CA2028261C - Non-invasive method and apparatus for measuring blood glucose concentration - Google Patents

Non-invasive method and apparatus for measuring blood glucose concentration

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Publication number
CA2028261C
CA2028261C CA002028261A CA2028261A CA2028261C CA 2028261 C CA2028261 C CA 2028261C CA 002028261 A CA002028261 A CA 002028261A CA 2028261 A CA2028261 A CA 2028261A CA 2028261 C CA2028261 C CA 2028261C
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Prior art keywords
laser diode
glucose concentration
blood glucose
blood
light
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Expired - Fee Related
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CA002028261A
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French (fr)
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CA2028261A1 (en
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Won Suck Yang
Yoon Ok Kim
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Priority claimed from KR1019890015584A external-priority patent/KR930011586B1/en
Priority claimed from KR1019900011241A external-priority patent/KR920002091A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Medical Informatics (AREA)
  • Surgery (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Optics & Photonics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Emergency Medicine (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

ABSTRACT OF THE INVENTION
A method and apparatus for measuring blood glucose concentration by irraditing blood vessels with electromagnetic radiation using near-infrared radiation diffuse-reflection laser spectroscopy. This invention uses electromagnetic radiation of a wavelength that is transmitted through the skin to the measurement part, for example, a blood vessel. Since skin is mostly composed of water (H2O), which absorbs IR radiation in nearly the entire IR spectral range, only radiation of a certain, narrow protion of the IR spectral range called the "water transmission window" is transmitted through the skin. The present invention uses electromagnetic radiation with a wavelength of 1.3µm?1.9µm radiation from a semiconductor diode laser.
When electromagnetic radiation of these wavelengths irradiates the skin, light is transmitted through the skin to the blood vessel where the light interacts with the heterogeneous components of the blood. The light which reaches the blood is then diffusely reflected by the blood. The reflected light will have been modulated by the characteristic vibrations of the molecules which are major components of blood. The reflected light is detected and provided as a digital signal to a one-chip microcomputer. The one-chip microcomputer calculates a blood glucose concentration from the digital signal by reference to a calibration curve stored in the memory of the one-chip microcomputer. The one-chip microcomputer causes the calculated blood glucose concentration to be displayed on a digital display.

Description

2~2~

BACIGROUND OF T~ INVENTIO~

FI~LD OF THL INV~NTIOR

The present invention relates to a aethod and apparatus for aeasuring blood glucose concentration, and ~ore particularly, to a non-invasive technique for aeasuring blood glucose concentration using near-infrared radiation diffuse-reflection laser spectroscopy.

PRIOR ART

Generally, diabetics ~easure blood glucose concentration t~o to eight ti~es daily using a portable neasure-ent apparatus consisting of an injector (to obtain a blood saaple) and test Paper (to easure the a ount of gluco~e in the blood). This is known as the "enzyaatic" ethod or test.

The enzy~atic test for glucose concentration is undesirable both because it requires that blood be drawn and because it iB expensive. Less expensive techniques based on test paper have been introduced, but they are less accurate and still require that blood be drawn. Accordingly, research has been conducted to addres~ these proble~s.

It is desired to provide a ~ethod for neasuring blood glucose concentration that is accurate and does not require the drawing oi blood.

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Therefore, it is an object of the present invention i~ to provide a non-invasive technique for easuring blood glucose concentration, that is, to eliainate the need for drawing blood ior this aeasure~ent A further object o~ the present invention i8 to provide a convenient, - inexpensive, portable, easy-to-use apparatus ior aeasuring blood glucose concentration .~ , '' : ' ', :~' ' ' ~ ~ ' . ' ' 2~ 26~

~UH~ARY OF THE INVE~TION

The present invention i8 based on near-in~rared radiation diffuse-reflection laser spectroscopy which Deasures blood gluco~e concentration by irradiating blood ves6els with haraless electroaagnetic radiation This invention uses electroaagnetic radiation of a vavelength that is transnitted through the skin to the aeasureaent part, for exa Ple, a blood vessel Since skin is nostly conposed of water (HzO), which absorbs IR
radiation in nearlY the entire IR spectral range, only radiation of a certain, narrow portion of the IR spectral range called the "water trans~ission window" will be transnitted through the s~in Until recently, the water transaission window was thouRth to only include wavelengths between 3~ 5~ However, according to investigations by the present inventors, the wavelength which is able to reach a blood vessel through the water transnission window includes wavelenBths between 1 3~ 1 9~

Accordingly, the present invention uses electronagnetic radiation with a wavelength of 1 3~ 1 9~ radiation froe a seniconductor diode laser When electronagnetic radiation of these wavelengths irradates the skin, ligth is trans~itted through the 6kin to the blood vessel where the light interacts with the heterogeneous co~ponents of the blood The light which reaches the blood is then diffuselY reflected by the blood The reflected light will ... . , - .............. ,: , ... .
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have been nodulated by the characteristic vibrations of the nolecules ~hich are aior co~ponents of blood In the present invention, the diffusely reflected light described above is integrated by an integrating sphere The photons (hv) integrated as described above, are converted into an electrical neasureaent value by a detector, and that vlaue is supplied to a processing eans, such as a one-chip ~icroco~puter The one-chip nicrocoaputer calculates the blood glucose concentration using an accurate calibration aethod Near-infrared radiation is de~ined in the present invention (in accordance ~ith the International Union of Pure and Applied Che-istry (IUPAC) definition) as follows; frequency of about 10l8~ 3 75x lOl~Hz; energy of about 0 951~ 35 8(Rcal/-ol), 0 0412~ 1 55eV; wavelength oi about 0 8~ 30y The present invention is based on phYsical and chevical principles describing the vibrational aotion of the blood glucose ~olecules as easured with near-infrared radiation diffuse-reflection laser spectroscoPy Such vibrational notion includes both rotational and translational otion, and includes overtone vibrations and co-bination vibrations Of these vibrations, the overtone vibrations are do-inant The analysis nethod incorporated in the Present invention includes a satheuatical eodel based on nultiPle linear regression analysis and ~ultivariate analysis as ~odified by the Present inventor~ to deter-in~ the blood glucose concentration t ,', ~, " ':' ' ' , 2 ~ 6 ~

The present invention provides a nethod and apparatus for e~fiurin~
blood glucose concentration, which has the advantage oi ease oi u~e and ainiaal expense for patients The present invention ha~ no consu able parts and is portable, allowing easy out-oi-hooe testing The present invention is aore convenient than the prior art techniques Also, this invention does not present the possible physical daaa8e associated with the long-tern use of syringes The easurenent apparatus of the present invention can easure blood glucose concentration in a short tiae and unobtrusively Thereiore, the prior art techniques, with their inconvenience and expense are rendered obsolete The object and other objects oi the present invention are achieved by neasuring blood glucose concentration in a non-invasive technique, where .
a Power source, for exanple, a battery is supplied to a one-chip nicro-conputer, a digtal display, a laser diode pover supply, a detector (as needed), and an optical unit (as needed) by aeans of a power switch The one-chip icroco~puter controls the laser diode power supply so that it gradually applies current at a stable voltage and tenperature to the laser diode, which eaits the neces6ary wavelengths oi radiation bY aeans of a start/reset switch The one-chip eicroconputer i8 operated so that the D/A
converter controlled by said one-chip vicroco-puter and driving said laser dioed power supply converts a digital control signal into an analog control '., '. : ~ , ' ; " ' '`, ; ;' ~

2 ~ 1 signal.

Thus, the laser diode power supply causes the laser diode to eoit a wavelength suitable for neasurement. The light fron said laser diode iB
colli~ated, or otherNise optically controlled, separated and conbined. The optically controlled light is used to irradiate the skin adjacent to a blood vessel. ~he light absorbed, dispersed and diffusely re~lected by the blood back throu~h the skin is integrated by an inteBrating sphere. The photons collected by the integratinB sphere are converted into an analog electrical signal with a detector. The analog electrical signal is trans~itted to a preanplifier where the analog electrical signal is amplified. The aupli~ied analog electrical signal is provided to an analog to digital (A/D) converter that converts the anplified analog electrical signal to a corresPonding digital signal and outputs the digital signal to a one-chip uicrocomPuter.
The one-chip microcomputer calculates a blood glucose concentration ~rom the digital signal by reference to a calibration curve ~tored in the ~enorY of the one~chip ~icrocomputer. The one-chiP ~icroconputer causes the calculated blood glucose concentration to be disPlaYed on a di~ital display.

An apparatus for easuriDg blood glucose concentration using a non-invasive technique according to the present invention comprises:
one-chip oicrocomputer which controls the laser diode power supply so that current is gradually applied to a laser diode at a stable voltage and te~perature. The one- chip ~icrocomputer calculates the blood glucose concentration by co~paring a detected value with a calibration curve stroed . .. . . , , , ., . :

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. : . .. .. . .
.. . .. .
.,, : .

~2~'2611 in aeaory of the one-chip icrocoaputer A D/A converter converts the digital control signal output fron said one-chip microconputer into an analog control signal for control of the laser diode power supply that supplies power to the laser diode The laser diode is a light source for the blood glucose concentration ~easure-ent There ~ay be a pluralitY of laser diodes for emitting light of different wavelengths or for eaitting light of like wavelengths in accordance with the current supplied froa the laser diode power supply A teoperature controller for controlling the teuperature of the laser diode is connected bet~een the laser diode po~er supply and the laser diode An optical unit colliaates the light enitted fron the laser diode, or opticallY controls, separates and co bines the light fron the laser diode An integrating sphere integrates the light dispersed and difiusely reilected iroa the blood ~hen the blood is illuainated throu8h the skin by light froa the optical unit A detector for converts the photons collected by the intergrating sphere into an analog electrical value ~hich is then a-plified in the preasplifie~ An A/D
converter converts the electrical analog aeasurenent value into a digital value A digital disPlaY dispalys the blood glucose concentration calculated by the one-chip aicroco~puter : ~. . - .. . .: ~ . ;; .

.. ...
., . : : . - ~ ; . :~

2~2~

BRIEF DESCRIPTION OF THF DRAWING$

These and other objects and features of ths present invention will be understood through the various enbodi~ents by reference to the acconpanying drawings in which Figure 1 is a block diagran showing an apparatus for neasuring blood glucose concentration according to the present invention; and Figure 2 is a detailed circuit diagraa showing the apparatu~ for Figure 1.

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, ~02~261 DETAIL~D DESCRIPTION OF T~E IN~ENTION

A preferred eabodi~ent of a ~easureaent apparatus according to the present invention will be described hereinafter with reference to the acco-panying drawings Referring to Pigure 1, when a power BWitCh 1 iB switched oa. a power i8 supplied fron the battery (generally 4 5~ 9~ and i8 suited to a charging battery of 6V aaong other possibilities) to a one-chiP wicrocoePUter 2 At the sa-e tine, the power source iB aupplied to a digital displaY 3, a laser diode power supplY 4, and optical unit ~ (as needed) If the start/reset sNitch 8 is then switched ON, the laser diode power supply 4 supplies the laser diode 5 with power in accordance ~ith the control signal supplied by the one-chip icroconputer 2 AB a result, the laser diode current gradually increases if the current exceeds the threshold current (approxiDately 20aA) Thus, laser diode 5 starts e~itting light The laser diode 5 enits light (for exauple, light having a wavelength of 1 3~a~ 1 9~, and light having a wavelenBth of 1 4~e~ 1 8~s, aaong others), of a wavelength necessary for blood glucose concentration eacure~ent This wavelength iB achieved by gradually increasinB the current supplied with in the range of approxiaatelY 20~ 200~A at a stable voltage and te~perature in accordance with the characteristics of the laser diode In the present .:.: , . .. . .
, ~; . . .:, .,: .
. ., . . ~ . , . , : , -. ; ~. ~.. :,: :
... ..

2~26~

invention, the laser diode 5 is coaposed of between 1 and 30 diodes, and each nay enit light of a diiferent ~avelength, or each ~ay e-it light of the sane wavelength The light enitted froa the collective diodes in the la~er diode ~ naY be si-ultaneously e-itted by the diodes or 6equentially eaitted by each diode In case of sinultaneous operation, length ~ill be selected, for exa ple, using the ~ourier Transforn The light outputted frou the collective diodes oi the laser diode 5 i~
supplied to an optical unit 8, and colliaated, or the light is optically controlled, separated and coebined Thereafter, the light is pa~sed through an integrating sphere 9 and divided in one or eore directions The light which Pas~es through the integrating sphere 9 i~ successively irradiated to the skin of a subject, or is successively irradiated to a reierence port which ~as ready beforehand as the case nay be Here, the .
~ reference port i6 not necessarily needed , . .

The light absorbed, dispersed and diffusely reflected froa the blood is detected by a detector 7 after being integrated bY neans of the integrating sphere 9 The integrating 6phere i8 of a globular or like shape Here, the size of integrating sphere 9, ~hich i6 integrated ~ith light dispersed and reflected frou the blood, has a ~idth, length and height under 2 56CR, and is ~uitable for under 1 28cn, and nore Particularly~ is suitable for under . . : ........ . ~ ...... ,.- .: ..... ..

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An electrical analog aeasureaent value detected as above described is a-plified by a prea plifier connected to the detector 7 Thereafter, the electrical analoB neasureaent value is converted into a digital easurenent value by aeans of an A/D converter 11 Next, the one-chiP uicrocoaputer 2 calcolates and coaputes the neasured value by coaparing the signal converted into a digital neasureaent value by the A/D converter 11 with a calibration curve stored in aeaory of the one-chip icroco puter 2 The resultant value i8 difiplayed on the digital display 3 The di-ension~ of the above-described aeasureaent apparatus waY be widthx lengthxheight under 170nnX80H X 25n , and is suitable for under lS0~aX 75-nx 22 , a ong others, and aore particularly, is suitable for under 130- x70- x 20na "
A photo diode is suitable as the detector 7 aod aay be a 6e detector, and aore particularly, nay be a Ge detector connected to a preaaplifier Horeover, the optical unit 6 i9 co~posed of conponents which constitute a light which has a diaueter under 0 5N 5~r (under 2ee aaong others) in order to condense and diffuse the light in parallel ~urthereore, the present invention is not li-ited to an inteBrating - : .: :: ,. . . ~ .: :

2~26 ~

sphere 9 having a globular or li~e shape, but it aay also be o~ an oval or a half-oval or dii~erent shape In the present invention, the port ean be separated fron the above neasureaent apparatus In this case, the light euitted froa the laser diode 5 can be transnitted to the port through the optie ~iber, and the distanee between the port and the neasureaent apparatus is 100~ 1,OOO~e and is suitable for 500~ aaong others, and nore Partieularly, aay be 300 0 course, the port cannot be separated fro- the easureaent apparatu6 The present invention is not li-ited for one-chiP ieroeoaputer 2 separated froa the D/A converter 10 and the A/D converter 11, but can also be a one-chip ieroco puter 2 which is included in the D/A eonverter ln and the A/D eonverter 11 ,.~

Moreover, in the present invention, it ean be u~ed with au~iliary eireuit 12 which is conposed of RAM 12l and EPROM 12z in order to aid an operation of one-ehip ieroco-puter 2 ` .
The present invention is not li-ited for the easure-ent of blood glueose eoncentration and, for exanple, can be applied to a neasurenent of a cholesterol concentration or an alcohol concentration According to the Present invention as above described, there is Provided an econo~ic cethod and apparatus for easuring blood glucose concentration ::: , : :.

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in a non-invasive technique, which can easily aeasure the blood d ucose concentration by putting port of the apParatus to a certain part of the hu an bodY sight of a blood ve~sel without using an equip ent, such as a conventional iniector.

,, . - .,: . . .

Claims (8)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A non-invasive method for measuring blood glucose concentration comprising the steps of;
supplying a power source from a battery to a processing means, a digital display, a laser diode power supply, a detector and an optical unit by means of a power switch;
controlling said processing means so that said laser diode power supply gradually applies current to said laser diode at a stable voltage and temperature by means of start/reset switch;
controlling said processing means so that a D/A converter coupled between said processing means and said laser diode power supply converts a digital control signal into an electrical control signal;
emitting a wavelength sufficient for measurement in said laser diode by means of said laser diode power supply;
callimating the light emitted from the laser diode parallel to a corresponding object, or optically controlling, separating and combining the light emitted from said laser diode;
irradiating through an integrating sphere said optically controlled light to a blood vessel to measure blood glucose concentration integrating by means of said integrating sphere the light absorbed, dispersed and diffusely reflected by the blood after the light reaches the skin to the blood;
transmitting the signal amplified by a preamplifier connected to said detector to an A/D converter, after converting photons integrated by said integrating sphere and detected by said detector into an electrical analog measurement value;
transmitting the signal to said processing means, after converting said electrical analog measurement value into a digital measurement value by means of said A/D converter;
calculating and computing blood glucose concentration by comparing a calibration curve stored in memory region of said processing means with a digital measurement value converted by said A/D converter;
displaying a calculated blood glucose concentration on said digital display.
2. A method for measuring blood glucose concentration according to claim 1, wherein said measurement method is based on physical and chemical principles of vibrational motion of blood glucose molecules is nesr-infrared radiation diffuse-reflection laser spectroscopy due to vibrational, rotational and translational motion, utilizing overtone vibrations and a combination of other types of vibrations.
3. A method for measuring blood glucose concentration according to claim 1, wherein in the step of calculating and computing blood glucose concentration by comparing a calibration curve stored in the memory of said processing means with a digital measurement value converted by said A/D converter, utilizes a mathematical method such as a multiple linear regression analysis and a multivariate analysis.
4. A non-invasive apparatus for measuring blood glucose concentration comprising;
processing means for controlling the flow of current supplied from a laser diode power supply to a laser diode so that current is applied gradually and at stable voltage and temperature levels, said processing means for calculating and computing blood glucose concentration by comparing and electrical analog measurement value detected and converted by a detector with a calibration curve stored in a memory of said processing means;
a D/A converter for controlling the laser diode power supply by converting a digital control signal to an analog control signal, wherein said laser diode power supply applies a power source to said laser diode as a light source for blood glucose concentration measurement, and said laser diode consisting of a plurality of diodes for emitting light of different wavelengths or emitting light of the sane wavelength, in accordance with the current supplied from said laser diode power supply;
a temperature controller which controls the temperature of said laser diode, said temperature controller being connected between said laser diode power supply and said laser diode;
an optical unit which collimates light emitted from said laser diode parallel to corresponding object and optically controls, separates or combines the light emitted from said laser diode;
an integrating sphere which integrates light dispersed and diffusely reflected from the blood by irradiating light controlled by said optical unit to the skin of a diabetics as a measurement part;
a detector which amplifies a signal by means of a preamplifier connected its own after converting photon integrated by said integrating sphere into an electrical analog measurement value; and an A/D convertor converts said electrical analog measurement value into a digital measurement value; and a digital display for displaying the calculated and computed blood glucose concentration
5. An apparatus for measuring blood glucose concentration according to claim 4, wherein the wavelength of the electromagnetic radiation emitted from said laser diode is in the near-infrared region, and is 1.3 to 1.9µm among others, and more particularly, is 1.4 to 1.8µm, and the light emitted from said laser diode simultaneously irradiates the blood through the skin, or sequentially irradiates the blood through the skin.
8. An apparatus for measuring blood glucose concentration according to claim 4, wherein said integrating sphere is globular or like shape, oval or half oval or different shape, and said integrating sphere has a width, length and height under 2.56cm, and is suitable for under 1.28cm among others, and more particularly, is suitable for under 0.64cm, and said measurement apparatus has a width x length x height under 130mm x 70mm x20mm, and is suitable for under 150mm x 75mm x 22mm among others, and more particularly, is suitable for under 130mm x 70mm x 20mm.
7. In apparatus for measuring blood glucose concentration according to claim 4, wherein said port can be separated from the measurement apparatus by means of an optic fiber, and the distance between port and measurement apparatus is 100 ? 1,000mm, and is suitable for 500mm among others, and more particularly, is suitable for 300mm.
8. An apparatus for measuring blood glucose concentration according to claim 4, wherein a photo diode is utilized as said detector which detects photons integrated by said integrating sphere, and is utilized a Ge detector, and more particularly, is utilized a Ge detector coupled to a preamplifier, and said D/A converter and A/D converter are separated from said processing means, or are included in said processing means, and said battery used as a power source is 4.5 to 9V, and is suitable for a charging battery of 6V among others.
CA002028261A 1989-10-28 1990-10-22 Non-invasive method and apparatus for measuring blood glucose concentration Expired - Fee Related CA2028261C (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR89-15584 1989-10-28
KR1019890015584A KR930011586B1 (en) 1989-10-28 1989-10-28 Non-invasive method and apparatus for measuring blood glucose concentration
KR90-11241 1990-07-24
KR1019900011241A KR920002091A (en) 1990-07-24 1990-07-24 Egg-Invasive Blood Glucose Measurement Method and Apparatus

Publications (2)

Publication Number Publication Date
CA2028261A1 CA2028261A1 (en) 1991-04-29
CA2028261C true CA2028261C (en) 1995-01-17

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EP (1) EP0426358B1 (en)
JP (2) JPH03146032A (en)
CN (1) CN1025410C (en)
AT (1) ATE179874T1 (en)
CA (1) CA2028261C (en)
DE (1) DE69033104T2 (en)
HU (1) HU213438B (en)
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DE69033104T2 (en) 1999-10-28
JPH0581253B2 (en) 1993-11-12
EP0426358B1 (en) 1999-05-12
RU2122208C1 (en) 1998-11-20
HU906914D0 (en) 1991-05-28
CA2028261A1 (en) 1991-04-29
CN1025410C (en) 1994-07-13
JP2588468Y2 (en) 1999-01-13
CN1051297A (en) 1991-05-15
EP0426358A1 (en) 1991-05-08
JPH10181U (en) 1998-08-25
HU213438B (en) 1997-06-30
JPH03146032A (en) 1991-06-21
ATE179874T1 (en) 1999-05-15
DE69033104D1 (en) 1999-06-17
HUT58145A (en) 1992-01-28
US5267152A (en) 1993-11-30

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