US5487897A
Expired / Lapsed
US
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Biodegradable implant precursor
Assignee: Tolmar Therapeutics Inc
•
Filing: 1993-09-28
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Granted: 1996-01-30
•
Expires: 2013-09-28
Abstract
Abstract The invention is directed to a biodegradable implant precursor having a two-part structure made of an outer sac and a liquid content. The implant precursor is composed of a biodegradable, water-coagulable thermoplastic polymer and a water-miscible organic solvent. When administered to an implant site in an animal, the implant precursor will solidify in situ to a solid, microporous matrix by dissipation of the organic solvent to surrounding tissue fluids and coagulation of the polymer. The invention also includes methods of making the implant precursor, an apparatus for forming the precursor, and a kit containing the apparatus. Also provided are methods of using the implant precursor for treating a tissue defect in an animal, for example, for enhancing cell growth and tissue regeneration, wound and organ repair, nerve regeneration, soft and hard tissue regeneration, and the like, for delivery of biologically-active substances to tissue or organs, and other like therapies.
Inventors
- 👤 Alan M. Polson
- 👤 Deryl D. Swanbom
- 👤 Richard L. Dunn
- 👤 Charles P. Cox
- 👤 Richard L. Norton
- 👤 Bryan K. Lowe
- 👤 Kenneth S. Peterson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 10:40
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61L; A61L15/00; A61L15/07; A61L15/12; A61K31/00; A61K31/74; A61K33/00; A61K33/42; A61K47/00; A61K47/30; A61K47/34; A61K9/0053; A61K9/0063; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/1647; A61L27/00; A61L27/14; A61L27/16; A61L27/18; A61L27/50; A61L27/54; A61L27/56; A61L27/58; A61L31/00; A61L31/14; A61L31/148; B; B29; B29C; B29C41/00; B29C41/02; B29C41/08; B29C41/12; B29C67/00; B29C67/02; B29C67/06; A61L2300/00; A61L2300/40; A61L2300/404; A61L2300/406; A61L2300/41; A61L2300/412; A61L2300/414; A61L2300/416; A61L2300/43; A61L2300/60; A61L2300/602; B29K; B29K2995/00; B29K2995/0037; B29K2995/0056; B29K2995/0059; B29K2995/006
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
68 words
An implant precursor for implantation in a tissue defect in an animal, comprising: a two-part structure composed of an outer sac and a liquid content; the implant precursor comprising a mixture of a biocompatible, biodegradable, water-coagulable thermoplastic polymer, and a pharmaceutically-acceptable, water-soluble organic solvent; wherein the implant precursor is capable of reverting to an all liquid form if the implant precursor is not contacted by an aqueous medium.
Claim 2
Dependent Claim
68 words
An implant precursor for implantation in a tissue defect in an animal, comprising: a two-part structure composed of an outer sac and a liquid content; the implant precursor comprising a mixture of a biocompatible, biodegradable, water-coagulable thermoplastic polymer, and a pharmaceutically-acceptable, water-soluble organic solvent; wherein the implant precursor is capable of reverting to an all liquid form if the implant precursor is not contacted by an aqueous medium.
Claim 3
Dependent Claim
37 words
The implant precursor according to claim 1, wherein the liquid content of the implant precursor has a consistency ranging from watery to viscous, and the outer sac has a consistency ranging from gelatinous to moldable and waxen.
Claim 4
Dependent Claim
34 words
The implant precursor according to claim 1, wherein the implant precursor is capable of reverting to an all-liquid form after about 30-90 minutes within being formed, and without subsequent contact with an aqueous medium.
Claim 5
Dependent Claim
51 words
The implant precursor according to claim 1, wherein the thermoplastic polymer is selected from the group consisting of polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, polyamino acids, polymethyl vinyl ether, chitin, and copolymers, terpolymers, and any combination thereof.
Claim 6
Dependent Claim
48 words
The implant precursor according to claim 1, wherein the solvent is selected from the group consisting of N-methyl-2-pyrrolidone, 2-pyrrolidone, ethanol, propylene glycol, propylene carbonate, acetone, acetic acid, ethyl acetate, ethyl lactate, methyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, dimethyl sulfone, tetrahydrofuran, caprolactam, N,N-diethyl-m-toluamide, and any combination thereof.
Claim 7
Dependent Claim
37 words
The implant precursor according to claim 1, further comprising a pore-forming agent selected from the group consisting of a sugar, a salt, a water-soluble polymer, and a water-insoluble substance that rapidly degrades to a water soluble substance.
Claim 8
Dependent Claim
28 words
The implant precursor according to claim 1, further comprising a biologically-active agent selected from the group consisting of an antibacterial agent, an antifungal agent, and an antiviral agent.
Claim 9
Dependent Claim
69 words
The implant precursor according to claim 1, further comprising a biologically-active agent selected from the group consisting of an anti-inflammatory agent, an antiparasitic agent, anti-neoplastic agent, an analgesic agent, an anaesthetic agent, a vaccine, a central nervous system agent, a growth factor, a hormone, an antihistamine, an osteoinductive agent, a cardiovascular agent, an anti-ulcer agent, a bronchodilating agent, a vasodilating agent, a birth control agent, and a fertility-enhancing agent.
Claim 10
Dependent Claim
30 words
The implant precursor according to claim 1, further comprising a release rate modification agent for controlling the rate of release of a bioactive agent in vivo from the implant matrix.
Claim 11
Dependent Claim
56 words
The implant precursor according to claim 9, wherein the release rate modification agent is selected from the group consisting of an ester of a monocarboxylic acid, an ester of a dicarboxylic acid, an ester of a tricarboxylic acid, a polyhydroxy alcohol, a fatty acid, a triester of glycerol, a sterol, an alcohol, and any combination thereof.
Claim 12
Dependent Claim
74 words
The implant precursor according to claim 10, wherein the release rate modification agent is selected from the group consisting of 2-ethoxyethyl acetate, methyl acetate, ethyl acetate, diethyl phthalate, dimethyl phthalate, dibutyl phthalate, dimethyl adipate, dimethyl succinate, dimethyl oxalate, dimethyl citrate, triethyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, glycerol triacetate, di(n-butyl) sebecate, propylene glycol, polyethylene glycol, glycerin, sorbitol, triglyceride, epoxidized soybean oil, cholesterol, a C 6 -C 12 alkanol, 2-ethoxyethanol, and any combination thereof.
Claim 13
Dependent Claim
32 words
The implant precursor according to claim 10, wherein the release rate modification agent is selected from the group consisting of dimethyl citrate, triethyl citrate, ethyl heptanoate, glycerin, hexanediol, and any combination thereof.
Claim 14
Independent Claim
134 words
A method of making an implant precursor, comprising: (a) applying an effective amount of an aqueous medium to a surface of a solid support substrate to form an aqueous layer; (b) dispensing an effective amount of a liquid polymer solution onto the aqueous layer; the polymer solution comprising a water-coagulable, biocompatible, biodegradable thermoplastic polymer and a water-soluble, pharmaceutically-acceptable organic solvent; (c) applying an effective amount of an aqueous medium onto the surface of the polymer solution; and (d) allowing the polymer adjacent the aqueous medium to coagulate to form the implant precursor comprising a two-part structure composed of an outer sac and a liquid content; the amount of aqueous medium applied in steps (a) and (c) being effective to cause surface coagulation of the polymer to form the outer sac of the implant precursor.
Claim 15
Independent Claim
134 words
A method of making an implant precursor, comprising: (a) applying an effective amount of an aqueous medium to a surface of a solid support substrate to form an aqueous layer; (b) dispensing an effective amount of a liquid polymer solution onto the aqueous layer; the polymer solution comprising a water-coagulable, biocompatible, biodegradable thermoplastic polymer and a water-soluble, pharmaceutically-acceptable organic solvent; (c) applying an effective amount of an aqueous medium onto the surface of the polymer solution; and (d) allowing the polymer adjacent the aqueous medium to coagulate to form the implant precursor comprising a two-part structure composed of an outer sac and a liquid content; the amount of aqueous medium applied in steps (a) and (c) being effective to cause surface coagulation of the polymer to form the outer sac of the implant precursor.
Claim 16
Dependent Claim
22 words
The method according to claim 13, further comprising step (e) of maintaining the implant precursor at a thickness of about 400-1500 μm.
Claim 17
Dependent Claim
24 words
The method according to claim 13, wherein the thickness of the implant precursor is maintained by compressing the coagulating polymer solution during step (d).
Claim 18
Dependent Claim
14 words
The method according to claim 13, wherein the implant precursor is formed ex vivo.
Claim 19
Dependent Claim
42 words
The method according to claim 13, wherein the support substrate is selected from the group consisting of glass, porous plastic, sintered stainless steel, porcelain, bone material, bone, oxidized cellulose foam, biocompatible polymer foam, particles of biocompatible polymer, tricalcium phosphate and blood materials.
Claim 20
Dependent Claim
14 words
The method according to claim 13, wherein the implant precursor is formed in vivo.
Claim 21
Dependent Claim
14 words
The method according to claim 13, wherein the support substrate is a hard tissue.
Claim 22
Dependent Claim
13 words
The method according to claim 19, wherein the substrate is a bone tissue.
Claim 23
Dependent Claim
131 words
The method according to claim 13, further comprising prior to step (a), the steps of: (i) applying a minor but effective amount of an aqueous medium as a layer on the surface of the support substrate; (ii) dispensing an effective amount of a polymer solution onto the aqueous layer to form a line defining an area thereon; the polymer solution comprising a biocompatible, biodegradable, water-coagulable thermoplastic polymer, and a pharmaceutically-acceptable, water-soluble organic solvent; (iii) applying an effective amount of an aqueous medium to the surface of the line; and (iv) allowing the polymer to coagulate to form a boundary line comprising a two-part structure composed of an outer sac with a liquid content; wherein the implant precursor is formed on the support substrate within the area confined by the boundary line.
Claim 24
Dependent Claim
48 words
The method according to claim 13, further comprising prior to step (a), the step of applying a support layer to the surface of the tissue defect, the support layer comprising a bioabsorbable or bioerodible material; wherein the implant precursor is formed on the surface of the support layer.
Claim 25
Dependent Claim
38 words
The method according to claim 22, wherein the support layer comprises a polymer solution coated onto the surface of the tissue defect; the polymer solution comprising a biocompatible, biodegradable, water-coagulable thermoplastic polymer, and a pharmaceutically-acceptable, water-miscible organic solvent.
Claim 26
Dependent Claim
26 words
The method according to claim 23, further comprising incorporating a gas-forming agent into a polymer solution, and forming the support layer as a porous, foam structure.
Claim 27
Dependent Claim
15 words
The method according to claim 22, wherein the support layer comprises a natural body substance.
Claim 28
Dependent Claim
13 words
The method according to claim 22, wherein the support layer comprises clotted blood.
Claim 29
Dependent Claim
16 words
The method according to claim 22, wherein the support layer comprises an oxidized cellulose or gelatin.
Claim 30
Dependent Claim
14 words
The method according to claim 22, wherein the support layer comprises a water-soluble polymer.
Claim 31
Dependent Claim
23 words
The method according to claim 22, wherein the support layer is selected from the group consisting of tricalcium phosphate, calcium sulfate or hydroxyapatite.
Claim 32
Dependent Claim
59 words
The method according to claim 22, wherein the support layer is selected from the group consisting of polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, polymalic acid, polyethylene glycol, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyamino acids, polymethyl vinyl ether, chitin, chitosan, and copolymers, terpolymers, and any combination thereof.
Claim 33
Independent Claim
79 words
A method for treating a tissue defect in a mammal, comprising: (a) administering to the tissue defect, an implant precursor comprising a two-part structure composed of an outer sac and a liquid content; the implant precursor comprising a mixture of a biocompatible, biodegradable, water-coagulable thermoplastic polymer, and a pharmaceutically-acceptable, water-soluble organic solvent; and (b) allowing the implant precursor to coagulate in situ to an implant comprising a solid, microporous matrix; the implant being effective for treating the tissue defect.
Claim 34
Independent Claim
79 words
A method for treating a tissue defect in a mammal, comprising: (a) administering to the tissue defect, an implant precursor comprising a two-part structure composed of an outer sac and a liquid content; the implant precursor comprising a mixture of a biocompatible, biodegradable, water-coagulable thermoplastic polymer, and a pharmaceutically-acceptable, water-soluble organic solvent; and (b) allowing the implant precursor to coagulate in situ to an implant comprising a solid, microporous matrix; the implant being effective for treating the tissue defect.
Claim 35
Dependent Claim
32 words
The method according to claim 31, wherein the implant precursor further comprises a biologically active agent selected from the group consisting of an antibacterial agent, an antifungal agent, and an antiviral agent.
Claim 36
Dependent Claim
72 words
The method according to claim 32, wherein the implant precursor further comprises a biologically-active agent selected from the group consisting of an anti-inflammatory agent, an antiparasitic agent, anti-neoplastic agent, an analgesic agent, an anaesthetic agent, a vaccine, a central nervous system agent, a growth factor, a hormone, an antihistamine, an osteoinductive agent, a cardiovascular agent, an anti-ulcer agent, a bronchodilating agent, a vasodilating agent, a birth control agent, and a fertility-enhancing agent.
Claim 37
Dependent Claim
33 words
The method according to claim 32, wherein the implant precursor further comprises a release rate modification agent for controlling the rate of release of a bioactive agent in vivo from the implant matrix.
Claim 38
Dependent Claim
23 words
The method according to claim 13, wherein the thermoplastic polymer is a copolymer of lactide with glycolide or caprolactone, or a terpolymer thereof.
Claim 39
Dependent Claim
23 words
The method according to claim 31, wherein the thermoplastic polymer is a copolymer of lactide with glycolide or caprolactone, or a terpolymer thereof.
Claim 40
Dependent Claim
12 words
The method according to claim 32, wherein the biologically-active agent is doxycycline.
Claim 41
Dependent Claim
24 words
The implant precursor according to claim 1, wherein the thermoplastic polymer is a copolymer of lactide with glycolide or caprolactone, or a terpolymer thereof.
Claim 42
Dependent Claim
13 words
The implant precursor according to claim 7, wherein the biologically-active agent is doxycycline.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1999-01-29 | 1999-07-31 | 2000-01-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-01-29 | 2003-07-31 | 2004-01-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-01-29 | 2007-07-31 | 2008-01-30 | $7700.00 | Window Closed / Lapsed |