US5338770A
Expired / Lapsed
US
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Gas permeable thrombo-resistant coatings and methods of manufacture
Assignee: BIO SURFACE ENGINEERING TECHNOLOGIES Inc
•
Filing: 1990-04-12
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Granted: 1994-08-16
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Expires: 2010-04-12
Abstract
Abstract The present invention is directed to thrombo-resistant coatings for use with gas permeable biomedical devices and implants. The coatings include a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A quantity of at least one bioactive molecule designed to counteract a specific blood-material incompatibility reaction is covalently bonded to the poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain. The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is preferably achieved by plasma etching with ammonia gas. The amine-containing siloxane surface is reacted with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine groups on the siloxane surface. The material is then reacted with a solution of at least one bioactive molecule which counteracts a blood-material incompatibility reaction, such that a single bioactive molecule is coupled to a single poly(ethylene oxide) chain. The resulting siloxane surface is capable of resisting blood-material incompatibility reactions while maintaining high gas permeability.
Inventors
- 👤 Suzanne Winters
- 👤 Kenneth A. Solen
- 👤 Clifton G. Sanders
- 👤 JD Mortensen
- 👤 Gaylord Berry
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 18:30
CPC Classifications
B; B01; B01D; B01D67/00; B01D67/0081; B01D67/009; A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0011; A61L33/0029; A61L33/0047; A61L33/0094; A61M; A61M1/00; A61M1/14; A61M1/16; A61M1/1678; A61M1/36; A61M1/3672; A61M1/3673; B01D67/0093; B01D67/00931; B01D67/00933; B01D69/00; B01D69/12; B01D69/125; B01D69/127; C; C12; C12N; C12N11/00; C12N11/02; C12N11/06; A61M1/1698; A61M2205/00; A61M2205/04; B01D2323/00; B01D2323/30; Y; Y10; Y10S; Y10S530/00; Y10S530/81; Y10S530/812; Y10S530/815; Y10S530/816
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
190 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood, the method comprising the steps of: (a) obtaining a gas permeable material having a gas permeable siloxane surface onto which a plurality of amine functional groups have been bonded; (b) reacting the amine functional groups on the siloxane surface with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups on the siloxane surface, thereby resulting in a product having single poly(ethylene oxide) chains which are bonded to corresponding single amine functional groups, said product being gas permeable; (c) reacting the product of step (b) with at least one bioactive molecule capable of counteracting at least one blood-material incompatibility reaction such that a single bioactive molecule is correspondingly coupled to a single poly(ethylene oxide) chain, thereby resulting in a gas permeable siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of the at least one bioactive molecule which react with blood components which come in proximity to the siloxane surface of the gas permeable material in order to resist at least one blood-material incompatibility reaction.
Claim 2
Independent Claim
190 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood, the method comprising the steps of: (a) obtaining a gas permeable material having a gas permeable siloxane surface onto which a plurality of amine functional groups have been bonded; (b) reacting the amine functional groups on the siloxane surface with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups on the siloxane surface, thereby resulting in a product having single poly(ethylene oxide) chains which are bonded to corresponding single amine functional groups, said product being gas permeable; (c) reacting the product of step (b) with at least one bioactive molecule capable of counteracting at least one blood-material incompatibility reaction such that a single bioactive molecule is correspondingly coupled to a single poly(ethylene oxide) chain, thereby resulting in a gas permeable siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of the at least one bioactive molecule which react with blood components which come in proximity to the siloxane surface of the gas permeable material in order to resist at least one blood-material incompatibility reaction.
Claim 3
Dependent Claim
97 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the step of obtaining a gas permeable material having a siloxane surface onto which a plurality of amine functional groups have been bonded comprises the steps of: introducing ammonia gas within a plasma chamber capable of performing plasma etching; exposing the ammonia gas to a radio frequency of sufficient power to create a plasma; and exposing the siloxane surface to the ammonia plasma for sufficient time to introduce amine functional groups onto the siloxane surface.
Claim 4
Dependent Claim
36 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 2, further comprising the step of obtaining a microporous hollow fiber having a siloxane surface thereon.
Claim 5
Dependent Claim
43 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups comprises poly(ethylene oxide) bis(glycidyl ether).
Claim 6
Dependent Claim
42 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in Claim 1, wherein the poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups comprises poly(ethylene oxide) 2-(aminoalkyl)-1,4-benzoquinone.
Claim 7
Dependent Claim
74 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the product of step (b) is reacted with a solution of at least one bioactive molecule capable of resisting at least one of the following blood-material incompatibility reactions: extrinsic coagulation pathway activation, platelet destruction and injury, platelet adhesion activation, platelet aggregation, thrombus formation, complement activation, contact system activation, and fibrinolytic system activation.
Claim 8
Dependent Claim
31 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the product of step (b) is reacted with heparin.
Claim 9
Dependent Claim
46 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the product of step (b) is reacted with at least one bioactive molecule selected from the group consisting of heparin, urokinase, plasmin, and ticlopidine.
Claim 10
Dependent Claim
48 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the product of step (b) is reacted with at least one bioactive molecule selected from the group consisting of heparin, urokinase, and prostaglandin E 1 .
Claim 11
Dependent Claim
45 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the product of step (b) is reacted with at least one bioactive molecule selected from the group consisting of heparin, plasmin, and ticlopidine.
Claim 12
Dependent Claim
50 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 1, wherein the product of step (b) is reacted with at least one bioactive molecule selected from the group consisting of heparin, urokinase, plasmin, prostaglandin E 1 , and ticlopidine.
Claim 13
Independent Claim
238 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood, the method comprising the steps of: (a) obtaining a gas permeable material having a siloxane surface; (b) introducing ammonia gas within a plasma chamber capable of performing plasma etching; (c) exposing the ammonia gas to a radio frequency of sufficient power to create a plasma; (d) exposing the siloxane surface to the ammonia plasma for sufficient time to introduce amine functional groups onto the siloxane surface, thereby resulting in a product having a plurality of amine functional groups bonded onto the siloxane surface; (e) reacting the product of step (d) with a solution having a plurality of poly(ethylene oxide) spacer chains, having the following general formula R.sub.1 --(CH.sub.2 CH.sub.2 O).sub.n --R.sub.2 wherein R 1 and R 2 are suitable functional groups capable of reacting with the amine functional groups on the siloxane surface; and (f) reacting the product of step (e) with a solution of at least one bioactive molecule capable of counteracting specific blood-material incompatibility reactions such that a single bioactive molecule is correspondingly coupled to a single poly(ethylene oxide) spacer chain, thereby resulting in a siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of the at least one bioactive molecules which react with blood components which come in proximity to the surface of the material in order to resist at least one blood-material incompatibility reaction.
Claim 14
Independent Claim
238 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood, the method comprising the steps of: (a) obtaining a gas permeable material having a siloxane surface; (b) introducing ammonia gas within a plasma chamber capable of performing plasma etching; (c) exposing the ammonia gas to a radio frequency of sufficient power to create a plasma; (d) exposing the siloxane surface to the ammonia plasma for sufficient time to introduce amine functional groups onto the siloxane surface, thereby resulting in a product having a plurality of amine functional groups bonded onto the siloxane surface; (e) reacting the product of step (d) with a solution having a plurality of poly(ethylene oxide) spacer chains, having the following general formula R.sub.1 --(CH.sub.2 CH.sub.2 O).sub.n --R.sub.2 wherein R 1 and R 2 are suitable functional groups capable of reacting with the amine functional groups on the siloxane surface; and (f) reacting the product of step (e) with a solution of at least one bioactive molecule capable of counteracting specific blood-material incompatibility reactions such that a single bioactive molecule is correspondingly coupled to a single poly(ethylene oxide) spacer chain, thereby resulting in a siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of the at least one bioactive molecules which react with blood components which come in proximity to the surface of the material in order to resist at least one blood-material incompatibility reaction.
Claim 15
Dependent Claim
30 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 12, wherein R 1 and R 2 comprises glycidyl ether.
Claim 16
Dependent Claim
29 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 12, wherein R 1 and R 2 comprise 2-(aminoalkyl)-1,4-benzoquinone.
Claim 17
Dependent Claim
31 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 12, wherein the product of step (e) is reacted with heparin.
Claim 18
Dependent Claim
49 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 12, wherein the product of step (e) is reacted with a plurality of at least one bioactive molecule selected from the group consisting of heparin, urokinase, plasmin, and ticlopidine.
Claim 19
Dependent Claim
53 words
A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood as defined in claim 12, wherein the product of step (e) is reacted with a plurality of at least one bioactive molecule selected from the group consisting of heparin, urokinase, plasmin, ticlopidine, and prostaglandin E 1 .
Claim 20
Dependent Claim
106 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood comprising: a gas permeable material having a siloxane surface onto which a plurality of at least one bioactive molecule are covalently bonded, said at least one bioactive molecule counteracting at least one specific blood-material incompatibility reaction when the blood comes into proximity of the surface of the material; and a plurality of poly(ethylene oxide) chains covalently bonded to the bioactive molecules and covalently bonded to the siloxane surface such that a single bioactive molecule is correspondingly coupled to a single poly(ethylene oxide) chain which in turn is bonded to the gas permeable siloxane surface.
Claim 21
Dependent Claim
106 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood comprising: a gas permeable material having a siloxane surface onto which a plurality of at least one bioactive molecule are covalently bonded, said at least one bioactive molecule counteracting at least one specific blood-material incompatibility reaction when the blood comes into proximity of the surface of the material; and a plurality of poly(ethylene oxide) chains covalently bonded to the bioactive molecules and covalently bonded to the siloxane surface such that a single bioactive molecule is correspondingly coupled to a single poly(ethylene oxide) chain which in turn is bonded to the gas permeable siloxane surface.
Claim 22
Dependent Claim
55 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood as defined in claim 18, wherein the at least one bioactive molecule is capable of resisting at least one of the following blood material incompatibility reactions: extrinsic coagulation pathway activation, platelet destruction and injury, platelet adhesion, platelet aggregation, thrombus formation, and complement activation.
Claim 23
Dependent Claim
26 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood as defined in claim 18, wherein the at least one bioactive molecule is heparin.
Claim 24
Dependent Claim
40 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood as defined in claim 18, wherein the at least one bioactive molecule is selected from the group consisting of heparin, urokinase, plasmin, ticlopidine, and prostaglandin E 1 .
Claim 25
Dependent Claim
162 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood, the composition being made by a process comprising the steps of: (a) obtaining a gas permeable material having a siloxane surface onto which a plurality of amine functional groups have been bonded; (b) reacting the amine functional groups on the siloxane surface with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups on the siloxane surface such that a single poly(ethylene oxide) chain is bonded to a corresponding single amine functional group; and (c) reacting the product of step (b) with heparin such that a single heparin molecule is covalently bonded to a single poly(ethylene oxide) chain, thereby resulting in a siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of heparin molecules capable of reacting with blood components which come in proximity to the siloxane surface of the material in order to resist at least one blood-material incompatibility reactions.
Claim 26
Dependent Claim
162 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood, the composition being made by a process comprising the steps of: (a) obtaining a gas permeable material having a siloxane surface onto which a plurality of amine functional groups have been bonded; (b) reacting the amine functional groups on the siloxane surface with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups on the siloxane surface such that a single poly(ethylene oxide) chain is bonded to a corresponding single amine functional group; and (c) reacting the product of step (b) with heparin such that a single heparin molecule is covalently bonded to a single poly(ethylene oxide) chain, thereby resulting in a siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of heparin molecules capable of reacting with blood components which come in proximity to the siloxane surface of the material in order to resist at least one blood-material incompatibility reactions.
Claim 27
Dependent Claim
39 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood as defined in claim 22, wherein the poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups comprises poly(ethylene oxide) bis(glycidyl ether).
Claim 28
Dependent Claim
38 words
A thrombo-resistant composition for use on gas permeable surfaces which contact blood as defined in claim 22, wherein the poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups comprises poly(ethylene oxide) 2-(aminoalkyl)-1,4-benzoquinone.
Claim 29
Dependent Claim
74 words
A thrombo-resistant composition comprising a plurality of compounds having the formula X--NH--R.sub.1 ----(CH.sub.2 CH.sub.2 O).sub.n ----R.sub.2 --Y wherein X is a siloxane surface; and wherein R 1 are R 2 are the residue resulting from a reaction between a poly(ethylene oxide) terminal group capable of reacting with an amine and capable of reacting with a bioactive molecule, respectively; and wherein Y is a bioactive molecule capable of counteracting a specific blood material incompatibility reaction.
Claim 30
Dependent Claim
74 words
A thrombo-resistant composition comprising a plurality of compounds having the formula X--NH--R.sub.1 ----(CH.sub.2 CH.sub.2 O).sub.n ----R.sub.2 --Y wherein X is a siloxane surface; and wherein R 1 are R 2 are the residue resulting from a reaction between a poly(ethylene oxide) terminal group capable of reacting with an amine and capable of reacting with a bioactive molecule, respectively; and wherein Y is a bioactive molecule capable of counteracting a specific blood material incompatibility reaction.
Claim 31
Dependent Claim
19 words
A thrombo-resistant composition as defined in claim 25, wherein R 1 is ##STR5## and wherein R 2 is ##STR6##
Claim 32
Dependent Claim
12 words
A thrombo-resistant composition as defined in claim 25, wherein Y is heparin.
Claim 33
Dependent Claim
15 words
A thrombo-resistant composition as defined in claim 25, wherein Y is heparin, ticlopidine, or urokinase.
Claim 34
Dependent Claim
22 words
A thrombo-resistant composition as defined in claim 25, wherein Y is heparin, prostaglandin E 1 , plasmin, urokinase, or tissue plasminogen activator.
Claim 35
Dependent Claim
20 words
A thrombo-resistant composition as defined in claim 25, wherein Y is heparin, ticlopidine, plasmin, urokinase, tissue plasminogen activator, or FUT-175.
Claim 36
Dependent Claim
32 words
A thrombo-resistant composition as defined in claim 25, wherein Y is capable of resisting either extrinsic coagulation pathway activation, platelet destruction and injury, platelet adhesion, platelet aggregation, thrombus formation, or complement activation.
Claim 37
Independent Claim
258 words
An apparatus for effecting extrapulmonary blood gas exchange comprising: a plurality of gas permeable tubes, each tube having a proximal end and a distal end, said gas permeable tubes being coated with a thrombo-resistant composition comprising a plurality of compounds having the formula X--NH--R.sub.1 ----(CH.sub.2 CH.sub.2 O).sub.n ----R.sub.2 --Y wherein X is a siloxane surface on a gas permeable tube; and wherein R 1 are R 2 are the residue resulting from a reaction between a poly(ethylene oxide) terminal group capable of reacting with an amine and capable of reacting with a bioactive molecule, respectively; and wherein Y is a bioactive molecule capable of counteracting at least one blood-material incompatibility reaction; a dual lumen coaxial tube comprising an inner lumen and an outer lumen, said inner lumen extending between the proximal and distal ends of the gas permeable tubes and said outer lumen terminating adjacent to the proximal ends of the gas permeable tubes and the inner lumen terminating adjacent to the distal ends of the gas permeable tubes, such that the gas permeable tubes are in gaseous communication with both the inner lumen and the outer lumen; means for introducing oxygen from the inner lumen into the distal ends of the gas permeable tubes whereby blood in contact with the gas permeable tubes receives oxygen from the gas permeable tubes and releases carbon dioxide gas to the gas permeable tubes; and means for collecting carbon dioxide at the proximal ends of the gas permeable tubes and introducing said carbon dioxide into the outer lumen for removal therethrough.
Claim 38
Independent Claim
258 words
An apparatus for effecting extrapulmonary blood gas exchange comprising: a plurality of gas permeable tubes, each tube having a proximal end and a distal end, said gas permeable tubes being coated with a thrombo-resistant composition comprising a plurality of compounds having the formula X--NH--R.sub.1 ----(CH.sub.2 CH.sub.2 O).sub.n ----R.sub.2 --Y wherein X is a siloxane surface on a gas permeable tube; and wherein R 1 are R 2 are the residue resulting from a reaction between a poly(ethylene oxide) terminal group capable of reacting with an amine and capable of reacting with a bioactive molecule, respectively; and wherein Y is a bioactive molecule capable of counteracting at least one blood-material incompatibility reaction; a dual lumen coaxial tube comprising an inner lumen and an outer lumen, said inner lumen extending between the proximal and distal ends of the gas permeable tubes and said outer lumen terminating adjacent to the proximal ends of the gas permeable tubes and the inner lumen terminating adjacent to the distal ends of the gas permeable tubes, such that the gas permeable tubes are in gaseous communication with both the inner lumen and the outer lumen; means for introducing oxygen from the inner lumen into the distal ends of the gas permeable tubes whereby blood in contact with the gas permeable tubes receives oxygen from the gas permeable tubes and releases carbon dioxide gas to the gas permeable tubes; and means for collecting carbon dioxide at the proximal ends of the gas permeable tubes and introducing said carbon dioxide into the outer lumen for removal therethrough.
Claim 39
Dependent Claim
22 words
An apparatus for effecting extrapulmonary blood gas exchange as defined in claim 32, wherein the at least one bioactive molecule comprises heparin.
References Cited (Backward Citations)
US3453194A
Cited
US3639141A
Cited
US3846353A
Cited
US3826678A
Cited
GB1391028A
Cited
US3940506A
Cited
US3992495A
Cited
US4210529A
Cited
US3969240A
Cited
US4093515A
Cited
US4170559A
Cited
GB2001663A
Cited
US4243776A
Cited
US4214020A
Cited
JPS54135495A
Cited
US4828561A
Cited
US4666668A
Cited
US4861830A
Cited
EP0054919A2
Cited
US4810784A
Cited
US4613665A
Cited
US4483901A
Cited
US4673584A
Cited
US4613517A
Cited
US4781889A
Cited
US4622206A
Cited
EP0152699A2
Cited
US4521564A
Cited
US4879135A
Cited
GB2167665A
Cited
US4600652A
Cited
US4872867A
Cited
US4770852A
Cited
US4806595A
Cited
US4919659A
Cited
US5043278A
Cited
EP0263184A1
Cited
WO1988002623A1
Cited
EP0335972A1
Cited
US4822741A
Cited
US4846844A
Cited
US4844986A
Cited
EP0332261A1
Cited
US5013717A
Cited
US5061738A
Cited
EP0351314A2
Cited
WO1990001305A1
Cited
EP0357242A1
Cited
US5019393A
Cited
EP0354061A2
Cited
US5053048A
Cited
US5053453A
Cited
US5004461A
Cited
EP0423369A1
Cited
EP0404683A2
Cited
US5026607A
Cited
WO1991012886A1
Cited
WO1991016932A1
Cited
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