JP4361155B2 - Iontophoresis device - Google Patents

Description

【００７６】
(c).考察：
(1).Ａ室では還元反応、Ｃ室では酸化反応が生じ、Ａ室のＡｓ^- （アスコルビン酸イオン）がＢ室に輸送される。
明らかにＡ室ではｐＨは中性からアルカリ性側にシフトし、またＣ室では中性から強い酸性に変化している。従って、Ｃ室のグランド電極（２１）とＢ室、即ち皮膚（４）が直接接触している本実験のケースは非常に危険な状態にある。
このことは、Ｂ室が酸性にシフトしていること、そして前記酸性側へのシフトの原因がＣ室で生成した酸（ＨＣｌＯ₃） によるものであることから判る。なお、前記次亜塩素酸は強力な酸化剤として知られているものである。
(2).イオントフォレーゼ電極室であるＡ室と皮膚（Ｂ室）の間にアニオン交換膜（１５）が存在するため、多少、Ａ室がアルカリになっていくことが阻止されているが、Ａ室のＯＨ^-イオンは前記アニオン交換膜（１５）を介してＢ室側へ電気泳動により通過するため、皮膚表面が局所的にアルカリになっていると考えられる。即ち、Ｂ室においてはもっと酸性側に傾くと考えられるもののｐＨ＝４．２０で止まっており、ＯＨ^-イオンが皮膚面に到達しｐＨは局所的にアルカリ側にシフトしているものと考えられる。
(3).前記したことから、イオントフォレーゼを行なうにあたり、本実験のようにイオン交換膜を１枚のみ使用する態様は生体安全性の観点から避けるべきである。
(4).本実験において投与されたＡｓ^- （アスコルビン酸イオン）の量は約３００μｍｏｌ（理論値５６０μｍｏｌ）であり、Ａ室の減少量とＢ室の増加量にほぼ対応している。しかしながら、前記投与量は理論値の約１／２であり、Ａ室において多量のＯＨ^-イオンが生成し、これがＡｓ^-とともに輸送されるためＡｓ^-の輸送を５０％妨害している。この点からも、本実験装置はイオントフォレーゼ装置としては不適当なものである。
【００７７】
２．図６に示される実験装置でのイオントフォレーゼ実験
(a).実験条件：
前記図５に示される実験装置のＡ室とＢ室（皮膚）の構成を図示の態様でカチオン交換膜（１３）とアニオン交換膜（１５）を配設して再構成した実験装置を用い、かつＡ室の電極液及びＢ室のイオン性薬剤溶液として、それぞれ導電性媒体（１２）とイオン性薬剤（１４）を含む１ＭのＡｓ^-Ｎａ⁺を溶解した０．９％ＮａＣｌ水溶液を用いた以外は、前記「１」と同様に実験した。
(b).実験結果：
実験結果として、各室（Ａ〜Ｄ）のｐＨ変化を下記表２に示す。
【００７８】
【表２】

【００７９】
(c).考察
(1).イオントフォレーゼ電極室（Ａ室）と投与試薬であるイオン性薬剤としてのＡｓ^-Ｎａ⁺を含む溶液室（Ｂ室）の間をカチオン交換膜（１３）で仕切ることにより、Ｂ室のｐＨを一定に保つことができる。このことは、皮膚表面（Ｃ室）がアルカリ性になることを防止するものである。
また、イオン透過量は、前記「１」の実験と比較して改善され、ほぼ理論値に近い値が得られる。
(2).しかしながら、Ｃ室（仮想皮膚槽）（４）のｐＨの低下がみられる。
このことは、Ｃ室とＤ室の間、即ちグランド電極室（Ｄ）と仮想皮膚槽（４）の間を単なる隔膜（ｐｐ）でなくイオン交換膜で仕切ることの有効性を示唆している。更にまた、グランド電極室（Ｄ）において、導電性媒体である生理食塩水の酸化分解により次亜塩素酸イオンが生成し、これが皮膚に拡散する危険性がある。
【００８０】
３．図７に示される実験装置でのイオントフォレーゼ実験
(a).実験条件：
前記図６に示される実験装置のＣ室とＤ室の間のＰＰ製隔膜をカチオン交換膜（２３）に変更した以外は、前記「２」と同様に実験した。
(b).実験結果：
実験結果として各室（Ａ〜Ｄ）のｐＨ変化を下記表３に示す。
【００８１】
【表３】

【００８２】
(c).考察：
本実験は、本発明のイオントフォレーゼ装置（Ｘ）による実験に対応するものである。本実験装置は、グランド電極部（２）に１枚のカチオン交換膜（２３）を配設したもので構成される点に特徴がある。
(1).各電極室、即ち、Ａ室及びＤ室でのｐＨ変化が見られるものの、Ａｓ^-Ｎａ⁺溶液室（Ｂ室）及び皮膚（Ｃ室）でのｐＨ変化は抑制されており、効果的である。
更に、グランド電極室（Ｄ室）にカチオン交換膜（２３）を配置することにより、次亜塩素酸イオンなどの有害アニオンを皮膚に接触させずにＤ室内にとどめおくことができる。
(2).アスコルビン酸イオンの透過量は、ほぼ理論値の値を示すため、本実験装置はイオントフォレーゼ装置として有用なものである。
(3).ただし、本実験装置の改良点としては、仮想皮膚槽（Ｃ室）に接するグランド電極室（Ｄ室）において、グランド電極（２１）上で水の電気分解により生成したＨ⁺イオンがカチオン交換膜（２３）を通して泳動し、Ｃ室の酸性化をもたらしており、この点は改良すべきである。このため、グランド電極部側にもイントフォーゼ電極部側と同じようにカチオン交換膜とアニオン交換膜の二種のイオン交換膜を採用することが好ましい。
【００８３】
４．図８に示される実験装置でのイオントフォレーゼ実験
(a).実験条件：
前記図７に示される実験装置において、グランド電極室（Ｄ室）にカチオン交換膜（２３）に加えてアニオン交換膜（２５）を図示の態様で配設し、かつ新たに区画されたグランド電極室（Ｅ室）の電極液として、１ＭのＡｓ^-Ｎａ⁺を溶解した０．９％ＮａＣｌ水溶液を用いた以外は、前記「３」と同様に実験した。
(b).実験結果
実験結果として、各室（Ａ〜Ｅ）のｐＨ変化を下記表４に示す。
【００８４】
【表４】

【００８５】
(c).考察：
(1).図８に示されるイオントフォレーゼ電極部側に２枚のイオン交換膜（１３、１５）、及びグランド電極部側に２枚のイオン交換膜（２３、２５）を配設したイオントフォレーゼ装置において、イオントフォレーゼ電極部側（Ａ〜Ｂ室）から人間の体内（Ｃ室）にＡｓ^- のみが供給され、かつグランド電極部側（Ｅ〜Ｄ室）から人間の体内（Ｃ室）にＮａ⁺ のみが供給され、結果としてアスコルビン酸ナトリウム（Ａｓ^-Ｎａ⁺） が体内に注入されることになる。前記した以外の物質が体内に注入されることがないため、本実験装置は、極めて安全かつ効果的なイオン性薬剤の投与（ドラッグデリバリー）手段となる。
(2).ｐＨ変化は、Ｂ室、Ｃ室、Ｄ室においてほとんどみられない。このことは、
(i).イオントフォレーゼ電極部において、Ｂ室のアスコルビン酸イオン（Ａｓ^-） が仮想皮膚槽（Ｃ室）へ移動、及びナトウムイオン（Ｎａ⁺） がイオントフォレーゼ電極室（Ａ室）へ移動したことを示し、かつ、
(ii).グランド電極部において、Ｄ室のナトリウムイオン（Ｎａ⁺）が仮想膚槽（Ｃ室）へ移動、及びアスコルビン酸イオン（Ａｓ^-）がグランド電極室（Ｅ室）へ移動したことを示しており、
これにより各室においてｐＨ変化が生じなかったものである。
【００８６】
【実施例】
次に、本発明のイオントフォレーゼによるイオン性薬剤を投与するために使用されるイオントフォレーゼ装置（Ｘ）の実施態様について、図面を参照して詳しく説明する。
なお、参照図面において、図示明確化のために、イオン交換膜（１３，１５，２３，２５）は波線で表示され、また、一部の構成要素（部材）、構成要素（部材）同志の結合様式、あるいはハッチングは省略されている。
しかしながら、図面において省略されている構成は、各実施態様の説明や他の添付図面などから容易に理解され得るものである。
【００８７】
図９は、本発明のイオントフォレーゼ装置（Ｘ）の第一実施態様を説明する図であり、縦断面図である。
本発明の第一実施態様のイオントフォレーゼ装置（Ｘ）は、図９に示されるように、大きく区分して、
(i).円筒状のイオントフォレーゼ電極部（１）、
(ii).前記円筒状のイオントフォレーゼ電極部（１）の周縁部に一体的に構成されたグランド電極部（２）、及び、
(iii).定電圧・定電流用電源（３）、
の三要素から構成される。
【００８８】
この種のイオントフォレーゼ装置は、前記イオントフォレーゼ電極部（１）とランド電極部（２）が別体のもので構成されるとともに、イオン性薬剤の投与中、利用者は接地（アース）をとるためにグランド電極部（２）を手で把持するなどの行為が強いられるものである。
しかしながら、本発明のイオントフォレーゼ装置（Ｘ）は、前記したようにイオントフォレーゼ電極部（１）とグランド電極部（２）の要素が一体化しているため、操作性、利便性に優れている。また、両要素（１、２）を一体化しているため、両要素（１、２）の間隔を所望に設定したり複数組の両要素を一体化することによりイオン性薬剤の投与量、投与の深さなどを調整することができる。
【００８９】
本発明において、両要素（１，２）を一体化できる大きな理由は、グランド電極部（２）の生体安全性が従来よりも格段に優れているためである。このため、本発明のイオントフォレーゼ装置（Ｘ）において、イオントフォレーゼ電極部（１）に一体化されたグランド電極部（２）は、手の皮膚よりも熱症、炎症、刺激などを受けやすい皮膚の部位に当接される場合であっても何等の問題はなく、イオン性薬剤を安全かつ効率的にイオン投与することができる。
【００９０】
本発明のイオントフォレーゼ装置（Ｘ）において、グランド電極部（２）は、イオントフォレーゼ電極部（１）と一体化されて（一体的に）構成されるものである。前記「一体化されて（一体的に）構成される」という意味は、図示のようにイオントフォレーゼ電極部（１）の構成部材の一部に一体化されているものである。なお、本発明において、前記一体化とは図９に示される態様のものに限定されず、一体化の態様は最広義に解釈されるべきである。
【００９１】
また、図９に示されるイオントフォレーゼ装置（Ｘ）は、イオン性薬剤（１４）としてアスコルビン酸Ｎａ（Ａｓ^-Ｎａ⁺）をイオントフォレーゼにより投与することを前提にして構成されている。
このため、図９に示されるイオントフォレーゼ装置（Ｘ）において、各構成要素の参照符号は、次のことを意味する。
(i).（１１）で示されるイオントフォレーゼ電極部（１）の電極板は、（−）極、
(ii).（１２）で示されるイオントフォレーゼ電極部（１）の導電性媒体は、生理食塩水、
(iii).（１３）で示されるイオントフォレーゼ電極部（１）のイオン交換膜は、カチオン交換膜、
(iv).（１４）で示されるイオントフォレーゼ電極部（１）のイオン性薬剤は、アルコルビン酸Ｎａ（Ａｓ^-Ｎａ⁺）、
(v).（１５）で示されるイオントフォレーゼ電極部（１）のイオン交換膜は、アニオン交換膜、
(vi).（２１）で示されるグランド電極部（２）の電極板は、（＋）極、
(vii).（２２）で示されるグランド電極部（２）の導電性媒体は、生理食塩水、及び、
(viii).（２３）で示されるグランド電極部（２）のイオン交換膜は、カチオン交換膜、
をそれぞれ示す。
【００９２】
図９に示されるように、本発明の第一実施態様のイオントフォレーゼ装置（Ｘ）において、イオントフォレーゼ電極部（１）とグランド電極部（２）の要素は、一体化されて構成されるものであるが、以下、説明の便宜上、それぞれの要素に区分して説明する。
【００９３】
本発明の第一実施態様のイオントフォレーゼ装置（Ｘ）において、イオントフォレーゼ電極部（１）は、図９に示されるように、大きく区分して、
(i).非導電性で円筒状の外筒体（ａ）、及び、
(ii).非導電性で円筒状の内筒体（ｂ）、
の要素から構成され、これら要素（ａ、ｂ）のもとに前記した参照符号（１１〜１５）で示される要素が保持または収容される。
なお、グランド電極部（２）は、前記絶縁性の円筒体（ａ）の外周縁において、かつ両要素（１，２）が皮膚（４）面に対して略面一になるように一体的に結合されて構成される。
【００９４】
前記図９に示されるイオントフォレーゼ電極部（１）は、図１に示されるように、その平面図は円形のものである。
そして、前記イオントフォレーゼ電極部（１）は、例えば、手によって把持されて所望患部に当接されるため、所望の大きさ（外径、高さ）のものに構成される。
また、図９に示されるように、前記外筒体（ａ）と内筒体（ｂ）は、両者の当接面に形成されたネジ部を介して螺合により一体化される螺合タイプのものである。
しかしながら、本発明において、前記外筒体（ａ）と内筒体（ｂ）の結合様式は、その他の方式であってもよく、例えば係合タイプ、係止タイプ、挿嵌タイプのものなどであってもよいものである。
【００９５】
前記円筒状の外筒体（ａ）において、イオントフォレーゼ電極部（１）を構成する部位は、図示されるように、
(i).前記内筒体（ｂ）と共働してカチオン交換膜（１３）を固定するためのカチオン交換膜（１３）用支持部（ａ１）、
(ii).イオン性薬剤（１４）を収容するためのイオン性薬剤（１４）用収容部（ａ２）、
(iii).アニオン交換膜（１５）を固定するためのアニオン交換膜（１５）用支持部（ａ３）、
(iv).アニオン交換膜（１５）を固定するためのアニオン交換膜（１５）用押圧リング（ａ３１）、
(v).アニオン交換膜（１５）を固定するための固定ピン（ａ３２）、
を有するもので構成される。
【００９６】
一方、前記円筒状の内筒体（ｂ）は、図示されるように、
(i).前記外筒体（ａ）のカチオン交換膜（１３）用支持部（ａ１）と共働してカチオン交換膜（１３）を固定するためのカチオン交換膜（１３）用押圧部（ｂ１）、
(ii).導電性媒体（１２）を収容するための導電性媒体（１２）用収容部（ｂ２）、
(iii).電極板（１１）を支持する電極板（１１）用支持部（ｂ３）、
(iv).電源部（３）からのリード線（３１）を案内するリード線（３１）用案内孔（ｂ４）、
(v).リード線（３１）を支持するリード線（３１）用支持具（ｂ５）、
(vi).頂部円板部（ｂ６）、
を有するもので構成される。
【００９７】
前記した構成の円筒体（ａ）及び内筒体（ｂ）からなるイオントフォレーゼ電極部（１）は、図９に示されるように（−）極電極板（１１）、ガーゼあるいは吸水性高分子材料などに含浸された酸化還元されやすい物質を含有する導電性媒体（１２）、カチオン交換膜（１３）、イオン性薬剤（Ａｓ^-Ｎａ⁺）（１４）、及びアニオン交換膜（１５）をその内部に確実に保持または収容するすることができる。
また、前記外筒体（ａ）と内筒体（ｂ）の構成において、両者が螺合されている場合、外筒体（ａ）に対して内筒体（ｂ）を相対的に変位させることにより、皮膚（４）に対してアニオン変換膜（１５）を密着させることができ、イオントフォレーゼ効果を向上させることができる。
【００９８】
次に、本発明の図９に示される第一実施態様のイオントフォレーゼ装置（Ｘ）の前記イオントフォレーゼ電極部（１）に一体的に結合されて構成されるグランド電極部（２）の構成について説明する。
本発明において、前記両要素（１、２）の一体化は、例えば非導電性のプラスチック材による一体成形により行なえばよい。
【００９９】
図９に示されるように、前記円筒状の外筒体（ａ）において、グランド電極部（２）を構成する部位は、大きく区分して、
(i).グランド電極部（２）側の電極板（２１）及び導電性媒体（２２）を収容するための電極板（２１）及び導電性媒体（２２）用収容部（ａ４）、
(ii).グランド電極部（２）側のカチオン交換膜（２３）を固定するためのカチオン交換膜（２３）用支持部（ａ５）、
(iii).グランド電極部（２）側のカチオン交換膜（２３）を固定するためのカチオン交換膜（２３）用押圧リング（ａ５１、ａ５２）、及び、
(iv).グランド電極部（２）側のカチオン交換膜（２３）を固定するための固定ピン（ａ５３）、
を有するもので構成され、これらの構成のもとで前記した参照符号（２１〜２３）で示される要素が保持または収容される。
【０１００】
図９において、グランド電極部（２）は、電源部（３）からのリード線（３２）を一体に埋設したもので構成されている。
しかしながら、グランド電極部（２）において、リード線（３２）の配設態様は、前記イオントフォレーゼ電極部（１）の内筒体（ｂ）のようにリード線を支持具（ｂ５）で支持するようにしてもよいものである。
【０１０１】
図９において、イオントフォレーゼ電極部（１）のアニオン交換膜（１５）及びグランド電極部（２）のカチオン交換膜（２３）の前面部に配設された要素（５）は、これらイオン交換膜（１５、２３）と皮膚（４）の間の導電性を良くするための生理食塩水などの導電性液体を含浸した媒体、例えばガーゼなどを示す。
なお、本発明において、前記要素（５）を省略してもよいことはいうまでもないことである。この場合、アニオン交換膜（１５）と皮膚（４）が当接するため、イオン輸率（イオン性薬剤の帯電イオンの輸率）が向上する。
【０１０２】
図９に示される本発明のイオントフォレーゼ装置（Ｘ）において、図示明確化のために図示しないが、イオントフォレーゼ電極部（１）及び／又はグランド電極部（２）に対し、導電性媒体（１２，２２）やイオン性薬剤（１４）の供給路、各電極板（１１，１２）から発生するガスのガス抜き孔、あるいは前記ガスを吸着するための吸着体の収容部などを配設してもよいことはいうまでもないことである。
【０１０３】
図１０は、本発明のイオントフォレーゼ装置（Ｘ）の第二実施態様を説明する図であり、前記図９に対応する図である。
本発明の第二実施態様のイオントフォレーゼ装置（Ｘ）は、前記図９に示される第一実施態様のものの変形例ということができる。
【０１０４】
本発明の図１０に示される第二実施態様のイオントフォレーゼ装置（Ｘ）は、前記図９に示される第一実施態様のものと比較して、次の構成が相違するだけであり、他の構成は実質的に同一である。
(i).イオントフォレーゼ電極部（１）を、第一実施態様のイオントフォレーゼ電極部（１）の内筒体（ｂ）を２つに区分し、内筒体（ｂ）と中間筒（ｃ）とから成るものに構成した。第二実施態様における構成要素（ａ，ｂ，ｃ）の具体的な構成は、図１０から明らかである。
図１０に示される円弧状破線で示されるゾーン（ｍ，ｎ）において、（ｍ）ゾーンはイオン性薬剤を投与するゾーンであり、（ｎ）ゾーンは皮膚内に流れる電流をグランド（アース）電極部へ導くゾーンである。なお、図中、（ｍｎ）は、負極（１１）と正極（２１）の絶縁部（シールド部）を示している。
【０１０５】
本発明において、図１０に示される第二実施態様の変形例として、カチオン交換膜（１３）を外筒体（ａ）と中間筒（ｃ）で保持する構成に代えて、内筒体（ｂ）と中間筒（ｃ）で保持する構成にしてもよいことはいうまでもないことである。この場合、外筒体（ａ）のカチオン交換膜（１３）用支持部（ａ１）を除去し、例えば、中間筒（ｃ）として下部の内側に突出部を配設したものを使用し、かつ、内筒体（ｂ）として前記図９に示される第一実施態様の構造のものを使用し、前記中間筒（ｃ）の突出部と内筒体（ｂ）の下端部（図９のｂ１参照）でカチオン交換膜（１３）を保持するようにすればよい。
【０１０６】
図１１は、本発明のイオントフォレーゼ装置（Ｘ）の第三実施態様を説明する図であり、前記図１０に対応する図である。
本発明の第三実施態様のイオントフォレーゼ装置（Ｘ）は、前記図１０に示される第二実施態様のものの変形例ということができる。
【０１０７】
本発明の図１１に示される第三実施態様のイオントフォレーゼ装置（Ｘ）は、前記図１０に示される第二実施態様のものと比較して、次の構成が相違するだけであり、他は実質的に同一である。
(i).イオントフォレーゼ電極部（１）の導電性媒体（１２）の収容部を、電極板（１１）の上部を下部の二つに区分するように内筒体（ｂ）と中間筒（ｃ）の構成を再構成した。
(ii).グランド電極部（２）の導電性媒体（２２）の収容部（ａ４）に収容される導電性媒体（２２）を、酸化還元しやすい物質を含有する生理食塩水で構成した。
【０１０８】
図１２は、本発明のイオントフォレーゼ装置（Ｘ）の第四実施態様を説明する図であり、前記図９に対応する図である。但し、イオントフォレーゼ電極部（１）は省略してある。なお、図１２は、グランド電極部（２）の要部拡大図である。
【０１０９】
本発明の図１２に示される第四実施態様のイオントフォレーゼ装置（Ｘ）は、前記図９に示される第一実施態様のものと比較して、次の構成が相違するだけであり、他の構成は実質的に同一である。
(i).グランド電極部（２）の電極板（２１）及び導電性媒体（２２）用収容部（ａ４）の構成を、図９に示される構成要素（２１，２２，２３）に加えて、更に導電性媒体（２４）とアニオン交換膜（２５）を収容できるように構成した。前記導電性媒体（２４）とアニオン交換膜（２５）は、前記収容部（ａ４）の内部において、図示される部材（ａ６，ａ７）により保持もしくは収容される。即ち、アニオン交換膜（２５）は保持部材（ａ６）、カチオン交換膜（２３）は保持部材（ａ７）により保持され、両イオン交換膜（２３、２５）の間で導電性媒体（２４）が収容される。
(ii). イオントフォレーゼ電極部（１）のアニオン交換膜（１５）（図示せず）及びグランド電極部（２）のカチオン交換膜（２３）の前面部に配設した構成要素（５）を除去した。
【０１１０】
図１２に示される第四実施態様のイオントフォレーゼ装置（Ｘ）は、イオントフォレーゼ電極部（１）とグランド電極部（２）のそれぞれにカチオン交換膜とアニオン交換膜を２枚ずつ合計４枚のイオン交換膜を配設したものであり、他の実施態様のものと異なる。そして、この第四実施態様のイオントフォレーゼ装置（Ｘ）は、図８に示される実験装置でのイオントフォレーゼ実験において実証されたように優れた効果を奏するものである。
なお、図１２に示される第四実施態様のイオントフォレーゼ装置（Ｘ）において、グランド電極部（２）のカチオン交換膜（２３）は、図示しないイオントフォレーゼ電極部（１）のアニオン交換膜（１５）と面一になるように配設されることが好ましいことはいうまでもないことである。
【０１１１】
本発明のイオントフォレーゼ電極部（１）とグランド電極部（２）を一体化したイオントフォレーゼ装置（Ｘ）は、種々の変形例が可能である。
【０１１２】
(i).図１３は、本発明のイオントフォレーゼ装置（Ｘ）の構成を、イオン性薬剤の投与ゾーンを図示のように同心円状に複数個（ｍ１〜ｍＸ）設けるように構成できることを示している。なお、グランド（アース）ゾーンは（ｎ１）〜（ｎＸ）で示されている。
前記した本発明の図１３に示される同心円状のイオン性薬剤の投与ゾーンを形成することができる第五実施態様のイオントフォレーゼ装置（Ｘ）の具体的な構成は、例えば図１０の第二実施態様のものから容易に理解することができる。このため、第五実施態様のイオントフォレーゼ装置（Ｘ）の図示を省略する。
【０１１３】
(ii). 図１４は、本発明のイオントフォレーゼ装置（Ｘ）の構成を、イオン性薬剤の投与ゾーンを図示のように直列状に複数個（ｍ１〜ｍＸ）設けるように構成できることを示している。なお、グランド（アース）ゾーンは（ｎ１）〜（ｎＸ）で示されている。
前記した本発明の図１４に示されるイオン性薬剤の投与ゾーンを形成することができる第六実施態様のイオントフォレーゼ装置（Ｘ）の具体的な構成は、例えば図１０の第二実施態様のものから容易に理解することができる。このため、第六実施態様のイオントフォレーゼ装置（Ｘ）の図示を省略する。
【０１１４】
前記図１３〜図１４において、各投与ゾーンとグランド（アース）ゾーンの境界部には、絶縁部（シールド部）、即ち、図１０に示される（ｍｎ）ゾーンが示されるべきであるが、図示明確化のために（ｍｎ）ゾーンは省略されている。
【０１１５】
前記図１３〜図１４に示される投与ゾーンとグランド（アース）ゾーンを形成することができる第五〜第六実施態様のイオントフォレーゼ装置（Ｘ）は、各投与ゾーンの幅を所望に設定することにより、イオン性薬剤の皮膚内への浸透度（皮膚表面からの浸透深さ）を調整できるという利点を享受することができる。
【０１１６】
【発明の効果】
本発明により、以下の優れた特性を有するイオントフォレーゼ装置が提供される。
(i).イオントフォレーゼ電極部（作用側電極部）及びグランド電極部（非作用側電極部）が長期安定した通電状態（通電流及び／又は定電圧）を維持することができるため、イオントフォレーゼ電極部においてイオン性薬剤の正（＋）もしくは負（−）に帯電した薬剤成分を効率よく皮膚（もしくは粘膜）へ輸送（ドラッグデリバリー）することができる。
(ii). イオントフォレーゼ電極部（作用側電極部）及びグランド電極部（非作用側電極部）が前記した安定した通電状態の維持に貢献するとともに特定のイオン交換膜の使用態様（配設態様）により電極反応による皮膚への悪影響（皮膚刺激、熱症、炎症など）を排除することができる。
(iii).イオントフォレーゼ電極部（作用側電極部）とグランド電極部（非作用側電極部）が一体化されているために、従来のように治療者においてグランド（アース）を取る作業が解放され、操作性、利便性が向上する。
また、前記一体化構造のイオントフォレーゼ電極部とグランド電極部の対（つい）を複数組配設することにより、イオン性薬剤の皮膚内への浸透度（皮膚表面からの浸透深さ）及びイオン性薬剤の投与領域を所望に調整することができる。
【図面の簡単な説明】
【図１】 本発明のイオンと装置（Ｘ）の基本構成を説明する図（概略斜視図）である。
【図２】 本発明のイオントフォレーゼ装置（Ｘ）の基本構成を説明するための図（概略断面図）である。
【図３】 イオン性薬剤としてアスコルビン酸ナトリウム（Ａｓ^-Ｎａ⁺）を投与するときに使用される本発明のイオントフォレーゼ装置（Ｘ）の基本構成を説明する図である。
【図４】 イオン性薬剤としてアスコルビン酸ナトリウム（Ａｓ^-Ｎａ⁺）を投与するときに使用される本発明のイオントフォレーゼ装置（Ｘ）の他の基本構成を説明する図である。
【図５】 イオントフォレーゼ効果を試験するための第一実験装置（本発明に対して比較対象となる装置）の概略図である。
【図６】 イオントフォレーゼ効果を試験するための第二実験装置（本発明に対して比較対象となる装置）の概略図である。
【図７】 イオントフォレーゼ効果を試験するための第三実験装置（本発明に係る装置）の概略図である。
【図８】 イオントフォレーゼ効果を試験するための第四実験装置（本発明に係る装置）の概略図である。
【図９】 本発明の第一実施態様のイオントフォレーゼ装置（Ｘ）を説明する図である。
【図１０】 本発明の第二実施態様のイオントフォレーゼ装置（Ｘ）を説明する図である。
【図１１】 本発明の第三実施態様のイオントフォレーゼ装置（Ｘ）を説明する図である。
【図１２】 本発明の第四実施態様のイオントフォレーゼ装置（Ｘ）を説明するための図である。
【図１３】 本発明の第五実施態様のイオントフォレーゼ装置（Ｘ）を説明するための図である。
【図１４】 本発明の第六実施態様のイオントフォレーゼ装置（Ｘ）を説明するための図である。
【符号の説明】
Ｘ …………… イオントフォレーゼ装置
１ …………… イオントフォレーゼ電極部
１１ ………… 電極材
１２ ………… 導電性媒体
１３ ………… イオン（カチオン）交換膜
１４ ………… イオン性薬剤
１５ ………… イオン（アニオン）交換膜
２ …………… イオントフォレーゼ電極部（１）と一体化されたグランド電極部
２１ ………… 電極材
２２ ………… 導電性媒体
２３ ………… イオン（カチオン）交換膜
３ …………… 電源部
３１，３２…… リード線
４ …………… 皮膚
５ …………… 導電性液体を含浸したガーゼ
ａ …………… イオントフォレーゼ電極部（１）側の外筒体
ａ1 …………… イオン交換膜（１３）用支持部
ａ2 …………… イオン薬剤（１４）用収容部
ａ3 …………… イオン交換膜（１５）用支持部
ａ31…………… イオン交換膜（１５）用押圧リング
ａ32…………… 固定ピン
ａ4 …………… 電極板（２１）及び導電性媒体（２２）用収容部
ａ5 …………… イオン交換膜（２３）用支持部
ａ51,ａ52 …………… イオン交換膜（２３）用押圧リング
ａ53…………… 固定ピン
ａ6，ａ7……… 保持部材
ｂ …………… イオントフォレーゼ電極部（１）側の内筒体
ｂ1 …………… イオン交換膜（１３）用押圧部
ｂ2 …………… 導電性媒体（１２）用収容部
ｂ3 …………… 電極板（１１）用支持部
ｂ4 …………… リード線（３１）用案内孔
ｂ5 …………… リード線（３１）用支持具
ｂ6 …………… 頂部円板部
ｃ …………… イオントフォレーゼ電極部（１）側の中間筒
ｍ１〜ｍＸ…………… イオン性薬剤の投与ゾーン
ｎ１〜ｎＸ…………… グランド（アース）ゾーン[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an apparatus (hereinafter referred to as an iontophoresis apparatus) used when various ionic drugs are administered transcutaneously (transdermal drug delivery) by iontophoresis.
More specifically, according to the present invention, a stable energization state (constant current and / or constant voltage) is ensured for a long time in the iontophoresis electrode portion (working side electrode portion) and the ground electrode portion (non-working side electrode portion). Therefore, the positive (+) or negative (−) charged drug component of the ionic drug can be efficiently transported (driven) to the skin (or mucosa) side at the iontophoresis electrode part. The electrode part (working side electrode part) and the ground electrode part (non-working side electrode part) can contribute to the maintenance of the above-mentioned stable energized state and can eliminate the adverse effects on the skin due to the electrode reaction. Operability (convenience) can be improved because the tophoresis electrode and the ground electrode are integrated, and the iontophoresis and ground electrode portions are alternated. An ionic drug by integrating a plurality of sets may be percutaneously delivered to a desired depth, it relates to the iontophoretic device having excellent characteristics that.
[0002]
[Prior art]
An ionic drug (ionic chemical substance) placed on the skin or mucous membrane (hereinafter simply referred to as skin) at a desired site is applied to the skin with an electromotive force that drives the ionic drug, and these ionic drugs Is introduced into the body through the skin (iontophoresis, iontophoresis, iontophoresis, iontophoresis) (for the definition of iontophoresis, for example, Japanese Patent Laid-Open No. 63-35266 is a reference).
[0003]
As described above, iontophoresis is to drive (transport) an ionizable ionic drug placed on the skin under a predetermined electromotive force and to penetrate the skin.
For example, positively charged ions are driven (transported) into the skin on the anode side of the electrical system of the iontophoresis device.
On the other hand, negatively charged ions are driven (transported) into the skin on the cathode side of the electrical system of the iontophoresis device.
[0004]
Examples of ionic drugs applied to the iontophoresis described above include the following.
(1). Positively charged ionic drugs:
Anesthetics (procaine hydrochloride, lidocaine hydrochloride, etc.), gastrointestinal disease treatments (carnitine chloride, etc.), skeletal muscle relaxants (bancronium bromide, etc.), antibiotics (theocycline preparations, kanamycin preparations, gentamicin preparations).
(2). Negatively charged ionic drugs:
Vitamin (hereinafter abbreviated as V) agent (VB ₂ , VB ₁₂ , VC, VE, folic acid, etc.), corticosteroids (hydrocortisone water-soluble preparations, dexamethasone water-soluble preparations, prednisolone aqueous solution preparations, etc.), antibiotics (penicillin aqueous solution preparations, chromiumphenicol aqueous solution preparations).
[0005]
A method of administering an ionic drug by iontophoresis and a device applied thereto have been researched and developed for a long time, and various types have been proposed.
As a conventional technique related to this type of iontophoresis, there is a technique using an ion exchange membrane. In addition, although mentioned later in detail, this invention also belongs to the category using an ion exchange membrane.
For this reason, in order to help understand the difference between the present invention using an ion exchange membrane and the prior art, the prior art using an ion exchange membrane will be described in detail below.
[0006]
1. Japanese Patent Application Publication No. 3-504343 (hereinafter referred to as Prior Art 1)
(1). This prior art 1 includes, as an iontophoresis electrode, (i) an electrode plate, (ii) a reservoir containing an ionic (or ionizable) drug to be permeated, and (iii) the reservoir And an ion exchange membrane for selecting ions having a charge of the same polarity as that of the ionic drug.
(2). In this prior art 1, when the ion exchange membrane is transported (driven) to the skin side, the function of the ion exchange membrane exceeds the interface between the electrode and the skin by the ion exchange membrane to the electrode side. Constrain the movement of counter-charged ions to be transferred, for example sodium, chlorine, or other ionic species that can exist in the skin and create ionic current paths that are different from ionic drugs, Explained.
(3) In addition, this prior art 1 can reduce the number of other mobile charging carriers in the reservoir that stores the ionic drug by the ion exchange membrane, thereby improving the administration efficiency of the ionic drug. It can be increased.
[0007]
2. U.S. Pat. No. 4,722,726 (hereinafter referred to as Prior Art 2)
(1) This prior art 2 is described as a related art in the publication of the prior art 1, but as an iontophoresis electrode,
(i). divided into an upper chamber filled with a buffer solution (buffer solution) and a lower chamber filled with an ionic drug, and
(ii) An electrode having a structure in which the upper chamber is separated from the lower chamber by an ion exchange membrane is disclosed.
(2). This prior art 2 explains that the upper chamber filled with buffer solution mitigates the adverse effects of water hydrolysis, and that the ion exchange membrane isolates the ionic drug from the contents of the upper chamber. is doing.
However, the technique using the buffer solution disclosed in the prior art 2 obviously increases the concentration of additional ionic species in the system, and thus clearly reduces the transport efficiency of charged ions of the active drug component of the ionic drug. It also has undesirable aspects.
Therefore, attention should be paid to the technique of simply using a buffer solution.
[0008]
3. Japanese Patent Laid-Open No. 3-94771 (hereinafter referred to as Prior Art 3)
(1). This prior art 3 is (i) a water retaining part surrounded by a flexible support member and having an electrode plate inside; (ii) disposed on the front surface (skin side) of the water retaining part. An iontophoresis electrode comprising an ion exchange membrane and (iii) a drug layer (ionic drug layer) disposed on the front surface (skin side) of the ion exchange membrane is disclosed.
(2). This prior art 3 is intended to administer a drug at a high concentration while preventing dilution with water during administration of an ionic drug.
(3) For this reason, this prior art 3 uses a water-permeable ion exchange membrane that is substantially impermeable to the drug, and spray-drys the drug on the living body (skin) contact surface. An electrode for iontophoresis is configured using a material adhered or adhered by spraying or the like.
[0009]
4). Japanese Patent Laid-Open No. 4-297277 (hereinafter referred to as Prior Art 4)
(1). This prior art 4 relates to an earlier application related to the present applicant. For example, in FIG. 2, an iontophoresis electrode portion (working side electrode portion) (in the case of FIG. 2, the ionicity used) The cathode is the working electrode part in relation to the polarity of the ion of the drug.) Comprises a cathode plate / gauze containing an ionic drug / cation exchange membrane / gauze containing an ionic drug / anion exchange membrane. A multi-layer structure is disclosed.
(2) The iontophoresis technique disclosed in the prior art 4 is an object of the improvement of the present invention, and the limitations of the prior art 4 will be described in detail when the present invention is described later. .
[0010]
In the prior art described above, the prior art 4 is a single-layer structure in which the prior arts 1 to 3 use one ion exchange membrane when focusing on the number of used (arranged) ion exchange membranes. Thus, it is different from the others in that a multilayer structure using two ion exchange membranes is disclosed.
When attention is paid to the number of ion exchange membranes used, the present invention belongs to a multilayer structure as in the prior art 4. However, although the present invention will be described in detail later, it is based on a technical idea that is completely different from the prior art 4. In addition to the working side electrode portion, the ground side electrode portion (ground side electrode portion, neutral electrode portion) has ions. A major feature is that a three-layer or four-layer structure in which an exchange membrane is provided is employed.
[0011]
[Problems to be solved by the invention]
As described above, there is a technique using an ion exchange membrane in a method of transdermally administering an ionic drug by iontophoresis.
However, the iontophoresis technique using the conventional ion exchange membrane described above is based on the electrochemical process on the surface of the electrode plate in the iontophoresis electrode part (working side electrode part) and / or the ground electrode part (non-working side electrode part). It lacks ingenuity and ingenuity to prevent and eliminate various drawbacks based on reactions.
In other words, the conventional iontophoresis technology using an ion exchange membrane is the total electrochemical reaction of the iontophoresis electrode part (working electrode part) and the ground electrode part (non-working side electrode part). Attention is paid to the problem, and there is a lack of attitude to resolve the disadvantages induced from the problem and to establish high-value-added iontophoresis technology.
[0012]
For this reason, the iontophoresis technology using a conventional ion exchange membrane, more specifically, the ion exchange membrane is used in the working side electrode portion as seen in the above-described conventional technology, but in the ground electrode portion, The conventional iontophoresis technology that is not used has the following disadvantages.
[0013]
(i). It is difficult to administer an ionic drug (drug delivery) under a stable energized state for a long period of time (operating under conditions of constant voltage or constant current that is stable for a long period of time) Have difficulty). For example, the polarity of the working electrode portion varies depending on the polarity of the charged ions of the active ingredient of the ionic drug, but in the working electrode portion of the positive (+) electrode, physiological saline as a conductive medium is electrically connected at the electrode plate interface. Since it decomposes to generate bubbles (oxygen gas, chlorine gas, etc.), the energization resistance increases, and the iontophoresis effect (ion transport efficiency) decreases rapidly with time. The foregoing also occurs due to bubbles (hydrogen gas or the like) generated at the negative (−) electrode ground electrode.
[0014]
(ii). Burns and inflammation (current burns induced by the current itself, H generated by electrolysis on the contact surface between the working electrode part and / or the ground electrode part and the skin. ⁺ Or OH ^- PH-induced burns due to rapid pH changes. ) Etc. occur.
[0015]
(iii). At the contact surface between the electrode plate (for example, + electrode) of the ground electrode part and the skin, harmful substances generated by electrolysis of the skin surface sweat or physiological saline, which is a conductive medium, for example, Cl ^- Skin damage caused by hypochlorous acid (which is known as a strong oxidant) based on (chlorine ions) occurs.
[0016]
(iv). At the contact surface between the electrode plate (for example, one electrode) of the ground electrode portion and the skin, harmful substances generated by the electrolysis of the skin surface sweat or physiological saline, which is a conductive medium, for example, high alkalinity Skin damage caused by (NaOH) occurs.
[0017]
The present invention was devised in view of the drawbacks and limitations of the conventional iontophoresis technique using the above-described ion exchange membrane.
The present inventor has intensively studied the conventional iontophoresis technology using an ion exchange membrane in order to increase the added value.
[0018]
As a result, the present inventor has made the configuration of the iontophoresis electrode part (working side electrode part) of the iontophoresis device into an active drug component of an ionic drug disclosed in, for example, Japanese Patent Application Publication No. 3-504343. An iontophoresis electrode material (working side electrode material) connected to the same type of power source as the charged ions, an ionic drug disposed on the front surface of the iontophoresis electrode material, and the skin on the front surface of the ionic drug In an iontophoresis electrode part (working side electrode part) comprising an ion exchange membrane that selects ions of the same type as charged ions of the active drug component of the ionic drug disposed on the side in contact with the iontophoresis, the iontophoresis The configuration between the electrode material and the ionic drug is viewed from the side of the iontophoretic electrode material,
(i). disposing a conductive medium such as physiological saline on at least the front surface of the iontophoretic electrode material;
(ii) When the ion exchange membrane for selecting ions opposite to the charged ions of the active drug component of the ionic drug is disposed on the front surface of the conductive medium,
It has been found that the above-described drawbacks in the iontophoresis electrode portion are eliminated.
[0019]
Furthermore, the inventor is not known at all to dispose an ion exchange membrane on the side of the ground electrode portion (non-working side electrode portion) in an iontophoresis device using a conventional ion exchange membrane. The configuration of the electrode part (non-working side electrode part) is viewed from the electrode material side of the ground electrode part,
(iii) A conductive medium such as physiological saline is disposed on at least the front surface portion of the ground electrode material,
(iv) When the ion exchange membrane for selecting ions opposite to the charged ions of the active drug component of the ionic drug is arranged on the front surface of the conductive medium,
It has been found that the above-mentioned drawbacks in the ground electrode portion are eliminated.
[0020]
The present invention is based on the above knowledge, and an iontophoresis electrode portion (working side electrode portion) and a ground electrode portion (non-working side electrode portion) in which the configurations of (i) to (iv) are integrated. ) To provide an iontophoresis device.
According to the present invention, the administration efficiency of an ionic drug is high under a stable energized state (constant current and / or constant voltage state) for a long period of time, and the biosafety prevents skin burns and inflammation. A novel iontophoresis device capable of realizing administration of an ionic drug (drug delivery) by high iontophoresis is provided.
[0021]
[Means for Solving the Problems]
Briefly describing the present invention, the present invention relates to an iontophoresis electrode portion (working side electrode portion) and a ground electrode portion (non-working side electrode) connected to a power source used for administering an ionic drug by iontophoresis. In the iontophoresis device having
(1) The iontophoresis electrode portion is
(1) -1. Electrode material connected to a power source of the same polarity as the charged ion of the ionic drug,
(1) -2. A conductive medium disposed at least on the front surface of the electrode material;
(1) -3. An ion exchange membrane that selects ions opposite to the charged ions of the ionic agent disposed on the front surface of the conductive medium;
(1) -4. An ionic drug disposed on the front surface of an ion exchange membrane that selects ions opposite to the charged ions of the ionic drug, and
(1) -5. An iontophoresis device comprising: an ion exchange membrane that selects ions of the same type as charged ions of an ionic drug disposed in front of the ionic drug.
[0022]
Furthermore, the present invention provides
(2) The ground electrode portion is adjacent to the iontophoretic electrode portion and is integrally formed,
(2) -1. An electrode material having a polarity opposite to the electrode material of the iontophoresis electrode part,
(2) -2. A conductive medium disposed on at least the front surface of the electrode material; and
(2) -3. An iontophoresis device comprising: an ion exchange membrane that selects ions opposite to charged ions of an ionic drug disposed on the front surface of the conductive medium.
[0023]
Further, the present invention is to improve the performance of the iontophoresis device having the iontophoresis electrode part (working side electrode part) and the ground side electrode part (non-working side electrode part).
(i). The conductive medium of the iontophoresis electrode portion and the ground electrode portion is composed of a material containing a substance that is easily oxidized or reduced, and more specifically,
(ii). The conductive medium of the iontophoresis electrode portion and the ground electrode portion contains ferrous sulfate and ferric sulfate, or an organic acid and / or a salt thereof as substances that are easily oxidized or reduced. It is characterized by being configured.
[0024]
Furthermore, the present invention is characterized in that, in order to improve the performance of the iontophoresis device, the ground electrode part (non-working side electrode part) is composed of a combination of a chaotic exchange membrane and an anion exchange membrane. To do. It should be noted that one ion exchange membrane (the ion selectivity of the ion conversion membrane differs depending on the charging polarity of the ionic agent) is used for the ground electrode portion, and further, the ion selectivity is different for the ground electrode portion. The point of using two types of ion exchange membranes is not found at all in the prior art.
[0025]
Hereinafter, the technical configuration of the present invention will be described in more detail.
First, in order to gain an understanding of the present invention, a conventional configuration of an ionic drug by iontophoresis using the basic configuration diagram of the iontophoresis apparatus of the present invention and its problems, and further, the ionic drug of the present invention The features of the administration method will be described. Next, a specific configuration of the iontophoresis device of the present invention will be described.
It should be noted that although the drawings are referred to in order to explain the technical configuration of the present invention, those shown in the drawings should be construed as merely one embodiment, and the present invention is not limited to those in the drawings. There is nothing.
[0026]
1 to 2 show basic configuration diagrams of the iontophoresis device (X) of the present invention. FIG. 1 is a perspective view, and FIG.
1 to 2 simultaneously show an ionic drug administration method (drug delivery) by a new iontophoresis realized by the iontophoresis device (X) of the present invention.
[0027]
FIG. 3 is a basic configuration diagram of the iontophoresis device (X) when the ionic drug is administered under the following conditions in the iontophoresis device (X) of the present invention shown in FIG. Sectional view).
(i) As an ionic drug, sodium (Na) salt of ascorbic acid (vitamin C) (hereinafter referred to as As) ^- Na ⁺ May be abbreviated. ).
(ii). Saline (Na ⁺ Cl ^- Aqueous solution). In the present invention, as the physiological saline, ferrous sulfate and ferric sulfate having an oxidation-reduction potential lower than the electrolytic potential of water, an organic acid, or the like is used in order to remove a defect derived from an electrode reaction. In some cases, a substance to which a substance that is easily oxidized and reduced is added is used.
(iii) The iontophoresis electrode portion (working side electrode portion) is the cathode (-electrode).
(iv) The ground electrode part (non-working side electrode part) is the anode (+ electrode).
(v) The type of ion exchange membrane to be used (selective permeability of ions) and the arrangement site are as shown in the figure.
[0028]
FIG. 4 shows a basic configuration diagram of the iontophoresis device (X) of the present invention in which the performance of the iontophoresis device (X) shown in FIG. 3 is further improved.
As shown in FIG. 4, the ion exchange membrane of the ground electrode portion (2) uses a combination of a cation exchange membrane (23) and an anion exchange membrane (25) as compared with the one shown in FIG. It differs in that it is configured.
[0029]
1 to 4, the reference numerals in the drawings correspond to the reference numerals of the components of the iontophoresis device described in the section of “Means for Solving the Problems”. For example, “(1) -1” of the component of the iontophoresis device (X) of the present invention is indicated as “11” in the drawing.
[0030]
The greatest feature of the iontophoresis device (X) of the present invention is that the purpose of this kind of iontophoresis is to drive an ionic drug into the body through the skin (or mucous membrane) under a predetermined electromotive force ( In the prior art, it is well known that the amount of ions moved by a constant electromotive force (which depends on the concentration of ions, the mobility of ions, and the valence of ions). However, the present invention pays attention to the electrochemical reaction of each electrode portion, and particularly pays attention to the defect factor (negative factor) based on the electrochemical reaction, from which the iontophoresis technique is re-established. It is in the point which is constructing.
[0031]
In iontophoresis, the electrode portion inevitably undergoes an electrochemical reaction, that is, some oxidation reaction (anode) and reduction reaction (cathode).
Then, due to the electrochemical reaction, for example, generation of harmful substances by electrolysis of physiological saline, which is a conductive medium (for example, Cl known as a strong oxidizing agent at the anode) ^- Generation of hypochlorous acid due to water), rapid pH change (rapid acidification at the anode, rapid alkalinization at the cathode), or generation of bubbles (eg H at the cathode) ₂ O at gas and anode ₂ Gas or Cl ₂ Gas generation), which causes fatal drawbacks in the implementation of iontophoresis, such as adverse effects on human skin, skin irritation, and inability to energize (increase in resistance due to gas generation).
[0032]
The present invention aims to enhance iontophoresis technology and increase the added value based on eliminating the drawbacks caused by electrochemical reactions occurring in the electrode portion of iontophoresis.
[0033]
The iontophoresis device (X) of the present invention is as shown in FIG. 2 to FIG. 3 in comparison with the prior art in order to eliminate the above-mentioned drawbacks found in the conventional ionic drug administration methods. In addition,
(i). As the configuration of the iontophoresis electrode portion (working side electrode portion) (1), the technical components (1) -2 to (1) to 3 of the present invention described above (in FIGS. 2 to 3, Indicated by reference numerals 12 to 13), and
(ii). As the configuration of the ground electrode portion (non-working side electrode portion) (2), the technical components (2) -2 to (2) to 3 described above (refer to FIGS. 2 to 3). Indicated by reference numerals 22 to 23), and
(iii) There is a feature point in adopting a configuration in which the iontophoresis electrode portion (working side electrode portion) (1) and the ground electrode portion (2) are integrated.
[0034]
In addition, the iontophoresis device (X) of the present invention, as shown in FIG.
(iv). As a constitution of the ground electrode part (non-working side electrode part) (2), a cation exchange membrane (23) and an anion exchange membrane (25) are used in combination as an ion exchange membrane, and
(v). A structure in which the ground electrode portion (2) having the above-mentioned feature point (iv) is integrated with the iontophoresis electrode portion (working-side electrode portion) (1) having the above-described feature point (i) is adopted. There is a feature point in doing.
[0035]
In short, the iontophoresis device (X) of the present invention is focused on the use of an ion exchange membrane in order to eliminate the drawbacks caused by the electrode reaction described above in the conventional ionic drug administration methods. In view of the selective permeability of ions, there is a feature in that two ion exchange membranes are used for the iontophoresis electrode portion and at least one ion exchange membrane is used for the ground electrode portion side.
[0036]
Furthermore, the iontophoresis device (X) of the present invention is provided with the above-mentioned specific ion exchange membrane in order to eliminate the disadvantages caused by the electrode reaction described in the conventional administration method of an ionic drug. In addition to aspects
(vi). The feature is that a conductive medium for both electrode parts (iontophoresis electrode part and ground electrode part) containing a substance that is easily oxidized or reduced as compared with water electrolysis is adopted. There is.
[0037]
Hereinafter, the above-mentioned features of the iontophoresis device (X) of the present invention are described as sodium corcorbate (As ^- Na ⁺ ). In this case, the charged ion of the active drug component of the ionic drug is an anion (As ^- It goes without saying that it is).
For this reason, as shown in FIGS. 3 to 4, the iontophoresis electrode portion (1) becomes a cathode (− pole), and the ground electrode portion (2) becomes an anode (+ pole).
Needless to say, when the ionic agent is dissociated into positively charged ions, the polarity of the electrode part and the type of ion exchange membrane (ion selection characteristics) are opposite to each other. It goes without saying that it becomes something.
[0038]
1 to 4 showing the basic configuration of the iontophoresis device (X) of the present invention, 1 is an iontophoresis electrode part (working side electrode part), 2 is a ground electrode part (non-working side electrode part), 3 Indicates the power supply device, and 4 indicates the skin (or mucous membrane).
[0039]
The iontophoresis electrode part (working side electrode part) (1) is as shown in FIGS.
(i). Negative (-) pole (11),
(ii). Conductive medium (12), specifically 1 MAs ^- Na ⁺ 0.9% NaCl aqueous solution containing
(iii) Cation exchange membrane (13),
(iv). Ionic drugs (14), specifically 1 MAs ^- Na ⁺ Aqueous solution,
(v). anion exchange membrane (15),
Consists of.
[0040]
In the case of FIG. 3, the ground electrode portion (2)
(i). Positive (+) pole (21),
(ii). Conductive medium (22), specifically 0.9% NaCl aqueous solution,
(iii) Cation exchange membrane (23),
Consists of.
[0041]
In the present invention, the ground electrode portion (2) is viewed from the positive (+) pole (21) to the skin (4) as shown in FIG.
(i). Positive (+) pole (21),
(ii). Conductive medium (22), specifically 1 MAs ^- Na ⁺ 0.9% NaCl aqueous solution containing
(iii) anion exchange membrane (25),
(iv). Conductive medium (24), specifically 1 MAs ^- Na ⁺ 0.9% NaCl aqueous solution containing
(v). Cation exchange membrane (23),
May be configured.
[0042]
In the present invention, the conductive media (12, 22) of both electrode parts (1, 2) contain a compound that is easily oxidized and reduced as compared with water electrolysis reaction (water oxidation and reduction reaction). It may consist of things.
In the present invention, the conductive medium (12, 22) of the electrode portions (1, 2) may be an ionic agent (for example, As described above). ^- Na ⁺ ) Generally has a lower oxidation-reduction potential than water, and these ionic drugs may be contained as compounds that are easily oxidized and reduced. The same can be said for the conductive medium (24) of the ground electrode portion (2) shown in FIG.
[0043]
Hereinafter, with reference to the basic configuration diagram of the iontophoresis device (X) of the present invention, a more specific configuration of the iontophoresis device (X) for realizing a new administration method of an ionic drug, that is, an ion The specific configuration of the tophoresis electrode portion (working side electrode portion) (1) and then the specific configuration of the ground electrode portion (non-working side electrode portion, ground electrode portion) (2) will be described in this order.
[0044]
In the iontophoresis device (X) of the present invention, the electrode material (11) of the iontophoresis electrode portion (working side electrode portion) (1) may be formed of a desired material. Moreover, what is necessary is just to comprise about the electrode material (12) of a ground electrode part (non-working side electrode part) (2) by a desired thing.
For example, what is necessary is just to comprise by the inert electrode which consists of electroconductive materials, such as carbon and platinum.
[0045]
In the iontophoresis device (X) of the present invention, as the electrode material (11, 12), an active electrode known in the field of iontophoresis may be employed instead of the inactive electrode described above. is there.
As an example of the active electrode described above, when the drug component of the ionic drug is positive (+) ion, specifically, morphine hydrochloride or lithium chloride (in this case, morphine ion as the drug component or In the case of using lithium ions as positive ions and counter ion chlorine as negative ions, an anode (+) material includes a silver electrode that reacts with these counter ions.
In the case of the active electrode described above, a silver electrode and chlorine ions (Cl ^- ) Reacts easily, Ag + Cl ^- → AgCl + e ^- Produces insoluble AgCl. The advantage of using the active electrode is that the electrolysis reaction of water can be prevented because the standard potential of the reaction is lower than the standard potential of electrolysis of water at the anode (+). Therefore, H at the anode (positive electrode) ⁺ Rapid acidification based on ions and OH at the cathode (negative electrode) ^- Rapid alkalinization based on ions is prevented.
[0046]
However, in the iontophoresis device (X) of the present invention, as described above, a plurality of ion exchange membranes having different ion selectivity are used in the iontophoresis system. It should be noted that insoluble substances (insoluble fine particles) such as silver chloride (AgCl) may interfere with the properties of the ion exchange membrane.
As described above, since the iontophoresis device (X) of the present invention uses a plurality of ion exchange membranes having different ion selectivity, it does not use a special electrode material called an active electrode, and is more economical. It is preferable to use an active electrode.
Further, in the iontophoresis system, metal ions inevitably generated from the electrode material are also transported, and the iontophoresis effect is reduced by this amount. Therefore, as the electrode material of the iontophoresis device (X) of the present invention. Is preferably a carbon electrode.
[0047]
In the iontophoresis device (X) of the present invention shown in FIG. 3, a conductive medium disposed so as to be in contact with the periphery of the negative (−) electrode material (11) of the iontophoresis electrode portion (1). (12) includes a compound that is easily reduced.
Further, in the iontophoresis device (X) of the present invention shown in FIG. 3, a conductive medium disposed so as to be in contact with the periphery of the positive (+) electrode material (21) of the ground electrode portion (2). (22) is composed of a compound that easily oxidizes.
The arrangement site of the compound that is easily oxidized or reduced corresponds to the electrochemical reaction in each electrode plate, that is, the reduction reaction at the negative (−) electrode and the oxidation reaction at the positive (+) electrode. Needless to say.
[0048]
In the iontophoresis electrode portion (1) of the iontophoresis device (X) of the present invention shown in FIG. 3, a conductive medium (12) containing a compound that is easily reduced as shown and an ionic agent (As ^- Na ⁺ ) (14) is provided with a cation exchange membrane (13).
In the present invention, the conductive medium (12) containing the compound that is easily reduced is disposed so as to be in contact with the negative (−) electrode material (11). The sex medium (12) plays an important role as will be described later. The same applies to the conductive medium (22) containing a compound that is easily oxidized on the ground electrode portion (2) side.
[0049]
In the present invention, the compound that is easily oxidized or reduced added to the conductive medium (12) is preferably a compound that is excellent in biological safety, economy (inexpensive and easily available), such as sulfuric acid. Inorganic compounds such as ferrous and ferric sulfate, pharmaceutical agents such as ascorbic acid (vitamin C) and sodium ascorbate, acidic compounds such as lactic acid, or oxalic acid, malic acid, succinic acid, fumaric acid Examples thereof include organic acids and / or salts thereof.
[0050]
In a compound that is easier to oxidize or reduce than the water electrolysis described above (oxidation at the positive electrode and reduction at the negative electrode), for example, ferric sulfate is easily reduced to ferrous ions at the negative electrode. To do. In addition, ferrous sulfate is easily oxidized from ferrous ions to ferric ions at the positive electrode.
As a result, as will be described in detail later, it is possible to remove the disadvantages derived from the water electrolysis reaction, and excellent performance such as high biosafety related to the specific ion exchange membrane arrangement of the present invention. An iontophoresis device (X) is provided.
[0051]
In the present invention, the conductive medium (12) is for ensuring conductivity, and typical examples are saline and physiological saline.
In the iontophoresis device (X) of the present invention, the configuration for accommodating or holding the conductive medium (12) may be configured as desired. The conductive medium (12) may be, for example, a solution type or a type impregnated in a desired medium (gauze, water-absorbing polymer material, etc.).
[0052]
Here, the advantage of using the conductive medium (12) containing the compound that is easily oxidized or reduced will be described in detail.
In the iontophoresis electrode portion (1) and the ground electrode portion (2), an electrochemical reaction occurs, and the electrolyte solution and the ionic drug are decomposed. As a result, bubbles are generated in the electrode chamber and the contact between the electrode portion and the electrolytic chamber solution is prevented.
For example, H ₂ Gas, Cl for positive electrode ₂ And O ₂ Gas is generated.
When such a situation occurs, resistance increases due to bubbles, and no current flows no matter how much voltage is applied. As mentioned above ^- Na ⁺ In the case of delivery, stable energization is impossible for a long time (30 minutes or more). This is a very big problem from the viewpoint of practicality of the iontophoresis device.
[0053]
In order to remove the instability factors described above and perform iontophoresis stably, it is extremely important to suppress the generation of bubbles.
In order to achieve the above object, it is useful to put a substance that easily undergoes oxidation or reduction reaction without generating bubbles into each electrode chamber.
That is, when water is oxidized or reduced, oxygen or hydrogen is generated. In order to suppress these reactions, for example, ferrous sulfate, ferric sulfate, ascorbic acid or a sodium salt thereof is added to the electrode chamber solution. Add to (electrode solution). For example, when sodium ascorbate is used, an electrode that undergoes an oxidation reaction undergoes oxidative decomposition instead of generating oxygen, and an electrode that undergoes a reductive reaction undergoes reductive decomposition of sodium ascorbate instead of producing hydrogen. Thus, the generation of oxygen or hydrogen bubbles that impair the stability of the current-carrying characteristics can be suppressed.
[0054]
As described above, an electrode such as sodium ascorbate that is oxidized or reduced more easily than water in an electrochemical reaction (a substance having a redox potential lower than the redox potential of water) can be used at the sacrificial position. The iontophoresis device (X) that can suppress the generation of gas (gas) in the room and enables more stable operation is obtained.
In the present invention, as the sacrificial substance, in addition to the aforementioned ferrous sulfate, ferric sulfate, and ascorbic acid, any substance may be used as long as it undergoes oxidation-reduction and suppresses decomposition of water. It goes without saying that it is possible.
In the case of sodium ascorbate as the sacrificial substance, sodium ascorbate is
(i) At the electrode (-electrode) where the reduction reaction occurs, CO ₂ And H ₂ CO _Three Etc.
(ii). In an electrode (+ electrode) where an oxidation reaction occurs, dehydroascorbic acid, 2,3 diketo 6-gulonic acid, etc.
Will change.
[0055]
In the iontophoresis device (X) of the present invention, any desired cation exchange membrane (13) can be used.
As described above, the iontophoresis device (X) of the present invention uses the anion exchange membrane (15) in addition to the cation exchange membrane (13).
Here, specific examples of both the cation exchange membrane (13) and the anion exchange membrane (15) used in the present invention will be described.
[0056]
In the present invention, Neoceptor (CM-1, CM-2, CMX, CMS, CMB, etc.) manufactured by Tokuyama Corporation can be used as the cation exchange membrane (13).
[0057]
In the present invention, Neoceptor (AM-1, AM-3, AMX, AHA, ACH, ACS, ACS-3, etc.) manufactured by Tokuyama Corporation can be used as the anion exchange membrane (15). .
[0058]
In the iontophoresis device (X) of the present invention, an ionic drug (As ^- Na ⁺ The configuration for accommodating or holding (14) may be configured as desired. The ionic drug (14) may be, for example, a solution type or a type impregnated in a desired medium (gauze, water-absorbing polymer material, etc.).
[0059]
In the iontophoresis device (X) of the present invention, the ionic drug (As ^- Na ⁺ ) The ion exchange membrane disposed on the front surface of (14), that is, on the skin side is charged ions (As) of the drug component of the ionic drug. ^- ) And an anion exchange membrane (15) having the same ion selectivity.
[0060]
Due to the technical configuration of the iontophoresis electrode portion (1) of the iontophoresis device (X) of the present invention described above, it is possible to obtain a longer and more stable iontophoresis effect and biological safety than the conventional method.
In other words, the above-described technical configuration can provide a long-term and stable energization characteristic. In other words, an ionic drug can efficiently penetrate into the body (drug delivery) through the skin (4). In addition, the generation of harmful substances due to the electrolysis reaction at the electrode portion can be eliminated.
[0061]
Next, the structure of the ground electrode part (+ electrode) (2) of the iontophoresis device (X) of the present invention will be described.
[0062]
The conventional technology related to iontophoresis is because the simple idea of simply grounding the ground electrode part (earth electrode part) is working strongly, ensuring stable current-carrying characteristics and biosafety. The current situation is that no proposal has been made for securing.
This can be seen from the patent application publications No. 3-504343, JP-A-3-94771, and JP-A-4-297277 related to the applicant of the present application described in the section of “Prior Art”. It is just about to be confirmed.
[0063]
In the present invention, in addition to the configuration of the iontophoresis electrode portion (1) of the iontophoresis device (X), the iontophoresis of the ionic drug by the iontophoresis can be stably performed for a long time in relation to the overall configuration of the device. Ground electrode part from the viewpoint that administration is possible, high biological safety is obtained, and further convenience of operation and desired iontophoresis effect (adjustment of ionic drug administration depth, etc.) can be obtained. Regarding (2), a technical configuration different from the conventional one is adopted.
[0064]
As shown in FIGS. 1 to 2, the ground electrode part (2) of the iontophoresis device (X) of the present invention has a polarity opposite to that of the electrode material (11) of the iontophoresis electrode part (1). An electrode material (21), a conductive medium (22) disposed at least on the front surface of the electrode material (21), and a front surface portion of the conductive medium (22), that is, disposed on the skin (4) side. And an ion exchange membrane (23) that selects ions opposite to the charged ions of the ionic drug, and is configured integrally with the iontophoresis electrode portion (1).
[0065]
In the iontophoresis device (X) of the present invention, the ion exchange membrane (23) is disposed on the ground electrode portion (2) in order to enhance biological safety, which is a significant feature not found in the prior art. is there.
Further, in the iontophoresis device (X) of the present invention, in order to achieve a long-term stable operation as well as biological safety, a ground electrode portion (like the conductive medium (12) of the iontophoresis electrode portion (1)) The conductive medium (2) of 2) may be composed of a substance containing a substance having a redox potential lower than that of water. Then, a combination of the point of disposing the ion exchange membrane (23) in the ground electrode part (2) and the point of using the substance that is easily oxidized and reduced provides a high added value iontophoresis device (X). This is also a major feature not seen in the prior art.
[0066]
In the iontophoresis device (X) of the present invention, the ground electrode portion (2) is composed of a single ion exchange membrane (23) having a predetermined ion selectivity as shown in FIG. It may be done.
The advantage of disposing the ion exchange membrane (23) on the ground electrode portion (2) will be described later with demonstration data.
Further, the advantage of adding a substance that is easily oxidized / reduced to the conductive medium (22) of the ground electrode part (2) is the same as already described in the case of the conductive medium (12) of the iontophoresis electrode part (1). It is.
[0067]
As shown in FIG. 3, the ionic drug is sodium ascorbate (As ^- Na ⁺ ) Or the like, in the ground electrode portion (2) of the iontophoresis device (X) of the present invention, the electrode material (21) is the anode (+), and the conductive medium (22) is, for example, The physiological saline and the ion exchange membrane (23) are constituted by a cation exchange membrane.
[0068]
In the present invention, the conductive medium (22) of the ground electrode portion (2) is a material that is easily oxidized and reduced, for example, ferric sulfate or ferric sulfate containing ferrous sulfate (equal molar solutions of both). , Physiological saline containing ascorbic acid, sodium ascorbate, or the like may be used.
Furthermore, as shown in FIG. 4, the ground electrode portion (2) of the present invention may use two types of ion exchange membranes having different ion selectivity as the ion exchange membrane.
[0069]
The iontophoresis administration method described with reference to the iontophoresis device (X) shown in FIG. 3 is an ascorbine in which the active drug component of the ionic drug is negatively charged (−) as described above. Acid Na (As ^- Na ⁺ ) Case.
In the present invention, even if the active drug component of the ionic drug is positively (+) charged, it can be similarly administered.
[0070]
Examples of those in which the active drug component of the ionic drug is positively (+) charged include procaine hydrochloride and lidocaine hydrochloride as anesthetic agents.
In this case, the polarity of each of the electrode materials (11, 12) and the ion exchange characteristics of the ion exchange membrane are determined using the ascorbic acid Na (As ^- Na ⁺ It goes without saying that the administration case must be completely reversed.
When the positive (+) charged ionic drug is used, the features of the present invention can be easily understood by analogizing the administration case of the negative (−) charged sodium ascorbate.
[0071]
As the power supply device (3) shown in FIGS. 1 to 4, a desired one can be used.
In the present invention, as the power supply device (3), a battery, a constant voltage device, a constant current device, a constant voltage / constant current device (galvano device), or the like can be used.
[0072]
Next, an experimental device equivalent to the basic configuration diagram of the iontophoresis device (X) shown in FIGS. 3 to 4 and an experimental device manufactured by changing the experimental device for collecting comparison data are used. Ascorbic acid sodium (As ^- Na ⁺ ) Will be described experimental examples / comparative experimental examples.
In the iontophoresis device (X) of the present invention, the importance of disposing an ion exchange membrane in the ground electrode portion (2) can be understood from the experimental examples / comparative experimental examples described below. .
[0073]
5 to 8 are schematic views of the experimental apparatus used. 5 to 6 are apparatuses for comparative experiments. 7 to 8 are experimental devices equivalent to the iontophoresis device (X) of the present invention.
The meanings of the reference symbols of the experimental apparatus are as follows.
(1) Reference numerals 11, 21, 12, 13, 14, 15, 22, 23, 24, and 25 are the same as those in FIGS. As the cation exchange membrane (13, 23) and the anion exchange membrane (15, 25), Neoceptor CMX (cation) and AMX (anion) manufactured by Tokuyama Corporation were used, respectively.
(2). Reference numeral 4 indicates a virtual skin tank in which the skin is assumed.
(3) Reference symbol PP indicates a polypropylene porous diaphragm (AN filter, AN06, manufactured by Nippon Millipore Limited).
(Note) PP does not have selective ion permeability.
(4). Reference symbols A to E denote each tank partitioned by an ion exchange membrane or PP.
[0074]
1. Iontophoresis experiment in the experimental device shown in Fig. 5
(a) Experimental conditions
(1). Electrode solution in chamber A (iontophoresis electrode chamber, negative electrode chamber) contains a conductive medium (12) and an ionic agent (14). ^- Na ⁺ 0.9% NaCl aqueous solution in which was dissolved was used.
(2) A 0.9% NaCl aqueous solution was used as a medium for the room B (virtual skin room simulating skin).
(3) 0.9% NaCl aqueous solution was used as the conductive medium (22) in the C chamber (ground electrode chamber).
(4) Energizing conditions
Voltage 30V (initial setting value), current 10mA (constant current), energization time 30 minutes.
(b). Experimental results:
As an experimental result, the pH change of each chamber (A to C) is shown in Table 1 below.
[0075]
[Table 1]

[0076]
(c) .Consideration:
(1). Reduction reaction occurs in the A chamber, and oxidation reaction occurs in the C chamber. ^- (Ascorbate ion) is transported to the B chamber.
Apparently, in chamber A, the pH shifts from neutral to alkaline, and in chamber C, the pH changes from neutral to strongly acidic. Therefore, the case of this experiment in which the ground electrode (21) in the C chamber and the B chamber, that is, the skin (4) are in direct contact is in a very dangerous state.
This is because the B chamber is shifted to the acidic side, and the cause of the shift to the acidic side is the acid (HClO generated in the C chamber). _Three ). The hypochlorous acid is known as a strong oxidizing agent.
(2) Although the anion exchange membrane (15) exists between the A chamber, which is an iontophoresis electrode chamber, and the skin (B chamber), it is somewhat prevented that the A chamber becomes alkaline. OH in room A ^- Since ions pass through the anion exchange membrane (15) to the B chamber side by electrophoresis, the skin surface is considered to be locally alkaline. That is, it is considered that the chamber B is inclined to the more acidic side, but it stops at pH = 4.20, and OH ^- It is considered that ions reach the skin surface and the pH is locally shifted to the alkali side.
(3) From the above, when performing iontophoresis, an embodiment in which only one ion exchange membrane is used as in this experiment should be avoided from the viewpoint of biological safety.
(4). As administered in this experiment ^- The amount of (ascorbate ion) is about 300 μmol (theoretical value: 560 μmol), which roughly corresponds to the decrease in the A chamber and the increase in the B chamber. However, the dose is about ½ of the theoretical value, and a large amount of OH in room A ^- Ions are generated and this is As ^- As to be transported with ^- 50% of the transport of Also from this point, this experimental apparatus is unsuitable as an iontophoresis apparatus.
[0077]
2. Iontophoresis experiment in the experimental apparatus shown in FIG.
(a). Experimental conditions:
Using the experimental apparatus in which the configurations of the chamber A and the chamber B (skin) of the experimental apparatus shown in FIG. 5 are reconfigured by arranging the cation exchange membrane (13) and the anion exchange membrane (15) in the illustrated manner, 1M As containing the conductive medium (12) and the ionic drug (14), respectively, as the electrode solution in the A chamber and the ionic drug solution in the B chamber. ^- Na ⁺ An experiment was conducted in the same manner as in the above “1” except that a 0.9% NaCl aqueous solution in which was dissolved was used.
(b). Experimental results:
As an experimental result, the pH change of each chamber (A to D) is shown in Table 2 below.
[0078]
[Table 2]

[0079]
(c) Consideration
(1). Iontophoresis electrode chamber (A chamber) and As as ionic drug as administration reagent ^- Na ⁺ The pH of the B chamber can be kept constant by partitioning the solution chamber (B chamber) containing the cation exchange membrane (13). This prevents the skin surface (C chamber) from becoming alkaline.
Further, the ion permeation amount is improved as compared with the experiment “1”, and a value close to the theoretical value is obtained.
(2) However, the pH of the C chamber (virtual skin tank) (4) is lowered.
This suggests the effectiveness of partitioning between the C chamber and the D chamber, that is, between the ground electrode chamber (D) and the virtual skin tank (4) with an ion exchange membrane instead of a simple diaphragm (pp). . Furthermore, in the ground electrode chamber (D), there is a risk that hypochlorite ions are generated by oxidative decomposition of physiological saline, which is a conductive medium, and diffuses into the skin.
[0080]
3. Iontophoresis experiment in the experimental apparatus shown in Fig. 7
(a). Experimental conditions:
The experiment was performed in the same manner as in “2” except that the PP diaphragm between the C chamber and the D chamber of the experimental apparatus shown in FIG. 6 was changed to a cation exchange membrane (23).
(b). Experimental results:
Table 3 shows the pH change in each chamber (A to D) as an experimental result.
[0081]
[Table 3]

[0082]
(c) .Consideration:
This experiment corresponds to the experiment using the iontophoresis device (X) of the present invention. This experimental apparatus is characterized in that it is composed of a ground electrode portion (2) provided with a single cation exchange membrane (23).
(1) Although the pH change is observed in each electrode chamber, that is, the A chamber and the D chamber, As ^- Na ⁺ The pH change in the solution chamber (B chamber) and skin (C chamber) is suppressed and effective.
Furthermore, by arranging the cation exchange membrane (23) in the ground electrode chamber (D chamber), harmful anions such as hypochlorite ions can be kept in the D chamber without contacting the skin.
(2) Since the amount of ascorbate ion permeation shows a theoretical value, this experimental apparatus is useful as an iontophoresis apparatus.
(3). However, as an improvement of this experimental apparatus, H generated by electrolysis of water on the ground electrode (21) in the ground electrode chamber (D room) in contact with the virtual skin tank (C room) ⁺ Ions migrate through the cation exchange membrane (23), resulting in acidification of the C chamber, which should be improved. For this reason, it is preferable to employ two types of ion exchange membranes, that is, a cation exchange membrane and an anion exchange membrane on the ground electrode portion side as in the case of the ontoze electrode portion side.
[0083]
4). Iontophoresis experiment in the experimental device shown in Fig. 8
(a). Experimental conditions:
In the experimental apparatus shown in FIG. 7, an anion exchange membrane (25) is arranged in the illustrated manner in addition to the cation exchange membrane (23) in the ground electrode chamber (D chamber), and a newly partitioned ground electrode is provided. 1M As as electrode solution for chamber (E chamber) ^- Na ⁺ An experiment was conducted in the same manner as in the above “3” except that a 0.9% NaCl aqueous solution in which was dissolved was used.
(b) Experimental results
As an experimental result, the pH change of each chamber (A to E) is shown in Table 4 below.
[0084]
[Table 4]

[0085]
(c) .Consideration:
(1). Ions having two ion exchange membranes (13, 15) on the iontophoresis electrode portion side shown in FIG. 8 and two ion exchange membranes (23, 25) on the ground electrode portion side In the tophoresis device, As from the iontophoresis electrode part side (A to B room) to the human body (C room) ^- Only from the ground electrode side (E to D chambers) into the human body (C chamber). ⁺ Only as a result, sodium ascorbate (As ^- Na ⁺ ) Will be injected into the body. Since substances other than those described above are not injected into the body, this experimental apparatus is an extremely safe and effective means for administering an ionic drug (drug delivery).
(2) Almost no pH change is observed in the B, C and D chambers. This means
(i). Ascorbate ion (As ^- ) Moved to the virtual skin tank (room C), and sodium ions (Na ⁺ ) Has moved to the iontophoresis electrode chamber (room A), and
(ii). In the ground electrode section, sodium ions (Na ⁺ ) Moved to virtual skin tank (C room), and ascorbate ion (As ^- ) Has moved to the ground electrode chamber (E chamber),
As a result, no pH change occurred in each chamber.
[0086]
【Example】
Next, an embodiment of the iontophoresis device (X) used for administering an ionic drug by the iontophoresis of the present invention will be described in detail with reference to the drawings.
In the reference drawings, the ion exchange membranes (13, 15, 23, 25) are indicated by wavy lines for clarity of illustration, and some components (members) and components (members) are coupled to each other. Style or hatching is omitted.
However, configurations omitted in the drawings can be easily understood from the description of each embodiment, other attached drawings, and the like.
[0087]
FIG. 9 is a longitudinal sectional view for explaining the first embodiment of the iontophoresis device (X) of the present invention.
The iontophoresis device (X) of the first embodiment of the present invention is roughly divided as shown in FIG.
(i). Cylindrical iontophoresis electrode (1),
(ii) a ground electrode part (2) integrally formed on the peripheral edge of the cylindrical iontophoresis electrode part (1), and
(iii) Power source for constant voltage and constant current (3),
It consists of three elements.
[0088]
In this type of iontophoresis device, the iontophoresis electrode portion (1) and the land electrode portion (2) are constituted separately, and the user is grounded (earth) during the administration of the ionic drug. For this reason, an action such as holding the ground electrode part (2) by hand is forced.
However, the iontophoresis device (X) of the present invention is excellent in operability and convenience because the elements of the iontophoresis electrode portion (1) and the ground electrode portion (2) are integrated as described above. Yes. In addition, since both elements (1, 2) are integrated, the dose and administration of the ionic drug can be achieved by setting the distance between both elements (1, 2) as desired, or by integrating multiple sets of both elements. The depth of the can be adjusted.
[0089]
In the present invention, the main reason why both elements (1, 2) can be integrated is that the biosafety of the ground electrode portion (2) is much better than before. For this reason, in the iontophoresis device (X) of the present invention, the ground electrode part (2) integrated with the iontophoresis electrode part (1) receives fever, inflammation, irritation, etc. from the skin of the hand. There is no problem even when it is brought into contact with an easy-to-skin part of the skin, and the ionic drug can be safely and efficiently ion-administered.
[0090]
In the iontophoresis device (X) of the present invention, the ground electrode portion (2) is configured integrally with the iontophoresis electrode portion (1). The meaning of “integrated (integrally configured)” is integrated with a part of the constituent members of the iontophoretic electrode portion (1) as shown in the figure. In the present invention, the integration is not limited to the embodiment shown in FIG. 9, and the integration mode should be interpreted in the broadest sense.
[0091]
Further, the iontophoresis device (X) shown in FIG. 9 has an ascorbic acid Na (As ^- Na ⁺ ) Is administered on the assumption that it is administered by iontophoresis.
For this reason, in the iontophoresis device (X) shown in FIG. 9, the reference numerals of the respective components mean the following.
(i) The electrode plate of the iontophoresis electrode part (1) shown in (11) is a (−) electrode,
(ii) The conductive medium of the iontophoresis electrode part (1) shown in (12) is a physiological saline,
(iii). The ion exchange membrane of the iontophoresis electrode part (1) shown in (13) is a cation exchange membrane,
(iv) The ionic drug of the iontophoresis electrode part (1) represented by (14) is Alcorbic acid Na (As ^- Na ⁺ ),
(v). The ion exchange membrane of the iontophoresis electrode part (1) shown in (15) is an anion exchange membrane,
(vi). The electrode plate of the ground electrode part (2) shown in (21) is a (+) electrode,
(vii). The conductive medium of the ground electrode part (2) indicated by (22) is a physiological saline and
(viii). The ion exchange membrane of the ground electrode part (2) represented by (23) is a cation exchange membrane,
Respectively.
[0092]
As shown in FIG. 9, in the iontophoresis device (X) of the first embodiment of the present invention, the elements of the iontophoresis electrode portion (1) and the ground electrode portion (2) are integrated. However, for the sake of convenience of explanation, the following description will be divided into respective elements.
[0093]
In the iontophoresis device (X) of the first embodiment of the present invention, the iontophoresis electrode portion (1) is roughly divided as shown in FIG.
(i) a non-conductive cylindrical outer cylinder (a), and
(ii). Non-conductive cylindrical inner cylinder (b),
The elements indicated by the reference numerals (11 to 15) are held or accommodated under these elements (a, b).
The ground electrode portion (2) is integrated with the outer peripheral edge of the insulating cylindrical body (a) so that both elements (1, 2) are substantially flush with the skin (4) surface. It is combined and configured.
[0094]
The iontophoresis electrode portion (1) shown in FIG. 9 has a circular plan view as shown in FIG.
The iontophoresis electrode part (1) is configured to have a desired size (outer diameter, height) since it is held by a hand and brought into contact with a desired affected part.
Further, as shown in FIG. 9, the outer cylinder (a) and the inner cylinder (b) are integrated by screwing through a screw portion formed on the contact surface of both. belongs to.
However, in the present invention, the coupling manner of the outer cylinder (a) and the inner cylinder (b) may be other methods, for example, an engagement type, a locking type, an insertion type, etc. It may be.
[0095]
In the cylindrical outer cylindrical body (a), as shown in FIG.
(i) a support (a1) for the cation exchange membrane (13) for fixing the cation exchange membrane (13) in cooperation with the inner cylinder (b),
(ii). Storage section (a2) for ionic drug (14) for storing ionic drug (14),
(iii). Anion exchange membrane (15) support (a3) for fixing the anion exchange membrane (15),
(iv) a pressure ring (a31) for anion exchange membrane (15) for fixing the anion exchange membrane (15),
(v) a fixing pin (a32) for fixing the anion exchange membrane (15),
It is comprised with what has.
[0096]
On the other hand, the cylindrical inner cylinder (b), as shown,
(i). Cushion exchange membrane (13) pressing portion for fixing the cation exchange membrane (13) in cooperation with the cation exchange membrane (13) support portion (a1) of the outer cylinder (a) b1),
(ii). Containment part (b2) for conductive medium (12) for accommodating conductive medium (12),
(iii). Electrode plate (11) support part (b3) for supporting the electrode plate (11),
(iv) A guide hole (b4) for the lead wire (31) for guiding the lead wire (31) from the power supply unit (3),
(v) a support (b5) for the lead wire (31) that supports the lead wire (31),
(vi). top disc part (b6),
It is comprised with what has.
[0097]
As shown in FIG. 9, the iontophoresis electrode portion (1) composed of the cylindrical body (a) and the inner cylindrical body (b) having the above-described configuration is composed of a (−) electrode plate (11), gauze or high water absorption. Conductive medium (12) containing a material easily impregnated by oxidation and impregnation in molecular material, cation exchange membrane (13), ionic drug (As ^- Na ⁺ ) (14) and the anion exchange membrane (15) can be reliably held or accommodated therein.
Moreover, in the structure of the said outer cylinder (a) and an inner cylinder (b), when both are screwed together, an inner cylinder (b) is displaced relatively with respect to an outer cylinder (a). Thus, the anion conversion membrane (15) can be brought into close contact with the skin (4), and the iontophoresis effect can be improved.
[0098]
Next, the ground electrode portion (2) constructed integrally with the iontophoresis electrode portion (1) of the iontophoresis device (X) of the first embodiment shown in FIG. 9 of the present invention. The configuration will be described.
In the present invention, the elements (1, 2) may be integrated by, for example, integral molding using a non-conductive plastic material.
[0099]
As shown in FIG. 9, in the cylindrical outer cylinder (a), the part constituting the ground electrode part (2) is roughly divided,
(i). Electrode plate (21) for accommodating the electrode plate (21) and the conductive medium (22) on the side of the ground electrode part (2) and the accommodating part (a4) for the conductive medium (22),
(ii) a support portion (a5) for the cation exchange membrane (23) for fixing the cation exchange membrane (23) on the ground electrode portion (2) side,
(iii) a cation exchange membrane (23) pressing ring (a51, a52) for fixing the cation exchange membrane (23) on the ground electrode part (2) side, and
(iv) A fixing pin (a53) for fixing the cation exchange membrane (23) on the ground electrode part (2) side,
The elements indicated by the reference numerals (21 to 23) described above are held or accommodated under these configurations.
[0100]
In FIG. 9, the ground electrode part (2) is constituted by a lead wire (32) from the power supply part (3) embedded integrally.
However, in the ground electrode portion (2), the lead wire (32) is arranged in such a manner that the lead wire is supported by the support (b5) like the inner cylindrical body (b) of the iontophoresis electrode portion (1). It may be made to do.
[0101]
In FIG. 9, the element (5) disposed on the front surface of the anion exchange membrane (15) of the iontophoresis electrode portion (1) and the cation exchange membrane (23) of the ground electrode portion (2) A medium impregnated with a conductive liquid such as physiological saline for improving the conductivity between the membrane (15, 23) and the skin (4), such as gauze, is shown.
In the present invention, it goes without saying that the element (5) may be omitted. In this case, since the anion exchange membrane (15) and the skin (4) are in contact with each other, the ion transport number (transport number of charged ions of the ionic drug) is improved.
[0102]
In the iontophoresis device (X) of the present invention shown in FIG. 9, although not shown for clarity of illustration, a conductive medium is used for the iontophoresis electrode portion (1) and / or the ground electrode portion (2). (12, 22) or an ionic drug (14) supply path, gas vent holes generated from the electrode plates (11, 12), or an adsorbent container for adsorbing the gas. It goes without saying that it may be done.
[0103]
FIG. 10 is a view for explaining a second embodiment of the iontophoresis device (X) of the present invention, and corresponds to FIG.
The iontophoresis device (X) of the second embodiment of the present invention can be said to be a modification of the first embodiment shown in FIG.
[0104]
The iontophoresis device (X) of the second embodiment shown in FIG. 10 of the present invention is different from that of the first embodiment shown in FIG. The configuration is substantially the same.
(i). The iontophoresis electrode part (1) is divided into two inner cylinders (b) of the iontophoresis electrode part (1) of the first embodiment, and the inner cylinder (b) and the intermediate cylinder (C). The specific configuration of the components (a, b, c) in the second embodiment is apparent from FIG.
In the zone (m, n) indicated by the arc-like broken line shown in FIG. 10, the (m) zone is a zone for administering an ionic drug, and the (n) zone is a ground (earth) electrode for current flowing in the skin. This is the zone leading to the part. In the figure, (mn) indicates an insulating part (shield part) of the negative electrode (11) and the positive electrode (21).
[0105]
In the present invention, as a modification of the second embodiment shown in FIG. 10, instead of the configuration in which the cation exchange membrane (13) is held by the outer cylinder (a) and the intermediate cylinder (c), the inner cylinder (b Needless to say, it may be configured to be held by the intermediate cylinder (c). In this case, the support (a1) for the cation exchange membrane (13) of the outer cylinder (a) is removed, and, for example, an intermediate cylinder (c) is used in which a protrusion is provided on the lower inner side, and The inner cylinder (b) having the structure of the first embodiment shown in FIG. 9 is used, and the projecting part of the intermediate cylinder (c) and the lower end part of the inner cylinder (b) (b1 in FIG. 9). The cation exchange membrane (13) may be held at (see).
[0106]
FIG. 11 is a view for explaining a third embodiment of the iontophoresis device (X) of the present invention, and corresponds to FIG.
The iontophoresis device (X) of the third embodiment of the present invention can be said to be a modification of the second embodiment shown in FIG.
[0107]
The iontophoresis device (X) of the third embodiment shown in FIG. 11 of the present invention is different from that of the second embodiment shown in FIG. Are substantially identical.
(i) The inner cylindrical body (b) and the intermediate cylinder so that the conductive medium (12) containing part of the iontophoretic electrode part (1) is divided into two parts, the upper part of the electrode plate (11). The configuration of (c) was reconfigured.
(ii) The conductive medium (22) accommodated in the accommodating part (a4) of the conductive medium (22) of the ground electrode part (2) was composed of physiological saline containing a substance that is easily oxidized and reduced.
[0108]
FIG. 12 is a view for explaining a fourth embodiment of the iontophoresis device (X) of the present invention, and corresponds to FIG. However, the iontophoresis electrode part (1) is omitted. FIG. 12 is an enlarged view of a main part of the ground electrode portion (2).
[0109]
The iontophoresis device (X) of the fourth embodiment shown in FIG. 12 of the present invention is only different from the first embodiment shown in FIG. The configuration is substantially the same.
(i) The configuration of the electrode plate (21) of the ground electrode portion (2) and the accommodating portion (a4) for the conductive medium (22) is added to the components (21, 22, 23) shown in FIG. Further, the conductive medium (24) and the anion exchange membrane (25) can be accommodated. The conductive medium (24) and the anion exchange membrane (25) are held or accommodated by the illustrated members (a6, a7) inside the accommodating portion (a4). That is, the anion exchange membrane (25) is held by the holding member (a6), the cation exchange membrane (23) is held by the holding member (a7), and the conductive medium (24) is interposed between the two ion exchange membranes (23, 25). Be contained.
(ii). Component (5) disposed on the front surface of the anion exchange membrane (15) (not shown) of the iontophoresis electrode portion (1) and the cation exchange membrane (23) of the ground electrode portion (2) Was removed.
[0110]
The iontophoresis device (X) of the fourth embodiment shown in FIG. 12 has a total of four cation exchange membranes and two anion exchange membranes in each of the iontophoresis electrode portion (1) and the ground electrode portion (2). A sheet of ion exchange membrane is provided, which is different from the other embodiments. And the iontophoresis apparatus (X) of this 4th embodiment has an outstanding effect as demonstrated in the iontophoresis experiment by the experimental apparatus shown by FIG.
In the iontophoresis device (X) of the fourth embodiment shown in FIG. 12, the cation exchange membrane (23) of the ground electrode portion (2) is an anion exchange membrane of the iontophoresis electrode portion (1) (not shown). It goes without saying that it is preferable to be arranged so as to be flush with (15).
[0111]
The iontophoresis device (X) in which the iontophoresis electrode portion (1) and the ground electrode portion (2) of the present invention are integrated can be variously modified.
[0112]
(i) FIG. 13 shows that the configuration of the iontophoresis device (X) of the present invention can be configured to provide a plurality (m1 to mX) of ionic drug administration zones concentrically as shown. ing. The ground (earth) zone is indicated by (n1) to (nX).
A specific configuration of the iontophoresis device (X) of the fifth embodiment capable of forming the concentric ionic drug administration zone shown in FIG. 13 of the present invention described above is, for example, the second of FIG. It can be easily understood from the embodiment. For this reason, illustration of the iontophoresis device (X) of the fifth embodiment is omitted.
[0113]
(ii). FIG. 14 shows that the iontophoresis device (X) of the present invention can be configured so that a plurality of administration zones (m1 to mX) are provided in series as shown in the figure. ing. The ground (earth) zone is indicated by (n1) to (nX).
The specific configuration of the iontophoresis device (X) of the sixth embodiment capable of forming the administration zone of the ionic drug shown in FIG. 14 of the present invention described above is, for example, that of the second embodiment of FIG. Easy to understand from things. For this reason, illustration of the iontophoresis device (X) of the sixth embodiment is omitted.
[0114]
13 to 14, an insulating part (shield part), that is, the (mn) zone shown in FIG. 10 should be shown at the boundary between each administration zone and the ground (earth) zone. For clarity, the (mn) zone is omitted.
[0115]
The iontophoresis devices (X) of the fifth to sixth embodiments capable of forming the administration zone and the ground (earth) zone shown in FIGS. 13 to 14 set the width of each administration zone as desired. Thereby, the advantage that the penetration degree (penetration depth from the skin surface) of the ionic drug into the skin can be adjusted.
[0116]
【The invention's effect】
According to the present invention, an iontophoresis device having the following excellent characteristics is provided.
(i) Since the iontophoresis electrode part (working side electrode part) and the ground electrode part (non-working side electrode part) can maintain a stable energized state (current and / or constant voltage) for a long time, The positively (+) or negatively (−) charged drug component of the ionic drug can be efficiently transported (drug delivery) to the skin (or mucosa) at the tophoresis electrode part.
(ii). The iontophoresis electrode part (working side electrode part) and the ground electrode part (non-working side electrode part) contribute to maintenance of the above-described stable energization state and use mode (arrangement of specific ion exchange membrane) Aspect) can eliminate adverse effects on the skin due to electrode reactions (skin irritation, fever, inflammation, etc.).
(iii). Since the iontophoresis electrode part (working side electrode part) and the ground electrode part (non-working side electrode part) are integrated, it is possible for the therapist to take the ground (earth) as in the past. It is released and operability and convenience are improved.
Further, by arranging a plurality of pairs of iontophoresis electrode portions and ground electrode portions having the integrated structure, the penetration degree of the ionic drug into the skin (depth of penetration from the skin surface) and The administration area of the ionic drug can be adjusted as desired.
[Brief description of the drawings]
FIG. 1 is a diagram (schematic perspective view) for explaining the basic configuration of an ion and apparatus (X) according to the present invention.
FIG. 2 is a diagram (schematic cross-sectional view) for explaining the basic configuration of the iontophoresis device (X) of the present invention.
[FIG. 3] Sodium ascorbate (As ^- Na ⁺ FIG. 2 is a diagram for explaining the basic configuration of the iontophoresis device (X) of the present invention that is used when administering).
[FIG. 4] Sodium ascorbate (As ^- Na ⁺ It is a figure explaining the other basic composition of the iontophoresis apparatus (X) of this invention used when administering).
FIG. 5 is a schematic view of a first experimental apparatus (apparatus to be compared with the present invention) for testing the iontophoresis effect.
FIG. 6 is a schematic view of a second experimental apparatus (apparatus to be compared with the present invention) for testing the iontophoresis effect.
FIG. 7 is a schematic view of a third experimental apparatus (apparatus according to the present invention) for testing the iontophoresis effect.
FIG. 8 is a schematic view of a fourth experimental apparatus (apparatus according to the present invention) for testing the iontophoresis effect.
FIG. 9 is a diagram illustrating an iontophoresis device (X) according to the first embodiment of the present invention.
FIG. 10 is a diagram for explaining an iontophoresis device (X) according to a second embodiment of the present invention.
FIG. 11 is a diagram for explaining an iontophoresis device (X) according to a third embodiment of the present invention.
FIG. 12 is a diagram for explaining an iontophoresis device (X) according to a fourth embodiment of the present invention.
FIG. 13 is a view for explaining an iontophoresis device (X) according to a fifth embodiment of the present invention.
FIG. 14 is a view for explaining an iontophoresis device (X) according to a sixth embodiment of the present invention.
[Explanation of symbols]
X …………… IONTOFORESE
1 …………… Iontophoresis electrode
11 ………… Electrode material
12 ………… Conductive medium
13 ………… Ion (cation) exchange membrane
14 ………… Ionic drugs
15 ………… Ion (anion) exchange membrane
2 …………… The ground electrode unit integrated with the iontophoresis electrode unit (1)
21 ………… Electrode material
22 ………… Conductive medium
23 ………… Ion (cation) exchange membrane
3 …………… Power supply
31, 32 ... Lead wire
4 …………… Skin
5 …………… Gauze impregnated with conductive liquid
a …………… The outer cylinder on the iontophoresis electrode (1) side
a1 …………… Support for ion exchange membrane (13)
a2 …………… Container for ionic drug (14)
a3 …………… Support for ion exchange membrane (15)
a31 ......... Pressure ring for ion exchange membrane (15)
a32 ……………… Fixing pin
a4 …………… Electrode plate (21) and conductive medium (22) housing
a5 …………… Support for ion exchange membrane (23)
a51, a52 …………… Press ring for ion exchange membrane (23)
a53 ……………… Fixing pin
a6, a7 ... Holding member
b …………… Inner cylinder on the iontophoresis electrode (1) side
b1 …………… Pressing part for ion exchange membrane (13)
b2 …………… Container for conductive medium (12)
b3 …………… Support for electrode plate (11)
b4 …………… Guide hole for lead wire (31)
b5 …………… Support for lead wire (31)
b6 …………… Top disc part
c …………… Intermediate tube on the iontophoresis electrode (1) side
m1 to mX ……………… Ionic drug administration zone
n1-nX ............ Ground (earth) zone

Claims (5)

In an iontophoresis device having an iontophoresis electrode part (working side electrode part) and a ground electrode part (non-working side electrode part) connected to a power source used for administering an ionic drug by iontophoresis,
(1) The iontophoresis electrode portion is
(1) -1. Electrode material connected to a power source of the same polarity as the charged ion of the ionic drug, (1) -2. Conductive medium disposed at least on the front surface of the electrode material
(1) -3. An ion exchange membrane that selects ions opposite to the charged ions of the ionic agent disposed on the front surface of the conductive medium;
(1) -4. An ionic drug disposed on the front surface of an ion exchange membrane that selects ions opposite to the charged ions of the ionic drug, and
(1) -5. Composed of an ion exchange membrane that selects ions of the same type as the charged ions of the ionic drug disposed in front of the ionic drug, and
(2) The ground electrode portion is adjacent to the iontophoretic electrode portion and is integrally formed,
(2) -1. An electrode material having a polarity opposite to the electrode material of the iontophoresis electrode part,
(2) -2. A conductive medium disposed on at least the front surface of the electrode material; and
(2) -3. An ion exchange membrane that selects ions opposite to the charged ions of the ionic agent disposed on the front surface of the conductive medium, and “(2) -2. Between “at least the conductive medium disposed on the front surface” and “(2) -3. Ion exchange membrane for selecting ions opposite to charged ions of the ionic drug disposed on the front surface of the conductive medium” Having an ion exchange membrane that selects ions opposite to the ion exchange membrane;
An iontophoresis device characterized by this.   The iontophoresis device according to claim 1, wherein the conductive medium of the iontophoresis electrode portion and the ground electrode portion is configured to include a substance that is easily oxidized or reduced.   The iontophoresis according to claim 2, wherein the conductive medium of the iontophoresis electrode portion and the grant electrode portion is composed of a solution containing ferrous sulfate and ferric sulfate as a substance that is easily oxidized or reduced. apparatus.   The iontophoresis device according to claim 2, wherein the conductive medium of the iontophoresis electrode portion and the ground electrode portion is composed of a solution containing an organic acid and / or a salt thereof as a substance that is easily oxidized or reduced.   `` (2) -3. Ion conversion membrane that selects ions opposite to charged ions of ionic agent arranged on the front surface of the conductive medium '' of the ground electrode part is `` (1) 5. An ion exchange membrane that selects ions of the same kind as charged ions of an ionic drug disposed on the front surface of the ionic drug, and is disposed at a level that is substantially flush with the ion exchange membrane. Iontophoresis device.

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