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Ab-remover, ab-removing apparatus, and ab removal method

a technology of ab removal apparatus and ab removal method, which is applied in the direction of catalyst activation/preparation, other blood circulation devices, drug compositions, etc., can solve the problems of high cost, long time-consuming and laborious, and short effect, and achieves high adsorption ability, high hydrophobicity, and high adsorption ability.

Inactive Publication Date: 2011-11-10
FUJITA HEALTH UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016]The present inventors repeatedly studied in order to solve the above described problems. Firstly, Aβ adsorption abilities (removal abilities) of existing medical adsorbing materials were evaluated in comparison. As a result, high Aβ adsorption abilities were shown in an adsorbent obtained by fixing a hexadecyl group (C16) as a ligand to a carrier made of cellulose beads, an adsorbent obtained by covering a surface of a bead-like activated carbon with a hydrophilic polymer, and an adsorbent obtained by fixing tryptophan as a ligand to a carrier made of a polyvinyl alcohol gel. On the other hand, on the assumption that higher hydrophobicity of the surface is excellent in an adsorption ability of Aβ having higher hydrophobicity, a relationship between a length of an alkyl group (ligand) fixed to a carrier and an Aβ adsorption ability was examined. As a result, contrary to the initial assumption, it was revealed in an experiment using silica as a carrier that as a length of an alkyl group is short (that is, as hydrophobicity is weak), an Aβ adsorption ability is enhanced. After this finding was obtained, in order to confirm whether an Aβ adsorption ability is shown even in a hydrophilic carrier or not, an Aβ adsorption ability of a cellulose bead that is a hydrophilic carrier was examined, an excellent Aβ adsorption ability was shown. Subsequently, usefulness of an adsorbent showing an excellent Aβ adsorption ability was studied in an experimental system modeled after a clinical use (continuously supplying an Aβ solution to an adsorbent column with a pump.) The result was positive, and it was suggested that a clinical application is sufficiently possible. For a further experiment, an extracorporeal circulation system incorporated serially with a column for an adsorbent that has showed an excellent Aβ adsorption ability, and a dialysis apparatus was constructed to try removal of Aβ from blood; as a result, it was shown that the column of the adsorbent enabled efficiently removing Aβ, and an Aβ removal ratio was improved due to using a dialysis apparatus in combination. As described above, as a result of the intensive studies made by the present inventors, they succeeded in finding out a material having a high Aβ adsorption ability. Use of the material makes it possible to efficiently remove Aβ in a body fluid extracorporeally and to realize a therapeutic or preventive method of Alzheimer's disease providing excellent characteristics as shown in (1) to (3) below.
[0019](3) The method can be inexpensively carried out as compared to an immunotherapy, etc.

Problems solved by technology

On the other hand, development of an anti-Aβ antibody excellent in therapeutic effects has progressed by a number of research groups, but a therapy with an anti-Aβ antibody is expensive and takes over a long period of time, and thus, burden on a patient is severe.
In addition, an anti-Aβ antibody has a problem such that its effects are comparatively short, which thus requires repeated administrations.

Method used

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  • Ab-remover, ab-removing apparatus, and ab removal method
  • Ab-remover, ab-removing apparatus, and ab removal method
  • Ab-remover, ab-removing apparatus, and ab removal method

Examples

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Effect test

example 1

Evaluation of Aβ1-40 Adsorption Abilities of 6 Medical Materials (Using Simulated Plasma, Adsorption by Batch Treatment)

[0076]750 μL of a cellulose gel bound with dextran sulfate on the surface (the sample name is referred to as “SLS”, manufactured by KANEKA CORPORATION, product name: Selesorb (trade name)), 4.38 ml of petroleum pitch-based bead-like activated carbon (the sample name is referred to as “Hm”, polyHEMA=hydroxy ethyl methacrylate polymer is coated on the surface in order to improve blood compatibility, manufactured by Asahi Kasei Kuraray Medical Co., Ltd., product name: Hemosorba (trade name)), 4.38 ml of a polyvinyl alcohol gel bound with tryptophan on the surface (the sample name is referred to as “Im”, manufactured by Asahi Kasei Kuraray Medical Co., Ltd., product name: Immusorba (trade name)), 4.38 ml of cellulose beads bound with a hexadecy group on the surface (the sample name is referred to as “Lx”, manufactured by KANEKA CORPORATION, product name: Lixelle (trade...

example 2

Evaluation of Aβ1-42 Adsorption Abilities of 6 Medical Materials (Using Simulated Plasma, Adsorption by Batch Treatment)

[0077]An experiment was carried out in the same conditions as in Example 1 except for using 16.7 ng / ml of Aβ1-42 as an Aβ solution and an ELISA kit for Aβ1-42 measuring (manufactured by Wako Pure Chemical Industries, Ltd.) to evaluate Aβ1-42 adsorption abilities of 6 medical materials. Decrease ratios of Aβ1-42 (adsorption ratios) when that of the control after shaking for 16 hours was assumed to be 100% were sample name SLS: 0.0%. sample name Hm: 99.0%, sample name Im: 39.1%, sample name Lx: 97.7%, sample name Ad: 14.9%, and sample name CS: 33.9% (FIG. 3). Namely, Hm and Lx showed high adsorption abilities also to Aβ1-42. On the other hand, Im showed moderate adsorption ability.

example 3

Time Lapse Evaluation of Aβ1-40 Adsorption Abilities of 3 Medical Materials (Using Simulated Plasma, Adsorption by Batch Treatment)

[0078]Aβ1-40 adsorption abilities were measured on 3 materials of Hm, Im and Lx under room temperature at each point of shaking times of 1 hour, 4 hours, and 16 hours. The experimental conditions were in accordance with Example 1. Aβ1-40 decrease ratios (adsorption ratios) when that of the control at each time was assumed to be 100% were sample name Hm: 92.8%, sample name Im: 63.4%, and sample name Lx: 93.0% at the time point of 1 hour; sample name Hm: 93.5%, sample name Im: 58.6%, and sample name Lx: 93.9% at the time point of 4 hours; and sample name Hm: 93.0%, sample name Im: 66.8%, and sample name Lx: 90.2% at the time point of 16 hours (FIG. 4). It was found that Hm and Lx adsorb Aβ1-40 rapidly and efficiently. In addition. desorption of Aβ1-40 after adsorption was not observed.

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Abstract

An object is to provide a material capable of removing Aβ from a body fluid efficiently and use of the material, which are developed for the purpose of establishing a therapeutic or preventive method for Alzheimer's disease. Provided is an amyloid β protein remover, containing a carrier made of any one material selected from the group consisting of cellulose, silica, polyvinyl alcohol, and activated carbon, wherein the carrier does not have an alkyl chain on the surface thereof or has an alkyl chain having 1 to 18 carbon atoms on the surface thereof.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of international application No. PCT / JP2009 / 007051. filed Dec. 21, 2009, which claims priority to Japanese application No. 2008-326174, filed Dec. 22, 2008. The contents of these applications are hereby incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to an Aβ remover for removing an amyloid β protein (Aβ) from a body fluid. The invention also relates to an Aβ removing apparatus and an Aβ removal system which use the Aβ remover.BACKGROUND OF THE INVENTION[0003]Alzheimer's disease is cognitive disorder that denatures intracerebral nerve cells due to accumulating an amyloid β protein (hereinafter, abbreviated as “Aβ”) in the brain. For the pathogenesis, the most prevailing is the “amyloid hypothesis” such that soluble Aβ strongly inhibits long-term enhancement of memory and Aβ that is coagulated and deposited forms fibrils to thus lead nerve cell...

Claims

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Application Information

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IPC IPC(8): B01D21/00C07F7/02C08F116/06C01B31/08B01J20/26C08B1/00C01B33/12A61K35/14A61M1/16A61M1/36A61P25/28
CPCA61M1/3679G01N2800/2821G01N2333/4709A61P25/28A61M1/02A61M1/14A61M1/3496A61M1/3479B01D15/08B01J20/3268B01J20/3204B01J20/3208A61M2202/07
Inventor KITAGUCHI, NOBUYAKAWAGUCHI, KAZUNORI
Owner FUJITA HEALTH UNIVERSITY