# US 11,999,848 B2 · Hydrophilic polyarylene ether ketone polymer and methods of forming same

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- Number: US 11,999,848 B2
- Document ID: US11999848B2
- Status: Granted
- Kind: B2
- Application number: 16/967,456
- Filed: 2019-02-05
- Published: 2021-07-22
- Granted: 2024-06-04
- Earliest claimed: 2018-02-06
- Assignees: Allegheny-Singer Research Institute
- Applicants: Allegheny Singer Research Institute
- Inventors: Saadyah Averick; Boyle Cheng; Andrew Kassick; Michael Oh
- Web page: https://patentgrep.com/patent/US11999848B2

## CPC

- C08G 65/48: Polymers modified by chemical after-treatment
- C08L 71/12: Polyphenylene oxides
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- C08G 65/485: {Polyphenylene oxides}
- C08K 5/17: Amines; Quaternary ammonium compounds
- C09D 171/00: Coating compositions based on polyethers obtained by reactions forming an ether link in the main chain (based on polyacetals C09D159/00; based on epoxy resins C09D163/00; based on polythioether-ethers C09D181/02; based on polyethersulfones C09D181/06); Coating compositions based on derivatives of such polymers
- A61L 2430/38: for reconstruction of the spine, vertebrae or intervertebral discs
- C08G 2650/40: containing ketone groups, e.g. polyarylethylketones, PEEK or PEK
- C08L 2203/02: for biomedical use
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C08K: Use of inorganic or non-macromolecular organic substances as compounding ingredients (paints, inks, varnishes, dyes, polishes, adhesives C09)
- C09D: COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR (cosmetics A61K; processes for applying liquids or other fluent materials to surfaces, in general, B05D; staining wood B27K5/02; glazes or vitreous enamels C03C; natural resins, French polish, drying-oils, driers, turpentine, per se, C09F; polishing compositions other than French polish, ski waxes C09G; adhesives or use of materials as adhesives C09J; materials for sealing or packing joints or covers C09K3/10; materials for stopping leaks C09K3/12; processes for the electrolytic or electrophoretic production of coatings C25D)

## Abstract

This patent document discloses a modified polymer having increased hydrophilicity and a method of preparing the same. A polyarylene ether ketone polymer having a plurality of repeating units, wherein one or more units of the plurality of repeating units contains a hydrophilic N-substituted imine, which is derived from a ketone in the one or more units.

## Claims

### Claim 1

A polyarylene ether ketone polymer having a plurality of repeating units, wherein a ketone group in one or more units of the plurality of repeating units comprises a hydrophilic N-substituted imine,
wherein the one or more units comprising the hydrophilic N-substituted imine are independently represented by Formula I,
wherein:
Ar1, Ar2, Ar3, and Ar4 are each an optionally substituted aryl;
each of X1 and X2 is independently selected from the group consisting of O,
wherein:
Y is a C1-C10 alkylene, wherein one or more carbons in the C1-C10 alkylene are independently and optionally replaced with a heteroatom, a carbonyl, or NR1R2,
Ra is selected from the group consisting of OR1, NR1R2, C1-C5 alkyl, a primary, secondary, tertiary, or quaternary ammonium salt moiety, a pyridinium salt moiety, a guanidino or guanidinium salt moiety, a peptide, an amino acid, and a zwitterionic species, wherein R1 and R2 are independently an H or a C1-C5 alkyl, and
provided that at least one of all the X1s and all the X2s in each of the one or more units is not O;
m and n are each an integer of 1, 2, or 3; and
o and p are each an integer of 0, 1, or 2.

### Claim 2 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein the one or more units account for about 0.1% to about 25% of the plurality of repeating units.

### Claim 3 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein the one or more units account for about 0.1% to about 10% of the plurality of repeating units.

### Claim 4 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein o and p are each 0.

### Claim 5 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein m is 1, n is 1, and o and p are each 0.

### Claim 6 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein m is 1, n is 1, o is 0, and p is 1.

### Claim 7 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein only one of all the X1s and all the X2s in each of the one or more units is selected from the group consisting of

### Claim 8 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein at least one of all the X1s and all the X2s in the one or more units is

### Claim 9 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein at least one of all the X1s and all the X2s in the one or more units is

### Claim 10 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein at least one of all the X1s and all the X2s in the one or more units is

### Claim 11 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein Ra is selected from the group consisting of OR1, NR1R2, a quaternary ammonium salt moiety, a pyridinium salt moiety, a guanidino salt moiety, a guanidinium salt moiety, and a peptide.

### Claim 12 (depends on 1)

The polyarylene ether ketone polymer of claim 1, wherein Ar1, Ar2, Ar3, and Ar4 are each a phenyl group.

### Claim 13

A medical device comprising a surface coating comprising a polyarylene ether ketone polymer having a plurality of repeating units, wherein a ketone group in one or more units of the plurality of repeating units comprises a hydrophilic N-substituted imine, wherein the device is an implant,
wherein the one or more units comprising the hydrophilic N-substituted imine are independently represented by Formula I,
wherein:
Ar1, Ar2, Ar3, and Ar4 are each an optionally substituted aryl;
each of X1 and X2 is independently selected from the group consisting of O,
wherein:
Y is a C1-C10 alkylene, wherein one or more carbons in the C1-C10 alkylene are independently and optionally replaced with a heteroatom, a carbonyl, or NR1R2,
Ra is selected from the group consisting of OR1, NR1R2, C1-C5 alkyl, a primary, secondary, tertiary, or quaternary ammonium salt moiety, a pyridinium salt moiety, a guanidino or guanidinium salt moiety, a peptide, an amino acid, and a zwitterionic species, wherein R1 and R2 are independently an H or a C1-C5 alkyl, and
provided that at least one of all the X1s and all the X2s in each of the one or more units is not O;
m and n are each an integer of 1, 2, or 3; and
o and p are each an integer of 0, 1, or 2.

### Claim 14 (depends on 13)

The medical device of claim 13, which is an orthopedic implant.

### Claim 15 (depends on 13)

The medical device of claim 13, wherein the one or more units account for about 0.1% to about 25% of the plurality of repeating units.

### Claim 16 (depends on 13)

The medical device of claim 13, wherein the one or more units account for about 0.1% to about 10% of the plurality of repeating units.

### Claim 17 (depends on 13)

The medical device of claim 13, wherein at least one of all the X1s and all the X2s in the one or more units is

### Claim 18 (depends on 13)

The medical device of claim 13, wherein at least one of all the X1s and all the X2s in the one or more units is

### Claim 19 (depends on 13)

The medical device of claim 13, wherein at least one of all the X1s and all the X2s in the one or more units is

### Claim 20 (depends on 13)

The medical device of claim 13, wherein at least one of all the X1s and all the X2s in the one or more units is

### Claim 21 (depends on 13)

The medical device of claim 13, wherein Ra is selected from the group consisting of OR1, NR1R2, a quaternary ammonium salt moiety, a pyridinium salt moiety, a guanidino salt moiety, a guanidinium salt moiety, and a peptide.

### Claim 22 (depends on 13)

The medical device of claim 13, wherein Ar1, Ar2, Ar3, and Ar4 are each a phenyl group.

### Claim 23 (depends on 13)

The medical device of claim 13, wherein Ra is OR1 or NR1R2.

### Claim 24 (depends on 13)

The medical device of claim 13, wherein o and p are each 0.

### Claim 25 (depends on 13)

The medical device of claim 13, wherein m is 1, n is 1, and o and p are each 0.

### Claim 26 (depends on 13)

The medical device of claim 13, wherein m is 1, n is 1, o is 0, and p is 1.

### Claim 27

A medical device comprising a surface coating comprising a polyarylene ether ketone polymer having a plurality of repeating units, wherein a ketone group in one or more units of the plurality of repeating units comprises a hydrophilic N-substituted imine, wherein the one or more units comprising the hydrophilic N-substituted imine are independently represented by Formula I,
wherein:
Ar1, Ar2, Ar3, and Ar4 are each an optionally substituted aryl;
each of X1 and X2 is independently selected from the group consisting of O,
wherein:
Y is a C1-C10 alkylene, wherein one or more carbons in the C1-C10 alkylene are independently and optionally replaced with a heteroatom, a carbonyl, or NR1R2,
Ra is selected from the group consisting of OR1, NR1R2, C1-C5 alkyl, a primary, secondary, tertiary, or quaternary ammonium salt moiety, a pyridinium salt moiety, a guanidino or guanidinium salt moiety, a peptide, an amino acid, and a zwitterionic species, wherein R1 and R2 are independently an H or a C1-C5 alkyl, and
provided that at least one of all the X1s and all the X2s in each of the one or more units is not O;
m and n are each an integer of 1, 2, or 3; and
o and p are each an integer of 0, 1, or 2.

### Claim 28 (depends on 13)

A method of promoting spinal fusion, comprising implanting to a subject in need the medical device of claim 13.

### Claim 29 (depends on 28)

The method of claim 28, which promotes osseointegration of new bone tissue into the medical device.

### Claim 30

A method of modifying a medical device comprising a surface polymer comprising a plurality of repeating units, comprising
(a) contacting the surface polymer with an agent selected from the group consisting of
in a reaction medium
wherein:
Y is a C1-C10 alkylene, wherein one or more carbons in the C1-C10 alkylene is optionally replaced with a heteroatom or a carbonyl; and
Ra is selected from the group consisting of OR1, NR1R2, C1-C5 alkyl, a primary, secondary, tertiary, or quaternary ammonium moiety, a pyridinium salt moiety, a guanidino or guanidinium salt moiety, a peptide, an amino acid, and a zwitterionic species, wherein R1 and R2 are each an H or a C1-C5 alkyl; and
(b) allowing a ketone group of one or more units of the plurality of repeating units to react with the agent, whereby the ketone group of the one or more units is converted to a hydrophilic derivative group;
wherein each of the plurality of repeating units in the hydrophilic derivative group is independently represented by Formula I,
wherein:
Ar1, Ar2, Ar3, and Ar4 are each an optionally substituted aryl;
each of X1 and X2 is independently selected from O,
wherein:
Y is a C1-C10 alkylene, wherein one or more carbons in the C1-C10 alkylene is optionally replaced with a heteroatom, a carbonyl or NR1R2,
Ra is selected from the group consisting of OR1, NR1R2, C1-C5 alkyl, a primary, secondary, tertiary, or quaternary ammonium salt moiety, a pyridinium salt moiety, a guanidino or guanidinium salt moiety, a peptide, an amino acid, or a zwitterionic species, wherein R1 and R2 are independently an H or a C1-C5 alkyl, and
provided that at least one of all the X1s and all the X2s in each of the one or more units is not O;
m and n are each an integer of 1, 2, or 3; and
o and p are each an integer of 0, 1, or 2.

### Claim 31 (depends on 30)

The method of claim 30, wherein the molar ratio between the surface polymer and the agent ranges from about 10:1 to about 1:100.

### Claim 32 (depends on 30)

The method of claim 30, wherein the reaction medium has a pH ranging from about 1.5 to about 3.

### Claim 33 (depends on 30)

The method of claim 30, wherein the reaction medium has a pH about 2.0.

### Claim 34 (depends on 30)

The method of claim 30, wherein the reaction medium comprises an acid, and the acid and the surface polymer are in a molar ratio ranging from about 100:1 to about 1:100.

### Claim 35 (depends on 30)

The method of claim 30, wherein the agent is in a form of an acid salt.

### Claim 36 (depends on 30)

The method of claim 30, wherein the agent is in a concentration ranging from about 0.1 mg/ml to about 1000 mg/ml.

### Claim 37 (depends on 30)

The method of claim 30, wherein the agent is in a concentration ranging from about 0.1 mg/ml to about 50 mg/ml.

### Claim 38 (depends on 30)

The method of claim 30, wherein the surface polymer is submerged in the reaction medium.

### Claim 39 (depends on 30)

The method of claim 30, wherein the reaction medium comprises a polar solvent.

### Claim 40 (depends on 30)

The method of claim 30, wherein step (b) takes place at a temperature of less than about 65° C.

### Claim 41 (depends on 30)

The method of claim 30, wherein the medical device is an implant.