KR20230153107A - Bone graft composition and kit including the same - Google Patents

Abstract

The present invention is a bone graft material composition containing demineralized bone powder (DBM, Demineralized Bone, Matrix), wherein the demineralized bone powder is unpulverized ultrafine particle demineralized bone with an average particle diameter of 0.1 to 80 ㎛ or less, 300 to 750 ㎛. Provided is a bone graft material composition comprising effective particle demineralized bone having an average particle diameter of less than or equal to 750 to 6000 ㎛, fibrous demineralized bone having an average particle size of less than or equal to 6000㎛, and a biocompatible hydrating material, and a kit containing the same.

Description

Bone graft material composition and kit containing the same {BONE GRAFT COMPOSITION AND KIT INCLUDING THE SAME}

The present invention relates to a bone graft material composition and a kit containing the same.

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, as an allogeneic bone graft material, DBM (Demineralized bone matrix) is also called demineralized bone matrix. It was discovered by Marshall Urist et al. in 1965 that its osteoinductive ability is significantly superior to that of non-demineralized bone or freeze-dried bone, and it has been standardized and used to this day. . In particular, bone morphogenic protein (BMP), which is surrounded by organic substances (minerals), is a protein that has a significant impact on the bone formation mechanism, and can be isolated or extracted by a manufacturing method that demineralizes bone with hydrochloric acid (Hcl).

Since bone morphogenetic proteins were discovered in demineralized bone in the 1960s, numerous manufacturers have supplied products that can be applied clinically. However, these products had the disadvantage of being easily eroded or dissolved in the body during the period of bone formation and could not be maintained, but as technology developed, the above disadvantages were overcome by mixing demineralized bone matrix with a carrier. In particular, in the case of carriers, products with maximized practicality have been developed so that they can be easily fixed to the implanted part, such as the development of a putty type that changes viscosity depending on temperature changes and maintains solidification for a long time.

However, depending on the type, these carriers are miscible and may not do their job properly in an aqueous environment and may dissolve, or may have a negative effect on the biocompatibility and bone inductive properties of the DBM composition. In addition, since the carrier accounts for the largest proportion of the composition, the content of the DBM composition is inevitably reduced, so the bone formation effect can be expected to be significantly reduced compared to products made only with 100% DBM composition.

Therefore, although the DBM demineralized bone matrix mixed with the carrier has the advantage of far superior retention in the body, there is still a need for a non-carrier hydrated DBM demineralized bone matrix with excellent biocompatibility and no side effects from the carrier.

Korean Patent Registration Notice No. 10-0401941 (Publication Date: 2002.02.25)

The present invention was developed to solve the above-described technical problem. The bone graft material composition according to the present invention has properties such as bone formation activation, biocompatibility, and ease of use, as well as demineralized bone powder (DBM) containing ultrafine powder in a specific range. The purpose is to provide a bone graft material composition that can sufficiently maintain bone induction ability by demineralized bone, matrix, and a kit containing the same.

In order to achieve the above problems, the bone graft material composition according to the present invention,

A bone graft material composition containing demineralized bone powder (DBM, Demineralized Bone, Matrix), wherein the demineralized bone powder is unpulverized ultrafine particle demineralized bone with an average particle diameter of 0.1 to 80 ㎛ or less, and 300 to 750 ㎛ or less. It may include non-pulverized effective particle demineralized bone with an average particle size, non-pulverized fibrous demineralized bone with an average particle size of 750 to 6000 ㎛ or less, and a biocompatible hydration material.

In one embodiment of the present invention, the content ratio of the unpulverized ultrafine particle demineralized bone, non-pulverized effective particle demineralized bone, non-pulverized fibrous demineralized bone, and biocompatible hydration material in the demineralized bone powder is 0.1 to 1.5. : 0.1~1.5 : 0.1~1.5 : Can be included in the range of 1~10.

In one embodiment of the present invention, the porous bone graft material may be a naturally derived bone graft material.

In one embodiment of the present invention, the bone graft material composition may further include hydroxypropyl methylcellulose.

Here, the content of the hydroxypropyl methylcellulose may be 0.1 to 1.5 parts by weight relative to 1 part by weight of the porous bone graft material. Preferably, it may be included in 0.25 to 0.4 parts by weight.

In one embodiment of the present invention, the bone graft material composition may further include an additive with cross-linking properties and a thickener.

In one embodiment of the present invention, the additive includes a synthetic polymer material, and the synthetic polymer material includes polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), poly-ε -(Caprolactone) (PCL), polyanhydrides, polyorthoesters, polyvinyl alcohol, polyethylene glycol, polyurethane, polyacrylic acid, It may include at least one member selected from the group consisting of poly-N-isopropylacrylamide.

In one embodiment of the present invention, the additive includes a natural polymer material, and the natural polymer material includes cellulose, carboxycellulose, methylcellulose, carboxymetylcellouse, and poloxamer. (poloxamer), collagen peptide, starch, glycerol (glycerin), polyethylene glycol, collagen, chitosan, hyaluronic acid, dextran (dextran) and hydroxypropylmethylcellulose (HPMC).

In one embodiment of the present invention, the bone graft material composition may include a sponge form including a porous structure.

Meanwhile, the present invention can provide a bone graft material composition kit including the bone graft material composition and a syringe for mounting the bone graft material composition.

The bone graft material composition according to the present invention and the kit containing the same have the properties of activating bone formation, biocompatibility, and ease of use, as well as bone induction by demineralized bone powder (DBM, Demineralized Bone, Matrix) containing a specific range of ultrafine powder. It has the effect of maintaining sufficient ability.

Figure 1 is a photograph showing the results of a physical property test of a bone graft material according to an embodiment of the present invention.

Examples of one embodiment of the present invention use ultra-fine powder demineralized bone, which greatly reduces the size of the fine particle demineralized bone of demineralized bone powder, to improve formability and fixation force like putty remodeling, and at the same time produce effective particle demineralized bone. It relates to a bone graft material composition that can sufficiently maintain and improve osteoinduction ability by preventing excessively rapid absorption of residual demineralized bone in the donor's body by including it in a certain ratio, and a kit containing the same.

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.

Additionally, the bone graft material composition of the present invention may include decalcified bone powder, a thickener, 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 according to the present invention contains different ultra-fine powder sizes of demineralized bone powder (DBM, Demineralized Bone, Matrix) within a specific range, thereby preventing excessively rapid absorption of the remaining demineralized bone, thereby improving bone induction ability. It can be sufficiently maintained and improved.

Here, according to the present invention, the bone graft material composition includes the demineralized bone powder (DBM), unpulverized ultrafine particle demineralized bone with an average particle diameter (D) of 0.1-80㎛, and non-pulverized bone with an average particle diameter (D) of 300-750㎛. It may contain effective particle demineralized bone, non-pulverized fibrous demineralized bone of 750-6000㎛, and biocompatible hydration material in the ratio of 0.1~1.5:0.1~1.5:0.1~1.5:1~10. At this time, when the content ratio of the ultrafine particle demineralized bone is less than 0.1, the ultrafine particle content, which plays a role in strengthening cohesion, is insufficient in the composition, so the cohesion may not be good and may be scattered. If the ultrafine particle demineralized bone content ratio exceeds 1.5, the ultrafine demineralized bone content with small particle size may be destroyed by macrophages and may not fully play its original role of bone regeneration.

In addition, if the content ratio of the pulverized effective particle demineralized bone (300 ~ 750㎛) is less than 0.1, the moldability may be reduced during the handling process to mold into a specific shape, resulting in severe separation from the hand, and the content ratio exceeds 1.5. In this case, bone regeneration ability may temporarily decrease due to excessive formability due to loss of shape fixity.

Preferably, the bone graft material composition includes the demineralized bone powder (DBM) as unpulverized ultra-fine particle demineralized bone with an average particle diameter (D) of 0.1-80㎛, or non-pulverized effective particle demineralized bone with an average particle diameter (D) of 300-750㎛. , 750-6000㎛, non-pulverized fibrous demineralized bone and biocompatible hydrated material may be included in the ratio of 0.1~0.2:0.8~0.9:0.6~0.9:4~5. More preferably, the demineralized bone powder (DBM) is composed of unground ultrafine particle demineralized bone with an average particle diameter (D) of 0.1-80㎛, non-pulverized effective particle demineralized bone of 300-750㎛, and 750-6000㎛. It may contain non-pulverized fibrous demineralized bone and biocompatible hydrated material in the ratio of 0.15:0.85:0.7:4.5.

Additionally, 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.

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 may further include hydroxypropyl methylcellulose as an additive along with demineralized bone powder and a 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 50% of the additive may be dissolved within a predetermined period of time. The predetermined period may be 3 to 7 days.

If the additive is dissolved by more than 50% within 3 days, excessive amounts of bioactive substances are released and the inflammatory reaction continues in a sustained manner, making it impossible to eliminate inflammation. Additionally, if it takes more than 7 days for more than 50% of the additive to dissolve, bioactive substances may remain in places where bone cells should enter, which may interfere with bone formation. Accordingly, in order for the bone graft material composition to have adhesion to the bone defect, the additive must be dissolved within 3 to 7 days.

The content of the additive may be 0.1 part by weight or more and 4 parts by weight or less compared to 1 part by weight of the bone graft material. The composition ratio of the additive may be physiologically active material: thickener: additive = 0.1 to 1: 0.1 to 1: 0.1 to 1.

The bioactive substance may be asiatic coside or ipecalocadetin 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.

Meanwhile, the method for producing a bone graft material composition according to the present invention is to use demineralized bone powder (DBM) as unground ultrafine particle demineralized bone with an average particle diameter (D) of 0.1-80㎛, and non-pulverized bone with an average particle diameter (D) of 300-750㎛. Preparing effective particle demineralized bone, non-pulverized fibrous demineralized bone of 750-6000㎛, and biocompatible hydrated material in a ratio of 0.1~1.5:0.1~1.5:0.1~1.5:1:10, bone forming protein in solvent A step of preparing a bone morphogenic protein solution by dissolving the bone morphogenic protein in the solvent by adding or adding the bone morphogenic protein to a solvent, adding the bone morphogenic protein solution to a pre-prepared ultra-fine demineralized bone powder (DBM, Demineralized Bone, Matrix). Adsorbing the bone morphogenetic protein to the decalcified bone powder by immersing the graft material powder in the bone morphogenetic protein solution by flowing or dropping the graft material powder into the bone morphogenetic protein solution, the demineralized bone powder to which the bone morphogenetic protein is adsorbed and mixing and stirring the hydroxypropyl methylcellulose powder to form a viscous gel, and drying the mixed and stirred mixture of the decalcified bone powder and the hydroxypropyl methylcellulose powder while freezing at a low temperature in a vacuum to form a viscous gel, thereby forming a viscous gel. By including the step of forming a sponge shape containing a structure, the effects of activating bone formation, biocompatibility, and ease of use can be excellent.

First, prepare a bone morphogenetic protein solution by dissolving the bone morphogenetic protein in a solvent. A bone forming protein solution can be prepared by adding bone forming protein to a solvent or dissolving the bone forming protein in the solvent by adding bone forming protein to the solvent.

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 demineralized bone powder is immersed in the bone forming protein solution, and the bone forming protein is adsorbed onto the demineralized bone powder. By pouring the bone forming protein solution into a previously prepared demineralized bone powder or dropping the demineralized bone powder into the bone forming protein solution, the demineralized bone powder is immersed in the bone forming protein solution and adding bone forming protein to the demineralized bone powder. can be adsorbed.

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

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

In some cases, bone morphogenetic proteins may be suspended in the solution, and when adsorbed while rotating using a centrifuge, the bone morphogenetic proteins can be prevented from floating in the solution and thus within the surface or pores of the demineralized bone powder. Bone morphogenetic proteins can be well absorbed. It must be adsorbed while rotating rapidly to prevent the bone forming proteins from detaching from the demineralized bone powder and resuspending. If it is slow, bone morphogenetic proteins may float and adsorption may be poor. Bone morphogenetic proteins can be rapidly adsorbed onto the surface or within the pores of demineralized bone 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°C or lower, the temperature of the solution is prevented from rising due to rotation, thereby preventing deformation of the bone-forming protein that is vulnerable to heat, and decalcified bone powder of the bone-forming protein through rotation. The adsorption effect on the surface or in 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, demineralized bone powder adsorbed with bone forming protein, thickener, and 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 demineralized bone powder. For example, the stirring can be performed with a mixer. By mixing demineralized bone powder with hydroxypropyl methylcellulose in powder form along with a thickener, a result with uniform quality can be obtained.

Next, the mixed and stirred mixture of decalcified bone powder and hydroxypropyl methylcellulose powder is vacuum freeze-dried to form a form containing a porous structure. The mixed and stirred mixture of the demineralized bone 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 demineralized bone 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 450 to 1200 mg/l. Here, when the Ethylene Oxide Gas concentration is less than 450 mg/l, sterilization may be insufficient, and when it is more than 1200 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 irradiation dose of gamma rays may be 10 to 25 kGy. When the gamma ray irradiation amount is less than 10 kGy, sterilization may be insufficient, and when it is more than 25 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.

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.

[Example]

A composition for bone regeneration was prepared in a general environment at room temperature with the composition ratio according to <Table 1> below, and then the same volume (5 cc) was filled into a syringe to prepare a total of 11 test groups.

Ultrafine powder (㎛) Fine powder (㎛) Effective particles ( ㎛) Fibrous matrix ( ㎛) Distilled water
(D.W) Below 80 250 or less 300-400 400-500 500-600 700-6000 One 0.05 0.95 0.7 4.5 2 0.15 0.85 0.7 4.5 3 0.15 0.85 0.7 4.5 4 0.15 0.85 0.7 4.5 5 0.3 0.7 0.7 4.5 6 0.6 0.4 0.7 4.5 7 0.9 0.1 0.7 4.5 8 One 0.7 4.5 9 One 0.7 4.5 10 0.7 0.3 0.7 4.5 11 One 0.7 4.5

[Experimental example]

First, a shape retention test during discharge was conducted, which indicates the degree to which the composition sticks together rather than being easily broken when the composition is discharged by pressing the syringe pusher. If the discharged composition maintained its shape without cracking or breaking, it was rated at a maximum of 3 points, and the weaker the degree, the lower the rating.

Next, considering that it is a putty type for attaching to a bone defect of an unspecified shape, the composition is molded into a square or circular shape and tested for cohesion, which can easily create a lumped shape without breaking. The better the cohesion, the better. It was easy to create shapes such as squares and circles, and once the cohesive shape was formed, it was not easily broken. The better the cohesion, the maximum score was 3, and the worse the ability, the lower the rating.

Finally, a break-off deterrence test was conducted to check the extent to which stains were left on the hands while touching the manufactured test specimen during the test. At this time, it is also a test that can indirectly evaluate the cohesiveness and fixation power of the composition. The more it sticks to the hands, the lower the rating, and if there is almost nothing on the hand, it is rated at a maximum of 3 points. The results of measuring the shape retention, cohesion, and dissipation inhibition power of the test specimens for experiments of test groups with different content ratios and particle sizes of each composition according to Table 1 below are shown in <Table 2> below.

fixation force cohesion Degree of deviation Sum One 2 2 2 6 2 3 3 3 9 3 2 2 2 6 4 2 One One 4 5 3 3 3 9 6 3 3 3 9 7 3 3 3 9 8 3 2 2 7 9 One 2 2 5 10 2 One One 4 11 3 2 2 7
<Evaluation criteria>

1. Holding power: No cracks or breaks from start to finish (3 points)
When fully ejected, it is segmented into 1-2 segments (2 points)
It comes out partly in clumps, but breaks right away (1 point)
Everything breaks down and spits out from the beginning (0 points)

2. Cohesion: Easily change shape or feel sticky (3 points)
It comes together as a whole, but breaks or splits whenever the shape is changed (2 points)
It clumps together at first but quickly falls apart (1 point)
Crumbling (0 points)

3. Degree of breakaway: Almost nothing on hands (3 points)
Some substance on hands (2 points)
A lot of substance on hands (1 point)
Crumbles in hand (0 points)

As shown in Table 2, in the case of test groups (3, 4) composed of effective particle sizes of 400㎛ or more, cohesion was clearly reduced and fixation strength was poor. Even if the ultrafine powder content was more than 0.15, the cohesion and fixation power were not significantly improved. However, in the case of the test group (2, 5, 6, 7) in which the effective particle size of the demineralized bone powder (DBM) contained only 300 to 400㎛ or less, the fixation strength was reduced even if more than 0.15 ultrafine powders of 80㎛ or less were included. It was confirmed that the cohesion was excellent.

However, in the test group where the ultrafine powder content was less than 0.15, cohesion and fixation power showed a clear decrease. Therefore, the higher the content of effective particles, the longer they remain in the body and the more advantageous it is for bone repair, so it was confirmed that the most appropriate content was the second test group.

Above, an embodiment according to the present invention has been described in detail. However, the embodiments of the present invention are not necessarily limited to the above-described embodiment, and it is natural that various modifications and equivalent implementations can be made by those skilled in the art. will be. Therefore, the true scope of rights of the present invention will be determined by the claims described later.

Claims (10)

A bone graft material composition containing demineralized bone powder (DBM, Demineralized Bone, Matrix), wherein the demineralized bone powder is ultrafine particle demineralized bone with an average particle size of 0.1 to 80 ㎛ or less, and an average particle size of 300 to 750 ㎛ or less. A bone graft material composition comprising at least one of effective particle demineralized bone having an average particle diameter of 750 to 6000 ㎛ or less, and a biocompatible hydrating material.
According to claim 1,
The content ratio of the unpulverized ultrafine particle demineralized bone, non-pulverized effective particle demineralized bone, non-pulverized fibrous demineralized bone, and biocompatible hydration material in the demineralized bone powder is 0.10 to 1.5: 0.1 to 1.5: 0.1 to 1.5. : Bone graft material composition included in the range of 1 to 10.
According to claim 1,
The porous bone graft material is a bone graft material of natural origin.
According to claim 1,
The bone graft material composition further includes hydroxypropyl methylcellulose.
According to claim 4,
A bone graft material composition comprising 0.1 to 1.5 parts by weight of the hydroxypropyl methylcellulose relative to 1 part by weight of the porous bone graft material.
According to claim 1,
The bone graft material composition further includes a cross-linking additive and a thickener.
According to claim 6,
The additive includes a synthetic polymer material,
The synthetic polymer materials include polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), poly-ε-(caprolactone) (PCL), polyanhydrides, poly At least one selected from the group consisting of polyorthoesters, polyvinyl alcohol, polyethylene glycol, polyurethane, polyacrylic acid, and poly-N-isopropylacrylamide. A bone graft material composition comprising:
According to claim 6,
The additive includes a natural polymer material,
The natural polymer materials include cellulose, carboxycellulose, methylcellulose, carboxymetylcellouse, poloxamer, collagen peptide, starch, and glycerol ( At least one selected from the group consisting of glycerol (glycerin), polyethylene glycol, collagen, chitosan, hyaluronic acid, dextran, and hydroxypropylmethylcellulose (HPMC). A bone graft material composition comprising one or more types.
According to claim 1,
The bone graft material composition includes a sponge form including a porous structure.
A bone graft material composition kit, comprising the bone graft material composition according to any one of claims 1 to 9 and a syringe for mounting the bone graft material composition.