US5262451A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Multifunctional thrombo-resistant coatings and methods of manufacture
Assignee: Biosurface Engineering Technologies Inc
•
Filing: 1988-07-05
•
Granted: 1993-11-16
•
Expires: 2008-07-05
Abstract
Abstract The present invention is directed to multifunctional thrombo-resistant coatings for use with biomedical devices and implants, such as a coating which includes 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 plurality of different bioactive molecules, designed to counteract specific blood-material incompatibility reactions, are covalently bonded to 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 achieved by plasma etching with ammonia gas or by plasma polymerization of a siloxane monomer in the presence of 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 plurality of different bioactive molecules which counteract the specific blood-material incompatibility reactions, such that a single bioactive molecule is coupled to a single poly(ethylene oxide) chain. The resulting siloxane surface contains a plurality of different bioactive molecules capable of reacting with blood components which come in proximity to the siloxane surface in order to resist blood-material incompatibility reactions.
Inventors
- 👤 Suzanne Winters
- 👤 Kenneth A. Solen
- 👤 Clifton G. Sanders
- 👤 J. D. Mortensen
- 👤 Gaylord Berry
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 05:09
CPC Classifications
A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0047; A61L33/0011; A61L33/0029; A61L33/0094; A61M; A61M1/00; A61M1/14; A61M1/16; A61M1/1678; A61M1/36; A61M1/3672; A61M1/3673; B; B01; B01D; B01D67/00; B01D67/0081; B01D67/009; B01D67/0093; 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: 30
Claim 1
Independent Claim
123 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood comprising a material having a siloxane surface which is permeable to a gas onto which a plurality of at lest two different bioactive molecules are covalently bonded, and further comprising a plurality of poly(ethylene oxide) chains, the at least two different bioactive molecules being covalently bonded to the siloxane surface through the plurality of poly(ethyl oxide) chains such that a single bioactive molecule is correspondingly coupled to a single poly(ethyl oxide) chain which in turn is bonded to the siloxane surface, said bioactive molecules counteracting specific blood-material incompatibility reactions when the blood comes into proximity of the surface of the material without precluding the siloxane surface from being permeable to the gas.
Claim 2
Dependent Claim
123 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood comprising a material having a siloxane surface which is permeable to a gas onto which a plurality of at lest two different bioactive molecules are covalently bonded, and further comprising a plurality of poly(ethylene oxide) chains, the at least two different bioactive molecules being covalently bonded to the siloxane surface through the plurality of poly(ethyl oxide) chains such that a single bioactive molecule is correspondingly coupled to a single poly(ethyl oxide) chain which in turn is bonded to the siloxane surface, said bioactive molecules counteracting specific blood-material incompatibility reactions when the blood comes into proximity of the surface of the material without precluding the siloxane surface from being permeable to the gas.
Claim 3
Dependent Claim
54 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 1, wherein the plurality of different bioactive molecules are capable of resisting at least two 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 4
Dependent Claim
39 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 1, wherein the plurality of different bioactive molecules are selected from the group including heparin, urokinase, plasmin, ticlopine, TPA, and prostaglandin E 1 .
Claim 5
Dependent Claim
206 words
A multifunctional thrombo-resistant composition for use on surfaces which contact load, the composition being made by a process comprising the steps of: (a) obtaining a 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(ethyl 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 a plurality of at least two different bioactive molecules capable of counteracting specific blood-material incompatibility reaction such that a single bioactive molecule is covalently bonded to a single poly(ethylene oxide) chain, thereby resulting is a siloxane surface to which are attached, by a poly(ethylene oxide) chain a plurality of at least two different bioactive molecules which react with blood components which come in proximity to the siloxane surface of the material in order to resist blood-material incompatibility reactions, the at least two different bioactive molecules being attached by the poly(ethylene oxide) chain away from the siloxane surface such that gas permeability of the siloxane surface is not precluded.
Claim 6
Dependent Claim
206 words
A multifunctional thrombo-resistant composition for use on surfaces which contact load, the composition being made by a process comprising the steps of: (a) obtaining a 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(ethyl 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 a plurality of at least two different bioactive molecules capable of counteracting specific blood-material incompatibility reaction such that a single bioactive molecule is covalently bonded to a single poly(ethylene oxide) chain, thereby resulting is a siloxane surface to which are attached, by a poly(ethylene oxide) chain a plurality of at least two different bioactive molecules which react with blood components which come in proximity to the siloxane surface of the material in order to resist blood-material incompatibility reactions, the at least two different bioactive molecules being attached by the poly(ethylene oxide) chain away from the siloxane surface such that gas permeability of the siloxane surface is not precluded.
Claim 7
Dependent Claim
120 words
A multifunctional thrombo-resistant composition comprising a plurality of compounds having the formula X--NH--R 1 --(CH 2 CH 2 O) n --R 2 --Y and X--NH--R 1 --(CH 2 CH 2 O) n --R 2 --Z wherein X is a gas permeable siloxane surface; and wherein R 1 and 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 and Z are different bioactive molecules capable of counteracting a specific blood material incompatibility reaction, and which are covalently bonded to the siloxane surface through the ploy(ethylene oxide) terminal groups without precluding the gas permeability of the siloxane surface.
Claim 8
Dependent Claim
120 words
A multifunctional thrombo-resistant composition comprising a plurality of compounds having the formula X--NH--R 1 --(CH 2 CH 2 O) n --R 2 --Y and X--NH--R 1 --(CH 2 CH 2 O) n --R 2 --Z wherein X is a gas permeable siloxane surface; and wherein R 1 and 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 and Z are different bioactive molecules capable of counteracting a specific blood material incompatibility reaction, and which are covalently bonded to the siloxane surface through the ploy(ethylene oxide) terminal groups without precluding the gas permeability of the siloxane surface.
Claim 9
Dependent Claim
14 words
A multifunctional thrombo-resistant composition as defined in claim 5, wherein R 1 is ##STR5##
Claim 10
Dependent Claim
20 words
A multifunctional thrombo-resistant composition as defined in claim 5, wherein R 1 is --CONH-- and wherein R 2 is --NHCO--.
Claim 11
Dependent Claim
21 words
A multifunctional thrombo-resistant composition as defined in claim 5, wherein X or Y is heparin, urokinase, tissue plasminogen activator, or plasmin.
Claim 12
Dependent Claim
18 words
A multifunctional thrombo-resistant coating as defined in claim 5, wherein X or Y is heparin, ticlopidine, or urokinase.
Claim 13
Dependent Claim
25 words
A multifunctional thrombo-resistant coating as defined in claim 5, wherein X or Y is heparin, prostaglandin E 1 , plasmin, urokinase, or tissue plasminogen activator.
Claim 14
Dependent Claim
23 words
A multifunctional thrombo-resistant coating as defined in claim 5, wherein X or Y is heparin, ticlopidine, plasmin, urokinase, tissue plasminogen activator, or FUT-175.
Claim 15
Dependent Claim
35 words
A multifunctional thrombo-resistant coating as defined in claim 5, wherein X or Y is capable of resisting either extrinsic coagulation pathway activation, platelet destruction and injury, platelet adhesion, platelet aggregation, thrombus formation, or complement activation.
Claim 16
Dependent Claim
100 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, wherein composition being made by a process wherein the step of obtaining a material having a siloxane surface onto which a plurality of amine functional groups have been bonded comprises the steps of: (a) introducing ammonia gas within a plasma chamber capable of performing plasma etching; (b) exposing the ammonia gas to a radio frequency of sufficient power to create a plasma; and (c) exposing the siloxane surface to the ammonia plasma for sufficient time to introduce amine functional groups onto the siloxane surface.
Claim 17
Dependent Claim
37 words
A multifunctional thrombo-resistant coating for use on surfaces which contact blood as defined in claim 13, the composition being made by a process further comprising the step of obtaining a hollow fiber having a siloxane surface thereon.
Claim 18
Dependent Claim
115 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the step of obtaining a material having a siloxane surface onto which a plurality of amine functional groups have been bonded comprises the steps of: (a) introducing a gaseous mixture of siloxane monomer and ammonia into a plasma chamber capable of performing plasma polymerization; (b) exposing the gaseous mixture of siloxane monomer and ammonia to a radio frequency of sufficient power to create a plasma; and (c) exposing the material to the plasma for sufficient time to deposit thereon a siloxane plasma polymer onto which amine functional groups have been bonded.
Claim 19
Dependent Claim
51 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 15, the composition being made by a process wherein the mixture of siloxane monomer and ammonia gas is introduced at a ratio of siloxane monomer to ammonia gas in the range from about 10:1 about 1:10.
Claim 20
Dependent Claim
114 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the step of obtaining a material having a siloxane surface onto which a plurality of a mine functional groups have been bonded comprises the steps of: (a) introducing a gaseous mixture of tetramethyldisiloxane and ammonia into a plasma chamber capable of performing plasma polymerization; (b) exposing the gaseous mixture of tetramethyldisiloxane and ammonia to a radio frequency of sufficient power to create a plasma; and (c) exposing the material to the plasma for sufficient time to deposit thereon a siloxane plasma polymer onto which amine functional groups have been bonded.
Claim 21
Dependent Claim
52 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 17, the composition being made by a process wherein the mixture of siloxane monomer and ammonia gas is introduced into the plasma chamber in the range from about 3:1 to about 1:1 siloxane monomer to ammonia gas.
Claim 22
Dependent Claim
33 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process further comprising the step of obtaining a microporous hollow fiber.
Claim 23
Dependent Claim
45 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process 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 24
Dependent Claim
44 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups comprises poly(ethylene oxide) bis(isocyanate).
Claim 25
Dependent Claim
40 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the poly(ethylene oxide) chains have a molecular weight in the range from about 1500 to 6000.
Claim 26
Dependent Claim
67 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the product of step (b) is reacted with a solution having different bioactive molecules capable of resisting at least two 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 27
Dependent Claim
51 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the product of step (b) is reacted with a plurality of at least two different bioactive molecules selected from the group including heparin, urokinase, plasmin, and ticlopidine.
Claim 28
Dependent Claim
54 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the product of step (b) is reacted with a plurality of at least two different bioactive molecules selected from the group including heparin, urokinase, TPA, and prostaglandin E 1 .
Claim 29
Dependent Claim
50 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the product of step (b) is reacted with a plurality of at least two different bioactive molecules selected from the group including heparin, plasmin, and ticlopidine.
Claim 30
Dependent Claim
56 words
A multifunctional thrombo-resistant composition for use on surfaces which contact blood as defined in claim 4, the composition being made by a process wherein the product of step (b) is reacted with a plurality of at least two different bioactive molecules selected from the group including heparin, urokinase, TPA, plasmin, prostaglandin E 1 , and ticlopidine.
References Cited (Backward Citations)
US3279996A
Cited
US3453194A
Cited
US3522346A
Cited
US3639141A
Cited
US4061141A
Cited
US3759788A
Cited
US3846353A
Cited
US3673612A
Cited
US3810781A
Cited
US3888833A
Cited
GB1391028A
Cited
US3826678A
Cited
US3865615A
Cited
US3940506A
Cited
US3992495A
Cited
US4210529A
Cited
US4008047A
Cited
US4059512A
Cited
US3959128A
Cited
US3969240A
Cited
US4093515A
Cited
US4170559A
Cited
US4349467A
Cited
GB2001663A
Cited
US4213962A
Cited
US4243776A
Cited
US4214020A
Cited
US4378803A
Cited
US4828561A
Cited
US4410338A
Cited
US4329383A
Cited
US4666668A
Cited
US4444662A
Cited
US4861830A
Cited
US4331697A
Cited
EP0054919A2
Cited
US4810784A
Cited
US4613665A
Cited
US4483901A
Cited
US4673584A
Cited
US4613517A
Cited
US4781889A
Cited
US4622206A
Cited
US4500676A
Cited
EP0152699A2
Cited
US4521564A
Cited
US4879135A
Cited
GB2167665A
Cited
US4600652A
Cited
US4686975A
Cited
WO1986007541A1
Cited
US4872867A
Cited
US4770852A
Cited
US4806595A
Cited
US4919659A
Cited
EP0263184A1
Cited
US4824444A
Cited
US4806246A
Cited
WO1988002623A1
Cited
EP0335972A1
Cited
US4822741A
Cited
US4846844A
Cited
US4844986A
Cited
EP0332261A1
Cited
US5013717A
Cited
US5061738A
Cited
EP0351314A2
Cited
EP0357242A1
Cited
WO1990001305A1
Cited
EP0354061A2
Cited
US5053048A
Cited
EP0404683A2
Cited
US5026607A
Cited
WO1991012866A1
Cited
WO1991012886A1
Cited
WO1991016932A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1996-11-15 | 1997-05-17 | 1997-11-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-11-15 | 2001-05-17 | 2001-11-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-11-15 | 2005-05-17 | 2005-11-16 | $7700.00 | Window Closed / Lapsed |