Patent US4341706A successfully refreshed from Google Patents.
Patent US5739176A successfully refreshed from Google Patents.
US5739176A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Biodegradable in-situ forming implants and methods of producing the same
Assignee: Tolmar Therapeutics Inc
•
Filing: 1994-03-18
•
Granted: 1998-04-14
•
Expires: 2014-03-18
Abstract
Abstract A biodegradable polymer is provided for use in providing syringeable, in-situ forming, solid biodegradable implants for animals. The polymer is placed into the animal in liquid form and cures to form the implant in-situ. A thermoplastic system to form said implant comprises the steps of dissolving a non-reactive polymer in biocompatible solvent to form a liquid, placing the liquid within the animal, and allowing the solvent to dissipate to produce the implant. An alternative, thermosetting system comprises mixing together effective amounts of a liquid acrylic ester terminated, biodegradable prepolymer and a curing agent, placing the liquid mixture within an animal and allowing the prepolymer to cure to form the implant. Both systems provide a syringeable, solid biodegradable delivery system by the addition of an effective level of biologically active agent to the liquid before injection into the body.
Inventors
- 👤 Richard L. Dunn
- 👤 James P. English
- 👤 Donald R. Cowsar
- 👤 David D. Vanderbilt
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 12:36
CPC Classifications
A; A61; A61F; A61F2/00; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61K47/00; A61K47/30; A61K47/34; A61L; A61L15/00; A61L15/16; A61L15/42; A61L15/44; A61L15/62; A61L24/00; A61L24/001; A61L24/0015; A61L24/0026; A61L24/0042; A61L24/04; A61L24/046; A61L24/06; A61L26/00; A61L26/0009; A61L26/0019; A61L26/0061; A61L26/0066; A61L26/0076; A61L26/009; A61L27/00; A61L27/14; A61L27/16; A61L27/18; A61L27/26; A61L27/28; A61L27/34; A61L27/50; A61L27/54; A61L27/58; A61F2/02; A61F2/30; A61F2002/30001; A61F2002/30003; A61F2002/3006; A61F2002/30062; A61F2002/30316; A61F2002/30535; A61F2002/30581; A61F2002/30583; A61F2210/00; A61F2210/0004; A61F2210/0085; A61L2300/00; A61L2300/20; A61L2300/25; A61L2300/252; A61L2300/40; A61L2300/404; A61L2300/406; A61L2300/41; A61L2300/60; A61L2300/602; A61L2300/604; Y; Y10; Y10S; Y10S525/00; Y10S525/937
Claims Analysis
Total Claims: 47
Claim 1
Independent Claim
197 words
A method of forming a solid, biodegradable implant in-situ, in a body, comprising: (a) dissolving a biocompatible, water-insoluble, biodegradable thermoplastic polymer in a biocompatible, water-soluble organic solvent to form a composition; the organic solvent being capable of dissipating or diffusing into a body fluid upon placement within a body tissue; and the thermoplastic polymer being selected from the group consisting of: (i) a copolymer of a biodegradable, water-insoluble monomer or polymer and a biodegradable, water-soluble monomer or polymer, wherein the amount of water-insoluble monomer or polymer is sufficient to render the copolymer water-insoluble; (ii) a copolymer of polyethylene glycol with polylactide, polyglycolide or polycaprolactone, or a terpolymer thereof; (iii) a copolymer of lactide with glycolide or caprolactone, or a terpolymer thereof; (iv) a copolymer of lactide with a carbonate; and (v) a polyanhydride; and (b) placing the composition into an implant site within the body; and (c) allowing the organic solvent to dissipate or diffuse into body fluid, and the thermoplastic polymer to coagulate or solidify to produce the biodegradable solid implant; wherein the proportion of polymer in solvent and the molecular weight of the polymer are effective to provide said dissipation or diffusion and said coagulation.
Claim 2
Independent Claim
197 words
A method of forming a solid, biodegradable implant in-situ, in a body, comprising: (a) dissolving a biocompatible, water-insoluble, biodegradable thermoplastic polymer in a biocompatible, water-soluble organic solvent to form a composition; the organic solvent being capable of dissipating or diffusing into a body fluid upon placement within a body tissue; and the thermoplastic polymer being selected from the group consisting of: (i) a copolymer of a biodegradable, water-insoluble monomer or polymer and a biodegradable, water-soluble monomer or polymer, wherein the amount of water-insoluble monomer or polymer is sufficient to render the copolymer water-insoluble; (ii) a copolymer of polyethylene glycol with polylactide, polyglycolide or polycaprolactone, or a terpolymer thereof; (iii) a copolymer of lactide with glycolide or caprolactone, or a terpolymer thereof; (iv) a copolymer of lactide with a carbonate; and (v) a polyanhydride; and (b) placing the composition into an implant site within the body; and (c) allowing the organic solvent to dissipate or diffuse into body fluid, and the thermoplastic polymer to coagulate or solidify to produce the biodegradable solid implant; wherein the proportion of polymer in solvent and the molecular weight of the polymer are effective to provide said dissipation or diffusion and said coagulation.
Claim 3
Dependent Claim
44 words
The method of claim 1, wherein said solvent is selected from the group consisting essentially of N-methyl-2-pyrrolidone, 2-pyrrolidone, ethanol, propylene glycol, acetone, ethyl acetate, methyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid and 1-dodecylazacycloheptan-2-one and combinations and mixtures thereof.
Claim 4
Dependent Claim
28 words
The method of claim 1, wherein said solvent is selected from the group consisting essentially of N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide and acetone, and a combination or mixture thereof.
Claim 5
Dependent Claim
40 words
The method of claim 1, further comprising combining an effective amount of a biologically active agent with the thermoplastic polymer and water-soluble, organic solvent, the implant releasing said agent by diffusion, erosion or a combination thereof as the implant biodegrades.
Claim 6
Dependent Claim
15 words
The method of claim 1, and further comprising delivering the composition in-situ through a needle.
Claim 7
Dependent Claim
86 words
The method of claim 1, wherein the organic solvent is a mixture of a first organic solvent capable of dissolving the thermoplastic polymer and a second organic solvent incapable or less capable than the first solvent of dissolving the thermoplastic polymer, said first and second solvents included in said mixture at a ratio such that the thermoplastic polymer is soluble therein, and coagulates to form a solid matrix upon placing the composition within the body and the dissipation or diffusion of the solvent into body fluid.
Claim 8
Dependent Claim
21 words
The method of claim 6, wherein said second solvent is selected from the group consisting of water, ethanol and propylene glycol.
Claim 9
Dependent Claim
41 words
The method of claim 6, wherein the first solvent is selected from the group consisting of: N-methyl-2-pyrrolidone, 2-pyrrolidone, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, and 1-dodecylazacycloheptan-2-one, and combinations and mixtures thereof.
Claim 10
Dependent Claim
41 words
The method of claim 1, wherein step (b) comprises applying the composition to a tissue, such that the implant functions to adhere a first tissue to a second tissue, to adhere a second implant to a tissue, or a combination thereof.
Claim 11
Dependent Claim
23 words
The method of claim 1, wherein step (b) comprises injecting the composition subdermally such that the implant functions to build up a tissue.
Claim 12
Dependent Claim
24 words
The method of claim 1, wherein step (b) comprises placing the composition into a wound such that the implant functions to inhibit scar formation.
Claim 13
Dependent Claim
31 words
The method of claim 1, wherein step (b) comprises placing the composition into a bone defect or a gap in a bone such that the implant functions as a filler material.
Claim 14
Dependent Claim
29 words
The method of claim 1, wherein step (b) comprises placing the composition into a soft tissue defect such that the implant provides a scaffold for growth of tissue thereon.
Claim 15
Dependent Claim
33 words
The method of claim 1, wherein step (b) comprising placing the composition into a cavity selected from the group consisting of periodontal, oral, vaginal, rectal, and nasal, and the implant is formed therein.
Claim 16
Dependent Claim
21 words
The method of claim 1, wherein step (b) comprises placing the composition into a periodontal pocket for treatment of periodontal disease.
Claim 17
Dependent Claim
38 words
The method of claim 1, further comprising combining a biologically active agent with the thermoplastic polymer and water-soluble organic solvent; the biologically active agent selected from the group consisting of anti-inflammatory agent, antimicrobial agent, antibiotic, and mixtures thereof.
Claim 18
Dependent Claim
18 words
The method of claim 1, wherein step (b) comprises placing the composition into the cul-de-sac of an eye.
Claim 19
Dependent Claim
178 words
A pharmaceutical composition for forming a biodegradable implant in-situ within a body, comprising: an effective amount of a biocompatible, water-insoluble, biodegradable thermoplastic polymer dissolved in an effective amount of a biocompatible, water-soluble organic solvent; wherein, the solvent is capable of dissipating or diffusing into a body fluid and the polymer is capable of coagulating or solidifying upon contact with body fluid; the thermoplastic polymer is selected from the group consisting of: (i) a copolymer of a biodegradable, water-insoluble monomer or polymer and a biodegradable, water-soluble monomer or polymer, wherein the amount of water-insoluble monomer or polymer is sufficient to render the copolymer water-insoluble; (ii) a copolymer of polyethylene glycol with polylactide, polyglycolide or polycaprolactone, or a terpolymer thereof; (iii) a copolymer of lactide with glycolide or caprolactone, or a terpolymer thereof; (iv) a copolymer of lactide with a carbonate; and (v) a polyanhydride; and the amounts of the polymer and the solvent and the polymer molecular weight in the pharmaceutical composition are effective to form a coherent, solid implant in situ when the pharmaceutical composition contacts body fluid.
Claim 20
Dependent Claim
178 words
A pharmaceutical composition for forming a biodegradable implant in-situ within a body, comprising: an effective amount of a biocompatible, water-insoluble, biodegradable thermoplastic polymer dissolved in an effective amount of a biocompatible, water-soluble organic solvent; wherein, the solvent is capable of dissipating or diffusing into a body fluid and the polymer is capable of coagulating or solidifying upon contact with body fluid; the thermoplastic polymer is selected from the group consisting of: (i) a copolymer of a biodegradable, water-insoluble monomer or polymer and a biodegradable, water-soluble monomer or polymer, wherein the amount of water-insoluble monomer or polymer is sufficient to render the copolymer water-insoluble; (ii) a copolymer of polyethylene glycol with polylactide, polyglycolide or polycaprolactone, or a terpolymer thereof; (iii) a copolymer of lactide with glycolide or caprolactone, or a terpolymer thereof; (iv) a copolymer of lactide with a carbonate; and (v) a polyanhydride; and the amounts of the polymer and the solvent and the polymer molecular weight in the pharmaceutical composition are effective to form a coherent, solid implant in situ when the pharmaceutical composition contacts body fluid.
Claim 21
Independent Claim
196 words
A method of forming a solid, biodegradable implant in-situ, in a body, comprising: (a) dissolving a water-insoluble, biodegradable thermoplastic polymer a biocompatible, water-soluble organic solvent to form a composition; the organic solvent being capable of dissipating or diffusing into a body fluid upon placement within a body tissue; wherein the organic solvent is comprised of a mixture of a first organic solvent capable of dissolving the polymer, and a second organic solvent incapable or less capable than the first organic solvent of dissolving the thermoplastic polymer; said first and second solvents included in said mixture at a ratio such that the thermoplastic polymer is soluble therein and coagulates to form a solid implant upon placing the composition within the body and the dissipation or diffusion of the solvent into body fluid; and (b) placing the composition into an implant site within the body; and (c) allowing the organic solvent to dissipate or diffuse into the body fluid, and the thermoplastic polymer to coagulate or solidify to produce the biodegradable, solid implant; wherein the proportion of polymer in solvent and the molecular weight of the polymer are effective to provide said dissipation or diffusion and said coagulation.
Claim 22
Independent Claim
196 words
A method of forming a solid, biodegradable implant in-situ, in a body, comprising: (a) dissolving a water-insoluble, biodegradable thermoplastic polymer a biocompatible, water-soluble organic solvent to form a composition; the organic solvent being capable of dissipating or diffusing into a body fluid upon placement within a body tissue; wherein the organic solvent is comprised of a mixture of a first organic solvent capable of dissolving the polymer, and a second organic solvent incapable or less capable than the first organic solvent of dissolving the thermoplastic polymer; said first and second solvents included in said mixture at a ratio such that the thermoplastic polymer is soluble therein and coagulates to form a solid implant upon placing the composition within the body and the dissipation or diffusion of the solvent into body fluid; and (b) placing the composition into an implant site within the body; and (c) allowing the organic solvent to dissipate or diffuse into the body fluid, and the thermoplastic polymer to coagulate or solidify to produce the biodegradable, solid implant; wherein the proportion of polymer in solvent and the molecular weight of the polymer are effective to provide said dissipation or diffusion and said coagulation.
Claim 23
Dependent Claim
21 words
The method of claim 19, wherein said second solvent is selected from the group consisting of water, ethanol and propylene glycol.
Claim 24
Dependent Claim
41 words
The method of claim 19, wherein the first solvent is selected from the group consisting of: N-methyl-2-pyrrolidone, 2-pyrrolidone, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, and 1-dodecylazacycloheptan-2-one, and combinations and mixtures thereof.
Claim 25
Dependent Claim
39 words
The composition of claim 18, wherein said polymer is the copolymer or terpolymer of a water-insoluble polymer and a water-soluble polymer; wherein the water-insoluble polymer is polylactide, polyglycolide or polycaprolactone; and the water-soluble polymer is polyethylene glycol or polyvinylpyrrolidone.
Claim 26
Dependent Claim
43 words
The composition of claim 18, wherein the solvent is selected from the group consisting of: N-methyl-2-pyrrolidone, 2-pyrrolidone, ethanol, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid and 1-dodecylazacycloheptan-2-one, and combinations and mixtures thereof.
Claim 27
Dependent Claim
52 words
The composition of claim 18, wherein the solvent is a mixture of water, ethanol or propylene glycol with a solvent selected from the group consisting of: N-methyl-2-pyrrolidone, 2-pyrrolidone, ethanol, acetone, ethyl acetate, methyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid and 1-dodecylazacycloheptan-2-one, and combinations and mixtures thereof.
Claim 28
Dependent Claim
86 words
The composition of claim 18, wherein the organic solvent is a mixture of a first organic solvent capable of dissolving the thermoplastic polymer, and a second organic solvent incapable or less capable than the first solvent of dissolving the thermoplastic polymer; said first and second solvents included in said mixture at a ratio such that the thermoplastic polymer is soluble therein, and coagulates to form a solid matrix upon placing the composition within the body and the dissipation or diffusion of the solvent into body fluid.
Claim 29
Dependent Claim
21 words
The composition of claim 25, wherein the second solvent is selected from the group consisting of water, ethanol and propylene glycol.
Claim 30
Dependent Claim
41 words
The composition of claim 25, wherein the first solvent is selected from the group consisting of: N-methyl-2-pyrrolidone, 2-pyrrolidone, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid and 1-dodecylazacycloheptan-2-one, and combinations and mixtures thereof.
Claim 31
Dependent Claim
11 words
The composition of claim 18, further comprising a biologically active agent.
Claim 32
Dependent Claim
68 words
The composition of claim 28, wherein the biologically active agent is selected from the group consisting of: a peptide drug, protein drug, desensitizing agent, antigen, vaccine, anti-infective, antibiotic, antimicrobial, antiallergenic, anti-inflammatory agent, decongestant, miotic, anticholinergic, sympathomimetic, sedative, hypnotic, psychic energizer, tranquilizer, steroid, estrogen, progestational agent, humoral agent, prostaglandin, analgesic, antispasmodic, antimalarial, antihistamine, cardioactive agent, antiparkinsonian agent, antihypertensive agent, β-adrenergic blocking agent, nutritional agent, benzophenanthridine alkaloid, and mixtures thereof.
Claim 33
Dependent Claim
16 words
The composition of claim 29, wherein the biologically active agent comprises a protein or peptide drug.
Claim 34
Dependent Claim
15 words
The composition of claim 29, wherein the biologically active agent comprises an antigen or vaccine.
Claim 35
Dependent Claim
35 words
The composition of claim 28, wherein the biologically active agent is in the form of an uncharged molecule, molecular complex, salt, ether, ester, or amide; said form becoming biologically activated upon placement within a body.
Claim 36
Dependent Claim
169 words
A pharmaceutical composition for forming a solid biodegradable implant in situ within a body, comprising: an effective amount of a biocompatible, water-insoluble, biodegradable thermoplastic polymer dissolved in an effective amount of a biocompatible, water-soluble organic solvent; wherein the solvent is capable of dissipating or diffusing into a body fluid and the thermoplastic polymer is capable of coagulating or solidifying upon contact with body fluid; and the organic solvent is a mixture of a first organic solvent capable of dissolving the thermoplastic polymer, and a second organic solvent incapable or less capable than the first solvent of dissolving the thermoplastic polymer; said first and second solvents included in said mixture at a ratio such that the thermoplastic polymer is soluble therein, and coagulates to form a coherent solid implant upon placement of the composition within the body; and the amounts of the polymer and the solvent and the polymer molecular weight in the composition are effective to form the coherent, solid implant in situ when the composition contacts body fluid.
Claim 37
Dependent Claim
169 words
A pharmaceutical composition for forming a solid biodegradable implant in situ within a body, comprising: an effective amount of a biocompatible, water-insoluble, biodegradable thermoplastic polymer dissolved in an effective amount of a biocompatible, water-soluble organic solvent; wherein the solvent is capable of dissipating or diffusing into a body fluid and the thermoplastic polymer is capable of coagulating or solidifying upon contact with body fluid; and the organic solvent is a mixture of a first organic solvent capable of dissolving the thermoplastic polymer, and a second organic solvent incapable or less capable than the first solvent of dissolving the thermoplastic polymer; said first and second solvents included in said mixture at a ratio such that the thermoplastic polymer is soluble therein, and coagulates to form a coherent solid implant upon placement of the composition within the body; and the amounts of the polymer and the solvent and the polymer molecular weight in the composition are effective to form the coherent, solid implant in situ when the composition contacts body fluid.
Claim 38
Dependent Claim
41 words
The composition of claim 33, wherein the first solvent is selected from the group consisting of: N-methyl-2-pyrrolidone, 2-pyrrolidone, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid and 1-dodecylazacycloheptan-2-one, and combinations and mixtures thereof.
Claim 39
Dependent Claim
21 words
The composition of claim 33, wherein the second solvent is selected from the group consisting of water, ethanol and propylene glycol.
Claim 40
Dependent Claim
47 words
The composition of claim 33, wherein said polymer is selected from the group consisting of: polylactides, polyglycolides, polycaprolactones, polydioxanones, polycarbonates, polyhydroxybutyrates, polyalkylene oxalates, polyanhydrides, polyamides, polyesteramides, polyurethanes, polyacetates, polyketals, polyorthocarbonates, polyphosphazenes, polyhydroxyvalerates, polyalkylene succinates, poly(malic acid), poly(amino acids), polyorthoesters, and copolymers, terpolymers, or combinations and mixtures thereof.
Claim 41
Dependent Claim
21 words
The composition of claim 36, wherein the polymer is selected from the group consisting of: polylactides, polyglycolides, polycaprolactones, and copolymers thereof.
Claim 42
Dependent Claim
11 words
The composition of claim 33, further comprising a biologically active agent.
Claim 43
Dependent Claim
68 words
The composition of claim 38, wherein the biologically active agent is selected from the group consisting of: a peptide drug, protein drug, desensitizing agent, antigen, vaccine, anti-infective, antibiotic, antimicrobial, antiallergenic, anti-inflammatory agent, decongestant, miotic, anticholinergic, sympathomimetic, sedative, ⃡hypnotic, psychic energizer, tranquilizer, steroid, estrogen, progestational agent, humoral agent, prostaglandin, analgesic, antispasmodic, antimalarial, antihistamine, cardioactive agent, antiparkinsonian agent, antihypertensive agent, β-adrenergic blocking agent, nutritional agent, benzophenanthridine alkaloid, and mixtures thereof.
Claim 44
Dependent Claim
16 words
The composition of claim 39, wherein the biologically active agent comprises a protein or peptide drug.
Claim 45
Dependent Claim
15 words
The composition of claim 39, wherein the biologically active agent comprises an antigen or vaccine.
Claim 46
Dependent Claim
35 words
The composition of claim 38, wherein the biologically active agent is in the form of an uncharged molecule, molecular complex, salt, ether, ester, or amide; said form becoming biologically activated upon placement within a body.
Claim 47
Dependent Claim
13 words
The composition of claim 28, wherein the biologically active agent is a tetracycline.
References Cited (Backward Citations)
US2155658A
Cited
US3068188A
Cited
US3328246A
Cited
US3218283A
Cited
US3219527A
Cited
US3463158A
Cited
US3520949A
Cited
US3887699A
Cited
US3767784A
Cited
US3760034A
Cited
US3755558A
Cited
FR2126270A1
Cited
US3696811A
Cited
US4450150A
Cited
US3939111A
Cited
US3935308A
Cited
US3931678A
Cited
US4161948A
Cited
US4148871A
Cited
US4408023A
Cited
US4715369A
Cited
US4793336A
Cited
US4447562A
Cited
US4582640A
Cited
US4570629A
Cited
US4677139A
Cited
US4491479A
Cited
US4439420A
Cited
US4443430A
Cited
US5286763A
Cited
WO1985000969A1
Cited
US4631188A
Cited
EP0140766A2
Cited
WO1985002092A1
Cited
EP0159293A1
Cited
US4663077A
Cited
US4745160A
Cited
EP0169016A2
Cited
CA1261549A
Cited
US4595713A
Cited
US4568536A
Cited
US4650665A
Cited
US4772470A
Cited
US4767627A
Cited
US4702917A
Cited
US4767861A
Cited
US4774227A
Cited
EP0241178A1
Cited
US4780320A
Cited
EP0244118A1
Cited
US4857602A
Cited
US4981696A
Cited
US4983689A
Cited
US5013553A
Cited
US4920203A
Cited
US4938763A
Cited
US4938763B1
Cited
US5340849A
Cited
US5278202A
Cited
US5278201A
Cited
US5324520A
Cited
US5007940A
Cited
US5077049A
Cited
US5324519A
Cited
US5368859A
Cited
EP0537559A1
Cited
EP0539751A1
Cited
EP0560014A1
Cited
EP0649662A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-04-13 | 2001-10-13 | 2002-04-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-04-13 | 2005-10-13 | 2006-04-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-04-13 | 2009-10-13 | 2010-04-14 | $7700.00 | Window Closed / Lapsed |