Patent Description:
Implantable medical devices including filaments made from pure polylactic acid (PLA) are known. Pure PLA is considered beneficial as a long term biodegradable material suitable for implantation with enhanced strength. However, pure PLA can also be very brittle and/or stiff to work with thereby making it difficult to extrude and/or spin into filaments. In addition, when successfully formed into filaments, pure PLA filaments can be prone to premature failure when stressed because of their brittle and/or stiff nature. The failure being premature because the failure or break can occur well before the pure PLA material has been fully degraded. For example, pure PLA filaments can take <NUM> months or longer to fully degrade at <NUM> (body temperature) but may fail between <NUM> and <NUM> months at <NUM> rendering the broken pure PLA filaments significantly less effective long term. It would be advantageous to provide a biodegradable material suitable for filament formation which provides better long term persistence and better handling and strength characteristics than pure PLA.

<CIT> describes the use of polycarbonate to increase the crystallization rate of polylactides while maintaining their mechanical properties. The disclosed compositions include diblock and triblock copolymers containing suitably <NUM>-7wt. % of polytrimethylene carbonate (PTMC) to achieve a suitable balance of nucleating power and mechanical properties.

<CIT> describes implantable medical devices fabricated from block copolymers. In one embodiment, the block copolymer is a copolymer of PLA, glycolic acid (GA) and PTMS in the weight ratio PLA:PTMC:GA <NUM>:<NUM>:<NUM>, which corresponds to a mol% ratio of approximately <NUM>:<NUM>:<NUM>.

The present disclosure provides an implantable medical device comprising at least one filament including a biodegradable triblock copolymer comprising: an A-B-A' structure wherein the A and A' blocks each include polylactide, the B block includes from about <NUM> to about <NUM> mole percent of polytrimethylene carbonate (PTMC) and <NUM> to about <NUM> mole percent polylactide or polylactic acid, and the biodegradable triblock copolymer overall includes from about <NUM> to about <NUM> mole percent of the polytrimethylene carbonate and from about <NUM> to about <NUM> mole percent of the polylactide or polylactic acid.

Suitable additional features of the implantable medical devices according to the present invention are defined in claims <NUM> to <NUM>.

The present invention further provides methods of forming the implantable medical devices of the present invention, the methods being defined in claims <NUM>-<NUM>.

The present disclosure provides implantable medical devices comprising at least one filament including a biodegradable ABA' triblock copolymers including polylactic acid and polytrimethylene carbonate, as defined in claim <NUM>. The biodegradable ABA' triblock copolymers being suitable for forming implantable medical devices, in particular medical devices including filaments. Methods of forming the implantable medical devices of the invention comprising the biodegradable ABA' triblock copolymers are also described.

The term "ABA' triblock copolymer(s)" is defined herein as a block copolymer having moieties A, B and A' arranged according to the general formula -{[A-]a-[B]b-[A']a'}-d, where each of "a," "b," "a'" and "d" independently is greater than or equal to (≥) <NUM>. For example, each of "a," "b," "a'," and "d" may independently range from <NUM> to <NUM>,<NUM>. In embodiments, each "a," "b," "a'," and "d" may independently range from about <NUM> to <NUM>. In embodiments, each "a," "b," "a'," and "d" may independently range from about <NUM> to <NUM>. In embodiments, each "a," "b," "a'," and "d" may independently range from about <NUM> to <NUM>.

In some embodiments, each "a" and "a'" may independently range from about <NUM> to about <NUM>. In embodiments, each "a" and "a'" may independently range from about <NUM> to about <NUM>. In embodiments, each "a" and "a'" may independently range from about <NUM> to about <NUM>.

In some embodiments, each "a" and "a'" may be about the same number ranging from about <NUM> to about <NUM>. In embodiments, each "a" and "a'" may be about the same number ranging from about <NUM> to about <NUM>. In embodiments, each "a" and "a'" may be about the same number ranging from about <NUM> to about <NUM>.

In some embodiments, "b" may range from about <NUM> to about <NUM>. In embodiments, "b" may range from about <NUM> to about <NUM>. In embodiments, "b" may range from about <NUM> to about <NUM>.

In some embodiments, each "a" and "a'" may independently range from about <NUM> to about <NUM> and "b" may range from about <NUM> to about <NUM>.

In some embodiments, each "a" and "a'" may be about the same number ranging from about <NUM> to about <NUM> and "b" may range from about <NUM> to about <NUM>.

In addition, any ranges provided herein are intended to encompass the entire range inclusively, including not only the starting and ending number of the range but also any whole number or fraction of a number which falls within the range, individually or in any combination of narrower ranges. For example, a B block including <NUM> to <NUM> mole percent polytrimethylene carbonate (pTMC) and <NUM> to <NUM> mole percent polylactide or polylactic acid (PLA) may include pTMC/PLA in the following: individual whole number ratios, such as <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>;<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, and <NUM>/<NUM>; individual fractional number ratios, such as the following non-limiting examples, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, and the like; or narrower ranges, such as the following non-limiting examples, <NUM> to <NUM> mole percent pTMC and <NUM> to <NUM> mole percent PLA or <NUM> to <NUM> mole percent pTMC and <NUM> to <NUM> mole percent PLA, etc..

The A and A' blocks of the ABA' triblock copolymers in the implantable medical devices of the present invention each independently include polylactide. In embodiments, the A and A' blocks consist or consist essentially of polylactide or polylactic acid. In other embodiments, up to about 10mol%, 20mol%, 30mol% or 40mol% of other monomer units may be present.

The terms "polylactide" and "polylactic acid" are used interchangeably throughout the present disclosure. To the extent "polylactide" and "polylactic acid" may be interpreted differently, each of the embodiments described herein may include "polylactide", "polylactic acid" or both. The terms "polylactide" and "polylactic acid" refer to polymers comprising residues obtainable by polymerization of lactide, that is to say polymer residues of formula - OCH(CH<NUM>)COOCH(CH<NUM>)CO- as shown in Formula (I) below. The term "polytrimethylene carbonate" refers to polymers containing residues obtainable by polymerization of trimethylene carbonate, that is to say residues of formula -OCH<NUM>CH<NUM>CH<NUM>OCO- as shown in Formula (I) below. The mole percentages of polylactide/polyglycolide or polytrimethylene carbonate recited herein refer to the mole percentages of residues of formula OCH(CH<NUM>)COOCH(CH<NUM>)CO- as shown in Formula (I) below or -OCH<NUM>CH<NUM>CH<NUM>OCO- as shown in Formula (I) below, respectively, in the polymers of the invention.

There are several different types of polylactide and/or polylactic acid polymers including poly-L-lactic acid (PLLA), poly-D-lactic acid (PDLA), and combinations and/or racemic versions of both, such as poly-DL-lactic acid (PDLLA). The A and A' blocks of the ABA' triblock copolymers described herein each independently include at least one type of polylactide. In some embodiments, the A and A' blocks include the same type of polylactic acid. In some embodiments, the A and A' blocks include different types of polylactic acid.

The B block of the ABA' triblock copolymers described herein includes from about <NUM> to about <NUM> mole percent polytrimethylene carbonate and <NUM> to about <NUM> mole percent polylactic acid. The B block may be a random copolymer of polytrimethylene carbonate and polylactic acid in these mole percent ranges. Suitably, the B block of the ABA' triblock copolymers consists or consists essentially of the polytrimethylene carbonate and polylactic acid monomer units, substantially free from other monomer units. In embodiments, up to about 10mol%, <NUM> mol. %, 30mol% or 40mol% of other monomer units may be present.

In some embodiments, the B block of the ABA' triblock copolymers described herein include from about <NUM> to about <NUM> mole percent polytrimethylene carbonate and about <NUM> to about <NUM> mole percent polylactic acid.

In some embodiments, the A and A' blocks are both pure polylactic acid and the B block is a random copolymer of polytrimethylene carbonate and polylactic acid.

In some particular embodiments, the B block includes about <NUM> mole percent polytrimethylene carbonate and about <NUM> mole percent polylactic acid.

In some particular embodiments, the B block includes about <NUM> mole percent polytrimethylene carbonate and about <NUM> mole percent polylactic acid.

While the B block of the biodegradable ABA' triblock copolymers described herein is predominantly polytrimethylene carbonate, the ABA' triblock copolymer(s) overall, i.e., including all <NUM> blocks A, B, and A', is predominantly polylactic acid. By predominantly, the material represents greater than or equal to <NUM> mole percent of the block, i.e., the B block and/or the overall triblock. In some embodiments, the ABA' triblock copolymer(s) are overall predominantly polylactic acid while including a B block which is predominantly polytrimethylene carbonate.

In accordance with the present invention, the biodegradable ABA' triblock copolymers overall include from about <NUM> to about <NUM> mole percent of the polytrimethylene carbonate and from about <NUM> to about <NUM> mole percent of the polylactic acid.

In some embodiments, the biodegradable ABA' triblock copolymer overall includes about <NUM> mole percent polytrimethylene carbonate and about <NUM> mole percent polylactic acid.

In some embodiments, the biodegradable ABA' triblock copolymer overall includes about <NUM> mole percent polytrimethylene carbonate and about <NUM> mole percent polylactic acid.

In some particular embodiments, the biodegradable ABA' triblock copolymer are described wherein the A and A' blocks each include polylactic acid, the B block includes about <NUM> mole percent of polytrimethylene carbonate and <NUM> mole percent polylactic acid, and the biodegradable triblock copolymer overall includes about <NUM> mole percent of the polytrimethylene carbonate and about <NUM> mole percent of the polylactic acid.

In all of the above definitions, references to the ABA' block copolymer including specified amounts of polylactide and/or trimethylene carbonate suitably refer to the copolymer block consisting essentially of or consisting of these components.

The biodegradable ABA' triblock copolymer(s) described herein display a melting temperature (Tm) ranging from about <NUM> to about <NUM>. In embodiments, the copolymers described herein display a Tm ranging from about <NUM> to about <NUM>. In embodiments, the copolymers described herein display a Tm ranging from about <NUM> to about <NUM>, wherein the melting temperature Tm is determined by differential scanning calorimetry (DSC) by the methods disclosed in the present specification.

The biodegradable ABA' triblock copolymer(s) described herein display a glass transition temperature (Tg) ranging from about <NUM> to about <NUM>. In embodiments, the copolymers described herein display a Tg ranging from about <NUM> to about <NUM>. In embodiments, the copolymers described herein display a Tg ranging from about <NUM> to about <NUM>, wherein the glass transition temperature Tg is determined by differential scanning calorimetry (DSC) by the methods disclosed in the present specification.

For forming filaments for medical devices, the triblock copolymer(s) described herein need to have sufficient molar mass, i.e., weight average molecular weight (Mw) and/or number average molecular weight (Mn) as measured by size exclusion chromatography by the methods disclosed in the present specification. Accordingly, in some embodiments, optionally in combination with one or more other embodiments described herein, the triblock copolymers have a molecular weight (Mw) of at least about <NUM>,<NUM>/mol. In some embodiments, the triblock copolymers have an Mw of at least about <NUM>,<NUM>/mol. In some embodiments, the triblock copolymers have an Mw of at least about <NUM>,<NUM>/mol.

In some embodiments, optionally in combination with one or more other embodiments described herein, the triblock copolymers range in Mw from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In other embodiments, the triblock copolymers range in Mw from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In still other embodiments, the triblock copolymers range in Mw from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In yet other embodiments, the triblock copolymers range in Mw from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol.

In some embodiments, optionally in combination with one or more other embodiments described herein, the triblock copolymers have a polymer number-average molecular weight (Mn) of at least about <NUM>,<NUM>/mol. In some embodiments, the triblock copolymers have a Mn of at least about <NUM>,<NUM>/mol.

In some embodiments, optionally in combination with one or more other embodiments described herein, the triblock copolymers range in Mn from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In some embodiments, the triblock copolymers range in Mn from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In some embodiments, the triblock copolymers range in Mn from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In some embodiments, the triblock copolymers range in Mn from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In some embodiments, the triblock copolymers range in Mn from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol.

Biodegradable triblock copolymers of the present disclosure having a Mw and a Mn from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol may be more suitable for forming filaments for medical devices. In some embodiments, the biodegradable triblock copolymers of the present disclosure have a Mw and a Mn from about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol In some embodiments, the biodegradable triblock copolymers of the present disclosure have a Mw and a Mn ratio, i.e., polydisperse index (PDI), ranging from <NUM>:<NUM> to <NUM>:<NUM>, in some embodiments from <NUM>:<NUM> to <NUM>:<NUM>, for being processed into filaments for medical devices.

The Mw, Mn, and PDI of the ABA' triblock copolymers described herein may be determined using size-exclusion chromatography (SEC). For example, in some embodiments, absolute molar mass measurements can be performed using a chromatography system such as Waters APC (Advanced polymer chromatography system, Waters Corporation, Milford, USA) with light scattering and RI detection. Such systems may operate using various solvents, including but not limited to HFIP (<NUM>,<NUM>,<NUM>,<NUM>,<NUM>,<NUM>-hexafluoro-<NUM>-propanol) and at various temperatures. Analysis can be performed in some instances at a temperature of about <NUM> C, with an injection volume of about <NUM>µl, a flow rate of about <NUM>/min and a sample concentration of about <NUM>/ml. In some instances, the systems may include columns from Agilent Technologies (Santa Clara, CA, USA) such as columns PL HFIP gel Guard <NUM>*<NUM> and/or columns PL HFIP gel <NUM>*<NUM>. In some instances, the systems may include an RI detector such as Optilab T-rEX from Wyatt technologies (Santa Barbara, CA, USA) and/or a multi-angle light scattering detector Dawn Heleos II (wavelength of <NUM>) also from Wyatt technologies. The light scattering measurements and the RI measurements may be calculated using Astra <NUM>. <NUM> software also from Wyatt technologies.

The Tm and Tg of the ABA' triblock copolymers described herein may be determined using differential scanning calorimetry (DSC). For example, in some embodiments, DSC measurements can be carried out on a Mettler Toledo DSC thermal analyzer, integrated with software STARe. In some instances, for each of the references measured, five samples (<NUM>-<NUM>) were submitted to a heating scan to <NUM> (<NUM>/ min), a cooling scan to <NUM> (<NUM>/min) and a second heating scan to <NUM> (<NUM>/min). The Tm, Tg, and degree of crystallinity (Xc) was determined from the second heating ramp. A reference enthalpy of melting of <NUM> J/g was used to calculate the crystallinity of PLA.

In some particular embodiments, the biodegradable ABA' triblock copolymer can be of the following formula:
<CHM>
wherein m and n are independently <NUM>-<NUM>, and in some embodiments m and n are independently <NUM>-<NUM>.

Formula I depicts a biodegradable ABA' triblock copolymer wherein the end blocks, i.e., A and A' blocks, each include polylactide or polylactic acid and the middle block, i.e., the B block, includes <NUM> mole percent of polytrimethylene carbonate and <NUM> mole percent polylactide or polylactic acid and the biodegradable triblock copolymer overall includes from about <NUM> to about <NUM> mole percent of the polytrimethylene carbonate and from about <NUM> to about <NUM> mole percent of the polylactide or polylactic acid.

In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>. In embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>. In embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM>.

In some embodiments, "n" of Formula I may range from about <NUM> to about <NUM>. In embodiments, "n" of Formula I may range from about <NUM> to about <NUM>. In embodiments, "n" of Formula I may range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula I may independently range from about <NUM> to about <NUM> and "n" of Formula I may range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula I may be the same number ranging from about <NUM> to about <NUM> and "n" of Formula I may range from about <NUM> to about <NUM>.

In some embodiments, "m" and "n" of Formula I are independently about <NUM> to about <NUM>. In some particular embodiments, "m" of Formula I is about <NUM> and "n" of Formula I is about <NUM>.

In some embodiments, the Mn and Mw of the triblock copolymer of Formula I are about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In some particular embodiments, the Mn of the triblock copolymer of Formula I is about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol and the Mw of the triblock copolymer of Formula I is about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol.

In some particular embodiments, the biodegradable ABA' triblock copolymer can be of the following formula
<CHM>
wherein m, n<NUM> and n<NUM> are independently <NUM>-<NUM>, and I some embodiments <NUM>-<NUM>.

Formula II depicts a biodegradable ABA' triblock copolymer wherein the end blocks, i.e., A and A' blocks, each include polylactide or polylactic acid and the middle block, i.e., the B block, includes from about <NUM> to about <NUM> mole percent of polytrimethylene carbonate and <NUM> to about <NUM> mole percent polylactide or polylactic acid and the biodegradable triblock copolymer overall includes from about <NUM> to about <NUM> mole percent of the polytrimethylene carbonate and from about <NUM> to about <NUM> mole percent of the polylactide or polylactic acid.

In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>. In embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>. In embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>. In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM>.

In some embodiments, "m" of Formula II may range from about <NUM> to about <NUM>. In embodiments, "m" of Formula II may range from about <NUM> to about <NUM>. In embodiments, "m" of Formula II may range from about <NUM> to about <NUM>. In embodiments, "m" of Formula II may range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM> and "m" of Formula II may range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM> and "m" of Formula II may range from about <NUM> to about <NUM>.

In some embodiments, "m" and "m" of Formula II are independently about <NUM> to about <NUM>. In some particular embodiments, "m" of Formula II is about <NUM> and "m" of Formula II is about <NUM>.

In some embodiments, "n<NUM>" of Formula II may range from about <NUM> to about <NUM>. In embodiments, "n<NUM>" of Formula II may range from about <NUM> to about <NUM>. In embodiments, "n<NUM>" of Formula II may range from about <NUM> to about <NUM>. In embodiments, "n<NUM>" of Formula II may range from about <NUM> to about <NUM>.

In some embodiments, "m" is greater than "n<NUM>".

In some embodiments, "m" is greater than (<NUM>)("n<NUM>").

In some embodiments, "m" is greater than "m" which is greater than "n<NUM>".

In some embodiments, each "m" of Formula II may independently range from about <NUM> to about <NUM> and "n<NUM>" of Formula II may range from about <NUM> to about <NUM>.

In some embodiments, each "m" of Formula II may be the same number ranging from about <NUM> to about <NUM> and "n<NUM>" of Formula II may range from about <NUM> to about <NUM>.

In some embodiments, "m" and "n<NUM>" of Formula II are independently about <NUM> to about <NUM>. In some particular embodiments, "m" of Formula II is about <NUM> and "n<NUM>" of Formula II is about <NUM>.

In some embodiments, "m", "m", and "n<NUM>" of Formula II are independently about <NUM> to about <NUM>. In some particular embodiments, "m" and "m" of Formula II is about <NUM> and "n<NUM>" of Formula II is about <NUM>.

In some embodiments, "m" of Formula II may range from about <NUM> to about <NUM> and "n<NUM>" of Formula II may range from about <NUM> to about <NUM>, wherein "n<NUM>" is greater than "n<NUM>". In embodiments, "m" of Formula II may range from about <NUM> to about <NUM> and "n<NUM>" of Formula II may range from about <NUM> to about <NUM>, wherein "n<NUM>" is greater than "n<NUM>". In embodiments, "m" of Formula II may range from about <NUM> to about <NUM> and "n<NUM>" of Formula II may range from about <NUM> to about <NUM>, wherein "n<NUM>" is greater than "n<NUM>". In embodiments, "m" of Formula II may range from about <NUM> to about <NUM> and "n<NUM>" of Formula II may range from about <NUM> to about <NUM>, wherein "m" is greater than "n<NUM>".

In some embodiments, the Mn and Mw of the triblock copolymer of Formula II are about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol. In some particular embodiments, the Mn of the triblock copolymer of Formula II is about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol and the Mw of the triblock copolymer of Formula II is about <NUM>,<NUM>/mol to about <NUM>,<NUM>/mol.

The triblock copolymers of the present disclosure can be prepared using a single or multi-step polymerization process. In embodiments, the triblock copolymers are formed using a multi-step process wherein the B block is formed in a first step and the A and A' blocks can be combined with the B block either individually in at least two different steps, or in a single step simultaneously.

One example of a multi-step process suitable for forming the ABA' triblock copolymers described herein includes a first step which includes mixing of the monomers units of the B block (e.g., monomers of lactic acid and/or trimethylene carbonate), an initiator, and a catalyst, in a dry form and under dry conditions, in a reactor. Each of the ingredients mixed are in a dry form. The reactor may include a means for mixing, such as mixing blades or magnetic stirrer. The mixing also occurs under a nitrogen atmosphere and initially at room temperature, but the temperature is increased to drive the reaction to form the B block of the triblock copolymer. After formation of the B block, at least a second step of mixing is performed wherein monomer units of the A and A' blocks (e.g., lactide monomer) and a second catalyst in dry form are mixed with the B block in the reactor to form the ABA' triblock copolymers described herein. The second step may be performed under a nitrogen atmosphere and/or while actively mixing with a mixing means. The temperature during the second step is also increased to drive the reaction. When the reaction is complete the polymer is extruded, pelletized, and dried under heat and vacuum to remove any moisture and unreacted monomer.

Any suitable initiator and/or catalyst may be used in each of the steps provided herein for forming the ABA' triblock copolymers. Some non-limiting examples of suitable initiators include diethylene glycol, triethylene glycol, tetraethylene glycol, poly(ethylene glycol), polypropylene glycol), poly(tetramethylene glycol), and poly(caprolactone) diol. The first and second initiators may be the same or different. Some non-limiting examples of suitable catalysts include stannous chloride, stannous octoate, stannous oxide, zinc chloride and zinc oxide. In some embodiments, the initiator of the first step is diethylene glycol and the catalyst is stannous octoate. In some embodiments, the initiator of the first step is diethylene glycol and the catalyst is stannous octoate.

In another example of a multi-step process suitable for forming at least one of the ABA' triblock copolymers described herein, a mono-alcohol, such as ethanol or lactic acid, may be initially mixed with monomer units of the A block, i.e., monomers of lactic acid, with a catalyst to form the A block. Monomer units of the B block, i.e., monomers of lactic acid and/or trimethylene carbonate, may be added to the A block with a catalyst to form an A-B copolymer. Then monomer units of the A' block, i.e., monomers of lactic acid, may be added to the A-B copolymer with a catalyst to form an ABA' triblock copolymer.

The compositions forming the at least one filament of the implantable medical devices of the present invention may comprise, consist essentially of, or consist of the triblock copolymers disclosed hereinSuitably, the compositions comprise, by weight, at least <NUM>%, at least about <NUM>%, at least about <NUM>%, at least about <NUM>%, at least about <NUM>%, at least about <NUM>%, or at least about <NUM>% of the triblock copolymers disclosed herein.

For example, in addition to standing alone as a triblock copolymer, the biodegradable ABA' triblock copolymers described herein may be combined with at least one additional biocompatible material including non-biodegradable polymeric materials, biodegradable polymeric materials, and/or biologically active agents. Each of the additional biocompatible materials may suitably be present in an amount from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%.

In the present application, "biocompatible" is understood as meaning that the materials having this property can be implanted in the human or animal body.

All biocompatible materials may be synthetic or natural, biodegradable, non-biodegradable or a combination of biodegradable and non-biodegradable. The term "biodegradable" as used herein is defined to include both bioabsorbable and bioresorbable materials. By biodegradable, it is meant that the materials decompose, or lose structural integrity under body conditions (e.g. enzymatic degradation or hydrolysis) or are broken down (physically or chemically) under physiologic conditions in the body such that the degradation products are excretable or absorbable by the body.

Suitable biodegradable materials include, but are not limited to, polyglycolic acid (PGA), oxidized cellulose, polycaprolactone (PCL), polydioxanone (PDO, polyvinyl alcohol (PVA), polyhydroxyalkanoates (PHAs), copolymers of these compounds and mixtures thereof. The biodegradable materials may also include biopolymeric materials derived from materials such as gelatin, collagen, chitosan, keratin, elastin, cellulose, alginates, and derivatives and combinations thereof.

Suitable non-biodegradable materials include, but are not limited to, polyolefins, such as polyethylene, polypropylene, copolymers of polyethylene and polypropylene, and blends of polyethylene and polypropylene; polyamides, such as nylon; polyamines, polyimines, polyesters such as polyethylene terephthalate (PET), polytetrafluoroethylene, polyether-esters such as polybutesters, polytetramethylene ether glycol; <NUM>,<NUM>-butanediol; polyurethanes, and combinations thereof. In embodiments, non-biodegradable materials may include silk, cotton, linen, carbon fibers, and combinations thereof. The polypropylene may be isotactic polypropylene or a mixture of isotactic and syndiotactic or atactic polypropylene.

Biologically active agents include any agent which provides a therapeutic or prophylactic effect, a compound that affects or participates in tissue growth, cell growth, and cell differentiation, a compound that may be able to invoke a biological action such as an immune response, or could play any other role in one or more biological processes.

Examples of classes of biologically active agents which may be utilized in accordance with the present disclosure include anti-adhesives, antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics, antihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinomimetics, antimuscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, antineoplastics, immunogenic agents, immunosuppressants, gastrointestinal drugs, diuretics, steroids, lipids, lipopolysaccharides, polysaccharides, platelet activating drugs, clotting factors and enzymes. It is also intended that combinations of these agents may be used.

Suitable antimicrobial agents which may be combined with the triblock copolymers described herein include triclosan, also known as <NUM>,<NUM>,<NUM>'-trichloro-<NUM>'-hydroxydiphenyl ether, chlorhexidine and its salts, including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate, silver and its salts, including silver acetate, silver benzoate, silver carbonate, silver citrate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such as tobramycin and gentamicin, rifampicin, bacitracin, neomycin, chloramphenicol, miconazole, quinolones such as oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin, penicillins such as oxacillin and pipracil, nonoxynol <NUM>, fusidic acid, cephalosporins, and combinations thereof. In addition, antimicrobial proteins and peptides such as bovine lactoferrin and lactoferricin B may also be combined with the triblock copolymers.

Other suitable biologically active agents include: local anesthetics; non-steroidal antifertility agents; parasympathomimetic agents; psychotherapeutic agents; tranquilizers; decongestants; sedative hypnotics; steroids; sulfonamides; sympathomimetic agents; vaccines; vitamins; antimalarials; anti-migraine agents; anti-parkinson agents such as L-dopa; antispasmodics; anticholinergic agents (e.g., oxybutynin); antitussives; bronchodilators; cardiovascular agents such as coronary vasodilators and nitroglycerin; alkaloids; analgesics; narcotics such as codeine, dihydrocodeinone, meperidine, morphine and the like; non-narcotics such as salicylates, aspirin, acetaminophen, d-propoxyphene and the like; opioid receptor antagonists, such as naltrexone and naloxone; anti-cancer agents; anti-convulsants; anti-emetics; antihistamines; anti-inflammatory agents such as hormonal agents, hydrocortisone, prednisolone, prednisone, non-hormonal agents, allopurinol, indomethacin, phenylbutazone and the like; prostaglandins and cytotoxic drugs; chemotherapeutics, estrogens; antibacterials; antibiotics; anti-fungals; anti-virals; anticoagulants; anticonvulsants; antidepressants; antihistamines; and immunological agents.

Still other examples of suitable agents include viruses and cells, peptides, polypeptides and proteins, analogs, muteins, and active fragments thereof, such as immunoglobulins, antibodies, cytokines (e.g., lymphokines, monokines, chemokines), blood clotting factors, hemopoietic factors, interleukins (IL-<NUM>, IL-<NUM>, IL-<NUM>, IL-<NUM>), interferons (β-IFN, (α-IFN and γ-IFN), erythropoietin, nucleases, tumor necrosis factor, colony stimulating factors (e.g., GCSF, GM-CSF, MCSF), insulin, anti-tumor agents and tumor suppressors, blood proteins, fibrin, thrombin, fibrinogen, synthetic thrombin, synthetic fibrin, synthetic fibrinogen, gonadotropins (e.g., FSH, LH, CG, etc.), hormones and hormone analogs (e.g., growth hormone), vaccines (e.g., tumoral, bacterial and viral antigens); somatostatin; antigens; blood coagulation factors; growth factors (e.g., nerve growth factor, insulin-like growth factor); bone morphogenic proteins, TGF-B, protein inhibitors, protein antagonists, and protein agonists; nucleic acids, such as antisense molecules, DNA, RNA, RNAi; oligonucleotides; polynucleotides; and ribozymes.

The additional biocompatible material may be combined with the triblock copolymers described herein in any suitable manner to form a composition suitable for forming a medical device. For example, in some embodiments, the triblock copolymer and the additional biocompatible material may be mixed to form a blend. In other embodiments, the additional biocompatible material may be bonded and/or crosslinked directly to a pendant part of the triblock copolymers described herein, wherein the ABA' triblock copolymer remains intact. For example, the additional biocompatible material may be represented by the letter "C" and may be bonded to the triblock copolymer to form a format such as, but not limited to, CABA', ABA'C, or CABA'C. Any suitable manner known to those of ordinary skill may be used to bond C to a pendant part of the ABA' triblock copolymer. Some non-limiting examples include the use of crosslinking agents, as well as the use of specific binding pairs of complimentary reactive functional groups, i.e., electrophilic/nucleophilic functional groups, or click chemistry reactive groups, such as azides and alkynes.

In some embodiments, the ABA' triblock copolymer(s) described herein may be used alone or in combination with an additional biocompatible material to form at least a portion of an implantable device, if not the entire implantable medical device.

As used herein, an "implantable medical device" may be any device that can be implanted in an animal. In accordance with the present invention, the implantable medical device comprises at least one filament including at least the ABA' triblock copolymers described herein. Examples of implantable medical devices comprising at least one filament include, but are not limited to, surgical sutures, surgical staples, surgical pins, surgical screws, surgical suture pledgets, surgical staple buttresses, surgical mesh, surgical plugs, vaso-occlusive devices, and combinations thereof.

In some embodiments, the biodegradable ABA' triblock copolymers described herein may be used alone or in combination with additional biocompatible materials to form a filament of an implantable medical device. The filament may be formed using any suitable method known to those skilled in the art. Some non-limiting examples include extruding, wet-spinning, gel-spinning, electro-spinning, molding, and the like. Some additional non-limiting examples of methods suitable for forming filaments are described in <CIT><CIT><CIT> and <CIT>.

<FIG> schematically illustrates at least one format suitable for manufacturing filaments made from the biodegradable ABA' triblock copolymers described herein. Extruder unit <NUM> is of a known or conventional type and is equipped with controls for regulating the temperature of barrel <NUM> in various zones thereof. In embodiments, the temperature progressively increases in three consecutive zones A, B and C along the length of the barrel. Pellets or powder including the ABA' triblock copolymers of the present disclosure are introduced to the extruder through hopper <NUM>. Any of the ABA' triblock copolymers described herein can be used, alone or in a composition with additional biocompatible materials.

Motor-driven metering pump <NUM> delivers melt extruded ABA' triblock copolymer, alone or in a composition, at a constant rate to spin pack <NUM> and thereafter through spinneret <NUM> possessing one or more orifices of desired diameter to provide a molten monofilament <NUM> which then enters quench bath <NUM>, e.g., containing a cooling liquid such as water, where the monofilament solidifies.

Monofilament <NUM> is passed through quench bath <NUM> around driven roller <NUM> and over idle roller <NUM>. Optionally, a wiper (not shown) may remove excess water from the monofilament as it is removed from quench bath <NUM>. On exiting the quench bath the monofilament is wrapped around a first godet <NUM> provided with nip roll <NUM> to prevent slippage which might otherwise result from the subsequent stretching operation. The monofilament is subsequently drawn through a combination of alternating godets <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> and heating chambers <NUM> and <NUM> to stretch and/or anneal the monofilament into a usable form and size.

Filaments made from the biodegradable ABA' triblock copolymers described herein, alone or in combination with other additional biocompatible materials, can be used to form at least one of a monofilament suture, a multifilament suture, a barbed suture, an armed suture, a looped suture, a knotted suture, and the like. For example, as shown in <FIG>, suture <NUM>, attached on one end to needle <NUM>, is made from at least one of the biodegradable ABA' triblock copolymers described herein, alone or in combination with other additional biocompatible materials. In embodiments, suture <NUM> is made solely from at least one of the biodegradable ABA' triblock copolymers described herein. The sutures described herein may be monofilament or multifilament sutures.

In another example, as depicted in <FIG>, barbed suture <NUM>, including a plurality of barbs <NUM> a, <NUM> b extending from a periphery of elongate body <NUM> and attached on both ends to needles 116a, 116b, is made from at least one of the biodegradable ABA' triblock copolymers described herein, alone or in combination with other additional biocompatible materials. In embodiments, barbed suture <NUM> is made solely from at least one of the biodegradable ABA' triblock copolymers described herein. The barbed sutures described herein may be monodirectional, bi-directional, or multi-directional barbed sutures. The barbed sutures described herein may also be monofilament or multifilament sutures.

In some embodiments, the biodegradable ABA' triblock copolymers described herein, alone or in combination with additional biocompatible materials, are used to form filaments which may be further processed to form a fabric. The fabric may be formed of interwoven filaments. The filaments may be interwoven using any suitable method including, but not limited to, braiding, weaving, knitting, and the like. The fabric may be used to form an implantable medical device such as a suture pledget, staple buttress, or surgical mesh. For example, as depicted in <FIG> surgical mesh <NUM> includes interwoven filaments <NUM> made from at least one of the biodegradable ABA' triblock copolymers described herein, alone or in combination with other additional biocompatible materials. In embodiments, surgical mesh <NUM> including filaments <NUM> is made solely from at least one of the biodegradable ABA' triblock copolymers described herein. The interwoven filaments <NUM> make pores <NUM> therebetween creating at least one porous surface. Although shown as rectangular, the mesh <NUM> may be any suitable shape and may be a two-dimensional or three-dimensional mesh. In embodiments, mesh <NUM> is a knit wherein the filaments <NUM> are knitted together to form mesh <NUM>. The filaments <NUM> may be a monofilament or multifilament.

As shown in <FIG>, in some embodiments the filaments described herein can be knitted together to form a self-gripping surgical mesh <NUM> (e.g., Progrip ® mesh) including grip-members <NUM> such as spiked naps, which have a head 205a wider than a body 205b and are configured to attach directly to tissue and/or other mesh materials. Filaments including the triblock copolymers described herein, alone or in combination with additional biocompatible materials, can be used to form any and all elements of the self-gripping surgical mesh <NUM> including the grip-members <NUM>. In embodiments, self-gripping surgical mesh <NUM> is made solely from the biodegradable ABA' triblock copolymers described herein. For example, the self-gripping surgical mesh may be made from a biodegradable ABA' triblock copolymer wherein the A and A' blocks are pure PLA, the B block is <NUM>-<NUM>/<NUM>-<NUM> mole percent PLA/TMC, and overall the biodegradable triblock copolymer is <NUM>/<NUM> mole percent PLA/TMC.

The fabric can be used to treat any type of hernia including a ventral hernia, inguinal hernia, femoral hernia, umbilical hernia, and epigastric hernia. The fabric can be used to treat any type of prolapse including but not limited to, bladder prolapse, rectum prolapse, small bowel prolapse, urethral prolapse, uterine prolapse, and vaginal prolapse.

As shown in <FIG>, the fabric may be used to form is a suture pledget <NUM>, attached to a central region of suture <NUM> (suture/pledget junctions <NUM> a and <NUM> b illustrate where suture <NUM> passes through pledget <NUM> with the portion of suture <NUM> shown in phantom disposed behind pledget <NUM>) including needles <NUM> a and 518b, is made from at least one of the biodegradable ABA' triblock copolymers described herein, alone or in combination with additional biocompatible materials. In embodiments, suture pledget <NUM> is made solely of at least one of the biodegradable ABA' triblock copolymers described herein.

In some embodiments, suture pledget <NUM> and suture <NUM> may be both made from at least one of the biodegradable ABA' triblock copolymers described herein, alone or in combination with additional biocompatible materials. In some embodiments, the suture pledget <NUM> and suture <NUM> are both made from the same biodegradable ABA' triblock copolymer. In some embodiments, the suture pledget <NUM> and suture <NUM> are both made from different biodegradable ABA' triblock copolymers described herein.

The following examples are given to aid in understanding the information provided in the present disclosure and is in no way meant to limit the scope of the present disclosure.

Synthesis of an ABA' triblock copolymer of poly(lactic acid)-[poly(lactic acid)-poly(trimethylene carbonate)]- poly(lactic acid) (PLA-[PLA-pTMC]-PLA) including <NUM> mole % PLA and <NUM> mole % pTMC overall and the B block [PLA-pTMC] is <NUM> mole % PLA and <NUM> mole % pTMC.

In a first stage of polymerization, <NUM>,<NUM> of trimethylene carbonate, <NUM> of diethylene glycol, and <NUM>% stannous octoate were added to a clean and dry stainless steel conical vessel reactor outfitted with two helicone-style mixing blades and mixed dry under a nitrogen atmosphere and at room temperature initially. The reactor temperature was increased to <NUM> and the first stage reaction monitored until formation of the B block, in the present example <NUM>% poly(TMC), was complete.

In a second stage of polymerization, with the helicone-type mixing blades on and under a nitrogen atmosphere, <NUM>,<NUM> of dry lactide monomer and <NUM>% stannous octoate were added to the stainless steel conical vessel reactor including the B block from the first stage of polymerization. The reactor temperature was increased to <NUM> and the second stage reaction monitored until formation of the ABA' triblock copolymer, in the present example PLA-pTMC-PLA (PLA/pTMC <NUM>/<NUM> mole % overall with a B block of PLA/pTMC <NUM>/<NUM> mole %), was complete and removed from the reactor.

Synthesis of an ABA' triblock copolymer of poly(lactic acid)-[poly(lactic acid)-poly(trimethylene carbonate)]- poly(lactic acid) (PLA-[PLA-pTMC]-PLA) <NUM> mole % PLA and <NUM> mole % pTMC overall, wherein the B block [PLA-pTMC] is <NUM> mole % PLA and <NUM> mole % pTMC.

In a first stage of polymerization, <NUM>,<NUM> of trimethylene carbonate, <NUM> of dry L-lactide monomer, <NUM> of diethylene glycol, and <NUM> stannous octoate were added to a clean and dry stainless steel conical vessel reactor outfitted with two helicone-style mixing blades and mixed dry under a nitrogen atmosphere and at room temperature initially. The reactor temperature was increased to <NUM> and the first stage reaction monitored until formation of the B block, in the present example a random copolymer including <NUM> mole percent PLA and <NUM> mole percent pTMC, was complete.

In a second stage of polymerization, with the helicone-type mixing blades on and under a nitrogen atmosphere, <NUM>,<NUM> of dry lactide monomer was added to the stainless steel conical vessel reactor including the B block from the first stage of polymerization. The reactor temperature was increased to <NUM> and the second stage reaction monitored until formation of the ABA' triblock copolymer, in the present example PLA-[PLA-pTMC]-PLA (PLA/pTMC <NUM>/<NUM> mole % overall with a B block of PLA/pTMC <NUM>/<NUM> mole %), was complete and removed from the reactor.

Each of the ABA' triblock copolymers formed in Examples <NUM> and <NUM> hereinabove, as well pure PLA alone, and a few additional PLA/TMC triblock copolymers having various overall mole percentages and/or middle block mole percentages, were extruded to form filaments of various diameters. The tensile strength and molar mass of the polymeric filaments were tested in vitro to provide a degradation profile of each of the filaments. Specifically a tensile strength retention profile at <NUM> and a molar mass retention profile at <NUM> were studied. The degradation was performed in a <NUM>/<NUM> molar phosphate buffer at pH=<NUM> at <NUM>. Degradation and measurements of tensile strength and molar mass were carried out in accordance with ISO <NUM>:<NUM> "Poly(L-lactide) resins and fabricated forms for surgical implants - in vitro degradation testing". The terms "tensile strength retention at <NUM>" and "molar mass retention at <NUM>" in the present specification refer to these parameters as measured by this method. Different yarn diameters between <NUM>-<NUM> micrometers were tested and the diameter was found to have no impact on the results (molar mass or percentage force retention). The results of the studies are depicted in <FIG> and <FIG>, respectively.

As depicted in <FIG>, the force retention (tensile strength retention) percent of the filaments made of pure PLA alone stays above <NUM>% after about <NUM> weeks and maintains about <NUM>% after about <NUM> weeks, but fail thereafter at <NUM>. The filaments made from PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] and PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>], i.e., non-limiting examples of ABA' triblock copolymers of the present application, display a force retention percent above <NUM>% after about <NUM> weeks and maintain a force retention percent of about <NUM>% or greater after about <NUM> weeks and do not fail after <NUM> or <NUM> weeks at <NUM>. However, the force retention percent of the filaments made of: PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] and PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] drop below <NUM>% before <NUM> weeks and drop well below <NUM>% around weeks <NUM> and <NUM>, respectively; and, PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] drops below <NUM>% around week <NUM>. Additionally worth noting, the force retention percent of these three last-described filaments drops below <NUM>% (and even <NUM>% for <NUM> of these <NUM> filaments) by week <NUM>, making these three last-described filaments unsuitable for providing tissue support long term, i.e., greater than <NUM> months and/or greater than <NUM> months. While the force retention percent of the filaments made from PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] and PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] remains greater than about <NUM>% (and greater than about <NUM>% for at least <NUM> of these <NUM> filaments) after <NUM> weeks, suggesting these filaments are suitable for providing tissue support long term, i.e., greater than <NUM> months and/or greater than <NUM> months under normal conditions.

As depicted in <FIG>, the molar mass retention percent of the filaments made of PLA alone stays above <NUM>% after about <NUM> week, stays above about <NUM>% after about <NUM> weeks, and is still around about <NUM>% after about <NUM> weeks. However, the filaments made from PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] and PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>], i.e., non-limiting examples of ABA' triblock copolymers of the present application, display a molar mass retention percent above <NUM>% after about <NUM> week, a molar mass retention percent of about <NUM>% or greater after about <NUM> weeks, and a molar mass retention percent of about <NUM>% or greater after <NUM> weeks. While the molar mass retention percent of the filaments made of PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>], PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>], and PLA/pTMC <NUM>/<NUM> [<NUM>/<NUM>] drop below <NUM>% before <NUM> week and fail by about week <NUM> and are below <NUM>% before week <NUM> (about week <NUM>).

The combination of the force retention percent and the molar mass retention percent results suggests that the ABA' triblock copolymers described herein and/or the filaments and medical devices made therefrom are suitable for providing tissue support long term, i.e., greater than <NUM> months and/or greater than <NUM> months, without structural failure under normal conditions.

Claim 1:
An implantable medical device comprising:
at least one filament including a biodegradable triblock copolymer comprising:
an A-B-A' structure wherein the A and A' blocks each include polylactide, the B block includes from about <NUM> to about <NUM> mole percent of polytrimethylene carbonate and <NUM> to about <NUM> mole percent polylactide, and the biodegradable triblock copolymer overall includes from about <NUM> to about <NUM> mole percent of the polytrimethylene carbonate and from about <NUM> to about <NUM> mole percent of the polylactide.