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1. 发明授权

US5491082A Plasminogen activator covalently bonded to a porous body of .beta.-tricalcium phosphate 失效
标题翻译：共价键合到β-磷酸三钙的多孔体上的纤溶酶原激活物
公开(公告)号：US5491082A
公开(公告)日：1996-02-13
申请号：US246940
申请日：1994-05-20
申请人： Takahiro Suzuki , Sukezo Kawamura , Motohiro Toriyama , Yoshiyuki Yokokawa , Yukari Kawamoto , Yasuharu Hakamatsuka , Hiroyuki Irie
发明人： Takahiro Suzuki , Sukezo Kawamura , Motohiro Toriyama , Yoshiyuki Yokokawa , Yukari Kawamoto , Yasuharu Hakamatsuka , Hiroyuki Irie
IPC分类号： A61K38/00 , C12N9/72 , C12N11/14 , A61K38/48
CPC分类号： C12N9/6456 , C12N11/14 , A61K38/00
摘要： A plasminogen activator such as urokinase or tissue plasminogen activator is covalently bonded to a porous body composed of calcium phosphate to form a plasminogen activator-porous body complex. The tricalcium phosphate can be .alpha.-tricalcium phosphate, .beta.-tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, octacalcium phosphate and mixtures thereof. In a preferred embodiment, .beta.-tricalcium phosphate which has excellent biocompatibility with the body or a mixture of .beta.-tricalcium phosphate and hydroxyapatite is used. Preferably, synthetic calcium phosphate is used is to avoid impurities contained by natural calcium phosphate. Covalent bonding is by crosslinking with glutaraldehyde, bismaleimides, dihalogenic aryls or diisocyanates, or by using cyanogen bromide, diazotization or periodic acid. The complex can be filled into a column to form a bioreactor. A granular complex can be intravascularly injected into the blood of a patient to provide thrombotic activity for a long period of time. In another embodiment, a complex of a predetermined shape can be implanted to provide thrombotic activity.
摘要翻译：纤维蛋白溶酶原激活剂如尿激酶或组织纤溶酶原激活剂共价键合到由磷酸钙组成的多孔体上以形成纤溶酶原激活剂多孔体复合体。磷酸三钙可以是α-磷酸三钙，β-磷酸三钙，羟基磷灰石，磷酸四钙，磷酸八钙及其混合物。在优选的实施方案中，使用与身体具有优异生物相容性的β-磷酸三钙或磷酸β-磷酸钙和羟基磷灰石的混合物。优选地，合成磷酸钙是为了避免天然磷酸钙含有的杂质。共价键是通过与戊二醛，双马来酰亚胺，二卤代芳基或二异氰酸酯交联，或通过使用溴化氰，重氮化或高碘酸进行交联。复合物可以填充到柱中以形成生物反应器。颗粒状复合物可以血管内注射到患者的血液中以长时间提供血栓形成活性。在另一个实施方案中，可以植入预定形状的复合物以提供血栓形成活性。

2. 发明授权

US5322675A Method of preparing calcium phosphate 失效
标题翻译：磷酸钙的制备方法
公开(公告)号：US5322675A
公开(公告)日：1994-06-21
申请号：US4777
申请日：1993-01-14
申请人： Yasuharu Hakamatsuka , Hiroyuki Irie , Sukezo Kawamura , Motohiro Toriyama
发明人： Yasuharu Hakamatsuka , Hiroyuki Irie , Sukezo Kawamura , Motohiro Toriyama
IPC分类号： C01B25/32 , C04B35/447
CPC分类号： C04B35/447 , C01B25/327
摘要： Powdery calcium carbonate and a powdery dihydrate of calcium monohydrogenohosphate are weighed to get a Ca/P ratio of 1.45 to 1.67. The powdery mixture thus prepared is then added pure water at a temperature of 30.degree. C. or higher to obtain an aqueous slurry having a concentration of about 10% by weight. Thereafter, the aqueous slurry is subjected to a rotational attrition by using a ball mill to conduct a mechanochemical reaction of the calcium carbonate with the dihydrate of calcium monohydrogenphosphate. The slurry is then dried completely at 80.degree. C., followed by pulverization to yield a dry powder of calcium phosphate hydrate. The dry powder is calcinated at a temperature ranging from 720.degree. to 1,150.degree. C. for 1-10 hours or more to give calcium phosphate powder, which is molded in a desired shape and is sintered at a certain temperature to obtain a sintered body of calcium phosphate. The calcium phosphate and the sintered body thereof, thus prepared, have an assured biological safety in that the calcium phosphate is free from hemolysis, antigenicity and cytotoxicity.
摘要翻译：称量粉状碳酸钙和一水合磷酸二氢钙粉末，得到1.45〜1.67的Ca / P比。然后将如此制备的粉末混合物在30℃或更高的温度下加入纯水，得到浓度为约10重量％的含水浆料。然后，使用球磨机对含水浆料进行旋转磨耗，进行碳酸钙与磷酸一氢钙的二水合物的机械化学反应。然后将浆液在80℃下完全干燥，随后粉碎，得到磷酸钙水合物的干燥粉末。将干燥粉末在720〜1150℃的温度下煅烧1-10小时以上，得到磷酸钙粉末，其以所需形状成型并在一定温度下烧结，得到烧结体磷酸钙由此制备的磷酸钙及其烧结体具有确保的生物安全性，因为磷酸钙不含溶血，抗原性和细胞毒性。

3. 发明授权

US4770943A Method of forming rigid film of calcium phosphate compound 失效
标题翻译：形成磷酸钙化合物刚性膜的方法
公开(公告)号：US4770943A
公开(公告)日：1988-09-13
申请号：US123221
申请日：1987-11-20
申请人： Yasuharu Hakamatsuka , Sukezo Kawamura , Motohiro Toriyama
发明人： Yasuharu Hakamatsuka , Sukezo Kawamura , Motohiro Toriyama
IPC分类号： C04B41/87 , A61F2/00 , A61L27/00 , A61L27/32 , C04B41/52 , C04B41/89 , C23C22/03 , B05D1/36 , B05D3/02 , B05D7/00 , B32B9/00
CPC分类号： A61L27/32 , C04B41/009 , C04B41/52 , C04B41/89 , A61F2310/00796 , C04B2103/008 , C04B2111/00836
摘要： A method of forming a rigid film of calcium phosphate compound having good bio-conformance on a surface of a ceramic or metal substrate is disclosed. According to this method, a slurry of a fine powder of phosphate-series glass of CaO-Na.sub.2 O-P.sub.2 O.sub.5 -Al.sub.2 O.sub.3 is applied to the surface of the substrate and is dried and heat-treated to form a binder layer which covers the surface of the substrate. A peptisation agent such as ammonium polyacrylate and water are mixed with a fine powder of a calcium phosphate compound having a particle size of 1 .mu.m or less to prepare a slurry, and this slurry is applied to the surface of the binder layer. The slurry on the binder layer is dried and heat-treated to form a film of the calcium phosphate compound. The film of the calcium phosphate compound formed by this method is uniform and has high adhesion strength with the substrate.
摘要翻译：公开了一种在陶瓷或金属基材的表面上形成具有良好生物一致性的磷酸钙化合物刚性膜的方法。根据该方法，将CaO-Na 2 O-P 2 O 5·Al 2 O 3的磷酸盐系玻璃微粉的浆料涂布在基材的表面上，进行干燥，热处理，形成覆盖表面的粘合剂层基质。将聚丙烯酸铵和水等胶溶剂与粒径为1μm以下的磷酸钙化合物的细粉末混合，制成浆料，将该浆料涂布在粘合剂层的表面。将粘合剂层上的浆料干燥并热处理以形成磷酸钙化合物的膜。通过该方法形成的磷酸钙化合物的膜是均匀的并且与基材具有高粘附强度。

4. 发明申请

US20050158846A1 Cell culture system apparatus for checking cultured cells and apparatus for culturing cells 有权
标题翻译：用于检测培养细胞的细胞培养系统装置和用于培养细胞的装置
公开(公告)号：US20050158846A1
公开(公告)日：2005-07-21
申请号：US10509447
申请日：2003-04-09
申请人： Hiroki Hibino , Shin Katayama , Hiroyuki Irie , Hikaru Inoue , Hitoshi Mizuno , Yasuharu Hakamatsuka , Yoshiharu Saito , Hideki Koyanagi
发明人： Hiroki Hibino , Shin Katayama , Hiroyuki Irie , Hikaru Inoue , Hitoshi Mizuno , Yasuharu Hakamatsuka , Yoshiharu Saito , Hideki Koyanagi
IPC分类号： C12M1/34 , C12M3/00 , C12N5/00 , C12N5/07 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： G06Q10/08 , G06Q10/06
摘要： The present invention discloses a cell culturing system that cultures predetermined cells collected from a patient and supplies cultured cells to the original patient, which together with enabling correlations between the cultured cells and the supplier of the cells to be managed accurately and easily at all times, allows cultured cells and patients to be collated rapidly. In a cell culturing system 20 that carries in cells containing stem cells and contains them in an incoming transport container to which is attached unique identification information, transfers the transported cells to and cultures them in a culture container to which is attached unique identification information, and carries out the cultured cells by transferring them to an outgoing transport container to which is attached unique identification information, ID numbers attached to the containers before and after transfer are input from a barcode reader 31 whenever the cells are transferred to a different container. The input ID numbers are then stored in a database provided in a managing server 40 in mutual correlation.
摘要翻译：本发明公开了一种细胞培养系统，其对从患者收集的预定细胞进行培养，并向原始患者提供培养的细胞，同时能够随时准确，容易地管理培养细胞和细胞供应者之间的相关性，允许培养细胞和患者快速整理。在携带含有干细胞的细胞的细胞培养系统20中，将其包含在附有唯一识别信息的输入运输容器中，将所运送的细胞转移到培养容器中并将其培养至附有唯一识别信息的培养容器中，以及通过将培养的细胞转移到附着的唯一识别信息的输送输送容器，每当将细胞转移到不同的容器时，从条形码读取器31输入附着到转移前后的容器的ID号码。然后将输入的ID号码相互相关地存储在管理服务器40中提供的数据库中。

5. 发明授权

US5318779A Drug-impregnated ceramic 失效
标题翻译：药物浸渍陶瓷
公开(公告)号：US5318779A
公开(公告)日：1994-06-07
申请号：US494849
申请日：1990-03-15
申请人： Yasuharu Hakamatsuka , Hiroyuki Irie
发明人： Yasuharu Hakamatsuka , Hiroyuki Irie
IPC分类号： A61K9/00 , A61K9/20 , A61K9/28 , A61K9/52 , A61K47/02
CPC分类号： A61K9/0024 , A61K9/2009 , A61K9/2813
摘要： A drug-impregnated ceramic to be embedded in a living body is disclosed, and includes a porous ceramic having pores with a pore size of 10 to 300 .mu.m, a drug impregnating the porous ceramic via the pores, and a surface layer for controlling the release of the drug. The surface layer is formed to cover at least a portion of the outer surface of the porous ceramic and has a porosity lower than that of the porous ceramic.
摘要翻译：公开了一种嵌入生物体中的药物浸渍陶瓷，其特征在于，具有孔径为10〜300μm的多孔陶瓷，通过所述孔浸渍多孔质陶瓷的药物，以及用于控制释放药物。形成表面层以覆盖多孔陶瓷的外表面的至少一部分，并且具有低于多孔陶瓷的孔隙率的孔隙率。

6. 发明授权

US5156623A Sustained release material and method of manufacturing the same 失效
标题翻译：缓释材料及其制造方法
公开(公告)号：US5156623A
公开(公告)日：1992-10-20
申请号：US681084
申请日：1991-04-05
申请人： Yasuharu Hakamatsuka , Hiroyuki Irie
发明人： Yasuharu Hakamatsuka , Hiroyuki Irie
IPC分类号： A61K9/00 , A61K9/16 , A61K9/50 , A61M31/00
CPC分类号： A61K9/0024 , A61K9/1611 , A61K9/501 , A61M31/002
摘要： A sustained release material to be buried at a position close to a diseased part in a living body to slowly release an impregnated liquid drug includes a core mainly consisting of a ceramic material and having a plurality of pores formed at a predetermined porosity, and a surface layer mainly consisting of a ceramic material, formed around the outer surface of the core, and having a plurality of pores having a pore size or porosity smaller than that of the pores formed in the core.
摘要翻译：要在生物体内靠近患病部位的部位埋藏缓释材料，以缓慢释放浸渍液体药物，其主要由陶瓷材料构成，具有以规定的孔隙率形成的多个孔的表面主要由陶瓷材料组成的层，形成在芯的外表面周围，并且具有多个孔，其孔径或孔隙率小于在芯中形成的孔的孔径或孔隙。

7. 发明授权

US07550287B2 Cell culture system apparatus for checking cultured cells and apparatus for culturing cells 有权
标题翻译：用于检测培养细胞的细胞培养系统装置和用于培养细胞的装置
公开(公告)号：US07550287B2
公开(公告)日：2009-06-23
申请号：US10509447
申请日：2003-04-09
申请人： Hiroki Hibino , Shin Katayama , Hiroyuki Irie , Hikaru Inoue , Hitoshi Mizuno , Yasuharu Hakamatsuka , Yoshiharu Saito , Hideki Koyanagi
发明人： Hiroki Hibino , Shin Katayama , Hiroyuki Irie , Hikaru Inoue , Hitoshi Mizuno , Yasuharu Hakamatsuka , Yoshiharu Saito , Hideki Koyanagi
IPC分类号： C12M3/00 , C12M1/36 , C12M1/38
CPC分类号： G06Q10/08 , G06Q10/06
摘要： The present invention discloses a cell culturing system that cultures predetermined cells collected from a patient and supplies cultured cells to the original patient, which together with enabling correlations between the cultured cells and the supplier of the cells to be managed accurately and easily at all times, allows cultured cells and patients to be collated rapidly.
摘要翻译：本发明公开了一种细胞培养系统，其对从患者收集的预定细胞进行培养，并向原始患者提供培养的细胞，同时能够随时准确，容易地管理培养细胞和细胞供应者之间的相关性，允许培养细胞和患者快速整理。

8. 发明授权

US06350462B1 Hollow porous ceramic carrier for embedding in patient for sustained medicament release and method of preparation thereof 失效
标题翻译：中空多孔陶瓷载体，用于包埋在患者中用于持续的药物释放及其制备方法
公开(公告)号：US06350462B1
公开(公告)日：2002-02-26
申请号：US08044549
申请日：1993-04-07
申请人： Yasuharu Hakamatsuka , Hiroyuki Irie , Gen Horie
发明人： Yasuharu Hakamatsuka , Hiroyuki Irie , Gen Horie
IPC分类号： A61K952
CPC分类号： A61K9/0024 , A61K9/2009
摘要： An improved porous ceramic body to be embedded in a patient for sustained release of a medicament, and a method of making the ceramic body is provided. To control the release of the medicament, the pores of the ceramic body decrease in diameter from the inner surface to the outer surface of the body whereby the pore diameter is substantially proportional to the distance from the outer surface of the carrier. First, raw ceramic slurry is made from the blend of &bgr;-TCP, deflocculating agent, and water. Next, using a syringe the ceramic slurry is supplied to the internal region of a solvent-absorbable mold from an aperture along the inner wall surface. Then, the ceramic slurry is quickly dehydrated before thinly adhering itself onto the inner wall surface of the mold. Therefore, a preformed body having a hollow is obtained. Next, after fully being dried, the dried preformed body is fired at 1,050° C. for an hour before eventually yielding a spherical carrier for use in sustained release preparation. Substantially, the carrier is composed of a porous ceramic body which having the hollow for retaining the medicament and permits permeation of the medicament. The pore diameter corresponding to the peak value of the distribution thereof decreases toward to the outer periphery of the preformed body and yet, width of the distribution of the pore diameter becomes narrower.
摘要翻译：一种改进的多孔陶瓷体，其被埋设在患者体内，用于药物的持续释放，并且提供了制造该陶瓷体的方法。为了控制药物的释放，陶瓷体的孔直径从主体的内表面到外表面减小，因此孔径基本上与离开载体的外表面的距离成比例。首先，生陶瓷浆料由β-TCP，抗絮凝剂和水的混合物制成。接下来，使用注射器，陶瓷浆料从沿着内壁表面的孔口供应到吸收溶剂的模具的内部区域。然后，在将其自身轻轻地粘附到模具的内壁表面之前，陶瓷浆料快速脱水。因此，获得具有中空部的预制体。接下来，完全干燥后，将干燥的预成型体在1050℃下烧制1小时，最后得到用于缓释制剂的球形载体。基本上，载体由具有用于保持药物的中空部并允许药物渗透的多孔陶瓷体组成。对应于其分布的峰值的孔径朝向预成形体的外周减小，而孔径分布的宽度变窄。

9. 发明授权

US5152791A Prosthetic artificial bone having ceramic layers of different porosity 失效
标题翻译：具有不同孔隙度的陶瓷层的假体人造骨
公开(公告)号：US5152791A
公开(公告)日：1992-10-06
申请号：US839060
申请日：1992-02-18
申请人： Yasuharu Hakamatsuka , Hiroyuki Irie
发明人： Yasuharu Hakamatsuka , Hiroyuki Irie
IPC分类号： A61F2/00 , A61F2/02 , A61F2/28 , A61F2/30 , A61L27/12
CPC分类号： A61L27/12 , A61F2/28 , A61F2/30756 , A61F2002/2839 , A61F2002/30011 , A61F2002/30062 , A61F2002/30224 , A61F2002/30971 , A61F2210/0004 , A61F2230/0069 , A61F2240/001 , A61F2250/0023 , A61F2310/00293
摘要： A prosthetic artificial bone having a double-layered structure obtained by forming a high porosity portion having a porosity of from 40 to 90% and a lower porosity portion having a porosity of 50% or less, into an integral body, and wherein the high porosity portion and the lower porosity portion each comprise a ceramics containing calcium and phosphorus.
摘要翻译：将具有孔隙率为40〜90％的高孔隙率部分和孔隙率为50％以下的孔隙率低的孔隙率部分形成为具有双层结构的假体人造骨制成整体，其中高孔隙率部分和较低孔隙率部分各自包含含有钙和磷的陶瓷。

10. 发明授权

US5135394A Extraction cavity filling member and a manufacturing method thereof 失效
标题翻译：抽取腔填充构件及其制造方法
公开(公告)号：US5135394A
公开(公告)日：1992-08-04
申请号：US754358
申请日：1991-08-29
申请人： Yasuharu Hakamatsuka , Hiroyuki Irie , Hiroshi Fukuda
发明人： Yasuharu Hakamatsuka , Hiroyuki Irie , Hiroshi Fukuda
IPC分类号： A61C8/00 , A61F2/00 , A61L27/12 , A61L27/56
CPC分类号： A61C8/00 , A61K6/0008 , A61K6/0085 , A61K6/0643 , A61L27/12 , A61L27/56 , A61F2310/00293
摘要： A ceramic member for a living body includes a first end portion formed of a material having affinity with a living body and consisting of a dense material, and a second end portion formed of a material having affinity with a living body and consisting of a porous material. A method of manufacturing a ceramic member for a living body, includes the steps of mixing a ceramic powder having affinity with a living body, water, and a binder to prepare a dense material slurry, mixing a ceramic powder having affinity with a living body, water, a binder, and a foaming agent to prepare a porous material slurry, injecting, in order to form a two-layered base material consisting of the dense material slurry and the porous material slurry, the dense material slurry and the porous material slurry obtained in the two steps in a mold such that the dense and porous material slurries are not mixed with each other, and drying the base material, and after the drying step, heating the base material at a predetermined rate, and sintering the base material at a predetermined temperature.
摘要翻译：用于生物体的陶瓷构件包括由与活体亲和并由致密材料组成的材料形成的第一端部和由与活体亲和力并由多孔材料组成的材料形成的第二端部。一种制造生物体用陶瓷构件的方法包括以下步骤：将具有亲和力的陶瓷粉末与生物体，水和粘合剂混合以制备致密材料浆料，将与活体具有亲和力的陶瓷粉末混合，水，粘合剂和发泡剂以制备多孔材料浆料，注入以形成由致密材料浆料和多孔材料浆料组成的两层基材，得到致密材料浆料和多孔材料浆料在模具中的两个步骤中，使致密多孔材料浆料彼此不混合，并干燥基材，并且在干燥步骤之后，以预定速率加热基材，并将基材以预定温度。

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