Patent Application
20240246285
This disclosure relates to a filament for 3D printer containing a polyester and a method of producing the same.
A fused deposition modeling 3D printer has increasingly become popular, which performs shaping by feeding a filament containing a thermoplastic resin by a feeder, followed by melting and discharging the filament from a nozzle part, and has been widely used not only for personal applications but also for industrial applications such as manufacturing of parts.
As resins constituting filaments, hard materials such as polylactic acid and an acrylonitrile-butadiene-styrene copolymer synthetic resin (ABS resin), have been mainly used. However, in recent years, there has been a demand for highly flexible materials, and the development of flexible materials is progressing. As such materials, for example, a filament containing a polyester thermoplastic elastomer (JP 6647749 B) and a polymer composition containing a polylactic acid and a dilactide/ε-caprolactone copolymer (WO 2020/241624) have been reported.
In recent years, 3D printers have been developed also for medical applications, and personalized medicine has drawn attention, in which custom-made medical devices fitted to shapes of bones or organs different in each patient are manufactured using 3D printers, and then implanted into living bodies.
However, since the filament described in JP 6647749 B uses a non-biodegradable elastomer and a molded substance is non-biodegradable, the filament is not suitable for medical appliances required to be decomposed and discharged from the body after finishing its role. The composition described in WO 2020/241624 is biodegradable, and therefore suitable for applications as medical appliances. However, filaments manufactured using the composition described in WO 2020/241624 are sticky in many instances, and the filaments are bonded to each other or adhere to the inner wall of a guide tube supporting feeding, which has caused a problem of poor printability.
It could therefore be helpful to provide a flexible and biodegradable filament having excellent printability.
We thus provide:
Our method can obtain a flexible and biodegradable filament having excellent printability, and can produce a molded body having biodegradability or bioabsorbability and having flexibility, which is suitable for medical applications.
Our method provides a biodegradable filament for 3D printer including: an amorphous biodegradable polyester; and a water-soluble polymer different from the biodegradable polyester, in which the water-soluble polymer has a melting point of 30° C. or more and 220° C. or less.
The filament for a 3D printer as disclosed herein has biodegradability. Herein, the biodegradability refers to a property of being decomposed in living bodies or in the environments. More specifically, the biodegradability refers to the fact that the biodegradation degree determined according to Measurement Example 6 described later is 60% or more. Terms that can be used interchangeably with the biodegradability include bioabsorbability, biocompatibility and the like, but these terms mainly refer to the property of being decomposed in living bodies in many instances.
The biodegradable polyester contained in the filament for 3D printer refers to a polymer in which monomers are connected mainly through ester bonds. Polymers in which monomers are partially connected through bonds other than the ester bonds such as a urethane bond or an amide bond, are also referred to as the polyester. To control the biodegradability in a suitable range, the number of bonds other than the ester bonds among the bonds used for connecting the monomers is preferably 30% or less, more preferably 10% or less, still more preferably 5% or less, and most preferably 0%, i.e., when the bonds other than the ester bonds are not contained and when the number of bonds used to connect the monomers is set to 100%.
The biodegradable polyester contained in the filament for 3D printer is amorphous. The crystallinity of the polyester can be measured by differential scanning calorimetry (hereinafter referred to as “DSC”). When the crystallization degree of an ester-bonding monomer residue obtained by the method described in Measurement Example 8 described later is 20% or less it is considered to be amorphous. When the polyester is composed of a plurality of ester-bonding monomer residues and the crystallization degree of all the monomer residues is 20% or less it is considered to be amorphous. From the viewpoint of obtaining a flexible filament, the crystallization degree is preferably lower. The crystallization degree of each ester-bonding monomer residue is preferably 14% or less, more preferably 10% or less, and still more preferably 5% or less. When the polyester is composed of a plurality kinds of ester-bonding monomer residues, it is preferable that all the monomer residues have a low crystallization degree, but it may be also acceptable that only some monomer residues have a low crystallization degree.
The ester-bonding monomer refers to a monomer that can form an ester bond by reacting between monomer-derived functional groups to form a polyester.
The crystallization degree of the monomer residue herein refers to a ratio of the heat of fusion derived from the monomer residue per unit mass of the polyester to the product of the heat of fusion per unit mass of a homopolymer containing only a certain monomer residue and the mass fraction of the monomer residue in the polyester.
The weight average molecular weight of the biodegradable polyester contained in the filament for 3D printer is preferably 100,000 or more and 1,000,000 or less, more preferably 150,000 or more and 500,000 or less, and still more preferably 200,000 or more and 400,000 or less from the viewpoint of printability. The weight average molecular weight of the polyester is the weight average molecular weight in terms of polystyrene, which is measured by gel permeation chromatography (hereinafter referred to as “GPC”).
The filament for 3D printer contains a water-soluble polymer different from the above-described biodegradable polyester, and the water-soluble polymer has a melting point of 30° C. or more and 220° C. or less.
The filament for 3D printer can be produced, for example, by the following method.
A composition obtained by coating a biodegradable polyester with a powdery or flake-like water-soluble polymer is charged into an extruder, the temperature is raised to a predetermined temperature, and the composition is extruded to obtain a filament. In polyester, the temperature when the extrusion is performed is generally 70° C. or more and 250° C. or less. When the filament is produced by the above-described method, it is necessary to raise the temperature to a temperature higher than the melting point of the water-soluble polymer and the melting point or the glass transition temperature of the polyester. However, when the melting point of the water-soluble polymer is higher than the decomposition temperature of the polyester, the extrusion becomes difficult. When the water-soluble polymer is a liquid, the water-soluble polymer oozes out from the obtained filament, which results in reducing the printability. Thus, the water-soluble polymer is preferably a solid, i.e., has a melting point equal to or higher than room temperature. Therefore, the melting point of the water-soluble polymer is preferably 35° C. or more and 200° C. or less, more preferably 40° C. or more and 150° C. or less, still more preferably 45° C. or more and 120° C. or less, and most preferably 50° C. or more and 100° C. or less. The melting point of the water-soluble polymer can be measured by the DSC.
Further, there is a method which includes adding a water-soluble polymer to a solution obtained by dissolving the biodegradable polyester in a good solvent, adding a poor solvent, and charging a composition containing the biodegradable polyester and the water-soluble polymer obtained by re-precipitation into an extruder, raising the temperature to a predetermined temperature, and extruding the composition to obtain a filament.
It is considered that mixing the water-soluble polymer with the biodegradable polyester as described above reduces the stickiness of the composition containing the biodegradable polyester and the water-soluble polymer, and stabilizes the extrusion of the filament. This can reduce the variation coefficient of the diameter of the filament described later, and provide a filament having excellent printability.
In particular, the method including charging a composition obtained by coating a biodegradable polyester with a powdery or flake-like water-soluble polymer into an extruder, raising the temperature to a predetermined temperature, and extruding the composition to obtain a filament is preferable because the method does not require an operation of dissolving the water-soluble polymer in a solvent to add the water-soluble polymer and a drying operation, and the water-soluble polymer can be easily added to the biodegradable polyester.
Since the water-soluble polymer needs to be a solid, the weight average molecular weight of the water-soluble polymer is preferably 2,000 or more. On the other hand, when the weight average molecular weight of the water-soluble polymer is too high, the printability decreases, and therefore the weight average molecular weight of the water-soluble polymer is preferably 1,500,000 or less. Further, when medical appliances that are required to be decomposed and discharged to the outside of the body after finishing its role are produced using the filament, the water-soluble polymer is also required to be discharged from the body. Therefore, the weight average molecular weight of the water-soluble polymer is more preferably 170,000 or less, still more preferably 100,000 or less, and most preferably 20,000 or less. By setting the weight average molecular weight of the water-soluble polymer to 170,000 or less, the water-soluble polymer is easily and appropriately discharged from the kidneys. The weight average molecular weight of the water-soluble polymer is the weight average molecular weight in terms of polystyrene measured by the GPC.
As the content of the water-soluble polymer different from the biodegradable polyester, the water-soluble polymer different from the polyester is contained in an amount of preferably 0.1% by mass or more and 50% by mass or less, more preferably 0.1% by mass or more and 25% by mass or less, still more preferably 0.5% by mass or more and 10% by mass or less, and most preferably 1.0% by mass or more and 5% by mass or less with respect to 100% by mass of the filament.
The water-soluble polymer different from the biodegradable polyester refers to a polymer other than the biodegradable polyester and a polymer that dissolves in water. More specifically, the determination can be performed by evaluating whether the polymer dissolves in water according to Measurement Example 7 described later.
The water-soluble polymer different from the biodegradable polyester contained in the filament for 3D printer includes, for example, polyethylene glycol (hereinafter referred to as “PEG”), polypropylene glycol, polyacrylic acid, polymethacrylic acid, polyacrylamide, polyvinylpyrrolidone (hereinafter referred to as “PVP”), polyvinyl acetamide, polymaleic acid, polysulfonic acid, polyvinyl alcohol (hereinafter referred to as “PVA”), polyethyleneimine, carboxymethylcellulose, alginic acid, polyphosphoric acid, starch, agar, gelatin, pullulan, dextrin, xanthan gum, and salts, copolymers, or copolymer salts thereof and the like. Among them, PEG, polypropylene glycol, polyacrylic acid, polymethacrylic acid, polyacrylamide, PVP, PVA, polyethyleneimine, carboxymethylcellulose, and salts, copolymers, or copolymer salts thereof are preferable from the viewpoint of affinity with the biodegradable polyester. From the viewpoint of the melting point, PEG, polypropylene glycol, polyacrylic acid, polymethacrylic acid, PVP, PVA, polyethyleneimine, and salts, copolymers, or copolymer salts thereof are more preferable; PEG, polypropylene glycol, PVP, PVA, and salts, copolymers, or copolymer salts thereof are still more preferable; and PEG, polypropylene glycol, PVP, and salts, copolymers, or copolymer salts thereof are most preferable.
Our filament is the biodegradable filament for 3D printer containing the amorphous biodegradable polyester and the biodegradable polymer different from the above-described biodegradable polyester, and is the filament for 3D printer in which the above-described biodegradable polymer is crystalline.
The biodegradable polymer different from the above-described biodegradable polyester is crystalline. The crystallinity of the biodegradable polymer can be measured by wide-angle X-ray scattering (hereinafter referred to as “WAXS”). The biodegradable polymer is determined to be crystalline when the crystallization degree obtained by the method described in Measurement Example 9 described later is larger than 20% that. When the biodegradable polymer is a copolymer, the crystallinity may be evaluated by the DSC described in Measurement Example 8. The biodegradable polymer is determined to be crystalline when any of the obtained crystallization degrees derived from the monomers is larger than 20%.
The biodegradable polymer different from the biodegradable polyester is a polymer having the property of being decomposed in living bodies or in the environments, i.e., a polymer having the biodegradation degree determined by Measurement Example 6 described later of 60% or more.
In the filament for 3D printer, the content of the biodegradable polymer different from the biodegradable polyester is preferably 0.1% by mass or more and less than 20% by mass, more preferably 0.5% by mass or more and 15% by mass or less, and still more preferably 1.0% by mass or more and 10% by mass or less with respect to 100% by mass of the filament from the viewpoint of obtaining a flexible filament.
To keep suitable biodegradability of the filament, the weight average molecular weight of the biodegradable polymer different from the amorphous biodegradable polyester is preferably 1,000 or more and 300,000 or less, more preferably 5,000 or more and 250,000 or less, and still more preferably 10,000 or more and 200,000 or less. The weight average molecular weight of the biodegradable polymer is the weight average molecular weight in terms of polystyrene measured by the GPC.
The biodegradable polymer different from the biodegradable polyester contained in the filament for 3D printer is preferably a polymer that does not satisfy the requirements of polyhydroxycarboxylic acid with an R-value described later of 0.45 or more and 0.99 or less. In this example, the biodegradable polymer different from the amorphous biodegradable polyester includes polyester, but does not include at least the polyhydroxycarboxylic acid with the R-value of 0.45 or more and 0.99 or less. The biodegradable polymer different from the amorphous biodegradable polyester include, for example, polylactic acid (hereinafter referred to as “PLA), polyglycolic acid, polycaprolactone (hereinafter referred to as “PCL”), polydioxanone, polyvalerolactone, polyhydroxybutyrate, polyhydroxyvalerate, polyhydroxyhexanoate, polybutylene succinate (hereinafter referred to as “PBS”), polybutylene succinate adipate, polybutylene succinate carbonate, polybutylene adipate terephthalate, polytetramethylene adipate terephthalate, polyethylene terephthalate succinate, PVA, pullulan, and copolymers thereof that do not satisfy the requirements of the polyhydroxycarboxylic acid with the R-value of 0.45 or more and 0.99 or less. From the viewpoint of obtaining a flexible filament, PLA, polyglycolic acid, PCL, polydioxanone, polyvalerolactone, polyhydroxybutyrate, polyhydroxyhexanoate, PBS, and copolymers thereof are particularly preferable. As described above, PVA and pullulan are also water-soluble polymers, and therefore are polymers having water-solubility and biodegradability. When the biodegradation degree of the polymer is determined according to Measurement Example 6 described later, the evaluation can be performed, for example, using one obtained by molding the polymer into a film or a pellet.
The filament for 3D printer containing the amorphous biodegradable polyester and the biodegradable polymer different from the biodegradable polyester can be produced by the following method:
Dissolving the biodegradable polymer in a solution containing the biodegradable polyester, removing the solvent from the resultant solution to yield a composition; charging that composition into an extruder, raising the temperature to a predetermined temperature, and extruding the composition to obtain a filament.
It is considered that, by mixing the biodegradable polymer different from the biodegradable polyester with the biodegradable polyester as described above, the stickiness of the composition containing the biodegradable polyester and the biodegradable polymer decreases, and the extrusion of the filament is stabilized. This can reduce the variation coefficient of the diameter of the filament described later and can provide a filament having excellent printability.
The amorphous biodegradable polyester contained in the filament for 3D printer preferably contains polyhydroxycarboxylic acid from the viewpoint of flexibility and biodegradability. The polyhydroxycarboxylic acid refers to a polymer constituted from hydroxy carboxylic acid residues. The hydroxycarboxylic acid refers to a compound having both a hydroxy group and a carboxy group in the same molecule.
The polyhydroxycarboxylic acid can be obtained by polymerization of the hydroxycarboxylic acid, polymerization of lactone, which is a cyclic compound obtained by intramolecular dehydration condensation of the hydroxy group and the carboxyl group of the hydroxycarboxylic acid, polymerization of lactide which is a cyclic compound obtained by dehydration condensation of the hydroxy group and the carboxyl group between two molecules of the hydroxycarboxylic acids or the like. That is, the hydroxycarboxylic acid, lactone, or lactide is usable as hydroxycarboxylic acid monomers.
The hydroxycarboxylic acid used as the hydroxycarboxylic acid monomer include lactic acid, glycolic acid, hydroxybutyric acid, hydroxyvaleric acid, hydroxycaproic acid, hydroxyheptanoic acid, hydroxyoctanoic acid, hydroxynonanoic acid, hydroxydecanoic acid, hydroxyundecanoic acid, hydroxydodecanoic acid, (2-hydroxyethoxy)acetic acid and the like. Among these, lactic acid, glycolic acid, hydroxyvaleric acid, and hydroxycaproic acid are preferable, and lactic acid and hydroxycaproic acid are particularly preferable.
A lactone used as the hydroxycarboxylic acid monomer, includes butyrolactone, valerolactone, caprolactone (hereinafter referred to as “CL”), dioxepanone, ethylene oxalate, p-dioxanone, trimethylene carbonate, β-propiolactone, pivalolactone and the like are. In particular, butyrolactone, valerolactone, CL, p-dioxanone, and trimethylene carbonate are preferable, and valerolactone and CL are more preferable.
A lactide used as the hydroxycarboxylic acid monomer, includes dilactide (hereinafter referred to as “LA”) obtained by dehydration condensation of two molecules of lactic acids, glycolide obtained by dehydration condensation of two molecules of glycolic acids, and tetramethyl glycolide are usable, and in particular LA and glycolide are preferable.
When the biodegradable polyester contained in the filament for 3D printer is the polyhydroxycarboxylic acid, polyhydroxycarboxylic acid containing two kinds of hydroxycarboxylic acid monomers as the main constituent unit is preferable from the viewpoint of obtaining a flexible filament. The phrase that the polyhydroxycarboxylic acid has two kinds of hydroxycarboxylic acid monomers as the main constituent unit means that the sum of the number of the two kinds of monomer residues is 50% by mole or more when the sum of the number of all monomer residues, including the other monomer residues, contained in the whole polyhydroxycarboxylic acid is set to 100% by mole; and each of the residues is 20% by mole or more when the sum of the number of all monomer residues contained in the whole polyhydroxycarboxylic acid is set to 100% by mole. Herein, the “monomer residue” refers to, in principle, a repeating unit of a chemical structure derived from the monomer in the chemical structure of the polyhydroxycarboxylic acid obtained by polymerizing two or more kinds of monomers including the monomer.
For example, the phrase that the monomer A residue and the monomer B residue are contained as the main constituent units means that the sum of the residue numbers of the monomer A residue and the monomer B residue is 50% by mole or more, the monomer A residue is 20% by mole or more, and the monomer B residue is 20% by mole or more, when the sum of the number of all monomer residues contained in the whole polyhydroxycarboxylic acid is set to 100% by mole. Herein, the mole fractions (%) of the monomer A residue, the monomer B residue, and the other residues can be determined from the area value of a signal derived from each of the residues by nuclear magnetic resonance (hereinafter referred to as “NMR”) measurement. For example, when the monomer A residue is an LA residue and the monomer B residue is a CL residue, the mole fraction can be determined by Measurement Example 4 described later. When the mole fractions (%) of the monomer A residue, the monomer B residue, and the other residues are calculated, the mole fractions (%) are calculated using the molecular weight of the repeating unit of the chemical structure derived from the monomer. For example, when the monomer A residue is an LA residue and the monomer B residue is a CL residue, the molecular weight of the repeating unit of the monomer A residue is 144, and the molecular weight of the repeating unit of the monomer B residue is 114.
From the definition above, the sum of the monomer A residue and the monomer B residue is 50% by mole or more, preferably 75% by mole or more, and more preferably 90% by mole or more when the sum of all monomer residues, including the other monomer residues, contained in the whole polymer is set to 100% by mole. The monomer A residue and the monomer B residue each are 20% by mole or more, preferably 30% by mole or more, and more preferably 40% by mole or more from the above-described same definition. A particularly preferable aspect is a polymer in which the sum of the monomer A residue and the monomer B residue is 100% by mole of the whole polymer, i.e., a polymer containing only the monomer A and the monomer B.
A more preferable aspect is when the two kinds of hydroxycarboxylic acid monomers are individually referred to as the “monomer A” and the “monomer B”, the R-value represented by Equation (1) below is 0.45 or more and 0.99 or less (the polyhydroxycarboxylic acid with the R-value of 0.45 or more and 0.99 or less is referred to as a “random polymer”).
wherein
The use of the random polymer as the polyhydroxycarboxylic acid, i.e., setting the R-value of the polyhydroxycarboxylic acid in the range above, is preferable because a flexible filament can be obtained.
Among these, the monomer A and the monomer B are preferably monomers selected from the group consisting of lactic acid, glycolic acid, hydroxybutyric acid, hydroxyvaleric acid, hydroxycaproic acid, hydroxyheptanoic acid, hydroxyoctanoic acid, hydroxynonanoic acid, hydroxydecanoic acid, hydroxyundecanoic acid, hydroxydodecanoic acid, (2-hydroxyethoxy)acetic acid, butyrolactone, valerolactone, CL, dioxepanone, ethylene oxalate, p-dioxanone, trimethylene carbonate, ß-propiolactone, pivalolactone, LA, glycolide, or tetramethyl glycolide. The monomer A is particularly preferably a monomer selected from lactic acid, glycolic acid, LA, and glycolide. The monomer B is particularly preferably a monomer selected from hydroxyvaleric acid, hydroxycaproic acid, valerolactone, and CL.
The filament for 3D printer preferably contains the above-described random polymer in an amount of 50% by mass or more and 100% by mass or less with respect to 100% by mass of the filament. By setting the amount of the random polymer in the range above, a filament having excellent flexibility and biodegradability can be obtained.
The elastic modulus of the filament for 3D printer is preferably 2.0 or more and 100.0 MPa or less. From the viewpoint of setting the flexibility of the filament in a suitable range, the elastic modulus of the filament is more preferably 50.0 MPa or less, still more preferably 35.0 MPa or less, particularly preferably 20.0 MPa or less, and most preferably 10.0 MPa or less. On the other hand, from the viewpoint of the printability of the filament, the elastic modulus of the filament is preferably 3.0 MPa or more, more preferably 3.5 MPa or more, and still more preferably 4.0 MPa or more. The elastic modulus of the filament can be determined by Measurement Example 1 described later. The elastic modulus of the filament can be controlled in a suitable range by adjusting the crystallization degree of the monomer, the R-value, or the weight average molecular weight of the biodegradable polyester or the content of the water-soluble polymer or the biodegradable polymer. For example, when the crystallization degree of the monomer of polyester is increased, the elastic modulus increases, and when the R-value is increased, the elastic modulus decreases. When the weight average molecular weight is increased, the elastic modulus increases. When the content of the water-soluble polymer or the biodegradable polymer is increased, the elastic modulus increases. By appropriately selecting the crystallization degree, the R-value, or the weight average molecular weight of the polyester monomer or the content of the water-soluble polymer or the biodegradable polymer as described above, the elastic modulus can be controlled in a suitable range, and a filament having excellent printability can be obtained.
The diameter of the filament for 3D printer is preferably 1.0 mm or more and 5.0 mm or less. In 3D printers, filaments having a diameter of 1.0 mm or more and 5.0 mm or less are suitably used. For 3D printer applications, the diameter of the filament is more preferably 1.5 mm or more and 3.5 mm or less, still more preferably 1.6 mm or more and 3.3 mm or less, and most preferably 1.7 mm or more and 3.0 mm or less. The diameter of the filament is the longest distance among the straight-line distances between optional two points on the circumference in the cross section of the filament cut perpendicular to the longitudinal direction. The longest distance among the straight-line distances between optional two points on the circumference in the cross section of the filament cut perpendicular to the longitudinal direction can be determined by measuring the straight-line distances between optional two points on the circumference a plurality of times using a digital caliper while the filament is rotated as appropriate in the circumferential direction without cutting the filament.
When the diameter of the filament is uniform in the longitudinal direction of the filament, the filament can be stably discharged from a nozzle. Thus, the variation coefficient of the diameter, which is an index of the uniformity of the diameter of the filament, is preferably 10% or less, more preferably 8% or less, still more preferably 5% or less, and most preferably 3% or less. Since the more uniform diameter of the filament is preferable, the lower limit of the variation coefficient of the diameter of the filament is not particularly determined, and is preferably 0% or more from the viewpoint of practicality. A value obtained by rounding off the first decimal place is used for the variation coefficient. Therefore, for example, when the variation coefficient is 0.1% it is described as 0%. The variation coefficient of the diameter of the filament can be calculated by the method described in Measurement Example 2 described later.
The recovery rate of the filament for 3D printer is preferably 50% or more. To set the flexibility in a suitable range, the recovery rate of the filament is more preferably 60% or more and still more preferably 70% or more. The recovery rate of the filament can be measured according to the method specified in JIS K7161 (2014), and more specifically can be measured according to Measurement Example 3 described later. Since the higher recovery rate of the filament is preferable, the upper limit is 100%. However, from the viewpoint of practical producibility, the recovery rate is preferably 100% or less. Our method uses a value obtained by rounding off the first decimal place for the recovery rate. Thus, for example, when the recovery rate is 99.9% it is described as 100%.
Our method is the filament for 3D printer. The 3D printer is a device that prints a three-dimensional object by stacking resin or metal layer by layer based on three-dimensional data, and includes methods such as a fused deposition modeling method, a stereolithography method (SLA method or DLP method), an inkjet method, a powder sintering method (SLS method or SLM method), and a powder fixing method. The filament can be particularly suitably used for an application as a fused deposition modeling 3D printer.
As described above, the filament as disclosed herein is suitably used for 3D printer applications. The use of the filament for 3D printer can produce molded bodies. More specifically, a molded body can be produced through the following steps using the filament for 3D printer. In other words, a method of producing a molded body as disclosed herein is a method including the following steps:
In step 1, to melt the filament for 3D printer, the temperature of the nozzle part is preferably set to 50° C. or more and 300° C. or less, more preferably set to 75° C. or more and 280° C. or less, and still more preferably set to 100° C. or more and 250° C. or less.
The molded body refers to an object molded into any of various shapes according to the purpose by conventional methods. For example, the shapes include film-like bodies (membranes, films, and sheets), plate-like bodies (boards), rod-like bodies (rods), cylindrical bodies (pipes and tubes), thread-like bodies (filaments), net-like bodies (meshes), bag-like bodies, woven fabric or non-woven fabric and the like; and a complex shape combining the shapes above may also be acceptable. A medical molded body is the above-described molded body used for medical applications. The medical applications include, but are not limited to, sutures, artificial bones, artificial skin, wound dressings, stents, DDS carriers, microneedles, scaffolding materials for regenerating tissues or organs and the like. The filament can be suitably used for producing medical molded bodies.
Our method is described in detail with reference to Examples and Comparative Examples, but is not limited thereto.
The filament was cut into a length of 3 to 4 cm, and a tensile test was performed under the following conditions according to the method specified in JIS K7161 (2014) to measure the elastic modulus. The elastic modulus of the filament was determined by measuring the elastic modulus three times and calculating the number-average value thereof. For the elastic modulus, a value obtained by rounding off the second decimal place was used.
The diameters of optional ten locations of the filament were measured using a digital caliper, the average value thereof was determined, and a value obtained by rounding off the second decimal place was used as the diameter of the filament. The variation coefficient of the diameter was determined from Equation (2) below by calculating the standard deviation (sample standard deviation) of the diameters of the ten locations. For the variation coefficient, a value obtained by rounding off the first decimal place was used.
The filament was cut into a length of 3 to 4 cm, and a tensile test was performed under the following conditions according to the method specified in JIS K7161 (2014) to measure the recovery rate. The recovery rate was calculated from the following equation by repeating 90 mm stretching 30 times. The recovery rate of the filament was determined by measuring the recovery rate three times and calculating the average value thereof. For the filament broken during the stretching, “-” is indicated in the table.
When a marked line was attached to test pieces, two marked lines were attached to the test pieces using appropriate markers. When the marked lines were attached, the test piece was not subjected to tension, and then the lines were accurately and clearly attached at right angles to parallel parts of the test piece and equidistant from the center of the test piece.
More specifically, the test piece was stretched by 90 mm at a tensile speed of 500 mm/min to cause a tensile strain (operation 1). Immediately after the operation 1 (i.e., the shape retention time was set to 0 second), the tensile strain was relaxed at a rate of 500 mm/min, and the distance between the grippers was returned to 10 mm (operation 2). Immediately after the operation 2 (i.e., the shape retention time was set to 0 second), the above-described operations 1 and 2 were performed again. The operations 1 and 2 above were repeated to perform 30 times in total. Thereafter, the recovery rate was determined from Equation (3) below using the obtained L1 and L2 values. For the recovery rate, a value obtained by rounding off the first decimal place was used.
Purified polyhydroxycarboxylic acid was dissolved in heavy chloroform, 1H-NMR was measured to calculate the mole fraction (%) of the monomer residue in the polyhydroxycarboxylic acid.
When the polyhydroxycarboxylic acid had two kinds of hydroxycarboxylic acid monomers as the main constituent unit, the two kinds of hydroxycarboxylic acid monomers were individually referred to as the “monomer A” and the “monomer B”, and the mole fractions (%) of the monomer A residue and the monomer B residue were individually calculated. As necessary, for the peaks of the monomer A and the monomer B, each peak area was quantified by decoupling by a signal, in which adjacent monomer residues are derived from the monomer A or the monomer B, by 1H homo-spin decoupling method. [AB] was calculated from the peak area ratio thereof, and the R-value was calculated from Equation (1) below.
Herein, [AB] is the mole fraction (%) of the structure (A-B and B-A) in which the monomer A residue and the monomer B residue are adjacent to each other in the polyhydroxycarboxylic acid, and is specifically the ratio of the number of A-B and B-A to the total number of A-A, A-B, B-A, and B-B.
For example, when the monomer A is LA and the monomer B is CL, the peak area was quantified for each of a methine group of LA (around 5.10 ppm), an α-methylene group of CL (around 2.35 ppm), and an & methylene group (around 4.10 ppm) by decoupling by a signal, in which adjacent monomer residues are derived from LA or CL, by the 1H homo-spin decoupling. Equipment name: JNM-ECZ400R (manufactured by JEOL Ltd.)
The evaluation was performed using a fused deposition modeling 3D printer having a temperature-controllable nozzle part. Specifically, a cube having each side of 1 cm was produced by repeating discharging a resin composition constituting a melted filament while the nozzle part of the 3D printer was horizontally moved, to form a layer, and stacking the resin composition to form a layer.
At that time, the printability of the filament capable of providing a fine cube having a height of 0.8 cm or more was evaluated as “good”; the printability of the filament providing a cube having a height of 0.8 cm or more but having slight defects was evaluated as “somewhat good”; and the printability of the filament which did not fall under either “Good” or “Somewhat good” due to poor stacking or the like of the resin composition due to clogging or the like was evaluated as “Poor”.
The measurement was performed according to the method specified in JIS K6950 (2000). Specifically, an inorganic salt solution (300 mL), activated sludge (9 mg), and the filament (30 mg) were added to a culture bottle, and the mixture was stirred at 25° C. for 90 days. At that time, the biodegradation degree was calculated according to Equation (4) below based on the oxygen consumption amount, and those having the biodegradation degree of 60% or more were determined to have biodegradability.
Herein, the method of evaluating the biodegradability of the filament is described, but a method of evaluating the biodegradability of the polymer was also performed by a similar procedure.
1 g of the polymer was added into 100 ml of water warmed to 37ºC, and the resultant was stirred for 3 hours. When it was visually confirmed that the polymer was dissolved, the polymer was determined to have water-solubility.
The polyester or the biodegradable polymer was dissolved in chloroform such that the concentration was 5% by mass, and the solution was transferred onto a polytetrafluoroethylene (PTFE) petri dish and dried at normal pressure and room temperature for twenty-four hours. The resultant was dried under reduced pressure at 50° C. for twenty-four hours to obtain a film having a thickness of about 100 μm.
The obtained film (about 10 mg) was collected in an alumina PAN, and the DSC measurement was performed under the following conditions. Then, the crystallization degree was calculated from the measurement results under the temperature conditions (D) to (E) using Equations (5) and (6) below.
Herein, the heat of fusion per unit mass of the homopolymer was determined as follows. The homopolymer was dissolved in chloroform such that the concentration was 5% by mass, and the solution was transferred onto a PTFE petri dish and dried at normal pressure and room temperature for twenty-four hours. The resultant was dried under reduced pressure to obtain a film. The obtained film was collected in an alumina PAN, and the DSC measurement was performed under the following conditions. Then, the heat of fusion was read from the fusion peak area of a graph obtained from the measurement results under the temperature conditions (D) to (E)
The biodegradable polymer was dissolved in chloroform such that the concentration was 5% by mass, and the solution was transferred onto a PTFE petri dish and dried at normal pressure and room temperature for twenty-four hours. The resultant was dried under reduced pressure at 50° C. for twenty-four hours to obtain a film having a thickness of about 100 μm.
The obtained biodegradable polymer film (thickness of about 100 μm) was cut into strips (50 mm×5 mm), and WAXS measurement was performed under the following conditions. The obtained data were analyzed as follows to determine the crystallization degree of the biodegradable polymer.
A graph, in which 20 is plotted on the horizontal axis and the scattering intensity is plotted on the vertical axis, was created from the obtained scattering images. For images in which orientation was observed, the graph was created including a part having the highest intensity. The obtained graph was subjected to a fitting analysis, and the peaks were divided into the peak derived from the crystalline structure and the peak derived from the amorphous structure. The total sum of the areas of the peaks derived from the crystal structure to the total sum of the areas of the peaks derived from the crystal structure and the amorphous structure was defined as the crystallization degree.
The biodegradable polyester, the water-soluble polymer, or the biodegradable polymer was dissolved in chloroform, caused to pass through a 0.45 μm syringe filter (DISMIC-13HP; manufactured by ADVANTEC) to remove impurities, and then subjected to GPC measurement under the following conditions, thereby calculating the weight average molecular weight of the biodegradable polyester, the water-soluble polymer, or the biodegradable polymer.
The water-soluble polymer was dissolved in chloroform (The solvent may be changed as appropriate when the water-soluble polymer was not dissolved in chloroform.) such that the concentration reached 5% by mass, and the solution was transferred onto a PTFE petri dish and dried at normal pressure and room temperature for twenty-four hours. The resultant was dried for twenty-four hours to obtain a film having a thickness of about 100 μm.
The obtained film (about 10 mg) was collected in an alumina PAN, and the DSC measurement was performed under the following conditions. Then, the temperature at which the fusion peak was observed was defined as the melting point from the measurement results under the temperature conditions (D) to (E).
50.0 g of L,L-dilactide (“PURASORB” (registered trademark) L; manufactured by PURAC) and 39.6 g of ε-caprolactone (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) as monomers and 0.45 g of hydroxy pivalic acid as an initiator were collected in a separable flask. These substances were placed under an argon atmosphere, 0.27 g of tin (II) octylate (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) as a catalyst dissolved in 3.0 mL of toluene (super dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) was added thereto, and the mixture was reacted at 130° C. for 9.5 hours to obtain a coarse copolymer. The obtained coarse copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirring state to obtain a precipitate. The precipitate was dried under reduced pressure at 50° C. to give a macromer.
50 g of the macromer, 2.1 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (synthetic product) as a catalyst, and 0.80 g of 4,4-dimethylaminopyridine (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) were collected. These substances were placed under an argon atmosphere, dissolved in 200 mL of dichloromethane (dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.), and added with 1.7 mL of diisopropylcarbodiimide (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) as a condensing agent, followed by condensation polymerization at room temperature overnight.
The reaction mixture was diluted with 220 mL of chloroform, 470 mL of 0.5 mol/L hydrochloric acid was added to the resultant mixture, followed by stirring for 30 minutes, and the aqueous layer was removed by decantation. Thereafter, a step of adding 470 mL of ion-exchanged water, stirring the mixture for 10 minutes, and removing the aqueous layer by decantation was repeated until the pH of the removed aqueous layer reached 7. The remaining organic layer was added dropwise to 3000 mL of methanol in a stirring state to obtain a precipitate. This precipitate was dried under reduced pressure at 50° C. to obtain polyester 1. Next, the polyester 1 was dissolved in 420 mL of chloroform, 1.9 g of PEG (manufactured by Sigma-Aldrich Production GmbH) was further dissolved therein, and then the resultant solution was added to 3000 mL of hexane in a stirring state to obtain a precipitate. This precipitate was dried under reduced pressure at 50° C. to give a composition.
The obtained composition was cut into 5 mm squares, charged into an extruder, and extruded such that the diameter of a filament was 1.8 mm to obtain a filament 1. The obtained filament 1 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
50.0 g of L,L-dilactide (“PURASORB” (registered trademark) L; manufactured by PURAC) and 39.6 g of ε-caprolactone (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) as monomers and 0.45 g of hydroxy pivalic acid as an initiator were collected in a separable flask. These substances were placed under an argon atmosphere, 0.27 g of tin (II) octylate (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) as a catalyst dissolved in 3.0 mL of toluene (super dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) was added thereto, and the resulting mixture was reacted at 140° C. for 9.5 hours to obtain a coarse copolymer. The obtained coarse copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirring state to obtain a precipitate. The precipitate was dried under reduced pressure at 50° C. to obtain a macromer.
50 g of the macromer, 2.1 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (synthetic product) as a catalyst, and 0.80 g of 4,4-dimethylaminopyridine (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) were collected. These substances were placed under an argon atmosphere, dissolved in 200 mL of dichloromethane (dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.), and added with 1.7 mL of diisopropylcarbodiimide (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) as a condensing agent, followed by condensation polymerization at room temperature overnight.
The reaction mixture was diluted with 220 mL of chloroform, 470 mL of 0.5 mol/L hydrochloric acid was added to the resultant mixture, followed by stirring for 30 minutes, and the aqueous layer was removed by decantation. Thereafter, a step of adding 470 mL of ion-exchanged water, stirring the mixture for 10 minutes, and removing the aqueous layer by decantation was repeated until the pH of the removed aqueous layer reached 7. The remaining organic layer was added dropwise to 3000 mL of methanol in a stirring state to obtain a precipitate. This precipitate was dried under reduced pressure at 50° C. to obtain polyester 2.
The obtained polyester 2 was cut into 5 mm squares, and then coated with PEG (manufactured by Sigma-Aldrich Production GmbH) crushed using a mortar and a pestle to obtain a composition. The composition was charged into an extruder and extruded such that the diameter of the filament was 1.8 mm to obtain a filament 2. The obtained filament 2 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
Polyester 3 was obtained by performing operations in the same manner as in Example 1, except that the reaction temperature for obtaining a coarse copolymer was changed to 140° C., and then a filament 3 was obtained by performing operations in the same manner as in Example 1, except that the amount of PEG was changed to 2.5 g. The obtained filament 3 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
Polyester 4 was obtained by performing operations in the same manner as in Example 1, except that the amount of toluene was changed to 4.2 mL, the reaction temperature for obtaining a coarse copolymer was changed to 150° C., the amount of 4,4-dimethylaminopyridinium p-toluenesulfonate was changed to 1.8 g, the amount of 4,4-dimethylaminopyridine was changed to 0.60 g, and the amount of diisopropylcarbodiimide was changed to 1.5 mL, and then a filament 4 was obtained by performing operations in the same manner as in Example 1, except that the amount of PEG was changed to 2.3 g. The obtained filament 4 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 5 was obtained by performing operations in the same manner as in Example 1, except that 2.1 g of PLA (manufactured by Nature3D) was dissolved in place of 1.9 g of PEG. The obtained filament 5 was subjected to the measurements described in Measurement Examples 1 to 6 and 8 to 10. The results are shown in Table 1.
A filament 6 was obtained by performing operations in the same manner as in Example 1, except that 5.6 g of PLA (manufactured by Nature3D) was dissolved in place of 1.9 g of PEG. The obtained filament 6 was subjected to the measurements described in Measurement Examples 1 to 6 and 8 to 10. The results are shown in Table 1.
A filament 7 was obtained by performing operations in the same manner as in Example 1, except that 12.5 g of PLA (manufactured by Nature3D) was dissolved in place of 1.9 g of PEG. The obtained filament 7 was subjected to the measurements described in Measurement Examples 1 to 6 and 8 to 10. The results are shown in Table 1.
A filament 8 was obtained by performing operations in the same manner as in Example 1, except that 21.4 g of PLA (manufactured by Nature3D) was dissolved in place of 1.9 g of PEG. The obtained filament 8 was subjected to the measurements described in Measurement Examples 1 to 6 and 8 to 10. The results are shown in Table 1.
A filament 9 was obtained by performing operations in the same manner as in Example 1, except that 2.1 g of PCL (manufactured by Nature3D) was dissolved in place of 1.9 g of PEG. The obtained filament 9 was subjected to the measurements described in Measurement Examples 1 to 6 and 8 to 10. The results are shown in Table 1.
A filament 10 was obtained by performing operations in the same manner as in Example 1, except that 1.1 g of PBS (manufactured by Nature3D) was dissolved in place of 1.9 g of PEG. The obtained filament 10 was subjected to the measurements described in Measurement Examples 1 to 6 and 8 to 10. The results are shown in Table 1.
A filament 11 was obtained by performing operations in the same manner as in Example 1, except that 21.4 g of PLA (manufactured by Nature3D) was dissolved in place of 1.9 g of PEG and the resultant substance was extruded such that the diameter of the filament was 2.9 mm. The obtained filament 11 was subjected to the measurements described in Measurement Examples 1 to 6 and 8 to 10. The results are shown in Table 1.
Polyester 5 was obtained by performing operations in the same manner as in Example 1, except that the amount of hydroxypivalic acid was changed to 0.34 g and the reaction temperature for obtaining a coarse copolymer was changed to 140° C., and then a filament 12 was obtained by performing operations in the same manner as in Example 1, except that the amount of PEG was changed to 4.5 g. The obtained filament 12 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
Polyester 6 was obtained by performing operations in the same manner as in Example 1, except that the amount of hydroxypivalic acid was changed to 0.38 g and the reaction temperature for obtaining a coarse copolymer was changed to 150° C., and then a filament 13 was obtained by performing operations in the same manner as in Example 1, except that the amount of PEG was changed to 2.0 g. The obtained filament 13 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 14 was obtained by performing operations in the same manner as in Example 1, except that 2.5 g of PVP (manufactured by Tokyo Chemical Industry Co., Ltd.) was dissolved in place of 1.9 g of PEG. The obtained filament 14 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 15 was obtained by performing operations in the same manner as in Example 2, except that PVA (manufactured by Sigma-Aldrich Production GmbH) was used in place of PEG (manufactured by Sigma-Aldrich Production GmbH). The obtained filament 15 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 16 was obtained by performing operations in the same manner as in Example 1, except that the amount of PEG was changed to 7.5 g. The obtained filament 16 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 17 was obtained by performing operations in the same manner as in Example 1, except that the amount of PEG was changed to 16.1 g. The obtained filament 17 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 18 was obtained by performing operations in the same manner as in Example 1, except that the polyester 5 was used in place of the polyester 1 and the amount of PEG was changed to 10.0 g. The obtained filament 18 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 19 was obtained by performing operations in the same manner as in Example 2, except that the resultant substance was extruded such that the diameter of the filament to be obtained was 2.9 mm. The obtained filament 19 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
A filament 20 was obtained by charging PLA pellets (manufactured by Nature3D) into an extruder and extruding the pellets such that the diameter of the filament was 1.8 mm. The obtained filament 20 was subjected to the measurements described in Measurement Examples 1, 2, 5, 6 and 10. The results are shown in Table 1.
A filament 21 was obtained by cutting the polyester 1 into 5 mm squares, charging the cut polyester into an extruder, and extruded such that the diameter of the filament was 1.8 mm. The obtained filament 21 was subjected to the measurements described in Measurement Examples 1 to 6, 8, and 10. The results are shown in Table 1.
A filament 22 was obtained by performing operations in the same manner as in Example 1, except that 2.5 g of PEG (manufactured by Fujifilm Wako Pure Chemical Industries Ltd.) was used in place of 1.9 g of PEG (manufactured by Sigma-Aldrich Production GmbH). The obtained filament 22 was subjected to the measurements described in Measurement Examples 1 to 8, 10, and 11. The results are shown in Table 1.
In the table, the “Presence or absence of biodegradability” means the evaluation result of the presence or absence of biodegradability of each of the filaments.
In the table, “-” in the “Recovery rate” means that the filament was broken in the measurement.
In the table, [A] means the mole fraction (%) of the monomer A residue in the polyhydroxycarboxylic acid, [B] means the mole fraction (%) of the monomer B residue in the polyhydroxycarboxylic acid, and [AB] means the mole fraction (%) of the structure (A-B and B-A) in which the monomer A residue and the monomer B residue are adjacent to each other in the polyhydroxycarboxylic acid.
In the table, the “Polyester” means the polyhydroxycarboxylic acid with the R-value of 0.45 or more and 0.99 or less, i.e., random polymer.
In the table, the “Biodegradable polymer” means the biodegradable polymer, which does not fall under the biodegradable polyester.
Our filament is considered to be utilized to form molded bodies having shapes such as film-like bodies (membranes, films, and sheets), plate-like bodies (boards), rod-like bodies (rods), cylindrical bodies (pipes and tubes), thread-like bodies (filaments), net-like bodies (meshes), bag-like bodies, woven fabric or non-woven fabric and the like, and complex shapes combining the shapes above. In particular, medical applications include, but are not limited to, sutures, artificial bones, artificial skin, wound dressings, stents, DDS carriers, microneedles, scaffolding materials for regenerating tissues or organs and the like.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2021-164555 | Oct 2021 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2022/036701 | 9/30/2022 | WO |
