KR20230153119A - Bone graft composition - Google Patents

Abstract

The present invention relates to a bone graft material composition, and more specifically, to a bone graft material; A thickener with adhesive properties; A bioactive substance that is added to eliminate inflammation and that can release more than 90% of the added amount within a predetermined period of time; and an additive capable of combining with each of the bone graft material and the thickener.

Description

Bone graft material composition {BONE GRAFT COMPOSITION}

The present invention relates to a bone graft material composition.

For the reconstruction of missing bone, various materials and various methods can be used. For example, bone graft materials such as bone powder, bone chips, and bone blocks can be used, or autograft, allograft, and allograft can be used to reconstruct missing bone. Methods such as transplantation may be used.

Bone graft materials used to reconstruct missing bones can be used in orthopedics, neurosurgery, and dentistry. For example, they can be used in bone defects during disc surgery to induce bone regeneration, and can be used in implant procedures and oral jaw surgery. It can also be used to repair bone defects.

Meanwhile, Korean Patent No. 10-0401941 discloses a technology related to bone graft material and its manufacturing method. When using mesh bone composed of bioceramic powder and having a three-dimensionally connected pore structure, There may be limitations to the effectiveness of bone grafting in terms of biocompatibility, mechanical properties, toxicity, etc.

The purpose of the present invention is to provide a bone graft material composition containing hydroxypropyl methylcellulose, in which more than 90% of the biologically active substances can be released within 72 to 168 hours.

One embodiment of the present invention is a bone graft material; A thickener with adhesive properties; A bioactive substance that is added to eliminate inflammation and that can release more than 90% of the added amount within a predetermined period of time; and an additive capable of combining with each of the bone graft material and the thickener, wherein the additive is capable of maintaining its shape after being implanted into a bone defect.

The predetermined period may be 72 to 168 hours.

The bioactive substance may be asiatic coside or ipecalocadechin gallate.

The additive may be hydroxypropyl methylcellulose.

The content of the additive may be 0.3 parts by weight or more and 3 parts by weight or less compared to 1 part by weight of the bone graft material.

The bone graft material composition containing hydroxypropyl methylcellulose, which can release more than 90% of the bioactive substances in 72 to 168 hours according to the present invention, eliminates inflammation by continuously releasing the bioactive substances in a sustained release. It has excellent effects.

Figure 1 is a diagram schematically showing the procedure for manufacturing a bone graft material composition according to an embodiment of the present invention.
Figure 2 is a diagram showing the release rate (time) of more than 90% of ifecalocadechin gallate per weight part of hydroxypropyl methylcellulose, reflecting the result data (Table 1) for the experimental example of the present invention.
Figure 3 is a diagram showing the release rate (time) of more than 90% of ifecalocadechin gallate per weight part of hydroxypropyl methylcellulose, reflecting the result data (Table 2) for the experimental example of the present invention.
Figure 4 is a diagram showing the release rate (time) of more than 90% of ifecalocadechin gallate per weight part of hydroxypropyl methylcellulose, reflecting the result data (Table 3) for the experimental example of the present invention.
Figure 5 is a diagram showing the release rate (time) of more than 90% of ifecalocadechin gallate per weight part of hydroxypropyl methylcellulose, reflecting the result data (Table 4) for the experimental example of the present invention.

Examples of one embodiment of the present invention include a bone graft material, a thickener with adhesive properties, and hydroxypropyl methylcellulose, so that more than 90% of the bioactive substance can be released within 72 to 168 hours and the bioactive substance can be released over a sustained period of time. It relates to a bone graft material composition containing hydroxypropyl methylcellulose, which is continuously released and has an excellent effect in eliminating inflammation.

However, in the description of this embodiment, parts that overlap with other embodiments are omitted for clearer and concise description, and the omission of the description does not mean that the part is excluded from the present invention, and the scope of rights is limited to other embodiments. It must be recognized as the same as the form.

In describing the present invention, if it is determined that a detailed description of the known technology related to the present invention may unnecessarily obscure the gist of the present invention, the detailed description will be omitted. In addition, the terms described below are terms defined in consideration of functions in the present invention, and may vary depending on the intention or custom of the user or operator. Therefore, the definition should be made based on the contents throughout this specification.

The technical idea of the present invention is determined by the claims, and the following examples are only a means to efficiently explain the technical idea of the present invention to those skilled in the art in the technical field to which the present invention pertains.

In the present invention, when a repeating unit, compound or resin represented by a chemical formula has isomers thereof, the chemical formula representing the repeating unit, compound or resin means a representative chemical formula including the isomers.

Hereinafter, specific embodiments of the present invention will be described. However, this is only an example and the present invention is not limited thereto.

The bone graft material composition of the present invention includes a bone graft material, a thickening agent, and hydroxypropyl methylcellulose. The bone graft material composition can be used to repair the bone defect by implanting it into the bone defect and filling (or applying) it.

Here, 'filling' or 'application' includes both cases where the material is applied to the bone defect in a state without rigidity, or a case in which it is applied to the bone defect in a state that has rigidity. The bone graft material composition that is applied to the bone defect by imparting rigidity to it is a composition that is prepared with rigidity in a shape corresponding to the bone defect using a shape forming device (e.g., 3D printer, etc.) and then applied to the bone defect. It can mean something.

The bone graft material may be bone of natural origin, for example, autogenous bone, allogeneic bone, xenogeneic bone, or synthetic bone. By using bone of natural origin, it has excellent biocompatibility, and in addition, by containing a large number of pores, it has good wettability and hygroscopicity, so the bone formation effect can be excellent. In addition, it can be used to reconstruct missing bones and can be used in orthopedics, neurosurgery, plastic surgery, otolaryngology, oral and maxillofacial surgery, veterinary medicine (animal hospitals), dermatology, and dentistry.

The bone graft material composition may have adhesion to the bone defect by containing hydroxypropyl methylcellulose. Additionally, if a certain dissolution rate of hydroxypropyl methylcellulose is met within a certain time, its function becomes better. If the adhesion is excellent, the bone graft material composition may not flow down even if applied to the maxilla, and it can help prevent the bone graft material composition from being separated from the bone defect even if there is impact due to masticatory movements, etc.

Additionally, it can be used to reconstruct damaged bones in humans or animals. Below, cases mainly used in dentistry are described, but are not limited thereto.

When bone graft material is used alone, it easily disperses in water or blood, so a viscous thickener can be used to achieve the formative properties of bone graft material. However, when the thickener alone is used in a bone graft material, the thickening power may be reduced due to the hydroxyl groups on the surface of the bone graft material. For example, when only a thickener is mixed into a bone graft material and carboxyl methylcellulose is used as the thickener, carboxyl methylcellulose has one functional group, so when mixed with bone graft material with water or blood, the area around the bone graft material becomes alkalized. As a result, the thickening power decreases and the bonding power with the bone graft material decreases, so it can easily dissolve.

The bone graft material composition may have adhesion to the bone defect by including an additive. At the same time, shape retention can be imparted to the bone graft material composition using additives. If the shape retention is excellent, even if the bone graft material composition is applied to the upper jaw, it will not flow down and will be applied to the bone defect area, thereby helping to prevent the bone graft material composition from being separated from the bone defect area even if there is impact due to masticatory movements, etc.

Therefore, the bone graft material composition according to an embodiment of the present invention further includes hydroxypropyl methylcellulose as an additive along with the bone graft material and thickener. hydroxypropyl methylcellulose has two functional groups: hydroxyl group and methyl group. As a result, when the bone graft material composition is hydrated, it can bond with both the bone graft material and the thickener, and when mixed with the bone graft material and the thickener, it can play a bonding and barrier role due to its excellent bonding strength.

That is, since the thickener included in the bone graft material composition does not bind well to the bone graft material, it can perform its role by combining with hydroxypropyl methylcellulose as an additive. Here, the role refers to the role of maintaining the volume and internal space when the bone graft material composition is filled in the bone defect, as well as maintaining viscosity and bonding to ensure ease of application.

However, in order for blood or moisture to flow into the bone graft material composition from inside the bone defect to smoothly generate new bone, the thickener must be able to dissolve and come out of the bone graft material composition filled in the bone defect. Therefore, the amount of hydroxypropyl methylcellulose that crosslinks the bond between the porous bone graft material and the thickener may be limited in the amount included in the bone graft material composition. The limitation of hydroxypropyl methylcellulose according to the embodiment of the present invention applies when a thickening agent is included in the bone graft material composition.

The thickener included according to the embodiment of the present invention is a material having adhesive properties, and may be, for example, one of synthetic polymer materials, natural polymer materials, and thickener materials, or a mixture of two or more materials.

Here, the synthetic polymer materials include polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), poly-ε-(caprolactone) (PCL), polyanhydrides, It may be one or more of polyorthoesters, polyvinyl alcohol, polyethylene glycol, polyurethane, polyacrylic acid, and poly-N-isopropylacrylamide.

In addition, natural polymer materials include cellulose, carboxycellulose, methylcellulose, carboxymethylcellouse, poloxamer, collagen peptide, starch, and glycerol. It may be one or more of (glycerol (glycerin)), polyethylene glycol, collagen, chitosan, hyaluronic acid, and dextran.

Additionally, the thickener may be one or more of alginate, carrageenan, gelatin, guar gum, xantan gum, and gluten.

The hydroxypropyl methylcellulose included along with the thickener in the above bone graft material composition will be described in detail.

As previously explained, hydroxypropyl methylcellulose is an additive that forms a bone graft material composition with excellent procedureability and bone regeneration between bone graft material and thickener.

In the bone graft material composition according to an embodiment of the present invention, more than 90% of the added amount of the bioactive material may be released within a predetermined period of time. In this case, the bioactive material is continuously released in sustained release to reduce inflammation. can be removed.

The predetermined period may be 72 to 168 hours.

If more than 90% of the bioactive substances are released in less than 72 hours, the bioactive substances are released in excessive amounts and the inflammatory response is not released continuously in a sustained manner, making it impossible to eliminate inflammation. In addition, if more than 90% of the bioactive substance is released over 168 hours, the bioactive substance may remain in places where bone cells should enter, interfering with bone formation. Accordingly, in order for the bone graft material composition to have adhesion to the bone defect, more than 90% of the bioactive substances must be released within 72 to 168 hours.

The bioactive substance may be asiatic coside or ipecalocadechin gallate.

Bioactive substances are physiologically active substances/biological function modulators that are carried on porous silica particles and can be delivered to an organism to exhibit activity and have direct or indirect therapeutic, physiological and/or pharmacological effects on human or animal organisms. It may be a therapeutically active agent that can be provided.

The therapeutically active agent may be, for example, a general medicine, drug, prodrug or target group, or a drug or prodrug containing a target group.

The additive may be hydroxypropyl methylcellulose.

The additive may include one or more from the group consisting of methyl cellulose, carboxymethyl cellulose, and hydroxypropyl methylcellulose. In an embodiment according to the present invention, the additive will be HPMC, but the additive is not limited thereto, and the type may not be limited as long as it is a methylcellulose-based additive.

The content of the additive may be 0.3 parts by weight or more and 3 parts by weight or less compared to 1 part by weight of the bone graft material.

The bone graft material composition according to an embodiment of the present invention includes 0.3 to 3 parts by weight of hydroxypropyl methylcellulose relative to the bone graft material, along with the bone graft material and thickener. In this case, based on 48 hours after hydration of the bone graft material composition, the volume reduction rate was substantially about 10%, and it was confirmed that the bone graft material composition had excellent operability and bone regeneration ability.

On the other hand, when the thickener is combined with less than 0.1 part by weight of hydroxypropyl methylcellulose in the bone graft material composition, the function of hydroxypropyl methylcellulose as an additive is not expressed due to the insufficient amount of hydroxypropyl methylcellulose. This is because thickeners, which have a weak bonding power with bone graft materials due to the insufficient content of hydroxypropyl methylcellulose, are unable to bind to bone graft materials. Therefore, during hydration, hydroxypropyl methylcellulose and the thickener cannot properly function as a barrier, so the bone graft material quickly dissolves and disappears. That is, when the bone graft material composition is applied to the bone defect, the space of the bone graft material cannot be maintained, so the bone conduction effect is reduced and new bone formation is delayed or difficult as a result. As a result, blood, etc. penetrates, preventing the creation of blood vessels and new bone formation in the bone defect area, preventing the bone graft material composition from performing its original function of bone formation.

First, when more than 0.3 parts by weight of hydroxypropyl methylcellulose and the thickener are combined with the thickener in the bone graft material composition, the bonding and barrier role of the bone graft material composition rapidly and excessively increases. Excessive strengthening of this bonding and barrier role will prevent the thickener from dissolving despite hydration. This results in the fact that when the actual bone graft material composition is implanted into the bone defect, the volume of the bone graft material composition does not decrease over time, making penetration of blood or moisture difficult. As a result, the formation of blood vessels in the bone defect area is inhibited and new bone formation is hindered, preventing the bone graft material composition from performing its original function of bone formation.

In addition, when more than 0.3 parts by weight of hydroxypropyl methylcellulose and a thickener are combined with bone graft material, the water holding properties of hydroxyapatite and hydroxypropyl methylcellulose are similar, so when bone graft material and hydroxypropyl methylcellulose are mixed, a hydrogel is formed well even when mixed alone. Here, when a thickener is additionally used, more than 0.3 parts by weight of hydroxypropyl methylcellulose is combined with the thickener, resulting in excessive bonding between the bone graft material particles and the thickener. As a result, the hydroxypropyl methylcellulose excessively plays a bonding and barrier role, so the thickener does not dissolve and its volume increases. In this case, the volume does not decrease even after a long period of time, making it difficult for blood or moisture to penetrate, preventing the formation of blood vessels and hindering new bone formation.

Bone morphogenetic proteins are BMP-2, BMP-3, BMP-3b, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP- 12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, recombinant bone morphogenetic proteins thereof, and bone morphogenetic proteins equivalent thereto, In terms of the bone formation effect of the present invention, rhBMP-2 may be preferable.

The bone morphogenetic protein concentration of the bone morphogenetic protein solution according to an embodiment of the present invention may be 0.05 to 0.15 mg/ml, and preferably 0.08 to 0.12 mg/ml. By satisfying the above concentration range, bone formation of bone morphogenetic proteins can be activated. If the bone morphogenetic protein concentration is less than 0.05, the ability to form new bone may be reduced, and if it is more than 0.15, side effects may occur.

Additionally, the acidity of the bone morphogenetic protein solution according to an embodiment of the present invention may be, for example, pH 4.6 to 5. By satisfying the above acidity range, the bone formation of the bone morphogenetic protein can be activated. If the pH of the bone morphogenetic protein solution is less than 4.6, the new bone formation ability may be reduced, and if the pH is more than 5, the expression of the new bone formation ability may be reduced. For example, acidity can be adjusted using phosphate buffer saline. Adjusting acidity with phosphate buffer saline may have an effect on new bone formation.

Next, the graft powder is immersed in the bone morphogenetic protein solution to adsorb the bone morphogenetic protein to the graft powder. By flowing the bone morphogenetic protein solution into a previously prepared graft powder or dropping the graft powder into the bone morphogenetic protein solution, the graft powder can be immersed in the bone morphogenetic protein solution and the bone morphogenetic protein can be adsorbed onto the graft powder.

The graft material powder may be autologous bone, allogeneic bone, xenogeneic bone, or synthetic bone. For example, implant powder can be prepared by injecting it into a snap tube.

The average particle diameter (D50) of the implant powder may be 10 to 30,000 ㎛, preferably 200 to 5,000 ㎛, and more preferably 250 to 1,000 ㎛. If the average particle diameter of the powder is less than 10㎛, the graft material is absorbed quickly and bone conduction necessary for bone formation may be insufficient, and if it is more than 30,000㎛, precise processing may be difficult when applied to patients.

The step of adsorbing the bone morphogenetic protein to the implant powder according to an embodiment of the present invention may include adsorbing the bone morphogenetic protein using a refrigerated centrifuge.

In some cases, the bone morphogenetic protein may be suspended in the solution, and when adsorbed while rotating using a centrifuge, the bone morphogenetic protein can be prevented from floating in the solution, forming bone on the surface or within the pores of the graft powder. Proteins can be well adsorbed. It must be adsorbed while rotating rapidly to prevent bone morphogenetic proteins from falling off from the graft powder and re-suspending. If it is slow, bone morphogenetic proteins may float and adsorption may be poor. Bone morphogenetic proteins can be quickly adsorbed on the surface or in the pores of the implant powder.

The rotation speed of the refrigerated centrifuge according to an embodiment of the present invention may be 4000 rpm or more. When adsorbing using a centrifuge, the higher the rotation speed, the better the adsorption may be. For example, the rotation speed of the centrifuge may be 4000 rpm or more, and if the above-mentioned range is satisfied, the bone forming protein will float in the solution. You can prevent it from happening.

The adsorption step using a refrigerated centrifuge according to an embodiment of the present invention may be performed at a refrigeration temperature of 5°C or lower. By performing the adsorption step using a refrigerated centrifuge at a refrigerated temperature of 5℃ or lower, the temperature of the solution is prevented from rising due to rotation, thereby preventing deformation of the heat-vulnerable bone morphogenetic protein and the surface of the bone morphogenetic protein graft powder through rotation. Alternatively, the adsorption effect within the pores can be maximized. The refrigeration may be at a temperature at which the solution does not freeze, for example, 5°C or lower, and preferably 0.5 to 1.5°C.

Next, the graft powder adsorbed with bone morphogenetic protein, the thickener, and the hydroxypropyl methylcellulose powder are mixed and stirred to form a gel. This can form a viscous gel, and the formed gel can improve the adhesion of the implant powder. For example, the stirring can be performed with a mixer. By mixing the transplant material powder with hydroxypropyl methylcellulose in powder form along with a thickener, a result with uniform quality can be obtained.

Next, the mixed and stirred graft material powder and hydroxypropyl methylcellulose powder mixture is vacuum freeze-dried to form a form containing a porous structure. The mixed and stirred mixture of the implant powder and the hydroxypropyl methylcellulose powder may be dried while being frozen at a low temperature in a vacuum to form a sponge shape containing a structure containing multiple pores.

By vacuum freeze-drying, a sponge shape containing a porous structure can be formed. As the gel is absorbed into the implant powder, a sponge shape with a porous structure can be formed, and it is believed that vacuum treatment mainly contributes to the formation of a sponge shape with a porous structure.

The method for producing a bone graft material composition according to an embodiment of the present invention may further include a packaging step.

The method for manufacturing a bone graft material composition according to an embodiment of the present invention includes the step of mounting the manufactured bone graft material composition including a sponge form including a structure including a plurality of pores on a snap tube of a size that can be inserted into a syringe. More may be included. By further including the step of mounting on a snap tube of a size that can be inserted into a syringe, it can be directly inserted into the syringe without a separate process by having a size that can be inserted into a syringe, making it easy to work in the process of manufacturing the bone graft material composition. can do.

The method for manufacturing a bone graft material composition according to an embodiment of the present invention may further include the step of placing a bone graft material composition in the form of a sponge including a structure including a plurality of pores mounted on a snap tube into a syringe and sealing it. . By providing the bone graft material composition in a syringe, convenience of use can be ensured, and the possibility of contamination that may occur during use can be dramatically reduced.

The method for producing a bone graft material composition according to an embodiment of the present invention may further include the step of sterilizing the bone graft material composition.

One embodiment of the present invention can sterilize a bone graft material composition including a sponge-type structure including a plurality of pores through ethylene oxide gas. For example, the Ethylene Oxide Gas concentration may be 5 to 25000 mg/l, preferably 450 to 1200 mg/l.

When the Ethylene Oxide Gas concentration is less than 5 mg/l, sterilization may be insufficient, and when it is more than 25000 mg/l, deformation of bone formation proteins may occur.

In one embodiment of the present invention, a bone graft material composition including a sponge-like structure including a structure including a plurality of pores may be sterilized through gamma ray irradiation. For example, the dose of gamma rays may be 0.02 to 250 kGy, preferably 10 to 25 kGy. When the gamma ray irradiation dose is less than 0.02 kGy, sterilization may be insufficient, and when it is more than 250 kGy, deformation of bone morphogenetic proteins may occur.

In order to apply the bone graft material to the human body (e.g., teeth), the bone graft material manufactured according to this bone graft material manufacturing method has a viscosity that allows blood penetration and new bone formation while maintaining an internal space. (shape must be maintained). This viscosity and space retention can be determined by the content of hydroxypropyl methylcellulose, etc. contained in the bone graft material. Furthermore. When hydroxypropyl methylcellulose and a thickener are included together, viscosity and space retention can be determined with a smaller content.

For example, in the case of applying a bone graft material to a tooth, when the operator applies the bone graft material to a tooth defect, the hydroxypropyl methylcellulose contained in the bone graft material must have a certain dissolution rate or higher within a certain period of time to have adhesive properties and be applied to the tooth. It can be performed to suit the shape of the missing tooth. When the bone graft material is applied to the tooth defect during the procedure, it should not flow out or come off, and since hydroxypropyl methylcellulose does not dissolve in the bone graft material, the bone graft material cannot adhere to the bone defect, making the procedure impossible. This should not be done. Therefore, bone graft materials require a critical condition of hydroxypropyl methylcellulose, and differences in function may occur depending on the content of hydroxypropyl methylcellulose.

The thickener included according to the embodiment of the present invention is a material having adhesive properties, and may be, for example, one of synthetic polymer materials, natural polymer materials, and thickeners, or a mixture of two or more. Here, the synthetic polymer materials include polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), poly-ε-(caprolactone) (PCL), polyanhydrides, It may be one or more of polyorthoesters, polyvinyl alcohol, polyethylene glycol, polyurethane, polyacrylic acid, and poly-N-isopropylacrylamide. In addition, natural polymer materials include cellulose, carboxycellulose, methylcellulose, carboxymethylcellouse, poloxamer, collagen peptide, starch, and glycerol. It may be one or more of (glycerol (glycerin)), polyethylene glycol, collagen, chitosan, hyaluronic acid, and dextran. Additionally, the thickener may be one or more of alginate, carrageenan, gelatin, guar gum, xantan gum, and gluten.

Hereinafter, examples are presented to aid understanding of the present invention. However, these examples are only illustrative of the present invention and do not limit the scope of the appended claims, and are included in the examples within the scope and technical idea of the present invention. It is obvious to those skilled in the art that various changes and modifications are possible, and it is natural that such changes and modifications fall within the scope of the appended patent claims.

Experiment example

- 1. When the bone graft material is autologous bone, an experiment to confirm the release rate (time) of more than 90% of ipecalocadechin gallate according to the weight of hydroxypropyl methylcellulose

Carboxymethylcellulose as a thickening agent and hydroxypropyl methylcellulose as an additive are added to the bone graft material (0.25g) in varying parts by weight (hydroxypropyl methylcellulose 0.1 to 6.0) as shown in Table 1. A mixture of bone graft material, thickener, and bioactive substances ipecalocadechin gallate and hydroxypropyl methylcellulose is dissolved in a solvent (water), then the amount of ipecalocadechin gallate is measured, and more than 90% of ipecalocadechin gallate is released. The amount of ifecalocadechin gallate was measured and the time (hours) was measured.

Additive (HPMC) parts by weight More than 90% release rate (hours) 0.1 24 0.2 35 0.3 120 0.8 129 1.0 135 1.2 139 1.5 140 2.0 148 2.5 157 3.0 167 4.0 291 5.0 298 6.0 304

As shown in Table 1, in order to eliminate inflammation in an inflammatory response, ipecalocadechin gallate must be continuously released in sustained release, and 72 to 168 hours are required to release more than 90%. By checking the time at which more than 90% of ipecalocadechin gallate is released in Table 1 above, it can be seen that the content of hydroxypropyl methylcellulose is 0.3 parts by weight to 3 parts by weight compared to 1 part by weight of the bone graft material. Here, it can be seen that the content of hydroxypropyl methylcellulose, which takes 72 to 168 hours to release more than 90% of the amount of ipecalocadechin gallate, has critical significance at 0.3 parts by weight or more and 3 parts by weight or less compared to 1 part by weight of the bone graft material. You can.

Figure 2 reflects the result data for the above experiment (Table 1) and shows the release rate (time) of more than 90% of ifecalocadechin gallate per weight part of hydroxypropyl methylcellulose. The x-axis represents the weight portion of hydroxypropyl methylcellulose, and the y-axis represents the time at which more than 90% of ipecalocadechin gallate is released. It can be confirmed that when the weight part of hydroxypropyl methylcellulose is 0.3 parts by weight or more and 3 parts by weight or less, more than 90% of ifecalocadechin gallate is released within 72 to 168 hours. As a result, ifecalocadechin gallate is released rather than remaining in the bone graft material, thereby eliminating inflammation.

- 2. If the bone graft material is allogeneic bone, xenogeneic bone, or synthetic bone, an experiment to confirm the release rate (time) of more than 90% of ipecalocadechin gallate according to the weight of hydroxypropyl methylcellulose

Experiment as in experiment 1 above using allogeneic bone, xenogeneic bone, or synthetic bone instead of autologous bone, measure the amount of ifecalocadechin gallate, and release ifecalocadechin gallate until more than 90% of ifecalocadechin gallate is released. The amount of gallate was measured and the time (hours) was measured.

As shown in Table 2, when checking the time at which more than 90% of ipecalocadechin gallate is released in allogeneic bone, xenogeneic bone, and synthetic bone, the content of hydroxypropyl methylcellulose is 0.3 parts by weight or more and 3 parts by weight compared to 1 part by weight of the bone graft material. You can check the following. Here, it can be seen that the content of hydroxypropyl methylcellulose, which takes 72 to 168 hours to release more than 90% of the amount of ipecalocadechin gallate, has critical significance at 0.3 parts by weight or more and 3 parts by weight or less compared to 1 part by weight of the bone graft material. You can.

Figure 3 reflects the result data for the above experiment (Table 1) and shows the release rate (time) of more than 90% of ifecalocadechin gallate per weight part of hydroxypropyl methylcellulose. The x-axis represents the weight portion of hydroxypropyl methylcellulose, and the y-axis represents the time at which more than 90% of ipecalocadechin gallate is released. It can be confirmed that when the weight part of hydroxypropyl methylcellulose is 0.3 parts by weight or more and 3 parts by weight or less, more than 90% of ifecalocadechin gallate is released within 72 to 168 hours. As a result, ifecalocadechin gallate is released rather than remaining in the bone graft material, thereby eliminating inflammation.

- 3. Experiment to confirm the release rate (time) of more than 90% of ipecalocadechin gallate according to parts by weight of hydroxypropyl methylcellulose by type of thickener

Autologous bone was used and the thickener was polylactic acid-glycolic acid copolymer (PLGA), a synthetic polymer, and hyaluronic acid or xanthan gum, a natural polymer, in the same experiment as experiment 1 above, and the amount of ipecalocadechin gallate was measured. The amount of ifecalocadechin gallate was measured until more than 90% of ifecalocadechin gallate was released, and the time (hours) was measured.

As shown in Table 3 and Figure 3, similar to experiment 1, when the time at which more than 90% of ipecalocadechin gallate is released is confirmed, the content of hydroxypropyl methylcellulose is 0.3 parts by weight or more and 3 parts by weight compared to 1 part by weight of the bone graft material. You can check the following. Here, it can be seen that the content of hydroxypropyl methylcellulose, which takes 72 to 168 hours to release more than 90% of the amount of ipecalocadechin gallate, has critical significance at 0.3 parts by weight or more and 3 parts by weight or less compared to 1 part by weight of the bone graft material. You can.

- 4. Experiment to confirm the release rate (time) of more than 90% of ipecalocadechin gallate according to parts by weight of hydroxypropyl methylcellulose in a hydrophobic or hydrophilic environment.

Perform the same experiment as experiment 1 above using autologous bone, measure the amount of ifecalocadechin gallate, a bioactive substance, in a hydrophobic and hydrophilic environment, and release ifecalocadechin gallate until more than 90% of ifecalocadechin gallate is released. The amount of gallate was measured and the time (hours) was measured.

As shown in Table 4 and Figure 5, similar to experiment 1, when the time at which more than 90% of ipecalocadechin gallate is released is confirmed, the content of hydroxypropyl methylcellulose is 0.3 parts by weight or more and 3 parts by weight compared to 1 part by weight of the bone graft material. You can check the following. Here, it can be seen that the content of hydroxypropyl methylcellulose, which takes 72 to 168 hours to release more than 90% of the amount of ipecalocadechin gallate, has critical significance at 0.3 parts by weight or more and 3 parts by weight or less compared to 1 part by weight of the bone graft material. You can.

Claims (5)

Bone graft material;
A thickener with adhesive properties;
A bioactive substance that is added to eliminate inflammation and that can release more than 90% of the added amount within a predetermined period of time; and
Contains an additive that can be combined with each of the bone graft material and the thickener,
The additive is a bone graft material composition that maintains its shape after being implanted into a bone defect.
In claim 1,
The bone graft material composition wherein the predetermined period is 72 to 168 hours.
In claim 1,
A bone graft material composition in which the bioactive substance is asiatic coside or ipecalocadechin gallate.
In claim 1,
The bone graft material composition wherein the additive is hydroxypropyl methylcellulose.
In claim 1,
A bone graft material composition in which the content of the additive is 0.3 parts by weight or more and 3 parts by weight or less compared to 1 part by weight of the bone graft material.