US4963146A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Multi-layered, semi-permeable conduit for nerve regeneration
Assignee: Colla-Tec Inc
•
Filing: 1989-04-20
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Granted: 1990-10-16
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Expires: 2009-04-20
Abstract
Abstract The present invention is directed to hollow conduits whose walls are comprised of Type I collagen and are characterized by having a multi-layered, semi-permeable structure, which conduits are used to promote nerve regeneration across a gap of a severed nerve. Methods of making the nerve regeneration conduit are also disclosed.
Inventors
- 👤 Shu-Tung Li
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 07:53
CPC Classifications
A; A61; A61L; A61L31/00; A61L31/04; A61L31/043; A61L31/044; A61B; A61B17/00; A61B17/11; A61B17/1128; A61L31/14; A61L31/146; A61B2017/00004; A61F; A61F2/00; A61F2/02; A61F2/30; A61F2002/30001; A61F2002/30108; A61F2002/30199; A61F2002/30224; A61F2002/30235; A61F2230/00; A61F2230/0063; A61F2230/0069; A61L2430/00; A61L2430/32
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
85 words
A hollow conduit for promoting the in vivo regeneration of a severed mammalian nerve so as to bridge a gap between its severed ends having walls comprised of Type I collagen, said walls characterized by having at least one layer with a pore size in the range of from about 0.006 μm to about 5.0 μm which selectively allows for the diffusion of at least neuronotrophic factors through said layer while substantially preventing the diffusion of fibrogenic cells, and at least one substantially porous layer.
Claim 2
Dependent Claim
85 words
A hollow conduit for promoting the in vivo regeneration of a severed mammalian nerve so as to bridge a gap between its severed ends having walls comprised of Type I collagen, said walls characterized by having at least one layer with a pore size in the range of from about 0.006 μm to about 5.0 μm which selectively allows for the diffusion of at least neuronotrophic factors through said layer while substantially preventing the diffusion of fibrogenic cells, and at least one substantially porous layer.
Claim 3
Dependent Claim
58 words
The hollow conduit of claim 1, wherein the walls have an inner layer communicating with the hollow interior of the conduit and is the layer having the pore size in the range of from about 0.006 μm to about 5.0 μm and an outer layer communicating with the exterior of the conduit which is the substantially porous layer.
Claim 4
Dependent Claim
21 words
The hollow conduit of claim 2, wherein the inner layer has a thickness of about 0.05 μm to about 5 μm.
Claim 5
Dependent Claim
21 words
The hollow conduit of claim 3, wherein the inner layer has a thickness of about 0.1 μm to about 2.5 μm.
Claim 6
Dependent Claim
22 words
The hollow conduit of claim 2, wherein the outer layer has a thickness of from about 0.1 mm to about 1.0 mm.
Claim 7
Dependent Claim
22 words
The hollow conduit of claim 5, wherein the outer layer has a thickness of from about 0.2 mm to about 0.5 mm.
Claim 8
Dependent Claim
16 words
The hollow conduit of claim 1, wherein the Type I collagen is derived from bovine tendons.
Claim 9
Dependent Claim
23 words
The hollow conduit of claim 1, wherein the pore size is in the range of from about 0.007 μm to about 3.0 μm.
Claim 10
Dependent Claim
23 words
The hollow conduit of claim 8, wherein the pore size is in the range of from about 0.008 μm to about 2.0 μm.
Claim 11
Dependent Claim
19 words
The hollow conduit of claim 1 having an inner diameter of from about 1 mm to about 1 cm.
Claim 12
Dependent Claim
14 words
The hollow conduit of claim 1, wherein the walls further contain a laminin-containing material.
Claim 13
Dependent Claim
15 words
The hollow conduit of claim 11, wherein the laminin-containing material is purified human placenta laminin.
Claim 14
Dependent Claim
15 words
The hollow conduit of claim 11, wherein the laminin-containing material is derived from basement membrane.
Claim 15
Dependent Claim
34 words
The hollow conduit of claim 1 wherein the walls further contain any of the group consisting of glycoproteins, proteoglycans, heparan sulfate proteoglycan, glycosaminoglycans, fibronectin, epidermal growth factors or nerve growth factors, or combinations thereof.
Claim 16
Independent Claim
186 words
A method of making a hollow conduit for promoting in vivo regeneration of a severed mammalian nerve so as to bridge a gap between its severed ends comprising the steps of: (a) forming an aqueous dispersion containing Type I collagen; (b) adding a precipitating agent to the dispersion to form a fibrous precipitate; (c) contacting the fibrous precipitate with a spinning manderel so as to form a conduit; (d) compressing the conduit to reduce its overall diameter and remove supernatant liquid; (e) subjecting the conduit to freezing conditions so as to freeze water contained within the conduit; (f) subjecting the conduit to freeze-drying conditions to remove the frozen water; and then (g) cross-linking the collagen within the conduit by treating the conduit with a cross-linking agent, wherein the hollow conduit is formed having walls with at least one layer having a pore size in the range of from about 0.006 μm to about 5.0 μm which layer selectively allows for the diffusion of at least neuronotrophic factors through said layer while substantially preventiong the diffusion of fibrogenic cells, and at least one layer being substantially porous.
Claim 17
Independent Claim
186 words
A method of making a hollow conduit for promoting in vivo regeneration of a severed mammalian nerve so as to bridge a gap between its severed ends comprising the steps of: (a) forming an aqueous dispersion containing Type I collagen; (b) adding a precipitating agent to the dispersion to form a fibrous precipitate; (c) contacting the fibrous precipitate with a spinning manderel so as to form a conduit; (d) compressing the conduit to reduce its overall diameter and remove supernatant liquid; (e) subjecting the conduit to freezing conditions so as to freeze water contained within the conduit; (f) subjecting the conduit to freeze-drying conditions to remove the frozen water; and then (g) cross-linking the collagen within the conduit by treating the conduit with a cross-linking agent, wherein the hollow conduit is formed having walls with at least one layer having a pore size in the range of from about 0.006 μm to about 5.0 μm which layer selectively allows for the diffusion of at least neuronotrophic factors through said layer while substantially preventiong the diffusion of fibrogenic cells, and at least one layer being substantially porous.
Claim 18
Dependent Claim
15 words
The method of claim 15, wherein the Type I collagen is obtained from bovine tendons.
Claim 19
Dependent Claim
13 words
The method of claim 15, wherein the dispersion additionally contains a laminin-containing material.
Claim 20
Dependent Claim
14 words
The method of claim 17, wherein the laminin-containing material is purified human placenta laminin.
Claim 21
Dependent Claim
14 words
The method of claim 17, wherein the laminin-containing material is derived from basement membrane.
Claim 22
Dependent Claim
12 words
The method of claim 15, wherein the precipitating agent is a base.
Claim 23
Dependent Claim
12 words
The method of claim 20, wherein the precipitating agent is ammonium hydroxide.
Claim 24
Dependent Claim
16 words
The method of claim 15, wherein the dispersion is deaired after the precipitating agent is added.
Claim 25
Dependent Claim
21 words
The method of claim 15, wherein the mandrel is spun at a rate of from about 60 to about 700 RPM.
Claim 26
Dependent Claim
21 words
The method of claim 23, wherein the mandrel is spun at a rate of from about 200 to about 650 RPM.
Claim 27
Dependent Claim
21 words
The method of claim 23, wherein the mandrel is spun at a rate of from about 300 to about 600 RPM.
Claim 28
Dependent Claim
26 words
The method of claim 15, wherein the conduit is compressed to the extent that its overall outer diameter is reduced by about 25% to about 60%.
Claim 29
Dependent Claim
26 words
The method of claim 26, wherein the conduit is compressed to the extent that its overall outer diameter is reduced by about 35% to about 50%.
Claim 30
Dependent Claim
35 words
The method of claim 15, wherein the freezing conditions comprise a temperature in the range of from about -10° C. to about -30° C. for a period of from about 2 to about 24 hours.
Claim 31
Dependent Claim
46 words
The method of claim 15, wherein the freeze-drying conditions comprise a vacuum of from about 100 microns to about 200 microns of Hg at a temperature of from about -10° C. to about -40° C. for a period of from about 15 to about 24 hours.
Claim 32
Dependent Claim
12 words
The method of claim 15, wherein the collagen is crosslinked by formaldehyde.
Claim 33
Dependent Claim
10 words
The nerve conduit produced by the process of claim 15.
Claim 34
Independent Claim
187 words
A method of making a hollow conduit for promoting the in vivo regeneration of a severed mammalian nerve so as to bridge a gap between its severed ends comprising the steps of: (a) forming an aqueous dispersion containing Type I collagen; (b) adding a precipitating agent to the dispersion to form a fibrous precipitate; (c) contacting the fibrous precipitate with a spinning manderel so as to from a conduit; (d) compressing the conduit to reduce its overall diameter and remove supernatant liquid; (e) contacting the conduit with a water miscible organic solvent capable of replacing residual water contained within the conduit; (f) evacuating the solven-laden conduit to remove residual solvent; and then (g) cross-linking the collagen within the conduit by treating the conduit with a cross-linking agent, wherein the hollow conduit is formed having walls with at least one layer having a pore size in the range of from about 0.006 μm to about 5.0 μm which layer selectively allows for the diffusion of at least neuronotrophic factors through said layer while substantially preventing the diffusion of fibrogenic cells, and at least one layer being substantially porous.
Claim 35
Independent Claim
187 words
A method of making a hollow conduit for promoting the in vivo regeneration of a severed mammalian nerve so as to bridge a gap between its severed ends comprising the steps of: (a) forming an aqueous dispersion containing Type I collagen; (b) adding a precipitating agent to the dispersion to form a fibrous precipitate; (c) contacting the fibrous precipitate with a spinning manderel so as to from a conduit; (d) compressing the conduit to reduce its overall diameter and remove supernatant liquid; (e) contacting the conduit with a water miscible organic solvent capable of replacing residual water contained within the conduit; (f) evacuating the solven-laden conduit to remove residual solvent; and then (g) cross-linking the collagen within the conduit by treating the conduit with a cross-linking agent, wherein the hollow conduit is formed having walls with at least one layer having a pore size in the range of from about 0.006 μm to about 5.0 μm which layer selectively allows for the diffusion of at least neuronotrophic factors through said layer while substantially preventing the diffusion of fibrogenic cells, and at least one layer being substantially porous.
Claim 36
Dependent Claim
15 words
The method of claim 32, wherein the Type I collagen is obtained from bovine tendons.
Claim 37
Dependent Claim
13 words
The method of claim 32, wherein the dispersion additionally contains a laminin-containing material.
Claim 38
Dependent Claim
14 words
The method of claim 34, wherein the laminin-containing material is purified human placenta laminin.
Claim 39
Dependent Claim
14 words
The method of claim 34, wherein the laminin-containing material is derived from basement membrane.
Claim 40
Dependent Claim
12 words
The method of claim 32, wherein the precipitating agent is a base.
Claim 41
Dependent Claim
12 words
The method of claim 37, wherein the precipitating agent is ammonium hydroxide.
Claim 42
Dependent Claim
16 words
The method of claim 32, wherein the dispersion is deaired after the precipitating agent is added.
Claim 43
Dependent Claim
21 words
The method of claim 32, wherein the mandrel is spun at a rate of from about 60 to about 700 RPM.
Claim 44
Dependent Claim
21 words
The method of claim 40, wherein the mandrel is spun at a rate of from about 200 to about 650 RPM.
Claim 45
Dependent Claim
21 words
The method of claim 40, wherein the mandrel is spun at a rate of from about 300 to about 600 RPM.
Claim 46
Dependent Claim
26 words
The method of claim 32, wherein the conduit is compressed to the extent that its overall outer diameter is reduced by about 25% to about 60%.
Claim 47
Dependent Claim
26 words
The method of claim 43, wherein the conduit is compressed to the extent that its overall outer diameter is reduced by about 35% to about 50%.
Claim 48
Dependent Claim
45 words
The method of claim 32, wherein the organic solvent is selected from the group consisting of lower alkyl alcohols having from 1 to 3 carbon atoms, ketones having from 1 to 5 carbon atoms, ethers having from 1 to 5 carbon atoms and combinations thereof.
Claim 49
Dependent Claim
31 words
The method of claim 45, wherein the organic solvent is selected from the group consisting of methanol, ethanol, isopropanol, acetone, methyl ethyl ketone, methyl ethyl ether, diethyl ether, and combinations thereof.
Claim 50
Dependent Claim
12 words
The method of claim 32, wherein the collagen is crosslinked by formaldehyde.
Claim 51
Dependent Claim
10 words
The nerve conduit produced by the process of claim 32.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-10-15 | 1994-04-16 | 1994-10-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-10-15 | 1998-04-16 | 1998-10-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-10-15 | 2002-04-16 | 2002-10-16 | $7700.00 | Window Closed / Lapsed |