Biocompatible adhesion in tissue repair

• US 5,876,743 A
• Filed: 09/22/1997
• Issued: 03/02/1999
• Est. Priority Date: 03/21/1995
• Status: Expired due to Fees

• Current Assignee: DenMat Holdings, LLC
• Original Assignee: Den-Mat Corporation
• Inventors: Ibsen, Robert L., Glace, William R.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US08/934,570
• Time in Patent Office: 526 Days
• Field of Search: 523/115, 424/426
• US Class Current: 424/426
• CPC Class Codes: A61F 2/30767 Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
• CPC Class Codes: A61F 2/3607 including proximal or total replacement of the femur
• CPC Class Codes: A61F 2/3676 Distal or diaphyseal parts of shafts
• CPC Class Codes: A61F 2/4601 for introducing bone substitute, for implanting bone graft implants or for compacting them in the bone cavity
• CPC Class Codes: A61F 2310/00017 Iron- or Fe-based alloys, e.g. stainless steel
• CPC Class Codes: A61F 2310/00023 Titanium or titanium-based alloys, e.g. Ti-Ni alloys
• CPC Class Codes: A61L 2300/106 Halogens or compounds thereof, e.g. iodine, chlorite
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61N 1/37512 Pacemakers
• CPC Class Codes: C08L 33/14 of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen

Abstract

A process for enhancing the

(a) normal healing processes involving a live mammalian body of

(i) injured non-dental-related soft tissue, and

(ii) non-dental-related osseous material, and

(b) for enhancing the biocompatibility and adhesion of bone and/or prosthetic device involved in a non-dental surgical or nonsurgical repair procedure, to ossified and non-ossified tissue components with which they are in contact, where there is an injury to either soft or hard tissue or a non-biocompatible prosthesis is placed in the body, that involves placing at the injury or on the prosthesis

a) a primary coating that is a tenaciously-bonded hydrophilic water insoluble crosslinked resin coating,

b) that optionally contains a measurable amount of a water/fluid leachable fluoride capable of (a) being leached from the coating in a metered amount, and (b) transporting a small amount of leached fluoride from the coating into the afflicted area ("the primary coating with fluoride").

Claims

1. A process for a non-dental-related wound treatment that comprises the step of applying, over a wound, a film or layer of a primary coating that comprises a hydrophilic water insoluble crosslinked resin coating, and, optionally, fluoride.

2. The process of claim 1 wherein the primary coating is cured as a thin film on a non-adhesive surface and is put in contact with the wound as a released film.

3. The process of claim 2, wherein the primary coating is coated on an adhesive receptive surface and cured, and then applied to the wound in the manner of a wound dressing.

4. A wound dressing comprising a primary coating that comprises a hydrophilic water insoluble crosslinked resin and, optionally, fluoride, that has been coated on an adhesive receptive surface and cured prior to application.

5. The wound dressing of claim 4 wherein the adhesive receptive surface is chosen from the group consisting of plastic and cloth.

6. The wound dressing of claim 5 wherein the adhesive receptive surface is a thermoplastic.

7. The wound dressing of claim 4 wherein the primary coating comprises fluoride.

8. The wound dressing of claim 4 wherein the adhesive receptive surface comprises a pressure sensitive adhesive.

9. A process for the treatment of a wound which comprises applying a wound dressing comprising a primary coating that comprises a hydrophilic water insoluble crosslinked resin and leachable fluoride dispersed therein onto an injured portion of a mammalian body, and allowing the fluoride to be released from the primary coating to contact and penetrate the injured area.

10. The process of claim 9, wherein the mammalian body is a human or a domesticated animal.

11. The process of claim 9, wherein the primary coating is formed from a thermoplastic hydrophilic resin that is water insoluble and the wherein the fluoride source is an inorganic fluoride from which the fluoride is leachable with water.

12. The process of claim 11, wherein the thermoplastic resin is a linear polymer that contains a hydroscopic group chosen from the group consisting of hydroxyl, carboxylic acid, amide, amine, aliphatic ether, hydroxyalkyl amine, hydroxyalkyl amide, pyrrolidone, and ureyl.

13. The process of claim 12 wherein the linear polymer comprises polymerized vinyl alcohol, polymerized hydroxyethylmethacrylate, or 2,3-dihydroxypropylacrylate.

14. The process of claim 13 wherein the linear polymer is chosen from the group consisting of a copolymers of vinyl alcohol and vinyl acetate, copolymers of vinyl alcohol and ethylene, copolymers of vinyl alcohol and acrylic acid, and polyacrylic acid.

15. In a non-dental-related surgical process wherein a repair is made by adhering one or more bones and/or prosthetic devices to each other and to any contacting soft tissue, the improvement being that the adherence of said bone(s) and/or prosthetic device(s) is accomplished by applying a primary coating comprising a hydrophilic water insoluble crosslinked resin containing both hard and soft crosslinkers and, optionally, fluoride, to one or more of the surfaces of the bone(s) or prosthetic device(s).

16. The process of claim 15 wherein a primer coating is provided on the surfaces before applying the primary coating.

17. The process of claim 15 wherein the primary coating contains fluoride that is released in small and safe quantities to the environ of the coating and the surfaces during the healing process.

18. In a non-dental-related surgical bone repair process comprising

(i) incising skin to expose an area in which bone undergoing restoration resides,

(ii) exposing the bone undergoing repair,

(iii) defining within the exposed area the manner of restoration of the bone,

(iv) preparing the area for said restoration,

(v) effecting restoration, and

(vi) closing the area after completion of the surgical procedure by closing the skin over the area and providing for the natural or aided healing of any wound associated with such procedure,

the improvement being that, during said restoration, the following steps are followed in sequence:

(v)(a) selecting at least one bone surface within the exposed area that is to be bonded,

(v)(b) coating that surface with a primary coating comprising a hydrophilic water insoluble crosslinked resin containing both hard and soft crosslinkers and, optionally, fluoride,

(v)(c) contacting the coated surface with bone or a prosthetic device,

(v)(d) curing the coating by exposing the coating to light or to ambient temperature.

19. In a non-dental-related surgical procedure to implant a prosthetic device within a body comprising

(i) incising skin to expose an area of the body in which the prosthetic device is to be inserted,

(ii) defining within the exposed area the manner of restoration therein by implantation of the prosthetic device,

(iii) preparing the area for restoration,

(iv) effecting restoration,

(v) and closing the area after completion of the surgical procedure by closing the skin over the area and providing for the natural or aided healing of any wound associated with such procedure,

the improvement which comprises, during said restoration, the following steps:

(iv)(a) selecting at least one prosthetic device surface within the exposed area that is to be bonded,

(iv)(b) coating that surface with a primary coating comprising a hydrophilic water insoluble crosslinked resin containing both hard and soft crosslinkers and, optionally, fluoride,

(iv)(c) contacting the coated surface with bone and/or tissue,

(iv)(d) optionally adding a patch of a cured film of the primary coating with fluoride, and

(iv)(e) curing the coating by exposing the coating to light or to ambient temperature.

20. In a non-dental-related process for aiding in the healing of an open wound or an exposed wound, the improvement which comprises superimposing a cured layer of a primary coating comprising a hydrophilic water insoluble crosslinked resin and fluoride onto the wound such that the tissues at the wound surface are in direct contact with the layer, and maintaining contact between the layer and the wound at least until such time as the wound is essentially closed as a result of the healing process.

21. In the process of claim 20 wherein the cured layer of primary coating with fluoride has, on one surface thereof, a layer of uncured primary coating with fluoride, and wherein the uncured primary coating is cured while both it and the cured primary coating are in contact with the wound by exposing the uncured primary coating to light and/or ambient temperature.

22. A non-dental-related process for repairing an injured or degenerated osseous material which comprises superimposing a patch of a cured layer of a primer coating comprising a hydrophilic water insoluble crosslinked resin with fluoride onto the injured or degenerated area of the osseous material, leaving such patch in contact with the area and allowing growth of the osseous material to encompass the patch and repair the injured or degenerated area.

23. In the process of claim 22 wherein the cured layer of primary coating with fluoride is formed having, one surface thereof, an uncured primary coating with fluoride, and wherein the uncured primary coating is cured while it and the associated cured primary coating are in contact with the area undergoing treatment by exposing the uncured primary coating to light and/or ambient temperature.

24. A process for enhancing the normal healing processes of injured non-dental-related soft tissue and non-dental-related osseous material, that involves placing at the injury a primary coating that is a hydrophilic water insoluble crosslinked resin coating that optionally contains a measurable amount of a water/fluid leachable fluoride capable of (a) being leached from the coating in a metered amount, and (b) transporting a small amount of leached fluoride from the coating into the afflicted area.

25. The process of claim 24 wherein the amount of fluoride provided in the primary coating is insufficient to cause fluorosis of any other toxic reaction, and the fluoride assists the normal processes of wound healing.

26. The process of claim 24 wherein the primary coating is one layer in a multilayer composite and wherein said composite further comprises a strongly adhesively bonded crosslinkable acrylic resin that rapidly that possesses less hydrophilicity than the primary coating and that cures in situ on an application surface to function as a primer for the primary coating.

27. The process of claim 24 wherein the resin is based on an ethylenically unsaturated functional monomer that contains a hygroscopic group.

28. The process of claim 27 wherein the ethylenically unsaturated functional monomer contains hygroscopic groups and exhibits hydrophilicity.

29. The process of claim 27 wherein the primary coating contains a polycarboxylic acid.

30. The process of claim 27 wherein the primary coating contains at least one crosslinking agent.

31. The process of claim 30 wherein the crosslinking agent is a combination of a hard crosslinker and a soft crosslinker.

32. The process of claim 27 wherein the primary coating contains a coupling agent.

33. The process of claim 27 wherein the primary coating contains leachable fluoride.

34. The process of claim 24 wherein the primary coating comprises a two component system that comprises:

(a) a first component comprising;

(1) a fluoride source including as a particulate siliceous fluoride containing filler in which the fluoride is water leachable;

(2) a coupling agent;

(3) a photoinitiator or a radiopaquing agent or a buffering agent; and

(b) a second component comprising;

(1) an ethylenically-unsaturated-functional monomer;

(2) a soft crosslinker;

(3) a hard crosslinker;

(4) a photoinitiator;

(5) a polymerized carboxylic acid;

(6) a free-radical scavenger; and

(7) a curing catalyst.

35. The process of claim 34 wherein the coupling agent is one or more of (i) N-phenylglycine, the alkali metal salt thereof, or the mixture of the foregoing two compounds, (ii) the adduct of N-(p-tolyl)glycine and glycidyl methacrylate, the alkali metal salt thereof, or the mixture of the foregoing two compounds, and (iii) the adduct of N-phenylglycine and glycidyl methacrylate, the alkali metal salt thereof, or the mixture of the foregoing two compounds.

36. The process of claim 34 wherein the soft crosslinker is one or more of 2,2-bis(4-methacryloxy-2-ethoxyphenyl)propane, and diethyleneglycol-bis-methacrylate.

37. The process of claim 34 wherein the hard crosslinker is one or more of (i) the adduct of pyromellitic acid dianhydride and 2-hydroxyethylmethacrylate, (ii) the adduct of 3,3'"'"',4,4'"'"'-benzophenonetetracarboxylic dianhydride and 2-hydroxyethylmethacrylate, (iii) 4-methacryloxytrimellitic anhydride, and (iv) other compounds containing at least one group or moiety capable of free radical polymerization and at least one aromatic ring or moiety containing electron-withdrawing substituents that do not interfere with free radical polymerization.

38. A process for enhancing the biocompatibility and adhesion of bone and/or prosthetic devices involved in a non-dental procedure to tissue components with which they are in contact and wherein there is an injury, that involves placing at the injury or on the prosthesis a primary coating that is a hydrophilic water insoluble crosslinked resin coating containing both hard and soft crosslinkers and, optionally, a measurable amount of a water/fluid leachable fluoride capable of (a) being leached from the coating in a metered amount, and (b) transporting a small amount of leached fluoride from the coating into the afflicted area.

39. The process of claim 38 wherein the prosthesis is made of one or more of metal, ceramic or plastic.

40. The process of claim 38 wherein the amount of fluoride provided in the primary coating is insufficient to cause fluorosis of any other toxic reaction, and the fluoride assists the normal processes of wound healing.

41. The process of claim 38 wherein bone and/or prosthetic device surfaces in a non-dental-related surgical procedure, are joined by applying the primary coating or the primary coating with fluoride to bond one or more of the surfaces prior to completion of a surgical repair.

42. The process of claim 38 wherein the primary coating is one layer in a multilayer composite and wherein said composite further comprises a strongly adhesively bonded crosslinkable acrylic resin that rapidly that possesses less hydrophilicity than the primary coating and that cures in situ on an application surface to function as a primer for the primary coating.

43. The process of claim 38 wherein the primary coating comprises a resin based on an ethylenically unsaturated functional monomer that contains a hygroscopic group.

44. The process of claim 43 wherein the ethylenically unsaturated functional monomer contains hygroscopic groups and exhibits hydrophilicity.

45. The process of claim 43 wherein the primary coating contains a polycarboxylic acid.

46. The process of claim 43 wherein the primary coating contains a coupling agent.

47. The process of claim 43 wherein the primary coating contains leachable fluoride.

48. The process of claim 43 wherein the primary coating comprise a two component system comprising:

(a) a first component comprising;

(1) a fluoride source including as a particulate siliceous fluoride containing filler in which the fluoride is water leachable;

(2) a coupling agent;

(3) a photoinitiator or a radiopaquing agent or a buffering agent; and

(b) a second component comprising;

(1) an ethylenically-unsaturated-functional monomer;

(2) a soft crosslinker;

(3) a hard crosslinker;

(4) a photoinitiator;

(5) a polymerized carboxylic acid;

(6) a free-radical scavenger; and

(7) a curing catalyst.

49. The process of claim 48 wherein the coupling agent is one or more of (i) N-phenylglycine, the alkali metal salt thereof, or the mixture of the foregoing two compounds, (ii) the adduct of N-(p-tolyl)glycine and glycidyl methacrylate, the alkali metal salt thereof, or the mixture of the foregoing two compounds, and (iii) the adduct of N-phenylglycine and glycidyl methacrylate, the alkali metal salt thereof, or the mixture of the foregoing two compounds.

50. The process of claim 48 wherein the soft crosslinker is one or more of 2,2-bis(4-methacryloxy-2-ethoxyphenyl)propane, and diethyleneglycol-bis-methacrylate.

51. The process of claim 48 wherein the hard crosslinker is one or more of (i) the adduct of pyromellitic acid dianhydride and 2-hydroxyethylmethacrylate, (ii) the adduct of 3,3'"'"',4,4'"'"'-benzophenonetetracarboxylic dianhydride and 2-hydroxyethylmethacrylate, (iii) 4-methacryloxytrimellitic anhydride, and (iv) other compounds containing at least one group or moiety capable of free radical polymerization and at least one aromatic ring or moiety containing electron-withdrawing substituents that do not interfere with free radical polymerization.