Pharmacokinetics, biological effects and distribution of (1*3)-beta-D-glucan

(1*3)-β-D-葡聚糖的药代动力学、生物效应和分布

• 批准号: 08670528
• 负责人: YOSHIDA Minoru
• 金额: $ 1.22万
• 依托单位: Teikyo University school of Medicine (1997)Jichi Medical University (1996)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670528/
• 关键词: (1*3)-beta-D-glucan; biological effects; pharmacokinetics; plasma concentration; tumor necrosis factor; lipid metabolism; ultracentrifugation; endotoxin

The pharmacokinetics, biological effects and distribution in blood and organs of <@D1125@>D1I-labeled (1*3)-beta-D-glucan purified from Candida albicans were analyzed in rabbits during the 24 hr period following its I.V.administration. The intravascular half-life (T<@D21/2@>D2alpha) of beta-glucan was 1.8 min in the low dose group (9.3mug/kg) and 1.4 min in the high dose group (222mug/kg), and the total body clearance was 1.12 (]SY.+-。[) 0.30 and 1.17 (]SY.+-。[) 0.16 (ml/min, mean (]SY.+-。[) SD), respectively. The serum concentration of (1*3)-beta-D-glucan was also biologically determined by a test using coagulation factor G of the Japanese horseshoe crab (G Test). There was a good correlation between the concentration of beta-glucan, measured biologically and isotopically, during the initial 2 hr period ; however, biological activity then decreased faster than the isotopic concentration of beta-glucan during the 3-24 hr period. During the 24 hr period of observation, the rabbits remained well and beta-glucan failed to alter blood cell counts, TNF levels, and lipid metabolism. <@D1125@>D1I-beta-glucan associated with the cellular compartment initially was less than 3% (the majority in the platelets), and decreased further during the following 2 hr period (p=0.0001). Over 97% of <@D1125@>D1I-beta-glucan was associated with the cell-free plasma and the majority in plasma appeared to be present in unbound form, i.e., not associated with lipoproteins or plasma proteins. The liver contained more than 80% of the <@D1125@>D1I-beta-glucan detected in the six major organs analyzed.

本文研究了<@D1125@> D1 I标记的白色念珠菌（Candida albicans）β-D-葡聚糖（1 × 3）在家兔体内的药代动力学、生物学效应及其在血液和器官中的分布。β-葡聚糖的血管内半衰期（T<@D21/2@> D2 α）在低剂量组（9.3 μ g/kg）中为1.8分钟，在高剂量组（222 μ g/kg）中为1.4分钟，全身清除率为1.12（± SY）。[）0.30和1.17（]SY. ±. [）0.16（ml/min，平均（SY. ±.（SD）。还通过使用日本鲎凝血因子G的试验（G试验），从生物学角度测定了（1*3）-β-D-葡聚糖的血清浓度。在最初的2小时期间，生物学和同位素测量的β-葡聚糖浓度之间存在良好的相关性;然而，在3-24小时期间，生物活性随后比β-葡聚糖的同位素浓度下降得更快。在24小时的观察期间，兔子保持良好，β-葡聚糖未能改变血细胞计数、TNF水平和脂质代谢。与细胞区室相关的<@D1125@> D1 I-β-葡聚糖最初低于3%（血小板中的大部分），并在随后的2小时内进一步降低（p=0.0001）。超过97%的<@D1125@> D1 I-β-葡聚糖与无细胞血浆相关，血浆中的大多数似乎以未结合形式存在，即，与脂蛋白或血浆蛋白无关。在分析的六个主要器官中检测到的<@D1125@> D1 I-β-葡聚糖中，肝脏含有80%以上。

项目成果

Minoru Yoshida, et al: "Pharmacokinetics, biological effects,and distribution of(1→3)-β-D-glucan in blood and organs in rabbits" Mediators of Inflammation. 6. 279-283 (1997)

Minoru Yoshida 等人：“(1→3)-β-D-葡聚糖在兔子血液和器官中的药代动力学、生物效应和分布”炎症介质 6. 279-283 (1997)。

Minoru Yoshida, et al: "Soluble(1→3)-β-D-glucan purified from Candida albicans:Biologic effects and distribution in blood and organs in rabbits" Journal of Laboratory and Clinical Medicine. 128. 103-114 (1996)

Minoru Yoshida 等人：“从白色念珠菌中纯化的可溶性 (1→3)-β-D-葡聚糖：兔子血液和器官中的生物效应和分布”实验与临床医学杂志 128. 103-114 (1996)。

Minoru Yoshida, et al: "Soluble (1*3)-beta-D-glucan purified from Candida albicans : Biologic effects and distribution in blood and organs in rabbits." J Lab Clin Med. 128. 103-114 (1996)

Minoru Yoshida 等人：“从白色念珠菌中纯化的可溶性 (1*3)-β-D-葡聚糖：生物效应以及在兔子血液和器官中的分布。”

Minoru Yoshida, et al: "Pharmacokinetics, biological effects, and distribution of (1*3)-beta-D-glucan in blood and organs in rabbits." Mediat Inflamm. 6. 279-283 (1997)

Minoru Yoshida 等人：“(1*3)-β-D-葡聚糖在兔子血液和器官中的药代动力学、生物效应和分布。”

Minoru Yoshida,et al: "Pharmacokinetics,biological effects,and distribution of(1→3)-β-D-glucan in blood and organs in rabbits" Mediators of Inflammation. 6(4). 279-283 (1997)

Minoru Yoshida 等人：“(1→3)-β-D-葡聚糖在兔子血液和器官中的药代动力学、生物效应和分布”炎症介质 6(4)。