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1. 发明授权

US06703013B1 Polystyrene sulfonate-containing gel preparation 失效
标题翻译：含聚苯乙烯磺酸盐的凝胶制剂
公开(公告)号：US06703013B1
公开(公告)日：2004-03-09
申请号：US09508539
申请日：2000-04-05
申请人： Hideaki Ninomiya , Masahiro Nakajima , Toshiyuki Kouzaki , Masaki Ando , Fumio Higuchi
发明人： Hideaki Ninomiya , Masahiro Nakajima , Toshiyuki Kouzaki , Masaki Ando , Fumio Higuchi
IPC分类号： A61K3774
CPC分类号： A61K9/006 , A61K9/06 , A61K31/795 , Y10S514/944
摘要： The invention relates to a polystyrene sulfonate-containing gel preparation for therapy of hyperpotassemia, wherein the particle size of polystyrene sulfonate is controlled within the range of at least 5-100 &mgr;m, the viscosity of its solution before gelation is adjusted depending on the particle size by adding a thickening agent, and the polystyrene sulfonate particles after gelation is uniformly dispersed therein. More preferably, a water-displacing agent is contained, whereby the amount of water in the preparation is reduced. This gel preparation does not cause a sense of foreign matter or a sense of roughness in the oral cavity upon ingestion and intake, thus making it unnecessary to drink water for ingestion, and further its water content is low, so that control of water intake is made easy, even in the case of a patient with renal insufficiency who is subjecting to restriction in intake of water to significant improve the quality of life of the patient.
摘要翻译：本发明涉及一种用于治疗高钾血症的聚苯乙烯磺酸盐凝胶制剂，其中聚苯乙烯磺酸盐的粒径控制在至少5-100μm的范围内，凝胶化前溶液的粘度根据粒径通过添加增稠剂，凝胶化后的聚苯乙烯磺酸酯粒子均匀分散。更优选含有取代剂，由此减少制剂中的水量。这种凝胶制剂在摄入和摄入时不会引起口腔感和异味，因此不必饮用水摄取，进一步其含水量低，从而控制摄入水量即使在患有肾功能不全的患者进行限制摄入水以显着改善患者的生活质量的情况下也是容易的。

2. 发明授权

US5733877A Pharmaceutical composition containing biologically active peptide or protein 失效
标题翻译：含有生物活性肽或蛋白质的药物组合物
公开(公告)号：US5733877A
公开(公告)日：1998-03-31
申请号：US503479
申请日：1995-07-18
申请人： Makoto Sato , Toshiyuki Kouzaki , Yoko Ishihara , Shigeaki Yoshina , Masanao Nakoshi , Tatsushi Maeda
发明人： Makoto Sato , Toshiyuki Kouzaki , Yoko Ishihara , Shigeaki Yoshina , Masanao Nakoshi , Tatsushi Maeda
IPC分类号： A61K9/107 , A61K38/00 , A61K38/22 , A61K38/23 , A61K47/12 , A61K47/24 , A61K47/28 , C07K14/575 , C07K14/585 , C07K14/63 , A61K38/02
CPC分类号： A61K38/23 , A61K38/2214 , A61K38/2278 , A61K47/12 , A61K47/24 , A61K9/0019 , A61K9/107 , Y10S514/938
摘要： A pharmaceutical composition is disclosed comprising a fat emulsion containing microspheres and having its electric charge adjusted to a negative value and a biologically active substance selected from the group consisting of a basic peptide and a basic protein, which biologically active substance is adsorbed to the microspheres in the fat emulsion. An acidic phospholipid, a fatty acid, a bilic acid and a salt of such substances is preferred as an agent for adjusting the electric charge of the fat emulsion. Motilin derivatives, vasoactive intestinal polypeptide derivatives and calcitonin are preferred biologically active substances.
摘要翻译：公开了一种药物组合物，其包含含有微球并将其电荷调节至负值的脂肪乳剂和选自碱性肽和碱性蛋白质的生物活性物质，所述生物活性物质被吸附到微球体上脂肪乳液。优选酸性磷脂，脂肪酸，二胆酸和这些物质的盐作为调节脂肪乳剂电荷的试剂。胃动素衍生物，血管活性肠多肽衍生物和降钙素是优选的生物活性物质。

3. 发明申请

US20060194720A1 Glp-1 derivatives and transmicosal absorption preparations thereof 失效
标题翻译： Glp-1衍生物及其经半吸收制剂
公开(公告)号：US20060194720A1
公开(公告)日：2006-08-31
申请号：US10530125
申请日：2003-10-10
申请人： Yuji Hayashi , Mitsuhiro Makino , Toshiyuki Kouzaki , Motohiro Takeda , Takahito Jomori
发明人： Yuji Hayashi , Mitsuhiro Makino , Toshiyuki Kouzaki , Motohiro Takeda , Takahito Jomori
IPC分类号： C07K14/605 , A61K38/22
CPC分类号： C07K14/605 , A61K38/26 , Y10S514/866
摘要： 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.
摘要翻译：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。

4. 发明授权

US07291594B2 GLP-1 derivative and preparation thereof absorbable via mucous membrane 失效
标题翻译： GLP-1衍生物及其可通过粘膜吸收的制剂
公开(公告)号：US07291594B2
公开(公告)日：2007-11-06
申请号：US10530125
申请日：2003-10-10
申请人： Yuji Hayashi , Mitsuhiro Makino , Toshiyuki Kouzaki , Motohiro Takeda , Takahito Jomori
发明人： Yuji Hayashi , Mitsuhiro Makino , Toshiyuki Kouzaki , Motohiro Takeda , Takahito Jomori
IPC分类号： A61K38/26 , C07K14/605
CPC分类号： C07K14/605 , A61K38/26 , Y10S514/866
摘要： 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.
摘要翻译：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。

5. 发明授权

US5308836A Pharmaceutical composition of stabilized [Leu.sup.13 ]-motilin-Hse 失效
标题翻译：稳定[Leu13] -motilin-Hse的药物组合物
公开(公告)号：US5308836A
公开(公告)日：1994-05-03
申请号：US116682
申请日：1993-09-07
申请人： Kiichi Sawai , Masayasu Kurono , Yasuaki Kondo , Makoto Sato , Toshiyuki Kouzaki
发明人： Kiichi Sawai , Masayasu Kurono , Yasuaki Kondo , Makoto Sato , Toshiyuki Kouzaki
IPC分类号： A61K9/08 , A61K38/22 , A61K47/02 , A61K47/10 , A61K47/12 , A61K47/18 , A61K47/26 , A61K47/36 , A61K47/42 , A61P1/00 , C07K1/00 , C07K14/00 , C07K14/575 , A61K37/24 , A61K37/36
CPC分类号： A61K38/2214
摘要： There is disclosed a pharmaceutical composition of stabilized [Leu.sup.13 ]-motilin-Hse. The composition comprises at least one of organic acids and salts thereof, as a first stabilizer, and pH thereof is adjusted in a range of 5.5-8.0. The composition may contain at least one of substances selected from saccharides, amino acids, proteins and salts thereof, as a second stabilizer. Conversion of [Leu.sup.13 ]-motilin-Hse into [Leu.sup.13 ]-motilin-Hse-lactone is suppressed by increasing pH value and deamidization in asparagine residue at 19-position is suppressed by the presence of the organic acid or salt thereof.
摘要翻译：公开了一种稳定的[Leu13] -Motilin-Hse的药物组合物。该组合物包含至少一种有机酸及其盐作为第一稳定剂，其pH调节在5.5-8.0的范围内。该组合物可以含有选自糖，氨基酸，蛋白质和盐的至少一种物质作为第二稳定剂。通过增加pH值可以抑制[Leu13] -motilin-Hse转化为[Leu13] - 肌动蛋白-Hse-内酯，并且通过存在有机酸或其盐来抑制在19位的天冬酰胺残基中的脱酰胺化。

6. 发明授权

US5279835A Binder-free orally administrable tablet containing 3-oxygermylpropionic acid 失效
标题翻译：无粘合剂的含3-氧基甲基丙酸的口服片剂
公开(公告)号：US5279835A
公开(公告)日：1994-01-18
申请号：US906465
申请日：1992-06-30
申请人： Kiichi Sawai , Masayasu Kurono , Takahiko Mitani , Yasuaki Kondo , Makoto Sato , Yoshiro Ishiwata , Syoji Yokochi , Toshiyuki Kouzaki
发明人： Kiichi Sawai , Masayasu Kurono , Takahiko Mitani , Yasuaki Kondo , Makoto Sato , Yoshiro Ishiwata , Syoji Yokochi , Toshiyuki Kouzaki
IPC分类号： A61K9/20 , A61K31/28 , A61K31/80 , A61K47/02 , A61K47/26 , A61P43/00
CPC分类号： A61K31/80 , A61K31/28 , A61K9/2009 , A61K9/2018
摘要： A 3-oxygermylpropionic acid preparation is provided, which activates the action of 3-oxygermylpropionic acid having the general formula:[(O.sub.1/2).sub.3 GeCH.sub.2 CH.sub.2 COOH]n wherein n=an integer of at least 1 and is readily solubilized and disintegrated in vivo. The present preparation is manufactured by compression-molding at high pressure a composition comprising 3-oxygermylpropionic acid and two or more low-molecular substance of high solubility in water. The low-molecular substances are selected from the group consisting of white sugar, sorbitol, fructose, sucrose, glucose, lactose, mannitol and sodium chloride.
摘要翻译：提供了3-氧基甲基丙酸制剂，其活化具有以下通式的3-氧基甲基丙酸的作用：（（O1 / 2）3GeCH2CH2COOH）n，其中n =至少为1的整数，并且在体内容易溶解和分解。本制剂通过高压压缩成型制备，该组合物包含3-氧基甲基丙酸和两种或更多种在水中的高溶解度的低分子量物质。低分子物质选自白糖，山梨糖醇，果糖，蔗糖，葡萄糖，乳糖，甘露醇和氯化钠。

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