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Euglena-Derived Paramylon Derivatives:Next-Generation Glucose & Lipid Metabolism Improver

Creating innovative next-generation substances from the microalgae Euglena

Research Overview

Artisan Lab Co., Ltd. focuses on paramylon, a unique polysaccharide accumulated inside the cells of the microalgae Euglena (also known as Midorimushi), and creates innovative next-generation substances (paramylon derivatives) that exert powerful effects on improving diabetes and obesity by chemically modifying its structure.

WO2019107471A1産総研神鋼環境ソリューションEASD2018
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Background: The Unique Properties of Paramylon

Paramylon has an exceptionally rare structure in nature (β-1,3-glucan). Almost no organisms try to use it as nutrition, and almost no digestive enzymes can break it down. Therefore, even when taken orally, it is not digested or absorbed in the body and passes safely through the gastrointestinal tract.

We maximally exploit this property of "passing through the intestine without being absorbed" by applying chemical modifications (such as cationization and amination) that add water solubility and functionality, creating the following novel substances with few gastrointestinal side effects and powerful pharmacological activity.

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Key Paramylon Derivatives Developed by Artisan Lab

① HTAP

Cationic Paramylon Derivative / Amino-Paramylon

Development team: Artisan Lab Co., Ltd. · National Institute of Advanced Industrial Science and Technology (AIST) · Kobelco Eco-Solutions Co., Ltd. (joint research)

A novel bile salt sequestrant based on paramylon. In obese model mice fed a high-fat diet, it was demonstrated to dramatically increase GLP-1 (the "slimming hormone") secretion approximately 3-fold and powerfully suppress visceral fat accumulation (announced in an AIST press release in May 2018). A paper proving its synthesis method and high potential as an anti-diabetic drug was also published in the international pharmaceutical journal Pharmaceutical Research that same year, receiving high academic acclaim.

6-Amino-6-deoxy paramylon

Development team: Artisan Lab Co., Ltd. · Kobelco Eco-Solutions Co., Ltd. (joint research)

A specialized linear high-molecular-weight polymer created by aminating the carbon at position 6 of the sugar comprising paramylon. At the 54th Annual Meeting of the European Association for the Study of Diabetes (EASD 2018, Berlin, Germany) — one of the world's largest academic conferences — its "effects on obesity and glucose metabolism improvement in diet-induced obese model mice" were presented as joint research with Dr. Suzuki et al., attracting significant international attention.

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Mechanism of Action: How Dramatic Effects Are Achieved

These cationic (positively charged) paramylon derivatives primarily improve metabolism at its root through the following mechanisms upon reaching the intestinal tract.

STEP 1

Powerful Adsorption and Excretion of Bile Acids

They strongly bind to bile acids (which carry negative charges) in the intestine and excrete them from the body along with the substance itself. Since the substance itself is not broken down or absorbed by digestive enzymes, it can efficiently carry bile acids out of the body.

STEP 2

Promotion of GLP-1 Secretion and Metabolic Improvement

During the excretion of bile acids, intestinal receptors are stimulated and GLP-1 (the "slimming hormone") is secreted. This suppresses rises in blood sugar. Furthermore, since the liver consumes blood cholesterol to produce new bile acids, this also leads to improvement of dyslipidemia.

The greatest strength of these next-generation paramylon derivatives is that they exert powerful effects safely with minimal burden, without causing the severe gastrointestinal disorders (constipation, bloating, etc.) associated with conventional insoluble resin-based bile acid sequestrants.

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Academic Evaluation & Patent Record

Peer-Reviewed Publication

Shibata K, et al. “Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid β-1,3-Glucan as Potential Antidiabetic Agents

Pharmaceutical Research, 2018 — DOI: 10.1007/s11095-018-2553-8

EASD 2018 Presentation

Research findings presented at the 54th Annual Meeting of EASD 2018 (Berlin, Germany), receiving significant interest from the international diabetes research community.

International Patent (PCT)
Patent No.WO2019107471A1
ApplicantArtisan Lab Co., Ltd. · National Institute of Advanced Industrial Science and Technology (AIST) · Kobelco Eco-Solutions Co., Ltd.
Target SubstanceLinear cationic paramylon derivatives (bile salt sequestrants / anti-diabetic drug candidates)