Lactide

Williams and co-workers prepared a zinc bulky alkoxide complex, 8, which was dimer in solid state but they strictly proved that in solution cleaved and existed as monomer [12]. Then they used it in LA ROP in CH Clj at ambient temperature (Table 7.2, entry 4). They showed that reaction rate had first-order dependence to catalyst and the produced polymer found atactic microstructure through coordination-insertion mechanism. 

Chmura et al. also prepared air and moisture resistant chiral imino phenoxide complexes of zirconium and titanium, 14 [16]. They envisioned to study the effect of supporting ligand chirality on the stereoselectivity of LA ROP reaction. But at the end, they did not gain acceptable evidence enable to support any relationship. They showed that all isolated polymers had similar and moderate heterotactic microstructure which implied simple chain end control mechanism and resulted to the selective racemic enchainment during the propagation process. First, they investigate polymerization in toluene at 80°C and ambient temperature in which titanium complexes were absolutely inactive and zirconium coxmterparts showed moderate activity after 2 and 24 hours, respectively. Then they checked out solvent free conditions at 130°C and received almost complete conversion after 30 minutes for both titanium and zirconium alkoxide complexes (Table 7.2, entry 33-36). In this condition, titanium coxmterpart, in contrast to zirconium, resulted to full atactic polymer. Their investigation also showed that zirconium complex retained its activity in moisture or with lactic acid impurity in crude monomer which is deleterious for most metal alkoxide catalysts. 

Chisholm and Delbridge studied ROP of LA by PhjSnX where X= OMe, OTr, OCH(CFj)2, 0 Bu and OPh [18]. They revealed the combination of electronic and steric effect of different alkoxide groups on the rate of LA ROP by the order 0Me 0Tr 0 Bu 0Ph 0CH(CF3)2. 

Chisholm research group also reported a Schiff base complex of magnesium t-butoxide, 16, which is highly active in LA ROP but did not perform very stereoselective [19]. 

Their earlier report on [ / -HB(3- Bupz)jMgOEt, 17 [20] revealed that this complex had particularly high reactivity (Table 7.2, entry 43), but it was also enormously water- and air-sensitive. This high activity and sensitivity 

FIGURE 1.3 During conversion of glucose to pyruvate, chemical energy (ATP) is generated as well as reducing equivalents (NADH). 

The phosphoketolase pathway is a route where a is transformed to a C5 sugar (and CO2) and split into a C2 and a C3 molecule. The C3 molecule is then converted to lactic acid whereas the C2 molecule is converted to acetate or ethanol. In the same traditional view, C5 sugars were regarded as leading to this heterofermentative metabolism, which is less interesting from the point of view of industrial production as a lot of acetic acid or ethanol is produced simultaneously. Although some bacteria seem to fit well in this paradigm, more recent literature has shown that this view is oversimplified and somewhat obsolete for a number of reasons. 

The uniformity in this biochemistry is in sharp contrast with the degrees of freedom one has in choosing the microbes, the acid-neutralizing agent, nutrients, and carbohydrates needed for industrial lactic acid fermentation. Only delicate weighing of the pros and cons of every possibility leads to an economically feasible fermentation. 

1 The Microbes There are several important features a microorganism used for the production of lactic acid must have in order to be industrially attractive  

Every microorganism has its own benefits and drawbacks, but lactobacilh (present in many food fermentations) and Rhizopus (a fungus) are the most reported [40]. Besides lactobacilh and Rhizopus, Streptococcus, Pediococcus, Sporolactobacillus inulinus. Bacillus coagulans, and several yeasts are mentioned in the excellent overview by Vaidya etal. [41]. 

---

C, b.p. 150 C/25mm. Prepared from l-lactic acid. It is partially converted to lactic acid by water. o-Lactide is similar. DL-Lactide crystallizes in colourless needles, m.p. 124-5 "C, b.p. l42°C/8mm. Obtained from DL-lactic acid. 

Lactic acid tends to pass into the lactide I [ when heated in... 

Lactides, intermolecular cyclic esters, are named as heterocycles. Lactams and lactims, containing a —CO—NH— and —C(OH)=N— group, respectively, are named as heterocycles, but they may also be named with -lactam or -lactim in place of -olide. For example. 

Polylactide is the generaUy accepted term for highly polymeric poly(lactic acid)s. Such polymers are usuaUy produced by polymerization of dilactide the polymerization of lactic acid as such does not produce high molecular weight polymers. The polymers produced from the enantiomeric lactides are highly crystalline, whereas those from the meso lactide are generaUy amorphous. UsuaUy dilactide from L-lactic acid is preferred as a polymerization feedstock because of the avaUabUity of L-lactic acid by fermentation and for the desirable properties of the polymers for various appUcations (1,25). 

Polymer—polymer iacompatibiHty encapsulation processes can be carried out ia aqueous or nonaqueous media, but thus far have primarily been carried out ia organic media. Core materials encapsulated tend to be polar soHds with a finite degree of water solubiHty. EthylceUulose historically has been the sheU material used. Biodegradable sheU materials such as poly(D,L-lactide) and lactide—glycoHde copolymers have received much attention. In these latter cases, the object has been to produce biodegradable capsules that carry proteias or polypeptides. Such capsules tend to be below 100 p.m ia diameter and are for oral or parenteral administration (9). 

Several parenteral microencapsulated products have been commercialized the cote materials ate polypeptides with hormonal activity. Poly(lactide— glycohde) copolymers ate the sheU materials used. The capsules ate produced by solvent evaporation, polymer-polymer phase separation, or spray-dry encapsulation processes. They release their cote material over a 30 day period in vivo, although not at a constant rate. 

Noncrystalline aromatic polycarbonates (qv) and polyesters (polyarylates) and alloys of polycarbonate with other thermoplastics are considered elsewhere, as are aHphatic polyesters derived from natural or biological sources such as poly(3-hydroxybutyrate), poly(glycoHde), or poly(lactide) these, too, are separately covered (see Polymers, environmentally degradable Sutures). Thermoplastic elastomers derived from poly(ester—ether) block copolymers such as PBT/PTMEG-T [82662-36-0] and known by commercial names such as Hytrel and Riteflex are included here in the section on poly(butylene terephthalate). Specific polymers are dealt with largely in order of volume, which puts PET first by virtue of its enormous market volume in bottie resin. 

Polylactic acid, also known as polylactide, is prepared from the cycHc diester of lactic acid (lactide) by ring-opening addition polymerization, as shown below ... 

The actual time required for poly-L-lactide implants to be completely absorbed is relatively long, and depends on polymer purity, processing conditions, implant site, and physical dimensions of the implant. For instance, 50—90 mg samples of radiolabeled poly-DL-lactide implanted in the abdominal walls of rats had an absorption time of 1.5 years with metaboHsm resulting primarily from respiratory excretion (24). In contrast, pure poly-L-lactide bone plates attached to sheep femora showed mechanical deterioration, but Httie evidence of significant mass loss even after four years (25). 

Poly(lactide-coglycolide). Mixtures of lactide and glycolide monomers have been copolymerised in an effort to extend the range of polymer properties and rates of in vivo absorption. Poly(lactide- (9-glycolide) polymers undergo a simple hydrolysis degradation mechanism, which is sensitive to both pH and the presence of ensymes (32). 

Similar to pure polyglycoHc acid and pure polylactic acid, the 90 10 glycolide lactide copolymer is also weakened by gamma irradiation. The normal in vivo absorption time of about 70 days for fibrous material can be decreased to less than about 28 days by simple exposure to gamma radiation in excess of 50 kGy (5 Mrads) (35). 

The crystallinity of poly(lactide- (9-glycoHde) samples has been studied (36). These copolymers are amorphous between the compositional range of 25—70 mol % glycoHde. Pure polyglycoHde was found to be about 50% crystalline whereas pure poly-L-lactide was about 37% crystalline. An amorphous poly(L-lactide-i (9-glycoHde) copolymer is used in surgical cHps and staples (37). The preferred composition chosen for manufacture of cHps and staples is the 70/30 L-lactide/glycoHde copolymer. 

Copolymers of S-caprolactone and L-lactide are elastomeric when prepared from 25% S-caprolactone and 75% L-lactide, and rigid when prepared from 10% S-caprolactone and 90% L-lactide (47). Blends of poly-DL-lactide and polycaprolactone polymers are another way to achieve unique elastomeric properties. Copolymers of S-caprolactone and glycoHde have been evaluated in fiber form as potential absorbable sutures. Strong, flexible monofilaments have been produced which maintain 11—37% of initial tensile strength after two weeks in vivo (48). 

Braided Synthetic Absorbable Sutures. Suture manufacturers have searched for many years to find a synthetic alternative to surgical gut. The first successful attempt to make a synthetic absorbable suture was the invention of polylactic acid [26023-30-3] suture (15). The polymer was made by the ring-opening polymerization of L-lactide [95-96-5] (1), the cycUc dimer of L-lactic acid. 

The lac resin is associated with two lac dyes, lac wax and an odiferous substance, and these materials may be present to a variable extent in shellac. The resin itself appears to be a polycondensate of aldehydic and hydroxy acids either as lactides or inter-esters. The resin constituents can be placed into two groups, an ether-soluble fraction (25% of the total) with an acid value of 100 and molecular weight of about 550, and an insoluble fraction with an acid value of 55 and a molecular weight of about 2000. 

Throughout the 1990s a large portion of the research and development effort for hot melt adhesives focused on developing adhesives that are either environmentally friendly or functional [69,81,82]. Environmentally friendly attributes include biodegradability, water dispersibility (repulpability), renewability, and water releasability. Biodegradable adhesives have been developed based on starch esters [83-86] and polyesters such as poly (hydroxy butyrate/hydroxy valerate) [87], poly(lactide) [88-91], and poly(hydroxy ether esters) [92-94]. All but the... 

Lactic acid and levulinic acid are two key intermediates prepared from carbohydrates [7]. Lipinsky [7] compared the properties of the lactide copolymers [130] obtained from lactic acid with those of polystyrene and polyvinyl chloride (see Scheme 4 and Table 5) and showed that the lactide polymer can effectively replace the synthetics if the cost of production of lactic acid is made viable. Poly(lactic acid) and poly(l-lactide) have been shown to be good candidates for biodegradeable biomaterials. Tsuji [131] and Kaspercejk [132] have recently reported studies concerning their microstructure and morphology. 

Table 5 Comparison of Properties of Lactide Polymers with Polystyrene and Poly(vinyl chloride) ...

Polymer/Property Polystyrene 95/5 Lactide/Caprolactone 95/15 Lactide/Caprolactone Flexible PVC... 

---