JP6708623B2 - 害虫忌避剤の皮膚への浸透を抑制する方法及び害虫忌避剤の皮膚への浸透抑制剤 - Google Patents
害虫忌避剤の皮膚への浸透を抑制する方法及び害虫忌避剤の皮膚への浸透抑制剤 Download PDFInfo
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Description
1.ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚への浸透を抑制する方法。
2.前記害虫忌避剤のlogP値が1以上である、前記1に記載の方法。
3.前記ポリアルキレングリコールの分子量が200〜20000である前記1または2に記載の方法。
4.前記ポリアルキレングリコールが、ポリプロピレングリコールである、前記1〜3のいずれか1に記載の方法。
5.ポリアルキレングリコールを含有する、害虫忌避剤の皮膚への浸透抑制剤。
6.ポリアルキレングリコールの、皮膚上に適用した害虫忌避剤の皮膚への浸透を抑制させるための使用。
<試験例1−1(実施例1〜3、比較例1)>
(害虫忌避組成物の調製)
下記表1に示す処方に従い、各成分を撹拌下で混合して、害虫忌避組成物を調製した(実施例1〜3、比較例1)。なお、ディートのlogP値は2.0である。またPEG−200(マクロゴール200)、PEG−1000(マクロゴール1000)、及びPP−1000(ニューポールPP−1000)は、三洋化成工業株式会社から入手したものを用いた。
以下の手順により試験を行った。なお、試験装置として、図1に示す水平型拡散セル(ビードレックス社製、平板膜用水平型パームセル)を使用した。
1.マウスの皮膚1(ラボスキン、株式会社星野実験動物飼育所より入手)を水平型拡散セル10に、皮膚1の真皮側がレセプターセル2側に位置するように取り付けた。
2.皮膚1の角層側(4.9cm2)に、上記調製した害虫忌避組成物を約45μL処理し、アルミ箔8で覆い、締め付けノブ6で皮膚1を固定した。
3.レセプターセル2にはディートを含まない生理食塩水9を50mL満たした。
4.実験の間、レセプターセル2はスターラー3でセル内の生理食塩水を撹拌させ、レセプターセル2を覆っているウォータージャケット4には、ヒーター/サーキュレーター5により、37℃の温水を循環させることで、レセプターセル2内の温度を37℃で一定に保った。
5.レセプターセル2内の温度が37℃になった時点から、0.5、1時間後に、レセプターセル2のサンプリング・ポート7より生理食塩水9を3mLサンプリングし、その後同量のディートを含まない生理食塩水を戻し、液量を一定にした。
6.サンプリング液中のディート量をHPLCによって測定した。ディート量の測定結果より、下記式により、皮膚上残存量、皮膚上残存率を算出した。
0.5時間後の皮膚上残存量(mg/cm2)=(処理ディート量−0.5時間後にサンプリングした液のディート量×50/3)/処理面積
1時間後の皮膚上残存量(mg/cm2)=(処理ディート量−1時間後にサンプリングした液のディート量×50/3−0.5時間後にサンプリングした液のディート量)/処理面積
皮膚上残存率(%)=各時間の皮膚上残存量/処理ディート量×100
皮膚上残存量(mg/cm2)は小数第三位を四捨五入した数値とし、皮膚上残存率(%)は小数第一位を四捨五入した数値とした。
試験例1−1の結果を表2(皮膚上残存量(mg/cm2))および表3(皮膚上残存率(%))に示す。
この結果により、ディート等の害虫忌避剤を単独で皮膚に適用するよりも、ポリエチレングリコールやポリプロピレングリコール等のポリアルキレングリコールと合わせて害虫忌避剤を皮膚に適用することにより、害虫忌避剤がより長い時間皮膚上に残存することがわかった。
下記表4に示す処方に従い、害虫忌避剤組成物を調製し(実施例4〜8、比較例1)、試験例1−1と同様に皮膚吸収抑制試験を行った。表4中、PP2000(ニューポールPP−2000)は、三洋化成工業株式会社から入手したものを用いた。
試験例1−2の結果を表5(皮膚上残存量(mg/cm2))および表6(皮膚上残存率(%))に示す。
また、ディートの含有量に対してポリプロピングリコールの含有量が最も少ない(ディートの含有量を1としたときのポリプロピングリコールの含有量が質量比で0.05である)実施例4の害虫忌避組成物においても、ポリプロピングリコールを含有しない試験例1−1の比較例1の害虫忌避組成物と比較して、一定時間の経過後の皮膚上の害虫忌避剤の残存量および残存率が多いまたは高い結果となった。
下記表7に示す処方に従い、害虫忌避剤組成物を調製し(実施例9、比較例2)、試験例1−1と同様に皮膚吸収抑制試験を行った。表7中、PP2000(ニューポールPP−2000)は、三洋化成工業株式会社から入手したものを用いた。
試験例1−3の結果を表8(皮膚上残存量(mg/cm2))および表9(皮膚上残存率(%))に示す。
下記表10に示す処方に従い、害虫忌避剤組成物を調製し(実施例10〜11、比較例3〜4)、試験例1−1と同様に皮膚吸収抑制試験を行った。
なお、メントールのlogP値は3.4、p−メンタン3,8−ジオールのlogP値は1.4である。
試験例1−3の結果を表11(皮膚上残存量(mg/cm2))および表12(皮膚上残存率(%))に示す。
この結果により、ディートの代わりに害虫忌避剤のメントールまたはp‐メンタン3,8−ジオールを使用した場合であっても、これら害虫忌避剤を単独で皮膚に適用するよりも、ポリプロピレングリコール等のポリアルキレングリコールと合わせて害虫忌避剤を皮膚に適用することにより、害虫忌避剤がより長い時間、皮膚上に残存することがわかった。
下記表13に示す処方に従い、害虫忌避剤組成物を調製し(参考例1〜4)、試験例1−1と同様に皮膚吸収抑制試験を行った。
なお、イミダクロプリドのlogP値は0.8、アセタミプリドのlogP値は0.6である。
試験例1−5の結果を表14(皮膚上残存量(mg/cm2))および表15(皮膚上残存率(%))に示す。
<試験例2−1(実施例12〜14、比較例5)>
(害虫忌避組成物の調製)
下記表16に示す処方に従い、各成分を撹拌下で混合して、害虫忌避組成物を調製した(実施例12〜14、比較例5)。なお、実施例12は試験例1−2の実施例6と、比較例5は試験例1−1の比較例1と同様の処方である。
以下の手順により試験を行った。
1.ヘアレスマウス(オス、20〜40g)1頭にコントロール区はエタノールを、処理区は表16に示す各害虫忌避組成物を全身に塗布し(0.5mL処理)、金網ゲージ内に動けないように固定した。
2.マウスを固定したゲージを試験ボックス内(30cm×30cm×30cm)に吊るした後、ケージ内にヒトスジシマカの雌を約40頭放した。
3.ケージ内にヒトスジシマカを放して5分後に、ケージ内からマウスを取り出した後、40〜100℃の恒温器にケージを1分程度入れ、ケージ内のヒトスジシマカを不動状態にし、放したヒトスジシマカ全てをつぶし、吸血頭数を計測し、下記の式より、吸血率および吸血阻止率を算出した。
吸血率(%)=(吸血数/供試虫数)×100
吸血阻止率(%)={(コントロール区の吸血率−処理区の吸血率)/コントロール区の吸血率}×100
吸血率(%)は小数第一位を四捨五入した数値とした。
4.上記2〜3を繰り返し、1時間ごとに吸血阻止率を算出した。
試験例2−1の結果を表17に示す。
下記表18に示す処方に従い、害虫忌避剤組成物を調製し(実施例15〜16、比較例6)、試験例2−1と同様の手順により試験を行った。
試験例2−2の結果を表19に示す。
この結果により、ディート等の害虫忌避剤を単独で皮膚に適用するよりも、ポリエチレングリコール、ポリプロピレングリコール等のポリアルキレングリコールと合わせて害虫忌避剤を皮膚に適用することにより、皮膚における害虫忌避剤の害虫忌避効果の持続性が向上することがわかった。
本試験では被験者10名(男性5人、女性5人;No.1〜10)の皮膚に本発明の害虫忌避組成物を適用し、害虫忌避剤の皮膚に対する刺激が抑制されるかについて試験を行った。
(害虫忌避組成物の調製)
[実施例17〜19、比較例7]
下記表20〜23に示す処方に従い、各成分を撹拌下で混合して、実施例17〜19、比較例7の害虫忌避組成物を調製した。
本試験は、(1)事前検診、(2)被験薬貼付、(3)被験薬除去、(4)自覚症状の質問、(5)皮膚反応の観察・判定を以下の表24に示すスケジュールで行った。
試験開始直前に被験者に自覚症状(薬剤アレルギー、痛み、痒み等)について質問し、試験への参加の適否を判断した。
(2)被験薬貼付
上記調整した各被験薬(実施例17〜19、及び比較例7の害虫忌避組成物)と、対照薬(精製水)を皮膚テスト用パッチテープ(リバテープ製薬社製)のパッドに約0.03mL滴下し、各被験者の両上腕内側部に貼付した。なお、各被験薬の濃度は等倍に設定した。
(3)被験薬除去
被験薬を貼付してから24時間後に被験薬を除去した。
(4)自覚症状の質問
被験薬貼付直後、被験薬貼付24時間後、被験薬除去1時間後に被験者に痛みや痒みの有無についての質問を行い、自覚症状を確認した。
(5)皮膚反応の観察・判定
皮膚反応の出やすい被験薬除去1時間後に対照薬(精製水)貼付部位の皮膚反応を対照として、被験薬貼付部位の皮膚反応を観察し、判定した。判定は以下のICDRG(国際接触皮膚炎研究会)基準に従い行った。
[ICDRG基準]
−:全く無反応
±:かすかな紅斑のみ
1+:弱い(小水疱なし)陽性反応、軽度紅斑、丘疹
2+:強い(小水疱あり)陽性反応、明らかな紅斑、丘疹
3+:非常に強い陽性反応、強度紅斑、腫脹、大水疱
2.レセプターセル
3.スターラー
4.ウォータージャケット
5.ヒーター/サーキュレーター
6.締め付けノブ
7.サンプリング・ポート
8.アルミ箔
9.生理食塩水
10.水平型拡散セル
Claims (4)
- ポリプロピレングリコールを、N,N−ジエチル−m−トルアミド、メントール及びp−メンタン−3,8−ジオールから選択される少なくとも1種の害虫忌避剤とともに皮膚に適用することにより、前記害虫忌避剤の皮膚への浸透を抑制する方法。
- 前記ポリプロピレングリコールの分子量が200〜20000である請求項1に記載の方法。
- ポリプロピレングリコールを含有する、N,N−ジエチル−m−トルアミド、メントール及びp−メンタン−3,8−ジオールから選択される少なくとも1種の害虫忌避剤の皮膚への浸透抑制剤。
- ポリプロピレングリコールの、皮膚上に適用したN,N−ジエチル−m−トルアミド、メントール及びp−メンタン−3,8−ジオールから選択される少なくとも1種の害虫忌避剤の皮膚への浸透を抑制させるための使用。
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