POROUS INORGANIC PARTICLE, AND COMPOSITE FILLER, PRODUCT USING THE SAME

Abstract

The present disclosure relates to a porous inorganic particle which comprises a sintered body of calcium-based particles, and pores distributed in the sintered body, and has a core-shell structure of a core having a high porosity and a shell having a porosity lower than that of the core, wherein the calcium-based particles comprise first calcium-based particles having a maximum diameter of 10 nm to 500 nm, and second calcium-based particles having a maximum diameter of 1 ?m to 10 ?m, and to a composite fillers and product using the same.

Claims

1. A porous inorganic particle comprising: a sintered body of calcium-based particles, pores distributed in the sintered body, and a core-shell structure of a core having a high porosity and a shell having a porosity lower than that of the core, wherein the calcium-based particles comprise first calcium-based particles having a maximum diameter of 10 nm to 500 nm, and second calcium-based particles having a maximum diameter of 1 ?m to 10 ?m.

2. The porous inorganic particle of claim 1, wherein: a content of the second calcium-based particles is 2 parts by weigh to 10 parts by weight with respect to 1 part by weight of the first calcium-based particles.

3. The porous inorganic particle of claim 1, wherein: 70 vol. % or more of the entire first calcium-based particles is contained in the shell.

4. The porous inorganic particle of claim 1, wherein: 70 vol. % or more of the entire second calcium-based particles is contained in the core.

5. The porous inorganic particle of claim 1, wherein: the porous inorganic particle has a core diameter of 20 ?m to 90 ?m and a shell thickness of 0.2 ?m to 50 ?m.

6. The porous inorganic particle of claim 1, wherein: the porous inorganic particle has a ratio of a core diameter to a shell thickness (core diameter:shell thickness) of 1:1 to 100:1.

7. The porous inorganic particle of claim 1, wherein: the porous inorganic particle has a total pore volume of at least 0.001 cm.sup.3/g.

8. The porous inorganic particle of claim 1, wherein: the porous inorganic particle has a specific surface area of more than 0.1 m.sup.2/g.

9. The porous inorganic particle of claim 1, wherein: the porous inorganic particle has a compressive strength of at least 20 MPa.

10. The porous inorganic particle of claim 1, wherein: the first calcium-based particles and the second calcium-based particles each have spherical shapes.

11. The porous inorganic particle of claim 1, wherein: the first calcium-based particles and the second calcium-based particles each comprise hydroxyapatite.

12. The porous inorganic particle of claim 1, wherein: the porous inorganic particle comprises the resultant product of heat treatment of composite particles containing a biocompatible binder, the first calcium-based particles, and the second calcium-based particles.

13. The porous inorganic particle of claim 12, wherein: the biocompatible binder comprises one or more polymers selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, carboxymethylcellulose, and polyethylene glycol.

14. The porous inorganic particle of claim 12, wherein: the heat treatment of the composite particles comprises, subjecting the composite particles to first heat treatment at a temperature of 450? C. to 550? C., and subjecting them to second heat treatment at a temperature of 600? C. to 1200? C.

15. The porous inorganic particle of claim 12, wherein: a content of the first calcium-based particles is 5 parts by weight to 30 parts by weight with respect to 1 part by weight of the biocompatible binder.

16. The porous inorganic particle of claim 12, wherein: a content of the second calcium-based particles is 35 parts by weight to 100 parts by weight with respect to 1 part by weight of the biocompatible binder.

17. A composite filler comprising the porous inorganic particle of claim 1 and a biodegradable carrier.

18. The composite filler of claim 17, wherein: the composite filler has a bioactivity of at least 15 mg/(kg.Math.g) according to the following Equation 1:
Bioactivity={[Content of ion (either calcium ion or phosphorus ion) in body fluid (mg/kg)]?[Content of ion (either calcium ion or phosphorus ion) in the body fluid after immersing a composite filler in the body fluid for 8 days (mg/kg)]}/(Content of inorganic particles (g) in the composite filler).[Equation 1]

19. The composite filler of claim 17, wherein: the biodegradable carrier comprises hyaluronic acid.

20. A product comprising the composite filler of claim 17.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0106] FIG. 1 shows surface and cross-section SEM images of porous inorganic particles obtained in Example 1.

[0107] FIG. 2 shows surface and cross-section SEM images of porous inorganic particles obtained in Example 2.

[0108] FIG. 3 shows surface and cross-section SEM images of porous inorganic particles obtained in Comparative Example 1.

[0109] FIG. 4 shows surface and cross-section SEM images of porous inorganic particles obtained in Comparative Example 2.

[0110] Hereinafter, the invention is described in more detail with reference to the following examples. However, these examples are for illustrative purposes only, and are not intended to limit the subject matter of the present disclosure.

EXAMPLE

Example 1

(1) Production of Porous Inorganic Particles

[0111] Polyvinyl alcohol (PVA, weight average molecular weight: 146,000?186,000 Da, 99+% hydrolyzed) was stirred in water at 90? C. to prepare a 1 wt. % PVA aqueous solution.

[0112] Spherical hydroxyapatite (HAp) powder (1st HAp) having a maximum diameter of 200 nm and spherical hydroxyapatite (HAp) powder (2nd HAp) having a maximum diameter of 2.5 ?m were added to a PVA aqueous solution so that the weight ratio of 1st HAp/2nd HAp/PVA satisfies 10/40/1 to prepare a suspension.

[0113] The suspension is spray-dried (Buchi mini spray dryer B-290). When drying was completed, particles were obtained, placed in a crucible, maintained at 500? C. for 2 hours in a box furnace to remove PVA, and then sintered at 1000? C. for 2 hours to produce a porous inorganic particle.

(2) Production of Composite Filler

[0114] 0.4 g of the porous inorganic particle was mixed with 9.6 g of hyaluronic acid to produce a composite filler.

Example 2

[0115] A porous inorganic particle and a composite filler were produced in the same manner as in Example 1, except that the sintering temperature was changed to 1200? C. as shown in Table 1 below.

COMPARATIVE EXAMPLE

Comparative Example 1

[0116] A porous inorganic particle and a composite filler were produced in the same manner as in Example 2, except that spherical hydroxyapatite (HAp) powder (2nd HAp) having a maximum diameter of 2.5 ?m was added at a weight ratio of the 1st HAp/2nd HAp/PVA of 0/50/1 without using the 1st HAp as shown in Table 1 below.

Comparative Example 2

[0117] A porous inorganic particle and a composite filler were produced in the same manner as in Example 2, except that needle-shaped hydroxyapatite (HAp) powder (1st HAp) having a maximum diameter of 150 nm was added at a weight ratio of the 1st HAp/2nd HAp/PVA of 12/0/1 without using the 2nd HAp as shown in Table 1 below.

Experimental Example

[0118] The physical properties of the inorganic particles and composite fillers obtained in the Examples and Comparative Examples were measured by the following methods, and the results are shown in Table 1, Table 2 and Figures.

1. Particle Shape

[0119] The surface and cross-section shapes of the inorganic particles obtained in the Examples and Comparative Examples were confirmed through SEM images, which are shown in FIGS. 1 to 4, respectively.

2. Particle Size

[0120] For the inorganic particles obtained in the Examples and Comparative Examples, the maximum diameter of each 100 particles was measured through SEM images, and the arithmetic mean of these values was calculated.

3. Porosity

[0121] For the inorganic particles obtained in the Examples and Comparative Examples, the shape of the particle cross section was confirmed through SEM images, and the porosity was expressed as follows according to the presence or absence of pores. [0122] ?: presence of pores on the cross-section SEM image inside the particle [0123] X: absence of pores on the cross-section SEM image inside the particle

4. Specific Surface Area and Total Pore Volume

[0124] The specific surface area and total pore volume of the inorganic particles obtained in the Examples and Comparative Examples were measured using a BET analyzer.

5. Particle Strength

[0125] The compressive strength of the inorganic particles obtained in the Examples and Comparative Examples was measured using a micro-compression device, which was evaluated as particle strength.

TABLE-US-00001 TABLE 1 Experimental Example Measurement Results of Examples and Comparative Examples Weight Maximum Maximum ratio of diameter diameter Specific Total 1st and and Particle surface pore Compressive HAp/2nd shape of shape of Sintering Particle size area volume strength Category HAp/PVA 1st HAp 2nd HAp temperature shape (?m) Porosity (m.sup.2/g) (cm.sup.3/g) (MPa) Example 1 10/40/1 200 nm 2.5 ?m 1000? C. FIG. 1 42 ? 5 0.0155 22 Spherical Spherical Example 2 10/40/1 200 nm 2.5 ?m 1200? C. FIG. 2 44 ? 4 0.0131 38 Spherical Spherical Comparative 0/50/1 2.5 ?m 1200? C. FIG. 3 34 ? 4 0.0123 15 Example 1 Spherical Comparative 12/0/1 150 nm 1200? C. FIG. 4 49 X 0.1 0.0009 75 Example 2 needle shape

[0126] As shown in Table 1, it was confirmed that in the case of inorganic particles contained in the composite fillers of Examples, the porous inorganic particle having pores inside the particles were obtained, and both the specific surface area and the pore volume were significantly improved as compared to Comparative Example 2. Further, it was confirmed that in the case of the inorganic particles contained in the composite fillers of Examples was obtained, the compressive strength of the porous inorganic particle was 22 MPa to 38 MPa, which was significantly improved as compared to Comparative Example 1.

[0127] On the other hand, it was confirmed that the compressive strength of the porous inorganic particle contained in the composite filler of Comparative Example 1 was 15 MPa which was reduced as compared to Examples. In addition, it was confirmed that in the case of inorganic particles contained in the composite filler of Comparative Example 2, non-porous inorganic particles with no pores inside the particles were obtained,

6. Bioactivity

[0128] After immersing the composite filler obtained in the Examples and Comparative Examples in simulated body fluid for 8 days, a sample was prepared by acid digestion method, the content of Ca ions and Pions in the sample (unit: mg/kg) were measured using an ICP-OES device, and the bioactivity was evaluated by the following Equation 1. The content of Ca ions and P ions in the simulated body fluid was measured to be 42 mg/kg, which means that the larger the value of the following Equation 1, the better the bioactivity.

[00004]$\begin{array}{cc}\mathrm{Bioactivity}=\left\{\left[\mathrm{Content}\mathrm{of}\mathrm{ion}\left(\mathrm{either}\mathrm{calcium}\mathrm{ion}\mathrm{or}\mathrm{phosphorus}\mathrm{ion}\right)\mathrm{in}\mathrm{body}\mathrm{fluid}\left(\mathrm{mg}/\mathrm{kg}\right)\right]-[\mathrm{Content}\mathrm{of}\mathrm{ion}\left(\mathrm{either}\mathrm{calcium}\mathrm{ion}\mathrm{or}\mathrm{phosphorus}\mathrm{ion}\right)\mathrm{in}\mathrm{body}\mathrm{fluid}\mathrm{after}\mathrm{immersing}\mathrm{the}\mathrm{composite}\mathrm{filler}\mathrm{in}\mathrm{the}\mathrm{body}\mathrm{fluid}\mathrm{for}8\mathrm{days}\left(\mathrm{mg}/\mathrm{kg}\right)\right\}/\left(\mathrm{Content}\mathrm{of}\mathrm{inorganic}\mathrm{particles}\left(g\right)\mathrm{in}\mathrm{the}\mathrm{composite}\mathrm{filler}\right).& \left[\mathrm{Equation}1\right]\end{array}$

TABLE-US-00002 TABLE 2 Experimental Example Measurement Results of Examples and Comparative Examples Category Ca ion bioactivity P ion bioactivity (mg/(kg .Math. g)) (mg/(kg .Math. g)) Example 1 29.2 22.2 Example 2 27.8 19.4 Comparative Example 1 27.8 20.8 Comparative Example 2 20.8 12.5

[0129] As shown in Table 2, it was confirmed that in the case of the composite filler of Example 1, Ca ion bioactivity was 29.2 mg/(kg.Math.g) and the Pion bioactivity was 22.2 mg/(kg.Math.g), which were larger than those of Comparative Examples, and thus excellent in the bioactivity. On the other hand, the composite filler of Example 2 exhibited the same level of bioactivity as Comparative Example 1, and exhibited improved bioactivity compared to Comparative Example 2.