JP2004245818A - Absorber for diagnosis and absorbent article - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an absorber, an absorbent sheet and an absorbent article capable of diagnosing by coloring used for health examination and disease diagnosis of animals or human being. <P>SOLUTION: This absorber and this absorbent article include an absorber for animal diagnosis including a water-absorbing resin A and a diagnostics M; an absorber for diagnosis including a specific derivative a1 of an aliphatic unsaturated mono-carboxylic acid as A and, if necessary, one or more kinds of monomers a2 selected from a group comprising unsaturated anionic monomers, unsaturated cationic monomers and salts thereof as constitutive monomers; an absorber for diagnosis comprising at least 40 wt.% water-absorbing resin and 25 ppm-2.5 wt.% diagnostics M based on the weight of A, wherein M is carried by a support or coated with a water-soluble or water-decayable coating material; an absorber for diagnosis including the water-absorbing resin and a diagnostics M0 for an antigen-antibody reaction; and an absorbent sheet for diagnosis having a water-absorbing resin layer and a labeled antibody My, or the like. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

ただし、ろ過水量（ｇ）＝｛Ｆ０（ｇ）＋Ｗ０（ｇ）｝−ＦＷ（ｇ）であり、２５±１℃の水の比重としては、１．０００（ｇ／ｍＬ）の値を使用する。
【００４９】
（Ｃ）は、（Ｍｙ）もしくは（Ｍｘ）と、体液中の（ｘ）もしくは（ｙ）とが抗原抗体反応することによって生成した結合体［以下、標識結合体と称し（Ｍｘｙ）と略記する］と未反応の（Ｍｙ）または（Ｍｘ）とを分離するＢ／Ｆ分離層である。
（Ｃ）には、未反応の（Ｍｙ）もしくは（Ｍｘ）と反応する固定化抗原（ｆｘ）または固定化抗体（ｆｙ）を有するＢ／Ｆ分離層（Ｃ１）（以下（Ｃ１）ともいう）、および分離層の孔径の大きさにより（Ｍｘｙ）を分離するＢ／Ｆ分離層（Ｃ２）（以下（Ｃ２）ともいう）が含まれる。好ましいのは（Ｃ１）である。（Ｃ１）には、通常、支持体の表面もしくは内部に、診断しようとする体液中の（ｘ）もしくは（ｙ）と同じ種類の（ｘ）もしくは（ｙ）が固定化されている。支持体の形状および材質は上記の（Ｂ１）または（Ｂ２）で挙げた支持体と同様のものが例示され、好ましいものは、紙（例えば濾紙）などのシート状物、および粒状吸水性樹脂とパルプなどからなるシート状物である。
（Ｃ１）に固定化されている（ｘ）または（ｙ）の量は、支持体の層状物の単位表面積当たり、好ましくは０．１ｎｇ／ｃｍ^２〜５００ｍｇ／ｃｍ２、とくに１ｎｇ／ｃｍ^２〜２５０ｍｇ／ｃｍ^２であり、（Ｂ）に担持されている（Ｍｘ）または（Ｍｙ）の量よりも多い［例えば、（Ｂ）に担持されている量の１．２〜１０倍、好ましくは１．５〜５倍］ことが好ましい。
支持体に（ｘ）または（ｙ）を固定化する方法としては、物理的に吸着させる方法と化学反応で結合させる方法が挙げられる。物理吸着の例としては、タンパク質と吸着性の高い支持体、例えばセルロースのエステル化物（セルロースアセテート等のシート）に（ｘ）を物理吸着させる方法、化学反応の例としては、支持体（例えばニトロセルロース等のシート）をγ−アミノプロピルエトキシシランでシリル化後、Ｎ−スルホサクシニミジル−４−（Ｎ−マレイミドメチル）シクロヘキサン−１−カルボキシレートを結合し、さらに（ｘ）に存在するアミノ基と架橋反応する方法等が挙げられる。
（Ｃ２）としては、シート状またはフィルム状であって、分画分子量が（Ｍｘｙ）の分子量よりも小さく、未反応の（ｘ）または（ｙ）の分子量よりも大きいものが好ましい。 （Ｃ２）の分画分子量は好ましくは１０，０００〜３００，０００、とくに３０，０００〜２００，０００であり、（Ｃ２）の分画分子量と（Ｍｘｙ）の分子量との差、または分画分子量と未反応の（ｘ）または（ｙ）の分子量との差の絶対値が５，０００以上が好ましい。
（Ｃ２）としては、市販されているもの［例えば、Ｄｉａｆｌｏ ＵＭシリーズ（Ａｍｉｃｏｎ社）、ウルトラフィルター Ｑシリーズ（アドバンテック東洋社）等］も使用できる。
（Ｃ）の透水速度は吸収性シート中での抗原抗体反応率に関係する。例えば、吸収性シートの最下部に（Ｃ）を配し、最上部に検体液を滴下した場合、（Ｃ）の透水速度が遅いほど、（ｘ）または（ｙ）が（ｆｙ）または（ｆｘ）と接触できる回数が増加し、反応率が高まり、（Ｃ）での分離度が増加する。ただし、透水速度が極めて遅くなると分離した液の浸出速度が低下し、測定に要する時間が長くなる。
（Ｃ）は、好ましくは０．０１〜３ｍＬ／分、とくに０．０５〜２．５ｍＬ／分の透水速度（２５℃、１気圧）を有する［測定法は上記の（Ｂ）の場合と同じ］。
この範囲であれば、Ｂ／Ｆ分離が行われ易く、かつ診断速度も速い。
【００５０】
本発明の吸収体は、さらに発色剤層（Ｄ）（以下（Ｃ）ともいう）、ＯＦおよび／またはＵＦなどから構成されていてもよい。
（Ｄ）に担持される（ｄ）としては、前述のものが挙げられ、支持体としては、上記の（Ｂ１）または（Ｃ）で例示した形状および材質と同様のものが例示される。好ましいものも同様である。
（ｄ）の担持量は、支持体の単位表面積当たり、好ましくは１００ｆｍｏｌ／ｃｍ２〜５００ｍｍｏｌ／ｃｍ２、とくに１ｐｍｏｌ／ｃｍ２〜５０ｍｍｏｌ／ｃｍ２である。
担持の方法としては、上記（Ｃ１）で例示した（Ｍｙ）または（Ｍｘ）を基材に担持させる方法と同様の方法が例示できる。
（Ｄ）による診断は、（Ｍｙ）または（ｘ）が（Ｄ）に到達後に発色反応させ、発色強度を目視や装置（分光分析器等）にて観察または測定して行う。発色反応は、（Ｄ）に発色反応に関わる全ての試薬を担持させておき後処理なしに発色させる方法（ｄ１）、（Ｄ）へ（Ｍｙ）または（ｘ）の到達後に発色に関わる試薬の一部を後添加し発色させる方法（ｄ２）のいずれでもよい。
（ｄ１）の場合の（Ｄ）には、（ｄ）の他、前述の発色助剤を同時に担持させてもよい。 発色助剤の量は（ｄ）の担持量と同重量〜１／１００が好ましい。（ｄ２）の場合は、（Ｄ）を取り出して、発色助剤を噴霧、塗布、浸漬または滴下などして発色反応を実施してもよい。発色強度の観察または測定は、発色反応後の（Ｄ）を元の位置に固定したまま実施してもよいし、取り出して実施してもよい。
必要により使用されるＯＦおよびＵＦとしては、前述のＯＦと同様のものを使用することができる。
【００５１】
本発明の第５の態様における吸収性シートにおける必須構成材料のうち（Ｂ）および（Ｃ）の順序は、通常、体液が供給される側（以下、体液側と称する）に（Ｂ）が配置され、その外側に（Ｃ）が配置されている。 また、（ＡＬ）の位置は、好ましくは（Ｂ）のさらに体液側、（Ｂ）と（Ｃ）の間、（Ｃ）の外側、およびこれらの位置の２種以上の併用でもよい。
本発明の第５の態様における吸収性シートは、（ＡＬ）、（Ｂ）、（Ｃ）および必要により（Ｄ）のそれぞれの層を上記の順に積層してから目的の大きさに裁断するか、またはそれぞれの層の好ましい大きさと形状の層を製造してから、それぞれの層を積層または接着することにより製造できる。
【００５２】
本発明の第５の態様における吸収性シートによる診断の例を図１〜図３において説明する。
図１に示される吸収性シートは、吸水性樹脂層（ＡＬ）、標識抗体（Ｍｙ）を担持した層（Ｂ１）および固定化抗原（ｆｘ）を有するＢ／Ｆ分離層（Ｃ１）から構成される。
図１の吸収性シートに、抗原（ｘ）を含む尿（Ｕ）が接触すると、図２に示されるように（Ｕ）が浸透する。浸透した（Ｕ）は（ＡＬ）で一部が吸収されるが、一部は（Ｂ１）に浸透して、（Ｍｙ）を遊離させ、尿中の（ｘ）と（Ｍｙ）とが反応し、（Ｍｘｙ）が生成する。
一部に未反応の遊離の（Ｍｙ）を含む（Ｕ）は、図３に示されるようにさらに浸透して（Ｃ１）に到達した状態となる。
ここで、遊離したままの（Ｍｙ）は、（ｆｘ）と反応して（Ｃ１）に固定化される。一方、（Ｍｘｙ）は、もはや（ｆｘ）と反応しないので（Ｃ１）を通過する。
従って、（Ｃ１）を通過して出てくる（Ｍｘｙ）の濃度は、（Ｕ）中の（ｘ）の濃度と相関することになる。従って、（Ｍｘｙ）の濃度を発色剤法などで測定することにより診断可能になる。
【００５３】
図４に示される吸収性シートは、前述の図１の層にさらに発色剤層（Ｄ）、表面フィルム（ＯＦ）および裏面フィルム（ＵＦ）から構成される。
図５に示される吸収性シートは、標識抗体（Ｍｙ）を吸水性樹脂（Ａ）に担持した層（Ｂ２）、固定化抗原（ｆｘ）を有する層（Ｃ１）、（ＯＦ）および（ＵＦ）から構成される。
図６に示される吸収性シートは、図４の構成における（Ｃ１）の代わりに孔径の大きさによって分離する（Ｃ２）を使用した構成である。
本発明の診断用吸収性シートは、そのまま、排泄物処理材として用いることができる。
また、吸収性シートの上に吸水性樹脂と繊維状物からなるペレット状排泄物処理材、（例えば特開平７−３２７５３６号公報に記載のもの）もしくは砂等からなる公知の排泄物処理材などを積層（穴の開いた板状物もしくは網状物を介して積層されていてもよい）または散布してもよい。
【００５４】
診断用吸収性物品
本発明の紙おむつ、ペット用トイレ、簡易トイレ、携帯トイレ、生理用ナプキン、失禁者用パットおよび傷口シートは、前述の吸収材もしくは吸収性シートと、トレイ、袋および／またはびん等を用いて構成されるものであり、診断用吸収性物品である。
本発明のペット用トイレは、（１）トレイ等の上に猫砂をのせたもの、（２）トレイやビニールシートの上に前述の尿シートを載せたもの、さらに（１）と（２）を組み合わせたもの（トレイの上に尿シートを敷き、その上に底面が網状になったトレイを載せ、さらにその上に猫砂を載せた複合型のトイレなど）が挙げられる。
紙オムツは、吸収体に、腹部、腰部、大腿部や股間への密着性を高めるためにギャザー等を取り付け、ずり落ち防止のために装着用テープ等を取り付けたものが挙げられる。ギャザー及び装着用テープ等の材質及び種類は特に限定されず、従来の紙オムツに用いられている公知のものが使用できる。
なお、吸収性シートまたは吸収性物品による診断は、必要により（ＯＦ）もしくは（ＵＦ）の一部を開閉可能な構造としておいてフィルムを開けて色の変化を確認して診断する。
【００５５】
本発明の吸収性シートおよび吸収性物品は、陸棲動物および／または人間に使用できるものであり、例えばペットおよび家畜などの飼育される動物、特に哺乳類および鳥類用として好適に使用できる。
哺乳類のうち、ペットとしては、イヌ、ネコ、ウサギ、サル、ハムスター、フィレット、タヌキおよびリスなど、家畜としてはウマ、ウシ、ヒツジ、ブタなど、その他の飼育される哺乳類としてはイノシシ、キツネ、シカ、ラクダ、ゾウおよびキリンなどがあげられる。
鳥類のうち、ペットとしては、カナリア、インコ、ハト、文鳥およびウグイスなど、その他の飼育される鳥類としてはニワトリ、カモ、ウ、タカおよびカラスなどがあげられる。
人間用としては、子供用（新生児用、乳児用、幼児用を含む）および大人用（老人用を含む）があげられる。
本発明の診断用吸収性シートまたは吸収性物品を使用して診断することにより、上記の動物および人間の体調の変化、妊娠の有無、疾病の有無・進行状況などを確認することが可能であり、対象となる疾病および体調の変化としては、癌（胃癌、大腸癌、肺癌、肝癌、甲状腺癌、乳癌、子宮癌、尿路系癌、卵巣癌、前立腺癌等）、感染症、ステロイド剤の服用、腎尿路腫瘍、無症候性細菌症、抗生物質投与およびホルモン異常等があげられる。
【００５６】
以下に実施例を挙げて本発明をさらに説明するが、本発明はこれに限定されるものではない。
【００５７】
実施例１；尿比重測定用吸収材（第１の態様の吸収材）
吸収材の作製：
０．０２Ｍリン酸緩衝液（ｐＨ７）５００ｍＬに、ＢＴＢ０．５ｇおよびポリアクリル酸（Ｍｗ＝１０，５００）２．５ｇを溶解させて診断薬溶液を作成した。
吸水性樹脂「アクアパールＡＰ２１１ＤＳ」（アクリル酸を主体としたポリマー、サンダイヤポリマー株式会社製：吸水能＝６００倍、吸収速度＝４０秒、Ａｂ−Ｌ＝１０ｇ／ｇ、Ｄａｖ＝２１０μｍ、顆粒状）１００ｇに上記溶液の全量を添加し、ガラス棒でよくかき混ぜた後、５０℃で−０．０５ＭＰａで２４時間減圧乾燥をした。乾燥後、部分的にブロッキングしている箇所を、ガラス棒にて粉砕し、吸収材を得た（ブロッキング箇所の粉砕は、以下の実施例および比較例においても同様に行った）。吸収材のＤａｖを測定したところ２１３μｍであり、顆粒状であった。
【００５８】
標準色見本の作成：
浮き秤り式比重計で測定した比重１．００５の犬の尿に食塩を適量加えて、比重１．０１０、１．０２０、１．０２５および１．０３０の標準尿を作成した。それぞれの標準尿２５ｇを上記の吸収材（作成１時間後の吸収材）５ｇに添加したものを作成し標準色見本とした。比重１．００５の見本は緑色であり、比重が増加するに従って、黄色味が増した。色見本は容積７０ｍＬのフタ付きのガラスビン中に保存した（以下において、色見本は全て同様の容器に保存した）。
【００５９】
尿比重の測定：
８検体の犬の尿のそれぞれ２５ｇに上記の吸収材を５ｇ添加した試料について、色見本と見比べて、比重を目視判定した。
判定は、例えば試料の色が比重１．０１５と比重１．０２０の色見本の中間にある場合には、色調を観察して０．００１刻みで比重を決定した。判定は３人が行い平均値を比重とした。
発色速度は、尿を添加してから発色が完了するまでを目視で確認し、所要時間を測定した。
また、発色完了後に上記吸収材を開放状態で静置し、比重の読み値が０．０１０変化するまでの時間を測定し、発色持続性を評価した。
一方、上記８検体の犬の尿について、浮きばかり式比重計で比重を測定した。本発明の吸収材で測定した比重と浮きばかり式比重計で測定した比重の相関係数は０．８７（ｎ＝８）であり良好な相関関係が得られ、本発明の吸収材によって尿比重が測定できることが実証できた。結果を表１に示す。
【００６０】
【表１】

【００６１】
比較例１；
吸収材の作製：
「アクアパールＡＰ２１１ＤＳ」の代わりに、「サンフレッシュＡＴ−３０」（アクリルアミドを主体としたポリマー、三洋化成工業株式会社製：吸水能＝４５倍、吸収速度＝１００秒、Ａｂ−Ｌ＝７ｇ／ｇ、Ｄａｖ＝１２００μｍ、破砕状）を使用したこと以外は実施例１と同様にして、吸収材（Ｄａｖ＝１２１０μｍ、破砕状）を作成した。また、該吸収材を用いたこと以外は実施例１と同様にして色見本を作成し、さらに該吸収材を用いたこと以外は実施例と同様にして犬の尿の比重を測定した。
しかし、実施例１と比較して発色速度が遅く、発色が不安定であり、持続性に劣ることが判明した。
比較例の吸収材で測定した比重と浮きばかり式比重計で測定した比重の相関係数は０．６３（ｎ＝８）であり相関関係が低く、比較例の吸収材によっては精度の高い尿比重が測定できないとがわかった。
結果を表２に示す。
【００６２】
【表２】

【００６３】
実施例２；ブドウ糖測定用吸収材（第１の態様の吸収材）
吸収材の作製：
０．０２Ｍリン酸緩衝液（ｐＨ６）５ｍＬに、グルコースオキシダーゼ（Ａｓｐｅｒｇｉｌｌｕｓ ｓｐ．由来、１００ｕ／ｍｇ）１０ｍｇとペルオキシダーゼ（Ｈｏｒｓｅｒａｄｉｓｈ由来、４５０ｕ／ｍｇ）１０ｍｇを溶解し酵素溶液を作成する。
「アクアパールＡＰ２１１ＤＳ」１００ｇに、ｏ−トリジン５重量％メタノール溶液１０ｇを全量添加し、ガラス棒でよくかき混ぜた後、２５℃で−０．０５ＭＰａで１時間減圧乾燥をした。その後、赤外線水分計を用いて１０５℃で乾燥し、乾燥減量率が０．０７％であることを確認した。さらに、部分的にブロッキングしている箇所があれば、ガラス棒にて粉砕し、撹拌下に上記酵素溶液５ｍＬをスプレーした後、２５℃で−０．０５ＭＰａで２４時間減圧乾燥を実施し吸収材−１（Ｄａｖ＝２１２μｍ：顆粒状）を得た。赤外線水分計にて該吸収材の乾燥減量率を測定し、水分が１．２０％であることを確認した。
また、この吸収材に水を添加し、水分を６．５％にした吸収材−２（Ｄａｖ＝２１５μｍ：顆粒状）を作製した。
【００６４】
標準色見本の作成：
尿試験紙「Ｐｒｅｔｅｓｔ」（Ｗａｋｏ Ｐｕｒｅ Ｃｈｅｍｉｃａｌ Ｉｎｄ．，Ｌｔｄ．）でブドウ糖陰性（−）の猫の尿にＤ−グルコースを溶解して１００、２５０、５００、１０００および２０００ｍｇ／ｄＬの標準尿を作成した。それぞれの標準尿は、ブドウ糖（±）尿、ブドウ糖（＋）尿、ブドウ糖（２＋）尿、ブドウ糖（３＋）尿、ブドウ糖（４＋）尿とした。それぞれの標準尿２５ｇ（標準尿作成後５時間経過したものを使用、特に限定しない限り以下の標準尿においても同様）を上記のブドウ糖測定用吸収材−１または吸収材−２の５ｇ（吸収材作成後１時間経過したものを使用、特に限定しない限り以下の吸収材においても同様）に添加したものを作成し色見本とした。ブドウ糖濃度が高くなるに従い、青味が増した。
【００６５】
ブドウ糖含量測定：
８検体の猫の尿のそれぞれ２５ｇに上記のブドウ糖測定用吸収材−１または吸収材２を５ｇ添加した試料について、色見本と見比べて、ブドウ糖濃度を上記の（−）〜（４＋）の６段階に区分けして目視判定した。
判定は３人で実施し、それぞれの判定結果を平均化（例えば、（＋）、（＋）、（２＋）の場合には（＋）と判定）してそれぞれの検体のブドウ糖濃度とした。なお、発色速度は、尿を添加してから発色が完了するまでを目視で確認し、所要時間を測定した。
また、発色完了後に上記吸収材を開放状態で静置し、発色後のブドウ糖の判定値から１段階以上変化するまでの時間を測定し、発色持続性を評価した。
一方、上記８検体の猫の尿について、「Ｐｒｅｔｅｓｔ」でブドウ糖濃度を測定し、６段階判定を行った。
本発明の吸収材で測定したブドウ糖濃度と尿試験紙で測定したブドウ糖濃度は８検体とも一致し、本発明の吸収材によってブドウ糖濃度が測定できることが実証できた。結果を表３および表４に示す。
【００６６】
【表３】

【００６７】
【表４】

【００６８】
また、上記の吸収材−１および吸収材−２の作製後、５℃または５０℃で３ヶ月間に保存した吸収材を使用したこと以外は、上記と同様にしてブドウ糖濃度を測定した。結果を表５および表６に示す。
【００６９】
【表５】

【００７０】
【表６】

【００７１】
本発明の吸収材は、５℃保存では３ヶ月後でも経日変化が少なく、十分に測定できることがわかったが、５０℃保存では水分が少ない方が経日変化が少なく好ましいことがわかった。
【００７２】
比較例２；
吸収材の作成：
「アクアパールＡＰ２１１ＤＳ」の代わりに、「サンフレッシュＡＴ−３０」を使用したこと以外は実施例２と同様にして、吸収材（但し、水分１．１％：Ｄａｖ＝１２００μｍ）および色見本を作成し、実施例２と同様にして猫の尿のブドウ糖濃度を測定した。
しかし、発色速度のばらつきが大きく、発色が不安定であり、経時的（数分経過後）に退色する場合もあった。
比較例の吸収材で測定したブドウ糖濃度と尿試験紙で測定したブドウ糖濃度は８検体のうち６検体しか一致せず、比較例の吸収材では精度の高いブドウ糖濃度が測定できないとがわかった。
結果を表７に示す。
【００７３】
【表７】

【００７４】
また、比較例の吸収材を使用したこと以外は、実施例２と同様にして５℃または５０℃で３ヶ月間に保存した吸収材を使用してブドウ糖濃度を測定した。結果を表８に示す。
【００７５】
【表８】

【００７６】
実施例３；タンパク測定用吸収材（第２の態様の吸収材）
吸収材の作製：
吸水性樹脂「サンフレッシュＡＴ−０３」（アクリルアミドを主体としたポリマー、（ａ１）含量は９０−９９重量モル％の範囲内、三洋化成工業株式会社製）をミキサー（三菱電機製、ＪＭ−Ｋ３１）にて１０分間粉砕し、２４２μｍ金網を通過し、１０９μｍ金網に残る粒状物を回収しサンフレッシュ−０３細粒品（吸水能４０倍、Ｄａｖ＝１８５μｍ、ｐＨ４−９のの中和滴定による酸当量０．９ミリ当量／ｇ）を得た。クエン酸１１．７ｇ、クエン酸２水素カリウム１１．５ｇ、およびＴＢＰＢ９．５ｇを５０ｇの水に溶解した診断薬溶液とＤａｖ＝３６０μｍのシリカパウダー１０ｇを、サンフレッシュ−０３細粒品１００ｇに添加し、ガラス棒でよくかき混ぜた後、５０℃で−０．０５ＭＰａで２４時間減圧乾燥し吸収材（吸水性樹脂部分のＤａｖ＝２４５μｍ、シリカパウダー部分のＤａｖ＝３６３μｍであった）を得た。
【００７７】
標準色見本の作成：
「Ｐｒｅｔｅｓｔ」でタンパク陰性（−）のウシ尿にウシアルブミンを溶解して１５、３０、１００および１０００ｍｇ／ｄＬの標準尿を作成した。それぞれの標準尿は、タンパク（±）尿、タンパク（＋）尿、タンパク（２＋）尿およびタンパク（３＋）尿とした。それぞれの標準尿２５ｇを上記の吸収材５ｇに添加したものを作成し色見本とした。タンパクが存在すると黄色から緑色に変色し、タンパク濃度が高くなるに従い、緑味が増した。
【００７８】
タンパクの測定：
８検体のウシ尿のそれぞれ２５ｇに上記の吸収材を５ｇ添加した試料について、色見本と見比べて、タンパク濃度を上記の５段階に区分けして目視判定した。
判定は、実施例２と同様にして行った。
一方、上記８検体のウシ尿について、「Ｐｒｅｔｅｓｔ」でタンパク濃度を測定し、５段階判定を行った。
本発明の吸収材で測定したタンパク濃度と尿試験紙で測定したタンパク濃度は８検体とも一致し、本発明の吸収材によってタンパク濃度が測定できることが実証できた。結果を表９に示す。
【００７９】
比較例３；
吸収材の作製：
「サンフレッシュ−０３」の代わりに、「サンフレッシュＡＴ−３０」（ｐＨ４〜９の中和滴定による酸当量９．７ミリ当量／ｇ）を使用したこと以外は実施例３と同様にして、吸収材および色見本を作成し、実施例３と同様にしてウシ尿のタンパク濃度を測定した。
しかし、比較例の吸収材で測定したタンパク濃度と尿試験紙で測定したタンパク濃度は８検体のうち５検体しか一致せず、さらに尿試験紙で陰性であった尿を擬陽性に、擬陽性であった尿を陽性に判定する場合が認められた。比較例の吸収材では信頼性の高いタンパク濃度が測定できないとがわかった。
結果を表９に示す。
【００８０】
【表９】

【００８１】
実施例４；潜血測定用吸収材（第３の態様の吸収材）
吸収材の作製：
クメンヒドロペルオキシド１ｇをメタノール２５ｇに溶解し、Ｄａｖ＝３６０μｍのシリカパウダー５ｇに添加し、減圧乾燥機にて２５℃、−０．０５ＭＰａで１時間乾燥し、クメンペルオキシド担持シリカパウダーを作成した。その後、水５０ｇを添加し攪拌し十分に分散させ、水溶性デンプン（「パインフローＳ」松谷化学（株）製）１５ｇを添加した。さらに、メタノールを５ｇ添加して１分間攪拌を行う操作を１０回繰り返し、メタノールを全量で５０ｇ添加した。メタノールの添加量が増えるにつれて、水溶液中に溶解していたデンプンが不溶化し、シリカパウダー表面に吸着した。該分散液をろ紙（東洋ろ紙、Ｎｏ．２）でろ過し、固形分を回収し、減圧乾燥機にて５０℃、−０．０５ＭＰａで１日乾燥し、過酸化物被覆粒状物（Ｄａｖ＝９４５μｍ、顆粒状）を作成した。
「アクアパールＡＰ２１１ＤＳ」４５ｇと吸水性樹脂「アクアパールＤＳ−５０Ｔ」（サンダイヤポリマー株式会社製：吸水能＝６００倍、吸収速度＝４８秒、Ａｂ−Ｌ＝１２ｇ／ｇ、Ｄａｖ＝３５０μｍ）５５ｇ（吸水性樹脂として合計１００ｇ）に、ｏ−トリジン５％メタノール溶液１０ｇを全量添加し、ガラス棒でよくかき混ぜた後、２５℃で−０．０５ＭＰａで１時間減圧乾燥をした。これに、上記の過酸化物被覆粉体を添加・混合し、吸収材（Ｄａｖ＝２１３μｍの顆粒状吸水性樹脂、Ｄａｖ＝３５４μｍの顆粒状吸水性樹脂およびＤａｖ＝９４５μｍの顆粒状過酸化物被覆との混合物）を得た。
【００８２】
標準色見本の作成：
「Ｐｒｅｔｅｓｔ」で潜血陰性（−）の人尿に、正常人血から血漿部分を除去して得られたヒトヘモグロビンを溶解して０．０６、０．１５、０．７５ｍｇ／ｄＬの標準尿を作成した。それぞれの標準尿は、潜血（＋）尿、潜血（２＋）尿、潜血（３＋）尿とした。それぞれの標準尿２５ｇを上記吸収材（作成１時間後の吸収材）５ｇに添加したものを色見本とした。潜血濃度が高くなるに従い、青味が増した。
【００８３】
潜血測定：
８検体の人尿のそれぞれ２５ｇに上記の吸収材を５ｇ添加した試料について、標準色見本と見比べて、潜血濃度を上記の４段階に区分けして目視判定した。 判定は、実施例２と同様にして行った。
一方、上記８検体の人尿について、「Ｐｒｅｔｅｓｔ」で潜血濃度を測定し、４段階判定を行った。
本発明の吸収材で測定したによる潜血濃度と尿試験紙で測定した潜血濃度は８検体とも一致し、本発明の吸収材によって潜血濃度が測定できることが実証できた。結果を表１０に示す。
なお、発色速度は、尿を添加してから発色が完了するまでを目視で確認し、所要時間を測定した。
また、ドライ感は次の方法で評価した。ポリエチレン製フィルム（５ｃｍ×５ｃｍ）の上に吸収紙（５ｃｍ×５ｃｍ）を配し、その上に尿添加後の吸収材を高さ２ｍｍになるように敷き、その上にポリエチレン製フィルム（５ｃｍ×５ｃｍ）とポリプロピレン製不織布（５ｃｍ×５ｃｍ）をこの順に載せた（全体の厚さは２．５ｍｍ）。不織布の上から触感判定にてドライ感を評価した。３人が以下の５段階評価で評価し、平均値を求めた。
評点１；軽く触るだけで液が浮いてくる
評点２；軽く触ると濡れた感じがあり、強く触ると液が浮いてくる。
評点３；軽く触るとわすかに湿っぽく、強く触ると濡れた感じがする。
評点４；軽く触っても湿った感じは無いが、強く触ると湿っぽい感じ。
評点５；強く触っても湿った感じが無く、トライ感良好。
【００８４】
【表１０】

【００８５】
比較例４；
吸収材の作成：
「アクアパールＡＰ２１１ＤＳ」１００ｇを用いて実施例４と同様の方法でｏ−トリジンを含有する吸水性樹脂の乾燥物を得た後、クメンヒドロペルオキシド１ｇをメタノール２５ｇに溶解した液を添加し、ガラス棒でよくかき混ぜた後、２５℃で−０．０５ＭＰａで１時間減圧乾燥し、潜血測定用吸収材（Ｄａｖ＝２１４μｍ、顆粒状）を得た。
該吸収材を用いたこと以外は実施例４と同様にして色見本を作成し、さらに該吸収材を用いたこと以外は実施例４と同様にして人尿の潜血濃度を測定した。
比較例の吸収材を用いて、実施例４の測定法で測定した潜血濃度と尿試験紙で測定した潜血濃度は８検体とも一致したが、ドライ感が実施例の吸収材より劣ることが判明した。結果を表１１に示す。
【００８６】
【表１１】

【００８７】
また、実施例および比較例の吸収材を作成後１ヶ月間、５０℃で静置した後、上記と同様の潜血測定を行った。結果を表１２に示す。
【００８８】
【表１２】

【００８９】
表１２から、本発明の吸収材は、１ヶ月後でも経日変化が少なく、十分に測定できることのに対して、比較例の吸収材は作成時には十分測定できるが、１ヶ月後は、経日変化が激しいために測定できないことが判明した。
【００９０】
実施例５［第５の態様の抗原測定用吸収性シート：ヒト尿中のβ２−マイクログロブリンの測定］
吸収性シートの作製：
図７は、実施例５の吸収性シートの一部の断面図であり、各構成材料は以下の通りである。
表面フィルム（ＯＦ）：厚さ１００μｍのポリエチレンテレフタレート不織布（１５ｃｍ×４５ｃｍ）。
吸水性樹脂層（ＡＬ）：「アクアパールＤＳ−５０Ｔ」１２ｇと日本薬局方脱脂綿（川本産業株式会社製）１２ｇとを外観上均質となるまで、混合しながら手で約５００回解繊した。 その後、解繊した混合物を１５ｃｍ×４５ｃｍの大きさに積繊した後、ＮＰＡシステム（株）製ヒータプレートプレス機（型番Ｎ４００８−００）を用い、５０℃において、８Ｋｇ／ｃｍ^２で３０秒間プレスした。
標識抗体担持層（Ｂ１）：ろ紙（Ｎｏ．２、アドバンテック社製、５ｍｍ×５ｍｍに裁断したもの）一枚を、下記（Ｍｙ）のリン酸緩衝液溶液に含浸（２５℃、３０分間）させた後、ろ紙を取り出し、乾燥（２５℃、２時間、−７５５ｍｍＨｇ）したもの。
リン酸緩衝液中の（Ｍｙ）の濃度は３００μｇ／ｍｌ、ｐＨ７、０で．１％牛血清アルブミンを含む。
標識抗体（Ｍｙ）：ペルオキシダーゼ標識抗β２−マイクログロブリンポリクローナル抗体。
Ｍｙの作製は、抗β２−マイクログロブリンポリクローナル抗体（ダコジャパン社製）および西洋ワサビ由来ペルオキシダーゼ（東洋紡社製）を用い、文献［エス・ヨシタケ、エム・イマガワ、イー・イシカワ、エトール；ジェイ．バイオケム，Ｖｏｌ．９２（１９８２）１４１３−１４２４］に記載の方法で作製した。
Ｂ／Ｆ分離層（Ｃ１）：メンブレンフィルター（混合セルロースエステル型、孔径０．３μｍ、直径４７ｍｍ、アドバンテック社製）を抗原β２−マイクログロブリン（ＳＩＰＡＣ社製）のリン酸緩衝液溶液（抗原濃度５μｇ／ｍｌ、ｐＨ７、０．１％牛血清アルブミンを含む）に２５℃で１時間浸漬後、シートを取り出し、乾燥（２５℃、−７５５ｍｍＨｇで３時間）させたもの。
発色剤層（Ｄ）：ろ紙（Ｎｏ．２、アドバンテック社製、直径２０ｍｍに裁断したもの）一枚をｏ−トリジンのメタノール溶液（０．１％（ｗ／ｗ））に２５℃で５分間浸漬後、ろ紙を取り出し、乾燥（２５℃、−７５５ｍｍＨｇで３０分間）させたもの。
裏面フィルム（ＵＦ）：厚さ４０μｍのポリプロピレンフィルム（１５ｃｍ×４５ｃｍ）、
上記の構成材料を用いて以下の様に加工を施し吸収性シートを作製した。
まず、ＯＦの下に（ＡＬ）を配し、この下に（ＡＬ）の中心に位置するように（Ｂ１）と（Ｃ１）をこの順に配し、中心に直径２０ｍｍの穴の開いたＵＦを配し、この穴の中に、（Ｄ）を配した後、さらに、円周に沿って５ｍｍの幅で両面テープを貼り付けた直径５０ｍｍのＵＦにて穴をふさいだ。
上記の各層を重ねあわせたもの（１５ｃｍ×４５ｃｍの四辺形）の四辺を各１ｃｍ幅で熱プレスして診断用吸収体とした。
発色助剤液： リン酸−クエン酸緩衝液（ｐＨ５．０）に過酸化水素を０．０２重量％含有させた溶液。
試験した検体：ヒトの尿を試験直前に２０検体入手した。
標準尿の作成：人工尿（尿素２０．０ｇ、ＮａＣｌ８．０ｇ、ＭｇＳＯ４・６Ｈ２Ｏ０．８ｇ、ＣａＣｌ２・２Ｈ２Ｏ０．３ｇにイオン交換水を加え、１０００ｇとしたもの）に、β２−マイクログロブリンを、それぞれ０、２０、４０、６０、８０、１００、１２０、１４０、１６０、１８０および２００ｎｇ／ｍｌの濃度になるように添加・調整した。
試験方法：
検体８０ｍｌを２００ｍｌビーカーにとり、ビーカーの口が上記吸収性シートに接するようにして除々に傾けながら、５ｍｌ／秒の速度で流下させた。
全量流下させてから５分後に、ＵＦをはがし、（Ｄ）に発色助剤液を塗布し、発色後シートとした。上記の操作を２０検体のヒトの尿について実施した。また、標準尿についても同様の試験を行い発色反応を実施し、β２−マイクログロブリン濃度に対応した標準発色後色シートを作製した。検体から得られた発色後シートの発色強度と標準発色後シートの発色強度を目視にて比較し、
最も近い標準発色後シートのβ２−マイクログロブリン濃度を検体中のβ２−マイクログロブリン濃度とした。
本発明の吸収性シートを用いたβ２−マイクログロブリン濃度の測定結果を表１３に示す。
【００９１】
従来法でのβ２−マイクログロブリン濃度の測定：
実施例５で使用したヒトの尿２０検体について、グラザイムβ２−Ｍｉｃｒｏｇｌｏｂｕｌｉｎ−ＥＩＡ ＴＥＳＴ（発売元：和光純薬工業）を用いてβ２−マイクログロブリンの濃度の測定をした。
測定手順を以下の通りである。
検体を緩衝液（試薬は全てキットに付属）にて１１倍希釈し、試験管に２０μｌとり、抗体ビーズ１個入れた後、３７℃で１時間静置加温し、アスピレータで反応液を除去した。さらに３ｍｌの緩衝液で洗浄（注入→振とう→吸引除去）を２回行い、抗体ビーズを新しい試験管に移して、基質発色液５００μｌを加え、３７℃で３０分間静置加温した。酵素反応停止液を３ｍｌ添加し、よく混和後、４９２ｎｍにて吸光度を測定した。別途、標準抗原液を用いて上記と同様の操作にて吸光度測定を実施し、検量線を作成した後、検体濃度の算出を行った。
従来法でのβ２−マイクログロブリン濃度の測定値を表１３に示す。
なお、いずれの方法においてもβ２−マイクログロブリン濃度が１００ｎｇ／ｍｌ以下であれば通常尿と判定し、１００ｎｇ／ｍｌを越える場合は高含有尿（異常である可能性が高い）と判定した。
判定結果を表１３に示した。
【００９２】
【表１３】

【００９３】
本発明の方法および従来の方法での測定結果は良好な相関関係（相関係数＝０．９１）が認められた。
【００９４】
実施例６［第５の態様の抗原測定用吸収性シート：ヒト血清中のβ２−マイクログロブリンの測定］
診断用吸収性シートおよび発色助剤液は実施例５と同様のものを使用した。
【００９５】
標準血清の作成：
生理食塩水に、β２−マイクログロブリンを加え、０〜０．２２μｇ／ｍｌの間で０．０１μｇ／ｍｌづつ濃度を変えた標準血清を調製した。
【００９６】
試験用検体：
ヒトの血清を２０検体入手した。試験には、血清をリン酸緩衝液（０．０２Ｍ、ｐＨ７．０）で２０倍希釈したものを試験用検体として使用した。
【００９７】
試験方法：
標準尿のかわりに標準血清を使用し、検体として尿のかわりに上記の試験用検体を使用する以外は実施例５と同様の方法で測定した。なお、発色後シートの発色強度判定から求めた試験用検体のβ２−マイクログロブリン濃度を２０倍したものを、元の検体のβ２−マイクログロブリン濃度とした。
【００９８】
従来法でのβ２−マイクログロブリン濃度の測定：
上記のヒトの血清２０検体（緩衝液にて希釈する前のもの）について、グラザイムβ２−Ｍｉｃｒｏｇｌｏｂｕｌｉｎ−ＥＩＡ ＴＥＳＴ（発売元：和光純薬工業）を用いてβ２−マイクログロブリンの濃度の測定をした。
本発明の吸収性シートによる方法および従来法での測定結果を表１４に示した。
なお、いずれの方法においてもβ２−マイクログロブリン濃度が１．８μｇ／ｍｌ以下であれば通常血清と判定し、１．８μｇ／ｍｌを越える場合は高含有血清（異常である可能性が高い）と判定した。
【００９９】
【表１４】

【０１００】
本発明の方法と従来法のβ２−マイクログロブリン濃度測定値は良好な相関関係（相関係数＝０．８８）が認められた。
【０１０１】
【発明の効果】
本発明の診断用吸収材、吸収性シートまたは吸収性物品を使用して診断することにより、動物および人間の体調の変化、妊娠の有無、疾病の有無・進行状況などを確認することが可能であり、ガンの診断にも有効である。また、本発明の診断用吸収材、吸収性シートまたは吸収性物品は、動物または人間の体液がこれらの材料に浸透してからの発色速度が速いのですぐに診断でき、さらに、発色の持続性（経時的な色調の安定性）が良好である。さらに吸収材の経日安定性が良好であることから、長期間保存後の吸収材でも使用できるという利点を有する。
【図面の簡単な説明】
【図１】尿Ｕおよび本発明の診断用吸収性シートの一部の断面を模式的に示した図である。ＡＬは吸水性樹脂層、Ｂ１は標識抗体を坦持した層、Ｃ１はＢ／Ｆ分離層である。
【図２】尿ＵがＡＬ層、Ｂ１層に浸透した吸収性シートの一部の断面を模式的に示した図である。
【図３】尿Ｕが浸透してＢ／Ｆ分離層Ｃ１に到達した吸収性シートの一部の断面を模式的に示す図である。
【図４】吸収性シートの一部の断面を模式的に示した図である。
【図５】吸水性シートの一部の断面を模式的に示した図である。
【図６】吸水性シートの一部の断面を模式的に示した図である。
【図７】実施例５および６で作製した吸収性シートの一部の断面図である。
【符号の説明】
ＡＬ 吸水性樹脂層
Ｂ１ 標識抗体担持層
Ｂ２ 標識抗体を担持した吸水性樹脂層
Ｃ１ Ｂ／Ｆ分離層
Ｃ２ 孔を有するＢ／Ｆ分離層
Ｄ 発色剤層
Ｍｙ 標識抗体
Ｍｘｙ 標識結合体
Ｐ 孔
Ｕ 尿
ＯＦ 表面シート
ＵＦ 裏面シート
ｘ 抗原
ｙ 抗体
ｆｘ 固定化抗体[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an absorbent material for diagnosis of animals or humans, more specifically, an absorbent material, an absorbent sheet, and a diagnostic absorbent comprising the same, which can be used for health diagnosis of animals or humans, disease diagnosis, pregnancy test and the like. Related to sexual products.
[0002]
[Prior art]
Conventionally, a urine test test material in which a urine test agent is contained in a water-absorbent resin having a water absorption amount of 10 to 550 g per 10 g (see Patent Document 1), and discoloration on the inner surface of the diaper depending on components in urine. A urine test diaper characterized by impregnation with a reaction reagent has been proposed (see Patent Document 2).
[0003]
[Patent Document 1] Japanese Patent Application Laid-Open No. 11-295306
[Patent Document-2] JP-A-2001-289845
[0004]
[Problems to be solved by the invention]
However, the conventional urine test materials and urine test diapers have the problems that the speed until color development is slow and the color development is short-lived.
[0005]
[Means to solve the problem]
The present inventors have conducted intensive studies and as a result, by using a specific water-absorbent resin, or by using an absorbent having a specific configuration, the color development speed is high, the color persistence
A long absorbent was found and led to the present invention. That is, the present invention relates to a [first aspect] an animal diagnostic absorption, which comprises a water-absorbent resin (A) and a diagnostic agent (M), wherein (A) has a water absorption capacity of at least 60 times its own weight. [Second embodiment] a water-absorbent resin (A) and a diagnostic agent (M), wherein the absorbent resin (A) is an amidated aliphatic unsaturated monocarboxylic acid and an alkylene oxide adduct, and their adducts An acid or base containing 2 or more meq / g or less as determined by neutralization titration at pH 4 to 9, containing one or more monomers (a1) selected from the group consisting of alkylated products and alkyl etherified products. [Third embodiment] at least 40% by weight of water-absorbent resin (A) and 25 ppm to 2.5% by weight of diagnostic agent based on the weight of (A) (M), where (M) is the support A diagnostic absorbent comprising a supported or coated with a water-soluble or water-disintegrable coating material, and a mixture of (A) and the supported or coated (M); [Fourth embodiment] water-absorbent resin (A ) And a diagnostic agent for antigen-antibody reaction (M0) (hereinafter also referred to as (M0)), and a [fifth embodiment] the following (1) or (2) and a B / F separation layer (C), a diagnostic absorbent sheet having;
(1) a water-absorbent resin layer (AL) and a layer (B1) supporting a labeled antibody (My) or a labeled antigen (Mx); or
(2) A layer (B2) in which the labeled antibody (My) or the labeled antigen (Mx) is supported on the water absorbent resin (A).
[0006]
BEST MODE FOR CARRYING OUT THE INVENTION
Water absorbent resin (A)
The water-absorbing resin (A) that can be used in the present invention is a hydrophilic cross-linked polymer that can absorb 10 to 2,000 times its own weight of water.
These polymers usually have hydrophilic groups such as carboxylic acid (salt) groups (ie, carboxyl and / or carboxylate groups), sulfonic acid (salt) groups, phosphoric acid (salt) groups, and tertiary amino groups. A quaternary ammonium base, a hydroxyl group or a polyethylene oxide group. Preferred (A) include the following.
(1) A starch-acrylic acid (salt) graft-crosslinked copolymer described in JP-B-53-46199.
(2) Crosslinked polyacrylic acid (salt) obtained by aqueous solution polymerization (adiabatic polymerization, thin film polymerization, spray polymerization, etc.) described in JP-A-55-133413.
(3) Crosslinked polyacrylic acid (salt) obtained by reversed-phase suspension polymerization described in JP-B-54-30710, JP-A-56-26909 or JP-A-11-5808.
(4) Saponified products of a copolymer of a vinyl ester and an unsaturated carboxylic acid or a derivative thereof described in JP-A-52-14689 or JP-A-52-27455.
(5) Copolymers of acrylic acid (salt) and sulfonic acid (salt) group-containing monomer described in JP-A-58-2312 or JP-A-61-36309.
(6) A crosslinked isobutylene-maleic anhydride copolymer described in U.S. Pat. No. 4,389,513.
(7) A hydrolyzate of a starch-acrylonitrile copolymer described in JP-A-46-43995.
(8) A crosslinked carboxymethylcellulose derivative described in US Pat. No. 4,650,716.
(9) Water-swellable polyurethane, and a mixture of the polyurethane and ordinary rubber.
[0007]
Of these (A), preferred is a water-absorbing agent having a water-absorbing capacity of at least 60 times, more preferably 60 to 1,000 times, particularly 80 to 1,000 times, especially 100 to 1,000 times the own weight. Resin (A1) (hereinafter also referred to as (A1)), and amidated aliphatic alkylene oxide or alkylene oxide adduct (a11) (hereinafter also referred to as (a11)) and alkylated or alkyl etherified product thereof One or more monomers (a1) (hereinafter also referred to as (a1)) selected from the group consisting of (a12) (hereinafter also referred to as (a12)), and an unsaturated carboxylic acid, an unsaturated sulfonic acid, It contains, as a constituent monomer, at least one kind of monomer (a2) (hereinafter also referred to as (a2)) selected from the group consisting of saturated phosphoric acid and salts thereof. Eq / g or less, preferably the water-absorbing resin (A2) having an acid or base equivalents which is determined by neutralization titration of 1 meq / g or less of pH4-9 (hereinafter (A2) and also referred to).
As (A1), a starch-acrylic acid (salt) graft crosslinked copolymer and a crosslinked polyacrylic acid (salt) are preferable. (A1) has the advantage that the color development duration after the development of the diagnostic agent is long.
[0008]
Water absorption can be measured in the following way:
0.2 g of (A1) is put into a known tea bag (defined by JIS, K7223) having a size of 20 cm in length and 10 cm in width made of a 250 mesh nylon net, and immersed in 500 mL of ion-exchanged water. After 5 minutes, the tea bag is taken out, the weight is measured, and the weight of the absorbed water is determined. Calculate the water absorption capacity from the following formula.
Water absorption capacity (fold) = [weight of absorbed water (g)] / 0.2 (g) (1)
For example, if it can absorb 60 times its own weight of water, its water absorption capacity is 60 times.
[0009]
(A1) has an absorption rate of preferably 80 seconds or less, particularly 70 seconds or less. An absorption rate of 80 seconds or less is preferable because the time from the start of absorption of body fluid to the color development of the diagnostic agent is short.
The rate of absorption can be measured by the following methods:
50 mL of physiological saline is put in a 100 ml beaker, and the temperature is adjusted to 25 ° C., and then a magnetic stirrer is put in and stirred at 600 rpm. Into this, 2.00 g of (A1) is quickly introduced into the vortex, and at the same time, measurement by a stopwatch is started. The time (seconds) required for the vortex to disappear and the liquid level to become horizontal is defined as the absorption rate.
[0010]
(A1) is preferably 8 to 20 g / g or more, especially 10 to 18 g / g, 40 g / cm for sheet and disposable diaper applications. ² It has an absorption amount under load (hereinafter abbreviated as Ab-L). When Ab-L is 8 to 20 g / g, problems such as liquid return hardly occur. Ab-L can be measured by the method described in U.S. Patent No. 6,156,678.
[0011]
Among (a1) constituting (A2), (a11) includes an amidated product of an aliphatic unsaturated monocarboxylic acid (having 3 to 5 carbon atoms, hereinafter abbreviated as C) [for example, (meth) Acrylamide, crotonic amide] and their alkylene oxide (C2-4) adducts (addition mole number 1 to 200) [1 to 100 mol of ethylene oxide adduct of (meth) acrylic acid, 2 to 50 mol of ethylene oxide of maleic acid Thing etc.].
Examples of (a12) include an alkyl (C1-4) compound [mono or dimethyl (meth) acrylamide, monoisopropyl (meth) acrylamide] of (a11) and an alkyl (C1-4) etherified product of (a11) [(meth) A) Methyl etherified product of 1 to 100 mol ethylene oxide adduct of acrylic acid].
Among (a2), examples of the unsaturated anionic monomer include unsaturated carboxylic acids, unsaturated sulfonic acids, unsaturated phosphoric acids and salts thereof, and the following are exemplified.
Examples of the unsaturated carboxylic acids include the above-mentioned aliphatic unsaturated monocarboxylic acids, C9-12 aromatic monocarboxylic acids [such as cinnamic acid and vinyl benzoate] and C4-12 unsaturated dicarboxylic acids [maleic acid and fumaric acid]. , Itaconic acid and aconitic acid].
Examples of unsaturated sulfonic acids include alkene (C2-6) sulfonic acid [such as vinyl sulfonic acid and (meth) allyl sulfonic acid] and unsaturated aromatic (C6-18) sulfonic acid (styrene sulfonic acid and α-methylstyrene sulfonic acid). Alkenyl and alkyl (C1-18) alkenyl esters of sulfocarboxylic acids (such as α-sulfoalkanoic acid and sulfosuccinic acid) [methylvinyl, propyl (meth) allyl and stearyl (meth) allyl sulfosuccinate, and Meth) allyl sulfollaurate], sulfo (hydroxy) alkyl (C2-6) (meth) acrylate and the corresponding (meth) acrylamide [e.g. sulfoethyl and sulfopropyl (meth) acrylate, 3- (meth) acryloyloxy-2 -Hydroxy Cypropanesulfonic acid, 2- (meth) acrylamide-2-methylpropanesulfonic acid, 3- (meth) acrylamide-2-hydroxypropanesulfonic acid, etc.].
Examples of the unsaturated phosphoric acid include (meth) acryloyloxyalkyl (C2-24) mono- and diphosphate, [2- (meth) acryloyloxyethyl phosphate and phenyl-2- (meth) acryloyloxyethyl phosphate, etc.]. No.
These salts include alkali metal (such as sodium, potassium and lithium), alkaline earth metal (such as calcium and magnesium) salts, ammonium salts, organic amine (such as dimethylamine, trimethylamine, diethanolamine, triethanolamine) salts, and And quaternary ammonium (such as tetramethylammonium) salts.
Among (a2), unsaturated cationic monomers and salts thereof include C3-6 alkenylamines (such as allylamine and crotylamine), unsubstituted or mono- or di-alkyl (C1-6) aminoalkyl ( C2-6) (meth) acrylate or (meth) acrylamide [aminoethyl (meth) acrylate or (meth) acrylamide, dimethylaminoethyl (meth) acrylate or (meth) acrylamide, diethylaminoethyl (meth) acrylate or (meth) acrylamide , Morpholinoethyl (meth) acrylate, and the like], and salts of inorganic acids (such as hydrochloric acid and sulfuric acid) and salts of organic acids (such as carboxylic acids with C1-12: acetic acid and propionic acid).
[0012]
(A2) has an acid or base equivalent of less than 2 meq / g, preferably less than 1 meq / g, as determined by neutralization titration at pH 4-9. When it is 2 meq / g or less, the diagnostic accuracy of the diagnostic agent (M), particularly the pH diagnostic agent (M1) and the protein diagnostic agent (M2) described below is improved.
The acid or base equivalent of pH 4 to 9 can be measured as follows.
A 0.5 g sample of the water-absorbent resin is precisely weighed, and 1000 mL of ion-exchanged water is added and stirred for 30 minutes. Then, 3% (hereinafter, unless otherwise specified,% represents% by weight) aqueous hydrogen chloride solution is added dropwise to adjust the pH to 3-4. Using a potentiometric titrator, titration is performed using an N / 10 NaOH aqueous solution, and the number of titration mL from pH 4 to pH 9 is read and calculated by the following equation (2).
Acid or base equivalent = (f × AmL) / (10 × S) (2)
(F is a factor of N / 10 NaOH, AmL is a titration mL number, and S represents the weight (g) of the water-absorbing resin.)
Preferred among (A2) are 90 to 100 mol%, especially 100 mol% of units of (a1), 0 to 10 mol%, especially 0 mol% of units of (a2), and 0.01 to 3 mol. % Of the unit (b).
[0013]
The crosslinkable monomer (b) is a compound having 2 to 4 or more functional groups capable of reacting with (a1) or (a2), and is a bis (meth) acrylamide, a di- or polyunsaturated carboxylic acid of a polyol. Acid esters, and di or poly (meth) allyl ethers of polyols, and the compounds described in US Pat. No. 5,728,792.
[0014]
The water absorption capacity of (A2) (the measurement method is the same as that of (A1)) is preferably 10 to 1000 times, more preferably 15 to 800 times.
[0015]
The shape of (A) is granular (spherical, granular, crushed, etc.), needle-like, flake-like, block-like, agglomerated form in which granular primary particles are fused together, and foam-like. , Flakes and aggregates.
[0016]
When (A) is granular or aggregated, when the absorbent described below is used as cat sand, the particle size of 90% or more of (A) is preferably 1 to 850 μm, Particularly, it is 3 to 500 μm. This range is preferable because the absorption rate is particularly high.
When the absorbent sheet described below is used as a urine sheet for dogs, 90% or more of (A) is preferably 38 to 1180 µm, particularly 63 to 1000 µm. If it is 38 μm or more, gel blocking is less likely to be generated in the sheet when it comes into contact with an aqueous solution, and the absorption rate is improved. If it is 1180 μm or less, the surface area per volume of the absorbent does not decrease, and the absorption rate is reduced. Tends to be faster.
[0017]
The size of the granular or agglomerated (A) was measured using a low tap test sieve shaker and a sieve specified in JIS Z8801-2000, Perry's Chemical Engineers Handbook, 6th edition (Mac Glow Hill). Book Company, 1984, p. 21) (hereinafter, the particle size is measured by this method).
[0018]
The average particle size (weight average particle size, hereinafter abbreviated as Dav) is used as (A) for use in absorbent articles for humans (diapers, urine absorbing pads, etc.). A mixture of two types of particles (hereinafter the same) is preferable because it can achieve both an absorption rate and prevention of return of water after water absorption.
The water-absorbent resin (A ′) having a smaller Dav (hereinafter also referred to as (A ′)) preferably has a Dav of 50 to 400 μm, particularly 100 to 350 μm, and mainly contributes to the absorption rate. If it is 50 μm or more, gel blocking is unlikely to occur, and if it is 400 μm or less, the surface area increases and the absorption rate tends to improve. The water-absorbent resin (A ″) having a large Dav (hereinafter also referred to as (A ″)) preferably has a Dav of 410 to 750 μm, particularly 450 to 650 μm. If it is 410 μm or more, the return of water after water absorption tends to be small, and if it is 750 μm or less, it is easy to exhibit sufficient water absorption capacity. The weight ratio of (A ′) :( A ″) is usually (3: 7) to (7: 3), preferably (4: 6) to (6: 4).
[0019]
When (A) is used as an absorbent in combination with the occult blood diagnostic agent (M4) described below (hereinafter also referred to as (M4)), the stability of the peroxide contained in (M4) is determined over time. For the purpose of keeping, the content of the water-soluble inorganic salt based on the weight of (A) is preferably 2% or less, more preferably 1% or less, especially 0.3% or less. Examples of the inorganic salt include catalyst residues [sulfate (sodium sulfate, potassium sulfate) and sulfite (sodium sulfite, potassium sulfite)], and other inorganic salts (salt, calcium chloride, magnesium chloride, and the like).
The operation of reducing the inorganic salt is, for example, adding (A) to a large amount of ethanol / water = 1/1 (weight ratio), stirring sufficiently, filtering through a nylon net (for example, 250 mesh), and removing the filtration residue. Can be achieved by adding a large amount of the same solvent to the mixture and repeating the same operation several times.
[0020]
The inorganic salt content can be measured as follows.
2.0 g of (A) was added to 1 L of ethanol / water = 1/1 (weight ratio) at 25 ° C., and the mixture was gently stirred for 30 minutes, then filtered through a 250 mesh nylon net, and further filtered. 1 L of the same solvent is added, and the same operation is repeated four times. About 5 L of the obtained solvent is concentrated to 500 mL by an evaporator, and anion and cation groups are quantified by an ion chromatography device, and the total is defined as the inorganic salt content.
[0021]
Diagnostic (M)
(M) includes a qualitative or quantitative component to be detected in a body fluid (urine or blood), or a diagnostic agent that diagnoses by measuring a characteristic value of urine.
In the present invention, the “diagnostic agent” includes a part or all of the reagents involved in the diagnosis, that is, a compound that reacts with a component in a body fluid, and a label and / or a color former as necessary.
[0022]
(M) includes the following.
pH diagnostic agent (M1): For example, methyl red / bromthymol blue (BTB) (in the following, / represents a combination).
Protein diagnostic agent (M2): For example, tetrabromophenol blue (TBPB) / citric acid / potassium dihydrogen citrate (for measuring albumin content).
Glucose diagnostic agent (M3) (hereinafter also referred to as (M3)): For example, glucose oxidase / peroxidase / color former (potassium iodide, o-tolidine, 3-amino-6-chloro-9-dimethylaminopropylcarbazole hydrochloride, 2 , 7-diaminofluorine dihydrochloride or N- (3-sulfopropyl) -3,3 ', 5,5'-tetramethylbenzidine).
Occult blood diagnostic agent (M4): For example, cumene hydroperoxide / o-tolidine, citrate buffer / 2,5-dimethylhexane-2,5-dihydroperoxide / tetramethylbenzidine, cumenehydroperoxide / tetramethylbenzidine hydrochloride salt.
Pyrirubin diagnostic agent (M5): For example, 2,4-dichloroaniline, 2,6-dichlorobenzeneazonium tetrafluoroborate, or 2-trifluoromethylbenzenediazonium tetrafluoroborate.
Urobilinogen diagnostic agent (M6): For example, p-dimethylaminobenzaldehyde, 4-methoxybenzenediazonium tetrafluoroborate, 3,4-methylenedioxybenzene-1-diazonium tetrafluoroborate or 4-fluoro-3 -Nitrobenzenediazonium trifluoromethylsulfonate.
Nitrite diagnostic agent (M7): For example, N- (1-naphthyl) ethylenediamine dihydrochloride, 3-hydroxy-1,2,3,4-tetrahydro-7,8-benzoquinoline, or N- (1-naphthyl) Amino) -3-propanesulfonic acid.
Leukocyte diagnostic agent (M8): For example, indoxycarboxylic acid ester.
Specific gravity diagnostic agent (M9): for example, BTB / methoxyethylene maleic anhydride copolymer, or BTB / polyacrylic acid.
Amylase diagnostic (M10): eg carboxymethyl starch / remazol dye.
Ascorbic acid diagnostic agent (M11): For example, methylene green / neutral red, 2,6-dichlorophenol sodium indophenol.
Salt diagnostic agent (M12): for example, silver chloride / 2,7-dichlorofluorescein.
Ketone body diagnostic agent (M13): For example, sodium nitroprusside dihydrate.
[0023]
(M0) is a reagent for diagnosing a disease utilizing an antigen-antibody reaction, and is an antibody (y) (hereinafter also referred to as (y)) or an antigen (x) (hereinafter referred to as (x)) immobilized on a support. ) Binds to (x) or (y) in the body fluid to form a conjugate, and the conjugate further includes a labeled antibody (My) (hereinafter also referred to as (My)) or a labeled antigen (Mx) (hereinafter (Mx)). Mx)), and a so-called two-site sandwich based on the principle that the label can be diagnosed by a change in the color of the label or, if necessary, the label can be colored by a coloring agent (d) and diagnosed by the degree of color development. A diagnostic agent using a measuring method is exemplified.
[0024]
(X) and (y) include the antigens and antibodies described in US Pat. No. 5,073,485.
Among (x), preferred are protein-related substances, particularly CEA, TPA, polyamine, β2-microglobulin, IAP, γ-GTP, FDP, amylase, α1 antitrypsin, esterase, hemoglobin from the viewpoint of simplicity of measurement. , Amylase, albumin, globulin and NAG; and hormone-related substances, especially HCG, E3 and FDP.
Preferred among (y) are IgA and microglobulin.
The type of labeling substance that can be used differs depending on the diagnostic method, and examples thereof include those described in US Pat. No. 5,073,485. Preferred are chemiluminescent substances, and especially enzymes, latexes and metals.
[0025]
For example, when the labeling substance is a chemiluminescent substance (e.g., acridinium ester, N-aminobutyl-N-ethylisoluminol (ABEI), etc.), the dialyzed antigen may be combined with the labeling substance (x). A method of reacting a solution with a sulfonate (JP-A-05-340946) can be mentioned.
[0026]
For example, when the labeling substance is an enzyme (for example, peroxidase, alkaline phosphatase, glucose oxidase, β-D-galactosidase, etc.), the enzyme and N-succinimide-4- ( After reacting (N-maleimidomethyl) cyclohexane-1-carboxylate, fractionating with an ion exchange resin to obtain maleimide peroxidase, and fractionating with a gel filtration column (Biochemical Experiment Method 27, Enzyme) Labeling method (Eiji Ishikawa: Gakkai Shuppan Center)).
When the labeling substance is latex (for example, SBR latex), 0.5 mg of the antibody is added to a buffer solution (pH 7.0 to 9.0), dissolved, and 10% latex particles (usually 0.3 to 0.5 μm) are dissolved. After adding 0.5 mL and reacting (for example, at 25 ° C. for 1 hour), centrifugation (for example, 5 ° C., 10,000 rpm, 30 minutes) is performed, and the sediment is stabilized with a stabilizing agent (Block Ace (Dainippon Pharmaceutical Co., Ltd.) )) To prepare a 0.2% latex-labeled antibody.
When the labeling substance is a metal (for example, a method using colloidal gold), a method reported by Slot & Geuze (Eur. J. Cell Biol., 38, 87, 1985) can be mentioned.
The binding amount and binding ratio of the labeling substance are usually 70 to 100% based on the number of moles of the labeled antibody.
[0027]
When the label is an enzyme, (d) for coloring the label is required, and (d) includes a redox color former [orthotrizine, 1,2-phenylenediamine, etc.], a fluorescent reagent [4-hydroxy] Phenylacetic acid, 3- (4-hydroxyphenyl) propionic acid, etc.), a bioluminescent reagent [2-nitrophenyl.beta.-D-galactoside, luciferin and its derivatives], and a chemiluminescent reagent [luminumol and its derivatives (N- Aminobutyl-N-ethylisoluminol, etc.)]. The amount of (d) is usually 100 to 10,000,000 times based on the equivalent of the label.
The diagnosis according to (d) is performed by spraying, applying, dipping, or dropping a coloring aid to form a color, and observing or measuring the coloring intensity visually or with a device (such as a spectroscopic analyzer).
In addition to (d), as a coloring aid, a reagent relating to a coloring reaction such as an oxidizing agent (eg, peroxide) or an enzyme (eg, luciferase, glucose-6-phosphate dehydrogenase) may be used at the same time.
The weight ratio of the coloring aid to (d) is preferably from 1/1 to 1/100.
[0028]
Diagnostic absorber
The diagnostic absorbent of the present invention is composed of (A), (M) and, if necessary, other constituent materials.
The shape of the absorbent is granular (spherical, granular, crushed, etc.), needle-like, flake-like, block-like, or agglomerated form in which primary particles are fused to each other. Agglomerated is preferred.
As for the size of the absorbent, the major axis and the minor axis are usually 5 to 20,000 μm, preferably 15 to 10,000 μm.
[0029]
The absorbent material of the present invention comprises (A) and an absorbent material (M) supported thereon; and a water-soluble or water-degradable coating material supported on a support other than (A). An absorbent composed of (M) and (A) is included.
In the present invention, "support" means that (M) is present on the surface of the support and, if necessary, inside the support, and "coating" means that (M) is present only inside the support. To indicate that
Of the components (M), the components to be carried or coated may be all components of the components (M), or may be some components of the components (M).
For example, in the case of (M0), a method of spraying or applying (My) and (d) at the time of diagnosis / determination, a method of carrying (y) and coating A method of spraying or applying (d) at the time of diagnosis / determination, and a method of carrying (y), coated (My) and (d) And a method of forming a material.
The absorbent material in which (M) or a part of (M) is coated with a coating material is excellent in that storage stability can be enhanced as compared with an absorbent material in which all of (M) is supported on a support. This is particularly preferable when (M) contains an enzyme or a peroxide.
[0030]
Examples of the support other than (A) include the following fibers, granules and chips.
The fibers include natural fibers, man-made fibers and synthetic fibers, and mixtures thereof, and regenerated fibers thereof, and examples thereof include the following.
Natural fibers [cotton, absorbent cotton, fibrous sawdust, straw, peat, wool, microfibrils, bacterial cellulose, hardwood bleached kraft pulp (LBKP), softwood bleached kraft pulp (NBKP), flat pulp and other waste materials (eg, disposable diaper production) Waste materials)], artificial fibers [rayon and acetate, etc.], synthetic fibers [polyolefin fibers (polyethylene fiber, polypropylene fiber, polyethylene-polypropylene composite fiber, etc.), polyester fibers (polyethylene terephthalate fiber and polyethylene terephthalate / polyethylene isophthalate). Composite fiber, etc.), polyolefin / polyester fiber (polyethylene / polyethylene terephthalate fiber, polypropylene / polyethylene terephthalate fiber) , Polyamide fibers (polyterephthalic acid ethylene diamide fiber, polyisoterephthalic acid ethylene diamide fiber, polyterephthalic acid propylene diamide fiber, polyisoterephthalic acid propylene diamide fiber, etc.), polyacrylic fiber (polybutyl acrylate fiber and polyacrylic acid 2) -Ethylhexyl fiber etc.) and polyacrylonitrile fiber etc.].
Among these, preferred are natural fibers and synthetic fibers, more preferred are natural fibers, particularly cotton, absorbent cotton and fibrous sawdust from the viewpoint that the strength of the absorbent is easily provided, and most preferred is pulp or disposable diaper. Waste from the production of
Further, the granular material includes an inorganic granular material and an organic granular material, and the inorganic granular material is preferable.
Examples of the composition of the inorganic particles include oxides (silicon oxide, aluminum oxide, iron oxide, titanium oxide, magnesium oxide, and zirconium oxide), calcium carbonate, kaolin, talc, mica, bentonite, clay, sericite, carbon black, Glass (powder and balloon), shirasu, graphite, metal (iron, copper, aluminum and gold, etc.), zeolite and asbestos, and the like.
Two or more of these may be used in combination, or two or more of these may be combined. Of these, preferred are silicon oxide, aluminum oxide and titanium oxide, and more preferred are silicon oxide and aluminum oxide, particularly amorphous silicon oxide.
The inorganic particles include porous inorganic particles (P1) and nonporous inorganic single particles (P2).
Examples of the porous inorganic particles (P1) include hollow, porous, petal, aggregated, and granulated particles.
The preferred Dav of the porous inorganic particles (P1) is 0.1 μm to 1000 μm. The preferred Dav of the porous inorganic particles (P2) is 0.003 to 0.07 μm, and more preferably 0.01 to 0.054 μm.
Examples of the organic particulates include particulates made of natural, semi-synthetic, or synthetic resins other than (A).
Examples of natural resins include mannan, starch, plant mucilage (gum arabic, guar gum, locust bean gum, carrageenan, etc.), seaweed-derived products (sodium alginate, agar (galactan), etc.), and microbial mucilage (dextran, leban, etc.) , Proteins (gelatin, casein, collagen, keratin, etc.), granular sawdust, and the like.
Semi-synthetic resins include cellulose derivatives (viscose, methylcellulose, ethylcellulose, hydroxycellulose, carboxymethylcellulose, carboxymethylethylcellulose, nitrocellulose, cationized cellulose, acetylated cellulose, cellulose acetate, etc.), and starch derivatives (acetylated starch). , Allylated starch, solubilized starch, carboxymethyl starch, dialdehyde starch, oxidized starch, cationized starch, dextrin, etc.), pulp (hardwood bleached kraft pulp (LBKP), softwood bleached kraft pulp (NBKP), flat pulp, etc.) , And the like.
As the synthetic resin, a thermoplastic resin (polyamide resin, polyester resin, polyurethane resin, polyolefin resin, polystyrene resin, acrylic resin, polyvinyl alcohol, polyether resin, etc.) or a thermosetting resin (epoxy resin, urea resin, phenol resin) Etc.) (including powder). Examples of chips include pulp chips and chip-shaped sawdust.
[0031]
The mode of loading of (M) includes physisorption, chemisorption or chemical bonding.
The method for supporting (M) on a support includes the following method.
(1): Powder or liquid (M) is simply mixed with the support.
(2): The support is impregnated with water of (M) or a mixed solvent solution of water and a hydrophilic organic solvent, and then dried.
In each step, if necessary, heating (preferably 30 to 90 ° C.) can promote adsorption or binding.
The absorbent obtained by physical adsorption by the above method (2) is, for example, a mixed solvent of water and a hydrophilic organic solvent (such as methanol, ethanol or acetone) or a pH buffer solution of (M) such as bromthymol blue. Into a solution, (A) is added thereto, and the mixture is gently stirred at room temperature for a certain period of time (usually 1 to 120 minutes) to sufficiently swell (A), and then dried under reduced pressure (40 to 60 ° C). ). The preferred concentration of (M) based on the weight of the solution in the solution is usually 10 ppm to 50%, preferably 50 ppm to 30%.
When a support other than (A) is used, the weight ratio of support / (A) is preferably 95/5 to 55/45, and more preferably 80/20 to 60/40.
[0032]
When all the components of (M) or a part of the components of (M) are coated with a coating material, the coating material may be a water-soluble or water-disintegrable polymer, and micelles, vesicles or liposomes in an aqueous solution. One or more of the amphiphiles that form
Examples of the water-soluble or water-disintegrable polymer include the aforementioned seaweed-derived products, proteins (gelatin, casein, etc.), cellulose derivatives (methylcellulose, ethylcellulose, hydroxycellulose, carboxymethylcellulose, etc.), solubilized starch, polyvinyl alcohol, poly Oxyalkylene oxide and the like.
Examples of the amphiphilic substance include known surfactants (for example, those described in US Pat. No. 4,331,447), as well as biosurfactants such as amino acids, phospholipids and bile salts, and cyclodextrin derivatives. And crown ether derivatives.
As a method of coating, a method of spraying or applying a coating material from the outside of (M) to solidify, and a method of coating (M) in a solvent (water and / or the above-mentioned hydrophilic organic solvent) with vesicles, micelles or micelles of the coating material A method of removing the solvent after trapping in a liposome may be mentioned.
The absorbing material of the third aspect is composed of (A) and (M) supported and / or coated, and includes a mixture of both, and a molded product thereof. The method of mixing may be powder mixing, or liquid mixing in a solvent followed by solvent removal.
[0033]
The absorbent of the present invention may further contain other constituent materials.
Other constituent materials include, for example, the aforementioned fibers, granules and chips.
Other additives include preservatives, fungicides, antibacterial agents, antioxidants, ultraviolet absorbers, coloring agents, fragrances, deodorants and additives described in US Pat. No. 5,743,213. One or more selected ones can be added.
[0034]
The content of each component based on the weight of the absorbent of the present invention is as follows.
(A) is preferably at least 40%, more preferably at least 60%, especially at least 70%.
It is preferable that (A) be 40% or more, since a sufficient diagnostic speed and sufficient water return prevention after water absorption can be maintained.
The content of (M) (however, only those supported or coated) is preferably 1 ppm to 4%, particularly preferably 10 ppm to 1%.
The content of the support other than (A) is 0.1 to 60%, preferably 3 to 50%.
Other constituent materials are 0 to 60%, preferably 5 to 50%.
Other additives are preferably 0.00001 to 10%, particularly preferably 0.00005 to 5%.
The content of (M) based on the weight of (A) is preferably from 2.5 ppm to 10%, more preferably from 25 ppm to 2.5%.
[0035]
As a method for obtaining the absorbent material of the present invention,
(1): (A) carrying (M) [or a mixture of (A) with another support carrying or coating (M)] and, if necessary, other constituent materials and / or other additives described above. (Hereinafter, abbreviated as a substrate including all of them), a method of granulating by adding a small amount of water while mechanically stirring, and
(2): a method of molding a substrate by pressure molding.
[0036]
Examples of devices that can be used in (1) include a Nauta mixer, a ribbon mixer, a conical blender, a mortar mixer, and a universal mixer. Examples of the method of adding water include a method of spraying water onto a substrate, a method of blowing steam, and a method of absorbing moisture while holding the substrate under high humidity. Monohydric alcohol (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohol (ethylene glycol, propylene glycol, glycerin, etc.), polyalkylene (C2-4) glycol (polyethylene glycol, etc.) in water as required , Polyvinyl alcohol and the aforementioned surfactants can be added for the purpose of improving the effect as a binder and the effect of water permeating into the base material and the granulated material.
The amount of water to be added varies depending on the type of the substrate, but is usually 1 to 30%, preferably 2 to 15% based on the weight of the substrate. If the amount of water to be added is 30% or less, the granulated material is not too soft, and the shape of the granulated material is less likely to collapse and the granulated materials are less likely to stick together. On the other hand, if the amount of water to be added is 1% or more, the granulation speed is high and a granulated product having a uniform shape is likely to be obtained.
[0037]
When the diagnostic agent is (M3), the water content is preferably suppressed to 3% or less, particularly 2% or less, for the purpose of stabilizing the enzyme activity for a long period of time. In order to suppress the water content to 3% or less, a method of drying the absorbent under reduced pressure, adding a desiccant such as silica gel, and storing the absorbent in a bag may be used.
[0038]
Examples of the method (2) include a method in which the base material is pressure-formed into a pellet or the like in a mold having an appropriate shape and size, or a method in which the substrate is once formed into a sheet, rod, or block. Then, a method of cutting or pulverizing to a desired size and shape can be mentioned. The pressure molding is usually performed at normal temperature, but may be performed under heating (for example, 30 to 300 ° C.) or humidification (for example, 50 to 100% RH). The pressure at the time of pressure molding can be appropriately selected according to the type, particle size or properties of the substrate, but is usually 1 to 3000 Kg / cm. ² , Preferably 10 to 2,000 kg / cm ² It is. Roll press machines (compacting press, briquetting press, etc.), piston press machines, screw press machines, or perforated extrusion machines are used as press machines. it can.
Among the shapes of the absorbent obtained by molding as described above, spherical, pellet-like, and column-like shapes are preferable.
Among the absorbent materials of the present invention, the absorbent material of the first embodiment is for animal diagnosis, and the absorbent material of the other embodiments is for animal and human diagnosis.
The absorbent of the present invention can be suitably used as it is as an absorbent for animal diagnosis, for example, an absorbent for pets, particularly cat litter.
[0039]
Diagnostic absorbent sheet
The diagnostic absorbent sheet for animals or humans composed of the absorbent material according to the first to fourth aspects of the present invention is selected from the group consisting of the above absorbent material, and further, fibers, nonwoven fabric, paper and synthetic resin film. An absorbent sheet comprising at least one kind.
These absorbent sheets include a single-layer sheet composed of one sheet containing an absorbent and a multilayer sheet composed of 2 to 5 or more layers.
[0040]
As the fiber, the above-mentioned fiber can be used.
As the nonwoven fabric, a nonwoven fabric made of a thermoplastic resin (for example, a polyolefin resin, a polyester resin or a polyolefin / polyester copolymer, etc.), as the paper, a paper (Japanese paper and tissue paper) made of a cellulose fiber, and as the film, A film made of a thermoplastic resin is preferably used.
[0041]
The size of the absorbent sheet is usually 25 to 2500 cm in area. ² , A square, a circle or an ellipse, and the thickness is 0.5 to 50 mm, preferably 1 to 20 mm.
[0042]
Absorbent sheets include, for example, a method of simultaneously mixing and laminating the above-described absorbent material and fibers in an air stream, a method of preliminarily mixing an absorbent material and fibers and laminating the fibers in an air stream, and a method of absorbing fibers on fibers. It can be manufactured by a method of stacking materials and further stacking fibers.
An apparatus used in these methods includes, for example, a drum forming apparatus.
[0043]
The basis weight of (A) contained in the absorbent sheet {content of (A) per unit area of the absorbent sheet} is 10 to 1000 g / m. ² And more preferably 50 to 700 g / m. ² It is.
When the basis weight is in this range, the water retention of the absorbent sheet is increased, and the absorbent sheet tends to exhibit more excellent dryness and moisture resistance under load.
The basis weight of the fibers contained in the absorbent sheet (excluding the fibers contained in the absorbent) is 10 to 1000 g / m ² Is preferred, and particularly preferably 50 to 700 g / m ² It is. The content of the absorbent in the absorbent sheet is preferably 40 to 99.9%, more preferably 62 to 80%, based on the weight of the absorbent sheet. Within this range, the absorbent sheet can be made thinner.
[0044]
A preferred configuration of the absorbent sheet is a configuration in which a liquid-permeable front film (hereinafter abbreviated as OF) and a liquid-impermeable back film (hereinafter abbreviated as UF) are arranged on both sides of the absorbent sheet.
For example, a structure (K1) in which OF is arranged in the uppermost layer, UF is arranged in the lowermost layer, and an absorbent sheet (one layer) made of the above-mentioned absorbent and fiber is arranged as an intermediate layer, and OF is arranged in the uppermost layer UF is disposed on the lowermost layer, and two to four layers of the same absorbent sheet as in the case of (K1) are laminated as an intermediate layer, and one or more kinds of In the structure (K2) provided with a liquid-permeable intermediate film (hereinafter abbreviated as CF), and in the (K1) or (K2) structure, between the uppermost layer and the intermediate layer and / or between the intermediate layer and the lowermost layer. (K3) in which at least one type of CF is disposed (in this case, the diffusivity of the bodily fluid absorbed by the absorbent sheet is easily improved).
Among them, (K3) is preferable from the viewpoint of the leakage of the absorbent from the absorbent sheet.
The OF is not particularly limited as long as the bodily fluid that comes into contact with the absorbent sheet easily penetrates and reaches the absorbent inside. For example, paper made of cellulose fiber (such as Japanese paper and tissue paper), thermoplastic resin A nonwoven fabric, a woven or knitted fabric made of a resin or the like, and a perforated film made of a thermoplastic resin (for example, a polyolefin resin, a polyester resin, or a polyolefin / polyester copolymer) are preferably used. The hole diameter of the perforated film is preferably 0.01 to 1 mm.
The thickness of the OF is preferably 5 to 5000 μm, particularly preferably 20 to 750 μm.
Note that the preferred range of the material, pore diameter, and thickness of CF is the same as that of OF.
The UF is not particularly limited as long as it can prevent the bodily fluid absorbed by the absorbent sheet from seeping out to the back surface. For example, a film made of the above-described thermoplastic resin or the like is used. Among these, a sheet made of polyolefin is preferable, a sheet made of polyethylene, polypropylene or polyethylene / polypropylene is particularly preferable, and a sheet made of polyethylene is particularly preferable. The thickness of the UF is preferably in the same range as the thickness of the above-mentioned OF.
The absorbent sheet of the present invention can be suitably used, for example, as a urine sheet for dogs.
[0045]
The diagnostic absorbent sheet according to the fifth aspect of the present invention is a diagnostic absorbent sheet having the following (1) or (2) and a B / F separation layer (C).
(1) a layer (B1) (hereinafter also referred to as (B1)) in which a water-absorbent resin layer (AL) and (My) or (Mx) are supported on a support;
(2) A layer (B2) carrying (My) or (Mx) on (A) (hereinafter also referred to as (B2)).
[0046]
In the above (1), (AL), (B1) and (C) are all layered, and these layers are laminated to form the absorbent sheet of the present invention.
In the above (1), (AL) is a layered mixture or composite of (A) and the above-mentioned fiber, nonwoven fabric or paper.
In (B1) in the above (1), a labeled antibody carrying layer (BMy) (hereinafter also referred to as (BMy)) in which (My) is carried on a support and a label in which (Mx) is carried on a support An antigen-carrying layer (BMx) (hereinafter also referred to as (BMx)) is included. Among (B1), (BMy) is preferable.
Examples of the material of the support constituting (B1) include the aforementioned fibers, paper (eg, filter paper), nonwoven fabric, synthetic resin, and the aforementioned natural resin. The shape of the support may be any of sheet, powder, granule and fiber. Preferred are sheets, powders and granules.
In the above (2), both (B2) and (C) are layered, and these layers are laminated to form the absorbent sheet of the present invention.
(B2) is obtained by using (A) as a support and carrying (My) or (Mx) on (A).
[0047]
The size of (B) [hereinafter referred to as (B) including (B1) and (B2)] is usually 30 × 30 cm or less, preferably 10 × 10 cm or less, particularly 3 × 3 cm to 1 × 1 cm. And the preferred size and shape are different depending on the type and size of the target human or animal, but it is necessary that (My) or (Mx) be completely released by the body fluid. From a certain viewpoint, it is usually an area smaller than (AL) (for example, an area of 1/5 to 1/100), which is an area where one body fluid of the target animal permeates sufficiently. The thickness is usually 0.1 to 10 mm, preferably 0.1 to 3 mm.
As a method of supporting (My) or (Mx) on a support, water, a buffer (for example, pH 6.8, 0.02 M phosphate buffer), a hydrophilic organic solvent (for example, alcohols such as methanol and ethanol) are used. (My) or (Mx) is dissolved (in a concentration of 100 ppb to 20% by weight) in a mixed solvent of water and a mixed solvent of a buffer and a hydrophilic organic solvent (solvent, ketone solvents such as acetone and methyl ethyl ketone) and water. In advance, a method of mixing with or impregnating the support, drying under reduced pressure or freeze-drying, and the like can be given.
It should be noted that (My) or (Mx) carried on the support is generally released from the support at the same time as the body fluid permeates.
The amount of (My) or (Mx) supported per unit area of the layered body of the support is preferably 0.1 ng / cm. ² ~ 100mg / cm ² , Especially 10ng / cm ² -10mg / cm ² It is.
The ratio of (My) or (Mx) based on the weight of (A) is preferably from 0.1 ppb to 1,000 ppm, more preferably from 1 ppb to 100 ppm.
[0048]
(B) preferably has a water permeation rate (25 ° C., 1 atm) of 0.01 to 3 mL / min, particularly 0.05 to 2.5 mL / min. If the water permeation speed is in this range, the diagnosis speed is high and the diagnosis can be performed with high accuracy.
The water permeation rate can be measured by the following method.
(1) In a room adjusted to a humidity of 65% at 25 ° C., the weight (F0) of the set with (B) sandwiched between filter holders for filtration under reduced pressure <glass type> (manufactured by ADVANTEC, KGS-47) is precisely weighed. (To 1 mg unit), fix the set with a clamp so that the filtration surface is horizontal, and install a receiver (no decompression is performed).
(2) Next, about 300 g (W0) of ion-exchanged water at 25 ± 1 ° C. precisely weighed (to 1 mg unit) is injected from above, and the stopwatch is started.
(3) When 60 minutes have elapsed, water adhering to the lower branch of the filter is quickly wiped off and removed, and the weight (FW) of the filter holder set with unfiltered ion-exchanged water remaining is measured.
(4) The water permeability is calculated by the following equation (3).

However, the amount of filtered water (g) = {F0 (g) + W0 (g)} − FW (g), and the specific gravity of water at 25 ± 1 ° C. is 1.000 (g / mL). .
[0049]
(C) is a conjugate formed by an antigen-antibody reaction between (My) or (Mx) and (x) or (y) in a body fluid [hereinafter referred to as a labeled conjugate and abbreviated as (Mxy). ] And unreacted (My) or (Mx).
(C) includes a B / F separation layer (C1) having an immobilized antigen (fx) or an immobilized antibody (fy) that reacts with unreacted (My) or (Mx) (hereinafter also referred to as (C1)). , And a B / F separation layer (C2) (hereinafter also referred to as (C2)) for separating (Mxy) depending on the size of the pore diameter of the separation layer. Preferred is (C1). Usually, (x) or (y) of the same type as (x) or (y) in the body fluid to be diagnosed is immobilized on (C1) the surface or inside of the support. Examples of the shape and material of the support include those similar to the support described in the above (B1) or (B2), and preferred examples are a sheet-like material such as paper (eg, filter paper) and a granular water-absorbing resin. It is a sheet made of pulp or the like.
The amount of (x) or (y) immobilized on (C1) is preferably 0.1 ng / cm per unit surface area of the layered material of the support. ² ~ 500mg / cm2, especially 1ng / cm ² ~ 250mg / cm ² Which is larger than the amount of (Mx) or (My) carried on (B) [for example, 1.2 to 10 times, preferably 1.5 to 5 times the amount carried on (B)] Times].
Examples of the method of immobilizing (x) or (y) on the support include a method of physically adsorbing and a method of bonding by chemical reaction. Examples of the physical adsorption include a method in which (x) is physically adsorbed on a support having a high adsorptivity to a protein, for example, an esterified product of cellulose (a sheet of cellulose acetate or the like). Sheet of cellulose or the like) is silylated with γ-aminopropylethoxysilane, N-sulfosuccinimidyl-4- (N-maleimidomethyl) cyclohexane-1-carboxylate is bound, and the amino present in (x) And a method of performing a crosslinking reaction with a group.
(C2) is preferably a sheet or film having a molecular weight cut-off smaller than the molecular weight of (Mxy) and larger than the molecular weight of unreacted (x) or (y). The molecular weight cut off of (C2) is preferably from 10,000 to 300,000, particularly from 30,000 to 200,000, and the difference between the molecular weight cut off of (C2) and the molecular weight of (Mxy) or the molecular weight cut off The absolute value of the difference between the molecular weight of the unreacted (x) and (y) is preferably 5,000 or more.
As (C2), commercially available ones (for example, Diaflo UM series (Amicon), Ultrafilter Q series (Advantech Toyo), etc.) can also be used.
The water permeation rate in (C) is related to the antigen-antibody reaction rate in the absorbent sheet. For example, when (C) is arranged at the bottom of the absorbent sheet and the sample liquid is dropped at the top, (x) or (y) becomes (fy) or (fx) as the water permeation rate of (C) is lower. ) Increases the reaction rate, and the degree of separation in (C) increases. However, when the water permeation speed becomes extremely slow, the leaching speed of the separated liquid decreases, and the time required for the measurement becomes longer.
(C) preferably has a water permeation rate (25 ° C., 1 atm) of 0.01 to 3 mL / min, particularly 0.05 to 2.5 mL / min [The measurement method is the same as that of the above (B). ].
Within this range, B / F separation is easily performed, and the diagnosis speed is high.
[0050]
The absorber of the present invention may be further composed of a color former layer (D) (hereinafter also referred to as (C)), OF and / or UF.
Examples of (d) carried on (D) include those described above, and examples of the support include those having the same shape and material as those exemplified in (B1) or (C) above. The same applies to preferred ones.
The supporting amount of (d) is preferably 100 fmol / cm2 to 500 mmol / cm2, particularly 1 pmol / cm2 to 50 mmol / cm2, per unit surface area of the support.
As a method of loading, the same method as the method of loading (My) or (Mx) on the base material exemplified in the above (C1) can be exemplified.
The diagnosis by (D) is performed by causing a color development reaction after (My) or (x) reaches (D), and observing or measuring the color intensity visually or with a device (such as a spectroscopic analyzer). The color-forming reaction is carried out by carrying all the reagents related to the color-forming reaction in (D) and developing the color without any post-treatment (d1), or by using the reagents related to the color-forming after reaching (My) or (x) in (D). Any of the methods (d2) in which a part is added later to form a color may be used.
In the case of (d1) in the case of (d1), in addition to (d), the above-mentioned color-forming auxiliary may be carried simultaneously. The amount of the coloring aid is preferably the same weight to 1/100 as the amount of (d) carried. In the case of (d2), (D) may be taken out and a coloring reaction may be carried out by spraying, applying, dipping or dropping a coloring aid. The observation or measurement of the coloring intensity may be carried out with (D) after the coloring reaction fixed at the original position, or may be taken out and carried out.
The same OF and UF as described above can be used as necessary OF and UF.
[0051]
In the order of (B) and (C) among the essential constituent materials in the absorbent sheet according to the fifth aspect of the present invention, (B) is usually arranged on the side to which the body fluid is supplied (hereinafter referred to as the body fluid side). And (C) is arranged outside thereof. Further, the position of (AL) may preferably be further on the body fluid side of (B), between (B) and (C), outside of (C), or a combination of two or more of these positions.
The absorbent sheet according to the fifth aspect of the present invention is obtained by laminating each layer of (AL), (B), (C) and, if necessary, (D) in the above order, and then cutting the layer to a target size. Alternatively, it can be manufactured by manufacturing a layer having a preferred size and shape of each layer, and then laminating or bonding the respective layers.
[0052]
An example of the diagnosis using the absorbent sheet according to the fifth embodiment of the present invention will be described with reference to FIGS.
The absorbent sheet shown in FIG. 1 includes a water-absorbent resin layer (AL), a layer (B1) supporting a labeled antibody (My), and a B / F separation layer (C1) having an immobilized antigen (fx). You.
When urine (U) containing the antigen (x) comes into contact with the absorbent sheet of FIG. 1, (U) penetrates as shown in FIG. Part of the permeated (U) is absorbed by (AL), but part of it penetrates into (B1) to release (My), and (x) and (My) in urine react with each other. , (Mxy) are generated.
(U) partially containing unreacted free (My) is further permeated to reach (C1) as shown in FIG.
Here, the free (My) is reacted with (fx) and immobilized to (C1). On the other hand, (Mxy) passes through (C1) because it no longer reacts with (fx).
Therefore, the density of (Mxy) coming out through (C1) is correlated with the density of (x) in (U). Therefore, the diagnosis can be made by measuring the concentration of (Mxy) by a coloring agent method or the like.
[0053]
The absorptive sheet shown in FIG. 4 further includes a color former layer (D), a front film (OF), and a back film (UF) in addition to the above-described layers in FIG.
The absorbent sheet shown in FIG. 5 includes a layer (B2) carrying the labeled antibody (My) on the water-absorbent resin (A), layers (C1) having the immobilized antigen (fx), (OF) and (UF). Consists of
The absorbent sheet shown in FIG. 6 has a configuration using (C2) that separates according to the size of the hole diameter instead of (C1) in the configuration of FIG.
The diagnostic absorbent sheet of the present invention can be used as it is as an excrement disposal material.
Also, a pellet-shaped excrement disposal material composed of a water-absorbent resin and a fibrous material on an absorbent sheet (for example, one described in JP-A-7-327536) or a known excrement disposal material composed of sand or the like (May be laminated via a perforated plate or mesh) or may be sprayed.
[0054]
Diagnostic absorbent articles
The disposable diaper, pet toilet, portable toilet, portable toilet, sanitary napkin, pad for incontinent person and wound sheet of the present invention are constituted by using the above-mentioned absorbent or absorbent sheet, tray, bag and / or bottle and the like. It is a diagnostic absorbent article.
The pet toilet of the present invention includes (1) a cat litter placed on a tray or the like, (2) a urine sheet placed on a tray or a vinyl sheet, and further (1) and (2). (A urinal sheet is laid on the tray, a tray with a net-like bottom is placed on the tray, and a cat toilet is placed on top of the tray, etc.).
Examples of the disposable diaper include a disposable diaper in which gathers and the like are attached to the absorber to improve the adhesion to the abdomen, waist, thighs, and crotch, and a mounting tape and the like are attached to prevent slipping. The material and type of the gather and the mounting tape are not particularly limited, and known materials used in conventional paper diapers can be used.
In the diagnosis using an absorbent sheet or an absorbent article, a part of (OF) or (UF) is opened / closed as necessary, and a film is opened to check a change in color.
[0055]
The absorbent sheet and absorbent article of the present invention can be used for terrestrial animals and / or humans, and can be suitably used for breeding animals such as pets and livestock, particularly mammals and birds.
Among mammals, pets include dogs, cats, rabbits, monkeys, hamsters, fillets, raccoons, and squirrels; domestic animals include horses, cows, sheep, and pigs; and other bred mammals include wild boars, foxes, and deer. , Camels, elephants and giraffes.
Among birds, pets include canaries, parakeets, pigeons, birds and warbler, and other bred birds include chickens, ducks, cormorants, hawks and crows.
Human use includes for children (including for newborns, babies, and infants) and for adults (including for the elderly).
By diagnosing using the diagnostic absorbent sheet or absorbent article of the present invention, it is possible to confirm the above-mentioned changes in the physical condition of animals and humans, the presence or absence of pregnancy, the presence / absence / progress of disease, and the like. , The target diseases and changes in physical condition include cancer (stomach cancer, colon cancer, lung cancer, liver cancer, thyroid cancer, breast cancer, uterine cancer, urinary tract cancer, ovarian cancer, prostate cancer, etc.), infectious diseases, Dosing, renal urinary tract tumors, asymptomatic bacteriosis, antibiotic administration and hormonal abnormalities.
[0056]
Hereinafter, the present invention will be further described with reference to Examples, but the present invention is not limited thereto.
[0057]
Example 1: Absorbent for measuring specific gravity of urine (absorbent of first embodiment)
Preparation of absorbent material:
0.5 g of BTB and 2.5 g of polyacrylic acid (Mw = 10,500) were dissolved in 500 mL of 0.02 M phosphate buffer (pH 7) to prepare a diagnostic solution.
Water-absorbent resin "Aquapearl AP211DS" (Acrylic acid-based polymer, manufactured by Sun Diamond Polymer Co., Ltd .: water absorption capacity = 600 times, absorption speed = 40 seconds, Ab-L = 10 g / g, Dav = 210 μm, granular) The total amount of the above solution was added to 100 g, mixed well with a glass rod, and dried at 50 ° C. under reduced pressure at −0.05 MPa for 24 hours. After drying, the partially blocked portion was crushed with a glass rod to obtain an absorbent (the blocking portion was crushed in the same manner in the following Examples and Comparative Examples). The Dav of the absorbent was measured and found to be 213 μm, which was granular.
[0058]
Creating a standard color sample:
An appropriate amount of sodium chloride was added to urine of a dog having a specific gravity of 1.005 measured by a floating pycnometer to prepare standard urine having a specific gravity of 1.010, 1.020, 1.025, and 1.030. A standard color sample was prepared by adding 25 g of each standard urine to 5 g of the above-mentioned absorbent (absorbent one hour after the preparation). The sample having a specific gravity of 1.005 was green, and the yellow color increased as the specific gravity increased. The color samples were stored in a glass bottle with a capacity of 70 mL with a lid (hereinafter, all color samples were stored in the same container).
[0059]
Measurement of urine specific gravity:
The specific gravity of each sample obtained by adding 5 g of the above absorbent material to 25 g of urine of each of eight dogs was visually determined by comparing with a color sample.
For example, when the color of the sample was between the color samples having the specific gravity of 1.015 and 1.020, the color tone was observed and the specific gravity was determined in 0.001 steps. The judgment was made by three persons and the average value was defined as the specific gravity.
The color development speed was visually confirmed from the time urine was added to the time color development was completed, and the required time was measured.
After the coloring was completed, the absorbent was allowed to stand in an open state, and the time until the specific gravity reading changed by 0.010 was measured to evaluate the coloring persistence.
On the other hand, the specific gravity of urine of the above eight dogs was measured by a floating specific gravity meter. The correlation coefficient between the specific gravity measured with the absorbent of the present invention and the specific gravity measured with the floating-type hydrometer was 0.87 (n = 8), and a good correlation was obtained. Can be measured. Table 1 shows the results.
[0060]
[Table 1]

[0061]
Comparative Example 1;
Preparation of absorbent material:
Instead of "Aquapearl AP211DS", "Sunfresh AT-30" (a polymer mainly composed of acrylamide, manufactured by Sanyo Chemical Industries, Ltd .: water absorption capacity = 45 times, absorption speed = 100 seconds, Ab-L = 7 g / g) , Dav = 1200 μm, crushed), in the same manner as in Example 1, except that Dav = 1200 μm, crushed. A color sample was prepared in the same manner as in Example 1 except that the absorbent was used, and the specific gravity of dog urine was measured in the same manner as in Example except that the absorbent was used.
However, as compared with Example 1, it was found that the coloring speed was slow, the coloring was unstable, and the persistence was poor.
The correlation coefficient between the specific gravity measured with the absorbent of the comparative example and the specific gravity measured with the floating-type hydrometer is 0.63 (n = 8), which indicates a low correlation, and the urine with high accuracy depends on the absorbent of the comparative example. It turned out that the specific gravity could not be measured.
Table 2 shows the results.
[0062]
[Table 2]

[0063]
Example 2 Absorbent for Measuring Glucose (Absorbent of First Embodiment)
Preparation of absorbent material:
10 mg of glucose oxidase (from Aspergillus sp., 100 u / mg) and 10 mg of peroxidase (from Horseradish, 450 u / mg) are dissolved in 5 mL of 0.02 M phosphate buffer (pH 6) to prepare an enzyme solution.
A total of 10 g of a 5 wt% methanol solution of o-tolidine was added to 100 g of "Aquapearl AP211DS" and thoroughly stirred with a glass rod, followed by drying under reduced pressure at -0.05 MPa at 25C for 1 hour. Then, it dried at 105 degreeC using the infrared moisture meter, and confirmed that the drying loss rate was 0.07%. Further, if there is a part that is partially blocked, it is pulverized with a glass rod, sprayed with 5 mL of the above enzyme solution under stirring, and then dried under reduced pressure at −0.05 MPa at 25 ° C. for 24 hours to perform absorption. -1 (Dav = 212 μm: granular) was obtained. The drying loss rate of the absorbent was measured with an infrared moisture meter, and it was confirmed that the moisture was 1.20%.
In addition, water was added to this absorbent material to prepare an absorbent material-2 (Dav = 215 μm: granular) having a water content of 6.5%.
[0064]
Creating a standard color sample:
D-glucose is dissolved in urine of a glucose-negative (-) cat using urine test paper "Pretest" (Wako Pure Chemical Ind., Ltd.) to prepare standard urine of 100, 250, 500, 1000 and 2000 mg / dL. did. The standard urine was glucose (±) urine, glucose (+) urine, glucose (2+) urine, glucose (3+) urine, glucose (4+) urine. 25 g of each standard urine (5 hours after the preparation of the standard urine was used, and the same applies to the following standard urine unless otherwise specified) was used for 5 g of the above-mentioned glucose measuring absorbent-1 or absorbent-2 (absorbent) One hour after the preparation was used, and unless otherwise specified, the same was added to the following absorbents) to prepare a color sample. The blueness increased with increasing glucose concentration.
[0065]
Glucose content measurement:
For a sample obtained by adding 5 g of the above-mentioned absorbent for glucose measurement-1 or 2 to each of 25 g of urine of 8 cats, the glucose concentration was calculated from the above (-) to (4+) of 6 as compared with the color sample. It was visually determined in stages.
The determination was performed by three persons, and the results of each determination were averaged (for example, (+) in the case of (+), (+), (2+), and determined as (+)), and the glucose concentration of each sample was determined. The color development speed was determined by visually checking from the time urine was added to the time color development was completed, and the required time was measured.
Further, after the color development was completed, the absorbent was allowed to stand in an open state, and the time required for changing the glucose value after the color development by one or more steps was measured to evaluate the color development continuity.
On the other hand, the glucose concentration was measured by “Pretest” for the urine of the above eight cats, and a six-step determination was performed.
The glucose concentration measured with the absorbent of the present invention and the glucose concentration measured with the urine test paper were consistent with all eight samples, demonstrating that the glucose concentration can be measured with the absorbent of the present invention. The results are shown in Tables 3 and 4.
[0066]
[Table 3]

[0067]
[Table 4]

[0068]
In addition, glucose concentration was measured in the same manner as described above, except that the absorbents 1 and 2 were prepared and then stored at 5 ° C. or 50 ° C. for 3 months. The results are shown in Tables 5 and 6.
[0069]
[Table 5]

[0070]
[Table 6]

[0071]
It has been found that the absorbent of the present invention has a small change over time even after 3 months after storage at 5 ° C., and can be measured sufficiently.
[0072]
Comparative Example 2;
Creating Absorbent:
An absorbent (1.1% moisture: Dav = 1200 μm) and a color sample were prepared in the same manner as in Example 2 except that “Sun Fresh AT-30” was used instead of “Aqua Pearl AP211DS”. Then, the glucose concentration of cat urine was measured in the same manner as in Example 2.
However, there was a case where the coloration speed was large, the coloration was unstable, and the color faded over time (after several minutes).
The glucose concentration measured with the absorbent of the comparative example and the glucose concentration measured with the urine test paper only matched 6 out of 8 samples, and it was found that the glucose concentration of the comparative example could not be measured with high accuracy.
Table 7 shows the results.
[0073]
[Table 7]

[0074]
Moreover, glucose concentration was measured using the absorbent material stored at 5 ° C. or 50 ° C. for 3 months in the same manner as in Example 2 except that the absorbent material of the comparative example was used. Table 8 shows the results.
[0075]
[Table 8]

[0076]
Example 3: Absorbent for protein measurement (absorbent of second embodiment)
Preparation of absorbent material:
A water-absorbent resin “Sunfresh AT-03” (a polymer mainly composed of acrylamide, (a1) content within a range of 90 to 99% by weight, manufactured by Sanyo Chemical Industries, Ltd.) was mixed with a mixer (Mitsubishi Electric, JM-K31). ) For 10 minutes, pass through a 242 μm wire mesh, collect the particulate matter remaining on the 109 μm wire mesh, and recover the fine particles of Sunfresh-03 (water absorption capacity 40 times, Dav = 185 μm, acid by neutralization titration of pH 4-9) (Equivalent of 0.9 meq / g). 11.7 g of citric acid, 11.5 g of potassium dihydrogen citrate, and 9.5 g of TBPB dissolved in 50 g of water and 10 g of Dav = 360 μm silica powder were added to 100 g of Sunfresh-03 fine granules. The mixture was thoroughly stirred with a glass rod, and dried under reduced pressure at -0.05 MPa at 50 ° C. for 24 hours to obtain an absorbent (Dav of the water-absorbent resin portion: 245 μm, Dav of the silica powder portion: 363 μm).
[0077]
Creating a standard color sample:
Bovine albumin was dissolved in protein negative (-) bovine urine by "Pretest" to prepare standard urine of 15, 30, 100 and 1000 mg / dL. The standard urine was protein (±) urine, protein (+) urine, protein (2+) urine, and protein (3+) urine. A color sample was prepared by adding 25 g of each standard urine to 5 g of the above absorbent material. When the protein was present, the color changed from yellow to green, and the greenness increased as the protein concentration increased.
[0078]
Protein measurement:
For a sample in which 5 g of the above-mentioned absorbent was added to 25 g of each of eight bovine urine samples, the protein concentration was classified into the above-described five stages and visually judged as compared with a color sample.
The determination was made in the same manner as in Example 2.
On the other hand, the protein concentrations of the above eight bovine urines were measured by “Pretest”, and a five-step determination was performed.
The protein concentration measured with the absorbent of the present invention and the protein concentration measured with urine test paper were in agreement with all eight samples, demonstrating that the protein concentration can be measured with the absorbent of the present invention. Table 9 shows the results.
[0079]
Comparative Example 3;
Preparation of absorbent material:
In the same manner as in Example 3, except that "Sunfresh AT-30" (acid equivalent by neutralization titration at pH 4 to 9: 9.7 meq / g) was used instead of "Sunfresh-03", An absorbent and a color sample were prepared, and the protein concentration of bovine urine was measured in the same manner as in Example 3.
However, the protein concentration measured with the absorbent material of the comparative example and the protein concentration measured with the urine test paper matched only 5 out of 8 samples, and urine that was negative on the urine test paper was false positive and false positive. In some cases, urine was determined to be positive. It was found that a reliable protein concentration could not be measured with the absorbent of the comparative example.
Table 9 shows the results.
[0080]
[Table 9]

[0081]
Example 4; Absorbent for Occult Blood Measurement (Absorbent of Third Embodiment)
Preparation of absorbent material:
1 g of cumene hydroperoxide was dissolved in 25 g of methanol, added to 5 g of silica powder with Dav = 360 μm, and dried in a vacuum dryer at 25 ° C. and −0.05 MPa for 1 hour to prepare a cumene peroxide-supported silica powder. Thereafter, 50 g of water was added, stirred and sufficiently dispersed, and 15 g of water-soluble starch ("Pine Flow S" manufactured by Matsutani Chemical Co., Ltd.) was added. Further, the operation of adding 5 g of methanol and stirring for 1 minute was repeated 10 times, and 50 g of methanol was added in total. As the amount of methanol added increased, the starch dissolved in the aqueous solution became insoluble and was adsorbed on the silica powder surface. The dispersion was filtered through filter paper (Toyo Filter Paper, No. 2), the solid content was collected, and dried at 50 ° C. and −0.05 MPa for 1 day in a vacuum dryer to obtain peroxide-coated granules (Dav = 945 μm, granular).
45 g of “Aquapearl AP211DS” and 55 g of a water-absorbent resin “Aquapearl DS-50T” (manufactured by Sun Diamond Polymer Co., Ltd .: water absorption capacity = 600 times, absorption speed = 48 seconds, Ab-L = 12 g / g, Dav = 350 μm) ( To a total of 100 g of water-absorbent resin), 10 g of a 5% methanol solution of o-tolidine was added in its entirety, mixed well with a glass rod, and dried at 25 ° C. at −0.05 MPa for 1 hour under reduced pressure. The above-mentioned peroxide-coated powder was added to and mixed with the absorbent material (Dav = 213 μm granular water-absorbent resin, Dav = 354 μm granular water-absorbent resin, and Dav = 945 μm granular peroxide-coated resin). ).
[0082]
Creating a standard color sample:
In “Pretest”, human hemoglobin obtained by removing the plasma part from normal human blood is dissolved in human urine of occult blood negative (−) to obtain standard urine of 0.06, 0.15, 0.75 mg / dL. Created. The standard urine was occult blood (+) urine, occult blood (2+) urine, and occult blood (3+) urine. A color sample was prepared by adding 25 g of each standard urine to 5 g of the above-mentioned absorbent (absorbent one hour after preparation). Blueness increased as the occult blood concentration increased.
[0083]
Occult blood measurement:
A sample in which 5 g of the above-mentioned absorbent was added to 25 g of each of the human urine samples of 8 samples was compared with a standard color sample, and the occult blood concentration was classified into the above four stages and visually determined. The determination was made in the same manner as in Example 2.
On the other hand, the occult blood concentration was measured by “Pretest” for the human urine of the above eight samples, and four-stage determination was performed.
The occult blood concentration measured by the absorbent of the present invention and the occult blood concentration measured by urine test paper were in agreement with all eight samples, demonstrating that the occult blood concentration can be measured by the absorbent of the present invention. Table 10 shows the results.
The color development speed was determined by visually checking from the time urine was added to the time color development was completed, and the required time was measured.
The dry feeling was evaluated by the following method. Absorbing paper (5 cm × 5 cm) is placed on a polyethylene film (5 cm × 5 cm), and an absorbent after urine is laid thereon to a height of 2 mm, and a polyethylene film (5 cm × 5 cm) is placed thereon. 5 cm) and a polypropylene nonwoven fabric (5 cm × 5 cm) were placed in this order (the overall thickness was 2.5 mm). The dry feeling was evaluated from the top of the nonwoven fabric by touch feeling determination. Three persons evaluated in the following five-step evaluation, and calculated | required the average value.
Rating 1: The liquid floats with just a light touch
Rating 2: The liquid feels wet when touched lightly, and floats when strongly touched.
Rating 3: a slight wet touch when touched lightly and a wet touch when strongly touched.
Rating 4: No touch when touched lightly, but wet when touched strongly.
Rating 5: There is no wet feeling even when strongly touched, and the feeling of try is good.
[0084]
[Table 10]

[0085]
Comparative Example 4;
Creating Absorbent:
A dried product of a water-absorbing resin containing o-tolidine was obtained in the same manner as in Example 4 using 100 g of "Aquapearl AP211DS", and a solution obtained by dissolving 1 g of cumene hydroperoxide in 25 g of methanol was added. After thoroughly stirring with a stick, the mixture was dried under reduced pressure at -0.05 MPa at 25 ° C. for 1 hour to obtain an absorbent for occult blood measurement (Dav = 214 μm, granular).
A color sample was prepared in the same manner as in Example 4 except that the absorbent was used, and the occult blood concentration of human urine was measured in the same manner as in Example 4 except that the absorbent was used.
Using the absorbent of the comparative example, the occult blood concentration measured by the measurement method of Example 4 and the occult blood concentration measured by the urine test paper were in agreement with all eight samples, but the dry feeling was found to be inferior to the absorbent of the example. did. Table 11 shows the results.
[0086]
[Table 11]

[0087]
After the absorbents of the examples and comparative examples were allowed to stand at 50 ° C. for one month after preparation, occult blood measurement was performed in the same manner as described above. Table 12 shows the results.
[0088]
[Table 12]

[0089]
From Table 12, it can be seen that the absorbent of the present invention has a small change over time even after one month and can be sufficiently measured, whereas the absorbent of the comparative example can be sufficiently measured at the time of preparation. It turned out that the measurement could not be performed due to the drastic change.
[0090]
Example 5 [Absorbent sheet for antigen measurement according to fifth embodiment: measurement of β2-microglobulin in human urine]
Preparation of absorbent sheet:
FIG. 7 is a cross-sectional view of a part of the absorbent sheet of Example 5, and each constituent material is as follows.
Surface film (OF): Polyethylene terephthalate non-woven fabric (15 cm × 45 cm) having a thickness of 100 μm.
Water-absorbent resin layer (AL): 12 g of "Aqua Pearl DS-50T" and 12 g of absorbent cotton (made by Kawamoto Sangyo Co., Ltd.) were pulverized by hand approximately 500 times by hand until they were homogeneous in appearance. Thereafter, the defibrated mixture was spread to a size of 15 cm × 45 cm, and then 8 kg / cm at 50 ° C. using a heater plate press (Model N4008-00) manufactured by NPA System Co., Ltd. ² For 30 seconds.
Labeled antibody carrying layer (B1): One piece of filter paper (No. 2, cut to 5 mm × 5 mm, manufactured by Advantech) is impregnated (25 ° C., 30 minutes) with a phosphate buffer solution of the following (My). After that, the filter paper was taken out and dried (25 ° C., 2 hours, −755 mmHg).
The concentration of (My) in the phosphate buffer was 300 μg / ml at pH 7.0. Contains 1% bovine serum albumin.
Labeled antibody (My): a peroxidase-labeled anti-β2-microglobulin polyclonal antibody.
My was prepared using an anti-β2-microglobulin polyclonal antibody (manufactured by Dako Japan) and horseradish-derived peroxidase (manufactured by Toyobo Co., Ltd.) and published in the literature [S. Yoshitake, M. Imagawa, E. Ishikawa, Ethol; Biochem, Vol. 92 (1982) 1413-1424].
B / F separation layer (C1): a membrane filter (mixed cellulose ester type, pore diameter 0.3 μm, diameter 47 mm, manufactured by Advantech) is used to prepare a phosphate buffer solution of antigen β2-microglobulin (manufactured by SIPAC) (antigen concentration: 5 μg) / Ml, pH 7, containing 0.1% bovine serum albumin) at 25 ° C for 1 hour, then take out the sheet and dry (25 ° C, -755 mmHg for 3 hours).
Coloring agent layer (D): A filter paper (No. 2, manufactured by Advantech Co., cut to a diameter of 20 mm) was placed in a methanol solution of o-tolidine (0.1% (w / w)) at 25 ° C. for 5 minutes. After immersion, the filter paper was taken out and dried (25 ° C., −755 mmHg for 30 minutes).
Back film (UF): polypropylene film (15 cm × 45 cm) with a thickness of 40 μm,
Using the above constituent materials, processing was performed as follows to produce an absorbent sheet.
First, (AL) is placed under the OF, (B1) and (C1) are placed in this order so as to be located at the center of (AL), and the UF with a 20 mm diameter hole at the center is placed. After arranging (D) in the hole, the hole was covered with a UF having a diameter of 50 mm to which a double-sided tape was attached with a width of 5 mm along the circumference.
The four layers of the above-mentioned superposed layers (quadrilateral of 15 cm × 45 cm) were hot-pressed with a width of 1 cm each to obtain a diagnostic absorber.
Coloring aid liquid: A solution in which 0.02% by weight of hydrogen peroxide is contained in a phosphate-citrate buffer (pH 5.0).
Tested Samples: Twenty human urine samples were obtained immediately before the test.
Preparation of standard urine: β2-microglobulin was added to artificial urine (20.0 g of urea, 8.0 g of NaCl, 0.8 g of MgSO4.6H2O, 0.3 g of CaCl2.2H2O, and ion-exchanged water was added to make 1000 g), and β2-microglobulin was added at 0 g each. , 20, 40, 60, 80, 100, 120, 140, 160, 180 and 200 ng / ml.
Test method:
A sample of 80 ml was placed in a 200 ml beaker, and the sample was allowed to flow down at a speed of 5 ml / sec while gradually tilting the beaker so that the mouth was in contact with the absorbent sheet.
Five minutes after the entire amount was allowed to flow, the UF was peeled off, and a coloring aid liquid was applied to (D) to form a sheet after coloring. The above operation was performed on 20 human urines. In addition, a similar test was performed on the standard urine to perform a color development reaction, and a color sheet after the standard color development corresponding to the β2-microglobulin concentration was prepared. Compare the color intensity of the sheet after color development obtained from the sample with the color intensity of the standard color development sheet visually,
The β2-microglobulin concentration of the sheet after the closest standard color development was defined as the β2-microglobulin concentration in the sample.
Table 13 shows the measurement results of the concentration of β2-microglobulin using the absorbent sheet of the present invention.
[0091]
Measurement of β2-microglobulin concentration by conventional method:
For 20 human urine samples used in Example 5, the concentration of β2-microglobulin was measured using glazyme β2-Microglobulin-EIA TEST (released by Wako Pure Chemical Industries).
The measurement procedure is as follows.
The sample is diluted 11-fold with a buffer solution (all reagents are included in the kit), 20 μl is placed in a test tube, one antibody bead is added, the mixture is left standing at 37 ° C. for 1 hour, and the reaction solution is removed with an aspirator did. Further, washing (injection → shake → aspiration removal) was performed twice with 3 ml of a buffer solution, the antibody beads were transferred to a new test tube, 500 μl of a substrate color developing solution was added, and the mixture was allowed to stand still at 37 ° C. for 30 minutes. 3 ml of the enzyme reaction stop solution was added, mixed well, and the absorbance was measured at 492 nm. Separately, the absorbance was measured using the standard antigen solution in the same manner as described above, and a calibration curve was prepared. Then, the analyte concentration was calculated.
Table 13 shows the measured values of the concentration of β2-microglobulin according to the conventional method.
In any of the methods, if the β2-microglobulin concentration was 100 ng / ml or less, it was determined that the urine was normal, and if it exceeded 100 ng / ml, it was determined that the urine had a high urine content (the possibility of abnormalities was high).
Table 13 shows the results of the determination.
[0092]
[Table 13]

[0093]
Good correlation (correlation coefficient = 0.91) was observed between the measurement results obtained by the method of the present invention and the conventional method.
[0094]
Example 6 [Absorbent sheet for antigen measurement according to fifth embodiment: measurement of β2-microglobulin in human serum]
The same absorptive sheet for diagnosis and the color-forming aid liquid as in Example 5 were used.
[0095]
Preparation of standard serum:
Β2-microglobulin was added to physiological saline to prepare a standard serum having a concentration of 0.01 μg / ml between 0 and 0.22 μg / ml.
[0096]
Test sample:
Twenty human sera were obtained. For the test, serum diluted 20-fold with a phosphate buffer (0.02 M, pH 7.0) was used as a test sample.
[0097]
Test method:
The measurement was performed in the same manner as in Example 5 except that the standard serum was used instead of the standard urine, and the test sample was used instead of the urine as the sample. The β2-microglobulin concentration of the test sample obtained from the color intensity determination of the sheet after color development was 20 times, and the result was defined as the β2-microglobulin concentration of the original sample.
[0098]
Measurement of β2-microglobulin concentration by conventional method:
The concentration of β2-microglobulin was measured using 20 samples of the above human serum (before dilution with a buffer) using GLAZYME β2-Microglobulin-EIA TEST (released by Wako Pure Chemical Industries, Ltd.).
Table 14 shows the measurement results by the method using the absorbent sheet of the present invention and the conventional method.
In any method, if the β2-microglobulin concentration is 1.8 μg / ml or less, the serum is determined to be normal. If the β2-microglobulin concentration exceeds 1.8 μg / ml, the serum is determined to be high-content serum (highly likely to be abnormal). Judged.
[0099]
[Table 14]

[0100]
A good correlation (correlation coefficient = 0.88) was observed between the β2-microglobulin concentration measurement values of the method of the present invention and the conventional method.
[0101]
【The invention's effect】
Diagnosis using the diagnostic absorbent, the absorbent sheet or the absorbent article of the present invention makes it possible to confirm changes in the physical condition of animals and humans, the presence or absence of pregnancy, the presence / absence / progress of diseases, and the like. Yes, it is also effective for cancer diagnosis. In addition, the diagnostic absorbent, absorbent sheet or absorbent article of the present invention has a high color development rate after the body fluid of an animal or a human has penetrated these materials, so that it can be diagnosed immediately, and furthermore, the persistence of color development (Stability of color tone over time) is good. Furthermore, since the absorbent has good aging stability, there is an advantage that the absorbent can be used even after storage for a long period of time.
[Brief description of the drawings]
FIG. 1 is a diagram schematically showing a cross section of urine U and a part of a diagnostic absorbent sheet of the present invention. AL is a water-absorbent resin layer, B1 is a layer carrying a labeled antibody, and C1 is a B / F separation layer.
FIG. 2 is a diagram schematically showing a cross section of a part of an absorbent sheet in which urine U has penetrated an AL layer and a B1 layer.
FIG. 3 is a diagram schematically showing a cross section of a part of an absorbent sheet in which urine U has penetrated to reach a B / F separation layer C1.
FIG. 4 is a diagram schematically showing a partial cross section of an absorbent sheet.
FIG. 5 is a diagram schematically showing a partial cross section of a water absorbent sheet.
FIG. 6 is a diagram schematically showing a partial cross section of a water absorbent sheet.
FIG. 7 is a cross-sectional view of a part of the absorbent sheet prepared in Examples 5 and 6.
[Explanation of symbols]
AL Water absorbent resin layer
B1 Labeled antibody carrying layer
B2 Water-absorbing resin layer carrying labeled antibody
C1 B / F separation layer
B / F separation layer having C2 holes
D Color former layer
My-labeled antibody
Mxy labeled conjugate
P hole
U urine
OF surface sheet
UF back sheet
x antigen
y antibody
fx immobilized antibody

Claims (15)

An absorbent material for animal diagnosis, comprising a water absorbent resin (A) and a diagnostic agent (M), wherein the absorbent resin (A) has at least 60 times the water absorbing ability. It contains a water-absorbent resin (A) and a diagnostic agent (M), and the absorbent resin (A) comprises an amidated product of an aliphatic unsaturated monocarboxylic acid and an alkylene oxide adduct, and an alkylated product and an alkyl etherified product thereof. It contains at least one monomer (a1) selected from the group as a constituent unit, and has an acid or base equivalent of 2 meq / g or less as determined by neutralization titration at pH 4 to 9. Diagnostic absorber. The water-absorbent resin (A) further comprises one or more monomers (a2) selected from the group consisting of unsaturated anionic monomers, unsaturated cationic monomers and salts thereof as constituent monomers The absorbent according to claim 2, which contains. The absorbent according to claim 2, wherein the water-absorbent resin (A) further contains 0.01 to 3 mol% of the crosslinkable monomer (b). The water-absorbent resin (A) is 90 to 99 mol% of the monomer (a1), 1 to 10 mol% of the monomer (a2), and 0.01 to 3 mol of the crosslinkable monomer (b). %. Consisting of at least 40% by weight of a water-absorbent resin (A) and 25 ppm to 2.5% by weight of a diagnostic agent (M) based on the weight of the water-absorbent resin (A), the diagnostic agent (M) being carried on a support. Alternatively, a diagnostic absorbent material which is coated with a water-soluble or water-disintegrable coating material, and which is a mixture of the water-absorbent resin (A) and the supported or coated (M). The diagnostic agent (M) is at least one selected from the group consisting of a pH diagnostic agent (M1), a protein diagnostic agent (M2), a glucose diagnostic agent (M3) and an occult blood diagnostic agent (M4). Or the absorbent material of any one of 6. A diagnostic absorbent comprising a water-absorbent resin (A) and a diagnostic agent for antigen-antibody reaction (M0). The absorbent according to claim 8, wherein the diagnostic reagent for antigen-antibody reaction (M0) comprises a labeled antibody (My) or a labeled antigen (Mx), and if necessary, a color former (d). 9. The absorbent material according to claim 2, wherein the water-absorbent resin (A) has at least 60 times the water-absorbing ability. The absorbent according to any one of claims 1, 2, 6, and 8, wherein the absorbent is granular or aggregated. A diagnostic absorbent sheet comprising, as a constituent material, the absorbent material according to any one of claims 1, 2, 6, and 8, and one or more members selected from the group consisting of a fiber, a nonwoven fabric, a paper, and a synthetic resin film. A diagnostic absorbent sheet having the following (1) or (2) and a B / F separation layer (C):
(1) a layer (B1) supporting a water-absorbent resin layer (AL) and a labeled antibody (My) or a labeled antigen (Mx); or (2) a labeled antibody (My) or a labeled antigen (Mx) is added to the water-absorbent resin ( Layer (B2) supported on A). The absorbent sheet according to claim 13, wherein the water permeation rate of the B / F separation layer (C) is 0.01 to 3 mL / min at 25C and 1 atm. 14. A disposable diaper, a toilet for pets, a simple toilet, a sanitary napkin, a pad for incontinent persons, or a wound sheet, comprising the absorbent sheet according to claim 12 as a constituent material.

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