Method for making a porous polymeric material

a technology of porous polymer and polymer, which is applied in the field of improving porous polymer, can solve the problems of high failure rate increased failure rate with decreasing caliber of blood vessel substitute, and formation of aneurysms

Inactive Publication Date: 2014-08-14
KENSEY NASH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The technique produces a vascular graft with improved biocompatibility, reduced thrombosis risk, enhanced tissue integration, and compliance matching with the host vessel, allowing for stable cellular ingrowth and reduced blood leakage, thereby increasing the longevity and effectiveness of the graft.

Problems solved by technology

Despite intensive efforts td improve the nature of blood vessel substitutes many problems remain, such as increasing failure rate with decreasing caliber of the blood vessel substitute, a high failure rate when infection occurs, and aneurysm formation.
This results in supply problems being some intermediate and most small diameter arteries are replaced or bypassed using an autologous saphenous vein, the long vein extending down the inside of the leg, with a secondary source being the radial veins of the arms.
In a given patient, suitable veins may be absent, diseased or too small to be used, and removal of the vein is an additional surgical procedure that carries attendant risk.
Due to the constant punishment these grafts undergo, there is a high occurrence of thrombosis, bleeding, infections, and pseudoaneurysm.
Problems associated with this type of implantation include thrombosis, infection and new aneurysm formation at the location of the stent.
Initially, autografts were used to restore continuity; however, limited supply and inadequate sizes forced the use of allografts from both donor and umbilical cord harvest such as that described in U.S. Pat. No. 3,974,526.
Even though these products were widely used they did have many drawbacks including infection, clot formation, occlusions and the inability to be used in grafts smaller than 6 mm inside diameter due to clotting.
Unfortunately, despite these positive qualities, it became clear in the early 1980s that conventional ether-based polyurethane elastomers presented long-term biostabilty issues as well as some concern over potential carcinogenic degradation products.
Further, in contrast to excellent performance in animal trials, clinically disappointing results with PU-based grafts diminished the attractiveness of the material for this application.
Specifically, the new generation of polyurethanes solved the biostability problems but still provide clinically disappointing results.
Poor performance is largely due to limitations of current manufacturing techniques that create a random or non-optimal fibrous structure for cell attachment using crude precipitation and / or filament manufacturing techniques.
However, there is no disclosure in Dunn of mixing or combining solvents, let alone a disclosure or suggestion of applying liquids in sequential fashion to gel a polymer solution.
In each instance, there are severe shape-making limitations, e.g., the known non-fibrous methods appear to be limited to working with a relatively low viscosity liquid that can be coated onto a surface, or into which a shape-forming mandrel can be dipped.
Thus, the prior at does not seem to appreciate the desirability of a prosthesis such as a vascular graft containing channels or porosity extending continuously from the exterior surface to the luminal surface of the graft.
This plug continues to grow, resulting in occlusion of the graft.
If the graft is not immediately occluded the plug functions as a cell matrix increasing the potential for rapid smooth muscle cell hyperplasia.
Other reasons for artificial graft failure are neointima sloughing due to poor attachment and aneurysm formation resulting from compliance mismatch of the new graft material to the existing vascular system.
This mismatch may increase stress at the anastomotic site, as well as create flow disturbances and turbulence.
Additionally, poor attachment geometry can lead to the problematic results above, due to flow disturbances and turbulence.
For example, the harvesting of autograft veins typically causes a surgeon to use a graft of non-optimal diameter or length.
Such flow disturbances may lead to para-anastomotic intimal hyperplasia, anastomotic aneurysms, and the acceleration of downstream atherosclerotic change.
Finally, artificial graft failures have been linked to leaking of blood through the device.
One problem with this approach is that the same open fibrous weave that permits blood leaking also allows the viscous bioabsorbable substances and clotted blood to accumulate on the luminal surface and easily detach resulting in complications (e.g., emboli) downstream from the device.

Method used

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  • Method for making a porous polymeric material
  • Method for making a porous polymeric material
  • Method for making a porous polymeric material

Examples

Experimental program
Comparison scheme
Effect test

example i

[0114]This Example demonstrates the production of a porous polymeric material using the gel enhanced phase separation technique of the instant invention.

[0115]A siloxane-based macrodiol, aromatic polyurethane, supplied by Aortech Biomaterials, was selected for this example.

[0116]The manufacturer identified dimethyl acetimide, n-methyl pyrrolidinone, and tetrahydrofuran as (dissolving) solvents for the polymer.

[0117]A 0.25-gram sample of polymer was placed into the bottom of 20 small bottles. Five milliliters of 20 common laboratory solvents, including the three listed by the manufacturer, was added to the bottles, one solvent to each bottle. The bottles were left for 48 hours at room temperature, after which they were observed visually to identify those solvents that dissolved or resulted in swelling of the polymer. Twelve polymers were identified and are listed below in Table II along with freezing point (“F.P.”, also known as melt point), boiling point (“B.P.”), vapor pressure (“V...

example ii

[0127]This Example demonstrates that the role of a particular liquid, e.g., dissolving agent (“solvent”) or gelling agent, depends to some degree on the nature of the polymer being acted upon.

[0128]Table III below show the results of screening tests of various liquids on two candidate polymers. Again, in these screening tests, individual liquids were contacted with solid polymer and observed for effects.

TABLE IIISilioxaneCarbonateLiquidPolyurethanePolyurethane1Acetic acidNon-solventNon-Solvent2AcetoneSwelling solventSwelling solvent3AcetonitrileNon-solventNon-solvent4Tert-butyl alcoholNon-solventNon-solvent5ChloroformSwelling solventSwelling solvent6CyclohexaneNon-solventNon-solvent7p-dioxaneSwelling solventSwelling solvent8EthanolNon-solventNon-solvent9IsopropanolNon-solventNon-solvent10MethanolNon-solventNon-solvent11Methylene chlorideSwelling solventSwelling solvent12N,n-dimethyl acetimideSolventSolvent13Dimethyl sulfoxideSwelling solventSwelling solvent141-methyl-2 pyrrolidoneSo...

example iii

[0132]This Example demonstrates the dual-tiered drug delivery technique of the instant invention.

[0133]A polycarbonate-siloxane macrostructure may be prepared in accordance with the macrostructure process described above, where the polymer may be solvated in a suitable first solvent (i.e., one that dissolves the polymer fully), and a suitable gelling solvent may be added to cause the gelation of the polymer solution. The gel is then shaped and the solvents removed as described above, resulting in a porous polymer material, e.g., a macrostructure. A microstructure is created within the chambers of the macrostructure, through the incorporation of a soluble collagen and hyaluronan, which is preferably lyophilized within the macrostructure. In order to create a dual-tiered drug delivery device, an amount of heparin is embedded in the microstructure for early elution, preferably by being added to the polymer of the microstructure before incorporation into the macrostructure. A second bio...

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Abstract

Porous polymers having a plurality of openings or chambers that are highly convoluted, with each chamber being defined by multiple, thin, flat partitions are produced by a new gel enhanced phase separation technique. In a preferred embodiment, a second liquid is added to a polymer solution, the second liquid causing the solution to increase in viscosity. With sufficient polymer and second liquid present, the increase in viscosity can be up to that of a gel. The gel can then be shaped as needed. Subsequent solvent extraction leaves the porous polymeric body of defined shape. The porous polymers have utility as medical prostheses, the porosity permitting ingrowth of neighboring tissue. A second material may be incorporated into the chambers, thereby creating a microstructure filling the voids of the macrostructure. A porous polymeric body manufactured by this process may incorporate biologically active agents, and which agents may be delivered in a time-staged delivery manner, where differing drugs may be delivered over differing periods.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation in Part of U.S. patent application Ser. No. 10 / 864,143, filed on Jun. 9, 2004, entitled “Method for Making a Porous Polymeric Material”, which was a Continuation in Part of U.S. patent application Ser. No. 10 / 856,329, filed on May 28, 2004 entitled Method For Making A Porous Polymeric Material, which is a continuation of U.S. patent application Ser. No. 10 / 010,304 filed on Nov. 8, 2001 entitled Method For Making A Porous Polymeric Material. This application is also a Continuation in Part of U.S. patent application Ser. No. 10 / 830,267 filed on Apr. 21, 2004 entitled Device For Regeneration Of Articular Cartilage And Other Tissue, itself a continuation of U.S. patent application Ser. No. 10 / 199,961, filed Jul. 19, 2002, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 909,027, filed Jul. 19, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 206,604, filed Dec. ...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): C08J9/00B29C41/12B29C45/00B29C41/14A61L27/34A61L27/54C08J9/28
CPCC08J9/0033C08J9/0028C08J9/0023C08J9/0014B29C41/12A61L27/54B29C45/0001B29C41/14A61L27/34C08J9/28C08J2201/054
InventorRINGEISEN, TIMOTHY A.
OwnerKENSEY NASH CORP