公开(公告)号：US06420171B1

公开(公告)日：2002-07-16

申请号：US09549493

申请日：2000-04-14

申请人： Osamu Nakamura ,  Hideki Ohba ,  Imre Sallay ,  Fumio Yagi ,  Sawako Moriwaki ,  Seiji Yasuda

发明人： Osamu Nakamura ,  Hideki Ohba ,  Imre Sallay ,  Fumio Yagi ,  Sawako Moriwaki ,  Seiji Yasuda

IPC分类号： C12N506

CPC分类号： C12N5/0093 ,  A61M1/3679 ,  A61M2202/0439 ,  C07K14/37 ,  C07K14/42 ,  C07K17/10 ,  Y10S530/812 ,  Y10S530/813

摘要： An efficient method for therapeutic treatment of leukemia is provided in which a patient's body fluid during external circulation is brought into direct contact with an adsorbent material capable of specifically and selectively adsorbing leukemic cells in the body fluid. The leukemic cell-adsorbing material is a composite of a lectin protein coupled with a physiologically inert carrier material such as a galactan polysaccharide in the form of beads. The lectin protein may be obtained from a mushroom fungus such as Agrocybe cylindracea or a leguminous seed such as from the jequirity bean plant. The lectin protein and carrier material can be bound by forming chemical linkages between amino groups in the lectin protein and functional groups in the carrier material, and unreacted functional groups of the carrier material may be blocked with an amino acid. A leukemic cell-adsorbing column may be formed by filling the leukemic cell-adsorbing material into a tubular body to form an adsorbent bed. The tubular body may have an inner diameter of from 10 to 20 mm and a height of from 50 to 200 mm.

摘要翻译： 提供了一种治疗白血病的有效方法，其中外部循环期间的患者体液与能够特异性和选择性地吸收体液中的白血病细胞的吸附材料直接接触。 白血病细胞吸附材料是凝集素蛋白与生理惰性载体材料如珠粒形式的半乳聚糖多糖的复合物。 凝集素蛋白质可以从蘑菇真菌如花椰菜（Agrocybe cylindracea）或豆科植物种子（例如来自不育豆）得到。 凝集素蛋白质和载体材料可以通过在凝集素蛋白中的氨基和载体材料中的官能团之间形成化学键而结合，载体材料的未反应的官能团可以用氨基酸封闭。 可以通过将白血病细胞吸附材料填充到管状体中以形成吸附床来形成白血病细胞吸附柱。 管状体的内径可以为10〜20mm，高度为50〜200mm。

公开(公告)号：US06987022B2

公开(公告)日：2006-01-17

申请号：US10158157

申请日：2002-05-31

申请人： Osamu Nakamura ,  Hideki Ohba ,  Imre Sallay ,  Fumio Yagi ,  Sawako Moriwaki ,  Seiji Yasuda

发明人： Osamu Nakamura ,  Hideki Ohba ,  Imre Sallay ,  Fumio Yagi ,  Sawako Moriwaki ,  Seiji Yasuda

IPC分类号： C12N5/06 ,  C12N5/08 ,  C12N11/10 ,  C07K17/02 ,  C07K17/10

CPC分类号： C12N5/0093 ,  A61M1/3679 ,  A61M2202/0439 ,  C07K14/37 ,  C07K14/42 ,  C07K17/10 ,  C12N5/0694 ,  Y10S530/812 ,  Y10S530/813

摘要： An efficient method for therapeutic treatment of a leukemic patient is disclosed in which the patient's body fluid under external circulation is brought into direct contact with an adsorbent material capable of adsorbing the leukemic cells in the body fluid specifically and selectively. The leukemic cell-adsorbent material, which is used by filling a column to form an adsorbent bed, is a conjugate of a lectin protein extracted from, e.g., Dolichos beans or soybeans coupled with a physiologically inert carrier material such as a polysaccharide in the form of beads or a superparamagnetic material in the form of iron oxide-based magnetic beads.

摘要翻译： 公开了一种用于治疗白血病患者的有效方法，其中将外部循环下的患者体液与能够特异性且选择性地吸收体液中的白血病细胞的吸附材料直接接触。 用于填充柱以形成吸附床的白血病细胞吸附材料是从例如Dolichos豆或大豆与生理惰性载体材料如多糖形式的提取的凝集素蛋白的缀合物，其形式为 的珠子或以铁氧化物基磁珠形式的超顺磁性材料。

公开(公告)号：US06465512B2

公开(公告)日：2002-10-15

申请号：US09733947

申请日：2000-12-12

申请人： Osamu Nakamura ,  Yoko Fuke ,  Hideki Ohba ,  Seiji Yasuda

发明人： Osamu Nakamura ,  Yoko Fuke ,  Hideki Ohba ,  Seiji Yasuda

IPC分类号： A61K3126

CPC分类号： A61K31/26 ,  Y10S514/885 ,  Y10S514/908

摘要： Disclosed is a method for growth inhibition of human leukemic cells or therapeutic treatment method of a leukemic patient by using a medicament of which the effective ingredient is a methylsulfinylalkyl isothiocyanate such as 4-(methylsulfinyl)butyl isothiocyanate and 6-(methylsulfinyl)hexyl isothiocyanate, which can be prepared by extraction from the tissues of certain plants and can induce apoptosis in human leukemic cells. This medicament compound is little growth-inhibitive against normal cells as compared with leukemic cells, so that a remarkable therapeutic effect can be expected.

公开(公告)号：US6143533A

公开(公告)日：2000-11-07

申请号：US525323

申请日：2000-03-13

申请人： Toshihisa Sumi ,  Hideki Ohba ,  Toru Ikegami ,  Masao Shibata ,  Tsuyoshi Sakaki ,  Imre Sallay ,  Sung Soo Park

发明人： Toshihisa Sumi ,  Hideki Ohba ,  Toru Ikegami ,  Masao Shibata ,  Tsuyoshi Sakaki ,  Imre Sallay ,  Sung Soo Park

IPC分类号： C07H7/027 ,  A61K35/56 ,  C07H1/08 ,  C12P7/58 ,  C12P7/40 ,  A61K35/12

CPC分类号： C12P7/58

摘要： Disclosed is an efficient and economical method for the preparation of N-glycolyl neuraminic acid in a high purity from an inexpensive abundant source material. The method comprises dispersing body tissues of an echinodermatous marine animal Cucumaria echinata in an aqueous medium, preferably, using a dry powder of the tissues prepared in advance, in which the tissues are proteolytically decomposed to isolate N-glycolyl neuraminic acid in the form of an aqueous solution containing polypeptides as a by-product, followed by separation of N-glycolyl neuraminic acid from the aqueous solution by removing the polypeptides and purification of the compound in a process utilizing an ion-exchange treatments.

摘要翻译： 公开了一种从廉价丰富的原料制备高纯度的N-羟乙酰神经氨酸的有效和经济的方法。 该方法包括将棘皮动物海洋动物黄瓜（Cucumaria echinata）的身体组织分散在水性介质中，优选使用预先制备的组织的干粉末，其中组织被蛋白水解分解以分离出N-羟乙酰神经氨酸 水溶液，其含有作为副产物的多肽，随后通过在使用离子交换处理的方法中除去多肽和化合物的纯化从水溶液中分离N-羟乙酰神经氨酸。

公开(公告)号：US06342367B1

公开(公告)日：2002-01-29

申请号：US09513191

申请日：2000-02-25

申请人： Toshihisa Sumi ,  Hideki Ohba ,  Toru Ikegami ,  Masao Shibata ,  Tsuyoshi Sakaki ,  Imre Sallay ,  Sung Soo Park

发明人： Toshihisa Sumi ,  Hideki Ohba ,  Toru Ikegami ,  Masao Shibata ,  Tsuyoshi Sakaki ,  Imre Sallay ,  Sung Soo Park

IPC分类号： C12P2106

CPC分类号： C12P19/26

摘要： Disclosed is an economical method for the preparation of chondroitin sulfates A and C useful as an effective ingredient of medicaments from fish scales as a waste material discharged from fishery in large quantities. Fish scales are enzymatically decomposed in an aqueous medium in the presence of a protease to isolate the chondroitin sulfate compounds and by-product polypeptides followed by removal of the by-product polypeptides from the aqueous solution by a cation-exchange treatment and then the aqueous solution of the chondroitin sulfate compounds is subjected to fractional precipitation by the addition of ethyl alcohol as the precipitant.

摘要翻译： 公开了一种用于制备硫酸软骨素A和C的经济方法，其用作作为大量从渔业排放的废物的鱼鳞的药物的有效成分。 鱼鳞在蛋白酶存在下在水性介质中酶促分解，分离出硫酸软骨素化合物和副产物多肽，然后通过阳离子交换处理从水溶液中除去副产物多肽，然后将水溶液 的硫酸软骨素化合物通过加入乙醇作为沉淀剂进行分级沉淀。

公开(公告)号：US20090263356A1

公开(公告)日：2009-10-22

申请号：US12088186

申请日：2006-09-26

申请人： Toshiro Omori ,  Hideki Hokazono ,  Mihoko Furutera ,  Yasufumi Umemoto ,  Kei Hayashi ,  Naoki Takeshima ,  Hideki Ohba

发明人： Toshiro Omori ,  Hideki Hokazono ,  Mihoko Furutera ,  Yasufumi Umemoto ,  Kei Hayashi ,  Naoki Takeshima ,  Hideki Ohba

IPC分类号： A61K35/74 ,  A61K36/8998 ,  A61P9/00

CPC分类号： A61K36/8998 ,  A23K10/38 ,  A23K50/10 ,  A23K50/40 ,  A23K50/75 ,  A23L7/10 ,  A23L33/105 ,  A23L33/135 ,  A23V2002/00 ,  Y02P60/873 ,  A23V2200/308 ,  A23V2250/21

摘要： It is an object of the invention to provide a composition with an excellent action of inhibiting vascularization, as prepared by a simple method suitable for actual production from an inexpensive, relatively readily available material without any problematic safety profile at an industrial scale without any complicated purification step. The composition is a composition for inhibiting vascularization, which contains a barley-derived ingredient selected from the group consisting of an unpolished barley ethyl alcohol extract fraction, an unpolished barley alkali extract fraction and fermented barley (preferably, a residual solution from the distillation of barley distilled spirits) as the active component with an action of inhibiting vascularization. The composition for inhibiting vascularization is a composition for therapeutically treating or preventing diseases which vascularization should be inhibited, specifically diseases with an etiology of abnormal vascularization in tumor or cancer, chronic inflammation or retinopathy. The composition is in a form selected from the group consisting of food additives, food materials, foods and drinks, pharmaceutical products under regulations by the Ministry of Health and Labor in Japan and quasi-pharmaceutical products under regulations by the Ministry of Health and Labor in Japan, and feeds.

摘要翻译： 本发明的目的是提供一种具有极好的抑制血管形成作用的组合物，其通过一种简单的方法制备，该方法适用于廉价的，相对容易获得的材料，在工业规模上没有任何有问题的安全性，无需任何复杂的纯化 步。 该组合物是用于抑制血管形成的组合物，其含有选自未抛光的大麦乙醇提取物部分，未磨光的大麦碱提取物部分和发酵的大麦（优选来自蒸馏大麦的残留溶液）的大麦来源的成分 蒸馏酒）作为活性成分，具有抑制血管形成的作用。 用于抑制血管形成的组合物是用于治疗或预防血管形成应被抑制的疾病的组合物，特别是具有肿瘤或癌症异常血管化病因，慢性炎症或视网膜病变的疾病。 该组合物为选自食品添加剂，食品材料，食品和饮料，日本卫生和劳动部规定的药品，卫生劳动部规定的准药品 日本，饲料。

公开(公告)号：US20110034545A1

公开(公告)日：2011-02-10

申请号：US12935546

申请日：2009-03-31

申请人： Takanori Kubo ,  Hideki Ohba ,  Hidekazu Toyobuku ,  Hirotake Hayashi

发明人： Takanori Kubo ,  Hideki Ohba ,  Hidekazu Toyobuku ,  Hirotake Hayashi

IPC分类号： A61K31/713 ,  C07H21/02 ,  C12N5/071 ,  A61P35/00 ,  A61P31/18

CPC分类号： C12N15/111 ,  C12N2310/3515 ,  C12N2320/32

摘要： An object of the present invention is to provide a novel double-stranded RNA that has high resistance to nuclease and cellular uptake efficiency and that can produce an excellent RNA interference effect. The present invention provides a double-stranded lipid-modified RNA comprising a sense strand having a nucleotide sequence complementary to a target sequence in a target gene, and an antisense strand having a nucleotide sequence complementary to the sense strand, the double-stranded RNA being capable of suppressing the expression of the target gene, and the sense strand having a double-stranded lipid bound directly or via a linker to at least one of the first to sixth nucleotides from the 5′ end.

摘要翻译： 本发明的目的是提供对核酸酶和细胞摄取效率具有高抗性并且可以产生优异的RNA干扰效果的新型双链RNA。 本发明提供了包含具有与靶基因中的靶序列互补的核苷酸序列的有义链和具有与有义链互补的核苷酸序列的反义链的双链脂质修饰的RNA，所述双链RNA为 能够抑制靶基因的表达，并且将具有直链或经由连接基结合的双链脂质的有义链与5'末端的至少一个第一至第六个核苷酸结合。

公开(公告)号：US20100298411A1

公开(公告)日：2010-11-25

申请号：US12738797

申请日：2008-10-24

申请人： Takanori Kubo ,  Hideki Ohba ,  Hidekazu Toyobuku ,  Hirotake Hayashi

发明人： Takanori Kubo ,  Hideki Ohba ,  Hidekazu Toyobuku ,  Hirotake Hayashi

IPC分类号： A61K31/713 ,  C07H21/02 ,  C12N15/113 ,  A61P5/00

CPC分类号： A61K47/48038 ,  A61K47/542 ,  A61K47/543

摘要： An object of the present invention is to provide a novel double-stranded RNA that has high nuclease resistance and high cellular uptake efficiency, and that is capable of producing an excellent RNA interference effect. The present invention provides a lipid-modified double-stranded RNA comprising a sense strand having a nucleotide sequence complementary to a target sequence, and an antisense strand having a nucleotide sequence complementary to the sense strand, the double-stranded RNA being capable of inhibiting the expression of the target gene, the sense strand having a lipid linked to at least one of the first to sixth nucleotides from the 5′ end side directly or via a linker.

摘要翻译： 本发明的目的是提供具有高核酸酶抗性和高细胞摄取效率的新型双链RNA，并能够产生优异的RNA干扰效果。 本发明提供脂质修饰的双链RNA，其包含具有与靶序列互补的核苷酸序列的有义链和具有与有义链互补的核苷酸序列的反义链，所述双链RNA能够抑制 靶基因的表达，有义链具有从5'末端侧的至少一个第一至第六个核苷酸直接或通过连接体连接的脂质。

公开(公告)号：US10738304B2

公开(公告)日：2020-08-11

申请号：US12808504

申请日：2008-12-18

申请人： Takanori Kubo ,  Hideki Ohba ,  Kazuo Sakurai ,  Jusaku Minari ,  Atsushi Uno

发明人： Takanori Kubo ,  Hideki Ohba ,  Kazuo Sakurai ,  Jusaku Minari ,  Atsushi Uno

IPC分类号： C12N5/00 ,  C12N15/11 ,  C07H21/02

摘要： An object of the present invention is to provide novel double-stranded RNA having an RNA interference effect, in which the cellular uptake and the resistance to enzymatic degradation are improved, without reducing the RNA interference effect.The cellular uptake and the resistance to enzymatic degradation of a complex of a polysaccharide having a β-1,3-glucan skeleton and double-stranded RNA can be significantly improved while maintaining the RNA interference effect, by fulfilling the following conditions (i) to (iii): (i) the double-stranded RNA has a sense strand consisting of a base sequence complementary to a target sequence in a target gene and an antisense strand containing a base sequence complementary to the sense strand, and the double-stranded RNA can inhibit expression of the target gene; (ii) the double-stranded RNA has a single-stranded polydeoxyadenine bound directly or via a linker to the end of at least one of the sense strand and the antisense strand; and (iii) the polysaccharide and the single-stranded polydeoxyadenine form a complex.

公开(公告)号：US09040492B2

公开(公告)日：2015-05-26

申请号：US12935546

申请日：2009-03-31

申请人： Takanori Kubo ,  Hideki Ohba ,  Hidekazu Toyobuku ,  Hirotake Hayashi

发明人： Takanori Kubo ,  Hideki Ohba ,  Hidekazu Toyobuku ,  Hirotake Hayashi

IPC分类号： A01N43/04 ,  C12N15/11

CPC分类号： C12N15/111 ,  C12N2310/3515 ,  C12N2320/32

摘要： An object of the present invention is to provide a novel double-stranded RNA that has high resistance to nuclease and cellular uptake efficiency and that can produce an excellent RNA interference effect. The present invention provides a double-stranded lipid-modified RNA comprising an antisense strand having a nucleotide sequence complementary to a target sequence in a target gene, and a sense strand having a nucleotide sequence complementary to the antisense strand, the double-stranded RNA being capable of suppressing the expression of the target gene, and the sense strand having a double-stranded lipid bound directly or via a linker to at least one of the first to sixth nucleotides from the 5′ end.

摘要翻译： 本发明的目的是提供对核酸酶和细胞摄取效率具有高抗性并且可以产生优异的RNA干扰效果的新型双链RNA。 本发明提供了包含具有与靶基因中的靶序列互补的核苷酸序列的反义链和具有与反义链互补的核苷酸序列的有义链的双链脂质修饰的RNA，所述双链RNA为 能够抑制靶基因的表达，并且将具有直链或经由连接基结合的双链脂质的有义链与5'末端的至少一个第一至第六个核苷酸结合。