JP2822906B2 - Method and apparatus for producing lactide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and an apparatus for producing lactide, and more particularly to a method and an apparatus for producing lactide while purifying the lactide. Lactide produced according to the present invention is a raw material for producing polylactic acid.

[0002]

2. Description of the Related Art Polylactic acid has high biological safety, and lactic acid, which is a decomposition product, is absorbed in vivo. As described above, polylactic acid is a high biosafety polymer compound, and is used for medical purposes such as surgical sutures, drug delivery (sustained release capsules), and reinforcing materials for bone fractures, and decomposes in the natural environment. For this reason, it is attracting attention as a degradable plastic. It is also used for various applications as uniaxially and biaxially stretched films, fibers, injection molded products and the like.

As a method for producing such polylactic acid, cyclic lactide (dimer) is once synthesized and purified from lactic acid,
Next, a method of performing ring-opening polymerization is known. In summary, this synthesis method involves polymerizing the corresponding lactic acid into a relatively low molecular weight (oligomer) polylactic acid, which is then heated in the presence of a catalyst (such as antimony trioxide) well known in the art, Lactide is obtained as a component of the product stream.

However, impurities other than lactide in the steam product are water, lactic acid monomers, dimers,
And the like. Since these impurities act as inhibitors when polymerizing lactide, high-molecular-weight polylactic acid cannot be obtained unless high-purity lactide is used. For this reason, it is necessary to purify lactide containing impurities, and a conventional lactide purification method includes a purification method using a solvent. For example, Japanese Patent Application Laid-Open No. 63-101378 discloses that
Recrystallization from single alcohol, preferably isopropyl alcohol, or precipitation from solution using a non-solvent is described.

[0005]

However, in the conventional purification method, water, lactic acid and lactic acid oligomer have the ability to cause ring opening of lactide at the stage of purification, and as a result, the yield of lactide is reduced. In addition, the use of a solvent requires storage and recovery equipment, which requires considerable capital investment.

[0006] In order to solve this problem, there has been proposed a purification method using no solvent (Japanese Patent Application Laid-Open No. 6-256340). This is what is called melt crystallization, and is performed by repeating selective phase conversion from a liquid phase to a solid phase. But,
In this method, hydroxy impurities such as oligomers, lactic acid, and water must be supplied in a molten state (melt), and the lactide is ring-opened to lower the yield as in the method using a solvent. In addition, the operation of returning the oligomer and lactic acid recovered as impurities to the reactor for purification by melt crystallization to increase the yield not only complicates the process but also causes a large thermal loss.

Accordingly, an object of the present invention is to provide a novel method for producing lactide without using a solvent and which has solved the drawbacks of the conventional melt crystallization, and an apparatus therefor.

[0008]

SUMMARY OF THE INVENTION In order to solve the above-mentioned problems, the present invention provides a step of synthesizing lactide using lactic acid as a starting material, a step of extracting the lactide and impurities during the synthesis in a gaseous state, Provided is a method for producing lactide, comprising: a step of coagulating only lactide of gaseous lactide and impurities to separate lactide and impurities; and a step of refluxing the separated impurities to the synthesis step.

Further, the present invention provides an apparatus for performing the above-mentioned production method, that is, a reactor for synthesizing lactide, a gasification section for gasifying and purging synthesized lactide and impurities during synthesis, and cooling the gas. Provided is an apparatus for producing lactide, comprising: a cooling section for causing only a lactide in a gas component to solidify, and a reflux channel for returning a component not solidified in the cooling section to a reactor.

Here, the lactic acid as a starting material may be either L-lactic acid or D-lactic acid. As such a lactic acid, any one produced by a conventionally known method is used, and in particular, a purity of 80% or more produced by a fermentation method,
Preferably, the optical purity is 99% or more. Such lactic acid is dehydrated and concentrated to produce an intermediate lactic acid oligomer. Dehydration is generally performed at a temperature of 130 to 170 ° C. under a reduced pressure of 10 to 100 Torr. The molecular weight of the resulting lactic acid oligomer is about 400-2000, preferably 1000-2000. The resulting lactic acid oligomer is cyclically dimerized. That is, a cyclic dimerization (ester exchange reaction) catalyst is added, and the mixture is heated under reduced pressure to distill lactide. As the catalyst used here, any conventionally known catalyst can be used, and for example, tin octylate, antimony trioxide, zinc oxide, lead stearate and the like are used. Heating is performed under reduced pressure of 10 to 50 Torr, preferably 19
Perform at 0-210 ° C.

The reactor used for the synthesis of lactide is
A vertical reactor or a horizontal reactor may be used. When a vertical reactor is used, paddle blades, turbine blades, anchor blades, double motion blades, helical ribbon blades and the like can be used as stirring blades, but when high viscosity is used, helical ribbon blades are used. When a horizontal reactor is used, a single-screw and twin-screw extruder can be used as the stirring blade.

The vapor pressure of the synthesized lactide and impurities (water, lactic acid monomer, lactic acid oligomer) during the synthesis is from 6 to
Since the pressure is 20 mmHg, lactide and impurities can be taken out in a gas state according to the lactide synthesis conditions.
Therefore, the gasification section which gasifies and drives out can also be used in the reactor. Note that heating to the above temperature can be performed using a known heating mechanism (such as a heater).
Perform with a vacuum pump.

The gasified lactide and impurities are cooled to the freezing point of lactide or slightly lower than that temperature, for example, 80 to 95 ° C., and only lactide is solidified to liquefy the impurities. The cooling can be performed, for example, by flowing a refrigerant through a heat exchanger, but is not limited thereto. As the refrigerant, a known refrigerant such as ethylene glycol, cooling water or hot water can be used. The number of cooling units is not particularly limited, and a plurality of cooling units having different temperatures may be provided in series and passed in order.

Further, it is not necessary to keep the temperature of one cooling unit constant, but the temperature is gradually increased to such an extent that the solidified lactide does not melt so that impurities adhering to the surface of the solidified material are exuded. Is preferred. This exudation is called sweating, and can mainly remove a small amount of oligomer attached to the surface of lactide. The temperature control when sweating is performed can be performed by, for example, providing a heater in the cooling unit and changing the amount of current supplied thereto, or when using cooling water for cooling, by changing the temperature of the cooling water. Not done.

In the separation of lactide and impurities, lactide is solidified in the cooling section and impurities are in a liquefied two-phase state, so that it is not necessary to provide any special separation means. For example, by installing the cooling unit in the direction of gravity, the cooling unit is separated by gravity. Lactide solidified in the cooling section can be taken out by heating and melting, and the lactide taken out may be solidified again in the cooling section. The lactide is heated and melted within a range that does not greatly exceed the melting point in order to avoid decomposition of the product.

The reflux of the separated impurities can be returned to the reactor by the action of gravity by installing the reactor at the lower stage of the cooling section, but is not limited to this. it can. Since the impurities are mainly lactic acid oligomers, they can be used again in the reaction for producing lactide.

[0017]

According to the present invention, of the lactide and impurities taken out in gaseous form, only lactide is coagulated, and the impurities are returned to the reactor to react again to improve the yield.

Further, since lactide and impurities are not supplied in a molten state as in melt crystallization, ring opening of lactide does not occur.

[0019]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the apparatus according to the present invention will be described with reference to the drawings. FIG. 1 is a schematic view of an apparatus according to the present invention, in which R
Numeral -1 is a hollow cylindrical reactor, at the upper part of which is provided an opening for a raw material supply port and an outlet for a lactic acid oligomer as a raw material for lactide production, a catalyst, etc. An extraction pipe 11 is connected. Further, the turbine blades 14 are housed in the reactor R-1, and a driving source (motor) M is installed at another opening side of the reactor R-1. Vacuum line 1 for reducing the pressure inside reactor R-1
3 and a connection port connected to a reflux pipe 12 described later. Although not shown around the reactor R-1,
A heating mechanism (heater) for heating the reactor R-1 is provided, and the temperature in the reactor R-1 is monitored by a temperature sensor (not shown).

C ₁ , C ₂ , C ₃ , C ₄ , C ₅ ... C _n
Is a heat exchanger composed of a double cylinder. Synthesized lactide and the like flow into the inner cylinder, and a refrigerant such as ethylene glycol flows into the outer cylinder. Therefore, heat exchange is performed between the inner cylinder and the outer cylinder, and a cooling unit is provided. In addition, when the coagulated material (lactide) is melted in the heat exchangers C _{1 to} C _n , the temperature of the refrigerant is increased. The inlets of the heat exchangers C _{1 to} C _n may be either upper or lower, but preferably the inlet is upper and the outlet is lower (in this embodiment, the inlet side is the upper part of the figure and the outlet side is the upper part of the figure). At the bottom). The inlet side of the heat exchanger C ₁ is connected to outlet pipe 11 described above, the heat exchanger on the exit side C _2, C
The connection pipe 15 to ₃ is connected. The connecting pipe 15 is connected connecting pipe 17 which connects the outlet pipe 18 of the heat exchanger C _4, it is possible from the heat exchanger C ₄ to return the product to the heat exchanger C _2, C _3. The heat exchanger C _2, outlet pipe 16, 16 'of the C ₃ will is connected to the return line 12 to the reactor R-1 in the middle, a supply pipe of the junction unit to the heat exchanger C ₄ 19 Connected to. Incidentally, the supply pipe 19 is connected to the return line 12 via the connecting pipe 12 ', the outlet pipe 18 is also connected pipe 1 of the heat exchanger C ₄ described above
It is connected to the reflux line 12 via 2 ".

Reference numeral 20 denotes a connecting pipe for returning the product from the heat exchanger C ₅ to C ₄ , which is connected to an outlet pipe 22 on the outlet side of the heat exchanger C ₅ , and a pipe 21 is connected to an outlet of the heat exchanger C ₄ . Piping 1
A feed pipe connected 8 and is connected to the inlet side of the heat exchanger C _5. Following a similar connection is to heat exchanger C ₅ -C _n. Incidentally, V ₁ ~V _16, the valve (ON-OFF only)
Is shown.

The production of lactide with the above configuration is performed as follows. First, the raw material lactic acid or oligomer is charged into the reactor R-1. After charging the catalyst, vacuum line 13
And a heating mechanism (not shown) is operated to heat and synthesize lactide. (Referred to as these crude lactide) generated lactide and impurities such as oligomers has become gaseous, entering the heat exchanger C ₁ through outlet pipe 11.

In the heat exchanger C ₁ , a refrigerant having a temperature at which crude lactide is liquefied flows therein, where the crude lactide is liquefied.
In this case only the valve V _{1 Hirakide, V 2, V 3, V} 4, V 16
Etc. are closed. Liquefied crude lactide is introduced into the heat exchanger C ₂ through the V _1. The heat exchanger C ₂ is cooled to freezing point temperature lactide beforehand by the refrigerant, lactide solidifies (crystallization). However, impurities such as oligomers so liquid does not solidify, and the valve V ₃ is opened, and refluxed from the reflux pipe 12 to the reactor R-1.
Then perform slightly raised sweating by the heating mechanism (not shown) the temperature of the heat exchanger C _2. The perspiration component is similarly refluxed to reactor R-1. And out performs the sweating, the valve V ₁ closed, V ₂
The in the open put effluent from heat exchanger C ₁ to the heat exchanger C _3.

After the perspiration, the temperature of the heat exchanger C ₂ is further raised to a temperature at which L-lactide melts, the valve V ₃ is closed, the valves V ₅ and V ₈ are opened, and the outlet pipe 16 and the supply pipe 19 are opened. It is pumped to the heat exchanger C ₄ through. Heat exchanger C ₄
Is cooled beforehand, and the liquid sent is solidified again here. Again sweating in the heat exchanger C _4, the dissolution performed. When included sweating lactide many components Here, the valve V ₁₆ is opened, the outlet pipe 18, back to the connecting pipe 17 by again heat exchanger C ₂ (or C _3), coagulation, Sweats and dissolves. Thereafter, this operation is repeated until the desired purity is obtained. Depending on the lactide content, the perspiration component may be one or more previous steps (eg, C ₂ → R1, C
₅ → Return to C ₄ ). That is, when sweating at C _n , if the amount of lactide is small, the reaction proceeds to the reactor R-1. If the amount of lactide is large, coagulation is again performed at C _n-1 and impurities are removed by sweating.
Dissolved sent to C _n.

The melting point of L- or D-lactide is 9
DL-lactide is 127 ° C while 8 ° C. Thus, when sweating, L- or D-lactide dissolves before DL-lactide. After dissolution of L-lactide, the temperature is further increased to dissolve DL-lactide, and this component may be returned to reactor R-1 or may be received in another tank (not shown). However, again the reactor R-1
When the concentration is returned to the above range, a reaction of racemizing the D-form into the L-form also occurs, so that the yield of the L-form increases. The heat exchanger C ₁ is not necessarily required.

[Experimental Example] The following experiment was conducted using the above-described apparatus. 1000 kg of a 90% lactic acid solution (10% is water) (L-lactide: D-lactide = 99: 1) was used as a raw material. After concentration, dehydration condensation was further performed to obtain 280 kg of water. As a result of GPC measurement, the molecular weight of this oligomer was found to be 1,000 to 2
000. Take 25 mg of this oligomer,
Add 2 cc of N, NaOH, put in a test tube, seal and heat at 100 ° C for 10 minutes, add 2 cc of 1N sulfuric acid, neutralize and add 1 cc of distilled water
It was diluted to 0 times.

When this was measured by HPLC, the content of L-lactide was reduced to 90% by heating. to this,
3 kg of tin octylate was added, and the solution was discharged at 200 ° C. and 15 mmHg. The generated gas was heated to a gas temperature of 95 ° C. by a heat exchanger (C ₁ ) made of carbait having a heat transfer area of 3 m ² . Liquefied impurities such as lactide and oligomer were deposited on the inner surface of a heat exchanger (C ₂ ) made of carbait with a heat transfer area of 10 m ² at a temperature of 93 ° C. At this time, the oligomer was not solidified and returned to the reactor R-1.

The temperature of the heat exchanger C ₂ was set to 96 ° C., and sweating was performed. The components at this time were also refluxed, that is, returned to the reactor R-1. Furthermore the temperature of the heat exchanger C ₂ and 100 ° C., to dissolve the crystals, which was fed into a multi-tube heat exchanger C ₄ of the heat transfer area 10 m ^2. Temperature of the heat exchanger C ₄ is an advance 93 ° C., the same, sweating, dissolution was performed. The sweat component at this time was also returned to the reactor R-1.

By the above operation, the yield of lactide was 70% when the reflux was not carried out, whereas the yield of 95% was obtained. The content of DL-lactide was also 1% or less.

10 g of the lactide thus obtained was placed in a test tube, and 100 ppm of tin octylate was added thereto.
As a result, a polymer having a molecular weight of 270,000 was obtained.

In the above experimental example, GPC measurement,
The optical purity was examined under the following conditions. GPC measurement: Detector; RID-6A pump; LC-9A column oven; CTO-6A column; Shim-pack GPC-801C, -804C, -806C, 8025C in series All of the above (manufactured by Shimadzu Corporation) Solvent; chloroform Flow rate: 1 ml / min Sample amount: 200 μl (0.5 W / W% of sample was dissolved in chloroform) Column temperature; 40 ° C. Optical purity (HPLC): pump; LC-6A column; CRS10W (Mitsubishi Chemical ) Detector; Spectrophotometer (SPD-6AV) Column temperature; 30 ° C. Flow rate; 0.5 ml / min Eluent; 2 mM copper sulfate solution

[0032]

According to the present invention, since lactide and impurities are removed in gaseous form, ring opening of lactide does not occur during synthesis unlike melt crystallization. In addition, since lactide synthesis raw materials such as lactic acid oligomers are returned to the reactor, the yield of lactide also increases.

[Brief description of the drawings]

FIG. 1 is a schematic diagram of an apparatus for performing the method of the present invention.

[Explanation of symbols]

R-1 ... reactor C ₁ -C _n ... heat exchanger 11 ... outlet pipe 12 ... return line

Claims (2)

(57) [Claims] 1. A step of synthesizing lactide using lactic acid as a starting material, a step of extracting the lactide and impurities at the time of its synthesis in gaseous form, and coagulating only lactide of the gaseous lactide and impurities to form lactide And a step of separating impurities and a step of refluxing the separated impurities to the synthesis step. 2. A reactor for synthesizing lactide, a gasification unit for gasifying and purging synthesized lactide and impurities during synthesis, and a cooling unit for cooling the gas to solidify only lactide in a gas component. An apparatus for producing lactide, comprising: a reflux channel for returning components not solidified in the cooling section to the reactor.