WO2018140912A1 - Biodegradable and/or bioabsorbable thermoplastic polyurethanes - Google Patents

Abstract

The thermoplastic polyurethane (TPU) compositions described herein have biodegradable and/or bioabsorbable hard segments and soft segments. The TPU hard segment is formed from one or more polyisocyanates capable of breaking down into one or more non-toxic degradants and one or more short chain diols capable of breaking down into one or more non-toxic degradants. The TPU soft segment is formed from one or more polyols capable of breaking down into one or more non-toxic degradants. The resulting TPU has a controllable degradation rate and can be formulated to have good physical properties making it ideal for use in medical articles and devices.

Description

BIODEGRADABLE AND/OR BIO ABSORB ABLE THERMOPLASTIC

POLYURETHANES

FIELD OF THE INVENTION

[0001] There is provided herein thermoplastic polyurethane (TPU) compositions having biodegradable and/or bioabsorbable hard and soft segments while still maintaining good physical properties.

BACKGROUND

[0002] Thermoplastic polyurethanes (TPUs) are a widely used class of polymer with specific physical and chemical properties which make them particularly suitable for in vivo applications. Conventional TPUs are among biomaterials not intended to degrade, but some conventional TPUs are susceptible to hydrolytic, oxidative and enzymatic degradation in vivo. Such degradation can be utilized to design biodegradable TPUs.

[0003] While thermoplastic polyurethanes have many mechanical properties which make them attractive for biomedical applications, degradation of the polymer presents challenges. It is known that degradation of the TPU soft segment can be achieved by appropriate selection of the soft segment chemistry. Frequently utilized biodegradable TPU soft segments include poly(e-caprolactone), poly(lactic acid), polyglycolic acid and poly(ethylene glycol) polyols. Hard segment degradation is more of a challenge owing to the urethane bonds being less susceptible to degradation. Hard segment modification has focused on varying diisocyanate structures and chain extenders. These modifications, however, often lead to inferior mechanical properties of the TPUs.

[0004] Thus, it would be desirable to provide a thermoplastic polyurethane composition that is biodegradable and/or bioabsorbable in bodily environments where both the soft segments of the TPU and the hard segments of the TPU can be biodegradable and/or bioabsorbable, breaking down at a controlled rate, without degrading to toxic byproducts, and while maintaining favorable mechanical properties in bodily environments. SUMMARY

[0005] The disclosed technology provides thermoplastic polyurethane (TPU) compositions having biodegradable and/or bioabsorbable hard and biodegradable and/or bioabsorbable soft segments while still maintaining good physical properties.

[0006] The disclosed technology provides a biodegradable and/or bioabsorbable TPU which may be described as the reaction product of: (a) a polyisocyanate component including one or more polyisocyanates capable of breaking down into one or more non-toxic degradants; (b) a polyol component including one or more polyol s capable of breaking down into one or more non-toxic degradants; and (c) at least one chain extender component including one or more short chain diols capable of breaking down into one or more non-toxic degradants, where the short chain diol is a linear, fully saturated alkylene diol.

[0007] The disclosed technology further provides described TPU where the polyisocyanate component includes an aliphatic diisocyanate. In some embodiments, the polyisocyanate component is free of aromatic diisocyanate and/or aromatic polyisocyanates. In some embodiments, the overall TPU is free of aromatic diisocyanate and/or aromatic polyisocyanates, and also free of segments and/blocks derived from the same.

[0008] The disclosed technology further provides the described TPU where the polyisocyanate component is 1,4-butane diisocyanate (BDI), Lysine diisocyanate (LDI), 1 ,6-hexane diisocyanate (HDI), 4,4' -methylene dicyclohexyl diisocyanate (H12MDI), or any combination thereof.

[0009] The disclosed technology further provides the described TPU where the polyol component is poly(L-lactide) (PLA), polglycolide (PGA), polycaprolactone (PCL), polytri methylene carbonate, or any combination thereof.

[0010] The disclosed technology further provides the described TPU where the polyol component further includes a polyether polyol, which may be poly(propylene glycol), poly(ethylene glycol), poly(tetram ethylene ether glycol), or combinations thereof. However in other embodiments the polyol component is free of any of these additional polyether polyols. [0011] The disclosed technology further provides the described TPU where the chain extender component includes at least one chain extender of the general formula HO-(CH2)n-X-(CH2)_n-OH wherein n is an integer from 2 to 4 and X is oxygen (-0-) or disulfide (-S-S-).

[0012] The disclosed technology further provides the described TPU where the chain extender component includes dipropylene glycol, di-(2-hydroxyethyl) disulfide, diethylene glycol, or any combination thereof.

[0013] The disclosed technology further provides the described TPU where the chain extender component further includes one or more additional chain extenders, wherein said additional chain extenders includes at least one diol chain extender of the general formula HO-(CH2)_m-OH wherein m is an integer from 2 to 6.

[0014] The disclosed technology further provides the described TPU where the polyol component further includes poly(propylene glycol), poly(ethylene glycol), poly(tetram ethylene ether glycol), or any combination thereof; and where the chain extender component further includes one or more additional chain extenders, wherein said additional chain extenders includes at least one diol chain extender of the general formula HO-(CH2)_m-OH wherein m is an integer from 2 to 6.

[0015] The disclosed technology further provides the described TPU where the polyisocyanate component includes 1,4-butane diisocyanate (BDI), Lysine diisocyanate (LDI), 1,6-hexane diisocyanate (HDI), 4,4 '-methylene dicyclohexyl diisocyanate (H12MDI), or any combination thereof; the polyol component is poly(L- lactide) (PLA), polglycolide (PGA), or polycaprolactone (PCL) or combinations thereof; and the chain extender component is dipropylene glycol, di-(2-hydroxyethyl) disulfide, diethylene glycol, or any combination thereof.

[0016] The disclosed technology further provides the described TPU where the polyisocyanate component includes 1,6-hexane diisocyanate (HDI); the polyol component includes poly(L-lactide) (PLA), polycaprolactone (PCL) or combinations thereof; and the chain extender component includes dipropylene glycol.

[0017] The disclosed technology further provides the described TPU where the polyisocyanate component includes 1,6-hexane diisocyanate (HDI); the polyol component includes a combination of poly(L-lactide) (PLA) and polycaprolactone (PCL); and the chain extender component includes dipropylene glycol. [0018] The disclosed technology further provides the described TPU where the polyisocyanate component includes 1,6-hexane diisocyanate (HDI); the polyol component includes polycaprolactone (PCL); and the chain extender component includes dipropylene glycol.

[0019] The disclosed technology further provides for medical articles made from the described TPU. In some embodiments such medical articles, which include medical devices, are made from the described TPU. In some embodiments such medical articles, which include medical devices, are made from the described TPU in combination with one or more other materials, and in some embodiments one or more other polymeric materials. In some embodiments such medical articles, which include medical devices, are coated with the described TPU. In some embodiments such medical articles, which include medical devices, are coated with the described TPU where the TPU further includes a compound, such as a drug or medicine, that elutes from the TPU over time as the TPU biodegrades and/or bioabsorbs.

[0020] The disclosed technology further provides for a method of making a bioabsorbable TPU, where the method includes the step of (I) reacting: (a) a polyisocyanate component that includes one or more polyisocyanate capable of breaking down into one or more non-toxic degradants; with (b) a polyol component that includes one or more polyols capable of breaking down into one or more non- toxic degradants; and with (c) at least one chain extender component that includes one or more short chain diols capable of breaking down into one or more non-toxic degradants, where the short chain diol is a linear, fully saturated alkylene diol.

DETAILED DESCRIPTION

[0021] Various preferred features and embodiments will be described below by way of non-limiting illustration.

[0022] The disclosed technology provides thermoplastic polyurethane (TPU) compositions having biodegradable and/or bioabsorbable hard and biodegradable and/or bioabsorbable soft segments while still maintaining good physical properties. The described TPU are the reaction product of: (a) a polyisocyanate component including one or more polyisocyanates capable of breaking down into one or more non-toxic degradants; (b) a polyol component including one or more polyols capable of breaking down into one or more non-toxic degradants; and (c) at least one chain extender component including one or more short chain diols capable of breaking down into one or more non-toxic degradants, where the short chain diol is a linear, fully saturated alkylene diol.

The polyisocyanate

[0023] The bioabsorbable thermoplastic polyurethane described herein are made using: (a) a polyisocyanate component. The polyisocyanate component includes one or more polyisocyanate capable of breaking down into one or more non-toxic degradants.

[0024] The polyisocyanate component may include aliphatic or aromatic diisocyanates. However, in some embodiments the polyisocyanate component includes an aliphatic diisocyanate. In some embodiments, the polyisocyanate component is free of aromatic diisocyanate.

[0025] In some embodiments, the polyisocyanate component includes 1,4-butane diisocyanate (BDI), Lysine diisocyanate (LDI), 1,6-hexane diisocyanate (HDI), 4,4'- methylene dicyclohexyl diisocyanate (H12MDI), or any combination thereof. In some embodiments, the polyisocyanate component includes 1,4-butane diisocyanate (BDI). In some embodiments, the polyisocyanate component includes Lysine diisocyanate (LDI). In some embodiments, the polyisocyanate component includes 1,6-hexane diisocyanate (HDI).

[0026] In some embodiments, an additional polyisocyanate may be present and used in combination with the polyisocyanates described above to form the polyisocyanate component.

[0027] Suitable polyisocyanate which may be used in the invention include aromatic diisocyanates, aliphatic diisocyanates, or combinations thereof. In some embodiments, the polyisocyanate component includes one or more aliphatic diisocyanates. In some embodiments, the polyisocyanate component is essentially free of, or even completely free of, aromatic diisocyanates. In other embodiments, the polyisocyanate component includes one or more aliphatic diisocyanates in combination with one or more aromatic polyisocyanate. In some embodiments, the polyisocyanate component is essentially free of, or even completely free of, aromatic diisocyanates.

[0028] Examples of useful polyisocyanate may include aromatic diisocyanates such as 4,4'-methylenebis(phenyl isocyanate) (MDI), m-xylene diisocyanate (XDI), phenylene-l,4-diisocyanate, 3,3 '-dimethyl-4,4' -biphenylene diisocyanate (TODI), naphthalene-l,5-diisocyanate (NDI), and toluene diisocyanate (TDI); as well as aliphatic diisocyanates such as hexamethylene dissocyanate (HDI) 4,4'-Diisocyanato dicyclohexylmethane (HMD I), isophorone diisocyanate (IPDI), 1 ,4-cyclohexyl diisocyanate (CHDI), decane-l, 10-diisocyanate, lysine diisocyanate (LDI), 1 ,4- butane diisocyanate (BDI), isophorone diisocyanate (PDI), and dicyclohexylmethane-4,4^'-diisocyanate (H12MDI). Mixtures of two or more polyisocyanates may be used. In some embodiments, the polyisocyanate is MDI and/or H12MDI. In some embodiments, the polyisocyanate includes MDI. In some embodiments, the polyisocyanate includes H12MDI.

[0029] In some embodiments, the mixtures of two or more polyisocyanates may be used.

[0030] In some embodiments, the thermoplastic polyurethane is prepared with a polyisocyanate component that includes HDI. In some embodiments, the thermoplastic polyurethane HDI prepared with a polyisocyanate component that consists essentially of H12MDI. In some embodiments, the thermoplastic polyurethane is prepared with a polyisocyanate component that consists of HDI.

[0031] In some embodiments, the polyisocyanate used to prepare the TPU and/or TPU compositions described herein is at least 50%, on a weight basis, a cycloaliphatic diisocyanate. In some embodiments, the polyisocyanate includes an a, co-alkylene diisocyanate having from 5 to 20 carbon atoms.

[0032] In some embodiments, the polyisocyanate used to prepare the TPU and/or TPU compositions described herein includes hexamethylene-l,6-diisocyanate, 1, 12-dodecane diisocyanate, 2,2,4-trimethyl-hexamethylene diisocyanate, 2,4,4-trimethyl- hexamethylene diisocyanate, 2-methyl-l,5-pentamethylene diisocyanate, or combinations thereof.

[0033] In some embodiments, the described TPU is prepared with a polyisocyanate component that includes HDI, H12MDI, LDI, IPDI, or combinations thereof. In some embodiments, the TPU is prepared with a polyisocyanate component consists of, or even consists essentially of HDI.

[0034] In still other embodiments, the polyisocyanate component is essentially free of (or even completely free of) any non-linear aliphatic diisocyanates, any aromatic diisocyanates, or both. In still other embodiments, the polyisocyanate component is essentially free of (or even completely free of) any polyisocyanate other than the linear aliphatic diisocyanates described above.

The polyol component

[0035] The bioabsorbable thermoplastic polyurethane compositions described herein are made using (b) a polyol component that includes one or more polyol s capable of breaking down into one or more non-toxic degradants.

[0036] In some embodiments, the polyol component includes poly(L-lactide) (PLA). In some embodiments, the polyol component includes polyol polglycolide (PGA). In some embodiments, the polyol component includes a polycaprolactone (PCL).

[0037] In some embodiments, the polyol component includes an additional polyol. In some embodiments, the additional polyol includes a polyether polyol. In some embodiments the additional polyol is poly(propylene glycol), poly(ethylene glycol), poly(tetramethylene ether glycol), or any combination thereof.

[0038] In some embodiments, an additional polyol may be present and used in combination with the polyols described above to form the polyol component.

[0039] Polyols suitable for use in the invention may include polyether polyols, polyester polyols, polycarbonate polyols, polysiloxane polyols, polyhydrocarbon polyols and combinations thereof. Suitable polyols, which may also be described as hydroxyl terminated intermediates, when present, may include one or more hydroxyl terminated polyesters, one or more hydroxyl terminated polyethers, one or more hydroxyl terminated polycarbonates, one or more hydroxyl terminated polysiloxanes, or mixtures thereof.

[0040] Suitable hydroxyl terminated polyester intermediates include linear polyesters having a number average molecular weight (Mn) of from about 500 to about 10,000, from about 700 to about 5,000, or from about 700 to about 4,000, and generally have an acid number less than 1.3 or less than 0.5. The molecular weight is determined by assay of the terminal functional groups and is related to the number average molecular weight. The polyester intermediates may be produced by (1) an esterification reaction of one or more glycols with one or more dicarboxylic acids or anhydrides or (2) by transesterification reaction, i.e., the reaction of one or more glycols with esters of dicarboxylic acids. Mole ratios generally in excess of more than one mole of glycol to acid are preferred so as to obtain linear chains having a preponderance of terminal hydroxyl groups. Suitable polyester intermediates also include various lactones such as polycaprolactone typically made from ε- caprolactone and a Afunctional initiator such as di ethylene glycol. The dicarboxylic acids of the desired polyester can be aliphatic, cycloaliphatic, aromatic, or combinations thereof. Suitable dicarboxylic acids which may be used alone or in mixtures generally have a total of from 4 to 15 carbon atoms and include: succinic, glutaric, adipic, pimelic, suberic, azelaic, sebacic, dodecanedioic, isophthalic, terephthalic, cyclohexane dicarboxylic, and the like. Anhydrides of the above dicarboxylic acids such as phthalic anhydride, tetrahydrophthalic anhydride, or the like, can also be used. Adipic acid is a preferred acid. The glycols which are reacted to form a desirable polyester intermediate can be aliphatic, aromatic, or combinations thereof, including any of the glycols described above in the chain extender section, and have a total of from 2 to 20 or from 2 to 12 carbon atoms. Suitable examples include ethylene glycol, 1,2-propanediol, 1,3 -propanediol, 1,3-butanediol, 1,4- butanediol, 1,5-pentanediol, 1,6-hexanediol, 2, 2-dimethyl- 1,3 -propanediol, 1 ,4- cyclohexanedimethanol, decamethylene glycol, dodecamethylene glycol, and mixtures thereof.

[0041] The polyol component may also include one or more polycaprolactone polyester polyols. The polycaprolactone polyester polyols useful in the technology described herein include polyester diols derived from caprolactone monomers. The polycaprolactone polyester polyols are terminated by primary hydroxyl groups. Suitable polycaprolactone polyester polyols may be made from ε-caprolactone and a bifunctional initiator such as di ethylene glycol, 1,4-butanediol, or any of the other glycols and/or diols listed herein. In some embodiments, the polycaprolactone polyester polyols are linear polyester diols derived from caprolactone monomers.

[0042] Useful examples include CAPA™ 2202A, a 2,000 number average molecular weight (Mn) linear polyester diol, and CAPA™ 2302A, a 3,000 Mn linear polyester diol, both of which are commercially available from Perstorp Polyols Inc. These materials may also be described as polymers of 2-oxepanone and 1,4- butanediol.

[0043] The polycaprolactone polyester polyols may be prepared from 2- oxepanone and a diol, where the diol may be 1,4-butanediol, di ethylene glycol, monoethylene glycol, 1 ,6-hexanediol, 2, 2-dimethyl- 1,3 -propanediol, or any combination thereof. In some embodiments, the diol used to prepare the polycaprolactone polyester polyol is linear. In some embodiments, the polycaprolactone polyester polyol has a number average molecular weight from 500 to 10,000, or from 500 to 3,000, or 600 to 1,000, or 1,000 to 3,000 or from 500, or 600, or from 1,000 or even 2,000 to 4,000 or even 3,000, or even about 2,000.

[0044] Suitable hydroxyl terminated polyether intermediates include polyether polyols derived from a diol or polyol having a total of from 2 to 15 carbon atoms, in some embodiments an alkyl diol or glycol which is reacted with an ether comprising an alkylene oxide having from 2 to 6 carbon atoms, typically ethylene oxide or propylene oxide or mixtures thereof. For example, hydroxyl functional polyether can be produced by first reacting propylene glycol with propylene oxide followed by subsequent reaction with ethylene oxide. Primary hydroxyl groups resulting from ethylene oxide are more reactive than secondary hydroxyl groups and thus are preferred. Useful commercial polyether polyols include poly(ethylene glycol) comprising ethylene oxide reacted with ethylene glycol, poly(propylene glycol) comprising propylene oxide reacted with propylene glycol, poly(tetramethylene ether glycol) comprising water reacted with tetrahydrofuran which can also be described as polymerized tetrahydrofuran, and which is commonly referred to as PTMEG. In some embodiments, the polyether intermediate includes PTMEG. Suitable polyether polyols also include polyamide adducts of an alkylene oxide and can include, for example, ethylenediamine adduct comprising the reaction product of ethylenediamine and propylene oxide, diethylenetriamine adduct comprising the reaction product of diethylenetriamine with propylene oxide, and similar polyamide type polyether polyols. Copolyethers can also be utilized in the described compositions. Typical copolyethers include the reaction product of THF and ethylene oxide or THF and propylene oxide. These are available from BASF as PolyTHF® B, a block copolymer, and PolyTHF® R, a random copolymer. The various polyether intermediates generally have a number average molecular weight (Mn) as determined by assay of the terminal functional groups which is an average molecular weight greater than about 700, such as from about 700 to about 10,000, from about 1,000 to about 5,000, or from about 1 ,000 to about 2,500. In some embodiments, the polyether intermediate includes a blend of two or more different molecular weight polyethers, such as a blend of 2,000 Mn and 1,000 Mn PTMEG.

[0045] Suitable hydroxyl terminated polycarbonates include those prepared by reacting a glycol with a carbonate. U. S. Patent No. 4, 131,73 1 is hereby incorporated by reference for its disclosure of hydroxyl terminated polycarbonates and their preparation. Such polycarbonates are linear and have terminal hydroxyl groups with essential exclusion of other terminal groups. The essential reactants are glycols and carbonates. Suitable glycols are selected from cycloaliphatic and aliphatic diols containing 4 to 40, and or even 4 to 12 carbon atoms, and from polyoxyalkylene glycols containing 2 to 20 alkoxy groups per molecule with each alkoxy group containing 2 to 4 carbon atoms. Suitable diols include aliphatic diols containing 4 to 12 carbon atoms such as 1,4-butanediol, 1,5-pentanediol, neopentyl glycol, 1,6- hexanediol, 2,2,4-trimethyl- l,6-hexanediol, 1, 10-decanediol, hydrogenated dilinoleylglycol, hydrogenated dioleylglycol, 3 -methyl -1,5-pentanediol; and cycloaliphatic diols such as 1,3-cyclohexanediol, 1 ,4-dimethylolcyclohexane, 1,4- cyclohexanediol-, 1,3-dimethylolcyclohexane-, l,4-endomethylene-2-hydroxy-5- hydroxymethyl cyclohexane, and polyalkylene glycols. The diols used in the reaction may be a single diol or a mixture of diols depending on the properties desired in the finished product. Polycarbonate intermediates which are hydroxyl terminated are generally those known to the art and in the literature. Suitable carbonates are selected from alkylene carbonates composed of a 5 to 7 member ring. Suitable carbonates for use herein include ethylene carbonate, trimethylene carbonate, tetramethylene carbonate, 1,2-propylene carbonate, 1,2-butylene carbonate, 2,3-butylene carbonate, 1,2-ethylene carbonate, 1,3-pentylene carbonate, 1 ,4-pentylene carbonate, 2,3- pentylene carbonate, and 2,4-pentylene carbonate. Also, suitable herein are dialkylcarbonates, cycloaliphatic carbonates, and diarylcarbonates. The dialkylcarbonates can contain 2 to 5 carbon atoms in each alkyl group and specific examples thereof are diethylcarbonate and dipropylcarbonate. Cycloaliphatic carbonates, especially dicycloaliphatic carbonates, can contain 4 to 7 carbon atoms in each cyclic structure, and there can be one or two of such structures. When one group is cycloaliphatic, the other can be either alkyl or aryl. On the other hand, if one group is aryl, the other can be alkyl or cycloaliphatic. Examples of suitable diarylcarbonates, which can contain 6 to 20 carbon atoms in each aryl group, are diphenylcarbonate, ditolylcarbonate, and dinaphthylcarbonate.

[0046] Suitable polysiloxane polyols include α-ω-hydroxyl or amine or carboxylic acid or thiol or epoxy terminated polysiloxanes. Examples include poly(dimethysiloxane) terminated with a hydroxyl or amine or carboxylic acid or thiol or epoxy group. In some embodiments, the polysiloxane polyols are hydroxyl terminated polysiloxanes. In some embodiments, the polysiloxane polyols have a number-average molecular weight in the range from 300 to 5,000, or from 400 to 3,000.

[0047] Polysiloxane polyols may be obtained by the dehydrogenation reaction between a polysiloxane hydride and an aliphatic polyhydric alcohol or polyoxyalkylene alcohol to introduce the alcoholic hydroxy groups onto the polysiloxane backbone.

[0048] In some embodiments, the polysiloxanes may be represented by one or more compounds having the following formula:

[0049] in which: each Rl and R2 are independently a 1 to 4 carbon atom alkyl group, a benzyl, or a phenyl group; each E is OH or NHR³ where R³ is hydrogen, a 1 to 6 carbon atoms alkyl group, or a 5 to 8 carbon atoms cyclo-alkyl group; a and b are each independently an integer from 2 to 8; c is an integer from 3 to 50. In amino- containing polysiloxanes, at least one of the E groups is NHR³. In the hydroxyl- containing polysiloxanes, at least one of the E groups is OH. In some embodiments, both R¹ and R² are methyl groups.

[0050] Suitable examples include α,ω-hydroxypropyl terminated poly(dimethysiloxane) and α,ω-amino propyl terminated poly(dimethysiloxane), both of which are commercially available materials. Further examples include copolymers of the poly(dimethysiloxane) materials with a poly(alkylene oxide).

[0051] The polyol component, when present, may include poly(ethylene glycol), poly(tetramethylene ether glycol), poly(trimethylene oxide), ethylene oxide capped poly(propylene glycol), poly(butylene adipate), poly(ethylene adipate), poly(hexamethylene adipate), poly(tetramethylene-co-hexamethylene adipate), poly(3-methyl-l,5-pentamethylene adipate), polycaprolactone diol, poly(hexamethylene carbonate) glycol, poly(pentamethylene carbonate) glycol, poly(trimethylene carbonate) glycol, dimer fatty acid based polyester polyols, vegetable oil based polyols, or any combination thereof.

[0052] Examples of dimer fatty acids that may be used to prepare suitable polyester polyols include Priplast™ polyester glycols/polyols commercially available from Croda and Radia® polyester glycols commercially available from Oleon.

[0053] In some embodiments, the polyol component includes a polyether polyol, a polycarbonate polyol, a polycaprolactone polyol, or any combination thereof.

[0054] In some embodiments, the polyol component includes a polyether polyol.

In some embodiments, the polyol component is essentially free of or even completely free of polyester polyols. In some embodiments, the polyol component used to prepare the TPU is substantially free of, or even completely free of polysiloxanes.

[0055] In some embodiments, the polyol component includes ethylene oxide, propylene oxide, butylene oxide, styrene oxide, poly(tetram ethylene ether glycol), poly(propylene glycol), poly(ethylene glycol), copolymers of poly(ethylene glycol) and poly(propylene glycol), epichlorohydrin, and the like, or combinations thereof.

In some embodiments the polyol component includes poly(tetramethylene ether glycol).

[0056] In other embodiments, the polyol component is essentially free of (or even completely free of) any polyester polyols, polycarbonate polyols, polysiloxane polyols, or all of the above.

[0057] Suitable polyamide oligomers, including telechelic polyamide polyols, are not overly limited and include low molecular weight polyamide oligomers and telechelic polyamides (including copolymers) that include N-alkylated amide groups in the backbone structure. Telechelic polymers are macromolecules that contain two reactive end groups. Amine terminated polyamide oligomers can be useful as polyols in the disclosed technology. The term polyamide oligomer refers to an oligomer with two or more amide linkages, or sometimes the amount of amide linkages will be specified. A subset of polyamide oligomers are telechelic polyamides. Telechelic polyamides are polyamide oligomers with high percentages, or specified percentages, of two functional groups of a single chemical type, e.g. two terminal amine groups (meaning either primary, secondary, or mixtures), two terminal carboxyl groups, two terminal hydroxyl groups (again meaning primary, secondary, or mixtures), or two terminal isocyanate groups (meaning aliphatic, aromatic, or mixtures). Ranges for the percent difunctional that can meet the definition of telechelic include at least 70, 80, 90 or 95 mole% of the oligomers being difunctional as opposed to higher or lower functionality. Reactive amine terminated telechelic polyamides are telechelic polyamide oligomers where the terminal groups are both amine types, either primary or secondary and mixtures thereof, i.e. excluding tertiary amine groups.

[0058] In some embodiments, the thermoplastic polyurethane is prepared with a polyol component that consists essentially of a polyester polyol. In some embodiments, the polyester polyol is polycaprolactone.

The chain extender

[0059] The TPU compositions described herein are made using: (c) at least one chain extender component including one or more short chain diols capable of breaking down into one or more non-toxic degradants, where the short chain diol is a linear, fully saturated alkylene diol.

[0060] The disclosed technology further provides the described TPU where the chain extender component includes at least one chain extender of the general formula HO-(CH2)n-X-(CH2)n-OH wherein n is an integer from 2 to 4 and X is oxygen (-0-) or disulfide (-S-S-).

[0061] The disclosed technology further provides the described TPU where the chain extender component includes dipropylene glycol, di-(2-hydroxyethyl) disulfide, diethylene glycol, or any combination thereof.

[0062] The disclosed technology further provides the described TPU where the chain extender component further includes one or more additional chain extenders, where these additional chain extenders includes at least one diol chain extender of the general formula HO-(CH2)_m-OH wherein m is an integer from 2 to 6.

[0063] In some embodiments, the chain extender component includes dipropylene glycol, di-(2-hydroxyethyl) disulfide, diethylene glycol, or any combination thereof. [0064] In some embodiments, an additional chain extender may be present and used in combination with the chain extenders described above to form the chain extender component.

[0065] In some embodiments, the TPU compositions are co-extended and are made using an additional chain extender component that includes at least one diol chain extender of the general formula HO-(CH2)_x-OH wherein x is an integer from 2 to 6 or even from 4 to 6. In other embodiments, x is the integer 4.

[0066] Useful additional coextenders include diol chain extenders include relatively small polyhydroxy compounds, for example lower aliphatic or short chain glycols having from 2 to 20, or 2 to 12, or 2 to 10 carbon atoms. Suitable examples include ethylene glycol, di ethylene glycol, propylene glycol, dipropylene glycol, 1,4-butanediol (BDO), 1,6-hexanediol (HDO), 1,3-butanediol, 1,5-pentanediol, neopentylglycol, 1,4- cyclohexanedimethanol (CHDM), 2,2-bis[4-(2-hydroxyethoxy)phenyl]propane (HEPP), heptanediol, nonanediol, dodecanediol, ethylenediamine, butanediamine, hexamethylenediamine, and hydroxyethyl resorcinol (HER), and the like, as well as mixtures thereof. In some embodiments, the chain extender includes BDO, HDO, or a combination thereof. In some embodiments, the chain extender includes BDO. Other glycols, such as aromatic glycols could be used, but in some embodiments the TPUs described herein are essentially free of or even completely free of such materials, or a combination thereof.

[0067] In some embodiments, the additional chain extender includes a cyclic chain extender. Suitable examples include CHDM, HEPP, HER, and combinations thereof. In some embodiments, the additional chain extender may include an aromatic cyclic chain extender, for example HEPP, HER, or a combination thereof. In some embodiments, the additional chain extender may include an aliphatic cyclic chain extender, for example CHDM. In some embodiments, the additional chain extender is substantially free of, or even completely free of aromatic chain extenders, for example aromatic cyclic chain extenders. In some embodiments, the additional chain extender is substantially free of, or even completely free of polysiloxanes. The thermoplastic polyur ethane compositions

[0068] The compositions described herein are TPU compositions. These TPU are prepared by reacting: a) the polyisocyanate component described above; b) the polyol component described above; and c) the chain extender component described above.

[0069] In some embodiments, the TPU compositions of the invention have a hard segment content of 10 to 50 percent by weight, where the hard segment content is the portion of the TPU derived from the polyisocyanate component and the chain extender component (the hard segment content of the TPU may be calculated by adding the weight percent content of chain extender and polyisocyanate in the TPU and dividing that total by the sum of the weight percent contents of the chain extender, polyisocyanate, and polyol in the TPU). In other embodiments, the hard segment content is at least 10, or at least 15, or from 10 to 60, or from 15 to 45 percent by weight.

[0070] The described compositions include the TPU materials described above and also TPU compositions that include such TPU materials and one or more additional components. These additional components include other polymeric materials that may be blended with the TPU described herein. These additional components also include one or more additives that may be added to the TPU, or blends containing the TPU, to impact the properties of the composition.

[0071] The TPU described herein may also be blended with one or more other polymers. The polymers with which the TPU described herein may be blended are not overly limited. In some embodiments, the described compositions include a two or more of the described TPU materials. In some embodiments, the compositions include at least one of the described TPU materials and at least one other polymer, which is not one of the described TPU materials. In some embodiments, the described blends will have the same combination of properties described above for the TPU composition. In other embodiments, the TPU composition will of course have the described combination of properties, while the blend of the TPU composition with one or more of the other polymeric materials described above may or may not.

[0072] Polymers that may be used in combination with the TPU materials described herein also include more conventional TPU materials such as non- caprolactone polyester-based TPU, polyether-based TPU, or TPU containing both non-caprolactone polyester and polyether groups. Other suitable materials that may be blended with the TPU materials described herein include polycarbonates, polyolefins, styrenic polymers, acrylic polymers, polyoxymethylene polymers, polyamides, polyphenylene oxides, polyphenylene sulfides, polyvinylchlorides, chlorinated polyvinylchlorides, polylactic acids, or combinations thereof.

[0073] Polymers for use in the blends described herein include homopolymers and copolymers. Suitable examples include: (i) a polyolefin (PO), such as polyethylene (PE), polypropylene (PP), polybutene, ethylene propylene rubber (EPR), polyoxyethylene (POE), cyclic olefin copolymer (COC), or combinations thereof; (ii) a styrenic, such as polystyrene (PS), acrylonitrile butadiene styrene (ABS), styrene acrylonitrile (SAN), styrene butadiene rubber (SBR or HIPS), polyalphamethylstyrene, styrene maleic anhydride (SMA), styrene-butadiene copolymer (SBC) (such as styrene-butadiene-styrene copolymer (SBS) and styrene- ethylene/butadiene-styrene copolymer (SEBS)), styrene-ethylene/propylene-styrene copolymer (SEPS), styrene butadiene latex (SBL), SAN modified with ethylene propylene diene monomer (EPDM) and/or acrylic elastomers (for example, PS-SBR copolymers), or combinations thereof; (iii) a thermoplastic polyurethane (TPU) other than those described above; (iv) a polyamide, such as Nylon™, including polyamide 6,6 (PA66), polyamide 1 , 1 (PA1 1), polyamide 1,2 (PA12), a copolyamide (COP A), or combinations thereof; (v) an acrylic polymer, such as polymethyl acrylate, polymethylmethacrylate, a methyl methacrylate styrene (MS) copolymer, or combinations thereof; (vi) a polyvinylchloride (PVC), a chlorinated polyvinylchloride (CPVC), or combinations thereof; (vii) a polyoxyem ethylene, such as polyacetal; (viii) a polyester, such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT), copolyesters and/or polyester elastomers (COPE) including polyether-ester block copolymers such as glycol modified polyethylene terephthalate (PETG), polylactic acid (PLA), polyglycolic acid (PGA), copolymers of PLA and PGA, or combinations thereof; (ix) a polycarbonate (PC), a polyphenylene sulfide (PPS), a polyphenylene oxide (PPO), or combinations thereof; or combinations thereof.

[0074] In some embodiments, these blends include one or more additional polymeric materials selected from groups (i), (iii), (vii), (viii), or some combination thereof. In some embodiments, these blends include one or more additional polymeric materials selected from group (i). In some embodiments, these blends include one or more additional polymeric materials selected from group (iii). In some embodiments, these blends include one or more additional polymeric materials selected from group (vii). In some embodiments, these blends include one or more additional polymeric materials selected from group (viii).

[0075] The additional additives suitable for use in the TPU compositions described herein are not overly limited. Suitable additives include pigments, UV stabilizers, UV absorbers, antioxidants, lubricity agents, heat stabilizers, hydrolysis stabilizers, cross-linking activators, flame retardants, layered silicates, radio opacifiers, such as barium sulfate, tungsten metal, non-oxide bismuth salts, fillers, colorants, reinforcing agents, adhesion mediators, impact strength modifiers, antimicrobials, and any combination thereof.

[0076] The TPU compositions described herein may also include additional additives, which may be referred to as a stabilizer. The stabilizers may include antioxidants such as phenolics, phosphites, thioesters, and amines, light stabilizers such as hindered amine light stabilizers and benzothiazole UV absorbers, and other process stabilizers and combinations thereof. In one embodiment, the preferred stabilizer is Irganox®-1010 from BASF and Naugard®-445 from Chemtura. The stabilizer is used in the amount from about 0.1 weight percent to about 5 weight percent, in another embodiment from about 0.1 weight percent to about 3 weight percent, and in another embodiment from about 0.5 weight percent to about 1.5 weight percent of the TPU composition.

[0077] Still further optional additives may be used in the TPU compositions described herein. The additives include colorants, antioxidants (including phenolics, phosphites, thioesters, and/or amines), antiozonants, stabilizers, inert fillers, lubricants, inhibitors, hydrolysis stabilizers, light stabilizers, hindered amines light stabilizers, benzotriazole UV absorber, heat stabilizers, stabilizers to prevent discoloration, dyes, pigments, inorganic and organic fillers, reinforcing agents and combinations thereof.

[0078] All of the additives described above may be used in an effective amount customary for these substances. These additional additives can be incorporated into th e components of, or into the reaction mixture for, the preparation of the TPU resin, or after making the TPU resin. In another process, all the materials can be mixed with the TPU resin and then melted or they can be incorporated directly into the melt of the TPU resin.

[0079] The thermoplastic polyurethanes of the invention can be prepared by processes which are conventional in the art for the synthesis of polyurethane elastomers such as but not limited to a two-step, batch process or a one-shot technique. In a two-step process, a prepolymer intermediate is reacted with an excess amount of diisocyanate, followed by chain extending the same. In the batch process, the components, i.e., the diisocyanate(s), the polyol(s), and the chain extenders (s), as well as the catalyst(s) and any other additive(s), if desired, are introduced into a container, mixed, dispensed into trays and allowed to cure. The cured TPU can then be granulated and pelletized. The one-shot procedure is performed in an extruder, e.g., single screw, twin screw, wherein the formative components, introduced individually or as a mixture into the extruder, and reacted at a temperature generally in one embodiment from about 100°C to about 300°C, and in another embodiment from about 150°C to about 250°C, and even from about 150°C to about 240°C.

[0080] One or more polymerization catalysts may be present during the polymerization reaction. Generally, any conventional catalyst can be utilized to react the diisocyanate with the polyol intermediates or the chain extender. Examples of suitable catalysts which in particular accelerate the reaction between the NCO groups of the diisocyanates and the hydroxy groups of the polyols and chain extenders are the conventional tertiary amines known from the prior art, e.g. tri ethyl amine, dimethylcyclohexylamine, N-methylmorpholine, N,N'-dimethylpiperazine, 2- (dimethylaminoethoxy)ethanol, diazabicyclo[2.2.2]octane and the like, and also in particular organometallic compounds, such as titanic esters, iron compounds, e.g. ferric acetyl acetonate, tin compounds, e.g. stannous diacetate, stannous dioctoate, stannous dilaurate, or the dialkyltin salts of aliphatic carboxylic acids, e.g. dibutyltin diacetate, dibutyltin dilaurate, or the like. The amounts usually used of the catalysts are from 0.0001 to 0.1 part by weight per 100 parts by weight of polyhydroxy compound (b). In some embodiments, the TPU materials used in the compositions of the disclosed technology are made using l ,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. In some embodiments, the catalyst is used at a concentration of 5 mol % of macrodiol. In other embodiments, the TPU materials used in the compositions of the disclosed technology are made using stannous octoate as a catalyst. In some embodiments, the catalyst is used at a concentration of 8 mol % of macrodiol.

[0081] The TPU materials described above may be prepared by a process that includes the step of (I) reacting: a) the polyisocyanate component described above, that includes at least one aliphatic diisocyanate; b) the polyol component described above, that includes at least one polyester polyol; and c) the chain extender component described above that includes a substituted 2,5-diketopiperazine, as described above.

[0082] The process may further include the step of: (II) mixing the TPU composition of step (I) with one or more blend components, including one or more additional TPU materials and/or polymers, including any of those described above.

[0083] The process may further include the step of: (II) mixing the TPU composition of step (I) with one or more additional additives selected from the group consisting of pigments, UV stabilizers, UV absorbers, antioxidants, lubricity agents, heat stabilizers, hydrolysis stabilizers, cross-linking activators, flame retardants, layered silicates, fillers, colorants, reinforcing agents, adhesion mediators, impact strength modifiers, and antimicrobials.

[0084] The process may further include the step of: (II) mixing the TPU composition of step (I) with one or more blend components, including one or more additional TPU materials and/or polymers, including any of those described above, and/or the step of: (III) mixing the TPU composition of step (I) with one or more additional additives selected from the group consisting of pigments, UV stabilizers, UV absorbers, antioxidants, lubricity agents, heat stabilizers, hydrolysis stabilizers, cross-linking activators, flame retardants, layered silicates, fillers, colorants, reinforcing agents, adhesion mediators, impact strength modifiers, and antimicrobials.

[0085] The process may further include in step I of including a co-extender component that includes at least one diol chain extender of the general formula HO- (CH2)x-OH wherein x is an integer from 2 to 6. [0086] The TPU materials and/or compositions described herein may be used in the preparation of one or more articles. The specific type of articles that may be made from the TPU materials and/or compositions described herein are not overly limited.

[0087] The invention further provides an article made with the TPU materials and/or compositions described herein. Examples include but are not limited to medical applications, as well as used in, personal care applications, pharmaceutical applications, health care product applications, or any other number of applications. In some embodiments, these articles are prepared by extruding, injection molding, or any combination thereof.

[0088] In one embodiment, the TPU materials and/or compositions described herein may be used as medical devices, such as implants or coatings on implants, where the TPU delivers one or more therapeutic agents at the site of implantation. The terms "therapeutic agents" and "drugs" are used herein interchangeably to mean any material that has a therapeutic effect at an implantation site. Also, as used herein, the device of the present invention is said to "deliver" or "elute" therapeutic agent— these terms are used synonymously and generally to refer to any mechanism by which the therapeutic agent comes into contact with tissue.

[0089] The therapeutic agent(s) may be delivered in a number of ways. In one example, the therapeutic agent(s) are embedded within a coating that is made using the TPU materials and/or compositions described herein that adheres to one or more surfaces of an implant or other medical article or medical device. In some embodiments, the coating is made from one or more of the TPU materials and/or compositions described herein admixed with the therapeutic agent(s) such that the agent is eluted from the polymer over time, or is released from the coating as it degrades in-vivo. In some embodiments one or more therapeutic agents are applied in discrete areas on one or more individual section or surfaces of the implant or other medical article or medical device.

[0090] The TPU materials and/or compositions described herein are meant to biodegrade and/or bioabsorb slowly enough that the materials may have physical properties suitable for and sufficiently long lasting enough to be used in the construction of medical devices. Further, they are meant to biodegrade and/or bioabsorb quickly enough that the materials are suitable for use in the construction of medical devices meant to break down in the body. Still further, they are meant to break down in such a way that there are no toxic byproducts caused by their biodegrading and/or bioabsorbing. The compositions described herein have been found to meet this unique set of conditions.

[0091] In some embodiments, in order to be suitable for certain applications, the TPU materials and/or compositions described herein retain at least 30% of their initial ultimate tensile strength after 1 week of exposure to the degradation protocol described herein. In other embodiments, the compositions retain at least 50% of their initial ultimate tensile strength after 1 week. In some of these embodiments the materials also lose 100% of their initial ultimate tensile strength after 5 weeks, or even 4 weeks, of exposure to the degradation protocol described herein. In other embodiments, the materials also lose at least 80% of their initial ultimate tensile strength after 3 weeks of exposure to the degradation protocol described herein. This combination of tensile strength retention for so long and then so much tensile strength loss by such a point in time, which are indicators of the controlled degradation rate of the material, can be important for medical device application where these materials may be used.

[0092] The amount of each chemical component described is presented exclusive of any solvent which may be customarily present in the commercial material, that is, on an active chemical basis, unless otherwise indicated. However, unless otherwise indicated, each chemical or composition referred to herein should be interpreted as being a commercial grade material which may contain the isomers, by-products, derivatives, and other such materials which are normally understood to be present in the commercial grade.

[0093] It is known that some of the materials described above may interact in the final formulation, so that the components of the final formulation may be different from those that are initially added. For instance, metal ions can migrate to other acidic or anionic sites of other molecules. The products formed thereby, including the products formed upon employing the composition of the technology described herein in its intended use, may not be susceptible of easy description. Nevertheless, all such modifications and reaction products are included within the scope of the technology described herein; the technology described herein encompasses the composition prepared by admixing the components described above.

EXAMPLES

|0094| The technology described herein may be better understood with reference to the following non-limiting examples.

Materials

[O095J Polyurethanes are synthesized in either a 2-step or 1-step bulk polymerization reaction. In general, the first step of the 2-step reaction is the formation of the

prepolymer by the reaction of the polyol component with an excess amount of the polyisocyanate component. The reaction is catalyzed by using stannous octoate (8 mol % of macrodiol) as catalyst. The reaction exotherms and levels off at 80°C to 90°C. The reaction mixture is then allowed to cool to ~60°C and the chain extender is added. The reaction is again allowed to exotherm to ~80°C and then the contents are poured in a pan. The pan is then put in curing oven to cure and complete the reaction at 125°C for 5 hours.

f(Hi96| The 1-pot reaction is conducted by adding calculated equivalent amounts of the macrodiol, chain extender and the isocyanate in the reaction vessel at 60°C while mixing using overhead stirrer and then adding catalyst. Once the exotherm is complete, the contents of the vessel are transferred in to a pan and cured similar to the 2-step procedure. The hard segment of the polyurethanes is calculated according to the following formula:

100 (R - 1) (M_di + M_da)

[M_E + R (M_di) + (R - lXM_da)]

where,

R = ratio of diisocyanates divided by polyols; M = molecular weight; di = diisocyanate; da = diol; and

ε = polydiol.

|O09?J The following Table 1 summarizes the formulation of the Samples, where Inventive Examples 1 and 2 are thermoplastic polyurethanes made with components that degrade into non-toxic components, and Comparative Example 3 which is thermoplastic polyurethane made with more conventional materials. Table 1 Formulations of Examples

[00 8J Inventive Example 1 and Inventive Example 2 contain hydrolysable soft segments and oxidizable hard segments. Comparative Example 3 contains neither oxidizable nor hydrolysable moieties.

f0099| Each sample in Table 1 is tested to verify its mechanical properties (strength, modulus and elongation as measured by ASTM D412) and degradation rates where degradation was measured using the following protocol: (1) each example is extruded into a tape and small (ASTM D1708) dogbones are punched out; three dogbones per sample were tested at each time point. (2) A degradation solution is prepared by making a solution of 20% H2O2 (hydrogen peroxide) and 0.1M Cobalt Chloride (oxidative solution) meant to simulate an in-vivo environment. (3) The dogbones of each sample are immersed in the degradation solution and held at 50 °C. (4) dogbones are removed once a week for up to ten weeks and tested for mechanical properties (strength, modulus and elongation as measured by ASTM D412). The degradation solution is changed two times every week to maintain the concentration of the free radicals in the solution.

Properties tested: Tensile strength and tensile elongation every week; molecular weight @ at 0, 3 and 6 weeks. These test is referred to herein as the "degradation protocol."

[0100] Table 2 below summarizes the results of this testing: Table 2 Results

UTS is ultimate tensile strength and is tested by ASTM Dl 708 and reported in MP a.

ELG is elongation and is tested by ASTM D 1708 and reported as a percent.

Mw is weight average molecular weight as is measured by GPC using polystyrene calibration standards.

[0101] Using this data, percent loss in tensile strength and percent elongation are calculated and presented in Table 3 below.

Table 3 Results

Inventive Ex 1 Inventive Ex 2 Comparative Ex 3

Week %Loss %Loss %Loss %Loss %Loss %Loss

UTS ELG UTS ELG UTS ELG

0 0 0 0 0 0 0

1 68.7 75.7 43.7 78.5 1 1.0 1.2

2 82.4 94.0 54.5 90.5 9.4 -4.8

3 92.7 97.4 86.4 93.7 14.4 -10.4

4 100 100 100 100 26.7 -3.2

5 100 100 34.9 -2.6

6 100 100 46.1 3.8

7 100 100 62.4 23.3

8 100 100 74.0 44.1

9 100 100 83.4 60.4

10 100 100 88.5 60.3

11 100 100 89.9 60.4

12 100 100 100 100

13 100 100 100 100

14 100 100

15 100 100 %Loss UTS is the percent the ultimate tensile strength has dropped compared to the original result at time zero.

%Loss ELG is the percent the elongation has dropped compared to the original result at time zero.

[0102] The results in Table 3 show the percent loss in tensile strength and tensile elongation over time for the 3 samples tested. As can be seen from the results, Inventive Example 1 and Inventive Example 2 show rapid loss in tensile properties over a period of just 4 weeks. Comparative Example 3 shows a very gradual loss in strength and elongation over a period of 1 1 weeks. The urethane linkage in a thermoplastic polyurethane is also susceptible to degradation and the Comparative Example 3 data proves that, it just occurs very slowly compared to the inventive examples. The Inventive Example 1 and Inventive Example 2 have hydrolysable soft segment and so the polymer breaks down faster in presence of water which is further enhanced by the presence of oxidizable hard segments which break down in the presence of peroxides. So, there is a dual degradation mechanism responsible for the degradation of the TPUs of the invention.

[0103] Several sets of additional inventive examples are also included. Tables 4 to 8 below summarizes the formulation of these inventive examples. These examples may be made by the same processes described above and may be tested by the same methods described above.

Table 4 Formulations of Additional Examples using HDI

% Hard

Example Polyol Chain Extender Diisocyanate

Segment

Inv Ex 1 PCL DEG HDI 25

Inv Ex 2 PCL DEG HDI 25

Inv Ex 3 PCL DEG HDI 75

Inv Ex 4 PGA DEG HDI 25

Inv Ex 5 PGA DEG HDI 50

Inv Ex 6 PGA DEG HDI 75

Inv Ex 7 PLA DEG HDI 25

Inv Ex 8 PLA DEG HDI 50

Inv Ex 9 PLA DEG HDI 75

Inv Ex 10 50: 50 PCL:PGA DEG HDI 25

Inv Ex 1 1 50: 50 PCL:PGA DEG HDI 50

Inv Ex 12 50: 50 PCL:PGA DEG HDI 75

Inv Ex 13 50:50 PCL:PLA DEG HDI 25

Inv Ex 14 50:50 PCL:PLA DEG HDI 50 % Hard

Example Polyol Chain Extender Diisocyanate

Segment

Inv Ex 15 50:50 PCL:PLA DEG HDI 75

Inv Ex 16 50: 50 PGA: PL A DEG HDI 25

Inv Ex 17 50: 50 PGA: PL A DEG HDI 50

Inv Ex 18 50: 50 PGA: PL A DEG HDI 75

BDI is 1, 4-butane diisocyanate; LDI is Lysine diisocyanate; HDI is 1, 6-hexane diisocyanate; PLA is poly(L-lactide) ; PGA is polglycolide; PCL is polycaprolactone ; DPG is dirpopylene glycol; DHS is di-(2-hydroxyethyl) disulfide; DEG is diethylene glycol.

Table 5 Formulations of Additional Examples using BDI

BDI is 1, 4-butane diisocyanate; LDI is Lysine diisocyanate; HDI is 1, 6-hexane diisocyanate; PLA is poly(L-lactide) ; PGA is polglycolide; PCL is polycaprolactone ; DPG is dirpopylene glycol; DHS is di-(2-hydroxyethyl) disulfide; DEG is diethylene glycol.

Table 6 Formulations of Additional Examples using LDI

% Hard

Example Polyol Chain Extender Diisocyanate

Segment

Inv Ex 37 PCL DEG LDI 25

Inv Ex 38 PCL DEG LDI 50

Inv Ex 39 PCL DEG LDI 75

Inv Ex 40 PGA DEG LDI 25 % Hard

Example Polyol Chain Extender Diisocyanate

Segment

Inv Ex 41 PGA DEG LDI 50

Inv Ex 42 PGA DEG LDI 75

Inv Ex 43 PLA DEG LDI 25

Inv Ex 44 PLA DEG LDI 50

Inv Ex 45 PLA DEG LDI 75

Inv Ex 46 50: 50 PCL:PGA DEG LDI 25

Inv Ex 47 50: 50 PCL:PGA DEG LDI 50

Inv Ex 48 50: 50 PCL:PGA DEG LDI 75

Inv Ex 49 50:50 PCL:PLA DEG LDI 25

Inv Ex 50 50:50 PCL:PLA DEG LDI 50

Inv Ex 51 50:50 PCL:PLA DEG LDI 75

Inv Ex 52 50: 50 PGA: PLA DEG LDI 25

Inv Ex 53 50: 50 PGA: PLA DEG LDI 50

Inv Ex 54 50: 50 PGA: PLA DEG LDI 75

BDI is 1,4-butane diisocyanate; LDI is Lysine diisocyanate; HDI is 1,6-hexane diisocyanate; PLA is poly(L-lactide) ; PGA is polglycolide; PCL is polycaprolactone ; DPG is dirpopylene glycol; DHS is di-(2-hydroxyethyl) disulfide; DEG is diethylene glycol.

Table 7 Formulations of Additional Examples using DPG

BDI is 1,4-butane diisocyanate; LDI is Lysine diisocyanate; HDI is 1,6-hexane diisocyanate; PLA is poly(L-lactide) ; PGA is polglycolide; PCL is polycaprolactone ; dirpopylene glycol; DHS is di-(2-hydroxyethyl) disulfide; DEG is diethylene

Table 8 Formulations of Additional Examples using DHS

BDI is 1, 4-butane diisocyanate; LDI is Lysine diisocyanate; HDI is 1, 6-hexane diisocyanate; PLA is poly(L-lactide) ; PGA is polglycolide; PCL is polycaprolactone ; DPG is dirpopylene glycol; DHS is di-(2-hydroxyethyl) disulfide; DEG is diethylene glycol. [0104] Each of the documents referred to above is incorporated herein by reference, including any prior applications, whether or not specifically listed above, from which priority is claimed. The mention of any document is not an admission that such document qualifies as prior art or constitutes the general knowledge of the skilled person in any jurisdiction. Except in the Examples, or where otherwise explicitly indicated, all numerical quantities in this description specifying amounts of materials, reaction conditions, molecular weights, number of carbon atoms, and the like, are to be understood as modified by the word "about." It is to be understood that the upper and lower amount, range, and ratio limits set forth herein may be independently combined. Similarly, the ranges and amounts for each element of the technology described herein can be used together with ranges or amounts for any of the other elements.

[0105] As described hereinafter the molecular weight of the materials described above have been determined using known methods, such as GPC analysis using polystyrene standards. Methods for determining molecular weights of polymers are well known. The methods are described for instance: (i) P.J. Flory, "Principles of star polymer Chemistry", Cornell University Press 91953), Chapter VII, pp 266-315; or (ii) "Macromolecules, an Introduction to star polymer Science", F. A. Bovey and F. H. Winslow, Editors, Academic Press (1979), pp 296-312. As used herein the weight average and number weight average molecular weights of the materials described are obtained by integrating the area under the peak corresponding to the material of interest, excluding peaks associated with diluents, impurities, uncoupled star polymer chains and other additives.

[0106] As used herein, the transitional term "comprising," which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, un-recited elements or method steps. However, in each recitation of "comprising" herein, it is intended that the term also encompass, as alternative embodiments, the phrases "consisting essentially of and "consisting of," where "consisting of excludes any element or step not specified and "consisting essentially of permits the inclusion of additional un-recited elements or steps that do not materially affect the basic and novel characteristics of the composition or method under consideration. That is "consisting essentially of permits the inclusion of substances that do not materially affect the basic and novel characteristics of the composition under consideration.

[0107] While certain representative embodiments and details have been shown for the purpose of illustrating the subject technology described herein, it will be apparent to those skilled in this art that various changes and modifications can be made therein without departing from the scope of the subject invention. In this regard, the scope of the technology described herein is to be limited only by the following claims.

Claims

What is claimed is:

1. A bioabsorbable thermoplastic polyurethane, comprising the reaction product of:

a. a polyisocyanate component comprising one or more polyisocyanate capable of breaking down into one or more non-toxic degradants;

b. a polyol component comprising one or more polyols capable of breaking down into one or more non-toxic degradants; and

c. at least one chain extender component comprising one or more short chain diols capable of breaking down into one or more non-toxic degradants

wherein said short chain diol comprises a linear, fully saturated alkylene diol.

2. The bioabsorbable thermoplastic polyurethane of claim 1, wherein the polyisocyanate component comprises an aliphatic diisocyanate.

3. The bioabsorbable thermoplastic polyurethane of claim 1 wherein the polyisocyanate component comprises 1,4-butane diisocyanate (BDI), Lysine diisocyanate (LDI), 1,6-hexane diisocyanate (HDI), 4,4 '-methylene dicyclohexyl diisocyanate (H12MDI), or any combination thereof.

4. The bioabsorbable thermoplastic polyurethane of claim 1, wherein the polyol component comprises poly(L-lactide) (PLA), polglycolide (PGA), polycaprolactone (PCL), polytri methylene carbonate, or any combination thereof.

5. The bioabsorbable thermoplastic polyurethane of claim 4, wherein the polyol component further comprises a polyether polyol comprising poly(propylene glycol), poly(ethylene glycol), poly(tetramethylene ether glycol), and combinations thereof.

6. The bioabsorbable thermoplastic polyurethane of claim 1, wherein the chain extender component comprises at least one chain extender of the general formula HO- (CH2)n-X-(CH2)_n-OH wherein n is an integer from 2 to 4 and X is oxygen (-0-) or disulfide (-S-S-).

7. The bioabsorbable thermoplastic polyurethane of claim 1, wherein the chain extender component comprises dipropylene glycol, di-(2-hydroxyethyl) disulfide, diethylene glycol, or any combination thereof.

8. The bioabsorbable thermoplastic polyurethane of claim 7, wherein the chain extender component further comprises one or more additional chain extenders, wherein said additional chain extenders comprise at least one diol chain extender of the general formula HO-(CH2)_m-OH wherein m is an integer from 2 to 6.

9. The bioabsorbable thermoplastic polyurethane of claim 1,

wherein the polyol component further comprises a polyether polyol comprising poly(propylene glycol), poly(ethylene glycol), poly(tetramethylene ether glycol), and combinations thereof; and

wherein the chain extender component further comprises one or more additional chain extenders, wherein said additional chain extenders comprise at least one diol chain extender of the general formula HO-(CH2)_m-OH wherein m is an integer from 2 to 6.

10. The bioabsorbable thermoplastic polyurethane of claim 1,

wherein the polyisocyanate component comprises 1,4-butane diisocyanate (BDI), Lysine diisocyanate (LDI), 1 ,6-hexane diisocyanate (HDI), or any combination thereof;

wherein the polyol component comprises a polyester polyol comprising poly(L-lactide) (PLA), polglycolide (PGA), or polycaprolactone (PCL) or combinations thereof; and

wherein the chain extender component comprises dipropylene glycol, di-(2- hydroxyethyl) disulfide, diethylene glycol, or any combination thereof.

1 1. The bioabsorbable thermoplastic polyurethane of claim 1,

wherein the polyisocyanate component comprises 1,6-hexane diisocyanate

(HDI); wherein the polyol component comprises a polyester polyol comprising poly(L-lactide) (PLA), polycaprolactone (PCL) or combinations thereof; and

wherein the chain extender component comprises dipropylene glycol.

12. The bioabsorbable thermoplastic polyurethane of claim 1,

wherein the polyisocyanate component comprises 1,6-hexane diisocyanate

(HDI);

wherein the polyol component comprises poly(L-lactide) (PLA) and polycaprolactone (PCL); and

wherein the chain extender component comprises dipropylene glycol.

13. The bioabsorbable thermoplastic polyurethane of claim 1,

wherein the polyisocyanate component comprises 1,6-hexane diisocyanate

(HDI);

wherein the polyol component comprises polycaprolactone (PCL); and wherein the chain extender component comprises dipropylene glycol.

14. A medical article comprising the bioabsorbable thermoplastic polyurethane of claim 1.

15. A method of making a bioabsorbable thermoplastic polyurethane, comprising the step of (I) reacting:

a. a polyisocyanate component comprising one or more polyisocyanate capable of breaking down into one or more non-toxic degradants;

b. a polyol component comprising one or more polyols capable of breaking down into one or more non-toxic degradants; and

c. at least one chain extender component comprising one or more short chain diols capable of breaking down into one or more non-toxic degradants

wherein said short chain diol comprises a linear, fully saturated alkylene diol.