KR20200008225A - Biomedical implants comprising surface-modified basic ceramic particles and biodegradable polymers, and preparation method thereof - Google Patents

Abstract

The present invention relates to a biomedical implant comprising biodegradable polymers and surface-modified basic ceramic particles, or a method for manufacturing the same. The biomedical implant according to one aspect includes biodegradable polymers of different lengths, thereby having high dispersibility, and high safety properties, and has improved mechanical properties by thermal processing. In addition, inflammatory reactions, cytotoxicity, and tissue necrosis problems caused by acidic byproducts produced during the degradation of the biodegradable polymers can be suppressed.

Description

Biomedical implants comprising surface-modified basic ceramic particles and biodegradable polymers, and preparation method

The present invention relates to a bio-implant comprising a surface-modified basic ceramic particles and a biodegradable polymer and a method for producing the same.

A stent is a tube structure of a net that can be applied to most coronary body organs such as blood vessels, esophagus, bile ducts, etc. and uses a catheter to reduce the narrowing of the coronary organs to smooth the flow of internal contents. It is a medical device. Previously, metal stents remained permanent in the human body, causing inflammation or causing other diseases such as late thrombosis, which required additional removal surgery. In order to solve this problem, natural or synthetic polymers having biodegradability have been used, and biodegradable natural polymers have advantages of not using fossil fuels as raw materials and improving physical properties by increasing molecular weight, but using biosynthetic methods. Because of its high production cost, it has limitations in commercialization. Therefore, synthetic polymers, which are mostly non-toxic, have excellent mechanical properties and have a controlled biodegradability, are used. Therefore, researches on biodegradable synthetic polymer materials have been actively conducted, and among them, many studies have been conducted mainly on aliphatic polyesters having excellent physical and hydrolytic properties.

     In general, biodegradable polymers are widely used in implants for living organisms because of their ability to completely degrade after a certain time in vivo. However, these biodegradable polymers are relatively poor in physical properties compared to other general-purpose polymers. Acidic substances such as methylene glycol, amino acids, formalin, alkylcyanoacrylates, etc. are generated to cause inflammatory reactions and cytotoxicity problems in the human body.

In order to overcome these disadvantages, a technology (Korean Patent Application No. 10-2010-0091028) capable of fundamentally inhibiting acidic substances through the neutralizing effect of basic ceramic particles has been proposed. The basic ceramic particles are contained in a biodegradable polymer to inhibit the generation of acidic substances. The basic ceramic particles have a nano unit size in order to neutralize efficiency, mechanical properties, and usefulness for application and storage in a living implant. It is suitable. However, when applied to biodegradable polymers, there is a limit in improving mechanical properties due to aggregation of ceramic particles having hydrophilicity.

Accordingly, it is necessary to study the preparation of degradable implants having high dispersibility, high stability and high mechanical properties on the polymer matrix through surface modification of ceramic particles.

One aspect relates to a bio implant comprising a surface-modified basic ceramic particle and a biodegradable polymer, wherein the bio implant is characterized by high dispersibility, high stability, improved mechanical properties, and suppresses inflammatory response and cell necrosis. To provide.

One aspect provides a living implant comprising a biodegradable polymer and surface modified basic ceramic particles, wherein the surface modified basic ceramic particles are thermally processed after surface modification.

The bio-implant is prepared by surface modification of the basic ceramic particles with biodegradable polymers of different lengths and thermally processed to have high dispersibility and high stability, structural defects are suppressed, and mechanical properties are improved.

By containing the basic ceramic particles, the bio-implant can neutralize the acidic material generated when the biodegradable polymer material is decomposed, and can suppress inflammation and cell necrosis due to acidification of the biodegradable polymer.

As used herein, the term "surface modification" is to change the chemical structure and physical structure of the particle surface, in the present invention means that the structural change occurs by introducing various functional groups on the surface of the basic ceramic particles using a biodegradable polymer. do.

The basic ceramic particles are at least one metal particle selected from the group consisting of alkali metals, rare earth metals, alkaline earth metals, and rare earth earth metals, hydroxides of alkali metals, oxides of alkali metals, hydroxides of rare earth metals, oxides of rare earth metals, and alkalis. It may be at least one selected from the group consisting of a hydroxide of an earth metal, an oxide of an alkaline earth metal, a hydroxide of a rare earth earth metal, and an oxide of a rare earth earth metal. The alkali metal, alkaline earth metal, rare earth metal, or rare earth metal may be, for example, lithium (Li), berylnium (Be), sodium (Na), magnesium (Mg), potassium (K), calcium (Ca), or rubidium ( Rb), strontium (Sr), barium (Ba), cesium (Cs), cerium (Ce), francium (Fr), or radium (Ra). Oxides of the alkali metals, alkaline earth metals, rare earth metals, or rare earth metals or hydroxides of alkali metals, alkaline earth metals, rare earth metals, or rare earth metals are, for example, lithium hydroxide, beryllium hydroxide, sodium hydroxide, magnesium hydroxide, potassium hydroxide, calcium hydroxide, and the like. , Rubidium hydroxide, strontium hydroxide, barium hydroxide, cesium hydroxide, cerium hydroxide, francium hydroxide, radium hydroxide, magnesium oxide, sodium oxide, lithium oxide, sodium oxide, manganese oxide, potassium oxide, calcium oxide, barium oxide, cesium oxide, It may be one or more selected from the group consisting of cerium oxide and radium oxide, and more specifically, may be magnesium oxide or magnesium hydroxide, but is not limited thereto.

The size of the basic ceramic particles may be about 1 nm to 1 mm, but is not limited thereto. The surface area is changed according to the size of the basic ceramic particles, so that the characteristics of the neutralization degree and the neutralization rate of the ceramic particles may be changed. In addition, in order to modify the surface of the ceramic particles, the particle size should be at least 1 nm. If the size of the metal particles is greater than 1 mm, precipitation occurs due to the weight of the ceramic particles, causing cracking in the biodegradable polymer matrix. Can be reduced.

Depending on the size of the basic ceramic particles, the difference in solubility of the ceramic particles in the solvent may be used to adjust the neutralization rate of the living implant to 1 minute to 2 years or more.

As the content of the basic ceramic particles increases, the degree of neutralization and the rate of neutralization may increase.

The basic ceramic particles are lactide, glycolide, caprolactone, dioxanone, trimethylene carbonate, alkanoate hydroxide, peptide, cyanoacrylate, lactic acid, glycolic acid, caprohydric acid hydroxide, maleic acid, phosphazene, Polymers produced by the polymerization of one or more monomers selected from the group consisting of amino acids, butyric acid hydroxide, sebacic acid, ethoxyacetic acid hydroxide and trimethylene glycol, or polylactide, polyglycolide, polycaprolactone, Polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylenecarbonate, polyglycolide-co-dioxone, polyamide Ester, Polypeptide, Polyorthoester type, Polymaleic acid, Polyphosphazene, Polyanhydride, Polyseba anhydride , And poly hydroxide alkanoates, poly hydroxide butyrate and policies of one or more polymers selected from the group consisting of cyano acrylate may have been surface-modified.

The polymer may have a molecular weight in the range of about 1 to about 1,000 kDa, and the polymer modified to the basic ceramic particles may have different lengths.

The modified polymer has a different length on the surface of the basic ceramic particles, and has a wide range of molecular weight, the modified basic ceramic particles can have a high dispersibility, high stability properties on the biodegradable polymer matrix.

Surface modification of the basic ceramic particles may be performed according to a grafting from method or a grafting to method. In addition, the surface modification may be performed by ring-opening polymerization or condensation polymerization of monomers to form a biodegradable polymer.

The surface-modified basic ceramic particles may be heat processed after surface modification.

As used herein, the term “thermal processing” is one of polymer molding methods, and may refer to a processing method for effectively mixing a polymer in a molten state with an additive at a predetermined temperature or more. For example, compression molding, It may be one or more selected from injection molding, blow molding, thermoforming, rotation molding, and bag molding.

The surface-modified basic ceramic particles may be thermally processed to suppress interfacial separation between the basic ceramic particles and the biodegradable polymer and to improve mechanical properties.

As used herein, the term “biodegradable polymer” refers to a substance that can be degraded by body fluids or microorganisms in a living body.

As used herein, “biodegradable” may be used interchangeably with biocompatible.

The biodegradable polymer is polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone , Polytrimethylene carbonate, polyglycolide-co-dioxone, polyamide ester, polypeptide, polyol isoester type, polymaleic acid, polyphosphazene, polyanhydride, polycephaanhydride, polyhydroxide alkano It may be one or more selected from the group consisting of eight, polyhydroxybutyrate and polycyanoacrylate.

In the living implant, the surface-modified basic ceramic particles comprise about 1 to 60% by weight, about 2 to 55% by weight, about 3 to 50% by weight, and about 4 to 45% by weight relative to the total weight of the biodegradable polymer. %, About 5-40% by weight, or about 10-40% by weight. When the content of the basic ceramic particles with the modified surface is less than about 1% by weight relative to the total weight of the biodegradable polymer, the acid neutralization effect of the ceramic particles is insignificant, and when the content of the basic ceramic particles is greater than about 60% by weight, the mechanical properties of the biodegradable polymer matrix The proportion of reduced or modified biodegradable polymers may increase and affect the rate of degradation.

The bio-implant may be a cardiovascular material selected from stents, surgical sutures, tissue regeneration supports, bio nanofibers, hydrogels and bio sponges, dental materials selected from pins, screws, rods, and implants, and nerve / orthopedic It may be selected from the group consisting of plastic surgery implants.

Another aspect includes modifying the basic ceramic particle surface; Thermally processing the basic ceramic particles whose surface is modified; And it provides a method for producing a living implant comprising the step of mixing the thermally processed basic ceramic particles and biodegradable polymer.

The method may further comprise molding the living implant by performing injection, extrusion, thermoforming or compression after the mixing.

The modifying of the surface of the basic ceramic particles may be ring-opening polymerization or condensation polymerization of monomers on the surface of the basic ceramic particles.

The ring-opening polymerization is organometallic catalyst such as tin, aluminum, titanium, zinc, or tin octosan, dibutyl tin dilaurate, dibutyl tin dibromide, dibutyl tin dichloride, tin oxide, zinc powder, diethyl zinc, oxo It may be carried out using one or more catalysts selected from the group of zinc acid, zinc chloride and dodecylbenzenesulfonic acid. The catalyst may be included in an amount of about 0.001 to 5.0 parts by weight based on the total weight of the basic ceramic particles, and may react for about 1 to 72 hours at a reaction temperature of about 20 to 300 ° C., but is not limited thereto.

The condensation polymerization may be reacted for about 1 to 72 hours at a reaction temperature of about 20 to 300 ° C., but is not limited thereto.

The thermal processing may be performed at a reaction temperature of about 20 to 300 ^° C. for about 1 to 48 hours.

The step of thermal processing may also comprise an esterification reaction step.

In the mixing step, the biodegradable polymer may include about 1 to 60% by weight based on the total weight of the thermally processed basic ceramic particles.

The mixing step may vary depending on the amount to which the particles are added, but may preferably be performed for about 1 to about 10 minutes. If the mixing is less than 1 minute, the reaction may not be sufficient to produce a living implant, and if the mixing is greater than 10 minutes there is a possibility that the biodegradable polymer is degraded.

According to one aspect, a living implant includes biodegradable polymers having different lengths, has high dispersibility and high safety properties, and improves mechanical properties according to heat processing. In addition, it is possible to suppress inflammatory reactions, cytotoxicity, and tissue necrosis problems caused by acid byproducts produced during the degradation of biodegradable polymers.

1 is a graph confirming the pH neutralizing effect of a living implant according to one aspect.
Figure 2 is a graph confirming the cell survival rate by the treatment of a living implant according to one aspect.
Figure 3 is a graph confirming the inflammation inhibitory effect of the living implant according to one aspect.
4 is a result of measuring the mechanical modulus of a living implant according to one aspect.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following examples are only preferred examples of the present invention, and the present invention is not limited to the scope of these examples.

Example  One.

1.1 Surface Modification of Ceramic Particles

Surface modification of the ceramic particles was carried out by choosing between two methods.

In the first method (grafting from method), 80 parts by weight of magnesium hydroxide and 20 parts by weight of DL-lactide are mixed based on the total weight of the entire mixture, and as a catalyst to the total weight of the reactants (magnesium hydroxide and DL-lactide) 0.05 wt% of octosan tin was diluted in toluene and added. The glass reactor containing the reactants was maintained under vacuum at 70 ° C. for 6 hours with stirring to completely remove toluene and water. The sealed glass reactor was subjected to a ring-opening polymerization reaction for 48 hours with stirring in an oil bath adjusted to 150 ° C. The surface-modified magnesium hydroxide particles were prepared by placing the recovered polymer in a sufficient amount of chloroform to remove the homopolymer and unreacted residue for at least 1 hour.

In a second method (grafting to method), first, polymers having various molecular weights were prepared using monomers of respective polymers as follows. DL-lactide polymers having various molecular weights were synthesized by varying the molar ratio of initiator ([monomer] / [initiator] = 20, 50, 100, 200) to monomeric DL-lactide under the same catalyst amount under a nitrogen atmosphere. . Toluene, a solvent, was added thereto, stirred at 110 ° C. for 12 hours, and then the polymerization was stopped. After completion of the reaction, precipitated and stirred in methanol, and then separated from the solvent by vacuum filtration. The resulting polymer was vacuum dried for one day. Thereafter, poly-DL-lactide having a molecular weight of 1 to 100 kDa and magnesium hydroxide particles were put together in toluene, and stirred at 120 ° C. for 12 hours to proceed with the esterification reaction. The reaction product was then placed in chloroform and homogenized by centrifugation. The polymer and unreacted material were removed.

1.2 biome Implant  Produce

Biografts were prepared using surface-modified ceramic particles and biodegradable polymers, and were prepared by a thermal processing method that undergoes heating, mixing, and compression processes for uniform mixing of the particles.

Specifically, the bulk-degradable biodegradable material is mixed with 20 parts by weight of surface-modified magnesium hydroxide particles prepared as described above and 80 parts by weight of polycaprolactone having a molecular weight of 150 kDa in a thermal processing apparatus set to a temperature higher than the melting point of the biodegradable polymer. The polymer composite was extruded to prepare a living implant.

Example  2.

2.1 Surface Modification of Ceramic Particles

The first method of Example 1.1 was carried out except that ring-opening polymerization was used by mixing 70 parts by weight of magnesium hydroxide as ceramic particles, 15 parts by weight of DL-lactide and 15 parts by weight of glycolide as surface modifying materials. It was done in the same way.

2.2 biological Implant  Produce

In the same manner as in Example 1.2, except that 20 parts by weight of surface-modified magnesium hydroxide particles and 80 parts by weight of poly-DL-lactide-co-caprolactone (50:50) having a molecular weight of 200 kDa were used. Was performed.

Example  3.

3.1 Surface Modification of Ceramic Particles

Same as the first method of Example 1.1, except that 20 parts by weight of potassium hydroxide as a ceramic particle, 15 parts by weight of L-lactide and 5 parts by weight of caprolactone were mixed to use a ring-opening polymerization. It was performed by the method.

3.2 biome Implant  Produce

In the same manner as in Example 1.2, except that 20 parts by weight of surface-modified potassium hydroxide particles and 80 parts by weight of poly-DL-lactide-co-caprolactone (80:20) having a molecular weight of 250 kDa were used. Was performed.

Example  4.

4.1 Surface Modification of Ceramic Particles

Magnesium oxide was used as ceramic particles, and poly-DL-lactide having a molecular weight of 5 kDa was used as the surface modifying material, except that the second method of Example 1.1 was performed.

4.2 vivo Implant  Produce

The process was carried out in the same manner as in Example 1.2, except that 20 parts by weight of the surface-modified magnesium oxide particles and 80 parts by weight of the poly-L-lactide biodegradable polymer having a molecular weight of 200 kDa were used.

Example  5.

5.1 Surface Modification of Ceramic Particles

Magnesium oxide was used as ceramic particles and poly-L-lactide having a molecular weight of 10 kDa was used as the surface modifying material, except that the second method of Example 1.1 was used.

5.2 living bodies Implant  Produce

Example 1.2, except that 30 parts by weight of surface-modified magnesium oxide particles and 70 parts by weight of a poly-L-lactide-co-glycolide (75:25) biodegradable polymer having a molecular weight of 200 kDa were used. The same procedure was followed.

Example  6.

6.1 Surface Modification of Ceramic Particles

Second method of Example 1.1, except that cerium hydroxide was used as the ceramic particles and poly-L-lactide-co-caprolactone (75:25) having a molecular weight of 3 kDa was used as the surface modifying material. The same procedure was followed.

6.2 living bodies Implant  Produce

Example 1.2, except that 20 parts by weight of surface-modified cerium hydroxide particles and 80 parts by weight of poly-L-lactide-co-glycolide (50:50) biodegradable polymer having a molecular weight of 100 kDa were used. The same procedure was followed.

Example  7.

7.1 Surface Modification of Ceramic Particles

The second method of Example 1.1 was used except that calcium hydroxide was used as the ceramic particles and poly-L-lactide-co-caprolactone (50:50) having a molecular weight of 8 kDa was used as the surface modifying material. It was done in the same way.

7.2 living Implant  Produce

Same as Example 1.2, except that 20 parts by weight of surface-modified calcium hydroxide particles and 80 parts by weight of a poly-L-lactide-co-caprolactone (80:20) biodegradable polymer having a molecular weight of 150 kDa were used. It was performed by the method.

Example  8.

8.1 Surface Modification of Ceramic Particles

Magnesium hydroxide was used as the ceramic particles, and polycaprolactone having a molecular weight of 5 KDa was used as the surface modifying material, except that the second method of Example 1.1 was used.

8.2 biological Implant  Produce

The process was carried out in the same manner as in Example 1.2, except that 20 parts by weight of the surface-modified magnesium hydroxide particles and 80 parts by weight of the poly-DL-lactide biodegradable polymer having a molecular weight of 230 kDa were used.

Example  9.

9.1 Surface Modification of Ceramic Particles

Cerium hydroxide was used as the ceramic particles, and polycaprolactone having a molecular weight of 8 KDa was used as the surface modifying material, in the same manner as in the second method of Example 1.1.

9.2 biome Implant  Produce

Example 1.2 except that 20 parts by weight of the surface-modified cerium hydroxide particles and 80 parts by weight of a poly-L-lactide-co-caprolactone (75:25) biodegradable polymer having a molecular weight of 250 kDa was used. It was done in the same way.

Example  10.

10.1 Surface Modification of Ceramic Particles

The second embodiment of Example 1.1 except that cerium oxide was used as the ceramic particles and poly-DL-lactide-co-glycol (75:25) having a molecular weight of 810 KDa was used as the surface modifying material. It was carried out in the same manner as the method.

10.2 biome Implant  Produce

Example 1.2, except that 30 parts by weight of the surface-modified cerium oxide particles and 70 parts by weight of the poly-L-lactide-co-glycol (80:20) biodegradable polymer having a molecular weight of 100 kDa were used. The same procedure was followed.

Example  11.

11.1 Surface Modification of Ceramic Particles

Cerium hydroxide was used as the ceramic particles, and poly-D-lactide having a molecular weight of 100 KDa was used as the surface modifying material, except that the second method of Example 1.1 was used.

11.2 Biome Implant  Produce

The same method as in Example 1.2, except that 30 parts by weight of the surface-modified cerium hydroxide particles and 70 parts by weight of poly-L-lactide-caprolactone (80:20) biodegradable polymer having a molecular weight of 100 kDa was used. Was performed.

Comparative example  One.

The implant was extruded with a 220 kDa polylactide biodegradable polymer alone to prepare a living implant.

Comparative example  2.

10 parts by weight of the surface-modified magnesium hydroxide particles and 90 parts by weight of the polylactide biodegradable polymer were mixed and extruded to prepare a living implant.

Example 1-10 and Comparative Example 1-2 are collectively shown in Table 1 below.

division Biodegradable polymer Surface modification materials Ceramic particles Produce
Way Example 1 Polycaprolactone
(150 kDa) DL-lactide
Magnesium hydroxide Extruder Example 2 Poly-DL-lactide-co-caprolactone
(50:50, 200 kDa) DL-Lactide: Glycolide
(50:50) Magnesium hydroxide Extruder Example 3 Poly-DL-lactide-co-caprolactone
(80:20, 250 kDa) Poly-L-lactide-co-caprolactone
(75:25) Potassium hydroxide Extruder Example 4 Poly-L-Lactide
(200 kDa) Poly-DL-Lactide
(5 kDa) Magnesium oxide Extruder Example 5 Poly-L-lactide-co-glycolide
(75:25, 200 kDa) Poly-L-Lactide
(10 kDa) Magnesium oxide Injection machine Example 6 Poly-L-lactide-co-glycolide
(50:50, 100 kDa) Poly-L-lactide-co-glycolide
(75:25, 3 kDa) Cerium hydroxide Injection machine Example 7 Poly-L-lactide-co-caprolactone
(80:20, 150 kDa) Poly-L-lactide-co-caprolactone
(50:50, 8 kDa)  Calcium hydroxide Extruder Example 8 Poly-DL-Lactide
(230 kDa) Polycaprolactone
(5 kDa) Magnesium hydroxide Injection machine Example 9 Poly-L-lactide-co-caprolactone
(75:25, 250 kDa) Polycaprolactone
(8 kDa) Cerium hydroxide Extruder Example 10 Poly-L-lactide-co-glycolide
(80:20, 300 kDa) Poly-L-lactide-co-caprolactone
(75:25, 10 kDa) Cerium oxide Extruder Example 11 Poly-L-lactide-co-caprolactone
(80:20, 100 kDa) Poly-D-Lactide
(100 kDa) Cerium hydroxide Extruder Comparative Example 1 Poly-L-Lactide
(220kDa) - - Extruder Comparative Example 2 Poly-L-Lactide
(220kDa) - Magnesium hydroxide Extruder

Experimental Example  1. vivo Implant  Biological Characterization

1.1 Confirm pH neutralizing effect

The pH change after 7 weeks of biodegradation of the biological implants prepared in Examples 1-11 and Comparative Examples 1-2 was confirmed. Specifically, the change in pH was confirmed by checking the acidity of the living implants over time, and the degree of neutralization was measured by using a shaking tank (BS-20, Jeio Tech, Korea) set at 60 ° C and 100 rpm. The pH of the solution was measured using a pH meter (HANNA instrument, USA). The measurement results are shown in Table 2 and FIG. 1.

division PH value after 7 weeks Inflammatory response Cytotoxicity Modulus (GPa) Example 1 6.90 Full suppression X 2.1 Example 2 6.81 Fairly restrained X 2.3 Example 3 7.18 Fairly restrained X 1.8 Example 4 7.12 Full suppression X 2.0 Example 5 7.09 Full suppression X 1.9 Example 6 6.36 Fairly restrained X 2.4 Example 7 7.19 Fairly restrained X 1.7 Example 8 7.03 Full suppression X 1.9 Example 9 6.22 Fairly restrained X 2.2 Example 10 6.19 Fairly restrained X 2.1 Example 11 6.20 Fairly restrained X 2.0 Comparative Example 1 2.55 Severe O 1.1 Comparative Example 2 6.51 control △ 1.0

(X: less than 10% cell death, △: cell death 10% ~ 30%, O: cell death 30% or more)

As a result, as shown in Table 2 and Figure 1, in the case of Comparative Example 1 showed a strong acidity of less than pH 3.7 after 4 weeks, the pH of the initial stage of Comparative Example 2 showed a high basicity of 10.7 and neutral after 6 weeks Was maintained. On the other hand, in the case of Example 1-11 there was no sharp change in pH in the living implant, it was confirmed the neutralizing effect.

1.2 Cytotoxicity Assessment

The cytotoxicity of the living organisms prepared in Examples 1-11 and Comparative Examples 1-2 was confirmed. Specifically, the living implants were biodegraded at 80 ° C. for 4 weeks, and then treated with vascular endothelial cells (HCAEC) at a concentration of 1 mg / ml, and then cultured for 1 or 3 days after the CCK-8 assay. The kit was used for evaluation. Living implants were transferred to fresh 24-well culture plates and 10% CCK-8 solution was added to the medium. Thereafter, the samples were incubated at 37 ° C. for 3 hours, 100 μl of the reaction solution was transferred to a new 96-well plate, and the optical density was measured at 450 nm using a microplate reader (Multiskan Microplate Reader, Thermo Scientific). The measurement results are shown in Table 2 and FIG.

2 is a graph confirming cell viability. As a result, in Example 1-11, there was no cytotoxicity or significantly inhibited, whereas in Comparative Example 1, cytotoxicity was very strong, and in Comparative Example 2, cytotoxicity was somewhat suppressed compared to Comparative Example 1. And cytotoxicity as compared with Example 1-11.

1.3 Inhibition of Inflammatory Response

The cellular inflammatory response of the living body implants prepared in Examples 1-11 and Comparative Examples 1-2 was confirmed by the expression level of inflammation-related cytokines. Specifically, after culturing NHOst cells in a living implant for 7 days, cell supernatants were collected and evaluated using IL-6 and IL-8 ELISA kits. The evaluation results are shown in Table 2 and FIG. 3.

3 is a graph measuring the expression of IL-8 and IL-6 by ELISA to assess the inflammatory response of a living implant.

As a result, it was confirmed that the inflammatory response inhibitory effect in Example 1-11 was superior to that of Comparative Example 1-2 in HCAEC cells.

1.4 Physical Property Assessment

Modulus was measured to confirm the mechanical strength, which is the physical property of the living body implants prepared in Examples 1-11 and Comparative Examples 1-2. Mechanical modulus was measured by Instron according to the method of ASTM D638, the measurement results are shown in Table 2, and FIG.

As a result, it was confirmed that the mechanical modulus of the living body implants of Examples 1-11 was significantly increased compared to Comparative Examples 1-2.

Therefore, it can be seen that the living body implants of Examples 1-11 have excellent mechanical strength due to improved mechanical properties.

Claims (17)

And a biodegradable polymer and a surface-modified basic ceramic particle, wherein the surface-modified basic ceramic particle is heat processed after surface modification. The living body implant of claim 1, wherein the surface-modified basic ceramic particles comprise about 1 to 60 weight percent based on the total weight of the biodegradable polymer. The method of claim 1, wherein the basic ceramic particles are one or more metal particles selected from the group consisting of alkali metals, alkaline earth metals, rare earth metals, and rare earth metals or hydroxides of alkali metals, oxides of alkali metals, hydroxides of rare earth metals, rare earths A living body implant, which is at least one selected from the group consisting of metal oxides, alkaline earth metal hydroxides, alkaline earth metal oxides, rare earth earth metal hydroxides, and rare earth earth metal oxides. The method of claim 3, wherein the alkali metal, alkaline earth metal, rare earth metal, or rare earth metal is lithium (Li), berylnium (Be), sodium (Na), magnesium (Mg), potassium (K), calcium (Ca), The living implant, which is rubidium (Rb), strontium (Sr), barium (Ba), cesium (Cs), cerium (Ce), francium (Fr) or radium (Ra). The method of claim 3, wherein the hydroxide of alkali metal, oxide of alkali metal, hydroxide of rare earth metal, oxide of rare earth metal, hydroxide of alkaline earth metal, oxide of alkaline earth metal, hydroxide of rare earth earth metal, or oxide of rare earth metal is lithium hydroxide, Beryllium hydroxide, sodium hydroxide, magnesium hydroxide, potassium hydroxide, calcium hydroxide, rubidium hydroxide, strontium hydroxide, barium hydroxide, cesium hydroxide, cerium hydroxide, francium hydroxide, radium hydroxide, magnesium oxide, sodium oxide, lithium oxide, sodium oxide, manganese oxide And at least one member selected from the group consisting of potassium oxide, calcium oxide, barium oxide, cesium oxide, cerium oxide, and radium oxide. The method of claim 1, wherein the ceramic particles are lactide, glycolide, caprolactone, dioxanone, trimethylene carbonate, alkanoate hydroxide, peptide, cyanoacrylate, lactic acid, glycolic acid, capric acid hydroxide, maleic acid , Polymers produced by polymerization of at least one monomer selected from the group consisting of phosphazenes, amino acids, butyric acid hydroxides, sebacic acid, ethoxyacetic acid hydroxides and trimethylene glycols, or polylactides, polyglycolides, Polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylenecarbonate, polyglycolide-co-dioxane On, polyamide ester, polypeptide, polyorthoester type, polymaleic acid, polyphosphazene, polyanhydride, polycephalic Id fluoride, poly hydroxide alkanoates, poly hydroxide butyrate and policies of cyano to at least one polymer selected from the group consisting of acrylates that the surface is modified, in vivo implants. The living implant of claim 6, wherein the polymer has a different length in the range of 1 to 1,000 kDa molecular weight. The method according to claim 1, wherein the biodegradable polymer is polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-capro Lactones, polydioxaneones, polytrimethylenecarbonates, polyglycolide-co-dioxoneones, polyamide esters, polypeptides, polyol isoesters, polymaleic acid, polyphosphazenes, polyanhydrides, polysebaxanhydrides And at least one selected from the group consisting of polyhydroxyalkanoate, polyhydroxybutyrate and polycyanoacrylate. The living implant of claim 1, wherein the ceramic particles are between 1 nm and 1 mm in size. The implant of claim 1, wherein the basic ceramic particles inhibit inflammation following acidification of the biodegradable polymer. The living body implant of claim 1, wherein the interfacial separation between the basic ceramic particles and the biodegradable polymer is suppressed and the mechanical properties are improved. The cardiovascular material of claim 1, wherein the cardiovascular material is selected from stents, surgical sutures, support for tissue regeneration, bio nanofibers, hydrogels and biosponges, dental materials selected from pins, screws, rods, and implants, and nerves / orthoses. A living implant, selected from the group consisting of plastic surgery implants. The living implant of claim 1, wherein the thermal processing is performed at 20 to 300 ° C. for 1 to 48 hours. Modifying the basic ceramic particle surface;
Thermally processing the basic ceramic particles whose surface is modified; And
Mixing the thermally processed basic ceramic particles with a biodegradable polymer. The method of claim 14, further comprising molding the living implant by performing injection, extrusion, thermoforming or compression. The method of claim 14, wherein modifying the surface of the basic ceramic particles is ring-opening polymerization or condensation polymerization of monomers on the surface of the basic ceramic particles. The method of claim 14, wherein the thermal processing is performed at 20 to 300 ° C. for 1 to 48 hours.

Images