US5817328A
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US
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Material for buffered resorbable internal fixation devices and method for making same
Assignee: Muscletech Research and Development Inc
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Filing: 1996-04-03
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Granted: 1998-10-06
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Expires: 2016-04-03
Abstract
Abstract A bioerodible implantable material, comprising a bioerodible polymer that produces acidic products upon hydrolytic degradation, and a buffering compound that buffers the acidic products and maintains the local pH within a desired range. The buffer compound acts to reduce the inflammatory foreign body response generated by the acidic products and reduces the sterile abscess condition that occurs at the site of the bioerodible implant materials of the prior art. Materials made according to the invention may be used for internal fixation devices (IFDs) for bone repair.
Inventors
- 👤 Joseph D. Gresser
- 👤 Debra J. Trantolo
- 👤 Robert Langer
- 👤 Alexander M. Klibanov
- 👤 Donald L. Wise
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 05:25
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/50; A61L27/58; A61K; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1611; A61K9/1617; A61K9/1629; A61K9/1641; A61K9/1647; A61K9/20; A61K9/2004; A61K9/2009; A61K9/2022; A61K9/2027; A61K9/2031; A61K9/204; A61L27/14; A61L27/18; A61F; A61F2210/00; A61F2210/0004
Claims Analysis
Total Claims: 66
Claim 1
Independent Claim
57 words
A bioerodible implantable material, comprising: a bioerodible polymer, said bioerodible polymer producing acidic products upon hydrolytic degradation; and a buffer in sufficiently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated.
Claim 2
Dependent Claim
57 words
A bioerodible implantable material, comprising: a bioerodible polymer, said bioerodible polymer producing acidic products upon hydrolytic degradation; and a buffer in sufficiently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated.
Claim 3
Dependent Claim
31 words
The bioerodible implantable material of claim 1, wherein said bioerodible polymer is selected from the group consisting of polydioxanone, poly(ε-caprolactone), polyanhydride, poly(ortho ester), copoly(ether-ester), polyamide, polylactone, poly(propylene fumarate), and combinations thereof.
Claim 4
Dependent Claim
27 words
The bioerodible implantable material of claim 1, wherein said bioerodible polymer comprises poly(lactide-co-glycolide) with a lactide to glycolide ratio in the range of 0:100% to 100:0% inclusive.
Claim 5
Dependent Claim
17 words
The bioerodible implantable material of claim 1, wherein said buffer is the salt of an inorganic acid.
Claim 6
Dependent Claim
17 words
The bioerodible implantable material of claim 1, wherein said buffer is the salt of an organic acid.
Claim 7
Dependent Claim
19 words
The bioerodible implantable material of claim 1, wherein said buffer is a polymer comprising at least one basic group.
Claim 8
Dependent Claim
34 words
The bioerodible implantable material of claim 6, wherein said polymer comprising at least one basic group is selected from the group consisting of hydrolyzable polyamines, hydrolyzable polyesters, vinyl polymers, and copolymers of acrylic acid.
Claim 9
Dependent Claim
20 words
The bioerodible implantable material of claim 6, wherein said at least one basic group is covalently bonded within said polymer.
Claim 10
Dependent Claim
23 words
The bioerodible implantable material of claim 1, wherein said buffer is a compound which, on exposure to water, hydrolyzes to form a base.
Claim 11
Dependent Claim
31 words
The bioerodible implantable material of claim 9, wherein the quantity of said base generated upon hydrolysis is equivalent to the quantity of said acidic products formed by said bioerodible polymer hydrolysis.
Claim 12
Dependent Claim
23 words
The bioerodible implantable material of claim 1, wherein said buffer is selected from the group consisting of carbonates, phosphates, acetates, succinates, and citrates.
Claim 13
Dependent Claim
14 words
The bioerodible, implantable material of claim 1, wherein said buffer is a calcium salt.
Claim 14
Dependent Claim
13 words
The bioerodible, implantable material of claim 1, wherein said buffer is calcium carbonate.
Claim 15
Dependent Claim
31 words
The bioerodible implantable material of claim 1, wherein the parent acid of said buffer has an acid dissociation constant that is smaller than the acid dissociation constant of said acidic products.
Claim 16
Dependent Claim
25 words
The bioerodible implantable material of claim 1, wherein said buffer has a hydrolysis constant that is greater than the hydrolysis constant of said acidic products.
Claim 17
Dependent Claim
13 words
The bioerodible implantable material of claim 1, wherein said pH range is 6.8-7.4.
Claim 18
Independent Claim
94 words
A method of making a buffered bioerodible, implantable material, comprising the steps of: dissolving a bioerodible polymer in a solvent, said bioerodible polymer producing acidic products upon hydrolytic degradation; mixing a buffer with said dissolved bioerodible polymer, said buffer present in sufficently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; casting said mixture; and evaporating said solvent of said mixture to produce a buffered bioerodible implantable material.
Claim 19
Independent Claim
94 words
A method of making a buffered bioerodible, implantable material, comprising the steps of: dissolving a bioerodible polymer in a solvent, said bioerodible polymer producing acidic products upon hydrolytic degradation; mixing a buffer with said dissolved bioerodible polymer, said buffer present in sufficently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; casting said mixture; and evaporating said solvent of said mixture to produce a buffered bioerodible implantable material.
Claim 20
Dependent Claim
29 words
The method of claim 17, wherein said bioerodible polymer is selected from the group consisting of polydioxanone, poly(ε-caprolactone), polyanhydride, poly(ortho ester), copoly(ether-ester), polyamide, polylactone, poly(propylene fumarate), and combinations thereof.
Claim 21
Dependent Claim
25 words
The method of claim 17, wherein said bioerodible polymer comprises poly(lactide-co-glycolide) with a lactide to glycolide ratio in the range of 0:100% to 100:0% inclusive.
Claim 22
Dependent Claim
15 words
The method of claim 17, wherein said buffer is the salt of an inorganic acid.
Claim 23
Dependent Claim
15 words
The method of claim 17, wherein said buffer is the salt of an organic acid.
Claim 24
Dependent Claim
17 words
The method of claim 17, wherein said buffer is a polymer comprising at least one basic group.
Claim 25
Dependent Claim
21 words
The method of claim 17, wherein said buffer is a compound which, on exposure to water, hydrolyzes to form a base.
Claim 26
Dependent Claim
17 words
The method of claim 17, further comprising the step of milling said buffer in said polymer solution.
Claim 27
Dependent Claim
20 words
The method of claim 17, further comprising the step of processing said buffered bioerodible implantable material into a desired form.
Claim 28
Dependent Claim
25 words
The method of claim 17, further comprising the step of coating said buffer with a polymeric material that degrades at a slower rate than PLGA.
Claim 29
Dependent Claim
53 words
The method of claim 17, further comprising the steps of: providing a first solution comprising a soluble calcium salt; providing a second solution comprising a soluble ionic carbonate; mixing said first solution and said second solution to form a calcium carbonate precipitate; and collecting said calcium carbonate precipitate for use as said buffer.
Claim 30
Dependent Claim
14 words
The method of claim 27, wherein said calcium carbonate precipitate comprises calcite and aragonite.
Claim 31
Dependent Claim
29 words
The method of claim 17, further comprising the steps of: providing a salt comprising a metal ion and a carboxylate ion; and combusting said salt to form said buffer.
Claim 32
Dependent Claim
19 words
The method of claim 29, wherein said combusting step takes place at temperatures between 450° and 1000° C., inclusive.
Claim 33
Independent Claim
96 words
A method for making a buffered bioerodible implantable PLGA material, comprising the steps of: providing bioerodible polymer particles having a specific size, said bioerodible polymer producing acidic products upon hydrolytic degradation; providing buffer particles having a specific size, said buffer particles comprising a buffer present in sufficently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; and mixing said bioerodible polymer particles and said buffer particles in a predetermined proportion.
Claim 34
Independent Claim
96 words
A method for making a buffered bioerodible implantable PLGA material, comprising the steps of: providing bioerodible polymer particles having a specific size, said bioerodible polymer producing acidic products upon hydrolytic degradation; providing buffer particles having a specific size, said buffer particles comprising a buffer present in sufficently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; and mixing said bioerodible polymer particles and said buffer particles in a predetermined proportion.
Claim 35
Dependent Claim
26 words
The method of claim 31, wherein said bioerodible polymer particles comprise poly(lactide-co-glycolide) with a lactide to glycolide ratio in the range of 0:100% to 100:0% inclusive.
Claim 36
Dependent Claim
15 words
The method of claim 31, wherein said buffer is the salt of an inorganic acid.
Claim 37
Dependent Claim
15 words
The method of claim 31, wherein said buffer is the salt of an organic acid.
Claim 38
Dependent Claim
17 words
The method of claim 31, wherein said buffer is a polymer comprising at least one basic group.
Claim 39
Dependent Claim
21 words
The method of claim 31, wherein said buffer is a compound which, on exposure to water, hydrolyzes to form a base.
Claim 40
Dependent Claim
20 words
The method of claim 31, further comprising the step of processing said buffered bioerodible implantable material into a desired form.
Claim 41
Dependent Claim
26 words
The method of claim 31, further comprising the step of coating said buffer particles with a polymeric material that degrades at a slower rate than PLGA.
Claim 42
Dependent Claim
54 words
The method of claim 31, further comprising the steps of: providing a first solution comprising a soluble calcium salt; providing a second solution comprising a soluble ionic carbonate; mixing said first solution and said second solution to form a calcium carbonate precipitate; and collecting said calcium carbonate precipitate for use as said buffer particles.
Claim 43
Dependent Claim
14 words
The method of claim 39, wherein said calcium carbonate precipitate comprises calcite and aragonite.
Claim 44
Dependent Claim
29 words
The method of claim 31, further comprising the steps of: providing a salt comprising a metal ion and a carboxylate ion; and combusting said salt to form said buffer.
Claim 45
Dependent Claim
19 words
The method of claim 41, wherein said combusting step takes place at temperatures between 450° and 1000° C., inclusive.
Claim 46
Independent Claim
111 words
A method for making a buffered bioerodible implantable material, comprising the steps of: providing an open celled bioerodible foam polymer of controlled density, said bioerodible foam polymer producing acidic products upon hydrolytic degradation; providing a buffer dissolved in a solvent, said foam polymer not soluble in said solvent, present in sufficiently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; loading said buffer compound dissolved in said solvent into said PLGA foam polymer; and freeze drying said buffer loaded foam polymer to remove said solvent.
Claim 47
Independent Claim
111 words
A method for making a buffered bioerodible implantable material, comprising the steps of: providing an open celled bioerodible foam polymer of controlled density, said bioerodible foam polymer producing acidic products upon hydrolytic degradation; providing a buffer dissolved in a solvent, said foam polymer not soluble in said solvent, present in sufficiently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; loading said buffer compound dissolved in said solvent into said PLGA foam polymer; and freeze drying said buffer loaded foam polymer to remove said solvent.
Claim 48
Dependent Claim
20 words
The method of claim 43, further comprising the step of processing said buffered bioerodible implantable material into a desired form.
Claim 49
Dependent Claim
26 words
The method of claim 43, further comprising the step of coating said buffer particles with a polymeric material that degrades at a slower rate than PLGA.
Claim 50
Dependent Claim
25 words
The method of claim 43, wherein said bioerodible polymer comprises poly(lactide-co-glycolide) with a lactide to glycolide ratio in the range of 100:0 to 0:100 inclusive.
Claim 51
Dependent Claim
15 words
The method of claim 43, wherein said buffer is the salt of an inorganic acid.
Claim 52
Dependent Claim
15 words
The method of claim 43, wherein said buffer is the salt of an organic acid.
Claim 53
Dependent Claim
17 words
The method of claim 43, wherein said buffer is a polymer comprising at least one basic group.
Claim 54
Dependent Claim
21 words
The method of claim 43, wherein said buffer is a compound which, on exposure to water, hydrolyzes to form a base.
Claim 55
Independent Claim
135 words
A method for making a buffered bioerodible implantable material, comprising the steps of: providing a bioerodible polymer having a first melting temperature, said bioerodible polymer producing acidic products upon hydrolytic degradation; providing buffer particles comprising buffer material coated with a protective polymer, said protective polymer having a second melting temperature, said second melting temperature greater than said first melting temperature, said buffer particles comprising a buffer present in sufficiently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; heating said bioerodible polymer to a temperature between said first melting temperature and said second melting temperature; mixing said heated bioerodible polymer and said coated buffer particles; and cooling said mixture.
Claim 56
Independent Claim
135 words
A method for making a buffered bioerodible implantable material, comprising the steps of: providing a bioerodible polymer having a first melting temperature, said bioerodible polymer producing acidic products upon hydrolytic degradation; providing buffer particles comprising buffer material coated with a protective polymer, said protective polymer having a second melting temperature, said second melting temperature greater than said first melting temperature, said buffer particles comprising a buffer present in sufficiently high concentration so as to buffer said acidic products within a pH range within which physiological irritation, inflammation, and swelling (sterile abscess formation) caused by said unbuffered acidic products in vivo is prevented or ameliorated; heating said bioerodible polymer to a temperature between said first melting temperature and said second melting temperature; mixing said heated bioerodible polymer and said coated buffer particles; and cooling said mixture.
Claim 57
Dependent Claim
20 words
The method of claim 51, further comprising the step of processing said buffered bioerodible implantable material into a desired form.
Claim 58
Dependent Claim
25 words
The method of claim 51, wherein said bioerodible polymer comprises poly(lactide-co-glycolide) with a lactide to glycolide ratio in the range of 100:0 to 0:100 inclusive.
Claim 59
Dependent Claim
15 words
The method of claim 51, wherein said buffer is the salt of an inorganic acid.
Claim 60
Dependent Claim
15 words
The method of claim 51, wherein said buffer is the salt of an organic acid.
Claim 61
Dependent Claim
17 words
The method of claim 51, wherein said buffer is a polymer comprising at least one basic group.
Claim 62
Dependent Claim
21 words
The method of claim 51, wherein said buffer is a compound which, on exposure to water, hydrolyzes to form a base.
Claim 63
Dependent Claim
53 words
The method of claim 51, further comprising the steps of: providing a first solution comprising a soluble calcium salt; providing a second solution comprising a soluble ionic carbonate; mixing said first solution and said second solution to form a calcium carbonate precipitate; and collecting said calcium carbonate precipitate for use as said buffer.
Claim 64
Dependent Claim
14 words
The method of claim 58, wherein said calcium carbonate precipitate comprises calcite and aragonite.
Claim 65
Dependent Claim
30 words
The method of claim 51, further comprising the steps of: providing a salt comprising a metal ion and a carboxylate ion; and combusting said salt to form said buffer material.
Claim 66
Dependent Claim
19 words
The method of claim 60, wherein said combusting step takes place at temperatures between 450° and 1000° C., inclusive.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-10-05 | 2002-04-06 | 2002-10-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-10-05 | 2006-04-06 | 2006-10-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-10-05 | 2010-04-06 | 2010-10-06 | $7700.00 | Window Closed / Lapsed |