JPH01207072A - Bone forming material and its preparation - Google Patents
Bone forming material and its preparationInfo
- Publication number
- JPH01207072A JPH01207072A JP63033220A JP3322088A JPH01207072A JP H01207072 A JPH01207072 A JP H01207072A JP 63033220 A JP63033220 A JP 63033220A JP 3322088 A JP3322088 A JP 3322088A JP H01207072 A JPH01207072 A JP H01207072A
- Authority
- JP
- Japan
- Prior art keywords
- bone
- forming material
- calcium phosphate
- bone forming
- sodium alginate
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 239000000463 material Substances 0.000 title claims abstract description 49
- 210000000988 bone and bone Anatomy 0.000 title abstract description 32
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 22
- 102000008186 Collagen Human genes 0.000 claims abstract description 18
- 108010035532 Collagen Proteins 0.000 claims abstract description 18
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 18
- 229920001436 collagen Polymers 0.000 claims abstract description 18
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000000661 sodium alginate Substances 0.000 claims abstract description 17
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 17
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 17
- 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 claims abstract description 17
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 15
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 230000002188 osteogenic effect Effects 0.000 claims description 16
- 230000001070 adhesive effect Effects 0.000 claims description 2
- 238000007493 shaping process Methods 0.000 claims 1
- 239000011575 calcium Substances 0.000 abstract description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 5
- 229910052791 calcium Inorganic materials 0.000 abstract description 5
- 238000000465 moulding Methods 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 8
- 235000019691 monocalcium phosphate Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 6
- -1 and moreover Substances 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 239000010440 gypsum Substances 0.000 description 5
- 229910052602 gypsum Inorganic materials 0.000 description 5
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 4
- 229920002567 Chondroitin Polymers 0.000 description 4
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 235000010445 lecithin Nutrition 0.000 description 4
- 239000000787 lecithin Substances 0.000 description 4
- 229940067606 lecithin Drugs 0.000 description 4
- 239000011812 mixed powder Substances 0.000 description 4
- 235000019731 tricalcium phosphate Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 201000001245 periodontitis Diseases 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- ODINCKMPIJJUCX-UHFFFAOYSA-N Calcium oxide Chemical compound [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 2
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 2
- 108010087806 Carnosine Proteins 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 229920000288 Keratan sulfate Polymers 0.000 description 2
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000000316 bone substitute Substances 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 239000004068 calcium phosphate ceramic Substances 0.000 description 2
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 2
- 229940044199 carnosine Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 150000002410 histidine derivatives Chemical class 0.000 description 2
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000003761 preservation solution Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 229920000045 Dermatan sulfate Polymers 0.000 description 1
- 208000014151 Stomatognathic disease Diseases 0.000 description 1
- 229910052776 Thorium Inorganic materials 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229910052586 apatite Inorganic materials 0.000 description 1
- 239000012227 artificial bone substitute Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- 235000012255 calcium oxide Nutrition 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229940051593 dermatan sulfate Drugs 0.000 description 1
- 229910000393 dicalcium diphosphate Inorganic materials 0.000 description 1
- 235000019821 dicalcium diphosphate Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229910000150 monocalcium phosphate Inorganic materials 0.000 description 1
- 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 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、歯槽膿漏の疾患治療に際して歯と歯茎の間に
挿入され歯骨を形成させる用途等に用いられる骨形成材
料およびその製法に関するものである。[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to a bone-forming material that is inserted between teeth and gums to form dental bone in the treatment of alveolar pyorrhea, and a method for producing the same. It is something.
従来から歯槽膿漏等の治療には、歯と歯茎の間に、人工
骨および骨補填材を挿入することが行われている。すな
わち、歯槽膿漏は、歯骨等が溶出し痩せてゆくものであ
り、歯のぐらつき等が生しる。その治療には、痩せた部
分に、粒状等の人工骨を充填し補強することがなされる
。このような人工骨および骨補填材としては、アバタイ
） ＨＡＰ、リン酸三カルシウムＴＣＰ等のリン酸カル
シウム系セラミックスあるいは多孔質体セラミックスに
コラーゲン、ムコ多ＩＪ！ｇ溶液を含浸させたものが使
用されている。しかしながら、上記リン酸カルシウム系
セラミックスからなる人工骨および骨補填材は、生体に
対、してなじみ性を有してはいるがあくまで人工骨に過
ぎず、生体骨の組成Ｍｉ織になることはない。したがっ
て、挿入された人工骨および骨補填材の一部または全部
が天然骨と融合せず経時的に脱離する。すなわち、充填
後、暫くの間に殆どのものが歯と歯茎の間から脱離して
しまい、残存しているものも、単に物質的に歯と歯茎の
間に存在しているに過ぎない。そこで、本発明者らは、
コラーゲン、ムコ多楯類、レシチンおよびヒスチジン系
化合物を必須成分とする水性液に、リン酸カルシウムを
必須成分とし焼石灰または水酸化カルシウムを任意成分
とする混合物を混合し、これを乾燥させ粉末状にしたも
のが天然骨の組成と同様の組成を有するため、天然骨と
融合して歯骨等を形成し、歯の疾患治療に使用される骨
形成材料として有効であることを見出し、すでに特許出
願（特願昭６２−６３４２７号）している。BACKGROUND ART Conventionally, in the treatment of alveolar pyorrhea and the like, artificial bone and bone substitute materials have been inserted between teeth and gums. That is, in alveolar pyorrhea, tooth bones etc. elute and become thinner, resulting in looseness of the teeth. The treatment involves reinforcing the thinned area by filling it with granular artificial bone. Examples of such artificial bones and bone replacement materials include calcium phosphate ceramics such as HAP (Abatai), tricalcium phosphate TCP, or porous ceramics, collagen, and Mukota IJ! A material impregnated with g solution is used. However, although the artificial bones and bone grafting materials made of calcium phosphate ceramics are compatible with living bodies, they are only artificial bones, and do not have the composition Mi texture of living bones. Therefore, part or all of the inserted artificial bone and bone grafting material do not fuse with the natural bone and come off over time. That is, after filling, most of the material falls off from between the teeth and gums for a while, and the remaining materials merely physically exist between the teeth and gums. Therefore, the present inventors
A mixture containing calcium phosphate as an essential ingredient and burnt lime or calcium hydroxide as an optional ingredient is mixed with an aqueous liquid containing collagen, mucoplasma, lecithin, and histidine compounds as essential ingredients, and this is dried and made into a powder. Because it has a composition similar to that of natural bone, it fuses with natural bone to form dental bones, etc., and has been found to be effective as an osteogenic material used in the treatment of dental diseases. (Patent Application No. 62-63427).
しかしながら、上記の製法により得られる骨形成材料は
、粉末状態であるため、治療等に使用するためにはさら
に糊剤等のバインダー等を加えタブレット状にしなけれ
ばならず、そのための工程を新たに設けなければならな
い。したがって、得られる骨形成材料は、上記バインダ
ー成分の混入により純度が低くなり、また粉末とバイン
ダー成分の混合工程により製造工程が長くなるという難
点も生じる。However, since the bone-forming material obtained by the above manufacturing method is in a powder state, in order to use it for treatment, it is necessary to add a binder such as glue and make it into a tablet form, which requires a new process. must be established. Therefore, the resulting osteogenic material has a low purity due to the contamination of the binder component, and also has the disadvantage that the mixing process of the powder and the binder component lengthens the manufacturing process.
本発明は、このような事情に鑑みなされたもので、純度
が高く製造工程の省略化を実現できる骨形成材料および
その製法の提供をその目的とする。The present invention was made in view of the above circumstances, and an object of the present invention is to provide an osteogenic material that has high purity and can simplify the manufacturing process, and a method for manufacturing the same.
上記の目的を達成するため、本発明は、コラーゲンとア
ルギン酸ナトリウムを必須成分し、さらに、リン酸カル
シウムが含有され、それ自体の粘着性によりタブレット
形状を保持していることを特徴とする骨形成材料を第１
の要旨とし、コラーゲンとアルギン酸ナトリウムを必須
成分とする水溶液を混合撹拌し、これにリン酸カルシウ
ムを加えたものを乾燥させ所定の形状に賦形することを
特徴とする骨形成材料の製法を第２の要旨とする。In order to achieve the above object, the present invention provides an osteogenic material which contains collagen and sodium alginate as essential components, further contains calcium phosphate, and maintains its tablet shape due to its own adhesive properties. 1st
A second method for producing an osteogenic material, which is characterized in that an aqueous solution containing collagen and sodium alginate as essential components is mixed and stirred, calcium phosphate is added thereto, and the resulting mixture is dried and shaped into a predetermined shape. This is the summary.
すなわち、上記骨形成材料は、法本的には、コラーゲン
、リン酸カルシウムおよびアルギン酸ナトリウムとから
なるものである。本発明者は、コラーゲン、リン酸カル
シウムを主成分とする水溶液を中心に研究を重ねた結果
、上記コラーゲン。That is, the above-mentioned bone forming material essentially consists of collagen, calcium phosphate, and sodium alginate. The inventor of the present invention has developed the above-mentioned collagen as a result of repeated research focusing on aqueous solutions containing collagen and calcium phosphate as main components.
リン酸カルシウムを主成分とする水溶液にアルギン酸ナ
トリウムを添加すると、上記水溶液がゲル化し、いわゆ
るアメ状に固まるため、これをそのまま乾燥させるだけ
でタブレット化できるようになることを突き止めた。そ
して、このように、アルギン酸ナトリウムを添加するこ
とにより、得られる骨形成材料は、糊剤等のバインダー
成分を含有していないため極めて純度が高く、しかもこ
れを用いた場合のカルシウム沈着が良好となる。そのた
め、これを歯の疾患部に挿入した後、生体内の骨組識に
一層迅速に融合されるようになる。They discovered that when sodium alginate is added to an aqueous solution containing calcium phosphate as its main component, the aqueous solution gels and hardens into a so-called candy-like consistency, making it possible to form tablets by simply drying the solution. In this way, by adding sodium alginate, the resulting bone-forming material has extremely high purity because it does not contain binder components such as glue, and moreover, calcium deposition is good when using this material. Become. Therefore, after it is inserted into the diseased part of the tooth, it is more quickly fused to the bone structure in the living body.
本発明の骨形成材料は、コラーゲン、リン酸カルシウム
およびアルギン酸ナトリウム等を用いて得られる。The osteogenic material of the present invention is obtained using collagen, calcium phosphate, sodium alginate, and the like.
上記骨形成材料に用いられるコラーゲン（Ａ成分）とし
ては、従来公知のものが用いられ、例えば、セルマトリ
ックス（Ｔｙｐｅ ＩＩ ） 、 セルマトリックスＬ
Ａ （Ｔｙｐｅ Ｉ ）があげられる。As the collagen (component A) used in the above osteogenic material, conventionally known collagens are used, such as Cell Matrix (Type II), Cell Matrix L
A (Type I) is mentioned.
上記骨形成材料に用いられるリン酸カルシウム（日成分
）としては、第一リン酸カルシウム（Ｃａ（１１２ＰＯ
４） ２ ・＋１２０） ） 、第ニリン酸カルシウム
（ＣａｌｌＰＯｌ・２１１□Ｏ）および第三リン酸カル
シウムＣＣａｘ（ＰＯ４）２〕等があげられる。場合に
より、これらに焼石膏（ＣａＳＯ，・１／２Ｈ２０）が
加えられる。焼石膏粉末の粒径は、微小特に０．３μｍ
未満が好ましい。Calcium phosphate (daily component) used in the above osteogenic material includes monobasic calcium phosphate (Ca(112PO)
4) 2 ・+120) ), calcium diphosphate (CallPOl・211□O), and tricalcium phosphate CCax (PO4) 2]. In some cases, calcined gypsum (CaSO, .1/2H20) is added to these. The particle size of calcined gypsum powder is very small, especially 0.3 μm.
Less than is preferred.
これらは第一リン酸カルシウム単独で用いてもよいし、
上記４成分混合粉末として用いてもよい。These may be used alone as monobasic calcium phosphate, or
It may also be used as a mixed powder of the above four components.
なお、上記リン酸カルシウム系化合物３成分の割合は、
第一リン酸カルシウムが２０〜４０重景％（以下「％」
と略す）、特に好適なのは３０％であり、第二リン成力
ルウシムは５〜２０％、特に好適なのは１０％、第三リ
ン酸カルシウムは５０〜７０％、特に好適なのは６０％
である。この３成分混合粉末の粒径は、微細、特に０．
１μｍ未満が好ましい。上記３成分混合粉末と焼石膏粉
末の混合割合は３成分混合粉末が６０〜９０％、焼石膏
ワ〕末が４０〜１０％が好適である。このＢ成分は、前
記Ａ成分１００重量部に対して６０〜１５重量部の割合
で使用される。The proportions of the three components of the above calcium phosphate compound are as follows:
Monobasic calcium phosphate is 20-40% (hereinafter referred to as "%")
), particularly preferred is 30%, secondary calcium phosphate is 5 to 20%, particularly preferred is 10%, and tribasic calcium phosphate is 50 to 70%, particularly preferred is 60%.
It is. The particle size of this three-component mixed powder is fine, especially 0.
Preferably less than 1 μm. The mixing ratio of the three-component mixed powder and the calcined gypsum powder is preferably 60 to 90% for the three-component mixed powder and 40 to 10% for the calcined gypsum powder. Component B is used in an amount of 60 to 15 parts by weight based on 100 parts by weight of component A.
また、第三成分のアルギン酸す、トリウム（Ｃ成分）と
しては、特に限定するものではなく、通常の市販品をそ
のまま使用することができる。このＣ成分は、重量基準
で前記Ａ成分とＢ成分の合計量１００重量部に対して１
５〜０．６重量部の割合で使用される。Further, the third component, thorium alginic acid (component C), is not particularly limited, and ordinary commercially available products can be used as they are. This component C is added in an amount of 1 part by weight per 100 parts by weight of the total amount of components A and B.
It is used in a proportion of 5 to 0.6 parts by weight.
さらに、上記原料以外に、ヒスチジン系化合物、レシチ
ンおよびムコ多糖類等を用いてもよい。Furthermore, in addition to the above raw materials, histidine compounds, lecithin, mucopolysaccharides, etc. may be used.
上記ヒスチジン系化合物としては、例えばカルノシン（
Ｃ９ＨＩ４Ｎ４０３ 、 β−アラニル−し−ヒスチ
ジン）があげられる。また、ヒスチジン自体を用いても
よい。Examples of the above-mentioned histidine-based compounds include carnosine (
C9HI4N403, β-alanyl-cytidine). Alternatively, histidine itself may be used.
上記レシチンとしては、従来公知のエラグレシチン等が
あげられる。Examples of the lecithin include conventionally known elagrecithin and the like.
上記ムコ多糖類としては、ヒアルロン酸、コンドロイチ
ン、コンドロイチン四硫酸、コンドロイチン六硫酸、デ
ルマタン硫酸、ケラタン硫酸■およびケラタン硫酸■が
あげられる。これらは単独で用いてもよい併用してもよ
い。Examples of the mucopolysaccharides include hyaluronic acid, chondroitin, chondroitin tetrasulfate, chondroitin hexasulfate, dermatan sulfate, keratan sulfate (1), and keratan sulfate (2). These may be used alone or in combination.
本発明は、上記原料の水性液を用いて骨形成材料を製造
するものであり、その水性液をつくるための水溶液とし
ては、リン酸緩衝液、ＮａＯＨ水溶液および保存液（第
一薬品社製、プレサーヘーションリキッドＳＳ）が用い
られる。この保存液の組成成分は、下記の第１表のとお
りである。The present invention is to produce bone forming materials using an aqueous solution of the above-mentioned raw materials, and examples of the aqueous solution used to prepare the aqueous solution include a phosphate buffer solution, an aqueous NaOH solution, and a preservation solution (manufactured by Daiichi Yakuhin Co., Ltd.). Presurgence Liquid SS) is used. The composition of this preservation solution is shown in Table 1 below.
本発明の骨形成材料の製法は、前記の各材料を用い、例
えばつぎのようにして行うことができる。すなわち、第
一リン酸カルシウム（Ｃａ（Ｉｔ□ＰＯ４）２・１１□
０）〕に少量のリン酸緩衝液を加えてペースト状にする
。つぎに、コラーゲンにリン酸緩衝食塩水を加え、Ｎａ
ＯＨでｐＨ６〜８に中和する。これにアルギン酸ナトリ
ウムを加えて混合溶液を作製する。この混合溶液を撹拌
しながら上記ペースト状の第一リン酸カルシウムを徐々
に加えると、ゲル状のものが得られる。このゲル状物質
を凍結乾燥しタブレット状に成形する。The method for producing the osteogenic material of the present invention can be carried out using the above-mentioned materials, for example, as follows. That is, monobasic calcium phosphate (Ca(It□PO4)2.11□
0)] and add a small amount of phosphate buffer to make it into a paste. Next, phosphate buffered saline was added to the collagen, and Na
Neutralize to pH 6-8 with OH. Add sodium alginate to this to prepare a mixed solution. By gradually adding the paste-like monobasic calcium phosphate to this mixed solution while stirring, a gel-like solution is obtained. This gel-like substance is freeze-dried and shaped into a tablet.
このようにして得られた骨形成材料は、通常、タブレッ
ト状等であって、体内に挿入された場合、アルギン酸ナ
トリウムを含有しているため、カルシウム沈着が良好で
あり生体の骨組ｉｉになりうる。The osteogenic material obtained in this way is usually in the form of a tablet, etc., and when inserted into the body, it contains sodium alginate, so it has good calcium deposition and can become the skeleton of the living body. .
つぎに、実施例について比較例と併せて説明する。Next, examples will be described together with comparative examples.
〔実施例１〜６〕 後記の第２表に示す割合で混合材料を卓備する。[Examples 1 to 6] Prepare mixed materials in the proportions shown in Table 2 below.
上記混合材料のうち、まず、第一リン酸カルシウムに少
量のリン酸緩衝液を加えべ一−スト状にする。Of the above mixed materials, first, a small amount of phosphate buffer is added to monobasic calcium phosphate to form a paste.
つぎに、コラーゲン（実施例５．６ではさらにコンドロ
イチン硫酸を加える）にリン酸緩衝食塩水３〜６ｃｃを
加え、Ｎ ａ ＯＨでｐＨ６〜Ｂに調整する。Next, 3 to 6 cc of phosphate buffered saline is added to the collagen (chondroitin sulfate is further added in Example 5.6), and the pH is adjusted to 6 to B with NaOH.
そして、これにアルギン酸ナトリウムを加えて混合？８
？（ｌをつくる。この混合溶液に上記ペースト状の第
一リン酸カルシウムを徐々に加えると、ゲル状の物質が
得られる。このゲル状物質を凍結乾燥（条件：温度−２
０″Ｃ２真空）させてタブレット状の骨形成材料を得た
。And then add sodium alginate to this and mix? 8
? (Create l). Gradually add the paste-like monocalcium phosphate to this mixed solution to obtain a gel-like substance. This gel-like substance is freeze-dried (conditions: temperature -2
0″C2 vacuum) to obtain a tablet-shaped osteogenic material.
（以下余白） ０ 。(Margin below) 0.
：〉 、
〔実施例７〕
リン酸カルシウム系化合物を下記に示す割合で準備する
。:〉, [Example 7] Calcium phosphate compounds are prepared in the proportions shown below.
〈混 合 材 料〉 く混 合 比〉第一リン酸
カルシウム １５％５％第二リンルウシム
６０％第三リンす力成力シム １５％焼
石膏 １０％
つぎに、コラーゲン０．６ｇ、コンドロイチン０゜３ｇ
、カルノシン０．３ｇおよびレシチン０．３ｇに約５〜
１０ｃｃの水を加え、さらに、アルギン酸ナトリウム（
大洋漁業宇都宮社製、コンドロイチン硫酸ナトリウム、
Ｌｏｔ 、 Ｎｏ、００８６３５） ０．６ ｇを加
えオイルバス温度３６〜４５°Ｃ下において溶解させる
。この溶液にリン酸緩衝液ｐＨ７，４（０，１Ｍ）約０
、６ ｃｃおよびＮ ａ ＯＨ水溶液（０，０６Ｍ）約
０．４ ｃｃを加える。この溶液に上記リン酸カルシウ
ム系化合物３ｇを投入したのち撹拌する。つぎに、この
ようにして得られた溶液（ゲル状）を凍結乾燥（条件：
温度−２０°Ｃ１真空）し、タブレット状の゛骨形成材
料を得た。<Mixed materials> Mixing ratio> Monobasic calcium phosphate 15% 5% secondary calcium phosphate
60% third rinsing force shim 15% calcined gypsum 10% Next, collagen 0.6g, chondroitin 0°3g
, about 5 to 0.3 g of carnosine and 0.3 g of lecithin
Add 10cc of water and add sodium alginate (
Manufactured by Taiyo Fisheries Utsunomiya Co., Ltd., sodium chondroitin sulfate,
Lot, No. 008635) 0.6 g was added and dissolved in an oil bath temperature of 36-45°C. Add phosphate buffer pH 7.4 (0.1M) to this solution.
, 6 cc and approximately 0.4 cc of an aqueous NaOH solution (0.06M). 3 g of the above calcium phosphate compound was added to this solution and stirred. Next, the solution (gel-like) obtained in this way was freeze-dried (conditions:
The mixture was heated to -20° C. (1 vacuum) to obtain a tablet-shaped bone forming material.
以上の実施例１〜７で得られた骨形成材料を比較例（ア
パタイトＨＡＰ）と対比してカルシウムの沈着状況等を
みるため、臨床実験に供した結果を第３表に示す。The osteogenic materials obtained in Examples 1 to 7 above were subjected to a clinical experiment in order to compare with a comparative example (apatite HAP) to determine the state of calcium deposition, etc. Table 3 shows the results.
以上のように、本発明は、生体の骨組織成分と同様の材
料の他にアルギン酸ナトリウムを加えて骨形成材料を製
造するため、タブレット状に成形する工程を省略化でき
、得られた骨形成材料は、バインダー等を加える必要が
ないため、純度が高くカルシウムの沈着性に優れている
。したがって、例えば歯と歯茎に挿入後、これまでの人
工骨および骨補填材のように早期に離脱するという不都
合を招かず、天然骨と融合し、速やかに歯骨等を形成す
るという効果を奏する。As described above, the present invention produces an osteogenic material by adding sodium alginate to a material similar to the bone tissue components of a living body, so that the step of forming into a tablet can be omitted, and the resulting osteogenic material can be omitted. The material has high purity and excellent calcium deposition properties since there is no need to add a binder or the like. Therefore, for example, after being inserted into the teeth and gums, the material does not have the disadvantage of premature detachment unlike conventional artificial bones and bone grafting materials, and has the effect of fusing with natural bone and quickly forming dentary bones, etc. .
特許出願人 大 鳥 泰 雅 今西久是律 馬込 正読 代理人 弁理士 西 藤 征 彦Patent applicant Yasutori Otori Hisa Ritsu Imanishi Magome correct reading Agent: Patent attorney Yukihiko Nishifuji
Claims (2)
、さらに、リン酸カルシウムが含有され、それ自体の粘
着性によりタブレット形状を保持していることを特徴と
する骨形成材料。(1) An osteogenic material that contains collagen and sodium alginate as essential components, further contains calcium phosphate, and maintains its tablet shape due to its own adhesive properties.
する水溶液を混合撹拌し、これにリン酸カルシウムを加
えたものを乾燥させ所定の形状に賦形することを特徴と
する骨形成材料の製法。(2) A method for producing an osteogenic material, which comprises mixing and stirring an aqueous solution containing collagen and sodium alginate as essential components, adding calcium phosphate to the mixture, drying it, and shaping it into a predetermined shape.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63033220A JPH01207072A (en) | 1988-02-15 | 1988-02-15 | Bone forming material and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63033220A JPH01207072A (en) | 1988-02-15 | 1988-02-15 | Bone forming material and its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01207072A true JPH01207072A (en) | 1989-08-21 |
Family
ID=12380366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63033220A Pending JPH01207072A (en) | 1988-02-15 | 1988-02-15 | Bone forming material and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01207072A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002058736A (en) * | 2000-08-17 | 2002-02-26 | Seikagaku Kogyo Co Ltd | Composition, medical instrument and kit for bone implantation |
| WO2003035128A1 (en) * | 2001-10-25 | 2003-05-01 | Japan Science And Technology Agency | Composite biological material |
| JP2010163421A (en) * | 2008-12-19 | 2010-07-29 | Tadao Fukushima | Antibacterial agent for periodontal disease-causing bacteria, and medical or dental material using the same |
-
1988
- 1988-02-15 JP JP63033220A patent/JPH01207072A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002058736A (en) * | 2000-08-17 | 2002-02-26 | Seikagaku Kogyo Co Ltd | Composition, medical instrument and kit for bone implantation |
| WO2003035128A1 (en) * | 2001-10-25 | 2003-05-01 | Japan Science And Technology Agency | Composite biological material |
| US7494664B2 (en) | 2001-10-25 | 2009-02-24 | Japan Science And Technology Agency | Composite biomaterials |
| JP2010163421A (en) * | 2008-12-19 | 2010-07-29 | Tadao Fukushima | Antibacterial agent for periodontal disease-causing bacteria, and medical or dental material using the same |
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