TW420604B - An absorbable calcium phosphate biomedical compound material particle and it's manufacturing procedure - Google Patents
An absorbable calcium phosphate biomedical compound material particle and it's manufacturing procedure Download PDFInfo
- Publication number
- TW420604B TW420604B TW89107812A TW89107812A TW420604B TW 420604 B TW420604 B TW 420604B TW 89107812 A TW89107812 A TW 89107812A TW 89107812 A TW89107812 A TW 89107812A TW 420604 B TW420604 B TW 420604B
- Authority
- TW
- Taiwan
- Prior art keywords
- calcium phosphate
- scope
- biomedical
- absorbable
- item
- Prior art date
Links
Landscapes
- Materials For Medical Uses (AREA)
Abstract
Description
420604 五、發明說明(1) -- 【發明的應用範圍】 本發明係有關於一種生醫複合材料顆粒及其製程,特 別是一種應用於骨科手術之磷酸鈣生醫複合材料的組 其製程。 【發明的相關技術】 因X外力或病變切除後所造成的骨骼缺損是骨科等手 術上的一大難題’雖然自體移植骨含有骨形成蛋白質與數 種活的骨細胞,故可加迷骨組織之癒合,遂為骨移植之最 佳的選擇。但由於自體移植骨填補材料(autQgenous bone graft)須在病患本身中以手術取得,所以易造成病人之術 後感染、且取量少是其缺點。異體移植骨填補材料 UUogenous bone graft)則可能會有病毒感染的現象發 生(、如後天免疫不全症),且癒合不良為其缺點。因此為了 促進骨骼缺損之癒合,且避免自體移植或異體移植所潛在 的問題,合成式骨頭缺陷填補材料(b〇ne graft substitutes)的發展是不可或缺的。而目前合成式骨缺陷 填補材料在人體内無法分解被吸收,而且操作性或可塑性 差,於臨床應用頗不方便,因此需開發人體可吸收式 (resorbable)’ 操作性(handling)與可塑性(01〇1(1&};)111^) 佳之骨缺陷之填補物以滿足顱骨顏面整型、齒科或骨科等 骨缺陷填補與骨再生之需要。 習知商品化的產品c〇ilagraft,其組成是由生醫陶瓷 (bl〇Ceramics)與膠原蛋白(collagen)所形成的複合材 料’但其中所揭露之膠原蛋白與陶瓷材料的重量比與骨組420604 V. Description of the invention (1)-[Scope of application of the invention] The present invention relates to a biomedical composite material particle and its manufacturing process, especially a group of calcium phosphate biomedical composite material used in orthopedic surgery. [Related technology of the invention] Bone defect caused by X external force or lesion resection is a major problem in orthopedics and other surgical operations. 'Although autograft bone contains bone-forming proteins and several types of living bone cells, it can add vaginous bone. Tissue healing is the best choice for bone transplantation. However, since the autQgenous bone graft must be obtained by surgery in the patient itself, it is easy to cause postoperative infection of the patient and the amount is small. UUogenous bone graft) may cause viral infection (such as acquired immunodeficiency syndrome), and poor healing is its disadvantage. Therefore, in order to promote the healing of bone defects and avoid the potential problems of autograft or allograft, the development of synthetic bone graft substitutes (bone graft substitutes) is indispensable. At present, synthetic bone defect filling materials cannot be decomposed and absorbed in the human body, and have poor operability or plasticity, which is inconvenient for clinical application. Therefore, it is necessary to develop human absorbable 'handling and plasticity (01 〇1 (1 &};) 111 ^) Excellent bone defect filling material to meet the needs of skull face plastic surgery, dental or orthopedic bone defect filling and bone regeneration needs. The conventional commercial product coilagraft is composed of a composite material formed of bioceramics and collagen ’, but the weight ratio of the collagen to the ceramic material and the bone group disclosed therein
42〇6〇4 五、發明說明(2) - —--- 甚多。雖然許多的研究顯示Collagraft植入動物體 尤很好的骨再生的能力,但陶瓷成分中含有60%的生 解性氫氧基磷灰石,在體内會造成新生骨形成的 ,使骨組織的整合性受到限制,為其主要的缺點。 另外在美國專利編號5, 658, 5 93與5, 424, 084所揭示 的技術,則是製作此種膠原蛋白微粒的方法。 膠原蛋白的網狀纖維結構(netw〇rk structure)是細 ,外間質的主要型態,所以具有網狀纖維結構的膠原蛋白 U粒與組織更為相似β但在前揭的已知專利技術中卻未提 出其所形成的膠原蛋白微粒具有網狀纖維結構,至於如何 在膠原蛋白形成網狀纖維結構的技術亦未有任何的揭露。 此外’目前已知膠原蛋白與陶瓷粉末所形成的複合材 料’其中勝原蛋白所佔的比例均遠低於骨組織中勝原蛋白 所佔整體的比例。 【發明之概述及目的】 有鑒於此,本發明之主要目的是要解決上述習知合成 式骨缺陷填補材料在人體内無法分解被吸收,而且操作性 或可塑性差’於臨床應用頗不方便之問題,而提供一種可 吸收式磷酸鈣生醫複合材料顆粒及其製程。 本發明係利用膠原蛋白具有再重組(reconstructed) 成網狀纖維結構特性之可溶解性之骨傳導性 (osteo-conduct i ve),結合鱗酸鈣系陶瓷粉末,如氫氛基 磷灰石(hydroxy 1 apatite),使磷酸鈣系陶瓷粉末能均勻 的散佈於重組的膠原蛋白網狀纖維結構中。在骨組織的顯42〇6〇 5. Description of the invention (2)---- --- Many. Although many studies have shown that Collagraft has a particularly good bone regeneration capacity when implanted in animals, the ceramic component contains 60% of biodegradable hydroxyapatite, which can cause new bone formation in the body and integrate bone tissue Sexual limitations are its main disadvantage. In addition, the techniques disclosed in U.S. Patent Nos. 5,658,593 and 5,424,084 are methods for making such collagen microparticles. The network structure of collagen is thin and the main form of the outer stroma, so collagen U particles with a netlike structure are more similar to the tissue β, but previously known patented technology disclosed However, it has not been proposed that the collagen particles formed by the collagen particles have a reticular fibrous structure, and the technology of how to form a reticular fibrous structure in collagen has not been disclosed. In addition, "complex materials formed by collagen and ceramic powder are currently known" in which the proportion of victorin is much lower than the proportion of victorin in bone tissue. [Summary and purpose of the invention] In view of this, the main purpose of the present invention is to solve the above-mentioned conventional synthetic bone defect filling material which cannot be decomposed and absorbed in the human body, and has poor operability or plasticity, which is inconvenient for clinical application The problem is to provide an absorbable calcium phosphate biomedical composite particle and its manufacturing process. The present invention utilizes the soluble osteo-conduct i ve of collagen which has the characteristics of reconstructed into a network fiber structure, combined with calcium scaly-based ceramic powder, such as hydrogen-apatite-based apatite ( hydroxy 1 apatite), so that the calcium phosphate ceramic powder can be uniformly dispersed in the recombinant collagen network fiber structure. Significant in bone tissue
420604 五、發明說明⑶ 微結構中’生物磷灰石(bio_apatite)是成核於骨傳導性 有機質的纖維上,而本發明中由磷酸鈣系陶瓷粉末與膠原-蛋白網狀纖維結構所形成之複合材料顆粒的微觀結構上與 骨組織的顯微結構是相似的。 另外,本發明所製成的新型骨填補再生用可吸收性續 酸鈣系複合材料顆粒,可以達到膠原蛋白與陶瓷粉末的重 量比為3 5 : 6 5,而此比例是與骨组織相類似的,且其中陶 瓷粉末的粒徑各5 y m ’因此具有可被人體吸收之特性,而 且成份結構、組成與骨組織相似、不需二次手術,不但可 操作與可塑性佳,且可充份利用骨組織的再生功能而達到 迅速有效的骨再生效果。 本發明的另一目的便是使研製出之可吸收性璃酸I弓系 (calcium phosphate -based)生醫複合材料,除了可單獨 使用,也可配合病患自身的骨锻(bone marrow),或應用組 織工程(tissue engineering)的理念,將可吸收式麟酸轉 系生醫複合材料作為植入細胞(seecjed cells)之基底 (scaffolds)與相關生長因子的(growth factors)的載體 (carriers),以充分應用骨組織本生的再生功能以達到更 迅速有效的骨再生功用,使骨缺陷處更迅速的修補再生。 本發明的再一目的便是在於提供一種可吸收式磷酸鈣 生醫複合材料顆粒的製造技術。 、 根據上述本發明之目的,提供的可吸收式磷酸鈣生醫 複合材料顆粒的製程至少包括以下步驟: 將膠原蛋白與氫氧基碟灰石混合均勻後,滴入油相中420604 V. Description of the invention (3) In the microstructure, 'bioapatite' (bio_apatite) is nucleated on osteoconductive organic fibers, and in the present invention, it is formed by calcium phosphate ceramic powder and collagen-protein network fiber structure. The microstructure of composite particles is similar to that of bone tissue. In addition, the novel resorbable calcium carbonate-based composite material particles for bone filling regeneration produced by the present invention can achieve a weight ratio of collagen to ceramic powder of 3 5: 6 5 and this ratio is related to bone tissue. Similar, and the ceramic powder has a particle size of 5 μm each, so it has the characteristics of being absorbed by the human body, and its composition and composition are similar to those of bone tissue, without the need for secondary surgery, it is not only manipulable and plastic, but also adequate Utilize the regeneration function of bone tissue to achieve rapid and effective bone regeneration effect. Another object of the present invention is to make the developed absorbable hyaluronic acid I-based (calcium phosphate-based) biomedical composite material, which can be used alone or in combination with bone marrow of the patient, Or apply the concept of tissue engineering to use absorbable linoleic acid-based biomedical composites as scaffolds for implanted cells (seecjed cells) and carriers for growth factors In order to fully apply the natural regeneration function of bone tissue to achieve a more rapid and effective bone regeneration function, the bone defect can be repaired and regenerated more quickly. Another object of the present invention is to provide a manufacturing technology of absorbable calcium phosphate biomedical composite particles. According to the above purpose of the present invention, the process for providing the absorbable calcium phosphate biomedical composite particles includes at least the following steps: After the collagen and the hydroxyl ash are mixed uniformly, they are dropped into the oil phase.
4 ?〇β〇44? 〇β〇4
五、發明說明(4) 使 膠原蛋白/氫氧基磷灰石混合物在油相中右g I . 進行重組而形成網狀纖維結構顆粒’再經由交聯 八时間 到所需之可吸收式磷酸鈣生醫複合材料顆粒。"及分離得· 有關本發明之詳細内容及技術1就配合圖式說明如 【較佳之實施例說明】 本發明所提之可吸收式磷酸鈣系生醫複合材_ 、 製程包含:牛皮之除脂處理、膠原蛋白之萃取、=顆粒之 之純化及可吸收式磷酸鈣系生醫複合材料顆粒之製備曰 個步驟。請參考第1圖所示,為本發明所提之可吸收气鱗 酸約糸生醫複合材料顆粒之製程流程圖,首先為牛皮之^ 脂處理(10);接著進行膠原蛋白之萃取(20);再將取得^ 膠原蛋白純化(3 0 );及可吸收式磷酸鈣系生醫複合材料顆 粒之製備(40)等步驟。 現就整個可吸收式磷酸鈣系生醫複合材料顆粒之製備 步驟’以一較佳實施例說明如下··首先,在牛皮之除脂處 理步驟中’提供一剛自活體取下之牛皮置於—7〇。〇冰箱中 冷凍、儲存,接著在4它下以剃刀進行除毛的工作後,以4 °C、〇. 〇2M的磷酸系(PBS )缓衝溶液沖洗。再將牛皮切成 大小約5mm後’置入等體積比的氣仿甲醇溶液十進行脫 脂’待其溶液呈淡黃色後置換新的氯仿甲醇溶液,直到溶 液呈透明為止。將除脂後的牛皮碎片置入1〇〇%的曱醇 中’除去殘留的氣仿。再將牛皮碎片置入5〇 %的甲醇溶液 中’隨後置於0.15 Μ氣化鈉,50mW[羥基甲基氨甲烷緩衝V. Description of the invention (4) The collagen / hydroxyapatite mixture is made to the right g I in the oil phase. Recombination to form the network fiber structure particles' and then cross-linking for eight hours to the required absorbable formula Calcium phosphate biomedical composite particles. " and separation · Detailed information and technology related to the present invention 1 will be described in conjunction with the drawings, such as [the description of the preferred embodiment] The absorbable calcium phosphate-based biomedical composite material of the present invention_, The process includes: leather Degreasing treatment, collagen extraction, purification of particles, and preparation of absorbable calcium phosphate-based biomedical composite particles. Please refer to FIG. 1, which is a process flow chart of the absorbable pterosin acid biomedical composite particles according to the present invention. The first step is the treatment of fat from cowhide (10); then the extraction of collagen (20 ); And then obtaining collagen purification (30); and preparation of absorbable calcium phosphate-based biomedical composite particles (40) and other steps. Now, the preparation steps of the whole absorbable calcium phosphate-based biomedical composite particles are described in a preferred embodiment as follows. First, in the degreasing treatment step of the cowhide, a cowhide that has been removed from a living body is provided and placed. —70. 〇 Freeze and store in a refrigerator, and then perform hair removal with a razor under 4 ° C, then rinse with 4 ° C, 0.02M phosphate-based (PBS) buffer solution. The cowhide was cut into a size of about 5 mm, and then 'placed in an aerosol-like methanol solution of equal volume ratio and then degreased'. After the solution was pale yellow, the new chloroform methanol solution was replaced until the solution became transparent. The degreased cowhide fragments were placed in 100% methanol to remove residual aeroform. The cowhide fragments were then placed in a 50% methanol solution ’followed by 0.15 M sodium gaseous solution, 50 mW [hydroxymethylaminomethane buffer
420604 五、發明說明(5) 溶液(Tris buffer ),pH 7. 4 的溶液中。420604 V. Description of the invention (5) Solution (Tris buffer), pH 7.4 solution.
在勝原蛋白之萃取步驟中,將經清洗過後的除脂牛皮 置於0. 5 Μ的醋酸溶液令’於溶液中加入5mg/ml胃液素 (pepsin ),並以均質攪拌機攪拌均勻。靜置約2〇小時 後’以高速離心約1小時後收集上層澄清液,並加入氣化 鈉使溶液中氯化鈉濃度為2, 5Μ,靜置約20小時°再高速離 心收集沉澱物’將沉澱物與5〇mM羥基甲基氨甲烷緩衝溶 液(pH = 7_ 2-7. 4)混合均勻,靜置約2〇小時’再以高速離 心收集上層澄清液,並對IM氣化鈉、pH = 7. 2_7. 4、5〇mM 羥基甲基氨f烷緩衝溶液進行透析至系統平衡於 PH = 7_ 2〜7.4。加入氣化鈉於溶液中,使溶液中氯化鈉濃度 為1.8M,以均質授拌機攪掉均勻,靜置雜小時。以高速 ,。收集上層澄e :¾。再加入氣化鈉於溶液中,使溶液中 ί 2 5濃度達2. 5M ’以高速離心收集沉澱物。此時所得到 萨2 ::為1^1^ ^的膠原蛋白。將沉澱物加入適量的0· 5M 醋鲅洛液,以均質機攪拌均勻。 在耀·原蛋白純化步驟Φ,故地, , /那〒’將攪拌均勻之沉澱物灌入透 析袋中,並對〇. 5M醋酸溶液推 > 泳> ^ ,^ ^ 履進仃透析’直到透析袋中的膠 原蛋白溶液呈透明狀,將此腺 保存。 此膠原蛋白溶液放置於-20 °C下 酸二製備之步驟中’其中- 氧基石生醫複合材料;備;=酸鹽等。以氮 取5ml之膠原蛋白溶汸f R y mg ml)與80mg的氫氧基鱗灰In the extraction step of vicin protein, the washed degreased cowhide was placed in a 0.5 M acetic acid solution, and 5 mg / ml pepsin was added to the solution, and stirred with a homomixer. After standing for about 20 hours, 'the upper clear solution was collected after centrifugation at high speed for about 1 hour, and sodium gaseous solution was added to make the sodium chloride concentration in the solution to 2, 5M. After standing for about 20 hours, the precipitate was collected by high speed centrifugation' Mix the precipitate with 50 mM hydroxymethylaminomethane buffer solution (pH = 7_ 2-7. 4), and leave it to stand for about 20 hours', then collect the upper clear solution by high-speed centrifugation, and IM vaporized sodium, pH = 7. 2-7. 4, 50mM hydroxymethylaminofane buffer solution was dialyzed to the system equilibrium at pH = 7-2 ~ 7.4. Add sodium gaseous solution to the solution so that the sodium chloride concentration in the solution is 1.8M. Stir off evenly with a homomixer and leave to stand for an hour. At high speed. Collect the upper layer e: ¾. Then add sodium gasification to the solution, so that the concentration of 2.5 in the solution reaches 2.5 M ′ and collect the precipitate by high-speed centrifugation. At this time, Sa 2 ::: 1 ^ 1 ^^ collagen was obtained. Add the precipitate to an appropriate amount of 0.5M acetonol, and stir with a homogenizer. In the step of purifying the original protein Φ, therefore, / / 〒 'Pour the well-mixed precipitate into the dialysis bag, and push the 0.5 M acetic acid solution > swimming > ^, ^ ^ into the dialysis' Save the glands until the collagen solution in the dialysis bag is transparent. This collagen solution is placed at -20 ° C in the preparation step of acid two, in which-oxystone biomedical composite material; prepared; = acid salt, etc. Take 5ml of collagen (f R y mg ml) with nitrogen and 80mg of hydroxide scale gray
五、發明說明(6) 石於4 °C下混合均勻後,將混合液置入平頭不鏽鋼針頭之 針筒中’再以注射泵擠壓成球滴。球滴滴入3 7 °C之撖欖油 (或其他不具生物毒性之油類)中,以攪拌器持續攪拌1 小時,使膠原蛋白/氫氧基磷灰石混合物有足夠的時間重V. Description of the invention (6) After the stones are mixed uniformly at 4 ° C, the mixed solution is placed in a syringe of a flat-head stainless steel needle, and then extruded into a ball drop by a syringe pump. The ball is dropped into the olive oil (or other non-biotoxic oil) at 37 ° C, and continuously stirred with an agitator for 1 hour, so that the collagen / hydroxyapatite mixture has sufficient time to re-
I 组成網狀結構。在橄欖油中逐漸缓慢的加入2. 5wt%之交聯 劑’交聯劑可為戊二盤(glutaraldehyde)、苟藥萃取液 (genipin)或氰胺(carbodiimide)等,使已重组之膠 原蛋白/氫氧基磷灰石球體在交聯劑中產生交聯,交聯後 的顆粒其尺寸範圍係介於50/zin~5nim。吸出油相,加入填 酸系缓衝溶液後再離心以分離殘留之油相。將清洗後之含 氫氧基碟灰石的膠原蛋白顆粒經冷凍乾燥後置於-20 下 保存。 【發明之功效】 (1 )本發明所製作出之磷酸鈣系生醫複合材料顆粒,其 中提供之磷酸鮮系陶瓷粉末粒徑均$ 5以m,相較於前 案美國專利編破5,658,593與5,424,084,直有可吸 收性’且此膠原蛋白具有再重組的特性而能形成與骨 組織相似之網狀纖維結構’並利用此特性使細微之磷 酸鈣系陶瓷粉末’如氫氧基磷灰石 (hydroxylapatite) ’均勻的分佈於膠原蛋白網狀纖 維結構中。 (2)本發明所製作出之磷酸鈣系生醫複合材料 其I forms a network structure. Slowly add 2.5% by weight of cross-linking agent in olive oil. The cross-linking agent can be glutaraldehyde, genipin, or carbodiimide, so that the collagen has been reconstituted. / Hydroxyapatite spheres are cross-linked in the cross-linking agent. The size of the cross-linked particles ranges from 50 / zin to 5 nm. Aspirate the oil phase, add an acidic buffer solution and centrifuge again to separate the remaining oil phase. The washed collagen granules containing hydroxide ash were freeze-dried and stored at -20. [Effects of the invention] (1) The calcium phosphate-based biomedical composite particles produced by the present invention, the fresh phosphate-based ceramic powders provided therein all have a particle size of $ 5 to m, compared with the previous US patent compilation of 5, 658,593 and 5,424,084, which are directly absorbable 'and this collagen has the property of recombination to form a reticular fibrous structure similar to bone tissue' and use this property to make fine calcium phosphate ceramic powder 'Like hydroxylapatite (hydroxylapatite)' is evenly distributed in the collagen network fiber structure. (2) The calcium phosphate-based biomedical composite material produced by the present invention
第9頁 420604 五、發明說明(7) - 而達到迅速有效的骨再生效果。 (3 )本發明所製作出之磷酸鈣系生醫複合材料顆粒,除 了可以單獨使用,也可配合病患自身的骨髓(b〇ne marrow),或應用組織工程(tissue engineering)的理 念’將可吸收式磷酸鈣系生醫複合材料作為植入細胞 (seeded cells)之基底(scaffolds)與相關生長因子 的(growth factors)的載體(carriers),以充分應用 骨組織本生的再生功能以達到更迅速有效的骨再生功 用,使骨缺陷處更迅速的修補再生。 (4 )本發明所製作出之磷酸鈣系生醫複合材料顆粒,可 以達到膠原蛋白與陶瓷粉末的重量比為35 : 65,而此 比例是與骨組織相類似的。 C5)本發明所製作出之磷酸鈣系生醫複合材料顆粒,其 中膠原蛋白與陶瓷粉末的重量比例可依臨床上不同的 需求而製作出1 〇 : 9 0到1 〇 0:0之複合材料顆粒。 (6)本發明所製作出之磷酸鈣系生醫複合材料顆粒,可 包埋骨質疏鬆(osteoporos i s)用藥劑或荷爾蒙,以治 療骨質疏鬆(osteoporosis),骨質流失 (osteolysis);或可包埋相關中藥以治療骨折等骨科 疾病。 (7 )本發明所製作出之磷酸鈣系生醫複合材料顆粒,可 以應用的範圍包括: 骨科(orthopedics),齒科(dental applicati〇n),顧 顆顏面(crani〇-and maxillofacial)整容之缺陷修Page 9 420604 V. Description of the invention (7)-To achieve rapid and effective bone regeneration. (3) In addition to being used alone, the calcium phosphate-based biomedical composite particles produced by the present invention can also be used with the patient's own bone marrow (bone marrow) or by applying the concept of tissue engineering. Absorbable calcium phosphate-based biomedical composites are used as scaffolds for implanted cells and carriers for growth factors in order to fully utilize the natural regeneration function of bone tissue to achieve The more rapid and effective bone regeneration function enables the bone defects to be repaired and regenerated more quickly. (4) The calcium phosphate-based biomedical composite particles produced by the present invention can achieve a weight ratio of collagen to ceramic powder of 35:65, and this ratio is similar to bone tissue. C5) The calcium phosphate-based biomedical composite particles produced by the present invention, wherein the weight ratio of collagen to ceramic powder can be made according to different clinical needs to produce composite materials ranging from 1: 0: 90 to 1: 0: 0 Particles. (6) The calcium phosphate-based biomedical composite particles produced by the present invention can be embedded with osteoporos is a drug or hormone to treat osteoporosis, osteolysis, or can be embedded. Related Chinese medicine is used to treat orthopedic diseases such as fractures. (7) The calcium phosphate-based biomedical composite particles produced by the present invention can be applied in the following fields: orthopedics, dental applicati, cranio-and maxillofacial cosmetic surgery Defect repair
第10頁 42〇e〇4 五、發明說明(8) 補; 骨科骨折(bone fracture)之補骨材料; 組織工程產品之基底材料(scaffolds); 脊椎融合(spinal fusion);Page 10 42〇e〇4 V. Description of the invention (8) Supplement; bone fracture materials for orthopedic fractures; scaffolds for tissue engineering products; spinal fusion;
I 骨質疏鬆(osteo-porosis); 生物相關產品(biological agents)之載體 (carriers), 例如:用以包埋與釋放抗骨質疏鬆荷爾蒙或藥劑、 抗感染或抗發炎之抗生素、血管再生 (angio-genesis)生長因子、骨再生的生長 因子’如:骨生長因子(BMPs )、轉形生^ 因子(TGF-Beta );治療骨科疾病之中 藥。 如上,然其並非 不脫離本發明之 ’因此本發明之 者為準。 雖然本發明以前述之較佳實施例揭露 用以限定本發明,任何熟習此技藝者,在 精神和範圍內,當可作些許之更動與潤飾 保護範圍當視後附之申請專利範圍所界定I osteo-porosis; carriers of biological agents, such as: embedding and releasing anti-osteoporotic hormones or agents, anti-infection or anti-inflammatory antibiotics, angio-regeneration (angio- genesis) growth factors, growth factors for bone regeneration, such as: bone growth factors (BMPs), transforming growth factor (TGF-Beta); traditional Chinese medicine for the treatment of orthopedic diseases. As above, however, it is not inseparable from the present invention, therefore, the present invention shall prevail. Although the present invention is disclosed in the foregoing preferred embodiments to limit the present invention, anyone skilled in the art can, within the spirit and scope, make a few changes and retouches. The scope of protection is defined by the scope of the attached patent
^20〇 Q4 圖式簡單說明 【圖式說明】 第1圖為本發明所提之可吸收式磷酸鈣生醫複合材料 顆粒之製作流程圖。 【圖式符號說明】 10........牛皮之除脂處理 20........膠原蛋白之萃取 30........膠原蛋白之純化 40........可吸收式磷酸鈣系生醫複合材料顆粒之製備^ 20〇 Q4 Brief Description of Drawings [Illustration of Drawings] Figure 1 is a flow chart for the production of the absorbable calcium phosphate biomedical composite particles according to the present invention. [Illustration of Symbols] 10 ........ Degreasing treatment of cowhide 20 ........ Extraction of collagen 30 ........ Purification of collagen 40 ... ..... Preparation of Absorbable Calcium Phosphate Biomedical Composite Particles
第12頁Page 12
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TW89107812A TW420604B (en) | 2000-04-26 | 2000-04-26 | An absorbable calcium phosphate biomedical compound material particle and it's manufacturing procedure |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TW89107812A TW420604B (en) | 2000-04-26 | 2000-04-26 | An absorbable calcium phosphate biomedical compound material particle and it's manufacturing procedure |
Publications (1)
Publication Number | Publication Date |
---|---|
TW420604B true TW420604B (en) | 2001-02-01 |
Family
ID=21659517
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW89107812A TW420604B (en) | 2000-04-26 | 2000-04-26 | An absorbable calcium phosphate biomedical compound material particle and it's manufacturing procedure |
Country Status (1)
Country | Link |
---|---|
TW (1) | TW420604B (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6752938B2 (en) | 2001-10-13 | 2004-06-22 | Invigor Biotechnology Co., Ltd. | Method of preparing microsphere composite of collagen and bioceramic powder |
CN102247299A (en) * | 2010-05-18 | 2011-11-23 | 双美生物科技股份有限公司 | Biodegradable filling for restoration of alveolar bone |
-
2000
- 2000-04-26 TW TW89107812A patent/TW420604B/en not_active IP Right Cessation
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6752938B2 (en) | 2001-10-13 | 2004-06-22 | Invigor Biotechnology Co., Ltd. | Method of preparing microsphere composite of collagen and bioceramic powder |
CN102247299A (en) * | 2010-05-18 | 2011-11-23 | 双美生物科技股份有限公司 | Biodegradable filling for restoration of alveolar bone |
CN102247299B (en) * | 2010-05-18 | 2013-05-29 | 双美生物科技股份有限公司 | Biodegradable filling for restoration of alveolar bone |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Fleming et al. | Bone cells and matrices in orthopedic tissue engineering | |
JP6284982B2 (en) | Compositions and methods for arthrodetic procedures | |
Tiedeman et al. | The role of a composite, demineralized bone matrix and bone marrow in the treatment of osseous defects | |
Kim et al. | Ridge preservation using demineralized bone matrix gel with recombinant human bone morphogenetic protein-2 after tooth extraction: a randomized controlled clinical trial | |
US6703038B1 (en) | Injectable bone substitute material containing non-ceramic hydroxyapatite cement | |
US7045125B2 (en) | Biologically active composites and methods for their production and use | |
Xiong et al. | BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects | |
Jenis et al. | A prospective study of Autologous Growth Factors (AGF) in lumbar interbody fusion | |
US8524253B2 (en) | Bone regeneration device | |
Liao et al. | Combination of guided osteogenesis with autologous platelet-rich fibrin glue and mesenchymal stem cell for mandibular reconstruction | |
Schützenberger et al. | The optimal carrier for BMP-2: a comparison of collagen versus fibrin matrix | |
EP3530295B1 (en) | Demineralized bone matrix having improved handling characteristics | |
S Shekkeris et al. | Clinical applications of mesenchymal stem cells in the treatment of fracture non-union and bone defects | |
Cassaro et al. | Fibrin biopolymer as scaffold candidate to treat bone defects in rats | |
JP2003530363A (en) | Injectable bone mineral replacement material | |
KR20140038348A (en) | Compositions and methods for spine fusion procedures | |
KR20120092632A (en) | Material for induction of hard tissue regeneration | |
US6485751B1 (en) | Resorbable calcium phosphate-based bio-compound particles and the manufacturing procedure thereof | |
Grosfeld et al. | Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration | |
Hao et al. | The first 3D-bioprinted personalized active bone to repair bone defects: A case report | |
Kalia et al. | Do autologous mesenchymal stem cells augment bone growth and contact to massive bone tumor implants? | |
EP1890713A1 (en) | Osteoblast composition of semi-solidified mixed fibrin for bone fracture agglutination and its manufacturing method | |
Chen et al. | Cranioplasty using osteoconductive scaffold and platelet glue | |
TW420604B (en) | An absorbable calcium phosphate biomedical compound material particle and it's manufacturing procedure | |
Lobo et al. | Quantification of bone mass gain in response to the application of biphasic bioceramics and platelet concentrate in critical-size bone defects |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
GD4A | Issue of patent certificate for granted invention patent | ||
MM4A | Annulment or lapse of patent due to non-payment of fees |