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SULFATED OLIGOSACCHAARIDES, USE THEREOF FOR TREATING WAR-BLOODED ANIMAL PATIENT

机译:硫酸盐寡糖,用于治疗战血动物

摘要

1. A sulfated oligosaccharide, having the general formula I: R1-(Rx)n-R2.(I) wherein R1 and R2 and each Rx represents a monosaccharide unit, all of which may be the same or different, adjacent monosaccharide units being linked by 1-2, 1-3, 1-4 and/or 1-6 glycosidic bonds and n is an integer of from 1 to 6, provided that polysaccharide is not a compound containing 1-4 linked glucose residues. 2. A sulfated oligosaccharide according to claim 1 wherein n is from 1 to 4, preferably 3 or 4. 3. A sulfated oligosaccharide according to claim 1 or claim 2, wherein the monosaccharide units are hexoses selected from the group consisting of fructose, glucose, mannose, altrose, allose, talose, galactose, idose and gulose. 4. A sulfated oligosaccharide according to claim 1, having the general formula II: Ry-(Ry)n-Ry.(II) wherein each Ry group is the same and each represents a monosaccharide unit, adjacent monosaccharide units being linked by 1-3, 1-4 and/or 1-6 glycosidic bonds; and n is an integer of from 1 to 6 provided that polysaccharide is not a compound containing 1-4 linked glucose residues. 5. A sulfated oligosaccharide according to claim 4, wherein n is from 1 to 4, preferably 3 or 4. 6. A sulfated oligosaccharide according to claim 4 or claim 5, wherein Ry represents a monosaccharide unit which is a hexose selected from the group consisting of glucose, mannose, altrose, allose, talose, galactose, idose and gulose. 7. A sulfated oligosaccharide according to claim 6, wherein Ry represents glucose, mannose or galactose. 8. A sulfated oligosaccharide according to claim 1 or 4, wherein the oligosaccharide is a naturally occurring oligosaccharide. 9. A sulfated oligosaccharide according to claim 8, wherein the oligosaccharide is selected from raffinose and stachyose. 10. A sulfated oligosaccharide according to claim 1 or 4, wherein the oligosaccharide is prepared by enzymatic or chemical degradation of a naturally occurring polysaccharide. 11. A sulfated oligosaccharide according to claim 10, wherein the oligosaccharide is a compound from chondroitin or expopolysaccharide prepared from the diploid yeast Pichia holstii. 12. A sulfated oligosaccharide according to claim 11, wherein the oligosaccharide is selected from chondroitin tetra-, hexa- and octasaccharides. 13. A sulfated oligosaccharide according to claim 11, wherein the oligosaccharide is mannopentaose phosphate from the yeast Pichia holster. 14. A use for the anti-angiogenic, anti-metastatic and/or anti-inflammatory treatment of a human or other warm-blooded animal patient in need of such treatment, which comprises administration to the patient of an effective amount of at least one sulfated oligosaccharide according to any of claims 1 to 13. 15. A use according to claim 14, wherein the treatment comprises treatment of an angiogenesis-dependent disease, including angiogenesis associated with the growth of solid tumours, proliferative retinopathies and rheumatoid arthritis. 16. A use according to claim 14, wherein the treatment comprises treatment of inflammatory diseases and conditions in which the heparanase-inhibitory activity inhibits leukocyte infiltration, including chronic inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, insulin dependent diabetes mellitus, diseases such as ulcerative colitis and Crohn's inflammatory bowel disease, allograft rejection and chronic asthma. 17. A use according to claims 1-13 for the anti-angiogenic, anti-metastatic and/or anti-inflammatory agent in the treatment of a warm-blooded animal (including a human) patient. 18. A use according to claim 17, wherein the treatment comprises treatment of an angiogenesis-dependent disease, including angiogenesis associated with the growth of solid tumours, proliferative retinopathies and rheumatoid arthritis. 19. A use according to claim 17, wherein the treatment comprises treatment of inflammatory diseases and conditions in which the heparanase-inhibitory activity inhibits leukocyte infiltration, including chronic inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, insulin dependent diabetes mellitus, diseases such as ulcerative colitis and Crohn's inflammatory bowel disease, allograft rejection and chronic asthma. 20. A pharmaceutical or veterinary composition for anti-angiogenic, anti-metastatic and/or anti-inflammatory treatment, which comprises at least one sulfated oligosaccharide according to any of claims 1 to 13, together with a pharmaceutically and veterinarily acceptable carrier or diluent therefor. 21. A medicament for the anti-angiogenic, anti-metastatic and/or anti-inflammatory treatment of a human or other warm-blooded animal patient of at least one sulfated oligosaccharide according to any of claims 1 to 13.
机译:1.一种硫酸化的寡糖,其具有通式I:R1-(Rx)n-R2。(I),其中R1和R2以及每个Rx代表一个单糖单元,所有这些单元可以相同或不同,相邻的单糖单元为通过1-> 2、1-> 3、1-> 4和/或1-> 6糖苷键连接,且n为1至6的整数,条件是多糖不是包含1-4个连接的葡萄糖残基的化合物。 2.根据权利要求1的硫酸化的低聚糖,其中n是1-4,优选3或4。3.根据权利要求1或2的硫酸化的低聚糖,其中所述单糖单元是选自由果糖,葡萄糖组成的组的己糖。 ,甘露糖,艾特罗斯,艾洛糖,塔洛糖,半乳糖,乳糖和古洛糖。 4.根据权利要求1的硫酸化低聚糖,其具有通式II:Ry-(Ry)n-Ry。(II),其中每个Ry基团相同并且各自表示单糖单元,相邻的单糖单元通过1-连接。 > 3、1-> 4和/或1-> 6糖苷键; n为1至6的整数,条件是多糖不是含有1-4个连接的葡萄糖残基的化合物。 5.根据权利要求4的硫酸化的低聚糖,其中n为1-4,优选3或4。6.根据权利要求4或5的硫酸化的低聚糖,其中Ry代表单糖单元,其为选自以下组中的己糖由葡萄糖,甘露糖,麦芽糖,阿洛糖,塔洛糖,半乳糖,乳糖和古洛糖组成。 7.根据权利要求6的硫酸化寡糖,其中Ry代表葡萄糖,甘露糖或半乳糖。 8.根据权利要求1或4的硫酸化低聚糖,其中所述低聚糖是天然存在的低聚糖。 9.根据权利要求8的硫酸化的寡糖,其中所述寡糖选自棉子糖和水苏糖。 10.根据权利要求1或4的硫酸化的寡糖,其中所述寡糖通过天然存在的多糖的酶促或化学降解来制备。 11.根据权利要求10的硫酸化的寡糖,其中所述寡糖是来自软骨素或由二倍体酵母毕赤酵母(Pichia holstii)制备的外多糖的化合物。 12.根据权利要求11的硫酸化低聚糖,其中所述低聚糖选自软骨素四,六和八糖。 13.根据权利要求11的硫酸化的寡糖,其中所述寡糖是来自酵母毕赤酵母皮套的磷酸甘露戊糖。 14.用于需要这种治疗的人或其他温血动物患者的抗血管生成,抗转移和/或抗炎治疗的用途,其包括向患者施用有效量的至少一种14.根据权利要求1至13中任一项的硫酸化的寡糖。15.根据权利要求14的用途,其中所述治疗包括治疗血管新生依赖性疾病,包括与实体瘤的生长,增生性视网膜病和类风湿性关节炎相关的血管新生。 16.根据权利要求14的用途,其中所述治疗包括其中乙酰肝素酶抑制活性抑制白细胞浸润的炎性疾病和病症的治疗,包括慢性炎性疾病,例如类风湿性关节炎,多发性硬化,胰岛素依赖型糖尿病,疾病例如溃疡性结肠炎和克罗恩氏炎性肠病,同种异体排斥反应和慢性哮喘。 17.根据权利要求1-13的用途,其用于在治疗温血动物(包括人)患者中使用抗血管生成,抗转移和/或抗炎剂。 18.根据权利要求17的用途,其中所述治疗包括治疗血管新生依赖性疾病,包括与实体瘤的生长,增生性视网膜病和类风湿性关节炎相关的血管新生。 19.权利要求17的用途,其中所述治疗包括其中乙酰肝素酶抑制活性抑制白细胞浸润的炎性疾病和病症的治疗,包括慢性炎性疾病,例如类风湿性关节炎,多发性硬化,胰岛素依赖型糖尿病,疾病例如溃疡性结肠炎和克罗恩氏炎性肠病,同种异体排斥反应和慢性哮喘。 20.用于抗血管生成,抗转移和/或抗炎治疗的药物或兽医学组合物,其包含至少一种根据权利要求1至13中任一项的硫酸化寡糖,以及其药学和兽医学可接受的载体或稀释剂。 。 21.一种用于抗人血管生成,抗转移和/或抗炎治疗至少一种根据权利要求1至13中任一项的硫酸化低聚糖的人或其他温血动物患者的药物。

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