JPH03210270A - 流動性のある脱ミネラル化した骨粉組成物及びその骨治療での使用 - Google Patents
流動性のある脱ミネラル化した骨粉組成物及びその骨治療での使用Info
- Publication number
- JPH03210270A JPH03210270A JP2250407A JP25040790A JPH03210270A JP H03210270 A JPH03210270 A JP H03210270A JP 2250407 A JP2250407 A JP 2250407A JP 25040790 A JP25040790 A JP 25040790A JP H03210270 A JPH03210270 A JP H03210270A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- bone
- carrier
- derivative
- glycerol
- 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.)
- Granted
Links
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Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。
め要約のデータは記録されません。
Description
【発明の詳細な説明】
(産業上の利用分野)
本発明は流動性のある脱ミネラル化した骨粉組成物は骨
欠陥の外科的治療での該組成物の使用に関する。
欠陥の外科的治療での該組成物の使用に関する。
(従来技術)
肯欠陥の治療に脱ミネラル化した骨粉を用いる検討は既
になされている。骨粉は1以上の部質、多分骨形成性蛋
白質(BMP)′1に富有しており、これが欠陥部位に
おける骨の再生を誘発する。たとえばCovav叫の0
デgkopaadicReview、Vol、XVII
、/168.857−863(1989年8月)参照。
になされている。骨粉は1以上の部質、多分骨形成性蛋
白質(BMP)′1に富有しており、これが欠陥部位に
おける骨の再生を誘発する。たとえばCovav叫の0
デgkopaadicReview、Vol、XVII
、/168.857−863(1989年8月)参照。
Ha&@J等のAss@la of Plaatie
S*rgar11゜)’oj、15、/%2.138−
142(1985年8月)Kよれば、ペースト状物質に
まで粉砕し自生血液と混合した自生骨を犬の長い骨の欠
陥の治療(代替)K用いている。
S*rgar11゜)’oj、15、/%2.138−
142(1985年8月)Kよれば、ペースト状物質に
まで粉砕し自生血液と混合した自生骨を犬の長い骨の欠
陥の治療(代替)K用いている。
(発明の開示)
本発明の目的は外科的な骨の治療(リペア)K用いる流
動性のある脱ミネラル化した骨粉組成物を提供すること
にある。
動性のある脱ミネラル化した骨粉組成物を提供すること
にある。
更に詳しくは不発明の目的は脱ミネラル化した骨粉と骨
粉用キャリヤとし【の液状ポリヒドロキシ化合物とから
なる液状又はペースト状の組成物(チキソトロピー剤や
医薬等の任意成分はあってもなくてもよい)及び該組成
物を骨欠陥部位に付与して新しい骨の内部生長を誘発す
る方法な提供することにある。
粉用キャリヤとし【の液状ポリヒドロキシ化合物とから
なる液状又はペースト状の組成物(チキソトロピー剤や
医薬等の任意成分はあってもなくてもよい)及び該組成
物を骨欠陥部位に付与して新しい骨の内部生長を誘発す
る方法な提供することにある。
本発明は液状ポリヒドロキシ化合物、液状ポリヒドロキ
シ化合物誘導体、固体状ポリヒドロキシ化合物の溶液、
固体状ポリヒドロキシ化合物誘導体の溶液及びそれらの
混合物からなる群から選ばれた生体適合性キャリヤと脱
ミネラル化した骨粉からなることを特徴とする骨の欠陥
部位の新しい骨の生長を促進するために骨欠陥部位に付
与するための流動性組成物にある。
シ化合物誘導体、固体状ポリヒドロキシ化合物の溶液、
固体状ポリヒドロキシ化合物誘導体の溶液及びそれらの
混合物からなる群から選ばれた生体適合性キャリヤと脱
ミネラル化した骨粉からなることを特徴とする骨の欠陥
部位の新しい骨の生長を促進するために骨欠陥部位に付
与するための流動性組成物にある。
本発明の組成物を骨欠陥部位、たとえばけが、感染、悪
性もしくは進行性の奇形等に基づく欠陥部位に付与する
と骨生成、骨#S尋及び骨酵兄等の1又は2以上の機構
によって急速な骨の内部生成かもたらされる。
性もしくは進行性の奇形等に基づく欠陥部位に付与する
と骨生成、骨#S尋及び骨酵兄等の1又は2以上の機構
によって急速な骨の内部生成かもたらされる。
本発明の骨粉組成物はそれが必要なときに容易に調製す
ることができ、好ましくは本発明組成物の成分を混合す
るための部材と該組成物を骨欠陥部位に付与する部材を
一体形キットの形で用意する。また本発明の骨粉組成物
を予じめp4製し、後日の使用のために無I!i条件下
に保存することもできる。
ることができ、好ましくは本発明組成物の成分を混合す
るための部材と該組成物を骨欠陥部位に付与する部材を
一体形キットの形で用意する。また本発明の骨粉組成物
を予じめp4製し、後日の使用のために無I!i条件下
に保存することもできる。
本発明組成物における脱ミネラル化した破砕又は粉末化
した骨成分は公知の物質であり公知の方法でつくられる
。
した骨成分は公知の物質であり公知の方法でつくられる
。
ここで1゛破砕した骨」、「粉末化した骨」、「骨粉」
は比較的微細な粉末から粗粒さらには大きなチップも含
む広い範囲の骨粒子を包含するものである。従ってたと
えば本発明組成物中に存在する骨粉は約0.1〜約1.
21、より好ましくは約0.2〜約1.0CILの平均
粒径をもちうる。骨粉は皮質室、がん性及び/又は副腎
皮質の自生、変異性及び/又は他生の骨組織から得られ
る。通常変異性の骨組織が骨粉源とし【好ましく用いら
れる。
は比較的微細な粉末から粗粒さらには大きなチップも含
む広い範囲の骨粒子を包含するものである。従ってたと
えば本発明組成物中に存在する骨粉は約0.1〜約1.
21、より好ましくは約0.2〜約1.0CILの平均
粒径をもちうる。骨粉は皮質室、がん性及び/又は副腎
皮質の自生、変異性及び/又は他生の骨組織から得られ
る。通常変異性の骨組織が骨粉源とし【好ましく用いら
れる。
好ましい骨の脱ミネラル化法において、まず骨を所望の
平均粒径に破砕し次いで脱脂/殺菌し、酸による脱ミネ
ラル化処理をする。好ましい脱脂/殺菌溶液としてはエ
タノール水溶液がある。エタノールは脂質分に対する良
溶媒であり、水はすぐれた親水性キャリヤであり該溶液
を骨中により深<&透させる。エタノール水浴液はまた
植物性微生物及びウィルスを殺すことにより骨を殺菌す
る。通常束なくとも約10%〜40%の水(即ち約60
%〜90%のアルコール等の脱脂剤)を脱脂、殺M浴液
中に存在させることが、最適の脂質除去と殺菌とを最も
短時間で達成する上で好ましい。脱脂溶液の好ましい濃
度はアルコール濃度約60%〜85%であり、最も好ま
しいアルコール濃度は約70%である。脱脂に続き、骨
を脱ミネラル化するに足る時間酸中に浸漬する。この操
作で用いる酸としては塩酸等の無機酸及び過酢酸等の有
機酸がある。酸処理後骨粉を射出用に無陳水ですすぎ、
バッファで最終の予めきめた。Hに調整し最後に水です
すぎ残存する酸とバッファを除く。
平均粒径に破砕し次いで脱脂/殺菌し、酸による脱ミネ
ラル化処理をする。好ましい脱脂/殺菌溶液としてはエ
タノール水溶液がある。エタノールは脂質分に対する良
溶媒であり、水はすぐれた親水性キャリヤであり該溶液
を骨中により深<&透させる。エタノール水浴液はまた
植物性微生物及びウィルスを殺すことにより骨を殺菌す
る。通常束なくとも約10%〜40%の水(即ち約60
%〜90%のアルコール等の脱脂剤)を脱脂、殺M浴液
中に存在させることが、最適の脂質除去と殺菌とを最も
短時間で達成する上で好ましい。脱脂溶液の好ましい濃
度はアルコール濃度約60%〜85%であり、最も好ま
しいアルコール濃度は約70%である。脱脂に続き、骨
を脱ミネラル化するに足る時間酸中に浸漬する。この操
作で用いる酸としては塩酸等の無機酸及び過酢酸等の有
機酸がある。酸処理後骨粉を射出用に無陳水ですすぎ、
バッファで最終の予めきめた。Hに調整し最後に水です
すぎ残存する酸とバッファを除く。
脱ミネラル化した骨粉は直ちに本発明の組成物の製造に
用いることもできるし無菌条件下、好ましくは凍結乾燥
状態で保存して後は組成物の製造に供することもできる
。
用いることもできるし無菌条件下、好ましくは凍結乾燥
状態で保存して後は組成物の製造に供することもできる
。
所望により、骨粉を1又は2以上の方法で変性すること
もできる。たとえば骨粉の多孔度を増加させ及び/又は
骨粉を1又は2以上の変性剤、たとえばグルタルアルデ
ヒド(米国特許第4.678,470 )等で処理する
ことができる。
もできる。たとえば骨粉の多孔度を増加させ及び/又は
骨粉を1又は2以上の変性剤、たとえばグルタルアルデ
ヒド(米国特許第4.678,470 )等で処理する
ことができる。
また米国特許第4,743,259号及び4,902,
296号に開示されているように、骨粉の骨蛋白含量を
増加又は変化させることもできる。
296号に開示されているように、骨粉の骨蛋白含量を
増加又は変化させることもできる。
本発明の流動性のある骨粉組成物には程々の製薬上/外
科上有用な物質を、たとえば所望の物質の浴液又は分散
液に骨粉を浸漬したり、これら物lxをポリヒドロキシ
化合物成分に添加したり又は直接流動性のある骨粉組成
物に添加する等の手段によって導入することができる。
科上有用な物質を、たとえば所望の物質の浴液又は分散
液に骨粉を浸漬したり、これら物lxをポリヒドロキシ
化合物成分に添加したり又は直接流動性のある骨粉組成
物に添加する等の手段によって導入することができる。
本発明組成物に容易に導入しうる製薬上/外科上有用な
物質には、たとえばコラーゲン及び不溶性コラーゲン誘
導体、ヒドロキシアペタイト等、及び可溶性固体及び/
又は液体、たとえば、抗ウィルス剤、特にl1lV及び
肝炎に対し有効なもの;抗菌剤及び/又は抗生物質、た
とえばエリスロマイシン、バシトラシン、ネオマイシン
、ペニシリン、ポリミキシンB、テトラサイクリン、バ
イオマイシン、クロロマイセチン、ストレプトマイシン
、セファゾリン、アムピシリン、アザクタム、トブラマ
イシン、エリスロマイシン及びゲンタマイシン等;アミ
ノ酸、ペプチド、ビタミン、無機元素、蛋白合成用コフ
ァクター、ホルモン、内分路線組織又は組織フラグメン
ト、シンセサイザー、#木、たとえばコラ−ケン、ペプ
チダーゼ、オキシダーゼ等、実JJK細胞を伴なったポ
リマーセル骨組剤、脈管形成剤及びこれら医薬を含有す
るポリマーキャリヤ、コラーゲン格子、生化学的相溶性
のある表面活性剤、抗原剤、細胞骨格剤、軟骨フラグメ
ント、生細胞、たとえばコンドロサイト、骨髄細胞、開
業ステム細胞、天然抽出物、組織移植体、生化学接着剤
、組織形成性蛋白(BMP)、トランスフォーミング生
長因子(TGF−β)、インシュリン様生長因子(70
F−1)、生長ホルモン、たとえばツマ))ロピン、骨
分解剤、抗腫瘍剤、フィブロネクチン、細胞誘引剤、細
胞接着剤、免疫抑制311.透過性増強剤、たとえばポ
リエチレングリコールのラウレート、ミリステート及び
ステアレート等の脂肪酸エステル、エナミン誘導体、ア
ルファケトアルデヒド等、核酸、及び米国特許第4,7
64.364号、4,765,973号及びヨーロッパ
特許出願第168,277号に開示されているような生
化学分解性ポリマー等がある。これら任意添加成分の量
は広範囲で変化させうるが、それぞれの最適量は通常の
実験で容易に決定し5る。
物質には、たとえばコラーゲン及び不溶性コラーゲン誘
導体、ヒドロキシアペタイト等、及び可溶性固体及び/
又は液体、たとえば、抗ウィルス剤、特にl1lV及び
肝炎に対し有効なもの;抗菌剤及び/又は抗生物質、た
とえばエリスロマイシン、バシトラシン、ネオマイシン
、ペニシリン、ポリミキシンB、テトラサイクリン、バ
イオマイシン、クロロマイセチン、ストレプトマイシン
、セファゾリン、アムピシリン、アザクタム、トブラマ
イシン、エリスロマイシン及びゲンタマイシン等;アミ
ノ酸、ペプチド、ビタミン、無機元素、蛋白合成用コフ
ァクター、ホルモン、内分路線組織又は組織フラグメン
ト、シンセサイザー、#木、たとえばコラ−ケン、ペプ
チダーゼ、オキシダーゼ等、実JJK細胞を伴なったポ
リマーセル骨組剤、脈管形成剤及びこれら医薬を含有す
るポリマーキャリヤ、コラーゲン格子、生化学的相溶性
のある表面活性剤、抗原剤、細胞骨格剤、軟骨フラグメ
ント、生細胞、たとえばコンドロサイト、骨髄細胞、開
業ステム細胞、天然抽出物、組織移植体、生化学接着剤
、組織形成性蛋白(BMP)、トランスフォーミング生
長因子(TGF−β)、インシュリン様生長因子(70
F−1)、生長ホルモン、たとえばツマ))ロピン、骨
分解剤、抗腫瘍剤、フィブロネクチン、細胞誘引剤、細
胞接着剤、免疫抑制311.透過性増強剤、たとえばポ
リエチレングリコールのラウレート、ミリステート及び
ステアレート等の脂肪酸エステル、エナミン誘導体、ア
ルファケトアルデヒド等、核酸、及び米国特許第4,7
64.364号、4,765,973号及びヨーロッパ
特許出願第168,277号に開示されているような生
化学分解性ポリマー等がある。これら任意添加成分の量
は広範囲で変化させうるが、それぞれの最適量は通常の
実験で容易に決定し5る。
本発明の脱ミネラル化した骨粉組成物は、前記した如き
脱ミネラル化した骨粉を、骨粉用のキャリヤ又は懸濁剤
として機能する生化学的相溶性のある液状ポリヒドロキ
シ化合物と組合せることによって得られる。
脱ミネラル化した骨粉を、骨粉用のキャリヤ又は懸濁剤
として機能する生化学的相溶性のある液状ポリヒドロキ
シ化合物と組合せることによって得られる。
ここで「液状ポリヒドロキシ化合物」、「液状ポリヒド
ロキシ化合物誘導体」とは、純粋又は高濃度状態で且つ
周囲温度、たとえば15〜40℃で、流動性のある液体
である形の化合物を包含するものである。ここで用いる
「固体状ポリヒドロキシ化合物」、「固体状ポリヒドロ
キシ化合物誘導体」とは、純粋又は高濃度状態で且つ周
囲温度にて、通常固体又は半固体であるが、適当な溶媒
、たとえば水、生理的食塩水、エタノール、グリセロー
ル、グルコース、プロピレングリコール、ポリエチレン
グリコール(分子量200〜1000)婢又はそれらの
混合物には溶けて液状組成物となる形の化合物を包含す
るものである。機能的には、骨粉組成物のキャリヤ成分
は広範囲の濃度の流動性物質をもたらしうるものである
。ここで「流動性(のある)」とは形状保持性はあるが
容易に変形しうる濃度は、たとえばパテのような挙動な
示すもの等をも包含するものである。
ロキシ化合物誘導体」とは、純粋又は高濃度状態で且つ
周囲温度、たとえば15〜40℃で、流動性のある液体
である形の化合物を包含するものである。ここで用いる
「固体状ポリヒドロキシ化合物」、「固体状ポリヒドロ
キシ化合物誘導体」とは、純粋又は高濃度状態で且つ周
囲温度にて、通常固体又は半固体であるが、適当な溶媒
、たとえば水、生理的食塩水、エタノール、グリセロー
ル、グルコース、プロピレングリコール、ポリエチレン
グリコール(分子量200〜1000)婢又はそれらの
混合物には溶けて液状組成物となる形の化合物を包含す
るものである。機能的には、骨粉組成物のキャリヤ成分
は広範囲の濃度の流動性物質をもたらしうるものである
。ここで「流動性(のある)」とは形状保持性はあるが
容易に変形しうる濃度は、たとえばパテのような挙動な
示すもの等をも包含するものである。
流動性のある骨粉組成物の特殊な形にはケーキ、ペース
ト、クリーム、フィラー等がある。
ト、クリーム、フィラー等がある。
有用なポリヒドロキシ化合物は2〜約18の炭素をもち
非環状多価アルコール、非還元性シュガー、シュガーア
ルコール、シュガー酸、モノサッカライド、ジサッカラ
イド、水溶性又は水分散性オリゴサツカライド、ポリサ
ッカライド、及びこれらの公知の誘導体等がある。ポリ
ヒドロキシ化合物の更なる例にはエチレングリコール、
ジエチレングリコール、トリエチレングリコール、1.
2−プロパンジオール、トリメチロールエタン、トリメ
チロールプロパン、エリスリトール、ペンタエリスリト
ール、ホリアルキレングリコール、たとえばポリエチレ
ングリコール、キシリトール、ソルビトール、マンニト
ール、ダルシトール、アラビノース、キシロース、リボ
ース、アドニトール、アラビトール、ラモーゼ、イノシ
トール、フラクトース、ガラクトース、クルコース、マ
ンノース、ソルボース、スクロース、マルトース、ラク
トース、マルチトール、ラクチトール、スタチオース、
マルトペンタオース、シクロマルトヘキサオース、カラ
ギーナン、寒天、アルギン酸、グアーガム、ガムトラガ
カンス、〇−カストビーンガム、アラビアガム、キサン
タンガム、アミロース、前記いづれかの混合物等がある
。
非環状多価アルコール、非還元性シュガー、シュガーア
ルコール、シュガー酸、モノサッカライド、ジサッカラ
イド、水溶性又は水分散性オリゴサツカライド、ポリサ
ッカライド、及びこれらの公知の誘導体等がある。ポリ
ヒドロキシ化合物の更なる例にはエチレングリコール、
ジエチレングリコール、トリエチレングリコール、1.
2−プロパンジオール、トリメチロールエタン、トリメ
チロールプロパン、エリスリトール、ペンタエリスリト
ール、ホリアルキレングリコール、たとえばポリエチレ
ングリコール、キシリトール、ソルビトール、マンニト
ール、ダルシトール、アラビノース、キシロース、リボ
ース、アドニトール、アラビトール、ラモーゼ、イノシ
トール、フラクトース、ガラクトース、クルコース、マ
ンノース、ソルボース、スクロース、マルトース、ラク
トース、マルチトール、ラクチトール、スタチオース、
マルトペンタオース、シクロマルトヘキサオース、カラ
ギーナン、寒天、アルギン酸、グアーガム、ガムトラガ
カンス、〇−カストビーンガム、アラビアガム、キサン
タンガム、アミロース、前記いづれかの混合物等がある
。
前記ポリヒドロキシ化合物の騎導体、特にエステル訪導
体も有用である。たとえばグリセロールの液状及び固体
状モノエステル及びジエステルはすぐれた効果を示す。
体も有用である。たとえばグリセロールの液状及び固体
状モノエステル及びジエステルはすぐれた効果を示す。
この固体状エステルはプロピレングリコール、グリセロ
ール、ポリエチレングリコール(分子量200〜100
0)等の適当なビヒクルにそれらの溶解度限度まで溶解
される。液状グリセロールエステルには特に好ましいグ
リセロールモノラウレート、グリセロールパルミテート
、グリセロールモノステアレート等のグリセロールの脂
肪酸モノエステルがある。特に好ましいキャリヤはグリ
セロールに溶解したグリセリルモノラタレート又はグリ
セロールとプロピレングリコールとの4:1〜l:4混
合物からなるものである。
ール、ポリエチレングリコール(分子量200〜100
0)等の適当なビヒクルにそれらの溶解度限度まで溶解
される。液状グリセロールエステルには特に好ましいグ
リセロールモノラウレート、グリセロールパルミテート
、グリセロールモノステアレート等のグリセロールの脂
肪酸モノエステルがある。特に好ましいキャリヤはグリ
セロールに溶解したグリセリルモノラタレート又はグリ
セロールとプロピレングリコールとの4:1〜l:4混
合物からなるものである。
前記したポリヒドロキシ化合物のうち、グリセロール及
びその液状モノエステル及びジエステル、たとえばモノ
アセチン、ジアセチン、フラクトース、グルコース及び
スクロース及びそれらの混合物がより好ましい。ポリヒ
ドロキシ化合物がたとえばスクロースのように固体であ
る場合には、水、グリセロール、ポリエチレングリコー
ル(平均分子量200〜1000 )又はそれらの混合
物等の溶媒を用いてこの化合物の流動性のある溶液又は
ペーストにすることが好ましい。
びその液状モノエステル及びジエステル、たとえばモノ
アセチン、ジアセチン、フラクトース、グルコース及び
スクロース及びそれらの混合物がより好ましい。ポリヒ
ドロキシ化合物がたとえばスクロースのように固体であ
る場合には、水、グリセロール、ポリエチレングリコー
ル(平均分子量200〜1000 )又はそれらの混合
物等の溶媒を用いてこの化合物の流動性のある溶液又は
ペーストにすることが好ましい。
V粉かキャリヤからすぐに又は分離するとか沈澱する傾
向かあって均一組成物の付与が困難な場合には、その傾
向を抑え又は減少させるチキントロピー特性をもつ物質
を冷加することが好ましい。たとえばキャリヤ成分がグ
リセロールで骨粉の分離が過度に起こる場合には、ポリ
ビニルアルコール、ポリビニルピロリドン、セルロース
エステル、たとえばヒドロキシプロピルメチルセルロー
ス、カルボキシメチルセルロース、ペクチン、食品級の
テキスチャリング剤、ゼラチン、デキストラン、コラー
ゲン、でんぷん、氷解ポリアクリロニトリル、氷解ポリ
アクリルアミド、多電解質、たとえばポリアクリル除塩
等を組成物の懸濁維持特性を改良するに十分な菫でキャ
リヤに添加し5る。
向かあって均一組成物の付与が困難な場合には、その傾
向を抑え又は減少させるチキントロピー特性をもつ物質
を冷加することが好ましい。たとえばキャリヤ成分がグ
リセロールで骨粉の分離が過度に起こる場合には、ポリ
ビニルアルコール、ポリビニルピロリドン、セルロース
エステル、たとえばヒドロキシプロピルメチルセルロー
ス、カルボキシメチルセルロース、ペクチン、食品級の
テキスチャリング剤、ゼラチン、デキストラン、コラー
ゲン、でんぷん、氷解ポリアクリロニトリル、氷解ポリ
アクリルアミド、多電解質、たとえばポリアクリル除塩
等を組成物の懸濁維持特性を改良するに十分な菫でキャ
リヤに添加し5る。
前記したように、本発明の骨粉組成物は、骨粉とキャリ
ヤと任意成分を適宜の混合順序又は同時に混合すること
により、使用直前に調製することができる。骨粉はまず
任意成分と混合し、次いでキャリヤ成分と混合してもよ
いし、骨粉をキャリヤ成分と混合してから任意成分を添
加してもよいし、又は任意成分をキャリヤに添加してか
ら骨粉を添加し【もよい。これらの添加操作の順序の変
更は勿論可能である。本発明組成物に導入される骨粉の
量は約5〜約90重量%、好ましくは約20〜約80″
Ill[量%であり、残余はキャリヤか占め5る。本発
明組成物を使用時にlpl製するためK、骨粉、好まし
くは凍結状態の骨粉、とキャリヤ(前記した任意成分を
含有する)とを、無菌状態で、別々のパッケージ又は容
器中に保存し使用時に適宜の部材な用いて骨欠陥部位に
直ちに付与できるよ5にすることができる。この場合の
付与部材としてはシリンジへら等がある。
ヤと任意成分を適宜の混合順序又は同時に混合すること
により、使用直前に調製することができる。骨粉はまず
任意成分と混合し、次いでキャリヤ成分と混合してもよ
いし、骨粉をキャリヤ成分と混合してから任意成分を添
加してもよいし、又は任意成分をキャリヤに添加してか
ら骨粉を添加し【もよい。これらの添加操作の順序の変
更は勿論可能である。本発明組成物に導入される骨粉の
量は約5〜約90重量%、好ましくは約20〜約80″
Ill[量%であり、残余はキャリヤか占め5る。本発
明組成物を使用時にlpl製するためK、骨粉、好まし
くは凍結状態の骨粉、とキャリヤ(前記した任意成分を
含有する)とを、無菌状態で、別々のパッケージ又は容
器中に保存し使用時に適宜の部材な用いて骨欠陥部位に
直ちに付与できるよ5にすることができる。この場合の
付与部材としてはシリンジへら等がある。
米国特許第4.45&733号には前記の保存と混合と
付与を行なうに適する保存、混合、付与(塗布)部材が
開示されており、本発明にも有効である。また骨粉組成
物を多量に調製し使用時までシリンジその他の適当な塗
付装置の胴体内に無菌状態で保存することもできる。
付与を行なうに適する保存、混合、付与(塗布)部材が
開示されており、本発明にも有効である。また骨粉組成
物を多量に調製し使用時までシリンジその他の適当な塗
付装置の胴体内に無菌状態で保存することもできる。
本発明の骨粉組成物は糧々の方法で骨欠陥部位に付与し
うる。たとえば高粘性ペースト状の組成物で該部位を充
填する等の方法が用いうる。本発明組成物は、標準的な
関節形成性、骨格又は他の骨欠陥の再構成に有効に用い
うるしまた内部及び外S同定装置の有効性を増大する。
うる。たとえば高粘性ペースト状の組成物で該部位を充
填する等の方法が用いうる。本発明組成物は、標準的な
関節形成性、骨格又は他の骨欠陥の再構成に有効に用い
うるしまた内部及び外S同定装置の有効性を増大する。
次に実施例により本発明の流動性のある脱ミネラル化し
た骨粉組成物の調製について脱明する。
た骨粉組成物の調製について脱明する。
実施例1゜
一定量の四種の皮質性又は海綿質の肯を破砕して約10
0〜約500μの平均粒径のものをふるいとり、反応器
に入れ密封した。70%エタノール溶液を骨1f当り3
01の割合で反応器に入れ1時間攪拌しくBola%d
−r等、 Josrsal of Ba5s a
sd Joint Ssrgmry。
0〜約500μの平均粒径のものをふるいとり、反応器
に入れ密封した。70%エタノール溶液を骨1f当り3
01の割合で反応器に入れ1時間攪拌しくBola%d
−r等、 Josrsal of Ba5s a
sd Joint Ssrgmry。
Vol、 68−A、/%8 (1986年10月)、
骨粉の脱脂と消毒をした。エタノールをぬい【から0.
6NのHC1溶液を骨12当り50wLt反応器に入れ
(Bolasdat等上り、反応を3時間行な5 (G
lovaekig、 AATB 1Forkah−op
、 第11回年次会議(1987))。#CJをヌイ
てから骨をインジェクション(il’FI)用の水で3
回すすぎ、WFIは5分間隔で置きかえた。WFIをぬ
いてから、骨を0.1Mのリン酸ナトリウムで完全にカ
バーし溶液の、Hが6.8〜7.4の間になるまでこの
操作ケくりかえした。
骨粉の脱脂と消毒をした。エタノールをぬい【から0.
6NのHC1溶液を骨12当り50wLt反応器に入れ
(Bolasdat等上り、反応を3時間行な5 (G
lovaekig、 AATB 1Forkah−op
、 第11回年次会議(1987))。#CJをヌイ
てから骨をインジェクション(il’FI)用の水で3
回すすぎ、WFIは5分間隔で置きかえた。WFIをぬ
いてから、骨を0.1Mのリン酸ナトリウムで完全にカ
バーし溶液の、Hが6.8〜7.4の間になるまでこの
操作ケくりかえした。
WFIでのすすぎ法をくりかえして脱ミネラル化した皮
質性又は海綿質の骨粉をつくった。
質性又は海綿質の骨粉をつくった。
このようにしてつくった脱ミネラル化した骨粉25tと
注射級のグリセロール959を十分に混合してペースト
状績度の組成物をつくった。この組成物はシリンジ、ヘ
ラ、デンタルガムその他の適当な装置を用いて、骨欠陥
部位に容易に付与できる。
注射級のグリセロール959を十分に混合してペースト
状績度の組成物をつくった。この組成物はシリンジ、ヘ
ラ、デンタルガムその他の適当な装置を用いて、骨欠陥
部位に容易に付与できる。
実施例2゜
実施例1の脱ミネラル化した骨粉をフラクトース50重
量%、デキストロース50重量%の流動性混合物と3つ
の異なる濃度で混合してそれぞれ骨粉を25.35及び
50重量%含有する流動性のある脱ミネラル化した骨粉
ペーストなつ(つた。この骨粉ペーストは組成物全体が
堅牢且つなめらかで空気中で8〜12時間で硬化した。
量%、デキストロース50重量%の流動性混合物と3つ
の異なる濃度で混合してそれぞれ骨粉を25.35及び
50重量%含有する流動性のある脱ミネラル化した骨粉
ペーストなつ(つた。この骨粉ペーストは組成物全体が
堅牢且つなめらかで空気中で8〜12時間で硬化した。
骨粉用の液状ポリヒドロキシ化合物キャリヤとしてスク
ロース水浴液を用いて同様の結果を得た。
ロース水浴液を用いて同様の結果を得た。
手
続
補
正
書
平成2年10月15日
Claims (1)
- 【特許請求の範囲】 1、液状ポリヒドロキシ化合物、液状ポリヒドロキシ化
合物誘導体、固体状ポリヒドロキシ化合物の溶液、固体
状ポリヒドロキシ化合物誘導体の溶液及びそれらの混合
物からなる群から選ばれた生体適合性キャリヤと脱ミネ
ラル化した骨粉からなることを特徴とする骨の欠陥部位
の新しい骨の生長を促進するために骨欠陥部位に付与す
るための流動性組成物。 2、該キャリヤがグリセロール、グリセロールモノエス
テル又はグリセロールジエステルである請求項1記載の
組成物。 3、該キャリヤがモノサッカライド、モノサッカライド
誘導体、ジサツカライド、ジサツカライド誘導体、オリ
ゴサッカライド、オリゴサッカライド誘導体又はこれら
の混合物である請求項1記載の組成物。 4、該キャリヤがフラクトース、グルコース又はそれら
の混合物である請求項1記載の組成物。 5、該キャリヤがスクロースの溶液である請求項1記載
の組成物。 6、該キャリヤがスクロースの水溶液である請求項1記
載の組成物。 7、該キャリヤがグリセロールの脂肪酸モノエステルの
溶液である請求項1記載の組成物。 8、該キャリヤが異なる液状ポリヒドロキシ化合物及び
/又はその誘導体に溶解した脂肪酸モノエステルである
請求項1記載の組成物。 9、該キャリヤがクロロピレングリコール、グリセロー
ル、モノアセチン、ジアセチン、液状ポリエチレングリ
コール及びそれらの混合物からなる群から選ばれた溶媒
に溶かしした脂肪酸モノエステルである請求項1記載の
組成物。 10、キャリヤが溶媒に溶かしたグリセロールモノラウ
レートである請求項1記載の組成物。 11、該キャリヤが異なる液状ポリヒドロキシ化合物及
び/又はその誘導体に溶解した脂肪酸モノエステルであ
る請求項1記載の組成物。 12、該キャリヤがクロロピレングリコール、グリセロ
ール、モノアセチレン、ジアセチレン、液状ポリエチレ
ングリコール及びそれらの混合物からなる群から選ばれ
た溶媒に溶かした脂肪酸モノエステルである請求項1記
載の組成物。 13、該脱ミネラル化した骨粉の平均粒子径が約0.1
〜約1.2cmである請求項1記載の組成物。 14、該脱ミネラル化した骨粉の平均粒子径が約0.2
〜約1cmである請求項1記載の組成物。 15、該脱ミネラル化した骨粉が皮質骨、がん性及び/
又は副腎皮質の自生、変異性及び/又は他生の骨組織か
ら誘導されたものである請求項1記載の組成物。 16、脱ミネラル化した骨粉を約5〜約90重量%、キ
ャリヤを約10〜約95重量%含有する請求項1記載の
組成物。 17、脱ミネラル化した骨粉を約20〜約80重量%、
キャリヤを約20〜約80重量%含有する請求項1記載
の組成物。 18、抗菌剤、抗生物質、抗ウィルス剤、アミノ酸、ペ
プチド、ビタミン、無機元素、蛋白合成コフアクター、
ホルモン、内分泌腺組織、シンセサイザー、酵素、実質
細胞を伴なつたポリマー−セル骨組剤、脈管形成剤、ポ
リマー性の医薬キャリヤ、コラーゲン格子、抗原剤、細
胞骨格剤、間葉ステム細胞、骨分解剤、抗腫瘍剤、細胞
誘引剤、フイブロネクチン、生長ホルモン、細胞接着剤
、ヒドロキシアパタイト及び透過性増強剤からなる群か
ら選ばれる少なくとも1の添加成分を含有してなる請求
項1記載の組成物。 19、生化学分解性ポリマーを含有する請求項1記載の
組成物。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US410596 | 1989-09-21 | ||
US07/410,596 US5073373A (en) | 1989-09-21 | 1989-09-21 | Flowable demineralized bone powder composition and its use in bone repair |
US07/573,458 US5290558A (en) | 1989-09-21 | 1990-08-27 | Flowable demineralized bone powder composition and its use in bone repair |
US573458 | 1990-08-27 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH03210270A true JPH03210270A (ja) | 1991-09-13 |
JPH0555148B2 JPH0555148B2 (ja) | 1993-08-16 |
Family
ID=27021064
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2250407A Granted JPH03210270A (ja) | 1989-09-21 | 1990-09-21 | 流動性のある脱ミネラル化した骨粉組成物及びその骨治療での使用 |
Country Status (4)
Country | Link |
---|---|
US (4) | US5290558A (ja) |
EP (1) | EP0419275B1 (ja) |
JP (1) | JPH03210270A (ja) |
DE (1) | DE69016331T2 (ja) |
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US7959941B2 (en) | 2001-10-12 | 2011-06-14 | Warsaw Orthopedic, Inc. | Bone graft comprising a demineralized bone matrix and a stabilizing agent |
US8268008B2 (en) | 2003-06-11 | 2012-09-18 | Warsaw Orthopedic, Inc. | Osteoimplants and methods for their manufacture |
JP2007515196A (ja) * | 2003-09-23 | 2007-06-14 | オーソ・セラピューティクス・リミテッド・ライアビリティ・カンパニー | 吸収性のインプラントならびに止血および骨欠損の処置における、それらの使用 |
JP2016518115A (ja) * | 2013-03-15 | 2016-06-23 | テオコープ・ホールデイング・カンパニー・エルエルシー | 胎児の体重の増加および骨質の強化に役立つテオブロミン組成物 |
JP2019131608A (ja) * | 2013-03-15 | 2019-08-08 | テオコープ・ホールデイング・カンパニー・エルエルシー | 胎児の体重の増加および骨質の強化に役立つテオブロミン組成物 |
JP2022500071A (ja) * | 2018-08-23 | 2022-01-04 | テラセル コンサルティング エスピーアールエル | 組織マトリックスを生産するための生物組織を処理するための自動化プロセス |
Also Published As
Publication number | Publication date |
---|---|
EP0419275B1 (en) | 1995-01-25 |
US5439684A (en) | 1995-08-08 |
US5298254A (en) | 1994-03-29 |
EP0419275A1 (en) | 1991-03-27 |
DE69016331D1 (de) | 1995-03-09 |
US5290558A (en) | 1994-03-01 |
US5284655A (en) | 1994-02-08 |
DE69016331T2 (de) | 1995-09-21 |
JPH0555148B2 (ja) | 1993-08-16 |
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