying the medical composition to skin, mucosa, internal tissue, wound site, surgical site, implant, or bone.

20. The method of claim 16 , wherein administrating and/or applying the medical composition reduces or inhibits virulence of gram negative Pseudomonas aeruginosa

Assignees

• 3M Innovative Properties Company

Inventors

• Laskowski Carl A
• Gillard Timothy M
• Parthasarathy Ranjani V
• Cohen Hannah C
• Kruziki Max A

Classifications

• C08G2650/58

  Ethylene oxide or propylene oxide copolymers, e.g. pluronics · CPC title

• C08G81/00

  Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42}) · CPC title

• C08G65/08

  Saturated oxiranes · CPC title

• A61K31/80

  Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795 · CPC title

• A61L27/34

  Macromolecular materials · CPC title