RU2726362C1 - Method of producing polylactides - Google Patents

Abstract

FIELD: chemistry; manufacturing technology.SUBSTANCE: invention relates to a method of producing polylactides which can be used in various fields of science, engineering, medicine and the national economy. Method involves polymerisation of lactides with opening of a cycle (ROP) in a melt in the presence of a ROP catalyst and a cocatalyst. Method is carried out in the temperature range of 100–185 °C with thermal provision of the temperature mode in the reaction space by microwave (super-high-frequency) irradiation of the reaction space. ROP catalyst used is organometallic compound 1-hydroxygermatrane monohydrate, and the cocatalyst used is lauryl alcohol.EFFECT: method provides high efficiency of the end product due to reduction of polymerisation time, high thermal efficiency of the process, as well as obtaining a less toxic product.4 cl, 1 tbl, 4 ex

Description

The invention relates to organic chemistry, in particular to the production of synthetic biodegradable polymeric materials, namely to polylactides, which are used in various fields of science, technology, medicine and the national economy.

Currently, as the reserves of fossil raw materials decrease and their deficit increases, as well as the emerging environmental problems with the production and disposal of used polymer products, the development and use of new polymer materials from renewable plant raw materials - biodegradable polymers - are becoming increasingly important.

Biodegradable material can be completely degraded in the natural environment without any harmful effects on the ecological environment after fulfilling its purpose of use.

The priority of the development of biodegradable plastics is due to the harmlessness of polymers in products, the ability to maintain consumer properties throughout the entire period of operation, after which, under the influence of environmental factors, they break down into carbon dioxide, water and humus for several months.

In modern medicine, biopolymers are used for the manufacture of materials and products designed to replenish tissue and organ defects with subsequent replacement with biological structures in a strictly specified time frame [LasprillaA. J.R., Martinez G.A.R., Lunelli B.H., Jardini A.L., Filho R.M. Poly-lactic acid synthesis for application in biomedical devices - A review. Biotechnol. Adv. 30, 321-328. 2011.06.019.]. However, it is quite clear that commercial implementation of biopolymer production becomes possible only when products are obtained with low toxicity, and their production is carried out using the simplest and cheapest technology.

Among the degradable polymeric materials found so far, the most attractive are aliphatic polyesters, since in the natural environment they can completely decompose into substances that appear in the natural ecological cycle under the action of water, microorganisms and carbon dioxide. Such materials are biodegradable polymers based on lactic acid (MC) - polylactides (PLA), the raw material for which are the products of enzymatic fermentation of renewable plant raw materials (sugar beet dextrose or maltose of grain and potato wort). They are the best known of all commercially available polymers and are widely used materials. At the stage of use, these materials have very good physical properties comparable to engineering plastics. After completion of the use of such materials, physical or chemical methods can be extracted from them lactic acid monomer and reused [Gisha E. Luckach and C.K.S. Pillai, Biodegradable Polymers - A Review on Recent Trends and Emerging Perspectives. Journal of Polymers and the Environment. September 2011, Volume 19, Issue 3, pp 637-676].

Until now, for biomedical applications, the most widely used synthetic biodegradable (biodegradable) polymers are polylactide (PLA) polymers [Prokop A, Jubel A, Hahn U, Dietershagen M, Bleidistel M, Peters C, Hofl A, Rehm K E (2005) Biomater 26: 4129-4138]. At the same time, along with certain advantages of PLA, the high cost of their production with an ever-increasing demand in medicine, there is a need to search for new methods for their production, which will make their production more efficient and commercially attractive.

Currently, there are two known methods for producing polylactides: 1) catalytic polycondensation directly from lactic acid and 2) using the ROP technology (ring opening polymerization) - ring opening polymerization from lactide (LA) - a cyclic dimer of lactic acid [Aseel F. Alwanand Hussein I. Khalaf 2019 IOP Conf. Ser .: Mater. Sci. Eng. 571]. Polycondensation of MK in the presence of catalysts gives PLA and water as a by-product. One of the disadvantages of MK polycondensation is that a polymer with a low molecular weight and insufficient mechanical properties is usually obtained, which causes a serious increase in melt viscosity and higher operating temperatures during subsequent processing.

On the contrary, using ROP, it is possible to precisely control the polymerization chemistry, and thus to vary the properties of the resulting polymer required for a particular application. High molecular weight PLA is produced industrially by ROP lactides obtained by decomposition of low molecular weight polylactic acid. According to the ROP technology, first, as a preparatory step, the polycondensation of MC is carried out, followed by depolymerization of oligomeric lactic acid to a dehydrated cyclic dimer, lactide (3,6-dimethyl-1,4-dioxane-2,5-dione), which is then subjected to ROP to obtain PLA with high molecular weight.

In the description of the patent [Patent US 5,403,897 IPC C08F 20/00, 1995] it is noted that it is desirable to use a reaction temperature not lower than the melting point of lactide, since at such temperatures the reaction system can be homogeneous and a high polymerization rate can be achieved. In cases where the reaction is carried out in a system without solvents (in the melt), the reaction temperature is desirable not lower than the melting point of lactide (about 100 ° C) and not higher than 185 ° C, from the point of view of the reaction equilibrium, on the one hand, and from the point of view of preventing PLA from staining as a result of decomposition at elevated temperatures, on the other hand.

ROP lactides can be performed by methods of polymerization in solution, in bulk, melt and suspension polymerization [US Patent 5,247,058 IPC C08G 63/08, 1993]. The mechanism of ROP polymerization can be ionic, coordination or with free radicals, depending on the catalyst used [US Patent 5,357,035 IPC C08G 63/08/1994; patent GB779291 IPC C08G 63/08, 1957].

ROP of lactides can be catalyzed by transition and non-transition metals such as tin [Patent CN 1298892 IPC C08G 63/08, 2001; patent CN 1557853 IPC C08G 63/02, 63/80, 63/85, 2004; JP 59096123; Corothers W.H. et al. J. Amer. Chem. Soc. 1932, V. 54, P. 761-763; Schuls R.C. et al. Macromol. Chem. 1965, V. 87, P. 90-102], lead [Jalabert M. et al. J. Polym. Sci. A. 2007, V. 45, No. 10, P. 1944-1955], zinc [Treger Yu.A. Lactic acid in the book. "Chemical encyclopedia", vol. 3, ed. BRE, 1992, p. 130-131; patent RU 2435797 IPC C08G 65/00, 2010], bismuth [Jalabert M. et al. J. Polym. Sci. A. 2007, V. 45, No. 10, R. 1944-1955], yttrium [Angew. Chem. Int. Ed. 2002, V. 41, No. 23, P. 4510-4513], iron [Dalton. Trans., 2003, V. 2, P. 406-412], aluminum [Applications and Convercial Products, (Feb. 2002) Polilactides "Nature Works PLA", P. 235-250; Chemical encyclopedia. Ed. "Sov. Encyclopedia ", M., 1990, vol. 2], magnesium [Schlicht R. Kunstoffe, 1988, V. 88 No. 6], titanium [Perepelkin KE Polylactide fibers: production, properties, application, prospects. Chemical fibers. 2002, No. 2, p. 12-24.]. However, all of these catalysts (except for tin) are either difficult to obtain, expensive, or insufficiently active. The available and highly active catalysts obtained using tin compounds are unfortunately toxic. All over the world there is an intensive search for ways to replace tin-containing catalysts in the production of biodegradable (bioresorbable) polymers with less toxic ones. The known technologies for the purification of bioresorbable polymers from tin are very expensive and allow only a slight decrease in the residual tin content in the polymer. When such polymers are disposed of, tin does not decompose, but, on the contrary, accumulates and has a toxic effect on living organisms and the environment.

Known patent US 6,316,590 IPC C08G 63/82, 2001, disclosing a method of conducting polymerization under mild conditions (at room temperature) and with high conversion of lactide for several minutes in the presence of an organic catalyst based on magnesium or zinc with a β-diiminate ligand. However, as practice shows, such catalysts are much more difficult to obtain and expensive, as well as, what is very important, unstable and highly sensitive to moisture compounds, which calls into question their real practical application.

Described [US Patent 5,424,346 IPC C08L 67/04, 1995] a method for producing polylactides with different molecular weights using the ROP technology, with opening the lactic acid dimer ring, where tin octanoate Sn (Oct) _{2 is} used as a catalyst. The disadvantage of this method, which hinders the widespread use of these polymers, especially in medicine, is the residual tin content up to 1000 ppm. For example, for the direction of bioresorbable materials for medical purposes, biopolymers with a special set of physicochemical indicators are required that provide the necessary performance characteristics of medical devices with very stringent requirements for the residual tin content (no more than 10 ppm), with a tendency to be completely absent.

In addition, the duration of the polymerization process is from 4 to 16 hours, which significantly reduces the productivity and thermal efficiency of the process.

The closest in technical essence, and taken here as a prototype, is a method for producing polylactides, including the polymerization of lactides with ring opening (ROP), in a melt, using a ROP catalyst and a cocatalyst, in the temperature range from 100 ° C to 185 ° C, at thermal support of the temperature regime in the reaction space [Patent CN 1557853 IPC C08G 63/02, 63/80, 63/85, 2004]. In the known technical solution, the temperature regime is provided by supplying heat from the oil bath. PLA is produced using a binary catalyst. As a catalyst and cocatalyst, the authors of the known technical solution used compounds of tin and protic acid. The catalyst is a dihydrate compound of tin dioctoate or tin dichloride, that is, the most effective catalysts for the production of polylactides today. The proton-containing cocatalyst is boric acid, phosphoric acid, or p-toluenesulfonic acid. The resulting polymer product (PLA), as stated in the patent, has a molecular weight of 12,000 to 15,000, which may well provide satisfactory strength properties of products obtained from PLA. Polymerization in the melt takes 4-8 hours.

However, the described method of heat supply (heat transfer from the heated oil) is carried out due to convection, thermal conductivity and, to a lesser extent, thermal radiation. Hence, a temperature gradient (temperature difference) from the heat exchange surface to the depth of the reaction mass is inevitable, and the greater, the lower the thermal conductivity of the reaction mass. In this case, it is possible to avoid overheating of the layers of the processed material directly adjacent to the heating surfaces only due to slow heating, which increases the heating time of the reaction mixture and polymerization and, naturally, the heat loss flux, and thereby reduces the thermal efficiency of the process as a whole. The method of supplying heat through the heating surfaces does not ensure uniformity of temperatures throughout the entire volume of the reaction mass, which leads to a difference in the reaction conditions at different points of the reaction space and a decrease in the uniformity of the composition of the final product and, thus, reduces its consumer properties. In addition, relatively higher, in comparison with the reaction mass, temperatures of the heating surfaces reduce their corrosion resistance and contamination of the polymer with corrosion products.

The disadvantages of this method should also include the use of toxic tin-containing compounds as catalysts. This disadvantage is key and applies to all methods where tin compounds are used.

In general, the known method for producing PLA turns out to be low-productivity, energetically ineffective, and the resulting product has increased toxicity.

The objective of this technical solution is to eliminate the above disadvantages and develop a new method that provides high productivity for the target product by reducing the polymerization time, high thermal efficiency of the process, as well as obtaining a less toxic product.

This task is achieved by the fact that a new method for the production of polylactides is proposed, including the polymerization of lactides with ring opening (ROP), in a melt, using a ROP catalyst and a cocatalyst, in the temperature range from 100 ° C to 185 ° C, with thermal provision of a temperature regime in reaction space, characterized in that the temperature regime is provided by microwave (microwave) irradiation of the reaction space, while an organogermanium compound is used as the ROP catalyst. In the proposed technical solution, microwave radiation is used mainly with operating frequencies of 433, 915 and 2450 MHz; 1-hydroxygermatrane monohydrate is used as the organogermanium compound; the content of the ROP catalyst in the reaction mixture is from 0.025 to 0.25 wt% of the mass of lactides, and lauryl alcohol is used as a cocatalyst with a content of 0.05 - 0.1 wt% in the reaction mixture based on the mass of lactides.

The proposed method differs from the known technical solution in that the temperature regime is provided by microwave (microwave) irradiation of the reaction space, while an organogermanium compound is used as the ROP catalyst. In the proposed technical solution, microwave radiation is used mainly with operating frequencies of 433, 915 and 2450 MHz; 1-hydroxygermatrane monohydrate is used as the organogermanium compound; the content of the ROP catalyst in the reaction mixture is preferably from 0.025 to 0.25 wt.% of the mass of lactides, and lauryl alcohol is used as a cocatalyst with a content of 0.05 to 0.1 wt.% in the reaction mixture. % by weight of lactides.

The essence of the proposed technical solution is illustrated by the following examples.

Examples.

Dried and purified lactide prepared by a known method of depolymerization of lactic acid oligomer was used as a starting material.

The raw lactide obtained by depolymerization of the oligomer contains impurities (mainly lactic acid, linear oligolactides and oligomeric hydroxy acids), which do not allow its use for the synthesis of high molecular weight biocompatible biodegradable polymers.

The raw lactide was purified in a standard glass laboratory glassware using a water bath. The crude lactide was poured with ethyl acetate at a temperature of 70 ° C, brought to complete dissolution, and then cooled for 10-12 hours to a temperature of 20-25 ° C. The crystals of lactide that precipitated upon cooling were filtered off from the mother liquor.

After 3-fold purification, lactide crystals were dried in a vacuum shelf dryer at a pressure of 300-500 mm Hg. and a temperature of 60 ° C for 2-4 hours.

Example 1

The process of lactide polymerization was carried out in a laboratory reactor "Miniclave drive" from "Buchi AG". The reactor is a jacketed cylindrical stainless steel vessel for heating the reaction space. The apparatus is equipped with a variable speed stirrer, quick release lid and temperature and pressure sensors. There are fittings on the reactor lid: loading the reaction mixture, supplying nitrogen, leaving gaseous products, installing a pressure gauge, installing a safety membrane and a temperature sensor. In the lower part of the reactor, a bottom valve is mounted for unloading the polymer melt. To enter thermal energy into the reactor jacket, an HL-4 circulating thermostat (Julabo GmbH) was used with temperature control of the high-temperature organic coolant (oil) circulating through the reactor jacket.

Before the start of the synthesis, 100 g of purified and dried lactide was loaded into the reactor, the catalyst was 0.1 wt%. (based on the mass of lactide) and cocatalyst (also known as the molecular weight regulator of PLA - lauryl alcohol) in the amount of 0.043% of the mass. (from the mass of lactide). Tin octanoate was used as a catalyst.

After loading all the components, the reactor heating system was turned on and the temperature in the reaction volume was raised to 110 ° C, the heating was carried out in a nitrogen flow for 1.5 hours. When the temperature in the reactor reached 110 ° C, the stirrer drive was switched on. Stirring was carried out for 30 minutes, then the temperature was raised to 185 ° C with the stirrer operating for 1 hour. The lactide polymerization process was carried out at a temperature of 185 ° C for 4 hours. The heating power was W = 800Bt.

The resulting polymer melt was discharged from the reactor into a cooled bath. The polymer was then fed to a cutter where granulation was performed. Casting and pelletizing the polymer took up to 2 hours. The resulting granules were transferred to drying.

Drying was carried out in a vacuum oven at a temperature of 90-100 ° C for 12 hours. Upon completion of drying, the polymer was cooled to room temperature and sent for testing.

Samples were tested according to the following indicators:

- molecular mass;

- appearance;

- the presence of a toxic effect;

- biodegradability.

The molecular weight of PLA was determined by gel permeation chromatography using a Breeze HPLC system from Waters. The measurement method is based on chromatographic separation of solute molecules according to their size as a result of their different ability to penetrate into the pores of the column packing matrix filled with solvent.

The appearance of the obtained samples was evaluated visually. All PLA samples obtained were transparent granules with a slightly yellow tint; after drying and crystallization, they were opaque matte white granules with a weak yellow tint, which meets the requirements for biopolymers.

The presence of a toxic effect was investigated by the in vitro method on a special device, an AT-05 image analyzer. Rapid assessment of general acute toxicity was carried out using the semen of cattle as a cellular test object. The results of the study of the toxic effect are expressed by the toxicity index, in%.

The biodegradability of the polymer was assessed by a procedure including the assessment of degradation at 70 ° C in a buffer mixture with pH 7.4, followed by determination of changes in the intrinsic viscosity of a dilute polymer solution in chloroform. All tested samples are biodegradable.

Example 2

The amount of the mixture loaded into the reactor corresponded to Example 1. The lactide polymerization process was carried out as described in Example 1, however, instead of a tin compound, organogermanium compound monohydrate-1-hydroxygermatrane was used as a catalyst, known as the commercial product ASTRAGERM-S ™ ... The concentration of catalyst and cocatalyst corresponded to Example 1.

After loading all the components, the reactor heating system was turned on and the temperature in the reaction volume was raised to 110 ° C, the heating was carried out in a nitrogen flow for 1.5 hours. When the temperature in the reactor reached 110 ° C, the stirrer drive was switched on. Stirring was carried out for 30 minutes, then the temperature was raised to 185 ° C with the stirrer operating for 1 hour. The lactide polymerization process was carried out at a temperature of 185 ° C for 3 hours. The heating power was W = 800Bt.

Samples of the obtained PLA for testing were prepared in the same way as in Example 1.

Example 3

The amount and initial composition of the mixture fed into the reactor was as in Example 2. The lactide polymerization process was carried out in a Discover® SP microwave reactor, manufactured by CEM Corporation. Polymerization was carried out at a microwave frequency of 2.45 GHz at a power of W = 150 W.

In the first 4 minutes, the temperature of the reaction mixture increased linearly from 20 to 100 ° C. The power of 150 W, set at the beginning of the process, then, after reaching the preset temperature (185 ° C), dropped to 0. Maintaining the preset temperature was carried out automatically. To continue polymerization, after 9 minutes from the beginning of the process, the power value W = 50 W.

The lactide polymerization process was carried out at a temperature of 185 ° C for a predetermined duration of 0.5 hour.

Samples of the obtained PLA for testing were prepared in the same way as in Example 1.

Example 4

The amount and initial composition of the mixture fed into the reactor corresponded to Example 2. The lactide polymerization process was carried out in a microwave reactor according to Example 3.

The automatic recording of the temperature change after 20 minutes showed that the conversion of the monomer into the polymer practically stopped (the temperature changes took place in a decaying mode and by 20 minutes they became insignificant) and the temperature of the reaction space was maintained at a constant level only due to the absorption of microwave radiation. Further supply of thermal energy to the reaction space by MW radiation was terminated. Thus, the polymerization time was 20 minutes at a microwave power W = 50 W.

Samples of the obtained PLA for testing were prepared in the same way as in Example 1.

Polymerization conditions and test results of samples for all Examples are shown in the table.

As can be seen from the examples, the use of an organogermanium compound, 1-hydroxygermatrane monohydrate, as a ROP catalyst, while providing a thermal regime in the reaction space of the reactor by microwave irradiation (Examples 3 and 4), makes it possible to obtain non-toxic biodegradable PLA with high productivity and high thermal efficiency, which opens up wide opportunities for creating commercial production of a similar product.

Providing a temperature regime by microwave (microwave) irradiation of the reaction space, when using an organogermanium compound as a ROP catalyst, makes it possible to obtain a polymer with reduced toxicity at a rate an order of magnitude higher than the rate of PLA production using the conventional method of transferring thermal energy through heating surfaces. The simultaneous use of these two distinctive features, most likely, makes it possible to more fully realize the catalytic capabilities of the organogermanium compound, which is 1-hydroxygermatrane monohydrate, better known under the commercial name ASTRAGERM-S ™.

The term "temperature regime" used in the proposed technical solution should be understood broader than just maintaining the temperature at a given level. The process temperature can vary, as required, in a wide range. In addition, in the heating mode, the temperature of the reaction mixture changes from the temperature of almost ambient to the temperature of the actual polymerization, and this change can take place unevenly, since the composition of the reaction mixture changes rather quickly, and lactide and the resulting polylactide have different degrees of absorption of microwave radiation. During the polymerization, various temperature regimes can also be set (for example, a "sawtooth" mode of temperature variation, with different frequency of peaks repetition, in a decaying mode, etc.).

The term "microwave radiation" or "microwave (MB) radiation" refers to electromagnetic oscillations with a frequency from 300 MHz to 300 GHz (wavelength from several meters to fractions of a centimeter). In the spectrum of electromagnetic radiation, microwaves are located between infrared radiation and radio waves.

Currently, microwave intensification is used in many industrial processes: food drying, wood drying and gluing, porcelain and earthenware production, construction, oil development, etc. It was found that microwave (MB) radiation is capable of accelerating many chemical reactions tens and hundreds of times, causing rapid volumetric heating of liquid and solid substances, effectively (quickly and completely) removing moisture from solid, including highly porous preparations, modifying the properties of various sorbents. [A.N. Mikheev, N.A. Pankrushina Features and capabilities of microwave chemistry "Science in Siberia" No. 21 (2756) May 27, 2010].

Microwave radiation used in the proposed technical solution has many advantages over conventional heating through heat transfer surfaces: uniform heating of the reaction mixture throughout the volume, the ability to transfer high energy per unit time, improved yield, and the possibility of accelerating the synthesis process. Essentially, the heat supply during MB radiation is reduced to heat release in the reaction mixture being treated itself. In this case, the resistance to the heat transfer process from the heating surfaces, as well as the heating surfaces themselves, are completely eliminated, which contributes to an increase in the rate of heat and mass transfer processes occurring in the reaction volume and a decrease in the polymerization time.

The aforementioned disadvantages of the traditional method of heat supply for the prototype are completely eliminated using MW irradiation. The temperature gradient (temperature difference) from the heat exchange surface to the depth of the reaction mass disappears completely. This makes it possible to avoid overheating of the layers of the processed material, which reduces the time of the heating and polymerization process, as well as the heat loss flux, and, thereby, increases the thermal efficiency of the process as a whole. The MV method of heat supply ensures uniformity of temperatures throughout the entire volume of the reaction mass, which creates the same reaction conditions at different points in the reaction space and increases the uniformity of the composition of the final product and, thus, increases its consumer properties. In addition, the relatively lower temperatures of the walls of the reactor in comparison with the reaction mass, which is explained by the inversion of the temperature profile in the liquid heated in the MB-field (the temperature in the bulk of the liquid is slightly higher than at the walls on which the boiling centers are concentrated), contribute to an increase in their corrosion resistance and reduction of polymer contamination by corrosion products. Moreover, the homogeneous nature of MW heating eliminates the local overheating of the reaction space, in the case of the traditional method of heat supply, at the reactor walls, which can lead to the appearance of by-products. Therefore, reactions with MV irradiation not only proceed faster, but also with a higher purity and product yield. In an industry where “time is money” is known, the dramatic acceleration and improvement in the purity and yield of polymerization reactions make high-throughput microwave-heated polymer production attractive.

As for the effect of MV radiation on the kinetics of the polymerization reaction, i.e. of the so-called "non-thermal microwave effect", it is safe to say that the final answer to the question of whether there is a non-thermal microwave effect has not been found all over the world to this day. The complexity of carrying out kinetic studies is due to the imperfection of the used microwave equipment and measuring instruments in a high-frequency electric field.

At least, no data have been found in the literature for an increase in the reaction rate due to an increase in the activation energy in a microwave system. At the present stage of research in microwave chemistry, most researchers come to the conclusion that MW radiation does not affect the pathways of reactions, the composition of products, and the activation energy. It can only be assumed that the high frequency and efficiency of collisions of reacting molecules with the volumetric thermal effect and the absence of temperature gradients in the reaction mixture make it possible to most fully realize the catalytic properties of the organogermanium compound, which is the reason for such a significant acceleration of the polymerization reaction in the proposed technical solution.

The use of microwave radiation with operating frequencies of 433, 915 and 2450 MHz is due to the fact that the industry most often uses microwave generators (magnetrons) with operating frequencies: 433, 915 and 2450 MHz. In household and research microwave devices (microwave ovens), an operating frequency of 2450 MHz is used, which corresponds to a wavelength of electromagnetic radiation of 12.2 cm.

The use of an organogermanium compound, 1-hydroxygermatrane monohydrate (ASTRAGERM-S ™), as a ROP catalyst in the proposed technical solution, makes it possible to obtain a polymer that is practically non-toxic, and allows its use for biomedical applications.

The indicators of the toxicity index of the samples obtained using the organogermanium compound monohydrate-1-hydroxygermatrane (Examples 2-4) fit within the standard values (70-120%), which indicates the absence of toxic effects on cellular test objects. The PLA sample with a tin-containing catalyst (Example 1) went beyond the standard value, which indicates the toxic effect of the PDA sample on the cellular test objects.

ASTRAGERM-S ™ is a non-toxic biologically active compound (LD ₅₀ ≈8500 mg / kg), which is well suited for ROP in its structure and reactivity. ASTRAGERM-S ™ can be used as a catalyst in the production of PLA for any purpose - both domestic and medical, since it easily decomposes in vivo into harmless metabolites that are easily excreted from the body, is an antioxidant, an immunomodulator, enhances the effect of almost all drugs ( Patent RU 2104032 IPC A61K 47/22, 1998), has an interferon-inducing effect, reduces the toxicity of drugs and other toxins (Patent RU 2104033 IPC A61K 47/22, 1998), is used as raw material in the production of dietary supplements. Residual amounts of it in PLA for medical purposes, intended for the treatment of wound processes, play a positive role, since such material has the ability to activate the proliferative-reparative function, which affects the course of the wound process during surgical interventions and improves tissue epithelization, which helps to accelerate wound healing, improve morphological and biochemical properties of granulation-fibrous tissue in wound defects, as well as the improvement of tissue epithelialization (E. Ya. Lukevits, TK Gar, LM Ignatovich, VF Mironov. Biological activity of germanium compounds. Riga, Zinatne , 1990, 191 p.).

The content of the ROP catalyst in the reaction mixture is from 0.025 to 0.25 wt.% Of the mass of lactides due to the fact that less than the specified lower limit, the catalytic properties are practically not manifested, and the use of the catalyst in amounts exceeding the specified upper limit no longer gives an additional positive effect. but only increases the cost of the product.

The use of lauryl alcohol as a cocatalyst with a content of 0.05-0.1 wt% in the reaction mixture based on the mass of lactides is the most advantageous example of the claimed technical solution. Within the indicated limits, lauryl alcohol also acts as a regulator of the molecular weight of the resulting PLA.

Thus, the use of a set of distinctive features of the proposed technical solution allows you to achieve the stated goals.

Polymerization of lactides, accompanied by MB-irradiation when using an organogermanium compound as a ROP catalyst, provides a new approach to improve their consumer properties, as well as achieve economic benefits by conserving energy resources and increasing productivity.

Claims (4)

1. A method of producing polylactides, including the polymerization of lactides with ring opening (ROP), in a melt using an organogermanium compound as a ROP catalyst, and a cocatalyst, in the temperature range from 100 ° C to 185 ° C, with thermal maintenance of the temperature regime in the reaction space, characterized in that the temperature regime is provided by microwave (microwave) irradiation of the reaction space, while 1-hydroxygermatrane monohydrate is used as the organogermanium compound, and lauryl alcohol is used as the cocatalyst. 2. The method according to claim 1, characterized in that microwave radiation is used with operating frequencies of 433, 915 and 2450 MHz. 3. The method according to claim 1, characterized in that the content of the ROP catalyst in the reaction mixture is from 0.025 to 0.25 wt%. from the mass of lactides. 4. The method according to p. 1, characterized in that the content of lauryl alcohol in the reaction mixture is 0.05-0.1% of the mass. from the mass of lactides.