WO2009106524A4 - Method and device for complex metabolic analysis - Google Patents

Method and device for complex metabolic analysis Download PDF

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Publication number
WO2009106524A4
WO2009106524A4 PCT/EP2009/052171 EP2009052171W WO2009106524A4 WO 2009106524 A4 WO2009106524 A4 WO 2009106524A4 EP 2009052171 W EP2009052171 W EP 2009052171W WO 2009106524 A4 WO2009106524 A4 WO 2009106524A4
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WO
WIPO (PCT)
Prior art keywords
metabolic
correction
acid
status
statements
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Application number
PCT/EP2009/052171
Other languages
German (de)
French (fr)
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WO2009106524A2 (en
WO2009106524A3 (en
Inventor
Hermann Heinrich
Klaus-Jürgen KURTH
Fred Lange
Original Assignee
Labotech Labortechnik Gmbh
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Publication date
Application filed by Labotech Labortechnik Gmbh filed Critical Labotech Labortechnik Gmbh
Priority to EP09715141A priority Critical patent/EP2252197A2/en
Publication of WO2009106524A2 publication Critical patent/WO2009106524A2/en
Publication of WO2009106524A3 publication Critical patent/WO2009106524A3/en
Publication of WO2009106524A4 publication Critical patent/WO2009106524A4/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring 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 analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4866—Evaluating metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/411—Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance

Abstract

The invention relates to a method and a device for non-invasive or invasive measurement of control and regulation processes of plant, animal or human metabolism for the controlling of disruptions and for determining physical or chemical influencing factors on reaction conditions so as to be able to draw conclusions about specific illnesses from the changes in individual metabolic parameters. The object is to propose a method and a device that make it possible to measure metabolic control and regulation processes in order to draw conclusions about specific illness symptoms from changes in these processes. The method should make the measurement process repeatable non-invasively or invasively and rapidly in order not to induce stress from the measurement process. The characterizing feature is that metabolically relevant, biologically active autofluorescent substances are selected from the native fluorescence spectrum in the wavelength range of 287 nm to 600 nm and are linked together in biochemical and biophysical models in order to describe control and regulation processes in humans and animals and in plants.

Claims

GEÄNDERTE ANSPRÜCHE beim Internationalen Büro eingegangen am 15 Dezember 2009 (15.12.2009) AMENDED CLAIMS received by the International Bureau on 15 December 2009 (15.12.2009)
1. Verfahren zur nichtinvasiven und/oder invasiven komplexen Stoffwechselanalyse zur Kontrolle von Störungen sowie zur Bestimmung von physikalischen oder chemischen Einflussfaktoren auf die Reaktionsbedingungen durch stoffwechselrelevante Substanzen, welche alle Wege der stofflichen Umsetzung bestimmend beeinflussen und während der Stoffumsatzvorgänge entstehen, miteinander reagieren, sich einander umwandeln und/oder sich gegenseitig in ihrer Konzentration und Reaktionsfähigkeit beeinflussen und die eine (endogene) Autofluoreszenz aufweisen, über ihre Fluoreszenzintensität und somit mittelbar in ihrer Konzentration nebeneinander bestimmt werden, wobei die Fluoreszenzspektren, die aus den erfassten Wellenlängen im Bereich von 287 nm bis 600 nm und den dazugehörigen Fluoreszenzintensitäten bestehen, gespeichert und zur Auswertung vorbereitet werden, indem Wertepaarungen von Wellenlänge und Fluoreszenzintensität für die stoffwechselrelevanten Substanzen ausgewählt und in biophysikalischen und biochemischen Modellen verknüpft werden mit indikationsbezogenen Störmodellen, die unterschiedliche Möglichkeiten der Stoffwechselregulation und Änderung des Stoffwechselzustandes definieren, verglichen werden, gekennzeichnet dadurch, dass1. A method for noninvasive and / or invasive complex metabolic analysis for the control of disorders and for the determination of physical or chemical factors influencing the reaction conditions by metabolically relevant substances, which influence all pathways of material conversion and arise during the metabolic processes, react with each other, convert each other and / or influence each other in their concentration and reactivity and that have an (endogenous) autofluorescence, are determined by their fluorescence intensity and thus indirectly in their concentration next to each other, the fluorescence spectra, from the detected wavelengths in the range of 287 nm to 600 nm and the associated fluorescence intensities exist, stored and prepared for evaluation, by value pairs of wavelength and fluorescence intensity for the metabolically relevant substances selected and in biop Hysical and biochemical models are compared with indication-related interference models, which define different possibilities of metabolic regulation and change of the metabolic state, characterized in that
- die Abweichungen jeder Statusaussage zum Idealwert berechnet werden, wobei der gewichtete Mittelwert aus den Abweichungen der Statusaussagen zum Idealwert in einen mathematische Zusammenhang gesetzt wird, wobeithe deviations of each status statement to the ideal value are calculated, wherein the weighted mean value from the deviations of the status statements to the ideal value is put into a mathematical relationship, wherein
- der mathematische Zusammenhang zwischen einem gesuchten Mengenverhältnis und einem spezifischen Erfordernis an Wirkstoffen und den gegebenen Abweichungen der Statusaussagen durch eine Korrekturmatrix hergestellt wird.- The mathematical relationship between a sought quantity ratio and a specific requirement of drugs and the given deviations of the status statements is produced by a correction matrix.
2. Verfahren nach Anspruch 1 dadurch gekennzeichnet, dass die stoffwechselrelevanten Substanzen vorzugsweise ATP (Adenosin- triphosphat), GTP (Guanosintriphosphat), FAD (Flavinadenindinucleotid, reduziert), NADP (Nikotinamidadenindinukleotidphosphat, oxidiert), Kynurenin, Orotsäure, Thromboxan und Tryptophan sind. 182. Method according to claim 1, characterized in that the metabolically relevant substances are preferably ATP (adenosine triphosphate), GTP (guanosine triphosphate), FAD (flavin adenine dinucleotide, reduced), NADP (nicotinamide adenine dinucleotide phosphate, oxidized), kynurenine, orotic acid, thromboxane and tryptophan. 18
3. Verfahren nach Anspruch 1 oder 2 dadurch gekennzeichnet, dass die Fluoreszenzintensitäten im Wellenlängenbereich von 340 nm bis 600 nm, für stoffwechselrelevante Substanzen, deren Emissionswellenlängen bekannt sind, ATP, GTP, FAD, NADH, NADP, Kynurenin, Orotsäure, Thromboxan und Tryptophan gemessen werden.3. The method according to claim 1 or 2, characterized in that the fluorescence intensities in the wavelength range of 340 nm to 600 nm, for metabolically relevant substances whose emission wavelengths are known, ATP, GTP, FAD, NADH, NADP, Kynurenin, orotic acid, thromboxane and tryptophan measured become.
4. Verfahren nach einem der Ansprüche 1 bis 3 dadurch gekennzeichnet, dass die biologisch aktiven Substanzen und Stoffwechsel-Intermediate im zellulären und interzellulären (interstitiellen) Bereich mit Licht einer Exzitationswellenlänge von 287 nm bis 340 nm zur Emission angeregt werden.4. The method according to any one of claims 1 to 3, characterized in that the biologically active substances and metabolic intermediates in the cellular and intercellular (interstitial) region are excited to emission with light having an excitation wavelength of 287 nm to 340 nm.
5. Verfahren nach einem der Ansprüche 1 bis 4 dadurch gekennzeichnet, dass die Messung der Fluoreszenzintensitäten zu einem beliebigen Zeitpunkt und/oder in festgelegten zeitlichen Abständen erfolgt, so dass durch diese Verlaufsmessungen Steuer- und Regelungsprozesse erkannt werden.5. The method according to any one of claims 1 to 4, characterized in that the measurement of the fluorescence intensities at any time and / or at fixed time intervals, so that control and regulatory processes are detected by these progress measurements.
6. Verfahren nach einem der Ansprüche 1 bis 5 dadurch gekennzeichnet, dass zu einem beliebigen Zeitpunkt der Messung definierte physikalische, chemische oder kombinierte Störeinflüsse oder Schädigungseinwirkungen auf künstliche oder natürliche Testobjekte ausgelöst werden, die Fluoreszenzintensitäten vor und nach der Belastung mehrmals gemessen werden und der Einfluss auf die Regulation im Stoffwechsel bestimmt wird.6. The method according to any one of claims 1 to 5, characterized in that at any time of the measurement defined physical, chemical or combined interference or damage effects on artificial or natural test objects are triggered, the fluorescence intensities are measured several times before and after the load and the influence is determined on the regulation in metabolism.
7. Verfahren nach Anspruch 6 dadurch gekennzeichnet, dass die Störungen der Regulationsbereiche durch Wirkstoffe durch alle Vitalstoffe Jod, Selen, Calcium, Kalium, Magnesium, Chrom, Vanadium, Kupfer, Molybdän, L-Methionin, L-Cystein, Coenzym Q 10, Quercetin, Cholin, L-Carnitin, d-alpha- Tocopherol, Retinol, Cholecalciferol, Ascorbinsäure, Thiamin, Riboflavin, Niacin, Pantothensäure, Pyridoxin, Inositol, Folsäure, Cobalamin, Biotin, Pangaminsäure, Carotinoide, 3-Epigalockatechin-Galat, Omega-3-Fettsäuren, Vitamin E, Alphaliponsäure, Glutathion, Zink, Eisen, Taurin, Cholamin, Lutein, Lycopin ausgeglichen werden, indem die Abweichungen jeder Statusaussage zum Idealwert berechnet werden (100 % oder 0 % je nach Aussagetyp). 197. The method according to claim 6, characterized in that the disorders of the regulatory areas by active ingredients by all vital substances iodine, selenium, calcium, potassium, magnesium, chromium, vanadium, copper, molybdenum, L-methionine, L-cysteine, coenzyme Q 10, quercetin , Choline, L-carnitine, d-alpha-tocopherol, retinol, cholecalciferol, ascorbic acid, thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, inositol, folic acid, cobalamin, biotin, pangamic acid, carotenoids, 3-epigalockatechin-galat, omega-3 -Fatty acids, vitamin E, alpha-lipoic acid, glutathione, zinc, iron, taurine, cholamine, lutein, lycopene, by calculating the deviations of each status statement to the ideal value (100% or 0% depending on the type of statement). 19
8. Verfahren nach Anspruch 1 oder 7 dadurch gekennzeichnet, dass die Korrekturmatrix aus 22 Zeilen für je einen Korrektur-Wirkstoff und aus 13 Spalten für 13 Statusaussagen besteht.8. The method of claim 1 or 7, characterized in that the correction matrix consists of 22 lines for each correction drug and 13 columns for 13 status statements.
9. Verfahren nach Anspruch 8, dadurch gekennzeichnet, dass die Korrekturmatrix spezielle Koeffizienten als Wichtungsfaktoren für den Zusammenhang zwischen dem Korrektur-Bedarf und den Statusaussagen ausweist.A method according to claim 8, characterized in that the correction matrix identifies special coefficients as weighting factors for the relationship between the correction requirement and the status statements.
10. Verfahren nach Anspruch 1, 6, 7, 8 oder 9 dadurch gekennzeichnet, dass durch eine multivariate Regression die bestmögliche Übereinstimmung der Aussagen zum Korrekturbedarf aus zwei unabhängigen Messverfahren hergestellt wird, wie durch den Bezug auf die Korrekturempfehlung als Ableitung aus der Komplexen Serum-Redoxdifferenz-Provokationsanalyse und der nichtinvasiven Methode durch die Messung der spezifischen Fluoreszenz- Intensitäten. 10. The method of claim 1, 6, 7, 8 or 9, characterized in that by a multivariate regression the best possible agreement of the statements on the correction requirement from two independent measurement methods is prepared, as by reference to the correction recommendation as a derivative of the complex serum Redox difference provocation analysis and the non-invasive method by measuring the specific fluorescence intensities.
PCT/EP2009/052171 2008-02-25 2009-02-24 Method and device for complex metabolic analysis WO2009106524A2 (en)

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DE102008011013A1 (en) 2009-09-03
WO2009106524A2 (en) 2009-09-03
EP2252197A2 (en) 2010-11-24
WO2009106524A3 (en) 2009-12-17
DE102008011013B4 (en) 2014-11-13

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