【発明の詳細な説明】［産業上の利用分野］本発明は、血液中のグルコース濃度を測定する血糖値測
定装置に関し、特に、角質層が取り除かれた皮膚を減圧
吸引することにより得られる浸出液を利用して血糖値を
測定する血糖値測定装置に関する。[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a blood glucose level measuring device that measures the glucose concentration in blood, and in particular, to a blood glucose level measuring device that measures glucose concentration in blood, and in particular, to a blood glucose level measuring device that measures the glucose concentration in blood, and in particular, the present invention relates to a blood glucose level measuring device that measures the glucose concentration in the blood, and in particular, the present invention relates to a blood glucose level measuring device that measures the glucose concentration in blood. The present invention relates to a blood sugar level measuring device that measures blood sugar levels using.
［従来の技術］従来、血糖値の測定は、血液を採取し、これを血糖針で
測定することにより行われていた。しかし、この方法で
は測定の度に血液を採取する必要があり、１回の測定に
要する血液の量も多く、被測定者に苦痛および消耗を与
えていた。この他に、体内に微小なグルコースセンサを
挿入して血糖値を測定する方法も試みられている（山崎
義光、上田信性、関谷正志、河盛隆造、鎌田武信、七里
元亮＝「第６回化学センサ研究会発表会予稿集」。[Prior Art] Conventionally, blood sugar levels have been measured by collecting blood and measuring it with a blood sugar needle. However, with this method, it is necessary to collect blood every time a measurement is performed, and a large amount of blood is required for one measurement, causing pain and exhaustion to the subject. In addition, attempts have been made to measure blood sugar levels by inserting a minute glucose sensor into the body (Yoshimitsu Yamazaki, Nobuaki Ueda, Masashi Sekiya, Ryuzo Kawamori, Takenobu Kamata, Motosuke Shichiri = "6th Proceedings of the Chemical Sensor Research Group Presentation.”
１９８７年刊、７１頁）が、センサの安定性や生体との
適合性の上で問題があり、すぐに実用化することは難し
い。(Published in 1987, p. 71), but there are problems with the stability of the sensor and compatibility with living organisms, and it is difficult to put it into practical use right away.
一方、近年、角質層を取り除いた皮膚を減圧吸引するこ
とにより浸出液が得られ、この浸出液が血液中のグルコ
ースと良い相関を示すことが動物実験により発見されて
いる（伊藤成史、木村純、栗山敏秀、菊地真、荒井恒憲
、根岸直樹、富山端、千木良みどり：［第６回化学セン
サ研究会発表会予稿集Ｊ 、 １９８７年刊、８１頁）
。また、本発明者らは人体においても同様に浸出液が得
られ、この浸出液中のグルコース濃度が血液中のグルコ
ス濃度と良い相関を持つことを発見している（ Ｎａ
ｒｕｓｈ＋ Ｉｔｏ、 Ａｔ５ｕｓｉ ５ａｉｔｏ
、 ＳｈｉｇｅｙｕｋＭｉｙａｍｏｔｏ 、 ５ｈ
ｉｎｏ ５ｈｉｎｏｈａｒａ、 Ｔｏｓ旧旧ｄｅＫｕ
ｒ＋ｙａｍａ、 Ｊｕｎに＋ｍｕｒａ 、 Ｔｕｎ
ｅｎｏｒＩＡｒａｂ。On the other hand, in recent years, it has been discovered through animal experiments that an exudate can be obtained by vacuum suctioning the skin from which the stratum corneum has been removed, and that this exudate shows a good correlation with glucose in the blood (Seiji Ito, Jun Kimura, Toshihide Kuriyama, Makoto Kikuchi, Tsunenori Arai, Naoki Negishi, Hajime Toyama, Midori Chigira: [Proceedings of the 6th Chemical Sensor Research Group Presentation J, published in 1987, p. 81)
. In addition, the present inventors have discovered that exudate is similarly obtained in the human body, and that the glucose concentration in this exudate has a good correlation with the glucose concentration in the blood (Na
rush+ Ito, At5usi 5aito
, ShigeyukMiyamoto, 5h
ino 5 hinohara, Tos old and old deKu
r+yama, Jun +mura, Tun
enorIArab.
Ｈａｋｏｔｏ Ｋｉｋｕｃｈｉ 、 ５ｈｉｎｓｕｋ
ｅ Ｋａｙａｓｈｉｍａ 。Hakoto Kikuchi, 5hinsuk
e Kayashima.
Ｎａ０ｋａＺｕ Ｎａｇａｔａ 、 Ｏｓａｍｕ Ｔ
ａｋａｔａｎｌ ： “Ｐｒｏ−ｃｅｅｄｉｎｇ ｏ
ｆ ｔｈｅ ５ｔｈ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｃ
ｏｎｆｅｒｅｎｃｅｏｎ ５ｏｌｉｄ−３ｔａｔｅ
５ｅｎｓｏｒｓ ａｎｄ Ａｃｔｕａｔｏｒｓ
＆ Ｅｕｒｏ−ｓｅｎｓｏｒｓ ＩＩＩ” 、 １
９８９年刊、３０２頁）。Na0kaZu Nagata, Osamu T
akatanl: “Pro-ceeding o
f the 5th International C
onference 5solid-3tate
5ensors and actuators
& Euro-sensors III”, 1
(Published in 1989, 302 pages).
［発明が解決しようとする課題］しかしながら、減圧吸引によって得られる浸出液の量は
人によって異なるが、１ｃｍ２当たり毎分的０．０５μ
ｌと僅かであり、従来の血糖計ではこれを用いて血糖値
の連続的な測定を行うことは困難であった。[Problems to be Solved by the Invention] However, the amount of exudate obtained by vacuum suction varies from person to person, but is approximately 0.05μ per minute per cm2.
1, making it difficult to continuously measure blood sugar levels using conventional blood glucose meters.
更に、浸出液の中には血液中と同様にアスコルビン酸が
含まれ、通常のグルコースオキシダーゼ固定化膜と過酸
化水素電極からなるアンペロメトリック型グルコースセ
ンサはアスコルビン酸も検出するため、グルコース濃度
を精度よく測定することは困難であった。また、アスコ
ルビン酸のほか、尿酸、ビリルビン、薬物なども測定に
影響を与える。Furthermore, the exudate contains ascorbic acid just like blood, and an amperometric glucose sensor consisting of a normal glucose oxidase-immobilized membrane and a hydrogen peroxide electrode also detects ascorbic acid, making it difficult to accurately measure glucose concentrations. It was difficult to measure well. In addition to ascorbic acid, uric acid, bilirubin, and drugs also affect measurements.
本発明は、このような課題に鑑みて創案されたもので、
微量な浸出液を用いてグルコース濃度を精度よく測定で
き、血糖値の連続的なモニタを実現する血糖値測定装置
を提供することを目的とする。The present invention was created in view of these problems, and
It is an object of the present invention to provide a blood sugar level measuring device that can accurately measure glucose concentration using a small amount of exudate and realizes continuous monitoring of blood sugar levels.
［課題を解決するための手段］本発明は、真空ポンプに接続する減圧吸引口と、該減圧
吸引口に連通する皮膚吸引口とからなる吸引セルを有し
、該皮膚吸引口から角質層が取り除かれた皮膚を減圧吸
引することにより得られる浸出液中のグルコース濃度を
測定する血糖値測定装置において、皮膚吸引口の内部に
は網状または複数の穴が形成された金属板が皮膚と接し
て設けられ、該金属板を通過した浸出液の吸引経路上に
はグルコースオキシダーゼ固定化膜および過酸化水素電
極からなるアンペロメトリ型グルコースセンサが設けら
れてなり、前記金属板には過酸化水素が酸化される電圧
が加えられることを特徴とする血糖値測定装置である。[Means for Solving the Problems] The present invention has a suction cell consisting of a vacuum suction port connected to a vacuum pump and a skin suction port communicating with the vacuum suction port, and the stratum corneum is removed from the skin suction port. In a blood sugar level measuring device that measures the glucose concentration in the exudate obtained by suctioning removed skin under reduced pressure, a metal plate with a mesh or a plurality of holes is provided inside the skin suction port in contact with the skin. An amperometric glucose sensor consisting of a glucose oxidase immobilized membrane and a hydrogen peroxide electrode is provided on the suction path of the exudate that has passed through the metal plate, and the metal plate is provided with a voltage at which hydrogen peroxide is oxidized. This is a blood sugar level measuring device characterized in that:
なお、上記のアンペロメトリ型グルコースセンサは吸引
セル内部の浸出液の減圧吸引経路上に設けても、あるい
は吸引セルと真空ポンプをつなぐ管内に設けても差支え
ない。Note that the amperometric glucose sensor described above may be provided on the vacuum suction path for the exudate inside the suction cell, or may be provided within the pipe connecting the suction cell and the vacuum pump.
［作用］本発明の血糖値測定装置においては、角質層を除去され
た皮膚に上記の網状あるいは複数の穴があいた金属板が
接し、皮膚表面を均一に減圧するとともに、皮膚表面に
にじみでてきた浸出液は、金属板を通過して吸引セル内
部に移動する。したがって、この金属板に過酸化水素が
電気化学的に酸化される電圧を加えることにより、浸出
液中のアスコルビン酸はすべて酸化される。このため、
金属板後方の減圧吸引経路上に設けられたアンペロメト
リ型グル」−スセンサはアスコルビン酸を検出すること
がなくなり、グルコースのみを検出することができる。[Function] In the blood glucose level measuring device of the present invention, the above-mentioned net-like or metal plate with a plurality of holes is brought into contact with the skin from which the stratum corneum has been removed, thereby uniformly reducing the pressure on the skin surface and preventing any oozing from occurring on the skin surface. The exudate passes through the metal plate and moves inside the suction cell. Therefore, by applying a voltage that electrochemically oxidizes hydrogen peroxide to this metal plate, all ascorbic acid in the leachate is oxidized. For this reason,
The amperometric glucose sensor installed on the vacuum suction path behind the metal plate no longer detects ascorbic acid and can only detect glucose.
また、浸出液の減圧吸引経路、即ち吸引セルの内部ある
いは吸引セルと真空ポンプをつなぐ管の内部に微小なグ
ルコースセンサを設けることにより、浸出液中のグルコ
ース濃度を連続的に測定できる。Further, by providing a minute glucose sensor in the vacuum suction path of the exudate, that is, inside the suction cell or inside the tube connecting the suction cell and the vacuum pump, the glucose concentration in the exudate can be continuously measured.
［実施例］以下、本発明の一実施例について図面を参照して詳細に
説明する。[Example] Hereinafter, an example of the present invention will be described in detail with reference to the drawings.
第１図に示すように、吸引セル９は皮膚面に開口する皮
膚吸引口９ａと真空ポンプに続く管６に接続する減圧吸
引口９ｂよりなる。角質層を除去された皮膚１の表面に
は、皮膚吸引口９ａの内部に網状金属板２が形成された
吸引セル９が両面接着テープ１０により固定されていて
、管６を介して真空ポンプにより皮膚１を約４００ ｍ
ｍ＋＋ｇの減圧下で吸引することにより、皮膚１の表面
から浸出液７かにじみ出て、網状金属板２を通過する。As shown in FIG. 1, the suction cell 9 includes a skin suction port 9a that opens to the skin surface and a reduced pressure suction port 9b that is connected to a tube 6 leading to a vacuum pump. On the surface of the skin 1 from which the stratum corneum has been removed, a suction cell 9 in which a mesh metal plate 2 is formed inside the skin suction port 9a is fixed with double-sided adhesive tape 10, and a suction cell 9 is fixed to the surface of the skin 1 from which the stratum corneum has been removed using a vacuum pump through a tube 6. skin 1 about 400 m
By suctioning under a reduced pressure of m++g, the exudate 7 oozes out from the surface of the skin 1 and passes through the mesh metal plate 2.
この網状金属板２の材料としてプラチナを用いる場合、
過酸化水素を酸化する電圧として参照電極８と金属板用
リード線３を用いて浸出液に対して約０．７■の電圧を
加えると、アスコルビン酸などの物質は酸化される。し
たがって、網状金属板２の後方に設けられたグルコース
センサ４がアスコルビン酸を検出して誤差の原因をつく
るのを防ぐことができ、グルコースが酸化された時に発
生する過酸化水素だけを検出し、グルコースセンサ用リ
ード線５から信号が取り出される。When platinum is used as the material for this mesh metal plate 2,
Substances such as ascorbic acid are oxidized by applying a voltage of about 0.7 .mu. to the exudate using the reference electrode 8 and metal plate lead wire 3 as a voltage for oxidizing hydrogen peroxide. Therefore, the glucose sensor 4 installed behind the mesh metal plate 2 can be prevented from detecting ascorbic acid and causing an error, and can only detect hydrogen peroxide generated when glucose is oxidized. A signal is taken out from the glucose sensor lead wire 5.
第２図および第３図は、それぞれ上記の装置に用いられ
るグルコースセンサの一例の平面図および断面図で、両
図において、１１はプラチナ製の作用極、１２はプラチ
ナ製の対極、１３はグルコースオキシダーゼ固定化膜、
１４はシリコーン膜からなるグルコースの透過を酸素の
透過に比べ遅くする制限透過膜、１６は絶縁体、５はグ
ルコースセンサ用リード線である。2 and 3 are a plan view and a cross-sectional view, respectively, of an example of a glucose sensor used in the above device. In both figures, 11 is a working electrode made of platinum, 12 is a counter electrode made of platinum, and 13 is a glucose sensor. oxidase immobilized membrane,
14 is a limiting permeation membrane made of a silicone film that slows down the permeation of glucose compared to the permeation of oxygen; 16 is an insulator; and 5 is a lead wire for the glucose sensor.
第４図は、上記実施例の装置を用いた血糖値の連続測定
のための構成を示す図で、被測定者１８の上腕に吸引セ
ル９が設置され、圧力グージ１９で圧力を監視しながら
真空ポンプ２０で減圧する。グルコースセンサ４の信号
は測定回路２１で測定され、レコーダ１７により記録さ
れる。FIG. 4 is a diagram showing a configuration for continuous measurement of blood sugar level using the device of the above embodiment, in which a suction cell 9 is installed on the upper arm of a person to be measured 18, and a pressure gouge 19 is used to monitor the pressure. The pressure is reduced using the vacuum pump 20. The signal of the glucose sensor 4 is measured by the measurement circuit 21 and recorded by the recorder 17.
角質層を除去された皮膚を減圧吸引して得られる浸出液
は、非常に微量で、かつアスコルビン酸など過酸化水素
電極の信号に影響する物質を含んでいるが、実施例の血
糖値測定装置は、あらかじめ網状金属板によりこれらの
物質を酸化するため、グルコースセンサの信号に悪影響
せず、また減圧吸引経路上にグルコースセンサが設けら
れているため、微量な浸出液を用いて連続的に血糖値を
精度よく測定できる。The exudate obtained by vacuum suctioning the skin from which the stratum corneum has been removed is very small and contains substances such as ascorbic acid that affect the signal of the hydrogen peroxide electrode. Since these substances are oxidized in advance using a mesh metal plate, there is no negative effect on the glucose sensor signal, and since the glucose sensor is installed on the vacuum suction path, blood sugar levels can be continuously measured using a small amount of exudate. Can be measured with high accuracy.
例えば、内径３ｃｍの吸引セルを用いた場合の実験結果
を第５図に示す。この実験では、毎分的１μでの浸出液
が採取され、連続的にグルコース濃度が測定できた。第
５図中の曲線１は、本発明により吸引浸出液を用いて糖
負荷テストを行った結果で、曲線２は同時に血液を採取
して従来法で測定した血糖値（黒点）を結んだものであ
る。測定開始から１時間後に７５９のグルコースを採取
した。For example, experimental results using a suction cell with an inner diameter of 3 cm are shown in FIG. In this experiment, exudate was collected at 1 μm every minute, allowing continuous measurement of glucose concentration. Curve 1 in Figure 5 is the result of a glucose tolerance test using the aspiration exudate according to the present invention, and curve 2 is the result of blood glucose levels (black dots) measured using the conventional method when blood was simultaneously collected. be. One hour after the start of measurement, 759 glucose samples were collected.
同図かられかるように、血液を用いた場合に比べて約１
５分の時間遅れがあるが、非常によい相関が得られた。As can be seen from the figure, compared to the case using blood, the
Although there was a time delay of 5 minutes, very good correlation was obtained.
この時間遅れは、血液中のグルコスが皮膚の表面に浸出
液として出て、さらにセル内を通過してセンサに到達す
るのに時間がかかるためと考えられるが、血糖値のモニ
タには十分である。また、この測定装置をインシュリン
ポンプと組み合わせることにより、血糖値のコントロー
ルが可能になることは、以上の結果から明らかである。This time delay is thought to be due to the time it takes for glucos in the blood to come out as an exudate on the skin surface and then pass through the cell to reach the sensor, but it is sufficient for monitoring blood sugar levels. . Furthermore, it is clear from the above results that blood sugar levels can be controlled by combining this measuring device with an insulin pump.
［発明の効果］以上、説明したとあり、本発明によれば、微量な浸出液
を用いてグルコース濃度を精度よく測定でき、血糖値の
連続的なモニタを実現する血糖値測定装置を提供するこ
とができる。[Effects of the Invention] As described above, according to the present invention, there is provided a blood sugar level measuring device that can accurately measure glucose concentration using a small amount of exudate and realizes continuous monitoring of blood sugar level. I can do it.
第１図は本発明の一実施例の断面図、第２図は第１図実
施例で用いられるグルコースセンサの一例の平面図、第
３図はその断面図、第４図は血糖値の連続測定のための
構成図、第５図は本発明による血糖値測定装置を使用し
た血糖値の連続測定データを示す図である。１・・・皮膚 ２・・・網状金属板３・・
・金属板用リード線 ４・・・グルコースセンサ５・・
・グルコースセンサ用リード線６・・・管 ７・・・浸出液８・・・参
照電極 ９・・・吸引セル９ａ・・・皮膚吸引
口 ９ｂ・・・減圧吸引口１０・・・両面接着テー
プ １１・・・作用極１２・・・対極１３・・・グルコースオキシダーゼ固定化膜１４・・・
制限透過膜 １６・・・絶縁体１７・・・レコー
ダ １８・・・被測定者１９・・・圧力グージ
２０・・・真空ポンプ２１・・・測定回路Fig. 1 is a cross-sectional view of an embodiment of the present invention, Fig. 2 is a plan view of an example of the glucose sensor used in the embodiment shown in Fig. 1, Fig. 3 is a cross-sectional view thereof, and Fig. 4 is a continuous blood glucose level. FIG. 5, a block diagram for measurement, is a diagram showing continuous measurement data of blood sugar levels using the blood sugar level measuring device according to the present invention. 1...Skin 2...Mesh metal plate 3...
・Lead wire for metal plate 4...Glucose sensor 5...
- Glucose sensor lead wire 6...Tube 7...Exudate 8...Reference electrode 9...Suction cell 9a...Skin suction port 9b...Reduced pressure suction port 10...Double-sided adhesive tape 11 ... Working electrode 12 ... Counter electrode 13 ... Glucose oxidase immobilized membrane 14 ...
Limiting permeation membrane 16... Insulator 17... Recorder 18... Person to be measured 19... Pressure gouge 20... Vacuum pump 21... Measurement circuit
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2045533AJPH03251229A (en) | 1990-02-28 | 1990-02-28 | Blood sugar value measuring instrument |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2045533AJPH03251229A (en) | 1990-02-28 | 1990-02-28 | Blood sugar value measuring instrument |
| Publication Number | Publication Date |
|---|---|
| JPH03251229Atrue JPH03251229A (en) | 1991-11-08 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2045533APendingJPH03251229A (en) | 1990-02-28 | 1990-02-28 | Blood sugar value measuring instrument |
| Country | Link |
|---|---|
| JP (1) | JPH03251229A (en) |
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