• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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  • 优先权
    • 专利摘要:
    The present application relates to a method for assessing the lactose digestion of an individual. In a first step, the individual is given a lactose dose of at least 20 g orally. Then at least one sample of the individual's blood or urine is taken within a period of 6 hours after administration of the lactose dose. The at least one blood sample is preferably taken at least one hour after the administration of the lactose dose, while urine of the individual is collected and pooled over a period of at least 3 hours after the administration of the lactose dose to give a urine sample. In a next step, the amount of galactonate and / or the amount of galactitol in the at least one blood sample or in the urine sample is measured. Unaffected lactose digestion is determined in the individual, either: iii. by the presence of a statistically significant positive slope in the measured amount of galactonate and / or galactitol in several blood samples; or iv. by comparing the measured amount of galactonate and / or galactitol in the at least one blood sample or in the urine sample with a reference threshold.
    公开号:CH715409A2
    申请号:CH01186/18
    申请日:2018-09-28
    公开日:2020-03-31
    发明作者:Badertscher René；Burton Kathryn；Freiburghaus Carola；Münger Linda；Pimentel Grégory；Pralong François；Vionnet Nathalie
    申请人:Agroscope；
    IPC主号:
    专利说明:

    Technical field
    The invention relates to a method for assessing lactose digestion in blood and urine.
    State of the art
    Lactose is a disaccharide that is composed of glucose and galactose and is mainly found in milk and dairy products, but is also present in many processed foods. Digestion of lactose requires the presence of the enzyme lactase, which hydrolyses lactose in the brush border of the small intestine. After the hydrolysis of lactose to glucose and galactose, both saccharides are absorbed. Most people experience a reduction in lactase activity in late childhood. As a result, undigested lactose can be metabolized by the microbiota in the colon. In a third to a half of individuals with such lactose mis-digestion or lactose maldigestion (LM), these fermentation products can cause gastrointestinal symptoms, including diarrhea, abdominal pain, bloating, flatulence, and vomiting after eating dairy products, and thus define the clinical manifestations of the Lactose intolerance (LI). Conversely, approximately 35% of the world's adult population maintains lactase activity at a level similar to that in childhood, making them lactose-tolerant. This persistence of lactase is due to polymorphisms in the promoter of the lactase gene, which eliminate the programmed reduction in the activity of the promoter with increasing age.
    [0003] Several diagnostic methods are available to determine lactose maldigestion in humans. A jejunal biopsy allows direct measurement of lactase activity. However, this test is invasive and depends on the location of the sampling. Another method is to use genetic testing to assess lactase persistence genotypes as a proxy for lactose tolerance. In the case of genetic heterogeneity or if there are secondary causes, the genetic test may not reflect lactose maldigestion. Lactose maligestion can also be assessed with tests in which a given amount of lactose has to be taken orally, for example the hydrogen breath test or the measurement of the blood sugar level after lactose intake. WO 2004/035 814 A1 (Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid) describes the use of 4-galactosyl-xylose for the in vivo evaluation of intestinal lactase as a non-invasive diagnostic test to investigate the lactase deficiency. The method uses the measurement of the xylose concentration in the blood of an individual after oral administration of 4-galactosyl xylose.
    However, each of these test methods has limitations in terms of sensitivity and specificity and / or the interpretation of their results can prove to be difficult in clinical practice.
    Summary of the invention
    The aim of the invention is to create a novel method for assessing lactose digestion, which provides a reliable complementary method to the above tests by measuring the products of the galactose metabolism. For this purpose, galactonate and galactitol, two metabolites that originate from galactose metabolism, are measured in blood and / or urine and serve as representatives for lactose digestion. It should be noted that the use of lactose as an energy source requires active intestinal lactase and a number of active physiological processes, including the intestinal transport of galactose, the liver metabolism from galactose to galactonate and galactitol, and the renal excretion of these metabolites.
    [0006] The solution according to the invention is defined by the features of claim 1. According to the invention, the method for assessing the lactose digestion of an individual comprises, in a first step, the oral administration of a lactose dose of at least 20 g to the individual. In a second step, at least one sample of the blood or urine is taken within 6 hours. The at least one sample of the blood is preferably taken at least 1 hour after taking the lactose dose. The individual's urine collected over a period of at least 3 hours is pooled to obtain the urine sample. The amount of galactonate and / or galactitol in the at least one blood sample or in the urine sample is then measured. Lactose digestion, which is not impaired, is determined in the individual, either:<tb> i.) <SEP> due to the presence of a statistically significant positive slope when the measured amount of galactonate and / or galactitol is shown in several blood samples as a function of time;<tb> <SEP> or<tb> ii.) <SEP> by comparing the measured amount of galactonate and / or galactitol in the at least one blood sample or in the urine sample with a reference threshold value.
    It has been shown that the amount of galactitol and / or galactonate present in an individual's blood, particularly at least one hour after the lactose dose is administered, and in the urine during a period of at least 3 hours after the lactose dose is administered , reliable determination of lactose digestion in humans. This finding is surprising because the majority of the galactose that is metabolized from lactose is known to be metabolized to UDP-glucose via the Leloir metabolic pathway. Only a fraction of galactose (i.e. on the order of 1 mg per gram of lactose consumed) is metabolized via two alternative metabolic pathways, where it is either reduced to galactitol by aldose reductase or oxidized to galactonate by galactose dehydrogase. It is possible that the small amounts of galactose that are metabolized via these two metabolic pathways lead to a sufficiently high concentration of both galactitol and galactonate in blood or urine that it is possible to differentiate between individuals with undisturbed lactose digestion and individuals with impaired lactose digestion very surprising.
    The method according to the invention should preferably be carried out with fasting individuals, i.e. individuals should not have eaten for at least 12 hours. The lactose dose is preferably in liquid form. For example, at least 20 g of lactose powder are dissolved in water. Alternatively, the lactose dose can be in the form of a predetermined milk volume that contains at least 20 g of lactose. In this case, the lactose concentration in the milk must be known so that the volume of milk to be administered to the individual can be calculated in order to reach the predetermined lactose dose.
    [0009] The lactose dose is preferably taken orally by the individual within 15 minutes.
    [0010] Urine is then collected over a period of at least 3 hours after the oral administration of the lactose dose. The collected urine samples are then summarized, i.e. combined into a urine sample. A fasting urine sample can be taken to determine the initial levels of galactitol and / or galactonate, preferably after discarding the first morning urine and after the individual has drunk at least 2 dl of water.
    [0011] Alternatively, blood samples are taken at several times after oral administration of the lactose dose; blood samples are preferably taken at least five times during the 6-hour period after administration of the lactose dose. For example, the blood samples can be taken 15 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes and 180 minutes after oral administration of the lactose dose. In this case, the at least five blood samples are preferably taken at regular intervals throughout the 6 hour period, i.e. also within the first hour after administration of the lactose dose.
    [0012] The blood serum or the plasma from the at least one blood sample is then preferably separated from the blood sample.
    The term “and / or” as used in the present application means that the amount of galactonate or galactitol or the amount of both compounds is determined in the process. It has been shown that the determination of only one of the two compounds is sufficient for a clear determination of the lactose digestion. However, determining the amount of both galactonate and galactitol in the samples increases the robustness of the method.
    The term “amount” as used in the present application means a quantified amount of galactonate or galactitol in the blood and urine samples assessed.
    The amount is preferably given in mmol or mmol / 1. However, any other suitable unit of measurement can also be used.
    An unaffected lactose digestion is determined in an individual by determining a statistically significant positive slope if the measured amount of galactonate and / or galactitol is shown in several blood samples as a function of time. Preferably at least five blood samples taken at different times during the 6 hour period after lactose administration are used.
    Preferably, a linear regression is calculated for the measured amounts of galactonate and / or galactitol as a function of time and the significance of the slope is assessed by an analysis of variance ("analysis of variance"; ANOVA) to determine whether the slope is positive and statistically significant. The statistical significance of the slope can be determined using a p-value for the variance test of less than 0.05.
    Impaired lactose digestion is found in the individual if it is demonstrated that an increase in the measured amount of galactonate and / or galactitol in the blood samples as a function of time does not differ significantly from zero (P <0.05).
    Alternatively, the slope of the regression line is compared with a reference threshold slope. If the slope is greater than the reference threshold slope, it is assumed that the individual has an unimpaired lactose digestion. If the slope is less than the reference threshold slope, it is considered that the individual's lactose digestion is compromised.
    To determine the reference threshold slope, a set of individuals with known impaired lactose digestion, who were identified, for example, using the method according to the invention described above, is used to calculate a reference threshold slope in blood for impaired lactose digestion. A reference threshold slope in blood is determined from the sum of [average slope for galactitol or galactonate in the set of individuals with impaired lactose digestion] + [2 standard deviations of the data set].
    Alternatively, the criteria can be combined both for the ANOVA method and for the method of the reference threshold slope for determining an unaffected or an impaired lactose digestion as a means of increasing the sensitivity and specificity of the test.
    Alternatively, the identification of unaffected lactose digestion can be performed by comparing the measured amount of galactonate and / or galactitol in a single blood or urine sample with a reference threshold for the time (s) assessed. If the measured amount of galactonate and / or galactitol is above the reference threshold, the individual's lactose digestion is unaffected. If the measured amount is below the reference threshold, the individual's lactose digestion is impaired.
    To determine the reference threshold (s) in blood samples, a set of individuals with a known impaired lactose digestion, who were identified, for example, using the method according to the invention described above, is used to determine individual times during the 1-6 hour period administration of the lactose dose, at which a reference threshold in blood for impaired lactose digestion can be calculated. An absolute reference threshold in blood is determined from the sum of [average amount of galactitol or galactonate in the set of individuals with impaired lactose digestion] + [2 standard deviations of the data set].
    Alternatively, an absolute differential reference threshold in blood is determined as described for the absolute reference threshold, except that the amount of galactonate or galactitol in a fasting blood sample (ie, 0 to 15 minutes before the lactose dose is administered) is from the respective amount of galactonate or galactitol is subtracted at each time assessed.
    Alternatively, a dimensionless relative reference threshold in blood is determined as for the absolute reference threshold, except that the amount of galactonate or galactitol at the time is divided by the amount of galactonate or galactitol in the fasting blood sample. If the fasting value is below the detection limit (defined as the average of the noise plus 3 standard deviations), the detection limit is used as the fasting value.
    The use of a selection of seven individuals with impaired lactose digestion and blood measurements over the period of 1 to 6 hours after the administration of the lactose dose has been found to be appropriate to differentiate individuals with impaired lactose digestion from individuals with unaffected lactose digestion allow.
    To use this invention using the urine sample, a set of individuals with known impaired lactose digestion is used to determine a reference threshold for lactose digestion in urine. An absolute reference threshold in urine is determined based on the average of the [sum of the total amount of galactonate or galactitol for the set of individuals with impaired lactose digestion] + [2 standard deviations].
    Alternatively, an absolute differential reference threshold in urine is determined using the same method used for the absolute reference threshold, with the difference that the total amount of galactonate or galactitol is given under fasting conditions (ie after discarding morning urine and then drinking 2 dl water collected urine) is subtracted from the total amount of galactonate or galactitol in the combined urine sample.
    Alternatively, a dimensionless relative reference threshold in urine is determined as for the absolute reference threshold, except that the total amount of galactitol or galactonate in the urine sample is divided by the amount of galactitol or galactonate in urine under fasting conditions. If the fasting value is below the detection limit (defined as the average of the noise plus 3 standard deviations), the detection limit is used as the fasting value.
    Unaffected lactose digestion can be identified in an individual by measuring an amount of galactitol and / or galactonate in the urine sample and verifying that the value is above the reference threshold. Impaired lactose digestion is identified in the individual by measuring an amount of galactitol or galactonate in the urine sample and verifying that the value is below the reference threshold.
    The presence of a certain amount of galactonate and / or galactitol in urine or blood indicates that the lactose administered has been hydrolysed by lactase and the galactose units have been further metabolized by the liver to either galactonate or galactitol. The lack or only small amounts of these two metabolites can indicate that no or almost no lactose has been hydrolyzed, i.e. that lactose maldigestion is present. It should be noted that increased levels of galactitol and galactonate can be caused by dysfunction of the liver enzymes responsible for galactose metabolism via the leloir pathway, for example in the metabolic disorder galactosemia (1 in 16,000-60,000 individuals).
    Preferably, the method described in the present invention is carried out using only the urine sample. This procedure is less invasive for the individual because no blood collection is required.
    The assessment period can be only 1 hour if at least one blood sample is used, or 3 hours if the urine sample is used. It is preferred for the individual that the period be kept as short as possible, especially if the test is carried out at home.
    The method according to the invention can be carried out under the supervision of a medical specialist, for example a doctor or a nurse. Alternatively, especially when using the urine sample, all steps, with the exception of measuring the amount of galactitol and / or galactonate, can be carried out by the individual himself, e.g. be done at home.
    The measurement of galactonate and / or galactitol in the at least one blood sample is preferably compared with a reference threshold value which was defined for the specific point in time at which the at least one blood sample is taken.
    Alternatively, urine is collected for a period of at least 3 hours after administration of the lactose dose and the measured amount of galactonate and / or galactitol in the sample is compared to the reference threshold.
    Preferably the measurement of the amount of galactonate and / or the amount of galactitol is carried out using a gas chromatograph coupled to a mass spectrometer (GC-MS) or with an enzymatic assay.
    Measurement of the amount of compounds should be done by a professional laboratory using GC-MS or another validated test (e.g. enzymatic assay). Alternatively, the test could be performed at home using a validated kit based on an enzymatic assay.
    Methods for performing quantitative measurements with a GC-MS and quantitative enzymatic assays are well established. Enzymes used for such assays included D-galactonate dehydratase (see e.g. Szumilo: “Purification and properties of d-galactonate dehydratase from mycobacterium butyricum”; Biochimica Biophysica Acta; 661; 1981: 240–246) and Galaktitol 2- dehydrogenase (see for example US 4 923 803). Enzymatic tests can be performed using an ELISA (Enzyme Linked Immunosorbent Assay) test.
    The lactose dose is preferably between 25 g and 60 g. Using a lower lactose dose helps reduce the risk of symptoms caused by lactose intolerance. However, the dose must be high enough for the method to reliably determine lactase activity.
    [0041] Other advantages and features of the invention are set forth in the detailed description below and in the full description of the claims.
    Brief description of the drawings
    [0042] The drawings used to explain the embodiments show the following:<tb> Fig. 1 <SEP> the amount of galactitol in the serum of thirteen individuals after taking 38.8 g lactose;<tb> Fig. 2 <SEP> the amount of galactonate in the serum of thirteen individuals after taking 38.8 g lactose;<tb> Fig. 3 <SEP> the dynamic change in the amount of galactitol measured in serum after ingestion of 38.8 g lactose;<tb> Fig. 4 <SEP> the dynamic change in the amount of galactonate measured in serum after taking 38.8 g of lactose;<tb> Fig. 5 <SEP> serum galactonate from thirteen individuals after taking 38.8 g lactose;<tb> Fig. 6 <SEP> urine galactonate from thirteen individuals after taking 38.8 g lactose;<tb> Fig. 7 <SEP> serum galactitol from thirteen individuals after taking 38.8 g lactose;<tb> Fig. 8 <SEP> urine galactitol from thirteen individuals after taking 38.8 g lactose;<tb> Fig. 9 <SEP> serum galactonate from thirteen individuals after taking 38.8 g lactose;<tb> Fig. 10 <SEP> urine galactonate from thirteen individuals after taking 38.8 g lactose;<tb> Fig. 11 <SEP> an example of how to define a lactose digestion threshold for a single point in time, measured in serum, using the dimensionless relative reference threshold;<tb> Fig. 12 <SEP> an example of how to define a lactose digestion threshold for a urine bulk sample.
    example
    A group of 14 healthy individuals who regularly consume milk (mean age 25 years and mean body mass index 22 kg / m 2) were selected to carry out the test procedure using milk as the source of lactose. The milk consumed was homogenized and ultra-high-temperature whole milk (supplied by Emmi Mittelland Molkerei AG, Switzerland). The milk was acidified by adding 2% D - (+) - glucono-5-lactone (GDL <́ ́> 99.0%, Jungbunzlauer AG, Switzerland) to mimic the texture of yogurt.
    The postprandial tests were carried out in the Center for Clinical Research of the Center Hospitalier Universitaire Vaudois (CHUV) in Lausanne, Switzerland. A single dose of 800 g of acidified milk containing 38.8 g of lactose was orally administered to each individual. The dose was taken by fasting individuals over a period of 15 minutes. Blood samples were taken when fasting and then postprandially at 9 times (15 min, 30 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min and 360 min). Urine was collected in the morning before the lactose dose and during the six-hour postprandial period.
    The individuals were genotyped for rs4988235, the most common single nucleotide polymorphism associated with lactase persistence in the population of Northern Europe. Genotyping was carried out using the EliGene® Lactose Intolerance C-13910T LC Kit (Elisabeth <®> Pharmacon, Czech Republic) according to the manufacturer's instructions. RT-PCR was carried out with the Lightcycler 96 (Roche Diagnostics, Switzerland) with internal standards for positive and negative controls. Homozygous carriers of the wild-type alley (CC) were considered to be lactase-non-persistent (genotype with impaired lactose digestion), while heterozygous (CT) and homozygous carriers for the mutant allele (TT) were considered to be lactase-persistent (genotype with unaffected lactose digestion). An individual of African origin was excluded from statistical analysis using genotyping because genotypes in rs4988235 are not relevant for the diagnosis of persistence of lactase in this population.
    [0046] Serum from the blood samples and urine were evaluated using an undirected GC-MS metabolomics method. The concentrations of lactose, galactose, galactitol and galactonate were measured using reference standards. The GC-MS measurements were carried out using an Agilent 7890B / 5977A GC-MS system, 70 kV, equipped with a DB-5MS column 60 m × 0.25 mm × 0.25 μm (Agilent Technologies, USA).
    [0047] Although no statistically significant differences were found in the postprandial serum kinetics of lactose between CC carriers and CT / TT carriers, the postprandial kinetics of galactose and its two metabolites galactitol and galactonate showed clear patterns between CC carriers and CT / TT- Carriers.
    According to these observations, the incremental area under the curve (iAUC), which is used to approximate the amount of the metabolite for the entire time period assessed with ten points in time, was significantly higher for CT / TT carriers than for CC carriers for galactose , Galactitol and galactonate. In fact, the two groups could be clearly separated. No clear separation was observed in urine between the group of CT / TT carriers and the group of CC carriers based on postprandial lactose levels. However, the levels of galactose, galactitol and galactonate in postprandial urine were significantly higher in CT / TT carriers than in CC carriers. The separation of the two groups was very pronounced for both galactonate and galactitol, while galactose showed the least discriminatory results.
    Figure 1 shows the amount of galactitol in serum after milk intake for twelve individuals, including seven individuals with impaired lactose digestion (dashed line) and five individuals with unimpaired lactose digestion (solid lines).
    Fig. 2 shows the same comparison as Fig. 1, but instead based on the measurement of galactonate in the blood serum of each individual.
    As can clearly be seen in FIGS. 1 and 2, the group of individuals with unaffected lactose digestion can be distinguished from the group of individuals with impaired lactose digestion on the basis of the amounts of galactitol or galactonate measured in serum.
    Fig. 3 shows two adjusted regression lines with the corresponding upper and lower confidence bands (0.95% confidence) for the measured amount of galactitol over time for an individual with known impaired lactose digestion (crosses) and for an individual with known not impaired lactose digestion (circles). The ANOVA test for the regression model of the individual with unimpaired digestion shows a statistically significant positive slope (slope = 11.6, p <0.001). The ANOVA test for the regression model of the individual with impaired digestion shows that the slope is neither positive (slope = 0.567) nor significantly different from 0 (p = 0.38) (Table 1).<tb> Lactose metabolism of the individual <SEP> slope <SEP> p-value (ANOVA test slope ́ 0)<tb> inactive <SEP> - 0.57 <SEP> 0.38<tb> active <SEP> 12 <SEP> <0.001
    Table 1:Statistical characteristics of the postprandial slope of galactitol, measured in blood after lactose ingestion by an individual with an impaired lactose metabolism and an individual with an unaffected lactose metabolism.
    FIG. 4 shows two adjusted regression lines for the measured amounts of galactonate, similar to FIG. 3. The ANOVA test for the regression of the individual with unimpaired digestion confirms the existence of a statistically significant positive slope (slope = 14.18, p <0.001). The ANOVA test for the regression line for the individual with impaired digestion shows that the slope does not differ significantly from 0 (p = 0.94) (Table 2).<tb> Lactose metabolism of the individual <SEP> slope <SEP> p-value (ANOVA test slope ́ 0)<tb> inactive <SEP> 0.016 <SEP> 0.942<tb> active <SEP> 14 <SEP> <0.001
    Table 2:Statistical characteristics of the postprandial slope of galactonate measured in blood after lactose ingestion by an individual with an impaired lactose metabolism and an individual with an unaffected lactose metabolism.
    FIG. 5 compares the postprandial galactose changes (evaluated by means of iAUC) in serum for lactase-non-persistent CC carriers and lactase-persistent CT / TT carriers (CT circles and TT triangles), while FIG. 6 compares the galactose levels in urine Aggregate samples for the same groups are compared. In both comparisons it is possible to differentiate lactase-persistent individuals (here defined as CT / TT genotype) from the lactase-non-persistent individuals (here defined as CC genotype. It should be noted that the outlier for the CC genotype group is the test individual is of African origin, which despite its CC genotype clearly shows the metabolic phenotype of a lactase-persistent individual In contrast to the genetic test, the present method can differentiate between lactase-persistent and non-persistent individuals based solely on metabolic activity.
    Figure 7 compares the postprandial galactitol changes (evaluated using iAUC) in serum for lactase-non-persistent CC carriers and lactase-persistent CT / TT carriers (CT circles and TT triangles), while Figure 8 compares the galactitol levels in urine. Aggregate samples for the same groups are compared. When comparing FIGS. 7 and 8 with FIGS. 5 and 6, it is evident that the measurement of galactitol enables a clearer distinction between the two groups than the use of the galactose measurement.
    9 compares the postprandial galactonate changes (evaluated using iAUC) in serum for lactase-non-persistent CC carriers and lactase-persistent CT / TT carriers (CT circles and TT triangles), while FIG. 10 compares the galactonate levels in urine Aggregate samples for the same groups are compared.
    When comparing FIGS. 9 and 10 with FIGS. 5 and 6 or 7 and 8, it becomes apparent that the measurement of galactonate shows the highest degree of differentiation between the two groups and is therefore particularly suitable for the diagnosis of an unimpaired lactose digestion.
    Figure 11 shows an example in which unaffected lactose digestion was identified in six individuals by measuring the amount of galactitol at a single time in serum. In the example, the evaluation is completed at 180 minutes after taking 38.8 g of lactose using a relative amount of galactitol. This relative amount is obtained by dividing the measured concentration of galactitol at the time of each individual by the concentration of galactitol of each individual in a fasting state. The box plot on the left side of the figure shows the distribution of the relative amounts of galactitol in the serum of seven individuals with impaired lactose digestion, identified by evaluating their blood galactitol value using the linear regression method. The reference threshold was determined using the average of the measured relative amounts of galactitol at the time of these seven individuals and by adding twice the standard deviation. The reference threshold is shown as a dashed line in FIG. 11. The measured relative amounts of the six individuals in which unaffected lactose digestion can be identified are shown as dots on the right side of FIG. 11. As can be seen, the measured relative amounts of these six individuals are well above the reference threshold.
    Figure 12 shows an example in which lactose digestion was unaffected in six individuals by measuring the amount of galactonate in a urine pooled sample of urine for each individual over a 6 hour period after taking 38.8 g Lactose was collected, identified. The absolute amount of galactonate measured in the urine sample pooled over six hours was used in this example. The reference threshold was calculated using seven individuals with impaired lactose digestion identified by analyzing their blood galactonate concentrations. The reference threshold was determined using the mean of the measured absolute concentration of galactitol in urine pool samples from seven individuals collected over a 6 hour period after taking 38.8 g of lactose and by adding twice the standard deviation. The reference threshold is shown as a dashed line in FIG. 12. The box plot of the measured absolute concentration values of the seven individuals with impaired lactose digestion can be seen on the left in FIG. 12. The measured absolute concentrations of galactitol of the six individuals in which unaffected lactose digestion was identified are shown as dots on the right side of FIG. 12. As can be seen in the figure, the measured amounts of these six individuals are far above the reference threshold.
    权利要求:
    Claims (4)
    [1]
    1. A method for assessing an individual's lactose digestion, comprising the following steps:a) oral administration of a lactose dose of at least 20 g to the individual;b) taking at least one sample of blood or urine of the individual within a period of 6 hours after the administration of the lactose dose, the at least one blood sample preferably being taken at least one hour after administration of the lactose dose, while urine of the individual over a period of at least 3 hours collected and pooled after administration of the lactose dose to give a urine sample;c) measuring the amount of galactonate and / or the amount of galactitol in the at least one blood sample or in the urine sample;characterized in that unaffected lactose digestion is determined in the individual, either:i. by the presence of a statistically significant positive slope in the measured amount of galactonate and / or galactitol in several blood samples;orii. by comparing the measured amount of galactonate and / or galactitol in the at least one blood sample or in the urine sample with a reference threshold.
    [2]
    2. The method according to claim 1, characterized in that the comparison of the measured amount of galactonate and / or galactitol in the at least one blood sample with a reference threshold value is carried out using a single blood sample which is at a certain time at least 1 hour after the administration of the Lactose dose was taken.
    [3]
    3. The method according to any one of claims 1 to 2, characterized in that the measurement of the amount of galactonate and / or the amount of galactitol is carried out by means of GC-MS or an enzymatic assay.
    [4]
    4. The method according to any one of claims 1 to 4, characterized in that the lactose dose is between 25 g and 60 g.
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    同族专利:
    公开号 | 公开日
    CH715409A8|2020-06-15|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    2020-04-15| PK| Correction|Free format text: BERICHTIGUNG ERFINDER |
    2020-04-30| PK| Correction|Free format text: BERICHTIGUNG INHABER |
    2020-06-15| PK| Correction|Free format text: BERICHTIGUNG A8 |
    2020-09-30| PFA| Name/firm changed|Owner name: AGROSCOPE, CH Free format text: FORMER OWNER: AGROSCOPE, CH |
    2022-01-31| AZW| Rejection (application)|
    优先权:
    申请号 | 申请日 | 专利标题
    CH01186/18A|CH715409A8|2018-09-28|2018-09-28|Procedure for assessing lactose digestion.|CH01186/18A| CH715409A8|2018-09-28|2018-09-28|Procedure for assessing lactose digestion.|
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