WO2013005914A1

WO2013005914A1 - Biodegradable polymer for fixing bones in which chemically-treated nano-carbons are added

Info

Publication number: WO2013005914A1
Application number: PCT/KR2012/003202
Authority: WO
Inventors: 박종순; 김오진; 허수학; 정혜경
Original assignee: (주)글로텍
Priority date: 2011-07-06
Filing date: 2012-04-26
Publication date: 2013-01-10
Also published as: KR20130005389A

Abstract

The present invention relates to a material with enhanced biodegradability for fixing bones, and more specifically to a novel material in which physiochemical properties are remarkably improved by using polylactic acid, which is one of the existing biodegradable polymer materials widely used for fixing bones, as a main material, and adding nano-carbons in which the end is substituted.

Description

Biodegradable polymer for bone fixation with chemically treated nano carbon

The present invention relates to a material for fixing bones with improved biocompatibility, and more specifically, to the end of the nano-substituted nano-carbon substituted with polylactic acid, which is one of the biocompatible bone fixing polymer materials widely used. The present invention relates to a novel material which significantly improves physicochemical properties.

Polylactic acid (PLA) is a biodegradable and biocompatible thermoplastic polyester that is one of the materials with great potential to replace petrochemical polymers. In particular, it exhibits excellent thermal processing properties compared to other biopolymers such as polyethylene glycol and polycaprolactone. In particular, the FDA-approved material that can be used for direct contact with the physiological fluids of the human body is used for many purposes, but bioabsorbable plates and screws, which replace the metal plates and screws used for bone bonding, are also increasingly used. .

Bone fixation implants (implants) are used to fix bones or bones on the face, skull or other parts of the human body when they are fractured or fused.They consist of plates and screws. Three types of materials are used: metal, ceramic and organic polymers. have. In terms of material characteristics, metallic materials have excellent mechanical properties such as tensile strength and compressive strength, and are easily processed to desired shapes such as cutting, grinding, and forming, and are relatively stable to chemical reactions. However, in the case of a child in the growth phase, the metal material is firmly coupled to inhibit the growth of bone tissue, even in adults, there is a disadvantage that may be damaged by partial corrosion when mounted in the body for a long time.

Ceramic material is a material having a very high affinity for bone, but has a disadvantage of low impact strength, and it is difficult to cope with shape deformation and bone recovery since it is impossible to be deformed after manufacturing. Polymer material has excellent impact strength and high structure. Polylactide (poly- [L-lactide] and poly- [L / DL-lactide]; PLA), polyglycolide (PGA), polycaprolacton (polycaprolacton) with advantages such as affinity and ease of processing PCL), polydioxanone, and the like have been developed and used in a single or mixed form.

However, the strength and robustness required to support the bones are significantly smaller than those of metals and ceramics.In the case of screws, the screws of the screws are clumped or the heads are frequently broken during fixation using tools such as a screwdriver. Careful attention is required, and in particular, such biodegradable polymers undergo a process of being converted into an acidic substance in the body's decomposition process, which remains a problem that it involves bone damage and inflammation.

Generally, self-reinforcing and solid-state extrusion are known as methods for increasing the strength of polymer materials, but products having satisfactory strength by these methods alone have not been known.

In addition, US Pat. No. 4,781,183 uses hydroxyapatite as a biodegradable inorganic ceramic material as a polylactide and a reinforcing agent to add hydroxyapatite particles to the final stage of melt polymerization of polylactide. A method of making a composite material is known, and another method is known by using a method of melt blending, mixing, and mixing a polymer and a biodegradable inorganic ceramic material. However, in the above methods, the bioabsorbable polymers have a sudden decrease in molecular weight in the molten or solution state, so that the desired mechanical strength cannot be obtained. In order to obtain the reinforcing effect by mixing inorganic particles such as ceramics, the particle size should be good in dispersibility. While the specific gravity is different and the polymer is melted by heat, the inorganic particles are not melted even when heated, and simply stick to the surface of the polymer, so that simple mixing alone does not obtain uniform dispersibility.

Therefore, most of the researches combining the ceramic materials and organic polymers that have been made up to now have problems in simple mixing of ceramic particles and biodegradable polymers or using them as bone bonding materials at the level of impregnation of biodegradable polymers between ceramic fibers. Remains.

In addition, US Patent No. 4,655, 777 discloses a method of laminating an organic ceramic material in a fibrous form, followed by lamination with an organic polymer, or solution coating. However, this method is complicated, time-consuming, and it is difficult to decompose microbubbles with high viscosity due to the concern of contamination and decomposition due to exposure to air in a warm state, and thus it is difficult to expect effectiveness in improving strength.

The present invention has been made to solve the problems of the prior art as described above to improve the tensile and flexural strength by adding nanoparticles having excellent dispersibility to reduce the screw thread damage and screw head damage and biodegradable polymer in the body The present invention relates to a method for manufacturing a bone fixation material which minimizes side effects such as corrosion and inflammation of bone caused by acid by lowering acidity which is increased when decomposed in the present invention.

In order to achieve the above object, a catalyst and a residual metal are generally used to disperse biodegradable organic polymer materials such as polylactide and to align the biocompatible nanocarbon particles at regular intervals between the polymer materials. To the flake or granular polylactide, which is contained in the medical grade, which is significantly less contained, nanocarbon particles whose ends are substituted with amines, amides, etc. are added in a weight ratio of 0.1 to 10%, mixed by a mixer, etc. at a predetermined temperature, and introduced into an extruder. The product is pelletized by cold cutting through heating, kneading and extrusion. In addition, the obtained pellets are introduced into an injection molding machine to produce a product having a predetermined shape.

The biodegradable organic polymer is polyglycolide, poly [D-lactide], poly [L-lactide], polycaprolactone, polyesteramide, poly, already known as a medical biocompatible material. Oxalate copolymer (copoly-oxalate), polycarbonate, polyglutamic acid (poly [glutamic-co-leucine]) and a copolymer (copolymer) prepared by blending two or more of the above polymers It is preferable that it is any one chosen from the aliphatic polyester group, and average molecular weight is 150,000-300,000.

The nanocarbon particles whose terminals are substituted with amines or amides are oxidized to a purified nanodiamond obtained by a commercial explosion method with a solution of sulfuric acid and nitric acid (volume ratio 3: 1), and dried to obtain tetrahydrofuran (THF). And the powder obtained by reduction with Lithium aluminum hydride was added and stirred in an ultrasonic water bath to give a solution obtained by tetrahydrofuran (THF) and phthalimide diethylazodicarboxylate (DEAD). Nanodiamond substituted with amine by treatment with trifluoracetic acid is obtained. In addition, in the case of using amidated nanodiamonds, nanodiamonds substituted with amines are treated with ethylenediamine solution to use amidated powders.

When mixing the above polymer and nanocarbon particles, first weigh each of the weights, put them in a mixer such as a ball mill or a colorator, and run them for a certain time so that the nanocarbon particles can be evenly distributed on the surface of the polymer. The extrusion is carried out by heating to a melting temperature range of. At this time, in order to improve the strength and orientation of the polymer, it is preferable to draw 2 to 20 times in the cooling process before cutting into pellets. After the injection process is the same as the injection of the normal thermoplastic, but it is preferable to be less damaged by heat.

The present invention is a method for easily preparing a material used for bonding bone tissue by mixing and dispersing nano-carbon particles in a biodegradable organic polymer by extrusion molding, wherein the nano-carbon terminal is substituted with radicals such as amines and amides. By using diamond, the dispersibility is excellent, so that the mechanical strength is significantly increased, and the damaged bone tissue can be combined, and the effect of reducing acid damage when decomposing in the body can be reduced. have.

The specific contents for carrying out the present invention are not limited to the examples. In the case of commercially available polylactide, polylactide (poly [D-lactide]) and polylactide (poly [L-lactide]) are mixed or existed alone, and products mixed with polyglycolide are also sold. The present embodiment reveals that it is possible to use other raw materials, but the raw materials easily purchased are used.

Oxidized commercially available nanodiamond powder (average particle size 4 nm) in 100 g of polylactic acid (poly [L-lactide]) with biodegradable organic polymer in solution of sulfuric acid and nitric acid (volume ratio 3: 1) in an ultrasonic water bath. The powder obtained by drying the solution obtained by reducing the powder with tetrahydrofuran (THF) and lithium aluminum hydride was dried, and then stirred in an ultrasonic water bath. Obtained by reaction with a solution of tetrahydrofuran (THF) and phthalimide diethylazodicarboxylate (DEAD), the powder is treated with trifluoracetic acid and the terminal is substituted with an amine. After adding and stirring 1 g of nanodiamond, the mixture was put in a test extruder and heated and kneaded to prepare a bone fixing material.

The amount of nanocarbon added to 100 g of biodegradable organic polymer, 0.1 g, 0.5 g, 5 g, and 10 g, was mixed and stirred, and prepared by heating, kneading and extruding in a test extruder.

Table 1

	Biodegradable Organic Polymer	Nanocarbon
Example 2	100 g	0.1g
Example 3	100 g	0.5g
Example 4	100 g	5 g
Example 5	100 g	10 g

The physical properties of the prepared bone fixing material are shown in Table 2.

TABLE 2

	Diameter (mm)	Extension ratio (times)	The tensile strength	Flexural strength
Example 1	1.35	7.4	69	97.8
Example 2	1.33	7.5	67	95.1
Example 3	1.36	7.35	68.6	98
Example 4	1.38	7.24	70.1	99.5
Example 5	1.4	7.14	67.2	95.4

For reference, physical properties of polylactide (Comparative Example 1) without nanocarbon particles, polylactide with hydroxyapatite (Comparative Example 2), and polylactide with tricalcium phosphate added (Comparative Example 3) The test results are shown in Table 3.

TABLE 3

	Diameter (mm)	Extension ratio (times)	Tensile Strength (MPa)	Flexural Strength (MPa)
Comparative Example 1	1.45	6.89	64.5	90.9
Comparative Example 2	1.53	6.53	64.2	90.8
Comparative Example 3	1.52	6.57	64.1	90.7

As described above, as a method for compensating for the disadvantages of the biodegradable organic polymer, there have been various attempts such as adding hydroxyapatite or calcium phosphate, which is a bone-like material, but it has a deterioration in terms of mechanical strength. On the contrary, it was found that addition of nanocarbon substituted with an amine or amide group having excellent dispersibility as in the present invention resulted in an increase in strength. As is known, amine or amide radicals can neutralize lactide as a weak base. It has the advantage of lowering the acidity generated when polylactide is decomposed. Thus, polylactide prepared by adding nanocarbons substituted with amines or amides is a bone fixation material having biodegradability different from conventional materials.

Claims

Nanocarbon particles whose ends are substituted with amines or amides in biodegradable organic polymers are mixed at a constant temperature, and then put in an extruder, followed by stretching and cooling through heat kneading and extrusion to manufacture pellet-shaped products, and injection molding them into desired shapes. To mold materials for fixation of bones
The biodegradable organic polymer according to claim 1 is a polyglycolide, poly [l-lactide], poly [l-lactide], polycaprolactone, poly, already known as a medical biocompatible material. Esteramides, polyoxalate copolymers, polycarbonates, polyglutamic acid and polyleucine copolymers (poly [glutamic-co-leucine]) and blends or copolymers prepared by mixing two or more of the above polymers ( It is any one selected from aliphatic polyester group consisting of a copolymer) characterized in that the average molecular weight is 150,000 ~ 300,000.
The powder obtained by oxidizing and drying the purified nanodiamond obtained by a commercially available explosive method with a solution of sulfuric acid and nitric acid (volume ratio 3: 1) and drying the tetrahydrofuran according to claim 1. Tetrahydrofuran (THF) and powder obtained by reduction with lithium aluminum hydride (Lithium aluminum hydride) were added to the solution obtained by stirring in an ultrasonic water bath. Treatment of powder obtained by reaction with dicarboxylate (DEAD) solution with trifluoracetic acid (trifluoracetic acid) substituted with amine-substituted nanodiamonds or those treated with ethylenediamine solution and amidated How to feature.
The method of claim 1, wherein the amount of nanocarbon particles is 0.1 to 10% by weight relative to the biodegradable organic polymer.
The method according to claim 1, characterized in that it has an elongation of 2 to 20 times during extrusion stretching.