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    • 2. 发明申请
    • NOVEL PEPTIDES FOR HEPARIN AND LOW MOLECULAR WEIGHT HEPARIN ANTICOAGULATION REVERSAL
    • HEPARIN和低分子量HEPARIN抗体逆转的新肽
    • WO1995013083A1
    • 1995-05-18
    • PCT/US1994012981
    • 1994-11-10
    • UNIVERSITY OF MICHIGAN, THE BOARD OF REGENTSWAKEFIELD, Thomas, W.STANLEY, James, C.ANDREWS, Philip, C.
    • UNIVERSITY OF MICHIGAN, THE BOARD OF REGENTS
    • A61K37/00
    • C07K7/08A61K38/00C07K14/001C07K14/46
    • Less toxic agents for reversal of heparin or low molecular weight heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about [+14] to [+18], preferably [+16] to [+18]. In specific embodiments, there are sequences of 29 and 32 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids. The C-terminus and the N-terminus can be modified to mitigate against in vivo degradation by carboxypeptidases and aminopeptidases. Another modification, specifically use of alpha -helix forming amino acids, such as glutamic acid, further promotes anticoagulation reversal.
    • 用于逆转肝素或低分子量肝素抗凝剂的毒性较小的药物是具有小于正精蛋白的总阳离子电荷的合成鱼精蛋白样聚阳离子肽。 在优选的实施方案中,为了易于制造,将n-鱼精蛋白的精氨酸残基替换为赖氨酸残基。 选择性带正电的精氨酸残基已被不带电荷的氨基酸残基或其类似物(如甘氨酸或谷氨酰胺)替代,以便将聚阳离子肽上的总阳离子电荷降低至约[+ 14]至[+ 18] ,优选[+ 16]至[+ 18]。 在具体实施方案中,存在29和32个氨基酸残基的序列,其中2至4个带正电荷的氨基酸的4至5个簇被2至6个中性氨基酸分开。 可以修饰C-末端和N-末端以减轻羧肽酶和氨基肽酶的体内降解。 另一个修改,特别是使用α-螺旋形成氨基酸,如谷氨酸,进一步促进抗凝反转。
    • 3. 发明申请
    • NOVEL PEPTIDES FOR HEPARIN ANTICOAGULATION REVERSAL
    • HEPARIN抗体逆转的新肽
    • WO1994004176A1
    • 1994-03-03
    • PCT/US1992006829
    • 1992-08-14
    • UNIVERSITY OF MICHIGANWAKEFIELD, Thomas, W.STANLEY, James, C.ANDREWS, Philip, C.
    • UNIVERSITY OF MICHIGAN
    • A61K37/02
    • C07K14/46A61K38/00C07K14/001
    • Less toxic agents for reversal of heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about +14 to +18, preferably +16. In specific embodiments, there are sequences of 29 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids.
    • 具有逆转肝素抗凝剂的毒性较小的药物,其是具有小于正精蛋白的总阳离子电荷的合成鱼精蛋白样聚阳离子肽。 在优选的实施方案中,为了易于制造,将n-鱼精蛋白的精氨酸残基替换为赖氨酸残基。 选择性带正电的精氨酸残基已被不带电荷的氨基酸残基或其类似物如甘氨酸或谷氨酰胺替代,以便将聚阳离子肽上的总阳离子电荷降低至约+14至+18,优选+16 。 在具体实施方案中,存在29个氨基酸残基的序列,其中2至4个带正电荷的氨基酸的4至5个簇被2至6个中性氨基酸分离。
    • 4. 发明申请
    • ABSORBENT HYDROGEL COMPOSITES
    • 吸收水凝胶复合材料
    • WO2007113453A1
    • 2007-10-11
    • PCT/GB2006/001218
    • 2006-04-03
    • FIRST WATER LIMITEDMUNRO, Hugh, SempleANDREWS, PhilipSAINA GARCIA, Susana
    • MUNRO, Hugh, SempleANDREWS, PhilipSAINA GARCIA, Susana
    • A61L15/60A61L15/26A61L15/42
    • A61L15/26A61L15/42A61L15/60
    • The invention provides an absorbent material or article comprising an absorbent hydrogel composite sheet. The sheet includes an absorbent layer part having two major faces which comprises a flexible plasticised hydrophilic polymer matrix having an internal cellular structure, and a second part which comprises a flexible plasticised hydrophilic polymer matrix having a relatively continuous internal structure. The second part may be associated with the layer part such that the second part infiltrates some but not all of the cellular voids of the absorbent layer part over a major face of the absorbent layer part. Alternatively, the second part may be associated with the layer part such that the second part overlies a major face of the absorbent layer part. By this arrangement, some but not all of the absorbent layer part is effectively exposed for absorption of external water or other fluid through the side of the sheet corresponding to that said major face of the absorbent layer.
    • 本发明提供了一种包含吸收性水凝胶复合片材的吸收材料或制品。 片材包括具有两个主表面的吸收层部分,其包含具有内部细胞结构的柔性增塑的亲水性聚合物基质,和包含具有相对连续的内部结构的柔性增塑的亲水性聚合物基质的第二部分。 第二部分可以与层部分相关联,使得第二部分在吸收层部分的主表面上渗透吸收层部分的一些但不是全部的细胞空隙。 或者,第二部分可以与层部分相关联,使得第二部分覆盖在吸收层部分的主表面上。 通过这种布置,一些但不是全部的吸收层部分被有效地暴露以吸收外部水或其它流体通过与吸收层的所述主面对应的片材的侧面。