1329009 九、發明說明： 【發明所屬之技術領域】 本發明係有關一種生醫骨材之製造方法，尤指具有 混凝土特性的生醫骨材之製造方法。 【先前技術】1329009 IX. INSTRUCTIONS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a method for manufacturing a raw medical bone material, and more particularly to a method for manufacturing a raw medical bone material having concrete characteristics. [Prior Art]
硫酸妈(calcium sulfate)即是一般所謂的石賞，分為 無水石膏（CaS04)、半水石膏（CaS04.1/2H20)及二水石膏 (CaS〇4 . 2H20)三種，醫療上經常使用的高硬度石膏即是 半水硫酸約(hemiliydro calcium sulfate)。其加水後產生結 晶水，變成二水硫酸鈣就會有凝固硬化效果出現。化學 反應式如下：Calcium sulfate is a so-called stone reward. It is divided into three types: anhydrous gypsum (CaS04), hemihydrate gypsum (CaS04.1/2H20) and dihydrate gypsum (CaS〇4. 2H20). It is often used in medical treatment. The high hardness gypsum is hemiliydro calcium sulfate. When it is added with water, it produces crystallization water, and when it turns into calcium sulfate dihydrate, it has a solidification hardening effect. The chemical reaction formula is as follows:
CaS04 · 1/2Η2〇+3/2Η20 -► CaS04 · 2H20 整個反應過程中每摩爾（mole)的半水硫酸妈除了加 入3/2摩爾（mole)的水之外，還要加入更多的水使整個浆 體能攪拌均勻。所以加入越多的水會使凝固硬化過程越 慢’所需時間就越久。待整個反應結束後，過多的水留 在硫酸鈣内蒸發後即變成孔洞，所以加入越多的水，硬 化後的硫酸鈣強度就越差 磷酸鈣為人體骨骼的主要成份，為目前醫療上骨科 常用之填充材料’用來替代硬骨組織。磷酸鈣填充材料 具有骨傳導（osteoconductivity)之特性，其植入後促進 宿主骨與磷酸鈣填充物材料表面結合，提供一個弓丨導骨 形成。且磷酸鈣填充材料具有良好的生物相容性 (biocompatibility)，其pH值與人體相近，在植入動物 5 1329009 體或人體内將逐漸退化被主體所吸收，能和原組織(h〇st tissue)相互鍵結並能刺激周圍的組織生長，在骨填充物中 佔有重要的角色。一般生醫陶瓷材料的機械強度不佳， 特別是處於複雜的應力狀態時，所以其實際使用上受到 很到的限制。因此，對於生醫材料的要求則在於如何控 制植入體内後填充物的流失速率、改善機械強度，並同 時保有良好的生物相容性。 骨科手術中經常因骨折癒合不良、骨瘤、嚴重外傷 或骨，炎^需施行骨移植術，但臨床上往往難以取得足 夠之/母、、’$月來配合手術或因感染不適宜立即接受海棉骨 私植彳5近年來骨科在臨床上，常會遇到骨質老化及疏 鬆症等案例。隨著人們年紀增長，骨替代產品（bone SUbftUte)更是需求孔急。因疾病而造成局部的缺陷或因 外傷、骨路疾病而造成局部的缺陷，只需將該部位加以 修補即可。而填充材料除了自體骨移植、同種屍骨、加 工後之動物屍骨之傳統方式以外’骨科常用之填充材料 以石瓜酉义妈為主之骨水泥，如C〇uagraft及OsteoSet bone graft substitute等硫酸鈣材料。但常會因取得不易、病患 本身排斥、感染、二次手術、溶解速率太快、軟纖維組 織的長入等缺點。同時為了因應人體骨骼修補的各種複 雜形狀及其相對產生的應力，所以上述各種骨填充材料 在貫際上使用受到报大的限制。所以要如何避免二次手 術及降低植入材料之流失速率、促進骨細胞生長等特性 是目前的研究重點。希望能使填充材料的流失速率接近 6 1329009 骨頭的生長速率，财避免纖維組織的長入。 骨路填充材料是—種植人性的材料，可為單-材料 或疋多種材料組合之複合材料；其可藉骨生成 (〇ste〇genic)、骨誘導（〇ste〇mductive)或骨引導 (osteoeondued_的影響方式而具有促進⑽修復反應。 可促進月生成的材料為材料内含有具有分化成骨能 力的活細J包。月引導性材料為在骨的表面形成一個有功 能的有容納性的支架可增強骨的形成作用(b_ 材料。骨誘導性材料為材料本身可提供生物 ㈣刺激f誘導植人處局部位置的細胞或轉植入的細胞 /刀化為成4的成骨細胞(mature osteoblast)。一個具有骨生 成(osteogenic)特性的材料可定義A :包含有能力可分化 成^组織的活細胞。具㈣引導性(Qste_duetive)的材 料疋促進骨組織骨存在於材料的表面，具有部分功能類 ^ f^ f結構，幫助骨組織形成。而骨誘導(〇ste〇inductive) 材枓為提供-個生物學(bl〇1〇gic)的刺激，此刺激 (mduces)局部或轉化細胞進人可以分化成成熟骨母細胞 (osteoblasts)的通道。 站#疋由上可知，上述習知填充材料，在實際使用上， 顯然具^不便與缺失存在，而可待加以改善者。 緣是’本發明人有感上述缺失之可改善，且依據多 :來從事此方面之相關經驗’悉心觀察且研究之，並配 :學理之制，而提出一種設計合理且有效改善上 失之本發明。 < 7 【發明内容】 本發明之主要目的，在於提供一種具有混凝土特性 的生醫骨材之製造方法，該方法之特點在於利用不同粒 徑大小的生醫骨材，如半水硫酸妈鹽、鱗酸妈鹽系列之 生醫玻璃或生醫玻璃陶瓷或生醫陶瓷相，以不同比例進 行漿體混合後形成具有混凝土特徵與特性之骨骼填充 物。該方法所產出之生醫用骨材特徵，外觀上為一具有 大小顆粒混合之固體，並且具有一定強度之生醫骨材。 為了達成上述之目的，本發明係提供一種具有混凝 土特性的生醫骨材之製造方法，其步驟包括：混合水或 稀酸溶液與一骨水泥，以形成骨水泥漿體；將複數個細 骨材混入該骨水泥漿體，以形成骨水泥砂漿體；以及將 複數個粗骨材混入該骨水泥砂漿體，以形成具有混凝土 特性之生醫骨材。 為了使能更進一步瞭解本發明為達成預定目的所採 取之技術、手段及功效，請參閱以下有關本發明之詳細 說明與附圖，相信本發明之目的、特徵與特點，當可由 此得一深入且具體之瞭解，然而所附圖式僅提供參考與 說明用，並非用來對本發明加以限制者。 【實施方式】 請參閱第一圖所示’本發明係提供一種具有混凝土 特性的生醫骨材之製造方法，其步驟包括：混合水或稀 酸溶液與一骨水泥，以形成骨水泥漿體（S100);將複數 個細骨材1混入該骨水泥漿體，以形成骨水泥砂漿體 (S102);以及將複數個㈣材2混人射水泥砂聚體， 以形成具有混凝土特性之生醫骨材（sl〇4)。其中更包 括.將一特殊添加物混入該具有混凝土特性之生醫骨 材，以形成具有混凝土特性之特殊生醫骨材（Sl〇6)，該 特殊添加物為抗生素或成長因子（gr〇wthfactw)。 该稀酸溶液為稀磷酸加水之水溶液，該骨水泥為 α、/5相之半水硫酸鈣鹽。該細骨材丨為二水硫酸鈣顆 粒、磷酸鈣鹽之生醫玻璃、生醫破璃陶瓷、生醫陶瓷或 聚左旋乳酸（PLLA)。該細骨材1粒徑範圍為小於59〇 微米該粗骨材2為二水硫酸鈣顆粒、磷酸鈣鹽 之生醫玻璃、生醫玻璃陶瓷、生醫陶瓷或聚左旋乳酸 (PLLA )。該粗骨材2粒徑範圍為刚〜141〇微米（以m )。 其中有複數個中骨材3粒徑範圍為590〜840微米（ 本發明（1)將打鍵完成後醫療等級二水、半水硫酸I弓 叙劑與磷酸鈣系玻璃或玻璃陶瓷或陶瓷以均質機分別打 〜後’透過粉體震盪過薛機，進行粉體過篩。分別經過 ASTM(美國試驗材料學會）規範下之標準分析筛網325、 2()()、120、1〇〇震盪過篩。（2)將過筛後之碎裂體經過分 f後’將較細微粉體經雷射粒徑分析後，取特定比例的 最小极徑粉體。（3)利用兩種或兩種以上大小粒徑不同之 卷體造行混合漿體。其中將二水硫酸鈣鹽做為基材，半 水硫峻鈣鹽為砂體，混入磷酸鈣鹽(4)待漿體硬化完成後 即形戍。 請參閱第二圖與第三圖所示’為本發明混合細骨材 1329009 1、中骨材3及粗骨材2之示意圖，請參閱第四圖所示， 為本發明混合不同粒徑大小的生醫骨材之掃描式電子顯 微鏡圖，其中可看出有些混合為砂4,有些混合為石頭5。CaS04 · 1/2Η2〇+3/2Η20 -► CaS04 · 2H20 For every mole of hemihydrate sulfuric acid in the whole reaction, in addition to adding 3/2 moles of water, add more water. The entire slurry can be stirred evenly. So the more water you add, the slower the solidification hardening process. The longer it takes. After the end of the reaction, too much water remains in the calcium sulfate and becomes a hole after evaporation. Therefore, the more water is added, the worse the strength of the hardened calcium sulfate is. The calcium phosphate is the main component of human bones, and is currently medical orthopedics. Commonly used filler materials are used to replace hard bone tissue. The calcium phosphate filler has the property of osteoconductivity, which promotes the binding of the host bone to the surface of the calcium phosphate filler material after implantation, providing a bowel bone formation. And the calcium phosphate filling material has good biocompatibility, and its pH value is similar to that of the human body. It will gradually degenerate and be absorbed by the main body in the implanted animal 5 1329009 or human body, and can be compared with the original tissue (h〇st tissue). Mutual bonding and stimulating the growth of surrounding tissues plays an important role in bone filling. Generally, the mechanical strength of biomedical ceramic materials is not good, especially when it is in a complex stress state, so its practical use is very limited. Therefore, the requirement for biomedical materials is how to control the rate of loss of filler after implantation in the body, improve mechanical strength, and at the same time maintain good biocompatibility. In orthopedic surgery, bone grafting is often performed due to poor fracture healing, osteoma, severe trauma, or bone. It is often difficult to obtain enough mother/female, '$month to cooperate with surgery, or inappropriate for infection. In recent years, the orthopedics have been exposed to bone aging and looseness in clinical practice. As people age, bone substitutes (bone SUbftUte) are more urgent. If the disease is caused by local defects or local defects due to trauma or bone disease, it is only necessary to repair the site. In addition to the traditional methods of autologous bone grafting, the same kind of bones, and the processed bones of the animals, the filling materials commonly used in orthopedics are bone cements such as C. melon and mothers, such as C〇uagraft and OsteoSet bone graft substitute. Calcium material. However, it is often caused by shortcomings such as difficulty in obtaining, self-rejection of the patient, infection, secondary surgery, too fast dissolution rate, and long-term penetration of soft fiber tissue. At the same time, in order to cope with the various complex shapes of the human bone repair and the relative stress generated by them, the use of the above various bone filling materials in a continuous manner is limited. Therefore, how to avoid secondary surgery and reduce the loss rate of implant materials and promote the growth of bone cells is the current research focus. It is hoped that the rate of loss of the filling material will be close to the growth rate of the bones of 6 1329009, avoiding the growth of fibrous tissue. The bone filling material is a planting material, which can be a single material or a composite material of a plurality of materials; it can be produced by bone formation (〇ste〇genic), osteoinduction (〇ste〇mductive) or osteogenic (osteoeondued). _ The mode of influence has a promotion (10) repair reaction. The material that promotes the formation of the moon is a living J package containing the ability to differentiate into bone. The monthly guiding material is to form a functional and containable on the surface of the bone. The scaffold enhances bone formation (b_material. The osteoinductive material provides the organism itself (IV) stimulates f to induce localized cells at the implant site or transfects the cells/knife into 4 osteoblasts (mature Osteoblast. A material with osteogenic properties can define A: a living cell that has the ability to differentiate into tissue. (4) A Qste_duetive material that promotes the presence of bone tissue on the surface of the material. It has a partial functional class ^ f^ f structure to help the formation of bone tissue, while osteoinductive (〇ste〇inductive) material provides a biological (bl〇1〇gic) stimulus, this stimulation (mduces) local or The transformed cells can be differentiated into passages of mature osteoblasts. Station #疋 From the above, it can be seen that the above-mentioned conventional filling materials obviously have inconvenience and deficiency in actual use, and can be improved. The reason is that 'the inventor feels that the above-mentioned defects can be improved, and the basis is based on: the relevant experience in this aspect' is carefully observed and studied, and with the theory of academic theory, and proposes a reasonable design and effective improvement. The present invention is directed to a method for producing a biomedical aggregate having concrete characteristics, which is characterized by utilizing biomedical aggregates of different particle sizes, such as semi-water. The sulphuric acid mother salt, the squamous acid salt series of the raw medical glass or the biomedical glass ceramic or the biomedical ceramic phase, the slurry is mixed in different proportions to form a bone filler with concrete characteristics and characteristics. The medical bone material is characterized by a solid having a mixture of large and small particles and having a certain strength of the raw material. In order to achieve the above object, the present invention is Providing a method for manufacturing a biomedical aggregate having concrete characteristics, comprising the steps of: mixing water or a dilute acid solution with a bone cement to form a bone cement slurry; and mixing a plurality of fine aggregates into the bone cement slurry to Forming a cement mortar; and mixing a plurality of coarse aggregates into the bone cement mortar to form a biomedical aggregate having concrete characteristics. To enable further understanding of the techniques and means for achieving the intended purpose of the present invention The following is a detailed description of the invention and the accompanying drawings. It is believed that the objects, features, and characteristics of the present invention can be understood and understood. The invention is limited. [Embodiment] Please refer to the first figure. The present invention provides a method for manufacturing a biomedical aggregate having concrete characteristics, the steps comprising: mixing water or a dilute acid solution with a bone cement to form a bone cement slurry. (S100); mixing a plurality of fine aggregates 1 into the bone cement slurry to form a bone cement mortar body (S102); and mixing a plurality of (four) materials 2 with a cement sand aggregate to form a biomedicine having concrete characteristics Aged material (sl〇4). In addition, a special additive is mixed into the biomedical aggregate having concrete characteristics to form a special biomedical aggregate (Sl〇6) having concrete characteristics, which is an antibiotic or a growth factor (gr〇wthfactw) ). The dilute acid solution is an aqueous solution of dilute phosphoric acid and water, and the bone cement is a calcium sulfate hemihydrate of α and /5 phases. The fine aggregate material is calcium sulfate dihydrate particles, calcium phosphate salt biomedical glass, biomedical broken glass ceramics, biomedical ceramics or poly-L-lactic acid (PLLA). The fine aggregate 1 has a particle size ranging from less than 59 Å. The coarse aggregate 2 is calcium sulphate dihydrate granules, calcium phosphate salt biomedical glass, biomedical glass ceramics, biomedical ceramics or poly-L-lactic acid (PLLA). The coarse aggregate 2 has a particle size ranging from just 141 〇 micrometers (in m). There are a plurality of medium aggregates 3 having a particle size ranging from 590 to 840 micrometers (the present invention (1) is to be homogenized after the key is completed, the medical grade dihydrate, the hemihydrate sulfuric acid I and the calcium phosphate glass or the glass ceramic or ceramic. After the machine is hit, the machine is sifted through the powder and sifted through the powder. The standard analysis screens 325, 2()(), 120, 1〇〇 under the ASTM (American Society for Testing Materials) are respectively oscillated. Screening. (2) After passing the sieved crushed body through the fraction f, the fine powder is analyzed by laser particle size, and a specific proportion of the minimum polar diameter powder is taken. (3) Using two or two a mixed slurry of the above-mentioned rolls of different sizes and sizes, wherein calcium sulfate dihydrate is used as a substrate, and hemi-sulfur calcium salt is a sand body mixed with calcium phosphate (4) after the slurry is hardened. Referring to the second and third figures, a schematic view of the mixed fine aggregate 1329009 1, the middle aggregate 3 and the coarse aggregate 2 of the present invention, as shown in the fourth figure, is a mixture of the present invention. Scanning electron micrographs of biomedical aggregates of different particle sizes, some of which can be seen as sand 4, some 5 combined into stone.
本發明在於提供一種具有混凝土特性的生醫骨材之 製造方法，該方法之特點在於利用不同粒徑大小的生醫 骨材，如半水硫酸鈣鹽、磷酸鈣鹽系列之生醫玻璃或生 醫玻璃陶瓷或生醫陶瓷相，以不同比例進行漿體混合後 形成具有混凝土特徵與特性之骨骼填充物。該方法所產 出之生醫用骨材特徵，外觀上為一具有大小顆粒混合之 固體，並且具有一定強度之生醫骨材。The invention provides a method for manufacturing a biomedical bone material having concrete characteristics, which is characterized by utilizing biomedical bone materials of different particle sizes, such as a semi-aqueous calcium sulfate salt, a calcium phosphate salt series, or a raw medical glass or raw material. The medical glass ceramic or the biomedical ceramic phase is mixed with the slurry at different ratios to form a bone filler having the characteristics and characteristics of the concrete. The medical bone material produced by the method is characterized in that it is a solid having a mixture of large and small particles and having a certain strength.
惟，以上所述，僅為本發明最佳之一的具體實施例 之詳細說明與圖式，惟本發明之特徵並不侷限於此，並 非用以限制本發明，本發明之所有範圍應以下述之申請 專利範圍為準，凡合於本發明申請專利範圍之精神與其 類似變化之實施例，皆應包含於本發明之範疇中，任何 熟悉該項技藝者在本發明之領域内，可輕易思及之變化 或修飾皆可涵蓋在以下本案之專利範圍。 【圖式簡單說明】 第一圖為本發明具有混凝土特性的生醫骨材之製造方法 之流程圖； 第二圖為本發明不同粒徑大小的生醫骨材之示意圖； 第三圖為本發明混合不同粒徑大小的生醫骨材之示意 圖，以及 第四圖為本發明混合不同粒徑大小的生醫骨材之掃描式 10 1329009 電子顯微鏡圖； 【主要元件符號說明】 1 細骨材 3 中骨材 5 石頭 粗骨材 砂 11However, the above description is only a detailed description of the preferred embodiments of the present invention, and the present invention is not limited thereto, and is not intended to limit the present invention. The scope of the patent application is subject to the scope of the present invention, and any one skilled in the art can easily include it in the field of the present invention. Any changes or modifications considered may be covered by the patents in this case below. BRIEF DESCRIPTION OF THE DRAWINGS The first figure is a flow chart of a method for manufacturing a biomedical aggregate having concrete characteristics according to the present invention; the second figure is a schematic view of a raw material of different diameters and sizes of the present invention; The invention discloses a schematic diagram of mixing raw material aggregates of different particle sizes, and the fourth figure is a scanning microscope 10 1329009 electron micrograph of the raw material aggregates of different particle sizes of the invention; [Major component symbol description] 1 fine aggregate 3 medium aggregate 5 stone coarse aggregate sand 11