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    • 5. 发明授权
    • GLP-1 derivative and preparation thereof absorbable via mucous membrane
    • GLP-1衍生物及其可通过粘膜吸收的制剂
    • US07291594B2
    • 2007-11-06
    • US10530125
    • 2003-10-10
    • Yuji HayashiMitsuhiro MakinoToshiyuki KouzakiMotohiro TakedaTakahito Jomori
    • Yuji HayashiMitsuhiro MakinoToshiyuki KouzakiMotohiro TakedaTakahito Jomori
    • A61K38/26C07K14/605
    • C07K14/605A61K38/26Y10S514/866
    • A GLP-1 derivative is provided including an amino acid sequence of GLP-1 (7-35) having deletion, substitution and/or addition of one or more amino acids and having Waa-(Xaa)n-Yaa (in which Waa is Arg or Lys, Xaa is Arg or Lys, n is an integer of 0 to 14, and Yaa is Arg, Arg-NH2, Lys, Lys-NH2 or Hse) added to the C-terminus of the peptide having a GLP-1 activity. These derivatives are highly absorbable via a mucous membrane. The GLP-1 derivative can be conferred with resistance to dipeptidyl peptidase IV by substituting amino acid 8 in its GLP-1 amino acid sequence with Ser, or with resistance to trypsin by substituting amino acids 26 and 34 with Gln and Asn, respectively.The absorption efficiency of the GLP-1 derivatives via mucous membranes can be further improved by preparing a composition using a charge-regulated fat emulsion regulated to be negatively charged thereon.
    • 提供GLP-1衍生物,其包含具有缺失,取代和/或添加一个或多个氨基酸并具有Waa-(Xaa)n-Yaa的GLP-1(7-35)的氨基酸序列(其中Waa为 Arg或Lys,Xaa是Arg或Lys,n是0-14的整数,Yaa是Arg,Arg-NH 2,Lys,Lys-NH 2或 Hse)加入具有GLP-1活性的肽的C末端。 这些衍生物通过粘膜是高度可吸收的。 通过用Ser取代其GLP-1氨基酸序列中的氨基酸8,或分别用Gln和Asn取代氨基酸26和34,对胰蛋白酶具有抗性,GLP-1衍生物可赋予对二肽基肽酶IV的抗性。 通过使用调节为带负电荷的电荷调节脂肪乳液制备组合物,可以进一步提高通过粘膜的GLP-1衍生物的吸收效率。
    • 6. 发明申请
    • Glp-1 derivatives and transmicosal absorption preparations thereof
    • Glp-1衍生物及其经半吸收制剂
    • US20060194720A1
    • 2006-08-31
    • US10530125
    • 2003-10-10
    • Yuji HayashiMitsuhiro MakinoToshiyuki KouzakiMotohiro TakedaTakahito Jomori
    • Yuji HayashiMitsuhiro MakinoToshiyuki KouzakiMotohiro TakedaTakahito Jomori
    • C07K14/605A61K38/22
    • C07K14/605A61K38/26Y10S514/866
    • The invention relates to a GLP-1 derivative including an amino acid sequence of GLP-1 (7-35) having deletion, substitution and/or addition of one or more amino acids and having Waa-(Xaa)n-Yaa (in which Waa is Arg or Lys, Xaa is Arg or Lys, n is an integer of 0 to 14, and Yaa is Arg, Arg-NH2, Lys, Lys-NH2 or Hse) added to the C-terminus of the peptide having a GLP-1 activity. These derivatives are derivatives highly absorbable via a mucous membrane. In the invention, the GLP-1 derivative can be conferred with resistance to dipeptidyl peptidase IV by substituting amino acid 8 in its GLP-1 amino acid sequence with Ser, or with resistance to trypsin by substituting amino acids 26 and 34 with Gln and Asn, respectively. The efficiency of absorption of the GLP-1 derivatives of the invention via mucous membranes can be further improved by preparing a composition using a charge-regulated fat emulsion regulated to be negatively charged thereon.
    • 本发明涉及包含具有缺失,取代和/或添加一个或多个氨基酸并具有Waa-(Xaa)n-Yaa)的GLP-1(7-35)氨基酸序列的GLP-1衍生物(其中 Waa为Arg或Lys,Xaa为Arg或Lys,n为0〜14的整数,Yaa为Arg,Arg-NH 2 Lys,Lys-NH 2 >或Hse)加入具有GLP-1活性的肽的C末端。 这些衍生物是通过粘膜高度吸收的衍生物。 在本发明中,通过用Ser取代其GLP-1氨基酸序列中的氨基酸8或通过用Gln和Asn取代氨基酸26和34对胰蛋白酶具有抗性,GLP-1衍生物可赋予对二肽基肽酶IV的抗性 , 分别。 本发明的GLP-1衍生物通过粘膜吸收的效率可以通过使用调节为带负电荷的电荷调节脂肪乳剂制备组合物而进一步改善。
    • 9. 发明授权
    • Motorcycle
    • 摩托车
    • US08292017B2
    • 2012-10-23
    • US13196453
    • 2011-08-02
    • Yusuke InoueSatoshi MatsushimaTatsuya SasakiHiroshi NakashimaYuji Hayashi
    • Yusuke InoueSatoshi MatsushimaTatsuya SasakiHiroshi NakashimaYuji Hayashi
    • B62D61/02B62K11/00
    • F01N1/24F01N1/10F01N13/1811
    • A silencer for a motorcycle has a front cup which has a tapered tubular shape, a center sleeve which is connected to the front cup, and a tail cup which is connected to the center sleeve. Since the front cup has a tapered tubular shape, the front cup is arranged such that a front end of the front cup is positioned in the vicinity of a main frame. A distal end of the silencer can be shifted frontward in the longitudinal direction of a vehicle compared to a silencer of a prior art. As a result, a length of the silencer can be increased while avoiding interference between the silencer and legs of a rider and hence, silencing performance of the silencer can be enhanced. Since the distal end of the silencer can be shifted frontward in the longitudinal direction of the vehicle, the concentration of a mass can be acquired.
    • 用于摩托车的消声器具有锥形管状的前杯,连接到前杯的中心套和连接到中心套的尾杯。 由于前杯具有锥形管状,所以前杯配置成使前杯的前端位于主框架附近。 与现有技术的消声器相比,消声器的远端可以在车辆的纵向方向上向前移动。 结果,消音器的长度可以增加,同时避免消音器与骑手的消音器之间的干扰,从而可以提高消音器的消声性能。 由于消音器的远端可以沿着车辆的纵向方向向前移动,所以可以获得质量的集中。