US5679112A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Calcification-resistant materials and methods of making same through use of multivalent cations
Assignee: University of Michigan (System)
•
Filing: 1994-11-28
•
Granted: 1997-10-21
•
Expires: 2014-11-28
Abstract
Abstract Bioprosthetic materials, either natural or synthetic, are treated with trivalent iron cations, or salts, to prevent in vivo calcification. Such bioprosthetic materials include porcine aortic valve leaflets, bovine pericardium, aortic homografts, biocompatible elastomers, and the like which are intended for invasive, or in-dwelling use in a human or animal body. Simple incubation of the natural bioprosthetic materials in an iron ion-containing solution, such as aqueous FeCl3, particularly with the addition of an anticalcification agent, such as a diphosphonate, prior to implantation has been found to inhibit calcification of the biomaterial over a prolonged period, and to do so without adverse side effects. Incorporation of an iron-containing compound, with or without an additional anticalcification agent, into the formulation for polymers, such as polyurethane, has also been found to inhibit calcification with no adverse side effects.
Inventors
- 👤 Robert J. Levy
- 👤 Amnon Sintov
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 04:03
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/50; A61L27/36; A61L27/3604; A61L27/3683; A61L27/3687; A61L27/54; A61L2300/00; A61L2300/10; A61L2300/102; A61L2300/20; A61L2300/21; A61L2300/216; A61L2300/40; A61L2300/45; A61L2400/00; A61L2400/02; A61L2430/00; A61L2430/40; Y; Y10; Y10S; Y10S128/00; Y10S128/08; Y10S623/00; Y10S623/92; Y10S623/921
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
70 words
An implant formed of a biocompatible biomaterial which is a tissue which occurs naturally in a donor living being and is insoluble in the interior of the body of a host living being, said biomaterial having incorporated therein an effective amount of trivalent iron cations and at least one anticalcification agent selected from the group consisting of citrates and diphosphonates to render said biomaterial resistant to in vivo pathologic calcification.
Claim 2
Dependent Claim
70 words
An implant formed of a biocompatible biomaterial which is a tissue which occurs naturally in a donor living being and is insoluble in the interior of the body of a host living being, said biomaterial having incorporated therein an effective amount of trivalent iron cations and at least one anticalcification agent selected from the group consisting of citrates and diphosphonates to render said biomaterial resistant to in vivo pathologic calcification.
Claim 3
Dependent Claim
27 words
The implant of claim 1 wherein said biomaterial is selected from the group consisting of bovine pericardium, porcine heart valve leaflets, saphenous bypass grafts, and aortic homografts.
Claim 4
Dependent Claim
49 words
An implant formed of a biocompatible biomaterial which is a biocompatible synthetic polymer and is insoluble in the interior of the body of a host living being, said biomaterial having incorporated therein an effective amount of trivalent iron cations to render said biomaterial resistant to in vivo pathologic calcification.
Claim 5
Dependent Claim
49 words
An implant formed of a biocompatible biomaterial which is a biocompatible synthetic polymer and is insoluble in the interior of the body of a host living being, said biomaterial having incorporated therein an effective amount of trivalent iron cations to render said biomaterial resistant to in vivo pathologic calcification.
Claim 6
Dependent Claim
41 words
The implant of claim 3 wherein said biocompatible synthetic polymer is an organic synthetic material selected from the group consisting of polydimethylsiloxane, polyurethane, ethylene vinyl acetate, polymethyl methacrylate, polyamide, polycarbonate, polyester, polyethylene, polypropylene, polystyrene, polyvinyl chloride, polytetrafluoroethylene, polysulfone, and cellulose acetate.
Claim 7
Dependent Claim
13 words
The implant of claim 4 wherein said organic synthetic material is a polyurethane.
Claim 8
Dependent Claim
66 words
A material suitable for implantation in the interior of the body of a living being, the material being a tissue which occurs naturally in a donor living being having incorporated therein an effective amount of trivalent iron cations and at least one anticalcification agent selected from the group consisting of citrates and diphosphonates to render the tissue resistant to pathologic calcification in an in vivo environment.
Claim 9
Dependent Claim
66 words
A material suitable for implantation in the interior of the body of a living being, the material being a tissue which occurs naturally in a donor living being having incorporated therein an effective amount of trivalent iron cations and at least one anticalcification agent selected from the group consisting of citrates and diphosphonates to render the tissue resistant to pathologic calcification in an in vivo environment.
Claim 10
Dependent Claim
27 words
The material of claim 6 wherein said tissue is selected from the group consisting of bovine pericardium, porcine heart valve leaflets, saphenous bypass grafts, and aortic homografts.
Claim 11
Dependent Claim
49 words
A material suitable for implantation the interior of the body of a living being, the material being a biocompatible biomaterial which is a biocompatible synthetic polymer having incorporated therein an effective amount of trivalent iron cations to render the biomaterial resistant to pathologic calcification in an in vivo environment.
Claim 12
Dependent Claim
49 words
A material suitable for implantation the interior of the body of a living being, the material being a biocompatible biomaterial which is a biocompatible synthetic polymer having incorporated therein an effective amount of trivalent iron cations to render the biomaterial resistant to pathologic calcification in an in vivo environment.
Claim 13
Dependent Claim
37 words
The material of claim 8 wherein the biocompatible synthetic polymer is selected from the group consisting of polydimethylsiloxane, polyurethane, ethylene vinyl acetate, polymethyl methacrylate, polyamide, polycarbonate, polyester, polyethylene, polypropylene, polystyrene, polyvinyl chloride, polytetrafluoroethylene, polysulfone, and cellulose acetate.
Claim 14
Dependent Claim
62 words
A material for implanting in the interior of a human or animal living body, the material being prepared by the process of: (a) dissolving a biocompatible synthetic polymeric material in an organic solvent; (b) adding a soluble salt of trivalent iron cations to the dissolved biocompatible synthetic polymeric material to form a mixture; and (c) forming said mixture into a desired configuration.
Claim 15
Dependent Claim
62 words
A material for implanting in the interior of a human or animal living body, the material being prepared by the process of: (a) dissolving a biocompatible synthetic polymeric material in an organic solvent; (b) adding a soluble salt of trivalent iron cations to the dissolved biocompatible synthetic polymeric material to form a mixture; and (c) forming said mixture into a desired configuration.
Claim 16
Dependent Claim
42 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 10 wherein said step of forming said mixture into said desired configuration comprises the step of casting said mixture into a film.
Claim 17
Dependent Claim
39 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 11 further comprising the step of drying the cast film in a vacuum oven at 50° to 55° C.
Claim 18
Dependent Claim
39 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 10 wherein said step of forming said mixture into said desired configuration comprises the step of molding said mixture.
Claim 19
Dependent Claim
54 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 10 wherein said biocompatible synthetic polymeric material is selected from the group consisting of polydimethylsiloxane, polyurethane, ethylene vinyl acetate, polymethyl methacrylate, polyamide, polycarbonate, polyester, polyethylene, polypropylene, polystyrene, polyvinyl chloride, polytetrafluoroethylene, polysulfone, and cellulose acetate.
Claim 20
Dependent Claim
56 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 14 wherein said biocompatible synthetic polymeric material is selected from the group consisting of polyurethanes and polydimethylsiloxanes and copolymers thereof, and said organic solvent is selected from the group consisting of dimethyl sulfoxide, dimethylacetamide, and tetrahydrofuran.
Claim 21
Dependent Claim
35 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 15 wherein said synthetic polymeric material is polyurethane and said organic solvent is dimethyl sulfoxide.
Claim 22
Dependent Claim
51 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 10 wherein said soluble salt of trivalent iron is selected from the group consisting of ferric acetate, ferric chloride, ferric nitrate, ferric bromide, ferric sodium edentate, ferric sulfate, and ferric formate.
Claim 23
Dependent Claim
40 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 10 wherein step (b) further includes adding a soluble anticalcification agent selected from the group consisting of citrates and diphosphonates.
Claim 24
Dependent Claim
14 words
The implant of claim 3 having further incorporated therein at least one anticalcification agent.
Claim 25
Dependent Claim
22 words
The implant of claim 19 wherein the at least one anticalcification agent is selected from the group consisting of citrates and diphosphonates.
Claim 26
Dependent Claim
14 words
The material of claim 8 having further incorporated therein at least one anticalcification agent.
Claim 27
Dependent Claim
22 words
The material of claim 21 wherein the at least one anticalcification agent is selected from the group consisting of citrates and diphosphonates.
Claim 28
Dependent Claim
103 words
A material for implanting in the interior of a human or animal living body prepared by the process of: incubating a glutaraldehyde pre-treated bioprosthetic tissue in an aqueous solution of soluble salt of trivalent iron and an anticalcification agent selected from the group consisting of citrates and diphosphonates, the soluble salt of trivalent iron and the anticalcification agent selected from the group consisting of citrates and diphosphonates having concentrations in the range of from about 0.1M to 0.00001M for a period of time ranging from approximately between 1 hour to 24 hours at a temperature of approximately between 4° C. to 25° C.
Claim 29
Dependent Claim
103 words
A material for implanting in the interior of a human or animal living body prepared by the process of: incubating a glutaraldehyde pre-treated bioprosthetic tissue in an aqueous solution of soluble salt of trivalent iron and an anticalcification agent selected from the group consisting of citrates and diphosphonates, the soluble salt of trivalent iron and the anticalcification agent selected from the group consisting of citrates and diphosphonates having concentrations in the range of from about 0.1M to 0.00001M for a period of time ranging from approximately between 1 hour to 24 hours at a temperature of approximately between 4° C. to 25° C.
Claim 30
Dependent Claim
35 words
The material of claim 23 wherein the soluble salt of trivalent iron is selected from the group consisting of ferric acetate, ferric chloride, ferric nitrate, ferric bromide, ferric sodium edentate, ferric sulfate, and ferric formate.
References Cited (Backward Citations)
US714433A
Cited
US725648A
Cited
US2750251A
Cited
US2970031A
Cited
US3560141A
Cited
US4097234A
Cited
US4378224A
Cited
US4481009A
Cited
US4753652A
Cited
US4729139A
Cited
US4770665A
Cited
US4786287A
Cited
US5094661A
Cited
US5368608A
Cited
US5002566A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-10-20 | 2001-04-21 | 2001-10-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-10-20 | 2005-04-21 | 2005-10-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-10-20 | 2009-04-21 | 2009-10-21 | $7700.00 | Window Closed / Lapsed |