JP3614455B2 - Astringent and binding compounds and medical and cosmetic preparations - Google Patents

Description

【００１４】
【化４】

【００１５】
以下に、その詳細を述べる。
この発明に用いる化３の式で示されるグリチルリチン酸亜鉛（以下、ＧＺ−Ｚｎと略記する。）は、下記の化５の式に示されるグリチルリチン酸（Ｃ_４２Ｈ_６２Ｏ_１６）と亜鉛との組成比が１：０．０１〜３の化合物である。なぜなら、亜鉛の組成比が０．０１未満ではこの発明の所期した効果が得られず、また化合物の組成式からみて、亜鉛の組成比が３を越えることは不可能だからである。
【００１６】
【化５】

【００１７】
また、この発明に用いる化４の式で示されるグリチルレチン酸亜鉛（以下、ＧＴ−Ｚｎと略記する。）は、下記化６に示すようなグリチルレチン（Ｃ_３０Ｈ_４６Ｏ_４ ）と亜鉛との組成比が１：０．０１〜１の化合物である。なぜなら、亜鉛の組成比が０．０１未満ではこの発明に所期した作用が得られず、１を越えることは化合物の組成式からみて不可能だからである。
【００１８】
【化６】

【００１９】
【実施例】
〔実施例１〕
ＧＺ−Ｚｎの調製：
５０ｇのＧＺ−Ｈを５００ｍｌのエタノール水（１：１）に溶解し、かき混ぜながら１２０ｍｌの１Ｎの水酸化カリウム水溶液を加え、さらに５０ｍｌの水に溶解した８．６３ｇの硫酸亜鉛・七水和物を徐々に加えた。５０℃に加温した後、冷却し、析出物をろ過し、水洗、乾燥後３６ｇのＧＺ−Ｚｎを得た。
【００２０】
得られたＧＺ−Ｚｎに対して赤外線吸収スペクトルを測定し、極大吸収が認められた波長を表１に示した。また、原料のＧＺ−Ｈについても同様に赤外線吸収スペクトルを調べ、結果を表１中に併記した。
【００２１】
【表１】

【００２２】
表１の結果から、遊離のカルボン酸に特有の１７３２ｃｍ^−１がＧＺ−Ｚｎでは非常に減少した。また、原料のＧＺ−Ｈの１６４７ｃｍ^−１の吸収がＧＺ−Ｚｎでは幅広くなり、１６４０ｃｍ^−１に極大吸収が認められ、また糖質に見られる１０００〜１２００ｃｍ^−１の吸収は、いずれにも確認できた。これらのことから、生成物がＧＺ−Ｈの亜鉛塩であるＧＺ−Ｚｎであることがわかる。
【００２３】
得られたＧＺ−Ｚｎに対して、その止血作用、収斂作用、創傷治癒作用、抗炎症作用、付着作用、結合作用のあることを確認するため、以下の実験を行なった。
【００２４】
［止血作用確認実験］
Ｊ． Ｓｏｃ． Ｃｏｓｍｅｔ． Ｃｈｅｍ． Ｊａｐａｎ．， Ｖｏｌ．２４（３），ｐ１８７（１９９１）浅沼らの方法（改良 Ｂｌｅｅｄｉｎｇ 法）を応用して行なった。
【００２５】
すなわち、一晩絶食したＷｉｓｔａｒ系雄性ラット（体重２００〜２５０ｇ）をペントバルビタール（８０ｍｇ／ｋｇ）を腹腔内投与して麻酔後、肋骨より下２ｃｍの位置縦に２．５ｃｍ円形の腹膜を用いた。
【００２６】
その後、直ちに ｅｕｇｌｏｂｕｌｉｎ−ＳＫ ｍｉｘｔｕｒｅ ２ｍｌ／ｋｇ相当量を左足大腿静脈より投与した。投与後、すばやく出血している腹膜上に濾紙（２×２ｃｍ）をのせ、その濾紙に試験液０．２ｍｌを投与した。投与５分後、この濾紙を取り除き、前もって３７℃の温水に浸しておいた濾紙（１．５×３ｃｍ）を露出面の上にのせ、出血している血液を３０分間吸収させた。３０分毎にこの濾紙を取り替え、試験液投与後から２時間までこの操作を行なった。
【００２７】
血液を吸収させた濾紙を水４ｍｌの入った試験管に入れ、３７℃の水浴中で３０分間浸盪し血液を溶出させた。これの波長５４０ｎｍの吸光度を測定し、３０分毎の出血量とした。すなわち、出血量を吸光度で評価しこの結果を表２に示した。
【００２８】
【表２】

【００２９】
［収斂作用確認実験１］
１０名の正常な味覚保持者に２０ｍｌの試験液で口をゆすがせ、舌がひきしまり、渋い感覚が有るか否かを調べた。この結果は、１０名共に一致した回答であり表３に示した。なお、渋い味がするものを収斂作用有り、しないものを同作用無しと評価した。
【００３０】
【表３】

【００３１】
［収斂作用確認実験２］
３ｍｌのコラーゲン水溶液（市販品ソリュブルコラーゲン）を試験管に入れ、その上から１ｍｌの試験液を加え、緩やかにかき混ぜた。そして、直後に沈殿生成の有無を確認した。この場合、蛋白質の変質により沈殿が認められたものを収斂作用有り（＋）、沈殿が認められないものを収斂作用なし（−）と評価して、結果を表４に示した。
【００３２】
【表４】

【００３３】
［創傷治癒作用確認実験］
日本薬理学会誌Ｖｏｌ．１００，１６２（１９９２） 清水らの方法を参照し、以下のように行なった。
すなわち、ハートレイ系雄性モルモット（体重３００ｇ前後）をネンブタール麻酔下（３０ｍｇ／ｋｇ，ｉ．ｐ．）において背部を剪毛、消毒し、メスで左右対象に２箇所切創（１．５ｃｍ）を作り、絹糸で１つの創傷当たり２箇所等分縫合した。切創作成後、３日後に切創が１ｃｍとなるように幅１ｃｍで長さ２ｃｍの皮膚を摘出した。試験液は、２ｍｇ／０．４ｍｌ／個体となるように生理食塩水で溶解または分散し、創傷部周辺に０．１ｍｌ／サイトの割合で１つの創傷当たり２箇所、計４箇所に１日１回３日間皮下投与した。
【００３４】
切創の癒着度を判定するため、レオメーターで創傷部の耐創張力（ｇ／ｃｍ）を測定した。なお、左右２箇所の創傷張力の平均値をもって１個体の耐創張力とし、結果を表５に示した。
【００３５】
【表５】

【００３６】
［付着作用確認実験］
表６に示す組成のパウダー（実験例Ａ、実験例Ｂ）を調製し、成人１０名の被験者による官能試験を行なった。すなわち、実験例Ａまたは実験例Ｂの０．２ｇを前腕部に塗布させ、スムーズでむらのない付着性の優劣を判定させ、結果を表６中に併記した。
【００３７】
【表６】

【００３８】
［結合作用確認実験］
表７に示す組成のパウダー（実験例Ｃ、実験例Ｄ）を混合し、各０．５ｇずつを直径１６ｍｍの錠剤成形器に入れ、２００ｋｇの重さ（１００ｋｇ／ｃｍ^２ ）で１分間加圧した後、常圧とした。
【００３９】
得られた錠剤を試験材料としてレオメーターにて破壊強度を測定し、結果を表７に併記した。
【００４０】
【表７】

【００４１】
〔比較例１〕
一般試薬のグリチルリチン酸ジカリウム（以下、ＧＺ−Ｋ２と略記する。）を比較例１として用いた。
このＧＺ−Ｋ２をＧＺ−Ｚｎに代えて用いたこと以外は全く同様にして、上記した止血作用・収斂作用・創傷治癒作用の各確認試験を行ない、結果をそれぞれ表２、表３、表４、表５に併記した。
【００４２】
〔比較例２〕
一般試薬のグリチルリチン酸（ＧＺ−Ｈ）を比較例２として用いた。
このＧＺ−ＨをＧＺ−Ｚｎに代えて用いたこと以外は全く同様にして、上記した創傷治癒作用確認試験を行ない、結果を表５に併記した。
【００４３】
以上述べた実施例１と比較例１、２についてみると、表２の結果から明らかなように、比較例１は蒸留水（コントロール）に対して有意差が認められないが、実施例１は、Ｐ＜０．０５の有意差で止血作用が認められた。
【００４４】
表３または表４の結果からは、実施例１に収斂性のあることがわかる。
また、表５の結果からは、比較例１は生理食塩水（コントロール）に対して有意差が認められないが、実施例１は、Ｐ＜０．０１の有意差で耐創張力が認められ、創傷治癒作用のあることがわかる。
【００４５】
表６の官能試験の結果からは、実施例１を含む実験例Ｂの組成のパウダーにＧＺ−Ｚｎの良好な付着作用が認められた。
【００４６】
また、表７の結果から、実施例１を含む実験例Ｄの錠剤は、実施例１を含有しない実験例Ｃに比べて１．５倍以上の強度が得られた。
【００４７】
〔実施例２〕
ＧＴ−Ｚｎの調製：
５０ｇのＧＴ−Ｈに１０００ｍｌの水を加え、かき混ぜながら２１０ｍｌの０．５Ｎの水酸化カリウムのエタノール溶液を加え、溶解後３００ｍｌの水に溶解した１５．０１ｇの硫酸亜鉛・七水和物を徐々に加えた。５０℃に加温した後、冷却し、析出物をろ過し、水洗、乾燥後５２ｇのＧＴ−Ｚｎを得た。
【００４８】
得られたＧＴ−Ｚｎに対して赤外線吸収スペクトルを測定し、極大吸収が認められた波長を表８に示した。また、原料のＧＴ−Ｈについても同様に赤外線吸収スペクトルを調べ、結果を表８中に併記した。
【００４９】
【表８】

【００５０】
表８の結果から、遊離のカルボン酸に特有の１７０５ｃｍ^−１がＧＴ−Ｚｎでは消失した。また、原料のＧＴ−Ｈの１６６３ｃｍ^−１の吸収がＧＴ−Ｚｎでは幅広くなり、１６４７ｃｍ^−１に極大吸収が認められた。これらのことから、生成物はＧＴ−Ｈの亜鉛塩であるＧＴ−Ｚｎであることがわかる。
【００５１】
得られたＧＴ−Ｚｎに対して、その止血作用、創傷治癒作用、抗炎症作用、付着作用、結合作用のあることを確認するため、以下の実験を行なった。なお、付着作用、結合作用の各確認試験については、前記した試験方法と全く同様の条件で行ない、結果をそれぞれ、表９（付着作用確認実験）、表１０（結合作用確認実験）にまとめた。
【００５２】
【表９】

【００５３】
【表１０】

【００５４】
［創傷治癒作用確認実験］
日本薬理学会誌Ｖｏｌ．１００，１６２（１９９２） 清水らの方法を応用し、以下のように行なった。
すなわち、ハートレイ系雄性モルモット（体重３００ｇ前後）をネンブタール麻酔下（３０ｍｇ／ｋｇ，ｉ．ｐ．）において背部を剪毛、消毒し、メスで左右対象に２箇所切創（１．５ｃｍ）を作り、絹糸で１つの創傷当たり２箇所等分縫合した。切創作成後、３日後に切創が１ｃｍとなるように幅１ｃｍで長さ２ｃｍの皮膚を摘出した。試験液は、２ｍｇ／０．４ｍｌ／個体となるように白色ワセリンで分散し、１つの創傷当り、創傷部を中心に０．２ｍｌの量を１日１回の割合で３日間塗布した。
【００５５】
切創の癒着度を判定するため、レオメーターで創傷部の耐創張力（ｇ／ｃｍ）を測定した。なお、左右２箇所の創傷張力の平均値をもって１個体の耐創張力とし、結果を表１１に示した。
【００５６】
【表１１】

【００５７】
［抗炎症作用確認試験］
慶応医学４４（１）， ｐ１７ （１９６７） 富沢らの方法に準じた。すなわち、１５０ｇ前後の雄性Ｗｉｓｔｅｒ系ラットを使用し、試験液をそれぞれ１．０％ポリソルベート、ゴマ油に分散し、背部皮下に５００ｍｇ／２．０ｍｌ／ｋｇの割合で連日皮下投与し、７日後に抗炎症作用を調べた。
【００５８】
この場合の抗炎症作用の評価方法は、ｒａｔ ｆｏｏｔ ｔｅｓｔ を採用し、１０％ホルマリン−生理食塩水の０．１ｍｌをラットの片方の後足背皮下に投与し、１時間、２時間、３時間後の足嵩増加の平均値を算出し、コントロールに対する試験液投与群の抑制率を求め、表１２中に示した。
【００５９】
【表１２】

【００６０】
［止血作用確認実験］
Ｊ． Ｓｏｃ． Ｃｏｓｍｅｔ． Ｃｈｅｍ． Ｊａｐａｎ．， Ｖｏｌ．２４（３），ｐ１８７（１９９１）浅沼らの方法（改良 Ｂｌｅｅｄｉｎｇ 法）を応用して行なった。
【００６１】
すなわち、一晩絶食したＷｉｓｔａｒ系雄性ラット（体重２００〜２５０ｇ）にペントバルビタール（８０ｍｇ／ｋｇ）を腹腔内投与して麻酔後、肋骨より下２ｃｍの位置縦に２．５ｃｍ円形の腹膜を用いた。
【００６２】
その後、直ちに ｅｕｇｌｏｂｕｌｉｎ−ＳＫ ｍｉｘｔｕｒｅ ２ｍｌ／ｋｇ相当量を左足大腿静脈より投与した。すばやく出血している腹膜上に濾紙（２×２ｃｍ）をのせ、１０分後にこの濾紙を取り除き、試験品１００ｍｇを塗布した。そして、直ちに前もって３７℃の温水に浸しておいた濾紙（１．５×３ｃｍ）を露出面上にのせ、出血する血液を３０分間吸収させた。３０分毎にこの濾紙を取り替え、試験品塗布後から１時間３０分までこの操作を行なった。
【００６３】
血液を吸収させた濾紙を水４ｍｌの入った試験管に入れ、３７℃の水浴中で３０分間浸盪し血液を溶出させろ過した。これの波長５４０ｎｍの吸光度を測定し、３０分毎の出血量とした。すなわち、出血量を吸光度で評価し、結果を表１３に示した。
【００６４】
【表１３】

【００６５】
〔比較例３〕
一般試薬のグリチルリチン酸ステアリル：Ｃ_４８Ｈ_８２Ｏ_４ （以下、ＧＴ−Ｓｔと略記する。）を比較例３として用いた。
このＧＴ−ＳｔをＧＴ−Ｚｎに代えて用いたこと以外は全く同様にして、上記した創傷治癒作用および抗炎症作用の確認試験を行ない、結果をそれぞれ表９、表１２に併記した。
【００６６】
〔比較例４〕
一般試薬のグリチルレチン酸（ＧＴ−Ｈ）を比較例４として用いた。
このＧＴ−ＨをＧＴ−Ｚｎに代えて用いたこと以外は全く同様にして、上記した創傷治癒作用、抗炎症作用、および止血作用の確認試験を行ない、結果をそれぞれ表１１（創傷治癒性）、表１２（抗炎症性）、表１３（止血性）に併記した。
【００６７】
ここで、表１１の結果からは、比較例３および比較例４は、白色ワセリン（コントロール）に比べて耐創張力は大きいものの、有意差は認められなかった。しかし、実施例２は、Ｐ＜０．０５で有意差が認められ、創傷治癒作用があるといえる。
【００６８】
表９の結果からは、実施例２を含む実験例Ｆの組成のパウダーにＧＴ−Ｚｎの良好な付着作用が認められた。
【００６９】
また、表１０の結果から、実施例２を含む実験例Ｈの錠剤は、実施例２を含有しない実験例Ｇに比べて１．５倍以上の強度が得られパウダーを強く結合していることがわかる。
【００７０】
表１２の結果から明らかなように、抗炎症作用の程度は比較例４＜比較例３＜実施例２であり、等量においてＧＴ−Ｈに対しＧＴ−Ｓｔがその１．３４倍、ＧＴ−Ｚｎが１．４４倍の効果であった。
【００７１】
表１３の結果から、比較例４はコントロール（無投与）に対して有意差は認められないが、実施例２はＰ＜０．０５の有意差で止血作用が認められた。
【００７２】
次に、医療用・化粧用製剤の実施例について、以下に説明する。なお、配合割合は全て重量部（以下、単に部と記す。）である。
【００７３】

（１）〜（４）を６５〜７０℃に加温して溶解した後、固まるまで冷却・攪拌を行ない、マクロゴール軟膏を調製した。
得られた軟膏を軽度の擦傷に塗布すると、止血作用が認められた。
【００７４】

（１）〜（３）を６５〜７０℃に加温して溶解した後、固まるまで冷却・攪拌を行ない、軟膏を調製した。
得られた軟膏を潰瘍面に塗布すると、患部を保護し、分泌物の吸収および患部の乾燥が認められた。
【００７５】

（１）〜（３）を均一になるまで混合して散布剤を調製した。
得られた散布剤を創傷部位に塗布すると、患部を保護し、分泌物の吸収および患部の乾燥が認められた。
【００７６】

（１）〜（４）を均一になるまで混合してリニメント剤を調製した。
得られたリニメント剤を火傷した部位に塗布すると、患部を保護し、分泌物の吸収および患部の乾燥、さらには炎症の消退が認められた。
【００７７】

（１）〜（３）を６５〜７０℃に加温して均一になるまで攪拌し、座薬成型器にて成型した。
得られた座薬を痔疾患者の肛門より挿入すると、痔疾患部を保護し、分泌物の吸収および患部の乾燥さらには炎症の消退、止血などの効果が認められた。
【００７８】

（１）〜（６）を均一になるまで混合して散布剤（汗疹等予防パウダー）を調製した。
得られた散布剤を首、胸、背中、脇などの汗を多く分泌する部位に散布すると、汗疹予防に有効であった。また、汗疹の既にある部位に散布すると、患部を保護し、分泌物の吸収および患部の乾燥が認められた。
【００７９】

（１）〜（９）を均一になるまで混合して粉白粉（おしろい）を調製した。得られた粉白粉は、肌に対する付着性に大変優れたものであった。
【００８０】

（１）〜（１４）を均一になるまで混合し成型器で加圧成型して、固形白粉を得た。
得られた固形白粉は、室温で半年間以上ひび割れがなく安定した品質であり、その使用感は汗を抑え、落ちにくく付着性の良いものであった。
【００８１】

（１）と（２）を混合し、（３）と（４）を添加し溶解して制汗ローションを調製した。
得られた制汗ローションは、汗を抑え、さっぱりした良好な使用感であった。
【００８２】

（１）〜（５）を均一になるまで混合して制汗パウダーを得た。この制汗パウダーを脇などの汗を多く分泌する部位に散布したところ、散布部位を乾燥させると共に、汗のにおいを抑えて良好な使用感であった。
【００８３】

（１）〜（６）を均一になるまで攪拌して均一に溶解し、（７）と（８）を添加して溶解して収斂化粧水を得た。得られた収斂化粧水は、収斂性により良好な使用感であった。
【００８４】

（１）〜（５）を均一になるまで攪拌して均一に溶解し、（６）と（７）を添加して溶解してアフターシェービングローションを得た。得られたアフターシェービングローションは、収斂性、止血性、抗炎症作用を有し、さっぱりした感触でひげそり後に良好な使用感であった。
【００８５】

８０℃に加温した（１）に（２）を攪拌しつつ添加し、完全溶解させた。その後、冷却し、均一溶解した（３）〜（８）５０℃にて添加し、３５℃にて冷却と攪拌を止め、パック料を得た。得られたパック料は、毛穴が広がりすぎないでさっぱりしたパックのできるものであった。
【００８６】

８０℃に加温した（１）に（２）〜（７）を順次混練し、その後（８）を加えて混練し、練り歯磨きを得た。
得られた練り歯磨きは、収斂作用や抗炎症作用を有し、歯槽膿漏の予防やその治療に適したものであった。
【００８７】

（１）と（２）に（３）〜（５）を入れて練り込む。（６）〜（１４）を８０℃に加温し、攪拌しつつ前記（１）〜（５）を加え、さらに８０℃に加温した（１５）と（１６）を加える。そして、攪拌しつつ３５℃にまで冷却して下地クリームを得た。
得られた下地クリームは、収斂作用や抗炎症作用を合わせ持ち、汗ばむことのなく肌になじみのよい下地クリームであった。
【００８８】

（１）〜（９）を８０℃に加温溶解し、これに８０℃の（１０）を加え、攪拌し均一化後、攪拌しつつ４５℃にまで冷却して（１１）と（１２）を添加して３５℃まで攪拌と冷却を続けて洗顔料を得た。
得られた洗顔料は、洗い上がりがしっとりすると共に、さっぱりとして使用感の非常に優れたものであった。
【００８９】
【効果】
この発明は、以上説明したように、所定の化学組成で示されるグリチルリチン酸亜鉛もしくはグリチルレチン酸亜鉛からなる収斂・結着性化合物であり、またはそれぞれ単独または両者併用した混合物から構成した医療用または化粧用製剤としたので、収斂作用および止血作用、固形状の医薬品等や化粧品の結着作用、皮膚への付着作用のある化合物または医療用または化粧用製剤となる利点がある。[0001]
[Industrial application fields]
The present invention relates to an astringent / binding compound and a medical / cosmetic preparation used by adding to pharmaceuticals, quasi drugs or cosmetics.
[0002]
[Prior art]
In general, glycyrrhetinic acid (hereinafter abbreviated as GT-H) or a glycoside thereof, glycyrrhizic acid (same as glycyrrhizin or glycyrrhizin, hereinafter abbreviated as GZ-H), has many as shown below. The pharmacological action is known, and it is blended in various pharmaceuticals, quasi-drugs, and cosmetics in the form of free acid or ammonium salt, potassium salt, sodium salt, higher alcohol ester and the like.
[0003]
That is, the pharmacological action of GZ-H or GT-H includes water electrolyte of adrenal cortex, carbohydrate hormone-like action, estrogen-like action, antitussive action, anti-inflammatory action, antiallergic action, detoxification action, hyperlipidemia improvement The action and the action of increasing the cyclic AMP concentration in gastric mucosa cells have been known so far.
[0004]
Therefore, GZ-H or GT-H is antitussive, anti-inflammatory action, cold medicine as a pharmaceutical based on anti-allergic effect, be formulated antitussive, experimental liver damage recovery effect, the phospholipase A ₂ inhibitory action and the like It is also included in fatigue recovery nutrients.
[0005]
GZ-H or GT-H is a quasi-drug as a preventive agent for alveolar pyorrhea, formulated for medicated toothpaste, and as a rough skin preventive agent for medicated cream, medicated lotion, etc. It is also added to antiperspirants and medicinal baby powders.
[0006]
GZ-H or GT-H is a basic cosmetic skin cream, cleansing cream, milky lotion, emollient cream, skin lotion, hair cosmetics such as hair tonic, hair liquid, hair gel, etc. It is also used in cosmetics such as emulsions, other bath preparations, white powder, and makeup products.
[0007]
[Problems to be solved by the invention]
However, the conventional GZ-H or GT-H and their derivatives have a problem that there is no convergence or hemostasis as a pharmacological action, and even if these actions are found, they are very weak.
[0008]
In addition to such a pharmacological action, conventional GZ-H or GT-H and related compounds thereof are also used for binding properties effective in preventing cracks in cosmetics such as tablets formed with powders or solid white powder. Did not show its utility.
[0009]
Furthermore, conventional GZ-H or GT-H and related compounds have no effect on the adhesion property of improving the adhesion property to the skin in powdery cosmetics.
[0010]
Therefore, the present invention further relates to glycyrrhizic acid or a glycyrrhetinic acid-based compound as having an astringent action and a hemostatic action, and also has a binding action to a solid preparation, an adhesion action to the skin, that is, a binding action. It is an object to make it a high-quality medical / cosmetic preparation containing.
[0011]
[Means for Solving the Problems]
In order to solve the above problems, in the present invention, a convergent / binding compound composed of zinc glycyrrhizinate represented by the following formula 3 or composed of zinc glycyrrhetinate represented by the following formula 4 This is a convergent / binding glycyrrhizin compound.
[0012]
Alternatively, the medical preparation or cosmetic preparation is composed of zinc glycyrrhizinate represented by the following formula 3 or zinc glycyrrhetinate represented by the following formula 4 or a mixture of both.
[0013]
[Chemical 3]

[0014]
[Formula 4]

[0015]
The details will be described below.
Zinc glycyrrhizinate (hereinafter abbreviated as GZ-Zn) represented by the chemical formula 3 used in the present invention is composed of glycyrrhizic acid (C ₄₂ H ₆₂ O ₁₆ ) represented by the following chemical formula 5 and zinc. It is a compound having a composition ratio of 1: 0.01-3. This is because if the composition ratio of zinc is less than 0.01, the desired effect of the present invention cannot be obtained, and the composition ratio of zinc cannot exceed 3 in view of the composition formula of the compound.
[0016]
[Chemical formula 5]

[0017]
The zinc glycyrrhetinate (hereinafter abbreviated as GT-Zn) represented by the formula 4 used in the present invention is a composition of glycyrrhetin (C ₃₀ H ₄₆ O ₄ ) and zinc as shown in the following formula 6. A compound with a ratio of 1: 0.01-1. This is because if the composition ratio of zinc is less than 0.01, the desired effect of the present invention cannot be obtained, and exceeding 1 is impossible in view of the composition formula of the compound.
[0018]
[Chemical 6]

[0019]
【Example】
[Example 1]
Preparation of GZ-Zn:
Dissolve 50 g of GZ-H in 500 ml of ethanol water (1: 1), add 120 ml of 1N aqueous potassium hydroxide solution while stirring, and then add 8.63 g of zinc sulfate heptahydrate dissolved in 50 ml of water. Was gradually added. After heating to 50 ° C., the mixture was cooled and the precipitate was filtered, washed with water, and dried to obtain 36 g of GZ-Zn.
[0020]
An infrared absorption spectrum was measured for the obtained GZ-Zn, and the wavelength at which the maximum absorption was recognized is shown in Table 1. Further, the infrared absorption spectrum of GZ-H as a raw material was similarly examined, and the results are also shown in Table 1.
[0021]
[Table 1]

[0022]
From the results in Table 1, the 1732 cm ⁻¹ characteristic of free carboxylic acid was greatly reduced in GZ-Zn. In addition, absorption of 1647cm ^-1 of GZ-H of raw materials is a wide range in the GZ-Zn, maximum absorption was observed at 1640cm ^-1, also absorption of 1000~1200cm ^-1 found in the carbohydrate, confirmation to both did it. From these, it can be seen that the product is GZ-Zn which is a zinc salt of GZ-H.
[0023]
In order to confirm that the obtained GZ-Zn has hemostatic action, astringent action, wound healing action, anti-inflammatory action, adhesion action, and binding action, the following experiment was conducted.
[0024]
[Hemostatic action confirmation experiment]
J. et al. Soc. Cosmet. Chem. Japan. , Vol. 24 (3), p187 (1991) Asanuma et al. (Improved bleeding method).
[0025]
That is, Wistar male rats (body weight 200 to 250 g) fasted overnight were anesthetized with pentobarbital (80 mg / kg) intraperitoneally, and then a 2.5 cm circular peritoneum was used at a position 2 cm below the ribs. .
[0026]
Immediately thereafter, euglobulin-SK mixture 2 ml / kg equivalent was administered from the left foot femoral vein. After the administration, filter paper (2 × 2 cm) was placed on the peritoneum that was bleeding quickly, and 0.2 ml of the test solution was administered to the filter paper. Five minutes after administration, the filter paper was removed, and a filter paper (1.5 × 3 cm) previously soaked in warm water at 37 ° C. was placed on the exposed surface to absorb the bleeding blood for 30 minutes. The filter paper was replaced every 30 minutes, and this operation was performed for up to 2 hours after administration of the test solution.
[0027]
The blood-absorbed filter paper was placed in a test tube containing 4 ml of water, and the blood was eluted by shaking for 30 minutes in a 37 ° C. water bath. The absorbance at a wavelength of 540 nm was measured and taken as the amount of bleeding every 30 minutes. That is, the amount of bleeding was evaluated by absorbance, and the results are shown in Table 2.
[0028]
[Table 2]

[0029]
[Convergence Confirmation Experiment 1]
Ten normal taste holders were shaken with 20 ml of the test solution, and it was examined whether or not the tongue was tight and a pleasant sensation. The results are shown in Table 3, which are the same answers for all 10 people. In addition, it evaluated that the thing which has astringent taste has an astringent effect, and the thing which does not have the same effect.
[0030]
[Table 3]

[0031]
[Convergence Confirmation Experiment 2]
3 ml of an aqueous collagen solution (commercially available soluble collagen) was placed in a test tube, 1 ml of the test solution was added from above, and the mixture was gently stirred. Immediately thereafter, the presence or absence of precipitation was confirmed. In this case, those in which precipitation was observed due to protein alteration were evaluated as having a convergence effect (+), and those in which precipitation was not observed were evaluated as having no convergence effect (−), and the results are shown in Table 4.
[0032]
[Table 4]

[0033]
[Wound healing effect confirmation experiment]
Japanese Journal of Pharmacology Vol. 100, 162 (1992) Referring to the method of Shimizu et al.
That is, Hartley male guinea pigs (weight around 300 g) were shaved and disinfected under Nembutal anesthesia (30 mg / kg, ip), and two cuts (1.5 cm) were made on the left and right subjects with a scalpel, It was sutured in two equal parts per wound with silk thread. Three days after the creation of the cut, a skin having a width of 1 cm and a length of 2 cm was extracted so that the cut was 1 cm. The test solution is dissolved or dispersed with physiological saline so as to be 2 mg / 0.4 ml / individual, and 2 wounds per wound at a rate of 0.1 ml / site around the wound part, totaling 4 places per day. It was administered subcutaneously 3 times.
[0034]
In order to determine the degree of adhesion of the wound, the wound tension resistance (g / cm) of the wound was measured with a rheometer. The average value of the wound tension at the two left and right positions was defined as the wound resistance of one individual, and the results are shown in Table 5.
[0035]
[Table 5]

[0036]
[Adhesion action confirmation experiment]
Powders having the compositions shown in Table 6 (Experimental Example A and Experimental Example B) were prepared, and a sensory test was performed on 10 adult subjects. That is, 0.2 g of Experimental Example A or Experimental Example B was applied to the forearm, and the superiority or inferiority of adhesion without smoothness was determined. The results are also shown in Table 6.
[0037]
[Table 6]

[0038]
[Bonding confirmation experiment]
Powders of the compositions shown in Table 7 (Experimental Example C, Experimental Example D) were mixed, 0.5 g each was placed in a tableting machine with a diameter of 16 mm, and pressurized for 1 minute at a weight of 200 kg (100 kg / cm ² ). After that, the pressure was set to normal pressure.
[0039]
The breaking strength was measured with a rheometer using the obtained tablets as test materials, and the results are also shown in Table 7.
[0040]
[Table 7]

[0041]
[Comparative Example 1]
A general reagent dipotassium glycyrrhizinate (hereinafter abbreviated as GZ-K2) was used as Comparative Example 1.
Except that this GZ-K2 was used in place of GZ-Zn, the confirmation tests for hemostasis, convergence, and wound healing were performed in the same manner, and the results are shown in Table 2, Table 3, and Table 4, respectively. This is also shown in Table 5.
[0042]
[Comparative Example 2]
The general reagent glycyrrhizic acid (GZ-H) was used as Comparative Example 2.
Except that this GZ-H was used in place of GZ-Zn, the above wound healing action confirmation test was conducted in the same manner, and the results are shown in Table 5.
[0043]
Looking at Example 1 and Comparative Examples 1 and 2 described above, as is clear from the results in Table 2, Comparative Example 1 shows no significant difference with respect to distilled water (control). The hemostatic effect was observed with a significant difference of P <0.05.
[0044]
From the results in Table 3 or Table 4, it can be seen that Example 1 is astringent.
In addition, from the results of Table 5, Comparative Example 1 shows no significant difference with respect to physiological saline (control), but Example 1 shows a significant difference of P <0.01, and the wound tension resistance is recognized. It can be seen that there is a wound healing action.
[0045]
From the results of the sensory test in Table 6, a good adhesion action of GZ-Zn was observed on the powder having the composition of Experimental Example B including Example 1.
[0046]
In addition, from the results of Table 7, the tablet of Experimental Example D including Example 1 was 1.5 times or more stronger than Experimental Example C not including Example 1.
[0047]
[Example 2]
Preparation of GT-Zn:
Add 1000 ml of water to 50 g of GT-H, add 210 ml of 0.5N potassium hydroxide ethanol solution while stirring and gradually dissolve 15.01 g of zinc sulfate heptahydrate dissolved in 300 ml of water. Added to. After heating to 50 ° C., the mixture was cooled and the precipitate was filtered, washed with water and dried to obtain 52 g of GT-Zn.
[0048]
An infrared absorption spectrum was measured for the obtained GT-Zn, and the wavelengths at which the maximum absorption was recognized are shown in Table 8. Further, the infrared absorption spectrum of the raw material GT-H was similarly examined, and the results are also shown in Table 8.
[0049]
[Table 8]

[0050]
From the results in Table 8, 1705 cm ⁻¹ peculiar to free carboxylic acid disappeared in GT-Zn. Further, the absorption of 1663 cm ⁻¹ of the raw material GT-H was broadened with GT-Zn, and the maximum absorption was observed at 1647 cm ⁻¹ . From these facts, it is understood that the product is GT-Zn which is a zinc salt of GT-H.
[0051]
In order to confirm that the obtained GT-Zn has hemostatic action, wound healing action, anti-inflammatory action, adhesion action, and binding action, the following experiment was conducted. In addition, each confirmation test of the adhesion action and the binding action was performed under exactly the same conditions as the test method described above, and the results are summarized in Table 9 (adhesion action confirmation experiment) and Table 10 (bonding action confirmation experiment), respectively. .
[0052]
[Table 9]

[0053]
[Table 10]

[0054]
[Wound healing effect confirmation experiment]
Japanese Journal of Pharmacology Vol. 100, 162 (1992) The method of Shimizu et al. Was applied as follows.
That is, Hartley male guinea pigs (weight around 300 g) were shaved and disinfected under Nembutal anesthesia (30 mg / kg, ip), and two cuts (1.5 cm) were made on the left and right subjects with a scalpel, It was sutured in two equal parts per wound with silk thread. Three days after the creation of the cut, a skin having a width of 1 cm and a length of 2 cm was extracted so that the cut was 1 cm. The test solution was dispersed with white petrolatum so as to be 2 mg / 0.4 ml / individual, and 0.2 ml of the wound was applied once a day at a rate of once a day for 3 days per wound.
[0055]
In order to determine the degree of adhesion of the wound, the wound tension resistance (g / cm) of the wound was measured with a rheometer. In addition, the wound tension of one individual was defined as the average value of the wound tension at the two left and right, and the results are shown in Table 11.
[0056]
[Table 11]

[0057]
[Anti-inflammatory action confirmation test]
Keio Medical 44 (1), p17 (1967) The method of Tomizawa et al. That is, about 150 g of male Wister rats were used, the test solution was dispersed in 1.0% polysorbate and sesame oil, respectively, and subcutaneously administered daily at a ratio of 500 mg / 2.0 ml / kg in the back, and 7 days later The inflammatory effect was examined.
[0058]
In this case, the anti-inflammatory action was evaluated using a rat foot test, in which 0.1 ml of 10% formalin-saline was administered subcutaneously to the back of one hind foot of a rat for 1 hour, 2 hours, 3 hours. The average value of the subsequent increase in foot bulk was calculated, and the inhibition rate of the test solution administration group relative to the control was determined and is shown in Table 12.
[0059]
[Table 12]

[0060]
[Hemostatic action confirmation experiment]
J. et al. Soc. Cosmet. Chem. Japan. , Vol. 24 (3), p187 (1991) Asanuma et al. (Improved bleeding method).
[0061]
That is, pentobarbital (80 mg / kg) was intraperitoneally administered to Wistar male rats (body weight 200 to 250 g) fasted overnight, followed by anesthesia, and a 2.5 cm circular peritoneum was used at a position 2 cm below the ribs. .
[0062]
Immediately thereafter, euglobulin-SK mixture 2 ml / kg equivalent was administered from the left foot femoral vein. A filter paper (2 × 2 cm) was placed on the rapidly bleeding peritoneum, and after 10 minutes, the filter paper was removed and 100 mg of the test sample was applied. Immediately after that, a filter paper (1.5 × 3 cm) previously immersed in warm water at 37 ° C. was placed on the exposed surface, and bleeding blood was absorbed for 30 minutes. This filter paper was replaced every 30 minutes, and this operation was performed for 1 hour and 30 minutes after application of the test product.
[0063]
The filter paper on which blood was absorbed was placed in a test tube containing 4 ml of water, and the sample was immersed in a water bath at 37 ° C. for 30 minutes to elute and filter the blood. The absorbance at a wavelength of 540 nm was measured and taken as the amount of bleeding every 30 minutes. That is, the amount of bleeding was evaluated by absorbance, and the results are shown in Table 13.
[0064]
[Table 13]

[0065]
[Comparative Example 3]
A general reagent stearyl glycyrrhizinate: C ₄₈ H ₈₂ O ₄ (hereinafter abbreviated as GT-St) was used as Comparative Example 3.
Except that this GT-St was used in place of GT-Zn, the above-described wound healing action and anti-inflammatory action confirmation test was conducted, and the results are shown in Table 9 and Table 12, respectively.
[0066]
[Comparative Example 4]
The general reagent glycyrrhetinic acid (GT-H) was used as Comparative Example 4.
Except that this GT-H was used instead of GT-Zn, the above-mentioned wound healing action, anti-inflammatory action, and hemostatic action were confirmed, and the results are shown in Table 11 (Wound healing properties). Table 12 (anti-inflammatory) and Table 13 (hemostatic).
[0067]
Here, from the results of Table 11, although Comparative Example 3 and Comparative Example 4 had higher wound resistance than white petrolatum (control), no significant difference was observed. However, in Example 2, a significant difference was observed at P <0.05, and it can be said that there was a wound healing action.
[0068]
From the results in Table 9, a good adhesion effect of GT-Zn was recognized on the powder having the composition of Experimental Example F including Example 2.
[0069]
Moreover, from the result of Table 10, the tablet of Experimental Example H including Example 2 has a strength 1.5 times or more higher than that of Experimental Example G not including Example 2, and strongly binds the powder. I understand.
[0070]
As is clear from the results in Table 12, the degree of anti-inflammatory action is Comparative Example 4 <Comparative Example 3 <Example 2, and GT-St is 1.34 times that of GT-H in an equal amount, and GT- The effect of Zn was 1.44 times.
[0071]
From the results of Table 13, Comparative Example 4 showed no significant difference with respect to the control (no administration), but Example 2 showed a hemostatic action with a significant difference of P <0.05.
[0072]
Next, examples of medical and cosmetic preparations will be described below. In addition, all the mixture ratios are parts by weight (hereinafter, simply referred to as parts).
[0073]

(1) to (4) were heated to 65 to 70 ° C and dissolved, and then cooled and stirred until solidified to prepare macrogol ointment.
When the obtained ointment was applied to mild abrasions, a hemostatic effect was observed.
[0074]

(1) to (3) were heated to 65 to 70 ° C. and dissolved, and then cooled and stirred until solidified to prepare an ointment.
When the obtained ointment was applied to the ulcer surface, the affected area was protected, and secretion was absorbed and the affected area was dried.
[0075]

A spray was prepared by mixing (1) to (3) until uniform.
When the obtained spray was applied to the wound site, the affected area was protected, and secretion was absorbed and the affected area was dried.
[0076]

A liniment was prepared by mixing (1) to (4) until uniform.
When the obtained liniment was applied to the burned site, the affected area was protected, secretion was absorbed, the affected area was dried, and inflammation was also resolved.
[0077]

(1) to (3) were heated to 65 to 70 ° C., stirred until uniform, and molded with a suppository molding machine.
When the obtained suppository was inserted into the anus of a manic disease patient, the manic region was protected, and effects such as absorption of secretions, drying of the diseased part, elimination of inflammation, and hemostasis were observed.
[0078]

(1) to (6) were mixed until uniform to prepare a spray (preventive powder such as sweats).
When the obtained spray was sprayed on sites that secrete a lot of sweat, such as the neck, chest, back, and sides, it was effective in preventing sweat. Moreover, when it was sprayed on the site where sweat was already present, the affected area was protected, and secretion was absorbed and the affected area was dried.
[0079]

(1)-(9) was mixed until it became uniform, and the powdered white powder (white) was prepared. The obtained white powder was very excellent in adhesion to the skin.
[0080]

(1) to (14) were mixed until uniform and pressure molded with a molding machine to obtain a solid white powder.
The obtained solid white powder had a stable quality without cracking for more than half a year at room temperature, and its feeling of use suppressed sweat and was hard to fall off and had good adhesion.
[0081]

(1) and (2) were mixed, and (3) and (4) were added and dissolved to prepare an antiperspirant lotion.
The obtained antiperspirant lotion had a good feeling of use while suppressing perspiration.
[0082]

Antiperspirant powder was obtained by mixing (1) to (5) until uniform. When this antiperspirant powder was sprayed on a part that secretes a lot of sweat, such as aside, the sprayed part was dried and the smell of sweat was suppressed, giving a good feeling of use.
[0083]

(1) to (6) were stirred until uniform and dissolved uniformly, and (7) and (8) were added and dissolved to obtain an astringent lotion. The obtained astringent lotion had a good feeling of use due to astringency.
[0084]

(1) to (5) were stirred until uniform and dissolved uniformly, and (6) and (7) were added and dissolved to obtain an after shaving lotion. The obtained after shaving lotion had astringency, hemostasis, and anti-inflammatory action, and had a good feeling after shaving with a refreshing feel.
[0085]

(2) was added to (1) heated to 80 ° C. with stirring, and completely dissolved. Then, it cooled and added uniformly (3)-(8) at 50 degreeC, and cooling and stirring were stopped at 35 degreeC, and the pack material was obtained. The resulting pack charge was a refreshing pack without excessive pores.
[0086]

(2) to (7) were kneaded in order to (1) heated to 80 ° C., and then (8) was added and kneaded to obtain a toothpaste.
The obtained toothpaste had an astringent action and an anti-inflammatory action, and was suitable for prevention and treatment of alveolar pyorrhea.
[0087]

Add (3) to (5) to (1) and (2) and knead. (6) to (14) are heated to 80 ° C, the above (1) to (5) are added while stirring, and (15) and (16) heated to 80 ° C are further added. And it cooled to 35 degreeC, stirring, and obtained the base cream.
The obtained base cream was a base cream having an astringent action and an anti-inflammatory action, and was well adapted to the skin without sweating.
[0088]

(1) to (9) are heated and dissolved at 80 ° C., and 80 ° C. (10) is added thereto. After stirring and homogenizing, the mixture is cooled to 45 ° C. with stirring, and (11) and (12) Was added and stirring and cooling were continued to 35 ° C. to obtain a face wash.
The resulting facial cleanser was moisturized and refreshed with a very good feeling of use.
[0089]
【effect】
As described above, the present invention is a converging / binding compound composed of zinc glycyrrhizinate or zinc glycyrrhetinate having a predetermined chemical composition, or a medical or cosmetic composition composed of a single or a mixture of both. Therefore, there are advantages in that it is a compound or medical or cosmetic preparation that has an astringent action and hemostatic action, a solid drug or the like, a binding action of cosmetics, and an adhesion action to the skin.

Claims (2)

A convergent cosmetic preparation comprising zinc glycyrrhizinate represented by the following formula 1 or zinc glycyrrhetinate represented by the following formula 2 or a mixture of both.

A binder for solid cosmetics comprising zinc glycyrrhizinate represented by the formula 1 of formula 1 or zinc glycyrrhetinate represented by the formula of formula 2 of the same claim or a mixture of both.