Top > Search of International Patents > GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, METHOD FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, KIT FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, AND METHOD FOR FORMING BONE

GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, METHOD FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, KIT FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, AND METHOD FOR FORMING BONE

Foreign code F120007067
File No. S2011-0500-N0
Posted date Dec 5, 2012
Country WIPO
International application number 2012JP057829
International publication number WO 2012157339
Date of international filing Mar 26, 2012
Date of international publication Nov 22, 2012
Priority data
  • P2011-108650 (May 13, 2011) JP
Title GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, METHOD FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, KIT FOR PRODUCING GROWTH FACTOR ANCHORING TYPE BONE GRAFT MATERIAL, AND METHOD FOR FORMING BONE
Abstract This growth factor anchoring type bone graft material is characterized in that growth factor containing collagen-binding sites, which contains growth factor receptor agonist peptides and collagen-binding peptides, is bonded to a bone graft substrate obtained by exposing at least collagen fibers. The growth factor containing collagen-binding sites, which contains growth factor receptor agonist peptides and collagen-binding peptides, can be mixed with the bone graft substrate for preparation purposes, and has excellent osteogenic potential.
Outline of related art and contending technology BACKGROUND ART
Such as rheumatoid arthritis and osteoarthritis and for the treatment of a joint prosthesis is mounted, by long-term use of an artificial joint loosening between the bone tissue occurs, a new artificial joint Vda′ revision arthroplasty is performed. In the case of revision arthroplasty, to make up for the lost in a part of the bone, the bone from the patient in the bone graft is being performed and the like. The feature of the bone, the bone graft contained in the absorption and the autologous bone graft bone proteins to promote replacement, an artificial object is incapable of remodeling and also in cases in which there is an advantage in reconstructive joint function. In addition, the bone tissue and thus superior ability to reproduce, in the case of fracture reduction and fixation can be appropriately reproduced in the form of a substantially original is likely.
However, autologous bone transplantation, the subject of a portion of the patient in the bone is excised as a block, while the block, or granular, and then crushed to a powder, a method for implanting a portion of the bone is not sufficient. Of the bone itself in order to use the advantages of high safety, such as in the case of large bone defects, a portion of the collection of bone pain is severe, surgical procedures for bone transplantation is also long recovery after the hook, the bone graft of bone for securing the fluid supply part to supply a great deal of difficulty in some cases. In order to avoid such inconvenience, in place of the bone using a bone from the donor bone graft is performed and the like, further, various types of bone graft material has been developed.
For example, to promote arthrodesis bone formation in used, such as platelet-derived growth factor solution includes calcium phosphate scaffold material polysaccharides and that the composition is a biocompatible matrix (Patent Document 1). Embodiment, the average diameter of 1.0 mg/ml of the calcium phosphate to 1000-2000μm of the platelet-derived growth factor was added dropwise to prepare a composition, the composition is applied to the fusion site with the bone of the joint. As a result, the composition may be, the same autologous bone transplantation to the bone fusion and joint cross-linking, is called.
In addition, cell adhesion peptide having an amino acid sequence RGD or tissue growth factor-derived peptides immobilized on the surface of the bone graft material (Patent Document 2) also. Capable of obtaining a tissue regeneration effect tissue growth factors and extracellular matrix protein peptide and the active site of a bone grafting material may be attached to the surface, low concentrations of the peptide is adsorbed to stably and continuously even in the case where the pharmacological effects, is referred to. Embodiment, bovine bone-derived bone mineral particles having a surface 3 - treated with aminopropyltriethoxysilane to form amine, 1, 4 - - bis-crosslinking agent to this coupling of the maleimide butane was added, the cell adhesion peptide bound by the reaction of the bone graft material are prepared. Peptide has not been fixed relative to a bone graft material and the force for bone regeneration, is called.
In addition, cell-free tissue fragment of the substrate in accordance with the demineralized bone material is dried to a fragment of the bone graft composition (Patent Document 3) also. Such as epithelial cells taken from the substrate is a cell-free tissue such as collagen, cell recognition and cell binding as well as the cell extension, cell growth, cell differentiation and their ability to, demineralized bone material, it is important that the bone graft success physiological properties of natural bone. The resulting bone graft compositions implanted or after hydration is coated on the embedded portion, the stem cells to stimulate bone formation in the bone tissue of the recipient or the surface or the non-bony tissue or on the surface of the new bone formation can be induced, is called.
On the other hand, PTH/PTHrP receptor agonist such as collagenase-derived collagen binding polypeptide fragment composition comprising the fusion protein (Patent Document 4) also. Parathyroid hormone (PTH) is, for the elaboration of osteoporosis the use of a therapy, administration of 1 1 is required. The composition comprises, a collagen binding polypeptide fragments can be combined with collagen and stably, the circulating fluid from escaping from the treatment site remains long, PTH can have a longer half-life, and the administration of PTH exhibiting the effectiveness of equal to or more than is called. Embodiment, intraperitoneal administration, an increase in bone density is observed.
It should be noted that, in place of the PTH/PTHrP receptor agonist basic fibroblast growth factor (bFGF) and collagen binding polypeptide fragments or fusion protein is also known (Non-Patent Document 1).
Further, the treatment of fractures promote bone formation is useful from the discovery, fibronectin-derived collagen binding domain polypeptide that has a bone formation-promoting proteins and is connected to the bone formation-promoting fusion protein (Patent Document 5) also. BMP(Bone Morphogenetic Proteins) bone formation-promoting proteins belong to a family of growth factors or as a sub, bFGF, thyroid hormone and the like are illustrated. Embodiment, mRNA extracted from human kidney cells as a template to prepare the polypeptide, as the bone formation-promoting protein coupled BMP2 and BMP7 facilitate bone formation for producing the fusion protein. The effect of a mouse derived calvarial osteoblast cell was suspended, the administration of the bone formation-promoting fusion protein, in comparison with the administration of said polypeptide in a concentration dependent manner with respect to osteoblasts showed upregulation of alkaline phosphatase activity is called.
In addition, calcium sulfate and the like, the curved projection 4 at least one of the features with the particles and suspension liquid material and a composition for the treatment of bone defects (Patent Document 6) is. A plurality of shaped particles to each other that the projections can be filled with the defect and intends union can be stabilized, as a suspension in the gel may be filled with a collagen derivative such as binding agents, bone morphogenic protein (BMP) may be used.
In addition, calcium phosphate, a foaming agent, a coagulant and a biocompatible, physiologically-acceptable liquid self-curing are mixed with the porous calcium phosphate composition, the release of gas components of the blowing agent of the composition occurs by hydration, wherein the composition provides a porosity of at least 5%, and, after curing, the calcium phosphate composition has a compressive strength of 1 mpa or more, the composition (Patent Document 7) also. Biocompatible collagen is disclosed as an aggregating agent, the composition may, further contain a substrate processing that exposed collagen have been described. The invention is, a porous foaming agent to produce a composition of the calcium phosphate is characterized in that, in the embodiment of the collagen substrate and the exposure processing, the calcium phosphate and sodium hydrogen carbonate as a foaming agent, a mixture of carboxymethyl cellulose as a coagulant, and the self-curing to prepare a paste. The self-curable paste formed on the distal end of the rabbit femoral condyle defect was filled, referred to as shown in a nearly complete healing.
In addition, in the form of particles and fibrillar collagen component and a calcium phosphate component and, further, the purified bone growth factors, recombinant bone growth factors, bone marrow, a demineralized bone and the bone comprises a material selected from a group consisting of bone growth including (Patent Document 8) is also a composition. The collagen component, such as a particulate or a porous crosslinked collagen is insoluble collagen. Embodiment, the composite collagen dispersion by kneading a calcium phosphate gel, freeze-drying and thermal dehydration cross-linking step after, machined into the form of particles, the blood was added to the paste, and the ash scattering for implantation. Thus, are to be strongly fixed to the missing portion, is called.
Scope of claims (In Japanese)請求の範囲 [請求項1]
 成長因子受容体アゴニストペプチド部とコラーゲン結合性ペプチド部とを含むコラーゲン結合部位含有成長因子が、少なくともコラーゲン線維が露出してなる骨移植基材に結合されたことを特徴とする、成長因子アンカーリング型骨移植材料。

[請求項2]
 前記コラーゲン結合部位含有成長因子は、成長因子受容体アゴニストペプチド部とコラーゲン結合性ペプチド部とリンカー部とからなることを特徴とする、請求項1記載の成長因子アンカーリング型骨移植材料。

[請求項3]
 前記骨移植基材は、コラーゲン露出骨材、または高密度コラーゲン材である、請求項1または2記載の成長因子アンカーリング型骨移植材料。

[請求項4]
 前記成長因子受容体アゴニストペプチド部は、塩基性線維芽細胞増殖因子であることを特徴とする、請求項1~3のいずれかに記載の成長因子アンカーリング型骨移植材料。

[請求項5]
 少なくともコラーゲン線維が露出してなる骨移植基材に、成長因子受容体アゴニストペプチド部とコラーゲン結合性ペプチド部とを含むコラーゲン結合部位含有成長因子を混合することを特徴とする、成長因子アンカーリング型骨移植材料の製造方法。

[請求項6]
 前記骨移植基材は、骨を酸処理し、前記酸で溶解した無機鉱物成分を除去したコラーゲン露出骨材である、請求項5記載の成長因子アンカーリング型骨移植材料の製造方法。

[請求項7]
 成長因子受容体アゴニストペプチド部とコラーゲン結合性ペプチド部とを含むコラーゲン結合部位含有成長因子を含有する溶液と、骨移植基材とからなる成長因子アンカーリング型骨移植材料製造用キット。

[請求項8]
 成長因子受容体アゴニストペプチド部とコラーゲン結合性ペプチド部とを含むコラーゲン結合部位含有成長因子を含有する溶液と、コラーゲン露出骨材調製溶液とからなる成長因子アンカーリング型骨移植材料製造用キット。

[請求項9]
 請求項1~4のいずれかに記載の成長因子アンカーリング型骨移植材料を骨欠損部および/または偽関節部に移植することを特徴とする、骨形成方法。

[請求項10]
 前記成長因子アンカーリング型骨移植材料が、骨を粉砕して酸で1~60分処理してコラーゲン露出骨材を調製し、このコラーゲン露出骨材に成長因子受容体アゴニストペプチド部とコラーゲン結合性ペプチド部とを含むコラーゲン結合部位含有成長因子を結合したものである、請求項9記載の骨形成方法。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • SCHOOL JURIDICAL PERSON KITASATO INSTITUTE
  • NATIONAL UNIVERSITY CORPORATION KAGAWA UNIVERSITY
  • Inventor
  • UCHIDA Kentaro
  • NARUSE Koji
  • TAKASO Masashi
  • MIMA Takehiko
  • MATSUSHITA Osamu
  • HARAGUCHI Takashi
  • NISHI Nozomu
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

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