KR102641466B1 - Biodegradable composite compositions for 3d printing and methods of producing the same - Google Patents

Abstract

A biodegradable composite material composition for 3D printing and a method for manufacturing the same are disclosed. The manufacturing method includes a first step of immersing the first biodegradable component and the second biodegradable component of the powder formulation in chloroform and uniformly stirring to form a mixture of the sol formulation; A second step of first drying the sol formulation mixture to form a dry precursor; A third step of first pulverizing the dry precursor to form a pulverized precursor; A fourth step of secondary pulverizing the pulverized precursor to form a pulverized dried body; A fifth step of secondary drying the pulverized dried body to form a powdered dried body; It may include a sixth step of extruding the dried powder to obtain a biodegradable composite material composition in the form of a filament.

Description

Biodegradable composite material composition for 3D printing and method for manufacturing the same {BIODEGRADABLE COMPOSITE COMPOSITIONS FOR 3D PRINTING AND METHODS OF PRODUCING THE SAME}

The technical idea of the present disclosure relates to a biodegradable composite material composition for 3D printing and a method for manufacturing the same, and specifically to 3D printing for manufacturing a biodegradable stent manufactured using a low-temperature sol-gel (Sog-Gel) method. It relates to a biodegradable composite material composition and a method of manufacturing the same.

A medical stent is a medical device that is inserted into a blood vessel to expand the blood vessel when the blood vessel narrows due to various diseases occurring in the human body and poor blood circulation occurs.

Specifically, a stent is a medical device that is injected into the inside of a blood vessel to expand the blood vessel when the blood vessel is narrowed due to various diseases that occur in the human body and poor blood circulation occurs. There are various surgical procedures for stents, but they are mainly performed through balloon dilatation, which is inserted with a balloon catheter into blood vessels such as the heart, aorta, and cerebrovascular vessels and expands the coronary passage as the balloon expands. there is. Existing stents require elasticity and softness to expand outward as the balloon expands and expand to the original size of the blood vessel passage. That is, the stent requires flexibility for insertion into a complex and curved passage during a procedure in which a balloon catheter is inserted and fixed to the target area, and then the balloon is expanded to expand the narrowed area. In addition, conditions such as elasticity are required to prevent the structure of the stent from being deformed by the force of contraction of blood vessel (cardiovascular, aorta, cerebral artery, etc.) tissue after the procedure is completed. In addition, the material constituting the stent requires excellent biochemical properties, such as high biocompatibility and stability to the human body, and chemical properties, such as high corrosion resistance.

In the case of conventionally provided cardiovascular stents made of metal, biocompatibility is low as they are made of metal, there is a risk of vascular restenosis and thrombosis if the metal corrodes, and when the blood vessel regenerates, it is necessary to remove the installed stent. The disadvantage is that it requires additional procedures or requires taking thrombolytic medication for life.

In addition, as a drug-eluting stent proposed to solve the above-mentioned disadvantages of metal stents, a stent coated with a drug loaded on a polymer has been provided. However, such drug-eluting stents have a high risk of thrombosis, and metal stents are still used. As the shortcomings of stents could not be completely overcome, the need to replace metal materials with biodegradable materials was raised.

In response to this need, a biodegradable stent using biodegradable composite material has been proposed. However, when manufacturing a biodegradable stent using 3D printing, the difference in melting point of each component that makes up the composite material above If is above a certain level, the quality of the 3D printing filament produced is poor due to insufficient material mixing, and the extruded filament becomes brittle due to low uniformity, making it unsuitable for use in 3D printing. .

Accordingly, there is a continuing demand for a biodegradable composite material with sufficient physical properties to be used in 3D printing as a biodegradable composite material composition and a method for manufacturing the same.

The problem that the technical idea of the present disclosure seeks to solve is a biodegradable composite material composition for 3D printing and a method for manufacturing the same, which uses a low-temperature sol-gel process as a pre-mixing process to achieve dispersibility by dispersing the components in a solution state. The goal is to ensure that each component included in the final biodegradable composite material composition for 3D printing has a uniformly distributed composition, and on this basis, can be stably extruded to form a filament form suitable for 3D printing.

In addition, the problem that the technical idea of the present disclosure aims to solve is a biodegradable composite material composition for 3D printing and a method for manufacturing the same, which can be stably mixed to form a composite material composition even when a plurality of components with different melting points are used. The aim is to provide a biodegradable composite material composition for 3D printing that can be manufactured and has low brittleness even after extrusion in which a plurality of components are uniformly distributed in the composition.

In order to achieve the above object, a method for producing a biodegradable composite material composition for 3D printing according to one aspect of the technical idea of the present disclosure involves immersing the first biodegradable component and the second biodegradable component of the powder formulation in chloroform. A first step of forming a sol formulation mixture by uniformly stirring; A second step of first drying the sol formulation mixture to form a dry precursor; A third step of first pulverizing the dry precursor to form a pulverized precursor; A fourth step of secondary pulverizing the pulverized precursor to form a pulverized dried body; A fifth step of secondary drying the pulverized dried body to form a powdered dried body; It may include a sixth step of extruding the dried powder to obtain a biodegradable composite material composition in the form of a filament.

For example, the first biodegradable component may be polylactic acid, and the second biodegradable component may be poly(L-lactide-co-trimethylene carbonate).

For example, the first step may be performed as a sol-gel process performed by stirring at 40 to 60°C at 300 RPM for 2 to 4 hours.

For example, the weight ratio of polylactic acid and poly(L-lactide-co-trimethylene carbonate) in the first step may be 99:1 to 80:20.

For example, the weight of the chloroform in the first step may be 15 to 20 times the weight of the total weight of polylactic acid and poly (L-lactide-co-trimethylene carbonate) in the first step. there is.

For example, the primary drying in the second step may be performed at 25°C for 20 to 28 hours and then at 50 to 70°C for 20 to 28 hours.

For example, the first pulverization in the third step may be pulverizing the dry precursor to an average particle size of 0.5 to 1.5 cm.

For example, the secondary grinding in the fourth step may be performed using an atomizer under conditions where the cutter speed is 35 or more and 45 Hz or less.

For example, the secondary drying in the fifth step may be performed at 100 to 120°C for 20 to 28 hours.

For example, the dried powder in the fifth step may have a moisture content of 0.45% or less at 105°C based on the total weight of the composition, and a melt flow index of 2.0g/10 minutes or less at 190°C and 2.16kg. there is.

For example, the extrusion in the sixth step is performed at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz using an extruder including a heating unit and an extruding unit, the temperature of the heating unit is 210°C, and the temperature of the extruding unit is is 170°C, and the average particle size of the dried powder may be 0.1 to 3 mm.

In addition, the method for producing a biodegradable composite material composition for 3D printing according to an aspect of the technical idea of the present disclosure includes, in the first step, after the first biodegradable component and the second biodegradable component are immersed in chloroform. , Mg(OH)2 may be additionally immersed in chloroform.

For example, the Mg(OH)2 may be immersed in chloroform in an amount of 0.01 to 10 phr.

In addition, in the method of manufacturing a biodegradable composite material composition for 3D printing according to an aspect of the technical idea of the present disclosure, the first biodegradable component may be polylactic acid, and the second biodegradable component may be polycaprolactone. .

For example, the weight ratio of polylactic acid and polycaprolactone in the first step may be 1:99 to 70:30.

For example, the weight of the chloroform in the first step may be 13 to 17 times the weight of the total weight of polylactic acid and polycaprolactone in the first step.

For example, the extrusion in the sixth step is performed at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz using an extruder including a heating unit and an extruding unit, the temperature of the heating unit is 180°C, and the temperature of the extruding unit is is 130°C, and the average particle size of the dried powder may be 0.1 to 3 mm.

In addition, in the method for producing a biodegradable composite material composition for 3D printing according to an aspect of the technical idea of the present disclosure, the first biodegradable component is polylactic acid, and the second biodegradable component is poly(lactide-co- It may be glycolide).

For example, the weight ratio of polylactic acid and poly(lactide-co-glycolide) in the first step may be 99:1 to 40:60.

For example, the extrusion in the sixth step is performed at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz using an extruder including a heating unit and an extruding unit, the temperature of the heating unit is 240°C, and the temperature of the extruding unit is is 190°C, and the average particle size of the dried powder may be 0.1 to 3 mm.

The biodegradable composite material composition for 3D printing and its manufacturing method according to the technical idea of the present disclosure are finally obtained by improving dispersibility by dispersing the components in a solution state by using a low-temperature sol-gel process as a pre-mixing process. Each component included in the biodegradable composite material composition for 3D printing is made to have a uniformly distributed composition, and based on this, it can be stably extruded to form a filament shape suitable for 3D printing.

In addition, the biodegradable composite material composition for 3D printing and its manufacturing method according to the technical idea of the present disclosure can produce a composite material composition by stably mixing it even when using a plurality of components with different melting points. , it is possible to provide a biodegradable composite material composition for 3D printing that has low brittleness even after extrusion in which a plurality of components are uniformly distributed in the composition.

1 is a flowchart schematically showing a method of manufacturing a biodegradable composite material composition for 3D printing according to an exemplary embodiment of the present disclosure.
Figure 2 is a diagram showing the results of forming a dry precursor by first drying a sol formulation mixture according to an exemplary embodiment of the present disclosure.
Figure 3 is a diagram showing the results of forming a pulverized precursor by first pulverizing a dry precursor according to an exemplary embodiment of the present disclosure.
Figure 4 is a diagram showing the results of forming a ground dried body by secondary grinding a ground precursor according to an exemplary embodiment of the present disclosure.
Figure 5 is a diagram showing the results of forming a powdered dried body by secondary drying the pulverized dried body according to an exemplary embodiment of the present disclosure.
Figure 6 is a diagram showing the results of obtaining a biodegradable composite material composition in the form of a filament by extruding a dried powder according to an exemplary embodiment of the present disclosure.
Figure 7 is a diagram showing TGA and DSC analysis data of a biodegradable composite composition according to an exemplary embodiment of the present disclosure.
Figure 8 is a diagram showing NMR analysis data of a biodegradable composite material composition according to an exemplary embodiment of the present disclosure.
Figure 9 is a diagram showing FT-IR analysis data of a biodegradable composite composition according to an exemplary embodiment of the present disclosure.
Figure 10 is a diagram showing XRF analysis data of a biodegradable composite material composition according to an exemplary embodiment of the present disclosure.
Figure 11 is a diagram showing data measuring the amount of inorganic matter, residual moisture, and residual solvent of a biodegradable composite material composition according to an exemplary embodiment of the present disclosure.

Hereinafter, the description of the present invention with reference to the drawings is not limited to specific embodiments, and various changes may be made and various embodiments may be possible. In addition, the content described below should be understood to include all conversions, equivalents, and substitutes included in the spirit and technical scope of the present invention.

In the following description, the terms first, second, etc. are terms used to describe various components, and their meaning is not limited, and is used only for the purpose of distinguishing one component from other components. Additionally, the same reference numerals used throughout this specification represent the same elements.

Unless otherwise stated herein, specific steps or processes may be carried out at room temperature. Room temperature may be in the range of 15 to 30°C, preferably in the range of 20 to 25°C.

As used herein, singular expressions include plural expressions, unless the context clearly dictates otherwise. In addition, terms such as “comprise,” “provide,” or “have” used below are intended to designate the presence of features, numbers, steps, operations, components, parts, or a combination thereof described in the specification. It should be construed and understood as not excluding in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts or combinations thereof.

According to one aspect of the present disclosure, a method for manufacturing a biodegradable composite material composition for 3D printing may be provided.

The method for producing the biodegradable composite material composition for 3D printing includes a first step of immersing the first biodegradable component and the second biodegradable component of the powder formulation in chloroform and uniformly stirring to form a sol formulation mixture; A second step of first drying the sol formulation mixture to form a dry precursor; A third step of first pulverizing the dry precursor to form a pulverized precursor; A fourth step of secondary pulverizing the pulverized precursor to form a pulverized dried body; A fifth step of secondary drying the pulverized dried body to form a powdered dried body; It may include a sixth step of extruding the dried powder to obtain a biodegradable composite material composition in the form of a filament.

For example, the first biodegradable component may be polylactic acid, and the second biodegradable component may be poly(L-lactide-co-trimethylene carbonate).

As an example, the first step may be performed as a sol-gel process performed by stirring at 40 to 60°C at 300 RPM for 2 to 4 hours. Preferably, the first step may be performed as a sol-gel process performed by stirring at 45 to 55 ° C. and 300 RPM for 2.5 to 3.5 hours. For example, the first step may be performed as a sol-gel process performed by stirring at 50°C and 300RPM for 3 hours.

As an example, the weight ratio of polylactic acid and poly(L-lactide-co-trimethylene carbonate) in the first step may be 99:1 to 80:20. Preferably, the weight ratio of polylactic acid and poly(L-lactide-co-trimethylene carbonate) in the first step may be 95:5 to 85:15.

As an example, the weight of the chloroform in the first step may be 15 to 20 times the weight of the total weight of polylactic acid and poly (L-lactide-co-trimethylene carbonate) in the first step. . Preferably, the weight of the chloroform in the first step may be 17 to 19 times the weight of the total weight of polylactic acid and poly (L-lactide-co-trimethylene carbonate) in the first step. there is. For example, the weight of the chloroform in the first step may be 18 times the weight of the total weight of polylactic acid and poly(L-lactide-co-trimethylene carbonate) in the first step. When the weight of the chloroform satisfies the above numerical range, the obtained sol formulation may have a uniform transparent or translucent shape and may have a non-gelated shape.

As an example, the primary drying in the second step may be performed at 25°C for 20 to 28 hours and then at 50 to 70°C for 20 to 28 hours. For example, when the first biodegradable component is polylactic acid and the second biodegradable component is poly(L-lactide-co-trimethylene carbonate), preferably the first drying in the second step is 25 It may be performed at ℃ for 20 to 28 hours and then at 60℃ for 24 hours. When each of the conditions of the primary drying satisfies the above numerical range, a uniform sheet shape that is hard and elastic and does not cause pumping and is easy to grind and cut afterwards can be obtained.

As an example, the first pulverization in the third step may be pulverizing the dry precursor to an average particle size of 0.5 to 1.5 cm. Preferably, the blade used for the primary grinding is made of stainless steel, and in this case, rusting of the blade can be prevented and contamination of the material can be prevented.

As an example, the secondary grinding in the fourth step may be performed using an atomizer under conditions where the cutter speed is 35 or more and 45 Hz or less. When each of the conditions for the secondary grinding satisfies the above numerical range, a high yield can be achieved and the risk of carbonization can be reduced.

As an example, the secondary drying in the fifth step may be performed at 100 to 120°C for 20 to 28 hours. When each of the above conditions for secondary drying satisfies the above numerical range, excellent drying efficiency can be achieved while preventing deterioration of the material.

As an example, the dried powder in the fifth step may have a moisture content of 0.45% or less at 105°C based on the total weight of the composition, and a melt flow index of 2.0g/10 minutes or less at 190°C and 2.16kg. .

As an example, the extrusion in the sixth step is performed using an extruder including a heating unit and an extruding unit at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz, the temperature of the heating unit is 210 ° C., and the temperature of the extrusion unit is The temperature is 170°C, and the average particle size of the dried powder may be 0.1 to 3 mm.

In addition, the method for producing a biodegradable composite material composition for 3D printing according to an aspect of the technical idea of the present disclosure includes, in the first step, after the first biodegradable component and the second biodegradable component are immersed in chloroform. , Mg(OH) ₂ may be additionally immersed in chloroform.

As an example, the Mg(OH) ₂ may be immersed in chloroform in an amount of 0.01 to 10 phr.

As another example, the first biodegradable component may be polylactic acid, and the second biodegradable component may be polycaprolactone.

As an example, the weight ratio of polylactic acid and polycaprolactone in the first step may be 1:99 to 70:30. Preferably, the weight ratio of polylactic acid and polycaprolactone in the first step may be 10:90 to 60:40.

As an example, the weight of the chloroform in the first step may be 13 to 17 times the weight of the total weight of polylactic acid and polycaprolactone in the first step. Preferably, the weight of the chloroform in the first step may be 14 to 16 times the weight of the total weight of polylactic acid and polycaprolactone in the first step. For example, the weight of the chloroform in the first step may be 15 times the weight of the total weight of polylactic acid and polycaprolactone in the first step. When the weight of the chloroform satisfies the above numerical range, the obtained sol formulation may have a uniform transparent or translucent shape and may have a non-gelated shape.

As an example, the extrusion in the sixth step is performed at a stirring speed of 100 to 300 RPM and a withdrawal speed of 75 to 85 Hz using an extruder including a heating unit and an extrusion unit, the temperature of the heating unit is 180°C, and the temperature of the extrusion unit is The temperature is 130°C, and the average particle size of the dried powder may be 0.1 to 3 mm.

As another example, the first biodegradable component may be polylactic acid, and the second biodegradable component may be poly(lactide-co-glycolide).

As an example, the weight ratio of polylactic acid and poly(lactide-co-glycolide) in the first step may be 99:1 to 40:60. Preferably, the weight ratio of polylactic acid and poly(lactide-co-glycolide) in the first step may be 90:10 to 50:50.

As an example, the extrusion in the sixth step is performed using an extruder including a heating unit and an extruding unit at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz, the temperature of the heating unit is 240 ° C., and the temperature of the extrusion unit is 190°C, and the average particle size of the dried powder may be 0.1 to 3 mm.

Hereinafter, preferred embodiments of the present invention will be described. However, the following examples are merely illustrative of the present invention and are not intended to limit the content of the present invention to the following examples.

Examples 1 to 3: Preparation of compositions comprising polylactic acid and poly(L-lactide-co-trimethylene carbonate)

Polylactic acid (PLLA) and poly(L-lactide-co-trimethylene carbonate) (PLLA-co-TMC) in powder form were immersed in 1800 g of chloroform in the amounts shown in Table 1 below and heated at 300 RPM at 40 to 60°C. The mixture was uniformly stirred for 2 to 4 hours to form a sol formulation mixture.

Afterwards, primary drying was performed by maintaining the mixture of the sol formulation at 50 to 70° C. for 20 to 28 hours to form a dry precursor.

Afterwards, the dried precursor was first pulverized using an ultra-small mill to have an average particle diameter of 0.5 to 1.5 cm to form a pulverized precursor.

Afterwards, the pulverized precursor was subjected to secondary pulverization using an atomizer under the conditions of 2 mm mesh, supply speed of 45 Hz, and cutting speed of 35 Hz to form a pulverized dried body.

Afterwards, secondary drying was performed by maintaining the pulverized dried body at 100 to 120° C. for 20 to 28 hours to form a powdered dried body.

Thereafter, the dried powder was extruded using an extruder including two heating units and an extrusion unit at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz to obtain a filament-shaped biodegradable composite material composition as the composition of Example 1. The temperature of each of the two heating units was 210°C, the temperature of the extrusion unit was 170°C, and the average particle size of the dried powder was 0.1 to 3 mm.

Examples 4 to 9: Preparation of compositions comprising polylactic acid and polycaprolactone.

Instead of polylactic acid and poly(L-lactide-co-trimethylene carbonate) in powder formulation, polylactic acid and polycaprolactone (PCL) in powder formulation were used in the amounts shown in Table 1 below, and chloroform was used in the amount shown in Table 1 below. The method described in Example 1 was used in quantity and the powder dry body was used in an extruder including two heating units and an extrusion unit, except that the temperature of the heating unit was 180°C and the temperature of the extrusion unit was 130°C. The filament-type biodegradable composite material composition prepared according to was obtained as the composition of Example 3.

Examples 10-12: Preparation of compositions comprising polylactic acid and poly(lactide-co-glycolide).

Instead of polylactic acid and poly(L-lactide-co-trimethylene carbonate) in powder formulation, polylactic acid and poly(lactide-co-glycolide) (PLGA) in powder formulation are used in the amounts shown in Table 1 below, Filament manufactured according to the method described in Example 1, except that when using an extruder including two heating units and an extrusion unit for dry powder, the temperature of the heating unit is 240°C and the temperature of the extrusion unit is 190°C. A biodegradable composite composition in the form of Example 4 was obtained.

Examples 13 to 17: Mg(OH) ₂ Preparation of a composition further comprising

After the first biodegradable component and the second biodegradable component were immersed in chloroform, the method was followed in Example 1 except that Mg(OH) ₂ was additionally immersed in chloroform in the amount shown in Table 1 below. A biodegradable composite composition in filament form prepared according to the described method was obtained as the composition of Example 2.

Example PLLA (w/w%) PLLA-co-TMC
(w/w%) PCL(w/w%) PLGA (w/w%) Mg(OH) ₂
(phr) chloroform
(Drainage) One 95 5 - - - 18 2 90 10 - - - 18 3 85 15 - - - 18 4 10 - 90 - - 15 5 20 - 80 - - 15 6 30 - 70 - - 15 7 40 - 60 - - 15 8 50 - 50 - - 15 9 60 - 40 - - 15 10 90 - - 10 - 18 11 70 - - 30 - 18 12 50 - - 50 - 18 13 90 10 - - 5 or more 18 14 90 10 - - 3 18 15 90 10 - - One 18 16 90 10 - - 0.1 18 17 90 10 - - 0.05 18

Experimental Example 1: Evaluation of physical properties of compositions of Examples 1 to 17

Examples 1 to 17 Thermal properties of the compositions were analyzed using TGA and DSC, and in-process control (IPC) moisture measurement (105°C) was performed using a halogen moisture meter. Referring to FIG. 7, in Example 16, Tg was confirmed to be 62°C and Tm was confirmed to be 174°C. Additionally, in Examples 1 to 12, 16, and 17, it was confirmed that the moisture content at 105°C was 0.45% or less based on the total weight of the composition. Referring to Figure 10, in Example 16, it was confirmed that there was no chlorine as a residual solvent.

In addition, the melt mass flow rate (190℃, 2.16kg, procedure A) as the melt flow index at 190℃, 2.16kg, is based on ASTM D1238-20 (compliant), preheating time is 100 seconds, measurement time is 150 seconds, and number of measurements is 5. The evaluation was conducted under raw conditions. The results are shown in Table 2 below.

In addition, the inorganic content, residual moisture, and residual solvent were measured using WD-XRF (Wavelength Dispersive X-Ray Fluorescence Spectrometry) (see Figure 11). The results are shown in Table 2 below.

Example MFI(g/10min) Tg(℃) Tm(℃) Minerals (%) Residual moisture (%) residual solvent
(Cl%) One 0.5 66 179 - 0.25 0.00 2 0.6 67 179 - 0.38 0.00 3 1.0 70 179 - 0.39 0.00 4 2.8 58 144 - 0.42 - 5 2.6 58 146 - 0.23 - 6 2.5 57 146 - 0.32 - 7 2.1 57 145 - 0.33 - 8 2.0 54 144 - 0.40 - 9 1.9 56 145 - 0.32 - 10 0 - 212 - 0.32 - 11 0 - 205 - 0.25 - 12 0 - 200 - 0.21 - 13 6.8 - - 5 or more - 1.54 14 4.8 68 180 2.0 1.83 0.01 15 3.6 69 179 0.9 1.22 0.01 16 0.7 62 174 0.3 0.12 0.00 17 0.5 62 174 OK 0.38 -

Experimental Example 2: Evaluation of physical properties of the compositions of Examples 1 to 17

Examples 1 to 17 Regarding the physical properties of the composition, tensile strength and nominal tensile strain at break were measured under the condition of Type IV and test speed of 50 mm/min according to ASTM D638-22. The results are shown in Table 3 below.

Example Tensile strength (MPa) Elongation (%) One 55 2 2 52 5 3 37 6 4 21 500 or more 5 20 433 6 11 306 7 12 215 8 10 125 9 8 82 10 Impossibility of producing consistent specimens
(Injection molding machine performance and Mg(OH)2 issues) 11 12 13 14 15 16 53 5 17 53 5

Experimental Example 3: Cytotoxicity evaluation of the compositions of Examples 13 to 17

A cytotoxicity test was performed on the compositions of Examples 13 to 17 according to ISO 10993-5: 2009. Samples of the compositions of Examples 13 to 17 were implanted subcutaneously in 8-week-old female rats (Sprague-Dawley rats), and local and inflammatory reactions around the subcutaneous tissue due to the test specimens were evaluated. Each specimen was prepared as 2*10mm according to the transplantation test specifications, and three specimens were transplanted for each group.

Before the transplant test, the test animals were allowed to rest as much as possible, and after anesthetizing the animals, hair was removed on the left and right flanks. Additionally, the weight of the test animals was measured. The test specimen was implanted subcutaneously on the left and right flanks, and sutured to prevent the transplanted test specimen from moving.

After 4 days from the date of transplantation, the test animals were anesthetized and euthanized, and then the transplanted specimen area and 0.5cm of the surrounding area were extracted and fixed in formalin solution. The fixed tissue was made into a paraffin block, slided, and subjected to Hematoxylin and Eosin straining.

As a result, no inflammation, unusual clinical symptoms or acute death of animals was observed in the subcutaneous tissue where the test and control specimens for the compositions of Examples 16 and 17 were implanted, and the results were measured according to the evaluation criteria (p = 0.35. ns ), no specific findings regarding differences were observed in the transplanted area between the test specimen and the control specimen (grade “0”). The overall results are shown in Table 4 below.

Example Cytotoxicity (Grade) 13 4 14 2 15 2 16 0 17 0

As a result, the composition of Example 16 was confirmed to have excellent MFI properties, low mineral content, low residual moisture content, high tensile strength, low elongation, low cytotoxicity, low residual solvent content, and a Tg of 60°C or higher and a Tm of 170°C or higher. It was confirmed to have superior physical properties compared to the compositions of Examples 1 to 15 and Example 17, and it was also confirmed to have excellent quality when producing a filament-shaped composition through extrusion.

In addition, the compositions of Examples 1 to 9 and Example 17 were also confirmed to have excellent physical properties suitable for 3D printing and excellent physical properties suitable for manufacturing a biodegradable stent.

From this, the biodegradable composite material composition for 3D printing and its manufacturing method according to the present disclosure are biodegradable materials with different melting points, such as polylactic acid (PLLA), polycaprolactone (PCL), and poly(lactide-co-glycolide). A biodegradable composite material composition and method for manufacturing the same, which has excellent physical properties suitable for 3D printing and excellent physical properties suitable for use as a biodegradable stent, even when two or more of the biodegradable materials such as (PLGA) are used It has been confirmed that it can provide.

As above, exemplary embodiments have been disclosed in the drawings and specification. In this specification, embodiments have been described using specific terms, but this is only used for the purpose of explaining the technical idea of the present disclosure and is not used to limit the meaning or scope of the present disclosure described in the claims. Therefore, those skilled in the art will understand that various modifications and other equivalent embodiments are possible therefrom. Therefore, the true technical protection scope of the present disclosure should be determined by the technical spirit of the attached claims.

Claims (20)

A method for producing a biodegradable composite material composition for 3D printing,
A first step of immersing the first biodegradable component and the second biodegradable component of the powder formulation in chloroform and uniformly stirring to form a mixture of the sol formulation, wherein the first biodegradable component and the second biodegradable component are immersed in chloroform. After being immersed in, Mg(OH)2 is further immersed in chloroform, a first step;
A second step of first drying the sol formulation mixture to form a dry precursor;
A third step of first pulverizing the dry precursor to form a pulverized precursor;
A fourth step of secondary pulverizing the pulverized precursor to form a pulverized dried body;
A fifth step of secondary drying the pulverized dried body to form a powdered dried body;
Comprising a sixth step of extruding the dried powder to obtain a biodegradable composite material composition in the form of a filament,
Method for producing a biodegradable composite material composition for 3D printing. The method of claim 1, wherein the first biodegradable component is polylactic acid, and the second biodegradable component is poly(L-lactide-co-trimethylene carbonate). . The biodegradable composite material composition for 3D printing according to claim 2, wherein the first step is performed by a sol-gel process performed by stirring at 300 RPM for 2 to 4 hours at 40 to 60 ° C. Manufacturing method. The method of claim 3, wherein the weight ratio of polylactic acid and poly(L-lactide-co-trimethylene carbonate) in the first step is 99:1 to 80:20. . The method of claim 4, wherein the weight of the chloroform in the first step is 15 to 20 times the weight of the total weight of polylactic acid and poly (L-lactide-co-trimethylene carbonate) in the first step. , Method for producing a biodegradable composite material composition for 3D printing. The method of claim 1, wherein the Mg(OH)2 is immersed in chloroform in an amount of 0.01 to 10 phr. The biodegradable composite material composition for 3D printing according to claim 6, wherein the primary drying in the second step is performed at 25°C for 20 to 28 hours and then at 50 to 70°C for 20 to 28 hours. Manufacturing method. The method of claim 7, wherein the primary pulverization in the third step pulverizes the dry precursor to an average particle size of 0.5 to 1.5 cm. The biodegradable composite material for 3D printing according to claim 8, wherein the secondary pulverization in the fourth step is performed using an atomizer under conditions where the cutter speed is 35 or more and 45 Hz or less. Method for producing composition. The method of claim 9, wherein the secondary drying in the fifth step is performed at 100 to 120° C. for 20 to 28 hours. The method of claim 10, wherein the dried powder in the fifth step has a moisture content of 0.45% or less at 105°C based on the total weight of the composition, and a melt flow index of 2.0g/10 minutes or less at 190°C and 2.16kg. , Method for producing a biodegradable composite material composition for 3D printing. The method of claim 11, wherein the extrusion in the sixth step is performed at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz using an extruder including a heating unit and an extrusion unit, the temperature of the heating unit is 210°C, and the extrusion A method of producing a biodegradable composite material composition for 3D printing, wherein the temperature is 170°C and the average particle size of the dried powder is 0.1 to 3 mm. The method of claim 1, wherein the first biodegradable component is polylactic acid, and the second biodegradable component is polycaprolactone. The method of claim 13, wherein the weight ratio of polylactic acid and polycaprolactone in the first step is 1:99 to 70:30. The biodegradable composite material composition of claim 14, wherein the weight of the chloroform in the first step is 13 to 17 times the weight of the total weight of polylactic acid and polycaprolactone in the first step. Manufacturing method. The method of claim 15, wherein the extrusion in the sixth step is performed at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz using an extruder including a heating unit and an extrusion unit, the temperature of the heating unit is 180°C, and the extrusion A method of producing a biodegradable composite material composition for 3D printing, wherein the temperature is 130°C and the average particle size of the dried powder is 0.1 to 3 mm. The method of claim 1, wherein the first biodegradable component is polylactic acid, and the second biodegradable component is poly(lactide-co-glycolide). The method of claim 17, wherein the weight ratio of polylactic acid and poly(lactide-co-glycolide) in the first step is 99:1 to 40:60. The method of claim 18, wherein the extrusion in the sixth step is performed at a stirring speed of 100 to 300 RPM and a drawing speed of 75 to 85 Hz using an extruder including a heating unit and an extrusion unit, the temperature of the heating unit is 240°C, and the extrusion A method of producing a biodegradable composite material composition for 3D printing, wherein the temperature is 190°C and the average particle size of the dried powder is 0.1 to 3 mm.
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