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Treatment of shock, e.g. due to bacterial toxins or hemorrhagic shock associated with viral infections, comprises using peptides matching the inducible VE-cadherin binding moiety of human fibrin Bbeta-chain
Treatment of shock, e.g. due to bacterial toxins or hemorrhagic shock associated with viral infections, comprises using peptides matching the inducible VE-cadherin binding moiety of human fibrin Bbeta-chain
The use of peptides (I), which match the inducible VE-cadherin binding moiety of the Bbeta -chain of human fibrin (i.e. Bbeta 15-42), for the treatment of shock, is new, where (I) have a specific structure based on a glycyl-(histidyl or prolyl)-argininyl N-terminus and/or have a specific N-terminal sequence of 28 amino acids. The use of peptides (I), which match the inducible VE-cadherin binding moiety of the Bbeta -chain of human fibrin (i.e. Bbeta 15-42), is claimed for the production of a pharmaceutical preparation for the treatment of shock, where (I) are of formula R 1R 2N-CH 2-C(O)-Z 1-Z 2 (I') and/or have the N-terminal amino acid sequence Gly-His-Arg-Pro-Leu-Asp-Lys-Lys-Arg-Glu-Glu-Ala-Pro-Ser-Leu-Arg-Pro-Ala-Pro-Pro-Pro-Ile-Ser-Gly-Gly-Gly-Tyr-Arg (I''). R 1, R 2H or saturated or unsaturated 1-10C (preferably 1-3C) hydrocarbyl; Z 1histidine or proline residue; Z 2arginine residue or a peptide or protein residue (preferably of 2-30 amino acids) with an initial arginine residue. ACTIVITY : Vasotropic; Antibacterial; Immunosuppressive; Virucide. In tests in mice with dengue viruses associated shock, the degree of mortality in a group treated with Gly-His-Arg-Pro-Leu-Asp-Lys-Lys-Arg-Glu-Glu-Ala-Pro-Ser-Leu-Arg-Pro-Ala-Pro-Pro-Pro-Ile-Ser-Gly-Gly-Gly-Tyr-Arg (Ia) (Bbeta 15-42) at 4800 mu g/kg i.p. twice daily from day 3 to day 8 after infection was 0%, compared with 40% in an untreated control group. MECHANISM OF ACTION : Human fibrin Bbeta -chain inducible VE-cadherin binding moiety mimetic.
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机译:肽(I)与人血纤蛋白Bβ链的可诱导VE-钙粘着蛋白结合部分(即Bbeta 15-42)匹配,用于治疗休克是新的,其中(I)具有特定结构-基于糖基-(组氨酸或脯氨酰基)-精氨酸基N-末端和/或具有28个氨基酸的特定N-末端序列。要求使用与人血纤蛋白的Bbeta链的可诱导性VE-钙粘蛋白结合部分匹配的肽(I)(即Bbeta 15-42)来生产用于治疗休克的药物制剂,其中( I)具有式R 1R 2N-CH 2-C(O)-Z 1-Z 2(I')和/或具有N端氨基酸序列Gly-His-Arg-Pro-Leu-Asp-Lys -Lys-Arg-Glu-Glu-Ala-Pro-Ser-Leu-Arg-Pro-Ala-Pro-Pro-Pro-Ile-Ser-Gly-Gly-Gly-Tyr-Arg(I'')。 R 1,R 2H或饱和或不饱和的1-10C(最好是1-3C)烃基; Z 1组氨酸或脯氨酸残基; Z 2精氨酸残基或带有初始精氨酸残基的肽或蛋白质残基(优选2-30个氨基酸)。活性:趋溶性;抗菌;免疫抑制杀病毒剂。在与登革热病毒相关的休克小鼠的测试中,使用Gly-His-Arg-Pro-Leu-Asp-Lys-Lys-Arg-Glu-Glu-Ala-Pro-Ser-Leu-Arg治疗的组的死亡率Pro-Ala-Pro-Pro-Pro-Ile-Ser-Gly-Gly-Gly-Tyr-Arg(Ia)(Bbeta 15-42)在4800μg / kg ip感染后第3天到第8天每天两次,每次两次为0%,而未经治疗的对照组为40%。作用机理:人血纤蛋白Bβ链诱导的VE-钙粘蛋白结合部分模拟物。
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