Phase-separated polymer coatings

• US 20050100609A1
• Filed: 12/16/2004
• Published: 05/12/2005
• Est. Priority Date: 03/30/2001
• Status: Abandoned Application

• Current Assignee: Charles David Claude
• Original Assignee: Charles David Claude
• Inventors: Claude, Charles David
• Application Number:
  US11/015,617
• Publication Number:
  US 20050100609A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L

Abstract

The present invention includes a drug release system. The drug release system comprises a bulk polymer phase and a polymeric drug-enriched phase within the bulk polymer phase. At least one, drug is incorporated into the drug-enriched phase.

Claims

1-43. -43. (canceled)

44. a drug-delivery stent comprising a coating, wherein the coating includes:

a first-polymer phase comprising a first-polymer, a second-polymer phase comprising a second-polymer, and a drug;

wherein, the second-polymer phase is substantially or completely immiscible in the first-polymer phase, and the drug is preferentially incorporated in the second-polymer phase.

45. The stent of claim 44, wherein the first-polymer phase has a film forming property.

46. The stent of claim 44, wherein the drug comprises an antibiotic, antiproliferative, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antioxidant, or a combination thereof.

47. The stent of claim 44, wherein the second-polymer phase comprises sites that are substantially or completely disconnected in the coating, such that elution of the drug from the coating occurs through transport of the drug across both the second-polymer phase and the first-polymer phase.

48. The stent of claim 44, wherein the second-polymer phase comprises sites that are substantially or completely connected in the coating, such that elution of the drug from the coating includes transport of the drug primarily through the second-polymer phase.

49. The stent of claim 44, wherein the second-polymer phase comprises sites that are substantially or completely connected in the coating, such that elution of the drug from the coating includes transport of the drug exclusively through the second-polymer phase.

50. The stent of claim 44, wherein the concentration of the second-polymer phase in the coating is less than or equal to about 30% by volume.

51. The stent of claim 44, wherein the concentration of the second-polymer phase in the coating is greater than or equal to about 30% by volume.

52. The stent of claim 44, wherein the coating comprises the second-polymer phase in a concentration that is less than or equal to a percolation threshold of the coating.

53. The stent of claim 44, wherein the coating comprises the second-polymer phase in a concentration that is greater than or equal to a percolation threshold of the coating.

54. The stent of claim 44, wherein the second-polymer phase has a glass-transition temperature of less than about 37°

C.

55. The stent of claim 44, wherein the drug has a preferential solubility for the second-polymer phase, such that the drug becomes preferentially incorporated in the second-polymer phase in the coating.

56. The stent of claim 44, wherein the drug has a preferential solubility in a solvent used to form the coating, the solvent preferentially solubilizes the second polymer over the first polymer, and the drug becomes preferentially incorporated in the second-polymer phase upon removing the solvent to form the coating.

57. A method of coating a stent comprising incorporating a drug preferentially in a second-polymer phase during a coating process, wherein the coating process comprises:

forming a coating composition comprising a first polymer for a first polymer phase, a second polymer for a second polymer phase, a drug, and a solvent;

wherein the second polymer is substantially or completely immiscible in the first polymer;

applying the composition to a stent; and

removing the solvent from the composition to form a coating including the first-polymer phase, the second-polymer phase, and the drug, wherein the drug is preferentially in the second-polymer phase.

58. The method of claim 57, wherein the incorporating includes selecting a drug with a preferential solubility in the second-polymer phase, such that the drug becomes preferentially incorporated in the second-polymer phase in the coating.

59. The method of claim 57, wherein the incorporating includes selecting a drug with a preferential solubility in the solvent, and the solvent preferentially solubilizes the second polymer over the first polymer, such that the drug becomes preferentially incorporated in the second-polymer phase upon removing the solvent to form the coating.

60. The method of claim 57, wherein the drug comprises an antibiotic, antiproliferative, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antioxidant, or a combination thereof.

61. The method of claim 57, wherein the second-polymer phase has a glass-transition temperature of less than about 37°

C.

62. The method of claim 57, wherein the coating comprises the second-polymer phase in a concentration that is less than or equal to a percolation threshold of the coating composition.

63. The method of claim 57, wherein the coating comprises the second-polymer phase in a concentration that is greater than or equal to a percolation threshold of the coating composition.

64. The method of claim 57, wherein the concentration of the second-polymer phase in the coating is less than or equal to about 30% by volume.

65. The method of claim 57, wherein the second-polymer phase comprises sites that are substantially or completely disconnected throughout the coating, such that elution of the drug from the second-polymer phase occurs through transport of the drug across both the second-polymer phase and the first-polymer phase.

66. The method of claim 57, wherein the concentration of the second-polymer phase in the coating is greater than or equal to about 30% by volume.

67. The method of claim 57, wherein the second-polymer phase comprises sites that are substantially or completely connected throughout the coating, such that elution of the drug from the second-polymer phase includes transport of the drug primarily through the second-polymer phase.

68. The method of claim 57, wherein the second-polymer phase comprises sites that are substantially or completely connected throughout the coating, such that elution of the drug from the second-polymer phase includes transport of the drug exclusively through the second-polymer phase.

69. The method of claim 57, wherein the first polymer constitutes more in amount than the second polymer in the composition.

70. The method of claim 57, wherein the forming comprises:

blending the first polymer with the second polymer in the solvent to form a solution; and

adding the drug to the solution such that the drug is preferentially incorporated in the second-polymer phase in the coating.

71. A drug-delivery stent comprising a coating, wherein the coating includes:

a first-polymer phase comprising a first-polymer, a second-polymer phase comprising a second-polymer, and a drug;

wherein, the second-polymer phase is partially or substantially phase-separated from the first-polymer phase, and the drug is preferentially incorporated in the second-polymer phase.

72. A method of coating a stent comprising incorporating a drug preferentially in a second-polymer phase during a coating process, wherein the coating process comprises:

forming a coating composition comprising a first polymer for a first-polymer phase, a second polymer for a second-polymer phase, a drug, and a solvent;

applying the composition to a stent; and

removing the solvent from the composition to form a coating with the drug preferentially in the second-polymer phase, wherein the second-polymer phase is partially or substantially phase-separated from a first-polymer phase.

73. A therapeutic composition for coating stents comprising:

a first polymer component;

a second polymer component, wherein the second polymer component at least partially separates from the first polymer component when a coating is formed from the composition; and

a drug being preferentially enriched in the second polymer component when the coating is formed from the composition.

74. The composition of claim 73, wherein the first-polymer component has a film forming property.

75. The composition of claim 73, wherein the drug comprises an antibiotic, antiproliferative, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antioxidant, or a combination thereof.

76. The composition of claim 73, wherein the composition forms second-polymer component sites that are substantially or completely disconnected when a coating is formed from the composition, such that elution of the drug from the coating occurs through transport of the drug across both the second-polymer component and the first-polymer component.

77. The composition of claim 73, wherein the composition forms second-polymer component sites that are substantially or completely connected when a coating is formed from the composition, such that elution of the drug from the coating includes transport of the drug primarily through the second-polymer component.

78. The composition of claim 73, wherein the composition forms second-polymer component sites that are substantially or completely connected when a coating is formed from the composition, such that elution of the drug from the coating includes transport of the drug exclusively through the second-polymer component.

79. The composition of claim 73, wherein the concentration of the drug-enriched second-polymer component in the coating is less than or equal to about 30% by volume.

80. The composition of claim 73, wherein the concentration of the drug-enriched second-polymer component in the coating is greater than or equal to about 30% by volume.

81. The composition of claim 73, wherein the coating comprises the drug-enriched second-polymer component in a concentration that is less than or equal to a percolation threshold of the coating.

82. The composition of claim 73, wherein the coating comprises the drug-enriched second-polymer component in a concentration that is greater than or equal to a percolation threshold of the coating.

83. The composition of claim 73, wherein the drug-enriched second-polymer component has a glass-transition temperature of less than about 37°

C.

84. The composition of claim 73, wherein the drug has a preferential solubility for the second-polymer component, such that the drug becomes preferentially incorporated in the second-polymer component when the coating is formed from the composition.

85. The composition of claim 73 additionally including a solvent used to form the coating, such that the drug has a preferential solubility in the solvent, and the solvent preferentially solubilizes the second polymer over the first polymer, wherein the drug becomes preferentially incorporated in the second-polymer component upon removing the solvent to form the coating.