JPH0257238A - Apparatus for measuring blood sugar level - Google Patents
Apparatus for measuring blood sugar levelInfo
- Publication number
- JPH0257238A JPH0257238A JP63207300A JP20730088A JPH0257238A JP H0257238 A JPH0257238 A JP H0257238A JP 63207300 A JP63207300 A JP 63207300A JP 20730088 A JP20730088 A JP 20730088A JP H0257238 A JPH0257238 A JP H0257238A
- Authority
- JP
- Japan
- Prior art keywords
- glucose
- exudate
- blood sugar
- skin
- sugar level
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000008280 blood Substances 0.000 title claims abstract description 58
- 210000004369 blood Anatomy 0.000 title claims abstract description 58
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 40
- 239000008103 glucose Substances 0.000 claims abstract description 40
- 210000000416 exudates and transudate Anatomy 0.000 claims abstract description 26
- 108010015776 Glucose oxidase Proteins 0.000 claims abstract description 6
- 239000004366 Glucose oxidase Substances 0.000 claims abstract description 6
- 229940116332 glucose oxidase Drugs 0.000 claims abstract description 6
- 235000019420 glucose oxidase Nutrition 0.000 claims abstract description 6
- 210000003491 skin Anatomy 0.000 claims description 10
- 210000000434 stratum corneum Anatomy 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 abstract description 7
- 239000001301 oxygen Substances 0.000 abstract description 7
- WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 abstract description 4
- 238000012544 monitoring process Methods 0.000 abstract description 4
- 239000002390 adhesive tape Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 102000011782 Keratins Human genes 0.000 abstract 1
- 108010076876 Keratins Proteins 0.000 abstract 1
- 238000004082 amperometric method Methods 0.000 abstract 1
- 238000005259 measurement Methods 0.000 description 9
- 238000010586 diagram Methods 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000012209 glucono delta-lactone Nutrition 0.000 description 1
- 229960003681 gluconolactone Drugs 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Landscapes
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、人体における血糖値を測定する血糖値測定装
置に関し、特に、角質層が取除かれた皮膚を減圧吸引す
ることにより１７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 sugar level measuring device for measuring blood sugar levels in the human body, and in particular, the present invention relates to a blood sugar level measuring device for measuring blood sugar levels in the human body, and in particular, the present invention relates to a blood sugar level measuring device for measuring blood sugar levels in the human body, and in particular, the present invention relates to a blood sugar level measuring device for measuring blood sugar levels in the human body, and in particular, the present invention relates to a blood sugar level measuring device for measuring blood sugar levels in the human body, and in particular, the present invention relates to a blood sugar level measuring device for measuring blood sugar levels in the human body, and in particular, the present invention relates to a blood sugar level measuring device that measures blood sugar level in the human body, and in particular, the present invention relates to a blood sugar level measuring device that measures blood sugar level in the human body, and in particular, the present invention relates to a blood sugar level measuring device that measures blood sugar level in the human body, and in particular, to a blood sugar level measuring device that measures blood sugar levels in the human body. 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、これを血糖訂で測
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かあり、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回化学センサ研究発表会予稿集Ｊ 、 １９
８７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。[Prior Art] Conventionally, blood sugar levels have been measured by collecting blood and measuring it with a blood sugar analyzer. 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 Conference J, 19
(published in 1987, p. 71), but there are problems with the stability of the sensor and its compatibility with living organisms, making it difficult to put it into practical use right away.
一方、近年、角質層を取除いた皮膚を減圧吸弓すること
により浸出液が得られ、この浸出液が血液とほぼ等しい
濃度のグルコースを含むことが動物実験により発見され
ている（伊藤成史、木村紬、栗山敏秀、菊地真、荒井恒
憲、根岸直樹、富田端、千木良みどり：「第６回化学セ
ンサ研究発表会予稿集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、この浸出液が血液と同程度の濃度のグルコースを
含むことを発見している。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 contains glucose at a concentration almost equal to that of blood (Shigefumi Ito, Kimura Tsumugi, Toshihide Kuriyama, Makoto Kikuchi, Tsunenori Arai, Naoki Negishi, Hata Tomita, Midori Chigira: "Proceedings of the 6th Chemical Sensor Research Conference J, published in 1987, p. 81)
. Furthermore, the present inventors have discovered that exudate is similarly obtained in the human body, and that this exudate contains glucose at a concentration comparable to that of blood.
［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１ワられる浸出液の量
は人によって異なるが、１ ｃｍ２当り毎分的０．０５
μｌと僅かであり、従来の血糖訂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。更に、浸
出液中の酸素濃度は、浸出液が減圧下で取得されるため
低く、通常のグルコースオキシダーゼ（ＧＯＤ）を用い
たグルコースセンサでは下記の反応式に示すように酸素
も酵素反応における基質の１つであるため、酸素′ａ度
が低いと酵素反応が酸素により制限され、精度の良い測
定は不可能でおった。[Problem to be solved by the invention] However, the amount of exudate removed by vacuum suction varies from person to person, but is approximately 0.05 per minute per cm2.
It is as small as μl, and it has been difficult to continuously measure blood sugar levels using this in conventional blood sugar monitors. Furthermore, the oxygen concentration in the leachate is low because the leachate is obtained under reduced pressure, and in a glucose sensor using normal glucose oxidase (GOD), oxygen is also one of the substrates in the enzyme reaction, as shown in the reaction formula below. Therefore, when the oxygen concentration is low, the enzymatic reaction is limited by oxygen, making accurate measurement impossible.
グルコノラクトン十Ｈ２Ｏ２
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。Gluconolactone 10H2O2 The present invention was created in view of these problems,
It is an object of the present invention to provide a blood sugar level measuring device that can 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Ｊ
本発明は、角質層が取除かれた皮膚を減圧吸弓すること
により１７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、浸出液の減圧吸引経路上の内
部に、少なくともグルコースオキシダーゼとメデイエー
タが表面に固定化された電極からなるアンペロメトリ型
グルコースセンサが備えられていることを特徴とする血
糖値測定装置である。[Means for Solving the Problems J] The present invention provides a blood glucose level measuring device for measuring the glucose concentration in an exudate obtained by suctioning under reduced pressure the skin from which the stratum corneum has been removed. This blood glucose level measuring device is characterized in that an amperometric glucose sensor comprising an electrode on the surface of which at least glucose oxidase and a mediator are immobilized is provided inside the blood glucose level measuring device.
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、吸引セルにより集
められた浸出液は吸引セルから真空ポンプと繋がれた管
へと移動する。従って、浸出液の減圧吸引経路、′即も
吸引セルの内部あるいは吸弓セルと真空ポンプを繋ぐ管
の内部に微小なグルコ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。[Operation] In the blood glucose level measuring device of the present invention, the exudate collected by the suction cell moves from the suction cell to the tube connected to the vacuum pump. Therefore, the glucose concentration in the exudate can be continuously measured by providing a minute glucose sensor inside the vacuum suction path of the exudate, specifically inside the suction cell or inside the tube connecting the suction cell and the vacuum pump.
さらに、この微小なグルコースセンサはグルコースオキ
シダーゼの伯に、メデイエータ、例えばノ■ロセンやベ
ンゾキノンが表面に固定化されたアンベロメトリ型グル
コースセンナであるため、浸出液中め酸素濃度に影響さ
れずに精度良くグルコース濃度が測定できる（Ａ、 Ｅ
、 Ｇ、 Ｃａ５Ｓ、 Ｈ，Ａ。Furthermore, this minute glucose sensor is an amberometric type glucose sensor in which a mediator such as norocene or benzoquinone is immobilized on the surface of glucose oxidase, so it can accurately measure glucose without being affected by the oxygen concentration in the exudate. Concentration can be measured (A, E
, G, Ca5S, H,A.
０、 Ｈｉｌｌ、 Ｗ、 Ｊ、 Ａｓｔｏｎ、 １．
Ｊ、 ｔｌｉｇｇｉｎｓ、 Ｅ、 Ｖ。0, Hill, W. J., Aston, 1.
J, triggins, E, V.
Ｐｌｏｔｏｋｉｎ、 Ｌ、 Ｐ、 Ｌ、 ５ｃｏｔｔ
ａｎｄ Ａ、 Ｐ、 Ｆ、 Ｔｕｒｎｅｒ； Ａｎａｌ
、 Ｃｈｅｍ、、 Ｖｏｌ、５６． ｐ、６６７（１９
８４）） 、従って、本発明による血糖値測定装置は、
血液を採取することなく血糖値を連続的に精度良く測定
することか可能である。Plotkin, L. P. L., 5cott
and A, P, F, Turner; Anal
, Chem, , Vol. 56. p, 667 (19
84)) Therefore, the blood glucose level measuring device according to the present invention includes:
It is possible to measure blood sugar levels continuously and accurately without drawing blood.
［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、角質層を除去された皮膚１の表面
には、内部にメツシュ２が設けられた吸引セル３が両面
接着テープ８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４００ｍｍＨｇの減圧下で吸引
することにより、皮＠１の表面から浸出液７かにじみ出
る。この吸引セルの出口近傍にグルコースセンサ４が設
置されており、これにより浸出液７中のグルコース濃度
が電流値に変換され、その電流がリード線５により取出
される。メツシュ２は、皮膚１の表面を均一に減圧し、
浸出液７を効率良く取出すために用いられ、１００卯径
のステンレススチールを編んで作られている。吸引セル
の内径はメツシュ部分で約３ｃｍ、グルコースセンサが
設けられている部分で１．５ｍｍである。As shown in FIG. 1, on the surface of the skin 1 from which the stratum corneum has been removed, a suction cell 3 with a mesh 2 provided inside is fixed with double-sided adhesive tape 8, and a vacuum pump is connected via a tube 6. By suctioning the skin 1 under reduced pressure of about 400 mmHg, exudate 7 oozes out from the surface of the skin 1. A glucose sensor 4 is installed near the outlet of this suction cell, and thereby the glucose concentration in the exudate 7 is converted into a current value, and the current is extracted through a lead wire 5. The mesh 2 uniformly reduces pressure on the surface of the skin 1,
It is used to efficiently extract the leachate 7, and is made of woven stainless steel with a diameter of 100 mm. The inner diameter of the suction cell is approximately 3 cm at the mesh portion and 1.5 mm at the portion where the glucose sensor is provided.
第２図は、上記実施例の装置を用いた血糖（１０の連続
測定のための構成を示す図で、被測定者１３の上腕に吸
引セル３が設置され、圧力ゲージ１０で圧力を監視しな
がら真空ポンプ９で減圧する。グルコースセンサ４の信
号はリード線５により測定回路１１で測定され、レコー
ダ１２により記録される。FIG. 2 is a diagram showing a configuration for continuous measurement of blood glucose (10) using the device of the above embodiment, in which a suction cell 3 is installed on the upper arm of a subject 13, and the pressure is monitored with a pressure gauge 10. At the same time, the pressure is reduced by the vacuum pump 9. The signal from the glucose sensor 4 is measured by the measurement circuit 11 through the lead wire 5, and recorded by the recorder 12.
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、非常に微量でかつ酸素濃度が低いが、実施例の血糖
値測定装置はメデイエータを使用した微小なアンペロメ
トり型グルコースセンサを吸引セルあるいは吸引セルに
接続された管の中に設置して測定するものであるため、
Ｍ素濃度の低い浸出液中のグルコースを精度良く連続的
に測定することができる。The exudate obtained by vacuum suctioning the skin from which the stratum corneum has been removed is extremely small and has a low oxygen concentration, but the blood glucose level measuring device of this example uses a minute amperometric glucose sensor using a mediator as a suction cell. Or, because it is installed in a tube connected to a suction cell,
Glucose in a leachate with a low M concentration can be measured continuously 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３図に示す。この実験では、毎分的０．３５μ２の
浸出液が採取され、グルコースセンサのセンサ部分の大
きざが長さ１ ｍｍ、幅０．５ｍｍ、厚さ０．３ｍｍと
非常に小さいため、連続的にグルコース濃度が測定でき
た。第３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７５ｇのグルコースを採取し
た。For example, FIG. 3 shows experimental results using a suction cell with an inner diameter of 3 cm. In this experiment, 0.35μ2 of exudate was collected every minute, and since the size of the sensor part of the glucose sensor was very small: 1 mm in length, 0.5 mm in width, and 0.3 mm in thickness, the exudate was collected continuously. Concentration could be measured. Curve 1 in FIG. 3 is the result of a glucose tolerance test using the aspirated exudate according to the present invention, and curve 2 connects the blood glucose levels (black dots) measured by simultaneously collecting blood. One hour after the start of the measurement, 75 g of glucose was collected.
同図かられかるように、吸引浸出液を用いて測定した場
合、血液を用いた測定に比べ約１５分の時遅れがあるが
、非常に良い相関が得られた。この時間遅れは、血液中
のグルコー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許容できる
ものである。また、この測定装置は、インシュリンの注
入ポンプと組み合わせ、血糖値のコントロールを可能に
することは、以上の結果から明らかである。As can be seen from the figure, when measuring using suctioned exudate, there was a time lag of about 15 minutes compared to measuring using blood, but a very good correlation was obtained. This time delay is thought to be due to the time it takes for glucose in the blood to exude to the surface of the skin and then pass through the cell to reach the sensor, but it is acceptable enough for monitoring blood sugar levels. It is something. Furthermore, it is clear from the above results that this measuring device can be used in combination with an insulin infusion pump to control blood sugar levels.
［発明の効果コ
以上、説明したとおり、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 explained above, according to the present invention, it is possible to provide a blood sugar level measuring device that can measure glucose concentration using a small amount of exudate and realizes continuous monitoring of blood sugar level.
第１図は本発明の一実施例の断面図、第２図は血糖値の
連続測定のための構成図、第３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・・・メツシュ３・・・吸
引セル ４・・・グルコースセンサ５・・・リー
ド線 ６・・・管７・・・浸出液
９・・・真空ポンプ
１１・・・測定回路
１３・・・被測定者
代
理
人Fig. 1 is a cross-sectional view of an embodiment of the present invention, Fig. 2 is a configuration diagram for continuous measurement of blood sugar levels, and Fig. 3 shows data of continuous measurement of blood sugar levels using the blood sugar level measuring device according to the present invention. FIG. 1... Skin 2... Mesh 3... Suction cell 4... Glucose sensor 5... Lead wire 6... Tube 7... Exudate 9... Vacuum pump 11... Measurement circuit 13...Measureee representative
Claims (1)
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、浸出液の減圧吸引経路上の内部に、
少なくともグルコースオキシダーゼとメデイエータが表
面に固定化された電極からなるアンペロメトリ型グルコ
ースセンサが備えられていることを特徴とする血糖値測
定装置。(1) In a blood sugar level measuring device that measures the glucose concentration in an exudate obtained by vacuum suctioning the skin from which the stratum corneum has been removed, there is a
A blood glucose level measuring device comprising an amperometric glucose sensor comprising an electrode on the surface of which at least glucose oxidase and a mediator are immobilized.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63207300A JP2586594B2 (en) | 1988-08-23 | 1988-08-23 | Blood glucose measurement device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63207300A JP2586594B2 (en) | 1988-08-23 | 1988-08-23 | Blood glucose measurement device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0257238A true JPH0257238A (en) | 1990-02-27 |
| JP2586594B2 JP2586594B2 (en) | 1997-03-05 |
Family
ID=16537499
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63207300A Expired - Fee Related JP2586594B2 (en) | 1988-08-23 | 1988-08-23 | Blood glucose measurement device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2586594B2 (en) |
-
1988
- 1988-08-23 JP JP63207300A patent/JP2586594B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2586594B2 (en) | 1997-03-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |