公开(公告)号：US08835570B2

公开(公告)日：2014-09-16

申请号：US13121604

申请日：2009-09-29

申请人： Mitsuru Akashi ,  Michiya Matsusaki ,  Dongjian Shi ,  Makoto Onishi ,  Yotaro Fujita

发明人： Mitsuru Akashi ,  Michiya Matsusaki ,  Dongjian Shi ,  Makoto Onishi ,  Yotaro Fujita

IPC分类号： C08G63/664 ,  C08G63/91 ,  A61K9/51

CPC分类号： C08G63/912 ,  A61K9/5153 ,  C08G63/664 ,  G01N2203/00

摘要： A hydrophilic material having a hydrophilic nature and being biocompatible and processable into nanoparticles wherein a hydrophilic monomer such as threitol or a hydrophilic polymer such as polyethylene glycol is attached to the βposition of an α,β-unsaturated carboxyl group of a (co)polymer comprising an aromatic compound such as 4-hydroxycinnamic acid in which an aromatic ring is substituted by the α,β-unsaturated carboxyl group and one or more hydroxyl groups. In particular, a hydrophilic material having a nanoparticle size which is highly dispersible in water, can well migrate into the blood and is useful as a drug carrier, a medical material and a sustained drug release material.

摘要翻译： 亲水性材料具有亲水性并且可生物相容并可加工成纳米颗粒，其中亲水性单体例如苏糖醇或亲水性聚合物例如聚乙二醇被连接到（共聚物）的α，β-不饱和羧基的基团上 ）聚合物，其包含芳族化合物如4-羟基肉桂酸，其中芳环被α，β-不饱和羧基和一个或多个羟基取代。 具体而言，具有高度分散于水中的纳米粒子尺寸的亲水性材料能很好地迁移到血液中，可用作药物载体，医疗材料和持续的药物释放材料。

公开(公告)号：US06503632B1

公开(公告)日：2003-01-07

申请号：US09762962

申请日：2001-02-14

申请人： Akio Hayashi ,  Daijiro Shiino ,  Mitsuru Akashi ,  Ryuzo Hosotani ,  Kensaku Sonoda

发明人： Akio Hayashi ,  Daijiro Shiino ,  Mitsuru Akashi ,  Ryuzo Hosotani ,  Kensaku Sonoda

IPC分类号： B32B904

CPC分类号： C08G77/455 ,  A61K8/898 ,  A61L27/18 ,  A61Q1/10 ,  A61Q3/02 ,  C08G69/42 ,  Y10T428/31663 ,  Y10T428/31725 ,  C08L83/10

摘要： A novel polydialkylsiloxane/polyamide copolymer which is excellent in biocompatibility, mechanical strength, and heat moldability, applicable for use in medical materials, ophthalmic materials, cosmetics, and electronic materials, and has a main chain represented by the formula (4), one end represented by the formula (5) and another end represented by the formula (6): —(NH—A—NHCO—B—CO)m—  (4) —NH—A—NH—X2  (5) —X1  (6) wherein the ratio of —R1—(Si(R2) (R3)—O)n1-Si(R2) (R3)—R1— as A to the divalent organic group having 1 to 20 carbon atoms as A is within the range of 1:0.01˜100, and the proportion of X1 and X2 being hydrogen atoms is 10% or less relative to all the end groups, a process for producing the same, and a variety of its uses.

摘要翻译： 一种新型的聚二烷基硅氧烷/聚酰胺共聚物，其生物相容性，机械强度和热成型性优异，适用于医疗材料，眼用材料，化妆品和电子材料，具有式（4）所示的主链，一端 由式（5）表示的另一端和由式（6）表示的另一端：其中-R1-（Si（R2）（R3）-O）n1-Si（R2）（R3）-R1的比例为A 涉及具有1至20个碳原子的二价有机基团，因为A在1:0.01〜100的范围内，并且X 1和X 2为氢原子的比例相对于所有端基为10％以下，制备方法 相同，以及其各种用途。

公开(公告)号：US06387414B1

公开(公告)日：2002-05-14

申请号：US09368960

申请日：1999-08-05

申请人： Mitsuru Akashi ,  Tetsushi Taguchi ,  Akio Kishida ,  Akio Hayashi

发明人： Mitsuru Akashi ,  Tetsushi Taguchi ,  Akio Kishida ,  Akio Hayashi

IPC分类号： A61K3342

CPC分类号： A61K9/0024 ,  A61L27/46

摘要： A method for preparing a hydroxyapatite composite is disclosed. This method comprises alternately soaking a matrix which has been made hydrophilic at least on its surface, in a calcium ion aqueous solution containing calcium ions and substantially free of phosphate ions and in a phosphate ion aqueous solution containing phosphate ions and substantially free of calcium ions to securely form hydroxyapatite at least on the surface of the matrix. Also disclosed is a biocompatible material composed of the hydroxyapatite composite obtained by the method.

公开(公告)号：US06368631B1

公开(公告)日：2002-04-09

申请号：US09452371

申请日：1999-12-01

申请人： Mitsuru Akashi ,  Akio Kishida ,  Shinji Sakuma ,  Hiroshi Kikuchi

发明人： Mitsuru Akashi ,  Akio Kishida ,  Shinji Sakuma ,  Hiroshi Kikuchi

IPC分类号： A61K914

CPC分类号： A61K47/32 ,  A61K9/1635

摘要： The present invention is directed to particulate carriers useful as drug carriers in a drug delivery system (DDS) and to pharmaceutical compositions making use of such carriers. The invention is characterized by the use, as the particulate carrier, of: graft copolymer (A) whose graft chain is poly N-alkylacrylamide chain, poly N-alkylmethacrylamide chain, etc.; and a composition containing a combination of the graft copolymer (A) and at least one graft copolymers selected from the group consisting of graft copolymers (B-1) having polyacrylic acid or polymethacrylic acid as the graft chain and graft copolymers (B-2) having a polyvinyl amine compound as the graft chain.

摘要翻译： 本发明涉及用作药物递送系统（DDS）中的药物载体的颗粒载体和利用这种载体的药物组合物。 本发明的特征在于使用接枝共聚物（A）作为颗粒载体，其接枝链是聚N-烷基丙烯酰胺链，聚N-烷基甲基丙烯酰胺链等; 和含有接枝共聚物（A）和至少一种选自具有聚丙烯酸或聚甲基丙烯酸作为接枝链的接枝共聚物（B-1）和接枝共聚物（B-2）的组合的组合物， 具有聚乙烯胺化合物作为接枝链。

公开(公告)号：US10073085B2

公开(公告)日：2018-09-11

申请号：US14008348

申请日：2012-03-29

申请人： Mitsuru Akashi ,  Michiya Matsusaki ,  Takeshi Sakura ,  Koji Hashimoto ,  Yuji Shirakata ,  Satoshi Hirakawa

发明人： Mitsuru Akashi ,  Michiya Matsusaki ,  Takeshi Sakura ,  Koji Hashimoto ,  Yuji Shirakata ,  Satoshi Hirakawa

IPC分类号： G01N33/50 ,  C12N5/071

CPC分类号： G01N33/5088 ,  C12N5/0698 ,  C12N2502/094 ,  C12N2502/1192 ,  C12N2502/1323 ,  C12N2502/28 ,  C12N2503/06 ,  C12N2533/52 ,  C12N2533/54

摘要： Provided is a novel method capable of producing an artificial skin model. A method for producing an artificial skin model includes: providing coated cells (1), each of which is obtained by covering the surface of a cell (3) with a coating film (2) containing an extracellular matrix component; forming a dermis tissue layer (7), in which the coated cells (1) are laminated, by culturing the coated cells (1); and forming an epidermis layer (12) by arranging epidermis cells (8) on the dermis tissue layer (7).

公开(公告)号：US20140024010A1

公开(公告)日：2014-01-23

申请号：US14008348

申请日：2012-03-29

申请人： Mitsuru Akashi ,  Michiya Matsusaki ,  Takeshi Sakura ,  Koji Hashimoto ,  Yuji Shirakata ,  Satoshi Hirakawa

发明人： Mitsuru Akashi ,  Michiya Matsusaki ,  Takeshi Sakura ,  Koji Hashimoto ,  Yuji Shirakata ,  Satoshi Hirakawa

IPC分类号： G01N33/50

CPC分类号： G01N33/5088 ,  C12N5/0698 ,  C12N2502/094 ,  C12N2502/1192 ,  C12N2502/1323 ,  C12N2502/28 ,  C12N2503/06 ,  C12N2533/52 ,  C12N2533/54

摘要： Provided is a novel method capable of producing an artificial skin model. A method for producing an artificial skin model includes: providing coated cells (1), each of which is obtained by covering the surface of a cell (3) with a coating film (2) containing an extracellular matrix component; forming a dermis tissue layer (7), in which the coated cells (1) are laminated, by culturing the coated cells (1); and forming an epidermis layer (12) by arranging epidermis cells (8) on the dermis tissue layer (7).

摘要翻译： 提供了一种能够生产人造皮肤模型的新方法。 一种生产人造皮肤模型的方法包括：提供涂覆细胞（1），每个涂覆细胞通过用包含细胞外基质组分的涂膜（2）覆盖细胞（3）的表面而获得; 通过培养所述被覆细胞（1），形成层叠所述被覆细胞（1）的真皮组织层（7）。 以及通过在真皮组织层（7）上布置表皮细胞（8）形成表皮层（12）。

公开(公告)号：US20120095186A1

公开(公告)日：2012-04-19

申请号：US13258867

申请日：2010-03-26

申请人： Masanori Baba ,  Tomofumi Uto ,  Mitsuru Akashi ,  Takami Akagi ,  Chikateru Nozaki ,  Kazuyoshi Kaminaka

发明人： Masanori Baba ,  Tomofumi Uto ,  Mitsuru Akashi ,  Takami Akagi ,  Chikateru Nozaki ,  Kazuyoshi Kaminaka

IPC分类号： C07K2/00 ,  C07K14/005 ,  B32B5/16 ,  C07K14/77

CPC分类号： C07K14/00 ,  A61K47/645 ,  A61K47/6929 ,  C07K7/02 ,  C08G69/10 ,  C08G69/48 ,  Y10T428/2982

摘要： A polyion complex (PIC) or a PIC nanoparticle that may be easily prepared, and that is finally disappeared in vivo due to its suitable biodegradability while exhibiting high stability in vivo, an immunotherapy agent comprising the PIC nanoparticle to which various antigen proteins or peptides may be easily conjugated or incorporated and/or which may be easily mixed with the antigen proteins or peptides, as well as a process for preparing thereof are provided. Specifically, a polyion complex (PIC) comprising a hydrophobized poly(acidic amino acid) and a basic polypeptide, a nanoparticle thereof having a particle shape, an immunotherapy agent comprising the PIC nanoparticle, as well as a process for preparing the PIC, comprising steps of introducing a hydrophobic amino acid to a poly(acidic amino acid) to prepare a hydrophobized poly(acidic amino acid), and dissolving the hydrophobized poly(acidic amino acid) prepared to a buffer, and it is mixed with a basic polypeptide dissolved in a buffer.

摘要翻译： 可以容易地制备的polyion复合物（PIC）或PIC纳米颗粒，并且由于其在体内具有高度稳定性的适当的生物降解性而最终在体内消失，含有各种抗原蛋白或肽可能的PIC纳米颗粒的免疫治疗剂 可以容易地缀合或掺入和/或可以容易地与抗原蛋白质或肽混合，以及其制备方法。 具体而言，包含疏水化聚（酸性氨基酸）和碱性多肽的聚离子复合物（PIC），其具有颗粒形状的纳米颗粒，包含PIC纳米颗粒的免疫治疗剂以及制备PIC的方法，包括步骤 将疏水性氨基酸引入聚（酸性氨基酸）以制备疏水化聚（酸性氨基酸），并将制备的疏水化聚（酸性氨基酸）溶解在缓冲液中，并将其与溶于 一个缓冲区

公开(公告)号：US20110257338A1

公开(公告)日：2011-10-20

申请号：US13121604

申请日：2009-09-29

申请人： Mitsuru Akashi ,  Michiya Matsusaki ,  Dongjian Shi ,  Makoto Onishi ,  Yotaro Fujita

发明人： Mitsuru Akashi ,  Michiya Matsusaki ,  Dongjian Shi ,  Makoto Onishi ,  Yotaro Fujita

IPC分类号： C08F8/34 ,  B82Y30/00

CPC分类号： C08G63/912 ,  A61K9/5153 ,  C08G63/664 ,  G01N2203/00

摘要： A hydrophilic material having a hydrophilic nature and being biocompatible and processable into nanoparticles wherein a hydrophilic monomer such as threitol or a hydrophilic polymer such as polyethylene glycol is attached to the βposition of an α, β-unsaturated carboxyl group of a (co)polymer comprising an aromatic compound such as 4-hydroxycinnamic acid in which an aromatic ring is substituted by the α, β-unsaturated carboxyl group and one or more hydroxyl groups. In particular, a hydrophilic material having a nanoparticle size which is highly dispersible in water, can well migrate into the blood and is useful as a drug carrier, a medical material and a sustained drug release material.

摘要翻译： 亲水性材料具有亲水性并且可生物相容并可加工成纳米颗粒，其中亲水性单体例如苏糖醇或亲水性聚合物例如聚乙二醇被连接到（共聚物）的α，β-不饱和羧基的基团上 ）聚合物，其包含芳族化合物如4-羟基肉桂酸，其中芳环被α，β-不饱和羧基和一个或多个羟基取代。 具体而言，具有高度分散于水中的纳米粒子尺寸的亲水性材料能很好地迁移到血液中，可用作药物载体，医疗材料和持续的药物释放材料。

公开(公告)号：US20110217726A1

公开(公告)日：2011-09-08

申请号：US13128360

申请日：2009-11-10

申请人： Michiya Matsusaki ,  Mitsuru Akashi ,  Kazunori Okano

发明人： Michiya Matsusaki ,  Mitsuru Akashi ,  Kazunori Okano

IPC分类号： C12Q1/02 ,  C12N5/071

CPC分类号： G01N33/5032 ,  G01N33/5088 ,  G01N33/54313

摘要： Disclosed is a method for detecting a biological signal of a three-dimensional cell culture construct. The method for detecting a biological signal of a three-dimensional cell culture construct includes: providing a three-dimensional cell culture construct that contains at least two cell layers laminated to each other and a sensor particle capable of detecting a biological signal; and observing the sensor particle optically. Preferably, the three-dimensional cell culture construct contains an extracellular matrix including a combination of a protein or polymer having an RGD sequence and a protein or polymer that interacts with the protein or polymer having the RGD sequence, or a combination of a protein or polymer that is positively charged and a protein or polymer that is negatively charged.

摘要翻译： 公开了一种检测三维细胞培养构建体的生物信号的方法。 用于检测三维细胞培养构建体的生物信号的方法包括：提供包含彼此层压的至少两个细胞层的三维细胞培养构建体和能够检测生物信号的传感器粒子; 并且光学地观察传感器粒子。 优选地，三维细胞培养物构建体包含细胞外基质，其包括具有RGD序列的蛋白质或聚合物和与具有RGD序列的蛋白质或聚合物相互作用的蛋白质或聚合物或蛋白质或聚合物的组合的组合 带正电荷的蛋白质或聚合物带负电荷。

公开(公告)号：US20090117656A1

公开(公告)日：2009-05-07

申请号：US12094973

申请日：2006-11-24

申请人： Mitsuru Akashi ,  Yoshiki Sawa ,  Michiya Matsusaki

发明人： Mitsuru Akashi ,  Yoshiki Sawa ,  Michiya Matsusaki

IPC分类号： C12N5/02

CPC分类号： C12N5/0068 ,  A61L27/52 ,  A61L27/58 ,  C08B37/003 ,  C08B37/0084 ,  C08J3/075 ,  C08J2305/04 ,  C08J2305/08 ,  C08J2377/04 ,  C12N5/0062 ,  C12N2533/30

摘要： To provide a new reductive-stimuli-responsive degradable gel that allows any control of decomposition of the three-dimensional base material for cell culture and production of a completely biological three-dimensional cellular structure consisting only of cells and cells-produced extracellular matrix and that allows safe recovery of the cellular structure produced.A stimuli-responsive hydrogel, characterized by being produced by crosslinking a water-soluble polymer with a compound having a disulfide bond in the molecular chain.

摘要翻译： 提供新的还原刺激响应性可降解凝胶，其允许任何控制用于细胞培养的三维基质的分解和产生仅由细胞和细胞产生的细胞外基质组成的完全生物的三维细胞结构，并且 允许安全地回收所生产的细胞结构。 刺激响应性水凝胶，其特征在于通过在分子链中与具有二硫键的化合物交联水溶性聚合物来制备。