DILACTIDE COPOLYMER

The mechanisms of biodegradation of polylactide, polycaprolactone and caprolactone copolymers with dilactide copolymer, valerolactone copolymer, and decalactone copolymer in the rabbit were shown to be qualitatively similar. The rate of the first stage of the degradation process, non enzymatic random hydrolytic chain scission, was found to vary by an order of magnitude and was dependent on morphological as well as chemical effects. 17 refs. 

DUactide (5) exists as three stereoisomers, depending on the configurations of the lactic acid monomer used. The enantiomeric forms whereia the methyl groups are cis are formed from two identical lactic acid molecules, D- or L-, whereas the dilactide formed from a racemic mixture of lactic acid is the opticaUy iaactive meso form, with methyl groups trans. The physical properties of the enantiomeric dilactide differ from those of the meso form (6), as do the properties of the polymers and copolymers produced from the respective dilactide (23,24). 

The living nature of PCL obtained in the presence of Zn(OAl-(OPri)2)2 has been used to prepare both di- and triblock copolymers of e-caprolactone and lactic acid (42,43). Treatment of the initial living PCL with dilactide afforded a PCL-PLA diblock with M /Mn = 1.12, with each block length determined by the proportions of the reactants, i.e., the ratio of [monomer]/[Zn]. While the living diblock copolymer continued to initiate dilactide polymerization, it failed to initiate e-caprolactone polymerization. To obtain a PCL-PLA-PCL triblock, it was necessary to treat the living PCL-PLA-OAIR2 intermediate with ethylene oxide, then activate the hydroxy-terminated PCL-PLA-(OCH2CH2)nOH with a modified Teyssie catalyst (Fig. 5). 

Stannous octoate has the advantage of having been used to prepare polymers (Silastic, Capronor) for which substantial toxicological data are now available (6,48). Stannous octoate-initiated polymerization has been used to prepare copolymers of e-caprolactone with other lactones, including diglycolide, dilactide, 6-valerolactone, e-decalactone, and other alkyl-substituted e-caprolactones. Conducting... 

For example, the T values of copolymers with dilactide increase in proportion to the dilactide content according to the Fox equation ... 

For the production of polymers or their derivatives, the technology for producing the dilactide (the internal diester) is critically important. The processes include a multistage evaporation followed by polymerization to a low molecular weight prepolymer, which is then catalytically converted to the dilactide. The dilactide is purified in a distillation system by partial condensation and recycling. This diester can be used to synthesize high molecular weight polymers and copolymers. " ... 

Dilactide-co-g-Caprolactone. Copol3mierizations of dilactide and caprolactone were performed with stannous octoate, stannous chloride, and tetrabutyl titanate (TBT) as catalysts at 130 and 180 C either in bulk or in the presence of toluene. Copolymer compositions were determined by H-NMR spectroscopy, specific optical rotation in the case of L-dilactide, or by H-contents using labeled caprolactone. Agreement of the three analytical methods was generally good although spectroscopy soon reached its limit of applicability at lower lactide concentrations. 

Fig. 4 - Effect of composition on the ambient temperature stability of dilactide-caprolactone copolymers. Full circles DL-dilactide-co-caprolactone, open circles L-dilactide-co-caprolactone. Storage periods in days indicated...

The low ambient temperature stability of copolymers composed of dilactide and caprolactone indicated a fast rate of biodegradation to be expected. Indeed, in vivo studies with three copolymers containing 27, 43, and 90 mole-% lactide units revealed rapid biodegradation to take place with 50% weight loss occurring after about 6, 12, and 16 weeks, respectively. As shown in Fig. 9 the... 

Fig. 9 - In vivo degradation of dilactide-e-caprolac-tone (LA/CL) copolymers in tube form. Percent weight loss indicated...

In vitro release of progesterone from copolymers of DL-dilactide and glycolide are summarized in Fig. 13. Compositions and intrinsic viscosities in benzene were as follows ... 

Fig. 13 - In vitro release of progesterone from poly-(glycolide-co-dilactide) films containing 10% (w/w) steroid. For copolymer identification see text.

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