Method of preparing a bone graft composition

Abstract

The present invention relates to a method of preparing a bone graft composition, comprising the steps of: (1) preparing a bone morphogenetic protein solution by mixing a solvent and a bone morphogenetic protein; (2) mixing the bone morphogenetic protein solution with porous bone graft material powder having an average particle diameter of 200 μm to 5,000 μm, and performing centrifugal separation using a refrigerated centrifuge in a cold temperature state of 5°C or less to cause the bone morphogenetic protein to be physically adsorbed to the surface or inside the pores of the porous graft material powder; (3) mixing and stirring 1 part by weight of the graft material powder having the bone morphogenetic protein adsorbed thereto and 0.3 parts by weight to 3 parts by weight of hydroxypropyl methylcellulose powder based on 1 part by weight of the graft material powder to form a gel; and (4) forming a sponge-like structure in which the graft material powder is fixed within a high-molecular network formed by the hydroxypropyl methylcellulose by freeze-drying the gel under vacuum.

Description

[0001] This application is a divisional application of the invention patent application filed on June 24, 2020, with application number 202010586541.2 and invention title "Bone graft composition and preparation method thereof". Technical Field

[0002] This disclosure relates to a method for preparing a bone graft composition. Background Technology

[0003] Various materials and methods can be used for bone reconstruction of defects. For example, bone graft materials such as bone powder, bone fragments and bone blocks can be used for bone reconstruction, or methods such as autologous transplantation, allogeneic transplantation and xenograft transplantation can be used.

[0004] Bone graft materials used for bone reconstruction of defects can be used in orthopedic surgery, neurosurgery, plastic surgery, otolaryngology, oral and maxillofacial surgery, veterinary medicine (veterinary clinics), dermatology, and dentistry. For example, these materials can be used to induce bone regeneration in bone defects during intervertebral disc surgery, or for implantation and reconstruction of oral and maxillofacial bone defects.

[0005] Furthermore, Korean Patent No. 10-0401941 discloses technology related to bone graft materials and their preparation methods. As disclosed therein, when using mesh bone composed of bioceramic powder and having a three-dimensional interconnected pore structure, the effectiveness of bone grafting may be limited in terms of biocompatibility, mechanical properties, and toxicity. Summary of the Invention

[0006] The purpose of this disclosure is to provide a bone graft composition comprising hydroxypropyl methylcellulose and a method for preparing the same, wherein the bone graft composition has excellent shape retention.

[0007] One embodiment of this disclosure provides a bone graft composition having shape retention of 50 or greater, wherein shape retention is defined as a value obtained by dividing the maximum breaking force (Nmax) by the rate of change of the minor axis, wherein the maximum breaking force is the force that causes the shape of the spherical material to change, and the rate of change of the minor axis is the ratio of the reduction in the minor axis length of the spherical material after the shape change has occurred to the diameter of the spherical material.

[0008] The bone graft composition comprises 1 part by weight of bone graft material mixed with 0.3 to 3 parts by weight of hydroxypropyl methylcellulose.

[0009] One embodiment of this disclosure provides a bone graft composition with excellent shape retention, wherein the bone graft material is a natural bone graft material.

[0010] One embodiment of this disclosure provides a method for preparing a bone graft composition with excellent shape retention, the method comprising the following steps: (1) A bone morphogenetic protein solution is prepared by mixing a solvent and bone morphogenetic protein; (2) Bone morphogenetic protein is adsorbed onto the graft material powder by mixing the bone morphogenetic protein solution with the graft material powder; (3) The graft material powder with the bone morphogenetic protein adsorbed thereon and hydroxypropyl methylcellulose powder are mixed and stirred to form a gel that imparts shape retention to the bone graft composition; and (4) A structure containing multiple pores is formed by freeze-drying the gel under vacuum.

[0011] One embodiment of this disclosure provides a method for preparing a bone graft composition with excellent shape retention, wherein the bone morphogenetic protein is selected from at least one of the following groups: 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, their recombinant bone morphogenetic proteins, and bone morphogenetic proteins equivalent to them.

[0012] One embodiment of this disclosure provides a method for preparing a bone graft composition with excellent shape retention, wherein the concentration of bone morphogenetic protein in the bone morphogenetic protein solution can be from 0.05 mg / mL to 0.15 mg / mL.

[0013] One embodiment of this disclosure provides a method for preparing a bone graft composition with excellent shape retention, wherein the pH of a bone morphogenetic protein solution is adjusted to 4.6 to 5 using phosphate-buffered saline.

[0014] One embodiment of this disclosure provides a method for preparing a bone graft composition with excellent shape retention, wherein the volume ratio between the graft material powder having bone morphogenetic proteins adsorbed thereon and the hydroxypropyl methylcellulose powder in step (3) is 1:0.2 to 1:0.6.

[0015] One embodiment of this disclosure provides a method for preparing a bone graft composition with excellent shape retention, wherein the method further includes a step of sterilizing the bone graft composition by irradiation with ethylene oxide gas or gamma rays.

[0016] One embodiment of this disclosure provides a method for preparing a bone graft composition with excellent shape retention, wherein the concentration of ethylene oxide gas is from 450 mg / L to 1,200 mg / L, or the dose of gamma irradiation is from 10 kGy to 25 kGy. Attached Figure Description

[0017] Figure 1 This is a flowchart schematically illustrating a method for preparing a bone graft composition according to an embodiment of the present disclosure.

[0018] Figure 2 The maximum breaking force (N) of the bone graft composition sphere / the rate of change of the short axis of the bone graft composition sphere is shown as a function of the content (parts by weight) of hydroxypropyl methylcellulose, and the content (parts by weight) of hydroxypropyl methylcellulose for bone graft compositions with excellent shape retention is indicated. Detailed Implementation

[0019] Embodiments of this disclosure relate to a bone graft composition that, by comprising a porous bone graft material and hydroxypropyl methylcellulose, exhibits excellent effects in terms of bone formation activation, biocompatibility, and ease of use.

[0020] However, for the sake of clarity and conciseness, descriptions of specific embodiments that overlap with descriptions of other embodiments will be omitted. Even if such descriptions are omitted, they are not excluded from this disclosure and should be acknowledged in the same manner as other embodiments.

[0021] In the following description, detailed descriptions of well-known technologies related to this disclosure will be omitted where such descriptions may unnecessarily obscure the subject matter of this disclosure. Furthermore, the terms used in the following description are defined with regard to their function in this disclosure and may change according to the intent of the user or operator or as a matter of practice. Therefore, the definitions of these terms should be determined based on the content of the entire specification.

[0022] The technical spirit of this disclosure is defined by the claims, and the following embodiments are merely means for effectively explaining the technical spirit of this disclosure to those skilled in the art.

[0023] In this disclosure, when the repeating unit, compound, or resin represented by the formula includes its isomers, the corresponding formula representing the repeating unit, compound, or resin also means that it represents the representative formula of the isomers.

[0024] Specific embodiments of this disclosure will be described below. However, these embodiments are merely examples, and this disclosure is not limited thereto.

[0025] Bone graft compositions can be implanted into bone defects and can be used to repair bone defects by filling them. Hereinafter, "implantation" includes application to a bone defect in a non-rigid state or in a rigid state. Application to a bone defect in a rigid state can be performed after the bone defect has been shaped in a rigid state to correspond to the shape of the bone defect using a shape-forming device (e.g., a 3D printer).

[0026] The bone graft composition disclosed herein comprises a porous bone graft material and hydroxypropyl methylcellulose. The bone graft composition can be implanted into bone defects and can be used to repair bone defects by filling them.

[0027] Bone graft materials can be natural bone. For example, it can be autologous bone, allogeneic bone, or xenogeneic bone. When using natural bone, it exhibits excellent bone formation due to its superior biocompatibility and good wettability and hygroscopicity caused by its numerous pores. Furthermore, natural bone can be used for the reconstruction of missing bone in orthopedic surgery, neurosurgery, plastic surgery, otolaryngology, oral and maxillofacial surgery, veterinary medicine (veterinary clinics), dermatology, and dentistry.

[0028] In addition, bone graft materials can also be used for the reconstruction of missing bone in humans or animals. The following description focuses primarily on its dental applications; however, its uses are not limited to this.

[0029] Because the bone graft composition contains hydroxypropyl methylcellulose, it exhibits adhesiveness to bone defects. Furthermore, HPMC imparts shape retention to the bone graft composition. When the bone graft composition possesses excellent shape retention, even when applied to the maxilla, it can be applied appropriately to the bone defect without flowing downwards. Therefore, even with impacts from chewing movements, the bone graft composition can be prevented from detaching from the bone defect, and medical procedures can be performed more easily.

[0030] To ensure shape retention, based on 1 part by weight of porous bone graft material, the bone graft composition according to one embodiment of this disclosure may contain 0.3 to 3 parts by weight (more preferably, 0.4 to 2 parts by weight) of hydroxypropyl methylcellulose. In this case, the shape retention of the composition is further enhanced. As can be seen from the experimental examples described later, it is confirmed that with increasing hydroxypropyl methylcellulose content, the rate of change of the short axis increases, and the maximum breaking force tends to increase and then decrease. Figure 2As shown in the diagram, this increase or decrease is rapid. This confirms that a bone graft composition with shape retention can be provided when the content of hydroxypropyl methylcellulose (HPMC) is 0.3 to 3 parts by weight per 1 part by weight of bone graft material. If the content of HPMC is less than 0.3 parts by weight per 1 part by weight of bone graft material, the effect of adding HPMC may be insignificant due to the low HPMC content. Therefore, even under low pressure, the bone graft material is easily crushed and broken, and its shape cannot be properly maintained. On the other hand, if the content of HPMC is greater than 3 parts by weight per 1 part by weight of porous bone graft material, the high HPMC content causes the bone graft material to be easily crushed even under low force, and even the rate of change of the short axis may increase, resulting in the bone graft material not maintaining its shape properly.

[0031] A bone graft composition kit according to another embodiment of this disclosure includes the above-described bone graft composition and a syringe containing the composition. By providing a syringe that directly contains the bone graft composition, ease of use is ensured and the possibility of contamination that may occur during use is significantly reduced.

[0032] However, in the description of this embodiment, for the sake of clarity and conciseness, descriptions of parts that overlap with those in the above embodiments have been omitted. Even though such descriptions have been omitted, these parts are not excluded from this disclosure and should be acknowledged in the same manner as those in the above embodiments.

[0033] A method for preparing a bone graft composition according to another embodiment of the present disclosure includes the following steps: 1. Dissolve bone morphogenetic proteins to prepare bone morphogenetic protein solutions; 2. Impregnate the transplant material powder in the bone morphogenetic protein solution prepared in step 1; or 3. After adding the bone morphogenetic protein solution prepared in step 1 to the transplant material powder, stir to allow the bone morphogenetic protein to be adsorbed; 4. Mix and stir the bone morphogenetic protein solution and transplant material powder prepared in step 2 or 3 with hydroxypropyl methylcellulose (powder form) to form a gel; and 5. A sponge-like structure containing multiple pores is formed by mixing and stirring a mixture of graft material powder and hydroxypropyl methylcellulose powder obtained by low-temperature freeze-drying under vacuum. Bone graft compositions prepared through these steps exhibit excellent effects in activating bone formation, biocompatibility, and ease of use.

[0034] However, in the description of this embodiment, for the sake of clarity and conciseness, descriptions of parts that overlap with those in the above embodiments have been omitted. Even though these descriptions have been omitted, they are not excluded from this disclosure and should be acknowledged in the same manner as in the above embodiments.

[0035] Figure 1 This is a flowchart schematically illustrating a method for preparing a bone graft composition according to an embodiment of the present disclosure.

[0036] Figure 2 The maximum breaking force (N) of the bone graft composition sphere / the rate of change of the short axis of the bone graft composition sphere is shown as a function of the content (parts by weight) of hydroxypropyl methylcellulose, and the content (parts by weight) of hydroxypropyl methylcellulose for bone graft compositions with excellent shape retention is indicated.

[0037] First, a bone morphogenetic protein solution is prepared by dissolving the bone morphogenetic protein in a solvent. This can be done by adding the bone morphogenetic protein to a solvent or by adding the bone morphogenetic protein to a solvent and then dissolving it in the solvent.

[0038] Bone morphogenetic proteins may be selected from at least one group consisting of 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, their recombinant bone morphogenetic proteins, and their equivalents. Preferably, for the purposes of this disclosure regarding bone formation effects, the bone morphogenetic protein may be rhBMP-2.

[0039] According to one embodiment of this disclosure, the concentration of bone morphogenetic protein in the bone morphogenetic protein solution can be from 0.05 mg / mL to 0.15 mg / mL, preferably from 0.08 mg / mL to 0.12 mg / mL. When the concentration of bone morphogenetic protein is within the above range, bone formation via bone morphogenetic protein can be activated. If the concentration of bone morphogenetic protein is less than 0.05 mg / mL, its ability to form new bone is reduced, and if the concentration of bone morphogenetic protein is greater than 0.15 mg / mL, it will have adverse effects.

[0040] Furthermore, according to one embodiment of this disclosure, the pH of the bone morphogenetic protein solution can be, for example, 4.6 to 5. When the pH is within the above range, bone formation via bone morphogenetic protein can be activated. If the pH of the bone morphogenetic protein solution is less than 4.6, the ability to form new bone is reduced, and if the pH of the bone morphogenetic protein solution is greater than 5, the ability to form new bone is also reduced. For example, phosphate-buffered saline can be used to adjust the pH. When the pH is adjusted using phosphate-buffered saline, bone morphogenetic protein can have the effect of forming new bone.

[0041] Subsequently, the bone morphogenetic protein is adsorbed onto the graft material powder by soaking it in a bone morphogenetic protein solution. This can be achieved by rinsing the previously prepared graft material powder with the solution or by allowing the graft material powder to fall into the solution, thereby adsorbing the bone morphogenetic protein onto the graft material powder.

[0042] The graft material powder can be autologous bone, allogeneic bone, or xenogeneic bone. For example, graft material powder can be prepared by placing it in a snap (or occlusion or snap) tube.

[0043] The average particle size (D50) of the graft material powder can be from 200 μm to 5,000 μm, preferably from 250 μm to 1,000 μm. If the average particle size of the graft material powder is less than 200 μm, the graft material may be rapidly absorbed, resulting in insufficient osteoconduction required for bone formation. Furthermore, if the average particle size of the graft material powder is greater than 5,000 μm, precise handling of the graft material powder during administration to the patient becomes difficult.

[0044] According to one embodiment of this disclosure, the step of adsorbing bone morphogenetic proteins onto transplant material powder may include the step of adsorbing bone morphogenetic proteins using a refrigerated centrifuge.

[0045] In some cases, bone morphogenetic proteins may also be suspended in solution. However, by using a centrifuge to spin the bone morphogenetic protein at high speed while simultaneously adsorbing it, suspension in solution can be prevented, allowing it to readily adsorb onto the surface of the graft material powder or into its pores. Only by simultaneously spinning the bone morphogenetic protein at high speed and adsorbing it can re-suspension after detachment from the graft material powder be prevented. If the bone morphogenetic protein is spinned at low speed, it will remain suspended and is therefore difficult to adsorb. At high speed, bone morphogenetic proteins can be rapidly adsorbed onto the surface of the graft material powder or into its pores.

[0046] According to one embodiment of this disclosure, the speed of the refrigerated centrifuge can be 4,000 rpm or higher. When using a centrifuge to adsorb bone morphogenetic proteins, a higher speed results in better adsorption. For example, the centrifuge speed can be 4,000 rpm or higher, and when this speed range is met, it can prevent bone morphogenetic proteins from becoming suspended in the solution.

[0047] According to one embodiment of this disclosure, the step of adsorbing bone morphogenetic proteins using a refrigerated centrifuge can be performed at a cold temperature of 5°C or lower. Because the step of adsorbing bone morphogenetic proteins using a refrigerated centrifuge is performed at a cold temperature of 5°C or lower, the effect of adsorbing bone morphogenetic proteins onto the surface of the graft material powder or into the pores of the graft material powder by rotation can be maximized, while denaturation of heat-sensitive bone morphogenetic proteins is prevented by preventing the solution temperature from rising due to rotation. The cold temperature can be a temperature at which the solution does not freeze. For example, the cold temperature can be 5°C or lower, preferably 0.5°C to 1.5°C.

[0048] Subsequently, the graft material powder containing bone morphogenetic proteins adsorbed thereon and hydroxypropyl methylcellulose powder are mixed and stirred to form a viscous gel. The resulting viscous gel improves the adhesiveness of the graft material powder. For example, a mixer can be used for stirring. When the graft material powder is stirred with hydroxypropyl methylcellulose in powder form, a product with uniform quality can be obtained.

[0049] According to one embodiment of this disclosure, the volume ratio between the graft material powder having adsorbed bone morphogenetic proteins thereon and the hydroxypropyl methylcellulose powder can be from 1:0.2 to 1:0.6. If the volume ratio of the graft material powder having adsorbed bone morphogenetic proteins thereon to the hydroxypropyl methylcellulose powder is greater than 1:0.2, it may be difficult to form a gel, and if the volume ratio of the graft material powder having adsorbed bone morphogenetic proteins thereon to the hydroxypropyl methylcellulose powder is less than 1:0.6, it may be difficult to form an effective bone graft composition because the volume of the gel is larger than the volume of the graft material powder. For the purposes of this disclosure, the volume ratio between the graft material powder having adsorbed bone morphogenetic proteins thereon and the hydroxypropyl methylcellulose powder can preferably be from 1:0.25 to 1:0.35.

[0050] Subsequently, a mixture of transplant material powder and hydroxypropyl methylcellulose powder, obtained through a mixing and stirring process by freeze-drying under vacuum, is used to form a sponge-like structure containing multiple pores. Alternatively, a sponge-like structure containing multiple pores can be formed by freeze-drying a mixture of transplant material powder and hydroxypropyl methylcellulose powder under vacuum at low temperature through a mixing and stirring process.

[0051] A sponge-like structure with a porous structure can be formed by freeze-drying under vacuum. The gel can be absorbed into the transplant material powder to form a sponge-like structure with a porous structure, and it is believed that vacuum treatment primarily contributes to the formation of this sponge-like structure with a porous structure.

[0052] According to one embodiment of this disclosure, the method for preparing a bone graft composition may further include an encapsulation step.

[0053] According to one embodiment of this disclosure, a method for preparing a bone graft composition may further include the step of placing the prepared bone graft composition, comprising a sponge-like structure having multiple pores, into a graft tube sized for insertion into a syringe. When the method further includes the step of placing the composition into a graft tube sized for insertion into a syringe, the composition is sized to be inserted into the syringe and can therefore be directly inserted into the syringe without a separate process, thereby facilitating the operation of the process for preparing the bone graft composition.

[0054] According to embodiments of this disclosure, the method for preparing a bone graft composition may further include the step of placing the bone graft composition, comprising a sponge-like structure including multiple pores, placed in a graft tube into a syringe and sealing it. When the bone graft composition is placed into the syringe, ease of use is ensured and the possibility of contamination that may occur during use is significantly reduced.

[0055] According to one embodiment of this disclosure, the method for preparing a bone graft composition may further include a step of sterilizing the composition.

[0056] In one embodiment of this disclosure, a bone graft composition comprising a sponge-like structure with multiple pores can be sterilized using ethylene oxide gas. For example, the concentration of ethylene oxide gas can be from 450 mg / L to 1,200 mg / L.

[0057] If the concentration of ethylene oxide gas is less than 450 mg / L, sterilization may be inadequate, and if the concentration of ethylene oxide gas is greater than 1,200 mg / L, denaturation of bone morphogenetic proteins may occur.

[0058] According to one embodiment of this disclosure, a bone graft composition comprising a sponge-like structure with multiple pores can be sterilized by gamma irradiation. For example, the gamma irradiation dose can be from 10 kGy to 25 kGy. If the gamma irradiation dose is less than 10 kGy, sterilization may be insufficient, and if the gamma irradiation dose is greater than 25 kGy, denaturation of bone morphogenetic proteins may occur.

[0059] The bone graft composition prepared according to the methods described above, based on embodiments of this disclosure, can have shape retention properties for application to the human body, for example, for application to missing teeth. This shape retention property can be determined by factors such as the content of hydroxypropyl methylcellulose (HPMC) in the bone graft composition.

[0060] For example, when applying bone graft material to teeth, the bone graft material should possess a predetermined degree of plasticity so that it can deform to fit the shape of the missing tooth when applied by a dentist. Furthermore, after application, the bone graft composition should not flow out or detach. Therefore, the bone graft material should have a predetermined degree or higher of plasticity, and also a predetermined degree or higher of strength to resist gravity or movement of the bone (tooth) defect.

[0061] This degree of strength and plasticity can be defined as shape retention. To quantify the objectivity of shape retention, it can be defined by the rate of change of the minor axis, which can be quantified as: when a force of XXXN is applied to the sample, the spherical shape of a spherical sample with a diameter of XXX mm deforms into an elliptical shape.

[0062] To meet the aforementioned plasticity and stiffness requirements, the shape retention of the bone graft composition should be 50 or greater. If the shape retention is less than 50, the bone graft composition will be difficult to apply to the bone defect due to its high elasticity. That is, when a medical operator applies the bone graft composition to the bone defect, the composition should deform to fit the shape of the defect; however, if the composition is highly elastic, it will be difficult to deform due to its high resilience. On the other hand, if the shape retention is less than 50, the bone graft composition will leak out during medical procedures (such as hydration performed by a medical operator), making the procedure practically impossible.

[0063] Therefore, in order to ensure the suitability of the bone graft composition while ensuring ease of use in actual medical procedures, the "maximum breaking force (N) / minor axis change rate" of the bone graft composition should be 50 or greater. In this case, due to the excellent shape retention of the bone graft composition, it is easily deformable to fit the shape of the bone defect, and a bone graft composition without problems (such as leakage of the bone graft composition into the surrounding tissue during medical procedures, such as hydration performed by a medical operator) can be obtained. For this purpose, based on 1 part by weight of bone graft material, the content of hydroxypropyl methylcellulose is 0.3 to 3 parts by weight, and in this case, a bone graft composition with a shape retention of 50 or greater can be obtained.

[0064] Preferred examples will be given below to aid in understanding this disclosure. However, these examples are merely illustrative and are not intended to limit the scope of the disclosure as defined in the appended claims. Furthermore, it will be apparent to those skilled in the art that various changes and modifications to these examples are possible without departing from the scope and spirit of the disclosure. It will also be understood that such changes and modifications fall within the scope of the appended claims.

[0065] Experimental Example 1 1. An experiment used to examine shape retention that depends on the content of hydroxypropyl methylcellulose (HPMC). As shown in Table 1 below, different amounts (0.1 parts by weight to 6 parts by weight) of HPMC were each mixed with 0.25 g of bone graft material and then dissolved in a solvent (1,3;2,4-dibenzylsorbitol, DBS) to form a viscous gel, which was then shaped into spheres. The dimensions of each initial sphere are shown as the major and minor axis lengths in Table 1 below. A push-pull gauge was used to apply pressure to each sphere, and the minor axis length at the maximum breaking force (N) (i.e., maximum peak value) before each sphere was about to break was measured. The rate of change of the minor axis obtained by comparing the minor axis length at the maximum breaking force with the initial minor axis length is shown in Table 1 below.

[0066] 2. An experiment used to check the strength depending on the content of HPMC (hydroxypropyl methylcellulose). In Experiment Example 1 above, the maximum breaking force (N), i.e., the maximum peak value, was measured just before each sphere broke. The measurement results are shown in Table 1 below. It can be interpreted that the greater the maximum breaking force (N), the greater the strength.

[0067] Table 1

[0068] 3. Check the shape retention using the maximum breaking force (N) relative to the rate of change of the minor axis. To form a bone graft composition with excellent shape retention, optimal strength and non-rebound are required. Table 2 below shows the rate of change of maximum breaking force relative to the short axis, depending on the content of HPMC (hydroxypropyl methylcellulose). Figure 2 The maximum breaking force (N) of the bone graft composition sphere / the rate of change of the short axis of the bone graft composition sphere, calculated based on the results shown in Table 2, is presented as a function of the content (parts by weight) of hydroxypropyl methylcellulose.

[0069] Table 2

[0070] When the content of hydroxypropyl methylcellulose (HPMC) is 0.1 to 0.2 parts by weight, the rate of change of the minor axis is high and the maximum breaking force (N) is low. Therefore, in this case, the "maximum breaking force (N) / rate of change of minor axis" value is low, and thus the shape retention is not excellent. This means that the shape is easily altered even with slight forces, and such alteration is highly detrimental during medical procedures involving the application of the bone graft composition. This is understood to be a phenomenon occurring due to the small amount of HPMC that increases the stiffness of the bone graft composition.

[0071] Furthermore, in each of the bone graft compositions containing 4 parts by weight or more of hydroxypropyl methylcellulose (HPMC), the rate of change of the short axis is high and the maximum breaking force (N) is low. Therefore, in this case, the "maximum breaking force (N) / rate of change of short axis" value is low, and thus the shape retention is not excellent. That is to say, it can be seen that when the content of HPMC in the bone graft composition is too high (4 parts by weight or more), HPMC reduces the shape retention of the bone graft composition without increasing its stiffness.

[0072] When 1 part by weight of bone graft material contains 0.3 to 3 parts by weight of hydroxypropyl methylcellulose (HPMC), a bone graft composition with excellent shape retention can be obtained due to a maximum breaking force (N) / minor axis change rate of 50 or greater. In another example, when 1 part by weight of bone graft material contains 0.4 to 2 parts by weight of hydroxypropyl methylcellulose (HPMC), a bone graft composition with excellent shape retention can be obtained due to a maximum breaking force (N) / minor axis change rate of 60 or greater. In yet another example, when 1 part by weight of bone graft material contains 0.6 to 1.5 parts by weight of hydroxypropyl methylcellulose (HPMC), a bone graft composition with excellent shape retention can be obtained due to a maximum breaking force (N) / minor axis change rate of 70 or greater.

[0073] As described above, the bone graft composition containing hydroxypropyl methylcellulose according to this disclosure has excellent shape retention due to its high strength and non-resilient properties, and has excellent effects in activating bone formation, biocompatibility and ease of use.

Claims

1. A method for preparing a bone graft composition, the method comprising the following steps: (1) Bone morphogenetic protein solutions with concentrations from 0.05 mg / mL to 0.15 mg / mL were prepared by mixing the solvent and bone morphogenetic protein; (2) The bone morphogenetic protein solution is mixed with porous bone graft material powder with an average particle size of 200 μm to 5,000 μm, and centrifuged at 4,000 rpm or higher at a cold temperature of 5°C or lower using a refrigerated centrifuge, so that the bone morphogenetic protein is physically adsorbed onto the surface or pores of the porous graft material powder. (3) Mix and stir 1 part by weight of the graft material powder having the bone morphogenetic protein adsorbed thereon and 0.3 to 3 parts by weight of hydroxypropyl methylcellulose powder based on 1 part by weight of the graft material powder to form a gel; and (4) By freeze-drying the gel under vacuum, a sponge-like structure is formed in which the transplant material powder is fixed within a polymer network formed by the hydroxypropyl methylcellulose.

2. The method according to claim 1, wherein, Bone morphogenetic proteins are selected from at least one group consisting of 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, their recombinant bone morphogenetic proteins, and bone morphogenetic proteins equivalent to them.

3. The method according to claim 1, wherein, The concentration of the bone morphogenetic protein in the bone morphogenetic protein solution is from 0.05 mg / mL to 0.15 mg / mL.

4. The method according to claim 1, wherein, The pH of the bone morphogenetic protein solution was adjusted to 4.6 to 5 using phosphate-buffered saline.

5. The method according to claim 1, wherein, In step (3), the volume ratio between the transplant material powder containing bone morphogenetic proteins adsorbed thereon and the hydroxypropyl methylcellulose powder is 1:0.2 to 1:0.6.

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