MULTIFUNCTIONAL POLYMERIC TISSUE COATINGS

• US 20090264538A1
• Filed: 10/29/2007
• Published: 10/22/2009
• Est. Priority Date: 04/21/1997
• Status: Abandoned Application

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Herbert, Curtis B., Hubbell, Jeffrey A., Elbert, Donald L.
• Application Number:
  US11/927,334
• Publication Number:
  US 20090264538A1
• Time in Patent Office: Days
• US Class Current: 514/772.200
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 47/34 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 Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C08G 81/00 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 Class Codes: Y10T 428/31504 Composite [nonstructural laminate]
• CPC Class Codes: Y10T 428/31678 Of metal
• CPC Class Codes: Y10T 428/31725 Of polyamide
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31971 Of carbohydrate

Abstract

Compositions for coating biological and non-biological surfaces, which minimize or prevent cell-cell contact and tissue adhesion, and methods of preparation and use thereof are disclosed. Embodiments include polyethylene glycol/polylysine (PEG/PLL) block or comb-type copolymers with high molecular weight PLL (greater than 1000, more preferably greater than 100,000); PEG/PLL copolymers in which the PLL is a dendrimer which is attached to one end of the PEG; and multilayer compositions including alternating layers of polycationic and polyanionic materials. The multi-layer polymeric material is formed by the ionic interactions of a polycation and a polyanion. The molecular weights of the individual materials are selected such that the PEG portion of the copolymer inhibits cellular interactions, and the PLL portion adheres well to tissues. The compositions and methods are useful, for example, in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells. The compositions and methods are also useful for coating non-biological surfaces such as metallic surfaces.

Claims

1-3. -3. (canceled)

8-10. -10. (canceled)

12-40. -40. (canceled)

41. A method for coating a non-biological surface comprising applying to the surface a two-domain block copolymer

wherein the first domain comprises a non-ionic block, and wherein the second domain comprises a polycationic block,

wherein the surface has a net anionic charge at physiologic pH, and

wherein the polycationic block forms ionic bonds with the surface.

42. The method of claim 41, wherein the surface is a metal surface.

44. The method of claim 41, wherein the surface is the surface of a medical device.

43. (canceled)

45-47. -47. (canceled)

48. A composition comprising a dendritic copolymer, comprising

a polycationic dendrimer with a molecular weight sufficient to provide at least 8 cationic charges,

and a non-ionic polymer covalently linked to the dendrimer,

wherein the composition is in a form suitable for application to a biological or non-biological surface.

4. The composition of claim 48, wherein the non-ionic polymer is selected from the group consisting of polyethylene glycol, mixed polyalkylene oxides having a solubility of at least one gram/liter in aqueous solutions, neutral water-soluble polysaccharides, polyvinyl alcohol, poly-N-vinyl pyrrolidone, non-cationic poly(meth)acrylates and combinations thereof.

5. The composition of claim 4, wherein the non-ionic polymer is polyethylene glycol (PEG).

6. The composition of claim 48, wherein the polycationic dendrimer is selected from the group consisting of natural and unnatural polyamino acids having net positive charge at neutral pH, positively charged polysaccharides, and positively charged synthetic polymers.

7. The composition of claim 48, wherein the polycationic dendrimer comprises monomeric units selected from the group consisting of lysine, histidine, arginine and ornithine.

11. The composition of claim 48, further comprising a bioactive agent.

49. The composition of claim 11, wherein the bioactive agent is covalently attached to the dendritic copolymer.

50. The composition of claim 11, wherein the bioactive agent is linked to the copolymer via a biodegradable linkage.

51. The composition of claim 50, wherein the biodegradable linkage is selected from the group consisting of anhydride, ester, amide, and carbonate linkages.

52. The composition of claim 11, wherein the bioactive agent is selected from the group consisting of proteins, polysaccharides, organic compounds with drug activity, and nucleic acids.

53. The composition of claim 5, wherein the cationic dendrimer comprises poly-L-lysine (PLL).

54. A coating on a non-biological surface, comprising a two-domain block copolymer,

wherein the first domain comprises a non-ionic block, and

wherein the second domain comprises a polycationic block,

wherein the surface has a net anionic charge at physiologic pH, and

wherein the polycationic block forms ionic bonds with the surface.

55. The coating of claim 54, wherein the non-ionic block is selected from the group consisting of polyethylene glycol, mixed polyalkylene oxides having a solubility of at least one gram/liter in aqueous solutions, neutral water-soluble polysaccharides, polyvinyl alcohol, poly-N-vinyl pyrrolidone, non-cationic poly(meth)acrylates and combinations thereof.

56. The coating of claim 55, wherein the non-ionic block comprises polyethylene glycol (PEG).

57. The coating of claim 54, wherein the polycationic block comprises a polymer selected from the group consisting of natural and unnatural polyamino acids having net positive charge at neutral pH, positively charged polysaccharides, and positively charged synthetic polymers.

58. The coating of claim 54, wherein the polycationic block comprises monomeric units selected from the group consisting of lysine, histidine, arginine and ornithine.

59. The coating of claim 54, further comprising a bioactive agent.

60. The coating of claim 56, wherein the polycationic block comprises poly-L-lysine (PLL).

61. The coating of claim 54, wherein the surface is selected from the group consisting of hollow fibers, spiral modules, and flat sheets.

62. The coating of claim 54, wherein the non-biological surface is the surface of a medical device or implant.

63. The coating of claim 54, wherein the surface is formed of a material selected from the group consisting of metal, glass, ceramic, and polymer.