Patent Grant
11174336
The claimed invention was made subject to a joint research agreement between Boston Scientific Corporation and the University of Massachusetts Lowell. Cardiac Pacemakers, Inc. is a wholly-owned subsidiary of Boston Scientific Corporation.
Thermoplastic polyurethanes, polyureas and polyurethaneureas represent an important family of segmented block copolymer thermoplastic elastomers. They can be extruded, injection or compression molded or solution spun. They offer a broad range of physical properties and characteristics, including high tensile and tear strength, chemical and abrasion resistance, good processibility, and protective barrier properties. Depending on composition, i.e. on the volume fraction of the soft, elastomeric segments, these polymers can be soft, rubbery or hard and rigid materials. The hard segments of polyurethanes are composed of diisocyanate and a small molecule diol chain extender, while the soft segments are mostly low molecular weight polymeric diols. Similarly, polyureas or polyurethaneureas comprise diamines and a combination of diols and diamines, respectively, in addition to diisocyanate. Polymeric diols include polyester diols, polyether diols, and polydiene diols. The polyester component is prone to hydrolytic degradation, the polyether component does not have sufficient resistance to oxidative degradation, especially in vivo, and polydienes suffer from inadequate thermal and oxidative stability.
Polyurethanes are the most commonly used materials in the production of biomedical devices that come in contact with blood such as pacemakers, defibrillators, angioplasty balloons, surgical drains, dialysis devices, etc. However, polyurethanes generally exhibit insufficient long-term in vivo biostability due to oxidation of the polyether soft segment, especially when in contact with metals, which catalyze oxidative degradation. This deficiency, limits the use of polyurethanes for long-term applications.
(PIB)-based thermoplastic polyurethanes (TPUs) offer high thermal, oxidative, and hydrolytic stability, however, polyisobutylene polyurethanes exhibit insufficient mechanical properties.
Example 1 is a polyurethane or polyurea polymer including a hard segment and a soft segment. The hard segment is in an amount of 10% to 60% by weight of the polymer. The hard segment includes at least one of a urethane, a urea, or a urethane urea. The soft segment is in an amount of 40% to 90% by weight of the polymer. The soft segment includes at least one polycarbonate macrodiol and at least one of a polyisobutylene macrodiol and a polyisobutylene diamine. The at least one polycarbonate macrodiol is in the amount of 10% to 90% by weight of the soft segment. The at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is in amount of 10% to 90% by weight of the soft segment. The number average molecular weight of the polymer is greater than or equal to 40 kilodaltons.
Example 2 is the polymer of Example 1, wherein the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is of a formula:
Each X is independently —OH, —NH2 or —NHR4. R1 is an initiator residue. R2 and R3 and R4 is each independently a C1-C16 alkyl, a C3-C16 cycloalkyl, a C2-C16 alkenyl, a C3-C16 cycloalkenyl, or a C6-C18 aryl. For each occurrence, R2 or R3 is, independently, optionally substituted with one or more groups selected from halo, cyano, nitro, dialkylamino, trialkylamino, C1-C16 alkoxy and C1-C16 haloalkyl. n and m are each, independently, integers from 1 to 500.
Example 3 is the polymer of Example 1, wherein the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is hydroxyallyl telechelic polyisobutylene.
Example 4 is the polymer of Example 1, wherein the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is hydroxyalkyl telechelic polyisobutylene.
Example 5 is the polymer of Example 4, wherein the hydroxyalkyl telechelic polyisobutylene is hydroxypropyl telechelic polyisobutylene.
Example 6 is the polymer of Example 1, wherein the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is a polyisobutylene macrodiol and the number average molecular weight of the polyisobutylene macrodiol is about 400 Da to about 6000 Da.
Example 7 is the polymer of Example 1, wherein the at least one polycarbonate macrodiol includes at least one poly(alkylene carbonate).
Example 8 is the polymer of Example 1, wherein the hard segment further includes a diisocyanate residue and a chain extender.
Example 9 is the polymer of Example 8, wherein the diisocyanate is 4,4′-methylenephenyl diisocyanate and wherein the chain extender is 1,4-butanediol.
Example 10 is the polymer of Example 1, wherein the polyisobutylene macrodiol of the soft segment comprises a hydroxylalkyl telechelic polyisobutylene residue, and the hard segment comprises a 4,4′-methylenediphenyl diisocyanate and 1,4-butanediol chain extender.
Example 11 is the polymer of Example 1, wherein the at least one polycarbonate macrodiol is in an amount of 10% to 30% by weight of the soft segment, and the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is in an amount of 70% to 90% by weight of the soft segment.
Example 12 is a medical device including a polyurethane or polyurea polymer. The polymer includes a hard segment and a soft segment. The hard segment is in an amount of 10% to 60% by weight of the polymer. The hard segment includes at least one of a urethane, a urea, or a urethane urea. The soft segment is in an amount of 40% to 90% by weight of the polymer. The soft segment includes at least one polycarbonate macrodiol and at least one of a polyisobutylene macrodiol and a polyisobutylene diamine. The at least one polycarbonate macrodiol is in the amount of 10% to 90% by weight of the soft segment. The at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is in amount of 10% to 90% by weight of the soft segment. The number average molecular weight of the polymer is greater than or equal to 40 kilodaltons.
Example 13 is the medical device of Example 12, wherein the medical device is selected from the group consisting of a cardiac pacemaker, a defibrillator, a catheter, an implantable prosthesis, a cardiac assist device, an artificial organ, a pacemaker lead, a defibrillator lead, a blood pump, a balloon pump, an AV shunt, a biosensor, a membrane for cell encapsulation, a drug delivery device, a wound dressing, an artificial joint, an orthopedic implant or a soft tissue replacement.
Example 14 is a method for preparing a polyurethane or polyurea polymer. The method includes reacting a diisocyanate with a mixture that includes at least one polyisobutylene macrodiol and/or diamine, and at least one polycarbonate macrodiol, to form a prepolymer having terminally reactive diisocyanate groups; and reacting the prepolymer with a chain extender to yield the polymer, wherein the polymer includes a hard segment and a soft segment. The hard segment is in an amount of 10% to 60% by weight of the polymer. The hard segment includes at least one of a urethane, a urea, or a urethane urea. The soft segment is in an amount of 40% to 90% by weight of the polymer. The soft segment includes at least one polycarbonate macrodiol and at least one of a polyisobutylene macrodiol and a polyisobutylene diamine. The at least one polycarbonate macrodiol is in the amount of 10% to 90% by weight of the soft segment. The at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is in amount of 10% to 90% by weight of the soft segment. The number average molecular weight of the polymer is greater than or equal to 40 kilodaltons.
Example 15 is the method of Example 14, wherein the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is of formula:
Each X is independently —OH, —NH2 or —NHR4. R1 is an initiator residue. R2 and R3 and R4 is each independently a C1-C16 alkyl, a C3-C16 cycloalkyl, a C2-C16 alkenyl, a C3-C16 cycloalkenyl, or a C6-C18 aryl. For each occurrence, R2 or R3 is, independently, optionally substituted with one or more groups selected from halo, cyano, nitro, dialkylamino, trialkylamino, C1-C16 alkoxy and C1-C16 haloalkyl. n and m are each, independently, integers from 1 to 500.
Example 16 is the method of Example 14, wherein the at least one polycarbonate macrodiol includes at least one poly(alkylene carbonate).
Example 17 is the method of Example 14, wherein the chain extender includes at least one member of the group consisting of 1,4-butanediol; 1,5-pentanediol; 1,6-hexanediol; 1,8-octanediol; 1,9-nonanediol; 1,10-decanediol, 1,12-dodecanediol; 1,4-cyclohexane dimethanol; p-xyleneglycol and 1,4-bis(2-hydroxyethoxy) benzene.
Example 18 is the method of Example 14, wherein the chain extender includes at least one member of the group consisting of 1,4-diaminobutane; 1,5-diaminopentane; 1,6-diaminohexane; 1,8-diaminooctane; 1,9-diaminononane; 1,10-diamonodecane, 1,12-diaminododacane; 1,4-diaminocyclohexane; 2,5-diaminoxylene and isophoronediamine and water.
Example 19 is the method of Example 14, wherein the at least one polycarbonate macrodiol is in an amount of 10% to 30% by weight of the soft segment, and the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is in an amount of 70% to 90% by weight of the soft segment.
Example 20 is the method of Example 14, wherein the at least one of the polyisobutylene macrodiol and the polyisobutylene diamine is a polyisobutylene macrodiol and the number average molecular weight of the polyisobutylene macrodiol is about 400 Da to about 6000 Da.
While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.
The foregoing will be apparent from the following more particular description of example embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments of the present invention.
As used herein, the term “polydispersity index” (PDI) means is a measure of the distribution of molecular mass in a given polymer sample. The PDI calculated is the weight average molecular weight divided by the number average molecular weight.
As used herein, the term “macrodiol” means a polymeric diol. Examples include polyether compounds of formula
HO—[CH(R)—(CH2)k—O]l—H, (I)
Values and preferred values for the variables in formulas (I) and (II) are defined below.
Similarly, the phrase “macrodiol and/or diamine” is used, the reference is being made to a polymeric diamine similar in structure to the diols of formula (II), in which the terminal hydroxyl groups are replaced with amino or alkylamino groups, as defined below.
As used herein, the term “telechelic”, when referring to a polymer, means a polymer carrying functionalized endgroups. Examples of telechelic polymers are difunctional polymers of formulas (I) and (II), above. Telechelic polymers can be used, e.g., for the synthesis of block co-polymers.
As used herein, the term “BDO” refers to 1,4-butanediol.
As used herein, the term “MDI” refers to 4,4′-methylenebis(phenylisocyanate).
As used herein, the term “PTMO” refers to polytetramethylene oxide.
As used herein, the term “PIB” means a polyisobutylene, i.e. a compound formed by polymerization of an optionally substituted butadiene.
As used herein, the term “TPU” means a thermoplastic polyurethane.
As used herein, the term “PIB-TPU” means a polyisobutylene-based thermoplastic polyurethane obtained by any known process. The term includes the elastomeric polyurethanes materials described herein.
As used herein, the term “PIB-PTMO-TPU” means a polyisobutylene-based, polytetramethylene oxide-containing thermoplastic polyurethane obtained by any known process and includes the elastomeric polyurethanes materials described herein.
As used herein, the term “initiator residue” refers to a difunctional chemical moiety, that links two linear chains of a polymer. For example, in a polyisobutylene polymer of formula
where values and preferred values for the variables are defined below, R1 is an initiator residue. Examples of initiator residues include dicumyl and 5-tert-butyl-1,3 dicumyl that correspond to dicumyl chloride, methylether or ester, respectively, are used as initiator. Other examples include 2,4,4,6-tetramethylheptylene or 2,5-dimethylhexylene, which arise when 2,6-dichloro-2,4,4,6-tetramethylheptane or 2,5-dichloro-2,5-dimethylhexane is used as initiator. Many other cationic mono- and multifunctional initiators are known in the art.
The term “alkyl”, as used herein, unless otherwise indicated, means straight or branched saturated monovalent hydrocarbon radicals of formula CnH2n+1. In some embodiments, n is from 1 to 18. In other embodiments, n is from 1 to 12. Preferably, n is from 1 to 6. In some embodiments, n is 1-1000, for example, n is 1-100. Alkyl can optionally be substituted with —OH, —SH, halogen, amino, cyano, nitro, a C1-C12 alkyl, C1-C12 haloalkyl, C1-C12 alkoxy, C1-C12 haloalkoxy or C1-C12 alkyl sulfanyl. In some embodiments, alkyl can optionally be substituted with one or more halogen, hydroxyl, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl group, C1-C12 alkoxy, or C1-C12 haloalkyl. The term alkyl can also refer to cycloalkyl.
The term “cycloalkyl”, as used herein, means saturated cyclic hydrocarbons, i.e. compounds where all ring atoms are carbons. In some embodiments, a cycloalkyl comprises from 3 to 18 carbons. Preferably, a cycloalkyl comprises from 3 to 6 carbons. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. In some embodiments, cycloalkyl can optionally be substituted with one or more halogen, hydroxyl, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl group, C1-C12 alkoxy, or C1-C12 haloalkyl.
The term “haloalkyl”, as used herein, includes an alkyl substituted with one or more F, Cl, Br, or I, wherein alkyl is defined above.
The terms “alkoxy”, as used herein, means an “alkyl-O—” group, wherein alkyl is defined above. Examples of alkoxy group include methoxy or ethoxy groups.
The term “aryl”, as used herein, refers to a carbocyclic aromatic group. Preferably, an aryl comprises from 6 to 18 carbons. Examples of aryl groups include, but are not limited to phenyl and naphthyl. Examples of aryl groups include optionally substituted groups such as phenyl, biphenyl, naphthyl, phenanthryl, anthracenyl, pyrenyl, fluoranthyl or fluorenyl. An aryl can be optionally substituted. Examples of suitable substituents on an aryl include halogen, hydroxyl, C1-C12 alkyl, C2-C12 alkene or C2-C12 alkyne, C3-C12 cycloalkyl, C1-C12 haloalkyl, C1-C12 alkoxy, aryloxy, arylamino or aryl group.
The term “aryloxy”, as used herein, means an “aryl-O—” group, wherein aryl is defined above. Examples of an aryloxy group include phenoxy or naphthoxy groups.
The term arylamine, as used herein, means an “aryl-NH—”, an “aryl-N(alkyl)-”, or an “(aryl)2-N—” groups, wherein aryl and alkyl are defined above.
The term “heteroaryl”, as used herein, refers to aromatic groups containing one or more heteroatoms (O, S, or N). A heteroaryl group can be monocyclic or polycyclic, e.g. a monocyclic heteroaryl ring fused to one or more carbocyclic aromatic groups or other monocyclic heteroaryl groups. The heteroaryl groups of this invention can also include ring systems substituted with one or more oxo moieties. Examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, quinolyl, isoquinolyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, purinyl, oxadiazolyl, thiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, dihydroquinolyl, tetrahydroquinolyl, dihydroisoquinolyl, tetrahydroisoquinolyl, benzofuryl, furopyridinyl, pyrolopyrimidinyl, and azaindolyl.
The foregoing heteroaryl groups may be C-attached or N-attached (where such is possible). For instance, a group derived from pyrrole may be pyrrol-1-yl (N-attached) or pyrrol-3-yl (C-attached).
Suitable substituents for heteroaryl are as defined above with respect to aryl group.
Suitable substituents for an alkyl, cycloalkyl include a halogen, an alkyl, an alkenyl, a cycloalkyl, a cycloalkenyl, an aryl, a heteroaryl, a haloalkyl, cyano, nitro, haloalkoxy.
Further examples of suitable substituents for a substitutable carbon atom in an aryl, a heteroaryl, alkyl or cycloalkyl include but are not limited to —OH, halogen (—F, —Cl, —Br, and —I), —R, —OR, —CH2R, —CH2OR, —CH2CH2OR. Each R is independently an alkyl group.
In some embodiments, suitable substituents for a substitutable carbon atom in an aryl, a heteroaryl or an aryl portion of an arylalkenyl include halogen, hydroxyl, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl group, C1-C12 alkoxy, aryloxy group, arylamino group and C1-C12 haloalkyl.
In addition, the above-mentioned groups may also be substituted with ═O, ═S, ═N-alkyl.
In the context of the present invention, an amino group may be a primary (—NH2), secondary (—NHRp), or tertiary (—NRpRq), wherein Rp and Rq may be any of the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkoxy, aryl, heteroaryl, and a bicyclic carbocyclic group. A (di)alkylamino group is an instance of an amino group substituted with one or two alkyls.
A trialkylamino group is a group —N+(Rt)3, wherein Rt is an alkyl, as defined above.
As used herein, a “polyurethane” is any polymer consisting of a chain of organic units joined by urethane (carbamate, —NH—COO—) links. Polyurethane polymers can be formed by reacting a molecules containing at least two isocyanate functional groups with another molecule containing at least two alcohol (hydroxyl) groups. By reacting an isocyanate group, —N═C═O, with a hydroxyl group, —OH, a urethane linkage is produced. A catalyst can be used. Similarly, in polyureas the links are urea groups (—NH—CO—NH—) that are obtained by reacting an isocyanate group with an amine group —NH2.
For example, polyurethanes can be produced by the polyaddition reaction of a polyisocyanate with a polyalcohol (a polyol, an example of which is a macrodiol). The reaction mixture can include other additives. A polyisocyanate is a molecule with two or more isocyanate functional groups, R1—(N═C═O)n≥2 and a polyol is a molecule with two or more hydroxyl functional groups, R2—(OH)n≥2. R1 and R2 are each independently an aliphatic or an aromatic moiety. The reaction product is a polymer containing the urethane linkage, —R1NHCOOR2—.
Polyisocyanate that contain two isocyanate groups are called diisocyanates. Isocyanates can be aromatic, such as diphenylmethane diisocyanate (MDI) or toluene diisocyanate (TDI); or aliphatic, such as hexamethylene diisocyanate (HDI) or isophorone diisocyanate (IPDI). An example of an isocyanate is polymeric diphenylmethane diisocyanate, which is a blend of molecules with two-, three-, and four- or more isocyanate groups, with an average functionality of 2.7.
Polyols that contain two hydroxyl groups are called macrodiols, those with three hydroxyl groups are called macrotriols. Examples of polyols include polycarbonate polyols, polycaprolactone polyols, polybutadiene polyols, and polysulfide polyols.
Additive such as catalysts, surfactants, blowing agents, cross linkers, flame retardants, light stabilizers, and fillers are used to control and modify the reaction process and performance characteristics of the polymer.
Examples of aromatic isocyanates are toluene diisocyanate (TDI) and diphenylmethane diisocyanate (MDI). TDI consists of a mixture of the 2,4- and 2,6-diisocyanatotoluene isomers. Another example of an aromatic isocyanate is TDI-80 (TD-80), consisting of 80% of the 2,4-isomer and 20% of the 2,6-isomer.
Examples of aliphatic (including cycloaliphatic) isocyanates are 1,6-hexamethylene diisocyanate (HDI), 1-isocyanato-3-isocyanatomethyl-3,5,5-trimethyl-cyclohexane (isophorone diisocyanate, IPDI), and 4,4′-diisocyanato dicyclohexylmethane (H12MDI). Other aliphatic isocyanates include cyclohexane diisocyanate (CNDI), tetramethylxylene diisocyanate (TMXDI), and 1,3-bis(isocyanatomethyl)cyclohexane (H6XDI).
Chain extenders (f=2) and cross linkers (f=3 or greater) are low molecular weight hydroxyl and amine terminated compounds that play an important role in the polymer morphology of polyurethane fibers, elastomers, adhesives, and certain integral skin and microcellular foams. Examples of chain extenders and cross linkers are ethylene glycol (EG), 1,4-butanediol (BDO), diethylene glycol (DEG), glycerine, and trimethylol propane (TMP).
The elastomeric properties of polyurethanes, polyureas and polyurethaneureas are derived from the phase separation of the “hard segment” and the “soft segment” domains of the polymer chain. For example, hard segments that comprise urethane units can serve as cross-links between the soft segments that comprise polyol (e.g., macrodiol) units (e.g., polyisobutane diols, polyether diols, and/or polyester diols). Without being limited to any particular theory, it is believed that the phase separation occurs because the mainly non-polar, low melting soft segments are incompatible with the polar, high melting hard segments. The polyol-containing soft segments are mobile and are normally present in coiled formation, while the isocyanate-containing hard segments (which can also include chain extenders) are stiff and immobile. Because the hard segments are covalently coupled to the soft segments, they inhibit plastic flow of the polymer chains, thus creating elastomeric resiliency. Upon mechanical deformation, a portion of the soft segments are stressed by uncoiling, and the hard segments become aligned in the stress direction. This reorientation of the hard segments and consequent powerful hydrogen bonding contributes to high tensile strength, elongation, and tear resistance values.
Although the synthesis of polyurethanes is usually presented as proceeding via formation of urethane (carbamate) linkages by the reaction of isocyanates and alcohols, this is an oversimplification. See, for example, G. ODIAN: PRINCIPLES OF POLYMERIZATION, FOURTH ED. Wiley Interscience, 2004. Accordingly, it is more convenient to define the polyurethane compositions via weight percent of the components rather than structurally.
Accordingly, in some embodiments, the present invention is an elastomeric polymer, comprising (1) a hard segment in the amount of 10% to 60% by weight of the elastomeric polymer, wherein the hard segment includes a urethane, urea or urethaneurea; and (2) a soft segment in the amount of 40% to 90% by weight of the elastomeric polymer. The soft segment comprises at least 2% by weight of the soft segment of at least one polyether macrodiol, and/or at least one polycarbonate macrodiol and at least 2% by weight of the soft segment of at least one polyisobutylene macrodiol and/or diamine.
In certain embodiments, the number average molecular weight of the elastomeric polymer is not less than about 40 kilodaltons (kDa). In other embodiments, the number average molecular weight of the elastomeric polymer is not less than about 50 kilodaltons. In alternative embodiments, wherein the number average molecular weight of the elastomeric polymer is not less than about 60 kDa, not less than about 70 kDa, not less than about 80 kDa, not less than about 90 kDa, not less than about 100 kDa, not less than about 110 kDa, not less than about 120 kDa, not less than about 130 kDa, not less than about 140 kDa or not less than about 150 kDa.
In certain embodiments, the hard segment can be present in the amount of 15, 20, 25, 30, 35, 40, 45, 50, or 55%.
In certain embodiments, soft segment is present in the amount of 45, 50, 55, 60, 65, 70, 75, 80, or 85%. Polyether and/or polycarbonate can be present in the amount of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 or 85%. Polyisobutylene can be present in the amount of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 or 85%.
One of ordinary skill can easily determine a suitable polyether macrodiol. Preferably, at least one polyether macrodiol is a compound of formula
HO—[CH(R)—(CH2)k—O]l—H,
wherein R, for each occurrence, is independently a C1-C12 alkyl or —H; k is an integer not less than 1; and l is an integer not less than 1.
One of ordinary skill can easily determine a suitable polyisobutylene macrodiol or diamine. Preferably, at least one polyisobutylene macrodiol and/or diamine is of formula:
wherein each X is independently —OH, —NH2 or —NHR4, and wherein R1 is an initiator residue (defined above). R2, R3 and R4 is each independently a C1-C16 alkyl, a C3-C16 cycloalkyl, a C2-C16 alkenyl, a C3-C16 cycloalkenyl, a C2-C16 alkynyl, a C3-C16 cycloalkynyl, or a C6-C18 aryl, wherein, for each occurrence, R2 or R3 is, independently, optionally substituted with one or more groups selected from halo, cyano, nitro, dialkylamino, trialkylamino, C1-C16 alkoxy and C1-C16 haloalkyl. Integers n and m are each, independently, from 1 to 500.
Preferably, the polyisobutylene macrodiol or diamine is hydroxy or amino allyl telechelic polyisobutylene. In one embodiment, the molecular weight of at least one polyisobutylene macrodiol or diamine is about 400 Da to about 6000 Da. For example, polyisobutylene macrodiol or diamine is about 500, 1000, 2000, 3000, 4000, or 5000 Da. In certain embodiments, the molecular weight of at least one polyisobutylene macrodiol or diamine is about 1000 Da to about 3000 Da. For example, the molecular weight of at least one polyisobutylene macrodiol or diamine is about 1000, 1500, 2000, or 2500 Da.
In preferred embodiments, R2 and R3 is each independently a moiety selected from —CH2—CH═CH—CH2—, —CH2—CH2—CH2—CH2—, —CH2—CH2—CH2—, and —CH2—CH(CH3)—CH2—.
In one embodiment, the elastomeric polymer of the present invention comprises a soft segment that includes at least one polyether macrodiol and at least one polycarbonate macrodiol; and at least 2% by weight of the soft segment of the at least one polyisobutylene macrodiol, and/or diamine.
In another embodiment, the elastomeric polymer of the present invention comprises a soft segment that includes: (a) about 10% to about 90% by weight of the soft segment of the at least one polyisobutylene macrodiol, and/or diamine; and (b) either about 10% to about 90% by weight of the soft segment of the at least one polyether macrodiol, or about 10% to about 90% by weight of the soft segment of the at least one polycarbonate macrodiol, or about 10% to about 90% by weight of the soft segment of the at least one polyether macrodiol and the at least one polycarbonate macrodiol.
For example, the soft segment can include from about 10% to about 30% by weight of the soft segment of at least one polycarbonate macrodiol. For example, the soft segment can include at least one polycarbonate macrodiol in the amount of 15, 20 or 25%. Alternatively, the soft segment can include from about 10% to about 30% by weight of the soft segment of the at least one polyether macrodiol and the at least one polycarbonate macrodiol. For example, the soft segment can include at least one polyether macrodiol and the at least one polycarbonate macrodiol in the amount of 15, 20 or 25%.
In one embodiment, the soft segment can include from about 10% to about 30% by weight of the soft segment of the at least one polyether macrodiol. For example, the soft segment can include at least one polyether macrodiol in the amount of 15, 20 or 25%.
In another embodiment, the soft segment includes from about 10% to about 90% by weight of the soft segment of the at least one polyisobutylene macrodiol, and/or diamine. For example, the soft segment can include at least one polyisobutylene macrodiol, and/or diamine in the amount of 20, 30, 40, 50, 60, 70 or 80%.
In a further embodiment, the soft segment can include from about 70% to about 90% by weight of the soft segment of the at least one polyisobutylene macrodiol, and/or diamine. For example, the soft segment can include at least one polyisobutylene macrodiol, and/or diamine in the amount of 70, 75, 80 or 85%.
Preferably, at least one polyether macrodiol includes at least one member selected form the group consisting of poly(ethylene oxide) diol, poly(propylene oxide) diol, poly(trimethylene oxide) diol, poly(tetramethylene oxide) diol, poly(hexamethylene oxide) diol, poly(heptamethylene oxide) diol, poly(octamethylene oxide) diol and poly(decamethylene oxide) diol.
One of ordinary skill in the art will be able to easily determine a suitable polycarbonate macrodiol. Preferably, at least one polycarbonate macrodiol includes at least one member selected from the group consisting of a poly(alkylene carbonate) of a formula
where R7 is a hydrogen, a C1-C12 straight or branched alkyl, or a C3-C12 cycloalkyl, q is an integer greater than 1 and p is an integer greater than 2. Preferably, R7 is a hydrogen. Examples of poly(alkylene carbonate) include poly(tetramethylene carbonate) diol, poly(pentamethylene carbonate) diol, poly(hexamethylene carbonate) diol, or copolymers of thereof.
In certain embodiments, the elastomeric polymer of the present invention comprises a hard segment present in the amount of from about 30% to about 50% by weight of the elastomeric polymer. For example, the hard segment present in the amount of 35, 40, or 45%.
Examples of the hard segments include the hard segments formed by reacting a diisocyanate with a chain extender. One of ordinary skill in the art will easily determine a suitable diisocyanate or a chain extender. The diisocyanate can be at least one member selected from the group consisting of 4,4′-methylenephenyl diisocyanate; methylene diisocyanate; p-phenylene diisocyanate; cis-cyclohexane-1,4-diisocyanate; trans-cyclohexane-1,4-diisocyanate; a mixture of cis cis-cyclohexane-1,4-diisocyanate and trans-cyclohexane-1,4-diisocyanate; 1,6-hexamethylene diisocyanate; 2,4-toluene diisocyanate; cis-2,4-toluene diisocyanate; trans-2,4-toluene diisocyanate; a mixture of cis-2,4-toluene diisocyanate and trans-2,4-toluene diisocyanate; p-tetramethylxylene diisocyanate; and m-tetramethylxylene diisocyanate. The chain extender can be at least one member selected from the group consisting of 1,4-butanediol; 1,5 pentanediol; 1,6-hexanediol; 1,8-octanediol; 1,9-nonanediol; 1,10-decanediol, 1,12-dodacanediol; 1,4-cyclohexane dimethanol; p-xyleneglycol and 1,4-bis(2-hydroxyethoxy) benzene. Preferably, the diisocyanate is 4,4′-methylenephenyl diisocyanate and the chain extender is 1,4-butanediol.
In a preferred embodiment, the polyurethane elastomeric polymer of the present invention comprises the soft segment formed from a hydroxyallyl telechelic polyisobutylene and poly(tetramethylene oxide) diol and the hard segment formed from 4,4′-methylenediphenyl diisocyanate and 1,4-butanediol.
In another preferred embodiment, the polyurethane elastomeric polymer of the present invention comprises the soft segment is derived from a hydroxyallyl telechelic polyisobutylene and poly(hexamethylene oxide) diol and the hard segment is derived from 4,4′-methylenediphenyl diisocyanate and 1,4-butanediol.
In another preferred embodiment, the polyurethane elastomeric polymer of the present invention comprises the soft segment formed from (a) a hydroxyallyl difunctional polyisobutylene and (b) poly(tetramethylene oxide) diol or poly(hexamethylene oxide) diol; and the hard segment formed from (c) 4,4′-methylenediphenyl diisocyanate and (d) 1,4-butanediol.
In certain embodiments, the present invention is an article of manufacture comprising any of the polyurethane elastomeric polymers described above. In preferred embodiments, the article is a medical device or an implant. Examples of the article of the present invention include a cardiac pacemaker, a defibrillator, a catheter, an implantable prosthesis, a cardiac assist device, an artificial organ, a pacemaker lead, a defibrillator lead, a blood pump, a balloon pump, an a-V shunt, a biosensor, a membrane for cell encapsulation, a drug delivery device, a wound dressing, an artificial joint, an orthopedic implant or a soft tissue replacement. In other embodiments, the article is a fiber, film, engineering plastic, fabric, coating, and adhesive joint.
The methods of synthesis of polyurethane compositions are generally well known by one of ordinary skill in the art of polymer chemistry. See, for example, Gunter Oertel, “Polyurethane Handbook”, 2nd ed. Hanser Publishers (1993); or Malcolm P. Stevens, “Polymer Chemistry”, 3d ed. Oxford University Press (1999). The relevant portions of these publications are incorporated herein by reference.
The present invention is based, in part, on the discovery of new and improved methods of polyurethane synthesis. Accordingly, in some embodiments, the present invention is a process for preparing a polyurethane elastomeric polymer. (See
Any one or more of the isocyanates, polyols, chain extenders, or various additives can be employed with the synthetic method of the present invention. For example, polyether macrodiols and/or polyisobutylene macrodiol, described above, as well as any mixture thereof, can be used in the above-described process. Any amounts of the components and their combinations described above can be used.
Preferably, in the processes of the present invention, the mixture is formed at a temperature of about 45° C. to about 120° C. For example, the mixture is formed at a temperature of about 50, 60, 70, 80, 90, 100 or 110° C.
In some embodiments, the mixture is formed in the presence of a catalyst, such as stannous octoate. Other catalysts are well known in the art and can be used by one of ordinary skill in the art.
In an alternative embodiments, the present invention is a process for preparing a elastomeric polymer, comprising the steps of (a) reacting a diisocyanate with a mixture that includes at least one polyisobutylene macrodiol, and/or diamine and at least one polyether macrodiol to form a prepolymer having terminally reactive diisocyanate groups; and (b) reacting the prepolymer with a chain extender to yield a polyurethane elastomeric polymer. Preferably, the elastomeric polymer includes (i) a hard segment in the amount of 10% to 60% by weight of the elastomeric polymer, wherein the hard segment includes a urethane, urea or urethaneurea; and (ii) a soft segment in the amount of 40% to 90% by weight of the elastomeric polymer. Preferably, the soft segment includes at least 2% by weight of the soft segment of the at least one polyether macrodiol and/or at least one polycarbonate macrodiol, and at least 2% by weight of the soft segment of the at least one polyisobutylene macrodiol, and/or diamine.
Any one or more of the isocyanates, polyols, chain extenders, or various additives can be employed with the synthetic method of the present invention. For example, polyether macrodiols and/or polyisobutylene macrodiol, described above, as well as any mixture thereof, can be used in the above-described process. Any amounts of the components and their combinations described above can be used.
For example, at least one polyether macrodiol employed by the above-described process is poly(ethylene oxide) diol, poly(propylene oxide) diol, poly(trimethylene oxide) diol, poly(tetramethylene oxide) diol, poly(hexamethylene oxide) diol, poly(heptamethylene oxide) diol, poly(octamethylene oxide) diol or poly(decamethylene oxide) diol.
Preferably, at least one polycarbonate macrodiol employed by the above-described process is a poly(alkylene carbonate), as described above.
Examples of the chain extenders that can be employed in the above-described process are 1,4-butanediol; 1,5-pentanediol; 1,6-hexanediol; 1,8-octanediol; 1,9-nonanediol; 1,10-decanediol, 1,12-dodecanediol; 1,4-cyclohexane dimethanol; p-xyleneglycol and 1,4-bis(2-hydroxyethoxy) benzene. Other examples include diamine chain extenders
Materials
Sn(Oct)2 (stannous octoate, Polyscience), 4,4′-methylenebis(phenylisocyanate) (MDI, Aldrich, 98%), toluene (Aldrich, 99%), chloroform (Aldrich, at least 99.8%), 1,4-butanediol (BDO, Aldrich, 99%), Phthalimide, potassium (Aldrich, 98%), LiBr (Lithium bromide ReagentPlus®, Aldrich, at least 99%), KOH (potassium hydroxide, Aldrich), Na2SO4 (sodium sulfate, Aldrich), Trifluoroacetic acid (TFA, Aldrich), Tetra-n-butylammonium bromide (TBAB, Alfa Aesar, at least 98%) and Poly(tetramethylene oxide) (PTMO, TERATHANE® 1000 polyether glycol, Aldrich) were used as received. Tetrahydrofuran (THF) or toluene were refluxed over sodium metal and benzophenone over night and distilled under nitrogen atmosphere prior to use. Hexanes were purified by refluxing over sulfuric acid for 24 hours. They were washed with aqueous solution of KOH three times followed by distilled water. Then they were stored over sodium sulfate over night at room temperature. Finally they were distilled over CaH2 under nitrogen atmosphere before use.
Measurements
Molecular weights were measured with a Waters HPLC system equipped with a model 510 HPLC pump, model 410 differential refractometer, model 441 absorbance detector, on-line multiangle laser light scattering (MALLS) detector (MiniDawn, Wyatt Technology Inc.), Model 712 sample processor, and five Ultrastyragel GPC columns connected in the following series: 500, 103, 104, 105, and 100 Å. THF:TBAB (98:2, wt %) was used as a carrier solvent with a flow rate of 1 mL/min. Static tensile properties (Young's modulus, ultimate tensile strength, referred herein as “UTS”, elongation) were measured at room temperature (25° C.) and atmospheric conditions with a 50 N load cell on an Instron Model 4400R at 50 mm/min extension rate. All tests were carried out according to ASTM D412. Samples were cut into dog-bone shape using an ASTM die. All samples were kept at room temperature and atmospheric conditions prior to testing. The polymers were compression molded at 160° C. for 10 min using 17000 psi.
The synthesis of HO-Allyl-PIB-Allyl-OH was carried out by heating the THF solution of bromoallyl telechelic PIB with aqueous solution of KOH at 130° C. for 3 hours.
For example, Br-Allyl-PIB-Allyl-Br (Mn=2200, 50 g, 0.023 mol) was dissolved in dry THF (1 liter) and a solution of KOH (50 g, 0.9 mol) in distilled water (500 mL) was added to it. The mixture was heated for 3 hour at 130° C. in a reactor. The reaction was cooled to room temperature. The THF was evaporated using a rotary evaporator. Distilled methanol (500 mL) was added and the precipitate was allowed to settle down. The precipitate was further dissolved in hexanes (200 mL) and slowly added to methanol (600 mL). The sticky mass was allowed to settle down. The process was repeated two times and the purified polymer was finally dried under vacuum at room temperature for 24 hour. Yield: 99%, GPC-MALLS: Mn=2400, polydispersity index (PDI)=1.16.
Representative molecular weight data for the hydroxy telechelic PIBs are described in Table 1, below.
As used in Example 2, the terms “one-step procedure” and “two-step procedure” refer to the synthetic scheme exemplified in
The syntheses of polyurethanes (PUs) with the ratio of soft segment (SS) to hard segment (HS) 80:20 (wt:wt), i.e. PIB(4200)-TPU (Sample Code PIB-TPU-4321), PIB(2200)-TPU (Sample Code PIB-TPU-2211) and PIB(1500)-TPU (Sample Code PIB-TPU-1514) were carried out in toluene using MDI and BDO as the chain extender in presence of 1 mol % of stannous octoate (relative to MDI) at 80° C. The polymers were obtained by adding MDI as the last reagent (one-step procedure).
One-Step Procedure
For examples, the material PIB-TPU-2211 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 5.2 g, 2.36 mmol) and BDO (212 mg, 2.36 mmol) were azeotropically distilled from dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (20 mg, 0.05 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (1.24 g, 4.96 mmol) was added to this mixture and the mixture was stirred vigorously for 6 hours. The mixture was cooled to room temperature, poured into a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours. Representative molar ratio of the reactants and Shore hardness of the TPUs are described in Table 2.
1Mn of precursor HO-Allyl-PIB-Allyl-OH
The Mn of PIB-TPU-2211 after various polymerization times is noted in Table 3. The increase in Mn was observed till 6 hour time. The polyurethane was then cured for one week at room temperature. A further increase in Mn=105000, PDI=2.4 was observed for the cured sample.
1Mn of precursor HO-Allyl-PIB-Allyl-OH
The Mn of PIB-TPUs having Shore hardness of about 60 A hardness prepared with polyisobutylenes having different molecular weights are summarized in Table 4. PIB-TPU-1514 was not soluble in THF:TBAB (98:2 wt %), hence the Mn could not be determined.
The syntheses of polyurethanes with soft segment (SS) to hard segment (HS) ratio of 60:40 (wt %), e.g. PIB(4200)-TPU (Sample Code PIB-TPU-4761), PIB(2200)-TPU (Sample Code PIB-TPU-2431) and PIB(1500)-TPU (Sample Code PIB-TPU-1321) were carried out by a one-step synthetic procedure (see
For example, PIB-TPU-2431 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 5.2 g, 2.36 mmol) and BDO (637 mg, 7.08 mmol) were azeotropically distilled from dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (38 mg, 0.09 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (2.36 g, 9.44 mmol) was added to the mixture and the mixture was stirred vigorously for 6 hours. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
Representative molar ratio of the reactants and Shore hardness of the TPUs are described in Table 5, below.
The GPC analysis of the TPUs were carried out in THF:TBAB (98:2 wt %). The molecular weight values (Table 6) were obtained in the range of 83000-91000 with PDI in the range of 1.8-2.2.
Representative mechanical property data of the PIB-TPUs are listed in Table 7. The UTS was obtained in the range of 6-9 MPa with elongation at break in the range of 40-400%. With an increase in the hard segment to soft segment ratio, the Young's modulus increased and the elongation at break decreased. The thermal processing of TPUs with higher Shore hardness was difficult compared to the softer ones. PIB-TPU-2431 and PIB-TPU-1321 could not be molded into flat sheets for testing, so the tensile properties were not recorded.
Changing the catalyst of polymerization from tin octoate to 1,3-Diacetoxy-1,1,3,3-tetrabutyldistannoxane (DTDS) the UTS of PIB-TPU-2211 increased from 9 MPa to 12 MPa and the elongation at break decreased to 100% from 350% as shown in Table 8.
†not soluble in THF/TBAB, soluble in chloroform/TFA
Two-Step Synthesis
In subsequent experiments, the technique for the polyurethane synthesis was modified by adding 1,4-butanediol (BDO) as the last reagent. The process consisted of two steps. (See
The PIB-TPU-4321 was synthesized using the two-step procedure by adding BDO last. HO-Allyl-PIB-Allyl-OH (Mn=4200, 5.2 g, 1.24 mmol) was azeotropically distilled from dry toluene (10 mL). The polymer was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (15 mg, 0.037 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. To it MDI (930 mg, 3.72 mmol) was added and the mixture was stirred vigorously for 30 min. BDO (223 mg, 2.48 mmol) was added to this mixture and stirring continued for 4 hours. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
As can be seen in Table 9, a higher molecular weight with narrow molecular weight distribution was observed for the polymer obtained by two-step synthesis compared to the polymer synthesized by one-step procedure. The tensile properties were similar in both the cases. The processing was easier, compared to the same TPU synthesized by the one-step procedure.
TPUs having mixtures of PIB and PTMO in different proportions as soft segment were synthesized using the two-step procedure according to the synthetic procedure exemplified in
For example, PIB-PTMO-82-6 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 5.2 g, 2.36 mmol) and PTMO (Mn=1000, 1.3 g, 1.3 mmol) were azeotropically distilled from dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (28.3 mg, 0.07 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (1.76 g, 7.02 mmol) was added to this mixture and the mixture was stirred vigorously for 30 min. BDO (302 mg, 3.36 mmol) was added to the resulting reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The sample codes and weight percent values of PIB and PTMO is shown in Table 10.
1HO-PIB-OH, Mn = 2200,
2HO-PTMO-OH, Mn = 1000,
3soft:hard = 79:21 wt %
GPC-RI traces of the TPUs showed monomodal distribution of molecular weight with the values of molecular weight in the range of 55000-140000 and PDI of approximately 1.4-2.7. The molecular weight data of the TPUs synthesized according to the method described above are described in Table 11:
The ultimate tensile strength (UTS) of the PIB-PTMO TPUs was approximately 4-20 MPa with elongation at break in the range of 400-740%. The Young's moduli of the polymers were obtained in the range of 2-9 MPa. The Shore hardness and tensile property data of the TPUs are listed in Table 12 below:
With addition of a small amount of polytetramethyleneoxide diol (PTMO), the mechanical properties of the polymers increased dramatically. However, the properties remained similar with further increase in PTMO composition. TPU with 100% PTMO (PTMO-60 A) also exhibited similar tensile property.
PIB-PTMO TPUs with higher hard segment to soft segment ratio were synthesized using the two-step procedure described above. The soft segment to hard segment ratio (SS:HS) of 65:35 percent by weight was maintained in all the cases, while the PIB to PTMO ratio (in percent by weight of the soft segment) was varied. Results are presented in Table 13.
1HO-PIB-OH, Mn = 2200,
2HO-PTMO-OH, Mn = 1000,
3SS:HS = 65:35 wt %
Exemplary Synthesis of a PIB-PTMO-TPU
PIB-PTMO-82-8 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 5.2 g, 2.36 mmol) and PTMO (Mn=1000, 1.3 g, 1.3 mmol) were azeotropically distilled from dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (42 mg, 0.104 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (2.6 g, 10.38 mmol) was added to the reaction mixture, and the mixture was stirred vigorously for 30 min. BDO (605 mg, 6.72 mmol) was added to the reaction mixture, and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
Molecular weight data of PIB-PTMO TPUs with Shore hardness of 80 A is shown in Table 14. The molecular weight of the polymers is in the range of 42000-138000, with PDI of 1.9-3.8.
The ultimate tensile strength (UTS) of the PIB-PTMO TPUs (Shore hardness 80 A) were in the range of 18-25 MPa with elongation at break in the range of 150-550%. The Young's modulus of the polymers were higher compared to PIB-PTMO TPUs with lower Shore hardness (60 A) and varied between 11-32 MPa. Increase in PTMO concentration linearly increased the UTS as well as the elongation at break of the TPUs. The PIB-PTMO TPU comprising PTMO-80 A exhibited highest UTS and elongation at break. The Shore hardness and tensile property data of the TPUs are listed in Table 15 below.
Exemplary Synthesis of the PIB-PTMO TPU Performed at 120° C.
PIB-PTMO TPUs having not less than 80 percent by weight of the soft segment of the PTMO component were synthesized according to the synthetic scheme exemplified in
For example, PIB-PTMO-28-8 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 1.12 g, 0.51 mmol) and PTMO (Mn=1000, 4.48 g, 4.48 mmol) were azeotropically distilled from dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to the reaction mixture, followed by Sn(Oct)2 (44.6 mg, 0.11 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (2.67 g, 10.7 mmol) was added to the reaction mixture, and the mixture was stirred vigorously for 30 min. BDO (520 mg, 5.7 mmol) was added to the reaction mixture, and the temperature was raised to 120° C. After 15 minutes, the temperature was decreased to 100° C. and the mixture was kept under nitrogen for 4 hours. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The GPC data of the TPUs having PTMO in excess of 80% by weight of the soft segment is given in Table 16 below. The molecular weight values of these TPUs increased compared to the polymers that were synthesized from the same starting materials, but at a temperature of 100° C. (Table 11 and 14).
The UTS, ultimate elongation at break and Young's modulus data of the TPUs of Table 16 are listed in Table 17 below. The UTS of PTMO-60 A (compare to Table 12) increased from 10 MPa to 20 MPa when the synthetic procedure was modified by increasing the reaction temperature to 120° C. A 200% enhancement in ultimate elongation at break was also observed. Other TPUs also exhibited improved tensile properties, as shown in Table 17. The tensile data of the PIB-PTMO-28-6 (see Table 12) and PIB-PTMO-28-8 (see Table 15) synthesized at 100° C. are described previously.
Synthesis of PIB-PTMO-TPU (Shore Hardness about 95 A
PIB-PTMO TPUs with designed Shore hardness of about 95 A were synthesized using the two-step procedure described above. The soft segment to hard segment ratio (SS:HS) of 60:40 w:w was maintained in all the cases, while the PIB to PTMO weight ratio was varied as shown in Table 18.
1HO-PIB-OH, Mn = 2200,
2HO-PTMO-OH, Mn = 1000,
3SS:HS = 60:40 wt %
For example, PIB-PTMO-73-9 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 3.92 g, 1.78 mmol) and PTMO (Mn=1000, 1.68 g, 1.68 mmol) were azeotropically distilled from dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to the reaction mixture, followed by Sn(Oct)2 (49 mg, 0.121 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (3.03 g, 12.12 mmol) was added to the reaction mixture, and the mixture was stirred vigorously for 30 min. BDO (780 mg, 8.66 mmol) was added to the reaction mixture, and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally, the polymer was dried under vacuum at 50° C. for 12 hours.
The molecular weight data of PIB-PTMO TPUs with Shore 95 A hardness are shown in Table 19. The molecular weight of the polymers was in the range of 79000-111500, with PDI of 1.6-3.4.
The UTS, Shore hardness, tear strength and Young's modulus data for PIB-PTMO-TPU (Shore hardness of about 95 A) are presented in Table 20. The UTS and Young's modulus of the polymers were observed in the range of 14-42 MPa and 144-17 MPa respectively. The elongation at break was observed in the range of 30-510%. The UTS and Young's modulus of PIB-PTMO-73-9 was higher compared to the TPUs having same PIB/PTMO ratio of 70/30 by weight, such as PIB-PTMO-6 and PIB-PTMO-8 TPUs with Shore hardness 60 A (PIB-PTMO-73-6) and 80 A (PIB-PTMO-73-8).
TPU, having a mixture of PIB and poly(hexamethylene carbonate) (PHMC) in the ratio of 70:30 percent by weight of the soft segment was synthesized using the procedure similar to the one illustrated in
A synthetic procedure for PIB-PHMC-73-6 is given below. PIB-PHMC-73-6 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 4.5 g, 2.04 mmol) and PHMC (Mn=860, 1.93 g, 2.27 mmol) were azeotropically distilled from dry toluene (10 mL). The reaction mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to the reaction mixture, followed by Sn(Oct)2 (26.3 mg, 0.065 mmol) in toluene. The reaction mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (1.63 g, 6.51 mmol) was added to the reaction mixture and the mixture was stirred vigorously for 30 minutes. BDO (200 mg, 2.2 mmol) was added to the reaction mixture and the mixture was stirred for 4 hours at 100° C. The reaction mixture was cooled to room temperature, poured in a Teflon® mold, and the solvent was evaporated at room temperature in air for 48 hours. Finally, the polymer was dried under vacuum at 50° C. for 12 hours.
The ultimate tensile strength (UTS) of the PIB-PHMC-73-6 was 10 MPa with elongation at break of about 300%. The Young's modulus of the polymer was 10 MPa with Shore (A) hardness about 61 A.
The synthesis of H2N-Allyl-PIB-Allyl-NH2 was carried out by heating the THF:DMF (70:30, v:v) solution of chloroallyl telechelic PIB with phthalimide potassium under reflux conditions for 18 hours followed by hydrolysis in presence of NH2NH2.H2O.
For example, Phthalimide-Allyl-PIB-Allyl-Phthalimide was synthesized as follows. CI-Allyl-PIB-Allyl-CI (Mn=2100, 10 g, 0.0048 mol) was dissolved in dry THF (300 mL) and dry DMF (100 mL) followed by the addition of phthalimide potassium (50 g, 0.27 mol) and the mixture was refluxed under dry nitrogen atmosphere for 18 h. The reaction mixture was cooled to room temperature, filtered and THF was evaporated. Methanol was added to the sticky mass left over and the precipitate was separated and dissolved in hexanes. The solution was reprecipitated in methanol. The product obtained was further purified by dissolution and reprecipitation using hexanes and methanol.
A typical synthetic procedure for H2N-Allyl-PIB-Allyl-NH2 is as follows. Phthalimide-Allyl-PIB-Allyl-Phthalimide (9 g, 0.0042 mol) was dissolved in THF (200 mL) and hydrazine hydrate (15 g) was added. The mixture was refluxed for 24 h. The reaction was stopped and cooled to room temperature. A solution of KOH (10 g, in 25 mL of water) was added and stirred for 30 min. THF was evaporated under reduced pressure and methanol was added. The precipitate obtained was purified by dissolving in hexanes and reprecipitating in methanol. Yield: 98%, NMR: Mn=2100.
A series of PIB based polyurethaneurea with designed Shore 80 A hardness was synthesized by chain extension of H2N-Allyl-PIB-Allyl-NH2 and HO-PTMO-OH with BDO and MDI as exemplified in
1H2N-PIB-NH2 (Mn) = 2100,
2HO-PTMO-OH (Mn) = 1000
Exemplary Synthesis of a PIB-PTMO-TPUU
PIB-TPUU-82-8 was synthesized as follows. H2N-Allyl-PIB-Allyl-NH2 (Mn=2100, 5.2 g, 2.36 mmol) and PTMO (Mn=1000, 1.3 g, 1.3 mmol) were azeotropically distilled from dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (42 mg, 0.104 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (2.6 g, 10.38 mmol) was added to the reaction mixture, and the mixture was stirred vigorously for 30 min. BDO (605 mg, 6.72 mmol) was added to the reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
Molecular weight data of PIB-PTMO TPUUs with Shore 80 A hardness are shown in Table 22. The molecular weight of the polymers is in the range of 98700-119000, with PDI=1.6-2.8.
The UTS, Shore hardness, tear strength and Young's modulus data for PIB-PTMO-TPUU are presented in Table 23. The UTS of the polymers was observed in the range of 23-32 MPa and the Young's modulus varied between 5 to 50 MPa. The elongation at break was observed in the range of 250-675%.
Ultimate tensile strength (UTS) and elongation at break were measured as described above for eight samples:
A, PIB-TPU-2221 (shown in Table 7),
B, PIB-PTMO-91-6 (shown in Table 12),
C, PIB-PTMO-82-6 (shown in Table 12),
D, PIB-PTMO-73-6 (shown in Table 12),
E, PIB-PTMO-64-6 (shown in Table 12),
F, PIB-PTMO-55-6 (shown in Table 12),
G, PIB-PTMO-28-6 (shown in Table 12), and
H, PTMO-60 A (shown in Table 17).
These samples were synthesized according to the procedure described in Example 3, above. The samples differed in the content of PTMO, a polyether diol.
The results are presented in
TPU having mixture of PIB and PTMO in 80:20 weight proportion as soft segment was synthesized using the two-step procedure according to the synthetic procedure exemplified in
For example, PIB-PTMO-82-5 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2250, 5.0 g, 2.2 mmol) and PTMO (Mn=1000, 1.25 g, 1.25 mmol) were dried by azeotropic distillation from dry toluene (10 mL) solution. The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (20.3 mg, 0.05 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (1.32 g, 5.3 mmol) was added to this mixture and the mixture was stirred vigorously for 30 min. BDO (170 mg, 1.87 mmol) was added to the resulting reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The TPU exhibited the following characteristics: Mn=75000, PDI=1.7, UTS=14 MPa and elongation at break=800%, Young's modulus=3 MPa, flexural modulus=11 MPa, tear strength=292 pli.
TPU having mixture of PIB and PTMO in 80:20 weight proportion as soft segment was synthesized using the two-step procedure according to the synthetic procedure exemplified in
For example, PIB-PTMO-82-5.5 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2250, 5.4 g, 2.4 mmol) and PTMO (Mn=1000, 1.35 g, 1.35 mmol) were dried by azeotropic distillation from dry toluene (10 mL) solution. The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (25.9 mg, 0.06 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (1.55 g, 6.21 mmol) was added to this mixture and the mixture was stirred vigorously for 30 min. BDO (223 mg, 2.46 mmol) was added to the resulting reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The TPU exhibited the following characteristics: Mn=105000, PDI=2.0, UTS=13 MPa, elongation at break=900%, Young's modulus=3.6 MPa, tear strength is 295 pli.
TPU having mixtures of hydroxypropyl telechelic PIB and PTMO in different weight proportions as soft segment was synthesized using the two-step procedure according to the synthetic procedure exemplified in
For example, PIBsat-PTMO-82-6 was synthesized as follows. HO-propyl-PIB-propyl-OH (Mn=2000, 5.3 g, 2.65 mmol), obtained by hydroboration oxidation of allyl telechelic PIB (Iván, B.; Kennedy, J. P. J. Polym. Sci., Part A: Polym. Chem. 1990, 28, 89), and PTMO (Mn=1000, 1.33 g, 1.33 mmol) were dried by azeotropic distillation from dry toluene (10 mL) solution. The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (29.9 mg, 0.074 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (1.84 g, 7.36 mmol) was added to this mixture and the mixture was stirred vigorously for 30 min. BDO (308 mg, 3.38 mmol) was added to the resulting reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The TPU exhibited the following characteristics: M modun=140000, PDI=2.2, UTS=20 MPa, elongation at break=550%, Young's lus=6 MPa.
TPU having mixtures of hydroxypropyl telechelic PIB and PTMO in different weight proportions as soft segment was synthesized using the two-step procedure according to the synthetic procedure exemplified in
PIBsat-PTMO-82-8 was synthesized as follows. HO-propyl-PIB-propyl-OH (Mn=2000, 5.2 g, 2.6 mmol) and PTMO (Mn=1000, 1.3 g, 1.3 mmol) were dried by azeotropic distillation from dry toluene (10 mL) solution. The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (42.5 mg, 0.105 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (2.64 g, 10.54 mmol) was added to the reaction mixture, and the mixture was stirred vigorously for 30 min. BDO (604 mg, 6.64 mmol) was added to the reaction mixture, and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The TPU exhibited the following characteristics: Mn=85000, PDI=2.2, UTS=27 MPa, elongation at break=475%, Young's modulus=15 MPa.
TPU having mixtures of PIB and PHMO in different weight proportions as soft segment was synthesized using the two-step procedure according to the synthetic procedure exemplified in
For example, PIB-PHMO-82-8 was synthesized as follows. HO-Allyl-PIB-Allyl-OH (Mn=2200, 4.6 g, 2.1 mmol) and PHMO (Mn=920, 1.15 g, 1.25 mmol) were dried by azeotropic distillation from dry toluene (10 mL) solution. The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (37.26 mg, 0.092 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (2.3 g, 9.22 mmol) was added to this mixture and the mixture was stirred vigorously for 30 min. BDO (534 mg, 5.87 mmol) was added to the resulting reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The TPU exhibited the following characteristics: Mn=73000, PDI=3.4, UTS=18 MPa, elongation at break=280%, Young's modulus=27 MPa.
TPU having mixtures of hydroxypropyl telechelic PIB and PHMO in different weight proportions as soft segment was synthesized using the two-step procedure according to the synthetic procedure exemplified in
For example, PIBsat-PHMO-82-6 was synthesized as follows. HO-propyl-PIB-propyl-OH (Mn=2000, 4.6 g, 2.3 mmol) and PHMO (Mn=920, 1.15 g, 1.25 mmol) were dried by azeotropic distillation from dry toluene (10 mL) solution. The mixture was kept at 45° C. for 3 hours under vacuum. 25 mL of dry toluene was added to this mixture, followed by Sn(Oct)2 (26.3 mg, 0.065 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. MDI (1.62 g, 6.48 mmol) was added to this mixture and the mixture was stirred vigorously for 30 min. BDO (267 mg, 2.93 mmol) was added to the resulting reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The TPU exhibited the following characteristics: Mn=120000, PDI=3.4, UTS=16 MPa, elongation at break=550%, Young's modulus=6 MPa.
TPU having mixtures of hydroxypropyl telechelic PIB and PTMO-diol in different weight proportions as soft segment was synthesized using the two-step procedure according to the synthetic procedure exemplified in
For example, PIBsat-PTMO-82-9 was synthesized as follows. HO-propyl-PIB-propyl-OH (Mn=2000, 2.8 g, 1.4 mmol) and PTMO (Mn=1000, 0.8 g, 0.8 mmol) were dried by azeotropic distillation from dry toluene (10 mL) solution. The mixture was kept at 45° C. for 3 hours under vacuum and 25 mL of dry toluene was added to this mixture. The temperature of the mixture was raised to 100° C. under a slow stream of dry nitrogen gas. MDI (1.92 g, 7.7 mmol) was added to this mixture and the mixture was stirred vigorously for 1 h and 30 min. BDO (500 mg, 5.5 mmol) was added to the resulting reaction mixture and the mixture was stirred for 4 hours at 100° C. The mixture was cooled to room temperature, poured in a Teflon mold and the solvent was evaporated at room temperature in air for 48 hours. Finally the polymer was dried under vacuum at 50° C. for 12 hours.
The TPU exhibited the following characteristics: Mn=88000, PDI=3.7.
Long term in vitro biostability of termoplastic polyurethanes (TPUs) containing mixed polyisobutylene (PIB)/poly(tetramethylene oxide) (PTMO) soft segment was studied under accelerated conditions in 20% H2O2 solution containing 0.1M CoCl2 at 50° C. to predict resistance to metal ion oxidative degradation in vivo. The PIB-based TPUs containing PTMO showed significant oxidative stability as compared to the commercial controls such as Pellethane™ 2686-55D and 2686-80 A. After 12 weeks in vitro (equivalent of approximately 10 years in vivo) the PIB-PTMO TPUs with 10-20% PTMO in the soft segment showed 6-15% weight loss whereas the Pellethanes™ degraded completely in about 9 weeks. The weight loss was linearly proportional to the PTMO content in the PIB-PTMO TPUs. ATR-FTIR spectroscopy confirmed the degradation of Pellethanes™™ via MIO by the consistent loss of the approximately 1110 cm−1 aliphatic C—O—C stretching peak height attributed to chain scission, and the appearance of a new peak approximately 1174 cm−1 attributed crosslinking. No such absorption bands were apparent in the spectra of the PIB-based TPUs. The PIB-based TPUs exhibited 10-30% drop in tensile strength compared to 100% for the Pellethanes™ after 12 weeks. The drop in tensile strength correlated approximately with PTMO content in the TPU. Molecular weight results correlated well with tensile strength, showing a slight decrease 10-15% at 12 weeks. The Pellethanes™ showed a dramatic decrease in Mn as well as an increase in low molecular weight degradation product. SEM showed severe cracking in the Pellethanes™ after two weeks, whereas the PIB-based TPUs exhibited a continuous surface morphology. The weight loss, tensile, and SEM data correlate well with each other and indicate excellent biostability of these materials.
Polyurethanes
Control samples consisted of Pellethane™ 2363-55D and Pellethane™ 2363-80 A. Polyurethanes of varying hardness and PIB:PTMO compositions were synthesized as reported previously and are listed in Table 24. The two-stage process is described for a representative TPU (60 A 82) as follows: HO-Allyl-PIB-Allyl-OH (Mn=2200 g/mol, 5.2 g, 2.36 mmol) and PTMO (Mn=1000 g/mol, 1.3 g, 1.3 mmol) were dried by azeotropic distillation using dry toluene (10 mL). The mixture was kept at 45° C. for 3 hours under vacuum. To it 25 mL of dry toluene was added followed by Sn(Oct)2 (28.3 mg, 0.07 mmol) in toluene. The mixture was heated at 80° C. under a slow stream of dry nitrogen gas. To it MDI (1.76 g, 7.02 mmol) was added and the mixture was stirred vigorously for 30 min. To it BDO (302 mg, 3.36 mmol) was added and the mixture was stirred at 100° C. for 4 hours. The mixture was cooled to room temperature, poured into a Teflon® mold and the solvent was evaporated at room temperature in air for 48 hours. Finally, the polymer was dried under vacuum at 50° C. for 12 hours. A PIB TPU without PTMO was prepared similarly. The saturated PIB-PTMO polyurethane was synthesized using HO-propyl-PIB-propyl-OH, prepared using a method developed by Kennedy (Iván, B.; Kennedy, J. P. J. Polym. Sci., Part A: Polym. Chem. 1990, 28, 89). The polyurethanes were characterized prior to accelerated degradation using 1H NMR and GPC. The harder compositions (80 A 91, 100 A) did not dissolve in the GPC eluent.
aHO-PIB-OH, Mn = 2200 g/mol.
bHO-PTMO-OH, Mn = 1000 g/mol
The polyurethanes were compression molded using a Carver Laboratory Press model C at a load of 16,000 lbs. at 160° C. They were molded into thin films ranging in thickness from 0.2 mm-0.5 mm and cut into rectangular strips with approximate dimensions of 3 mm in width and 30 mm in length.
In Vitro Accelerated Degradation
The samples were placed in vials and soaked in a 20% H2O2 in aqueous 0.1 M CoCl2 solution and stored at 50° C. The solutions were changed every other day to ensure a steady concentration of radicals. At time points after 1, 2, 4, 6, and 12 weeks, dedicated samples were removed from the oxidative environment, washed 7 times in aqueous 1% Triton X-100 surfactant solution, 5 times in ethanol, and 5 times in distilled water and dried under vacuum at 80° C. until constant weight.
Characterization
Dry samples were characterized by weight loss, ATR-FTIR, ultimate tensile strength, elongation at break, SEM, and GPC. Each data point consisted of three identical samples. Of the quantitative data, the reported value is an average of the three samples.
ATR-FTIR
ATR-FTIR was performed on a Thermo Electron Corporation Nicolet 4700 FT-IR with a Thermo Electron Corporation Smart Orbit attachment for ATR with a diamond crystal. Thirty-two scans were averaged to obtain one representative spectrum for each sample. The respective dry clean TPU strip was placed on the crystal, firmly secured using the foot attachment, and scanned for analysis. The region of interest was between approximately 1700 cm−1 and 1100 cm−1, which includes HS degradation product (approximately 1650 cm−1), SS degradation moiety (approximately 1110 cm−1) and product (approximately 1170 cm−1) and the normalized reference peak (approximately 1410 cm−1).
Weight Loss
Weights were measured of dry polyurethane films before and after oxidative treatment on a Sartorius MC1 Analytic AC 210S balance.
Mechanical Testing
Tensile testing was performed at room temperature and atmospheric conditions with a 50 lb. load cell on an Instron Model Tensile Tester 4400R at 50 mm/min extension rate until failure. Ultimate tensile strength and elongation at break were recorded.
GPC Analysis
Molecular weights and molecular weight distributions were measured with a Waters HPLC system equipped with a model 510 HPLC pump, model 410 differential refractometer, model 441 absorbance detector, online multiangle laser light scattering (MALLS) detector (MiniDawn, Wyatt Technology Inc.), Model 712 sample processor, and five Ultrastyragel GPC columns connected in the following series: 500, 103, 104, 105, and 100 Å. THF:TBAB (98:2, wt:wt) was used as a carrier solvent with a flow rate of 1 mL/min.
Scanning Electron Microscopy
Portions of the dry treated films were isolated for SEM analysis. Surface morphology was observed on gold sputter coated samples using a Denton Vacuum Desk IV Cold Cathode Sputter Coater. The samples were sputter coated for 1.5 min at 25% power, corresponding to a thickness of approximately 15 Å of gold. The coated samples were observed using a JEOL model JSM 7401F field emission scanning electron microscope. Several representative pictures were taken at 30× and 300× magnification.
3. Results and discussion
ATR-FTIR
ATR-FTIR analysis was performed to confirm the presence and progression of the MIO mechanism as put forth by Schubert and coworkers. According to their suggested mechanism, a hydroxyl radical may abstract an α-hydrogen from the polyether segment. The resulting radical may combine with another chain radical to form a crosslink junction or react with another hydroxyl radical to form a hemiacetal. The hemiacetal oxidizes to ester which is subsequently acid hydrolyzed resulting in chain scission. Therefore progression of degradation can be observed by following the disappearance of the SS ether peak and/or the appearance of the crosslinking peak. All spectra were normalized to the peak at 1410 cm−1, which corresponds to the aromatic C—C stretch of the hard segment.
The PIB-PTMO polyurethanes all show very small changes in the FTIR spectrum. A representative spectrum, that of 60 A 82, is shown in
As can be seen, There is no appreciable change in the aliphatic ether C—O—C absorbance at 1110 cm−1 and C—O—C branching absorbance at approximately 1174 cm−1 is absent. However, an increase in the aliphatic absorbances with time is observed (aliphatic CH2 bending at 1470 cm−1, PIB dimethyl wag at 1388 cm−1, and aliphatic α-CH2 wag at 1365 cm−1). This behavior can be rationalized by migration of PIB segments to the surface during vacuum drying at 80° C. In these PIB-PTMO TPUs cross-linking may be absent since there is not a significant presence or mobility of PTMO to allow two polymer radicals to combine before they are otherwise cleaved. Similar results are observed in the other PIB-PTMO TPU spectra. The Sat 60 A 91 batch was included in this study to determine if the unsaturated allyl moiety in the PIB diol was vulnerable to oxidation. The FTIR spectrum of the TPU using the saturated diol appears identical to that of the TPU containing unsaturated diol. Additionally the PIB 60 A TPU was included to confirm that there is only polyether SS degradation, and not HS degradation in these TPUs. This hypothesis was confirmed as the spectrum shows no change at all. There is no change in the PIB absorbance at 1388 cm−1 or ether absorbance at 1111 cm−1 since there is no polyether to be degraded. There is also no evidence of HS degradation. In Table 25 are listed the IR absorbances where trends of change were observed.
The PeMethane™ samples showed the expected behavior as is consistent with previous studies. The spectra of P55D are shown in
The spectrum shows a significant decrease in aliphatic C—O—C absorption at 1109 cm−1 after 1 week, then more slowly until 6 weeks. Concurrently, we observe a rapid disappearance of the aliphatic α-CH2 absorbance at 1364 cm−1 after just one week. Also the C—O—C branching absorbance at 1172 cm−1 is observed immediately at 1 week, then stays constant in magnitude. As it will be seen later, the Pellethanes™ continued to degrade at a constant, if not accelerated rate after 1 week, and so an explanation is in order for the IR spectra. ATR-FTIR is a surface characterization technique and degradation is expected to begin at the surface. Therefore we conclude that the segments vulnerable at the surface are oxidized almost immediately and deeper oxidation occurs in the following weeks as observed from the rest of the analyses.
Weight Loss
The weight loss plotted against time is shown in
As can be seen for the PIB-PTMO TPUs there is approximately a linear relationship between the weight loss and the PTMO content. This discovery supports the notion that it is the polyether SS which degrades via MIO and it is these portions which are excised from the polyurethane. Interestingly, 60 A 82 showed a lower weight loss than expected for its PTMO content. The TPU which contained only PIB also showed a small weight loss, which fits the plot. Since there is such a large surface area to volume ratio, we expect to see some small erosion from the surface. The PeMethane™ control samples showed noticeable weight loss even after 1 week in vitro, and P80 A and P55D completely degraded after approximately 7 and 9 weeks, respectively. These findings are consistent with previous findings concerning such polyether based TPUs.
Mechanical Properties
Tensile strength is plotted as a percentage of the original untreated sample vs. time in
A drastic difference in the plots for P55D versus the PIB-PTMO TPUs can be seen. In the PIB-PTMO TPUs a minimal decrease in tensile strength is observed for all samples, although the rate of tensile loss varies for the different samples. The PIB-PTMO TPUs show differing losses which are roughly correlated to the PTMO content. Among the 60 A batch, the tensile losses from the different compositions are comparable. The 12 weeks data point for the 60 A 91 could not be obtained because of a poor sample set. Nevertheless, the trend observed up to 6 weeks follows very closely that of the Sat 60 A 91. Minimal decrease in tensile strength was also observed in the 60 A PIB sample, which showed no degradation as evident from weight loss and FTIR studies. This indicates that 1-2 MPa may be within experimental error with the load cell and instrument used. Among the 80 A batch the 80/20 composition shows ˜21% drop in tensile strength, whereas the 90/10 composition shows only a decrease of ˜13%. The 80 A 73 sample (not shown) showed an initial increase in tensile strength, then subsequently a slower decrease. This is attributed to be due to crosslinking initially, followed by chain scission consistent with the increased amount of PTMO in this sample. At this amount of PTMO (19.5% of total TPU), there are sufficient concentration of chain radicals such that crosslinking is able to occur as well as chain scission. Although the % tensile strength at 12 weeks is greater than the other PIB-PTMO TPUs, extrapolation of the data would predict that the tensile strength 80 A 73 would drop more sharply at longer time intervals.
P55D shows greater resistance to degradation compared to P80 A due to more crystallinity. Thus the 100 A 82 composition is expected to have comparable if not better strength than the 80 A 82 composition, yet we see greater tensile drop. This may suggest that PIB is a better protector of the surface than the hard segment. Some of the samples actually show inhibition periods wherein the tensile strength does not begin to decrease until 2, 4, or even 6 weeks (esp. 80 A 82). The ultimate elongation of the PIB-PTMO TPUs did not change significantly over the course of the treatment. The Pellethanes™ again showed expected of MIO behavior. P55D showed gradual tensile loss over time up to 6 weeks, and at 12 weeks there was no sample to test. P80 A (not shown) showed an initial increase in tensile strength after one week, then a gradual decrease.
This is explained by crosslinking of the chains initially, with chain scission occurring afterward as was observed with 80 A 73.
GPC Analysis
The TPU samples were dissolved in the carrier solvent of THF:TBAB (98:2, wt:wt). However, some of the harder compositions could not be dissolved. Representative GPC RI traces are shown
The loss in molecular weight is minimal in agreement with the weight loss and tensile data. Mn decreases slightly from 130,000 g/mol to 112,000 g/mol after 6 weeks, then negligibly to 110,000 g/mol at 12 weeks while the PDI remained unchanged at 1.6. These data are in agreement with the FTIR and tensile data.
In
SEM
Representative SEM pictures taken at 300× magnification are shown in
In
The 60 A series show analogous morphologies, with the 90/10 composition showing a less flawed surface. The 100 A 82 composition shows morphology comparable to 80 Å91.
Conclusion
After 12 weeks in vitro, which correlates to approximately 10 years in vivo, the thermoplastic polyurethanes of the present invention showed minimal degradation and minimal decrease in performance. Using unsaturated PIB diol rather than saturated PIB diol did not have an effect on the degradation of the thermoplastic polyurethanes of the invention. The PIB segment and the hard segment were not observed to degrade. Increasing the amount of polyether diol incorporated in the thermoplastic polyurethanes of the invention increased the degradation rate, suggesting a degradation mechanism identical to that postulated before for PTMO-based thermoplastic polyurethanes. Therefore, a low PTMO content was considered to be desirable to ensure biostability.
While this invention has been particularly shown and described with references to example embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.
This application is a divisional of U.S. application Ser. No. 15/417,262 filed Jan. 27, 2016, which is a continuation of U.S. application Ser. No. 12/685,858, filed Jan. 12, 2010, each of which claims the benefit of U.S. Provisional Application No. 61/204,856, filed on Jan. 12, 2009, U.S. Provisional Application No. 61/211,310, filed on Mar. 26, 2009, and U.S. Provisional Application No. 61/279,629, filed on Oct. 23, 2009, all of which are herein incorporated by reference in their entirety.
| Number | Name | Date | Kind |
|---|---|---|---|
| 2182513 | William | Dec 1939 | A |
| 2202877 | Stevens et al. | Jun 1940 | A |
| 2240558 | Ellis | May 1941 | A |
| 2451420 | Watkins | Oct 1948 | A |
| 2463452 | George | Mar 1949 | A |
| 3069236 | Schultz et al. | Dec 1962 | A |
| 3148028 | Schultz et al. | Sep 1964 | A |
| 3328372 | Thomas et al. | Jun 1967 | A |
| 3427366 | Verdol et al. | Feb 1969 | A |
| 3505252 | Brotherton et al. | Apr 1970 | A |
| 3642964 | Rausch et al. | Feb 1972 | A |
| 3755265 | Fletcher et al. | Aug 1973 | A |
| 3815611 | Denniston | Jun 1974 | A |
| 3966624 | Doling et al. | Jun 1976 | A |
| 4043331 | Martin et al. | Aug 1977 | A |
| 4103079 | Thaler | Jul 1978 | A |
| 4118427 | Rhein et al. | Oct 1978 | A |
| 4145515 | Pogozelski et al. | Mar 1979 | A |
| 4154913 | Ambrose et al. | May 1979 | A |
| 4157429 | Ambrose et al. | Jun 1979 | A |
| 4157430 | Ambrose et al. | Jun 1979 | A |
| 4230509 | Tulis et al. | Oct 1980 | A |
| 4276394 | Kennedy et al. | Jun 1981 | A |
| 4304771 | Suh et al. | Dec 1981 | A |
| 4316973 | Kennedy | Feb 1982 | A |
| 4342849 | Kennedy | Aug 1982 | A |
| 4352359 | Larimore et al. | Oct 1982 | A |
| 4374276 | Boden et al. | Feb 1983 | A |
| 4404297 | Fishler et al. | Sep 1983 | A |
| 4420411 | Boden et al. | Dec 1983 | A |
| 4423185 | Matsumoto et al. | Dec 1983 | A |
| 4425264 | Boden et al. | Jan 1984 | A |
| 4430233 | Boden et al. | Feb 1984 | A |
| 4477604 | Oechsle, III | Oct 1984 | A |
| 4484586 | McMickle et al. | Nov 1984 | A |
| 4486572 | Kennedy | Dec 1984 | A |
| 4508889 | Noren et al. | Apr 1985 | A |
| 4518615 | Cherukuri et al. | May 1985 | A |
| 4539996 | Engel | Sep 1985 | A |
| 4570270 | Oechsle, III | Feb 1986 | A |
| 4600652 | Solomon et al. | Jul 1986 | A |
| 4675361 | Ward, Jr. | Jun 1987 | A |
| 4686137 | Ward et al. | Aug 1987 | A |
| 4752626 | Hoye et al. | Jun 1988 | A |
| 4767885 | Kennedy | Aug 1988 | A |
| 4771082 | Solodovnik et al. | Sep 1988 | A |
| 4861830 | Ward, Jr. | Aug 1989 | A |
| 4880883 | Grasel et al. | Nov 1989 | A |
| 4888389 | Kennedy et al. | Dec 1989 | A |
| 4906673 | Mori et al. | Mar 1990 | A |
| 4910321 | Kennedy et al. | Mar 1990 | A |
| 4928689 | Hauser | May 1990 | A |
| 4939184 | Kennedy | Jul 1990 | A |
| 4982038 | Kimble et al. | Jan 1991 | A |
| 5000875 | Kolouch | Mar 1991 | A |
| 5017664 | Grasel et al. | May 1991 | A |
| 5026814 | Re et al. | Jun 1991 | A |
| 5029585 | Lieber et al. | Jul 1991 | A |
| 5090422 | Dahl et al. | Feb 1992 | A |
| 5103837 | Weidlich et al. | Apr 1992 | A |
| 5120813 | Ward, Jr. | Jun 1992 | A |
| 5129404 | Spehr et al. | Jul 1992 | A |
| 5149739 | Biing-Lin | Sep 1992 | A |
| 5152299 | Soukup | Oct 1992 | A |
| 5171760 | Kaszas et al. | Dec 1992 | A |
| 5194505 | Brugel | Mar 1993 | A |
| 5212248 | Knoll et al. | May 1993 | A |
| 5269810 | Hull et al. | Dec 1993 | A |
| 5282844 | Stokes et al. | Feb 1994 | A |
| 5285844 | Schneid | Feb 1994 | A |
| 5322520 | Milder | Jun 1994 | A |
| 5324324 | Vachon et al. | Jun 1994 | A |
| 5330520 | Maddison et al. | Jul 1994 | A |
| 5332791 | Knoll et al. | Jul 1994 | A |
| 5332798 | Ferreri et al. | Jul 1994 | A |
| 5340881 | Kennedy et al. | Aug 1994 | A |
| 5385579 | Helland | Jan 1995 | A |
| 5428123 | Ward et al. | Jun 1995 | A |
| 5433730 | Alt | Jul 1995 | A |
| 5442010 | Hauenstein et al. | Aug 1995 | A |
| 5442015 | Kennedy et al. | Aug 1995 | A |
| 5476496 | Strandberg et al. | Dec 1995 | A |
| 5554178 | Dahl et al. | Sep 1996 | A |
| 5559067 | Lerner et al. | Sep 1996 | A |
| 5585444 | Blackborow et al. | Dec 1996 | A |
| 5589563 | Ward et al. | Dec 1996 | A |
| 5609622 | Soukup et al. | Mar 1997 | A |
| 5630844 | Dogan | May 1997 | A |
| 5637647 | Faust | Jun 1997 | A |
| 5663234 | Kennedy et al. | Sep 1997 | A |
| 5665823 | Saxena et al. | Sep 1997 | A |
| 5677386 | Faust | Oct 1997 | A |
| 5681514 | Woody | Oct 1997 | A |
| 5741331 | Pinchuk | Apr 1998 | A |
| 5753764 | Boutevin et al. | May 1998 | A |
| 5755762 | Bush | May 1998 | A |
| 5766527 | Schildgen et al. | Jun 1998 | A |
| 5837313 | Ding et al. | Nov 1998 | A |
| 5849415 | Shalaby et al. | Dec 1998 | A |
| 5852118 | Horrion et al. | Dec 1998 | A |
| 5853652 | Schildgen et al. | Dec 1998 | A |
| 5861023 | Vachon | Jan 1999 | A |
| 5874484 | Dirckx et al. | Feb 1999 | A |
| 5886089 | Knowlton | Mar 1999 | A |
| 5898057 | Chiang et al. | Apr 1999 | A |
| 5902329 | Hoffmann et al. | May 1999 | A |
| 5912302 | Gadkari et al. | Jun 1999 | A |
| 5931862 | Carson | Aug 1999 | A |
| 5987746 | Williams | Nov 1999 | A |
| 5991667 | Feith | Nov 1999 | A |
| 6005051 | Kennedy et al. | Dec 1999 | A |
| 6010715 | Wick et al. | Jan 2000 | A |
| 6072003 | Horrion et al. | Jun 2000 | A |
| 6087454 | Vanhaeren et al. | Jul 2000 | A |
| 6093197 | Bakula et al. | Jul 2000 | A |
| 6117554 | Shalaby et al. | Sep 2000 | A |
| 6194487 | Morimoto et al. | Feb 2001 | B1 |
| 6200589 | Kennedy et al. | Mar 2001 | B1 |
| 6228945 | Kennedy et al. | May 2001 | B1 |
| 6236893 | Thong | May 2001 | B1 |
| 6242058 | Bahadur et al. | Jun 2001 | B1 |
| 6253110 | Brabec et al. | Jun 2001 | B1 |
| 6256541 | Heil et al. | Jul 2001 | B1 |
| 6284682 | Troczynski et al. | Sep 2001 | B1 |
| 6361780 | Ley et al. | Mar 2002 | B1 |
| 6363286 | Zhu et al. | Mar 2002 | B1 |
| 6365674 | Kaufhold et al. | Apr 2002 | B1 |
| 6426114 | Troczynski et al. | Jul 2002 | B1 |
| 6436136 | Flodin et al. | Aug 2002 | B1 |
| 6444334 | Doi et al. | Sep 2002 | B1 |
| 6545097 | Pinchuk et al. | Apr 2003 | B2 |
| 6555619 | Kennedy et al. | Apr 2003 | B1 |
| 6600956 | Maschino et al. | Jul 2003 | B2 |
| 6627724 | Meijs et al. | Sep 2003 | B2 |
| 6653365 | Jia | Nov 2003 | B2 |
| 6703433 | Bahadur et al. | Mar 2004 | B1 |
| 6706779 | Bahadur et al. | Mar 2004 | B2 |
| 6709514 | Hossainy | Mar 2004 | B1 |
| 6730324 | Troczynski et al. | May 2004 | B2 |
| 6770325 | Troczynski et al. | Aug 2004 | B2 |
| 6808766 | Miyama et al. | Oct 2004 | B1 |
| 6827881 | Molnar et al. | Dec 2004 | B2 |
| 6849667 | Haseyama et al. | Feb 2005 | B2 |
| 6852794 | Puhala et al. | Feb 2005 | B2 |
| 6869466 | Day et al. | Mar 2005 | B2 |
| 6870024 | Haubennestel et al. | Mar 2005 | B2 |
| 6889092 | Zhu et al. | May 2005 | B2 |
| 6896965 | Hossainy | May 2005 | B1 |
| 7013182 | Krishnan | Mar 2006 | B1 |
| 7065411 | Verness | Jun 2006 | B2 |
| 7101956 | Benz et al. | Sep 2006 | B2 |
| 7105622 | Kennedy et al. | Sep 2006 | B2 |
| 7115300 | Hossainy | Oct 2006 | B1 |
| 7119138 | Feeney et al. | Oct 2006 | B1 |
| 7160941 | Jin et al. | Jan 2007 | B2 |
| 7174221 | Chen et al. | Feb 2007 | B1 |
| 7180172 | Sethumadhavan et al. | Feb 2007 | B2 |
| 7196142 | Kennedy et al. | Mar 2007 | B2 |
| 7231259 | Jenney et al. | Jun 2007 | B2 |
| 7247364 | Hossainy et al. | Jul 2007 | B2 |
| 7279175 | Chen et al. | Oct 2007 | B2 |
| 7280875 | Chitre et al. | Oct 2007 | B1 |
| 7289856 | Karicherla | Oct 2007 | B1 |
| 7292890 | Whitehurst et al. | Nov 2007 | B2 |
| 7347751 | Sweeney et al. | Mar 2008 | B2 |
| 7358306 | Turri et al. | Apr 2008 | B2 |
| D579758 | Tanaka et al. | Nov 2008 | S |
| 7465777 | Zoromski et al. | Dec 2008 | B2 |
| 7470728 | Jia et al. | Dec 2008 | B2 |
| 7501179 | Song et al. | Mar 2009 | B2 |
| 7504052 | Ehbing et al. | Mar 2009 | B2 |
| 7524890 | Lee et al. | Apr 2009 | B2 |
| 7553546 | Tan | Jun 2009 | B1 |
| 7572515 | Sethumadhavan et al. | Aug 2009 | B2 |
| 7617004 | Bartels et al. | Nov 2009 | B2 |
| 7715922 | Jiahong | May 2010 | B1 |
| 7727541 | Richard et al. | Jun 2010 | B2 |
| 7756589 | Mohan | Jul 2010 | B2 |
| 7820769 | Seifalian et al. | Oct 2010 | B2 |
| 7825199 | Matyjaszewski et al. | Nov 2010 | B1 |
| 7881808 | Borgaonkar et al. | Feb 2011 | B2 |
| 7979142 | Krishnan | Jul 2011 | B2 |
| 8034874 | Strickler et al. | Oct 2011 | B2 |
| 8075906 | Richard et al. | Dec 2011 | B2 |
| 8163826 | Willberg et al. | Apr 2012 | B2 |
| 8304471 | Joseph et al. | Nov 2012 | B2 |
| 8304482 | Joseph et al. | Nov 2012 | B2 |
| 8324290 | Desai et al. | Dec 2012 | B2 |
| 8349123 | Zhang et al. | Jan 2013 | B2 |
| 8372468 | Desai et al. | Feb 2013 | B2 |
| 8374704 | Desai et al. | Feb 2013 | B2 |
| 8394393 | Mather et al. | Mar 2013 | B2 |
| 8501831 | Desai et al. | Aug 2013 | B2 |
| D689734 | Bock | Sep 2013 | S |
| 8529934 | Desai et al. | Sep 2013 | B2 |
| 8644952 | Desai et al. | Feb 2014 | B2 |
| 8660663 | Wolf et al. | Feb 2014 | B2 |
| 8674034 | Kennedy et al. | Mar 2014 | B2 |
| 8676344 | Desai et al. | Mar 2014 | B2 |
| 8765238 | Atanasoska et al. | Jul 2014 | B2 |
| 8889926 | Kennedy et al. | Nov 2014 | B2 |
| 8903507 | Desai et al. | Dec 2014 | B2 |
| 8927660 | Desai et al. | Jan 2015 | B2 |
| 8962785 | Faust et al. | Feb 2015 | B2 |
| 8969424 | Lin | Mar 2015 | B2 |
| 8992512 | Richard et al. | Mar 2015 | B2 |
| 9011516 | Weber et al. | Apr 2015 | B2 |
| 9574043 | Faust et al. | Feb 2017 | B2 |
| 9655720 | Bluestein et al. | May 2017 | B2 |
| 9926399 | Faust et al. | Mar 2018 | B2 |
| 10513576 | Faust et al. | Dec 2019 | B2 |
| 10526429 | Delaney et al. | Jan 2020 | B2 |
| 10562998 | Faust et al. | Feb 2020 | B2 |
| 20010021743 | Wakana et al. | Sep 2001 | A1 |
| 20020012694 | Moo-Young et al. | Jan 2002 | A1 |
| 20020022826 | Reynolds et al. | Feb 2002 | A1 |
| 20020028303 | Bahadur et al. | Mar 2002 | A1 |
| 20020058981 | Zhu et al. | May 2002 | A1 |
| 20020107133 | Troczynski et al. | Aug 2002 | A1 |
| 20020107330 | Pinchuk et al. | Aug 2002 | A1 |
| 20020138123 | Casas-Bejar et al. | Sep 2002 | A1 |
| 20020155144 | Troczynski et al. | Oct 2002 | A1 |
| 20020193459 | Haseyama et al. | Dec 2002 | A1 |
| 20020198282 | Jia | Dec 2002 | A1 |
| 20030018156 | Meijs et al. | Jan 2003 | A1 |
| 20030031699 | Van Antwerp | Feb 2003 | A1 |
| 20030040785 | Maschino et al. | Feb 2003 | A1 |
| 20030050408 | Puhala et al. | Mar 2003 | A1 |
| 20030055179 | Ota et al. | Mar 2003 | A1 |
| 20030073961 | Happ | Apr 2003 | A1 |
| 20030093136 | Osypka et al. | May 2003 | A1 |
| 20030108588 | Chen et al. | Jun 2003 | A1 |
| 20030125499 | Benz et al. | Jul 2003 | A1 |
| 20030140787 | Day et al. | Jul 2003 | A1 |
| 20030176613 | Hohberg et al. | Sep 2003 | A1 |
| 20030204022 | Kennedy et al. | Oct 2003 | A1 |
| 20030236558 | Whitehurst et al. | Dec 2003 | A1 |
| 20040037886 | Hsu | Feb 2004 | A1 |
| 20040054210 | Benz et al. | Mar 2004 | A1 |
| 20040059402 | Soukup et al. | Mar 2004 | A1 |
| 20040063805 | Pacetti et al. | Apr 2004 | A1 |
| 20040068036 | Halladay et al. | Apr 2004 | A1 |
| 20040127674 | Haubennestel et al. | Jul 2004 | A1 |
| 20040143255 | Vanney et al. | Jul 2004 | A1 |
| 20040171779 | Matyjaszewski et al. | Sep 2004 | A1 |
| 20040175558 | El-Nounou et al. | Sep 2004 | A1 |
| 20040186545 | Rosero et al. | Sep 2004 | A1 |
| 20040193139 | Armstrong et al. | Sep 2004 | A1 |
| 20040198901 | Graham et al. | Oct 2004 | A1 |
| 20040262739 | Sethumadhavan et al. | Dec 2004 | A1 |
| 20050031874 | Michal et al. | Feb 2005 | A1 |
| 20050037050 | Weber | Feb 2005 | A1 |
| 20050038135 | Jin et al. | Feb 2005 | A1 |
| 20050043585 | Datta | Feb 2005 | A1 |
| 20050060022 | Felt et al. | Mar 2005 | A1 |
| 20050070985 | Knapp et al. | Mar 2005 | A1 |
| 20050079199 | Heruth et al. | Apr 2005 | A1 |
| 20050080470 | Westlund et al. | Apr 2005 | A1 |
| 20050143808 | Hossainy et al. | Jun 2005 | A1 |
| 20050173780 | Sethumadhavan et al. | Aug 2005 | A1 |
| 20050180919 | Tedeschi | Aug 2005 | A1 |
| 20050272894 | Kennedy et al. | Dec 2005 | A1 |
| 20050288408 | Resendes et al. | Dec 2005 | A1 |
| 20050288476 | Yilgor et al. | Dec 2005 | A1 |
| 20060009540 | Jia et al. | Jan 2006 | A1 |
| 20060047083 | Yilgor et al. | Mar 2006 | A1 |
| 20060047098 | Anna et al. | Mar 2006 | A1 |
| 20060069419 | Sweeney et al. | Mar 2006 | A1 |
| 20060111465 | Jia et al. | May 2006 | A1 |
| 20060129217 | Krishnan | Jun 2006 | A1 |
| 20060135721 | Lange | Jun 2006 | A1 |
| 20060142503 | Lang et al. | Jun 2006 | A1 |
| 20060171981 | Richard et al. | Aug 2006 | A1 |
| 20060223946 | Faust et al. | Oct 2006 | A1 |
| 20060235499 | Heil et al. | Oct 2006 | A1 |
| 20060249446 | Yeager | Nov 2006 | A1 |
| 20060249447 | Yeager | Nov 2006 | A1 |
| 20060264577 | Faust et al. | Nov 2006 | A1 |
| 20070051531 | Borgaonkar et al. | Mar 2007 | A1 |
| 20070093604 | Kennedy et al. | Apr 2007 | A1 |
| 20070106144 | Squeri | May 2007 | A1 |
| 20070117925 | Strickler et al. | May 2007 | A1 |
| 20070122361 | Jia | May 2007 | A1 |
| 20070128246 | Hossainy et al. | Jun 2007 | A1 |
| 20070135601 | Diakoumakos et al. | Jun 2007 | A1 |
| 20070141339 | Song et al. | Jun 2007 | A1 |
| 20070142560 | Song et al. | Jun 2007 | A1 |
| 20070151531 | Masaoka et al. | Jul 2007 | A1 |
| 20070190104 | Kamath et al. | Aug 2007 | A1 |
| 20070190108 | Datta | Aug 2007 | A1 |
| 20070190319 | Kalayci | Aug 2007 | A1 |
| 20070203302 | Kennedy et al. | Aug 2007 | A1 |
| 20070208155 | Zoromski et al. | Sep 2007 | A1 |
| 20070232169 | Strickler et al. | Oct 2007 | A1 |
| 20070239245 | Borgaonkar et al. | Oct 2007 | A1 |
| 20070255378 | Hec et al. | Nov 2007 | A1 |
| 20070269485 | Richard et al. | Nov 2007 | A1 |
| 20070282411 | Franz et al. | Dec 2007 | A1 |
| 20080008739 | Hossainy et al. | Jan 2008 | A1 |
| 20080009939 | Gueriguian et al. | Jan 2008 | A1 |
| 20080051866 | Chen et al. | Feb 2008 | A1 |
| 20080095918 | Kleiner et al. | Apr 2008 | A1 |
| 20080108773 | Wicks et al. | May 2008 | A1 |
| 20080119374 | Willberg et al. | May 2008 | A1 |
| 20080161443 | Lee et al. | Jul 2008 | A1 |
| 20080161900 | Weber et al. | Jul 2008 | A1 |
| 20080167423 | Richards et al. | Jul 2008 | A1 |
| 20080167710 | Dave et al. | Jul 2008 | A1 |
| 20080175881 | Ippoliti et al. | Jul 2008 | A1 |
| 20080194736 | Minqiu | Aug 2008 | A1 |
| 20080208325 | Helmus et al. | Aug 2008 | A1 |
| 20080233164 | Seifalian et al. | Sep 2008 | A1 |
| 20080311173 | Schwarz et al. | Dec 2008 | A1 |
| 20090054961 | Borgaonkar et al. | Feb 2009 | A1 |
| 20090156772 | Strickler et al. | Jun 2009 | A1 |
| 20090187162 | Ohara et al. | Jul 2009 | A1 |
| 20090242123 | Zhang et al. | Oct 2009 | A1 |
| 20090292094 | Larichev et al. | Nov 2009 | A1 |
| 20090326077 | Desai et al. | Dec 2009 | A1 |
| 20100023104 | Desai et al. | Jan 2010 | A1 |
| 20100025703 | Towns et al. | Feb 2010 | A1 |
| 20100055470 | Klun et al. | Mar 2010 | A1 |
| 20100069578 | Faust et al. | Mar 2010 | A1 |
| 20100075018 | Desai et al. | Mar 2010 | A1 |
| 20100107967 | Tanaka et al. | May 2010 | A1 |
| 20100179298 | Faust et al. | Jul 2010 | A1 |
| 20100241071 | Atanasoska et al. | Sep 2010 | A1 |
| 20100241204 | Scheuermann | Sep 2010 | A1 |
| 20100241208 | Pinchuk | Sep 2010 | A1 |
| 20100241209 | Krishnan | Sep 2010 | A1 |
| 20100249296 | Kimura et al. | Sep 2010 | A1 |
| 20100267897 | Kennedy et al. | Oct 2010 | A1 |
| 20100323330 | Jia | Dec 2010 | A1 |
| 20100324200 | Joseph et al. | Dec 2010 | A1 |
| 20110015303 | Joseph et al. | Jan 2011 | A1 |
| 20110045030 | Desai et al. | Feb 2011 | A1 |
| 20110051581 | Janik et al. | Mar 2011 | A1 |
| 20110054580 | Desai et al. | Mar 2011 | A1 |
| 20110054581 | Desai et al. | Mar 2011 | A1 |
| 20110087317 | Borgaonkar et al. | Apr 2011 | A1 |
| 20110152989 | Tan | Jun 2011 | A1 |
| 20110213084 | Kennedy et al. | Sep 2011 | A1 |
| 20110244001 | Mather et al. | Oct 2011 | A1 |
| 20110263808 | Mather et al. | Oct 2011 | A1 |
| 20120077934 | Faust et al. | Mar 2012 | A1 |
| 20120083523 | Richard et al. | Apr 2012 | A1 |
| 20120158107 | Wolf et al. | Jun 2012 | A1 |
| 20120259069 | Kennedy et al. | Oct 2012 | A1 |
| 20120309661 | Adams et al. | Dec 2012 | A1 |
| 20130013040 | Desai et al. | Jan 2013 | A1 |
| 20130041108 | Kennedy et al. | Feb 2013 | A1 |
| 20130041442 | Arnholt et al. | Feb 2013 | A1 |
| 20130079487 | Faust et al. | Mar 2013 | A1 |
| 20130122185 | Desai et al. | May 2013 | A1 |
| 20130131765 | Polkinghorne et al. | May 2013 | A1 |
| 20130131767 | Desai et al. | May 2013 | A1 |
| 20130209716 | Custodero et al. | Aug 2013 | A1 |
| 20130216840 | Radhakrishnan et al. | Aug 2013 | A1 |
| 20130313118 | Lin | Nov 2013 | A1 |
| 20130317128 | Lin | Nov 2013 | A1 |
| 20130330390 | Pacetti | Dec 2013 | A1 |
| 20130331538 | Kennedy et al. | Dec 2013 | A1 |
| 20140074201 | Arnholt et al. | Mar 2014 | A1 |
| 20140088218 | Desai et al. | Mar 2014 | A1 |
| 20140096964 | Chakraborty et al. | Apr 2014 | A1 |
| 20140144580 | Desai et al. | May 2014 | A1 |
| 20140194963 | Desai et al. | Jul 2014 | A1 |
| 20140235905 | Kennedy et al. | Aug 2014 | A1 |
| 20140242141 | Atanasoska et al. | Aug 2014 | A1 |
| 20140256846 | Sevignon et al. | Sep 2014 | A1 |
| 20140272447 | Maye et al. | Sep 2014 | A1 |
| 20140275598 | Freeman et al. | Sep 2014 | A1 |
| 20140288222 | Yano et al. | Sep 2014 | A1 |
| 20140299249 | Oustodero et al. | Oct 2014 | A1 |
| 20140303724 | Bluestein et al. | Oct 2014 | A1 |
| 20140343190 | Oustodero et al. | Nov 2014 | A1 |
| 20140343216 | Oustodero et al. | Nov 2014 | A1 |
| 20140378575 | Sevignon et al. | Dec 2014 | A1 |
| 20150056553 | Huang et al. | Feb 2015 | A1 |
| 20150274876 | Faust et al. | Oct 2015 | A1 |
| 20160008607 | Kane et al. | Jan 2016 | A1 |
| 20160024340 | Rukavina | Jan 2016 | A1 |
| 20160145362 | Settling et al. | May 2016 | A1 |
| 20160311983 | Delaney et al. | Oct 2016 | A1 |
| 20170100237 | Anderson-Cunanan et al. | Apr 2017 | A1 |
| 20170137558 | Faust et al. | May 2017 | A1 |
| 20170174845 | Delaney et al. | Jun 2017 | A1 |
| 20170327622 | Delaney et al. | Nov 2017 | A1 |
| 20180208698 | Faust et al. | Jul 2018 | A1 |
| 20180258196 | Delaney et al. | Sep 2018 | A1 |
| 20190054204 | Delaney et al. | Feb 2019 | A1 |
| 20190218334 | Delaney et al. | Jul 2019 | A1 |
| Number | Date | Country |
|---|---|---|
| PI9003841 | Feb 1992 | BR |
| 1221430 | May 1987 | CA |
| 1248606 | Jan 1989 | CA |
| 2114874 | Aug 1994 | CA |
| 2278680 | Aug 1998 | CA |
| 1221430 | Jun 1999 | CN |
| 102131530 | Jul 2011 | CN |
| 102304679 | Jan 2012 | CN |
| 102365308 | Feb 2012 | CN |
| 102712808 | Oct 2012 | CN |
| 104231207 | Dec 2014 | CN |
| 102573940 | Apr 2015 | CN |
| 104520345 | Apr 2015 | CN |
| 104592850 | May 2015 | CN |
| 104602888 | May 2015 | CN |
| 104610902 | May 2015 | CN |
| 106129383 | Nov 2016 | CN |
| 2418075 | Oct 1975 | DE |
| 19610350 | Sep 1997 | DE |
| 0153520 | Sep 1985 | EP |
| 0259492 | Mar 1988 | EP |
| 0275907 | Jul 1988 | EP |
| 0353471 | Feb 1990 | EP |
| 0610714 | Aug 1994 | EP |
| 0732349 | Sep 1996 | EP |
| 0837097 | Apr 1998 | EP |
| 1061092 | Dec 2000 | EP |
| 1489109 | Dec 2004 | EP |
| 2006328 | Dec 2008 | EP |
| 2385960 | Nov 2011 | EP |
| 2922888 | Sep 2015 | EP |
| 46-025014 | Jul 1971 | JP |
| 61-031417 | Feb 1986 | JP |
| 61-073666 | Apr 1986 | JP |
| 61-236814 | Oct 1986 | JP |
| 63-199719 | Aug 1988 | JP |
| 01-087726 | Jun 1989 | JP |
| 02-088614 | Mar 1990 | JP |
| 02-202908 | Aug 1990 | JP |
| 04-154815 | May 1992 | JP |
| 06-345821 | Dec 1994 | JP |
| 07-102017 | Apr 1995 | JP |
| 07-330591 | Dec 1995 | JP |
| 07-331223 | Dec 1995 | JP |
| 10-087726 | Apr 1998 | JP |
| 11-131325 | May 1999 | JP |
| 11-256069 | Sep 1999 | JP |
| 2000-119363 | Apr 2000 | JP |
| 2000-169814 | Jun 2000 | JP |
| 2000-508368 | Jul 2000 | JP |
| 2000-264947 | Sep 2000 | JP |
| 2000-303255 | Oct 2000 | JP |
| 2001-011319 | Jan 2001 | JP |
| 2001-040064 | Feb 2001 | JP |
| 2001-131879 | May 2001 | JP |
| 2001-521788 | Nov 2001 | JP |
| 2002-202908 | Jul 2002 | JP |
| 2002-348317 | Dec 2002 | JP |
| 2003-137951 | May 2003 | JP |
| 2004-204181 | Jul 2004 | JP |
| 2006-515795 | Jun 2006 | JP |
| 2008-238761 | Oct 2008 | JP |
| 2009-132832 | Jun 2009 | JP |
| 2009-535182 | Oct 2009 | JP |
| 2009-540873 | Nov 2009 | JP |
| 2011-526326 | Oct 2011 | JP |
| 2012-515231 | Jul 2012 | JP |
| 2012-519053 | Aug 2012 | JP |
| 2013-502495 | Jan 2013 | JP |
| 2013-503711 | Feb 2013 | JP |
| 2013-166868 | Aug 2013 | JP |
| 2014-533580 | Dec 2014 | JP |
| 2015-523192 | Aug 2015 | JP |
| 2017-521163 | Aug 2017 | JP |
| 8704625 | Aug 1987 | WO |
| 9316131 | Aug 1993 | WO |
| 9322360 | Nov 1993 | WO |
| 9526993 | Oct 1995 | WO |
| 9700293 | Jan 1997 | WO |
| 9707161 | Feb 1997 | WO |
| 9747664 | Dec 1997 | WO |
| 9833832 | Aug 1998 | WO |
| 9834678 | Aug 1998 | WO |
| 9951656 | Oct 1999 | WO |
| 0213785 | Feb 2002 | WO |
| 0342273 | May 2003 | WO |
| 2004004412 | Jan 2004 | WO |
| 2004014453 | Feb 2004 | WO |
| 2004044012 | May 2004 | WO |
| 2004113400 | Dec 2004 | WO |
| 2005035655 | Apr 2005 | WO |
| 2006011647 | Feb 2006 | WO |
| 2006110647 | Oct 2006 | WO |
| 2007030722 | Mar 2007 | WO |
| 2007117566 | Oct 2007 | WO |
| 2007119687 | Oct 2007 | WO |
| 2007126806 | Nov 2007 | WO |
| 2007130900 | Nov 2007 | WO |
| 2008060333 | May 2008 | WO |
| 2008066914 | Jun 2008 | WO |
| 2008112190 | Sep 2008 | WO |
| 2008127730 | Oct 2008 | WO |
| 2008156806 | Dec 2008 | WO |
| 2009051945 | Apr 2009 | WO |
| 2009058397 | May 2009 | WO |
| 2009153600 | Dec 2009 | WO |
| 2009158600 | Dec 2009 | WO |
| 2009158609 | Dec 2009 | WO |
| 2010039986 | Apr 2010 | WO |
| 2010078552 | Jul 2010 | WO |
| 2010081132 | Jul 2010 | WO |
| 2010107530 | Sep 2010 | WO |
| 2010111280 | Sep 2010 | WO |
| 2010135418 | Nov 2010 | WO |
| 2011022583 | Feb 2011 | WO |
| 2011028873 | Mar 2011 | WO |
| 2011060161 | May 2011 | WO |
| 2012093597 | Jul 2012 | WO |
| 2013005004 | Jan 2013 | WO |
| 2013192186 | Dec 2013 | WO |
| 2014018509 | Jan 2014 | WO |
| 2014081916 | May 2014 | WO |
| 2015007553 | Jan 2015 | WO |
| 2016007367 | Jan 2016 | WO |
| 2017106774 | Jun 2017 | WO |
| 2017127642 | Jul 2017 | WO |
| Entry |
|---|
| Mitzner et. al. Modification of Segmented Poly(Ether Urethanes) by Incorporation of Poly(Isobutylene)Glycol. Journal of Macromolecular Science, Part A., Pure and Applied Chemistry, 34(1 ): 165-178,1997. (Year: 1997). |
| Ako, Masayuke et al., “Polyisobutylene-based urethane foams 1. Comparative reactivities of hydroxyl-terminated polyisobutylene-diols and-triols and other hydroxyl-capped polyols with isocyanate”, Polymer Bulletin 19(2), 137-143 K1988). |
| Bacaloglu, R. and Cotarca, L. “Reactions of Aryl isocyanates with Alcohols in the Presence Ob Tertiary Amines.” Journal f. prakt. Chemie., 330(4):530-540. |
| Bela et al., Living Carbocation Polymerization. XX. Synthesis of Allyl-Telechelic Polyisobutylenes by One-Pot Polymerization-Functionalization polymer. Mater. Sci. Eng. 1988; 58:869-872. |
| Butyl Rubber Properties and Applications, downloaded form URL: hiit://ww.iisrp.com/WebPolymers/02ButylRubberllR.pdf availale on the internet on Jul. 31, 2007 according to Wayback Web Archive. |
| Chang, Victor S.C et al. “Gas Permeability, Water Absorption, Hydrolytic Stability and Air-Oven Aging of Polyisobutylene-Based Polyurethane Networks”, Polymer Bulletin 8(2-3-4), 69-74 (1982). |
| Chen, Chi-Chang et al., “Solid Polymer Electrolytes III Preparation, Characterization, and Ionic Conductivity of New Gelled Polymer Electrolytes Based on Segmented, Perfluoropolyether-Modified Polyurethane”, Journal of Polymer Science: Part A: Polymer Chemistry, vol. 40, pp. 486-495 (2002). |
| Chen, D., et al. Amphiphilic Networks: 11. Biocompatibty and Controlled Drug Release of Poly[lsobutylene-co-2-(dimethy1arnino)Ethyl Methacrylate]. J. of Biomedical Materials Research, 23:1327-1342,1989. |
| Chen, T. K., et al. Glass Transition Behaviors of a Polyurethane Hard Segment based on 4,4'-Diisocyanatodiphenylmethane and 1,4-Butanediol and the Calculation of Microdomain Composition Macromolecules, 30:5068-5074, 1997. |
| Cho, J. C., et al. Synthesis, Characterization, Properties, and Drug Release of Poly(Alkyl Methacrylate-B-lsobutylene-B-Alkyl Methacrylate). Biomacromolecules, 7:2997-3007,2006. |
| Choi, T., et al. Segmented Polyurethanes Derived from Novel Siloxane-Carbonate Soft Segments for Biomedical Applications. Journal of Polymer Science Part B: Polymer Physics, 49:865-872, 2011. |
| Christenson, E. M., et al. Oxidative Mechanisms of Poly(Carbonate Urethane) and Poly(Ether Urethane) Biodegradation: In Vivo and In Vitro Correlations. J. Biomed. Mater. Res., 70A:245-255,2004. |
| Claiborne, T. E., Slepian, M. J., Hossainy, S., & Bluestein, D. (2013). Polymeric trileaflet prosthetic heart valves evolution and path to clinical reality. Expert Rev Med Devices., 9(6):577-594. |
| Communication in Cases for Which No. Other Form is Applicable, issued in PCT/US2013/053448, dated Jul. 28, 2014, 1 page. |
| Cozzens, David et al. Long Term in Vitro Biostability of Segmented Polyisobutylene-Based Thermoplastic Polyurethanes. Journal of Biomedicals Materials Research Journal, Part A, 774-782,2010. |
| De, Priyadarsi et al., “Carbocations Polymerization of Isobutylene Using Methylaliminum Bromide Cointaitors Synthesis of bromoally Functional Polyisobutylene” Macromolecules, Oct. 2006, 39(2), 7527-7533. |
| De, Priyadarsi et al., “Relative Reactivity of C4 Olefins toward the Polyisobutylene Cation” Macromolecules 2006, 39, 6861-6870. |
| Erdodi, G., et al., “Polyisobutylene-Based Polyurethanes. VI. Unprecedented Combination of Mechanical Properties and Oxidative/Hydrolytic Stability by H-Bond Acceptor Chain Extenders” J. Polym. Sci., Part A: Polym. Chem., 48:2361-2371 (2010). |
| Examination Report and Search Report for Chinese Application No. 201380042582.3, dated Dec. 4, 2015, consisting of 6 pages. |
| Extended European Search Report issued in EP appln. 16206626.0, dated Apr. 25, 2017, 8 pages. |
| Fan, L., et al. The Absolute Calibration of a Small-Angle Scattering Instrument with a Laboratory X-ray Souice. XIV International Conference on Small-Angle Scattering (SAS09), Journal of Physics: Conference Series 247, 11 pages, 2010. |
| Faust, R et al., “Method To Prepare Block Copolymers By The Combination Of Cationic And Anionic Polymerization”, U.S. Appl. No. 12/225,905, filed Apr. 5, 2007. |
| Fischer, Stefan; et al. “Synthesis and Biological Evaluation of Bromo-and Fluorodanicalipin A.” Angew. Chern. Int. Ed. 2016, 55,2555-2558. |
| Georgiou, Theoni K; et al. “Amphiphilic Model Conetworks of Polyisobutylene Methacrylate and 2-(Dimethylamino) ethyl Methacrylate Prepared by the Combination of Quasiliving Carbocationic and Group Transfer Polymerizations.” Macromolecules 2007, 40, 2335-2343. |
| Giusti et al., “Synthesis and Characterization of New Potentially Hemocompatible Thermoplastic Elastomers”, Proc. Iupac, I. U. P. A. C., Macromol. Symp., 28th (1982), 371. |
| Giusti, Paolo et al., “Synthesis and Characterization of New potentially Hemocompatible Thermoplastic Elastomers”, p. 371, Abstract. |
| Gunatillake, P.A et al., “Poly(dimethylsiloxane)/Poly(hexamethylene oxide) Mixed Macrodiol Based Polyurethane Elastomers. L Synthesis and Properties”, Journal of Appl. Polym. Sci. 2000, 76, 2026-2040, (Copyright) 2000. |
| Gunatillake, P.A., et al. Synthesis and Characterization of a Series of Poly(alkylene carbonate) Macrodiols and the Effect of Their Structure on the Properties of Polyurethanes. Journal of Applied Polymer Science, 69:1621-1633, 1998. |
| Gyor, M., et al. Living Carbocationic Polymerization of Isobutylene with Blocked Bifunctional Initiators in the Presence of Di-tert-butylpyridine as a Proton Trap. J. of Macromolecular Science, Part A, Pure Appl. Chern., 29 (8):639-653, 1992. |
| H. Mach and P. Rath. “Highly Reactive Polyisobutene as a Component of a New Generation of Lubricant and Fuel Additives,” Lubrication Science 11-2, Feb. 1999, pp. 175-185. |
| Hansen, Charles M. Hansen Solubility Parameters: A User's Handbook, 2nd ed. New York, CRC Press, Taylor & Francis Group, 2007, 546 pages. |
| Hernandez, et al. R. Microstructural Organization of Three-Phase Polydimethylsiloxane-Based Segmented Polyurethanes. Macromolecules, 40:5441-5449, 2007. |
| Hernandez, R., et al. A Comparison of Phase Organization of Model Segmented Polyurethanes with Different Intersegment Compatibilities. Macromolecules, 41:9767-9776,2008. |
| Higashihara, T et al., “Synthesis of Poly(isobutylene-block-methyl methacrylate) by a Novel Coupling Approach”, Macromoiecules, 39:5275-5279 (2006). |
| International Search Report and Written Opinion issued in PCT/US2006/013308, dated Aug. 25, 2006. |
| International Search Report and Written Opinion issued in PCT/US2006/035064, dated Jan. 23, 2007, 12 pages. |
| International Search Report and Written Opinion issued in PCT/US2007/008528, dated Oct. 2, 2007. |
| International Search Report and Written Opinion issued in PCT/US2007/012948, dated Nov. 28, 2007. |
| International Search Report and Written Opinion issued in PCT/US2010/028334, Dated May 6, 2010, 12 pages. |
| International Search Report and Written Opinion issued in PCT/US2010/046072, dated Oct. 15, 2010, 10 pages. |
| International Search Report and Written Opinion issued in PCT/US2010/047633, Dated Jun. 17, 2011, 12 pages. |
| International Search Report and Written Opinion issued in PCT/US2010/047703, Dated Jun. 17, 2011, 12 pages. |
| International Search Report and Written Opinion issued in PCT/US2011/061692, dated Feb. 9, 2012, 9 pages. |
| International Search Report and Written Opinion issued in PCT/US2013/053448, dated Jul. 28, 2014, correcting earlier version dated Apr. 28, 2014, 11 pages. |
| Lewis, S. (2000). Synthesis of polyisobutylene-silica hybrid stars and networks via sol-gel processing. Formal Seminar, pp. 1-25. |
| Li, J et al., “Polyisobutylene supports - a non-polar hydrocarbon analog of PEG supports”, Tetrahedron, 61 (51): 12081-12092, Dec. 2005. |
| Macias, A. et al., “Preparacion y reticulacion de poliisobutilenos de bajo peso molecular con grupos terminales Yeactivos”, Revista de Plasticos Modernos, No. 332 (April '83), pp. 412-418. |
| Martin, D. J., et al. Polydimethylsiloxane/Polyether-Mixed Macrodiol-Based Polyurethane Elastomers: Biostability. Biomaterials, 21:1021-1029,2000. |
| Miller, J. A., “New Directions in Polyurethane Research”, Organic Coatings and Applied Polymer Science Proceedings, vol. 47, Copyright 1982 by ACS, pp. 124-129. |
| Mitzner, E et al., “Modification of poly(ether urethane) elastomers by incorporation of poly(isobutylene) glycol Relation between polymer properties and thrombogenicity”, J. Biomater. Sci. Polymer edn. Vol. 7, No. 12, pp. 1105-1118 K1996). |
| Mitzner, E., et al. Modification of Segmented Poly(Ether Urethanes) by Incorporation of Poly(lsobutylene)Glycol. Journal of Macromolecular Science, Part A., Pure and Applied Chemistry, 34(1):165-178,1997. |
| Miyabayashi, Toshio et al., “Characterization of Polyisobutylene-Based Model Urethane Networks”, Journal of Applied Polymer Science, vol. 31, pp. 2523-2532 (1986). |
| Motte, S., & Kaufman, L. J. (2012). Strain stiffening in collagen I Networks. Biopolymers, 99(1):35-46. |
| Mulller et al., “Surface modification of polyurethanes by multicomponent polyaddition reaction”, Journal of Materials Science Letters 17 (1998) 115-118. |
| Non-Final Office Action issued in U.S. Appl. No. 12/492,483, dated Nov. 21, 2011, 11 pages. |
| Non-Final Office Action issued in U.S. Appl. No. 11/400,059, dated Apr. 11, 2011. |
| Notice of Allowance issued in U.S. Appl. No. 12/492,483, dated Jul. 13, 2012, 9 pages. |
| Odian, G. “Principles of Polymerization,” Wiley Interscience (2004), pp. 80-83. |
| Office Action issued in EP 07754128 dated Mar. 31, 2010. |
| Office Action issued in EP Application No. 07754128.2, dated Feb. 19, 2009, 3 pages. |
| Office Action issued in U.S. Appl. No. 11/400,059, dated Aug. 24, 2010. |
| Ojha et al., “Synthesis and Characterization of Thermoplastic Polyurethaneureas based on Polyisobutylene and Poly(tetramethylene oxide) Segments”, J. Macromolecular Science, Part A, vol. 47(3), pp. 186-191, Mar. 2010. |
| Ojha, Umaprasana et al., “Synthesis and Characterization of Endfunctionalized Polyisobutylenes for Sharpless-type Click Reactions”, Polymer Preprings 2007,48(2), 786. |
| Ojha, Umaprasana, et al. Syntheses and Characterization of Novel Biostable Polyisobutylene Based Thermoplastic Polyurethanes. Polymer 50:3448-3457, 2009. |
| Pinchuk, L. Review: A Review of the Biostability and Carcinogenicity of Polyurethanes in Medicine and the New Generation of 'Biostable1 Polyurethanes. J. Biomater. Sci., Polymer Edn., 6(3):225-267,1994. |
| Pistor, V. (2012). Research article: Microstructure and crystallization kinetics of polyurethane thermoplastics containing trisilanol isobutyl POSS. Hindawi Publishing Corporation, Journal of Nanomaterials, vol. 2012, Article ID 283031, 8 pages. |
| Prucker, 0., et al. Photochemical Attachment of Polymer Films to Solid Surfaces via Monolayers of Benzophenone Derivatives. J. Am. Chern. Soc. 121:8766-8770, 1999. |
| Puskas, J.E. et al., “polyisobutylene-based biomaterials”. Journal of Polymer Science Part A: Polymer Chemistry, vol. 42, Issue 13 (2004) pp. 3091-3109. |
| Raftopoulos, K. N., and Pielichowski, K. (2015). Segmental dynamics in hybrid polymer/POSS nanomaterials. Progress in Polymer Science, 52 pages. |
| Raftopoulos, K. N.; et al. (2013). POSS along the hard segments of polyurethane. Phase separation and molecular dynamics. Macromolecules, 46:7378-7386. |
| Rajkhowa, Ritimoni et al., “Efficient syntheses of hydroxyallyl end functional polyisobutylenes, a precursors to thermoplastic polyurethanes”, Polymer Reprints (American Chemical Society, Division of Polymer Chemistry) 2007, 48(2), 233-234. |
| Ranade, S. et al., “Physical characterization of coi ill oiled release of paclitaxel from the TAXUS(Trademark) Express2(Trademark) drug-eluting stent”, Journal of Biomedical Materials Research Part A, 71A (2004) 625-634. |
| Ranade, S.V et al., Styrenic Block copolymers for Biomaterial and Drug Delivery Applications, Acta Biomater. Jan. 2005; 1(1): 137-44. |
| Rashid, S. T.; et al. (2004). The use of animal models in developing the discipline of cardiovascular tissue engineering: a review. Biomaterials, 25:1627-1637. |
| Response filed Aug. 31, 2009 to Office Action dated Feb. 19, 2009, EP App 07754128. |
| Saiani, A., et al. Origin of Multiple Melting Endotherms in a High Hard Block Content Polyurethane. 1. Thermodynamic Investigation. Macromolecules, 34:9059-9068, 2001. |
| Saiani, A., et al. Origin of Multiple Melting Endotherms in a High Hard Block ContentPolyurethane. 2. Structural Investigation. Macromolecules, 37:1411-1421, 2004. |
| Santos, R. et al., “New Telechelic Polymers and Sequential Copolymers by Polyfunctional Initiator-Transfer-Agents (Inifers)”, Polymer Bulletin, 11:341-348(1984). |
| Schellekens, Yves, et al. “Tin-Free Catalysts for Production of Aliphatic Thermoplastic Polyurethanes.” Green Chemistry, 16:4401-4407, 2014. |
| Second Office Action for Chinese Application No. 201380042582.3, entitled “High Strength Polyisobutylene Polyurethanes” dated May 10, 2016 consisting of5 pages. |
| Siefken, Von Werner. “Mono- und Polyisocyanate, IV. Mitteiiung uber Polyurethane,” [With machine English translation]. Justus Liebigs Annalen Der Chemie, 562(2):75-136,1949. |
| Simmons, Anne, et al., “The effect of sterilisation on a poly(dimethylsiloxane)/poly(hexamethylene oxide) mixed macrodiol-based Polyurethane elastomer”, Biomaterials 2006, 27,4484-4497. |
| Singh, Vishwakarma; et al. “Molecular complexity from aromatics. Cycloaddition of spiroepoxycyclohexa-2,4-dienones and intramolecular Diels-Alder reaction: a stereoselective entry into tetracyclic core of atisane diterpenoids.” Tetrahedron 69 (2013) 137-146. |
| Soytas, S. H.; et al. (2009). Synthesis of POSS-functionalized polyisobutylene via direct initialization. Macromol. Rapid Commun., 30:2112-2115. |
| Speckhard, T.A.. “Properties of Polyisobutylene-Polyurethane Block Copolymers”, Journal of Elastomers and Plastics, vol. 15 (Jul. 1983), pp. 183-192. |
| Speckhard, T.A. et al., “New generation polyurethanes”, Polymer News 1984, 9(12), 354-358. |
| Speckhard, T.A. et al., “Properties of Polyisobutylene Polyurethane Block Copolymers: 3. hard segments based on 4,4'-dicyclohexylmethane diisocyanate (H12MD1) and butane dial”, Polymer, vol. 26, No. 1, Jan. 1985, pp. 70-78. |
| Speckhard, T.A. et al., “Properties of Polyisobutylene-Polyurethane Block Copolymers: I. Macroglycols from Ozonolysis of Isobutylene-lsoprene Copolymer”, Polymer Engineering and Science, Apr. 1983, vol. 23. No. 6, pp. 337-349. |
| International Search Report and Written Opinion issued in PCT/US2016/027294, dated Jul. 28, 2016, 10 pages. |
| International Search Report and Written Opinion issued in PCT/US2016/067363, dated Mar. 3, 2017, 10 pages. |
| International Search Report and Written Opinion issued in PCT/US2017/031856, dated Aug. 11, 2017, 9 pages. |
| International Search Report and Written Opinion issued in PCT/US2018/021311, dated May 24, 2018, 11 pages. |
| International Search Report and Written Opinion issued in PCT/US2018/046813, dated Dec. 11, 2018, 11 pages. |
| International Search Report and Written Opinion received for PCT Patent Application No. PCT/US2010/020733, dated May 6, 2010, 9 pages. |
| International Search Report and Written Opinion received for PCT Patent Application No. PCT/US2013/071170, dated Jun. 6, 2014, 10 pages. |
| International Search Report and Written Opinion received for PCT Patent Application No. PCT/US2017/031856, dated Aug. 11, 2017, 8 pages. |
| International Search Report and Written Opinion received for PCT Patent Application No. PCT/US2018/046813, dated Dec. 11, 2018, 9 pages. |
| International Search Report and Written Opinion received for PCT Patent Application No. PCT/US2019/013685, dated Jun. 19, 2019, 9 pages. |
| International Search Report from PCT/US2007/008528, dated Oct. 2, 2007. |
| International Search Report issued in PCT/US2009/048345, dated Oct. 6, 2009, 3 pages. |
| International Search Report issued in PCT/US2009/048827, dated Oct. 6, 2009, 3 pages. |
| International Search Report issued in PCT/US2010/020733, dated May 6, 2010. |
| Ioffe, David et al., “Bromine, Organic Compounds”, Kirk-Othmer Encyclopedia of Chemical Technology, vol. 4, pp. 340-365, (Copyright) 2002. |
| Ivan, B et al., “Synthesis of New Polyisobutylene-Based Polyurethanes”, Am. Chern. Soc., Div. Org. Coat. Plast. Prepr., 43, 908-913(1980). |
| Ivan, B., et al., Living Carbocationic Polymerization. XXX. One-Pot Synthesis of Allyl-Terminated Linear and Tri-Arm Star Polyisobutylenes, and Epoxy- and Polyisobutylenes, and Epoxy- and Hydroxy-Telechelics Therefrom. Journal of Polymer Science: Part A: Polymer Chemistry, 28:89-104,1990. |
| Ivan, Bela, et al. New Telechelic Polymers and Sequential Copolymers by Polyfunctional Initiator-Transfer Agents KInifers). VII. Synthesis and Characterization of (Alpha),(Omega)-Di(Hydroxy) Polyisobutylene. Journal of Polymer Science: Polymer Chemistry Edition, 18:3177-3191,1980. |
| Ivan, Bela; et al. “Living Carbocationic Polymerization. XXX. One-Pot Synthesis of Allyl-Terminated Linear and Tri-Arm Star Polyisobutylenes, and Epoxy- and Hydroxy-Telechelics Therefrom.” Journal of Polymer Science: Part A: Polymer Chemistry, vol. 28, 89-104 (1990). |
| Jenny, C. et al., “A New Insulation Material for Cardiac Leads with Potential for Improved performance”, HRS 2005, HeartRhythm, 2, S318-S319 (2005). |
| Jewrajka, Suresh K. et al., “Polyisobutylene-Based Polyurethanes. IL Polyureas Containing Mixed PIB/PTMO Soft Segments”, Journal of Polymer Science: Part A: Polymer Chemistry, vol. 47, 2787-2797 (2009). |
| Jewrajka, Suresh K. et al., “Polyisobutylene-Based Segmented Polyureas. I. Synthesis of Hydrolytically and Oxidatively Stable Polyureas”, Journal of Polymer Science: Part A: Polymer Chemistry, vol. 47, 38-48 (2009). |
| Kabalka, George W.; et al. “N-t-Butoxycarbonyl Protection of primary and Secondary Amines in the Hydroboration Reaction: Synthesis of Amino Alcohols.” Synthetic Communications: An International journal for Rapid Communication of Synthetic Organic Chemistry, 25(14), 2135-2143 (1995). |
| Kali, Gergely; et al. “Anionic Amphiphilic End-Linked Conetworks by the Combination of Quasiliving Carbocationic and Group Transfer Polymerizations.” Journal of Polymer Science, Part A—Polymer Chemistry, 2009, 47(17):4289-4301. |
| Kang, Jungmee et al., “PIB-Based Polyurethanes. IV. The Morphology of Polyurethanes Containing Soft Co-Segments”, Journal of Polymer Science Part A: Polymer Chemistry, vol. 47, 6180-6190 (2009). |
| Kang, Jungmee et al., “Rendering Polyureas Melt Processible”, Journal of Polymer Science Part A: Polymer Chemistry, vol. 49, 2461-2467 (2011). |
| Kang, Jungmee et al., Polyisobutylene-Based Polyurethanes. V. Oxidative-Hydrolytic Stability and Biocampatibility, Journal of Polymer Science: Part A: Polymer Chemistry, vol. 48,2194-2203 (2010). |
| Kang, Jungmee, et al. Polyisobutylene-Based Polyurethanes with Unprecedented Properties and How They Came About. Polymer Chemistry, 49:3891-3904. |
| Kanna, Y. (2006). The degradative resistance of polyhedral oligomeric silsesquioxane nanocore integrated polyurethanes: An in vitro study. Biomaterials, 27:1971-1979. |
| Kennedy, J.P et al., “Designed Polymers by Carbocationic Macromolecular Engineering: Theory and practice”, Hanser Publishers 1991, pp. 191-193 and 226-233. |
| Kennedy, J.P. et al., “Polyisobutylene-Based Diols and Polyurethanes”, Urethane Chemistry and Applications, Ed., K. H. Edwards, ACS Symp. Book Series, 172, Washington, D.C. 1981, pp. 383-391. |
| Kennedy, J.P. et al., “Polyisobutylene-Based Diols and Polyurethanes” Advances in Urethane Science and Technology, vol. 8, 1981, pp. 245-251. |
| Kennedy, Joseph P.“ Synthesis, Characterization and Properties of Polyisobutylene-Based Polyurethanes”, Journal of Elastomers and Plastics, vol. 17 (Jan. 1985), pp. 82-88. |
| Kennedy, Joseph P.“ Synthesis, Characterization and Properties of Polyisobutylene-Based Polyurethanes”, The Society of the Plastics Industry, Inc., polyurethane Division, Proceedings of the SPI - 6th International Technical/Marketing Conference, Nov. 2-4, 1983, San Diego, CA, pp. 514-516. |
| Kennedy, Joseph P. Synthesis, Characterization and Properties of Novel Polyisobutylene-Based urethane Model Networks, Journal of Applied Polymer Science, vol. 33(7), May 20, 1987, pp. 2449-2465. |
| Kennedy, Joseph P., “Polyurethanes Based on Polyisobutylenes”, Chemtech, Nov. 1986,16(11), pp. 694-697. |
| Kennedy, Joseph P., “Polyurethanes Based on Polyisobutylenes”, Cherntech, Nov. 1986,16(11), pp. 694-697. |
| Kidane, A. G.; et al. (2008). Review: Current developments and future prospects for heart valve replacement therapy, Wiley InterScience, pp. 290-303. |
| Kidane, A.G.; et al. (2009). A novel nanocomposite polymer for development of synthetic heart valve leaflets, Acta Biomaterialia, 5:2409-2417. |
| Kirby, Darren, “Use of a Bioactive Material on a Pacemaker Electrode for the Purpose of Enhancing Heart Pace/Sense Efficiency”, MSC Biomedical Engineering, Thesis, Trinity College Dublin (2003). |
| Koberstein, J. T., et al. Compression-Molded Polyurethane Block Copolymers. 1, Microdomain Morphology and ITherrnomechanical Properties. Macromolecules, 25:6195-6204,1992. |
| Koberstein, J. T., et al. Compression-Molded Polyurethane Block Copolymers. 2. Evaluation of Microphase Compositions. Macromolecules, 25:6205-6213,1992. |
| Koberstein, J. T., et al. Simultaneous SAXS-DSC Study of Multiple Endothermic Behavior in Polyether-Based Polyurethane Block Copolymers. Macromolecules, 19:714-720,1986. |
| Kunal, K., et al. Polyisobutylene: A Most Unusual Polymer Journal of Polymer Science: Part B: Polymer Physics, 46:1390-1399, 2008. |
| Lazzarato, Loretta; et al. “(Nitrooxyacyloxy)methyl Esters of Aspirin as Novel Nitric Oxide Releasing Aspirins.” J. Med., Chem. 2009, 52, 5058-5068. |
| Lelah, M.D. et al., “Polyurethanes in Medicine”, CRC Press, Boca Raton, FL 1986, Chapter 3. |
| Leung, L. M., et al. DSC Annealing Study of Microphase Separation and Multiple Endothermic Behavior in Polyether-Based Polyurethane Block Copolymers. Macromolecuies, 19:706-713,1986. |
| Speckhard, T.A. et al., “Ultimate Tensite Properties of Segmented Polyurethane Elastomers”, Rubber Chern. Technol., 59, 405-431 (1986). |
| Stokes, K., et al. Polyurethane Elastomer Biostability. Journal of Biomaterials Applications, 9:321-354,1995. |
| Storey, Robson F.; et al. “Carbocation Rearrangement in Controlled/Living Isobutylene Polymerization,” Macromolecules 1998, 31, pp. 1058-1063. |
| Tan, J et al., “In Vivo Biostability Study of A New Lead Insulation Material,” Cardiostim 2006, Europace Supplements, 8, 179PW/9 (2006). |
| Third Office Action for Chinese Application No. 201380042582.3, enitled “High Strength Polyisobutylene Polyurethanes” dated Jul. 27, 2016 consisting of 5 pages. |
| Third Office Action for Chinese Application No. 201380042582.3, entitled “High Strength Polyisobutylene Polyurethanes” dated Jul. 27, 2016 consisting of 5 pages. |
| Tonelli, C. et al., “New Fluoro-Modified Thermoplastic Polyurethanes” Journal of Applied Polymer Science, vol. 87, Issue 14 (2003) 2279-2294. |
| Tonelli, Claudio et al., “New Perfluoropolyether Soft Segment Containing Polyurethanes”, Journal of Applied Polymer Science, vol. 57, pp. 1031-1042 (1995). |
| Virmani, R. et al. Circulation Feb. 1, 20047,109(6) 701-5. |
| Viski, Peter, et al. “A Novel Procedure for the Cieavage of Olefin Derivatives to Aldehydes Using Potassium Permanganate.”J. Org. Chern., 51:3213-3214,1986. |
| Wang, F. Polydimethylsiloxane Modification of Segmented Thermoplastic Polyurethanes and Polyureas, PhD. Dissertation, Virginia Polytechnic Institute and State university, Apr. 13, 1998. |
| Weisberg, David M. et al., “Synthesis and Characterization of Amphiphilic Poly(urethaneurea)-comb-polyisobutylene Copolymers”, Macromolecules 2000, 33(12), pp. 4380-4389. |
| Weiss, H. G.; et al. “Diborane from the Sodium Borohydride-Sulfuric Acid Reaction.” Contribution From Research Laboratory, Olin Mathieson Chemical Corporation, Dec. 5, 1959, 81(23):6167-6168. |
| Weissmuller, M. et al., “Preparation and end-linking of hydroxyl-terminated polystyrene star macromolecules”, Macromolecular Chemistry and Physics 200(3), 1999, 541-551. |
| Wohlfarth, C., “Permittivity (Dielectric Constant) of Liquids”, CRC handbook, 91st ed. 2010-2011, p. 6-186 to 6-207. |
| Wright, James I., “Using Polyurethanes in Medical Applications”, 5 pages. Downloaded from http://www.cmdm.com on Oct. 17, 06. |
| Wu, Yuguang et al., “The role of adsorbed fibrinogen in platelet adhesion to polyurethane surfaces: A comparison of surface hydrophobicity, protein adsorption, monoclonal antibody binding, and platelet adhesion”, Journal of Biomedical Materials Research, Part A, Sep. 15, 2005, vol. 74A, No. 4, pp. 722-738. |
| Xu, Ruijian et al., “Low permeability biomedical polyurethane nanocomposites”. Journal of Miomedical Materials Resarch, 2003, vol. 64A, pp. 114-119. |
| Yang, M et al., J. biomed. Mater. Res. 48 (1999) 13-23. |
| Yeh, J. et al., “Moisture diffusivity of Blamer.RTM. versus Biomer.RTM.-coated Polyisobutylene polyurethane urea (PIB-PUU): a potential blood sac material for the artificial heart”, Journal of Materials Science Letters 13(19), 1994, pp. 1390-1391. |
| Yoon, Sung C. et al., “Surface and bulk structure of segmented poly(ether urethanes) with Periluoro Chain Extenders. 5. Incorporation of Poly(dimethylsiloxane) and Polyisobutylene Macroglycols”, Macromolecules Mar. 14, 1994, 27(6), pp. 1548-1554. |
| York, P., “New Materials and Systems for Drug Delivery and Targeting”, chemical Aspects of Drug Delivery Systems, Copyright 1996, pp. 1-10, proceedings from a symposium held Apr. 17-18, 1996 at Salford university. |
| Zhang, F., et al. Glassy Carbon as an Absolute Intensity Calibration Standard for Small-Angle Scattering. Metallurgical and Materials Transactions A, 41A:1151-1158, May 2010. |
| Ako, Masayuke et al., “Polyisobutylene-based urethane foams II. Synthesis and properties of novel polyisobutylene-based flexible polyurethane foams”, Journal of Applied Polymer Science, vol. 37(5), Feb. 5, 1989, pp. 1351-1361. |
| Ayandele, E.; et al. (2012). Polyhedral Oligomeric Silsequioxane (POSS)-Containing Polymer Nanocomposites. Nanomaterials, 2:445-475. |
| Bela et al., Living carbocation Polymerization. XX. Synthesis of Allyl-telechelicn Polyisobutyleenes by One-Pot Polymerization-Functionalization polymer. Mater. Sci. Eng. 1988; 58:869-872. |
| Chen, T. K , et al. Glass Transition Behaviors of a Polyurethane Hard Segment based on 4, 4'-Diisocyanatodiphenylrnethane and 1,4-Butanediol and the Calculation of Microdomain Composition. Macromolecules, 30:5068-5074, 1997. |
| Efrat, T.; et al. (2006). Nanotailoring of polyurethane adhesive by polyhedral oligomerica silsequioxane (Poss). J. Adhesion Sci. Technol., 20(12): 1413-1430. |
| Erdodi, G., et al., “Polyisobutylene-Based Polyurethanes. 111. Polyurethanes Containing PIB/PTMO Soft Co-Segments,” J. Polym. Sci., Part A: Polym. Chern, 47:5278-5290 (2009). |
| Fu, B.X.; et al. (2001). Structural development during deformation of polyurethane containing polyhedral oligomeric silsesquioxanes (POSS) molecules. Polymer, 42:599-611. |
| Gadkari A. et al., “Preparation and biocompatibility of Novel Polar-Nonpolar Networks. Osynthesis, Characterization and Histological-Bacterial Analysis Of Mixed Polytetrahydrofuran-Polyisobutylene Networks”, Polymer Bulletin, vol. 22, No. 1, Jul. 1, 1989, pp. 25-32. |
| Ghanbari, H.; et al. (2010). The anti-calcification potential of a silsesquioxane nanocomposite polymer under in vitro conditions: Potential material for synthetic leaflet heart valve. Acta Biomaterialia, 6:4249-4260. |
| Gu, W.; et al. (2011). Polyhedral oligomeric silsesquioxane (POSS) suppresses enzymatic degradation of PCL-based polyurethanes. Biomacromolecules, 12:3066-3077. |
| Higashihara, T. et al., “Synthesis of Poly(isobutylene-block-methyl methacrylate) by a Novel Coupling Approach”, Macromolecules, 39:5275-5279 (2006). |
| International Search Report and Written Opinion issued in PCT/US2007/007558, dated Sep. 20, 2007. |
| International Search Report and Written Opinion issued in PCT/US2013/053448, dated Apr. 28, 2014, 11 pgs. |
| International Search Report issued in PCT/U2009/048845, dated Oct. 6, 2009, 3 pages. |
| Kang, Jungmee, et al. Polyisobutylene-Based Polyurethanes with Unprecedented Properties and How They Carne About. Polymer Chemistry, 49:3891-3904. |
| Kennedy, J.P. et al., “Polyisobutylene-based Model urethane Networks, I. Initial characterization and Physical properties”, Polymeric Materials Science and Engineering, vol. 49, Copyright 1983 by ACS, pp. 69-77. |
| Kennedy, Joseph P. “Synthesis, Characterization and Properties of Polyisobutylene-Based Polyurethanes”, 6th International Technical/Marketing Conference: Polyurethane—New Paths to Progress-Marketing-Technology, Journal of Cellular Plastics, 1983, 19:288-307. |
| Kennedy, Joseph P. “Synthesis, Characterization and Properties of Polyisobutylene-Based Polyuretllanes”, Journal of Elastomers and Plastics, vol. 17 (Jan. 1985), pp. 82-88. |
| Kennedy, Joseph P. “Synthesis. Characterization and Properties of Polyisobutylene-Based Polyurethanes”, The Society of the Plastics industries, Inc., polyurethane Division, Proceedings of the SPI - 6th International Technical/Mrketing Conference, november2-4, 1983, San Diego, CA, pp. 514-516. |
| Knight, P. T.; et al. (2010). In vivo kinetic degradation analysis and biocompatibility of aliphatic polyester polyurethanes, Student Award Winner for Outstanding Research in the Ph.D. Category, 2010 Society for Biomaterials Annual Meeting, Seattle, Washington, Apr. 21-24, 2010; Wiley InterScience 2010, pp. 333-343. |
| Leung, L. M., et al. DSC Annealing Study of Microphase Separation and Multiple Endothermic Behavior in Polyether-Based Polyurethane Block Copolymers. Macromolecules, 19:706-713, 1986. |
| Macias, A. et al., “Preparacion y reticulacion de poliisobutilenos de bajo peso molecular con grupos terminates Yeactivos”, Revista de Plasticos Modernos, No. 332 (Apr. '83), pp. 412-418. |
| Mitzner, E., “Modification of segmented poly(ether urethanes) by incorporation of Poly(isobutylene)glycol”, J.M.S. -Pure Appl. Chern., A34(1), pp. 165-178 (1997). |
| Muller, J.P. et al., “Surface modification of polyurethanes by multicomponent polyaddition reaction”, Journal of Materials Science Letters 17(2), 1998, pp. 115-118. |
| Non-Final Office Action, issued in U.S. Appl. No. 12/685,858, dated Feb. 15, 2012, 18 pages. |
| Notification of Transmittal of the International Search Report and the Written Opinion of the International Searching Authority for Int'l Application No. PCT/US2013/071170, entitled: High Strength Polyisobutylene Polyurethanes, dated Jun. 6, 2014. |
| Official Action for European Application No. 13802190.2-1301, dated Dec. 21, 2016, consisting of 5 pages. |
| Ojha, Umaprasana et al., “Synthesis and characterization of novel biostable polyisobutylene based thermoplastic polyurethanes”, Polymer 50(2009), 3448-3457. |
| Prucker, O., et al. Photochemical Attachment of Polymer Films to Solid Surfaces via Monolayers of Benzophenone Derivatives. J. Am. Chem. Soc. 121:8766-8770,1999. |
| Raftopoulos, K. N. (2013). Direct and indirect effects of POSS on the molecular mobility of polyurethanes with varying segment Mw. Polymer, 54:2745-2754. |
| Rahmani, B.; et al. (2012). Manufacturing and hydrodynamic assessment of a novel aortic valve made of a new nanocomposite polymer. Journal of Biomechanics, 7 pages. |
| Salani, A., et al. Origin of Multiple Melting Endotherms in a High Hard Block Content Polyurethane. 1. Thermodynamic Investigation. Macromolecules, 34:9059-9068, 2001. |
| Six, Christian, et al. “Isocyanates, Organic.” Ullmann's Encyclopedia of Industrial Chemistry, vol. 20:63-82, 2012. |
| Speckhard et al., “New generation polyurethanes.” Polymer News (1984), 9(12), 354-8. |
| Speckhard, T.A. et al., “Properties of Polyisobutylene Polyurethane Block Copolymers: 2. Macroglycols produced by the inifer' technique”, Polymer, vol. 26, No. 1, Jan. 1985, pp. 55-78. |
| Tan, A.; et al. (2013). Surface modification of a polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) nanocomposite polymer as a stent coating for enhanced capture of endothelial preogenitor cells. Biointerphase, 8(23):1-18. |
| Viski, Peter, et al. “A Novel Procedure for the Cleavage of Olefin Derivatives to Aldehydes Using Potassium Permanganate.” J. Org. Chern., 51:3213-3214, 1986. |
| Weisberg et al., “Synthesis and Characterization of Amphiphilic Poly(urethaneura)-comb-polyisobutylene Copolymers”, Macromolecules 2000, 33, 4380-4389. |
| Wiggins, Michael J. et al., “Effect of soft-segment chemistry on polyurethane biostability during in vitro fatigue Toading”, Journal of biomedical materials research, 68(4), 2004, 668-683. |
| Zhang, W., and Muller, A. H.E. (2013). Architecture, self-assembly and properties of well-defined hybrid polymers based on polyhedral oligomeric silsequioxane (POSS). Progress in Polymer Science 38:1121-1162. |
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| Parent | 12685858 | Jan 2010 | US |
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