KR20160093520A - Method of producing bone grafting materials and a bone grafting materials produced thereby - Google Patents
Method of producing bone grafting materials and a bone grafting materials produced thereby Download PDFInfo
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- KR20160093520A KR20160093520A KR1020150131668A KR20150131668A KR20160093520A KR 20160093520 A KR20160093520 A KR 20160093520A KR 1020150131668 A KR1020150131668 A KR 1020150131668A KR 20150131668 A KR20150131668 A KR 20150131668A KR 20160093520 A KR20160093520 A KR 20160093520A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
- A61F2002/2835—Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00179—Ceramics or ceramic-like structures
- A61F2310/00293—Ceramics or ceramic-like structures containing a phosphorus-containing compound, e.g. apatite
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- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
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Abstract
Description
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bone graft material, and more particularly, to a bone graft material that is formed in the form of an amorphous gel or a sword and can be directly implanted in a patient's treatment area, A bone graft material, and a bone graft material produced by the method.
Vertebrate animals, including humans, have the ability to regenerate bones, but in order to aid in restoring lost bones in the event that some of the bones are lost due to disease, accident, or aging, A variety of bone graft materials have been developed and used. Particularly, such a bone graft material is also used when the bone mineral density at the implantation site is low or the bone is empty at the time of implantation of the teeth.
The bone graft material is made using a patient's own bone, another person's bone, or other animal's bones, or using a synthetic material having components similar to human bones.
The patient's own bones are advantageous in that they have no infection or immunity rejection, are excellent in bone formation through bone induction and bone conduction, but require secondary surgery to collect the patient's own bones There is also concern about secondary infection during the collection process.
In the case of using the bone of another person, there is an advantage that the bone formation is excellent as in the case of using the patient's own bone, but there is a possibility of infection due to the disease history of the subject. Although the use of other animal bones has the advantage of being easy to collect and supply, there is a disadvantage that additional treatment is required to prevent immune rejection and bone formation is slow.
Unlike animal bones, bone grafts made through synthesis include calcium phosphate compounds such as hydroxyapatite and beta-tricalcium phosphate, which are obtained from synthetic or natural extracts, Is mainly used.
The bone graft material using the calcium phosphate compound has low bone conduction and low bony restoration but is easy to obtain and process the material and has low moldability and no fear of infection. A variety of synthetic bone graft materials have been developed and used.
Such a bone graft material is supplied in the form of a granular powder containing only bone graft material containing calcium phosphate as a main material or mixed or coated with bone morphogenetic protein (BMP), and bone graft materials should be supplied After filling the bone graft material with granular bone graft material, physiological saline or the blood of the patient to be treated is filled to give viscosity. The transplanted bone graft material serves as a support for the restoration site in the process of restoration of the bones, allowing vascular tissue and osteoblasts to grow at the graft site.
However, in the above-described procedure using the granular powder-type bone graft material, as shown in FIG. 1, there is a problem that the bone graft material powder is separated from the treatment site and loss occurs. There arises a problem of leaving an empty space without filling it. Particularly, since such a graft material has a large granule size of 200 to 1,500 占 퐉, there is a problem that it takes a considerable time more than several months after bone graft restoration.
The present invention has been made in view of the above problems of the prior art, and it is an object of the present invention to provide a bone graft material which can be filled without leaving a bone graft site outside the graft site, Which is formed into a gel or a sword-like amorphous form so that the procedure of the bone graft material can be directly implanted in the treated region of the bone graft material.
Particularly, in the present invention, methylcellulose or carboxymethylcellulose, which exhibits an excellent function as a carrier of bone graft material but does not easily disperse due to high viscoelasticity, is used as a carrier, and a bone graft material and these carrier materials are mixed to form gel- In which a sufficient dispersion can be made to form a film.
In addition, the present invention provides a method of manufacturing a bone graft material which is formed into a solid shape and which is amorphous in gel form by adding distilled water or the like during implantation, and can be directly implanted in a treatment site.
In the present invention, hydroxyapatite (HA, hydroxyapatite), which is most similar to the inorganic component of bone as bone graft material and has excellent bone forming function, is mainly considered. However, the method of manufacturing a bone graft material according to the present invention and the material of the bone graft material produced by such a manufacturing method are not limited to hydroxyapatite, but may be selected from the group consisting of tricalcium phosphate (TCP), monocalcium phosphate, tetracalcium phosphate, And a calcium phosphate compound which is suitable as a bone graft material and contains such a calcium phosphate compound as a main raw material.
In the present specification, the term " as the main ingredient " means that the bone graft material may contain a substance that promotes bone formation, such as BMP, in addition to a calcium phosphate compound that replaces an inorganic component of the bone.
According to a first aspect of the present invention, there is provided a method of manufacturing a gel-type bone graft material, which comprises mixing a powder of a bone-grafting material containing a calcium phosphate compound with distilled water, wet-milling a mixture of distilled water and bone- A pulverized bone having a particle size of 200 to 2000 nm is prepared from a mixture of the edible material and distilled water,
The thus prepared bone sol of the edible material is heated to a temperature of 50 to 90 DEG C and 1 to 4 parts by weight of methylcellulose or carboxymethylcellulose powder is mixed with 40 parts by weight of the bone-
Agitating the mixture of the sol of edible material and the powder of methylcellulose or carboxymethylcellulose under the condition that moisture in the sol of the bone edible material can be evaporated while maintaining the temperature at 50 to 90 DEG C to form the methylcellulose or Carboxymethylcellulose is dispersed in the sol of the bone-digesting material, the moisture is evaporated so that the distilled water is 12 to 20 parts by weight per 40 parts by weight of the bone graft material,
Then, the gel of the bone graft material is formed by stirring the mixture of the bone grafting material and the methyl cellulose or carboxymethyl cellulose under conditions that moisture in the mixture does not evaporate.
As used herein, the term " bone-forming material containing a calcium phosphate compound " refers to a calcium phosphate compound that replaces an inorganic component of bone as a bone-forming material, as well as a BMP And the like are added to the bone.
On the other hand, it is generally known that when the size of the bone graft material is small, the space between the bone graft materials becomes small and the bone restoration speed becomes high. However, when the graft size of the bone graft material is low, the bone graft material is scattered, Therefore, the conventional bone graft material is manufactured as a powder having a particle size in the range of 200 to 1,500 μm, and thus there is a problem that the bone restoration speed is not sufficient.
However, in the present invention, since the bone graft material has a very small grain size, it is formed in gel or sword-shaped amorphous form. Therefore, there is no fear that the bone graft material will scatter during the grafting operation, .
It is costly and time consuming to crush bone graft materials with a particle size of less than 200 nm, and when the particle size exceeds 2,000 nm, the bone graft material is mixed with distilled water There is a problem that the bone graft material is not sufficiently dispersed. Therefore, in the present invention, the crushed material is pulverized to have a particle size of 200 to 2000 nm.
Meanwhile, as one embodiment of the present invention, it is preferable that the weight ratio of the distilled water to the powder of the bone-eating material is 1 to 4 in the step of preparing the sol of the bone-digesting material.
When the wet grinding is performed by mixing the ratio of the distilled water to the bone graft material to less than 1, the bone graft material may not be sufficiently pulverized and the grain size may be increased. Therefore, the weight of the bone graft material There is a disadvantage in that it takes a long drying time to adjust the ratio of the distilled water for forming the gel in the dispersion and drying step after forming the sol of the bone graft material.
As a further embodiment of the present invention, it is preferable that the powder of the bone graft material is pulverized by wet abrasive grinding using a ceramic ball having high hardness in the step of preparing the sol of the bone graft material. As the ceramic balls, zirconia balls, alumina balls, silicon nitride balls, and the like can be used.
Meanwhile, in the present invention, a mixture of methylcellulose and carboxymethylcellulose is mixed with a sol of a bone graft material prepared by mixing and pulverizing bone graft material with distilled water, and the mixture is stirred to form a gel bone graft material. Methylcellulose or carboxymethylcellulose is obtained by mixing the pulverized bone with the sol of the edible material so that the bone graft material according to the present invention is formed into a gel or a sword form so that it can be amorphously implanted into a treatment site at the time of surgery, To the sol of the bone graft material.
Methylcellulose and carboxymethylcellulose are used as a topical or suspending agent in cosmetics, pharmaceuticals, and chemical industries, or as a viscosity modifier in foods, and are commercially available in powder form and are excellent in affinity with body fluids and can be non-toxic and can be discharged as a liquid .
In the present invention, methylcellulose or carboxymethylcellulose is mixed with the sol of the bone graft material, and 1 to 4 parts by weight of the bone graft material is mixed with 40 parts by weight of the bone graft material.
If the content of these materials is less than 1 part by weight, the bone graft material will not be sufficiently dispersed and scattered. If the content exceeds 4 parts by weight, the viscosity of the bone graft material prepared according to the present invention becomes excessively high, There are disadvantages to come out.
The thus mixed mixture is dried at the same time while stirring to disperse methyl cellulose or carboxymethyl cellulose.
The powder of methylcellulose or carboxymethylcellulose is mixed with the sol of the bone graft material heated to 50 to 90 DEG C, and the mixture is maintained in the temperature range of 50 to 90 DEG C even in the stirring and drying of the mixture.
Methylcellulose has a minimum dissolution temperature of about 50 占 폚, wherein the sol or mixture of bone graft material maintains a temperature of 50 占 폚 or higher because it is easily dissolved below this temperature and is dispersed without dissolving in the solvent above this temperature.
On the other hand, when the temperature of the sol or the mixture of the bone graft material is more than 90 캜, the moisture in the sol or the mixture is rapidly vaporized, making it difficult to dry in order to maintain the proper material ratio for forming the gel.
On the other hand, in the dispersion and drying step, drying is performed so that the weight ratio of the distilled water to the bone graft material is 40 to 20 parts by weight. If the distilled water remains less than 12 parts by weight, the mixture does not become a complete gel, It can remain in powder form, and if the distilled water remains in excess of 20 parts by weight, the bone graft does not become a gel having sufficient viscosity.
The mixture which has been dispersed and dried is further dispersed and cooled through a secondary stirring process, and finally forms a gel-like bone graft. The gel-like bone graft material thus prepared may be implanted in a syringe or the like, and the doctor responsible for the implantation may be implanted into the patient's surgical site immediately after being discharged from the syringe at the step of implanting the bone graft material into the patient's operation site.
In one embodiment of the present invention, in the step of forming the gel of the bone graft material as the second stirring process, the mixture is agitated at a rotation speed of 600 to 1000 rpm and a revolution speed of 400 to 800 rpm using a paste mixer Followed by stirring at a high rotation speed for 10 to 20 minutes and then at a rotation speed of 50 to 150 rpm and a revolution speed of 50 to 150 rpm for 20 to 40 minutes and then cooled to room temperature.
High-speed agitation is a process that allows the materials to be well dispersed, but as the temperature of the material rises at high speed agitation, subsequent dispersion is achieved through low-speed agitation, resulting in cooling of the bone graft material.
In addition, if the stirring speed and time are not sufficient, the dispersion of the materials may not be sufficiently achieved, and if the stirring speed and time are higher than the above range, the dispersion effect can not be expected to be improved despite the high speed and long time.
As described above, according to the method of manufacturing a bone graft material according to the present invention, a bone graft material containing a calcium phosphate compound, which is the same as or similar to an inorganic ingredient of bone, is mixed with distilled water and pulverized to form a sol state. Methyl cellulose and carboxymethyl cellulose are mixed, primary agitated, dried, and then agitated to form amorphous gel or gel form, so that they can be transplanted immediately to the patient's operation site without any additional procedure.
Therefore, according to the proficiency of the physician in charge of the procedure, the bone graft material is not sufficiently implanted in the treatment site, and the bone graft material is prevented from being scattered around the treatment site.
Methylcellulose and carboxymethylcellulose are very useful as carriers for bone grafting materials. However, they are not well dispersed in a solvent such as water and have high viscoelasticity when they are dissolved in water. Therefore, when they are added to water in a large amount, they are not uniformly dispersed, Dispersion of particles such as apatite powder is very difficult.
However, according to the above-described method of the present invention, by mixing methyl cellulose and carboxymethyl cellulose in a state of forming a sol of a bone graft material and controlling the temperature of the sol, it is possible to sufficiently disperse the materials, So that bone graft materials can be formed.
Meanwhile, in another aspect of the present invention, the bone graft material formed in gel form as described above can be formed into a solid through the lyophilization step, and the bone graft material formed in such a solid form can be removed from the distilled water Etc. can be added and then reduced to gel form and used again.
The method for producing a bone graft material of the present invention for forming a solid bone graft material is characterized in that distilled water is added to the bone graft material when mixing methylcellulose or carboxymethylcellulose with the sol of the bone graft material as compared with the above- There is a difference in that the drying is carried out in the freeze-drying step following the stirring step without adding moisture in the subsequent stirring step.
Specifically, the method for producing a bone graft material of the present invention for forming a solid bone graft material,
The powder of the bone meal material containing the calcium phosphate compound is mixed with distilled water and the powder of the corrugated material mixed with the distilled water is subjected to wet pulverization to obtain a pulverized bone having a particle size of 200 to 2000 nm as a mixture of the edible material and distilled water Preparing a sol of a bone meal material;
Heating the sol of the bone-deficient material to a temperature of 50 to 90 DEG C, adding 3 to 4 parts by weight of methyl cellulose or carboxymethyl cellulose powder to 40 parts by weight of the bone-eating material and 40 to 120 parts by weight of 50 to 90 DEG C Of distilled water;
Preparing a gel-state bone graft material by stirring a mixture of the sol of the bone-forming material, the powder of methylcellulose or carboxymethyl cellulose, and distilled water; And
And a freeze-drying step of preparing a solid bone graft material by freeze-drying the gel graft material.
When methyl cellulose or carboxymethyl cellulose is mixed in an amount of less than 3 parts by weight, the binding force of the bone graft materials formed as solid in the subsequent lyophilization step may be weakened and may be broken. If the amount is more than 4 parts by weight, , The absorption of the distilled water may not be sufficiently performed when the gel is reduced to gel form.
If the content of distilled water added before lyophilization is less than 40 parts by weight, the binding force of the solid bone graft material is excessively large, so that the absorption of the distilled water may not be achieved well when the gel is reduced into the form, If the amount is more than the weight part, the bone graft material is excessively swollen at the lyophilization step, so that the separation of the calcium phosphate compound as the bone graft material and the binder methylcellulose or carboxymethyl cellulose may occur.
In a specific embodiment of the present invention, the lyophilization step includes a step of freezing the gel-grafted bone graft material at a temperature of -80 DEG C or lower, and a step of lyophilizing the frozen bone graft material at a temperature of -90 DEG C or lower and an air pressure of 67 Pa or lower Step < / RTI >
By adding distilled water, saline solution or blood of a subject to the solid bone graft material formed by such lyophilization, the solid bone graft material can be converted into a gel form and can be transplanted to the treatment site of the subject.
In the present invention, it is preferable that all of calcium phosphate compounds suitable as bone graft materials are included, but hydroxyapatite, which is similar to the bone components of human body and has excellent bone forming ability, is the main raw material.
FIG. 1 is a photograph showing a state in which a bone graft material powder is lost in the process of implanting a bone graft material according to the prior art,
FIG. 2 is a photograph showing a state in which a bone graft material formed in gel form is contained in a syringe according to an embodiment of the present invention,
3 is a photograph showing a bone graft material formed into a solid according to another embodiment of the present invention,
FIG. 4 is a photograph showing a state in which distilled water is added to the solid bone graft material shown in FIG. 3 and then reduced to a gel form.
Hereinafter, embodiments of a method of manufacturing a bone graft material according to the present invention will be described.
Example 1: Preparation of gel-type bone graft material
In Example 1, amorphous (putty type) gel-type bone graft materials were prepared using hydroxyapatite as a main raw material of bone graft material and methyl cellulose and distilled water as a binder.
Hydroxyapatite was obtained by grinding commercially available powders and pulverizing them with induction to obtain hydroxyapatite powders having particle sizes of 45 to 150 μm using 45 μm and 150 μm sieves.
200 g of the hydroxyapatite powder thus obtained was mixed with 200 g of distilled water, and then 400 g of zirconia balls having a diameter of 1 mm and 400 g of zirconia balls having a diameter of 2 mm were placed in an attrition mill, followed by wet grinding for 4 hours, .
Use of only a large diameter ball is not preferable because the particle size of the hydroxyapatite produced by the pulverization becomes high. Particularly, the use of a ball having a diameter exceeding 2 mm is not preferable in terms of particle size.
On the other hand, in the case of using a ball having a small diameter or using a ball having a diameter of less than 1 mm, the flowability of the ball at the time of pulverization is lowered.
In addition, zirconia balls weigh about twice as much as the mixture of hydroxyapatite powders and distilled water. When a smaller amount of the balls is used, the grinding effect is lowered and the particle size distribution becomes higher, and a larger amount of balls When used, the amount of hydroxyapatite sol adhered to the zirconia balls was increased and the recovery efficiency was lowered.
The thus prepared hydroxyapatite sol was analyzed by a particle size analyzer, and it was confirmed that the average particle size of the hydroxyapatite particles was 443.5 nm. In addition, the particle size analyzer does not measure the particle size of the submerged particles, which means that the hydroxyapatite is well dispersed in the sol.
The hydroxyapatite sol obtained in the above step was heated to 80 DEG C, and 5 g of methyl cellulose was mixed. Methylcellulose was used which had a viscosity of 400 cps in a 2% aqueous solution.
Next, while the mixture was kept at a temperature of about 80 캜, the mixture was stirred with a stirrer so that the materials in the mixture were dried to the ranges shown in Table 1 below.
The agitated mixture was rapidly stirred at a rotation speed of 800 RPM and an idle speed of 600 RPM for 15 minutes using a paste mixer and then cooled with stirring at a rotation speed of 100 RPM and a revolution speed of 100 RPM for 30 minutes, To obtain a gel-like bone graft sample. The sample thus obtained was placed in a syringe as shown in Fig.
Example 2: Preparation of lyophilized solid bone graft material
In Example 2, a bone graft material of amorphous type (gel type) was prepared by using hydroxyapatite as a main raw material of bone graft material and methylcellulose and distilled water as a binder, and then gel-type bone graft material was lyophilized to obtain solid bone graft material .
Hydroxyapatite sol was prepared under the same conditions as in Example 1, and then the sol of hydroxyapatite was heated to 80 DEG C, and methylcellulose and distilled water at 80 DEG C as in Example 1 were added to the ratio shown in Table 2 below. .
The mixture thus obtained was stirred in a paste mixer as in Example 1 to obtain a gel-like bone graft material. The gel-shaped bone grafts were transferred to a petri dish (20 g) and frozen at -80 ° C for 3 hours. The frozen sample was lyophilized in a freeze dryer at a temperature of -90 ° C or less and an air pressure of 500 mT or less for 36 hours.
A photograph of the lyophilized specimen is shown in FIG. As shown in Fig. 3, by adding distilled water to the lyophilized specimen, the specimen was reduced to a gel form that can be directly implanted in the patient's treatment site, as shown in the photograph shown in Fig.
Example 3: Evaluation of pH characteristics
The pH of the bone graft material prepared according to the above-described Examples 1 and 2 was measured according to the "Guideline for Evaluation of Physical / Chemical Properties of Dental Bone Implants" (according to ISO13779-3) of the Food and Drug Administration Respectively.
In this measurement, the blank test solution was used as the third distilled water, and the samples were each put into 20 mL of the third distilled water in 4 g portions and eluted at 36 ° C for 72 hours. A solution of 1 g of potassium chloride as a buffer solution in 1 L of distilled water was prepared, and 5 mL per 10 mL of the sample eluate was mixed.
The mixed solution was measured with a pH meter three times each, and averaged values are shown in Table 3.
According to the above-mentioned " Guideline for Evaluation of Physical / Chemical Properties of Dental Bone Implants ", the difference in pH between the eluent and the blank test solution of the sample should be within 1.5, It is shown in Table 3 that all of the samples meet this criterion.
Example 4: Evaluation of cytotoxicity
For the cytotoxicity, the eluate was prepared according to Korean Standards P-ISO 10993-12, "Biological Stability Evaluation Standard for Medical Devices", and the eluate was subjected to the toxicity test according to the standard P-ISO 10993-5.
In the toxicity test, L-929 was used as a cell line, DMEM (FBS 10%, PS 1%) was used as a medium, and
For the eluate, 4 g of
Cytotoxicity was calculated according to the formula% of 1 - 100 * (survival rate of sample / survival rate of negative control). If the cytotoxicity due to these calculations is less than 20%, it is judged to be non-toxic.
Table 4 shows the cell viability and cytotoxicity after a total of 4 replicates of the eluate and the blank stock solution were measured using CCK-8 kit.
As shown in the table above, the cytotoxicity for the
Although the results of the evaluation of the bone graft material manufactured according to the method of manufacturing a bone graft material according to the embodiments of the present invention and the method of manufacturing the bone graft material have been described above, the present invention is not limited to these embodiments, Various modifications and variations are possible within the scope of the present invention, and such modifications and variations are within the scope of the present invention.
Claims (8)
The powder of the bone meal material containing the calcium phosphate compound is mixed with distilled water and the powder of the corrugated material mixed with the distilled water is subjected to wet pulverization to obtain a pulverized bone having a particle size of 200 to 2000 nm as a mixture of the edible material and distilled water Preparing a sol of a bone meal material;
Heating the sol of the bone-forming material to a temperature of 50 to 90 DEG C and mixing 1 to 4 parts by weight of methylcellulose or carboxymethylcellulose powder with respect to 40 parts by weight of the bone-eating material;
The mixture of the sol of edible material and the powder of methylcellulose or carboxymethylcellulose is stirred while maintaining the temperature of 50 to 90 DEG C under the condition that the moisture in the sol of the bone-forming material can be evaporated to form the methylcellulose Or carboxymethyl cellulose is dispersed in the sol of the bone-digesting material, and water is evaporated so that 12 to 20 parts by weight of distilled water is added to 40 parts by weight of the bone graft material; And
Stirring the mixture of the bone-digesting material and the methylcellulose or carboxymethylcellulose under a condition that moisture in the mixture does not evaporate to form a gel of the bone graft material
≪ / RTI >
Wherein the weight ratio of the distilled water to the powder of the bone-forming material is 1 to 4 in the step of preparing the sol of the bone-digesting material
In the step of forming the gel of the bone graft material, the mixture is stirred at a rotating speed of 600 to 1000 rpm and an orbital speed of 400 to 800 rpm for 10 to 20 minutes using a paste mixer, and then the rotating speed of 50 to 150 rpm And the mixture is stirred at low speed for 20 to 40 minutes at a revolution speed of 50 to 150 rpm and cooled to room temperature.
The powder of the bone meal material containing the calcium phosphate compound is mixed with distilled water and the powder of the corrugated material mixed with the distilled water is subjected to wet pulverization to obtain a pulverized bone having a particle size of 200 to 2000 nm as a mixture of the edible material and distilled water Preparing a sol of a bone meal material;
The sol of the bone-forming material is heated to a temperature of 50 to 90 DEG C, and 3 to 4 parts by weight of a powder of methyl cellulose or carboxymethyl cellulose and 40 to 120 parts by weight of 50 to 90 DEG C Of distilled water;
Preparing a gel-state bone graft material by stirring a mixture of the sol of the bone-forming material, the powder of methylcellulose or carboxymethyl cellulose, and distilled water; And
Freeze-drying the gel-like bone graft material to prepare a solid bone graft material
≪ / RTI >
The freeze-
Freezing the gel-grafted bone graft material at a temperature of -80 占 폚 or less, and lyophilizing the frozen bone graft material at a temperature of -90 占 폚 or lower and an air pressure of 67 Pa or lower.
Wherein the powder of the bone graft material is pulverized by wet abrasive grinding using a ceramic ball in the step of preparing a sol of the bone graft material.
Wherein the bone graft material comprises hydroxyapatite.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20150014502 | 2015-01-29 | ||
| KR1020150014502 | 2015-01-29 |
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| KR101747697B1 KR101747697B1 (en) | 2017-06-15 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190069376A (en) | 2019-06-12 | 2019-06-19 | 주식회사 티앤알바이오팹 | Method of producing injectable adhesive composition for fixing bone grafting materials and a injectable adhesive composition for fixing bone grafting materials produced thereby |
| KR20220001529A (en) * | 2020-06-29 | 2022-01-06 | 김효민 | Manufacturing method for teeth bone graft and teeth bone graft manufacturied by the method |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20240052685A (en) | 2022-10-14 | 2024-04-23 | 연세대학교 산학협력단 | Bone graft material |
| KR20240052684A (en) | 2022-10-14 | 2024-04-23 | 연세대학교 산학협력단 | Bone graft material |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190069376A (en) | 2019-06-12 | 2019-06-19 | 주식회사 티앤알바이오팹 | Method of producing injectable adhesive composition for fixing bone grafting materials and a injectable adhesive composition for fixing bone grafting materials produced thereby |
| KR20220001529A (en) * | 2020-06-29 | 2022-01-06 | 김효민 | Manufacturing method for teeth bone graft and teeth bone graft manufacturied by the method |
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| Publication number | Publication date |
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| KR101747697B1 (en) | 2017-06-15 |
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