JPH0338858B2 - - Google Patents
Info
- Publication number
- JPH0338858B2 JPH0338858B2 JP58213280A JP21328083A JPH0338858B2 JP H0338858 B2 JPH0338858 B2 JP H0338858B2 JP 58213280 A JP58213280 A JP 58213280A JP 21328083 A JP21328083 A JP 21328083A JP H0338858 B2 JPH0338858 B2 JP H0338858B2
- Authority
- JP
- Japan
- Prior art keywords
- calcium phosphate
- beads
- hollow
- antibiotic
- small hole
- 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.)
- Expired - Lifetime
Links
- 239000011324 bead Substances 0.000 claims description 33
- 239000001506 calcium phosphate Substances 0.000 claims description 33
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 30
- 235000011010 calcium phosphates Nutrition 0.000 claims description 30
- 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 description 21
- 239000003242 anti bacterial agent Substances 0.000 claims description 19
- 230000003115 biocidal effect Effects 0.000 claims description 19
- 239000008188 pellet Substances 0.000 claims description 16
- -1 calcium phosphate compound Chemical class 0.000 claims description 15
- 239000000463 material Substances 0.000 claims description 10
- 229940088710 antibiotic agent Drugs 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000000945 filler Substances 0.000 claims description 7
- 238000007789 sealing Methods 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 description 18
- 238000000034 method Methods 0.000 description 11
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 8
- 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 8
- 239000011575 calcium Substances 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 208000033809 Suppuration Diseases 0.000 description 6
- 229910052587 fluorapatite Inorganic materials 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 6
- 239000004926 polymethyl methacrylate Substances 0.000 description 6
- 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 5
- 235000008429 bread Nutrition 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- JJCQSGDBDPYCEO-XVZSLQNASA-N dibekacin Chemical compound O1[C@H](CN)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N JJCQSGDBDPYCEO-XVZSLQNASA-N 0.000 description 4
- 229960003807 dibekacin Drugs 0.000 description 4
- 238000010304 firing Methods 0.000 description 4
- 230000007547 defect Effects 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 235000019731 tricalcium phosphate Nutrition 0.000 description 3
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 3
- 229940078499 tricalcium phosphate Drugs 0.000 description 3
- 206010031252 Osteomyelitis Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 208000005422 Foreign-Body reaction Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000006067 antibiotic powder Substances 0.000 description 1
- 239000012984 antibiotic solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 150000001782 cephems Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000003566 sealing material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
Description
本発明はリン酸カルシウム質充てん材、特に医
用材料として使用し得るリン酸カルシウム質充て
ん材及びその製造法に関する。
整形外科若しくは外科分野において、たとえば
骨髄が炎症化膿をきたし、その部位を除去する必
要にせまられることにしばしば遭遇する。かかる
場合、現状では骨を炎症化膿部位に相当する幅で
切断し、しかる後に炎症化膿部位を充分に掻爬
し、該部位に抗生物質入りリンゲル液を１〜２カ
月間炎症化膿のあつた部位に流し、炎症化膿の再
発を防止するという方法が取られている。しか
し、本方法では多量の骨切除を行うことから、治
療終了後もその部位でもとの形状にもどらず、細
くなり該部位での骨折等をおこしやすくなるとい
う欠点があり、さらに、抗生物質入りリンゲル液
の連続投与の必要から、患者にとつては長期入院
を余儀なくされ、その経済的負担も大きい。
一方、まだ実験的に行われているにすぎない
が、骨セメントとして用いられているPMMA
（Polymethyl methacrylate）と抗生物質とを混
合し、ビーズとしたものを上記掻爬後の欠損部に
入れ、徐々にPMMA中に入つた抗生物質を放出
させ１〜２カ月後ビーズを取り出して炎症化膿部
の治療を行う方法も考えられている。しかし、本
方法によつても多量の骨切除を行うことに変わり
なく、上記とほぼ同様の骨折の問題や、ビーズ除
去時の再手術を行う必要があるという欠点があ
る。
このようなことから、骨髄内等の炎症化膿の掻
爬部に充てんした場合、後になつて除去する必要
がなく炎症化膿の再発を防止し骨髄内等の治療の
ため切除した骨を再生させる能力のある材料の開
発が望まれている。
したがつて本発明の一つの目的は炎症化膿の再
発を防止するための抗生物質を包蔵し、長期間に
わたり抗生物質を放出しつづけうるリン酸カルシ
ウム質充てん材及びその製造法を提供することに
ある。
本発明の他の目的は治療を必要とする部位及び
その近傍にのみ、抗生物質を作用せしめ且つ新生
骨の生成を促進するリン酸カルシウム質充てん材
及びその製造法を提供することにある。
本発明の更に他の目的は炎症化膿の治療のため
切除した骨を元に近い状態又は元の状態にまで回
復しうるリン酸カルシウム質充てん材及びその製
造法を提供することにある。
本発明の更に別の目的は生体適合性にすぐれか
つ異物反応を伴わないリン酸カルシウム質充てん
材及びその製造法を提供することにある。
本発明の更に別の目的は術後、再びとり出す必
要のないリン酸カルシウム質充てん材及びその製
造法を提供することにある。
本発明の上記及びその目的は以下の記載から更
に明白となる。
本発明によれば、少なくとも１ケ所の小孔を有
するリン酸カルシウム化合物から成る中空ビーズ
又は中空ペレツトの該小孔より抗生物質を注入し
た後、該小孔を密封してなることを特徴とする中
心部に抗生物質を有するリン酸カルシウム質充て
ん材が提供される。
また本発明によれば少なくとも１ケ所の小孔を
有するリン酸カルシウム化合物から成る中空ビー
ズ又は中空ペレツトを作成した後、該小孔より抗
生物質を注入し、次いで該小孔を密封することを
特徴とする中心部に抗生物質を有するリン酸カル
シウム質充てん材の製造法が提供される。
以下本発明を更に詳述する。
本発明者らはリン酸カルシウム化合物を骨欠損
部に充てんすると新生骨が当該個所に生成するこ
とから、リン酸カルシウム化合物の骨形成能力を
利用することにまず着目した。本発明に使用し得
るリン酸カルシウム化合物としてはCaHPO4、
2H2O、CaHPO4、Ca3（PO4）2、Ca5（PO4）3OH、
Ca5（PO4）3F、Ca4O（PO4）2、Ca2P2O7等をあげる
ことができ、これら化合物を単独で若しくは２種
以上の混合物として用いることができる。これら
化合物のうちリン酸三カルシウム［Ca3（PO4）2］、
ヒドロキシアパタイト［Ca5（PO4）3OH］、リン酸
四カルシウム［Ca4O（PO4）2］又はフツ素アパタ
イト［Ca5（PO4）3F］を用いた場合に特に新生骨
の生成が早く、好ましい化合物といえる。これら
の中でもより好ましいものとしてはヒドロキシア
パタイト及びフツ素アパタイトを挙げることがで
き、ヒドロキシアパタイトが新生骨の生成が最も
早く特に好ましい化合物といえる。
本発明に使用しうるリン酸カルシウム化合物は
公知の製造方法により、人工的に合成されたもの
であつても、又、骨などから得られる天然のもの
を用いてもよい。
本発明で用いる抗生物質としては、たとえば、
Penicillins系、Cephems系、Aminoglycosidic
antibiotics系、Tetracyclines系、Macrolides系、
Anti−tumor antibiotics系など市販されている
ものを治療目的に応じ用いることができる。この
場合、抗生物質の２種以上の混合物をそれらの間
で特に反応が生じ別物質に変化しないかぎり用い
ることも可能である。
本発明のリン酸カルシウム質充てん材を製造す
るには、少なくとも１ケ所の小孔を有するリン酸
カルシウム化合物から成る中空ビーズ又は中空ペ
レツトを作製し、該小孔より上記抗生物質を入
れ、小孔を密封して作成することができる。かよ
うなリン酸カルシウム化合物からなる中空ビーズ
又は中空ペレツトは可燃物たとえばビーズ又はペ
レツト状のさとう、メチルセルロース、ポリビニ
ルアルコールを中心部に入れ、金型成型やラバー
プレスにより作るか又はパン造粒機などで可燃物
に、リン酸カルシウム化合物をコーテイングする
方法など種々の方法があげられる。このようにし
て作製した中空ビーズ又は中空ペレツト等に抗生
物質を入れるための小孔をあけ、しかる後に焼成
し、可燃物を除去し、少なくとも１カ所の小孔を
有する中空ビーズ又は中空ペレツトを作ることが
できる。また、抗生物質を入れるための小孔を上
記焼成後、超音波加工等によりあけることも可能
である。
このようにして作製したリン酸カルシエム化合
物からなる中空ビーズ又は中空ペレツトの中心部
に必要な抗生物質を入れ、そののち抗生物質を入
れた小孔を密封する。密封のためには毒性のない
有機樹脂、たとえばPMMA、PGA（ポリグリコ
ール酸）PLA（ポリ乳酸）やリン酸カルシウム化
合物の細棒に前記有機樹脂等をシール材として付
着させたものを用いることができる。また更に、
リン酸カルシウム質物質でコーテイングしてもよ
い。
中心部に注入する抗生物質の性状は特に限定さ
れないが、リン酸カルシウム化合物からなる中空
ビーズ又は中空ペレツトが小さい場合には中心部
の抗生物質を入れるスペースが小さく、抗生物質
の高濃度溶液か、又は粉末のものを用いることが
好ましい。
リン酸カルシウム化合物からなる中空ビーズ又
は中空ペレツトの大きさは、炎症化膿等の大きさ
及び骨の切除の大きさにより人間の場合には最大
でも通常約40mmφ程度であるが、動物等に充てん
する場合には大きさに応じ適宜変えることができ
る。下限については特に限定されるものではない
が、２mm以上が好ましい。
抗生物質の放出量のコントロールは、リン酸カ
ルシウム化合物の中空ビーズ又は中空ペレツトの
リン酸カルシウム化合物層の厚さ及びカサ密度を
変化させることにより可能である。一方まつたく
別の方法としてインプラント後に患部に超音波等
をあて、それをあてている間放出量を多くすると
いう手法も考えられる。
以下実施例により本発明を具体的に説明する。
実施例 １
パン造粒機により、さとうビーズ（４mmφ）を
核としてヒドロキシアパタイト（800℃仮焼）粉
末を周囲につけビーズを作り、これに径1.5mmの
小孔をあけ、しかるのち1000℃、1100℃、1200℃
及び1300℃にて各２時間焼成し、さとうビーズを
焼失させ、径約６mmの中空ビーズを作製した。該
空孔部にDibekacin粉末を入れ、PMMAにて小
孔を密封した。
一方、金型成形によりさとうペレツト（４mmφ
×４mmＬ）を中心に入れプレス圧500Kgｆ／cm2に
て成形し、1000℃にて焼成後６mmφ×６mmＬの中
空ペレツトも作製した。
上記各方法にて作製したビーズ、ペレツトを各
５ケを20mlの生理食塩水中に入れ、所定日数経過
後に空孔部に充てんしたDibekacinの溶出量を紫
外吸収法により測定した。結果を表１に示す。
The present invention relates to a calcium phosphate filler, particularly a calcium phosphate filler that can be used as a medical material, and a method for producing the same. In the field of orthopedics or surgery, it is often encountered, for example, that bone marrow becomes inflamed and suppurative, making it necessary to remove the site. In such cases, the current practice is to cut the bone to a width corresponding to the inflamed and purulent area, then thoroughly curettage the inflamed and purulent area, and pour Ringer's solution containing antibiotics into the area for 1 to 2 months. , methods are being taken to prevent recurrence of inflammation and suppuration. However, since this method involves resecting a large amount of bone, the bone does not return to its original shape even after treatment, and the bone becomes thinner, making it more likely to cause fractures. Because of the need for continuous administration of Ringer's solution, patients are forced to stay in the hospital for a long period of time, which imposes a large financial burden. On the other hand, PMMA is being used as bone cement, although it is still being tested experimentally.
(Polymethyl methacrylate) and an antibiotic are mixed and made into beads, which are placed into the defect after the curettage.The antibiotic that has entered the PMMA is gradually released, and after 1 to 2 months, the beads are removed and the inflamed and suppurated area is removed. Treatment methods are also being considered. However, even with this method, a large amount of bone is still resected, and there are drawbacks such as fracture problems similar to those described above and the need for reoperation when removing beads. For this reason, if the curettage of inflammation and suppuration within the bone marrow is filled, there is no need to remove it later, preventing the recurrence of inflammation and suppuration, and reducing the ability to regenerate the bone that has been excised for intramedullary treatment. The development of a certain material is desired. Accordingly, one object of the present invention is to provide a calcium phosphate filler that contains an antibiotic to prevent recurrence of inflammation and suppuration and can continue to release the antibiotic over a long period of time, and a method for producing the same. Another object of the present invention is to provide a calcium phosphate filling material that allows antibiotics to act only on areas requiring treatment and in the vicinity thereof and promotes the formation of new bone, and a method for producing the same. Still another object of the present invention is to provide a calcium phosphate filling material capable of restoring a bone resected for the treatment of inflammation and suppuration to a state close to or to its original state, and a method for producing the same. Still another object of the present invention is to provide a calcium phosphate filler that is highly biocompatible and does not cause foreign body reactions, and a method for producing the same. Still another object of the present invention is to provide a calcium phosphate filling material that does not need to be taken out again after surgery, and a method for manufacturing the same. The above and objects of the present invention will become more apparent from the following description. According to the present invention, the center portion is formed by injecting an antibiotic through the small hole of a hollow bead or hollow pellet made of a calcium phosphate compound having at least one small hole, and then sealing the small hole. Calcium phosphate fillers with antibiotics are provided. Further, according to the present invention, after preparing hollow beads or hollow pellets made of a calcium phosphate compound having at least one small hole, an antibiotic is injected through the small hole, and then the small hole is sealed. A method of making a calcium phosphate filler having an antibiotic in its core is provided. The present invention will be explained in more detail below. The present inventors first focused on utilizing the osteogenic ability of calcium phosphate compounds because when a calcium phosphate compound is filled into a bone defect, new bone is generated at the site. Calcium phosphate compounds that can be used in the present invention include CaHPO 4 ,
2H2O , CaHPO4 , Ca3 ( PO4 ) 2 , Ca5 ( PO4 ) 3OH ,
Examples include Ca 5 (PO 4 ) 3 F, Ca 4 O (PO 4 ) 2 , Ca 2 P 2 O 7, etc., and these compounds can be used alone or as a mixture of two or more. Among these compounds, tricalcium phosphate [Ca 3 (PO 4 ) 2 ],
Especially when using hydroxyapatite [Ca 5 (PO 4 ) 3 OH], tetracalcium phosphate [Ca 4 O (PO 4 ) 2 ] or fluoroapatite [Ca 5 (PO 4 ) 3 F] It can be said to be a preferable compound because it is produced quickly. Among these, hydroxyapatite and fluoroapatite are more preferable, and hydroxyapatite is a particularly preferable compound because it generates new bone the fastest. The calcium phosphate compound that can be used in the present invention may be artificially synthesized by a known production method, or it may be a natural compound obtained from bones or the like. Examples of antibiotics used in the present invention include:
Penicillins, Cephems, Aminoglycosidic
antibiotics, Tetracyclines, Macrolides,
Commercially available anti-tumor antibiotics can be used depending on the therapeutic purpose. In this case, it is also possible to use a mixture of two or more types of antibiotics, as long as a reaction occurs between them and the antibiotics do not change into different substances. In order to produce the calcium phosphate filling material of the present invention, hollow beads or hollow pellets made of a calcium phosphate compound having at least one small hole are prepared, the above-mentioned antibiotic is introduced through the small hole, and the small hole is sealed. can be created. Hollow beads or hollow pellets made of such calcium phosphate compounds are made by placing flammable materials such as beads or pellets of sugar, methyl cellulose, or polyvinyl alcohol in the center, and are made by molding or rubber pressing, or made using a bread granulator, etc. There are various methods such as coating the material with a calcium phosphate compound. A small hole is made in the hollow beads or hollow pellets, etc. prepared in this way to contain an antibiotic, and then calcined to remove combustible materials to produce hollow beads or hollow pellets having at least one small hole. be able to. Further, it is also possible to make a small hole for introducing an antibiotic by ultrasonic machining or the like after the above-mentioned firing. A necessary antibiotic is placed in the center of the hollow beads or hollow pellets made of the calcium phosphate compound thus prepared, and then the small hole containing the antibiotic is sealed. For sealing, a non-toxic organic resin such as PMMA, PGA (polyglycolic acid), PLA (polylactic acid), or a thin rod of a calcium phosphate compound to which the organic resin or the like is attached as a sealing material can be used. Furthermore,
It may also be coated with a calcium phosphate material. The nature of the antibiotic injected into the center is not particularly limited, but if the hollow beads or hollow pellets made of calcium phosphate compound are small, the space for the antibiotic in the center is small, and a highly concentrated antibiotic solution or powder is used. It is preferable to use one. The size of hollow beads or hollow pellets made of calcium phosphate compound is usually about 40 mm in diameter for humans, depending on the size of the inflammation, suppuration, etc. and the size of bone resection, but when filling animals etc. can be changed as appropriate depending on the size. The lower limit is not particularly limited, but is preferably 2 mm or more. The amount of antibiotic released can be controlled by varying the thickness and bulk density of the calcium phosphate compound layer of the calcium phosphate compound hollow beads or hollow pellets. On the other hand, another possible method is to apply ultrasonic waves or the like to the affected area after implantation, and increase the amount of radiation emitted while the ultrasound is being applied. The present invention will be specifically explained below using Examples. Example 1 Using a bread granulator, sugar beads (4 mmφ) were used as cores and hydroxyapatite (calcined at 800°C) powder was attached around them to make beads. Small holes with a diameter of 1.5 mm were made in the beads, and then the beads were heated at 1000°C and 1100°C. ℃、1200℃
and 1300° C. for 2 hours each to burn out the sugar beads and produce hollow beads with a diameter of about 6 mm. Dibekacin powder was put into the hole, and the small hole was sealed with PMMA. Meanwhile, sugar pellets (4mmφ
x 4 mm L) in the center and molded at a press pressure of 500 Kgf/cm 2 , and after firing at 1000° C., hollow pellets of 6 mm diameter x 6 mm L were also produced. Five beads and pellets prepared by each of the above methods were placed in 20 ml of physiological saline, and after a predetermined number of days had elapsed, the elution amount of Dibekacin filled into the pores was measured by ultraviolet absorption method. The results are shown in Table 1.
【表】
実施例 ２
実施例１のパン造粒法により、同様の大きさの
リン酸カルシウム、フツ素アパタイト、リン酸四
カルシウムを用いたDibekacin充てんビーズ（充
てん量各60mg）を作製した。この場合中空ビーズ
作製のための焼成温度は、リン酸カルシウム、フ
ツ素アパタイトで各1100℃、リン酸四カルシウム
で1400℃とし各２時間焼成した。
これを実施例１と同様の方法にてDibekacinの
溶出量を測定した。結果を表２にあげる。[Table] Example 2 By the bread granulation method of Example 1, Dibekacin-filled beads (filling amount each 60 mg) using calcium phosphate, fluoroapatite, and tetracalcium phosphate of similar size were produced. In this case, the firing temperature for producing hollow beads was 1100° C. for each of calcium phosphate and fluoroapatite, and 1400° C. for tetracalcium phosphate, and firing was performed for 2 hours each. The elution amount of Dibekacin was measured using the same method as in Example 1. The results are shown in Table 2.
【表】
実施例 ３
実施例１のパン造粒機にて作製した1100℃焼成
ヒドロキシアパタイト中空ビーズ、実施例２にて
作製したリン酸三カルシウム、フツ素アパタイト
及びリン酸四カルシウムの中空ビーズに
Gentamicinを各々60mgを充てんし、径1.3mmφの
ヒドロキシアパタイト細棒の周囲にPMMAを付
着せしめたものにより、ビーズの小孔を密封し、
抗生物質入りビーズを作製した。
一方、犬の大腿骨に人工的に骨髄炎を生じさ
せ、皮質骨を切除し炎症部を掻爬したのち該欠損
部に上記ビーズを充てんし、術後１カ月ののち、
該部位の観察を行つた。
この結果、リン酸カルシウム化合物としてヒド
ロキシアパタイトを用いた場合にはヒドロキシア
パタイトビーズの周囲に多量の新生骨の生成が認
められ、それら新生骨は連続しているのが観察さ
れた。リン酸三カルシウム、リン酸四カルシウム
を用いた場合には、新生骨はこれらのビーズ周囲
に認められるが、生成した新生骨の連続性は一部
においてみられた。フツ素アパタイトを用いた場
合ではこれらの中間的様子を呈していた。
また、上記いずれの場合においても骨髄炎が再
発していると見られる所見は得られなかつた。[Table] Example 3 Hollow beads of hydroxyapatite fired at 1100°C produced using the bread granulator in Example 1, hollow beads of tricalcium phosphate, fluoroapatite and tetracalcium phosphate produced in Example 2.
Each bead was filled with 60mg of Gentamicin and PMMA was attached around a hydroxyapatite thin rod with a diameter of 1.3mmφ to seal the small pores of the beads.
Antibiotic-containing beads were made. On the other hand, osteomyelitis was artificially caused in the femur of a dog, the cortical bone was excised, the inflamed area was curetted, the defect was filled with the beads, and one month after the surgery,
The site was observed. As a result, when hydroxyapatite was used as the calcium phosphate compound, a large amount of new bone was observed to be formed around the hydroxyapatite beads, and the new bone was observed to be continuous. When tricalcium phosphate and tetracalcium phosphate were used, new bone was observed around these beads, but continuity of the generated new bone was observed in some areas. When fluoroapatite was used, the appearance was intermediate between these. Furthermore, no findings indicating recurrence of osteomyelitis were observed in any of the above cases.
Claims (1)
シウム化合物から成る中空ビーズ又は中空ペレツ
トの該小孔より抗生物質を注入した後、該小孔を
密封してなることを特徴とする中心部に抗生物質
を有するリン酸カルシウム質充てん材。 ２ 少なくとも１ケ所の小孔を有するリン酸カル
シウム化合物から成る中空ビーズ又は中空ペレツ
トを作成した後、該小孔より抗生物質を注入し、
次いで該小孔を密封することを特徴とする中心部
に抗生物質を有するリン酸カルシウム質充てん材
の製造法。[Scope of Claims] 1. A center formed by injecting an antibiotic through the small hole of a hollow bead or hollow pellet made of a calcium phosphate compound having at least one small hole, and then sealing the small hole. Calcium phosphate filling material with antibiotics in the part. 2. After preparing hollow beads or hollow pellets made of a calcium phosphate compound having at least one small hole, injecting an antibiotic through the small hole,
A method for producing a calcium phosphate filler having an antibiotic in its center, which comprises then sealing the pores.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58213280A JPS60106459A (en) | 1983-11-15 | 1983-11-15 | Calcium phosphate filler |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58213280A JPS60106459A (en) | 1983-11-15 | 1983-11-15 | Calcium phosphate filler |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60106459A JPS60106459A (en) | 1985-06-11 |
| JPH0338858B2 true JPH0338858B2 (en) | 1991-06-12 |
Family
ID=16636488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58213280A Granted JPS60106459A (en) | 1983-11-15 | 1983-11-15 | Calcium phosphate filler |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60106459A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3613213A1 (en) * | 1986-04-18 | 1987-10-22 | Merck Patent Gmbh | TRICALCIUMPHOSPHATE FOR IMPLANTATION MATERIALS |
| US6350462B1 (en) | 1990-12-26 | 2002-02-26 | Olympus Optical Co., Ltd. | Hollow porous ceramic carrier for embedding in patient for sustained medicament release and method of preparation thereof |
| US5491082A (en) * | 1991-03-18 | 1996-02-13 | Director-General Of Agency Of Industrial Science And Technology | Plasminogen activator covalently bonded to a porous body of β-tricalcium phosphate |
| WO1998023556A1 (en) | 1996-11-25 | 1998-06-04 | Kabushiki Kaisya Advance | Method of production of ceramics |
| CN102805879B (en) * | 2012-07-20 | 2014-09-24 | 陈卓凡 | Preparation method for biogenic fluorinated porcine hydroxyapatite (FPHA) bone substitution material |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS574915A (en) * | 1980-06-10 | 1982-01-11 | Fujisawa Pharmaceut Co Ltd | Preparation of medical preparation with long-lasting activity |
| JPS59101145A (en) * | 1982-11-30 | 1984-06-11 | 日本特殊陶業株式会社 | Chemical liquid impregnated porous ceramic |
-
1983
- 1983-11-15 JP JP58213280A patent/JPS60106459A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS574915A (en) * | 1980-06-10 | 1982-01-11 | Fujisawa Pharmaceut Co Ltd | Preparation of medical preparation with long-lasting activity |
| JPS59101145A (en) * | 1982-11-30 | 1984-06-11 | 日本特殊陶業株式会社 | Chemical liquid impregnated porous ceramic |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60106459A (en) | 1985-06-11 |
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