JP2008035981A - Pasty bone filling material - Google Patents
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- JP2008035981A JP2008035981A JP2006211550A JP2006211550A JP2008035981A JP 2008035981 A JP2008035981 A JP 2008035981A JP 2006211550 A JP2006211550 A JP 2006211550A JP 2006211550 A JP2006211550 A JP 2006211550A JP 2008035981 A JP2008035981 A JP 2008035981A
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- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 47
- 239000000463 material Substances 0.000 title claims abstract description 39
- 235000011837 pasties Nutrition 0.000 title abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 18
- 239000003462 bioceramic Substances 0.000 claims abstract description 16
- 239000000843 powder Substances 0.000 claims abstract description 16
- 229920002988 biodegradable polymer Polymers 0.000 claims abstract description 13
- 239000004621 biodegradable polymer Substances 0.000 claims abstract description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims abstract description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims abstract description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims abstract description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims abstract description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract 6
- 230000007547 defect Effects 0.000 description 11
- 239000001506 calcium phosphate Substances 0.000 description 8
- 229910000389 calcium phosphate Inorganic materials 0.000 description 6
- 235000011010 calcium phosphates Nutrition 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 229920001577 copolymer Polymers 0.000 description 5
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 5
- 229910052586 apatite Inorganic materials 0.000 description 4
- -1 calcium phosphate compound Chemical class 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 239000000316 bone substitute Substances 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229920001432 poly(L-lactide) Polymers 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 description 1
- VPVXHAANQNHFSF-UHFFFAOYSA-N 1,4-dioxan-2-one Chemical compound O=C1COCCO1 VPVXHAANQNHFSF-UHFFFAOYSA-N 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000005312 bioglass Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052587 fluorapatite Inorganic materials 0.000 description 1
- 229940077441 fluorapatite Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
- 229910000392 octacalcium phosphate Inorganic materials 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 108010021753 peptide-Gly-Leu-amide Proteins 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YIGWVOWKHUSYER-UHFFFAOYSA-F tetracalcium;hydrogen phosphate;diphosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].OP([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O YIGWVOWKHUSYER-UHFFFAOYSA-F 0.000 description 1
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
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- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
Description
本発明は、骨腫瘍や骨髄炎等により病巣を取り除いた後に欠損部へ自家骨移植する際や、歯科用インプラント埋入のために顎骨の補強や補填に用いられる骨補填材に関するものである。 The present invention relates to a bone prosthetic material used for reinforcing or replenishing a jaw bone when transplanting autologous bone to a defect after removing a lesion due to a bone tumor, osteomyelitis, or the like.
整形外科や歯科の領域において、様々な疾患により生じる骨欠損の修復に骨補填材が用いられている。骨の成分の約７割はリン酸カルシウムであることから、リン酸カルシウム系化合物は優れた生体適合性を示し各種骨補填材として応用されている。 Bone prosthetic materials are used to repair bone defects caused by various diseases in the fields of orthopedics and dentistry. Since about 70% of bone components are calcium phosphate, calcium phosphate compounds show excellent biocompatibility and are applied as various bone substitutes.
このようなリン酸カルシウム系化合物製の骨補填材としては、ブロック状のものや顆粒状のものが知られている。しかし、ブロック状のものは術場で骨補填材を骨欠損部の形状に成形しなければならず手間がかかる。特に緊急性を必要とする手術の場合、その使用は困難であった。これに対し顆粒状のものは充填するだけで骨欠損部へ補填することができるので簡単にかつ迅速に手術を行うことが可能となる。 As such a bone filling material made of a calcium phosphate compound, there are known block-like and granule-like materials. However, in the case of a block shape, it is necessary to form the bone prosthetic material into the shape of the bone defect portion at the operation site, which is troublesome. Especially in the case of surgery requiring urgency, its use has been difficult. On the other hand, since a granular thing can be filled in a bone defect part only by filling, it becomes possible to operate easily and rapidly.
しかしながら、骨補填材をリン酸カルシウム系化合物の顆粒のみで構成した場合、使用時に顆粒がこぼれてしまう等術場における取り扱い性が悪い問題があった。また、欠損部の形状が開放性であり骨組織に囲まれていない場合には、補填後に補填材料を骨欠損部に留めておくことのが困難であるという問題もあった。 However, when the bone prosthetic material is composed only of calcium phosphate compound granules, there is a problem that handling properties in the surgical field are poor, such as granules spilling during use. Further, when the shape of the defect portion is open and not surrounded by bone tissue, there is a problem that it is difficult to keep the filling material in the bone defect portion after filling.
骨補填材は使用直前に任意の形状に賦形して目的に合った形状に成形してから使用することが望ましいのでリン酸カルシウム系化合物の顆粒と高分子材料とを混合した骨補填材も開発されている。例えば、ε-カプロラクトンとラクチッドとの共重合体を含有し、約４６〜７１℃に加熱した時は軽度の圧力下で成形可能であるが、約４３℃以下の温度では圧力下でも永久的に抵抗する組織増加のための医学用パテや（例えば、特許文献１参照。）、主成分のｐ-ジオキサノンと他の単量体との生体内分解吸収性の共重合体に生体活性なバイオセラミックス粉体が含有されており、３０℃より低い温度域では比較的固い個体であるが、ヒトの皮膚温度から体温（約３０〜４０℃）で粘着性、可塑性および形状保持性をもち、体温以上で流動性を増して自在に形状を付与することができる生体内分解吸収性可塑性粘着物や（例えば、特許文献２参照。）、再吸収性ペーストキャリヤーと骨形成因子と多孔質粒状無機質を含み、再吸収性キャリヤーが哺乳動物の体温よりも高い温度で流動性であるが、該体温もしくはそれよりやや高い温度で非流動性素材に転移する骨形成ペースト組成物（例えば、特許文献３参照。）等が開示されている。しかしながら、これらの材料は手術時に湯に浸す等して加熱する等手間がかかる上、このような操作自体が材料を生体内に埋入することを考慮すると不衛生であり好ましくない。 Since it is desirable to use the bone prosthetic material after shaping it into an arbitrary shape immediately before use and forming it into a shape suitable for the purpose, a bone prosthetic material in which granules of calcium phosphate compound and polymer material are mixed has also been developed. ing. For example, it contains a copolymer of ε-caprolactone and lactide and can be molded under mild pressure when heated to about 46-71 ° C., but permanently at temperatures below about 43 ° C. even under pressure. Medical putty for increasing resistant tissue (see, for example, Patent Document 1), bioactive bioceramics in biodegradable and absorbable copolymers of p-dioxanone as the main component and other monomers It contains powder and is relatively solid in the temperature range lower than 30 ° C, but has stickiness, plasticity and shape retention at body temperature (about 30-40 ° C) from the human skin temperature. Incorporating biodegradable and absorbable plastic adhesive that can be freely shaped with increased fluidity (for example, see Patent Document 2), resorbable paste carrier, osteogenic factor, and porous granular mineral , Resorbable carrier Is disclosed, for example, as a bone-forming paste composition that is fluid at a temperature higher than the body temperature of a mammal but is transferred to a non-flowable material at or slightly higher than the body temperature (see, for example, Patent Document 3). ing. However, these materials are not preferable because it takes time and effort to immerse them in hot water at the time of surgery, and such an operation itself is unsanitary in view of embedding the material in the living body.
また、リン酸カルシウム系化合物をフィブリン糊等で固め生分解性の多糖類やキチン類のゲルに分散させて顆粒状骨補填材を欠損部に保持する試みも行われている（例えば、特許文献４〜１０参照。）。このような骨補填材は高い操作性を有しており、容易かつ迅速に骨補填材を骨欠損部へ充填することができ、手術後、体内で骨補填材が骨欠損部から散逸してしまうことが防止される。 In addition, attempts have been made to retain a granular bone filling material in a defect by solidifying a calcium phosphate compound with fibrin glue or the like and dispersing it in a biodegradable polysaccharide or chitin gel (for example, Patent Documents 4 to 4). 10). Such a bone grafting material has high operability, and can easily and quickly fill the bone defect material into the bone defect part. After the operation, the bone grafting material is dissipated from the bone defect part in the body. Is prevented.
しかしながら、フィブリン糊等で固めたりコラーゲンを含む水溶液に分散させた場合には、フィブリンは自家由来の場合には採取・精製等煩雑な操作が必要であり、更に他家由来であれば肝炎等に感染する危険性もある。同様にコラーゲン等の生物由来の材料は人体に対する医療用具としての使用については未知の病原に対する安全性に不安が残る。 However, when fibrin is hardened with fibrin glue or dispersed in an aqueous solution containing collagen, fibrin requires complicated operations such as collection and purification if it is derived from the house. There is also a risk of infection. Similarly, biological materials such as collagen remain uneasy about the safety of unknown pathogens when used as a medical device for the human body.
そこで本発明は、生体に安全であり操作性に優れた骨補填材を提供することを課題とする。 Therefore, an object of the present invention is to provide a bone prosthetic material that is safe for living bodies and excellent in operability.
本発明者等は前記課題を解決するために鋭意検討した結果、バイオセラミックス粉末が混合された溶媒に、生分解性高分子が溶解されているペースト状骨補填材とすると、ペースト状なので術場において粉末がこぼれ落ちることがなく、補填患部に合わせて成形することも容易な上、粉末を骨欠損部に留めておくことが可能であり、バイオセラミックス粒子の粒径や配合量，生分解性高分子の分子量や配合量を調整することで生体内での分解速度を制御することが可能なペースト状の骨補填材を得ることができることを見出して本発明を完成した。 As a result of intensive studies to solve the above problems, the present inventors have found that a paste-like bone filling material in which a biodegradable polymer is dissolved in a solvent in which bioceramics powder is mixed is pasty because it is in a paste form. In addition, the powder does not spill and can be easily molded to the affected area, and the powder can be retained in the bone defect. The particle size, blending amount and biodegradability of the bioceramic particles The present invention was completed by finding that a paste-like bone grafting material capable of controlling the degradation rate in vivo can be obtained by adjusting the molecular weight and blending amount of the polymer.
即ち本発明は、バイオセラミックス粉末が混合された溶媒に、生分解性高分子が溶解されていることを特徴とするペースト状骨補填材である。 That is, the present invention is a paste-like bone filling material characterized in that a biodegradable polymer is dissolved in a solvent in which bioceramic powder is mixed.
本発明に係るペースト状骨補填材は、コラーゲン等の生物由来の材料を用いないので未知の病原に対して比較的安全である。そして、従来の例えば粉末状のリン酸カルシウム系骨補填材のようにこぼれ落ちることが無く、また従来のブロック状の骨補填材のように切削により成形する必要もないので良好な操作性（賦形性）を持つ優れたペースト状骨補填材である。 Since the paste-like bone filling material according to the present invention does not use biological materials such as collagen, it is relatively safe against unknown pathogens. In addition, there is no spillage unlike conventional powdered calcium phosphate bone substitutes, and there is no need to mold by cutting like conventional block bone substitutes. Is an excellent paste-like bone filling material.
本発明で使用する溶媒としては、生分解性高分子を溶解させるものであれば使用でき、例えば１−メチル−２−ピロリドン（Ｎ−メチル−２−ピロリドン），ポリエチレングリコール，２−ピロリドン，プロピレングリコール，アセトン，酢酸エチル，酢酸メチル，メチルエチルケトン，ジメチルスルホキシド，テトラヒドロフランを例示することができる。これらの中から選ばれる２種以上を混合して用いても良い。また、生体親和性・安全性が高いことから、特に、１−メチル−２−ピロリドン及びポリエチレングリコールが最も好ましい。 As the solvent used in the present invention, any solvent capable of dissolving the biodegradable polymer can be used. For example, 1-methyl-2-pyrrolidone (N-methyl-2-pyrrolidone), polyethylene glycol, 2-pyrrolidone, propylene Examples include glycol, acetone, ethyl acetate, methyl acetate, methyl ethyl ketone, dimethyl sulfoxide, and tetrahydrofuran. You may mix and use 2 or more types chosen from these. In addition, 1-methyl-2-pyrrolidone and polyethylene glycol are most preferable because of high biocompatibility and safety.
本発明で使用するバイオセラミックス粉末としては、人工骨や人工歯根として従来から用いられているアルミナ，ジルコニア，アパタイト等を使用でき、好ましくは生体内で活性を示すバイオガラス，水酸アパタイト，炭酸アパタイト，フッ素アパタイト，リン酸水素カルシウム（無水物または２水和物），リン酸三カルシウム，リン酸四カルシウム，リン酸八カルシウム等が挙げられ、これらを２種以上混合して用いても良い。特に生体内で崩壊性を示す低結晶性の炭酸アパタイトが最も好ましい。 As the bioceramic powder used in the present invention, alumina, zirconia, apatite and the like conventionally used as artificial bones and artificial tooth roots can be used, and preferably bioglass, hydroxyapatite, carbonate apatite exhibiting activity in vivo. , Fluorapatite, calcium hydrogen phosphate (anhydrous or dihydrate), tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate and the like, and a mixture of two or more of these may be used. In particular, low crystalline carbonate apatite that exhibits disintegration in vivo is most preferable.
本発明で使用するバイオセラミックス粉末の形状は、球形，粉砕形状，ウィスカー等、特に限定せず使用することができるが、粒径範囲が０．０１〜８００μｍであることが好ましく、０．０１μｍ未満の粒子を合成・精製することは困難であり、８００μｍを超えるとペースト状骨補填材の表面が粗くなる傾向がある。また、バイオセラミックス粉末の表面が多孔質であると、生分解性高分子が生体内で分解されることにより生じたスペースに生体組織が侵入した際にバイオセラミックス粉末の多孔質部分へも侵入することにより骨組織再生が促進されて好ましい。 The shape of the bioceramic powder used in the present invention can be used without any particular limitation, such as a spherical shape, a pulverized shape, a whisker, etc. It is difficult to synthesize and purify the particles, and when it exceeds 800 μm, the surface of the paste-like bone prosthetic material tends to become rough. In addition, when the surface of the bioceramic powder is porous, when the biological tissue enters the space generated by the biodegradable polymer being decomposed in vivo, the bioceramic powder also enters the porous portion of the bioceramic powder. This is preferable because bone tissue regeneration is promoted.
本発明で使用する生分解性高分子としては、従来から用いられている生体吸収性の高分子材料が使用でき、特にポリグリコール酸（ＰＧＡ）、ポリ乳酸（Ｄ体、Ｌ体、ＤＬ体）（ＰＬＡ）、ポリ−ε−カプロラクトン（ＰＣＬ），ポリアミノ酸，ポリアンハイドライド，ポリオルソエステルやそれらの共重合体を好ましく使用することができる。本発明においては、溶媒に溶解された生分解性高分子が増粘剤として作用するので別途増粘剤を配合する必要が無い。 As the biodegradable polymer used in the present invention, conventionally used bioabsorbable polymer materials can be used, and in particular, polyglycolic acid (PGA), polylactic acid (D-form, L-form, DL-form) (PLA), poly-ε-caprolactone (PCL), polyamino acid, polyanhydride, polyorthoester, and copolymers thereof can be preferably used. In the present invention, since the biodegradable polymer dissolved in the solvent acts as a thickener, it is not necessary to add a thickener separately.
本発明で溶媒に混合されるバイオセラミックス粉末の量は、ペースト状骨補填材中の溶媒１００重量部に対して３０〜１５０重量部であることが好ましい。３０重量部未満であるとペースト状骨補填材を欠損部へ補填した再の骨再生性に乏しく、１５０重量部を超えるとペースト状骨補填材が脆くなる傾向がある。 The amount of the bioceramic powder mixed with the solvent in the present invention is preferably 30 to 150 parts by weight with respect to 100 parts by weight of the solvent in the paste-like bone filling material. If the amount is less than 30 parts by weight, the regenerated bone reproducibility after the paste-like bone filling material is filled in the defective part is poor, and if it exceeds 150 parts by weight, the paste-like bone filling material tends to become brittle.
本発明で溶媒に溶解される生分解性高分子の量は、ペースト状骨補填材中の溶媒１００重量部に対して５〜５０重量部であることが好ましい。５重量部未満であるとペーストが軟らか過ぎて賦形性が悪化し易く、５０重量部を超えてもペーストが硬くなって補填時の賦形性が悪化する傾向がある。また、生分解性高分子は溶媒中に完全に溶解していても良いし、ペースト状骨補填材の操作性を妨げない程度であれば未溶解な部分が残存していても構わない。 The amount of the biodegradable polymer dissolved in the solvent in the present invention is preferably 5 to 50 parts by weight with respect to 100 parts by weight of the solvent in the paste-like bone filling material. If the amount is less than 5 parts by weight, the paste is too soft and the formability tends to deteriorate, and if it exceeds 50 parts by weight, the paste becomes hard and the shapeability during filling tends to deteriorate. In addition, the biodegradable polymer may be completely dissolved in the solvent, or an undissolved portion may remain as long as it does not hinder the operability of the paste-like bone grafting material.
表１に記した配合に従い溶媒にバイオセラミックス粉末を分散させ、続いて軟化点まで加熱して軟化させた生分解性高分子を加え撹拌してペースト状骨補填材を作製した。 A bioceramic powder was dispersed in a solvent according to the formulation shown in Table 1, and then a biodegradable polymer softened by heating to a softening point was added and stirred to prepare a paste-like bone filling material.
＜表１＞
※1 水酸アパタイト：平均粒径5μm；太平化学産業社製，製品名ヒドロキシアパタイト
※2 炭酸アパタイト：平均粒径1μm
※3 β型リン酸三カルシウム:オリンパス工業社製（平均粒径1000μｍ、気孔率約70％）
※4 乳酸−グリコール酸共重合体：株式会社ＢＭＧ社製，製品名ＰＧＬＡ
※5 乳酸−ε−カプロラクトン共重合体：株式会社ＢＭＧ社製，製品名ＬＣＬ
※6 ポリ−（L）−乳酸：株式会社ＢＭＧ社製，製品名ＰＬＬＡ
* 1 Hydroxyapatite: average particle size 5μm; manufactured by Taihei Chemical Industrial Co., Ltd., product name Hydroxyapatite * 2 Carbonate apatite: average particle size 1μm
* 3 β-type tricalcium phosphate: Olympus Kogyo Co., Ltd. (average particle size 1000μm, porosity 70%)
* 4 Lactic acid-glycolic acid copolymer: manufactured by BMG Corporation, product name PGLA
* 5 Lactic acid-ε-caprolactone copolymer: manufactured by BMG Corporation, product name LCL
* 6 Poly- (L) -lactic acid: manufactured by BMG Co., Ltd., product name PLLA
２５℃の環境下で、手指にて各実施例のペースト状骨補填材の賦形性を官能的に評価した。表１から明らかなように、特定の溶媒にバイオセラミックスを分散させ、生分解性高分子を溶解させた本発明に係るペースト状骨補填材は、取り扱い性及び賦形性が良いことが分かる。 In an environment of 25 ° C., the shapeability of the pasty bone filling material of each example was sensorially evaluated with fingers. As is clear from Table 1, it can be seen that the paste-like bone filling material according to the present invention in which bioceramics are dispersed in a specific solvent and the biodegradable polymer is dissolved has good handleability and formability.
Claims (5)
The paste-like bone grafting material according to any one of claims 1 to 6, wherein the concentration of the biodegradable polymer to be dissolved is 5 to 50 parts by weight with respect to 100 parts by weight of the solvent.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009148147A1 (en) * | 2008-06-05 | 2009-12-10 | 株式会社ブレーンベース | Bone prosthetic material and method of producing the same |
| JP2012070924A (en) * | 2010-09-28 | 2012-04-12 | Olympus Corp | Bone prosthetic material and method for producing the same |
| JP2013510611A (en) * | 2009-11-12 | 2013-03-28 | ボンアリベ ビオマテリアルス オサケユイチア | Embedding paste and its use |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005117919A2 (en) * | 2004-04-15 | 2005-12-15 | Etex Corporation | Delayed-setting calcium phosphate pastes |
| WO2005120595A2 (en) * | 2004-06-09 | 2005-12-22 | Scil Technology Gmbh | In situ hardening paste, its manufacture and use |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005117919A2 (en) * | 2004-04-15 | 2005-12-15 | Etex Corporation | Delayed-setting calcium phosphate pastes |
| WO2005120595A2 (en) * | 2004-06-09 | 2005-12-22 | Scil Technology Gmbh | In situ hardening paste, its manufacture and use |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009148147A1 (en) * | 2008-06-05 | 2009-12-10 | 株式会社ブレーンベース | Bone prosthetic material and method of producing the same |
| US8475821B2 (en) | 2008-06-05 | 2013-07-02 | Brain Base Corporation | Bone prosthetic material and method of manufacturing the same |
| JP5263992B2 (en) * | 2008-06-05 | 2013-08-14 | 株式会社ブレーンベース | Bone prosthetic material and method for producing the same |
| JP2013510611A (en) * | 2009-11-12 | 2013-03-28 | ボンアリベ ビオマテリアルス オサケユイチア | Embedding paste and its use |
| JP2012070924A (en) * | 2010-09-28 | 2012-04-12 | Olympus Corp | Bone prosthetic material and method for producing the same |
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