DE9117117U1 - Break-resistant polyurethane carbonate polymer prostheses - Google Patents

Description

Fracture-resistant polyurethane carbonate polymer prostheses

Background and description of the invention 5

The present invention relates generally to implantable prostheses and the like, and to methods of making or treating the same to substantially prevent cracking or crazing thereof when implanted or otherwise subjected to degradation conditions. A medical prosthesis or the like according to this invention comprises a polymeric polycarbonate urethane surface which will not crack or degrade when subjected to implantation for substantial periods of time during which other types of polyurethane surfaces would crack or degrade.

Several biocompatible materials which are highly suitable for use in making implantable medical devices, which can be broadly characterized as implantable prostheses, exhibit properties sought after in such devices, including one or more of exceptional biocompatibility, extrudability, moldability, good fiber-forming properties, tensile strength, elasticity, durability, and the like. However, some of these otherwise highly desirable materials exhibit serious weakness when implanted in the human body or otherwise subjected to harsh environments, such weakness typically manifesting itself by the development of strength-reducing and invisible cracks. After considerable exposure, which depends on the materials and the implantation conditions and exposure to body fluids and cells, such as those encountered during in vivo implantation and use,

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[File:ANM\CO0399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

For example, surface cracking or rupture occurs over a period of time that may be on the order of a month or more or shorter periods of time. Many implantable prostheses are intended to be permanent in nature and should not develop significant degradation or cracking during the years of implantation.

Various theories have been advanced in an attempt to define the cause of this cracking phenomenon. Proposed mechanisms include oxidative degradation, hydrolytic instability, enzymatic destruction, thermal and mechanical failure, immunochemical mechanisms, lipid uptake, and combinations of the above. Previous attempts to control surface cracking or tearing at implantation or the like have included incorporating antioxidants into a biocompatible polymer and subjecting the biocompatible polymer to various different annealing conditions, which typically involved attempts to remove stresses within the polymer by applying various heating and cooling conditions. Attempts such as these have largely been unsuccessful.

Other treatment approaches have been used or attempted to increase the structural stability of particularly desirable materials. Included among the biocompatible materials which are desirable from many points of view but which exhibit a noticeable tendency to crack or degrade over time are the polyurethane materials and other biocompatible polymers which are elastomeric in nature. It is particularly advantageous to use these types of materials to manufacture products in which compliance and/or flexibility, high tensile strength and excellent fatigue life may be desirable characteristics. A basic approach previously taken to achieve these

[File:ANM\C00399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

One way to make materials more suitable for implantation and other applications where degradation of the material may develop has been to treat the material with so-called crack inhibitors. Exemplary approaches in this regard can be found in U.S. Patents No. 4,769,030, No. 4,851,009, and No. 4,882,148, the subject matter of which is incorporated herein by reference. The treatments, of course, require additional processes and components, thereby somewhat complicating the manufacturing processes, and it would be advantageous if the material from which the product is made itself had the desired properties. It is also advantageous for the material to be compatible with other materials commonly used in the medical field, such as adhesives, surface coatings, and the like.

A particularly difficult problem in this regard is encountered when attempting to form prostheses by processes involving the extrusion or spinning of polymeric fibers, such as those involved in winding fiber-forming polymers into porous vascular grafts or similar products, such as those described in U.S. Patent No. 4,475,972, the subject matter of which is incorporated herein by reference. Such vascular grafts or the like comprise a plurality of strands which are sized to have a fairly fine diameter, so that when cracks develop after implantation, these cracks often manifest themselves in the form of complete disintegration of various strands of the device. Such rod dissolution cannot be tolerated to any great extent and there is still hope that a device can be provided which can be successfully implanted or installed on a generally permanent basis, thereby keeping the device useful for a number of years.

[File:ANM\C00399B1.docJ Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

Many polymeric structures, such as vascular grafts, made from spun fibers appear to perform very satisfactorily, as far as their viability is concerned, when subjected to physical loading conditions, e.g., conditions similar to those encountered during or after implantation, including loads transmitted through sutures, other fasteners, and the like. For example, certain polyurethane fibers, when subjected to constant loading under in vitro conditions, such as in saline at body temperatures, do not exhibit the tearing that is evident when substantially the same polyurethane spun fibers are subjected to in vivo conditions. Accordingly, while many materials, such as certain various polyurethanes, polypropylenes, polymethylmethacrylates, and the like, may provide seemingly superior medical devices or prostheses when subjected to stresses under in vitro conditions, they are found to be less than satisfactory when subjected to essentially the same types of stresses but under in vivo conditions.
25

Accordingly, there is a need for a material which will not experience surface cracking or tearing under implantation or in vivo conditions, and which is otherwise desirable and advantageous as a material for medical devices or prostheses which must successfully delay, if not eliminate, the tearing phenomenon even after implantation for months and years, in many cases a significant number of years. In addition, other products not necessarily intended for medical use may benefit from being made from such a non-tearing material. Products in this regard may

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[File:ANM\C00399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

include those subjected to harsh environmental conditions such as weathering and the like. Exemplary medical devices or prostheses for which such a non-rupturing material would be particularly advantageous include vascular grafts, compliant sutures, breast implants, heart valve leaflets, pacemaker lead insulators, intraocular lens loops or haptics, diaphragms for artificial hearts, tubing for infusion pumps, artificial ligaments, artificial skin, drug elution matrices, grids for cell seeding and artificial organs, and the like. Examples of non-medical applications of these urethanes include urethane for roof insulators, seals for sewage systems, industrial tubing and the like.
15

In summary, the present invention achieves these types of goals by providing a polycarbonate urethane polymer as the material from which tear-resistant products are made. The polycarbonate urethane polymer is exceptionally tear-resistant, even under in vivo conditions. The polymeric backbone has repeating urethane and/or urea groups, and the polymer is a reaction product of at least one polycarbonate glycol having terminal hydroxyl groups and a diisocyanate having terminal isocyanate groups. A chain extender having terminal hydroxyl or amine groups may or may not be added. It is particularly preferred that the resulting hardness of the polycarbonate urethane be at least as hard as about Shore 7OA, preferably between about Shore 8OA and Shore 75D.

It is accordingly a general object of the present invention to provide improved tear resistant devices and products.
35

It is another object of this invention to provide a polymeric material and products made therefrom

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IFile:ANM\CO0399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

which are particularly resistant to decomposition even under in vivo conditions.

It is another object of the present invention to provide an improved polyurethane type material which can be spun through a spinneret or extruded through and/or in suitable forming equipment into products which exhibit superior tear resistance properties.

It is another object of this invention to provide improved implantable devices and/or prostheses which exhibit an exceptional ability to prevent the formation of cracks and cord dissolution upon implantation for substantial periods of time, such as those required for generally permanent implantation procedures.

It is another object of the present invention to provide an improved vascular graft and the like made from spun fibers of a polycarbonate urethane polymer which exhibits exceptional stability under in vivo conditions with respect to the development of cracking and rod dissolution.

It is another object of the present invention to provide an improved extruded device or product which is unusually tear resistant even when subjected to harsh environmental conditions.

It is another object of the present invention to provide improved molded polymer products incorporating a polycarbonate urethane polymer which exhibits exceptional tear strength.

[Fi!e:ANM\CO0399B1 .doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

These and other objects, features and advantages of the present invention will be clearly understood by a consideration of the following detailed description.

Short description of the drawings

In the course of this description, reference is made to the attached drawings in which:

Figure 1 is a photomicrograph of a section of a vascular graft made by spinning a polyetherurethane polymer not in accordance with this invention, and after subcutaneous implantation, explantation and cleaning;

Fig. 2 is a photomicrograph of a section of a spun graft made from a polycarbonate urethane polymer after subcutaneous implantation, explantation and cleaning; and

Figure 3 is a photomicrograph of a section of a spun graft made from a polycarbonate urethane polymer formulated according to the present invention, also after subcutaneous implantation, explantation and cleaning.

Description of the special embodiments

Commonly known polyurethanes include those listed in U.S. Patent Nos. 4,739,013 and 4,810,749, the subject matter of which is incorporated herein by reference. As discussed in these patents and elsewhere, the term polyurethane encompasses a family of polymers that usually include three major components. These are: a macroglycol, a diisocyanate, and a chain extender. They are generally classified as polyurethanes because their backbone is urethane.

[File:ANM\CO0399B1 .doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Gorvita Corporation

groups and often also urea groups, where the groups are repeating units within the polymer backbone.

The formation of a typical polyurethane involves reacting an -OH or hydroxyl group of the macroglycol component with an -NCO or isocyanate group of the diisocyanate component. At another bonding site, another terminal -NCO or isocyanate group of the diisocyanate reactant reacts with a terminal hydroxyl (or amine) group of the chain extender. It should be understood that a polyurethane can also be synthesized with only a macroglycol and isocyanate; however, typical urethanes that are commercially available include a chain extender.

The polymerization will typically be carried out in the presence of a suitable solvent and under suitable reaction conditions, although reactions could be carried out without solvent, particularly if the polymer is not to be extruded into fibers, but is to be formed into pellets or the like for example for other extrusion and/or molding processes, or it is to be made into foams.

With particular reference to the macroglycol component of polyurethanes, in general there are currently three main families of macroglycols commercially available. These are the polyester glycols, the polyether glycols and the polycarbonate glycols. Also available are a family of macroglycols that are amine terminated and not hydroxyl terminated. Currently the polyester glycols are by far the most widely used macroglycols for polyurethanes. These are generally known to be unsuitable for many applications, such as long-term medical implantation applications, for the main reason that polyurethanes of this type are generally easily

[File:ANM\CO0399B1.docJ Description, 26.10.95 '

Fracture-resistant polyurethane carbonate polymer prostheses ·

Corvita Corporation

hydrolyzed because their ester bonds are easily cleaved by water molecules, which would naturally be present in numerous applications including various medicinal uses.
5

Polyetherurethanes have had some success and are used quite widely in medical applications. Polyetherurethanes are known to be degraded by cellular components and metal ions and will not survive the stresses of a physiological environment, necessitating the application of treatments to them to prevent biological degradation. This is especially true when the polyetherurethane is processed into devices with thin or fine structures or sections. Polycarbonateurethanes are typically more expensive and difficult to process and are not currently widely used. Other classes of polyurethanes could be prepared using other macroglycols such as a polyolefin glycol, a polyesteramide glycol, a polycaprolactone glycol, an amine-terminated macroglycol or a polyacrylate glycol. Similarly, polyols having a functionality greater than 2 can be used.

According to the present invention, the macroglycol is a polycarbonate glycol. A process for preparing polycarbonate glycols, which are linear polycarbonates with terminal hydroxyl groups, is described in U.S. Patent No. 4,131,731, the subject matter of which is incorporated herein by reference.

A polycarbonate component is characterized by

0
It

repeating -0-C-O- units, and a general formula for a polycarbonate macroglycol is as follows

0 0

¹¹ Ii

h R ¹ 'ear- CCO- R-OB

[File:ANM\CO0399B1.doc] Description, 10/26/95 Crush-resistant polyurethane carbonate polymer prostheses Corvita Corporation

where x is from 2 to 35, y is 0, 1 or 2, R is either a cycloaliphatic, aromatic or aliphatic group having from about 4 to about 40 carbon atoms or an alkoxy group having from about 2 to about 20 carbon atoms, and where R' has from about 2 to about 4 linear carbon atoms with or without additional carbon pendant groups.

Examples of typical aromatic polycarbonate macroglycols include those derived from phosgene and bisphenol A or by ester interchange between bisphenol A and diphenyl carbonate, such as (4,4'-dihydroxydiphenyl-2,2'-propane) shown below, where η is between about 1 and about 12.

H-(O

Typical aliphatic polycarbonates are formed by reacting cycloaliphatic or aliphatic diols with alkylene carbonates as shown by the general reaction below:

HO-R-OS

R'

wherein R is cyclic or linear and has between about 1 and about 40 carbon atoms and wherein R' is linear and has between about 1 and about 4 carbon atoms.

Typical examples of aliphatic polycarbonate diols include the reaction products of 1,6-hexanediol with ethylene carbonate, 1,4-butanediol with propylene carbonate, 1,5-pentanediol with ethylene carbonate, cyclohexanedimethanol with ethylene carbonate and the like and mixtures of the above, such as diethylene glycol and cyclohexanedimethanol with ethylene carbonate.

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[File:ANM\CO0399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

If desired, polycarbonates such as these can be copolymerized with components such as hindered polyesters, e.g., phthalic acid, to form carbonate/ester copolymer macroglycols. Copolymers formed in this manner can be fully aliphatic, fully aromatic, or mixed aliphatic and aromatic. The polycarbonate macroglycols typically have a molecular weight of between about 200 and about 4000 daltons.

Diisocyanate reactants according to this invention have the general structure OCN-R'-NCO, where R' is a hydrocarbon which may include aromatic or non-aromatic structures, including aliphatic and cycloaliphatic structures. Exemplary isocyanates include the preferred methylene diisocyanate (MDI), or 4,4-methylenebisphenyl isocyanate, or 4,4'-diphenylmethane diisocyanate and hydrogenated methylene diisocyanate (HMDI). Other exemplary isocyanates include hexamethylene diisocyanate and the toluene diisocyanates such as 2,4-toluene diisocyanate and 2,6-toluene diisocyanate, 4,4'-tolidine diisocyanate, m-phenylene diisocyanate, 4-chloro-1,3-phenylene diisocyanate, 4,4-tetramethylene diisocyanate, 1/6-hexamethylene diisocyanate, 1,10-decamethylene diisocyanate, 1,4-cyclohexylene diisocyanate, 4,4'-methylene bis(cyclohexyl isocyanate), 1,4-isophorone diisocyanate, 3,3'-dimethyl-4,4'-diphenylmethane diisocyanate, 1,5-tetrahydronaphthalene diisocyanate, and mixtures of such isocyanates. Also included among the isocyanates applicable to this invention are special isocyanates containing sulfonated groups for improved hemocompatibility and the like.

Suitable chain extenders which are included in the polymerization of the polycarbonate urethanes should have a functionality equal to or greater than

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[File:ANM\CO0399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

is greater than two. A preferred and well-known chain extender is 1,4-butanediol. Generally speaking, most diols or diamines are suitable, including the ethylenediols, the propylenediols, ethylenediamine, 1,4-butanediamine, methylene-dianiline heteromolecules such as ethanolamine, reaction products of the diisocyanates with water, a combination of the above, other macroglycols, and the like.

The polycarbonate urethane polymers according to the present invention should be substantially free of any substantial ether linkages (i.e., when y is 0, 1, or 2, as indicated in the general formula for a polycarbonate macroglycol above), and it is believed that ether linkages should not be present at levels above impurity or side reaction concentrations. While not wishing to be bound by any particular theory, it is currently believed that ether linkages are responsible for a large portion of the degradation experienced by polymers not according to the present invention because enzymes typically encountered in vivo or elsewhere attack the ether linkage. Oxidation will occur and living cells may catalyze the degradation of these other polymers.

Since minimal amounts of ether bonds are unavoidable in the polycarbonate-forming reaction, and since these ether bonds are suspected of causing biological degradation of polyurethanes, the amount of macroglycol should be minimized to thereby reduce the number of ether bonds in the polycarbonate urethane. To keep the total number of equivalents of terminal hydroxyl groups approximately equal to the total number of equivalents of terminal isocyanate groups, minimizing the soft polycarbonate segment requires a proportional increase in the hard chain extender segment in the

[File:ANM\CO0399B 1,doc] Description, 26.10.95 * *

Fracture-resistant polyurethane carbonate polymer prostheses . *

Corvita Corporation

Three-component polyurethane systems are necessary. Therefore, the ratio of chain extender to macroglycol equivalents should be as high as possible. A consequence of increasing this ratio (i.e. increasing the amount of chain extender relative to macroglycol) is an increase in the hardness of the polyurethane. Typically, polycarbonate urethanes with hardnesses, measured on the Shore scale, of less than 7OA show a small amount of biodegradation. Polycarbonate urethanes with Shore 75A and higher show virtually no biodegradation.

The ratio of equivalents of chain extender to polycarbonate and the resulting hardness is a complex function involving the chemical nature of the components of the urethane system and their relative proportions. However, hardness is generally a function of the molecular weight of both the chain extender segment and the polycarbonate segment and the ratio of their equivalents. For 4,4'-methylenebisphenyl diisocyanate (MDI) based systems, typically a 1,4-butanediol chain extender having a molecular weight of 90 and a polycarbonate urethane having a molecular weight of about 2000 are required in an equivalent ratio of at least about 1.5 to 1 and no greater than about 12 to 1 to provide polymers which do not biodegrade. Preferably, the ratio should be at least about 2 to 1 and less than about 6 to 1. Using a polycarbonate glycol segment with a molecular weight of about 1000, for a similar system the preferred ratio should be at least about 1 to 1 and no greater than about 3 to 1. A polycarbonate glycol with a molecular weight of about 500 would require a ratio in the range of about 1:2 to about 1.5:1.

The lower range of the preferred ratio of chain extender to macroglycol typically yields

[File:ANM\CO0399B1 .doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

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* r

Polyurethanes with a Shore hardness of 8OA. The upper range of ratios typically yields polycarbonate urethanes on the order of Shore 75D. The preferred elastomeric and biostable polycarbonate urethanes for most medical devices would have a Shore hardness of approximately 85A.

Generally speaking, it is desirable to have some control over the cross-linking that occurs during polymerization of the polycarbonate urethane polymer. A polymerized molecular weight of between about 80,000 and about 200,000 daltons, for example on the order of about 120,000 daltons (such molecular weights are determined by measurement according to the polystyrene standard) is desired, so that the resulting polymer at a solids content of 43% will have a viscosity of between about 900,000 and about 1,800,000 centipoise, typically on the order of about 1,000,000 centipoise. Cross-linking can be controlled by avoiding an isocyanate-rich situation. Of course, the general relationship between the isocyanate groups and the total hydroxyl (and/or amine) groups of the reactants should be on the order of approximately 1 to 1. Cross-linking can be controlled by controlling reaction temperatures and shading molar ratios to ensure that the reactant batch is not isocyanate-rich; optionally, a terminating reactant such as ethanol can be included to block excess isocyanate groups which could result in greater than desired cross-linking.

As for the preparation of the polycarbonate urethane polymer, they may be reacted in one step in a reactant batch, or they may be reacted in multiple steps, preferably in two steps, with or without a catalyst and heat. Other ingredients, such as

[File:ANM\C00399B1.doc] Description, 26.10.95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

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Antioxidants, extrusion agents and the like may be included, although typically there would be a tendency and preference to exclude such additional ingredients when preparing a medical grade polymer.

Additionally, the polycarbonate urethane polymers can be polymerized in suitable solvents, typically polar organic solvents, to ensure complete and homogeneous reaction. The solvents include dimethylacetamide, dimethylformamide, dimethyl sulfoxide, toluene, xylene, m-pyrrole, tetrahydrofuran, cyclohexanone, 2-pyrrolidone, and the like, or combinations thereof.
15

While no treatment of the polycarbonate urethane polymer product according to this invention is necessary, if desired, suitable treatments can be performed. For example, they can be subjected to treatment with a crack-inhibiting composition comprising an elastomeric silicone such as poly(dimethylsiloxane) as described in detail in U.S. Patent No. 4,851,009. Through this treatment, there is a bond between the product substrate and the silicone polymer. Preferably, steps are taken to help place the crack-inhibiting agent into interstices or corrugations of the device or product, and excess should be removed by suitable means to avoid reduction in porosity or other undesirable results due to residue or excess treatment material. Similarly, they can be grafted or coupled to the surface with drugs such as heparin, steroids, antibiotics, and the like. The surface can be made more hemocompatible by sulfonation and the like.

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[Fiie:ANM\C0039981.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

example 1

A spinnable or castable polycarbonate urethane polymer was prepared in the following manner. The following reactants were charged to a vessel at ⁸⁰ °C with constant mixing and dimethylacetamide to produce 1 kg of a reaction product containing 42.5% solids: 83.5 grams of methylene diisocyanate, 332.4 grams of polycarbonate diol (having a molecular weight of 1989), 7.5 grams of 1,4-butanediol chain extender, 1.5 grams of water, and 575 grams of dimethylacetamide. The reaction was continued for four hours and the polycarbonate urethane polymer formed had a Shore hardness of 60A. The ratio of chain extender to soft polycarbonate segment was 1:1.

The resulting thick solution was spun through a spinneret into a filamentous vascular graft, generally in accordance with the teachings of U.S. Patent No. 4,475,972, the subject matter of which is incorporated herein by reference. A more dilute solution can be used as a solvent casting system, where the polymer solution is poured over a suitable mold to form products such as breast implants and heart valve leaflets.

Example 2

A spinnable or castable polycarbonate urethane was prepared similarly to that in Example 1, except that the ratio of chain extender to soft polycarbonate segment was increased from 1:1 to 2.5:1. The polymer was prepared at 42.5% solids with 122.5 grams of MDI, 278.5 grams of 1989 molecular weight polycarbonate diol, 22.06 grams of 1,4-butanediol, and 1.89 grams of water. The solvent was dimethylacetamide (575 grams). Castable films prepared from this formulation had a Shore hardness of 8OA.

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[File:ANM\C00399B1.doc] Description, 26.10.95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

Example 3

A spinnable or castable polycarbonate urethane was prepared similarly to that in Examples 1 and 2; however, the ratio of chain extender to soft polycarbonate segment was increased to 4:1. The polymer was prepared at a solids content of 42.5% with 156 grams of MDI, 248 grams of 1989 molecular weight polycarbonate diol, 45 grams of 1,4-butanediol, and no water. The solvent was dimethylacetamide (550 grams). Castable films prepared from this formulation had a Shore hardness of 55D.

' Example 4

An extrudable polycarbonate polyurethane was prepared by charging a reaction vessel at 6O ⁰ C with 283 grams of MDI and 644 grams of 1989 molecular weight polycarbonate. After approximately one hour, 73 grams of 1,4-butanediol were introduced into the reaction chamber and thoroughly mixed and subjected to a vacuum to remove any bubbles that formed. The reaction was continued until solidification occurred. The solid sheet was annealed at HO ⁰ C for 24 hours and then pelletized. Pellets formed in this manner are thermoplastic, have a Shore 8OA hardness, and can be extruded at 18O ⁰ C to 22O ⁰ C into a product such as an insulating sheath for a pacemaker lead or fibers for textile applications.

Example 5

A spinnable or castable polycarbonate urethane was prepared similar to that in Example 1 with a ratio of chain extender to soft polycarbonate segment of 1:1, with a polycarbonate diol having a molecular weight

B IHI

[File:ANM\C00399B1,doc] Description, 26.10.95 * J

Fracture-resistant polyurethane carbonate polymer prostheses

Corvita Corporation

of 940. The polycarbonatediol (276.5 grams) was reacted with 147 grams of MDI in 550 grams of DMA for one hour, then the chain was extended with 26.5 grams of 1,4-butanediol. Castable films prepared in the above manner had a Shore hardness of 80A.

Example 6

Filamentous-type vascular grafts were formed by spinning on a rotating spindle in a manner generally described in U.S. Patent No. 4,474,972 to form a plurality of filamentous vascular grafts. The grafts were implanted subcutaneously into an animal. After a period of implantation, the grafts were explanted, cleaned in a solution of 10% sodium hydroxide and 4% sodium hypochlorate for one hour, and then examined under a scanning electron microscope for evidence of fiber breakage or tearing.

Fig. 1 is a photomicrograph of a scanning electron microscope reproduction of a typical untreated filamentous vascular graft made of a Shore 80A polyetherurethane polymer, implanted for only four weeks. Significant tearing and strand breaks are visible, even though the grafts were subjected to annealing conditions in an effort to reduce tearing and breakage.

Polycarbonate urethane polymer filamentous vascular grafts were subjected to tensile stress prior to implantation by the following procedure. A one-inch long Delrin mandrel or rod was placed into a vascular graft and opposite ends of the graft were stretched by an Instron machine to 70% of the ultimate tensile strength or elongation of the polycarbonate urethane polymer.

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[File:ANM\C00399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

mers. The opposite ends were held in place with constricting sutures around the mandrel to maintain the degree of stretch. The graft was removed from the Instron machine and implantation was performed under this stretched condition. Fig. 2 is a photomicrograph of the scanning electron microscope reproduction of a typical polycarbonate urethane polymer filamentous vascular graft explanted after 4 weeks. The particular polycarbonate urethane polymer was prepared from a reaction batch in which the ratio of soft segment polycarbonate diol equivalents to chain extender equivalents (hydroxyl groups) was 1 to 1 as in Example 1 to produce a Shore 60A polymeric graft. Some tearing is visible.

Figure 3 is a photomicrograph of the scanning electron microscope image typical of an explanted Shore 8OA polycarbonate urethane polymer filamentous graft (as in Example 2) implanted for six months. Fiber breakage is essentially absent and no surface cracking can be observed. Here, the ratio of chain extender equivalents to polycarbonate equivalents was 2.5 to 1. Findings similar to this Example 2 result were also obtained for devices fabricated with the polymers of Example 3, Example 4 and Example 5.

Example 7

A soft polycarbonate foam was prepared by reacting 192 grams of polycarbonatediol with a molecular weight of 1818 with 119 grams of MDI. The reaction was continued for one hour at 60 ⁰ C, after which 14 grams of 1,4-butanediol and 1.17 grams of water were added. The reaction

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[File.ANM\CO0399B1.doc] Description, 10/26/95 Fracture-resistant polyurethane carbonate polymer prostheses Corvita Corporation

continued until a soft, stable foam was produced.

Example 8
5

A rigid polycarbonate foam was prepared by reacting 151 grams of polycarbonatediol having a molecular weight of 1818 with 119 grams of MDI. The reaction was continued for one hour at 60 ⁰ C, after which 21 grams of 1,4-butanediol and 2.52 grams of water were added. The reaction proceeded until a rigid and durable foam was produced, which foam is suitable for use as a non-oxidizing roof insulator.

It will be understood that the embodiments of the present invention which have been described are illustrative of some of the applications of the principles of the present invention. Numerous modifications may be made by those skilled in the art without departing from the true spirit and scope of the invention.

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Claims (1)

[File:ANM\C00399A2.docj Claims, 21. i 2.95
G9117117.2 - ^: - - ■ ■" - Corvita Corporation Protection claims 1. A non-biodegradable polycarbonate urethane polymer for forming tear-resistant products, the polymer comprising: a polymeric backbone having repeating groups selected from the group consisting of urethane groups, urea groups, carbonate groups, and combinations of these; wherein the polymer is a reaction product of a reactant charge including: a polycarbonate glycol reactant having terminal hydroxyl groups, a diisocyanate reactant having terminal isocyanate groups, and a chain extender reactant having terminal hydroxyl or amine groups, the polymer reaction product having a hardness in the range of about Shore 7 0A to about Shore 75D; and wherein the polymeric backbone comprises: a bonding site at which at least one of the terminal isocyanate groups of a diisocyanate reactant moiety has reacted with at least one of the terminal hydroxyl groups of a polycarbonate glycol reactant moiety; and a bonding site at which another terminal isocyanate group of the diisocyanate reactant moiety has reacted with one of the terminal hydroxyl or amine groups of a polycarbonate glycol reactant moiety or a chain extender reactant moiety. The polymer of claim 1, wherein the ratio of equivalents of chain extender to polycarbonate glycol is at least about 1.5 to 1. [Fiie:ANM\C00399A2.doc] Claims, 21.12.95 Corvita Corporation 3. The polymer of claim 2, wherein the ratio of equivalents is between about 2 to 1 and about 4 to 1. 4. The polymer of claim 2, wherein the polycarbonate glycol has a molecular weight on the order of about 2000 daltons and the ratio of equivalents is at least about 2 to 1. 5. The polymer of claim 4, wherein the reactant charge further comprises water. 6. The polymer of claim 2, wherein the polycarbonate urethane polymer is substantially free of ether linkages above impurity or side reaction concentrations. 7. The polymer of claim 1, wherein the polycarbonate urethane polymer has a molecular weight between about 80,000 and about 200,000 Daltons. 8. The polymer of claim 1, wherein the reactant charge further comprises a polar organic solvent. 9. The polymer of claim 1, wherein the polycarbonate urethane polymer has a crack inhibitor composition bonded thereto. 10. The polymer of claim 9, wherein the crack inhibitor composition is an elastomeric silicone material. 11. A polycarbonate urethane polymer for forming tear-resistant products, the polymer comprising: [Fi!e:ANM\CO0399A2.doc] Claims, 2 ¹ .12.95 Corvita Corporation a polymeric backbone having repeating groups selected from the group consisting of urethane groups, urea groups, carbonate groups, and combinations thereof;
5 wherein the polymer is a reaction product of reactants including: a polycarbonate diol reactant having terminal hydroxyl groups, a diisocyanate reactant having terminal isocyanate groups, and a chain extender reactant having terminal hydroxyl or amine groups, wherein the polymer reaction product has a hardness of at least about 7OA or harder and the ratio of end group equivalents of the chain extender reactant to end group equivalents of the polycarbonate diol reactant is at least about 0.75 to 1 and no greater than about 12 to 1; and wherein the polymeric backbone comprises: a bonding site at which at least one of the terminal isocyanate groups of a diisocyanate reactant moiety has reacted with at least one of the terminal hydroxyl groups of a polycarbonate diol reactant moiety; and a bonding site at which another terminal isocyanate group of the diisocyanate reactant moiety has reacted with one of the terminal hydroxyl or amine groups of a polycarbonate diol reactant moiety or a chain extender reactant moiety has. 12. The polycarbonate urethane polymer of claim 11, wherein the polymer is substantially completely free of ether linkages above impurity or side reaction concentrations. 13. The polycarbonate urethane polymer according to claim 11, wherein the polycarbonate diol has a molecular weight in the [File:ANM\CO0399A2.doc] Claims, 2M2 95 Corvita Corporation fill order of magnitude of approximately 1000 Daltons and the ratio of equivalents is between approximately 1 to 1 and approximately 3 to 1.' 14. The polycarbonate urethane polymer of claim 11, wherein the polycarbonate diol has a molecular weight on the order of about 2000 daltons and the ratio of equivalents is between about 2 to 1 and about 6 to 1.
10 15. An article of manufacture including a segmented polycarbonate urethane polymer fiber, comprising: an extrusion formed in air from a polycarbonate urethane solution including a polar organic solvent and a polycarbonate urethane polymer, the polycarbonate urethane polymer comprising: a polymeric backbone having repeating groups selected from the group consisting of urethane groups, urea groups, carbonate groups, and combinations thereof; and wherein the polycarbonate urethane polymer is a reaction product of a polycarbonate glycol reactant having terminal hydroxyl groups, a diisocyanate reactant having terminal isocyanate groups, and a chain extender reactant having terminal hydroxyl or amine groups, wherein the polymer reaction product has a hardness in the range of about Shore 7OA to about Shore 75D. 16. The article of claim 15, wherein the hardness is between about Shore 8OA and about Shore 75D. [File:ANM\CO0399A2.doc] Claim 2 < 12.95 Corvita Corporation 17. The article of claim 15, wherein the polycarbonate urethane polymer is substantially free of ether groups and wherein the ratio of end group equivalents of the chain extender to end group equivalents of the polycarbonate glycol is at least about 1.5 to 1. 18. The article of claim 15, wherein the polymer fiber has a tear inhibitor composition bonded thereto. 19. The article of claim 15, wherein the polymer fiber has an elastomeric silicone material bonded thereto. 20. The article of claim 15, wherein the article comprises winding the polycarbonate urethane polymer fiber into an implant. 21. An article of manufacture having a surface which is a tear-resistant polycarbonate urethane polymer, the polycarbonate urethane polymer comprising: a polymeric backbone having repeating groups selected from the group consisting of urethane groups, urea groups, carbonate groups, and combinations of these; and wherein the polycarbonate urethane polymer is a reaction product of a polycarbonate glycol reactant having terminal hydroxyl groups, a diisocyanate reactant having terminal isocyanate groups, and a chain extender reactant having terminal hydroxyl or amine groups, wherein the polycarbonate urethane polymer has a hardness between about Shore 85A and about Shore 55D. [File:ANM\CO0399A2.doc] claims, 2>.*2<&THgr;5 · .·*·**·; Corvita Corporation 22. The article of claim 21, wherein the polycarbonate urethane polymer is substantially free of ether groups, and wherein the ratio of equivalents of chain extender to equivalents of polycarbonate glycol is between about 2 to 1 and about 4 to 1. 23. The article of claim 21, wherein the polymer surface has a crack inhibitor composition bonded thereto. '24. The article of claim 21, 'wherein the polymeric surface has an elastomeric silicone material bonded thereto. 25. The article of claim 21, wherein the article comprises a tubular member of the tear-resistant polycarbonate urethane polymer for a pacemaker lead. 26. The article of claim 21, wherein the article is a molding of the tear-resistant polycarbonate urethane polymer into a component of a breast implant. 27. The article of claim 21, wherein the polycarbonate urethane polymer is a rigid durable foam produced by a reaction between the reactants and water. 28. The article of claim 21, wherein the article comprises a filamentous element of the tear-resistant polycarbonate urethane polymer for a suture or textile fiber. 29. Biocompatible prosthesis, implant and the like, characterized in that it is obtainable by a process which comprises the following steps: .:. .:. :Seiie.-Qr : [FilEANM\CO0399A2.doc] Claim!, 2t.l2£5 · ,·***··· Corvita Corporation 10 polymerizing a reactant charge comprising a polycarbonate glycol reactant having terminal hydroxyl groups, a diisocyanate reactant having terminal isocyanate groups, and a chain extender reactant having terminal hydroxyl or amine groups, the reactant charge having a ratio of chain extender equivalent groups to polycarbonate equivalent groups of at least about 0.75 to 1 to provide a polycarbonate urethane polymer; and" 15 20 25 Extruding or molding the polycarbonate urethane polymer to form a prosthesis, implant, and the like'. 30. A biocompatible prosthesis, implant and the like according to claim 29, wherein the polymerization step includes incorporating a polar organic solvent into the reactant charge. 31. A biocompatible prosthesis, implant and the like according to claim 29 or 30, wherein the polymerization step includes adding water to the reactant charge. 32. Biocompatible prosthesis, implant and the like according to claim 29, comprising bonding an elastomeric silicone material to the prosthesis, implant and the like.