WO2009106524A2 - Procédé et dispositif d'analyse métabolique complexe - Google Patents

Procédé et dispositif d'analyse métabolique complexe Download PDF

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Publication number
WO2009106524A2
WO2009106524A2 PCT/EP2009/052171 EP2009052171W WO2009106524A2 WO 2009106524 A2 WO2009106524 A2 WO 2009106524A2 EP 2009052171 W EP2009052171 W EP 2009052171W WO 2009106524 A2 WO2009106524 A2 WO 2009106524A2
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WO
WIPO (PCT)
Prior art keywords
invasive
status
correction
substances
metabolic
Prior art date
Application number
PCT/EP2009/052171
Other languages
German (de)
English (en)
Other versions
WO2009106524A4 (fr
WO2009106524A3 (fr
Inventor
Hermann Heinrich
Klaus-Jürgen KURTH
Fred Lange
Original Assignee
Labotech Labortechnik Gmbh
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Labotech Labortechnik Gmbh filed Critical Labotech Labortechnik Gmbh
Priority to EP09715141A priority Critical patent/EP2252197A2/fr
Publication of WO2009106524A2 publication Critical patent/WO2009106524A2/fr
Publication of WO2009106524A3 publication Critical patent/WO2009106524A3/fr
Publication of WO2009106524A4 publication Critical patent/WO2009106524A4/fr

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Classifications

    • 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

Definitions

  • the invention relates to a method and a device for non-invasive or invasive measurement of control and regulatory processes of plant, animal or human metabolism to control disorders and for the determination of physical or chemical factors influencing the reaction conditions, from the changes of individual Metabolic parameters to draw conclusions about specific diseases.
  • the method is used in preventive examinations for early cancer detection or cancer aftercare, in all inflammatory diseases, damage to immune regulation, metabolic diseases, syndromes such as chronic fatigue or multiple chemical sensitivity, allergies in
  • Fluorescence spectrometric investigations have been known for some years as highly accurate and very specific methods in basic biological research on transport processes through biological membranes in all cellular compartments and biomedical investigations as a diagnostic tool and are z. Currently in a steady progressive development phase.
  • the basis of the measurement method is the knowledge of the properties of artificial fluorophores or the knowledge of the excitation and emission wavelength of autofluorophores.
  • a variety of metabolic parameters such as tryptophan, adenosine triphosphate (ATP), guanosine triphosphate (GTP), nicotinamide adenine dinucleotide phosphate (NADP), nicotinamide adenine dinucleotide reduced (NADH), kynurenine, flavin adenine dinucleotide (FAD) and thromboxane possess a so-called autofluorescence.
  • ATP adenosine triphosphate
  • GTP guanosine triphosphate
  • NADP nicotinamide adenine dinucleotide phosphate
  • NADH nicotinamide adenine dinucleotide reduced
  • kynurenine flavin adenine dinucleotide
  • FAD flavin adenine dinucleotide
  • thromboxane possess a so-called autofluorescence.
  • the invention is based on the object to propose a method and a device that make it possible to measure control and regulation processes of human and animal and also plant metabolism in order to detect changes in the metabolism of proteins, lipids, carbohydrates and Hormones to draw conclusions about specific clinical pictures.
  • the procedure is intended to make the actual measurement process noninvasive, or invasive and quickly repeatable, so as not to stress the measurement process.
  • Metabolic analysis for the control of disorders and for the determination of physical or chemical factors influencing the reaction conditions is characterized in that metabolically relevant substances, which influence all ways of the material conversion of proteins, lipids, carbohydrates and hormones decisive and arise during the metabolic processes, react with each other convert each other and / or influence each other in their concentration and reactivity and which have a (endogenous) autofluorescence, are determined by their fluorescence intensity and thus indirectly in their concentration side by side, the fluorescence spectra, from the detected wavelengths in the range of 287 nm 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 out are selected and combined in biophysical and biochemical models, are compared with indication-related glitch models that define different possibilities of metabolic regulation and change of metabolic state, the deviations of each status statement are calculated to the ideal value, wherein the weighted average from the deviations of the status statements to the ideal value into one mathematical relationship is established, which is made between a sought
  • Fluorescence spectrum in the wavelength range from 287 nm to 600 nm metabolically relevant biologically active substances that have an autofluorescence, are selected and in biochemical or
  • Biophysical models are linked together to describe control and regulatory processes in humans and animals or in plants.
  • the fluorescence spectra are detected via an optical measuring path, which consists of a light source, a light guide cable for supplying the excitation light to the measuring location, a light guide cable for the derivation of the fluorescent light to the spectrometer and an evaluation computer.
  • an optical measuring path which consists of a light source, a light guide cable for supplying the excitation light to the measuring location, a light guide cable for the derivation of the fluorescent light to the spectrometer and an evaluation computer.
  • Vital substance requirement, for a regulating influencing influence are determined from the non-invasive measured values by the determination of the deviations of status statements to the optimal health status.
  • the deviation values are weighted according to the importance of the nutrients for these deviations.
  • the weighted averages allow the calculation of the dosing units for the missing vital substances by inserting them into equalization polynomials of the third order.
  • the device proposed for carrying out the method consists of a light source, preferably a laser or xenon flash lamp, an optical filter, miniature spectrometer and connecting optical cables between the light source with probe at the site and an evaluation.
  • Fluorescence spectra and guaranteed freedom from stress As a result of this measurement process repeat measurements can take place in very short time intervals and thus regulatory processes in the metabolism can be detected. By altering these regulatory processes under defined stress conditions conclusions about pathological changes of the organism can be drawn.
  • FIG. 1 shows a block diagram of the measuring path for measuring value measurement
  • FIG. 2 shows examples of native fluorescence spectra
  • Fig. 5 Selection using the emission wavelengths 509 nm and 495 nm
  • Fig. 6 Example for determining the deviations of the status statements for optimal health status
  • FIG. 7 Example for the determination of the weighted average value for each substance to be recommended by multiplication
  • FIG. 8 Example of the calculation of the dosage via a 3rd-order equalization polynomial for manganese
  • excitation light is irradiated locally into the skin surface 6 via a glass fiber probe 3 from a light source 1.
  • An optical filter 4 (bandpass and notch filter), which is connected by means of optical fiber cable 2 with a miniature spectrometer 5, limits the excitation light to the UV range. This ensures that the fluorescence signal to be measured is not superimposed with the excitation light and the scattered light of the skin surface.
  • the light source 1 and the fluorescence signal to be measured represent excited autofluorescent components from the interstitium just below the skin surface. Both the intensity of the excitation light and the duration of the irradiation are well below the legal maximum limits.
  • a miniature spectrometer 5 allows the spectral separation of
  • the components 1 to 5 are identical to Fluorescence components of the measurement signal.
  • the components 1 to 5 are identical to Fluorescence components of the measurement signal.
  • the recorded spectrum represents a screening of the current health status of the subject.
  • a combined measurement and evaluation software which is installed on a computer known per se, is used for the detection, evaluation, interpretation and visualization of the measurement results.
  • the result of the screening results in a finding with percentage-disaggregated statements about the current state of health of the subject.
  • the components light source PX - 2 xenon lamp 1, optical fiber for the derivation of excitation light and fluorescence signal 2, probe / measuring head 3, optical filter 4, miniature spectrometer USB 2000 with OFVL - filter 5, represent the measuring path according to the invention and are in housing 7 as Measuring cell mounted.
  • the stored in the computer fluorescence spectra which consist of the detected wavelengths in the range of 287 nm to 600 nm and the associated fluorescence intensities are prepared in a suitable table format for evaluation.
  • Fig. 2 shows examples of these native spectra.
  • the value pairings (wavelength and fluorescence intensity) for metabolically relevant, biologically active substances such as ATP, GTP, tryptophan, orotic acid, NADP, NADH, FAD, etc. are selected.
  • the excitation wavelengths and emission wavelengths of these substances were determined in extensive preliminary experiments. Since different skin structures and skin constituents do not allow the use of the absolute values, a further evaluation can only be made with relative values. It is therefore necessary to determine value pairings of the relevant biologically active substances and to link them in biophysical and biochemical models. These models include substances that react with one another during metabolic processes, interconvert and / or influence each other's concentration and responsiveness.
  • Fig. 3 shows the representation of the result of a simple biochemical model, as the first selection stage of the diagnosis
  • Fig. 4 shows a separation between cancers or treated cancers and inflammatory diseases.
  • Fig. 5 shows an additional selection at the wavelengths 509 nm and 495 nm, the emitting substances are not yet known, but the use of this selection shows success.
  • active substances vitamin substances
  • the disorders of the regulatory areas by active substances may preferably be due to all vital substances, such as iodine, selenium, calcium, potassium, magnesium, chromium, vanadium, copper, molybdenum, L-methionine, L-
  • the weighted average from the deviations of the status statements to the ideal value represents the mathematical approach for an individual statement on the required for the correction drug qualities and quantities.
  • the correction matrix has special coefficients as weighting factors for the correlation between the correction requirement and the status statements.
  • the interference models are calculated from the fluorescence intensities and correspond to the metabolically relevant substances, preferably ATP (adenosine triphosphate), GTP (guanosine triphosphate), FAD (nicotinic adenine dinucleotide, reduced), NDAP (nicotinic adenine dinucleotide phosphate, oxidized), kynurenine, orotic acid, thromboxane and tryptophan , in proportions that are very different in different metabolic disorders, correspond to such real disturbed metabolic states and are represented as so-called thermographers. These thermographers (at least 13) allow in statistically secured different combinations statements on various regulatory areas of life functions of all organisms as a status statement, including preferably protection against hyperacidity, immune defense, metabolic rate quality,
  • the statements on health status are determined by the non-invasive measurement as percentages. Derived from this, the calculation of the deviations of the current percentages to the optimal value of the health status.
  • the weighted mean value is obtained for the various vital substances (FIG. 7).
  • the regression calculation thus allows a correction recommendation as a derivation from the measurement results of the method of complex serum redox difference provocation analysis and the measured values of the specific fluorescence intensities of the noninvasive method.

Abstract

L'invention porte sur un procédé et un dispositif de mesure non effractive ou effractive des processus de contrôle et de régulation du métabolisme végétal, animal ou humain, pour la surveillance des troubles, et pour l'identification de facteurs d'influence physiques ou chimiques sur les conditions de réaction, de façon que des enseignements sur certaines maladies spécifiques puissent être dérivés des modifications de paramètres particuliers du métabolisme. Le but de l'invention est de proposer un procédé et un dispositif qui permettent de mesurer les processus de contrôle et de régulation du métabolisme, afin qu'il soit possible de dériver des enseignements sur des tableaux pathologiques spécifiques à partir des modifications de ces processus. Ce procédé permet une répétition rapide du processus de mesure proprement dite, effractif ou non effractif, afin d'éviter que la procédure de mesure ne provoque un effet de stress. Ce procédé est caractérisé par la sélection dans le spectre de fluorescence natif, dans l'intervalle de longueur d'onde compris entre 287 nm et 600 nm, de substances bioactives importantes pour le métabolisme, possédant une autofluorescence, et l'association desdites substances dans des modèles biochimiques ou biophysiques, pour décrire les processus de contrôle et de régulation chez l'homme et l'animal ou chez les plantes.
PCT/EP2009/052171 2008-02-25 2009-02-24 Procédé et dispositif d'analyse métabolique complexe WO2009106524A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09715141A EP2252197A2 (fr) 2008-02-25 2009-02-24 Procédé et dispositif d'analyse métabolique complexe

Applications Claiming Priority (2)

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DE102008011013.2 2008-02-25
DE200810011013 DE102008011013B4 (de) 2008-02-25 2008-02-25 Verfahren und Einrichtung zur komplexen Stoffwechselanalyse

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WO2009106524A2 true WO2009106524A2 (fr) 2009-09-03
WO2009106524A3 WO2009106524A3 (fr) 2009-12-17
WO2009106524A4 WO2009106524A4 (fr) 2010-02-11

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DE (1) DE102008011013B4 (fr)
WO (1) WO2009106524A2 (fr)

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CN110376177A (zh) * 2019-09-02 2019-10-25 武汉格谱光电科技有限公司 烟酰胺腺嘌呤二核苷酸荧光光谱检测装置及使用方法

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DE102010023486A1 (de) * 2010-06-11 2011-12-15 B. Braun Avitum Ag Nachweisvorrichtung und -verfahren
DE102012002086A1 (de) 2012-02-06 2013-08-08 Carl Zeiss Meditec Ag Verfahren zum Untersuchen von biologischem Gewebe und Vorrichtungen zum Untersuchen und Behandeln des Gewebes
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Publication number Priority date Publication date Assignee Title
EP2387712A2 (fr) * 2009-01-13 2011-11-23 Mohsen Sharifzadeh Mesure non invasive des composés flavonoïdes dans un tissu biologique
EP2387712A4 (fr) * 2009-01-13 2013-04-17 Mohsen Sharifzadeh Mesure non invasive des composés flavonoïdes dans un tissu biologique
US9814417B2 (en) 2009-01-13 2017-11-14 Longevity Link Corporation Noninvasive measurement of flavonoid compounds in biological tissue
CN110376177A (zh) * 2019-09-02 2019-10-25 武汉格谱光电科技有限公司 烟酰胺腺嘌呤二核苷酸荧光光谱检测装置及使用方法

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DE102008011013A1 (de) 2009-09-03
WO2009106524A4 (fr) 2010-02-11
EP2252197A2 (fr) 2010-11-24
WO2009106524A3 (fr) 2009-12-17
DE102008011013B4 (de) 2014-11-13

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