WO2008032928A1 - Procédé permettant de préparer un substitut de greffe osseuse à partir d'os de cheval - Google Patents

Procédé permettant de préparer un substitut de greffe osseuse à partir d'os de cheval Download PDF

Info

Publication number
WO2008032928A1
WO2008032928A1 PCT/KR2007/003686 KR2007003686W WO2008032928A1 WO 2008032928 A1 WO2008032928 A1 WO 2008032928A1 KR 2007003686 W KR2007003686 W KR 2007003686W WO 2008032928 A1 WO2008032928 A1 WO 2008032928A1
Authority
WO
WIPO (PCT)
Prior art keywords
bone
powder
graft substitute
horse
preparing
Prior art date
Application number
PCT/KR2007/003686
Other languages
English (en)
Inventor
Sang Hoon Rhee
Chong-Pyoung Chung
Yoon-Jeong Park
Sang Hyuk Han
Original Assignee
Seoul National University Industry Foundation
Nano Intelligent Biomedical Engineering Corporation. Co. Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Seoul National University Industry Foundation, Nano Intelligent Biomedical Engineering Corporation. Co. Ltd filed Critical Seoul National University Industry Foundation
Publication of WO2008032928A1 publication Critical patent/WO2008032928A1/fr

Links

Classifications

    • 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
    • A61F2/30—Joints
    • A61F2/46—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4644—Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3608—Bone, e.g. demineralised bone matrix [DBM], bone powder
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3645—Connective tissue
    • A61L27/365—Bones
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61F2002/2817—Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
    • 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
    • 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
    • A61F2/30—Joints
    • A61F2/46—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4644—Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
    • A61F2002/4649—Bone graft or bone dowel harvest sites
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention relates to the method for preparing the bone graft substitute using horse bone, and more particularly to the method for preparing the bone r.graft substitute, which does not cause a xenogenic immune response and has no risk of infection with Creutzfeldt Jakob Disease, which has a potential to occur when bovine bone is used in xenogenic bone grafting.
  • the method comprising treating horse bone with sodium hypochlorite, treating hydrothermally the treated bone at the temperature higher than 121 ° C under a pressure, and then heat- treating the hydrothermally treated bone at the temperature higher than 500 ° C .
  • bone graft substitute refers to a graft material, which can be used to fill spaces in bone tissues and to promote the formation of new bone, when bone defects are created by various dental diseases, trauma, degeneration caused by disease, or other loss of tissue.
  • the best graft material is known to be autogenous bone which is taken from the patient's own bone.
  • the autogenous bone graft has problems in that it requires secondary surgery, is difficult to obtain the required amount, can be absorbed into the body early, is difficult to perform in small-size hospitals and can make the patient's pain and disease conditions severe.
  • bone graft substitutes including donated human bone, artificial bone, and synthetic materials comprising bone component (hydroxyapatite), have been used in bone grafting.
  • Commercial bone graft substitutes are available in several forms, including powders, gels, slurry/putties, tablets, chips, morsels, pellets, sticks, sheets and blocks.
  • Such bone graft substitutes have the following advantages: ensuring product consistency; less risk for infection and disease; no morbidity or pain caused by harvesting of the patient's own bone for grafting; and availability of the substitute in different volumes (that is, it is not limited by the harvest site in patients).
  • they are greatly different from human bone, and thus have various problems, including slow tissue regeneration rate.
  • bone graft substitutes have been prepared by physically and chemically treating animal bone, having a structure similar to that of human bone, to remove organic materials and recover only inorganic components from the animal bone, and processing the inorganic components into graft materials, which can be used in dental or orthopedic surgery.
  • Typical commercial products, prepared using this method may include Bio-Oss ® (Geistlich Biomaterials).
  • the method for preparing bone graft materials using animal bone comprises the steps of: degreasing bovine femur by refluxing it in a solvent having a boiling point of 80-120 ° C ; heating the degreased bovine bone with ammonia or primary amine to remove proteins and organic matter, thus producing bone mineral; heating the bone mineral at a high temperature of 250-600 °C for a few hours; and drying the heated material (US Patent Nos. 5,167,961 and 5,417,975).
  • prion that causes mad cow disease should be removed. Because the prion is not completely removed, even at a high temperature of 600 "C , it cannot be removed by the methods for preparing bone graft substitute, known to date. Thus, there is a need to develop a method of preparing bone graft substitutes using animal bone safe from mad cow disease.
  • a bone graft substitute safe from mad cow disease can be prepared using the method comprising the steps of treating horse bone with sodium hypochlorite, which can degrade and inactivate prion and other proteins, treating hydrothermally the treated bone in purified water at the temperature higher than 121 ° C under a pressure to inactivate proteins, and then heat-treated the hydrothermally treated bone at 600 ° C , thereby completing the present invention.
  • Another object of the present invention is to provide the bone graft substitute composition containing the bone graft substitute prepared according to said method.
  • the method for preparing the bone graft substitute using horse bone comprising the steps of: (a) boiling horse bone, from which blood components have been removed, in purified water, to remove fatty substances and proteins from the bone, and then drying the boiled bone; (b) powdering the dried bone, and then soaking and shaking the bone powder in an organic solvent; (c) removing the organic solvent and then drying the remaining bone powder; (d) treating the dried bone powder with the 2-20% (w/v) solution of sodium hypochlorite; (e) removing the sodium hypochlorite solution and impurities from the bone powder, and then drying the remaining bone powder; (f) adding purified water to the bone powder, treating hydrothermally the bone powder solution at 120-125 °C for the time range from 30 minutes to 5 hours under a pressure, and then drying the hydrothermally
  • the bone graft substitute composition containing, as an active ingredient, horse bone powder, which is prepared according to said method and has no risk of infection with mad cow disease and from which fatty substances, lipids and proteins have been removed so as not to cause a xenogenic immune response.
  • FIG. 1 shows the results of XRD measurement of bone powder thermally treated at 600 ° C .
  • the present invention relates to the method for preparing a bone graft substitute using horse bone, the method comprising the steps of: (a) boiling horse bone, from which blood components have been removed, in purified water, to remove fatty substances and proteins from the bone, and drying the boiled bone; (b) crushing the dried bone, and then soaking and shaking the bone powder in an organic solvent; (c) removing the organic solvent and then drying the remaining bone powder; (d) treating the dried bone powder with a 2-20% (w/v) solution of sodium hypochlorite; (e) removing the sodium hypochlorite solution and impurities from the bone powder, and then drying the remaining bone powder; (f) adding purified water to the bone powder, treating hydrothermally the bone powder solution at 120-125 °C for 30 minutes to 5 hours under a pressure, and then drying the hydrothermally treated powder; and (g) heat-treating the dried bone powder at 500-1000 ° C for 1-24 hours to completely remove lipids and proteins from the bone powder.
  • the term "bone graft substitute” refers to a material for filling spaces in bone tissues.
  • the bone graft substitute can be shaped in the form of, for example, putties, pastes, strips, blocks or chips, using a method such as pressing, compression, contact under pressure, packing, solidification or hardening.
  • it can be formulated in the form of, for example, gels, granules, pastes, tablets or pellets, using chemical additives.
  • it may also be used in the form of powder itself.
  • the bone graft substitute When the bone graft substitute is formulated as described above to use, it is preferably used in combination with a biologically active substance.
  • the biologically active substance include bone growth-promoting factors, fibrin, bone morphogenetic factors, bone growth-promoting agents, chemotherapeutic agents, antibiotic agents, analgesics, bisphosphonates, strontium salts, fluorine salts, magnesiukm salts, and sodium salts.
  • the step (b) of soaking the bone powder in the organic solvent is carried out to remove fatty substances remaining in the horse bone powder.
  • the organic solvent is preferably the mixed solvent of chloroform and methanol.
  • the ratio of chloroform: methanol in the mixed solvent may be 2-8: 8-2, and preferably 1 :1.
  • the step (d) of treating the bone powder with sodium hypochlorite solution is carried out to degrade and remove proteins remaining in the horse bone powder in a water-soluble state and to inactivate denatured prion proteins that cause mad cow disease.
  • sodium hypochlorite may be used in the 2-20% (w/v) solution of sodium hypochlorite, and preferably the 4% (w/v) solution of sodium hypochlorite.
  • the heat-treatment temperature in the step (g) is preferably 550-650 °C .
  • steps (d) and (e) are carried out to remove proteins and organic substances.
  • the bone powder is hydrothermally treated at 120-125 ° C for more than 30 minutes under a pressure, and preferably 3 hours, to degrade and remove proteins from the bone powder.
  • the preparation method according to the present invention may additionally comprise, after the step (g), the step of sieving the heat-treated bone powder through the sieves having mesh size range of 212-425 ⁇ m, 425-1000 ⁇ m, 1000-2000 ⁇ m and 1000-3000 ⁇ m, respectively.
  • the present invention relates to the bone graft substitute composition containing, as an active ingredient, horse bone powder, which is prepared according to the said method and has no risk of infection with mad cow disease and from which fatty substances, lipids and proteins have been removed so as not to cause a xenogenic immune response.
  • the bone graft substitute composition according to the present invention preferably additionally contains one or more biologically active substances selected from the group consisting of bone growth-promoting factors, fibrin, bone morphogenetic factors, bone growth agents, chemotherapeutic agents, antibiotic agents, analgesics, bisphosphonates, strontium salts, fluorine salts, magnesiukm salts, and sodium salts.
  • the bone graft substitute composition according to the present invention preferably additionally contains one or more chemical compounds selected from the group consisting of hyaluronic acid, chondroitin sulfate, alginate, chitosan, collagen, hydroxyapatite, calcium carbonate, calcium phosphate, calcium sulfate and ceramics.
  • the growth factors include BMP (bone morphogenic protein), PDGF (platelet-derived growth factor), TGF-beta (transgenic growth factor), IGF-I (insulin-like growth factor), IGF-II, FGF (fibroblast growth factor) and BGDF-II (beta-2-microglobulin).
  • BMP bone morphogenic protein
  • PDGF platelet-derived growth factor
  • TGF-beta transgenic growth factor
  • IGF-I insulin-like growth factor
  • IGF-II insulin-like growth factor
  • FGF fibroblast growth factor
  • BGDF-II beta-2-microglobulin
  • the bone morphogenetic factors include osteocalcin, bonesialoprotein, osteogenin and BMP.
  • the bone growth-promoting agent any substance may be used without limitation, as long as it is harmless to the human body and promote bone growth.
  • the bone growth-promoting agents include peptides or nucleic acids, which promote bone formation, and antagonists against substances which inhibit bone formation.
  • the chemical additives that are used to formulate the bone graft substitute include hyaluronic acid, collagen, hydroxyapatite, calcium carbonate, calcium phosphate, calcium sulfate and ceramics.
  • the bone graft substitute can be formulated in the form of gels, strips, granules, chips, tablets or pastes.
  • the bone graft substitute when the chemical compound is hyaluronic acid, can be formulated into a gel-type bone graft substitute composition.
  • the step of treating the bone powder with sodium hypochlorite is preferably carried out for more than 72 hours in order to remove prion and the remaining proteins.
  • Example 1 Method for preparing bone graft substitute
  • Bone taken from the equine femur was cut with a bone cutter into pieces having a size of about 5 cm 3 .
  • the bone pieces were soaked in purified water for 24 hours to remove blood components from the bone.
  • the bone pieces, washed with deionized water, were boiled in purified water for 72 hours while replacing purified water at the interval of 12 hours, thus primarily removing fatty substances and proteins from the bone.
  • the bone pieces, from which fat and proteins have been primarily removed, were completely dried in an oven at 60 "C for 24 hours and crushed with a pulverizer to a size of less than 10 mm 3 . [Degreasing process]
  • 1 g of the degreased dried bone powder was added to 20 ml of the 4% (w/v) solution of sodium hypochlorite and shaken at a revolution speed of 120 rpm for 72 hours to remove proteins from the bone powder and to inactivate a prion protein that causes mad cow disease.
  • 1 g of the bone powder was added to 50 g of purified water and shaken at 120 rpm for 72 hours, thus removing the remaining sodium hypochlorite.
  • the purified water was replaced with fresh purified water at a 2-hr interval for 12 hours after the start of shaking, and then replaced with fresh purified water at a 12-hr interval.
  • 1 g of the water- washed bone powder was added to 50 g of purified water and hydrothermally treated at 121 ° C for 3 hours under a pressure. Finally, the bone powder was completely dried in an oven at 60 ° C .
  • Thermal treatment process The degreased, deproteinized, dried bone powder was heat-treated at high temperature to remove the remaining lipids and proteins. An electric furnace used in the heat-treatment was heated at a rate of 2 ° C/min, and the bone powder was thermally treated at 600 °C for 3 hours, and then cooled in the furnace.
  • the thermally treated bone powder was sieved through sieves having mesh sizes of 212-425 ⁇ m, 425-1000 ⁇ m, 1000-2000 ⁇ m and 1000-3000 ⁇ m, respectively, and the sieved bone powder was washed several times with purified water to remove fine dust remaining on the surface thereof.
  • the water-washed powder was dried in an oven at 60 °C for 24 hours and then collected for use as a bone graft substitute.
  • the prepared bone graft substitute was analyzed by XRD and, as a result, it could be seen that the bone graft substitute consisted of pure apatite crystals (see FIG.
  • Example 2 Method for preparing bone graft substitute composition
  • the present invention provides a method for preparing a bone graft substitute, which comprises treating horse bone with a sodium hypochlorite solution, followed by hydrothermal treatment and high-temperature treatment. Also, the present invention provides the bone graft substitute composition containing the bone graft substitute prepared according to said method. According to the present invention, a bone graft substitute, which, when transplanted into the human body, does not cause immune responses and has no risk of infection with organic pathogenic substances such as a denatured prion protein that causes mad cow disease, can be prepared in a simple manner by effectively removing fatty substances and organic substances from horse bone having a structure highly similar to that of human bone.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Transplantation (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Materials For Medical Uses (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne un procédé permettant de préparer un substitut de greffe osseuse au moyen d'os de cheval. Plus particulièrement, cette invention concerne un procédé permettant de préparer un substitut de greffe osseuse n'induisant aucune réaction immunitaire xénogénique et ne présentant aucun risque d'infection par la maladie de la vache folle, ce qui n'est pas le cas lorsqu'un os bovin est utilisé pour la greffe osseuse xénogénique. Le procédé décrit dans cette invention consiste à traiter l'os de cheval avec de l'hypochlorite de sodium, à appliquer un traitement hydrothermal l'os traité sous pression à une température supérieure à 121°C, puis à appliquer un traitement thermique à l'os traité par traitement hydrothermal à une température supérieure à 500°C. Le mode de réalisation décrit dans cette invention concerne un substitut de greffe osseuse, qui, lorsqu'il est transplanté dans le corps humain, n'induit aucune réaction immunitaire et ne présente aucun risque d'infection par des substances pathogènes organiques, telles qu'une protéine prion dénaturée à l'origine de la maladie de la vache folle, lequel substitut de greffe osseuse peut être préparé de manière simple par élimination efficace des substances grasses et des substances organiques contenues dans l'os de cheval qui présente une structure presque similaire à celle de l'os humain.
PCT/KR2007/003686 2006-09-12 2007-07-31 Procédé permettant de préparer un substitut de greffe osseuse à partir d'os de cheval WO2008032928A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020060088257A KR100842012B1 (ko) 2006-09-12 2006-09-12 말뼈를 이용한 골이식재의 제조방법
KR10-2006-0088257 2006-09-12

Publications (1)

Publication Number Publication Date
WO2008032928A1 true WO2008032928A1 (fr) 2008-03-20

Family

ID=39183953

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2007/003686 WO2008032928A1 (fr) 2006-09-12 2007-07-31 Procédé permettant de préparer un substitut de greffe osseuse à partir d'os de cheval

Country Status (2)

Country Link
KR (1) KR100842012B1 (fr)
WO (1) WO2008032928A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2478394C1 (ru) * 2011-11-23 2013-04-10 Федеральное государственное бюджетное учреждение "Российский научный центр "Восстановительная травматология и ортопедия" имени академика Г.А. Илизарова" Министерства здравоохранения и социального развития Российской Федерации Биоматериал для возмещения дефектов костей и способ его получения
EP2760490A4 (fr) * 2011-09-29 2015-05-27 Collagen Matrix Inc Méthode de préparation d'apatite carbonatée poreuse à partir d'os naturel
US9238090B1 (en) 2014-12-24 2016-01-19 Fettech, Llc Tissue-based compositions
RU2574935C2 (ru) * 2014-04-09 2016-02-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Омский государственный университет им. Ф.М. Достоевского" Способ разделения органической и минеральной составляющей костной ткани
WO2017139250A1 (fr) 2016-02-09 2017-08-17 CreOsso LLC Composition antimicrobienne pour inhiber des organismes microbiens dans une allogreffe et procédé associé
US9855365B2 (en) 2011-11-23 2018-01-02 Chungbuk National University Industry-Academic Cooperation Foundation Production method for biomedical and industrial material using ceramic derived from birds' beaks
US10286104B2 (en) 2011-09-29 2019-05-14 Collagen Matrix, Inc. Method of preparing porous carbonate apatite from natural bone
WO2023027663A1 (fr) * 2021-08-27 2023-03-02 Erciyes Universitesi Greffon pour traitement de surélévation du sinus maxillaire et sa production

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101139337B1 (ko) * 2010-02-09 2012-05-03 조선대학교기술지주 주식회사 치아 골 이식재 및 이의 제조방법
KR101381108B1 (ko) * 2011-01-24 2014-04-11 서울대학교산학협력단 말뼈를 이용한 나노 세라믹 골시멘트 및 이의 제조 방법
KR101348335B1 (ko) * 2011-07-08 2014-01-03 주식회사 나이벡 이종골 유래 골이식재 및 그 제조방법
KR101379894B1 (ko) 2011-11-04 2014-04-04 전남대학교산학협력단 형질전환 돼지 뼈를 이용한 골 이식용 세라믹 입자, 그 제조방법 및 상기 입자를 포함하는 생체의료용 세라믹재료
KR20140045272A (ko) * 2012-10-08 2014-04-16 전남대학교산학협력단 동물뼈로부터 유래된 저결정성 세라믹재의 제조 방법
KR101348336B1 (ko) * 2012-12-12 2014-01-06 서울대학교산학협력단 이종골 유래 골이식재 및 그 제조방법
KR101473447B1 (ko) * 2014-03-14 2014-12-24 서울대학교산학협력단 말뼈를 이용한 나노 세라믹 골시멘트 및 이의 제조 방법
KR101848289B1 (ko) * 2016-05-20 2018-04-12 디엠씨휴먼사이언스 주식회사 동물 유래 조직을 이용한 천연 하이드록시 아파타이트 골 이식재 제조 방법
WO2020022870A1 (fr) * 2018-07-27 2020-01-30 서울대학교 산학협력단 Échafaudage, comprenant une nanocéramique à base d'os de cheval et du pcl, pour la régénération de tissu parodontal et son procédé de préparation
KR102209893B1 (ko) * 2018-08-20 2021-02-01 김범수 녹용 및 녹각 유래의 골이식재 및 그의 제조방법
KR20230092515A (ko) 2021-12-17 2023-06-26 농업회사법인 주식회사 천마 말의 대퇴부로부터 유래된 해면골을 이용한 이종골 이식재의 제조방법

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4678470A (en) * 1985-05-29 1987-07-07 American Hospital Supply Corporation Bone-grafting material
US5356629A (en) * 1991-07-12 1994-10-18 United States Surgical Corporation Composition for effecting bone repair
US5417975A (en) * 1988-06-02 1995-05-23 Osteomedical Limited Chemical Compound
US6214049B1 (en) * 1999-01-14 2001-04-10 Comfort Biomedical, Inc. Method and apparatus for augmentating osteointegration of prosthetic implant devices
US20040091459A1 (en) * 2001-09-10 2004-05-13 Nimni Marcel E. Bone graft material incorporating demineralized bone matrix and lipids
US20060014283A1 (en) * 1999-11-25 2006-01-19 Oscotec, Inc. Inorganic bone graft materials using animal bone and method for preparing thereof
US20060149362A1 (en) * 2004-12-30 2006-07-06 Pedrozo Hugo A Orthopaedic implant for vascularization of the femoral head

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0818829B2 (ja) * 1989-02-20 1996-02-28 久直 禅野 天然カルシウム化合物を主成分とするカルシウム素材の製造法
KR100244996B1 (ko) * 1995-12-25 2000-02-15 이마이 기요스케 릴랙스 유도장치
KR100393469B1 (ko) * 1999-01-02 2003-08-06 정필훈 동물 뼈를 이용한 골 대체물 제조방법

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4678470A (en) * 1985-05-29 1987-07-07 American Hospital Supply Corporation Bone-grafting material
US5417975A (en) * 1988-06-02 1995-05-23 Osteomedical Limited Chemical Compound
US5356629A (en) * 1991-07-12 1994-10-18 United States Surgical Corporation Composition for effecting bone repair
US6214049B1 (en) * 1999-01-14 2001-04-10 Comfort Biomedical, Inc. Method and apparatus for augmentating osteointegration of prosthetic implant devices
US20060014283A1 (en) * 1999-11-25 2006-01-19 Oscotec, Inc. Inorganic bone graft materials using animal bone and method for preparing thereof
US20040091459A1 (en) * 2001-09-10 2004-05-13 Nimni Marcel E. Bone graft material incorporating demineralized bone matrix and lipids
US20060149362A1 (en) * 2004-12-30 2006-07-06 Pedrozo Hugo A Orthopaedic implant for vascularization of the femoral head

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
"Office of Health and Safety (OHS), USA", BMBL SECTION VII - AGENT SUMMARY, 17 June 1999 (1999-06-17), Retrieved from the Internet <URL:http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s7d.htm> *
"WHO infection control guidelines for transmissible spongiform encephalopathies", REPORT OF A WHO CONSULTATION, GENEVA, SWITZERLAND, 23 March 1999 (1999-03-23) - 26 March 1999 (1999-03-26), Retrieved from the Internet <URL:http://www.whqlibdoc.who.int/hq/2000/WHO_CDS_CSR_APH_2002.3.pdf> *
ASLAN M. ET AL.: "The Effect of Hyaluronic Acid-supplement Bone Graft in Bone Healing: Experimental Study in Rabbits", JOURNAL OF BIOMATERIALS APPLICATIONS, vol. 20, January 2006 (2006-01-01), pages 209 - 220 *
CARDONE F. ET AL.: "Inactivation of transmissible spongiform encephalopathy agents in food products by ultra high pressure-temperature treatment", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1764, 24 February 2006 (2006-02-24), pages 558 - 562, Retrieved from the Internet <URL:http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B73DJ-4JBGGFR-1&_user=981501&_coverDate=03%F31%2F2006&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000048939&_version=1&_urlVersion=0&_userid=981501&md5-4557cdd707385010570db5a-4ac253eee> *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2760490A4 (fr) * 2011-09-29 2015-05-27 Collagen Matrix Inc Méthode de préparation d'apatite carbonatée poreuse à partir d'os naturel
US10286104B2 (en) 2011-09-29 2019-05-14 Collagen Matrix, Inc. Method of preparing porous carbonate apatite from natural bone
RU2478394C1 (ru) * 2011-11-23 2013-04-10 Федеральное государственное бюджетное учреждение "Российский научный центр "Восстановительная травматология и ортопедия" имени академика Г.А. Илизарова" Министерства здравоохранения и социального развития Российской Федерации Биоматериал для возмещения дефектов костей и способ его получения
US9855365B2 (en) 2011-11-23 2018-01-02 Chungbuk National University Industry-Academic Cooperation Foundation Production method for biomedical and industrial material using ceramic derived from birds' beaks
RU2574935C2 (ru) * 2014-04-09 2016-02-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Омский государственный университет им. Ф.М. Достоевского" Способ разделения органической и минеральной составляющей костной ткани
US9238090B1 (en) 2014-12-24 2016-01-19 Fettech, Llc Tissue-based compositions
US11938246B2 (en) 2014-12-24 2024-03-26 Fettech, Llc Tissue-based compositions and methods of use thereof
WO2017139250A1 (fr) 2016-02-09 2017-08-17 CreOsso LLC Composition antimicrobienne pour inhiber des organismes microbiens dans une allogreffe et procédé associé
EP3413844A4 (fr) * 2016-02-09 2019-10-02 Creosso LLC Composition antimicrobienne pour inhiber des organismes microbiens dans une allogreffe et procédé associé
AU2017218424B2 (en) * 2016-02-09 2022-01-06 Rutgers, The State University Of New Jersey Antimicrobial composition for inhibiting microbial organisms in allograft and the method thereof
US11224678B2 (en) 2016-02-09 2022-01-18 Rutgers, The State University Of New Jersey Antimicrobial composition for inhibiting microbial organisms in allograft and the method thereof
WO2023027663A1 (fr) * 2021-08-27 2023-03-02 Erciyes Universitesi Greffon pour traitement de surélévation du sinus maxillaire et sa production

Also Published As

Publication number Publication date
KR20080024006A (ko) 2008-03-17
KR100842012B1 (ko) 2008-06-27

Similar Documents

Publication Publication Date Title
WO2008032928A1 (fr) Procédé permettant de préparer un substitut de greffe osseuse à partir d&#39;os de cheval
EP1453434B1 (fr) Compositions pour reparation tissulaire et methodes de preparation et d&#39;utilisation associees
CA2353240C (fr) Combinaison de tissu osseux et de collagene pour la reparation des lesions articulaires
US4882149A (en) Pharmaceutical depot preparation
JP3471359B2 (ja) 細長い骨粒子から由来する成形材料及びそれを製造する方法
US20060216321A1 (en) Solvent based processing technologies for making tissue/polymer composites
WO2008102985A1 (fr) Apatite bioactive à structure duale, et procédé d&#39;élaboration correspondant
Mucalo Animal-bone derived hydroxyapatite in biomedical applications
CN112569406B (zh) 一种骨修复材料及其制备方法
KR101348335B1 (ko) 이종골 유래 골이식재 및 그 제조방법
AU2020202701A1 (en) Semi-synthetic powder material, obtained by modifying the composition of a natural marine biomaterial, method for producing same, and applications thereof
Luna-Domínguez et al. Development and in vivo response of hydroxyapatite/whitlockite from chicken bones as bone substitute using a chitosan membrane for guided bone regeneration
US8586099B2 (en) Method for preparing a prion-free bond grafting substitute
Karalashvili et al. Decellularized bovine bone graft for zygomatic bone reconstruction
PINHOLT et al. Alveolar ridge augmentation in rats by combined hydroxylapatite and osteoinductive material
KR20130115781A (ko) 인체뼈 유래 무기질을 포함하는 천연 골재생재
KR100635385B1 (ko) 프라이온-프리 골 이식 대체재의 제조방법
KR101139660B1 (ko) 탈회골(ｄｂｍ)을 포함하는 골 충진재의 제조방법
RU2393819C1 (ru) Способ приготовления заменителя костного трансплантата, не содержащего прионов
Aval et al. Histological Assessment of Bone Regeneration by Octacalcium Phosphate and Bone Matrix Gelatin Composites in a Rat Mandibular Defect Model
Katthagen et al. Bone-Replacement Materials
PL232501B1 (pl) Sposób otrzymywania przeszczepu do regeneracji tkanki kostnej, zwłaszcza ludzkiej oraz przeszczep do regeneracji tkanki kostnej, zwłaszcza ludzkiej
Paskalev et al. Experimental study on guided bone regeneration in canine segmental ulnar defects
AU2002324854A1 (en) Tissue repair compositions and methods for their manufacture and use
PL232494B1 (pl) Sposób otrzymywania przeszczepu gruzu korowo-gąbczastego do regeneracji tkanki kostnej, oraz przeszczep do tej regeneracji

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07793341

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07793341

Country of ref document: EP

Kind code of ref document: A1