200300666 玖、發明說明 [發明所屬之技術領域] 本發明係關於由具有活體活性且有分解吸收性的有機-無機複合多孔物所構成之植入材料及其製造方法，以及由 此複合多孔物與其他的活體材料所構成之植入材料。 [先前技術] 作爲以醫療用途爲目的之無機的多孔物，習知者爲例如 將生物陶瓷試燒或燒結所得之多孔性陶瓷。然而，此多孔 性陶瓷，於使用於活體骨組織重建用的植基構造或綴補材 等之用途時，雖硬卻脆是其缺點，故於手術後經常要擔心 因於些微的衝擊所造成的破壞。又，於手術現場，欲使多 孔性陶瓷的形狀以吻合活體骨組織的缺損部之方式來加工 與變形亦甚困難。再者，欲完全替換活體骨，有時須要長 達1 〇年以上的長期間，在該期間內之因於破壞所致的危 害性的顧慮會一直存在著。 另一方面，作爲以醫療用途爲目的之有機多孔物，習知 者有，例如，日本特公昭6 3 - 6 4 9 8 8號公報中所揭示之海 綿等。此海綿，通常係使用於手術時的止血及活體軟組織 (例如內臟等）的縫合時作爲綴補材料，故係由活體內分解 吸收性的聚乳酸所構成之有連續氣孔的海綿。此海綿，係 經由使聚乳酸溶解於苯或二噁烷中，將該聚合物溶液凍結 乾燥，使溶劑昇華的方法來製造。 然而，經由上述的海綿般的凍結乾燥法所製造的多孔 物，須長時間的昇華，欲完全地除去溶劑是困難的，其厚 5 312/專利說明書(補件)/92-02/91134292 200300666 度甚薄，僅爲imm以下（通常爲數百程度），欲製造數 mm以上的厚度的多孔物，於現況上是困難的。作爲製造具 有連續氣孔之多孔物的其他方法，於上述的凍結乾燥法之 外，也有各種方法被檢討著，但欲製得數mm以上的厚的 多孔物皆非容易。以這樣的薄的多孔物形狀吻合地補綴於 活體組織損傷部位之複雜且較大的三維空間上，固可發揮 作爲暫時性的補綴材之功能，然而，欲作爲謀求損傷部位 的立體組織之再建的材料則非可行。因此，厚度較厚、且 於手術前或手術中可精細加工成任意形狀的三維立體形狀 之能夠比較快速地被分解吸收以代替活體骨者，受到殷切 企盼。 又，作爲製作連續多孔物的另一有效的方法，係對聚合 物混以多量的水溶性之既定大小的N a C 1等之可溶性的顆 粒，作成爲片狀等之薄片的成形物後，浸漬到水（溶劑）中 使該顆粒溶出，藉此以形成與該顆粒同樣的孔徑的連續孔 的溶出法，是習知者，惟，欲使該顆粒完全溶出是困難的， 故僅限定於薄片的連續多孔物。又，若水溶性的顆粒之比 例若不夠高，則不易生成連續氣泡。而且，於將此多孔物 埋入活體內之時，殘留之該顆粒的毒性也會成爲煩惱源， 是其問題。 如上述的海綿般，未含有活體活性的生物陶瓷等之無機 顆粒的多孔物，由於缺乏與硬骨及軟骨等的活體骨組織間 的直接的結合性、傳導性、取代性等，故係非骨芽細胞之 線維芽細胞等之侵入與介在，因此，欲完全地取代活體組 6 312/專利說明書(補件)/92-〇2/91134292 200300666 織直到再生，須要相當的長期間，甚或終其一生均未能取 代。 因此，本申請人，過去曾提出：「可播種骨芽細胞作成 爲三維立方體的植基構造，用以在大的缺損部位架橋而植 入之由在內部含有具有活體活性的生物陶瓷顆粒之活體內 分解吸收性聚合物所構成的具有連續氣孔之厚度大的多孔 物」之申請案（日本特願平8-229280號）。 此多孔物，係藉由稱爲溶液沉澱法的多孔物之製造方法 所製得者。亦即，係藉由：使活體內分解吸收性聚合物溶 解於其溶劑與較其溶劑高沸點的非溶劑所成的混合溶劑 中，並使生物陶瓷顆粒分散調製成懸浮液，自此懸浮液將 混合溶劑依於溶劑的沸點在低溫下使其揮發，使內包著生 物陶瓷顆粒之活體內分解吸收性聚合物沈澱的方法者。 此使用溶液沉澱法之多孔物的形成原理，係如下述。亦 即，自上述的懸浮液將混合溶劑依於溶劑的沸點在低溫使 其揮發，則沸點低的溶劑會優先揮發，沸點高的溶劑會逐 漸上昇，當溶劑與非溶劑達到一定的比例下，溶劑即無法 再將聚合物溶解。因此，聚合物會開始析出·沈澱，將最 初即開始沈降的生物陶瓷顆粒內包起來，析出·沈澱之聚 合物因爲高比例的非溶劑而收縮、固化，而在含有生物陶 瓷顆粒之狀態下固定化，形成以連結的聚合物之薄的胞壁 將混合溶劑包住的狀態之胞狀構造。其後，殘存的溶劑， 於一邊將胞壁破壞之下產生氣孔而揮發·消失，沸點高的 非溶劑透過該氣孔徐徐地揮發，終至完全地揮發·消失。 7 312/專利說明書(補件)/92-02/91134292 200300666 其結果，被聚合物的胞壁所包住之混合溶液的殘跡成爲連 續氣孔，形成含有生物陶瓷顆粒之多孔物。 上述的溶液沉澱法，係用以形成自低發泡倍率至高發泡 倍率的厚度厚的多孔物之絕佳的方法，可製得具有由數mm 乃至於數十mm的厚度之塊狀的三維多孔物。因此之故， 於作成有大的起伏之立體形狀的骨再生的植基構造等是頗 爲有用的。 然而，此方法的缺點，於含有大量的生物陶瓷顆粒之懸 浮液中，屬於粒徑分布中之較大的粒徑之生物陶瓷顆粒， 在溶劑開始揮發之最初即開始沈降，於聚合物開始析出· 沈澱時，已經有甚多的生物陶瓷顆粒面著底部以濃度比例 沈降著，故得到之多孔物之生物陶瓷顆粒的含有量並非全 體均一的，自多孔物的上面側愈往底面側其含有量愈多是 無法避免的。這樣的含有量之有濃度比例之不均一的多孔 物，對於骨組織重建用的植基構造、補綴材或骨塡料等之 用途，難以一體有效地使用。此問題，經由設法控制生物 陶瓷顆粒的沈降速度，固可若干程度地改善，卻無法完全 解決。尤其是欲製作含有30重量百分比以上的生物陶瓷 顆粒的均質且有均等的濃度之三維的骨重建用的多孔物， 非只本方法，通常皆爲困難的。 以上述的方法製造之生物陶瓷顆粒的含有量少的多孔 物，生物陶瓷顆粒的大半係被聚合物的胞壁所包住而難以 露出到連續氣孔的裏面及多孔物的表面，故於埋入活體內 時，難以於埋入後立即發揮因於生物陶瓷顆粒之活體骨組 8 312/專利說明書(補件)/92-〇2/91134292 200300666 織的傳導作用’而須待用以形成表皮層之聚合物的分解而 露出’於時間落後之下才發揮活體活性，是其問題。 再者，以上述的方法製造的多孔物，即使選擇極細的顆 粒作爲生物陶瓷顆粒，其含有率也不過約爲3〇重量百分 比之程度，欲較此更多量地含有，則生物陶瓷顆粒會更容 易沈降，故得到之多孔物的底面側會含有多量的生物陶瓷 顆粒，而變得極脆。 又，以上述方法所製造之多孔物，通常，連續氣孔所佔 的比例雖高達8 〇 %以上，孔徑方面，一般而言，卻只能得 到數// m乃至數十// m之比較小的連續氣孔，因此，絕對 難以說是形成爲作爲骨芽細胞往多孔物內部侵入與生長之 理想的孔徑、孔的形態。 經由與上述本申請人的溶液沉澱法相異的方法使無機 顆粒物進行高塡充的方法也被檢討著，其中之有用的方法 之一，爲製作於聚合物中塡充有50重量百分比程度的生 物陶瓷顆粒之顆粒，藉由將此粒子加熱使其在表面融合之 燒結方法來製得連續多孔物的方法。此方法並非新的方 法，係於例如作爲環氧樹脂、氯乙烯樹脂等之顆粒狀的樹 脂的多孔物之製作方法上，是所周知者。此方法，由於必 須要表面融合，故塡充量有其界限，由於50重量百分比 以上的塡充會變脆，是其困難，且氣孔徑的控制也非容易， 品質上亦難以得到良好者。 本發明，以提供可完全解決此等問題之由無機粒子高塡 充的有機-無機複合多孔物所構成的各種植入材料及其製 9 312/專利說明書(補件)/92-02/91134292 200300666 造方法爲目的。並且，爲由此有機-無機複合多孔物與其 他活體材料的組合所構成之植入材料；而以提供作爲骨固 定材使用者、作爲脊椎固定材（椎間設置材、椎體補強材） 等使用者、作爲同種移植骨片或自身移植骨片、皮質骨、 海綿骨或其組合的替代物使用者、作爲骨缺損部分及變形 部分的綴補·塡充材等使用者、作爲用以形成硬·軟骨的 植基構造使用者、作爲人造軟骨使用者，爲其目的。 現今，骨固定材，於例如胸骨正中切開閉鎖的手術中係 使用在胸骨的切開部兩側的髓內架橋埋入之由活體內分解 吸收性聚合物所構成之固定軸釘。該固定軸釘在胸骨內會 徐徐地分解而被吸收，故不若非吸收性的陶瓷或金屬製的 軸釘般須再手術將其取出體外，是其優點，惟，由於沒有 骨傳導性且不會與骨組織直接結合，只能發揮作爲楔子的 作用，只具有將經閉鎖的胸骨暫時固定而將切開面閉鎖的 效用。因此之故，如同老人的胸骨的大半所看到的，只殘 留有海綿骨薄的皮質骨成爲晶圓狀而變脆的情況下，即使 將此胸骨用固定軸釘埋入，欲充分發揮作爲「楔子」的作 用以提高固定安定性亦有困難，且也不會代替骨組織，是 其問題。另一方面，胸骨以外的斷骨部位或骨折部位的接 合固定所使用之羥基磷灰石（HA)等之陶瓷多孔物易裂 開，且在活體內要被吸收須極長的時間，是其問題。也有 見解認爲即使須長時間，只要一旦埋入活體骨中，強度可 恢復，故沒有問題，惟，迄至全部埋入之期間的破損終究 有其顧慮。發明之作爲本骨固定材使用之植入材料，係謀 10 312/專利說明書(補件)/92-02/91134292 200300666 求解決此等問題者。 然而，向來的椎體固定材，例如，在對於腰椎病變性疾 病之前方椎體間固定術中作爲椎體間之間隔物使用之鈦製 或碳製的鋼骨結構（C a g e )，雖可滿足表面的化學活體親和 性，但於力學上的活體親和性係異於活體，故作爲異物長 期殘存之下，會有經過時日的破壞及腐蝕致發生對周圍組 織的危害性的顧慮，是其問題。亦有例如鋼骨結構與活體 的力學特性之不一致所致而產生之，經過藉鉸孔而暴露的 骨性終板，鋼骨結構會往椎體內沈降的問題。尤其是碳製 的鋼骨結構，雖硬且脆，故會沿著碳纖維破壞，有時甚至 會產生碎片，故因其導致之危害性的發生之顧慮一直都存 在著。又，塡充於此等的鋼骨結構的移植用自身骨，通常 係由腸骨擷取來供應，其數量的獲得之問題，及擷取後的 處理之繁雜（經擷取之部位的後處理及腸骨之粉碎、對鋼 骨結構之塡充、無菌下的處置等）皆爲問題。本發明之作 爲椎體固定材等使用之植入材料，主要係謀求解決此等問 題者。 另一方面，使用將死者之骨切斷、加工之同種移植骨 片、或自骨盤及肋骨等之大的骨部位擷取之自身移植骨片 來塡補骨缺損部位的手術係日常所進行者。同種移植骨 片，只要是在海綿骨的表面具有皮質骨經一體化的塊狀 者，即可將骨缺損部位的皮質骨部分以該骨片的皮質骨塡 補，將骨缺損部位的海綿骨部分以該骨片的海綿骨塡補。 然而，同種移植骨片，由於係將死者之骨切斷、加工者， 11 312/專利說明書(補件)/92-02/91134292 200300666 須大量獲得作爲原料的死者之骨且提供充分量的移植骨片 並非容易’是其問題，且可加工的形狀也有大的限制，亦 爲問題。又，雖說是同種移植骨片，經移植的骨片畢竟是 與本身的骨組織爲相異的骨組織，依於埋入條件，或有因 自然吸收而消滅、或有強度不足及降低的顧慮。此外，由 於係他人的屍骨故滅菌處理是必要的，依於處理條件，屍 骨會發生變性，故滅菌條件的充分的控制是必要的。然而， 時或處理不充分，於埋入後至死亡之間亦有發生嚴重的事 故的情事。於手術中所擷取之自己的移植骨片，雖可避免 此種事故的發生，其數量之不足是必然的。另一方面，以 羥磷灰石（HA)、磷酸三鈣（TCP)等之陶瓷製的植入材料埋 設於骨缺損部位也在施行著，惟，此情況，骨缺損部位的 皮質骨的部分與海綿骨的部分皆以一樣硬的陶瓷來塡補， 是爲問題，且，由於此陶瓷會半永久性地殘存著，使骨缺 損部位無法用本身的骨組織重建，是其問題。因此，製作 多孔質的該陶瓷以代替海綿骨的方法變成相當的實用。然 而，理想上，用此等合成人造骨來取代活體骨是最佳的， 由於須1 0〜2 0年後的長期間的進行代換，其間，其作爲 物理性的異物之事故有時需顧忌。本發明之作爲同種移植 骨片及自身移植骨片的代替物使用之植入材料，主要係謀 求解決此等問題者。 再者，作爲習知的骨缺損部位或變形部位的補綴·塡 充·覆被材，係使用著經由衝孔之形成有多數的孔之鈦等 金屬製的衝孔（網眼狀）板、經燒結之生物陶瓷的緻密物及 12 312/專利說明書(補件)/92-02/91134292 200300666 多孔物所構成之經穿孔的平板或凹凸板等。然而，金屬製 之衝孔板缺乏物理性的活體親和性，於塡補部位會作爲異 物而永久殘存，故於長期埋入中之腐蝕或金屬離子的溶出 等會有發生對周圍的組織之危害性的顧慮，永遠無法使缺 損部位經由骨組織來完全取代，是其問題。而且，燒結生 物陶瓷的多孔物，雖硬卻脆，容易裂開，使用中受到衝擊 會有破壞之顧慮，無法依骨缺損部位的立體形狀在手術中 進行後成形，是其問題。作爲本發明之補綴·塡充·覆被 材使用之植入材料，係謀求解決此等問題者。 又，習用之人造軟骨，例如，臨床上試用的全取代型的 自主性人造椎間板，係在活體非活性的聚乙烯或具有活體 適合性的橡膠所構成之芯的兩側（上下），疊合上鈦或鈷-鉻製的2片的金屬的端板（e n d p 1 a t e )，係所謂之三明治 構造的人造椎間板，芯部分在2片的聚乙烯之疊合的狀態 下作成近似於活體椎間板的動作，於橡膠的情況，由於其 彈性，而可進行模仿。而且，於插入椎間時可防止脫滯， 爲了賦予自主性的效果，於金屬板的表面使其突出數個 角，其係作成爲以突刺於椎體的凹面的方式而固定的構 造。然而，此人造椎間板由於係與活體的椎間板爲相異的 材料之三明治構造，故於反覆動作之間，於界面處會發生 摩擦’且其動作決不能說是與活體椎間板相同，又，自金 屬板突出的角，於會傷及上下的椎體之同時，在長期使用 下會徐徐地沈下到椎體中，侵入而導致更大的害處等，有 此等重大的缺點，無法與上下的椎體直接結合而自立、固 13 312/專利說明書(補件)/92-02/91134292 200300666 定。本發明之人造軟骨用之植入材料，主要係謀求解決此 等問題者，經由在與端板或椎體之間介在有本發明之多孔 物，可期將該人造椎間板之間的物理間隙塡埋使其密合， 並且經由骨傳導性可期與椎體間之直接結合，亦爲發明之 目的。 [發明內容] 本發明之最基本的植入材料，係在活體內分解吸收性聚 合物中均一分散著活體活性的生物陶瓷顆粒之活體活性的 活體內分解吸收性的多孔物，具有連續氣孔，且於氣孔裏 面或氣孔裏面與多孔物表面露出有部分的生物陶瓷顆粒的 有機-無機複合多孔物。此多孔物，如後述般，氣孔率爲 5 0〜9 0 % ’連續氣孔佔氣孔全體的5 〇〜9 〇 %，此連續氣孔， 係作成爲較佳之適合於骨芽細胞之侵入而增殖、安定化所 須之1 0 Q〜4 Q 0 // m的孔徑。且，生物陶瓷顆粒多量含有達 6 ◦〜90重量百分比，多孔物的厚度大，爲1〜50mm，且 具有三維立體形狀。此基本的植入材料，可使用於各種醫 療用途作爲例如取代型骨組織再生用的植基構造、補綴· 覆被材、骨塡料、海綿骨的代替物、骨組織於其他的人造 植入材之間的介在物、藥劑的載體等。 又，在活體內分解吸收性聚合物中均一分散著活體活性 的生物陶瓷顆粒之活體活性的活體內分解吸收性的多孔 物；其特徵在於，係由具有連續氣孔，且生物陶瓷顆粒的 含有率爲6 0〜9 0重量百分比的有機-無機複合多孔物所 構成之植入材料，亦爲本發明之基本的植入材料，可使用 14 312/專利說明書(補件)/92-〇2/91134292 200300666 於與上述相同的各種的醫療用途中。 上述由有機-無機複合多孔物所構成之植入材料，可經 由本發明之製造方法來製造。所述方法爲：在揮發性溶劑 中’使活體內分解吸收性聚合物溶解，使活體活性的生物 陶瓷顆粒分散，調製成混合液，由其作成無紡織物狀的纖 維集合物，將其在加熱下加壓成形，作成多孔質的纖維集 合成形物，然後將纖維集合成形物浸漬於揮發性溶劑中， 之後再將該溶劑除去的方法。 另一方面，應用上述有機-無機複合多孔物的本發明之 植入材料，係將上述有機-無機複合多孔物於其他質地緻 密的活體內分解吸收性聚構材作成爲結合物所成者。此植 入材料的主要者，有下述4種： 第一種植入材料，爲上述其他的活體內分解吸收性構材 爲軸釘，由該軸釘將上述多孔物貫穿作成爲結合物，軸釘 兩端部係自上述多孔物向外突出之骨固定用植入材料。此 植入材料，於例如胸骨正中切開閉鎖的手術中係適合於使 用在間切開閉鎖之胸骨固定的情況下者。 第二種植入材料，係其他的活體內分解吸收性構材爲由 含有具有通達外部的空洞且爲活體活性的生物陶瓷顆粒之 活體內分解吸收性聚合物所構成的母材；於該母材的空洞 內裝塡有上述多孔物作成爲結合物，上述多孔物自該母材 爲部分露出的狀態之植入材料。此植入材料，於前方或後 方椎體間固定術等中，適於使用作爲椎體間間隔物等之椎 體固定材之較佳者。 15 31Z/專利說明書(補件)/92-02/91134292 200300666 第三種植入材料’係其他的活體內分解吸收性構材爲由 含有活體活性的生物陶瓷顆粒的活體內分解吸收性聚合物 所構成的表皮層’該表皮層，疊合於塊狀的上述多孔物之 表面的一部份而結合爲一體所成之植入材料。此植入材 料’塊狀的多孔物可發揮海綿骨的功用，表皮層可發揮皮 質骨的功用’爲適合使用於同種移植骨片及自身移植骨片 的代替物等之全吸收取代性的人造骨之較佳者。 第四種植入材料’爲其他的活體內分解吸收性構材爲由 含有活體活性的生物陶瓷顆粒的活體內分解吸收性聚合物 所構成的網狀物，於該網狀物的網眼中充塡有上述多孔物 而結合爲一體之植入材料。此植入材料，爲適合使用作爲 於骨缺損部位或變形部位的補綴·覆被·支撐或塡充材等 之較佳者。 再者’應用上述多孔物的本發明之另一種植入材料，係 將上述多孔物多孔物積層於以有機纖維作成爲3軸以上的 多軸二維織造組織或編造組織或此等的複合組織之組織構 造物所構成的芯材之至少一面上而結合爲一體所成的人造 軟骨用植入材料。此植入材料，爲適合使用作爲與上下椎 體結合而自立、固定之人造椎間板或弓形板等。 [實施方式] 以下’就本發明之植入材料與製造方法的較佳之實施形 態加以詳述。 本發明之最基本的植入材料，係在活體內分解吸收性聚 合物中均一分散著活體活性的生物陶瓷顆粒之活體活性的 16 312/專利說明書(補件)/92-02/91134292 200300666 活體內分解吸收性的多孔物；其係由具有連續氣孔，且於 氣孔裏面或氣孔裏面與多孔物表面露出有部分的生物陶瓷 顆粒的有機-無機複合多孔物所構成者，於其較佳之實施 形態中，作爲活體內分解吸收性聚合物，可選擇使用既已 實用化且安全性亦經確認，分解比較快速，即使成爲多孔 物也不脆的聚合物。亦即，可使用非晶質或結晶與非晶的 混合存在之全吸收性的聚-D , L -乳酸、L -乳酸與D , L -乳酸 的區塊共聚物、乳酸與羧基乙酸的共聚物、乳酸與對二噁 烷酮的區塊共聚物、乳酸與乙二醇的區塊共聚物、乳酸與 己內酯的共聚物、或此等的混合物等之活體內分解吸收性 聚合物。其黏度平均分子量，就於本發明之製造方法中容 易形成無紡織物狀的纖維集合物、及活體內的多孔物的分 解吸收的期間考量，以使用5萬〜1 0 0萬者爲佳。 尤其，起因於單體比例而顯示非晶性之聚-D , L -乳酸、 L -乳酸與D , L -乳酸的區塊共聚物、乳酸與羧基乙酸的共 聚物、乳酸與對二噁烷酮的區塊共聚物等之活體內分解吸 收性聚合物，於依據本發明之製造方法形成無紡織物狀的 纖維集合物時，及將其在加熱下加壓成形所成之纖維集合 物以揮發性溶劑處理時的溶劑特性來看，係佳適者，若使 用此等之聚合物，可得到即使含有多量的生物陶瓷顆粒也 不會脆，具有比美海綿骨的壓縮強度，且與陶瓷單體之多 孔物相異，可在比較的低溫（7 Q °C )下使其熱變形，在活體 內可迅速地分解，於6〜1 2個月內全部被吸收之有機-無 機複合多孔物所構成的植入材料。具有此等特性之植入材 17 312/專利說明書(補件)/92-02/91134292 200300666 料。爲作爲活體骨的區損部之塡充材料之極佳者，由於係 複合物，與陶瓷單獨者相異，殘留有因於樹脂成分之黏彈 性’不若陶瓷般經接觸即因脆而缺損，於手術中可使其熱 變开彡以與缺損部吻合的方式來成形，具有熱可塑性聚合物 所特有的優點。 活體內分解吸收性聚合物的分子量，由於會影響到自水 解到全吸收爲止的時間及能否纖維化，宜使用上述般之具 有5萬〜1G萬的黏度平均分子量的聚合物。具有較5萬 小的黏度平均分子量的聚合物，其水解成寡聚物乃至於單 體單位的低分子的時間雖短，但由於牽絲性不足，依本發 明之製造方法以噴霧的手段.在一邊纖維化之下形成纖維集 合物是困難的。又，具有較1Q0萬高的黏度平均分子量之 聚合物，由於到完全水解須要長時間，於以與活體組織之 儘早取代爲目的之情況，作爲複合多孔物的聚合物並不適 當。固然依於聚合物而異，惟，較佳的黏度平均分子量宜 爲大約1 〇萬〜3 0萬，若使用具有此範圍的分子量之活體 內分解吸收性聚合物，則纖維集合物的形成容易，且，可 得到具有適當的水解完了時間之複合多孔物的植入材料。 又，於由此有機-無機複合多孔物所構成的植入材料 中，作爲分散於多孔物之生物陶瓷顆粒，可使用具有活體 活性，且具有良好的骨傳導能（有時以骨髓傳導能表示）與 良好的活體親和性者。作爲這樣的生物陶瓷顆粒，可列舉 例如：表面活體活性的燒結、試燒結的羥磷灰石、磷灰石 矽灰石陶瓷、活體活性且活體內全吸收性的未試燒、未燒 18 312/專利說明書(補件)/92-02/91134292 200300666 結的羥磷灰石、磷酸二鈣、磷酸三鈣、磷酸四鈣、磷酸八 1¾、方解石、ceravital、透輝石（diopside)、天然珊 瑚等之顆粒。又，在此等顆粒的表面附著有鹼性的無機化 合物或鹽基性的有機物等者亦可使用。基於由本身的骨組 織全取代而進行組織再生較理想的理由，此等之中，以可 在活體內全吸收並與骨組織完全取代之活體內全吸收性的 生物陶瓷顆粒爲佳，尤以未試燒、未燒結的羥磷灰石、磷 酸三鈣、磷酸八鈣，因其等之活性大、骨傳導能優異、活 體親和性優異危害性低、且短期間內可被活體吸收，故爲 最適者。 上述生物陶瓷顆粒，以使用平均粒徑（一次粒子的平均 粒徑）爲0.2〜10#m者爲佳，若使用較此大粒徑的生物陶 瓷顆粒，則於本發明之製造方法中將該顆粒所混合成的混 合液噴霧進行纖維化之時纖維會被切成較短，欲形成纖維 集合物有困難，即令形成纖維集合物，迄纖維固化之前生 物陶瓷顆粒會多少發生沈降致有不均一分散的顧慮。超過 2 0〜3 0 // m之大小者，即使爲全吸收性，完全吸收須長時 間，其間有時會發生之組織反應，故非良好。 生物陶瓷顆粒的更佳之粒徑爲〇 · 2〜5 // m，若使用這樣 的生物陶瓷顆粒，則即使於本發明之將該顆粒以高濃度混 合成之混合液，使其以作成爲1〜3 // m程度的纖維徑的方 式進行細纖維化來形成纖維集合物的情況，纖維也難以切 斷，於本發明般的高濃度之時該顆粒會在自纖維露出的狀 態下被纖維包住，於將纖維集合物在揮發性溶劑中施以浸 19 312/專利說明書(補件)/92-02/91134292 200300666 漬處理後，成爲該顆粒自表面及連續氣孔的裏面露出的複 合多孔物。 生物陶瓷顆粒的含有率，在以再生醫工學之植基構造及 DD S用的載體或骨塡料、異形海綿骨（同種移植骨片）的代 替物等之醫療用途爲目的之由有機-無機複合多孔物所構 成的植入材料之情況，定爲6 0〜9 0重量百分比的理由係 考慮活體活性效果之較佳者。如本發明之製造方法般，形 成含有生物陶瓷顆粒的纖維集合物，將其在加熱下加壓成 形所作成多孔質的纖維集合成形物浸漬在揮發性溶劑中製 得複合多孔物的情況，由於在可纖維化的範圍內，可使其 含有多量的生物陶瓷顆粒，故如上述般，生物陶瓷顆粒的 含有率可高達60〜90重量百分比（相當於用平均粒徑爲3 // m比重爲2 . 7的顆粒時的容積百分比爲約4 1〜8 1 %的高 比例）。生物陶瓷顆粒的含有率若超過9 Q重量百分比，則 於纖維化之時會切成較短，無法得到可滿足的纖維之故， 纖維集合物的形成會有困難，另一方面，若低於6 0重量 百分比，生物陶瓷顆粒會不足，露出於表面者較少，故自 植入材料埋入活體之初期起即無法發揮來自生物陶瓷顆粒 物之活體活性。 如此般可將活體活性的生物陶瓷顆粒以6 0〜9 0重量百 分比的高含有率均一地分散的複合多孔物，係迄今所沒有 的，爲本發明之基本的植入材料之一。 生物陶瓷顆粒的較佳之容積百分比，爲50〜85容積百 分比。此容積百分比，爲以複合多孔物的聚合物的氣孔率 20 312/專利說明書(補件)/92-02/91134292 200300666 作爲〇 %時之對於聚合物的容積之生物陶瓷顆粒的容積之 百分率，含有的生物陶瓷顆粒的重量即使相同，依於生物 陶瓷顆粒的比重及平均粒徑容積百分比會跟著變化。因 而，考量生物陶瓷顆粒的比重及平均粒徑，以使其成爲含 有50〜85容積百分比爲佳。更佳的容積百分比爲5〇〜80 容積百分比。 使羥磷灰石等之陶瓷燒結得到之多孔性陶瓷，由於雖硬 卻脆，薄物受到外力易於裂開或缺損，故作爲植入材料係 無法滿足者。相對於此，使生物陶瓷顆粒含有在非晶性之 活體內分解吸收性聚合物中之複合多孔物，於生物陶瓷顆 粒的含有率高達6 〇〜9 ◦重量百分比的情況，由於經由其 聚合物的結合效果，具有保持可撓性之不脆的可比美海綿 骨的壓縮強度（具體而言，爲IMPa〜5MPa程度的壓縮強 度），如上述般可較佳地使用於海綿骨的代替物及其他的 醫藥用途。又，上述的壓縮強度，係使用島津製作所（股） 製造之自動糸會圖機（Auto graph)AGS-2000D，依據JISK 7 1 8 1的試驗方法（惟’係將樣品的大小作成爲 1 〇 X 1 〇 X 15mm，使壓縮速度固定爲5mm/分）所測定之値。 此由有機-無機複合多孔物所構成之植入材料’氣孔率 (全氣孔率）爲5 0 %以上，於技術上雖可做到約9 〇 %，但就 此複合多孔物的物理強度與骨芽細胞的侵入及安定化兩者 考量，宜爲約6 Q〜8 Q %，又，就骨芽細胞侵入到複合多孔 物的中心部的效率考量，連續氣孔以佔氣孔全體的5 〇〜 9 0 %爲佳，尤以佔7 〇〜9 〇 %更佳。 21 312/專利說明書(補件)/92-02/91134292 200300666 此有機-無機複合多孔物的連續氣孔，其孔徑係作成爲 約1 Q Q〜4 ◦ Q // m。多孔質陶瓷的孔徑與骨芽細胞的侵入及 安定化的硏究業經數度進行，結果得知：以3 0 0〜4 0 0 // m 的孔徑於石灰化方面最有效果，愈與其偏離效果愈小。因 此，此複合多孔物的孔徑，如上述般雖係作成爲1 Q Q〜4 0 0 //m，亦可爲包含5〇〜5〇0//m的範圍的孔徑，而分布中心 爲 200 〜400// m 者。 因爲，於連續氣孔的孔徑較4 Q Q // m大、氣孔率（全氣孔 率）較9 0 %高的情況，由於複合多孔物的強度會降低，故 於活體內埋入中容易破壞的顧慮甚大。另一方面，孔徑若 較1 Q 0 // m小，氣孔率較5 〇 %低的情況，複合多孔物的強 度固可提高，骨芽細胞的侵入卻困難，自水解到完全吸收 的時間會變長。然而，這樣的孔徑小的複合多孔物，於作 爲D D S的載體之期望可維持與聚合物的分解並行之比較長 的徐放性的材料，依情況而有利用的可能。連續氣孔之較 佳的孔徑爲 150〜35〇#m，更佳之氣孔率（全氣孔率）爲 7 0〜8 0 % 。又，連續氣孔的孔徑，及對氣孔全體之連續氣 孔所佔的比例，於本發明之製造方法中，於將纖維集合物 加壓成形作成爲纖維集合成形物時的壓縮率之調節、及使 纖維集合成形物保持其形狀浸漬於揮發性溶劑中時之經由 調節用以保持形狀的外壓可加以控制。 由上述般的有機-無機複合多孔物所構成的植入材料， 可使用於例如活體骨的缺損部位，其時，利用活體內分解 吸收性聚合物的熱可塑性，經由將植入材料加熱至7 0 °C以 22 312/專利說明書(補件)/92-02/91134292 200300666 使其與缺損部位的形狀吻合的方式而變形，由於可無縫隙 地埋入缺損部分中，埋入作業可簡單而正確地進行。又’ 由於活體內分解吸收性聚合物所具有的韌性與陶瓷的^ 度，於手術中利用測量在不破壞形狀下剪切成任意的形狀 來使用。 將由此複合多孔物所構成之植入材料如上述般埋入活 體骨的缺損部位，則液體會自複合多孔物的表面通過連續 氣孔迅速地浸透到複合多孔物的內部，故自複合多孔物的 表面與連續氣孔的內部之雙方，活體內分解吸收性聚合物 的水解幾乎同時進行，於多孔物的全體均一地進行分解。 而且，經由露出於複合多孔物的表面的生物陶瓷顆粒的骨 傳導能，於複合多孔物的表層部骨組織可迅速地傳導形成 成爲骨的小柱而生長，於短期間內複合多孔物可和活體骨 的缺損部位結合，並同時經由露出於氣孔裏面的生物陶瓷 顆粒的骨傳導能，骨組織會侵入複合多孔物的內部，骨芽 細胞會傳導而生長，故會與周圍的骨直接結合。此現象， 隨著活體內分解吸收性聚合物的分解之進行而變得顯著， 徐徐地與周圍的骨代換。於是，最後聚合物會完全地被分 解吸收，又，全吸收性的生物陶瓷顆粒亦完全地被吸收， 經由生長的骨組織而完全地代換’完成骨缺損部位的再生。 由此複合多孔物所構成的植入材料之活體內的濡濕特 性，因於多量含有而露出於表面的生物陶瓷顆粒的濡濕特 性，較只有活體內分解吸收性聚合物的多孔物有顯著的提 高，惟，若對此複合多孔物施行電暈放電、電漿處理、過 23 312/專利說明書(補件)/92-02/91134292 200300666 氧化氫處理等之氧化處理，則聚合物的濡濕特性可得以改 善，增殖所須的骨芽細胞之侵入、生長可更有效果的進行。 又，將各種骨形成因子、成長因子、藥劑等預先塡充到 複合多孔物的氣孔內，預先溶解到活體內分解吸收性聚合 物中使其載持，則相應於複合多孔物被分解吸收的速度， 此等會徐徐放出，故可促進骨的再生及疾病的治癒使其有 成效。作爲主要的骨形成因子，可舉出：BMP，作爲主要 的生長因子，可舉出：工L-1、TNF-α、TNF-冷、IFN-y 等之莫諾卡因 （monocaine) 或淋 巴因子 (lymph〇kine)、或菌落（colony)朿[J》敷因子，或TGF-α 、 TGF-/3、IGF - 1、PDGF、FGF等等之所謂的生長分化因子。 又，作爲藥劑，可任意選擇可使骨生長之藥物（維他命D、 前列腺素類、或抗（制）癌劑等）、抗菌劑等。 其次，就本發明之由有機-無機複合多孔物所構成之植 入材料之製造方法具體地加以詳述。 本發明之製造方法，首先，於揮發性溶劑中，使活體內 分解吸收性聚合物溶解，並使活體活性的生物陶瓷顆粒分 散，調製成混合液。作爲揮發性溶劑，可使用於較常溫燒 高的溫度下容易揮發的低沸點的二氯甲烷 (dichl〇r〇methane)、二氯乙院、二氯甲院（methylene chloride)、三氯甲烷（chloroform)等之溶劑。又，亦 可使用對此等溶劑混合以較此等溶劑沸點高之非溶劑中之 一種或二種以上所成的揮發性混合溶劑；所述之非溶劑爲 例如：沸點爲6 0〜1 1 0 °C的範圍之甲醇、乙醇、1 -丙醇、 24 312/專利說明書(補件)/92-02/91134292 200300666 2 -丙醇、2 _ 丁醇、特丁醇、特戊醇等之醇類。 然後，由上述的混合液作成無紡織物狀的纖維集合物。 作爲其手段，以採用將溶解混合液噴霧而進行纖維化之手 段爲佳。亦即將上述的溶解混合液裝塡於噴霧器中，以氮 氣等多性的高壓噴射氣體自噴霧器的噴射孔將混合液噴射 到被噴塗物，則於揮發性溶劑揮發之下逐漸纖維化，含有 生物陶瓷顆粒之活體內分解吸收性聚合物的纖維互相絡 連，在相互的接點一邊融合之下集合固化而堆積，可形成 任意形狀的厚度的無紡織物狀的纖維集合物。此纖維集合 物，纖維間空隙的形狀係與細胞狀的孔相異，於融合固化 的纖維相互間形成數百// m程度的連續的空間，生物陶瓷 顆粒被纖維所包住（亦有部分露出於表面者）在纖維集合 物的全體中均一地分散著。 爲使如此般含有60重量百分比以上（有時爲50容積百 分比以上）的多量的生物陶瓷顆粒之樹脂，在不會沈澱分 離之下，均一地分散之狀態下固化而固定，且作成在內部 包含有作爲氣孔之連續空間的材料，採用如本製造方法般 經由噴霧方式於一邊形成細纖維之下使溶劑揮發，於生物 陶瓷顆粒分離之前的短時間內固化的手段，是極具道理 者，亦爲本發明之製造法之創新性之所在。 又，欲製得作爲醫療用途之植入材料時所必要的5〜 5 0 mm的極厚的複合多孔物，可經由噴霧形成此纖維集合 物之後，使溶劑揮發待其乾燥，再於其上進行噴霧反覆進 行增厚的操作，作成既定的厚度。 25 312/專利說明書(補件)/92-02/91134292 200300666 作爲上述被噴塗物，可使用由剝離性良好的聚乙烯、其 他的烯羥系樹脂、氟樹脂、矽系樹脂等所構成之網狀物或 板狀物。尤其，若使用網狀物般的可自由通氣的被噴塗物， 則經由噴霧會使混合液纖維化，於碰到網狀物後，揮發性 溶劑會通過網眼而揮發，故網狀物側表面的纖維會融合， 在不生成表皮層（只有樹脂的融合層）下，可形成其後的步 驟中的溶劑浸透處理可容易進行的纖維集合物，是其優 點。作爲網狀物，以5 0〜3 0 0網眼者爲佳，具有大於5 0 網眼之網狀物，由於纖維會通過網眼包入到裏側，故欲將 形成的纖維集合物自網狀物剝離會變得困難，而具有較 3 〇 〇網眼更小的網眼之網狀物，由於揮發性溶劑難以順暢 地揮發，網狀物側的纖維會融合而易於形成表皮層。又， 被噴塗物並不限於平坦的網狀物或板狀物，亦可使用凸曲 及/或凹曲之立體的網狀物或板狀物。若使用這樣的立體 的被噴塗物，可依其立體的形狀形成厚的纖維集合物，是 其優點。 如上述般將混合液噴霧進行纖維化所形成的纖維集合 物，纖維間的空隙大達數百// m，纖維空隙所佔的比例（空 隙率）爲6 0〜9 0 %程度。而且纖維中含有無機顆粒，於不 會沈降下，在纖維集合物的全體上均一地分散著。 此纖維集合物的纖維長度以3〜1 0 0 mm程度爲佳，纖維 徑以◦· 5〜5 0 // m爲佳。具有此程度的纖維長度及纖維徑 的纖維集合物，經由隨後之步驟的溶劑浸透處理，纖維可 容易地融合，可用以作成實質上纖維已消失之複合多孔 26 312/專利說明書(補件)/92-02/91134292 200300666 物，爲較佳者。 纖維長度，主要係依存於活體內分解吸收性聚合物的分 子量，混合液的聚合物濃度、生物陶瓷顆粒的含有率及粒 徑等，分子量愈大、聚合物的濃度愈高，生物陶瓷顆粒的 含有率愈少、生物陶瓷顆粒的粒徑愈小，則纖維有較長的 傾向。另一方面，纖維徑，主要係依存於混合液的聚合物 濃度、生物陶瓷顆粒的含有率、噴霧器的噴射孔的大小等， 聚合物的濃度愈高、生物陶瓷顆粒的含有率愈多、噴射孔 愈大，則纖維徑有增大的傾向。又，纖維徑亦依於噴射氣 體的壓力而變化。因而，爲了作成上述的纖維長度及纖維 徑，須就聚合物的分子量、聚合物濃度、生物陶瓷顆粒的 含有率與粒徑、噴射孔的大小、氣體壓力等加以調整。 接著，進入到將上述的纖維集合物在加熱下加壓成形作 成多孔質的纖維集合成形物的步驟。首先，將纖維集合物 在加熱加壓下固化，製作成具有連續的空隙之預成形物， 進而，在較此時的壓力爲高之壓力下對預成形物進行加壓 成形，作成連續空隙率與孔的大小經調整之強度佳的多孔 質的纖維集合成形物。又，加壓成形時的加熱，係使纖維 集合物稍微軟化的程度，又，加壓的程度，係以使最終得 到之複合多孔物的氣孔率成爲5 0〜9 0 %，且連續氣孔的孔 徑成爲約1 0 0〜4 0 0 // m的方式作調節即可。 然後，進入次一步驟中，將前步驟中得到之纖維集合成 形物浸漬到上述的揮發性溶劑中，使該溶劑充分地浸透到 成形物內部。然後’將此溶劑除去，於將纖維集合成形物 27 312/專利說明書(補件)/92-〇2/91134292 200300666 浸漬到揮發性溶劑中之時，將纖維集合成形物充塡到有著 具有多數的細孔的面之模具中，於自外側對纖維集合成形 物施加適度的壓力之狀態下，於保持其形狀下進行浸漬。 或，亦可對纖維集合成形物的上面以溶劑流過使其浸透的 方式進行亦可。又，爲保持既定的形狀，以將纖維集合成 形物內部的溶劑以真空吸引的方法儘早除去爲佳。 如上述般將纖維集合成形物浸漬到揮發性溶劑中使溶 劑浸透到成形物內部，則纖維由表面起溶解到溶劑中，於 一邊收縮下纖維彼此間進行融合，實質上使纖維消失形成 氣泡膜。然後，在形成具有空隙爲1 0 0〜4 0 0 // m程度的孔 徑的具有圓形的連續氣孔殘留之狀態下形成氣泡壁，使連 續氣孔進行形態變化。然後，多量地含於纖維中之生物陶 瓷顆粒的一部份，隨著此纖維的融合、成膜之形態變化， 在不沈降下被包埋於氣孔膜內（氣泡壁內），並同時，其一 部份自氣孔膜露出，於多孔物表面該顆粒也在不易脫落的 程度下塡入並露出。惟，依於條件而異，表皮層於表面上 形成而生物陶瓷顆粒不露出多孔物表面的情況也會發生， 此時，亦可施行以磨砂將表皮層去除使存在於表層的無機 顆粒露出的處置。 如此，可製得由具有連續氣孔，且在多量的生物陶瓷顆 粒均一地分散之同時，於氣孔裏面與多孔物表面露出有一 部份的生物陶瓷顆粒之有機-無機複合多孔物所構成的植 入材料。此複合多孔物，於將纖維集合成形物浸漬到揮發 性溶劑中之時，經由施加用以保持其形狀的外壓之調節， 28 312/專利說明書(補件)/92-02/91134292 200300666 可將連續氣孔的孔徑控制於適合於骨芽細胞之侵入與安定 化所須之較佳的1 Q Q〜4 0 0 // m程度，並且將氣孔率控制於 5 0〜9 0 %的程度。又，於5 0〜6 (TC的加熱下進行對纖維集 合成形物的揮發性溶劑之浸漬處理，則僅須將纖維集合成 形物短時間放置，纖維彼此即可充分地融合，可有效率地 得到複合多孔物。 本發明之製造方法中，於可纖維化之範圍內可將6 0〜9 0 重量百分比（於平均粒徑爲3 // m比重爲2 · 7的未燒結羥磷 灰石時爲相當於4 1〜8 1 %容積百分比）的生物陶瓷顆粒均 一地使其含有在複合多孔物中，即時是多量地含有，由於 在生物陶瓷顆粒沈降分離之前溶劑即會揮發使纖維融合， 故較上述溶液沉澱法中所得之多孔物，此法中生物陶瓷顆 粒可更均一地分散，而終於可製得迄今所無法製得之高含 有率之複合多孔物。惟，含有率若是過高，作爲結合劑之 活體內分解吸收性聚合物的量會變少，複合多孔物會變 脆，欲維持形狀會變得困難，故有其上限。 (實施例） 接著，就本發明之由有機-無機複合多孔物所構成之植 入材料，更進一步以具體的實施例加以說明。 (實施例1 ) 將黏度平均分子量爲 20萬的聚- D,L· -乳酸（PDLLA) (D , L -乳酸與L -乳酸的莫耳比爲5 〇 / 5 〇 )溶解於二氯甲烷 中所成之聚合物溶液（濃度·· PDLLA 4g /二氯甲烷 1 0 0 m 1 )，與平均粒徑 3 // m之未燒結的羥磷灰石顆粒 29 312/專利說明書(補件)/92-02/91134292 200300666 (u - HA顆粒）混合到乙醇中之混合液，進行均一地均質 化，藉此，調製成以使u - HA顆粒作成爲對於pDLLA 1 0 0 重量份爲2 3 0重量份的比例之方式所混合成之混合液。 作爲噴霧器，係使用 Η P - E氣刷（阿涅斯特岩田（股） 製），將上述懸浮液裝入其中，以壓力1 . 6kg/cm2的氮氣， 噴霧到約距離 1 2 0 c m之聚乙烯製的網狀物（1 5 0網眼） 上，形成纖維集合物，自網狀物將纖維集合物剝離。此纖 維集合物的纖維徑爲1 · Q // m程度，纖維長度爲1 0〜2 0 mm 程度，假比重爲〇 · 2。 將此纖維集合物切斷成適當的大小，充塡到直徑3 0 mm、 深3 0 mm的圓筒母模中，經由以使纖維集合物的假比重成 爲0 · 5的方式用公模進行壓縮，得到直徑3 0 mm、厚5 mm 的圓板狀的纖維集合成形物。 然後，將上述纖維集合物浸漬到由混合有乙醇的二氯甲 烷所成的溶劑中，使該溶劑浸透到成形物內部，於6 〇 °C下 放置1 〇分鐘後，將成形物內部的溶劑經由真空吸引除去， 得到直徑3Qmm、厚5mm、u-HA顆粒的含有率爲7〇%之有 機-無機複合多孔物。對此複合多孔物的部分截面以電子 顯微鏡觀察得知：纖維經融合而消失，形成具有1 〇 〇〜4 〇 〇 // m程度的大孔徑之連續氣孔、u - Η A顆粒均一地分散於氣 孔裏面與多孔物表面有u _ Η A顆粒的一部份露出著。此複 合多孔物的假比重爲0 . 5，連續氣孔佔氣孔全體的比例（連 續氣孔率）爲75%，壓縮強度爲l.IMPa。 30 312/專利說明書(補件)/92-02/91134292 200300666 (實施例2 ) 以與實施例同樣的作法，作成直徑3 0 mm、厚5 mm的圓 板狀的纖維集合成形物作爲預成形物，使其在齒輪式烘箱 中加熱至8 〇 °C後，置入具有直徑逐漸縮小的縮徑部的室 中’將其壓入下部的直徑爲1 0 . 6 mm的圓筒中。如此作法 之在加熱下加壓成形之圓柱棒狀的纖維集合成形物的壓縮 強度約爲2 · 5 Μ P a。 然後，將此圓柱棒狀的纖維集合成形物充塡到周圍有開 孔的同徑之圓筒中，自其上面與下面施加壓力，於對不改 變圓柱棒狀的纖維集合成形物的高度之程度下給予壓迫之 同時，將其浸漬到由混合有1 5重量百分比的甲醇之二氯 甲烷所成的溶液（6 0 °C )中1 0分鐘，之後，將該溶劑除去 得到複合多孔物。 對此複合多孔物的部分截面與經磨砂的表面以電子顯 微鏡照相觀察，得知：爲纖維消失之多孔質的形態，係由 孔徑1 5 0〜3 0 0 // m程度的混合孔所成，u - HA顆粒自多孔 物表面及氣孔裏面露出著。此複合多孔物的假比重爲約 0.55，連續氣孔率爲70%，壓縮強度上昇到約3.5MPa。 本複合多孔物，若由PDDLA的黏度平均分子量與所佔的比 例、平均粒徑3 // m的u - HA顆粒的在活體內之活體內分解 吸收性來推算，固依存於埋入部位及尺寸而異，推測可由 6個月至1 2個月間會完全吸收。 (實施例3 ) 合成黏度平均分子量爲1〇萬的PDLLA(D,L-乳酸與L - 31 312/專利說明書(補件)/92-02/91134292 200300666 乳酸的莫耳比爲3 0 / 7 0 )，以與實施例1同樣的方法，調 製成以平均粒徑3 // m程度的/3 -磷酸三鈣顆粒（0 - T c Ρ顆 粒）8 ◦重量百分比均一的混合所成之混合液。此沒—TCP 顆粒經確認係活體活性且爲活體內吸收性，其機制雖與 u - HA顆粒相異，但可得知其顯示有活體內HA生成之骨傳 導性。 用此混合液，以與實施例2同樣的噴霧法製作的纖維集 合物於加熱下壓縮成形成爲纖維集合成形物，經由對其進 行溶劑浸漬處理，得到假比重約0 . 6、連續氣孔率爲7 5 %、 壓縮強度爲 4 · 2 Μ P a的複合多孔物。此複合多孔物的石 -T C P顆粒的體積比例約爲6 5容量百分比，較u _ η A顆粒 爲7〇重量百分比（約55容量百分比）的實施例1、2的複 合多孔物，0 - T C P顆粒的體積比例大出甚多，故因於多 孔物的表面及氣孔裏面之/3 - T C P顆粒的露出，活體活性 可顯著地發揮。 此複合多孔物，於無紡織物狀的纖維集合物之時的纖維 消失而變化成/3 - TCP顆粒埋入於成塊狀（bulk)的胞壁的 形態，故即使於浸漬於活體內的體液中時也不易崩解致顆 粒分散到周圍，於5〜8個月程度間顯示良好的活體活性 並可完全地被分解吸收，得以確認。因而，此複合多孔物 可成爲良好的硬組織（硬骨、軟骨）用的植基構造。 (實施例4 ) 將D , L -乳酸（D / L·的莫耳比1 )與羧基乙酸（G A )，以使 32 312/專利說明書(補件)/92-02/91134292 200300666 莫耳比成爲8 ··2來配合，經由既知的方法，合成爲黏度平 均分子量爲 1 3萬的共聚物 P ( DLLA - GA )。以與實施例同 · 樣的作法，對此聚合物以磷酸八鈣顆粒（0 C P顆粒）調製成 _ 6 ◦重量百分比之均一混合之混合液，以與實施例2同樣的 噴霧法製作成纖維集合物，將其在加熱下壓縮成形作成纖 維集合成形物，經由對其進行溶劑浸漬處理，最後得到假 比重爲〇 · 5 0的複合多孔物。此複合多孔物之〇 c P的活性 度高，共聚物的分解吸收因於GA而較快速，故顯示出良 φ 好的骨傳導（容易轉變成新生骨），且於3〜4個月後其大 半都被吸收而代換爲骨。 (實施例5 ) 將 D, L-丙交酯與對二噁烷酮（p-DOX)以使莫耳比成爲 8 : 2配合，以既知的方法進行共聚合，得到黏度平均分子 量約爲1 〇萬的共聚物。p - D Ο X的聚合物，雖無揮發性的 泛用的優良溶劑，於上述的比例下，則可溶於氯仿、二氯 甲烷等中，以與上述實施例1同樣的方法可得到標的物之 β 複合多孔物。又，吾人認爲：上述共聚物，較實施例4的 D,L -乳酸與羧基乙酸之共聚物 P(DLLA-GA)更顯示具有 可塑性之橡膠般的性狀，故於生物陶瓷顆粒的粒徑爲3 // m 時之該顆粒的體積比例可高達 7 〇容量％ ( 8 5重量百分 比），故此複合多孔物，可極力地避免共聚物的分解生成 物之活體反應，而可極有效地發揮活體活性的生物陶瓷顆 ， 粒的活性度。尤其，自P - D Ο X的特性，其親水性較P D L L A 高，故此複合多孔物於活體外可使細胞增殖，因此於作爲 33 312/專利說明書(補件)/92-02/91134292 200300666 軟骨的再生之植基構造甚爲有效。 如上述般，由本發明之有機-無機複合多孔物所構成的 植入材料，含有均一地分散於活體內分解吸收性聚合物的 多量的生物陶瓷顆粒，通過形成於內部之孔徑大的連續氣 孔’體液等可迅速地浸入，經由露出於多孔物表面及連續 氣孔的裏面之生物陶瓷顆粒的骨傳導能，可更早期地與活 體骨結合並進行活體骨組織的再生，具有醫療用途所必須 的實用強度’爲可經由本發明之製造方法容易而確實地製 造者。因而，此植入材料，如上述般，可應用於作爲活體 骨組織重建用植基構造、補綴材、骨塡料、其他的植入材 料與活體骨組織之間的介在物、海綿骨的代替物、藥物徐 放用載體等。 其次’參照圖式，就應用上述的有機-無機複合多孔物 之本發明之植入材料的代表性實施形態詳加敘述。此植入 材料可槪分爲由上述多孔物與其他的緻密質的活體內分解 吸收性構材作成爲結合物所成的形態，與由上述多孔物與 活體內非吸收性構材作成爲結合物的形態；作爲前者之植 入材料之主要者，可舉出：圖1〜圖15所示之各種的實施 形態’而後者，則可舉出：圖1 6、圖1 7所示之實施形態。 圖1所示之植入材料10，爲用於：因於骨質疏鬆症之骨 量減少或骨骼組織萎縮致骨樑變粗、變細的部位的骨之切 開、鋸骨、或骨折之部位，將其經由手術進行閉鎖、接合 時所埋入之活體內活性且爲分解吸收性的骨固定用的植入 材料的代表例之正中切開閉鎖之胸骨固定用植入材料。 34 312/專利說明書(補件)/92-02/91134292 200300666 此植入材料1 0，爲具備有有機-無機複合多孔物1與作 爲活體內分解吸收性構材之軸釘2者，軸釘2貫穿著多孔 物1 ’軸釘兩端部自該軸釘2突出著。而且，爲使於埋入 胸骨中時不會旋轉，軸釘2係形成爲角柱狀，且多孔物1 係形成爲長方體狀。又，軸釘2的兩前端，係形成爲可容 易地插入形成於胸骨的骨髓（海綿骨）上的孔之角錐狀，在 此軸釘2的兩端部的表面，形成有用以阻止自上述的孔使 軸釘2拔出之截面爲鋸齒狀的凹凸2 a。又，於使軸釘2 形成爲圓柱狀之同時，多孔物1亦可形成爲圓筒狀，或將 軸釘兩端部的凹凸2 a省略亦可。 多孔物1，爲與上述有機-無機複合多孔物相同者，亦 即，係在活體內分解吸收性聚合物中實質上均一地分散著 活體活性的生物陶瓷顆粒所成之活體內分解吸收性的多孔 物，爲具有連續氣孔，且於氣孔裏面與多孔物表面有一部 份的生物陶瓷顆粒露出者。此多孔物1的氣孔率、連續氣 孔的孔徑、連續氣孔佔氣孔全體的比例、活體內分解吸收 性聚合物、生物陶瓷顆粒、該顆粒的含有率等，係如上述 者。 此多孔物1，係依據上述的製造方法，將無紡織物狀的 纖維集合物在加熱下加壓成形爲長方體形狀作成多孔質的 纖維集合成形物，將其浸漬於揮發性溶劑中得到長方體形 狀的有機-無機複合多孔物，經由對其穿孔作成用以插通 軸釘2的角孔（較軸釘2尺寸稍小的角孔）而製成。 此多孔物1的尺寸可依症例而選定，其大小並無特別限 35 312/專利說明書(補件V92-〇2/9l I34292 200300666 定，惟須留意不要使其成爲過大（多）。於胸骨固定用的植 入材料的情況，以將多孔物1的長度設定於10〜15 m m程 度、寬6〜2 0 mm程度、高6〜1 5 mm程度爲佳。此範圍內 之選定，須依存於患者的胸骨的構造是不言而喻者。多孔 物1的各尺寸，若低於上述範圍的下限，傳導形成到多孔 物1的骨組織會較少。又，此多孔物1之較佳的尺寸，亦 須因應所要埋入的骨而變化是不言而喻者。 在此多孔物 1，經由使其適量的含有上述的骨形成因 子、生長因子、藥劑等，可增進其功能。若含有骨形成因 子及生長因子，則會顯著地促進在多孔物1的內部的骨形 成，可較早期地使多孔物1代替骨組織，於切開閉鎖之雙 方的半胸骨可直接結合。而且，若使其含浸於藥劑中，則 藥劑可被雙方的半胸骨直接吸收而可充分地發揮藥效。 又，於此多孔物1的表面，施以上述的氧化處理以改善濡 濕特性，可更有效地使骨芽細胞侵入、生長，爲較佳者。 另一方面，上述軸釘2，可使用由安全性業經確認的結 晶性的聚乳酸及聚羧基乙酸等之活體內分解吸收性聚合物 所構成者，尤其以黏度平均分子量爲1 5萬以上（而以2 0 萬〜6 Q萬程度更佳）的活體內分解吸收性聚合物所構成的 高強度軸釘2爲更佳。又，由對此等活體內分解吸收性聚 合物以上述的活體活性的生物陶瓷顆粒，以1 〇〜6 0重量 百分比程度混合成的複合物所構成的軸釘，或經由壓縮成 形、鍛造成形、延伸等方法使上述的聚合物的分子或結晶 進行配向更加提高其強度的軸釘，亦爲較佳之可使用者。 36 312/專利說明書(補件)/92-02/91134292 200300666 尤其是經由鍛造成形使聚合物分子或結晶成三維配向之緻 密質者係較佳之可採用者。 於胸骨固定用之植入材料的情況，軸釘2的長度以2 0 〜4 0mm爲佳，若未滿2 0mm，則作爲胸骨固定用的軸釘會 太短，另一方面，若較4 〇 m m長，則會產生難以納入胸骨 的骨髓（海綿骨）中之不良的情況。又，軸釘2的寬以2〜 4tnm程度爲佳，局以2〜3mm爲佳。於軸釘2的寬較2mm 狹小、高較2 mm小的情況，會太細而有易於折斷的顧慮， 另一方面，若軸釘2的寬較4 mm寬、高較3 mm大的情況， 於多孔物1的組合上，會使胸骨固定用的厚度增加而不可 行。又，上述的軸釘的尺寸，不過是胸骨固定用的植入材 料的情況之較佳的尺寸，須因應於要埋入的骨而改變軸釘 的較佳尺寸是不言而喻者。 接著，參照圖2就上述胸骨固定用的植入材料1 0之使 用例加以說明。 首先，如圖2(a)所示般，經正中切開之左右的半胸骨 B，於B將2支的鋼線1 , 3使用突錐穿通，並以收束帶4 通過半胸骨B , B的肋骨間而捲繞。此收束帶4，於圖2 ( a ) 中只捲繞1支，惟，係以上下地隔開間隔捲繞著複數支（通 常爲4支）。然後，將雙方的半胸骨B , B的不要的海綿骨 以杓子等搔刮出，形成可將胸骨固定用的植入材料1 〇的 單側一半份插入的複數的孔5 (較植入材料1 0稍小的尺寸 之孔）。 接著，如圖2 ( b )所示般，將植入材料1 0的單側一半份 37 1 12/專利說明書(補件)/92-02/91134292 200300666 以使其不會拔出的方式強力擠壓入單片的半胸骨B的各孔 5。然後，如圖2 ( c )所示般穿引鋼線3 , 3，於一邊將分別 的植入材料1 〇的反對側半份擠壓入另一方的半胸骨B的 各孔5中，一邊將雙方的半胸骨B閉鎖，將鋼線3 , 3的端 部打結數次，紮實地綁牢。又，於此實施形態中，爲了將 半胸骨B , B固定雖係使用鋼線3及收束帶4，惟，亦可使 用上述聚乳酸般的活體內分解吸收性聚合物或使此聚合物 含入生物陶瓷顆粒經成形之條帶。 若將上述般的胸骨固定用之植入材料1 0埋入經切開、 閉鎖之胸骨的骨髓中，則於埋入初期，由於植入材料工〇 的軸釘2作爲「楔子」突刺於雙方的半胸骨B，將B固定 而發揮補強作用，故可提高雙方的半胸骨的固定安定性。 其後，經由露出於此植入材料1 0的多孔物1的表面之生 物陶瓷顆粒的骨傳導能，骨組織可傳導形成於多孔物的 表面，由於在短時間內多孔物1與雙方的半胸骨B , B的骨 髓會進行結合，故經由此結合可提高雙方的半胸骨B , B的 固定安定性與強度。 此植入材料 1 0，經由與骨髓中的體液之接觸，軸釘 2 與多孔物1皆會進行水解，由於多孔物1會通過連續氣 孔，使體液侵入到內部，故水解快速，且，此多孔物1， 經由露出於氣孔裏面之生物陶瓷顆粒物的骨傳導能，骨組 織會傳導形成到內部，於比較的短期間內與骨組織代換而 消失。尤其是，於對多孔物1以上述的生長因子含浸的情 況，骨組織的生長迅速，於短期間內骨組織可與多孔物1 38 312/專利說明書(補件)/92-02/91134292 200300666 代換。因而經閉鎖的胸骨（半胸骨B , B )，由於經由與多孔 物1代換之骨組織可直接結合，故即使疏鬆症的胸骨之海 綿骨爲極端地空洞化且多孔質化成爲晶圓般變脆，亦可經 由形成的新生骨胸骨的固定得以安定化。 另一方面，植入材料1 〇的軸釘2，經由與體液的接觸， 會徐徐地進行水解，於多孔物1與骨組織代換之時，水解 已進行甚多，不久即變成碎片，最後全部會被體內吸收而 消失。該情況下’軸釘2由於如上述般係由活體內分解吸 收性聚合物與生物陶瓷顆粒物的複合物所構成，且軸釘2 亦有骨傳導性，故經由水解與生物陶瓷顆粒之骨芽細胞與 破骨細胞的代換之反覆進行，藉其會傳導形成骨，倂同進 行分解碎片的貧食反應，軸釘2會與骨組織代換，軸釘2 所突刺著的孔最後會被新生骨埋沒而消失。 由本發明之有機-無機複合多孔物1與軸釘2所構成的 骨固定用之植入材料1 0，如上述般，於胸骨正中切開閉鎖 的手術中，不只可使用於埋入於經切開閉鎖之胸骨，於骨 質疏鬆症導致的骨量的減少或骨骼組織的萎縮致骨骼變粗 鬆且細的部位之切開、鋸骨、或骨折的部位之經由手術進 行閉鎖、接合時之埋入，亦可使用，最後，會代換骨組織 而可將骨強固地接合固定。 圖3所示之植入材料1 1，爲如圖6所示般之作爲椎體 間間隔物等之椎體固定材之主要用以插入頸椎C 3 - C 4或腰 椎L 4 - L 5間所使用者。此植入材料1 1，係由有機-無機複 合多孔物1與具備有通到外部的空洞6 a的活體內分解吸 39 312/專利說明書(補件)/92-02/91134292 200300666 收性構材之母材6所構成者，多孔物1係裝塡於母材6的 空洞6a中而自該空洞6a的入口 6b部分地露出著，又， 於母材6的上下，多孔物1亦疊合成板狀而設置著。此母 材6的上下之多孔物1係用於作爲自身骨的代替，如後述 般，係爲了可使母材6與頸椎C3-C4或腰椎L4-L5之間隙 消失並早期結合（固定）而設置者。又，母材6的上下之多 孔物1亦可省略。 此植入材料1 1的母材6，係由含有活體活性的生物陶瓷 顆粒物之活體內分解吸收性聚合物所構成的緻密質的強度 佳的母材，如圖4所示般，係形成爲長方體的形狀。於此 母材6中，係以可互相交絡的方式形成可通達外部之縱方 向的二個貫穿孔狀的空洞6 a與橫方向的二個貫穿孔狀的 空洞6a，此等空洞6a的入口 6b，於母材6的上下左右的 4面分別有2個開口。此等空洞6 a的入口 6 b，由於係液 體等之侵入口，故裝塡於空洞6a內之多孔物1自各入口 6 b爲部分露出的狀態。又，空洞6 a的入口 6 b亦可在母 材6的前面及後面形成，此情況下，以使後面的入口形成 爲螺絲孔狀以使插入之夾具的前端可鎖上的方式來作成爲 佳。 此植入材料11，爲了使其容易插入頸椎c3-c4或腰椎 L 4 - L· 5間，於母材6的前面6 c的四周削成倒角。因此，爲 了使其成爲於插入頸椎C 3 - C 4或腰椎L 4 - L 5間後不會位置 偏移或脫離之自立型（不要補助固定材）的植入材料1 1， 於母材6的上下兩面6d、6e上設置數個（圖中各爲6個） 40 312/專利說明書(補件)/92-02/91134292 200300666 固定用的突起6 f，各突起6 f的前端部係自母材6的上下 兩面的多孔物1突出著。此突起6 f ’如圖4所示般，係 於母材6的上下兩面形成有凹穴69，在由與母材6相同 之活體內分解吸收性聚合物所構成的前端，將圓錐狀之尖 的軸釘6 h ( 6 f )植設於凹穴6 g中者。又，代之以軸釘6 h， 亦可於前端植設尖的突片，又，亦可使突起6f與母材6 一體成形。 如圖5所示般，係作成爲：於母材6的縱方向的二個空 洞6 a , 6 a之間的壁部6 i，形成有連通孔6 j，如後述般， 在裝塡於空洞之多孔物1 , 1上傳導形成的骨組織，通過連 通孔6 j而可連結之構成。此壁部6 i，係用以提高母材1 的耐壓強度者。 母材6的尺寸，以前後尺寸爲18〜30mm程度，上下高 及左右寬的尺寸爲6〜24 mm程度，若採用此等範圍內的各 種此寸，則可選擇適合於頸椎C3-C4或腰椎L4-L5的尺寸 及椎間的尺寸者來插入。 植入材料1 1的母材6，係使縱方向及橫方向的空洞6 a 形成爲截面爲長圓形的貫穿孔形狀，惟，亦可形成爲四方 形、圓形、橢圓形等之各種的截面形狀的貫穿孔狀。又， 亦可將母材6的內部全體作成爲中空室狀的空洞，使該空 洞的入口形成在母材6的上下左右4面，使其與外部連通。 又，貫穿於母材6的橫方向之空洞6 a亦可省略，只要 有貫穿於縱方向的空洞 6 a，自上下頸椎 C 3 - C 4或腰椎 L 4 - L 5骨組織會傳導形成在裝塡於內部的多孔物1上而可 41 312/專利說明補件)/92·02/91134292 200300666 癒合、固定。又，母材6的左右2面的入口 lb亦可省略。 上述母材6，係由活體活性的含有生物陶瓷顆粒之活體 內分解吸收性聚合物所構成者，作爲原料的活體內分解吸 收性聚合物，佳適者爲與上述的植入材料Q的軸釘2同 樣的聚合物’亦即，可使用活體內之安全性經確認之結晶 性的聚L -乳酸或聚羧基乙酸等爲佳，尤其是使用黏度平均 分子量爲15萬以上（而以20萬〜60萬程度更佳）的聚L-乳酸之高強度的母材6爲較佳。這樣的母材6，可經由用 活體內分解吸收性聚合物進行射出成形、或對活體內分解 吸收性聚合物的成形塊狀物進行切削加工等的方法來製 作。於後者的方法中，將成形塊狀物以壓縮成形或鍛造成 形等的手段使聚合物分子或結晶進行配向作成塊狀物，將 其切削加工所製得的母材6，質地緻密且聚合物分子或結 晶成三維配向使強度更加提高，故爲極佳者。此外，亦可 使用作爲成形塊狀物之經延伸成形的塊狀物，並以使延伸 方向（配向方向）作爲縱方向的方式進行切削加工可提高 強度，是較佳者。 作爲此母材6中所含有之生物陶瓷顆粒，上述的活體活 性的全吸收性的生物陶瓷顆粒全都可使用，其含有率，與 上述的植入材料1 0的軸釘2同樣地，以作成爲1 〇〜6 0 重量百分比爲佳。若未滿1 0重量百分比，則因於生物陶 瓷顆粒之骨傳導形成不充分，若超過6 0重量百分比，則 會發生母材6脆弱化之不良情形。 另一方面，充塡於母材6的空洞6 a之多孔物1，爲與 42 312/專利說明書(補件)/92-02/91134292 200300666 上述的有機-無機複合多孔物相同者，亦即，係在活體內 分解吸收性聚合物中實質上均一地分散著活體活性的生物 陶瓷顆粒所成之活體內分解吸收性的多孔物，爲具有連續 氣孔，且於氣孔裏面與多孔物表面有一部份的生物陶瓷顆 粒露出者。此多孔物1的氣孔率、連續氣孔的孔徑、連續 氣孔佔氣孔全體的比例、活體內分解吸收性聚合物、生物 陶瓷顆粒、該顆粒的含有率等，係如上述者。 又，母材6的上下之多孔物1，形成有通過母材6的突 起6f的孔，疊合於母材6的上下兩面6d,6e上，以熱融 合等之手段固定。此母材6的上下的多孔物1之厚度以0.5 〜3 mm程度爲佳，於較〇 . 5 mm薄的情況，會難以吸收因於 壓縮變形之頸椎C3_C4或腰椎L4-L5的表面的凹凸，故與 頸椎C3-C4或腰椎L4-L5的密著性會有降低的顧慮，另一 方面，於較3 mm厚的情況，其分解吸收及與骨組織間的代 換所要的時間會變長。 對裝塡於母材6的空洞6 a之多孔物1，或疊合在母材6 的上下作成爲結合物之多孔物1，宜使其適量地含有上述 的骨形成因子、成長因子、藥劑等，又，亦可在多孔物1 的表面施以上述的氧化處理以改善濡濕特性。 將上述的植入材料11，用插入夾具，如圖6所示般在頸 椎C3-C4或腰椎L4-L5間插入左右一對，藉此，可矯正頸 椎C3- C4或腰椎L4-L5的間隔及樣態。如此般地將植入材 料1 1插入，則母材6的上下兩面的多孔物1 , 1會因於頸 椎c3-c4或腰椎L4-L5的夾壓力而受壓縮使頸椎〇3-(：4或 43 312/專利說明書(補件)/92-02/91134292 200300666 腰椎L 4 - L 5無空隙地密合，並且母材6的上下兩面的突起 6 f會嵌入頸椎C 3 - C 4或腰椎L 4 - L 5的海綿骨，使植入材料 11不會位置偏移或脫離之下固定住，與母材6之長方體形 狀相倚而可安定地設置。 這樣地於頸椎C 3 - C 4或腰椎L 4 - L 5間插入植入材料i工 而設置，則具有充分的強度之和活體的皮質骨有同樣的作 用之母材6會與體液接觸而自表面開始徐徐地進行水解。 其次，與海綿骨有同樣的作用之多孔物1，經由自其露出 部分通過連續氣孔浸透到內部之體液之水解會快速地進 行，且經由生物陶瓷顆粒的骨傳導能，骨芽細胞會侵入多 孔物1的內部而傳導形成骨組織，因此，在比較的短期間 內多孔物1會與骨組織代換。因而，上下的頸椎C 3 - C 4或 腰椎L4-L5，可經由此代換的骨組織而癒合、固定。另一 方面，母材6，自初期起，其壓縮強度係與習用的碳製的 鋼骨結構同樣地高，與多孔物1進行骨代換之後亦可繼續 維持強度，植入材料 11可完全地與頸椎 C3-C4或腰椎 L 4 - L 5癒合而力學上地固定，可發揮大的效用，其後經過 數年（約5年）與骨組織之代換可完成。於此時點。可獲得 完全地因於活體骨之固體狀的癒合。 骨組織的傳導形成，由於母材6的上下兩面的多孔物1 被壓縮而使頸椎C3-C4或腰椎L4-L5沒有空隙地密合著， 多孔物1係與上述有機-無機複合多孔物爲相同者，由於 含有具有骨傳導能之生物陶瓷顆粒60〜90重量百分比， 氣孔率爲5〇〜90%，連續氣孔佔氣孔全體的50〜90%，連 44 312/專利說明書(補件)/92-02/91134292 200300666 續氣孔的孔徑爲約1 Q 〇〜約4 〇 〇 # m ’故骨芽細胞容易侵入 而可確實地進行，骨組織傳導形成於母材6的上下兩面的 多孔物1的表層部之初期的階段中’植入材料1 1與上下 的頸椎c 3 - C 4或腰椎L 4 - L 5直接結合而可固定。 如上述般，由於此植入材料1 1之母材6與多孔物1都 會被分解吸收而與骨組織代換，非作爲異物而存在於活體 內，故習用之作爲椎體固定材使用之鈦製或碳製鋼骨結構 所掛慮的在活體內長期存在之危害性的發生之顧慮，及活 體與力學的特性的不一致所產生的於椎體內之下沈的問題 得以一掃而空。而且，多孔物1可進行與活體骨同樣的組 織學的作用，而與骨組織代換，故不若向來般爲了塡充於 鋼骨結構中作爲移植用自身骨而須擷取腸骨等，移植用自 身骨的獲得量的不足之問題，及擷取後的手術時處理之煩 瑣的問題亦得以一掃而空。 此植入材料1 1之母材6的上下兩面6 d , 6 e係成水平， 惟’亦可使上面6 d往前下傾斜，使下面6 e往前上傾斜， 亦可作成爲先端變狹窄狀的母材6，作成如此，則可成爲 適於將腰椎矯正爲前彎姿勢之植入材料。 又’母材6的形狀，並非限定於上述的長方體形狀，亦 可作成爲適合於頸椎、腰椎、脊椎及其他的使用部位之各 種的形狀。如圖7所示之植入材料1 2，係此等將形狀變更 者’於母材6的內側形成有具有空洞6 a (截面爲圓形的空 洞）的圓筒體形狀，在其兩端面各配置有大的圓形空洞的 入口 6 b各一，於外周面配置有小的長圓形的空洞的入口 45 312/專利說明書(補件)/92-02/91134292 200300666 6 b，配置成千鳥狀並形成多數個。而且，在此母材6的空 洞6 a裝塡有上述的有機-無機複合多孔物1 ,自形成於母 材6的兩端面及外周面的各入口 6b露出著多孔物1的一 部份。 這樣的植入材料1 2，如圖示般以縱向的姿勢將其插入頸 椎及腰椎等的椎體間，與上述植入材料11同樣地母材6 及多孔物1最後會與骨組織代換，使上下的錐體癒合、固 定。 又’某些情況下，在此植入材料i 2的外周面形成公螺 芽’以橫向的姿勢旋入上下的椎體間而設置亦可。 圖8所示之植入材料亦爲將母材的形狀變更者，母材6 係形成爲具有曲率小的部分6 η之高度低的環體形狀，於 其內側的空洞6 a中裝塡有上述的多孔物1，自該空洞的上 下的入口 Sb露出著多孔物i的上下兩面。在此環體形狀 的母材6的外周面雖未形成有空洞的入口，惟，依於須要 亦可形成複數之空洞的入口。又，於此環體形狀的母材6 的上下兩面亦可形成上述固定用的突起。 這樣的植入材料1 3，使母材6的曲率小的部分6 η移往 後側插入頸椎及腰椎等的椎體間，與上述的植入材料1 1、 1 2同樣地母材6及多孔物最後會與骨組織代換使上下 的椎體癒合、固定。 上述植入材料1 1 , 1 2 , 1 3，皆爲用以作爲椎體固定材以 插入、設置於頸椎或腰椎等的椎體間者，若將母材6的形 狀適當地變更亦可使用於各部位的骨關節中。 46 312/專利說明書(補件)/92-02/91134292 200300666 圖9所示之植入材料1 4，爲作爲同種移植骨片及自身移 f直骨片的代替物用以埋入骨缺損部位者，具有塊狀的有機 -無機複合多孔物1與活體內分解吸收性構材之表皮層 7 ’此表皮層7係疊合於多孔物1的表面之一部份作成爲 結合物。 塊狀的多孔物1，係與上述有機-無機複合多孔物爲相同 者’亦即，係在活體內分解吸收性聚合物中實質上均一地 分散著活體活性的生物陶瓷顆粒所成之活體內分解吸收性 的多孔物，爲具有連續氣孔，且於氣孔裏面與多孔物表面 有一部份的生物陶瓷顆粒露出者。此多孔物1可藉由本發 明之製造方法來製作，其氣孔率、連續氣孔的孔徑、連續 氣孔佔氣孔全體的比例、活體內分解吸收性聚合物、生物 陶瓷顆粒、該顆粒的含有率等，係如上述者。 由於此多孔物1可發揮海綿骨的作用，其形狀只要是塊 狀皆可，並無特別限定，對此多孔物1，可使其適量地含 有上述的骨形成因子、成長因子、藥劑等，又，亦可在多 孔物1的表面及表皮層7的表面施以上述的氧化處理以改 善濡濕特性。 表皮層7可發揮皮質骨的作用，係由含有活體活性的生 物陶瓷顆粒之活體內分解吸收性聚合物所構成之緻密質的 強度佳的層。於此植入材料i 4中，可將表皮層7疊合在 塊狀的多孔物1的凸彎曲之側面而一體設置，亦可疊合設 置於多孔物1的其他的側面、上面、底面之任一者上，又， 亦可疊合設置於多孔物1的二面乃至於三面以上。重點在 47 312/專利說明書(補件)/92-〇2/91134292 200300666 於，此表皮層7，只要疊合設置於塊狀的多孔物1的表面 之一部份上皆可。表皮層7的厚度，並無特別限定，就要 埋設植入材料1 4之骨缺損部位考量’以適當地設定於1 · 〇 〜5 . 0mm的範圍內爲佳。若較1 · omm薄，則有導致表皮層 7的強度不足的顧慮，若較5 · Q mm厚，則會產生表皮層7 之被分解吸收並與骨組織代換須要長時間的不良情形。 由於此表皮層7須要求有較塊狀的多孔物1大的強度， 作爲原料的活體內分解吸收性聚合物，以使用結晶性的聚 - L -乳酸或聚羧基乙酸等爲佳，尤其以黏度平均分子量爲 I5萬以上（而以20萬〜60萬程度更佳）的聚- L· -乳酸的高 強度的表皮層7爲佳適。 作爲含有於表皮層7中之生物陶瓷顆粒，上述多孔物1 中所含有之活體活性的生物陶瓷顆粒全都可使用，其含有 率’以作成爲10〜6〇重量百分比的範圍爲佳。若超過60 重量百分比，則表皮層7會脆弱化，若低於1 Q重量百分 比，則會產生因於生物陶瓷顆粒之骨傳導形成不充分的不 良情形。 此表皮層7 ’可經由用含有生物陶瓷顆粒之活體內分解 吸收性聚合物進行射出成形、或對含有生物陶瓷顆粒之活 體內分解吸收性聚合物的成形塊狀物進行切削加工等的方 法來製作。於後者的方法中，將成形塊狀物以壓縮成形或 鍛造成形等的手段使聚合物分子或結晶進行配向作成塊狀 物’將其切削加工所製得的表皮層7，由於質地緻密且聚 合物分子或結晶成三維配向使強度更加提高，故爲極佳 48 312/專利說明書(補件)/92-02/91134292 200300666 者。此外’將經延伸成形之成形塊狀物進行切削加工所得 之表皮層亦可使用。 此植入材料1 4，係將以上述的方法製作之表皮層7疊合 在塊狀的多孔物1的凸彎曲的一側面，經由熱融合等之手 段所作成之不可分離的結合物。將表皮層7與多孔物i 一 體化之手段，並非限定於熱融合法，亦可經由其他的手段 進行一體化。 將上述的植入材料1 4，作爲同種移植骨片或自身移植骨 片的代替物埋入於骨缺損部位，將骨缺損部位的海綿骨部 位以塊狀的多孔物1塡補，並將骨缺損部位的皮質骨的部 位以表皮層7補償，則由於塊狀的多孔物1可發揮海綿骨 的作用’強度大的表皮層7可發揮皮質骨的作用，正如使 骨缺損部位的海綿骨的部分以海綿骨塡補，皮質骨部分以 皮質骨塡補一般。 如此般，將骨缺損部位以植入材料1 4塡補，則體液透 過連續氣孔浸透到塊狀的多孔物1之內部，於快速進行水 解之同時，經由生物陶瓷顆粒的骨傳導能，骨芽細胞會侵 入多孔物1的內部使骨組織可傳導形成。因此，塊狀的多 孔物1可在比較的短期間內與骨組織代換。另一方面，表 皮層7較塊狀的多孔物1慢，自表面開時徐徐地進行水 解，於塊狀的多孔物 1與骨組織迄至某程度代換的期間 內，可維持充分的強度，最後，與骨組織代換至於消失。 此植入材料1 4，係無上述般的特異的活體反應，而於非特 異地分解、吸收、排出之途中，可經由侵入周圍的活體骨 49 312/專利說明書(補件)/92-02/91134292 200300666 與代換而變成自身骨者。亦即，塊狀的多孔物1與表皮層 7皆被分解而代換成骨組織，由於不會作爲異物而殘留在 活體內，習用的陶瓷製的植入材料所掛慮的因於活體內的 長期殘存之危害性的發生之顧慮可得以去除，藉由經代換 的自身的骨組織可將骨缺損部位修復與重建。 又，此植入材料1 4，由於多孔物1及表皮層7皆爲以 活體內分解吸收性聚合物作爲原料者，故不若以死體骨作 爲原料之習用的同種移植骨片般有原料獲得不足的顧慮， 可依需要無限制地量產必要且充分量的植入材料，經由成 形及切削加工等可製作成所要的形狀及尺寸者。 又，此植入材料1 4的表皮層7，雖含有生物陶瓷顆粒 物’由於係由活體內分解吸收性聚合物所構成者，沒有燒 結之陶瓷製的植入材料般的過硬且脆的缺點，有韌性不易 裂開，必要時亦可加熱變形。而且，塊狀的多孔物i雖含 有多量的生物陶瓷顆粒物，由於係以活體內分解吸收性聚 合物作爲原料之多孔物，故即使氣孔率高，不若高倍率的 多孔質陶瓷般之非常脆，埋入時不會零零落落地破片剝 落’必要時亦可加熱變形。如此般，本發明之植入材料1 4， 不脆而具有充分的實用強度，且可加熱變形，是取用性優 異者。 又’此植入材料1 4可作爲外科用代替品使用於多用途 中，尤其現在頓時受到愛用，作爲若干問題已得明朗化之 頸椎及腰椎的補綴材及間隔材方面甚有效。 圖1 〇及圖1 1所示之植入材料1 5，爲使用於以頭蓋骨、 50 312/專利說明書(補件)/92-02/91134292 200300666 顎、顏面部或胸部等之多種骨骼部位的缺損及變形 整復、矯正或增大爲目的，之作爲補綴、塡充材之 料；爲具備有機-無機複合多孔物1與活體內分解 構材之網狀物8，在此網狀物8的網眼8 a中充塡 物1所作成爲結合物。 此植入材料1 5的網狀物8，係由含有活體活性的 瓷顆粒的活體內分解吸收性聚合物所構成的緻密質 佳之網狀物；係經由對含有生物陶瓷顆粒的活體內 收性聚合物的片狀物或板狀物用打孔或切削加工的 成方形的網眼8 a而作成爲網狀物。網眼8 a的形狀 限定於方形，亦可作成爲圓形、菱形及其他所要的 狀。 網眼8 a的開口面積，以〇 · 1〜1 · 〇 c m2的程度爲 眼8 a佔網狀物8的面積比例以i 〇〜8 〇 %程度爲佳 狀物8的厚度，以0 . 3〜1 . 5 mm程度爲佳；網狀物 當於經紗部分8 b及相當於緯紗部分8 c的寬，以2 / 爲佳。網眼8 a的面積比例若未滿1 〇 %，則植入材彩 全體強度雖大，由於充塡於網眼8 a之水解速度快 物1之充塡量較少，水解慢的網狀物8所佔的比例 故植入材料1 5完全被分解吸收而與骨組織代換所 間會較長。另一方面，網眼8 a的面積比例若超過 網狀物8的厚度較0 . 3 mm薄、相當於經紗部分8 b 於緯紗部分8 c的寬較2 mm狹窄，則由於網狀物8 會降低甚多，欲得到強度佳的植入材料1 5會較困| 312/專利說明書(補件)/92-02/91134292 部位的 植入材 吸收性 有多孔 生物陶 的強度 分解吸 手段形 ，並不 網眼形 佳，網 。又網 8的相 ^ 10 mm 15的 之多孔 變大， 要的時 8 0%、 及相當 的強度 200300666 於欲得到折曲加工性良好的網狀物8的情況，作爲用以 作爲材料之上述片狀物或板狀物，可使用將含有生物陶瓷 顆粒之活體內分解吸收性聚合物的熔融成形物進行冷鍛造 (由聚合物的玻璃轉移溫度至熔融溫度間的溫度範圍）之 後，更進一步改變方向（機械方向MD)再度進行冷鍛造者， 對其進行打孔或切削加工等作成網眼8 a來製作成網狀 物。如此之改變方向進行2次鍛造之活體內分解吸收性聚 合物的片狀物或板狀物，由於活體內分解吸收性聚合物的 分子鏈、分子鏈集合之區域（domain)、結晶軸等係成爲 多軸配向，或成爲多軸配向的叢集所多數集合的構造，故 若於常溫域（0〜5 0 °C )使其折曲變形，則維持其形狀於體 溫附近（3 0〜4 0 °C )難以回復成原來的形狀，即令使其多次 折曲變形，也不易破壞或切斷。因而，用在此片狀物或板 狀物上形成網眼8 a的網狀物8所製作的植入材料1 5，由 於其折曲加工性良好，故例如如圖1 2所示般，以使其與 頭蓋骨2 0的缺損部分2 1的曲面吻合的方式於手術中在常 溫下進行折曲加工，可固定於該缺損部分2 1上。又，作 爲網狀物8的材料之片狀物或板狀物，當然亦可使用單軸 或二軸延伸者、無延伸者或壓縮成形者。 作爲網狀物8的原料之活體內分解吸收性聚合物，可使 用由安全性業經確認的結晶性的聚-L -乳酸、聚-D -乳酸、 聚- D/ L-乳酸、聚羧基乙酸等爲佳。此等之活體內分解吸 收性聚合物，就網狀物8的強度及水解速度等考量，以使 用黏度平均分子量爲15萬以上者爲佳，而以2〇萬〜60 52 3 U/專利說明書(補件)/92_〇2/91134292 200300666 萬程度者更佳。 作爲含有於此網狀物8的活體內分解吸收性聚合物中的 生物陶瓷顆粒，上述含有於多孔物1中的活體活性的生物 陶瓷顆粒全都可使用，其含有率以作成爲1◦〜6Q重量百 分比爲佳。若未滿1 〇重量百分比，依於生物陶瓷顆粒之 骨傳導形成會不充分，若超過6Q重量百分比，則會發生 網狀物8脆弱化之不良情形。 又，上述的網狀物8，亦可使用例如將含有生物陶瓷顆 粒的活體內分解吸收性聚合物的經紗與緯紗的交點融合之 網狀物等來代替。 另一方面，充塡於上述網狀物8的各網眼8 a之多孔物 1，係與上述有機-無機複合多孔物相同者，亦即，係在活 體內分解吸收性聚合物中實質上均一地分散著活體活性的 生物陶瓷顆粒所成之活體內分解吸收性的多孔物，爲具有 連續氣孔，且於氣孔裏面與多孔物表面有一部份的生物陶 瓷顆粒露出者。此多孔物1的氣孔率、連續氣孔的孔徑、 連續氣孔佔氣孔全體的比例、活體內分解吸收性聚合物、 生物陶瓷顆粒、該顆粒的含有率等，係如上述者。 對此多孔物 1，亦可使其適量地含有上述的骨形成因 子、成長因子、藥劑等，又，亦可在多孔物1的表面及網 狀物8的表面施以上述的氧化處理以改善濡濕特性。 上述構成的植入材料1 5，例如如圖1 2所示般，以將頭 蓋骨 20的缺損部分21覆蓋的方式緊靠貼在頭蓋骨20 上，其周緣部以由活體內分解吸收性聚合物所構成之螺絲 53 312/專利說明書(補件)/92-02/91134292 200300666 30作數處固定。此時，宜以與頭蓋骨2〇的缺損部分21 的曲面吻合之方式將植入材料1 5作折曲加工。 如此地將頭蓋骨2 0的缺損部分2 1以植入材料1 5覆 被，則經由網狀物8與液體的接觸，自表面開始會徐徐地 進行水解，由於體液會透過連續氣孔浸透到多孔物1的內 部，故水解會快速進行。其後，經由多孔物1中所含有的 生物陶瓷顆粒的骨傳導能，骨芽細胞會侵入到多孔物1的 內部使骨組織傳導形成，而使多孔物1在比較的短期間內 代換爲骨組織。另一方面，網狀物8較多孔物1慢進行水 解，於迄至多孔物1與骨組織達到一定程度的代換之前的 期間，可維持充分的強度以保護頭蓋骨2 0的缺損部分 2 1。最後，網狀物8亦與骨組織代換而消失。 此植入材料1 5，如上述般，多孔物1與網狀物8皆被 分解、吸收而代換爲骨組織，由於非作爲異物殘留在活體 內，故習用之作爲骨缺損部的補綴材使用之衝孔板所掛慮 的在活體內長期存在之危害性的發生之顧慮，可一掃而 空，並可經由代換的骨組織將頭蓋骨2 0的缺損部分2 1修 復、重建。 又，此植入材料1 5的網狀物8，雖含有生物陶瓷顆粒 物’由於係由活體內分解吸收性聚合物所構成者，不若經 由燒結之緻密的陶瓷般的過硬且脆的缺點，有韌性且不易 裂開，於常溫下可加熱變形。而且，多孔物1雖亦含有多 量的生物陶瓷顆粒物，由於係以活體內分解吸收性聚合物 作成矩陣者，故即使氣孔率高，不若高倍率的多孔質陶瓷 54 312/專利說明書(補件)/92_〇2/91134292 200300666 般之非常脆’埋入時不會零零落落地破片剝落，必要時亦 可加熱變形。如此般，本發明之植入材料1 5，不脆而具有 充分的實用強度，且可加熱變形，是取用性優異者。 此植入材料1 5，經由作成網狀物以發揮強度佳的皮質骨 之作用’將多孔物作成高空隙率以發揮海綿骨的作用，可 得到局面積且少材料的活體骨的代替物，由於係網狀物與 多孔物的組合’材料的總量可抑制於極少量，爲分解吸收 過程中活體的處理量甚少的活體適合性優異的植入材料。 又’此植入材料1 5，除了圖1 2所示之使用例之外，亦 可使用於顏面中的塌陷骨折的補償、骨腫瘍等之病巢之摘 除後的塡補等、比較大的骨缺損部位的修復與重建，且， 亦可作爲用以骨延長用的基材。 於上述將多孔物1與網狀物8組合而成的型態之植入材 料1 5中’不只是將多孔物充塡到網狀物8的網眼8 a中， 於網狀物8的單面或兩面將多孔物1設置爲層狀的構造 者，也是甚有用的實施形態。圖1 3、圖1 4係顯示這樣的 實施形態之植入材料1 6 , 1 7者，植入材料1 6係在上述的 植入材料1 5之單面上將上述有機-無機複合多孔物1設置 爲層狀者，植入材料1 7係在植入材料i 5的兩面將上述有 機-無機複合多孔物1設置爲層狀者。 層狀的多孔物1係與上述的有機-無機複合多孔物1相 同者，爲藉由上述本發明之製造方法製作成層狀（片狀） 者。此層狀的多孔物1 ’可經由熱融合等手段在植入材料 I5的單面或兩面上進行一體積層。此層狀的多孔物1的厚 55 312/專利說明書(補件)/92-02/91134292 200300666 度並無特別限定，就與骨缺損部位的周圍的骨之密合性、 分解吸收及與骨組織之代換所要的時間等考量，以設定爲 0.5〜3mm程度的厚度爲佳。 這樣的植入材料1 6 , 1 7，由於可在比較的短期間內在單 面或兩面上均等地形成骨組織，故骨缺損部位的表面之修 復、重建可快速地進行。又，由於設置爲層狀的多孔物1， 可發揮作爲緩衝材的作用密合於骨缺損部位的周圍的骨 上’骨芽細胞容易侵入層狀的多孔物1的內部，可早期地 骨組織可傳導形成於多孔物1的表層部，植入材料i 6 , i 7 與骨缺損部位的周圍的骨會直接結合，而可強固地固定。 又’於將上述多孔物1與網狀物8組合所成之型態的植 入材料1 5中，作成使網狀物8凹曲或凸曲，於其內側亦 以多孔物1充塡之構造者，亦爲有用的實施形態。圖工5 係顯示這樣的實施形態之植入材料 1 8者，此植入材料 1S，係使上述植入材料15的網狀物1凹曲成U字形，與 充塡於其網眼中之多孔物1同樣地對多孔物1亦充塡於網 狀物8的內側（即凹曲內部）。作爲網狀物8，由於以對改 變機械方向進行二次鍛造之上述的屈曲加工性良好的活體 內分解吸收性聚合物片狀物或板狀物形成網眼而製作的網 狀物’其機械強度高且可在常溫下進行加工，故爲特佳之 可使用者。 這樣的植入材料1 8，例如將其製作成可埋入、充塡於顎 骨等缺損部位的大小，如圖1 2中以假想線所示般地可使 用於顎骨的缺損部位的修復、重建。此外，當然可使用於 56 312/專利說明書(補件)/92-02/91134292 200300666 以因事故或癌症所失去的活體骨的塡補、再生爲目的之頭 蓋骨、顏面中、上顎及下顎等的顎顏面的缺損部分，於整 形外科方面之其他的較大的骨缺損部分的修復、重建亦可 佳適地使用。 又，上述植入材料i 8，雖爲將網狀物8凹曲成U字形， 惟，可依要重建之骨缺損部位之吻合的形狀將網狀物8凹 曲或凸曲’在其內側充塡多孔物i而製作成植入材料工8 即可，必要時，亦可在植入材料1 8的外側將多孔物1進 一步設置爲層狀。又’亦可作成將網狀物8折疊，於折疊 之網狀物8間亦以多孔物1充塡的構造之植入材料，再 者，亦可作成將植入材料1 5上下兩片疊合，於其間夾入 層狀的多孔物1的三明治構造的植入材料。 圖16及圖17係顯示人造軟骨用的植入材料19。此人 造軟骨用植入材料1 9，具備有上述的有機-無機複合多孔 物1、活體內非吸收性構材之芯材9、活體內分解吸收性 構材之固定用軸釘2 2，多孔物1係積層於活體內非吸收性 構材的芯材9之上下兩面作成爲結合物，固定用軸釘2 2 的前端係自多孔物1的表面突出著。 此人造軟骨用植入材料1 9，係具有如圖1 6所示般的結 合長方形與半圓形之大略前方後圓形的平面形狀的區塊 狀，爲可使用作爲人造椎間板之佳適者。 芯材9，爲將有機纖維作成爲3軸以上的多軸三維織組 織或編組織或此等的複合組織之組織構造物所構成者，具 有與椎間板等的軟骨同程度之機械強度與柔軟性，變形係 57 312/專利說明書(補件)/92-02/91134292 200300666 活體模仿性者。此芯材9的組織構造物，係與本申請人已 經提出申請之日本特願平6 - 2 5 4 5 1 5號中所記載之組織構 造物爲同樣者，將其幾何上的形狀以維數來表示，將纖維 排列的方位數以軸數來表示，以採用3軸以上的多軸-纖 維組織所構成之構造物爲佳。 3軸-三維組織，係將縱、橫、垂直的3軸的方向的纖維 進行立體的組織者，其構造物的代表的形狀爲上述芯材9 般的有厚度之成塊狀（板狀乃至於塊狀），亦可作成圓筒狀 或蜂巢狀。此3軸-三維組織，依於組織的不同，可分類 爲直交組織、非直交組織、絡連組織、圓筒組織等。又， 4 軸以上的多軸-三維組織的構造物，經由排列成 4,5,6, 7, 9,11軸等的多軸方位，可提高強度的等方向 性。而且，經由此等之選擇，可得到更酷似於活體的軟骨 組織、更活體模仿性的芯材。 由上述組織構造物所構成之芯材9的內部空隙，以2 0 〜9 〇 %的範圍爲佳，於低於2 0 %的情況，由於芯材9較緻 密而會損及柔軟性及變形性，爲無法滿足作爲人造軟骨用 植入材料的芯材者，又，於高於9 〇 %的情況，由於芯材9 的壓縮強度及保型性降低，終究不適於作爲人造軟骨用植 入材料的芯材。 作爲用以構成芯材9之有機纖維，可使用活體不活性的 合成纖維，例如，聚乙烯、聚丙烯、聚四氟乙烯等的纖維； 將有機的芯纖維以上述的活體不活性的樹脂覆被作成活體 不活性的覆被纖維等爲較佳之可使用者。尤其是，將超高 58 3127專利說明書(補件)/92-02/91134292 200300666 分子量聚乙烯的芯纖維（捻紗）以直鏈狀的低密度聚乙烯 的被膜覆被之直徑爲0 . 2〜〇 · 5 mm程度的覆被纖維，於強 度、硬度、彈性、編織的容易度等，是最適的纖維。又， 亦可選擇其他的有活體活性（例如，具有骨傳導或誘導能） 的纖維。 又，用以構成芯材 9的組織構造物，由於在特願平 6 - 2 5 4 5 1 5號中有詳細的揭示，故不作更多的說明。 積層於芯材9的上下兩面的多孔物1，係與上述有機一 無機複合多孔物相同者，亦即，係在活體內分解吸收性聚 合物中實質上均一地分散著活體活性的生物陶瓷顆粒所成 之活體內分解吸收性的多孔物，爲具有連續氣孔，且於氣 孔裏面與多孔物表面有一部份的生物陶瓷顆粒露出者。此 多孔物1係經由上述的本發明之製造方法所製作，其氣孔 率、連續氣孔的孔徑、連續氣孔佔氣孔全體的比例、活體 內分解吸收性聚合物、生物陶瓷顆粒、該顆粒的含有率等， 係如上述者。 此多孔物1爲具有作爲間隔物的作用者，此多孔物1積 層於芯材9的兩面，於將此植入材料1 6插入於頸椎及腰 椎等的椎體間（參照圖6的頸椎C 3 - C 4或腰椎L· 4 - L· 5 )時， 多孔物1因上下椎體之夾壓力而壓縮變形而無縫隙地與椎 體密合，隨著與體液的接觸之多孔物1的水解，骨組織經 由生物陶瓷顆粒物的骨傳導能可傳導形成到多孔物1的內 部，在比較的短期間內多孔物1會與骨組織代換而與椎體 及芯材9直接結合。此時，對芯材9的表面噴吹生物陶瓷 59 312/專利說明書(補件)/92-02/91134292 200300666 顆粒物，作成活體活性化的表面層’則由於經傳導的活體 骨會結合到此經活性化的表面層’椎體與芯材9的直接結 合可在比較的短期間內進行，強度亦可保持。再者’使骨 誘導因子含有於此多孔物1中，則可發揮骨誘導性而更有 效果。 此多孔物1的厚度以作成爲〇 ·5〜3 mm程度爲佳；於較 0 . 5 mm薄的情況，由於因於壓縮變形之椎體的表面的凹凸 之吸收會變難，故與椎體的密合性有降低的顧慮，另一方 面，於較3 mm厚的情況，分解吸收及與骨組織的代換所要 的時間會較長。又，此多孔物1，如圖1 7所示般，以使其 厚度的大約一半埋入芯材9中的方式進行積層，將多孔物 1以芯材9的周緣部圍住爲佳，如此作法，可抑制多孔物 1的周緣的磨損。 又，對此多孔物1，可使其適量地含有上述的骨形成因 子、成長因子、藥劑等，此情況下，於多孔物1的內部的 骨形成可顯著地促進，芯材9與椎體之直接結合可早期地 發揮效果。又，亦可在多孔物1的表面施以上述的氧化處 理以改善濡濕特性，使增殖之骨芽細胞的侵入、生長更有 效果。 固定用軸釘22，將上述芯材9與其兩面的多孔物1貫 通’其兩端則自多孔物1突出。有這樣的固定用軸釘2 2， 則於將此植入材料1 9插入上下的椎體間時，因上下的椎 體的夾壓力，自多孔物1突出的固定用軸釘22前端會咬 入椎體的接觸面，故植入材料i 9可固定於椎體間而不會 60 312/專利說明書(補件)/92-02/91134292 200300666 發生位置偏移的情形。 固定用軸釘2 2的支數以2支以上爲佳’最佳的支數爲 圖示般的3支，此情況下，經由3點支撐，可很安定地安 裝到上下的椎體間，是其優點。固定用軸釘2 2的兩前端， 以形成爲圓錐狀等之尖的形狀爲佳，又，軸釘2 2的直徑’ 爲可確保強度，以1〜3 mm程度爲佳。再者’固定用軸釘 2 2的兩前端的突出尺寸，以〇 . 3〜2 mm程度爲佳。 於將植入材料1插入之最初，由於上下的椎體的夾壓力 會對固定用軸釘2 2作用，故強度大的固定用軸釘是必要 的。因而，此固定用軸釘 22，以使用黏度平均分子量爲 1 5萬以上（而以2 0萬〜6 0萬程度更佳）的結晶性聚-L -乳 酸及聚羧基乙酸等的活體內分解吸收性聚合物所製造爲 佳，又，以使用對此等聚合物以活體活性的生物陶瓷顆粒 物混合者爲佳。又，必要時，亦可經由壓縮成形、鍛造成 形、延伸等方法，使聚合物分子配向以提高強度。 將上述構成的人造軟骨用植入材料1 9，作爲人造椎間板 安裝到上下的椎間板，則如上述般，由於自多孔物1的表 面突出之固定用軸釘22的兩前端會咬入椎體的接觸面， 植入材料1 9可固定於椎體間而不會發生位置偏移的情 形。因而，不須用補助固定具等來固定活體材料，故手術 可容易地進行。而且，如此般將植入材料1 9安裝到椎體 間，則芯材9表面的多孔物1會因上下的椎體的夾壓力而 壓縮變形而無縫隙地與椎體密合，隨著多孔物i的分解吸 收之進行，骨組織會傳導形成到多孔物1的內部，在比較 61 312/專利說明書(補件)/92-02/91134292 200300666 的短期間內多孔物1會與骨組織代換而與椎體及芯材9直 接結合。然而，由於芯材9爲活體不活性的合成纖維，故 骨組織不會傳導形成到其內部，可維持著柔軟性。此芯材 9，由於係將有機纖維作成爲3軸以上的多軸三維織組織 或編組織或此等的複合組織之組織構造物所構成者，具有 與椎間板等的軟骨同程度之機械強度與柔軟性，變形比較 容易，故可行使與椎間板大略相同的行爲而發揮椎間板的 作用。而且，固定用軸釘22亦可在比較的短期間內會被 分解而被吸收，故不會殘留。 如上述般，人造軟骨用植入材料1 9，芯材9係活體模仿 性，其舉動酷似於軟骨組織，而且爲具備與椎體骨的骨終 板之直接結合能與初期自立性者，固定用軸釘2 2前端會 突刺到骨組織，可防止本身之橫向偏移與脫開轉移，多孔 物1會與骨組織直接結合可於組織學上一體化者。因而， 此植入材料1 9，如上述習用的三明治構造之自立型人造椎 間板的缺點可完全消除。 又，上述的人造軟骨用植入材料19,係於芯材9的兩面 積層有多孔物1，固定用軸釘22的兩前端爲自多孔物1 突出，惟，亦可作成在芯材9的單面積層以多孔物1，並 使固定用軸釘2 2的前端突出的構成。這樣的構成的人造 軟骨用植入材料，由於將其單面以固定用軸釘2 2固定於 一方的椎體上，固定強度雖會降低，但可防止植入材料1 9 的位置偏移。又，亦可使多孔物1的厚度隨著由前面方型 部往後面圓狀部接近而徐徐地增大，若如此做，上下的椎 62 312/專利說明書(補件)/92-02/91134292 200300666 體之間的空間部分於前側會稍狹窄而於後側會較寬，故爲 可完全吻合該空間部而安裝之植入材料。又，依於須要， 代之以貫通的固定用軸釘2 2，亦能以短的固定用軸釘埋入 於芯材9的表層部中，亦可使該軸釘的前端自多孔物1突 出的方式來作成。 以上，係就人造椎間板用的植入材料1 9所作的說明， 惟，只要將其形狀適當地變更，可作成爲人造椎間板以外 的半月板及各種的關節軟骨用的植入材料是不言而喻的。 以上’雖係參照特定的實施形態詳細地做了說明，惟， 在不逸出本發明的精神與範圍可加以作各種的變更及修 正，對業者而言是不言而喻者。 本申請案，係依據2〇01年11月27日提出申請的曰本 專利申請案（特願2001-360766)、2001年12月〇3日提 出申請的日本專利申請案（特願2001-368558)、2002年 02月20日提出申請的日本專利申請案（特願 2002-043137)、2002年08月23日提出申請的日本專 手K申B円案（特願2002-242800)、2002年09月3〇日提出 申請的日本專利申請案（特願2 Q 0 2 _ 2 8 5 9 3 3 )、2 〇 〇 2年〇 9 月3 0日提出申請的日本專利申請案（特願2 〇 〇 2 _ 2 8 5 9 3 4 ) 者，將其內容取用於此作爲參照。 [產業上之可利用性] 本發明之植入材料，可實用於作爲活體骨組織重建用的 植基構造、補綴材、骨塡料、其他的人造植入材料與骨組 織之間的介在物、海綿骨的代替物、藥劑徐放用的載體等。 312/專利說明書(補件)/92-〇2/91134292 63 200300666 又，本發明之植入材料，與其他的活體內分解吸收性構材 及/或活體內非吸收性構材作成爲結合物，可實用於作爲 各種骨固定用材、椎體固定材、各種活體骨間間隔物、骨 缺損部位塡補材、補綴材或塡充材、人造軟骨材等。 [圖式簡單說明] 圖1爲顯示本發明之植入材料之一實施形態的立體圖。 圖2 (a)、（b)、（ c)爲同實施形態的植入材料之一使用 例的說明圖。 圖3爲顯示本發明之植入材料的其他實施形態之立體 圖。 圖4爲同實施形態之植入材料的母材之立體圖。 圖5爲同實施形態之植入材料的縱剖面圖。 圖6爲同實施形態之植入材料的一使用例的說明圖。 圖7爲顯示本發明之植入材料的又一其他實施形態之立 體圖。 圖8爲顯示本發明之植入材料的又一其他實施形態之立 體圖。 圖9爲顯示本發明之植入材料的又一其他實施形態之立 體圖。 圖1 Q爲顯不本發明之植入材料的又一其他實施形態之 立體圖。 圖11爲同實施形態的植入材料的剖面圖。 圖12爲同實施形態的植入材料的一使用例之說明圖。 圖^爲顯示本發明之植入材料之又一其他的實施形態 312/專利說明書(補件)/92-02/91134292 64 200300666 之剖面圖。 圖1 4爲顯示本發明之植入材料之又一其他的實施形態 之剖面圖。 Η 1 5爲顯不本發明之植入材料之又一其他的實施形態 之剖面圖。 圖爲顯示本發明之植入材料之又一其他的實施形態 之立體圖。 圖17爲同實施形態之植入材料的剖面圖。 元件符號說明 1 有機-無機複合多孔物 lb 入口 2 軸釘 2a 凹凸 3 鋼線 4 收束帶 5 孔 6 母材 6 a 空洞 6 b 空洞的入口 6d 母材的上面 6 e 母材的下面 固定用突起 6g 凹穴 6 h 尖的軸釘 312/專利說明書(補件)/92-02/91134292 65 200300666 6 i 壁部 6 j 連通孔 6 η 曲率小的部分 7 表皮層 8 網狀物 8 a 網眼 8 b 相當於經紗部分 8 c 相當於緯紗部分 9 芯材 1 0〜 1 9 植入材料 2 0 頭蓋骨 2 1 缺損部分 2 2 固定用軸釘 3 0 螺絲 312/專利說明書(補件)/92-02/91134292200300666 发明 Description of the invention [Technical field to which the invention belongs] The present invention relates to an implant material composed of an organic-inorganic composite porous material having bioactivity and decomposability, and a method for manufacturing the same, and the composite porous material and Implant materials made of other living materials. [Prior art] As an inorganic porous material for medical purposes, a known one is a porous ceramic obtained by trial firing or sintering a bioceramic. However, this porous ceramic is hard but brittle when it is used in the application of plant-based structures or supplemental materials for the reconstruction of living bone tissue. Therefore, it is often necessary to worry about the slight impact caused by surgery after surgery. Destruction. In addition, it is difficult to process and deform the shape of the porous ceramic in a surgical site so as to match the defect of the living bone tissue. Furthermore, in order to completely replace living bones, sometimes a long period of time of more than 10 years is required. During this period, concerns about the dangers caused by damage will always exist. On the other hand, as the organic porous material for medical purposes, there are known, for example, the sponges disclosed in Japanese Patent Publication No. 6 3-6 4 9 8. This sponge is usually used as a supplement material for hemostasis during surgery and for suture of living soft tissues (such as internal organs). Therefore, it is a sponge with continuous pores composed of polylactic acid which is decomposed and absorbed in vivo. This sponge is produced by dissolving polylactic acid in benzene or dioxane, freeze-drying the polymer solution, and subliming the solvent. However, the porous material produced by the above-mentioned sponge-like freeze-drying method requires sublimation for a long time, and it is difficult to completely remove the solvent. Its thickness is 5 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 degrees It is very thin, it is only less than imm (usually several hundred degrees), and it is difficult to produce a porous material with a thickness of several mm or more. As another method for producing a porous material having continuous pores, various methods have been reviewed in addition to the freeze-drying method described above. However, it is not easy to obtain a porous material having a thickness of several mm or more. Such a thin porous shape fits into the complicated and large three-dimensional space of the damaged part of living tissue, and can play a role as a temporary patch material. However, it is intended to reconstruct the three-dimensional tissue of the damaged part. Materials are not feasible. Therefore, those who have a thick thickness and can be finely processed into a three-dimensional three-dimensional shape of any shape before or during surgery can be relatively quickly decomposed and absorbed to replace living bones, and are eagerly awaited. In addition, as another effective method for producing a continuous porous material, a polymer is mixed with a large amount of water-soluble, soluble particles such as Na C 1 of a predetermined size, and is formed into a sheet-like thin sheet. The dissolution method of immersing the particles in water (solvent) to form continuous pores having the same pore size as the particles is a known method, but it is difficult to completely dissolve the particles, so it is limited to Thin continuous porous material. Further, if the ratio of the water-soluble particles is not sufficiently high, it is difficult to generate continuous bubbles. In addition, when the porous substance is buried in a living body, the toxicity of the particles remaining as a source of annoyance is a problem. Like the sponges mentioned above, porous materials that do not contain inorganic particles such as bioactive bioceramics are non-bone because they lack direct bonding, conductivity, and substitution with living bone tissue such as hard bones and cartilage. The invasion and presence of bud cell lines and bud cells, etc., therefore, to completely replace living group 6 312 / Patent Specification (Supplement) / 92-〇2 / 91134292 200300666 weaving until regeneration requires a considerable period of time, or even finally Never replaced in a lifetime. Therefore, the applicant has proposed in the past: "Bone bud cells can be seeded as a three-dimensional cube-based plant structure for bridging large defect sites and implanted by living cells containing biological ceramic particles with biological activity inside. Decomposition of the body with continuous pores and thick porous bodies made of absorbent polymers "(Japanese Patent Application No. 8-229280). This porous material was obtained by a method for producing a porous material called a solution precipitation method. In other words, the biodegradable absorbent polymer is dissolved in a mixed solvent of a solvent and a non-solvent having a higher boiling point than the solvent, and the bioceramic particles are dispersed and prepared into a suspension. A method in which a mixed solvent is volatilized at a low temperature depending on the boiling point of the solvent, and a biodegradable absorbent polymer is precipitated in vivo in which bioceramic particles are enclosed. The principle of forming a porous material using the solution precipitation method is as follows. That is, from the above suspension, the mixed solvent is volatilized at a low temperature depending on the boiling point of the solvent, the solvent with a lower boiling point will be preferentially volatilized, and the solvent with a higher boiling point will gradually rise. When the solvent and non-solvent reach a certain ratio, The solvent can no longer dissolve the polymer. Therefore, the polymer will begin to precipitate and precipitate, and the bioceramic particles that begin to settle will be enclosed. The precipitated and precipitated polymer will shrink and solidify due to a high proportion of non-solvent, and will be fixed in the state containing the bioceramic particles. And form a cell structure with a thin cell wall of the connected polymer enclosing the mixed solvent. After that, the remaining solvent evaporates and disappears when stomata are generated while the cell wall is destroyed, and the non-solvent with a high boiling point slowly volatilizes through the stomata and finally evaporates and disappears completely. 7 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 As a result, the remnants of the mixed solution enclosed by the cell wall of the polymer become continuous pores, forming a porous body containing bioceramic particles. The above-mentioned solution precipitation method is an excellent method for forming a thick porous material from a low foaming ratio to a high foaming ratio, and can produce a three-dimensional block having a thickness ranging from several mm to tens of mm. Porous. For this reason, it is useful to create a plant-regenerating structure for bone regeneration with a three-dimensional shape with large undulations. However, the disadvantage of this method is that in a suspension containing a large number of bioceramic particles, bioceramic particles that are larger in particle size distribution in the particle size distribution begin to settle when the solvent begins to evaporate, and the polymer begins to precipitate. · During the precipitation, there are already a lot of bioceramic particles settling in the concentration ratio toward the bottom. Therefore, the content of the bioceramic particles of the obtained porous material is not uniform, and the content of the bioceramic particles from the upper side of the porous body to the bottom side is more uniform. The larger the amount, it is unavoidable. It is difficult to effectively use the porous material having such a non-uniform content in a uniform concentration ratio for applications such as a plant base structure for repairing bone tissue, a patch material, and an epiphyseal material. This problem can be improved to some extent by controlling the sedimentation speed of the bioceramic particles, but it cannot be completely solved. In particular, it is difficult to produce a three-dimensional porous bone reconstruction material containing homogeneous and uniform concentrations of bioceramic particles of 30% by weight or more. The porous material with low content of the bioceramic particles produced by the above method, most of the bioceramic particles are covered by the cell wall of the polymer and are difficult to be exposed to the inside of the continuous pores and the surface of the porous material, so they are buried. In vivo, it is difficult to exert the conductive effect of the living bone group 8 312 / patent specification (supplement) / 92-〇2 / 91134292 200300666 due to bioceramic particles immediately after embedding, and it is necessary to wait for the formation of the epidermal layer. It is a problem that the polymer decomposes to reveal that the biological activity is exhibited under the lag of time. In addition, even if the porous material manufactured by the above method is selected as the fine ceramic particles, the content rate is only about 30% by weight. If it is contained in a larger amount, the bioceramic particles may It is easier to settle, so the bottom side of the obtained porous substance contains a large amount of bioceramic particles, and becomes extremely brittle. In addition, for porous materials manufactured by the above method, although the proportion of continuous pores is usually as high as 80% or more, in terms of pore diameter, generally, only a relatively small number / m or even several dozens / m can be obtained. Therefore, it is absolutely difficult to say that it is formed into an ideal pore size and morphology of pores that invade and grow into the porous body as bone bud cells. A method for making inorganic particles highly charged by a method different from the above-mentioned solution precipitation method of the applicant has also been reviewed. One of the useful methods is to make a polymer filled with about 50% by weight of organisms. The ceramic particles are produced by a sintering method in which the particles are heated and fused on the surface to obtain a continuous porous material. This method is not a new method, and it is a well-known method for producing a porous material such as an epoxy resin, a vinyl chloride resin, or the like in a granular form. This method requires surface fusion, so there is a limit to the amount of radon filling. It is difficult to make radon filling more than 50% by weight, and it is difficult to control the pore size. It is also difficult to obtain good quality. The present invention is to provide various implant materials composed of organic-inorganic composite porous materials with high filling capacity of inorganic particles, which can completely solve these problems, and the materials 9 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 manufacturing method for the purpose. In addition, it is an implant material composed of a combination of organic-inorganic composite porous materials and other living materials; it is provided as a bone fixation material user, as a spinal fixation material (intervertebral installation material, vertebral body reinforcement material), etc. Users, as substitutes for allograft bone grafts or autograft bone grafts, cortical bone, cancellous bone, or a combination thereof, as users of bone defect parts and deformed parts, and repair and filling materials, etc. For users of hard cartilage base structure, as artificial cartilage users. At present, bone fixation materials are used in, for example, sternal midsection incision and locking operations, in which fixed shaft nails composed of absorbable polymers decomposed in vivo are embedded in intramedullary bridges on both sides of the incision of the sternum. The fixed shaft nail will slowly disintegrate and be absorbed in the sternum. Therefore, it is not as good as a non-absorbable ceramic or metal shaft nail to have to be taken out of the body again. However, because it is not bone conductive and does not It can be directly combined with bone tissue and can only function as a wedge. It only has the effect of temporarily fixing the closed sternum and closing the incision surface. Therefore, as seen in the majority of the sternum of the elderly, only the thin cortical bone of the spongy bone remains in a wafer shape and becomes brittle. Even if this sternum is embedded with a fixed shaft nail, I want to give full play to The role of the "wedge" to improve the stability of the fixation is also difficult, and it will not replace bone tissue, which is a problem. On the other hand, ceramic porous materials such as hydroxyapatite (HA) used for the joint fixation of broken bones or fractures other than the sternum are easy to crack, and it takes a long time to be absorbed in the body. problem. There is also an opinion that even if it takes a long time, as long as it is embedded in the living bone, the strength can be restored, so there is no problem, but the damage during the entire implantation period has its concerns. The invention of the implant material used as the bone fixation material is designed to solve these problems 10 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666. However, conventional vertebral body fixing materials, for example, titanium or carbon steel structure (C age) used as a spacer between vertebral bodies during square vertebral body fixation before lumbar vertebral disease, can satisfy The chemical biological affinity on the surface, but the mechanical biological affinity is different from the living body. Therefore, under the long-term residual of foreign matter, there will be concerns about the harmfulness of surrounding tissues due to the destruction and corrosion over time. problem. There are also problems such as the inconsistency of the mechanical properties of the steel bone structure and the living body, and the problem that the steel bone structure will sink into the vertebral body through the bony end plate exposed through the reaming hole. In particular, the carbon steel structure is hard and brittle, so it will break along the carbon fiber, and sometimes even fragments will be generated. Therefore, there are always concerns about the harmfulness caused by it. In addition, autogenous bones filled with these steel-bone structures are usually supplied by intestinal bone extraction, the problem of obtaining the quantity, and the complexity of the post-extraction processing (after Treatment and crushing of the intestines and bones, filling of steel structures, and disposal under aseptic conditions) are all problems. The implant material used as the vertebral body fixation material of the present invention is mainly intended to solve these problems. On the other hand, the same type of bone grafts used to cut and process the bones of the deceased, or autograft bone fragments taken from large bone parts such as bone discs and ribs to repair the bone defect site are routine operations. . As long as the bone graft of the same kind has a cortical bone integrated block on the surface of the cancellous bone, the cortical bone portion of the bone defect can be supplemented with the cortical bone of the bone fragment, and the cancellous bone of the bone defect can be replaced. Partially supplemented with the spongy bone of the bone piece. However, because the same kind of bone graft is cut and processed from the deceased's bone, 11 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 must obtain a large amount of deceased's bone as a raw material and provide a sufficient amount of transplantation Bone fragments are not easy. This is a problem, and the shape that can be processed is also limited, which is also a problem. Also, although it is the same kind of transplanted bone piece, the transplanted bone piece is bone tissue different from its own bone tissue. Depending on the implantation conditions, it may be destroyed by natural absorption, or there may be concerns about insufficient strength and reduction. . In addition, sterilization is necessary because it is related to the bones of other people. Depending on the processing conditions, the bones may degenerate. Therefore, sufficient control of the sterilization conditions is necessary. However, the time or treatment was insufficient, and serious accidents occurred from the time of burial to death. Although it is possible to avoid such accidents, the number of bone grafts taken during the operation is inevitable. On the other hand, implantation of ceramic implant materials such as hydroxyapatite (HA) and tricalcium phosphate (TCP) in bone defect sites is also being performed. However, in this case, the cortical bone in bone defect sites It is a problem that the same parts as the sponge bone are repaired with ceramic that is as hard as it is, and because this ceramic remains semi-permanently, the bone defect cannot be reconstructed with its own bone tissue, which is a problem. Therefore, the method of making porous ceramics instead of sponge bone has become quite practical. However, ideally, these synthetic artificial bones are the best substitutes for living bones. Since they need to be replaced for a long period of time after 10 to 20 years, the accident as a physical foreign body is sometimes required. Regret. The implant materials used in the present invention as substitutes for homogeneous bone grafts and autograft bone slices are mainly intended to solve these problems. In addition, as a conventional patch, filling and covering material for a bone defect site or a deformed site, a perforated (mesh-shaped) plate made of metal such as titanium having a large number of holes formed therethrough is used. Sintered dense bioceramics and perforated flat or uneven plates made of porous materials, such as 12 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666. However, the metal punching plate lacks physical biocompatibility, and it will remain as a foreign body in the repair site. Therefore, the corrosion in the long-term embedding or the dissolution of metal ions will harm the surrounding tissues. Sexual concerns are never able to completely replace the defect site through bone tissue, which is the problem. In addition, the porous ceramic sintered body is hard but brittle, and easily cracks. There is a concern that it will be damaged when it is impacted during use. It cannot be post-formed during surgery according to the three-dimensional shape of the bone defect. This is a problem. The implant materials used as the patch, filling and covering material of the present invention are those who seek to solve these problems. In addition, the conventional artificial cartilage, for example, the fully-replaced autonomous artificial intervertebral plate that is clinically tried, is superimposed on both sides (upper and lower) of a core composed of a living body of inactive polyethylene or a body-fitting rubber. Two metal endplates made of upper titanium or cobalt-chromium (endp 1 ate) are so-called sandwich-shaped artificial intervertebral plates, and the core is made close to a living intervertebral plate in a state where two pieces of polyethylene are superimposed. The action, in the case of rubber, can be imitated due to its elasticity. In addition, it can prevent stagnation when inserted into the intervertebral body. In order to provide an autonomous effect, it protrudes from the surface of the metal plate by several angles, and it is a structure that is fixed by puncturing the concave surface of the vertebral body. However, since this artificial intervertebral plate is a sandwich structure of a material different from that of a living intervertebral plate, friction will occur at the interface between repeated actions', and its movement must not be said to be the same as a living intervertebral plate. The protruding angle of the plate, while hurting the upper and lower vertebral bodies, will slowly sink into the vertebral body under long-term use, invading and causing greater harm, etc. There are such major shortcomings that they cannot be compared with the upper and lower vertebrae. The body is directly combined and self-supporting and fixed. 13 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666. The implant material for artificial cartilage of the present invention is mainly for those who seek to solve these problems. By interposing the porous material of the present invention with the end plate or the vertebral body, the physical gap between the artificial intervertebral plate can be expected. It is also an object of the invention to bury it tightly, and to directly bond with the vertebral body through bone conduction. [Summary of the Invention] The most basic implant material of the present invention is a porous body with biodegradable and absorbable biodiversity in which the bioactive ceramic ceramic particles are uniformly dispersed in the biodegradable absorbent polymer, and has continuous pores. In addition, the organic-inorganic composite porous material with a part of the bioceramic particles exposed inside the stomata or inside the pores and the surface of the porous material. As described below, this porous material has a porosity of 50 to 90%. 'Continuous pores account for 50 to 90% of the total pores. This continuous pore is made to be suitable for the invasion and proliferation of bone bud cells. 1 Q ~ 4 Q 0 // m required for stabilization. Moreover, the bioceramic particles contain a large amount of 6 to 90% by weight, the thickness of the porous material is large, 1 to 50 mm, and the three-dimensional shape is formed. This basic implant material can be used in various medical applications as, for example, plant-based structures for replacement bone tissue regeneration, covering and covering materials, callus materials, substitutes for sponge bone, and bone tissue for other artificial implants. Intermediates between materials, carriers of medicines, etc. In addition, the in vivo biodegradable and absorbable porous material in which the bioactive bioceramic particles of the bioactive particles are uniformly dispersed in the biodegradable absorbent polymer is characterized by having continuous pores and a content ratio of the bioceramic particles. The implant material composed of 60-90 weight percent organic-inorganic composite porous material is also the basic implant material of the present invention. 14 312 / Patent Specification (Supplement) / 92-〇2 / 91134292 200300666 is used in the same various medical applications as above. The implant material composed of the organic-inorganic composite porous material described above can be manufactured by the manufacturing method of the present invention. The method is: dissolving in vivo decomposable and absorbent polymer in a volatile solvent, dispersing the bioactive ceramic particles in vivo, preparing a mixed solution, and preparing a non-woven fiber aggregate from the volatile solvent. A method of pressing and molding under heating to form a porous fiber assembly molded product, and then immersing the fiber assembly molded product in a volatile solvent, and then removing the solvent. On the other hand, the implant material of the present invention to which the above-mentioned organic-inorganic composite porous material is applied is formed by using the above-mentioned organic-inorganic composite porous material to decompose and absorb an absorbent polymeric material in other dense living bodies as a combination. The main types of this implant material are the following four: The first implant material is the above-mentioned other in-vivo decomposable absorbent structure as a stud, and the aforesaid porous material is used as a binder by the axle. Both ends of the shaft nail are implant materials for bone fixation that protrude outward from the porous material. This implant material is suitable for use in cases where the sternal fixation of the incision and lock is performed, for example, during the operation of the sternal fixation and lock. The second planting material is a base material composed of other biodegradable and absorbent materials composed of biodegradable and biodegradable polymers containing voids that are open to the outside and are bioactive in vivo; The porous material is filled with the above-mentioned porous material as a binding material, and the porous material is an implant material in a state where the porous material is partially exposed. This implant material is suitable for anterior or posterior vertebral body fixation, etc., and is preferably used as a vertebral body fixation material such as an intervertebral body spacer. 15 31Z / Patent Specification (Supplement) / 92-02 / 91134292 200300666 The third implant material is the other in vivo biodegradable absorbent structure which is a biodegradable bioabsorbable polymer containing bioactive bioceramic particles. The formed epidermal layer 'The epidermal layer is superimposed on a part of the surface of the above-mentioned porous material in a block shape and combined into an integrated implant material. This implant material 'block-like porous material can play the role of sponge bone, and the epidermal layer can play the role of cortical bone' is an artificial synthetic material which is suitable for full absorption and replacement of the same kind of bone grafts and substitutes for autograft bone slices. The better of bone. The fourth implant material is another in vivo biodegradable absorbent structure. It is a network composed of biodegradable bioabsorbable polymer containing bioactive bioceramic particles, and is charged in the mesh of the mesh. The implant material is combined with the above porous material. This implant material is suitable for use as a patch, coating, support, or filling material for bone defect or deformed parts. Furthermore, another implanting material of the present invention to which the above-mentioned porous material is applied is a laminate of the above-mentioned porous material on a multi-axis two-dimensional woven structure or a weaving structure or a composite structure of three or more axes with organic fibers. The artificial cartilage implant material is integrated into at least one side of a core material composed of a tissue structure. This implant material is suitable for use as an artificial intervertebral plate or arch plate which is self-supporting and fixed in combination with the upper and lower vertebral bodies. [Embodiment] Hereinafter, preferred embodiments of the implant material and the manufacturing method of the present invention will be described in detail. The most basic implant material of the present invention is the bioactivity of the bioactive ceramic particles uniformly dispersed in the biodegradable absorbent polymer in vivo 16 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 Live The body decomposes and absorbs porous materials; it is composed of organic-inorganic composite porous materials with continuous pores and part of bioceramic particles exposed in the pores or inside the pores and the surface of the porous material, in its preferred embodiment As a biodegradable absorbent polymer, a polymer that has been practically used and has been confirmed to be safe, and can be decomposed relatively quickly, and is not brittle even if it is porous. That is, a polyabsorbent poly-D, L-lactic acid, a block copolymer of L-lactic acid and D, L-lactic acid, and copolymerization of lactic acid and carboxyacetic acid can be used in the form of amorphous or a mixture of crystalline and amorphous polyabsorbents. Substances, block copolymers of lactic acid and p-dioxanone, block copolymers of lactic acid and ethylene glycol, copolymers of lactic acid and caprolactone, or mixtures thereof, and the like, decompose and absorb the polymers in vivo. The viscosity average molecular weight is considered in the production method of the present invention, and it is preferable to use a period of 50,000 to 1 million in consideration of the period during which the fibrous aggregate in the form of a non-woven fabric is easily decomposed and absorbed in a living body. In particular, poly-D, L-lactic acid, a block copolymer of L-lactic acid and D, L-lactic acid, a copolymer of lactic acid and carboxyacetic acid, a copolymer of lactic acid and p-dioxane, and amorphous due to monomer ratio. When a biodegradable absorbent polymer such as a ketone block copolymer is formed into a nonwoven fabric-like fiber assembly according to the manufacturing method of the present invention, and the fiber assembly formed by pressure-molding it under heating, From the point of view of the solvent characteristics during volatile solvent treatment, it is a good one. If these polymers are used, even if they contain a large amount of bioceramic particles, they will not be brittle, have the compressive strength of Bimei sponge bone, and have the same properties as ceramic monomers. The porous materials are different, and they can be thermally deformed at a relatively low temperature (7 Q ° C), and can be quickly decomposed in vivo. All organic-inorganic composite porous materials can be absorbed within 6 to 12 months. Composition of implant material. Implants with these characteristics 17 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666. It is an excellent filling material for the damaged part of living bone. Because it is a composite, it is different from ceramics alone, and there is a residual viscoelasticity due to the resin component. During surgery, it can be made into a thermally opened slit in a way that conforms to the defect, which has the unique advantages of thermoplastic polymers. Since the molecular weight of the in vivo decomposable absorbent polymer affects the time from hydrolysis to total absorption and whether it can be fibrillated, it is preferable to use a polymer having a viscosity average molecular weight of 50,000 to 1G as described above. Polymers with a viscosity average molecular weight smaller than 50,000, although the time to hydrolyze them into oligomers and even low molecular weights of monomer units is short, but due to insufficient silk drawability, spraying means according to the manufacturing method of the present invention. It is difficult to form a fibrous aggregate under one side of fibrosis. In addition, polymers having a viscosity average molecular weight higher than 10 million are not suitable as polymers for composite porous materials because it takes a long time to complete hydrolysis for the purpose of replacing them with living tissues as soon as possible. Although it varies depending on the polymer, the preferred average molecular weight of viscosity is preferably about 100,000 to 300,000. If an in vivo biodegradable polymer having a molecular weight in this range is used, the formation of the fiber assembly is easy. Moreover, an implant material having a composite porous body with an appropriate hydrolysis completion time can be obtained. Moreover, in the implant material composed of the organic-inorganic composite porous material, as the bioceramic particles dispersed in the porous material, it is possible to use bioactive particles with good bone conduction energy (sometimes expressed as bone marrow conduction energy). ) Those with good living affinity. Examples of such bioceramic particles include surface-active sintering, trial sintering of hydroxyapatite, apatite wollastonite ceramics, in-vivo tentative firing and total absorption in vivo 18 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 Knotted hydroxyapatite, dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, octaphosphate 1¾, calcite, ceravital, diopside, natural coral, etc. Of the particles. In addition, alkaline inorganic compounds or basic organic compounds can be used on the surfaces of these particles. For the reason that it is ideal to perform tissue regeneration by completely replacing the bone tissue itself, among them, the bioabsorbable bioceramic particles that can be fully absorbed in the body and completely replaced with the bone tissue are preferred, especially Untested and unsintered hydroxyapatite, tricalcium phosphate, and octacalcium phosphate have high activity, excellent bone conduction energy, excellent biocompatibility, low hazard, and can be absorbed by the body in a short period of time. For the fittest. The above bioceramic particles use an average particle size (average particle size of primary particles) of 0. 2 ~ 10 # m is better. If bioceramic particles with a larger particle size are used, the fiber will be cut into smaller fibers when the mixed solution prepared by mixing the particles is sprayed for fiberization in the manufacturing method of the present invention. Short, it is difficult to form a fiber assembly. Even if the fiber assembly is formed, the bioceramic particles will settle to some extent before the fiber is solidified, causing concerns about uneven dispersion. If the size exceeds 20 ~ 3 0 // m, even if it is fully absorbent, it takes a long time to completely absorb it, and the tissue reaction sometimes occurs during it, so it is not good. A more preferable particle size of the bioceramic particles is 0.2 to 5 // m. If such a bioceramic particle is used, even in the present invention, the particles are mixed at a high concentration to make the mixture 1 When the fiber aggregate is formed by a fiber diameter of about 3 // m to form a fiber aggregate, the fiber is also difficult to cut. At the high concentration of the present invention, the particles will be covered by the fiber in a state exposed from the fiber. After encapsulation, the fiber assembly was immersed in a volatile solvent. 19 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 After stain treatment, the particles became composite porous exposed from the surface and the inside of continuous pores. Thing. The content of bioceramic particles is organically used for medical purposes such as regenerative medical engineering-based plant structures and carriers or bone cement for DDs, substitutes for special-shaped sponge bone (same graft bone fragments), etc.- In the case of an implant material composed of an inorganic composite porous material, the reason for setting it to 60 to 90 weight percent is the one that takes into consideration the effect of biological activity. As in the manufacturing method of the present invention, a fiber aggregate containing bioceramic particles is formed, and the porous fiber aggregate formed product formed by pressing and forming under pressure under heating is immersed in a volatile solvent to obtain a composite porous material. In the range that can be fibrillated, it can contain a large amount of bioceramic particles, so as described above, the content rate of bioceramic particles can be as high as 60 ~ 90 weight percent (equivalent to using an average particle size of 3 // m as the specific gravity is 2 . The volume percentage of 7 particles is a high ratio of about 41 to 81%). If the content of bioceramic particles exceeds 9 Q% by weight, it will be cut short during fiberization, and it is difficult to obtain satisfactory fibers. The formation of fiber aggregates will be difficult. At 60 weight percent, the bioceramic particles will be insufficient and there will be fewer exposed on the surface. Therefore, the biological activity of the bioceramic particles cannot be exerted from the beginning of the implant material being buried in the living body. In this way, a composite porous material capable of uniformly dispersing biologically active bioceramic particles at a high content of 60 to 90% by weight is one of the basic implant materials of the present invention which has not been available so far. The preferred volume percentage of the bioceramic particles is 50 to 85 volume percentage. This volume percentage is the percentage of the volume of the bioceramic particles with respect to the volume of the polymer when the porosity of the polymer of the composite porous material is 20 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 as 0%, Even if the weight of the contained bioceramic particles is the same, it will change depending on the specific gravity of the bioceramic particles and the average particle size volume percentage. Therefore, it is preferable to consider the specific gravity and average particle size of the bioceramic particles so as to contain 50 to 85 volume percent. A more preferred volume percentage is 50 to 80 volume percent. Porous ceramics obtained by sintering ceramics such as hydroxyapatite are hard and brittle, and thin objects are easily cracked or damaged by external forces. Therefore, they are not satisfactory as implant materials. In contrast, bioceramic particles contain composite porous materials that decompose and absorb polymers in an amorphous living body, and the content of bioceramic particles is as high as 60 to 9 ◦ by weight of the polymer, Combining effect, it has the compressive strength of concrete brittle bone that is not brittle and maintains flexibility (specifically, compressive strength of about 1MPa ~ 5MPa). It can be used as a substitute for sponge bone and as above. Other medical uses. The compressive strength described above is an automatic graph machine (Auto graph) AGS-2000D manufactured by Shimadzu Corporation, in accordance with the test method of JISK 7 1 8 1 (however, the size of the sample is set to 1 〇 X 1 〇 X 15 mm, the compression rate was fixed at 5 mm / min). The implant material's porosity (total porosity) of the organic-inorganic composite porous material is 50% or more. Although it can technically achieve about 90%, the physical strength and bone of the composite porous material The consideration of both the invasion and stabilization of the bud cells is preferably about 6 Q to 8 Q%. In addition, in terms of the efficiency of the invasion of the bone bud cells into the center of the composite porous material, continuous stomata occupy 50 to 9 of the total stomata. 0% is better, especially 70% to 90%. 21 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 The continuous pores of this organic-inorganic composite porous material have a pore size of about 1 Q Q ~ 4 ◦ Q // m. The pore diameter of porous ceramics and the invasion and stabilization of osteoblasts were studied several times. As a result, it was learned that a pore size of 3 0 0 ~ 4 0 0 // m is most effective in calcification, and the more it deviates from it The effect is smaller. Therefore, although the pore diameter of the composite porous material is 1 QQ ~ 4 0 0 // m as described above, it can also be a pore diameter in a range of 50 ~ 500 // m, and the distribution center is 200 ~ 400 // m. Because the continuous pores are larger than 4 QQ // m, and the porosity (full porosity) is higher than 90%, because the strength of the composite porous material will be reduced, it is likely to be easily destroyed in the living body. Very big. On the other hand, if the pore size is smaller than 1 Q 0 // m and the porosity is lower than 50%, the strength of the composite porous material can be improved, but the invasion of bone bud cells is difficult. The time from hydrolysis to complete absorption will be lengthen. However, such a composite porous material having a small pore size is expected to be a carrier for D D S which can maintain a relatively long release property in parallel with the decomposition of the polymer, and may be used depending on the situation. The continuous pores have a better pore diameter of 150 ~ 350mm, and a more preferable porosity (full porosity) of 70 ~ 80%. In addition, in the manufacturing method of the present invention, the pore diameter of the continuous stomata and the ratio of the continuous stomata to the entire stomata are adjusted when the fiber assembly is press-formed into a fiber assembly molded product. The shape of the fiber assembly molded article can be controlled by adjusting the external pressure to maintain the shape while immersed in a volatile solvent. The implant material composed of the above-mentioned organic-inorganic composite porous material can be used, for example, in the defect site of living bone. At this time, the thermoplasticity of the biodegradable absorbent polymer is used to heat the implant material to 7 0 ° C is deformed in accordance with 22 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 so that it conforms to the shape of the defect. Since it can be buried in the defect seamlessly, the embedding operation can be simple and easy. Proceed correctly. In addition, due to the toughness of the absorbent polymer and the degree of ceramics of the decomposed absorbent polymer in vivo, it is used in surgery to cut into any shape without breaking the shape. When the implant material composed of the composite porous material is buried in the defect site of the living bone as described above, the liquid will quickly penetrate the inside of the composite porous material through the continuous pores from the surface of the composite porous material. On both the surface and the inside of the continuous pores, the hydrolysis of the decomposed absorbent polymer in vivo proceeds almost simultaneously, and the entire porous body is decomposed uniformly. In addition, through the bone conduction energy of the bioceramic particles exposed on the surface of the composite porous material, the bone tissue in the surface layer of the composite porous material can be quickly conducted to grow and form small pillars of bone and grow within a short period of time. The bone defect of the living body is combined, and at the same time, the bone conduction energy through the bioceramic particles exposed inside the stomata, the bone tissue will invade the inside of the composite porous material, and the bone bud cells will conduct and grow, so it will directly bind with the surrounding bone. This phenomenon becomes remarkable as the decomposition of the decomposable absorbent polymer in vivo progresses, and it is gradually replaced with the surrounding bone. Therefore, in the end, the polymer will be completely desorbed and absorbed, and the fully-absorbable bioceramic particles will be completely absorbed, and the bone defect site will be completely replaced by the growing bone tissue. The wetting characteristics of the implant material composed of the composite porous material in vivo are significantly improved due to the large amount of bioceramic particles that are exposed on the surface, compared with porous materials that only decompose and absorb polymers in vivo. However, if corona discharge, plasma treatment, 23 312 / patent specification (supplement) / 92-02 / 91134292 200300666 hydrogen oxide treatment are applied to this composite porous material, the wetting characteristics of the polymer may be As a result, the invasion and growth of osteoblasts required for proliferation can be performed more effectively. In addition, various osteogenic factors, growth factors, pharmaceuticals, etc. are filled into the pores of the composite porous material in advance, and they are dissolved and supported in the biodegradable absorbent polymer in advance. Speed, these will be released slowly, so it can promote bone regeneration and cure the disease to make it effective. Examples of the main bone formation factor include BMP, and examples of the main growth factor include monocaine or lymphadenine such as L-1, TNF-α, TNF-cold, and IFN-y. Factor (lymphokine), or colony (J) application factor, or the so-called growth differentiation factors of TGF-α, TGF- / 3, IGF-1, PDGF, FGF, and so on. In addition, as the drug, a drug (vitamin D, prostaglandins, or anti-cancer agent), an antibacterial agent, and the like that can grow bone can be arbitrarily selected. Next, the manufacturing method of the implant material made of the organic-inorganic composite porous material of the present invention will be specifically described in detail. The manufacturing method of the present invention firstly dissolves a biodegradable absorbent polymer in a volatile solvent, disperses the bioactive ceramic particles in vivo, and prepares a mixed solution. As a volatile solvent, it can be used in low-boiling dichloromethane, dichloromethane, methylene chloride, and trichloromethane (methylene chloride), which are easy to volatilize at a temperature higher than normal temperature. chloroform) and other solvents. In addition, a volatile mixed solvent formed by mixing one of these solvents with one or two or more non-solvents having a higher boiling point than these solvents may be used; the non-solvent is, for example, a boiling point of 60 to 1 1 0 ° C range of methanol, ethanol, 1-propanol, 24 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 2-propanol, 2-butanol, tert-butanol, tert-amyl alcohol, etc. Alcohols. Then, a nonwoven fabric-like fiber aggregate was prepared from the above-mentioned mixed solution. As a means thereof, it is preferable to adopt a method of spraying a dissolving mixed liquid to perform fibrillation. That is, the above-mentioned dissolving mixed liquid is contained in a sprayer, and the mixed liquid is sprayed to the sprayed object from the spray hole of the sprayer with a high-pressure spray gas such as nitrogen. The fibers of the ceramic particles decomposing the absorbent polymer in vivo are interconnected with each other, and they are fused and stacked under the fusion of one contact point to form a non-woven fiber-like fiber assembly of any shape and thickness. In this fiber assembly, the shape of the voids between the fibers is different from the cell-like pores, and the fusion-cured fibers form a continuous space of several hundred // m between each other, and the bioceramic particles are surrounded by the fibers (there are also some Those exposed on the surface) are uniformly dispersed throughout the entire fiber assembly. In order to make the resin containing a large amount of bioceramic particles more than 60% by weight (sometimes more than 50% by volume) solidified and uniformly dispersed without precipitation and separation, the resin is contained in the interior. The material with continuous space as pores is very justified by the method of volatilizing the solvent under the formation of fine fibers on one side by spraying as in this manufacturing method, and solidifying in a short time before the separation of bioceramic particles. This is the innovation of the manufacturing method of the present invention. In addition, if an extremely thick composite porous material of 5 to 50 mm is required to be used as an implant material for medical purposes, the fiber assembly can be formed by spraying, and then the solvent is volatilized and dried, and then Spraying is performed repeatedly to increase the thickness to achieve a predetermined thickness. 25 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 As the object to be sprayed, a net made of polyethylene, other olefinic resins, fluororesins, silicone resins, and the like having good peelability can be used. Or plate. In particular, if a spray-like object that can be freely ventilated like a mesh is used, the mixed liquid will be fibrillated by spraying. After it hits the mesh, the volatile solvent will volatilize through the mesh, so the mesh side The fibers on the surface are fused, and without forming a skin layer (only a resin fused layer), it is possible to form a fiber aggregate that can be easily processed by solvent impregnation in the subsequent steps, which is an advantage. As the mesh, it is preferable to have a mesh of 50 to 300, and a mesh having a mesh of greater than 50, because the fibers will be wrapped into the inside through the mesh, so the fiber assembly formed is intended to be drawn from the mesh. Peeling of the mesh becomes difficult, and a mesh with a mesh smaller than 300 meshes, because the volatile solvent is difficult to volatilize smoothly, the fibers on the mesh side will fuse and easily form a skin layer. In addition, the object to be sprayed is not limited to a flat mesh or a plate, and a three-dimensional mesh or a plate having a convex curve and / or a concave curve may be used. If such a three-dimensional object to be sprayed is used, a thick fiber aggregate can be formed according to the three-dimensional shape, which is an advantage. As described above, the fiber assembly formed by spraying and mixing the mixed solution into fibers has a space of several hundreds of meters per fiber, and the proportion (void ratio) of the fiber spaces is about 60 to 90%. In addition, the fibers contain inorganic particles and are uniformly dispersed throughout the entire fiber assembly without settling. The fiber length of the fiber assembly is preferably about 3 to 100 mm, and the fiber diameter is preferably 5 to 5 0 // m. A fiber aggregate having such a degree of fiber length and fiber diameter can be easily fused through a solvent impregnation treatment in a subsequent step, and can be used to form a composite porous material with substantially disappeared fibers 26 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666, which is better. The fiber length mainly depends on the molecular weight of the biodegradable absorbent polymer in the living body, the polymer concentration of the mixed solution, the content and particle size of the bioceramic particles, and the larger the molecular weight, the higher the polymer concentration, the higher the bioceramic particle's The smaller the content rate and the smaller the particle size of the bioceramic particles, the longer the fibers tend to be. On the other hand, the fiber diameter mainly depends on the polymer concentration of the mixed solution, the content ratio of the bioceramic particles, and the size of the spray hole of the sprayer. The higher the polymer concentration, the more the content ratio of the bioceramic particles, and the The larger the hole, the larger the fiber diameter. The fiber diameter also changes depending on the pressure of the jet gas. Therefore, in order to obtain the above-mentioned fiber length and fiber diameter, it is necessary to adjust the molecular weight of the polymer, the polymer concentration, the content and particle size of the bioceramic particles, the size of the injection holes, and the gas pressure. Next, the process proceeds to a step of forming the above-mentioned fiber assembly under pressure by heating to form a porous fiber assembly molded product. First, the fiber aggregate is cured under heat and pressure to produce a preform having continuous voids, and further, the preform is press-formed at a pressure higher than that at this time to obtain a continuous void ratio. Porous fiber aggregate shaped product with good strength and adjusted pore size. In addition, the heating during the press molding is to the extent that the fiber assembly is slightly softened, and the pressing is performed so that the porosity of the composite porous material finally obtained is 50 to 90%, and the continuous porosity The aperture can be adjusted in a manner of about 1 0 to 4 0 0 // m. Then, in the next step, the fiber aggregate formed in the previous step is immersed in the above-mentioned volatile solvent, so that the solvent sufficiently penetrates the inside of the formed article. Then, 'the solvent is removed, and when the fiber assembly molded product 27 312 / Patent Specification (Supplement) / 92-〇2 / 91134292 200300666 is immersed in a volatile solvent, the fiber assembly molded product is filled with In a mold having a fine pore surface, the fiber assembly molded product is immersed while maintaining its shape while applying a moderate pressure to the fiber assembly molded product from the outside. Alternatively, the upper surface of the fiber aggregate formed article may be made to flow through so as to penetrate the solvent. In order to maintain a predetermined shape, it is better to remove the solvent inside the fiber-formed product by vacuum suction as soon as possible. As described above, the fiber assembly molded product is immersed in a volatile solvent to penetrate the inside of the molded product, and the fibers are dissolved in the solvent from the surface, and the fibers are fused with each other while shrinking, so that the fibers substantially disappear to form a bubble film. . Then, a bubble wall is formed in a state where circular continuous pores with a pore diameter of about 100 to 4 0 // m are formed, and the continuous pores are changed in shape. Then, a part of the bioceramic particles contained in the fiber in a large amount is embedded in the stomata membrane (in the bubble wall) without sedimentation as the fiber fuses and changes in the form of the film, and at the same time, A part of it is exposed from the stomata membrane, and the particles are penetrated and exposed to the extent that the particles are not easy to fall off. However, depending on the conditions, it may happen that the epidermal layer is formed on the surface and the bioceramic particles are not exposed on the surface of the porous material. At this time, it is also possible to remove the epidermal layer by frosting to expose the inorganic particles existing on the surface layer. Disposal. In this way, an implant composed of an organic-inorganic composite porous material having continuous pores and having a large amount of bioceramic particles uniformly dispersed, and exposing a part of the bioceramic particles in the pores and the surface of the porous material can be obtained. material. This composite porous material is adjusted by applying an external pressure to maintain its shape when the fiber aggregate formed article is immersed in a volatile solvent. 28 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 may The pore size of the continuous stomata is controlled to a level of 1 QQ ~ 4 0 0 // m which is suitable for the invasion and stabilization of bone bud cells, and the porosity is controlled to 50 ~ 90%. In addition, if the volatile solvent is impregnated into the fiber assembly molded product under heating at 50 to 6 ° C., the fiber assembly molded product only needs to be left for a short time, and the fibers can be fully fused with each other, which can efficiently A composite porous material is obtained. In the manufacturing method of the present invention, 60 to 90% by weight (with an average particle diameter of 3 // m of unsintered hydroxyapatite having a specific gravity of 2 · 7) within a range that can be fiberized. It is equivalent to 4 1 ~ 8 1% volume percentage) of bioceramic particles uniformly contained in the composite porous material, even if it is contained in a large amount, because the solvent will volatilize and fuse the fibers before the bioceramic particles settle and separate. Therefore, compared with the porous material obtained by the above-mentioned solution precipitation method, the bioceramic particles in this method can be more uniformly dispersed, and finally a composite porous material with a high content rate that cannot be obtained so far can be obtained. However, if the content rate is too high, As the binding agent, the amount of the decomposable absorbent polymer in vivo will be reduced, the composite porous material will become brittle, and it will be difficult to maintain the shape, so there is an upper limit. (Examples) Next, the present invention The implant material composed of an organic-inorganic composite porous material will be further explained with specific examples. (Example 1) Poly-D, L · -lactic acid (PDLLA) (DDLLA) (D , The molar ratio of L-lactic acid to L-lactic acid is 5 0/5 0) a polymer solution (concentration · PDLLA 4 g / methylene chloride 100 m 1) dissolved in dichloromethane, and the average Unsintered hydroxyapatite particles with a particle size of 3 // m 29 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 (u-HA particles) mixed with ethanol and homogenized uniformly In this way, a mixed liquid is prepared so that u-HA particles are mixed in a proportion of 230 parts by weight to 100 parts by weight of pDLLA. As a sprayer, Η P-E air brush ( Anestast Iwata (stock) system), the above suspension was filled under pressure 1. 6 kg / cm2 of nitrogen was sprayed onto a polyethylene mesh (150 mesh) at a distance of 120 cm to form a fiber assembly, and the fiber assembly was peeled from the mesh. The fiber diameter of this fiber assembly is about 1 · Q // m, the fiber length is about 10 to 20 mm, and the false specific gravity is 0.2. This fiber aggregate was cut to an appropriate size, filled into a cylindrical master mold having a diameter of 30 mm and a depth of 30 mm, and performed with a male mold so that the pseudo specific gravity of the fiber aggregate became 0 · 5. Compression was performed to obtain a disc-shaped fiber assembly molded product having a diameter of 30 mm and a thickness of 5 mm. Then, the above-mentioned fiber assembly was immersed in a solvent made of dichloromethane mixed with ethanol, the solvent was impregnated into the molded article, and the solvent was left at 60 ° C for 10 minutes, and then the solvent inside the molded article was immersed. It was removed by vacuum suction to obtain an organic-inorganic composite porous material having a diameter of 3Qmm, a thickness of 5mm, and a content of u-HA particles of 70%. Partial cross-section of this composite porous material was observed with an electron microscope. The fibers disappeared after fusion, forming continuous pores with a large pore size of about 1000 to 400 // m, and u-Η A particles were uniformly dispersed in A part of u Η Η A particles inside the stomata and the surface of the porous material is exposed. This composite porous material has a false specific gravity of 0. 5, the ratio of continuous pores to the entire pores (continuous porosity) is 75%, and the compression strength is l. IMPa. 30 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 (Example 2) In the same manner as in the example, a disk-shaped fiber aggregate formed product having a diameter of 30 mm and a thickness of 5 mm was used as a preform. After heating it in a gear oven to 80 ° C, it is placed in a chamber with a diameter-reducing portion that is gradually reduced in diameter, and it is pressed into the lower part with a diameter of 10. 6 mm cylinder. In this way, the compression strength of the cylindrical rod-shaped fiber aggregate formed product that is press-formed under heating is about 2.5 M Pa. Then, the cylindrical rod-shaped fiber assembly molded product is filled into a cylinder having the same diameter as the surrounding hole, and pressure is applied from above and below to a degree that does not change the height of the cylindrical rod-shaped fiber assembly molded product. At the same time as the pressure was applied, it was immersed in a solution (60 ° C) of 15% by weight of methanol in dichloromethane, and then the solvent was removed to obtain a composite porous material. Partial cross-sections of the composite porous material and the frosted surface were observed with an electron microscope photograph, and it was found that the porous morphology of the fiber disappears, and it is formed by mixed pores with a pore size of about 15 0 to 3 0 0 , U-HA particles are exposed from the surface of the porous material and the pores. This composite porous material has a false specific gravity of about 0. 55, the continuous porosity is 70%, and the compressive strength rises to about 3. 5MPa. This composite porous material is estimated from the in vivo decomposition and absorption of u-HA particles with a viscosity average molecular weight of the PDDLA and the ratio of the average particle size of 3 // m in vivo, which depends on the embedded site and It varies in size and is expected to be completely absorbed from 6 months to 12 months. (Example 3) Synthetic PDLLA (D, L-lactic acid and L-31 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 The molar ratio of lactic acid having an average molecular weight of 100,000 is 3 0/7 0), in the same manner as in Example 1, prepared into a mixture of / 3 -tricalcium phosphate particles (0-T c Ρ particles) with an average particle size of about 3 // m 8 ◦ a mixture of uniform weight percentage liquid. This is not-TCP particles have been confirmed to be active in vivo and absorbable in vivo. Although the mechanism is different from that of u-HA particles, it can be seen that they show bone conduction of HA production in vivo. Using this mixed solution, the fiber assembly produced by the same spraying method as in Example 2 was compression-molded under heating to form a fiber assembly molded product, and by performing a solvent impregnation treatment thereon, a false specific gravity of about 0. 6. A composite porous material with a continuous porosity of 75% and a compressive strength of 4.2 MPa. The volume ratio of the stone-TCP particles of this composite porous material is about 65% by volume, which is 70% by weight (approximately 55% by volume) of the u_ηA particles. The composite porous materials of Examples 1 and 2 are 0-TCP. The volume ratio of the particles is much larger, so due to the exposure of the / 3-TCP particles on the surface of the porous material and the pores, the vitality of the body can be significantly exerted. In this composite porous material, fibers disappear when the non-woven fabric-like fiber aggregate is changed, and the shape becomes / 3-TCP particles are buried in bulk cell walls. It is not easy to disintegrate in body fluids and cause particles to disperse to the surroundings. It shows good bioactivity within 5 to 8 months and can be completely decomposed and absorbed, which has been confirmed. Therefore, this composite porous material can be used as a good plant-based structure for hard tissues (hard bone, cartilage). (Example 4) D, L-lactic acid (Molar ratio of D / L · 1) and carboxylic acid acetic acid (GA) so that 32 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 Molar ratio It was compounded as 8 ·· 2, and a copolymer P (DLLA-GA) having a viscosity average molecular weight of 130,000 was synthesized by a known method. In the same manner as in the example, this polymer was prepared with octacalcium phosphate particles (0 CP particles) to a mixture of _ 6 ◦ uniformly mixed by weight percentage, and a fiber assembly was produced by the same spray method as in Example 2. The composite was compacted under heat to form a fiber aggregate molded product, and a solvent impregnation treatment was performed thereon to obtain a composite porous material having a false specific gravity of 0.50. The composite porous occ is highly active, and the decomposition and absorption of the copolymer are fast due to GA, so it shows good φ good bone conduction (easy to transform into new bone), and after 3 to 4 months Most of it was absorbed and replaced with bone. (Example 5) D, L-lactide and p-dioxanone (p-DOX) were compounded so that the molar ratio was 8: 2, and copolymerization was performed by a known method to obtain a viscosity average molecular weight of about 1 0 million copolymer. The polymer of p-D 0 X, although it has no volatile and versatile solvent, can be dissolved in chloroform, dichloromethane, etc. at the above ratio, and the target can be obtained in the same manner as in Example 1 above. Β-composite porous material. In addition, I believe that the copolymer described above has a plastic-like property more than the copolymer P (DLLA-GA) of D, L-lactic acid and carboxyacetic acid in Example 4, so it is due to the particle size of the bioceramic particles. When it is 3 // m, the volume ratio of the particles can be as high as 70% by volume (85% by weight). Therefore, the composite porous material can effectively avoid the biological reaction of the decomposition product of the copolymer, and can effectively exert it. Bioactive ceramic particles in vivo, the activity of the particles. In particular, the characteristics of P-D OX are higher than that of PDLLA. Therefore, the composite porous material can proliferate cells in vitro. Therefore, it is used as 33 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 cartilage The regenerated base structure is very effective. As described above, the implant material composed of the organic-inorganic composite porous material of the present invention contains a large number of bioceramic particles uniformly dispersed in the living body to decompose and absorb the polymer, and passes through the continuous pores with large pores formed inside. Body fluids can be quickly immersed, and through the bone conduction energy of the bioceramic particles exposed on the surface of the porous material and the inside of the continuous pores, they can be combined with the living bone earlier and can be used to regenerate the living bone tissue. Strength 'is a manufacturer that can be easily and reliably manufactured by the manufacturing method of the present invention. Therefore, as described above, this implant material can be used as a substitute for plant-based structures, patch materials, callus materials, and other intervening materials between the implant material and the living bone tissue, and cancellous bone. Carriers for substances, drugs, etc. Next, referring to the drawings, a representative embodiment of the implant material of the present invention using the above-mentioned organic-inorganic composite porous material will be described in detail. This implant material can be divided into a form formed by dissolving the absorbent structure in the above-mentioned porous body and other dense materials into a combination, and combining it with the above-mentioned porous material and a non-absorbable structure in the body. The main implant material of the former includes the various embodiments shown in FIG. 1 to FIG. 15, and the latter includes the implementation shown in FIGS. 16 and 17. form. The implant material 10 shown in FIG. 1 is used for: incision, sawing, or fracture of a bone at a thicker and thinner ossicle due to a decrease in bone mass or atrophy of skeletal tissue due to osteoporosis, This is a representative example of an implant material for bone fixation that is active in vivo and is decomposed and resorbable when it is surgically closed and occluded during splicing. 34 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 This implant material 1 0 is an organic-inorganic composite porous material 1 and an axillary nail 2 which is a decomposing and absorbable material in vivo. 2 penetrates through the porous material 1 ′ and both ends of the shaft nail protrude from the shaft nail 2. Further, in order to prevent rotation when embedded in the sternum, the shaft pin 2 is formed into a prism shape, and the porous material 1 is formed into a rectangular parallelepiped shape. In addition, both front ends of the shaft nail 2 are formed into a pyramid shape that can be easily inserted into a hole formed in the bone marrow (sponge bone) of the sternum. The surfaces of both ends of the shaft nail 2 are formed to prevent the The hole has a zigzag unevenness 2 a in the cross-section of the shaft pin 2. In addition, while the shaft nail 2 is formed into a cylindrical shape, the porous material 1 may be formed into a cylindrical shape, or the irregularities 2 a at both ends of the shaft nail may be omitted. Porous body 1 is the same as the organic-inorganic composite porous body described above, that is, it is a biodegradable and absorbable body made of bioactive ceramic particles that are substantially uniformly dispersed in the biodegradable absorbent polymer. Porous objects are those with continuous pores, and a part of the bioceramic particles in the pores and the surface of the porous objects are exposed. The porosity of the porous material 1, the pore diameter of the continuous pores, the ratio of the continuous pores to the total pores, the degradable absorbent polymer in the living body, the bioceramic particles, and the content ratio of the particles are as described above. This porous material 1 is formed by pressing a non-woven fabric-like fiber assembly under heating into a rectangular parallelepiped shape under heating according to the above-mentioned manufacturing method to form a porous fiber assembly molded product, and immersing it in a volatile solvent to obtain a rectangular parallelepiped shape. The organic-inorganic composite porous material is made by perforating a corner hole (a corner hole with a smaller size than the shaft nail 2) for inserting the shaft nail 2. The size of this porous object 1 can be selected according to the symptoms, and its size is not particularly limited. 35 312 / Patent Specification (Supplement V92-〇2 / 9l I34292 200300666), but care must be taken not to make it too large (large). On the sternum In the case of an implant material for fixation, it is preferable to set the length of the porous object 1 to about 10 to 15 mm, width to 6 to 20 mm, and height to 6 to 15 mm. The selection within this range depends on The structure of the sternum of the patient is self-evident. If the size of the porous material 1 is lower than the lower limit of the above range, less bone tissue will be transmitted to the porous material 1. Furthermore, the porous material 1 is better It is self-evident that the size of the porous substance 1 must be changed according to the bone to be embedded. Here, the porous substance 1 can be improved in function by containing the above-mentioned bone forming factors, growth factors, and agents in an appropriate amount. If Containing bone formation factor and growth factor will significantly promote the bone formation inside the porous body 1, which can make the porous body 1 replace the bone tissue earlier, and the hemi-sternal bones on both sides of the incision and lock can be directly combined. Moreover, Make it immersed in the medicine, then the medicine It can be directly absorbed by the hemi-sternal bones of both sides and can fully exert its medicinal effect. In addition, the surface of the porous material 1 is subjected to the above-mentioned oxidation treatment to improve the moisturizing property, which can more effectively make bone bud cells invade and grow. On the other hand, the shaft pin 2 may be composed of a biodegradable and absorbable polymer such as crystalline polylactic acid and polycarboxyacetic acid, which has been confirmed in safety. Especially, the viscosity average molecular weight is 1 High-strength studs 2 composed of 50,000 or more (more preferably 200,000 to 60,000) in vivo decomposable absorbent polymers are more preferable. In addition, these in vivo decomposable absorbent polymers are decomposed. Axle nails composed of the above-mentioned bioactive bioceramic particles mixed with a composite of about 10 to 60% by weight, or the above-mentioned polymer molecules or crystals through compression molding, forging, and stretching Axial nails that are more oriented for alignment are also better users. 36 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 Especially forging polymer molecules or knots through forging. The dense three-dimensional alignment is the preferred one. In the case of implant materials for sternal fixation, the length of the shaft pin 2 is preferably 20 to 40 mm. If it is less than 20 mm, it is used for sternal fixation. The shaft pin will be too short. On the other hand, if it is longer than 40 mm, it will be difficult to incorporate it into the bone marrow (sponge bone) of the sternum. Also, the width of the shaft pin 2 is preferably about 2 to 4 tnm. It is better to use 2 ~ 3mm. In the case that the width of the shaft nail 2 is narrower than 2mm and the height is smaller than 2 mm, it will be too thin and easy to break. On the other hand, if the width of the shaft nail 2 is more than 4 mm When the width and height are larger than 3 mm, the combination of the porous material 1 will increase the thickness of the sternum for fixation. In addition, the size of the above-mentioned shaft nail is merely a preferable size in the case of implant material for fixing the sternum, and it is needless to say that the preferable size of the shaft nail must be changed according to the bone to be embedded. Next, a use example of the implant material 10 for sternal fixation will be described with reference to FIG. 2. First, as shown in FIG. 2 (a), the left and right half of the sternum B, which is cut in the middle, pass through the two steel wires 1 and 3 with a protruding cone at B, and pass through the half sternum B, B with a band 4 And rolled between the ribs. Only one bundle of this constricting belt 4 is wound in FIG. 2 (a), but a plurality of bundles (usually four bundles) are wound at intervals from top to bottom. Then, scrape out the unwanted spongy bones of both the sternal bones B and B with crickets, etc., to form a plurality of holes 5 into which one half of the implant material 10 for sternal fixation can be inserted. 1 0 slightly smaller size holes). Next, as shown in FIG. 2 (b), one half of the implant material 10, 37 1 12 / Patent Specification (Supplement) / 92-02 / 91134292 200300666, is strong so that it will not be pulled out. Squeezed into each hole 5 of a single piece of sternalbone B. Then, as shown in FIG. 2 (c), the lead wires 3 and 3 are threaded, and one half of the opposite side of each implant material 10 is pressed into each hole 5 of the other half breastbone B, while one side The hemi-sternal bones B on both sides were closed, and the ends of the steel wires 3 and 3 were tied several times to securely tie them. In this embodiment, although the steel wire 3 and the drawstring 4 are used to fix the semisternal bones B and B, the above-mentioned polylactic acid-like biodegradable absorbent polymer may be used or the polymer may be used. Shaped strips containing bioceramic particles. If the implant material 10 for sternum fixation as described above is buried in the bone marrow of the incision and occlusion of the sternum, in the initial stage of implantation, the shaft nail 2 of the implant material is used as a "wedge" to pierce both sides. The hemi-sternal B is fixed by B to strengthen it, so it can improve the stability and stability of the hemi-sternal. Thereafter, through the bone conduction energy of the bioceramic particles exposed on the surface of the porous body 1 of the implant material 10, bone tissue can be conducted on the surface of the porous body. The bone marrow of sternal bones B and B will be combined, so the stability and strength of the semisternal B and B of both sides can be improved through this combination. This implant material 10, through contact with the body fluids in the bone marrow, both the shaft pin 2 and the porous body 1 are hydrolyzed. Since the porous body 1 penetrates the body fluid through the continuous pores, the hydrolysis is fast, and, The porous object 1 is formed by the bone conduction energy of the bioceramic particles exposed inside the stomata, and the bone tissue is conducted to the inside, and it is replaced with the bone tissue and disappeared in a short period of time. In particular, in the case where the porous substance 1 is impregnated with the above-mentioned growth factor, bone tissue grows rapidly, and the bone tissue can interact with the porous substance 1 in a short period of time. 38 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 Substitution. Therefore, the closed sternum (half sternum B, B) can be directly combined through the replacement of the bone tissue with the porous material. Therefore, even if the spongy bone of the sternal bone of porosity is extremely hollow and porous, it becomes wafer-like. It becomes brittle and can be stabilized through the fixation of the formed new bone sternum. On the other hand, the axillary nail 2 of the implant material 10 will slowly hydrolyze through contact with body fluids. When the porous material 1 is replaced with bone tissue, the hydrolysis has already progressed a lot, and it will soon become fragments, and finally All will be absorbed by the body and disappear. In this case, the shaft pin 2 is composed of a composite of bioabsorbable polymer and bioceramic particles in vivo as described above, and the shaft pin 2 is also osteoconductive, so the bone buds of the bioceramic particles undergo hydrolysis through hydrolysis. The replacement of cells and osteoclasts is carried out repeatedly, by which it will conduct bone formation, and at the same time, it will perform a poor food response to decompose the fragments. The shaft nail 2 will be replaced with bone tissue. The hole pierced by the shaft nail 2 will be finally The new bone was buried and disappeared. The implant material 10 for bone fixation composed of the organic-inorganic composite porous material 1 and the shaft nail 2 of the present invention, as described above, can not only be used for the implantation of the incision and lock in the operation of the midline incision and lock of the sternum. The sternum is used for osteoporosis, bone loss, or skeletal tissue atrophy, which results in incisions of bones that have become loose and thin, bones that have been cut, or bones that have been fractured. It can be used. Finally, the bone can be replaced and the bone can be firmly joined and fixed. The implant material 11 shown in FIG. 3 is a vertebral body fixation material such as the intervertebral body spacer as shown in FIG. 6. It is mainly used to insert the cervical spine C 3-C 4 or the lumbar spine L 4-L 5 All users. This implant material 1 is composed of organic-inorganic composite porous material 1 and a living body with a cavity 6 a which is open to the outside. 39 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 In the case of the base material 6 of the material, the porous material 1 is installed in the cavity 6a of the base material 6 and partially exposed from the entrance 6b of the cavity 6a. The porous material 1 is stacked on the base material 6 It is formed in a synthetic plate shape. The porous material 1 above and below the base material 6 is used as a substitute for its own bone. As described later, it is to make the gap between the base material 6 and the cervical spine C3-C4 or the lumbar spine L4-L5 disappear and be combined (fixed) early. Setter. Further, the porous material 1 above and below the base material 6 may be omitted. The base material 6 of this implant material 1 1 is a dense and strong base material composed of biodegradable absorbent polymer containing bioactive ceramic particles in vivo. As shown in FIG. 4, it is formed as Cuboid shape. In the base material 6, two through-hole-like cavities 6a in the longitudinal direction and two horizontal through-hole-like cavities 6a that can reach the outside are formed so as to be able to intersect with each other. 6b, there are two openings on the four sides of the base material 6, the upper, lower and left sides. The entrances 6b of the hollows 6a are partially intruded from the entrances 6b because of the intrusions of liquids and the like. In addition, the entrance 6 b of the cavity 6 a may be formed in front and back of the base material 6. In this case, the entrance of the back is formed into a screw hole shape so that the front end of the inserted fixture can be locked. good. This implant material 11 is chamfered around the front face 6 c of the base material 6 so that it can be easily inserted between the cervical spine c3-c4 or the lumbar spine L 4-L · 5. Therefore, in order to make it a self-supporting implant material (without supplementary fixation material) 1 1 that is inserted into the cervical spine C 3-C 4 or the lumbar spine L 4-L 5, it will not be displaced or detached from the base material 6 There are several on the upper and lower sides 6d and 6e (6 in the figure) 40 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 The protrusion 6 f for fixing is fixed, and the front end of each protrusion 6 f is from The porous material 1 on the upper and lower sides of the base material 6 protrudes. As shown in FIG. 4, the protrusions 6 f ′ are formed on the upper and lower surfaces of the base material 6 with recesses 69. The front end of the protrusion 6 f is decomposed by an absorbent polymer in the same body as the base material 6, and the conical shape is formed. The sharp shaft nails were implanted in the recesses of 6 g for 6 h (6 f). In addition, instead of using a shaft pin for 6 hours, a pointed protrusion can be planted at the front end, and the protrusion 6f and the base material 6 can also be integrally formed. As shown in FIG. 5, the structure is such that a communication hole 6 j is formed in a wall portion 6 i between two cavities 6 a and 6 a in the longitudinal direction of the base material 6. The bone tissue formed by conduction on the hollow porous body 1, 1 can be connected through the communication hole 6 j. This wall portion 6 i is for improving the compressive strength of the base material 1. The size of the base material 6 is about 18 ~ 30mm, and the size of the upper and lower heights and the left and right widths is about 6 ~ 24 mm. If you use a variety of these sizes in this range, you can choose suitable for the cervical spine C3-C4 or The size of the lumbar spine L4-L5 and the intervertebral size are inserted. The base material 6 of the implant material 1 1 is formed in the vertical and horizontal cavities 6 a into a through-hole shape with a cross-section in the shape of an oval, but it can also be formed in various shapes such as a square, a circle, and an oval. The cross-sectional shape of the through-hole. Alternatively, the entire interior of the base material 6 may be formed as a hollow chamber-like cavity, and the entrance of the cavity may be formed on four surfaces of the base material 6 above and below, and communicate with the outside. In addition, the cavity 6a penetrating in the transverse direction of the base material 6 may be omitted. As long as the cavity 6a penetrating in the longitudinal direction is provided, bone tissues from the upper and lower cervical vertebrae C 3-C 4 or the lumbar vertebrae L 4-L 5 are conductively formed. It is installed on the inner porous material 1 and can be repaired and fixed by 41 312 / patent description) / 92 · 02/91134292 200300666. In addition, the entrances lb on the left and right sides of the base material 6 may be omitted. The base material 6 is composed of a bioactive biodegradable absorbent polymer containing bioceramic particles in vivo. The biodegradable absorbent polymer used as a raw material is preferably a shaft pin with the implant material Q described above. 2 The same polymer 'that is, it is better to use crystalline poly-L-lactic acid or polycarboxyacetic acid, etc. whose safety in vivo is confirmed, especially to use a viscosity average molecular weight of 150,000 or more (and 200,000 ~ 600,000 or more) high strength base material 6 of poly-L-lactic acid is preferred. Such a base material 6 can be produced by a method such as injection molding using a biodegradable absorptive polymer or cutting a shaped block of a biodegradable absorptive polymer. In the latter method, polymer blocks or crystals are aligned into blocks by means of compression molding or forging, etc., and the base material 6 obtained by cutting and processing is dense in texture and polymer. Molecules or crystals are three-dimensionally aligned to further increase the strength and are therefore excellent. In addition, it is also preferable to use an extended shaped block as a shaped block and perform a cutting process with the extending direction (alignment direction) as the longitudinal direction to increase the strength, which is preferable. As the bioceramic particles contained in this base material 6, all of the above-mentioned bioactive bioabsorbable bioceramic particles can be used. The content rate is the same as that of the axle 2 of the implant material 10 described above. It is preferably from 10 to 60 weight percent. If it is less than 10% by weight, due to insufficient bone conduction formation of the bioceramic particles, if it exceeds 60% by weight, a disadvantage of the fragility of the base material 6 may occur. On the other hand, the porous material 1 filled in the cavity 6 a of the base material 6 is the same as the organic-inorganic composite porous material described in 42 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666, that is, It is a porous body made of bio-active ceramic ceramic particles which is substantially uniformly dispersed in the living body decomposable absorbent polymer. It has continuous pores, and there is a part in the pores and the surface of the porous body. Parts of bioceramic particles exposed. The porosity of the porous material 1, the pore diameter of the continuous pores, the ratio of the continuous pores to the total pores, the degradable absorbent polymer in vivo, the bioceramic particles, and the content rate of the particles are as described above. The upper and lower porous materials 1 of the base material 6 are formed with holes passing through the protrusions 6f of the base material 6, and are superimposed on the upper and lower surfaces 6d, 6e of the base material 6, and fixed by means such as heat fusion. The thickness of the porous material 1 above and below this base material 6 is 0. 5 ~ 3 mm is better than 〇. In the case of 5 mm thin, it is difficult to absorb the unevenness of the surface of the cervical spine C3_C4 or the lumbar spine L4-L5 due to compression deformation. Therefore, the adhesion with the cervical spine C3-C4 or the lumbar spine L4-L5 may be reduced. In the case of a thickness of 3 mm, the time required for its decomposition and absorption and replacement with bone tissue will become longer. For the porous material 1 filled in the cavity 6a of the base material 6, or the porous material 1 superimposed on the top and bottom of the base material 6 as a combination, it is desirable to appropriately contain the above-mentioned bone formation factors, growth factors, and agents In addition, the surface of the porous material 1 may be subjected to the above-mentioned oxidation treatment to improve the wetting characteristics. By inserting the above-mentioned implant material 11 into the cervical spine C3-C4 or the lumbar spine L4-L5 as shown in FIG. 6 with an insertion jig, the interval between the cervical spine C3-C4 or the lumbar spine L4-L5 can be corrected. And appearance. When the implant material 1 1 is inserted like this, the porous material 1, 1 on the upper and lower sides of the base material 6 will be compressed due to the clamping pressure of the cervical spine c3-c4 or the lumbar spine L4-L5, and the cervical spine 〇3-(: 4 Or 43 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 The lumbar spine L 4-L 5 are tightly sealed without gaps, and the protrusions 6 f on the upper and lower sides of the base material 6 are embedded in the cervical spine C 3-C 4 or the lumbar spine The spongy bone of L 4-L 5 enables the implant material 11 to be fixed without being shifted or detached, and can be set in a stable manner depending on the shape of the cuboid of the base material 6. This is the cervical spine C 3-C 4 Or the lumbar vertebrae L 4-L 5 are inserted and implanted, and the base material 6 has sufficient strength and has the same effect as the living body's cortical bone. The base material 6 will contact body fluids and slowly hydrolyze from the surface. The porous body 1 which has the same effect as the sponge bone, will undergo the hydrolysis of the body fluid through the continuous pores soaking into the interior through the exposed part, and the bone conduction energy of the bioceramic particles will cause the bone bud cells to invade the porous body. 1 internally conducts and forms bone tissue, so in a relatively short period of time Hole 1 will be replaced with bone tissue. Therefore, the upper and lower cervical vertebrae C 3-C 4 or lumbar vertebrae L4-L5 can be healed and fixed through the replaced bone tissue. On the other hand, the base material 6 is from the initial stage. Its compressive strength is as high as the conventional carbon steel structure, and it can continue to maintain its strength after bone replacement with porous material 1. The implant material 11 can completely match the cervical spine C3-C4 or lumbar spine L 4- L 5 heals and is mechanically fixed, which can exert a large effect, and it can be completed after several years (about 5 years) with replacement of bone tissue. At this point, a solid solid completely due to living bone can be obtained. Healing. The conduction of bone tissue is formed. As the porous material 1 on the upper and lower sides of the base material 6 is compressed, the cervical vertebrae C3-C4 or lumbar vertebrae L4-L5 are tightly sealed without voids. The porous material 1 is porous with the organic-inorganic composite porous material described above. The same thing, because it contains bioceramic particles with bone conduction energy of 60 to 90% by weight, the porosity is 50 to 90%, the continuous pores account for 50 to 90% of the entire stomata, even 44 312 / Patent Specification (Supplement) ) / 92-02 / 91134292 200300666 The diameter of the air hole is about 1 Q 〇 ～ 4 〇〇 # m 'Therefore, bone bud cells are easy to invade and can be reliably carried out. Bone tissue conduction is formed at the initial stage of the surface layer portion of the porous material 1 formed on the upper and lower surfaces of the base material 6.' Implant material 1 1 and upper and lower The cervical spine c 3-C 4 or the lumbar spine L 4-L 5 can be directly combined and fixed. As mentioned above, since the parent material 6 and the porous material 1 of this implant material 1 1 will be decomposed and absorbed and replaced with bone tissue, non- It exists in the living body as a foreign body. Therefore, the worry about the occurrence of long-term harmfulness in the living body caused by the titanium or carbon steel bone structure used as a vertebral body fixing material, and the inconsistency between the living body and the mechanical characteristics. The problem of sinking in the vertebral body was swept away. In addition, the porous material 1 can perform the same histological function as the living bone, and can be replaced with bone tissue. Therefore, it is not necessary to extract the intestinal bone, etc. in order to fill the steel bone structure as its own bone for transplantation. The problem of insufficient acquisition of the bone for transplantation and the troublesome handling during the surgery after the extraction were also eliminated. The upper and lower sides 6 d and 6 e of the parent material 6 of this implant material 11 are horizontal, but the upper 6 d can also be tilted forward and lower, and the lower 6 e can be tilted forward and upward. In this way, the narrow base material 6 can be used as an implant material suitable for correcting the lumbar vertebra to a forward bending posture. The shape of the 'base material 6' is not limited to the rectangular parallelepiped shape described above, and it can be formed into various shapes suitable for the cervical spine, lumbar spine, spine, and other use sites. The implant material 12 shown in FIG. 7 is a cylindrical shape having a cavity 6 a (a circular cavity in a cross section) formed on the inside of the base material 6 by the shape changer. Each of the entrances 6 b with a large circular cavity is arranged one by one, and the entrances with a small oblong cavity are arranged on the outer surface 45 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 6 b, arranged as Thousands of birds form a majority. The cavity 6a of the base material 6 is filled with the organic-inorganic composite porous material 1 described above, and a part of the porous material 1 is exposed from each of the entrances 6b formed on both end surfaces and the outer peripheral surface of the base material 6. Such an implant material 12 is inserted between vertebrae such as the cervical and lumbar vertebrae in a vertical posture as shown in the figure, and the parent material 6 and the porous material 1 are finally replaced with bone tissue in the same manner as the implant material 11 described above. , Make the upper and lower cones heal and fix. In some cases, a male sprout is formed on the outer peripheral surface of the implant material i 2 and it can be installed by screwing it between the upper and lower vertebral bodies in a lateral posture. The implant material shown in FIG. 8 is also a person who changes the shape of the base material. The base material 6 is formed into a ring shape having a low curvature portion 6 η and has a low height. The inner cavity 6 a is provided with In the above-mentioned porous material 1, the upper and lower surfaces of the porous material i are exposed from the upper and lower entrances Sb of the cavity. Although a hollow entrance is not formed on the outer peripheral surface of the ring-shaped base material 6, a plurality of hollow entrances may be formed as required. The above-mentioned fixing protrusions may be formed on both the upper and lower surfaces of the ring-shaped base material 6. Such an implant material 1 3 moves the portion 6 η having a small curvature of the base material 6 and inserts it between the vertebrae such as the cervical spine and the lumbar spine. The base material 6 and the base material 6 are the same as the implant materials 1 1 and 1 2 described above. The porous material will be replaced with bone tissue to heal and fix the upper and lower vertebral bodies. The above-mentioned implant materials 1 1, 1 2, 1 3 are all used as vertebral body fixing materials to be inserted and installed between vertebral bodies such as the cervical spine or lumbar spine. The shape of the base material 6 can also be used if it is appropriately changed. In the bones and joints of various parts. 46 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 The implant material 14 shown in Fig. 9 is used as a substitute for the same kind of transplanted bone pieces and self-moving straight bone pieces for implanting bone defect sites. The block-shaped organic-inorganic composite porous material 1 and the skin layer 7 of the decomposable and absorbable structure in vivo are superimposed on a part of the surface of the porous material 1 as a combination. The block-shaped porous body 1 is the same as the organic-inorganic composite porous body described above, that is, a living body made of bio-ceramic particles that substantially uniformly disperse the living-active bioceramic particles in the living body to decompose and absorb the polymer. Decomposed and absorbable porous materials are those with continuous pores, and a part of the bioceramic particles in the pores and the surface of the porous material are exposed. This porous material 1 can be produced by the manufacturing method of the present invention, and its porosity, pore diameter of continuous pores, ratio of continuous pores to the total pores, in vivo degradable absorbent polymer, bioceramic particles, content ratio of the particles, etc. It is the one described above. Since the porous material 1 can play the role of cavernous bone, its shape is not particularly limited as long as it has a block shape. The porous material 1 may contain the above-mentioned bone formation factors, growth factors, agents, etc. in an appropriate amount. In addition, the surface of the porous material 1 and the surface of the skin layer 7 may be subjected to the above-mentioned oxidation treatment to improve the wetting characteristics. The epidermal layer 7 functions as a cortical bone and is a dense and dense layer composed of a bioactive bioceramic particle that decomposes and absorbs polymers in vivo. In this implant material i 4, the epidermal layer 7 may be superposed on the convexly curved side of the block-shaped porous material 1 and integrated, or may be superposed on other sides, upper surfaces, and bottom surfaces of the porous material 1. In either case, it may be superposed on two or more sides of the porous body 1. The key point is 47 312 / Patent Specification (Supplement) / 92-〇2 / 91134292 200300666. This skin layer 7 may be superimposed on a part of the surface of the block-shaped porous body 1. The thickness of the epidermal layer 7 is not particularly limited, it is necessary to consider the implantation of the bone defect site of the implant material 14 in order to appropriately set it at 1 · 〇 ~ 5. A range of 0 mm is preferred. If it is thinner than 1 · omm, there is a concern that the strength of the epidermal layer 7 is insufficient. If it is thicker than 5 · Q mm, it may cause a long time that the epidermal layer 7 is decomposed and absorbed and replaced with bone tissue. Since the skin layer 7 is required to have higher strength than the massive porous body 1, it is preferable to use crystalline poly-L-lactic acid or polycarboxylic acid as the raw material for decomposing and absorbing polymers in vivo, especially Poly-L · -lactic acid has a high-strength epidermal layer 7 having a viscosity average molecular weight of more than I50,000 (and preferably about 200,000 to 600,000). As the bioceramic particles contained in the epidermal layer 7, all of the bioactive bioceramic particles contained in the above-mentioned porous material 1 can be used, and the content rate 'is preferably in a range of 10 to 60% by weight. If it exceeds 60% by weight, the epidermal layer 7 will be weakened, and if it is less than 1Q% by weight, a defective condition due to insufficient bone conduction formation of the bioceramic particles may occur. This epidermal layer 7 'can be formed by injection molding using biodegradable absorbent polymer containing bioceramic particles, or cutting the shaped block of biodegradable absorbent polymer containing bioceramic particles. Production. In the latter method, the polymer blocks or crystals are aligned to form a block by means of compression molding or forging to form the block. The surface layer 7 obtained by cutting and processing has a dense texture and is polymerized. Biomolecules or crystals form a three-dimensional alignment to further increase the strength, so it is excellent 48 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666. In addition, a skin layer obtained by cutting the stretched shaped block can also be used. This implant material 14 is an inseparable combination made by superposing the epidermal layer 7 produced in the above-mentioned manner on the convexly curved side of the block-shaped porous body 1 through means such as thermal fusion. The means for integrating the skin layer 7 and the porous material i is not limited to the thermal fusion method, and may be integrated by other means. The above-mentioned implant material 14 is buried in the bone defect site as a substitute for the same kind of bone graft or autograft bone chip, the sponge bone site of the bone defect site is filled with a block-shaped porous material 1 and the bone The cortical bone at the defect site is compensated by the epidermal layer 7. The massive porous material 1 can play the role of cavernous bone. The strong epidermal layer 7 can play the role of cortical bone, just like the cavernous bone that makes the bone defect. Partially, it is supplemented with sponge bone, and partly with cortical bone. In this way, when the bone defect site is filled with implant material 14, the body fluid penetrates through the continuous pores and penetrates into the inside of the block-shaped porous body 1, and at the same time, it undergoes rapid hydrolysis, through the bone conduction energy of the bioceramic particles, and the bone bud. Cells invade the interior of the porous body 1 so that bone tissue can be conductively formed. Therefore, the massive porous material 1 can be replaced with bone tissue in a comparatively short period of time. On the other hand, the epidermal layer 7 is slower than the massive porous material 1 and slowly hydrolyzes when it is opened from the surface. During the period between the massive porous material 1 and the bone tissue, it can maintain sufficient strength. Finally, the replacement with bone tissue disappears. This implant material 1 4 does not have the above-mentioned specific biological response, and it can invade surrounding living bones during non-specific decomposition, absorption, and discharge 49 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 and substitutes to become self-bone. In other words, the massive porous material 1 and the epidermal layer 7 are both decomposed and replaced with bone tissue. Since they do not remain in the living body as foreign materials, conventional ceramic implant materials are concerned with the living body. The long-term residual harmfulness can be removed, and the bone defect can be repaired and reconstructed by replacing its own bone tissue. In addition, since the implant material 14 and the porous material 1 and the epidermal layer 7 are both made of a biodegradable absorbent polymer as a raw material, it is not as good as a conventional bone graft of the same kind using a dead bone as a raw material. If you have insufficient concerns, you can mass-produce the necessary and sufficient amount of implant material as needed, and you can make it into the desired shape and size through forming and cutting. In addition, although the epidermal layer 7 of the implant material 14 contains bioceramic particles' because it is composed of a biodegradable absorbent polymer, it does not have the disadvantages of being too hard and brittle like a sintered ceramic implant material, It has toughness and is not easy to crack, and can also be deformed by heating if necessary. In addition, although the massive porous material i contains a large amount of bioceramic particles, since it is a porous material that uses the biodegradable absorbent polymer as a raw material, even if the porosity is high, it is not as brittle as a high-rate porous ceramic. , Will not be scattered when burying the ground fragments' can also be heated and deformed if necessary. As such, the implant material 14 of the present invention is not brittle but has sufficient practical strength, and can be deformed by heating, which is excellent in accessibility. This implant material 14 can be used in a variety of applications as a surgical substitute, and is particularly favored nowadays. It is effective as a patch and spacer for cervical and lumbar vertebrae in which several problems have become clear. The implant material 15 shown in Fig. 10 and Fig. 11 is used for various skeletal parts such as the cranium, 50 312 / patent specification (supplement) / 92-02 / 91134292 200300666 jaw, face or chest For the purpose of repairing, correcting or increasing defects and deformations, it is used as a patch and filling material; it is a mesh 8 with organic-inorganic composite porous material 1 and in vivo decomposition materials. The mesh 8a is filled with the substance 1 and becomes a conjugate. The mesh 8 of the implant material 15 is a dense network composed of a biodegradable and absorbable polymer containing living ceramic particles; The polymer sheet or plate is formed into a mesh by punching or cutting into a square mesh 8a. The shape of the mesh 8a is limited to a square, and it can be made into a circle, a rhombus, and other desired shapes. The opening area of the mesh 8 a is in the range of 0.1 to 1.0 cm 2 as the area ratio of the area of the eye 8 to the mesh 8 is in the range of i 0 to 80%. . 3 ~ 1. 5 mm is preferred; the mesh is preferably 2 / for the warp portion 8 b and the width corresponding to the weft portion 8 c. If the area ratio of the mesh 8 a is less than 10%, the overall strength of the implant material is large, because the amount of the fast hydrolysis material 1 filled in the mesh 8 a is less, and the mesh is slower in hydrolysis. The proportion of the object 8 is therefore completely degraded and absorbed by the implant material 15 and there will be a longer period between the bone material replacement and the bone tissue replacement. On the other hand, if the area ratio of the mesh 8 a exceeds the thickness of the mesh 8, it is less than 0. 3 mm thin, equivalent to the warp portion 8 b and the weft portion 8 c, which is narrower than 2 mm, because the mesh 8 will be greatly reduced, it will be more difficult to obtain a strong implant material 15 | 312 / Patent Instruction (Supplement) / 92-02 / 91134292 The implant material in the part has absorbent shape of porous bioceramics, which is strong in strength and dissolves in suction means. The porosity of the phase ^ 10 mm 15 of the mesh 8 becomes larger, 80% when necessary, and equivalent strength 200300666. In the case of obtaining a mesh 8 with good bending processability, it is used as the material described above. The sheet or plate can be cold forged (melt-formed from the glass transition temperature of the polymer to the melting temperature) by cold-forging a melt-molded product containing bioceramic particles to decompose the absorbent polymer in vivo. Those who change the direction (machine direction MD) to cold forging again, and punch or cut it to form a mesh 8a to make a mesh. In this way, if the direction or direction of the absorbent polymer is decomposed twice, the sheet or plate of the absorbent polymer is decomposed in vivo, because the molecular chain of the absorbent polymer is decomposed in vivo, the domain of the molecular chain assembly, and the crystal axis It has a multi-axis alignment structure, or a structure where many clusters of multi-axis alignments are assembled. Therefore, if it is bent and deformed in the normal temperature range (0 to 50 ° C), its shape is maintained near the body temperature (30 to 40). ° C) It is difficult to return to the original shape, and even if it is bent and deformed many times, it is not easy to break or cut. Therefore, the implant material 15 produced by using the mesh 8 forming the mesh 8 a on the sheet or plate has good bending workability, and thus, for example, as shown in FIG. 12, Bending is performed at normal temperature during surgery so as to fit the curved surface of the defect portion 21 of the cranium 20 and can be fixed to the defect portion 21. In addition, as the sheet or plate as the material of the mesh 8, it is of course possible to use a uniaxial or biaxial stretcher, an unstretcher, or a compression molding. As the raw material for the biodegradable absorbent polymer of the mesh 8, poly-L-lactic acid, poly-D-lactic acid, poly-D / L-lactic acid, and polycarboxyacetic acid, which have been confirmed for safety by crystallinity, can be used. And so on. In view of the degradation of the absorbent polymer in vivo, it is better to use a viscosity average molecular weight of 150,000 or more in consideration of the strength of the network 8 and the rate of hydrolysis, and 200,000 to 60,52 3 U / Patent Specification (Supplement) / 92_〇2 / 91134292 200300666 million is better. As the bioceramic particles contained in the in vivo biodegradable and absorbent polymer of the mesh 8, all of the above-mentioned bioactive bioceramic particles contained in the porous material 1 can be used, and the content rate is set to be 1 to 6Q. A weight percentage is preferred. If it is less than 10% by weight, the bone conduction formation depending on the bioceramic particles will be insufficient. If it exceeds 6Q% by weight, a problem that the mesh 8 is weakened will occur. In addition, the above-mentioned mesh 8 may be replaced by, for example, a mesh in which the intersections of the warp and weft yarns of the biodegradable absorbent polymer containing bioceramic particles are fused. On the other hand, the porous material 1 filled in the meshes 8 a of the mesh 8 is the same as the organic-inorganic composite porous material, that is, it is substantially decomposed and absorbed in the living body. The biodegradable and porous body formed by bioactive ceramic particles uniformly dispersed in vivo is a bioceramic particle with continuous pores and a part of the bioceramic particles exposed inside the pores and on the surface of the porous body. The porosity of the porous material 1, the pore diameter of the continuous pores, the ratio of the continuous pores to the total pores, the degradable absorbent polymer in the living body, the bioceramic particles, and the content ratio of the particles are as described above. In this porous material 1, the above-mentioned bone formation factor, growth factor, medicine, etc. may be appropriately contained, and the surface of the porous material 1 and the surface of the mesh 8 may be subjected to the above-mentioned oxidation treatment to improve Wet properties. As shown in FIG. 12, the implant material 15 having the above structure is closely attached to the cranium 20 so as to cover the defect 21 of the cranium 20, and the peripheral edge portion thereof is made of a biodegradable absorbent polymer. The screw 53 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 30 is fixed at several places. At this time, the implant material 15 should be subjected to bending processing so as to conform to the curved surface of the defect portion 21 of the cranium 20. In this way, the defect portion 21 of the cranium 20 is covered with the implant material 15, and the contact with the liquid through the mesh 8 will slowly hydrolyze from the surface, because the body fluid will penetrate the porous material through the continuous pores. 1 inside, so hydrolysis will proceed quickly. Thereafter, through the bone conduction energy of the bioceramic particles contained in the porous material 1, the bone bud cells invade the inside of the porous material 1 to conduct the formation of bone tissue, and the porous material 1 is replaced by a short period of time. Bone tissue. On the other hand, the mesh 8 undergoes slower hydrolysis than the porous material 1 and, until the replacement of the porous material 1 and the bone tissue to a certain degree, sufficient strength can be maintained to protect the cranium 20's defective portion 2 1 . Finally, the mesh 8 is replaced with bone tissue and disappears. As mentioned above, the implant material 15 and the porous material 1 and the mesh 8 are both decomposed, absorbed, and replaced with bone tissue. Since they are not left in the body as foreign bodies, they are used as a patch material for bone defects. Concerns about the long-term harmfulness in the living body caused by the perforated plate used can be swept away, and the defective part 21 of the cranium 20 can be repaired and reconstructed through the replaced bone tissue. In addition, although the mesh 8 of the implant material 15 contains bioceramic particles' because it is composed of a biodegradable absorbent polymer, it is not as hard and brittle as sintered dense ceramic, Tough and not easy to crack, it can be deformed by heating under normal temperature. In addition, although the porous material 1 also contains a large amount of bioceramic particles, since it is a matrix formed by decomposing and absorbing polymers in the living body, even if the porosity is high, the porous ceramics with a high magnification are not high. ) / 92_〇2 / 91134292 200300666 It is very brittle. When it is buried, it will not be peeled off, and it can be deformed by heating if necessary. As such, the implant material 15 of the present invention is not brittle but has sufficient practical strength, can be deformed by heating, and is excellent in handling properties. This implant material 15 is formed into a mesh to play the role of strong cortical bone. 'The porous material is made to have a high porosity to play the role of spongy bone. A substitute for living bone with a small area and a small amount of material can be obtained. Since the total amount of the material of the combination of the network and the porous body can be suppressed to a very small amount, it is an implantable material with excellent biocompatibility, which has a small amount of living body treatment during the decomposition and absorption process. Also, in addition to the use example shown in FIG. 12, this implant material 15 can also be used for compensation of collapsed fractures in the face, repair of osteoma and other diseased nests, and other relatively large ones. The repair and reconstruction of bone defect sites can also be used as a substrate for bone extension. In the implant material 15 of the type combining the porous material 1 and the mesh 8 described above, 'the porous material is not only filled in the mesh 8 a of the mesh 8, but also in the mesh 8 of the mesh 8. A structure in which the porous material 1 is provided in a layered shape on one or both sides is also a very useful embodiment. Figures 1, 3, and 14 show the implant material 16, 17 of this embodiment. The implant material 16 is the organic-inorganic composite porous material on one side of the implant material 15 described above. 1 is provided in a layered form, and the implant material 17 is provided in which the above-mentioned organic-inorganic composite porous material 1 is provided on both sides of the implanted material i 5. The layered porous material 1 is the same as the organic-inorganic composite porous material 1 described above, and is formed into a layered (sheet-like) shape by the production method of the present invention described above. This layered porous material 1 'can be subjected to a volume layer on one or both sides of the implant material I5 through means such as thermal fusion. The thickness of this layered porous material 1 is 55 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666. There is no particular limitation on the adhesion to the bone around the bone defect site, decomposition and absorption, and bone The time required for the replacement of the organization should be set to 0. A thickness of about 5 to 3 mm is preferred. Such implant materials 16 and 17 can form bone tissue uniformly on one or both sides in a relatively short period of time, so repair and reconstruction of the surface of a bone defect site can be performed quickly. Furthermore, since the layered porous material 1 is provided, it can function as a cushioning material and can be tightly adhered to the bone around the bone defect site. The conductive material is formed on the surface layer of the porous material 1. The implant materials i 6 and i 7 are directly bonded to the bone around the bone defect site, and can be firmly fixed. In the implant material 15 formed by combining the porous material 1 and the mesh 8 as described above, the mesh 8 is made concave or convex, and the porous material 1 is also filled on the inside thereof. The constructor is also a useful embodiment. Figure 5 shows the implant material 18 of this embodiment. The implant material 1S is formed by making the mesh 1 of the implant material 15 concavely curved into a U-shape, and the porous material filled in the mesh. The object 1 similarly fills the inside of the mesh 8 (that is, the inside of the concave curve) to the porous object 1. As the mesh 8, a mesh produced by decomposing an absorbent polymer sheet or plate in vivo with the above-mentioned good buckling processability by subjecting the secondary forging to a change of the mechanical direction is performed. It has high strength and can be processed at normal temperature, so it is a very good user. Such an implant material 18 is made, for example, into a size that can be embedded and filled in a defect site such as the jawbone, and can be used to repair and reconstruct a defect site of the jawbone as shown by an imaginary line in FIG. 12. . In addition, of course, it can be used for 56 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 for cranium, middle face, upper jaw, and lower jaw for the purpose of repairing and regenerating living bone lost due to accident or cancer. The defect part of the jaw face can also be used for the repair and reconstruction of other large bone defect parts in plastic surgery. Moreover, although the implant material i 8 is concavely curved into a U-shape, the mesh 8 can be concavely or convexly curved according to the shape of the bone defect site to be reconstructed. The porous material i can be filled with the implant material 8 to produce the porous material 1. If necessary, the porous material 1 can be further arranged in a layered manner on the outside of the implant material 18. It can also be used as an implant material in which the mesh 8 is folded, and a porous material 1 is filled between the folded meshes 8. Furthermore, it can also be made as a stack of implant material 15 in two layers. Then, a sandwich-shaped implant material with a layered porous material 1 sandwiched therebetween. 16 and 17 show implant material 19 for artificial cartilage. This artificial cartilage implant material 19 is provided with the organic-inorganic composite porous material 1 described above, a core material 9 of a non-absorbable structure in a living body, and a fixing pin 22 for decomposing an absorbent structure in a living body 22, porous. The object 1 is laminated on the upper and lower surfaces of the core material 9 of the non-absorbable structural material in the living body as a combination, and the tip of the fixing pin 2 2 is protruded from the surface of the porous object 1. This artificial cartilage implant material 19 is a block shape having a planar shape of a rectangle and a semicircular shape, which are roughly forward and back, as shown in FIG. 16, and is suitable for use as an artificial intervertebral plate. The core material 9 is composed of organic fibers as a multi-axis three-dimensional multi-dimensional three-dimensional woven or knitted structure or a composite structure of such a composite structure, and has the same degree of mechanical strength and flexibility as cartilage of intervertebral plates , Deformation Department 57 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 Living imitation person. The structure of this core material 9 is the same as the structure described in Japanese Patent Application No. 6-2 5 4 5 1 5 which has been filed by the applicant, and its geometric shape is dimensioned. The number of orientations of the fiber arrangement is expressed by the number of axes, and a structure composed of a multiaxial-fibrous structure with three or more axes is preferred. The 3-axis-three-dimensional structure is an organizer that three-dimensionally, longitudinally, horizontally, and vertically-directional fibers. The representative shape of the structure is the thickness of the core material (plate-like or even plate-like). In a block shape), can also be made into a cylindrical shape or a honeycomb shape. This 3-axis-three-dimensional structure can be classified into an orthogonal structure, a non-orthogonal structure, a connected structure, and a cylindrical structure, depending on the structure. In addition, a structure having a multi-axis and three-dimensional structure with four or more axes can be arranged with a multi-axis orientation such as 4, 5, 6, 7, 9, and 11 axes to increase the iso-directionality of strength. Furthermore, through these selections, a cartilage tissue that is more similar to a living body and a core that is more imitative in a living body can be obtained. The internal voids of the core material 9 constituted by the above-mentioned structure and structure are preferably in a range of 20 to 90%. In the case of less than 20%, since the core material 9 is denser, softness and deformation may be impaired. For those who cannot satisfy the core material as an artificial cartilage implant material, and above 90%, the compression strength and shape retention of the core material 9 are lowered, which makes it unsuitable as an artificial cartilage implant. The core material of the material. As the organic fibers constituting the core material 9, living-inactive synthetic fibers such as fibers of polyethylene, polypropylene, polytetrafluoroethylene, etc. can be used; the organic core fibers are covered with the above-mentioned living-inactive resin. Coated fibers which are made into a living body are preferably used. In particular, the ultra-high 58 3127 patent specification (Supplement) / 92-02 / 91134292 200300666 molecular weight polyethylene core fiber (twisted yarn) is coated with a linear low-density polyethylene film with a diameter of 0. Coated fibers with a size of 2 to 0.5 mm are optimal fibers for strength, hardness, elasticity, and ease of weaving. Alternatively, other fibers that are active in vivo (for example, have bone conduction or inducibility) can be selected. The structure of the core material 9 is disclosed in detail in Japanese Patent Application No. 6-2 5 4 5 1 5 and will not be described further. The porous material 1 laminated on the upper and lower surfaces of the core material 9 is the same as the organic-inorganic composite porous material described above, that is, the biologically active bioceramic particles are substantially uniformly dispersed in the biodegradable absorbent polymer. The formed porous body which is decomposable and absorbable in vivo is a body with continuous pores, and a part of the bioceramic particles in the pores and the surface of the porous body are exposed. This porous material 1 is produced by the above-mentioned manufacturing method of the present invention, and its porosity, pore diameter of continuous pores, ratio of continuous pores to the total pores, in vivo degradable absorbent polymer, bioceramic particles, and content ratio of the particles And so on, as described above. The porous material 1 has a function as a spacer. The porous material 1 is laminated on both sides of the core material 9 and the implant material 16 is inserted between vertebrae such as the cervical spine and the lumbar spine (refer to the cervical spine C in FIG. 6). 3-C 4 or lumbar vertebra L · 4-L · 5), the porous body 1 is compressed and deformed by the compression pressure of the upper and lower vertebral bodies and tightly contacts the vertebral body. As the porous body 1 comes into contact with the body fluid, Hydrolysis, bone tissue can be conducted to the inside of the porous body 1 through the bone conduction energy of the bioceramic particles. In a relatively short period of time, the porous body 1 will replace the bone tissue and directly bind the vertebral body and the core material 9. At this time, the surface of the core material 9 is sprayed with bioceramic 59 312 / patent specification (supplement) / 92-02 / 91134292 200300666 particles to form a living body activated surface layer, which is bound by the conductive living bone The direct bonding of the activated surface layer 'vertebral body and the core material 9 can be performed in a comparatively short period of time, and the strength can also be maintained. Furthermore, when the osteoinductive factor is contained in the porous material 1, osteoinductivity is exhibited and the effect is more effective. The thickness of this porous material 1 is preferably about 0.5 to 3 mm; more than 0. In the case of 5 mm thin, it is difficult to absorb the unevenness of the surface of the vertebral body due to compression deformation, so there is a concern that the adhesion with the vertebral body is reduced. Resorption and replacement with bone tissue will take longer. Further, as shown in FIG. 17, the porous material 1 is laminated so that approximately half of its thickness is buried in the core material 9, and the porous material 1 is preferably surrounded by the peripheral edge portion of the core material 9. In this way, abrasion of the periphery of the porous material 1 can be suppressed. In addition, the porous material 1 may contain the above-mentioned bone formation factors, growth factors, agents, etc. in an appropriate amount. In this case, bone formation in the porous material 1 can be significantly promoted, and the core material 9 and the vertebral body The direct combination can be effective early. Further, the surface of the porous material 1 may be subjected to the above-mentioned oxidation treatment to improve the wetting characteristics, so that the invasion and growth of proliferating osteoblasts can be more effective. The fixing shaft pin 22 passes through the core material 9 and the porous material 1 on both sides thereof, and both ends protrude from the porous material 1. With such a fixing shaft pin 22, when the implant material 19 is inserted between the upper and lower vertebrae, the front end of the fixing shaft pin 22 protruding from the porous body 1 will bite due to the clamping pressure of the upper and lower vertebrae. The contact surface of the vertebral body is inserted, so the implant material i 9 can be fixed between the vertebral bodies without the position deviation of 60 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666. The number of fixing shaft pins 22 is preferably 2 or more. The optimal number is 3 as shown in the figure. In this case, it can be stably installed between the upper and lower vertebral bodies through a 3-point support. Is its advantage. Both ends of the fixing shaft pin 22 are preferably formed in a conical shape or the like, and the diameter of the shaft pin 22 is preferably 1 to 3 mm in order to ensure the strength. Furthermore, the protruding dimensions of the two front ends of the fixing pin 22 are set to 0. 3 to 2 mm is preferred. At the beginning of the insertion of the implant material 1, since the clamping pressure of the upper and lower vertebral bodies acts on the fixing shaft pin 22, a strong fixing shaft pin is necessary. Therefore, this fixing pin 22 is decomposed in vivo using crystalline poly-L-lactic acid and polycarboxyacetic acid having a viscosity average molecular weight of 150,000 or more (but preferably about 200,000 to 600,000). The absorbent polymer is preferably produced, and it is more preferable to use a bioceramic particle mixed with these polymers in vivo. If necessary, the polymer molecules may be aligned to increase the strength by methods such as compression molding, forging, and stretching. The artificial cartilage implant material 19 having the above-mentioned structure is attached to the upper and lower intervertebral plates as artificial intervertebral plates. As described above, the two front ends of the fixing shaft nails 22 protruding from the surface of the porous body 1 will bite into the vertebral body. At the contact surface, the implant material 19 can be fixed between the vertebral bodies without positional displacement. Therefore, there is no need to fix a living material with an auxiliary fixture or the like, and the operation can be easily performed. In addition, if the implant material 19 is installed between the vertebral bodies in this way, the porous material 1 on the surface of the core material 9 will be compressed and deformed by the compression force of the upper and lower vertebral bodies, and will closely fit the vertebral body. During the decomposition and absorption of the object i, bone tissue will be conductively formed inside the porous material 1. In a short period of time compared with 61 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666, the porous material 1 will replace Instead, it is directly combined with the vertebral body and the core material 9. However, since the core material 9 is a living-inactive synthetic fiber, bone tissue is not conductively formed into the inside thereof, and flexibility is maintained. This core material 9 is composed of organic fibers as a multi-axis three-dimensional multi-dimensional three-dimensional woven or knitted structure or a composite structure of such a composite structure. The flexibility and deformation are relatively easy, so it can perform almost the same behavior as the intervertebral plate to play the role of the intervertebral plate. In addition, the fixing pin 22 can be disassembled and absorbed in a relatively short period of time, so it does not remain. As mentioned above, the artificial cartilage implant material 19 and the core material 9 are imitative in nature. The behavior is similar to that of cartilage tissue, and it is directly fixed to the bone endplate of the vertebral bone and can be fixed in the initial stage. The front end of the shaft nail 2 2 will puncture the bone tissue, which can prevent its lateral displacement and disengagement. The porous material 1 will be directly combined with the bone tissue and can be integrated histologically. Therefore, the disadvantages of this implant material 19, such as the conventional self-supporting artificial intervertebral plate of the sandwich structure, can be completely eliminated. In addition, the above-mentioned artificial cartilage implant material 19 is attached to two areas of the core material 9 with the porous material 1 and the two front ends of the fixing studs 22 protrude from the porous material 1. However, it can also be made on the core material 9. The single-area layer is composed of a porous material 1 and a tip of a fixing shaft pin 22 is protruded. The artificial cartilage implant material having such a structure is fixed to one vertebral body on one side by a fixing shaft pin 22, and although the fixing strength is reduced, the positional displacement of the implant material 19 can be prevented. In addition, the thickness of the porous object 1 can be gradually increased as the front square part approaches the rear round part. If so, the upper and lower vertebrae 62 312 / Patent Specification (Supplement) / 92-02 / 91134292 200300666 The space between the bodies will be slightly narrower on the front side and wider on the back side, so the implant material can be installed to fit the space completely. In addition, if necessary, instead of a through fixing shaft pin 22, a short fixing shaft pin can be buried in the surface layer portion of the core material 9, and the tip of the shaft pin can be made from the porous material 1 Make it stand out. The above is the description of the implant material 19 for artificial intervertebral plates. However, as long as the shape is appropriately changed, it can be used as implant materials for menisci other than artificial intervertebral plates and various articular cartilages. Figurative. Although the above description has been described in detail with reference to specific embodiments, it is self-evident that various changes and modifications can be made without departing from the spirit and scope of the present invention. This application is based on the Japanese Patent Application (Japanese Patent Application No. 2001-360766) filed on November 27, 2001, and the Japanese Patent Application (Japanese Patent Application No. 2001-368558, filed on December 03, 2001). ), Japanese patent application filed on February 20, 2002 (Japanese Patent Application No. 2002-043137), Japanese patent application filed on August 23, 2002 (Japanese Patent Application No. 2002-242800), 2002 Japanese patent applications filed on September 30 (Japanese Patent Application No. 2 Q 0 2 _ 2 8 5 9 3 3), Japanese patent applications filed on September 30, 2002 (Japanese Patent Application No. 2 〇〇2 _ 2 8 5 9 3 4), the content of which is used here as a reference. [Industrial Applicability] The implant material of the present invention can be practically used as a plant-based structure, patch material, bone cement, other artificial implant materials and intervening materials for bone tissue reconstruction in vivo. , Substitute for cavernous bone, carrier for drug release. 312 / Patent Specification (Supplement) / 92-〇2 / 91134292 63 200300666 Furthermore, the implant material of the present invention is used as a combination with other living body decomposing absorbent materials and / or non-absorbable materials in vivo. , Can be used as a variety of bone fixation materials, vertebral body fixation materials, various living bone spacers, bone defect site 塡 supplement material, patch material or 塡 filling material, artificial cartilage material, etc. [Brief Description of the Drawings] Fig. 1 is a perspective view showing an embodiment of an implant material of the present invention. 2 (a), (b), and (c) are explanatory diagrams of an example of use of the implant material in the same embodiment. Fig. 3 is a perspective view showing another embodiment of the implant material of the present invention. FIG. 4 is a perspective view of a base material of the implant material in the same embodiment. Fig. 5 is a longitudinal sectional view of an implant material according to the same embodiment. FIG. 6 is an explanatory diagram of an example of use of the implant material in the same embodiment. Fig. 7 is a perspective view showing still another embodiment of the implant material of the present invention. Fig. 8 is a perspective view showing still another embodiment of the implant material of the present invention. Fig. 9 is a perspective view showing still another embodiment of the implant material of the present invention. Fig. 1 Q is a perspective view showing still another embodiment of the implant material of the present invention. Fig. 11 is a sectional view of an implant material according to the same embodiment. FIG. 12 is an explanatory diagram of an example of use of the implant material in the same embodiment. Figure ^ is a cross-sectional view showing still another embodiment of the implant material of the present invention 312 / Patent Specification (Supplement) / 92-02 / 91134292 64 200300666. Fig. 14 is a sectional view showing still another embodiment of the implant material of the present invention. Fig. 15 is a sectional view showing still another embodiment of the implant material of the present invention. The figure is a perspective view showing still another embodiment of the implant material of the present invention. FIG. 17 is a cross-sectional view of an implant material according to the same embodiment. Description of component symbols 1 Organic-inorganic composite porous object lb Entrance 2 Axle 2a Bump 3 Steel wire 4 Sash 5 Hole 6 Base material 6 a Hollow 6 b Hollow entrance 6d Top of base material 6 e Base of base material for fixing 6g protrusion 6h sharp shaft pin 312 / patent specification (supplement) / 92-02 / 91134292 65 200300666 6 i wall part 6 j communicating hole 6 η small curvature 7 skin layer 8 mesh 8 a mesh Eye 8 b Equivalent to warp yarn part 8 c Equivalent to weft yarn part 9 Core material 1 0 ~ 1 9 Implant material 2 0 Skull 2 1 Defective part 2 2 Fixing pin 3 0 Screw 312 / Patent Specification (Supplement) / 92 -02/91134292