Method for manufacturing lactide composite

Abstract

To provide a method for manufacturing a lactide composite.SOLUTION: Using lactide that is a cyclic dimer of lactic acid, a lactide composite is manufactured by heating a mixture of molten lactide and a low-molecular weight substance, followed by reaction of the molten lactide with the low-molecular weight substance without ring-opening of lactide.SELECTED DRAWING: Figure 7

Description

[Technical field]

[0001] The present invention relates to a method for producing a lactide complex. [Background technology]

[0002] Lactide, a dimer of lactic acid, is used as a raw material for synthesizing biodegradable polymers. In particular, polylactic acid obtained by ring-opening polymerization of lactide is widely used as a material to replace conventional plastics derived from petroleum. Patent Document 1 discloses a method for producing polyester by mixing a cyclic ester such as lactide with an alkylaluminum compound and ring-opening polymerizing the cyclic ester with a ring-opening polymerization catalyst. Patent Document 2 discloses polylactic acid having a number average molecular weight of 100,000 or more obtained by ring-opening polymerization of lactide. Patent Document 3 discloses a biodegradable block copolymer having L-lactide and D-lactide formed by random copolymerization or alternating copolymerization of lactide and a cyclic ester compound. At present, the use of lactide is limited to its use as a raw material for synthesizing biodegradable polymers as described above, and its use is premised on ring-opening polymerization of lactide. As disclosed in Patent Documents 1 to 3, various ring-opening polymerization catalysts, such as organolithium-based, organopotassium-based, organozinc-based, organomagnesium-based, organotin-based, organocalcium-based, organotitanium-based, and amine-based ring-opening polymerization catalysts, and ring-opening polymerization initiators, such as various alcohols, are used for the ring-opening polymerization of lactide. These catalysts and the like are necessary components for ring-opening lactide. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2016 / 117473 [Patent Document 2] JP 2015-30814 A [Patent Document 3] JP 2014-47317 A Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a novel method for producing a lactide complex using lactide. [Means for solving the problem]

[0005] A method for producing a lactide complex in one embodiment includes a reaction step of heating a mixture of molten lactide and a low molecular weight substance to react the molten lactide with the low molecular weight substance without ring-opening the lactide.

[0006] The above-mentioned manufacturing method preferably satisfies any one or more of the following (1) to (9). (1) The mixture is obtained by melting solid lactide and adding the low molecular weight substance to the molten lactide. (2) The heating is carried out at a temperature of 80°C or higher and 180°C or lower. (3) The reaction step is carried out under a reduced pressure environment of 5 mmHg or more and 300 mmHg or less. (4) Stirring the mixture during the reaction step. (5) The molten lactide is any one of L-lactide, D-lactide, and DL-lactide. (6) The molecular weight of the low molecular weight substance is 2000 or less. (7) The low molecular weight substance has any one of a C=O bond, a P=O bond, an N=O bond, an NH bond, and an S=O bond. (8) The number of moles of the molten lactide in the mixture is 5 times or more and 500 times or less the number of moles of the low molecular weight substance. (9) After the reaction step, a removal step is included in which unreacted lactide and unreacted low molecular weight substances are removed with an aqueous solvent. Effect of the Invention

[0007] The production method of the present invention can produce a novel lactide complex using lactide. [Brief description of the drawings]

[0008] [Figure 1] 1 is an IR spectrum of lactide. [Diagram 2] 1 is an IR spectrum of a lactic acid polymer. [Diagram 3] 1 is an IR spectrum of the lactide complex obtained in Example 1. [Figure 4] 1 is an IR spectrum of the lactide complex obtained in Example 2. [Diagram 5] 1 is a mass spectrum of lactide. [Figure 6] (a) and (b) are mass spectra of lactic acid polymer. [Figure 7] 4(a) and 4(b) are mass spectra of the lactide complex obtained in Example 1. [Figure 8] 4(a) and 4(b) are mass spectra of the lactide complex obtained in Example 2. [Figure 9] FIG. 1 is an explanatory diagram showing an example of a lactide complex production apparatus. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] <<How lactide complexes are manufactured>> A method for producing a lactide complex according to one embodiment of the present invention (hereinafter, referred to as the production method of one embodiment) will be described below. The production method of one embodiment includes a reaction step of heating a mixture of molten lactide and a low molecular weight substance, and reacting the molten lactide with the low molecular weight substance without ring-opening the lactide. According to the production method of one embodiment, a novel lactide complex can be produced.

[0010] The structure of the lactide complex produced by the production method of one embodiment is not necessarily clear at present. However, from the measurement results of IR spectrum and mass spectrum described below, it is presumed that the produced lactide complex is formed by multiple bonds between a plurality of lactide molecules that interact with each other via low molecular weight substances.

[0011] (Lactide) The lactide used in the production method of one embodiment is not limited, and any conventionally known lactide can be appropriately selected and used. In the present disclosure, lactide refers to a cyclic dimer of lactic acid. An example of lactide is any one of L-lactide, D-lactide, and DL-lactide. The melting point of L-lactide is about 94°C to 96°C. The melting point of D-lactide is about 95°C to 98°C. The melting point of DL-lactide is about 116°C to 124°C. The lactide used in the production method of one embodiment may be one type or two or more types.

[0012] (Low molecular substance) The low molecular weight substance used in the manufacturing method of the embodiment is not limited and can be appropriately selected depending on the application of the lactide complex to be manufactured. The low molecular weight substance used in the manufacturing method of the embodiment may be one type or two or more types.

[0013] The molecular weight of the low molecular weight substance is not limited, and as an example, the molecular weight of the low molecular weight substance is 2000 or less. As an example, the molecular weight of the low molecular weight substance is 10 or more. As another example, the molecular weight of the low molecular weight substance is 1500 or less. As another example, the molecular weight of the low molecular weight substance is 100 or more. In this disclosure, molecular weight means number average molecular weight (Mn). The molecular weight of the low molecular weight substance may be greater than 2000. Also, it may be less than 10 as long as it is greater than 0.

[0014] An example of a low molecular weight substance is a physiologically active substance, such as vitamins, amino acids, hydroxy acids, steroid hormones, and amino acid derivative hormones. Such physiologically active substances include retinol, thiamine, thiamine phosphate, riboflavin, niacin, pantothenic acid, pantetheine, pyridoxal, pyridoxal phosphate, pyridoxamine, pyridoxine, biotin, folic acid, tetrahydrofolic acid, cyanocobalamin, methylcobalamin, hydroxocobalamin, ascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ergocalciferol, cholecalciferol, tocopherol, and tocotrienol. Examples of such an acid include salicylic acid, calcium salicylate, citric acid, sodium citrate, glutamine, glutamic acid, sodium glutamate, alanine, arginine, asparagine, aspartic acid, cysteine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, malic acid, citric acid, cortisol, androgen, adrenaline, dopamine, acetylcholine, and thyroxine.

[0015] Exemplary small molecule substances are those used in fields such as reagents, synthetic raw materials, pharmaceuticals, agricultural chemicals, cosmetics, foods, functional foods, food additives, and feeds.

[0016] The low molecular weight substance used may be a water-soluble low molecular weight substance, or a water-insoluble or poorly water-soluble low molecular weight substance. Note that, in one embodiment, the production method can produce a water-insoluble or poorly water-soluble lactide complex while using a water-soluble low molecular weight substance. Therefore, a low molecular weight substance that is water-soluble but is desired to be used as a water-insoluble or poorly water-soluble substance can be suitably used. In the present disclosure, a water-soluble low molecular weight substance means a low molecular weight substance in which 0.1 g can be dissolved in 100 ml of water and no precipitation of the low molecular weight substance can be confirmed after 3 hours.

[0017] An example of a low molecular weight substance has any of a C=O bond (or a C=O group), a P=O bond (or a P=O group), an N=O bond (or an N=O group), an NH bond (or an NH group), and an S=O bond (or an S=O group). A low molecular weight substance having any of these bonds has good reactivity with lactide. The thermal decomposition temperature of the low molecular weight substance may be higher than, lower than, or the same as the melting point of lactide. In one example, the thermal decomposition temperature of the low molecular weight substance is higher than the melting point of lactide, and the mixture of molten lactide and the low molecular weight substance is heated at a temperature lower than the thermal decomposition temperature of the low molecular weight substance in the reaction process. The mixture of molten lactide and the low molecular weight substance may be heated at a temperature equal to or higher than the thermal decomposition temperature of the low molecular weight substance. The low molecular weight substance may be a solid, or may be dissolved or dispersed in an appropriate solvent.

[0018] 9 shows an example of a production apparatus 10 that can be used in the production method of one embodiment. The production apparatus 10 in the illustrated form includes a reaction vessel 1, an air-cooled tube 2, a vacuum gauge 3, a water-cooled tube 4, a thermometer 5, a stirring means (stirring rod) 6, a heating means 7, and a collection vessel 8. The production apparatus as an example has a pressure reducing means. The collection vessel 8 as an example collects lactide that can be sublimated by heating.

[0019] In one embodiment of the manufacturing method, solid lactide (or crystalline lactide) is added to the reaction vessel 1, and the solid lactide is melted before the low molecular weight substance is added. This embodiment can increase the yield of the lactide complex produced. The lactide can be melted by heating the reaction vessel 1 at a temperature higher than the melting point of lactide. The reaction vessel 1 can be heated by appropriately selecting various heating means. Examples of the heating means include various heaters such as a mantle heater. As an example, the reaction vessel 1 is heated by combining an oil bath and a heater. Next, the low molecular weight substance is added to the molten lactide. As a result, a mixture of the molten lactide and the low molecular weight substance is obtained. It is preferable to add the low molecular weight substance while stirring the molten lactide. This embodiment can increase the yield of the lactide complex produced. An example mixture is obtained by mixing solid lactide with a low molecular weight substance and then melting the solid lactide. Hereinafter, the term "mixture" refers to a mixture of molten lactide and a low molecular weight substance.

[0020] Although there is no limitation on the amounts of molten lactide and low molecular weight substance blended relative to the total mass of the mixture, it is preferable to blend them so that the number of moles of molten lactide is 5 to 500 times the number of moles of the low molecular weight substance. With such a blending, the molten lactide and the low molecular weight substance can be sufficiently reacted, and the yield of the produced lactide complex can be increased.

[0021] The low molecular weight substance used is preferably one that gives an aqueous solution in which 0.1 g of the low molecular weight substance is dissolved in 100 ml of water with a pH of 4 or more and 9 or less. By using such a low molecular weight substance, the yield of the lactide complex produced can be increased. An acid may be added to the functional group of the low molecular weight substance so that an aqueous solution in which 0.1 g of the low molecular weight substance is dissolved in 100 ml of water has a pH of 4 or more and 9 or less. Examples of such acids include hydrochloric acid, free carbonic acid, phosphoric acid, nitric acid, and sulfuric acid. In addition, metal salts in which the hydrogen atoms of these acids are replaced with metal ions may be used. Examples of metal ions include sodium ions, potassium ions, and calcium ions. In addition, the low molecular weight substance may be a derivative having an ester bond, an ether bond, or the like.

[0022] <Reaction process> The reaction step is a step of heating a mixture of molten lactide and a low molecular weight substance to react the molten lactide with the low molecular weight substance without ring-opening the lactide. Through this step, a lactide complex in which lactide and a low molecular weight substance have reacted can be produced.

[0023] In one embodiment of the manufacturing method, molten lactide is reacted with a low molecular weight substance without ring-opening lactide. There is no limitation on the method of reacting molten lactide with a low molecular weight substance without ring-opening lactide, but it is sufficient not to use various conventionally known means that can ring-open or ring-opening polymerize lactide. For example, the mixture may be heated without using various ring-opening polymerization catalysts, ring-opening polymerization initiators, etc. As the low molecular weight substance to be reacted with molten lactide, one that does not have the function of ring-opening lactide may be selected. In one example of the manufacturing method, a component that can ring-open lactide is not used.

[0024] Although the lactide used in the production method of one embodiment has the property of being easily decomposed in water, the produced lactide complex is not decomposed in water and is water-insoluble or poorly water-soluble. The mechanism by which the lactide complex becomes water-insoluble or poorly water-soluble is not currently clear; however, the results of the examples described below make clear that the lactide complex is water-insoluble or poorly water-soluble, even though it contains components derived from lactide and low molecular weight substances.

[0025] The heating in the reaction step is preferably carried out while stirring the mixture, which can increase the yield of the lactide complex produced. In the embodiment shown in the figure, the mixture in the reaction vessel 1 is stirred with a stirring rod 6, but it may be stirred by other means. Examples of other stirring means include a magnetic stirrer. The stirring speed of the mixture is preferably 50 rpm or more, and more preferably 150 rpm or more and 500 rpm or less.

[0026] The heating temperature in the reaction step is not limited, but is preferably 180° C. or lower. In this form, the produced lactide complex can be easily made into a powder form. There is no lower limit to the heating temperature, and it is sufficient that the lactide can be kept in a molten state during the reaction. The mixture in the reaction step may be heated to a temperature equal to or higher than the melting point of lactide, or may be heated below the melting point of lactide if a freezing point depression occurs when the molten lactide is mixed with the low molecular weight substance. As an example, the mixture is heated to a temperature of 80°C or higher and 180°C or lower. In the illustrated embodiment, the temperature of the mixture is measured by a contact thermometer, but the temperature of the mixture may be measured by a non-contact thermometer.

[0027] The heating time is not limited and may be appropriately determined depending on the low molecular weight substance used. In one embodiment of the production method, the mixture is heated at the above heating temperature for 0.5 hours to 8 hours.

[0028] The reaction step may be carried out under normal pressure or under reduced pressure. In a preferred embodiment, the reaction step is carried out under reduced pressure. In a more preferred embodiment, the reaction step is carried out under a reduced pressure environment of 5 mmHg to 300 mmHg. This embodiment can increase the yield of the lactide complex produced. In addition, the loss of lactide that may be partially sublimated by heating when collected in the collection vessel 8 can be suppressed. In the embodiment shown in the figure, the pressure inside the reaction vessel 1 is reduced by a pressure reducing means. Examples of the pressure reducing means include a vacuum pump, an aspirator, etc. The pressure inside the reaction vessel 1 may be reduced by other means.

[0029] <Removal process> The production method of one embodiment may include, after the reaction step, a removal step of removing unreacted lactide and unreacted low molecular weight substances.

[0030] As an example of the removal step, after the reaction step, an aqueous solvent is added to the reaction vessel 1. Examples of the aqueous solvent include water and alcohol. Since lactide has a property of being easily decomposed in water, when a water-soluble low molecular weight substance is used in the production method of one embodiment, the lactide and the low molecular weight substance can be dissolved in an aqueous solvent. On the other hand, since the produced lactide complex is water-insoluble or poorly water-soluble, it is not dissolved in the aqueous solvent and exists as a precipitate or a suspended matter in the reaction vessel 1. Therefore, by discharging the aqueous solvent in which the unreacted lactide and the unreacted low molecular weight substances are dissolved from the reaction vessel 1, the unreacted lactide and the unreacted low molecular weight substances can be removed. In other words, the removal of unreacted lactide and unreacted low molecular weight substances by the aqueous solvent 1 is an optional step in the production method of one embodiment. Note that the properties of the produced lactide complex do not change before and after the addition of the aqueous solvent 1.

[0031] The removing step is preferably carried out after the reaction step, when the temperature of the produced lactide complex has fallen to 100° C. or lower.

[0032] In one example of the removal step, after the reaction step, alcohol is added to a reaction vessel 1 containing the produced lactide complex, unreacted lactide, and unreacted low molecular weight substances (hereinafter collectively referred to as aggregates) in an amount about 1 to 5 times the amount of lactide used to obtain an aggregate liquid containing the aggregates. Examples of the alcohol include methyl alcohol and ethyl alcohol. The assembly liquid is removed from the reaction vessel 1, and the assembly liquid is gradually added to water in an amount 10 times or more the volume of the assembly liquid while stirring, and the stirring is continued for 24 hours or more. By replacing the water every 3 to 4 hours, unreacted lactide and unreacted low molecular weight substances can be removed.

[0033] In another example of the removal step, the assembly liquid obtained in the same manner as above is sealed in a dialysis tube or the like and dialyzed against running water for 5 days or more to remove unreacted lactide and unreacted low molecular weight substances. An example of the dialysis tube is a cellulose tube.

[0034] <Purification process> In one embodiment, the production method may include a purification step of purifying the produced lactide complex after the reaction step.

[0035] In one example of the purification step, the lactide complex obtained as a precipitate or a suspension is filtered or centrifuged, and then dried by various drying means, such as heat drying, freeze drying, and spray drying, to purify the lactide complex. Purified lactide complexes, for example, are available in powder, oil, and glass form. EXAMPLES

[0036] Next, a method for producing a lactide complex will be described with reference to examples.

[0037] Example 1 300 g of D-lactide was placed in a reaction vessel, and the reaction vessel was heated to 116° C. to melt the D-lactide. While maintaining the heating of the reaction vessel, 35.5 g of powdered pyridoxine hydrochloride was gradually added over 2 minutes while stirring the molten D-lactide at 300 rpm to obtain a mixture of D-lactide and pyridoxine hydrochloride. The pressure inside the reaction vessel was reduced to 30 mmHg, and the mixture was heated for 4 hours while stirring at 250 rpm and controlling the heating temperature of the reaction vessel to 135° C. to 145° C. to react D-lactide with pyridoxine hydrochloride. After the reaction was completed, the mixture was left at room temperature for 15 minutes, and then 500 ml of warmed methanol was added to the reaction vessel to obtain a suspension. The suspension was placed in a dialysis tube, and 300 ml of water was added to the tube and dialyzed for 10 days. The mixture was centrifuged (1000 rpm x 30 min) using a centrifuge, and the precipitate was collected. The precipitate was freeze-dried to obtain the lactide complex of Example 1. The lactide complex of Example 1 is a complex of D-lactide and pyridoxine hydrochloride. The mass of the resulting lactide complex was 179.42 g.

[0038] Example 2 300 g of D-lactide was placed in a reaction vessel, and the reaction vessel was heated to 122° C. to melt the D-lactide. While maintaining the heating of the reaction vessel and stirring the molten D-lactide at 300 rpm, 20.1 g of powdered sodium L-malate was gradually added over 2 minutes to obtain a mixture of D-lactide and sodium L-malate. The pressure inside the reaction vessel was reduced to 30 mmHg, and the mixture was heated for 4 hours while stirring at 250 rpm and controlling the heating temperature of the reaction vessel to 130° C. to 140° C. to react D-lactide with sodium L-malate. After the reaction was completed, the mixture was left at room temperature for 15 minutes, and then 500 ml of warm methyl alcohol was added to the reaction vessel to obtain a suspension. The suspension was placed in a dialysis tube, and 300 ml of water was added to the tube and dialyzed for 10 days. The mixture was centrifuged (1000 rpm x 30 min) using a centrifuge, and the precipitate was collected. The precipitate was freeze-dried to obtain the lactide complex of Example 2. The lactide complex of Example 2 was a complex of D-lactide and L-sodium malate. The mass of the resulting lactide complex was 167.1 g.

[0039] (IR spectrum measurement) The IR spectra of lactide, the lactic acid polymer, and the lactide complex of Example 2 were measured under the following measurement condition 1, and the IR spectrum of the lactide complex of Example 1 was measured under the following measurement condition 2. The measurement results are shown in Figs. 1 to 4. Fig. 1 is the IR spectrum of lactide, Fig. 2 is the IR spectrum of the lactic acid polymer, Fig. 3 is the IR spectrum of the lactide complex obtained in Example 1, and Fig. 4 is the IR spectrum of the lactide complex obtained in Example 2.

[0040] (Measurement condition 1) Test method: Infrared spectroscopy (FT-IR) Pretreatment: KBr pellet method (the frozen samples were returned to room temperature, crushed in a mortar, and molded into KBr pellets for testing) Measurement method: transmission method Measurement range: 4000cm -1 ~400cm -1 Resolution: 4cm -1 Number of times: 40 Equipment used: Nicolet 8700 FT-IR (Thermo Fisher Scientific)

[0041] (Measurement condition 2) Test method: Infrared spectroscopy (FT-IR) Measurement method: ATR method (ATR crystal ZnSe) Measurement range: 4000cm -1 ~650cm -1 Resolution: 4cm -1 Number of times: 40 Equipment used: Nicolet 8700 FT-IR (Thermo Fisher Scientific)

[0042] (Mass spectrum measurement) A solvent was added to lactide, the lactic acid polymer, the lactide conjugate of Example 1, and the lactide conjugate of Example 2 to dissolve them, and then mass spectrum measurement was performed under the following measurement condition 3. The solvent used to dissolve lactide was dimethyl sulfoxide, the solvent used to dissolve the lactic acid polymer and the lactide conjugate of Example 2 was acetone, and the solvent used to dissolve the lactide conjugate of Example 1 was methanol. The results of mass spectrum measurement are shown in Figures 5 to 8. Figure 5 is a mass spectrum of lactide, Figures 6(a) and 6(b) are mass spectra of a lactic acid polymer, Figures 7(a) and 7(b) are mass spectra of the lactide complex obtained in Example 1, and Figures 8(a) and 8(b) are FD mass spectra of the lactide complex obtained in Example 2.

[0043] (Measurement condition 3) Test method: FD / MS Equipment: JMS-T200GC mass spectrometer (manufactured by JEOL) Ionization method: FD(+) Counter electrode: -10kV Emitter: Carbon Measurement scanning range: m / z 25~2000

[0044] As shown in Figure 1, the specific absorption band in the IR spectrum of lactide is at 1770 cm -1 , 1270cm -1 , and 1097 cm -1 As shown in Figure 2, the specific absorption band in the IR spectrum of the lactic acid polymer is 1758 cm -1 , 1186cm -1 , and 1086 cm -1 The specific absorption bands of the two are clearly different. If the lactide complexes of Examples 1 and 2 are lactic acid polymers in which lactide has been ring-opened, lactide in a free state, or simple adsorbates of lactide, the specific absorption bands of the IR spectra of the lactide complexes of Examples 1 and 2 should completely coincide with the specific absorption bands of lactide or lactic acid polymers. As shown in Figs. 3 and 4, the specific absorption bands of the IR spectrum of the lactide complex of Example 1 are 1747 cm -1 , 1183cm -1 , and 1085 cm -1 The specific absorption band in the IR spectrum of the lactide complex of Example 2 is 1759 cm -1 , 1187cm -1 , and 1092 cm -1 The specific absorption band is clearly different from the specific absorption bands of lactide and lactic acid polymers. These absorption bands were also confirmed in the difference spectrum between the lactide complex and the low molecular weight compound. From these measurement results, it is clear that the lactide complexes of Examples 1 and 2 are not lactide ring-opened lactic acid polymers, lactide in a free state, or simple adsorbates of lactide.

[0045] In addition, as shown in FIG. 5, the specific fragment of the mass spectrum of lactide is 39, whereas as shown in FIG. 6(a) and (b), the specific fragment of the mass spectrum of the lactic acid polymer is 43, and the specific fragments of both are clearly different. Here, as shown in FIG. 7(a) and (b), in the lactide complex of Example 1 using pyridoxine hydrochloride, which can be measured by mass spectrometry, as the low molecular weight compound, the specific fragment 45 and a mountain-shaped fragment assembly can be confirmed at 300 to 1300. In this mountain-shaped fragment assembly, multiple fragments at intervals of 144, which corresponds to the molecular weight of lactide of 144, can be confirmed. On the other hand, in the lactide complex of Example 1, the specific fragment 39 of lactide and the specific fragment 43 of the lactic acid polymer cannot be confirmed.

[0046] 8(a) and 8(b), in the lactide complex of Example 2, in which sodium L-malate containing a metal salt that cannot be subjected to mass spectrometry is used as a low molecular weight substance, all of the specific fragments 39 of lactide, 43 of the lactic acid polymer, and 45 of the lactide complex of Example 1 can be confirmed. In the mass spectrometry of the lactide complex of Example 2, it is presumed that the complex of D-lactide and sodium L-malate is separated and decomposed due to the measurement environment (high temperature, high vacuum), and the multiply bonded lactide is released, and then re-reacted under high temperature and high vacuum conditions, resulting in a mixture of specific fragments of lactide, multiply bonded lactide, and the lactic acid polymer. Here, if the lactide complex of Example 2 is a product of ring-opening polymerization of lactide, it is presumed that only the specific fragment 43 of the lactic acid polymer is measured, or that sodium L-malate cannot be measured due to the metal salt.

[0047] The above IR spectrum and mass spectrum measurement results revealed that the lactide complexes of Examples 1 and 2 were formed by reacting with low molecular weight substances while maintaining the cyclic structure of lactide.

[0048] (Reference example 1) 225.12 g of D-lactide was placed in a reaction vessel, and the reaction vessel was heated to 120° C. to melt the D-lactide. While maintaining the heating of the reaction vessel, 14.9 g of powdered sodium salicylate was gradually added over 2 minutes while stirring the molten D-lactide at 250 rpm, to obtain a mixture of D-lactide and sodium salicylate. The pressure inside the reaction vessel was reduced to 30 mmHg, and the mixture was heated for 4 hours while stirring at 250 rpm and controlling the heating temperature of the reaction vessel to 125° C. to 135° C. to react D-lactide with sodium salicylate. After the reaction was completed, the mixture was left at room temperature for 15 minutes, and then 600 ml of methyl alcohol was added to the reaction vessel to obtain a suspension. The suspension was placed in a dialysis tube, and 600 ml of water was added and dialyzed for 7 days. The precipitate, which was a lactide complex, was collected by centrifuging (500 rpm x 30 min) using a centrifuge.

[0049] (Reference example 2) 22.5 g of D-lactide and 1.5 g of sodium salicylate were placed in a mortar and thoroughly ground and mixed to obtain a powder mixture of D-lactide and sodium salicylate. The powder mixture was placed in a beaker and left to stand in a desiccator at room temperature and under a reduced pressure of 30 mmHg for 4 hours. After that, 50 ml of methyl alcohol was added to the powder mixture to obtain a solution. The solution was placed in a dialysis tube, 50 ml of water was added, and dialyzed for 7 days. No floating matter was observed in the dialysis tube. The solution in the dialysis tube was placed in a flask, and the water was removed under reduced pressure. No residue was observed in the flask.

[0050] From the results of Reference Examples 1 and 2, it is clear that a lactide complex cannot be produced unless lactide is melted and the mixture of lactide and a low molecular weight substance is heated. [Explanation of symbols]

[0051] 1. Reaction vessel 2. Air-cooled tube 3...Vacuum gauge 4...Water cooling pipe 5...Thermometer 6. Mixing means 7... Heating means 8. Collection vessel 10. Lactide manufacturing equipment

Claims

1. A method for producing a lactide complex, comprising the steps of: Using lactide, a cyclic dimer of lactic acid, a reaction step of heating a mixture of the molten lactide and a low molecular weight substance to react the molten lactide with the low molecular weight substance without ring-opening the lactide, A method for producing a lactide complex.

2. The method for producing a lactide complex according to claim 1, wherein the mixture is obtained by melting solid lactide and adding the low molecular weight substance to the molten lactide.

3. The method for producing a lactide complex according to claim 1 or 2, wherein the heating is carried out at a temperature of 80°C or higher and 180°C or lower.

4. The method for producing a lactide complex according to claim 1 or 2, wherein the reaction step is carried out under a reduced pressure environment of 5 mmHg or more and 300 mmHg or less.

5. The method for producing a lactide complex according to claim 1 or 2, wherein the mixture is stirred in the reaction step.

6. 3. The method for producing a lactide complex according to claim 1, wherein the molten lactide is any one of L-lactide, D-lactide, and DL-lactide.

7. The method for producing a lactide complex according to claim 1 or 2, wherein the molecular weight of the low molecular weight substance is 2000 or less.

8. The method for producing a lactide complex according to claim 1 or 2, wherein the low molecular weight substance has any one of a C=O bond, a P=O bond, an N=O bond, an N-H bond, and an S=O bond.

9. The method for producing a lactide complex according to claim 1 or 2, wherein the number of moles of the molten lactide in the mixture is 5 to 500 times the number of moles of the low molecular weight substance.

10. 3. The method for producing a lactide complex according to claim 1, further comprising, after the reaction step, a removal step of removing unreacted lactide and unreacted low molecular weight substances with an aqueous solvent.

Images