WO2008036049A1

WO2008036049A1 - Process for production of high molecular weight polyhydroxy acid

Info

Publication number: WO2008036049A1
Application number: PCT/SG2007/000238
Authority: WO
Inventors: Wang Shaofeng; Huang Yuqiang
Original assignee: Hyflux Ltd
Priority date: 2006-09-21
Filing date: 2007-08-07
Publication date: 2008-03-27
Also published as: TW200815497A

Abstract

There is disclosed a process for producing a high molecular weight polyhydroxy acid comprising the steps of: (a) condensating a hydroxy acid with a functionalizing agent, said functionalizing agent being selected to form a polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon after said condensating; and (b) polymerizing said pre-polymer in the presence of a coupling agent under conditions to form said high molecular molecular weight polyhydroxy acid.

Description

Process for Production of High Molecular Weight

Polyhydroxy Acid

Technical Field The present invention generally relates to a process for producing a high molecular weight polyhydroxy acid. The present invention also relates to a system for performing the process.

Background

Polyhydroxy acids are highly useful materials due to their chemical, mechanical and physical properties. In recent years, polyhydroxy acids have gained increasing economic importance due to their biodegradability as they can be degraded, under natural conditions, to carbon dioxide and water by microorganisms.

Polyhydroxy acids, such as polylactic acid, have been woven into fibers using conventional melt-spinning processes. Spunbound and meltblown non-wovens fibers are also easily produced from polylactic acid. These materials may be used in various applications such as household and industrial wipes, diapers, feminine hygiene products, disposable garments, and UV resistant fabrics. Furthermore, because polylactic acid is bioasborable and can be assimilated by a biological system, it can be readily used for implants in bone or soft tissue and for resorbable sutures .

To be useful in certain applications, such as in medical implants, clothing, vehicle bodies, computer bodies and other related components, the polyhydroxy acids must have a high molecular weight in the order of at least 50,000 to exhibit mechanical strength beyond a certain level . One known processes for producing a polyhydroxycarboxylic acid comprises dehydrating via a condensation reaction, an aliphatic mono-hydroxycarboxylic acid in a reaction mixture containing an organic solvent and in the substantial absence of water to obtain polyhydroxycarboxylic acid having a weight average molecular weight of at least about 50,000. However, this process relies on the use of an organic solvent which may be harmful to the environment. Furthermore, the organic solvent must be removed from the final polymer, which increases processing costs.

One known process for producing high molecular weight polylactic acid involves ring-opening polymerization of a lactide using a stannous octoate catalyst. However, the process involves the formation of the lactide from a oligocondensate of lactic acid. The lactide must be isolated and purifyied ^' before making the high molecular weight polylactic acid, which increases the costs of production. A problem with these known methods is that the purification step is complex and therefore expensive, as it requires the use of multiple unit operations (i.e. distillation columns, evaporators, heat exchangers, pumps, etc) to separate the water and other impurities such as lactic acid and oligomers thereof from the cyclic dimers. As these unit operations are typically operated under highvacuum and temperatures, the capital, operating and maintenance costs are significant. It is possible to reduce the number of distillation steps, however this results in significant loss in the recovery of the cyclic dimer thereby reducing the yield and subsequently increasing the economic cost of, the production process.

Furthermore, the synthesis of high molecular weight polyhydroxy acids involves the production of water as a by-product in the polycondensation dehydration reaction. The production of water acts as an inhibitor of the polymerization reaction and it is difficult to efficiently and to substantially remove from the reactant polymer. Known synthetic methods have suggested complex water removal steps, such as successive distillation of water and the cyclic dimers . However, the equipment designs employed in these processes have been inefficient and have resulted in loss of both the feed product and the cyclic dimers.

There is a need to provide a process for producing high molecular weight polyhydroxy acids that overcome, or at least ameliorate, one or more of the disadvantages described above. There is also a need to provide a system for producing high molecular weight polyhydroxy acids that overcome, or at least ameliorate, one or more of the disadvantages described above.

Summary

According to a first aspect, there is provided a process for producing a high molecular weight polyhydroxy acid comprising the steps of: (a) condensating a hydroxy acid with a functionalizing agent, said functionalizing agent being selected to form a polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon after said condensating; and (b) polymerizing said pre-polymer in the presence of a coupling agent under conditions to form said high molecular weight polyhydroxy acid.

In one embodiment, the coupling agent is an isocyanate coupling agent. Advantageously, the polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon allows the formation of high molecular weight polyhydroxy acid in the polymerizing step. Advantageously, the polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon utilizes less isocyanate coupling agent relative to a prepolymer having less than three terminal hydroxyl groups. Advantageously, the polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon allows the formation of high molecular weight polyhydroxy acid in the polymerizing step.

According to a second aspect, there is provided the use of a polyhydroxy acid prepolymer having at least three terminal hydroxyl groups for producing high molecular weight polyhydroxy acid, the use comprising the step of:

(a) polymerizing said pre-polymer in the presence of a coupling agent under conditions to form said high molecular weight polyhydroxy acid.

According to a third aspect, there is provided a high molecular weight polyhydroxy acid made in a process comprising the steps of:

(a) condensating a hydroxy acid with a functionalizing agent, said functionalizing agent' being selected to form a polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon after said condensating; and

(b) polymerizing said pre-polymer in the presence of a coupling agent under conditions to form said high molecular weight polyhydroxy acid.

According to a fourth aspect, there is provided a reactor having a reaction zone containing a polymerizing monomeric mixture of polyhydroxy acid prepolymer having at least three terminal hydroxyl groups and a coupling agent, wherein said reaction zone is operated under conditions to form said high molecular weight polyhydroxy acid from said polymerizing monomeric mixture.

Definitions

The following words and terms used herein shall have the meaning indicated: The term "high molecular weight polyhydroxy acid" means a polyhydroxy acid having a molecular weight of more than 100,000, preferably more than 150,000. In some embodiments, the high molecular weight of the polyhydroxy acid is about 100,000 to about 450,000. The term "hydroxy acid" as used herein means a carboxylic acid in which one or more hydrogen atom of the aliphatic or aromatic group has been replaced by a hydroxyl group .

The term "polyhydroxy acid" as used herein means polymer of repeating hydroxy acid monomer units.

The term ""aliphatic hydroxycarboxylic acid" refers generally to acids having alcoholic hydroxyl and carboxyl in the molecule, such as lactic acid, glycolic acid, malic acid, tartaric acid, citric acid, hydroacrylic acid, α- hydroxybutyric acid, glyceric acid, tartronic acid and like aliphatic hydroxycarboxylic acids.

The term "functionalizing agent" in the context of this specification is to be interpreted broadly to include any compound capable of a condensation reaction with a hydroxy acid to form a prepolymer having at least three terminal hydroxyl groups. The functionalizing agent may include at least one polyalcohol and optionally at least one of a polycarboxylic and a diol or a polycarboxylic acid in combination with a diol. The term "polyalcohol" means alcohols having at least three hydroxyl groups and optionally encompasses other subsistent functional groups. Exemplary non-limitive examples of polyalcohols include (carbon chains may be straight chains, breached chains, aromatic, or alicyclic) , pentaerythritol, dipentaerythritol, tripentaerythritol, glycerol, open and cyclic condensation products of glycerol (and/or other polyalcohols) such as diglycerols, triglycerols, tetraglycerols, pentaglycerols, and hexaglycerols; diglycidyl ether, diglycidyl-di-ether, ethylene glycol diglycidyl ether, glycerol diglycidyl ether, butanediol-diglycidyl ether, trimethylolpropane triglycidyl ether, trimethylolmethane triglycidyl ether, glycerol, 1, 5, 6, 9-decanetetrol, 1,1,4,4- cyclohexanetetramethanol, 1,2,4,5- cyclohexanetetramethanol, 1, 2, 4, 7-hepanetetrol, 1,2,3,5- heptanetetrol, 1, 5, 8-nonanetriol, 1, 5, 9-nonanetriol, 1, 3, 5, 9-heptanetetrol, 1, 3, 5-heptanetriol, 2,4,6- heptanetriol, 4 , 4-dimethyl-l, 2, 3-pentanetriol, 1,1,3- cyclohexanetrimethanol, 1, 3, 4-cycloheptanetriol, 1,2,3- cyclopropanetriol, 1, 2, 3-cyclopropanetrimethanol, 1,2,3- cyclobutanetriol, 1, 2, 4-cyclobutanetriol, 1,2,3,4- cyclobutanetetrol, 1, 3-dimethyl-l, 2,3, 4-cyclobutanetetrol 1-hydroxcyclobutane methanol, 1, 2, 3-pentanetriol, 1,2,4- pentanetriol, 2, 3, 4-pentanetriol, 1, 2, 3-cyclopentanetriol, 1, 2, 3-hexanetriol, 1, 2, 4-hexanetriol, 1,2,3,4- hexanetetrol, 1, 2, 4-cyclohexanetriol, 1,2,5- cyclohexanetriol, 1, 2, 3, 4-cyclohexanetetrol, 1,2,3,5- cyclohexanetetrol, inositol and mixtures thereof. The term "polycarboxylic acids" comprises all acids having more than one carboxyl group. Exemplary non- limitive examples of polycarboxylic acids include citric acid (i.e., 2-hydroxy-l, 2, 3-propane tricarboxylic acid), 1, 2, 3-propane tricarboxylic acid, 1, 2, 3, 4-butane tetracarboxylic acid, tartrate monosuccinic acid, tartrate disuccinic acid, oxydisuccinic acid (i.e., 2,2'- oxybis (butanedioic acid) ) , thiodisuccinic acid, trans-1- propene-1, 2, 3-tricarboxylic acid, all cis-1, 2,3,4- cyclopentanetetracarboxylic acid, benzenehexacarboxylic acid, alkyl-cycloalkyltricarboxylic acid, trimethyl- cyclohexanetricarboxylic acid, 1, 3, 5-trimethyl-l, 3, 5- cyclohexanetricarboxylic acid,. 1, 2, 3-propanetricarboxylic acid, 1, 2, 3, 4-butanetetracarboxylic acid, 1,2,3,4,5,6- cyclohexanehexacarboxylic acid, cycloalkyltricarboxylic acid, cycloalkyltetracarboxylic acid, cycloalkylpentacarboxylic acid, cycloalkylhexacarboxylic acid and mixtures thereof.

As used herein, the term "diol" refers to all molecules which have at least two alcohol functionalities thereon. Exemplary, non-limiting diols include saturated and unsaturated alkyl diols such as ethanediol (ethylene glycol) , ethenediol, diethylene glycol, neopentyl glycol, 1, 2-propanediol (propylene glycol), 1, 3-propanediol, 2,3- propanediol, 1, 2-propenediol, 1, 3-propenediol, 2,3- propenediol, 1, 4-butanediol, 1, 3-butanediol, 1,2- butanediol, 2, 4-butanediol, 2, 3-butanediol, 3,4- butanediol, 1, 4-butenediol, 1, 3-butenediol, 1,2- butenediol, 2, 4-butenediol, 2, 3-butenediol, 3,4- butenediol, 1, 2-pentanediol, 1-3-pentanediol, 1,4- pentanediol, 2, 3-pentanediol, 2, 4-pentanediol, 1,2- pentenediol, 1-3-pentenediol, 1, 4-pentenediol, 2,3- pentenediol, 2, 4-pentenediol, alkyl substituted diols such as 2-methyl-l, 5-pentanediol and cycloalkane diols such as 1, 4-cyclohexanedimethanol, 1, 2-cyclohexanedimethanol, 1,4- cyclohexanediethanol, 1, 6-hexanediol, polyalkyleneglycols such as polyethyleneglycols, polypropyleneglycols, ethylenepropyleneglycol, polyethylenepropylene glycols, ethylenepropylene glycol copolymers, and ethylenebutylene glycol copolymers, 1, 4-cyclopentanedimethanol, 1,3- cyclopentanedimethanol, 1, 1-cyclopropanediol, 1,2- cyclopropanediol, 1, 1-cyclopropanediraethanol, 1,2- cyclopropanedimethanol, 1, 1-cyclobutanediol, 1,2- cyclobutanediol, 1, 3-cyclobutanediol, 1, 2-cyclobutane dimethanol, 2-methyl-l, 2-butanediol, 3-methyl-2, 2- butanediol, 1, 1-cyclopentanediol, 1, 2-cyclopentanediol, 1, 3-cyclopentanediol, 1, 2-hexanediol, 1, 3-hexanediol, 1,1- cyclohexanediol, 1, 2-cyclohexanediol, 1, 4-cyclohexanediol . The term "catalyst" is to be interpreted broadly to include any substance that increases the rate of reaction of the aliphatic hydroxycarboxylic acid, or polymerization of said polyhydroxy acid, without being substantially consumed in the reaction. The terms "polymerize", "polymerizing", "polymerization" and grammatical variations thereof, means not only "homopolymerization" but also "copolymerization" . The terms are to be interpreted broadly to include any process whereby monomer molecules react with each other, or with a polymer chain of polyhydroxy acid, in a chemical reaction to form larger molecular weight polymer chains of polyhydroxy acid. The polymerization mechanism can be cationic, anionic, coordination or free radical polymerization. The polyhydroxy acid polymer chains may be linear chains or a three-dimensional network of polymer chains. For example, the terms may include ring-opening reaction of cyclic dimers with polyhydroxy acid to thereby increase the molecular weight of said polyhydroxy acid.

The term "polymer" includes not only "homopolymers" but also "copolymers".

The term "prepolymer" denotes a low molecular weight polymer comprising monomers of hydroxycarboxylic acid monomer units that are further polymerizable. Typically, the molecular weight of said prepolymers is less than about 100,000, more typically between about 15,000 to about 60,000. For example, the term ^λλpolylactic acid prepolymer" would refer to a polylactic acid having a molecular weight less than 100,000 and which can be further polymerized to a higher molecular weight.

The term ⁿhydroxyl groups" describes the functional group -OH when it is a substituent in an organic compound.

The term "coupling agent" refers to any reagent capable of facilitating coupling between two or more prepolymers in a polymerization reaction.

The term "isocyanate coupling agent" refers to a reagent containing the functional group of atoms -N=C=O and capable of facilitating the formation of bonds between two polypeptides. The term "isocyanate coupling agent" includes mono isocyanates, diisocyanates and polyisocyanates . The term "diisocyanate" refers to any organic compound containing two isocyanate (-N=C=O) groups. The term "polyisocyanate" refers to any organic compound containing three or more isocyanate (-N=C=O) groups. Exemplary diisocyanate and polyisocyanate compounds include aromatic polyisocyanates such as 2,4- tolylene diisocyanate, 2, 6-tolylene diisocyanate, 4,4'- diphenylmethane diisocyanate, 2, 4 ' -diphenylmethane diisocyanate, p-phenylene diisocyanate, and polymethylene polyphenylene polyisocyanate; aliphatic polyisocyanates such as hexamethylene diisocyanate (HMDI) , and tetramethylxylylene diisocyanate (TMXDI) ; alicyclic polyisocyanates such as isophorone diisocyanate (IPDI) ; arylaliphatic polyisocyanates such as xylylene diisocyanate; and the polyisocyanate as mentioned above modified with carbodiimide or isocyanurate; which may be used either alone or in combination of two or more. Exemplary commercially available polyisocyanates are CORONATE HX™ of and CORONATE HXR™, both of Nippon Polyurethene Ind. Co. Ltd.

The term "polymerization conditions" and grammatical variations thereof is defined herein to mean conditions, such as temperature and pressure, which are sufficient to promote polymerization of the polyhydroxy acid.

The term "reaction zone" is to be interpreted broadly to include any region or space in which the dehydration condensation reaction of a polyhydroxy acid prepolymer occurs to form high molecular weight polyhydroxy acid.

Unless specified otherwise, the terms "comprising" and "comprise", and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, unrecited elements.

As used herein, the term "about", in the context of concentrations of components of the formulations, typically means +/- 5% of the stated value, more typically +/- 4% of the stated value, more typically +/- 3% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0.5% of the stated value.

Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to β should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Disclosure of Embodiments

Process for producing polyhydroxy acid

Exemplary, non-limiting embodiments of a process for producing a high molecular weight polyhydroxy acid, in particular a polyhydroxy carboxylic acid, more particularly a polylactic acid, will now be disclosed.

Advantageously, a high molecular weight polyhydroxy acid can be produced directly from aliphatic hydroxy acid. For example, in one embodiment, the process can be used to produce a high molecular weight polylactic acid directly from lactic acid.

The process comprises the steps of:

(a) condensating a hydroxy acid with a functionalizing agent, said functionalizing agent being selected to form a polyhydroxy acid prepolynαer having at least three terminal hydroxyl groups thereon after said condensating; and

(b) polymerizing said pre-polymer in the presence of an isocyanate coupling agent under conditions to form said high molecular weight polyhydroxy acid.

Exemplary aliphatic hydroxy acids include, for example, lactic acid, glycolic acid, 2-hydroxybutanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, 2- hydroxyheptanoic acid, 2-hydroxyoctanoic acid, 2-hydroxy- 2-methylpropanoic acid, 2-hydroxy-2-methylbutanoic acid, 2-hydroxy-2-ethylbutanoic acid, 2-hydroxy-2- methylpentanoic acid, 2-hydroxy-2-ethylpentanoic acid, 2- hydroxy-2-propylpentanoic acid, 2-hydroxy-2-butylpentanoic acid, 2-hydroxy-2-methylhexanoic acid, 2-hydroxy-2- ethylhexanoic acid, 2-hydroxy-2-propylhexanoic acid, 2- hydroxy-2-butylhexanoic acid, 2-hydroxy-2-pentylhexanoic acid, 2-hydroxy-2-methylheptanoic acid, 2-hydroxy-2- ethylheptanoic acid, 2-hydroxy-2-propylheptanoic acid, 2- hydroxy-2-butylheptanoic acid, 2-hydroxy-2-pentylheptanoic acid, 2-hydroxy-2-hexylheptanoic acid, 2-hydroxy-2- methyloctanoic acid, 2-hydroxy-2-ethyloctanoic acid, 2- hydroxy-2-proρyloctanoic acid, 2~hydroxy-2-butyloctanoic acid, 2-hydroxy-2-pentyloctanoic acid, 2-hydroxy-2- hexyloctanoic acid, 2-hydroxy-2-heptyloctanoic acid, 3- hydroxypropanoic acid, 3-hydroxybutanoic acid, 3- hydroxypentanoic acid, 3-hydroxyhexanoic acid, 3- hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3-hydroxy- 3-methylbutanoic acid, 3-hydroxy-3-methylpentanoic acid, 3-hydroxy-3-methylheptanoic acid, 3-hydroxy-3- ethylpentanoic acid, 3-hydroxy-3-methylhexanoic acid, 3~ hydroxy-3-ethylhexanoic acid, 3-hydroxy-3-propylhexanoic acid, 3-hydroxy-3-methylheptanoic acid, 3-hydroxy-3- ethylheptanoic acid, 3-hydroxy-3-propylheptanoic acid, 3- hydroxy-3-butylheptanoic acid, 3-hydroxy-3-methyloctanoic acid, 3-hydroxy-3-ethyloctanoic acid, 3-hydroxy-3- propyloctanoic acid, 3-hydroxy-3-butyloctanoic acid, 3- hydroxy-3-pentyloctanoic acid, 4-hydroxybutanoic acid, 4- hydroxypentanoic acid, 4-hydroxyhexanoic acid, 4- hydroxyheptanoic acid, 4-hydroxyoctanoic acid, 4-hydroxy- 4-methylpentanoic acid, 4-hydroxy-4-methylhexanoic acid, 4-hydroxy-4-ethylhexanoic acid, 4-hydroxy-4- methylheptanoic acid, 4-hydroxy-4-ethylheptanoic acid, 4- hydroxy-4-proρylheptanoic acid, 4-hydroxy-4-methyloctanoic acid, 4~hydroxy-4-ethyloctanoic acid, 4-hydroxy-4- propyloctanoic acid, 4-hydroxy-4-butyloctanoic acid, 5- hydroxypentanoic acid, 5-hydroxyhexanoic acid, 5- hydroxyheptanoic acid, 5-hydroxyoctanoic acid, 5-hydroxy- 5-methylhexanoic acid, 5-hydroxy-5-methylheptanoic acid, 5-hydroxy-5-ethylheptanoic acid, 5-hydroxy-5- methyloctanoic acid, 5-hydroxy-5--ethyloctanoic acid, 5- hydroxy-5-propyloctanoic acid, 6-hydroxyhexanoic acid, 6- hydroxyheptanoic acid, 6-hydroxyoctanoic acid, 6-hydroxy- 6-methylheptanoic acid, 6-hydroxy-6-methyloctanoic acid, 6-hydroxy-β-ethyloctanoic acid, 7-hydroxyheptanoic acid, 7-hydroxyoctanoic acid, 7-hydroxy-7-methyloctanoic acid, 8-hydroxyoctanoic acid, other aliphatic hydroxycarboxylic acids, mixtures of these acids and oligomers of these acids.

Some aliphatic hydroxy acid and the polymer of the same have optically active carbon in the molecule and are distinguished in the form of a D-isomer, L-isomer and D/L- isomer, respectively. Any of these isomers can be used in the disclosed process. For example, the aliphatic hydroxy acid may be lactic acid which may be either optically active (e.g., D- or L-lactide) or inactive (i.e., D, L- lactide) or a mixture of optical active and inactive forms . The condensating step (a) may comprise the step of:

(al) heating said hydroxy acid from about 50 degree C to about 210 degree C, or from about 100 degree C to about 200 degree C.

The heating step (al) may be undertaken in an inert atmosphere such as with nitrogen gas being injected through the hydroxy acid.

The condensating step (a) may comprise the step of: (a2) applying a vacuum to said hydroxy acid as it reacts with said functionalizing agent. The vacuum may be applied in the range of about 0.1 mmHg to about 600 mmHg. In one embodiment, the vacuum may be applied in the range of about 5 mmHg to about 200 mmHg. Advantageously, application of the vacuum ensures that the volatile phase is removed from the liquid phase during its formation. Advantageously, the vacuum can also be used to increase the passage of said water across the membrane and thereby facilitate formation of said permeate vapor stream.

The condensating step (a) may comprise the step of: (a3) agitating said mixture of hydroxy acid and functionalizing agent. The agitating may be undertaken at a speed of about 200 rpm.

The condensating step (a) may comprise the step of: (a4) removing condensed water formed during polycondensation by vacuum and/or nitrogen.

The condensating step (a) may comprise the step of: (a5) providing a catalyst to said hydroxy acid as it undergoes polymerization.

The catalyst may be suitable for dehydration. Exemplary catalysts which can be used in the invention are metals, metal salts, hydroxides and oxides in the group I, II, III, IV and V of the periodic table and include, for example, zinc, tin, aluminum, magnesium, antimony, titanium, zirconium and other metals such as tin oxide, antimony oxide, lead oxide, aluminum oxide, magnesium oxide, titanium oxide and other metal oxides; zinc chloride, stannous chloride, stannic chloride, stannous bromide, stannic bromide, antimony fluoride, magnesium chloride, aluminum chloride and other metal halogenides; sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, aluminum hydroxide, zinc hydroxide, iron hydroxide, cobalt hydroxide, nickel hydroxide, copper hydroxide, cesium hydroxide, strontium hydroxide, barium hydroxide, lithium hydroxide, zirconium hydroxide and other metal hydroxides; tin sulfate, zinc sulfate, aluminum sulfate and other metal sulfates; magnesium carbonate, zinc carbonate, calcium carbonate and other metal carbonates; tin acetate, stannous octoate, tin lactate, zinc acetate, aluminum acetate, iron lactate and other organic carboxylate metal salts; and tin trifluoromethanesulfonate, tin p- toluenesulfonate and other organic sulfonate metal salts, dibutyltin oxide and other organometal oxides of the above metals, titanium isopropoxide and other metal alkoxides of the above metals, diethylzinc and other alkyl metals of the above metals, and ion exchange resin. The amount of these catalysts are in the range of 0.0001-10% by weight in said liquid phase. In one embodiment the catalyst is selected from the group consisting of tin octoate (tin [II] 2-ethylhexanoate) , tin chloride (tin [II] 2- chloride) , toluene-4-sulfonic acid monohydrate (TSA) , zinc octoate and zinc chloride.

The condensating step (a) may comprise the step of: (aδ) adding of ε-caprolactone.

Advantageously, addition of ε-caprolactone results in mechanically tough but also ductile polymeric products.

It is important to note that the functionalizing agent should be carefully chosen to ensure that at least three, preferably four, hydroxyl groups are formed on the terminal ends of the prepolymer on reaction of the functionalizing agent with said hydroxy acid. To ensure that at least three hydroxyl groups are formed on the terminal ends of ■ the formed prepolymer, the functionalizing agent should comprise one or more of the following: (i) a polyalcohol;

(ii) a polyalcohol and a polycarboxylic acid; (iii) a polyalcohol and a diol; and (iv) a polycarboxylic acid and a diol. The composition of the functionalizing agent may be any one of:

(i) one or more polyalcohol;

(ii) 10% (wt) to 90% (wt) polyalcohol and the reminder being a polycarboxylic acid;

(iii) 10% (wt) to 90% (wt) polyalcohol and the reminder being a diol; and (iv) 10% (wt) to 90% (wt) polycarboxylic acid and the reminder being a diol. A prepolymer with at least three terminal hydroxyl groups is formed from said aliphatic hydroxy acid, or oligomer thereof. The said prepolymer may be in a molten state, and may have a weight average molecular mass of 15,000 to 60,000. Advantageously, the said prepolymer is formed by hydroxy acid, and 25 to 0.001% of said prepolymer is formed by functionalizing agent containing at least three functional end groups, and/or 50 to 0.001% of diol monomers and/or 50 to 0.001% of diacid, wherein the number of moles of hydroxyl groups are more than the acid groups

The process comprises adding a isocyanate coupling agent to said formed polyhydroxy acid to further polymerize said prepolymers by coupling.

The polymerizing step (b) may comprise the step of: (bl) heating said polyhydroxy acid from about 140 degree C to about 250 degree C, or from about 140 degree C to about 200 degree C, more preferably from about 160 degree C to about 180 degree C.

The polymerizing step (b) may comprise the step of: (b2) agitating said polyhydroxy acid at a rotational speed of about 30 rpm.

The polymerizing step (b) may comprise the step of adding a stabilizer to the prepolymers or the formed polyhydroxy acid. The stabilizer may be one or more peroxide. Suitable peroxides are taught in the published European Patent No. EP 0 737 219, and are incorporated herein.

Advantageously, the addition of peroxide slows down the decrease in molar mass. This effectively stabilizes the said formed polyhydroxy acid by reducing the scission of chains.

The peroxides acting as stabilizers may have a short half-life. In one embodiment, the half-life of the peroxide is below 10 seconds or below 5 seconds.

Exemplary peroxides which can be used are organic peroxy compounds and include, for example, dilauroyl peroxide, tert-butlyperoxy-diethylacetate, t-butylperoxy- 2-ethylhexanoate, tert-butylperoxyisobutyrate, tert- butylperoxyacetate, tert-butylperoxybenzoate and dibenzoylperoxide .

In one embodiment, there is provided a process for producing a polylactic acid from crude lactic acid comprising the steps of: (a) polymerizing said crude lactic acid with said functionalizing agent by heating at a temperature from 50 degree C to 210 degree C, or from 100 degree C to 200 degree C with agitation to form polylactic acid prepolymer having a molecular weight in the range of about 10,000 to about 100,000;

(b) polymerizing said polylactic acid prepolymer by mixing with said isocyanate coupling agent at a temperature between 140°C to 250°C, or 140°C to 200 °C, more preferably 160 °C to 180 °C, with agitation to obtain molecular weight of polylactic acid from about 100,000 to about 450,000, or 150,000 to about 350,000. It has been observed by the inventors that increasing the prepolymer chain can decrease the usage of isocyanate coupling agent. However, short prepolymer chains (ie less than 10,000 molecular weight) are more mobile than longer chains (i.e. more than 50,000 molecular weight), and therefore the reactions between the isocyanate and the hydroxyl group are more probable in a shorter prepolymer chain. Without being bound by theory, the introduction of at least three terminal hydroxyl groups into the prepolymer allows the prepolymer to be highly reactive even with longer chain prepolymers. Hence, a polyhydroxy acid prepolymer having at least three terminal hydroxyl groups facilitates the polymerization of larger weight polyhydroxy acid polymers within a shorter time frame relative to polyhydroxy acid polymers produced from short chain prepolymers. Furthermore, a more reactive polyhydroxy acid prepolymer may also result in less coupling agent having to be used to produce the high molecular weight polyhydroxy acid polymer.

System for producing polyhydroxy acid

Exemplary, non-limiting embodiments of a reactor and system for implementing the process for producing polyhydroxy acid described above will now be disclosed. The system comprising a reactor having a reaction zone containing a polymerizing monomeric mixture of polyhydroxy acid prepolymer having at least three terminal hydroxyl groups and an isocyanate coupling agent, wherein said reaction zone is operated under conditions to form said high molecular weight polyhydroxy acid from said polymerizing monomeric mixture.

The reactor may comprises a fluid jacket surrounding at least a portion of the outer surface of said enclosed chamber for receiving heated fluid therein in use. In use, said reaction zone is in fluid communication with a vacuum, said reactor comprises an agitator disposed within said enclosed chamber to agitate said liquid phase therein in use. The reactor may be a screw extruder. Different screws may be selected to obtain different desired compression ratios. The extruder has an acid-resistant barrel and screw, and the extruder screw has a compression ratio of between approximately 1.5:1 and 3:1. Also, different screw configurations provide different types of mixing. Some examples of screw designs include those with no mixing sections, one mixing section, and two mixing sections.

In one embodiment, the extruder is a twin screw extruder. A twin screw mixer may provide advantages of a more stable flow, easier feeding, and better control over the process relative to a single screw extruder although a single screw extruder could still be used. This is attributed to the positive pumping effect and lack of compression caused by the twin screw mixer. An exemplary twin screw extruder is disclosed in International PCT Published Application No. WO/2003/035349.

Examples

Non-limiting examples of the invention will be further described in greater detail by reference to specific embodiments and experimental examples, which should not be construed as in any way limiting the scope of the invention. For example, although the particular embodiments and experimental examples that will be described relate to formation of polylactic acids, it should be realized that the process and apparatus disclosed herein may be applied to produce other polyhydroxycarboxylic acids.

Example 1

A reactor under vacuum with 12 L of capacity was loaded with 9 kg of 88 wt% commercial L-lactic acid

(Archer Daniels Midland Co, Decatur, IL USA), 55 g 1,4- butanediol (99%, Lancaster), and 9 g glycerin (98%, Sigma-

Aldrich) , and 9 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rprrt. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and nitrogen. The prepolymer was obtained with Mw 24,449 and polydispersity 1.37. DSC- analysis indicated that the glass transition temperature of the prepolymer was 46.6 degree C with melting peaks at 141.4 degree C. Example 2

3 kg of the prepolymer prepared from Example 1 was mixed with 86.1 g of hexamethylene diisocyanate (99%, Merck) . The mixture was fed into a twin-screw extruder (TE35, L/D=54, Coperion Keya (Nanjing) Machinery Co., Ltd. Nanjing, China) with temperature profile of 160-180-180- 180-180-180-180-180-180-180-180-180-180-160 degree C along thirteen equally spaced temperature zones of the twin screw extruder and rotational speed 30 rpm. The total reaction time in twin-screw extruder was about 8 minutes. The product polymer obtained was transparent with Mw 227,189 and polydispersity 2.86. DSC-analysis indicated that the glass transition temperature of the polymer was 50 degree C.

Example 3

The polymerization was carried out as in Example 2 with the exception that the amount of hexamethylene diisocyanate (99%, Merck) used was 84.3 g. The product polymer obtained was transparent with Mw 187,397 and polydispersity 2.86. DSC-analysis indicated that the glass transition temperature of the polymer was 49 degree C.

Example 4

The reactor with 12 L of capacity was loaded with 9 kg of 88 wt% commercial L-lactic acid (ADM, USA) , 50 g 1, 4-butanediol (99%, Lancaster), and 12 g glycerin (98%, Sigma-Aldrich) , and 8 g stannous octoate (95%, Sigma- Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 20,508 and polydispersity 1.39. DSC- analysis indicated that the glass transition temperature of the prepolymer was 50.5 degree C with melting peaks at 141.7 degree C.

Example 5

80 g of the prepolymer prepared from Example 4 was fed into a Banbury mixer (Changzhou, China) at temperature 160 degree C and agitation speed 20 rpm. 1.9 g of hexamethylene diisocyanate (99%, Merck) was added into the homogeneously mixed prepolymer when the melting was completed. The temperature was then raised to 180 degree C and polymerization was further carried out for 10 minutes. The product polymer was obtained with Mw 313,983 and polydispersity 5.01. DSC-analysis indicated that the glass transition temperature of the polymer was 54.8 degree C.

Example 6

3.54 kg of the prepolymer prepared from Example 4 was mixed with 99.1 g of hexamethylene diisocyanate (99%,

Merck) . The mixture was fed into the twin-screw extruder of Example 2 with temperature profile of 160-180-180-180-

180-180-180-180-180-180-180-180-180-160 degree C along thirteen equally spaced temperature zones of the twin screw extruder and rotational speed 30 rpm. The total reaction time in twin-screw extruder was about 8 minutes.

The product polymer obtained was transparent with Mw

275,585 and polydispersity 5.06. DSC-analysis indicated that the glass transition temperature of the polymer was 52.0 degree C.

Example 7 The reactor with 12 L of capacity was loaded with 9 kg of 88 wt% commercial L-lactic acid (ADM, USA) , 720 g ε- caprolactone (99%, Lancaster), 62 g 1, 4-butanediol {99%, Lancaster), and 9.5 g glycerin (98%, Sigma-Aldrich) , and 9 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 19,258 and polydispersity 1.5. DSC-analysis indicated that the glass transition temperature of the prepolymer was 35.9 degree C.

Example 8

80 g of the prepolymer prepared from Example 7 was fed into a Banbury mixer (Changzhou, China) at temperature 160 degree C and agitation speed 20 rpm. 1.9 g of hexamethylene diisocyanate (99%, Merck) was added into the homogeneously mixed prepolymer when the melting was completed. The temperature was then raised to 180 degree C and polymerization was further carried out for 10 minutes. The product polymer was obtained with Mw 213,599 and polydispersity 4.07. DSC-analysis indicated that the glass transition temperature of the polymer was 41 degree C. Example 9

The polymerization was carried out as in Example 7 with the exception that the amount of hexamethylene diisocyanate (99%, Merck) used was 2.1 g. The product polymer obtained was transparent with Mw 254,492 and polydispersity 4.49. DSC-analysis indicated that the glass transition temperature of the polymer was 41 degree C.

Example 10

The reactor with 12 L of capacity was loaded with 9 kg of 88 wt% commercial L-lactic acid (Archer Daniels Midland Co, Decatur, Illinois, USA), 60.5 g 1, 4-butanediol (99%, Lancaster), and 5 g pentaerythritol (98%, Sigma- Aldrich) , and 9 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 21,916 and polydispersity 1.4. DSC- analysis indicated that the glass transition temperature of the prepolymer was 51.6 degree C with melting peaks at 141.3 degree C.

Example 11

3.05 kg of the prepolymer prepared from Example 10 was mixed with 85.7 g of hexamethylene diisocyanate (99%, Merck) . The mixture was fed into the twin-screw extruder of Example 2 with temperature temperature profile of 160- 180-180-180-180-180-180-180-180-180-180-180-180-160 degree C along thirteen equally spaced temperature zones of the twin screw extruder and rotational speed 30 rpm. The total reaction time in twin-screw extruder was about 8 minutes. The product polymer obtained was transparent with Mw 260,973 and polydispersity 3.42. DSC-analysis indicated that the glass transition temperature of the polymer was 51.6 degree C.

Example 12

The reactor with 500 ml of capacity was loaded with 400 g of 88 wt% commercial L-lactic acid (Archer Daniels Midland Co, Decatur, Illinois, USA), 0.8 g succinic acid (99%, Lancaster), 3.4 g 1, 4-butanediol (99%, Lancaster), and 0.2 g pentaerythritol (98%, Sigma-Aldrich) , and 0.4 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 20,266 and polydispersity 1.34. DSC-analysis indicated that the glass transition temperature of the prepolymer was 47 degree C with melting peaks at 147.4 degree C.

Example 13

80 g of the prepolymer prepared from Example 12 was fed into a Banbury mixer (Changzhou, China) at temperature 160 degree C and agitation speed 20 rpm. 1.9 g of hexamethylene diisocyanate (99%, Merck) was added into the homogeneously mixed prepolymer when the melting was completed. The temperature was then raised to 180 degree C and polymerization was further carried out for 10 minutes. The product polymer was obtained with Mw 211,585 and polydispersity 3.01. DSC-analysis indicated that the glass transition temperature of the polymer was 52.9 degree C.

Example 14

The reactor with 500 ml of capacity was loaded with

400 g of 88 wt% commercial L-lactic acid (Archer Daniels

Midland Co, Decatur, Illinois, USA), 2.7 g 1, 4-butanediol

(99%, Lancaster), and 0.25 g glycerol diglycidyl ether (tech. grade, Sigma-Aldrich) , and 0.4 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 20,392 and polydispersity 1.42. DSC-analysis indicated that the glass transition temperature of the prepolymer was 49.5 degree C with melting peaks at 151.2 degree C.

Example 15

80 g of the prepolymer prepared from Example 14 was fed into a Banbury mixer (Changzhou, China) at temperature 160 degree C and agitation speed 20 rpm. 1.9 g of hexamethylene diisocyanate (99%, Merck) was added into the homogeneously mixed prepolymer when the melting was completed. The temperature was then raised to 180 degree C and polymerization was further carried out for 10 minutes. The product polymer was obtained with Mw 215,962 and polydispersity 2.79. DSC-analysis indicated that the glass transition temperature of the polymer was 54.5 degree C.

Example 16 The reactor with 12 L of capacity was loaded with 400 g of 88 wt% commercial L-lactic acid (Archer Daniels

Midland Co, Decatur, Illinois, USA), and 2.82 g 1,4- butanediol (99%, Lancaster), and 0.4 g stannous octoate

(95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 21,370 and polydispersity 1.39. DSC-analysis indicated that the glass transition temperature of the prepolymer was 50.2 degree C with melting peaks at 150.5 degree C.

Example 17

The reactor with 500 ml of capacity was loaded with 500 g of 88 wt% commercial L-lactic acid (Archer Daniels Midland Co, Decatur, Illinois, USA), and 6.65 g pentaerythritol (98%, Sigma-Aldrich), and 0.4 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 14,754 and polydispersity 1.30. DSC-analysis indicated that the glass transition temperature of the prepolymer was 49.5 degree C with melting peaks at 151.2 degree C.

Example 18

76 g of the prepolymer prepared from Example 16 and 4 g the active center oligomer prepared from Example 17 were fed into a Banbury mixer (Changzhou, China) at temperature

160 degree C and agitation speed 20 rpm. 2.1 g of hexamethylene diisocyanate (99%, Merck) was added into the homogeneously mixed prepolymer and active center oligomer mixture when the melting was completed. The temperature was then raised to 180 degree C and polymerization was further carried out for 10 minutes. The product polymer was obtained with Mw 170,276 and polydispersity 3.73.

DSC-analysis indicated that the glass transition temperature of the polymer was 55 degree C.

Comparative Example 19

80 g of the prepolymer prepared from Example 16 was fed into a Banbury mixer (Changzhou, China) at temperature 160 degree C and agitation speed 20 rpm. 2.1 g of hexamethylene diisocyanate (99%, Merck) was added into the homogeneously mixed prepolymer when the melting was completed. The temperature was then raised to 180 degree C and polymerization was further carried out for 20 minutes, with sample product collected at every 10 minutes interval. After 10 minutes of polymerization, the product polymer was obtained with Mw 101,777 and polydispersity 2.17. DSC-analysis indicated that the glass transition temperature of the prepolymer was 54 degree C. With a further 10 minutes of polymerization, the product polymer was obtained with Mw 119,489 and polydispersity 2.43. DSC-analysis indicated that the glass transition temperature of the polymer was 54 degree C. It will be appreciated, that a low molecular weight polymer formed in this comparative example because this example only used a diol to form the prepolymer. Hence the prepolymer of Example 16 did not have three terminal hydroxyl groups and therefore it was not possible to obtain a high molecular weight polylactic acid in this comparative example.

Example 20

The reactor with 12 L of capacity was loaded with 9 kg of 88 wt% commercial L-lactic acid (Archer Daniels Midland Co, Decatur, Illinois, USA), 19.5 g 1, 4-butanediol (99%, Lancaster), and 9.0 g pentaerythritol (98%, Sigma- Aldrich) , and 8 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw 43,923 and polydispersity 1.72. DSC- analysis indicated that the glass transition temperature of the prepolymer was 53.1 degree C with melting peaks at 148 degree C.

Example 21 1.9 kg of the prepolymer prepared from Example 20 was mixed with 36.5 g of hexamethylene diisocyanate (99%,

Merck) . The mixture was fed into the twin-screw extruder

(L/D=40, Jieya, China) of with temperature profile of 160-

175-180-180-180-175-165 degree C along six equally spaced temperature zones of the twin screw extruder and rotational speed 60 rpm. The total reaction time in twin- screw extruder was about 2 minutes. The product polymer obtained was transparent with Mw 284,767 and polydispersity 5.37. DSC-analysis indicated that the glass transition temperature of the polymer was 56 degree C.

Example 22

The reactor with 12 L of capacity was loaded with 8776 g of 88 wt% commercial L-lactic acid (Archer Daniels

Midland Co, Decatur, Illinois, USA), 19.5 g 1, 4-butanediol

(99%, Lancaster), 250 g ε-caprolactone (99%, Lancaster), and 9.0 g pentaerythritol (98%, Sigma-Aldrich) , and 8 g stannous octoate (95%, Sigma-Aldrich) was added as a catalyst. The reaction mixture was heated at 100 degree C with an agitation speed of 200 rpm. The temperature was increased steadily from 100 degree C to 190 degree C with nitrogen bubbling. The vacuum was increased from 600 mmHg to 100 mmHg at a rate of 100 mmHg/h, and then steadily increased from 100 mmHg to 5 mmHg. The total polymerization was around 20 to 40 hours. The condensed water formed during polycondensation was removed by vacuum and/or nitrogen. The prepolymer was obtained with Mw

47,242 and polydispersity 1.75. DSC-analysis indicated that the glass transition temperature of the prepolymer was 48.1 degree C.

Example 23 80 g of the prepolymer prepared from Example 22 was fed into a Banbury mixer (Changzhou, China) at temperature 160 degree C and agitation speed 20 rpm. 1.0 g of hexamethylene diisocyanate (99%, Merck) was added into the homogeneously mixed prepolymer when the melting was completed. The temperature was then raised to 180 degree C and polymerization was further carried out for 5 minutes. The product polymer was obtained with Mw 252,322 and polydispersity 4.78. DSC-analysis indicated that the glass transition temperature of the polymer was 50.5 degree C.

Applications

It will be appreciated that the disclosed process produced a polylactic acid that has a high molecular weight. The produced high molecular weight polylactic acids exhibit sufficient mechanical strength such that they can be used in applications, such as in medical implants . The disclosed process efficiently produces high molecular weight polyhydroxy acids with minimal prepolymer and lactic acid loss from the system.

The disclosed process allows high molecular weight polygydroxy acid to be formed without complex and expensive purification steps (i.e. as for formation of HMW polylactic acid from lactides) . Hence, the disclosed process does not require the use of multiple unit operations (i.e. distillation columns, evaporators, heat exchangers, etc) to separate the water from the cyclic . . dimmers (i.e. lactides) . The disclosed process is not as capital-intensive as other known HMW polylactic acid processes .

It will be appreciated that disclosed process does not require elaborate equipment to handle the highly viscous polylactic acid product due to the short polymerization time from conversion of the prepolymers to polylactic acid. Consequently, it is not necessary to rely on multiple unit operations for production of high molecular weight polylactic acid. The production process can in fact occur in a single reactor followed by a twin- screw extruder.

Advantageously, the disclosed system and process are relatively simple to operate and maintain. Advantageously, the disclosed system and process do not produce any environmentally harmful by-products.

It will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims.

Claims

1. A process for producing a high molecular weight polyhydroxy acid comprising the steps of: (a) condensating a hydroxy acid with a functionalizing agent, said functionalizing agent being selected to form a polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon after said condensating; and (b) polymerizing said pre-polymer in the presence of a coupling agent under conditions to form said high molecular weight polyhydroxy acid.

2. A process as claimed in claim 1, wherein said coupling agent is an isocyanate coupling agent.

3. A process as claimed in claim 1, wherein said functionalizing agent comprises a polyalcohol and optionally at least one of a polycarboxylic and a diol or a polycarboxylic acid in combination with a diol.

4. A process as claimed in claim 1, wherein said formed high molecular weight polyhydroxy acid has a weight average molecular weight of at least 100,000.

5. A process as claimed in claim 1, wherein said polyhydroxy acid has a weight average molecular weight of 100,000 to 450,000.

6. A process as claimed in claim 1, wherein said diol is selected from the group consisting of alkanediols, alkenediols, cycloalkanediols, aromaticdiols, and mixtures thereof.

7. A process as claimed in claim 6, wherein said alkanediols are selected from the group consisting of optionally substituted ethanediols, branched or straight chain propanediols, butanediols, pentanediols hexanediols, heptanediols, octanediol and mixtures thereof.

8. A process as claimed in claim 6, wherein said cycloalkane diols are selected from the group consisting of, optionally substituted, cyclopropanediols, cyclobutanediols, cyclopentanediols cyclohexanediols, cycloheptanediols, cyclooctanediol and mixtures thereof.

9. A process as claimed in claim 6, wherein said aromatic diols are selected from the group consisting of, dihydroxybenzene, dihydroxybiphenyl, and dihydroxyanthraquinone .

10. A process as claimed in claim 3, wherein said polyalcohol is selected from the group consisting of pentaerythritols, glycerols, diglycerols, triglycerols, tetraglycerols, pentaglycerols, and hexaglycerols, glycerol diglycidyl ether and mixtures thereof.

11. A process as claimed in claim 1, wherein said condensating step (a) comprises the step of:

(al) heating said hydroxy acid from 50 degree C to 210 degree C.

12. A process as claimed in claim 11, wherein said heating step (al) is undertaken in an inert atmosphere.

13. A process as claimed in claim 1, wherein said condensating step (a) comprises the step of: (a2) applying a vacuum to said hydroxy acid as it reacts with said functionalizing agent.

14. A process as claimed in claim 13, wherein the vacuum is in the range of from 0.1 mmHg (0.013 kPa) to 600 mmHg

(80 kPa) .

15. A process as claimed in claim 1, wherein said condensating step (a) comprises the step of: (a3) agitating said mixture of hydroxy acid and functionalizing agent.

16. A process as claimed in claim 1, wherein said condensating step (a) comprises the step of: (a4) providing a catalyst to said hydroxy acid as it undergoes polymerization.

17. A process as claimed in claim 16, wherein the said catalyst is suitable for dehydration.

18. A process as claimed in claim 16, wherein the said catalyst is stannous chloride, stannous oxide, tin powder, antimony oxide, iron oxide, zinc acetate, or tin p-toluenesulfonic acid.

19. A process as claimed in claim 1, wherein said condensating step (a) comprises the step of:

(a5) adding of ε-caprolactone .

^■

20. A process as claimed in claim 1, wherein said functionalizing agent comprises one or more of the following:

(i) a polyalcohol;

(ii) a polyalcohol and a polycarboxylic acid; (iii) a polyalcohol and a diol; and (iv) a polycarboxylic acid and a diol.

21. A process as claimed in claim 1, wherein the condensating step (a) is undertaken for 20 hours to 40 hours .

22. A process as claimed in claim 1, wherein said prepolymer has a weight average molecular weight of 10,000 to 100,000.

23. A process as claimed in claim 1, wherein said polymerizing step (b) comprises the step of:

(bl) heating said polyhydroxy acid from 140 degree C to 250 degree C.

24. A process as claimed in claim 2, wherein the molar ratio of isocyanate groups in said isocyanate coupling agent to the hydroxyl groups of prepolymer said prepolymer is from 0.5 to 1.5 or from 0.8 to 1.2.

25. A process as claimed in claim 1, wherein said polymerizing step (b) comprises the step of:

(b2) adding a stabilizer to said prepolymers or said formed polyhydroxy acid.

26. A process as claimed in claim 25, wherein said stabilizer comprises one or more peroxide.

27. A process as claimed in claim 1, wherein the polymerizing step (b) is undertaken for 1 minute to 30 minutes .

28. A system for production of high molecular weight polyhydroxy acid comprising: a reactor having a reaction zone containing a polymerizing monomeric mixture of polyhydroxy acid prepolymer having at least three terminal hydroxyl groups and a coupling agent, wherein said reaction zone is operated under conditions to form said high molecular weight polyhydroxy acid from said polymerizing monomeric mixture .

29. A system as claimed in claim 28, wherein said coupling agent is an isocyanate coupling agent.

30. A system as claimed in claim 28, wherein said reactor zone is in fluid communication with a vacuum.

31. A high molecular weight polyhydroxy acid made in a process comprising the steps of:

(a) condensating a hydroxy acid with a functionalizing agent, said functionalizing agent being selected to form a polyhydroxy acid prepolymer having at least three terminal hydroxyl groups thereon after said condensating; and

(b) polymerizing said pre-polymer in the presence of a coupling agent under conditions to form said high molecular molecular weight polyhydroxy acid.

32. A high molecular weight polyhydroxy acid as claimed in claim 31, wherein said coupling agent is an isocyanate coupling agent.