Physicochemical and Structural Properties of Glycerin Gel Prepared using Glycyrrhizic Acid Diethyl Ester
Glycyrrhizic acid diethyl ester (GZ-DE) was developed as a prodrug of glycyrrhizic acid (GZ), a hepatitis therapeutic drug. We fortuitously found that GZ-DE gels with glycerin selectively while searching for a safe solvent with which to dissolve GZ-DE. Based on this gelation, the aim of this study w...
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Veröffentlicht in: | Journal of Oleo Science 2014, Vol.63(12), pp.1309-1322 |
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creator | Koga, Kenjiro Kimura, Toshiyuki Sakai, Kenichi Kushida, Hiroshi Yoshikawa, Nobuji |
description | Glycyrrhizic acid diethyl ester (GZ-DE) was developed as a prodrug of glycyrrhizic acid (GZ), a hepatitis therapeutic drug. We fortuitously found that GZ-DE gels with glycerin selectively while searching for a safe solvent with which to dissolve GZ-DE. Based on this gelation, the aim of this study was to investigate the preparation of the gel and study the rheology, physicochemical and structural properties of the glycerin gel by differential scanning calorimeter (DSC), capillary electrophoresis (CEP), nuclear magnetic resonance (NMR), and small angle X-ray scattering (SAXS). The glycerin gel was prepared by the addition of at least 2.0% w/w GZ-DE. This gel did not flow at room temperature. After mixing glycerin and GZ-DE, a gel was formed after 2 days at 25°C or 3 h at 60°C. Glycerin gel containing 2.4% w/w GZ-DE provided the following results: 1) The glycerin gel exhibited creep at a constant stress of less than 10 Pa, but it is a fragile gel, showing Newtonian flow at 10 Pa stress. 2) Dynamic viscoelastic measurements showed that the elastic modulus (G’) exceeds the viscous modulus (G’’), indicating that glycerin gel has solid-like properties. 3) DSC showed a significant difference between the glass transition temperature of glycerin and glycerin gel. 4) CEP did not reveal a new compound in the glycerin gel. 5) NMR confirmed that glycerin gel is a physical gel. 6) SAXS measurements revealed that the glycerin gel has an oval-shaped basic frame (119 nm long and 65 nm wide). |
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We fortuitously found that GZ-DE gels with glycerin selectively while searching for a safe solvent with which to dissolve GZ-DE. Based on this gelation, the aim of this study was to investigate the preparation of the gel and study the rheology, physicochemical and structural properties of the glycerin gel by differential scanning calorimeter (DSC), capillary electrophoresis (CEP), nuclear magnetic resonance (NMR), and small angle X-ray scattering (SAXS). The glycerin gel was prepared by the addition of at least 2.0% w/w GZ-DE. This gel did not flow at room temperature. After mixing glycerin and GZ-DE, a gel was formed after 2 days at 25°C or 3 h at 60°C. Glycerin gel containing 2.4% w/w GZ-DE provided the following results: 1) The glycerin gel exhibited creep at a constant stress of less than 10 Pa, but it is a fragile gel, showing Newtonian flow at 10 Pa stress. 2) Dynamic viscoelastic measurements showed that the elastic modulus (G’) exceeds the viscous modulus (G’’), indicating that glycerin gel has solid-like properties. 3) DSC showed a significant difference between the glass transition temperature of glycerin and glycerin gel. 4) CEP did not reveal a new compound in the glycerin gel. 5) NMR confirmed that glycerin gel is a physical gel. 6) SAXS measurements revealed that the glycerin gel has an oval-shaped basic frame (119 nm long and 65 nm wide).</description><identifier>ISSN: 1345-8957</identifier><identifier>EISSN: 1347-3352</identifier><identifier>DOI: 10.5650/jos.ess14086</identifier><identifier>PMID: 25452268</identifier><language>eng</language><publisher>Japan: Japan Oil Chemists' Society</publisher><subject>Calorimetry, Differential Scanning ; Chemical Phenomena ; Constants ; Drugs ; Electrophoresis ; Electrophoresis, Capillary ; Esters ; gelation ; Gels - chemistry ; glycerin ; Glycerol - chemical synthesis ; Glycerol - chemistry ; glycyrrhizic acid ; Glycyrrhizic Acid - analogs & derivatives ; Glycyrrhizic Acid - chemistry ; Magnetic Resonance Spectroscopy ; NMR ; Nuclear magnetic resonance ; Prodrugs - chemistry ; rheology ; SAXS ; Scattering, Small Angle ; Searching ; Stresses ; Temperature ; Time Factors</subject><ispartof>Journal of Oleo Science, 2014, Vol.63(12), pp.1309-1322</ispartof><rights>2014 by Japan Oil Chemists' Society</rights><rights>Copyright Japan Science and Technology Agency 2014</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c631t-f0417bb74695b0b6197c0935ca85c42a4641f8d2ca188883584f6929c0c17c1b3</citedby><cites>FETCH-LOGICAL-c631t-f0417bb74695b0b6197c0935ca85c42a4641f8d2ca188883584f6929c0c17c1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25452268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koga, Kenjiro</creatorcontrib><creatorcontrib>Kimura, Toshiyuki</creatorcontrib><creatorcontrib>Sakai, Kenichi</creatorcontrib><creatorcontrib>Kushida, Hiroshi</creatorcontrib><creatorcontrib>Yoshikawa, Nobuji</creatorcontrib><creatorcontrib>Faculty of Science and Technology</creatorcontrib><creatorcontrib>Faculty of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>Tokyo University of Science</creatorcontrib><creatorcontrib>Cokey Systems Co.Ltd</creatorcontrib><creatorcontrib>Hokuriku University</creatorcontrib><creatorcontrib>Research and Development Division</creatorcontrib><title>Physicochemical and Structural Properties of Glycerin Gel Prepared using Glycyrrhizic Acid Diethyl Ester</title><title>Journal of Oleo Science</title><addtitle>J Oleo Sci</addtitle><description>Glycyrrhizic acid diethyl ester (GZ-DE) was developed as a prodrug of glycyrrhizic acid (GZ), a hepatitis therapeutic drug. We fortuitously found that GZ-DE gels with glycerin selectively while searching for a safe solvent with which to dissolve GZ-DE. Based on this gelation, the aim of this study was to investigate the preparation of the gel and study the rheology, physicochemical and structural properties of the glycerin gel by differential scanning calorimeter (DSC), capillary electrophoresis (CEP), nuclear magnetic resonance (NMR), and small angle X-ray scattering (SAXS). The glycerin gel was prepared by the addition of at least 2.0% w/w GZ-DE. This gel did not flow at room temperature. After mixing glycerin and GZ-DE, a gel was formed after 2 days at 25°C or 3 h at 60°C. Glycerin gel containing 2.4% w/w GZ-DE provided the following results: 1) The glycerin gel exhibited creep at a constant stress of less than 10 Pa, but it is a fragile gel, showing Newtonian flow at 10 Pa stress. 2) Dynamic viscoelastic measurements showed that the elastic modulus (G’) exceeds the viscous modulus (G’’), indicating that glycerin gel has solid-like properties. 3) DSC showed a significant difference between the glass transition temperature of glycerin and glycerin gel. 4) CEP did not reveal a new compound in the glycerin gel. 5) NMR confirmed that glycerin gel is a physical gel. 6) SAXS measurements revealed that the glycerin gel has an oval-shaped basic frame (119 nm long and 65 nm wide).</description><subject>Calorimetry, Differential Scanning</subject><subject>Chemical Phenomena</subject><subject>Constants</subject><subject>Drugs</subject><subject>Electrophoresis</subject><subject>Electrophoresis, Capillary</subject><subject>Esters</subject><subject>gelation</subject><subject>Gels - chemistry</subject><subject>glycerin</subject><subject>Glycerol - chemical synthesis</subject><subject>Glycerol - chemistry</subject><subject>glycyrrhizic acid</subject><subject>Glycyrrhizic Acid - analogs & derivatives</subject><subject>Glycyrrhizic Acid - chemistry</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Prodrugs - chemistry</subject><subject>rheology</subject><subject>SAXS</subject><subject>Scattering, Small Angle</subject><subject>Searching</subject><subject>Stresses</subject><subject>Temperature</subject><subject>Time Factors</subject><issn>1345-8957</issn><issn>1347-3352</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUU2P0zAQjRCI_YAbZxSJCwey-NvOcVWWLtJKrAScLceZbFylcbGTQ_j1TNttkbDk8cd78-ZppijeUXIjlSSfNzHfQM5UEKNeFJeUC11xLtnLw11Wppb6orjKeUMI_kv9urhgUkjGlLks-sd-ycFH38M2eDeUbmzLH1Oa_TQnfD6muIM0Bchl7Mr1sHhIYSzXsIdg5xK05ZzD-HTAlpT68Cf48taHtvwSYOqXobzLE6Q3xavODRnePp_Xxa-vdz9X99XD9_W31e1D5RWnU9URQXXTaKFq2ZBG0Vp7UnPpnZFeMCeUoJ1pmXfU4OLSiE7VrPbEU-1pw6-Lj0fdXYq_Z8iT3YbsYRjcCHHOlhpChOKa1kj98B91E-c0ojtLtZTCoBWDrE9Hlk8x5wSd3aWwdWmxlNj9BDAr29MEkP7-WXRuttCeyaeWI2F9JCC673gchzDCv9LtRscBUJIRKiwh2BZmCW7KSY2BMcbRv9aotDoqbfLknuBcyuG8_AAHX4pbTMV4MnhGfe-ShZH_BUz5sK0</recordid><startdate>2014</startdate><enddate>2014</enddate><creator>Koga, Kenjiro</creator><creator>Kimura, Toshiyuki</creator><creator>Sakai, Kenichi</creator><creator>Kushida, Hiroshi</creator><creator>Yoshikawa, Nobuji</creator><general>Japan Oil Chemists' Society</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope></search><sort><creationdate>2014</creationdate><title>Physicochemical and Structural Properties of Glycerin Gel Prepared using Glycyrrhizic Acid Diethyl Ester</title><author>Koga, Kenjiro ; Kimura, Toshiyuki ; Sakai, Kenichi ; Kushida, Hiroshi ; Yoshikawa, Nobuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c631t-f0417bb74695b0b6197c0935ca85c42a4641f8d2ca188883584f6929c0c17c1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Calorimetry, Differential Scanning</topic><topic>Chemical Phenomena</topic><topic>Constants</topic><topic>Drugs</topic><topic>Electrophoresis</topic><topic>Electrophoresis, Capillary</topic><topic>Esters</topic><topic>gelation</topic><topic>Gels - chemistry</topic><topic>glycerin</topic><topic>Glycerol - chemical synthesis</topic><topic>Glycerol - chemistry</topic><topic>glycyrrhizic acid</topic><topic>Glycyrrhizic Acid - analogs & derivatives</topic><topic>Glycyrrhizic Acid - chemistry</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Prodrugs - chemistry</topic><topic>rheology</topic><topic>SAXS</topic><topic>Scattering, Small Angle</topic><topic>Searching</topic><topic>Stresses</topic><topic>Temperature</topic><topic>Time Factors</topic><toplevel>online_resources</toplevel><creatorcontrib>Koga, Kenjiro</creatorcontrib><creatorcontrib>Kimura, Toshiyuki</creatorcontrib><creatorcontrib>Sakai, Kenichi</creatorcontrib><creatorcontrib>Kushida, Hiroshi</creatorcontrib><creatorcontrib>Yoshikawa, Nobuji</creatorcontrib><creatorcontrib>Faculty of Science and Technology</creatorcontrib><creatorcontrib>Faculty of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>Tokyo University of Science</creatorcontrib><creatorcontrib>Cokey Systems Co.Ltd</creatorcontrib><creatorcontrib>Hokuriku University</creatorcontrib><creatorcontrib>Research and Development Division</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><jtitle>Journal of Oleo Science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koga, Kenjiro</au><au>Kimura, Toshiyuki</au><au>Sakai, Kenichi</au><au>Kushida, Hiroshi</au><au>Yoshikawa, Nobuji</au><aucorp>Faculty of Science and Technology</aucorp><aucorp>Faculty of Pharmaceutical Sciences</aucorp><aucorp>Tokyo University of Science</aucorp><aucorp>Cokey Systems Co.Ltd</aucorp><aucorp>Hokuriku University</aucorp><aucorp>Research and Development Division</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Physicochemical and Structural Properties of Glycerin Gel Prepared using Glycyrrhizic Acid Diethyl Ester</atitle><jtitle>Journal of Oleo Science</jtitle><addtitle>J Oleo Sci</addtitle><date>2014</date><risdate>2014</risdate><volume>63</volume><issue>12</issue><spage>1309</spage><epage>1322</epage><pages>1309-1322</pages><issn>1345-8957</issn><eissn>1347-3352</eissn><abstract>Glycyrrhizic acid diethyl ester (GZ-DE) was developed as a prodrug of glycyrrhizic acid (GZ), a hepatitis therapeutic drug. We fortuitously found that GZ-DE gels with glycerin selectively while searching for a safe solvent with which to dissolve GZ-DE. Based on this gelation, the aim of this study was to investigate the preparation of the gel and study the rheology, physicochemical and structural properties of the glycerin gel by differential scanning calorimeter (DSC), capillary electrophoresis (CEP), nuclear magnetic resonance (NMR), and small angle X-ray scattering (SAXS). The glycerin gel was prepared by the addition of at least 2.0% w/w GZ-DE. This gel did not flow at room temperature. After mixing glycerin and GZ-DE, a gel was formed after 2 days at 25°C or 3 h at 60°C. Glycerin gel containing 2.4% w/w GZ-DE provided the following results: 1) The glycerin gel exhibited creep at a constant stress of less than 10 Pa, but it is a fragile gel, showing Newtonian flow at 10 Pa stress. 2) Dynamic viscoelastic measurements showed that the elastic modulus (G’) exceeds the viscous modulus (G’’), indicating that glycerin gel has solid-like properties. 3) DSC showed a significant difference between the glass transition temperature of glycerin and glycerin gel. 4) CEP did not reveal a new compound in the glycerin gel. 5) NMR confirmed that glycerin gel is a physical gel. 6) SAXS measurements revealed that the glycerin gel has an oval-shaped basic frame (119 nm long and 65 nm wide).</abstract><cop>Japan</cop><pub>Japan Oil Chemists' Society</pub><pmid>25452268</pmid><doi>10.5650/jos.ess14086</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Calorimetry, Differential Scanning Chemical Phenomena Constants Drugs Electrophoresis Electrophoresis, Capillary Esters gelation Gels - chemistry glycerin Glycerol - chemical synthesis Glycerol - chemistry glycyrrhizic acid Glycyrrhizic Acid - analogs & derivatives Glycyrrhizic Acid - chemistry Magnetic Resonance Spectroscopy NMR Nuclear magnetic resonance Prodrugs - chemistry rheology SAXS Scattering, Small Angle Searching Stresses Temperature Time Factors |
title | Physicochemical and Structural Properties of Glycerin Gel Prepared using Glycyrrhizic Acid Diethyl Ester |
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