(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2004/0033364 A1
`(43) Pub. Date:
`Feb. 19, 2004
`Spiridigliozzi et al.
`
`US 20040033364A1
`
`(54) PLEATED COMPOSITE EPTFE/TEXTILE
`HYBRID COVERING
`
`(60) Provisional application No. 60/297,401, ?led on Jun.
`11, 2001.
`
`(75) Inventors: John Spiridigliozzi, Sharon, MA (US);
`William R. Quinn, SWampseott, MA
`(US); Ryan Cahill, Holmdel, NJ (US)
`
`Correspondence Address:
`HOFFMANN & BARON, LLP
`6900 J ERICHO TURNPIKE
`SYOSSET, NY 11791 (US)
`
`(73) Assignee: SCIMED Life Systems, Inc.
`
`(21) Appl. No.:
`
`10/643,315
`
`(22) Filed:
`
`Aug. 19, 2003
`
`Related US. Application Data
`
`(63) Continuation-in-part of application No. 10/166,842,
`?led on Jun. 11, 2002.
`
`Publication Classi?cation
`
`(51) Int. Cl? ...................................................... ..A61F 2/06
`(52) US. Cl. .
`..... ..428/411.1;623/1.49
`
`(57)
`
`ABSTRACT
`
`A composite multilayer implantable material having a ?rst
`inner tubular layer formed of expanded polytetra?uoroethy
`ene having a porous microstructure de?ned by nodes inter
`connected by ?brils, Wherein said ?rst layer has a plurality
`of pleated folds, a second tubular layer formed of textile
`material circumferentially disposed eXteriorly to said ?rst
`layer; and having an elastomeric bonding agent applied to
`one of said ?rst layer or second layer and disposed Within the
`pores of said microstructure for securing said ?rst layer to
`said second layer.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 1 of 20
`
`

`

`Patent Application Publication Feb. 19, 2004 Sheet 1 0f 8
`
`US 2004/0033364 A1
`
`FIG. 1
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 2 of 20
`
`

`

`Patent Application Publication
`
`Feb. 19, 2004 Sheet 2 of 8
`
`US 2004/0033364 A1
`
`
`
`FIG. 2
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 3 of 20
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 3 of 20
`
`

`

`Patent Application Publication Feb. 19, 2004 Sheet 3 0f 8
`
`US 2004/0033364 A1
`
`FIG. 3
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 4 of 20
`
`

`

`Patent Application Publication Feb. 19, 2004 Sheet 4 0f 8
`
`US 2004/0033364 A1
`
`‘401
`./
`./
`.
`
`‘IN
`
`A -.-*-j ‘
`
`A FIG. 4
`
`‘Section A-/\'
`
`FIG. 5
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 5 of 20
`
`

`

`Patent Application Publication Feb. 19, 2004 Sheet 5 0f 8
`
`US 2004/0033364 A1
`
`FIG. 6
`
`‘Section 3-13
`
`FIG. 7
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 6 of 20
`
`

`

`Patent Application Publication Feb. 19, 2004 Sheet 6 0f 8
`
`US 2004/0033364 A1
`
`—
`
`d
`
`A,
`
`\ La?ers
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`'- lJi‘en-eo > béswwn Fug’: a: ‘- QSPTFE ‘SEN? erS ~ ‘
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`jro saqopé eQTFE _
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`FIG. 8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 7 of 20
`
`

`

`Patent Application Publication Feb. 19, 2004 Sheet 7 0f 8
`
`US 2004/0033364 A1
`
`09 @ob
`
`
`
`4 .. 61“, i
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`on, M /q
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`FIG. 9
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 8 of 20
`
`

`

`Patent Application Publication Feb. 19, 2004 Sheet 8 0f 8
`
`US 2004/0033364 A1
`
`FIG. 10
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 9 of 20
`
`

`

`US 2004/0033364 A1
`
`Feb. 19, 2004
`
`PLEATED COMPOSITE EPTFE/TEXTILE HYBRID
`COVERING
`
`CROSS-REFERENCE TO RELATED
`APPLICATIONS
`
`[0001] This application is a continuation in part of appli
`cation Ser. No. 10/166,842, ?led Jun. 11, 2002, Which claims
`priority to US. Provisional Application No. 60/297,401,
`both of Which are incorporated by reference herein.
`
`FIELD OF THE INVENTION
`
`[0002] The present invention relates generally to a
`implantable prosthesis material and structure. More particu
`larly, the present invention relates to a composite multilayer
`implantable material and structure having a textile layer, an
`expanded polytetra?uoroethylene layer (ePTFE) formed in a
`pleated con?guration and an elastomeric bonding agent
`layer, Which joins the textile and ePTFE layer to form an
`integral structure.
`
`BACKGROUND OF THE INVENTION
`
`[0003] Implantable prostheses are commonly used in
`medical applications. One of the more common prosthetic
`structures is a tubular prosthesis Which may be used as a
`vascular graft to replace or repair damaged or diseased blood
`vessel. To maximiZe the effectiveness of such a prosthesis,
`it should be designed With characteristics Which closely
`resemble that of the natural body lumen Which it is repairing
`or replacing.
`
`[0004] One form of a conventional tubular prosthesis
`speci?cally used for vascular grafts includes a textile tubular
`structure formed by Weaving, knitting, braiding or any
`non-Woven textile technique processing synthetic ?bers into
`a tubular con?guration. Tubular textile structures have the
`advantage of being naturally porous, Which alloWs desired
`tissue ingroWth and assimilation into the body. This porosity,
`Which alloWs for ingroWth of surrounding tissue, must be
`balanced With ?uid tightness to minimiZe leakage during the
`initial implantation stage.
`[0005] Attempts to control the porosity of the graft While
`providing a suf?cient ?uid barrier have focused on increas
`ing the thickness of the textile structure, providing a tighter
`stitch construction and incorporating features such as
`velours to the graft structure. Further, most textile grafts
`require the application of a biodegradable natural coating,
`such as collagen or gelatin in order to render the graft blood
`tight. While grafts formed in this manner overcome certain
`disadvantages inherent in attempts to balance porosity and
`?uid tightness, these textile prostheses may exhibit certain
`undesirable characteristics. These characteristics may
`include an undesirable increase in the thickness of the
`tubular structure, Which makes implantation more dif?cult.
`These textile tubes may also be subject to kinking, bending,
`tWisting or collapsing during handling. Moreover, applica
`tion of a coating may render the grafts less desirable to
`handle from a tactility point of vieW.
`
`ePTFE exhibit certain bene?cial properties as compared
`With textile prostheses. The expanded PTFE tube has a
`unique structure de?ned by nodes interconnected by ?brils.
`The node and ?bril structure de?nes micropores, Which
`facilitate a desired degree of tissue ingroWth While remain
`ing substantially ?uid-tight. Tubes of ePTFE may be formed
`to be exceptionally thin and yet exhibit the requisite strength
`necessary to serve in the repair or replacement of a body
`lumen. The thinness of the ePTFE tube facilitates ease of
`implantation and deployment With minimal adverse impact
`on the body.
`
`[0007] While exhibiting certain superior attributes, ePTFE
`tubes are not Without certain disadvantages. Grafts formed
`of ePTFE tend to be relatively non-compliant as compared
`With textile grafts and natural vessels. Further, While exhib
`iting a high degree of tensile strength, ePTFE grafts are
`susceptible to tearing. Additionally, ePTFE grafts lack the
`suture compliance of coated textile grafts. This may cause
`undesirable bleeding at the suture hole. Thus, the ePTFE
`grafts lack many of the advantageous properties of certain
`textile grafts.
`
`[0008] It is also knoWn that it is extremely dif?cult to join
`PTFE and ePTFE to other materials via adhesives or bond
`ing agents due to its chemically inert and non-Wetting
`character. Wetting of the surface by the adhesive is necessary
`to achieve adhesive bonding, and PTFE and ePTFE are
`extremely dif?cult to Wet Without destroying the chemical
`properties of the polymer. Thus, heretofore, attempts to bond
`ePTFE to other dissimilar materials such as textiles have
`been dif?cult.
`
`[0009] It is also knoWn to use vascular grafts in conjunc
`tion With support structures. Such support structures typi
`cally come in the form of stents, Which are formed of metal
`or polymeric materials generally formed in a tubular struc
`ture and are used to hold a vein or artery open. Stents are
`Well knoWn in the art and may be self-expanding or radially
`expandable by balloon expansion. Examples of stent/graft
`con?gurations knoWn in the art can be seen in US. Pat. Nos.
`5,700,285; 5,749,880; and 5,123,917, each of Which are
`herein incorporated by reference. It is advantageous to use
`stent/graft con?gurations because the stent provides and
`ensures the patency of the prosthesis, While the vascular
`graft provides biocompatible properties in a vessel more
`suitable for blood to ?oW.
`
`[0010] While using a vascular graft in conjunction With
`support structures offers certain bene?ts, it is also knoWn
`that support structures such as a stent can result in axial
`elongation and radial shrinkage of the graft material due to
`the stresses applied to the graft material by the support
`structure during the contraction and expansion of the support
`structure.
`
`[0011] It is apparent that conventional textile prostheses as
`Well as ePTFE prostheses have acknoWledged advantages
`and disadvantages. Neither of the conventional prosthetic
`materials exhibits fully all of the bene?ts desirable for use as
`a vascular prosthesis.
`
`[0006] It is also Well knoWn to form a prosthesis, espe
`cially a tubular graft, from polymers such as polytetra?uo
`roethylene (PTFE). A tubular graft may be formed by
`stretching and expanding PTFE into a structure referred to as
`expanded polytetra?uoroethylene (ePTFE). Tubes formed of
`
`[0012] It is therefore desirable to provide an implantable
`material and structure, preferably in the form of a tubular
`vascular prosthesis, Which achieves many of the above
`stated bene?ts Without the resultant disadvantages associ
`ated thereWith.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 10 of 20
`
`

`

`US 2004/0033364 A1
`
`Feb. 19, 2004
`
`SUMMARY OF THE INVENTION
`
`[0013] The present invention provides a composite multi
`layered implantable prosthetic material and structure, Which
`may be used in various applications, especially vascular
`applications. The implantable structure of the present inven
`tion may include a pleated ePTFE-lined textile graft, a
`pleated ePTFE graft, covered With a textile covering. More
`over, additional ePTFE layers may be combined With any of
`these embodiments.
`
`[0014] In accordance With the present invention, pleats are
`provided along the length of the implantable material and
`structure. The number and length of the pleated sections can
`vary to control the resultant axial elongation, plastic defor
`mation, longitudinal foreshortening and radial shrinkage of
`the graft material due to the stresses applied to the graft
`material by the support structure during the contraction and
`expansion of the support structure.
`
`[0015] The composite multi-layered implantable structure
`of the present invention includes a ?rst layer formed of a
`textile material and a second layer formed of expanded
`polytetra?uoroethylene (ePTFE) being layered in a pleated
`pattern having a porous microstructure de?ned by nodes
`interconnected by ?brils. An elastomeric bonding agent may
`be applied to the second layer and disposed Within the pores
`of the microstructure for securing the ?rst layer to the second
`layer.
`[0016] In another embodiment, the composite multi-lay
`ered implantable structure of the present invention may have
`a ?rst inner tubular layer and a second outer tubular layer,
`both formed of ePTFE having a porous microstructure
`de?ned by nodes interconnected by ?brils. The ?rst and
`second layers of ePTFE also may have a support structure
`positioned therebetWeen. Typically, this support structure
`takes the form of a radially expandable member, preferably
`a stent. A third tubular layer formed of textile material may
`be circumferentially disposed exteriorly to the ?rst and
`second layers, and an elastomeric bonding agent may be
`applied to the second layer of ePTFE or the textile layer, and
`disposed Within the pores of the ePTFE microstructure When
`the layers are bonded together. The bonding agent helps
`secure the second outer layer of ePTFE to the third textile
`layer.
`[0017] In another embodiment, the multi-layered implant
`able structure further comprises a fourth layer of textile
`material circumferentially disposed interior to said ?rst and
`second ePTFE layer and bonded to the ?rst ePTFE layer
`With the elastomeric bonding agent. It is contemplated to
`further secure additional layers either interior or exterior
`said composite structure. The ?rst and second ePTFE layers
`are preferably pleated in the axial direction prior to the
`bonding step.
`
`[0018] The bonding agent may be selected from a group of
`materials including biocompatible elastomeric materials
`such as urethanes, silicones, isobutylene/styrene copoly
`mers, block polymers, and combinations thereof.
`
`[0019] The tubular composite material and structure of the
`present invention may also be formed from appropriately
`layered sheets Which can then be overlapped to form tubular
`structures. Bifurcated, tapered, conical, and stepped-diam
`eter tubular structures may also be formed from the present
`
`invention. The layered sheets may be pleated after being
`formed into a tubular structure.
`
`[0020] The textile layer may be formed of various textiles
`including knits, Weaves, stretch knits, braids, any non
`Woven processing techniques, and combinations thereof.
`Various biocompatible polymeric materials may be used to
`form the textile structures, including polyethylene tereph
`thalate (PET), naphthalene dicarboxylate derivatives such as
`polyethylene naphthalate, polybutylene naphthalate, polyt
`rimethylene naphthalate, trimethylenediol naphthalate,
`ePTFE, natural silk, polyethylene and polypropylene,
`among others. PET is a particularly desirable material for
`forming the textile layer.
`
`[0021] The bonding agent is applied in solution to one
`surface of the ePTFE layer, preferably by spray coating. The
`textile layer is then placed in contact With the coated surface
`of the ePTFE layer. The bonding agent may also be applied
`in poWder form by any knoWn techniques; eg electrostatic
`spray. The bonding agent may also be applied and activated
`by thermal and/or chemical processes Well knoWn in the art
`and may be disposed Within the pores of the coated surface.
`
`[0022] The present invention also provides an ePTFE
`lined textile graft. The lined textile graft includes a tubular
`textile substrate bonded using a biocompatible elastomeric
`material to a tubular liner of ePTFE. A coating of an
`elastomeric bonding agent may be applied to the surface of
`the ePTFE liner so that the bonding agent is present in the
`micropores thereof. The coated liner is then secured to the
`tubular textile structure via the elastomeric bonding agent.
`The liner and textile graft can each be made very thin and
`still maintain the advantages of both types of materials.
`
`[0023] The present invention further provides a textile
`covered ePTFE graft. The tubular ePTFE graft structure
`includes micropores de?ned by nodes interconnected by
`?brils. A coating of an elastomeric bonding agent is applied
`to the surface of the ePTFE tubular structure With the
`bonding agent being resident Within the microporous struc
`ture thereof. A tubular textile structure is applied to the
`coated surface of the ePTFE tubular structure and secured
`thereto by the elastomeric bonding agent.
`[0024] The composite multi-layered implantable struc
`tures of the present invention are designed to take advantage
`of the inherent bene?cial properties of the materials forming
`each of the layers. The textile layer provides for enhanced
`tissue ingroWth, high suture retention strength and longitu
`dinal compliance for ease of implantation. The ePTFE layer
`provides the bene?cial properties of sealing the textile layer
`Without need for coating the textile layer With a sealant such
`as collagen. The sealing properties of the ePTFE layer alloW
`the Wall thickness of the textile layer to be minimiZed.
`Further, the ePTFE layer exhibits enhanced thrombo-resis
`tance upon implantation. Moreover, the elastomeric bonding
`agent not only provides for an integral composite structure,
`but adds further puncture-sealing characteristics to the ?nal
`prosthesis. Additionally, plastic deformation of the ePTFE
`layer is controlled by the pleated structure, therefore detri
`mental effects on the bene?cial properties of the ePTFE are
`minimiZed.
`
`[0025] In further aspects of the invention, the implantable
`structure may be used in conjunction With radially-expand
`able members such as stents and other structures Which are
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 11 of 20
`
`

`

`US 2004/0033364 A1
`
`Feb. 19, 2004
`
`capable of maintaining patency of the implantable structure
`in a bodily vessel. For example, a stent may be disposed
`betWeen tWo ePTFE layers With the outer ePTFE layer being
`joined to a tubular textile structure via the elastomeric
`bonding agent. Optionally, a textile reinforcement may be
`secured to the inner ePTFE layer via the elastomeric bond
`ing agent, in addition to or in the alternative the outer tubular
`textile structure. Any stent construction knoWn to those
`skilled in the art may be used, including self-expanding
`stents, as Well as, balloon-expandable stents.
`[0026] Therefore, in accordance With the present inven
`tion, there is provided a composite multilayer implantable
`material having a ?rst inner tubular layer formed of
`expanded polytetra?uoroethyene having a porous micro
`structure de?ned by nodes interconnected by ?brils, Wherein
`said ?rst layer has a plurality of pleated folds, a second
`tubular layer formed of textile material circumferentially
`disposed exteriorly to said ?rst layer; and having an elasto
`meric bonding agent applied to one of said ?rst layer or
`second layer and disposed Within the pores of said micro
`structure for securing said ?rst layer to said second layer.
`
`[0027] In accordance With even further embodiment of the
`present invention, a method for producing a graft having
`pleated regions along it length is provided. The method
`includes forming a textile ePTFE composite graft material
`by providing a ?rst tubular ePTFE structure having a
`microporous structure of nodes interconnected by ?brils,
`providing a second tubular ePTFE structure having a
`microporous structure of nodes interconnected by ?brils,
`folding a plurality of pleats into said ?rst tubular ePTFE
`structure and said second tubular ePTFE structure, providing
`a tubular textile structure, placing a tubular support structure
`circumferentially around said ?rst ePTFE tubular structure,
`placing said second tubular ePTFE structure circumferen
`tially around said tubular support structure, applying a
`coating of an elastomeric bonding graft to a surface of said
`second ePTFE structure or said textile structure; and secur
`ing said coated liner surface to said textile structure.
`
`[0028] Various additives such as drugs, groWth-factors,
`anti-thrombogenic agents and the like may also be
`employed.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`[0029] FIG. 1 shoWs a schematic cross-section, a portion
`of a composite multi-layered implantable structure of the
`present invention.
`
`[0030] FIG. 2 shoWs a schematic cross-section of an
`embodiment of the present invention.
`
`[0031] FIG. 3 shoWs a schematic cross-section of an
`embodiment of the present invention.
`
`[0032] FIG. 4 shoWs a portion of a pleated composite
`multi-layered implantable structure of the present invention
`prior to stretching.
`
`[0033] FIG. 5 shoWs a schematic cross-section of the
`preferred embodiment of the present invention.
`
`[0034] FIG. 6 shoWs a portion of a pleated composite
`multi-layered implantable structure of the present invention
`after stretching.
`[0035] FIG. 7 shoWs a schematic cross-section of the
`preferred embodiment of the present invention.
`
`[0036] FIG. 8 is a How chart exemplifying a process for
`preparing one of the structures of the present invention.
`
`[0037] FIG. 9 is an illustration of a graft according to the
`present invention With varying pleat amplitude and fre
`quency.
`
`[0038] FIG. 10 is an illustration of a stent-graft assembly
`according to the present invention for implantation Within a
`body lumen.
`
`DETAILED DESCRIPTION OF THE
`PREFERRED EMBODIMENT:
`
`[0039] The present invention provides a composite
`implantable prosthesis material and structure, desirably a
`vascular prosthesis material includes tWo layers of ePTFE,
`typically surrounding a stent, and a layer of a textile mate
`rial. The ePTFE stent/graft layers are secured together, With
`the textile layer, by an elastomeric bonding agent. The
`vascular prosthesis material and vascular prosthesis of the
`present invention may include an ePTFE-lined textile vas
`cular graft, and a ePTFE vascular graft including a textile
`covering. While this invention is satis?ed by embodiments
`in many different forms, there are shoWn in the draWings and
`herein described in detail, embodiments of the invention
`With the understanding that the present disclosure is to be
`considered as exemplary of the principles of the present
`invention and is not intended to limit the scope of the
`invention to the embodiments illustrated. In this disclosure,
`the material and structure of the present invention may be
`described With respect to its application in the structure of a
`graft or stent-graft prosthesis device.
`
`[0040] Referring to FIG. 1, a schematic cross-section of a
`portion of an embodiment of the vascular prosthesis material
`10 is shoWn. As noted above, the material 10 may be a
`portion of a graft, or any other implantable structure.
`
`[0041] The material 10 includes a ?rst layer 12, Which is
`formed of a textile material. The textile material 12 of the
`present invention may be formed from synthetic yarns that
`may be ?at, shaped, tWisted, textured, pre-shrunk or un
`shrunk. Preferably, the yarns are made from thermoplastic
`materials including, but not limited to, polyesters, polypro
`pylenes, polyethylenes, polyurethanes, polynaphthalenes,
`polytetra?uoroethylenes and the like. The yarns may be of
`the multi?lament, mono?lament or spun types. In most
`vascular applications, multi?laments are preferred due to the
`increase in ?exibility. Where enhanced crush resistance is
`desired, the use of mono?laments have been found to be
`effective. As is Well knoWn, the type and denier of the yarn
`chosen are selected in a manner Which forms a pliable soft
`tissue prosthesis and, more particularly, a vascular structure
`have desirable properties.
`
`[0042] The material 10 further includes a second layer 14
`formed of expanded polytetra?uoroethylene (ePTFE). The
`ePTFE layer 14 may be produced from the expansion of
`PTFE formed in a paste extrusion process. The PTFE
`extrusion may be expanded and sintered in a manner Well
`knoWn in the art to form ePTFE having a microporous
`structure de?ned by nodes interconnected by elongate
`?brils. The distance betWeen the nodes, referred to as the
`intemodal distance (IND), may be varied by the parameters
`employed during the expansion and sintering process. The
`resulting process of expansion and sintering yields pores 18
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 12 of 20
`
`

`

`US 2004/0033364 A1
`
`Feb. 19, 2004
`
`Within the structure of the ePTFE layer. The siZe of the pores
`are de?ned by the IND of the ePTFE layer.
`
`[0050] A polycarbonate component is characteriZed by
`repeating
`
`[0043] The ePTFE of the present invention may also be
`“ultrathin” ePTFE as described in cornrnonly-oWned appli
`cations, U.S. Ser. Nos. 10/012,825 and 10/012,919, the
`disclosures of Which are herein incorporated by reference.
`
`[0044] The composite material 10 of the present invention
`may further include a bonding agent 20 applied to one
`surface 19 of ePTFE layer 18. The bonding agent 20 is
`preferably applied in solution by a spray coating process.
`HoWever, other processes may be employed to apply the
`bonding agent.
`
`[0045] In the present invention, the bonding agent may
`include various biocornpatible, elastorneric bonding agents
`such as urethanes, styrene/isobutylene/styrene block copoly
`rners (SIBS), silicones, and combinations thereof. Other
`similar materials are conternplated. Most desirably, the
`bonding agent may include polycarbonate urethanes identi
`?ed by the trade name CORETHANE®. This urethane is
`provided as an adhesive solution With preferably 7.5%
`Corethane, 2.5, in dirnethylacetarnide (DMAc) solvent.
`
`[0046] The term “elastorneric” as used herein refers to a
`substance having the characteristic that it tends to resume an
`original shape after any deforrnation thereto, such as stretch
`ing, expanding, or compression. It also refers to a substance
`Which has a non-rigid structure, or ?exible characteristics in
`
`O
`H
`
`[0051] units, and a general formula for a polycarbonate
`rnacroglycol is as folloWs:
`
`O
`
`O
`
`[0052] Wherein x is from 2 to 35, y is 0, 1 or 2, R either
`is cycloaliphatic, arornatic or aliphatic having from about 4
`to about 40 carbon atoms or is alkoxy having from about 2
`to about 20 carbon atoms, and Wherein R‘ has from about 2
`to about 4 linear carbon atoms With or Without additional
`pendant carbon groups.
`[0053] Examples of typical arornatic polycarbonate rnac
`roglycols include those derived from phosgene and bisphe
`nol A or by ester exchange betWeen bisphenol A and
`diphenyl carbonate such as (4,4‘-dihydroxy-diphenyl-2,2‘
`propane) shoWn beloW, Wherein n is betWeen about 1 and
`about 12.
`
`CH3
`
`C
`
`CH3 0%
`
`that it is not brittle, but rather has cornpliant characteristics
`contributing to its non-rigid nature.
`
`[0047] The polycarbonate urethane polyrners particularly
`useful in the present invention are more fully described in
`US. Pat. Nos. 5,133,742 and 5,229,431, Which are incor
`porated in their entirety herein by reference. These polymers
`are particularly resistant to degradation in the body over
`time and exhibit exceptional resistance to cracking in vivo.
`These polymers are segrnented polyurethanes which employ
`a combination of hard and soft segments to achieve their
`durability, biostability, ?exibility and elastorneric properties.
`
`[0048] The polycarbonate urethanes useful in the present
`invention are prepared from the reaction of an aliphatic or
`arornatic polycarbonate rnacroglycol and a diisocyanate in
`the presence of a chain extender. Aliphatic polycarbonate
`rnacroglycols such as polyhexane carbonate rnacroglycols
`and aromatic diisocyanates such as rnethylene diisocyanate
`are most desired due to the increased biostability, higher
`intrarnolecular bond strength, enhanced heat stability and
`?ex fatigue life, as compared to other materials.
`
`[0054] Typical aliphatic polycarbonates are formed by
`reacting cycloaliphatic or aliphatic diols With alkylene car
`bonates as shoWn by the general reaction beloW:
`
`O
`
`1
`
`[0055] Wherein R is cyclic or linear and has betWeen about
`1 and about 40 carbon atoms and Wherein R1 is linear and
`has betWeen about 1 and about 4 carbon atoms.
`
`[0056] Typical examples of aliphatic polycarbonate diols
`include the reaction products of 1,6-hexanediol With ethyl
`ene carbonate, 1,4-butanediol With propylene carbonate,
`1,5-pentanediol With ethylene carbonate, cyclohex
`anedirnethanol With ethylene carbonate and the like and
`mixtures of above such as diethyleneglycol and cyclohex
`anedirnethanol With ethylene carbonate.
`
`[0049] The polycarbonate urethanes particularly useful in
`the present invention are the reaction products of a macro
`glycol, a diisocyanate and a chain extender.
`
`[0057] When desired, polycarbonates such as these can be
`copolyrneriZed with components such as hindered polyes
`ters, for example phthalic acid, in order to form carbonate/
`
`Edwards Lifesciences Corporation, et al. Exhibit 1110, Page 13 of 20
`
`

`

`US 2004/0033364 A1
`
`Feb. 19, 2004
`
`ester copolymer macroglycols. Copolymers formed in this
`manner can be entirely aliphatic, entirely aromatic, or mixed
`aliphatic and aromatic. The polycarbonate macroglycols
`typically have a molecular Weight of betWeen about 200 and
`about 4000 Daltons.
`
`[0058] Diisocyanate reactants according to this invention
`have the general structure OCN—R‘—NCO, Wherein R‘ is a
`hydrocarbon that may include aromatic or nonaromatic
`structures, including aliphatic and cycloaliphatic structures.
`Exemplary isocyanates include the preferred methylene
`diisocyanate (MDI), or 4,4-methylene bisphenyl isocyanate,
`or 4,4‘-diphenylmethane diisocyanate and hydrogenated
`methylene diisocyanate (HMDI). Other exemplary isocyan
`ates include hexamethylene diisocyanate and other toluene
`diisocyanates such as 2,4-toluene diisocyanate and 2,6
`toluene diisocyanate, 4,4‘ tolidine diisocyanate, m-phe
`nylene diisocyanate, 4-chloro-1,3-phenylene diisocyanate,
`4,4-tetramethylene diisocyanate, 1,6-hexamethylene diiso
`cyanate, 1,10-decamethylene diisocyanate, 1,4-cyclohexy
`lene diisocyanate, 4,4‘-methylene bis (cyclohexylisocyan
`ate),
`1,4-isophorone diisocyanate,
`3,3‘-dimethyl-4,4‘
`diphenylmethane diisocyanate, 1,S-tetrahydronaphthalene
`diisocyanate, and mixtures of such diisocyanates. Also
`included among the isocyanates applicable to this invention
`are specialty isocyanates containing sulfonated groups for
`improved hemocompatibility and the like.
`
`[0059] Suitable chain extenders included in this polymer
`iZation of the polycarbonate urethanes should have a func
`tionality that is equal to or greater than tWo. Apreferred and
`Well-recognized chain extender is 1,4-butanediol. Generally
`speaking, most diols or diamines are suitable, including the
`ethylenediols, the propylenediols, ethylenediamine, 1,4-bu
`tanediamine methylene dianiline heteromolecules such as
`ethanolamine, reaction products of said diisocyanates With
`Water and combinations of the above.
`
`[0060] The polycarbonate urethane polymers according to
`the present invention should be substantially devoid of any
`signi?cant ether linkages (i.e., When y is 0, 1 or 2 as
`represented in the general formula hereinabove for a poly
`carbonate macroglycol), and it is believed that ether linkages
`should not be present at levels in excess of impurity or side
`reaction concentrations. While not Wishing to be bound by
`any speci?c theory, it is presently believed that ether link
`ages account for much of the degradation that is experienced
`by polymers not in accordance With the present invention
`due to enZymes that are typically encountered in vivo, or
`otherWise, attack the ether linkage via oxidation. Live cells
`probably catalyZe degradation of polymers containing link
`ages. The polycarbonate urethanes useful in the present
`invention avoid this problem.
`
`[0061] Because minimal quantities of ether linkages are
`unavoidable in the polycarbonate producing reaction, and
`because these ether linkages are suspect in the biodegrada
`tion of polyurethanes, the quantity of macroglycol should be
`minimiZed to thereby reduce the number of ether linkages in
`the polycarbonate urethane. In order to maintain the total
`number of equivalents of hydroxyl terminal groups approxi
`mately equal to the total number of equivalents of isocyanate
`terminal groups, minimiZing the polycarbonate soft segment
`necessitates proportionally increasing the chain extender
`hard segment in the three component polyurethane system.
`Therefore, the ratio of equivalents of chain extender to
`
`macroglycol should be as high as possible. Aconsequence of
`increasing this ratio (i.e., increasing the amount of chain
`extender With respect to macroglycol) is an increase in
`hardness of the polyurethane. Typically, polycarbonate ure
`thanes of hardnesses, measured on the Shore scale, less than
`70A shoW small amounts of biodegradation. Polycarbonate
`urethanes of Shore 75A and greater shoW virtually no
`biodegradation.
`
`[0062] The ratio of equivalents of chain extender to poly
`carbonate and the resultant hardness is a complex function
`that includes the chemical nature of the components of the
`urethane system and their relative proportions. HoWever, in
`general, the hardness is a function of the molecular Weight
`of both chain extender segment and polycarbonate segment
`and the ratio of equivalents thereof. Typically, the 4,4‘
`methylene bisphenyl diisocyanate (MDI) based systems, a
`1,4-butanediol chain extender of molecular Weight 90 and a
`polycarbonat