Immunosuppressive Effect of Newly Developed Tacrolimus Emulsion in Liver Transplantation

新研制的他克莫司乳剂在肝移植中的免疫抑制作用

• 批准号: 08671352
• 负责人: UNO Takeji
• 金额: $ 1.47万
• 依托单位: Hamamatsu University School of Medicine
• 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 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671352/
• 关键词: Tacrolimus; Water-in-Oil-in-Water-Type Multiple Emulsion; Oil-in-Water-Type Emulsion; Immunosuppressive effect; Wエマルション; ラット心移植; ラット肝移植; 急性移植片対宿主病治療; 経口用タクロリムス; o; wエマルション; 心移植; 肝移植; 薬物動態

1. We developed an oleic acid oil-in-water(o/w)-type emulsion of a new tacrolimus formulation that represented an improvement in the delivery of the drug for oral absorption. The whole blood concentration profiles after oral administration at dose of 2mg/kg and bone marrow, spleen, liver, lung, small intestine, kidney, brain, and whole blood distribution after oral administration at dose of 1mg/kg of o/w emulsion formulation of tacrolimus (O/W group) were compared with those of commercially available formulation (T group) in the rat. The mean diameters of the olw emulsion droplets were 0.47 mu m immediately after it's preparation. The tacrolimus entrapping efficiency of o/w emulsion was 71.3 5.0% in 12 hrs and did not change for 2 days. The value of area under the whole blood concentration- time curve in the 0/W group was significantly higher (p<0.01) than that in the T group. In contrast, the values of constant elimination rate and total clearance in the O/W group were significantly lower (p<0.01) than those in the T group. The value of comparative bioavailability was 115.9%. The tissue concentration values of tacrolimus in the O/W group demonstrated significantly increased levels in the bone marrow, spleen, liver, lung, and small intestine, and significantly decreased levels in the brain and kidney, relative to the T group.2. We investigated the immunosuppressive effects of tacrolimus o/w emulsion in rat cardiac allografts and liver allografts. It has found that the oral administration of tacrolimus o/w emulsion is not more effective in prolonging survival of cardiac and liver allografts in rats, relative to the commercially available formulation.

1。我们开发了一种新的他克莫司配方的水中油酸油（O/W） - 型乳液，这代表了药物递送口服吸收的改善。口服2mg/kg和骨髓，脾，肝，肺，小肠，小肠，肾脏，大脑和全血分布后口服口服后，以1mg/kg 1mg/w的乳酸乳液（O/W组的乳液）表达（O/W组）的整个血液浓度分布与仪式（O/W组）相比，均与compersercecraper（O/W组）相比（compersercaper）的表格（t）。制备后，OLW乳液液滴的平均直径为0.47 mu m。 O/W乳液的克莫司捕获效率为71.3 5.0％，在12小时内不变2天。 0/W组中整个血液浓度时间曲线下面积的值明显高于t组。相反，O/W组中恒定消除速率和总清除率的值明显低（P <0.01）（p <0.01）。比较生物利用度的价值为115.9％。 O/W组中他克莫司的组织浓度值在骨髓，脾脏，肝脏，肺和小肠中表现出显着增加的水平，相对于T组，大脑和肾脏的水平显着降低。我们研究了他克莫司O/W乳液对大鼠心脏同种异体移植物和同种异体移植物的免疫抑制作用。它发现，与市售的配方相比，口服他克莫司O/W乳液的口服在延长大鼠心脏和同种异体移植物的存活方面并不是更有效。

项目成果

Uno, T., et al.: "Pharmacokinetic Advantages of Newly Developed Tacrolimus Oil-inーWater-Type Emulsion via the Enteral Reute" Lipids. 34. (1999)

Uno, T., et al.：“新开发的他克莫司水包油型乳剂通过肠内途径的药代动力学优势”34。(1999)

Takeji Uno, Takaji Yamaguchi, Xiao Kang Li, Yoshinari Suzuki, Hisakuni Hashimoto, Yukio Harada, Taizo Kimura, and Teruhisa Kazui: "The Pharmacokinetics of Water-in-Oil-in-Water-Type Multiple Emulsion of a New Tacrolimus Formulation" Lipids. Vol.32, no.5.

Takeji Uno、Takaji Yamaguchi、Xiao Kang Li、Yoshinari Suzuki、Hisakuni Hashimoto、Yukio Harada、Taizo Kimura 和 Teruhisa Kazui：“他克莫司新配方的水包油包水型多重乳剂的药代动力学”

Takeji Uno, et al.: "The Pharmacokinetics of Water-in-Oil-in-Water-Type Multiple Emulsion of a New Tacrolimus Formulation" Lipids. 32・5. 543-548 (1997)

Takeji Uno等人：“新他克莫司制剂的水包油包水型多重乳剂的药代动力学”脂质32・5（1997）。

Takeji Uno, et al.: "Pharmacokinetic Advantages of Newly Developed Tacrolimus Oil-in Water-Type Emulsion via the Enteral Route" Lipids. 34. (1999)

Takeji Uno 等人：“新开发的他克莫司水包油型乳剂通过肠内途径的药代动力学优势”脂质。

Takeji Uno: "The Pharmacokinetics of Water-in Oil-in-Water-Type Multiple Emulsion of a New Tacrolimus Formulation" Lipids. 32・5. 543-548 (1997)

Takeji Uno：“他克莫司新制剂的水包油包水型多重乳剂的药代动力学”32・5（1997）。