Patent Application
20180155494
The present invention relates to a one step process for the palletization of poly lactic acid of molecular weight in the range of 6-8 lakhs without melt processing such that the pellets obtained exhibit minimal molecular weight reduction. The molecular weight of poly lactic acid (PLA) in the obtained pellets is retained in the range of 6-8 lakhs.
Poly-l-lactic acid is a biologically compatible and safe polymer. It displays degradation with time and its degradation product, lactic acid, is not hazardous and provides itself as a precursor for pyruvic acid, which is the fundamental molecule for Krebs cycle. Lactic acid is dispelled from the body and is not retained by the body as a toxic byproduct. As poly-l-lactic acid possesses the above said properties, it is useful for medical purposes, including resorb able sutures, reinforcing materials in orthopedic surgery, and drug delivery systems. Despite its use for such high end niche applications poly-l-lactic acid also finds use in commodity applications. The rising awareness about clean resources, which do not burden our reserves of fossil fuels, and depleting sources of oil are leading consumers away from traditionally used polyolefins, and other high volume polymers, to polymers that degrade over time under natural conditions. For commodity applications, high mechanical properties are not required and the desired properties are obtained by low molecular weight poly-l-lactic acid, which degrades faster compared to high molecular weight polymer. For application in orthopedic implants high molecular weight polymer which degrades at a slower rate upon biological exposure is desired. Methods for production of high molecular weight poly-l-lactic acid are known in literature.
Article titled “Recent advancements of biodegradable polylactic acid/polylactide: A review on synthesis, characterization and applications” by Asutosh Kumar Pandey published in Advanced Materials Letters, 2013, pp 1-56 reports the first step of the coordination-insertion mechanism (i) consists of the coordination of the monomer to the Lewis-acidic metal center. The monomer subsequently inserts into one of the aluminum alkoxide bonds via nucleophilic addition of the alkoxy group on the carbonyl carbon. (ii) followed by ring opening via acyl-oxygen cleavage. (iii) hydrolysis of the active metal-alkoxide bond leads to the formation of a hydroxyl end group. The most widely used complex for the industrial preparation of PLA is undoubtedly tin (II) bis (2-ethylhexanoate).
Article titled “Poly (lactide -co- glycolide) fiber: An overview” by Bahareh Azimi et al. published in Journal of Engineered Fibers and Fabrics, 2014, 9(1), pp 47-66 reports a review of the chemistry and different properties of PLGA and production of PLGA fiber by various methods, along with correlations between structure and properties of the fibers. The applications of these fibers in biological and medical domains are also discussed.
Article titled “Poly-lactic acid: production, applications, nanocomposites, and release studies” by Majid Jamshidian et al. published in Comprehensive Reviews in Food Science and Food Safety, 2010, 9(5) pp 552-571 reports production, applications, nanocomposites, and release studies of poly-lactic acid. PLA has a variable molecular weight and only its high molecular weight polymer is used in the packaging industry. Three ways are possible for the polymerization of lactic acid; (a) direct condensation polymerization; (b) direct polycondensation in an azeotropic solution (an azeotrope is a mixture of 2 or more chemical liquids in such a ratio that its composition cannot be changed by simple distillation. This occurs because, when an azeotrope is boiled, the resulting vapor has the same ratio of constituents as the original mixture); and (c) polymerization through lactide formation.
Article titled “Synthesis of poly(L-lactide) and polyglycolide by ring-opening polymerization” by Sachiko Kaihara et al. published in Nature Protocols, 2007, 2, pp 2767-2771 reports the synthesis of poly(L-lactide) by ring-opening polymerization of L-lactide using tin(II) 2-ethylhexanoate catalyst as well as the synthesis of polyglycolide by ring-opening polymerization of glycolide. Ring-opening polymerization of cyclic diesters synthesized from α-hydroxycarboxylic acids gives high-molecular-weight polyester in high yield. Tin(II) 2-ethylhexanoate catalyst is the most common catalyst for ring-opening polymerization of diesters owing to its high reactivity and low toxicity. Purity of monomers and the amount of water and alcohol in the reaction system are significant factors for increasing molecular weight and conversion of polyesters. The molecular weight of the polyesters is also dependent on reaction temperature and reaction time. This protocol can be completed in 3 d for the synthesis of poly(L-lactide) and 2 d for the synthesis of polyglycolide.
European patent 2607399 discloses a process is described for producing a high molar mass polylactic acid, which comprises the following steps: a) polycondensation in a reactor (R1) of a lactic acid solution, by heating in the form of temperature gradients and under controlled pressure, resulting in a polylactic acid oligomer within the range of 300 to 5000 g/mol; b) conversion, in reactor (200), of the polylactic acid of low molar mass obtained in step a) to a lactide, in the presence of a depolymerization catalyst; c) separation of the volatile fractions; d) recrystallization of the lactide in the vessel (R3), in order to obtain ethanol; e) polymerization, in a tube reactor (300), of the recrystallized lactide obtained in step d), via ring opening in the presence of the catalyst, producing a high molar mass polylactic acid; f) devolatilization, at (400), of the polymeric mass obtained in step e); and g) recovery of the final polylactic acid product with a high degree of purity, with a molar mass of between 50 000 and 200 000 g/mol and a reaction conversion of between 70% and 95%. Also described are the depolymerization reactor (200), polymerization reactor (300) and devolatilization reactor (400) used in the process of the invention.
Article titled “Synthesis of high-molecular-weight poly(L-lactic acid) through the direct condensation polymerization of L-lactic acid in bulk state” by Guang-Xin Chenet al. published in European Polymer Journal 2006; 42(2), pp 468-472 reports a strategy was attempted to produce high-molecular-weight poly(l-lactic acid) (PLLA) through the direct condensation polymerization of l-lactic acid in bulk state. Polymerizations were carried out with titanium (IV) butoxide (TNBT) as a catalyst employing different duration of decompression, esterification and polycondensation. The molecular weights were characterized by using the gel permeation chromatography (GPC).
Article titled “Synthesis and characterizations of poly (lactic acid) by ring-opening polymerization for biomedical applications” by Milena S. Lopes et al. published in Chemical Engineering Transactions, 2014, 38, pp 331-336 reports PLA can be obtained using different routes (
Article titled “Preparation of higher molecular weight poly (l-lactic acid) by chain extension” by Chenguang Liu et al. published in International Journal of Polymer Science, 2013, Article ID 315917 reports High molecular weight poly (lactic acid) (PLA) was obtained by chain extending with hexamethylene diisocyanate (HDI). The influences of the amount of chain extender, reaction time, and molecular weight changes of prepolymers on the poly(lactic acid) were investigated. PLA prepolymer with a viscosity, average molecular weight of 2×104 g/mol was synthesized from L-lactide using stannous octoate as the catalyst.
Article titled “Ring-opening polymerization of 1-lactic acid o-carboxyanhydrides initiated by alkoxy rare earth compounds” by Zhengguo He et al. published in Molecules, 2013, 18, pp 12768-12776 reports the ring-opening polymerization of L-lactic acid O-carboxyanhydrides was initiated by triisopropoxyneodymium in toluene-THF mixtures. Typically, high yields and relatively high molecular weight PLAs were obtained within 4 h at 25° C. The reaction was highly controllable and easy to conduct, and the molecular weight distribution of the PLAs was rather narrow (Mw/Mn=1.10-1.36). NMR analysis showed that one end of the PLA chain consisted of an isopropoxy group, while the other end of the chain contained a hydroxyl group. Due to their availability and high polymerizability, Lac-OCAs are promising monomers for the preparation of tailored architectures derived from well-defined PLAs.
Article titled “Reversible kinetics and thermodynamics of the homopolymerization of l-lactide with 2-Ethylhexanoic Acid Tin(II) Salt” by David R. Witzke et al. published in Macromolecules, 1997, 30 (23), pp 7075-7085 reports The reversible kinetics of l-lactide bulk polymerization with tin(II) ethylhexanoate was determined over a wide range of temperatures, 130-220° C., and monomer to initiator molar ratios, 1000-80 000. Both polymerization and depolymerization are accurately described by a reversible model with a propagation term that is first order in monomer and catalyst. The activation energy of propagation is 70.9±1.5 kJ mol−1. The enthalpy, entropy, and ceiling temperature of polymerization are −23.3±1.5 kJ mol−1, −22.0±3.2 J mol−1 K−1, and 786±87° C., respectively. Crystallization increases the propagation rate and decreases the apparent monomer equilibrium in proportion to the degree of crystallinity. Natural hydroxyl impurities stoichiometrically control the polymer molecular weight but do not significantly affect the propagation rate.
Article titled “Synthesis polylactide with varying molecular weights” by Minh Chau Truong published as thesis, 2013 reports polylactide with various molecular weights and molecular weight distributions were synthesized by solution ring opening polymerization. Molecular weight was controlled by varying the ratio of L-lactide monomer to palmityl alcohol initiator and tin(II) octanoate was used as a catalyst for precise control over molecular weight. Anhydrous toluene was used as a non-reactive solvent to prevent the contamination of catalyst. Besides, we also try to obtain the standard molecular weight of PLA (greater than 100,000 g/mol) to compare with commercial PLAs. Properties of different molecular weights of PLA were characterized by gel permeation chromatography, thermogravimetric analysis, differential scanning calorimety, and 1H NMR spectroscopy.
U.S. Pat. No. 5,770,682 discloses a method of producing poly-l-lactic acid by ring opening polymerization, wherein a compound is added to inhibit the catalytic activity at the end of the reaction. A method for residual lactide removal is also described in the same patent document, where pressure reduction and concurrent passage of an inert gas are used for the removal of unreacted monomer. The molecular weights obtained by this method can give polymer having molecular weights 200,000-500,000.
U.S. Pat. No. 5,136,017 discloses a method for continuous polymerization of l-, d-, d1-, or mesolactides. The poly-l-lactic acid produced by this method exhibits molecular weight in the range of 50,000 to 300,000.
US Pat Appl. No. 20140121347 discloses discloses a method for catalytic condensation synthesis of poly-l-lactic acid using bionic creatinine-guanidine chloride. Creatinine-guanidine chloride is used as a catalyst to convert industrial grade lactic acid into metal and toxic residue free poly lactic acid featuring high molecular weight and biological safety.
Currently reported techniques of poly lactic acid production employ polycondensation or ring opening polymerization to produce high molecular weight poly lactic acid. These techniques have a limitation of producing polymer having a molecular weight around 300,000-500,000. Also, the said polymerization reactions are carried out at higher temperatures, 140-220° C. Melt processing of poly-l-lactic acid has always come across as an issue of concern. Retention of molecular weight during processing of poly-l-lactic acid has been a problem as residual lactide or moisture leads to transesterification and main chain scission. Earlier reported polymerization techniques suggest carrying out reactions for long durations of time to obtain high molecular weights. This approach is not validated by the industry, as the time scales prove to be a hindrance for large scale production.
Article titled “Thermal decomposition of biodegradable polyesters-II. Poly(lactic acid)” by F. D. Kopinke et al. published in the Journal Polymer Degradation and Stability, 1996, 53(3), pp 329-342 reports thermal behavior of PLA with thermogravimetric analysis and Gas Chromatography/Mass Spectroscopy techniques. The degradation pathways proposed for PLA are as follows:
Article titled “Thermal degradation of poly(lactic acid) (PLA) and poly(butylene-adipate-co-terephthalate) (PBAT) and their blends upon melt processing” by Francesca Signori et al. published in the Journal Polymer Degradation and Stability,2009, 94(1):74-82 reports degradation behavior of PLA using Size Exclusion Chromatography Techniques and a significant drop in molecular weight values has been reported. It was also reported that as the temperature increases the drop in molecular weight is seen to be higher.
Article titled “Thermal oxidative degradation of poly-lactic acid” by M. C. Gupta et al published in the journal Colloid and Polymer Science, 1982, 260(3), pp 308-311 reports the isothermal weight loss in PLA by means of thermogravimetric analysis and the molecular weights are characterized using end group analysis. A significant drop in molecular weight is observed upon exposing PLA at elevated temperatures for varying periods of time. It is concluded that increasing temperature as well the amount of time at higher temperature has a detrimental effect on the molecular weight of PLA.
Article titled “Influence of melt processing conditions on poly(lactic acid) degradation: Molar mass distribution and crystallization” by Pierre Erwan Le Marec, et al. published in the journal Polymer Degradation and Stability, 2014, 110, 353-363 reports the effect of temperature and time on the PLA molecular weight. The polymer samples are characterized by Size Exclusion Chromatography coupled with Multi-angle light scattering to get molecular weight data. It is confirmed that significant drop in molecular weight is observed upon heating the sample at higher temperatures and maintaining the sample at higher temperatures for longer periods of time. Shear heating in polymers is a common occurrence. The presence of any shear in the presence of heat would lead to further heating of sample; hence chances of degradation are more.
Article titled “Processing technologies for poly(lactic acid)” by L. T. Tim, et al. published in the journal Progress in Polymer Science, 2008, 33(8), pp 820-852 have presented a review of PLA processing techniques. They have highlighted the fact that PLA degrades upon thermal exposure and have made clear the need to process PLA in the absence of heat.
Article titled “Injection Moulding of Biodegradable Implants” by R. von Oepen, et al. published in the journal Clinical Materials, 1992, 10 (1-2), pp 21-28 have studied the process of conversion of PLA into end-use biodegradable implants. The problem of molecular weight degradation upon heating is highlighted and ways to tackle are suggested none of which are prior art for our invention. The loss in molecular weight is to be avoided as it has a direct effect on the final mechanical properties of the polymer.
PLA is a polymer that is prone to degradation when melt processed. This is even more so if certain applications (like biomedical applications) require minimization of additives to control degradation. In this context, a process that can produce pellets (typical shape used to feed into processing setups) without involving a melt processing step is very valuable.
Prior art documents showed PLA degrades upon thermal exposure and molecular weight degradation upon heating So there is need to develop a process to convert the polymer to a filamentous or fibrous shape that can be pelletized without going through a melt processing/shaping step to get the filamentous/fibrous shape.
The problem of converting PLAs to shapes with minimum degradation and especially without use of additives and loss of molecular weight of polylactic acid are an outstanding problems in the literature. This invention has proposed an unexpected solution to these problem.
Therefore, there is a need to develop a process to convert the polymer to a filamentous or fibrous shape that can be pelletized without going through a melt processing/shaping step to get the filamentous/fibrous shape with minimal molecular weight reduction.
The main objective of the present invention is to provide a one step process for the palletization of poly lactic acid of molecular weight in the range of 6-8 lakhs without melt processing such that the pellets obtained exhibit minimal molecular weight reduction.
Another objective of the present invention is to provide pellets of poly lactic acid (PLA) with molecular weight range of 6-8 lakhs.
Still another objective of the present invention is to provide pellets of poly lactic acid with lactide content of the pellets is in a range from 0-10%.
Yet another objective of the present invention is to provide an efficient process for production of high molecular weight poly-l-lactic acid from l-lactide, which would undergo least degradation upon melt processing.
Accordingly, the present invention provides a one step process for the palletization of poly lactic acid of molecular weight in the range of 6-8 lakhs without melt processing such that the pellets obtained exhibit minimal molecular weight reduction.
In an embodiment, the present invention provides pellets of poly lactic acid (PLA) with molecular weight range of 6-8 lakhs.
In another embodiment, the present invention provides pellets of poly lactic acid with lactide content of the pellets is in a range from 0-10%.
In still another embodiment the present invention provides an efficient process for production of high molecular weight poly-l-lactic acid from l-lactide, which would undergo least degradation upon melt processing.
In yet another embodiment the present invention provides process for production of poly-l-lactic acid pellets having lactide content in the range of 0-10% and molecular weight in the range of 5-9 lakhs.
In still yet another embodiment, the present invention provides poly-l-lactic acid which is useful as a bio-compatible and biodegradable polymer and can be manufactured in various forms such as powder, pellets, and fibers.
Abbreviation:
GPC: Gel Permeation Chromatography
PLLA: Poly-l-lactic acid
TGA: Thermogravimetric analysis
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
The present invention discloses an efficient process for production of high molecular weight poly-l-lactic acid from l-lactide, having high monomer to polymer conversion ratios and low unreacted lactide content. It further shows a process, wherein the obtained polymer can be converted to pellets having an interesting morphology, wherein the pellets are observed to be hollow and non-porous.
In an embodiment, the present invention describes an efficient process for production of high molecular weight poly-l-lactic acid from lactide, wherein said process comprising the following steps:
In preferred embodiment, said ring opening polymerization is carried out at temperature in the range of 140-220° C. for a time period in the range of 0-60 hours. Preferably ring opening polymerization is carried out at 140° C. for 75 minutes.
In another preferred embodiment, said solid state polymerization is carried out at temperature in the range of 110-140° C. for a time period in the range of up to 384 hours to get high molecular weight poly-l-lactic acid. Preferably solid state polymerization is carried out at 110° C. for 12 hours.
In still another preferred embodiment, said high molecular weight poly-l-lactic acid is in the range of 5-9 lakhs. Preferably the molecular weight of poly-l-lactic acid obtained by above process is 6-8 lakhs. The lactide content observed in the said polymer is less than 10%. Preferably the lactide content is less than 2%.
In yet another preferred embodiment, the conversion of lactide into poly lactic acid may be carried out using various catalyst systems such as, tin (II) chloride, tin (II) ethyl hexanoate, zinc (II) alkoxides, etc.
In preferred embodiment, the catalyst used is tin (II) ethyl hexanoate.
In still yet another preferred embodiment, depending upon the final molecular weight that is targeted, the monomer to catalyst ratio may vary from 170:1 to 6300:1. More preferably, the monomer to catalyst ratio is 960:1.
The initiator-free catalytic ring opening polymerization is carried out at a temperature which is relatively lower than the conventional techniques. Upon polymerization for a small time period the polymer is subjected to even lower temperatures which lie between the initial polymerization temperature and melting point of the monomer. This ensures that highest conversion in the least possible time frame has taken place.
The obtained polymer is dissolved, filtered, and precipitated. The polymer is now extruded at room temperature in the form of a highly viscous solution. The fibre obtained can be cut into pellets which have to be dried thoroughly before use in any melt processing equipment.
Poly-l-lactic acid produced by this method is useful as a bio-compatible and biodegradable polymer and can be manufactured in various forms such as powder, pellets, and fibers.
PLA is a polymer that is prone to degradation when melt processed. This is even more so if certain applications (like biomedical applications) require minimization of additives to control degradation. In this context, a process that can produce pellets (typical shape used to feed into processing setups) without involving a melt processing step is very valuable. In this invention, the inventors have developed a process to convert the polymer to a filamentous or fibrous shape that can be pelletized without going through a melt processing/shaping step to get the filamentous/fibrous shape. This has been accomplished by extruding a solution of the polymer directly in the wet stage into filaments. The problem of converting PLAs to shapes with minimum degradation and especially without use of additives is an outstanding problem in the literature. This invention has proposed an unexpected solution to the problem.
In another embodiment, the present invention provides flat filament-like pellets, or oblong, non-porous pellets, or hollow, non-porous pellets of poly-l-lactic acid.
Still another rembodiment, the present invention provides a one step process for the synthesis of PLA pellets comprising dissolving poly lactic acid of molecular weight in the range of 6-8 lakhs in a solvent followed by extrusion at the temperature ranging from 25° C. to 30° C. to obtain fibre morphologies, said fibres are cut to obtain pellets, wherein the molecular weight of PLA in the pellets is retained in the range of 6-8 lakhs.
The obtained pellets exhibit minimal molecular weight in the range of 6-8 lakhs and lactide content in the range of 0-10%.
In preferred embodiment, said pellets are selected from flat-filaments, oblong non porous or hollow non porous pellets.
In preferred embodiment, said solvent for dissolution is selected from dichloromethane and chloroform. Preferably said solvent is chloroform.
Article titled “Thermal degradation of poly(lactic acid) (PLA) and poly(butylene-adipate-co-terephthalate) (PBAT) and their blends upon melt processing” by Francesca Signori et al. and article titled “Thermal oxidative degradation of poly-lactic acid” by M. C. Gupta et al published in the journal Colloid and Polymer Science, reports A significant drop in molecular weight is observed upon exposing PLA at elevated temperatures for varying periods of time.
Upon these prior arts inventors overcomes the drawbacks of prior art of reduction in molecular weight.
The novelty and inventive step of the invention lies in a process to synthesize polymer filaments of PLA at temperature ranging from 25-30 deg C., wherein this low temperature prevents degradation of the polymer. The process is devoid of the melt processing step and therefore prevents the degradation of PLA. So a long standing problem in the art is resolved by the process of the invention.
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.
The reaction mixture, comprising of l-lactide and stock solution, is added to a glass ampoule inside a glove box, under Argon atmosphere. The said stock solution consists of catalyst, tin-(II)-ethyl hexanoate, and toluene in 1% v/v proportion. The glass ampoule along with its contents is dried, under temperature and vacuum, thoroughly so as to remove to toluene from the reaction mixture. The glass ampoule is sealed under high vacuum and subjected to a temperature of 140° C. for 75 minutes so as to carry out ring opening polymerization. Observe here that an initiator less system is used. The initiation of the reaction takes place with the assistance of the residual hydroxyl groups that are present in the reaction mixture. A significant rise in viscosity is observed at the end of the time duration mentioned. Upon completion of ring opening polymerization the temperature is reduced to 110° C. The reduced temperature leads to solid state polymerization, during which the earlier unreacted monomer participates in the reaction and higher conversion ratios are obtained. The reduced temperature is maintained for 12 hours so as to effect higher monomer conversion which ultimately leads to low lactide content.
The polymer obtained from Example (1) is dissolved in chloroform in the ratio of 10 w/v %. The obtained polymer dope, which is highly viscous, is extruded through an orifice using a fixed volumetric displacement pump (Harvard Instruments PHD 1000). Extrusion is carried out at ambient temperature conditions with extrusion speed set at 0.25 ml/min. The take up of the fibres is on a plane surface. The fibres collected on the surface are dried under vacuum and temperature to remove the solvent from fibres. The resultant fibres present an interesting morphology, wherein said fibres possess a flat filament structure without the presence of any voids, or axial holes. These fibres are then pelletized.
The polymer obtained from Example (1) is dissolved in chloroform in the ratio of 20 w/v %. The obtained polymer dope, which is highly viscous, is extruded through an orifice using a fixed volumetric displacement pump (Harvard Instruments PHD 1000). Extrusion is carried out at ambient temperature conditions with extrusion speed set at 0.25 ml/min. The take up of the fibres is on a plane surface. The fibres collected on the surface are dried under vacuum and temperature to remove the solvent from fibres. The resultant fibres present an interesting morphology, wherein said fibres possess a cross-section that appears to be oblong in shape and does not possess a hollow core. These fibres are then pelletized.
The polymer obtained from Example (1) is dissolved in chloroform in the ratio of 30 w/v %. The obtained polymer dope, which is highly viscous, is extruded through an orifice using a fixed volumetric displacement pump (Harvard Instruments PHD 1000). Extrusion is carried out at ambient temperature conditions with extrusion speed set at 0.25 ml/min. The take up of the fibres is on a plane surface. The fibres collected on the surface are dried under vacuum and temperature to remove the solvent from fibres. The resultant fibres present an interesting morphology, wherein said fibres possess a hollow central core and non-porous walls. These fibres can then be pelletized.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1668/DEL/2015 | Jun 2015 | IN | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IN2016/050170 | 6/6/2016 | WO | 00 |
