US5368608A
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US
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Calcification-resistant materials and methods of making same through use of multivalent cations
Assignee: University of Michigan (System)
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Filing: 1991-04-23
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Granted: 1994-11-29
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Expires: 2011-04-23
Abstract
Abstract Bioprosthetic materials, either natural or synthetic, are treated with trivalent aluminum or 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 ion-containing solution, such as aqueous AlCl3 or FeCl3, 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 aluminum-containing compound 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
2026-10-25 21:12
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: 35
Claim 1
Independent Claim
43 words
An implant formed of a biocompatible biomaterial which is insoluble in the interior of the body of a host, living being, said biomaterial having incorporated therein an effective amount of trivalent aluminum cations to render said biomaterial resistant to in vivo pathologic calcification.
Claim 2
Dependent Claim
43 words
An implant formed of a biocompatible biomaterial which is insoluble in the interior of the body of a host, living being, said biomaterial having incorporated therein an effective amount of trivalent aluminum cations to render said biomaterial resistant to in vivo pathologic calcification.
Claim 3
Dependent Claim
20 words
The implant of claim 1 wherein said biocompatible biomaterial is a tissue which occurs naturally in a donor living being.
Claim 4
Dependent Claim
27 words
The implant of claim 2 wherein said biomaterial is selected from the group consisting of bovine pericardium, porcine heart valve leaflets, saphenous bypass grafts, and aortic homografts.
Claim 5
Dependent Claim
14 words
The implant of claim 1 wherein said biocompatible biomaterial is a biocompatible synthetic polymer.
Claim 6
Dependent Claim
41 words
The implant of claim 4 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
44 words
A material suitable for implantation in the interior of the body of a living being, the material being a biocompatible biomaterial having incorporated therein an effective amount of trivalent aluminum cations to render the biomaterial resistant to pathologic calcification in an in vivo environment.
Claim 8
Dependent Claim
44 words
A material suitable for implantation in the interior of the body of a living being, the material being a biocompatible biomaterial having incorporated therein an effective amount of trivalent aluminum cations to render the biomaterial resistant to pathologic calcification in an in vivo environment.
Claim 9
Dependent Claim
19 words
The material of claim 6 wherein said biomaterial is a tissue which occurs naturally in a donor living being.
Claim 10
Dependent Claim
27 words
The material of claim 7 wherein said biomaterial is selected from the group consisting of bovine pericardium, porcine heart valve leaflets, saphenous bypass grafts, and aortic homografts.
Claim 11
Dependent Claim
13 words
The material of claim 6 wherein the biomaterial is a biocompatible synthetic polymer.
Claim 12
Dependent Claim
37 words
The material of claim 9 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 13
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 aluminum cations to the dissolved biocompatible synthetic polymeric material to form a mixture; and (c) forming said mixture into a desired configuration.
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 aluminum 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
42 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 11 wherein said step of forming said mixture into said desired configuration comprises the step of casting said mixture into a film.
Claim 16
Dependent Claim
39 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 12 further comprising the step of drying the cast film in a vacuum oven at 50° to 55° C.
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 wherein said step of forming said mixture into said desired configuration comprises the step of molding said mixture.
Claim 18
Dependent Claim
62 words
The material for implanting in the interior of a human or animal living body prepared by the process of claim 11 wherein the salt of a metallic trivalent cation is selected from the group consisting of aluminum silicate, aluminum oxide, aluminum phosphate, aluminum palmitate, aluminum oleate, aluminum oxalate, aluminum magnesium silicate, aluminum stearate, aluminum diacetate, aluminum hydroxide, aluminum isopropoxide, and aluminum hypophosphite.
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 11 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 16 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
Independent Claim
68 words
A method of making a calcification-resistant synthetic polymeric material suitable for implanting in the interior of a human or animal living body, the method comprising the steps of: (a) combining biocompatible synthetic polymeric precursor materials with a salt of trivalent aluminum cations to form a mixture; and (b) polymerizing said mixture so that the trivalent aluminum cations become part of the matrix of the resulting synthetic polymeric material.
Claim 22
Independent Claim
68 words
A method of making a calcification-resistant synthetic polymeric material suitable for implanting in the interior of a human or animal living body, the method comprising the steps of: (a) combining biocompatible synthetic polymeric precursor materials with a salt of trivalent aluminum cations to form a mixture; and (b) polymerizing said mixture so that the trivalent aluminum cations become part of the matrix of the resulting synthetic polymeric material.
Claim 23
Independent Claim
48 words
A method of making a calcification-resistant biomaterial comprising the step of subjecting bioprosthetic tissue to a solution containing a soluble salt of trivalent aluminum ranging from 0.1 M to 0.001 M for a period of time sufficient to complex aluminum cations in the solution with the bioprosthetic tissue.
Claim 24
Independent Claim
48 words
A method of making a calcification-resistant biomaterial comprising the step of subjecting bioprosthetic tissue to a solution containing a soluble salt of trivalent aluminum ranging from 0.1 M to 0.001 M for a period of time sufficient to complex aluminum cations in the solution with the bioprosthetic tissue.
Claim 25
Dependent Claim
29 words
The method of claim 19 wherein the solution containing a soluble salt of trivalent aluminum further contains a soluble anticalcification agent selected from the group of citrates and diphosphonates.
Claim 26
Dependent Claim
24 words
The method of claim 20 wherein the soluble anticalcification agent is a citrate selected from the group consisting of citric acid and sodium citrate.
Claim 27
Dependent Claim
22 words
The method of claim 20 wherein the soluble anticalcification agent is a diphosphonate selected from the group consisting of ethanehydroxydiphosphonate and aminopropanehydroxydiphosponate.
Claim 28
Dependent Claim
27 words
The method of claim 20 wherein the soluble salt of trivalent aluminum and soluble anticalcification agent are both in the concentration range from 0.1 to 0.00001 M.
Claim 29
Dependent Claim
36 words
The method of claim 19 wherein the soluble salt of trivalent aluminum is selected from the group consisting of aluminum chlorate, aluminum lactate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, aluminum nitrate, and aluminum chloride.
Claim 30
Independent Claim
68 words
A method of making a calcification-resistant synthetic polymeric biomaterial suitable for implanting in the interior of a human or animal living body, the method comprising the steps of: (a) dissolving a biocompatible synthetic polymeric material in an organic solvent; (b) adding a soluble salt of trivalent aluminum cations to the dissolved biocompatible synthetic polymeric material to form a mixture; and (c) forming said mixture into a desired configuration.
Claim 31
Independent Claim
68 words
A method of making a calcification-resistant synthetic polymeric biomaterial suitable for implanting in the interior of a human or animal living body, the method comprising the steps of: (a) dissolving a biocompatible synthetic polymeric material in an organic solvent; (b) adding a soluble salt of trivalent aluminum cations to the dissolved biocompatible synthetic polymeric material to form a mixture; and (c) forming said mixture into a desired configuration.
Claim 32
Dependent Claim
26 words
The method of claim 25 wherein said step of forming said mixture into said desired configuration comprises the step of casting said mixture into a film.
Claim 33
Dependent Claim
23 words
The method of claim 25 wherein said step of forming said mixture into said desired configuration comprises the step of molding said mixture.
Claim 34
Dependent Claim
38 words
The method of claim 25 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 35
Dependent Claim
45 words
The method of claim 25 wherein the salt of trivalent aluminum cation is selected from the group consisting of aluminum silicate, aluminum oxide, aluminum phosphate, aluminum palmitate, aluminum oleate, aluminum oxalate, aluminum magnesium silicate, aluminum stearate, aluminum diacetate, aluminum hydroxide, aluminum isopropoxide, and aluminum hypophosphite.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1997-11-28 | 1998-05-30 | 1998-11-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-11-28 | 2002-05-30 | 2002-11-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-11-28 | 2006-05-30 | 2006-11-29 | $7700.00 | Window Closed / Lapsed |