Polymeric binder and hydrophilic polymer compositions

Abstract

Provided herein are compositions comprising: (a) a polymeric catechol binder, such as: polymeric dopamine, polymeric norepinephrine, polymeric epinephrine; polymeric pyrogallol, polymeric tannic acid, polymeric hydroxyhydroquinone, polymeric catechin, polymeric epigallocatechin etc.; and (b) a hydrophilic polymer, methods for using the compositions to coat a substrate, and methods for making the compositions. In particular, the substrate may form part of an apparatus on which it would be beneficial to limit biofouling and / or protein binding.

Description

CA 02986806 2017-11-22 ANTIFOULING POLYMERIC COATING COMPOSITIONS Technical Field

[0001] The present invention relates to catechol polymer and catechol derivative polymer coating field. In particular, the invention relates to catechol polymers or catechol derivative polymers in combination with certain hydrophilic polymers to form compositions, to provide methods for making the compositions and to provide uses for the compositions. Cross Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Patent Application Serial No. 62 / 166,255 filed on 26 May 2015, entitled “ONE-STEP APPROACH TO UNIVERSAL ANTIFOULING COATINGS”. Background

[0003] In an aging society, medical devices are increasingly used to improve a patients’ quality of life and to extend their life expectancy. For example, intravascular catheters are used to deliver fluids or drugs into bloodstream, and urinary catheters are used to drain waste fluids from the body. In spite of their extensive use, medical devices, such as catheters, are associated with two major challenges: thrombus formation and biofouling or biofilm formation. When such a medical device is inserted into the body of a living organism, a cascade of events is initiated, including protein adsorption, platelet adhesion and activation, complement proteins binding and activation, cellular activation, and cellular attachment on the device surface. These events may initiate host response to the device including the initiation of the coagulation cascade and an inflammatory response leading the formation thrombus and cell attachment on the device surface. In addition, devices having a hydrophobic surface may provide an initial attachment site for microorganisms, which may attach and grow on the device surface and form microbial biofilms. When such microbial growth and / or thrombus formation occurs in an already immune-compromised patient, this may lead to elongated treatment times or even death.

[0004] Although hydrophilic polymer coatings have shown significant advantages as antifouling coatings, it has proven challenging to translate the techniques that have been developed on model surfaces to real world biomedical plastics. For example, many commercially available biomedical devices consist of undefined polymeric components, and it is challenging to apply one coating method to all the polymeric devices. Many of the current coating technologies do not meet all the criteria needed for the translation to medical devices, including the prevention of thrombus and biofilm formation, adaptation to multiple materials and surfaces, easy application of the coating to devices of various sizes and shapes and materials, stability of the coating, and economic feasibility. 1

Claims

What is Claimed is:

1. A composition, the composition comprising: (a) a polymeric binder, wherein a monomer of the polymeric binder has the following structure: wherein, 48 Date Reçue / Date Received 2024-03-19 Date Reçue / Date Received 2024-03-19 wherein E1is H or OH wherein E2 is H or (b) a hydrophilic polymer, wherein the hydrophilic polymer is comprised of monomer units having the following structure: wherein, GisHorCH3; 50 Date Reçue / Date Received 2024-03-19 m is an integer between 400 and 5,000,000; and wherein the hydrophilic polymer has a number average molecular weight (Mn) of at least 100 kDa when measured by Gel Permeation Chromatography (GPC) and wherein the composition isin solution.

2. The composition of claim1,wherein the composition further comprises a buffer.

3. The composition of claim 1, wherein the composition further comprises an aqueous solution.

4. The composition of claim 3, wherein the aqueous solution lacks a salt. 51 Date Reçue / Date Received 2024-03-19 5- The composition of claim 1, wherein the composition further comprises a water soluble organicsolvent.

6. The composition of claim 5, wherein the composition further compriseswater.

7. The composition of claim 2, wherein the buffer has a pH of between 7 and 12.

8. The composition of claim 2 or 7, wherein the buffer comprises a salt.

9. The composition of any one of claims1-8, wherein the ratio of the polymeric binder to hydrophilic polymer is between 100:1and 1:100 by weight.

10. The composition of any one of claims1-9, wherein the ratio of the polymericbinder to hydrophilic polymer is between 1:1and1:30 by weight.

11. The composition of any one of claims1-10, wherein the ratio of the polymeric binder to hydrophilic polymer is between 1:5 and 1:15 by weight.

12. The composition of any one of claims 1-11, wherein the hydrophilic polymer has a number average molecular weight (Mn) of at least 200 kDa, when measured by Gel Permeation Chromatography (GPC).

13. The composition of any one of claims 1-12, wherein the hydrophilic polymer has a number average molecular weight (Mn) of at least 300 kDa, when measured by Gel Permeation Chromatography (GPC).

14. The composition of any one of claims 1-13, wherein the polymeric binder is selected from one or more of: polymeric dopamine (PDA); polymeric norepinephrine (PNE); polymeric epinephrine (PEPI); polymeric pyrogallol (PPG); polymeric tannic acid (PTA); polymeric hydroxyhydroquinone (PHHQ); polymeric catechin; and polymeric epigallocatechin. 52 Date Reçue / Date Received 2024-03-19 15- The composition of any one of claims 1-14, wherein the polymeric binder is selected from one or more of: polymeric dopamine (PDA); polymeric norepinephrine (PNE); polymeric epinephrine (PEPI); polymeric pyrogallol (PPG); and polymeric tannic add (PTA).

16. The composition of any one of claims 1-15, wherein the polymeric binderis selected from one or more of: polymeric dopamine (PDA); polymeric norepinephrine (PNE); polymeric pyrogallol (PPG); and polymeric tannic acid (PTA).

17. The composition of any one of claims 1-16, wherein the polymeric binder is polymeric dopamine (PDA).

18. The composition of any one of claims 1-17, wherein the hydrophilic polymer is selected from one or more of: poly(acrylamide) (PAM); poly(N,N-dimethyl acrylamide) (PDMA); poly(N-hydroxymethyl acrylamide) (PHMA); poly(N-hydroxyethyl acrylamide) (PHEA); poly{N-[tris(hydroxymethyl) methyl]acrylamide} (PTHMAM); poly(N-(2- hydroxypropyl)methacrylamide) (PHPMA); poly(N-(3-(methacryloylamino)propyl)- N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide) (PMPDSAH); andpoly(2- methacryloyloxyethyl phosphorylcholine) (PMPC).

19. The composition of any one of claims1-18, wherein the hydrophilic polymer is selected from one or more of: PAM; PDMA; PHMA; PHEA; and PHPMA.

20. The composition of any one of claims1-19, wherein the hydrophilic polymer is PDMA.

21. A coated substrate, the coated substrate comprising: (a) (b) a substrate;a polymeric binder bound to the substrate, wherein a monomer of the polymeric binder has the following structure: 53 Date Reçue / Date Received 2024-03-19 HO 1 TP HO^S^ D4 wherein, D1is selected from H, OH, 0 Yry™OH , OH 0 H and H D2 is selected from H, OH, 's5^xX^NH2 , ^À^x^^OH XXI 1 o I J OH , O 0 Ax^A^^ A^\n. H and H D2 ^D3 i A^NH2 A^\n / XNH2 oh OH H rOH X°H H 9 9 0 A^sh 9 -X^NH2 A^n^ OH OH H 9 9 xKOE1 0 C°E2 > 9 0 Jl^SH 9 54 Date Reçue / Date Received 2024-03-19 wherein E1is H or OH 55 Date Reçue / Date Received 2024-03-19 wherein E2 is H or (c) a hydrophilic polymer bound to the polymeric binder, wherein the hydrophilic polymeris comprised of monomer units having the following structure: wherein, GisHorCH3; 56 Date Reçue / Date Received 2024-03-19 and m is an integer between 400 and 5,000,000; and wherein the hydrophilic polymer has a number average molecular weight (MJ of at least 100 kDa when measured by Gel Permeation Chromatography (GPC); and wherein the polymeric binder and the hydrophilic polymer bound to the polymeric binder have been applied in a single step.

22. The coated substrate of claim 21, wherein thesubstrateis a plastic, a metal, a ceramic, a carbon based material, a metal oxide, a hydrogel, a biological tissue, a wood or a cement.

23. The coated substrate of claim 21or 22, wherein the substrate is poly(propylene) (PP); poly(urethane) (PU); poly(ethylene) (PE); unplasticized polyvinyl chloride (uPVC); plasticized polyvinyl chloride (pPVC); poly(imide) (PI); ethylene vinyl acetate (EVA); poly(tetrafluoroethylene) (PTFE); titanium dioxide (Ti02), or silicon dioxide (Si02).

24. The coated substrate of claim 21, 22 or 23, wherein the substrate is PP, PU, PE, uPVC, pPVC, PI, EVA, or PTFE.

25. The coated substrate of any one of claims 21-23, wherein the substrate is Ti02or Si02. 57 Date Reçue / Date Received 2024-03-19 26. The coated substrate of any one of claims 21-25, wherein the substrate forms part of an apparatus.

27. The coated substrate of any one of claims 21-26, wherein the substrate is part of an apparatus, the apparatusis selected from: a urinary device; a dental fixture; an artificial joint; a vascular device; a storage device; a microfluidic device; a filtration membrane; a feed tube; or a diagnostic device.

28. The coated substrate of claims 27, wherein the vascular device is a catheter, a lead, or a stent.

29. The coated substrate of claims 27, wherein the urinary device is a urine storage device, catheter, or a stent.

30. The coated substrate of claims 27, wherein the filtration membrane is a blood filtration membrane, a water purification membrane, or an air purification membrane.

31. A method of coating a substrate, the method comprising immersing the substrate in a solution comprising the composition of any one of claims 1-20.

32. A method of coating a substrate, the method comprising spraying the substrate with a solution comprising the composition of any one of claims 1-20.

33. The method of claim 31, further comprising mechanical agitation following immersing the substrate in the solution.

34. The method of claim 31, 32, or 33, wherein the method further comprises drying the substrate.

35. The method of claim 34, wherein the method further comprises applying a further coat of the solution following the drying of the substrate. 58 Date Reçue / Date Received 2024-03-19 36. The method of claim 35, wherein the method further comprises a second drying of the substrate.

37. The method of claim 36, wherein the method further comprises one or more repetitions of the applying a further coat of the solution followed by one or more subsequent drying steps.

38. The method of any one of claims 31-37, further comprising the application of a primer, prior to immersing in or spraying of the solution comprising the composition of any one of claims1-20.

39. The method of claim 35 or 36, wherein the drying is in a flow of argon gasor a flow of nitrogen gas.

40. The composition of any one of claims1-20, wherein the composition is for use as an anti¬ fouling agent.

41. The composition of any one of claims1-20, wherein the composition isfor use as an anti¬ adhesion agent.

42. The coated substrate of any one of claims 21-30, wherein the coated substrate reduces biofouling.

43. The coated substrate of any one of claims 21-30, wherein the coated substrate reduces adhesion.

44. The coated substrate of any one of claims 21-30, wherein the coated substrate reduces thrombusformation.

45. A coated substrate, the coated substrate comprising: (a) a substrate; 59 Date Reçue / Date Received 2024-03-19 (b) a polymeric binder bound to the substrate, wherein a monomer of the polymeric binder has the following structure: D H0^X,D2 HO^Y^D3 D4 I wherein, D1is selected from H, OH, , 0 Yrr w , OH OH 0 and H ; N Y D2 is selected from H, OH, ^H2 , OH 0 Y jS^Y^NH2 OH OH H 5 9 0 ° H H 9 x A I L nh2 -‘Y^n^ , OH H ? OH 0 . f? nH H and ; Date Reçue / Date Received 2024-03-19 (c) a hydrophilic polymer bound to the polymeric binder, wherein the hydrophilic polymeris comprised of monomer units having the following structure: 61 Date Reçue / Date Received 2024-03-19 wherein, GisHorCH3; m is an integer between 400 and 5,000,000; and wherein the hydrophilic polymer has a number average molecular weight (MJ of at least 100 kDa when measured by Gel Permeation Chromatography (GPC); and wherein the polymeric binder and the hydrophilic polymer bound to the polymeric binder in a single coating has a thickness in the range from 17.7to 33.8 nm.

46. The coated substrate of claim 45, wherein the substrate is a plastic, a metal, a ceramic, a carbon based material, a metal oxide, a hydrogel, a biological tissue, a wood or a cement. 62 Date Reçue / Date Received 2024-03-19 47- The coated substrate of claim 45 or 46, wherein the substrate is poly(propylene) (PP); poly(urethane) (PU); poly(ethylene) (PE); unplasticized polyvinyl chloride (uPVC); plasticized polyvinyl chloride (pPVC); poly(imide) (PI); ethylene vinyl acetate (EVA); poly(tetrafluoroethylene) (PTFE); titanium dioxide (Ti02), or silicon dioxide (Si02).

48. The coated substrate of claim 45, 46 or 47, wherein the substrate is PP, PU, PE, uPVC, pPVC, PI, EVA, or PTFE.

49. The coated substrate of any one of claims 45-47, wherein the substrate is Ti02or Si02.

50. The coated substrate of any one of claims 45-49, wherein the substrate forms part of an apparatus.

51. The coated substrate of any one of claims 45-50, wherein the substrate is part of an apparatus, the apparatusis selected from: a urinary device; a dental fixture; an artificial joint; a vascular device; a storage device; a microfluidic device; a filtration membrane; a feed tube; or a diagnostic device.

52. The coated substrate of claims 51, wherein the vascular device is a catheter, a lead, or a stent.

53. The coated substrate of claims 51, wherein the urinary device is a urine storage device, catheter, or a stent.

54. The coated substrate of claims 51, wherein the filtration membrane is a blood filtration membrane, a water purification membrane, or an air purification membrane.

55. The coated substrate of any one of claims 45-54, wherein the coated substrate reduces biofouling.

56. The coated substrate of any one of claims 45-54, wherein the coated substrate reduces adhesion. 63 Date Reçue / Date Received 2024-03-19 57- The coated substrate of any one of claims 45-54, wherein the coated substrate reduces thrombus formation. 64 Date Reçue / Date Received 2024-03-19