Antimicrobial coatings for medical devices and methods for making and using them
First Claim
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1. A method of inhibiting growth of a microorganism on a surface of a medical device comprising identifying a susceptible surface on the medical device that is observed to be colonized in vivo by a microorganism when the device is implanted in an individual and coating the surface of the medical device with:
- (a) a first layer comprising an antimicrobial composition that includes an enzyme that generates hydrogen peroxide upon exposure to a ligand of the enzyme; and
(b) a second layer disposed on the first layer comprising;
an antimicrobial composition comprising a polyurea-silicone copolymer having a quaternary amine moiety, wherein;
the first layer is disposed on the medical device so as to allow hydrogen peroxide generated by the enzyme in the first layer to diffuse away from the enzyme and contact a microorganism attempting to grow on the medical device thereby inhibiting its growth;
the second layer is formed from a reaction mixture comprising a diisocyanate, a hydrophilic polymer which is selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof, and a siloxane;
the quaternary amine moiety in the second layer inhibits the growth of a microorganism that contacts the second layer, so that microbial growth is inhibited on the surface of the medical device when the surface is exposed to a microorganism,and the device is a glucose sensor comprising a plurality of layers, wherein the plurality of layers include;
an electrode having an electrochemically reactive surface area;
an analyte sensing layer that detectably alters electrical current at the electrode in the presence of an analyte; and
an analyte modulating layer that modulates diffusion of an analyte therethrough.
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Abstract
Embodiments of the invention provide methods for using compositions to inhibit microbial growth on a surface of a medical device having the composition applied thereto, to medical devices having the composition applied to a surface thereof and to methods for using the compositions to coat medical devices.
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Citations
15 Claims
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1. A method of inhibiting growth of a microorganism on a surface of a medical device comprising identifying a susceptible surface on the medical device that is observed to be colonized in vivo by a microorganism when the device is implanted in an individual and coating the surface of the medical device with:
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(a) a first layer comprising an antimicrobial composition that includes an enzyme that generates hydrogen peroxide upon exposure to a ligand of the enzyme; and (b) a second layer disposed on the first layer comprising;
an antimicrobial composition comprising a polyurea-silicone copolymer having a quaternary amine moiety, wherein;the first layer is disposed on the medical device so as to allow hydrogen peroxide generated by the enzyme in the first layer to diffuse away from the enzyme and contact a microorganism attempting to grow on the medical device thereby inhibiting its growth; the second layer is formed from a reaction mixture comprising a diisocyanate, a hydrophilic polymer which is selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof, and a siloxane; the quaternary amine moiety in the second layer inhibits the growth of a microorganism that contacts the second layer, so that microbial growth is inhibited on the surface of the medical device when the surface is exposed to a microorganism, and the device is a glucose sensor comprising a plurality of layers, wherein the plurality of layers include; an electrode having an electrochemically reactive surface area; an analyte sensing layer that detectably alters electrical current at the electrode in the presence of an analyte; and an analyte modulating layer that modulates diffusion of an analyte therethrough. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A method of inhibiting formation of a biofilm on a medical device that is implanted in an individual having hyperglycemia, the method comprising:
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(a) identifying a surface on the medical device that is observed to be colonized by a biofilm forming microorganism; and (b) coating the surface with; a first layer that comprises an antimicrobial composition that includes an oxidoreductase that generates hydrogen peroxide upon exposure to a ligand for the oxidoreductase, wherein the amount of hydrogen peroxide generated by the oxidoreductase is proportional to the amount of ligand exposed to the oxidoreductase; and a second layer disposed over the first layer that comprises an antimicrobial composition comprising a polyurea-silicone copolymer, wherein; the first layer is disposed on the medical device so as to allow hydrogen peroxide generated by the oxidoreductase in the first layer to diffuse away from the oxidoreductase and contact a microorganism attempting to grow on the medical device thereby inhibiting its growth; the second layer is formed from a reaction mixture comprising a diisocyanate, a hydrophilic polymer which is selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof, and a siloxane; and a quaternary amine moiety in the second layer inhibits the growth of a microorganism that contacts the second layer; so that formation of a biofilm on the medical device is inhibited when the surface is exposed to the biofilm forming microorganism, wherein the device is a glucose sensor comprising a plurality of layers including; an electrode having an electrochemically reactive surface area; an analyte sensing layer that detectably alters electrical current at the electrode in the presence of an analyte; an adhesion promoting layer that promotes adhesion between one or more layers of the glucose sensor; an analyte modulating layer that modulates diffusion of an analyte therethrough; and a cover layer that is impermeable to blood glucose, wherein the cover layer includes an aperture. - View Dependent Claims (9, 10)
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11. A method of inhibiting microbial growth on a medical device that is implanted in a diabetic individual, the method comprising identifying a susceptible surface on the medical device that is observed to be colonized in vivo by a microorganism when the device is implanted in the diabetic individual and coating the surface of the medical device with at least two antimicrobial compositions, wherein the antimicrobial compositions include:
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a first layer comprising a glucose oxidase composition, wherein the glucose oxidase is disposed in the first layer so as to generate hydrogen peroxide upon exposure to glucose in the diabetic individual; and
the first layer is disposed on the device so as to allow hydrogen peroxide generated by the glucose oxidase in the first layer to diffuse away from the glucose oxidase and contact a microorganism attempting to grow on the medical device and inhibit its growth;
wherein the amount of hydrogen peroxide generated by the glucose oxidase fluctuates in response to fluctuating glucose levels within the diabetic individual; anda second layer disposed on the first layer comprising a polyurea-silicone copolymer composition having a quaternary amine, wherein; the second layer is formed from a reaction mixture comprising a diisocyanate, a hydrophilic polymer which is selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof, and a siloxane; and the second layer is disposed on the medical device in a location such that the quaternary amine in the second layer inhibits the growth of a microorganism that contacts the second layer;
so that microbial growth on the implanted medical device is inhibited, wherein the device is a glucose sensor comprising a plurality of layers, wherein at least one of the layers comprises;an electrode having an electrochemically reactive surface area; an analyte sensing layer that detectably alters electrical current at the electrode in the presence of an analyte; an adhesion promoting layer that promotes adhesion between one or more layers of the glucose sensor; an analyte modulating layer that modulates diffusion of an analyte therethrough;
or a cover layer that is impermeable to blood glucose, wherein the cover layer includes an aperture.
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12. A method of inhibiting formation of a biofilm on a medical device that is implanted in an individual having a pathological condition characterized by ischemia, the method comprising:
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(a) identifying a surface on the medical device that is observed to be colonized by a biofilm forming microorganism; and (b) coating the surface with; a first layer that comprises an antimicrobial composition that includes an oxidoreductase that generates hydrogen peroxide upon exposure to a ligand for the oxidoreductase; a second layer disposed on the first layer that comprises an antimicrobial composition comprising a polyurea-silicone copolymer, wherein; the first layer is disposed on the medical device so as to allow hydrogen peroxide generated by the oxidoreductase in the first layer to diffuse away from the oxidoreductase and contact a microorganism attempting to grow on the medical device thereby inhibiting its growth; the second layer is formed from a reaction mixture comprising a diisocyanate, a hydrophilic polymer which is selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof, and a siloxane; and a quaternary amine moiety in the second layer inhibits the growth of a microorganism that contacts the second layer; so that formation of a biofilm on the medical device is inhibited when the surface is exposed to the biofilm forming microorganism, wherein the medical device is a glucose sensor comprising a plurality of layers, wherein at least one of the layers comprises; an electrode having an electrochemically reactive surface area; an analyte sensing layer that detectably alters electrical current at the electrode in the presence of an analyte; an adhesion promoting layer that promotes adhesion between one or more layers of the glucose sensor; an analyte modulating layer that modulates diffusion of an analyte therethrough;
or a cover layer that is impermeable to blood glucose, wherein the cover layer includes an aperture. - View Dependent Claims (13, 14, 15)
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Specification