KR100793903B1 - Process for preparing lactones biodegradable solid polymer and apparatus for preparing the same - Google Patents

Abstract

A method and an apparatus for preparing lactone-based biodegradable solid polymers are provided to facilitate controlling of molecular weight and taking out of polymers using bulk polymerization and produce highly pure polymers with high yield. A method for preparing lactone-based biodegradable solid polymers includes a step of solid-phase polymerizing cyclic lactones at a temperature lower than a melting point of the polymer to be prepared in a reactor comprising at least one tubular reaction zone. An apparatus for preparing lactone-based biodegradable solid polymers includes: a mixer(R-101) which mixes a catalyst with cyclic lactones; and the reactor(R-102) which is fluid-connected with the mixer and has at least one tubular reaction zone(4) within, wherein the at least one tubular reaction zone has a diameter of 10-100 mm and is surface-treated to come off solid polymers.

Description

Process for preparing lactones biodegradable solid polymer and apparatus for preparing the same

1 is a process diagram showing a polymerization method according to an embodiment of the present invention.

The present invention relates to a method and a manufacturing apparatus for mass production of a high molecular weight lactone-based biodegradable resin with high yield and high purity, and more particularly, in a reactor including one or more tubular reaction zones having a diameter of 10 mm to 100 mm. It relates to a method for producing a lactone-based biodegradable resin characterized in that the cyclic lactones in the reaction.

Lactone-based biodegradable resins, especially polyparadioxanone, are bioabsorbable resins and are currently used for medical purposes such as surgical sutures or anti-reflective sheets. It can be used as an injection molded product (container) and a sheet (tray).

Ester-based biodegradable resins such as poly paradioxanone are unstable to heat and moisture, and the higher the polymerization temperature, the lower the polymerization yield.

For example, in the case of polyparadioxane, a higher molecular weight resin can be obtained at a lower polymerization temperature within a range of 60 ° C. to 100 ° C., but since the melting point of polyparadioxane is 105 ° C., polymerization is performed at a lower temperature range. There was a problem that the polymer is obtained as a solid.

The small amount of polyparadioxane was produced by solid phase polymerization using a round glass reactor, followed by cutting the reactor to take out a solid polymer, but not suitable for mass production. In addition, in the case of a polymer manufactured with a cylindrical reactor having a large diameter, there is a disadvantage in that a polymerization yield and a molecular weight difference occur due to a temperature difference depending on a site, thereby obtaining a non-uniform product.

European Patent Publication No. 0763559 discloses a method for producing polyparadioxane, in which a large amount of additive is used to prevent thermal decomposition of polyparadioxane. However, the method is commercially inexpensive, and there is a problem in safety when used as a food packaging agent. In addition, there was a problem that the residual monomer should be removed before the heat stabilizer prescription.

Japanese Patent Publication No. 2001-151878 discloses that polyparadioxane was quenched with liquid nitrogen, taken out of a reactor, freeze-pulverized to remove unreacted monomer, and then vacuum dried to obtain polyparadioxane. In this case, the reactor is quenched with liquid nitrogen, making it difficult to remove the polymer, and the method of producing unreacted monomer is not economical.

On the other hand, U.S. Patent No. 5,531,331 prepares polyparadioxane by liquid phase polymerization (polymer Tg or more) in order to maintain the fluidity of the polymer, and in order to prevent the molecular weight decrease due to the reversible reaction of the polymer and the monomer in the monomer removal process. A method of end-capping using Cyclic anhydrides is disclosed. However, there was a problem that a high molecular weight polymer could not be obtained by the above method and the reaction yield was low.

Therefore, in the bulk polymerization of cyclic lactones, there is a demand for a method for producing a high molecular weight lactone-based biodegradable resin having a narrow polymerizable molecular weight and easy control of the polymer from the reactor and a narrow molecular weight distribution.

The present invention is to solve the above problems, an object of the present invention is to prepare a lactone-based biodegradable resin that can easily control the molecular weight and take out the polymer by using a bulk polymerization and obtain a polymer of high yield and high purity It is to provide a method and a manufacturing apparatus used therefor.

The present invention relates to a method for producing a lactone-based biodegradable resin, characterized in that the cyclic lactones are polymerized in a reactor including at least one tubular reaction zone having a diameter of 10 mm to 100 mm.

When the cyclic lactones are reacted in the tubular reactor, the present inventors can produce lactone-based biodegradable resins having a uniform degree of polymerization because the heat transfer is uniform in the radial direction of the reactor and the temperature variation in the reactor is small. The present invention was found to be easy to discharge. Therefore, the present invention is characterized by using a tubular reactor having a specific diameter in the bulk reaction of ring-opening polymerization.

In the method for producing a lactone biodegradable resin according to the present invention, the diameter of the tubular reaction region is 10 to 100 mm, preferably 30 to 90 mm, more preferably 50 to 80 mm.

In the production method according to the present invention, the reactor may be a multi-tube reactor having two or more tubular reaction zones as well as a single-tube reactor having a tubular reaction zone having the diameter as described above.

When the diameter of the reaction zone exceeds 100mm, heat transfer is not performed in the radial direction (reactor inner direction), and thus a thermal deviation may occur, thereby obtaining a polymer having a uniform degree of polymerization. In addition, since the radial shrinkage of the polymer produced in the reaction tube is approximately 2.5% in the case of paradioxane, when the diameter is less than 10 mm, the gap between the polymer and the reaction tube is small and the discharge is not easy. In addition, if the diameter is too small, the reactor length becomes longer, and the number of irrigation required for the production of the unit is increased, which makes the handling complicated.

In the manufacturing method which concerns on this invention, although cyclic lactone is not specifically limited, Paradioxane, caprolactone, or lactide etc. are mentioned.

In addition, the tubular reaction region preferably has a length to diameter ratio of 1 to 40: 1, and more preferably 1:20 to 1. When the length-to-diameter ratio is less than 1: 1, heat transfer is not performed in the radial direction (reactor inner direction), resulting in a thermal deviation, thereby obtaining a polymer having a non-uniform degree of polymerization. The amount of irrigation required for the production of the unit can be complicated and the handling can be complicated.

The reaction conditions of the cyclic lactone according to the present invention are specified by the following.

In the polymer production method according to the invention, the reaction is preferably carried out in a temperature range of 25 ~ 150 ℃, more preferably the reaction temperature is 30 ~ 100 ℃. When the reaction temperature is less than 25 ℃ may be lower the reaction rate, the polymerization efficiency, and when the reaction temperature exceeds 150 ℃ low equilibrium conversion to the liquid phase polymerization conditions can be obtained a low molecular weight resin by depolymerization.

In addition, in the production method of the lactone-based biodegradable resin according to the present invention, in order to control the molecular weight, the reaction is preferably carried out in a multi-step at different temperatures. For example, the reaction may be performed for a predetermined time under relatively high temperature reaction conditions within the above temperature range, and then the reaction temperature may be changed to a relatively low temperature condition for further reaction. The reaction at the low temperature of the two reaction conditions as described above may increase the molecular weight of the polymer, reduce the unreacted monomer in the reactor to increase the overall yield.

On the other hand, the type of catalyst used in the production method of the lactone-based biodegradable resin according to the present invention is not particularly limited, but diethyl zinc, zirconium acetyl acetonate (Zirconium (IV) acetly acetonate), aluminum ispro Aluminum isopropoxide, Titanium tetrachloride, Ammonium Zinc Halide, Triethylaluminum (TEAL), p-toluene sulfonic acid, Boron trifluor Boron trifluoride diethyl etherate, Sodium hydroxide, Tin (II) Chloride, Yttrium chloride hexahydrate, Yttrium isopropoxide isopropoxide), or Tin Octoate catalyst. The amount of the catalyst is also not particularly limited, but may be 500 to 40,000 moles per 1 mole of the cyclic lactone monomer.

Method for producing a lactone-based biodegradable resin according to the present invention comprises the steps of mixing a catalyst and a cyclic lactone monomer; And

Preferably, the mixture comprises reacting in a reactor comprising one or more tubular reaction zones having a diameter of 10 mm to 100 mm. That is, the catalyst may be added to the reaction zone together with the lactone monomer, but it is preferable that the catalyst is added to the reaction zone after being uniformly mixed with the monomers before the reaction zone is added.

The invention also

A mixer for mixing the catalyst and the lactone monomers; And

A reactor in fluid communication with the mixer and including one or more tubular reaction zones having a diameter of 10 mm to 100 mm

It relates to a manufacturing apparatus of a lactone-based biodegradable resin comprising a.

In the above production apparatus, the length-to-diameter ratio of the tubular reaction region is preferably 1 to 40: 1 as described above.

On the other hand, the inner surface of the tubular reaction region is preferably subjected to a separate surface treatment for the detachment of the polymer. In-tube surface treatment includes chemical treatment or physical treatment. For example, the internal surface of a tube may be subjected to electronic polishing or coating with a hydrophobic fluorine resin, polyolefin resin, or the like.

Hereinafter, an embodiment of the present invention will be described in more detail with reference to the accompanying drawings.

The manufacturing apparatus according to the present invention comprises a mixer (R-101) for mixing a catalyst and a lactone monomer; And a reactor (R-102) in fluid connection with the mixer and the mixture transfer line (2) and comprising at least one tubular reaction zone (4) having a diameter of 10 mm to 100 mm.

First, before proceeding with the reaction, the entire system is replaced with the nitrogen (R-101) and the reactor (R-102) with inert gas through the nitrogen introduction line (3).

The lactone monomer and the catalyst are introduced into the mixer (R-101) with the stirrer through the feed line (1).

After sufficient mixing of the lactone monomer and catalyst, the mixture is transferred to the reactor (R-102) via the mixture transfer line (2). In this case, the reactor (R-102) may include one or more tubular reaction zone (4) having a diameter of 10mm ~ 100mm.

After raising the temperature of the reactor (R-102) to the reaction temperature (room temperature ~ 120 ℃), the polymerization reaction is carried out in a stationary state. When the polymerization is complete, the bottom of the reactor (R-102) is opened to obtain a solid polymer in the form of a rod.

Hereinafter, preferred examples are provided to help understanding of the present invention, but the following examples are merely to illustrate the present invention, and the scope of the present invention is not limited to the following examples.

The amount of monomer in the polymer was quantitatively analyzed using a nuclear magnetic resonance analyzer (1H-NMR), and the molecular weight was determined by dissolving a certain amount of polymer in chloroform. (Intrinsic viscosity: Inherent Viscosity) was measured as follows.

1) Measurement method of monomer amount in polymer

0.01g of the sample was dissolved in 1cc of chloroform, deutero-chloroform (CDCl ₃ ) was added to prepare a sample, and measured by 1H-NMR at 25 ° C.

2) I.V.Measuring Method

A 0.001 g sample was dissolved in 1 cc of tetrachloroethane (TCE) and measured at 25 ° C. using a Ubbelohde viscometer.

3) polymerization yield

In the above formula, Polymer represents the amount of the lactone-based biodegradable resin produced, and Monomer represents the amount of the lactone monomer introduced into the reaction.

Example 1.

A reactor having a mixer with a stirrer and a diameter of 70 mm and including seven tubular reaction zones whose inner surface was plastically coated with a fluororesin was replaced with nitrogen as an inert gas. Into the mixer, 25 kg of paradioxanone (PDX) and 84.73 g of TEAL (1M) diluted with hexane (PDX mole / catalyst molar ratio: 2,000) were introduced into the mixer. After the PDX and the catalyst were sufficiently mixed at 40 ° C. for 5 minutes, the mixed liquid was transferred to the reactor. The polymerization reaction was carried out for 4 hours while the reaction temperature was left at 80 ° C. After completion of the polymerization reaction, the lower part of the reactor was opened to obtain a solid polymer (polydioxanone, a lactone biodegradable resin) in the form of a rod.

As a result, the polymerization yield was 80 wt% and the inherent viscosity was 2.04 dl / g.

Example 2.

A reactor having a mixer with a stirrer and a diameter of 70 mm and including seven tubular reaction zones whose inner surface was plastically coated with a fluororesin was replaced with nitrogen as an inert gas. 25 kg PDX and 5 g tin octoate (PDX mole / catalyst molar ratio: 20,000) were introduced into the mixer. After the paradioxanone and the catalyst were sufficiently mixed at 40 ° C. for 10 minutes, the mixed solution was transferred to the reactor. The polymerization reaction was carried out for 72 hours while the reaction temperature was left at 80 ° C. After completion of the polymerization reaction, the bottom of the reactor was opened to obtain a solid polymer in the form of a rod.

As a result, the polymerization yield was 71 wt% and the inherent viscosity was 1.65 dl / g.

Example 3.

A reactor equipped with a mixer with a stirrer and a diameter of 70 mm and containing seven tubular reaction zones whose inner surface was calcined with a fluororesin was replaced with nitrogen as an inert gas. To the mixer was introduced 84.73 g of PDAL (1 M) (PDX mole / catalyst molar ratio: 2,000) diluted with 25 kg PDX and hexane. After the paradioxanone and the catalyst were sufficiently mixed at 40 ° C. for 5 minutes, the mixed solution was transferred to the reactor. After the polymerization reaction was carried out for 4 hours while the reaction temperature was left at 80 ° C., the reaction temperature was lowered to 60 ° C. for 2 hours of polymerization. After completion of the polymerization reaction, the bottom of the reactor was opened to obtain a solid polymer in the form of a rod.

As a result, the polymerization yield was 92 wt% and the inherent viscosity was 2.87 dl / g.

Conventional methods for producing lactone-based biodegradable resins have limitations in mass-producing high molecular weight biodegradable resins due to the limitations of the polymerization temperature depending on the melting point temperature of the polymerization product. Molecular weight control through polymerization can be made free and stable.

Claims (10)

A process for producing a lactone-based biodegradable solid resin, characterized in that the cyclic lactones are subjected to a solid phase polymerization at a temperature below the melting point of the resin to be produced in a reactor including at least one tubular reaction zone having a diameter of 10 mm to 100 mm. The method of claim 1, Cyclic lactones are paradioxane, caprolactone or lactide, the production method of lactone-based biodegradable solid resin. The method of claim 1, A process for producing a lactone-based biodegradable solid resin, characterized in that the length to diameter ratio of the tubular reaction zone is 1 to 40: 1. The method of claim 1, Process for producing a lactone-based biodegradable solid resin, characterized in that the reaction is carried out in a temperature range of 25 ~ 150 ℃. The method of claim 4, wherein Process for producing a lactone-based biodegradable solid resin, characterized in that the reaction is carried out in multiple stages at different temperatures. The method of claim 1, A process for producing a lactone-based biodegradable solid resin, characterized in that the reaction is carried out in the presence of triethylaluminum (TEAL) or tin octoate catalyst. The method of claim 6, Mixing the catalyst and the cyclic lactones; And Lactone-based biodegradability, comprising the step of solidifying the cyclic lactones at a temperature below the melting point of the resin to be prepared in the reactor including the mixture having one or more tubular reaction zones having a diameter of 10 mm to 100 mm. Method for producing a solid resin. A mixer for mixing the catalyst and the cyclic lactones; And Apparatus for producing a lactone-based biodegradable solid resin comprising a reactor in fluid communication with the mixer and having a diameter of 10 mm to 100 mm and including at least one tubular reaction zone having a surface treatment for desorption of the solid resin therein. . The method of claim 8, An apparatus for producing lactone-based biodegradable solid resins, wherein the length-to-diameter ratio of the tubular reaction zone is 1 to 40: 1. delete

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