KR20220117572A - Synthetic bone graft material derived from fish bone and its manufacturing method - Google Patents

Abstract

The present invention relates to a synthetic bone graft material or tooth graft material derived from fish bones, and to a preparation method therefor. A method for preparing a bone graft material according to one embodiment of the present invention comprises: a crushing step for preparing a crushed product by crushing fish bones; a reaction step for preparing an aqueous solution by mixing the crushed product with magnesium chloride, an organic acid, and a phosphoric acid compound; a heat treatment step for performing heat treatment of the aqueous solution at 90-150 ℃; a separation step for separating and purifying precipitate of the aqueous solution after the heat treatment step; and a molding step.

Description

Synthetic bone graft material derived from fish bone and manufacturing method thereof

The present invention relates to a synthetic bone graft material or tooth graft material derived from fish bones and a method for manufacturing the same. More specifically, it is to provide a graft material for tooth or bone graft derived from fishbone with improved formability along with physical properties such as crystallinity and rigidity as bioceramics using spines and bones as by-products of fish. The present invention also provides a method of manufacturing a tooth or bone graft material to which the bioceramic is applied.

In addition to the mechanical function of supporting the human body and performing movements, the bone also serves as a storage for calcium in regulating the concentration of calcium ions in the body, and also has an important physiological function of producing red blood cells and white blood cells necessary for the body in the bone marrow. Bone can be damaged due to aging and other physiological reasons, or from various accidents. Representative examples of physiological damage include osteoporosis and arthritis (osteoarthritis, osteoarthrosis), and there is also avascular necrosis caused by interruption of blood supply to the bone. Currently, bone damage is mainly treated with mechanical and physical methods. In oral surgery or orthopedic surgery caused by accident, disease, infection, etc., bone regeneration and treatment for bone loss are the most important goals.

One method for this is a bone grafting method. Bone grafting includes methods such as transplanting bones from other people or animals and transplanting the patient's own tissue. The disadvantage is that there are not enough materials available. In order to overcome these shortcomings, research on bone graft materials is being actively conducted. Bone graft substitute (BGS) is a bone graft substitute that fills the space in the bone tissue and promotes the formation of new bone by replacing the defect in the bone tissue due to various dental diseases, trauma, degeneration due to disease, or other tissue loss. It refers to the graft material used to make A typical bone graft material is a biomaterial composed of calcium phosphate (CaP). Among these biomaterials, tricalcium phosphate (Ca3(PO4)2, TCP) and hydroxyapatite (Ca10(PO4)6(Ca10(PO4)6( OH)2 and HAp) are known to have chemical components similar to those of natural bone or tooth tissue in physical properties and biocompatibility, and are therefore very usefully used as biomaterials. TCP and HAp can be artificially synthesized through chemical methods, and recent studies have reported that biocompatible HAp or TCP can be prepared from natural materials such as eggshell and coral.

Calcium phosphate (CaIcium phosphate)-based materials have been widely studied for a long time as a substitute for hard tissues such as human bones and teeth. This is because the calcium phosphate compound, which constitutes 69% of human bones, is composed of calcium phosphate, so it has the properties closest to that of natural bone.

In the case of autogenous bone graft materials, which are generally used for autograft methods in which a part of one's own bone is harvested and transplanted, autogenous cancellous bone (ACB) is transplanted, so there is almost no immune rejection reaction, and there is little bone resorption, so It has the advantage of good osteoinduction ability, and in the case of allograft and xenograft materials used in allograft methods and xenograft methods, allografts using the bones of other people than the recipient themselves or bones of other animals Because xenograft using a bone graft material is used, it has the advantage of eliminating the need for secondary surgery in areas other than the bone loss site of the graft, which is a disadvantage of autogenous bone graft materials.

Allogeneic bone is obtained from a cadaver or other living donor and is used after freezing the graft material, freeze-drying, demineralization-freeze-drying, and irradiation to remove antigenicity. Although the amount of bone required is small, the required amount can be used at any time and has the advantage of not creating an additional surgical site.

Types of these allografts include demineralized freeze dried bone allografts (DFDBA), freeze dried boneallografts (FDBA), and irradiated cancellous bone (ICB) among freeze-dried bones.

Xenograft bone is a graft material that expects bone conduction ability by lowering the immune response through several procedures obtained by collecting bone from animals such as cows and pigs. However, since it takes a long time to be absorbed and replaced, the current trend is that it is understood as a mechanism of bone conduction rather than osteoinduction. Examples of such xenografts include Bio-Oss, ABM/P-15, and BioCeraTM.

Synthetic bone is not real bone but artificially synthesized, so it has the lowest quality compared to other bone graft materials and the period required for bone formation is long, but has the advantage of being inexpensive. hydroxyapatite, beta tricalcium phosphate, polymethlymethacrylate (PMMA) and hydroxyet-hylmethacrylate (HEMA) polymers, and bioactive glass are used in clinical practice. HA, PMMA, and HEMA polymers are non-absorbable, and tricalcium phosphate and bioactive are absorbable. These types of synthetic bone include tricalcium phosphate, hard tissue polymer, and bioactive vitreous ceramics. Meanwhile, hydroxyapatite (HAp) has been widely used as a bone substitute in bone grafts and dental devices. HAp is a biocompatible and bioactive material with osteoconductive properties, and its chemical composition is similar to that of natural bone tissue. HAp is a kind of calcium phosphate bioceramic, and can be synthesized using chemicals containing calcium ions and phosphate ions as raw materials.

On the other hand, a biomaterial is a material capable of coping with some organs or parts of a damaged human body, and in order to apply it to the medical or dental field, it must be biocompatible. Biocompatibility refers to the ability of a material or device to be physiologically free from side effects or toxicity while functioning. Among the materials developed so far, the best biocompatibility is a calcium phosphate-based material.

Recently, metal, polymer, natural (coral, bovine bone, etc.) or artificial synthetic calcium phosphate-based biomaterials have been developed one after another to treat or partially replace human damaged bones. These materials are widely applied in dental and medical fields such as artificial bone, treatment of alveolar bone defects, artificial tooth root, ossicles, dental and orthopedic implants.

Therefore, there is a need to develop a material having higher cell proliferation and adhesion for use as a bone graft material that can be applied and applied throughout the dental and medical fields.

KR 10-2020-0012815 A KR 10-2019-0112991 A

An object of the present invention is to provide a synthetic bone graft material that can be applied to teeth or bones derived from fishbone with improved physical properties such as crystallinity and rigidity.

An object of the present invention is to achieve a high process yield by generating bioceramics having excellent physical properties in a low-temperature reaction.

An object of the present invention is to provide a bone graft material that can be applied to teeth or bones with improved physical properties by including hydroxyapatite (HAp) and whitlockite in an appropriate ratio.

An object of the present invention is to provide a bone graft material that can be applied to teeth or bones derived from fish bones with improved processability.

Another object of the present invention is to provide a method for preparing a bone graft material with improved physical properties and improved process efficiency by reacting at a low temperature.

In order to achieve the above object, a method for manufacturing a bone graft material according to an embodiment of the present invention includes a crushing step of crushing fish bones to prepare a crushed product; a reaction step of preparing an aqueous solution by mixing magnesium chloride, an organic acid and a phosphoric acid compound with the pulverized product; a heat treatment step of heat-treating the aqueous solution at 90 to 150 °C; and a separation step of separating and purifying the precipitate of the aqueous solution after the heat treatment step; and a molding step.

The method for producing the bone graft material may further include a mixing step of mixing any one selected from the group consisting of polymethyl methacrylate (PMMA), collagen, alginic acid, and mixtures thereof with respect to the product after the separation step. have.

The method for producing the bone graft material may further include a reaction rate control step of mixing 0.01 to 0.2 wt% of sodium dibasic with respect to 100 parts by weight of the pulverized product before the reaction step.

The method for preparing the bone graft material may further include a modifying step of mixing a compound represented by the following Chemical Formula 1 with the product after the separation step.

[Formula 1]

(In Formula 1, R ₁ is an alkyl group having 1 to 10 carbon atoms. R ₂ and R ₃ are either Cl, an alkoxy group having 1 to 10 carbon atoms, or an alkyl group having 1 to 10 carbon atoms.)

The bone graft material according to another embodiment of the present invention may be manufactured according to the manufacturing method.

A dental implant material according to another embodiment of the present invention may be manufactured according to the manufacturing method.

The composition may further include any one selected from the group consisting of polymethyl methacrylate (PMMA), collagen, alginic acid, and mixtures thereof.

Hereinafter, the present invention will be described in more detail.

A method of manufacturing a bone graft material according to an embodiment of the present invention includes a grinding step of grinding fish bones to prepare a pulverized product; a reaction step of preparing an aqueous solution by mixing magnesium chloride, an organic acid and a phosphoric acid compound with the pulverized product; a heat treatment step of heat-treating the aqueous solution at 90 to 150 °C; and a separation step of separating and purifying the precipitate of the aqueous solution after the heat treatment step; and a molding step.

Fish bones as used in the present invention include bones, fine bones, thorns, and fine thorns contained in fish. In addition, the fish includes all fish including bones or spines, and includes a range that can be selected by a person skilled in the art. Also, it is not limited to a particular species.

The composition for tooth or bone graft referred to in the present invention includes a material such as bone tissue or a graft material applied to dental tissue, bone cement or tooth resin.

The pulverization step means to pulverize the washed and dried fish bones to a certain size to prepare a powder. In addition, before the grinding step, the fish bones may be those from which impurities are removed by washing fish by-products with hot water and using sodium hydroxide and an organic solvent. In addition, if necessary, impurities may be removed through a certain acid treatment process.

Preferably, the grinding step may have an average particle diameter of 0.8 to 3.3 μm. When the average particle diameter is less than 0.8 μm, there is a problem in that the physical properties of the product generated in the reaction step are deteriorated because even dispersion is not achieved due to agglomeration between the fine particles. On the other hand, when the average particle diameter exceeds 3.3 μm, there is a problem in that the reactivity and the physical properties of the bone structure are deteriorated because a large amount of unreacted particles are generated.

On the other hand, the adjustment of the average particle diameter may be adjusted by applying a method that can be used by a person skilled in the art, such as a ball mill or a jet mill.

The reaction step may be prepared by dissolving the powder that has undergone the pulverization step, and mixing the lysate with magnesium chloride, an organic acid, and a phosphoric acid compound.

The organic acid is fumaric acid (Fumaric); Lactic acid; Citric acid; malic acid (Malic); butyric acid; formic acid (Formic); Acetic acid; propionic acid (Propionic); oleic acid; palmitoleic acid; It may be any one selected from the group consisting of linoleic acid and mixtures thereof.

The phosphate compound may be arbitrarily selected and determined by a person skilled in the art as a material for supplying phosphate ions. Preferably, phosphoric acid may be used.

In the reaction step, each reactant may be arbitrarily selected and determined based on the molar ratio of each ion provided in consideration of the characteristics of the raw material. This is not limited to a fixed molar ratio due to the characteristics of the raw material, and includes all ranges that can be determined by selection and adjustment by those of ordinary skill in the art.

Preferably, it may further include a pretreatment step of treating atmospheric pressure plasma to the fine particles that have undergone the pulverization step before the reaction step.

Hydroxyapatite is a representative mineral constituting bone and has high biocompatibility and is used as a material for restoration or artificial bone in various medical and dental fields. In addition, as calcium phosphate containing magnesium, whitrockite exists as another inorganic material with high biocompatibility. Whitrokite has the advantage of excellent biocompatibility, but has a disadvantage in that it is more unstable than hydroxyapatite in terms of its crystal structure. Therefore, when hydroxyapatite and whitrokite are present in a mixed phase in the range of 1: 3 to 3: 1, it is possible to provide a material with high stability and more biocompatibility.

When the pretreatment step is performed, cleaning and reactivity of the surface of the fine particles are increased, so that a mixture of hydroxyapatite and whitrokite can be effectively produced in the reaction step. In particular, when the pretreatment step is performed, the molar amounts of magnesium chloride, organic acid and phosphoric acid compound are adjusted so that hydroxyapatite and whitrokite are included in the product in the range of 1: 3 to 3: 1, and the plate-shaped wheat It may be such that lockite is included in a large amount. The reactant produced through this can be provided as a composition having excellent physical properties and biocompatibility.

The heat treatment step refers to a step of providing heat to the aqueous solution at 90 to 150 °C. Through the above steps, hydroxyapatite and whitrokite can be grown and obtained from the lysate. In particular, when the pre-treatment step and the reaction step are performed, hydroxyapatite and whitrokite in the product after the heat treatment step are included in the range of 1: 3 to 3: 1, so that a material with excellent reactivity and biocompatibility can be produced. have.

Preferably, the heat treatment step may be performed as a secondary heat treatment step at 90 to 110° C. after the first heat treatment step at 130 to 150° C.

When the heat treatment of the two steps is performed, calcium phosphate particles having excellent physical properties and compositions can be prepared at a relatively low heat source. In the case of the first heat treatment step, the generation of calcium phosphate particles rapidly proceeds, and when the second heat treatment step is performed after being left alone, the reaction of the heat treatment step proceeds more effectively and the shape and size of the particles are excellent in physical properties. can be manufactured. In particular, compared to a high-temperature heat treatment process, the process efficiency may be excellent, and the physical properties and biocompatibility of the obtained product may be excellent.

The separation step refers to a step of separating and purifying the precipitate of the aqueous solution after the heat treatment step, and includes all the ranges available to those skilled in the art.

In addition, after the separation step, it may be to use an additive or perform other post-treatment to apply a formulation according to the use or to improve the physical properties of the material.

The molding step includes compression molding, mold molding, support molding, laminate molding, and any other means that can be used to mold the product into a bone graft material according to a formulation required by those skilled in the art.

The method for producing the bone graft material may further include a mixing step of mixing any one selected from the group consisting of polymethyl methacrylate (PMMA), collagen, alginic acid, and mixtures thereof with respect to the product after the separation step. have.

Through the mixing step, the physical properties of the product can be reinforced. In particular, through the reinforcement of the soft material constituting the aggregate, the physical properties of the bone or tooth material can be improved, and the biocompatibility can be further improved.

The method for producing the bone graft material may further include a reaction rate control step of mixing 0.01 to 0.2 wt% of sodium dibasic with respect to 100 parts by weight of the pulverized product before the reaction step.

In the step of adjusting the reaction rate, it is possible to quickly control the production rate of the bioceramic and increase its rigidity. On the other hand, when the dibasic sodium phosphate is included in an amount of less than 0.01% by weight based on 100 parts by weight of the pulverized product, the effect of increasing the reaction rate cannot be obtained. In addition, when the sodium phosphate exceeds 0.2% by weight, there is a problem in that the reaction rate is slowed and ceramic particles having a uniform shape are not generated.

In particular, in the case of the reaction rate control step, it is possible to effectively produce ceramic particles in a relatively low temperature range of the heat treatment step, and to produce particles having excellent physical properties and shapes.

The method for preparing the bone graft material may further include a modifying step of mixing a compound represented by the following Chemical Formula 1 with the product after the separation step.

[Formula 1]

(In Formula 1, R ₁ is an alkyl group having 1 to 10 carbon atoms. R ₂ and R ₃ are either Cl, an alkoxy group having 1 to 10 carbon atoms, or an alkyl group having 1 to 10 carbon atoms.)

In the case of the modification step, the physical properties and adhesion of the composition may be improved. In addition, in the case of the composition of the modification step, there is no problem such as cytotoxicity of the compound itself, and the modified composition also has high stability and excellent biocompatibility.

Preferably, the compound consisting of [Formula 1] may be any one selected from the group consisting of any one of the following [Formula 1a] to [Formula 1c], or a mixture thereof.

[Formula 1a]

[Formula 1b]

[Formula 1c]

In the case of Formulas 1a to 1c, it is possible to exhibit an effect of excellent biocompatibility while improving the physical properties of the product.

More preferably, the composition of the reforming step may further include a compound consisting of the following [Formula 2] together with the [Formula 1].

[Formula 2]

(In Formula 2, n is an integer of 2 to 100)

When the compound of the above [Formula 2] is further included, physical properties including rigidity and adhesion may be excellent as well as processability may be increased.

The bone graft material according to another embodiment of the present invention may be manufactured according to the manufacturing method.

A dental implant material according to another embodiment of the present invention may be manufactured according to the manufacturing method.

The composition may further include any one selected from the group consisting of polymethyl methacrylate (PMMA), collagen, alginic acid, and mixtures thereof.

The present invention provides a synthetic bone graft material that can be applied to teeth or bones derived from fishbone with improved properties such as crystallinity and rigidity.

The present invention makes it possible to achieve a high process yield by generating bioceramics having excellent physical properties in a low-temperature reaction.

The present invention provides a bone graft material that can be applied to teeth or bones with improved physical properties by including hydroxy apatite (HAp) and whitlockite in an appropriate ratio.

The present invention provides a bone graft material that can be applied to teeth or bones derived from fish bones with improved processability.

The present invention provides a method for preparing a bone graft material with improved physical properties and improved process efficiency by reacting at a low temperature.

Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art can easily carry out the present invention. However, the present invention may be embodied in several different forms and is not limited to the embodiments described herein.

[Production Example 1: Preparation of bioceramics]

While controlling each step as shown in [Table 1] below, it was possible to evaluate the properties of the ceramic product in a low temperature heat treatment process of 90 to 150 °C. Whether or not bioceramics particles are generated under the low-temperature process was investigated through the process conditions of M1 to M9, which were distinguished for each process.

M1 M2 M3 M4 M5 M6 M7 M8 M9 S1 S1-1 S1-2 S1-2 S1-2 S1-2 S1-2 S1-2 S1-3 S1-2 S2 S2-3 - S2-1 S2-2 S2-3 S2-4 S2-5 S2-3 S2-3 S3 S3 S3 S3 S3 S3 S3 S3 S3 S3 S4 S4-2 S4-2 S4-2 S4-2 S4-2 S4-2 S4-2 S4-2 S4-1 S5 S5 S5 S5 S5 S5 S5 S5 S5 S5

<Grinding step S1>

S1-1: Conger eel bone crushing step (average particle diameter 0.4 to 0.7 μm)

S1-2: Conger eel bone crushing step (average particle size 0.8 to 3.3 μm)

S1-3: Conger eel bone crushing step (average particle size 3.4 to 5.2 μm)

<Reaction rate control step S2>

S2-1: 0.005 parts by weight of sodium phosphate mixed with 100 parts by weight of the pulverized product of S1

S2-2: 0.01 parts by weight of sodium phosphate mixed with 100 parts by weight of the pulverized product of S1

S2-3: 0.1 parts by weight of sodium phosphate mixed with 100 parts by weight of the pulverized product S1

S2-4: 0.2 parts by weight of sodium phosphate mixed with 100 parts by weight of the pulverized product of S1

S2-5: 0.3 parts by weight of sodium phosphate mixed with 100 parts by weight of the pulverized product S1

<Reaction step S3>: magnesium chloride (MgCl ₂ ), palmitoleic acid (C ₁₆ H ₃₀ O ₂ ) to the pulverized product provided in step S1; Phosphoric acid (H ₃ PO ₄ ) mixed

<Heat treatment step S4>

S4-1: heat treatment at 90 to 150 ℃

S4-2: After the primary heat treatment at 130 to 150 ℃ secondary heat treatment at 90 to 110 ℃

<Separation step S5>: Separation and purification of the precipitate

[Experimental Example 1: Generation of bioceramics particles]

By analyzing the shape of nanoparticles included in the products of M1 to M9, it was analyzed whether bioceramics were generated in a low-temperature process.

M1 M2 M3 M4 M5 M6 M7 M8 M9 S1 X X X O O O XX XX △

O: Generates particles of a shape that can be used as bioceramics

X: Bioceramics particle generation

XX: unreacted

△: Particles with a shape that can be used as bioceramics are generated

Referring to [Table 2], it can be seen that in general, it is difficult to form ceramic particles in a low-temperature process of heat treatment at 90 to 150 °C. However, referring to M4 to M6, when the reaction rate is controlled by pretreatment of dibasic sodium phosphate with 0.01 to 0.2 wt% of sodium phosphate for an average particle diameter range of 0.8 to 3.3 μm, bioceramics particles can be produced under a low temperature process. can be checked In addition, referring to M2 and M3, it was confirmed that the reaction activity does not appear when the content of the dibasic sodium phosphate is less than a certain range, and that when the content exceeds a certain amount, such as M7, the reaction does not occur. Therefore, it can be confirmed that particles of bioceramics can be produced in a low temperature range by controlling the particle size and controlling the reaction rate using dibasic sodium phosphate.

[Experimental Example 2: Experiment to improve physical properties of bioceramics]

In order to evaluate whether the physical properties were improved through the atmospheric pressure plasma pretreatment, the reaction proceeded to a process (M3P process) in which atmospheric pressure plasma was treated before the reaction step based on the M3 process, along with the M3 process (M3P process) to obtain a product. In the M3P process, each step was performed under the same conditions as in S3 except for adding an atmospheric pressure plasma treatment step before the reaction step (S3).

Thereafter, samples were taken for the products of the M3 and M3P processes, and the hydroxyapatite (HAp) and whitrokite (WH) contents within the sample specification range were analyzed and calculated. The results are shown in [Table 3] below.

M3 M3P HAp: HW 4:1 2.3:1

Referring to [Table 3], it can be seen that when the pretreatment process of atmospheric pressure plasma according to the present invention is performed, the contents of HAp and HW can be adjusted to be configured in a composition range of 1: 3 to 3: 1. . Through this, it can be confirmed that bioceramics having better biocompatibility and physical properties can be provided.

[Experimental Example 3: Experiment to improve physical properties through compound addition]

Using the product of M3P, a synthetic bone composition was prepared, applied to a dental model, and then the physical properties of a dental implant made by mold molding were evaluated. In addition, additive 1a represented by [Formula 1a] for reinforcing physical properties as shown in Table 4 below; Additive 1b represented by [Formula 1b]; The effect of reinforcing each property was evaluated by applying a mixed composition further comprising each of the additive 1c represented by [Formula 1c] as a reinforcing material, and by applying a mixed composition further comprising the additive 2 represented by [Formula 2] as a reinforcing material.

S1 S2 S3 S4 S5 S6 Additive 1a - O - - - - Additive 1b - - O - - - Additive 1c - - O - O Additive 2 - - - - O O

For objective evaluation, the degree of expansion, coagulation time, strength, adhesiveness, and color information of S1 were fixed to 1, and the remaining S2 to S6 were evaluated as indices of 1 to 10. In the index, the higher the number, the better the effect, and a value evaluated as less than 1 means that the effect is lower than that of S1. The results are shown in [Table 5] below.

S1 S2 S3 S4 S5 S6 degree of expansion One 3 2.4 3.1 1.2 2.6 coagulation time One 0.9 0.9 0.8 1.3 1.1 burglar One 3 3 5 1.1 7 adhesive One 3 5 5 1.2 7 color One One One One 0.8 One

(Unit: Index)

Referring to [Table 5], it can be seen that the strength and adhesiveness are improved in the case of S2 to S4. In addition, it can be seen that it is easy to apply the designed modeling because of its low expansibility. In particular, in the case of S4, the reinforcement effect on the coefficient of expansion was excellent along with strength and adhesion. Therefore, when according to the above range, it may be provided as a bone or tooth graft material with reinforced physical properties.

On the other hand, in the case of S6, an additional synergistic effect was confirmed. It was confirmed that the strength and adhesiveness were very high. It was confirmed that the reinforcement effect on the expansion coefficient was also very satisfactory.

Although preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention as defined in the following claims are also provided. is within the scope of the

Claims (7)

Grinding step of pulverizing fish bones to prepare a pulverized product;
a reaction step of preparing an aqueous solution by mixing magnesium chloride, an organic acid and a phosphoric acid compound with the pulverized product;
a heat treatment step of heat-treating the aqueous solution at 90 to 150 °C; and
Separation step of separating and purifying the precipitate of the aqueous solution after the heat treatment step; and
forming step
A method for manufacturing a bone graft material. The method of claim 1,
It further comprises a mixing step of mixing any one selected from the group consisting of polymethyl methacrylate (PMMA), collagen, alginic acid, and mixtures thereof with respect to the product after the separation step
A method for manufacturing a bone graft material. The method of claim 1,
It further comprises a reaction rate control step of mixing 0.01 to 0.2 wt% of sodium phosphate dibasic with respect to 100 parts by weight of the pulverized product before the reaction step
A method for manufacturing a bone graft material. The method of claim 1,
Further comprising a reforming step of mixing a compound represented by the following formula 1 with respect to the product after the separation step
A method for manufacturing a bone graft material.
[Formula 1]

(In Formula 1, R ₁ is an alkyl group having 1 to 10 carbon atoms. R ₂ and R ₃ are either Cl, an alkoxy group having 1 to 10 carbon atoms, or an alkyl group having 1 to 10 carbon atoms.) A bone graft material manufactured by the manufacturing method according to any one of claims 1 to 4. A tooth graft material manufactured by the manufacturing method according to any one of claims 1 to 4. 6. The method of claim 5,
The composition further comprises any one selected from the group consisting of polymethyl methacrylate (PMMA), collagen, alginic acid, and mixtures thereof.
bone graft material.