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EP-4736895-A1 - LOW-CRYSTALLINE CALCIUM PHOSPHATE-BASED ANTIBACTERIAL BONE GRAFT MATERIAL AND METHOD FOR PREPARING SAME

EP4736895A1EP 4736895 A1EP4736895 A1EP 4736895A1EP-4736895-A1

Abstract

One embodiment of the present disclosure provides a method for preparing a low-crystalline calcium phosphate-based antibacterial bone graft material, the method comprising: (a) synthesizing calcium phosphate by adding a calcium precursor and a phosphate precursor all at once; (b) introducing the calcium phosphate into an antibacterial material precursor solution to perform a reaction; (c) freeze-drying a product of step (b); (d) mixing a product of step (c) with a pore-forming agent and press-molding the mixture to prepare a molded body; and (e) removing the pore-forming agent of the molded body in a solvent at a temperature equal to or higher than the boiling point of the solvent, followed by drying.

Inventors

  • JO, Hee Ryeong
  • PARK, HYUNG JOON

Assignees

  • Osstemimplant Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240523

Claims (16)

  1. A method for preparing a low-crystalline calcium phosphate-based antibacterial bone graft material, the method comprising: (a) synthesizing calcium phosphate by adding a calcium precursor and a phosphate precursor all at once; (b) introducing the calcium phosphate into an antibacterial material precursor solution to perform a reaction; (c) freeze-drying a product of step (b); (d) mixing a product of step (c) with a pore-forming agent and press-molding the mixture to prepare a molded body; and (e) removing the pore-forming agent of the molded body in a solvent at a temperature equal to or higher than the boiling point of the solvent, followed by drying.
  2. The method of claim 1, wherein the calcium precursor comprises at least one selected from the group consisting of calcium nitrate, calcium chloride, calcium fluoride, calcium iodide, calcium acetate, ammonium carbonate, and ammonium bicarbonate.
  3. The method of claim 1, wherein the phosphate precursor comprises at least one selected from the group consisting of phosphorus oxide, ammonium phosphate monobasic, ammonium phosphate dibasic, ammonium phosphate tribasic, sodium phosphate monobasic, sodium phosphate dibasic, sodium phosphate tribasic, and potassium phosphate.
  4. The method of claim 1, wherein in step (a), a molar ratio of the calcium precursor and the phosphate precursor is 1:1.5 to 3.
  5. The method of claim 1, wherein step (a) is a wet precipitation method in which each precursor is dissolved in distilled water and mixed.
  6. The method of claim 1, wherein the antibacterial material comprises at least one selected from the group consisting of silver (Ag), magnesium (Mg), gallium (Ga), zinc (Zn), and copper (Cu).
  7. The method of claim 1, wherein the reaction of step (b) is performed at a temperature of 15 to 25°C for 10 to 20 hours.
  8. The method of claim 1, wherein in step (d), a weight ratio of the product of step (c) and the pore-forming is 1:1 to 1.5.
  9. The method of claim 1, wherein an average particle diameter of the pore-forming is 100 to 500 µm.
  10. The method of claim 1, further comprising, after step (e): (f) heat-treating the molded body at a temperature of 250°C or lower.
  11. The method of claim 1, wherein a content of an antibacterial material in the low-crystalline calcium phosphate-based antibacterial bone graft material is 0.2 to 1.8% by weight.
  12. The method of claim 1, wherein a content of an antibacterial material in the low-crystalline calcium phosphate-based antibacterial bone graft material is 0.5 to 0.9% by weight.
  13. A low-crystalline calcium phosphate-based antibacterial bone graft material comprising an antibacterial material, wherein the bone graft material includes at least one of grooves or pores having an average diameter of 100 to 500 µm, wherein the bone graft material has a BET specific surface area of 100 m 2 /g or more, wherein the bone graft material includes both crystalline apatite and amorphous calcium phosphate, and wherein the bone graft material has a crystallinity of 25% or less.
  14. The low-crystalline calcium phosphate-based antibacterial bone graft material of claim 13, wherein the antibacterial material comprises at least one selected from the group consisting of silver (Ag), magnesium (Mg), gallium (Ga), zinc (Zn), and copper (Cu).
  15. The low-crystalline calcium phosphate-based antibacterial bone graft material of claim 13, wherein a content of the antibacterial material is 0.2 to 1.8% by weight relative to total elements constituting the bone graft material.
  16. The low-crystalline calcium phosphate-based antibacterial bone graft material of claim 13, wherein a content of the antibacterial material is 0.5 to 0.9% by weight relative to total elements constituting the bone graft material.

Description

[Technical Field] The present disclosure relates to a low-crystalline calcium phosphate-based antibacterial bone graft material and a method for preparing the same. [Background Art] A bone graft material is a material for regenerating bone absorbed or destroyed due to factors such as disease, trauma, and aging. For example, in dental treatments such as implant placement surgery or periodontal surgery, osteoplasty is sometimes performed to artificially create alveolar bone using a bone graft material. Bone graft materials play a role in stimulating bone growth, and their mechanisms of action can be broadly classified into osteoconduction, osteoinduction, and osteogenesis. Osteoconduction is a mechanism in which osteoblasts migrate from surrounding bone tissue to form bone, and bone tissue or differentiated mesenchymal cells are essential at the graft site. Osteoinduction refers to a mechanism that influences the differentiation of undifferentiated mesenchymal cells into osteoprogenitor cells to form bone tissue. Osteogenesis refers to a mechanism of generating bone tissue by cells inside the graft material. Bone graft materials can be classified into autogenous bone, allogenic bone, xenograft, and synthetic bone (alloplastic bone) graft materials according to their origin. Autogenous bone graft materials use bone tissue harvested from a recipient subject, possess all of osteogenic, osteoconductive, and osteoinductive capabilities, and are the only ones among existing bone graft materials that have osteogenic capability. However, there are limitations in that additional surgery is required for harvesting bone tissue, which entails costs and time, and above all, the amount of available bone is limited. Allogenic bone graft materials harvest bone tissue from a cadaver and are generally obtained by receiving donated bone from a deceased person. Since they are graft materials obtained from the genetically same species, they have equivalent healing capabilities and are excellent in bone replacement effects due to absorbability and osteogenic capability. Xenograft graft materials are harvested from individuals of different species, and hydroxyapatite obtained mainly from bovine or porcine sources is used. Various components including calcium phosphate-based ceramics are used as synthetic bone graft materials, but they are generally known to be inferior in osteogenic capability and bone quality compared to autogenous or allogenic bone graft materials. Calcium phosphate-based biomaterials mainly used as synthetic bone graft materials include hydroxyapatite (HA) and tricalcium phosphate (TCP). However, hydroxyapatite has a limitation in that it is non-absorbable and remains in the body for a long period of time, and tricalcium phosphate has a drawback in that the rate of bone formation and the degradation rate of the graft material become unbalanced. In addition, if the site of bone graft procedure becomes infected, bone recovery is difficult and bone defects may accompany, requiring complex recovery means. In particular, in the case of dental bone graft materials, it is known that the possibility of bacterial infection is high due to the intraoral environment. Accordingly, there is a need for the development of a bone graft material that is a synthetic bone graft material having absorbability and osteogenic capability at a level similar to that of allogenic bone, and can actively control infection by inhibiting the growth of bacteria by the graft material itself. [Disclosure] [Technical Problem] The present disclosure is intended to solve the problems of the related art described above, and an object of the present disclosure is to provide a low-crystalline calcium phosphate-based antibacterial bone graft material having excellent antibacterial properties and osteogenic capability, and a method for preparing the same. [Technical Solution] According to an aspect, there is provided a method for preparing a low-crystalline calcium phosphate-based antibacterial bone graft material, the method comprising: (a) synthesizing calcium phosphate by adding a calcium precursor and a phosphate precursor all at once; (b) introducing the calcium phosphate into an antibacterial material precursor solution to perform a reaction; (c) freeze-drying a product of step (b); (d) mixing a product of step (c) with a pore-forming agent and press-molding the mixture to prepare a molded body; and (e) removing the pore-forming agent of the molded body in a solvent at a temperature equal to or higher than the boiling point of the solvent, followed by drying. In an embodiment, the calcium precursor may include at least one selected from the group consisting of calcium nitrate, calcium chloride, calcium fluoride, calcium iodide, calcium acetate, ammonium carbonate, and ammonium bicarbonate. In an embodiment, the phosphate precursor may include at least one selected from the group consisting of phosphorus oxide, ammonium phosphate monobasic, ammonium