CN101262891B - Measurement of gastric acid secretion - Google Patents
Measurement of gastric acid secretion Download PDFInfo
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- CN101262891B CN101262891B CN200680033499XA CN200680033499A CN101262891B CN 101262891 B CN101262891 B CN 101262891B CN 200680033499X A CN200680033499X A CN 200680033499XA CN 200680033499 A CN200680033499 A CN 200680033499A CN 101262891 B CN101262891 B CN 101262891B
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Abstract
A method of measuring the amount of gastric secretion in a mammal involves administering a substance or formulation containing an excess quantity of a water-insoluble carbonate to the mammal to react with acid in the stomach, in which the insoluble carbonate is enriched with at least one isotope selected from <13>C, <14>C, <17>O and <18>O in a known amount. The content of the or each selected isotope in the exhaled carbon dioxide is allowed to stabilise before obtaining a sample of exhaled air containing carbon dioxide, and determining the content of the selected or each selected isotope in the exhaled carbon dioxide.
Description
The present invention relates to be used for measuring the noninvasive method of mammal gastric acid secretion, said mammal comprises the people.
All mammals secrete gastric acid.Yet acid for the absorption of food not necessarily, neither be necessary for existence.The reason that acid secretion is retained is in UGI, to set up an acid barrier, the invasion and attack of the pathogenic microorganism of avoiding with other part of protection digestive system possibly existing in the food.
The acid secretion possibly cause the generation of duodenal ulcer, gastric ulcer and reflux esophagitis.Otherwise gastric acid secretion obstacle or shortage then possibly be easy to take place gastric cancer.
Developed the medicine that can help to reduce gastric acid secretion.The proton pump inhibitor omeprazole extensively is used for this purpose by doctor's evolution.After this many other proton pump inhibitors have also gone on the market and have been used for the treatment of sour associated conditions.
The mechanism of gastric acid secretion is complicated, and it is with psychology, nerve is all relevant with the hormone control mechanism.Secretion individual in daytime alters a great deal, and depends on the picked-up of food, and the ability of secretion acid is also different between individuality and colony.
The measurement of gastric acid secretion is difficult.Known method comprises uses nasogastric tube with acid sucking-off from stomach, gives stimulus object simultaneously to stimulate secretion.This is effective ways of measuring individual maximal acid secretion, but this invasive and undesirable technical limitations its application in research and clinical practice.The exploitation of noninvasive method is extremely expected.This will make it possible to carry out epidemiological study, and the more important thing is the effect that can in a large amount of individualities, measure antisecretory drug.This will make it possible to different anti-secretory drugs and dosage thereof are assessed.Yet, have special value in the research of clinicing aspect Noninvasive.Some patients are to the not reaction of antiacid Drug therapy, and unclear the reaction is that dosage is invalid in these cases, and to the result of used drug resistance, still reaction is not because disease itself is not sour relevant.
Therefore, sour excretory noninvasive method presses down in the sour medicine and in Clinical Processing, all has sizable value in that exploitation is more effective in epidemiological study.
On the one hand, the present invention provides the method for measuring stomachial secretion amount in the mammal, said method comprising the steps of:
A. give material or preparation that said mammal contains excessive water-insoluble carbonate, with stomach in acid reaction, at least a being selected from of wherein said insoluble carbonate enrichment
13C,
14C,
17O with
18The isotope of the known quantity of O,
B. make selected or every kind of selected isotopic stable content in the carbon dioxide of exhalation,
C. obtain to contain carbon dioxide the breath sample and
D. measure selected or every kind of selected isotopic content in the carbon dioxide of breathing out.
This method can be used for differentiating the patient with following situation: (a) to pressing down not reaction of acid treatment, (b) suffer from hypochlorhydria, (c) suffer from atrophic gastritis, and (d) have the risk of the generation gastric cancer of increase.
Said insoluble carbonate can itself give, promptly gives as pure material or the mixture of substances that do not have any excipient, and perhaps can be a part that contains the preparation of conventional pharmaceutical excipient.
Preferably, said material or preparation do not comprise except that said water-insoluble carbonate with stomach in any composition of acid reaction, said composition is for example so that increase the mode of pH and the acid reaction in the stomach.Said preparation can comprise soluble component and be beneficial to food intake, and said soluble component can be forms such as cover layer or filler.These compositions should be able to not react with gastric acid, for example make like this that pH significantly raises in the stomach, for example as the result of acid-base reaction or as the result of hydrolysis.The instance of the composition that can comprise is a gelatin, and it can be used for sealing the carbonate powder of a tittle in Capsule form.
On the other hand, the present invention provides a kind of pharmacy acceptable preparation, said preparation comprise can with the water-insoluble carbonate of acid reaction in the mammal stomach, at least a being selected from of wherein said insoluble carbonate enrichment
13C,
14C,
17O with
18The isotope of the known quantity of O, wherein said preparation do not comprise dewater beyond the insoluble carbonate with stomach in any composition of acid reaction.
On the other hand, the present invention provides that enrichment is at least a to be selected from
13C,
14C,
17O with
18The isotopic insoluble carbonate of the known quantity of O is used for treating or preventing the application of the medicine of gastric acid level rising in preparation.
On the other hand, the present invention provides that enrichment is at least a to be selected from
13C,
14C,
17O with
18The isotopic insoluble carbonate of the known quantity of O is used for detecting or treat the application of the medicine of pernicious anemia in preparation.
Preferably, before giving the step of carbonate, method of the present invention comprises selected or every kind of selected isotopic content in the carbon dioxide that obtains to contain the breath sample of carbon dioxide and measure exhalation.
Selected or every kind of selected isotopic content can be through using for example mass spectral analysis, infrared spectrum analysis, analysiss of laser assist ratio, gas chromatograph-mass spectrometer analysis, scintillation counter analysis and acceleration spectrometer analysis technical measurement in the carbon dioxide of breathing out.When the carbonate enrichment
13During C, can preferably use mass spectral analysis or infrared spectrum.When the carbonate enrichment
14During C, can preferably use the scintillation counter analysis and quicken spectrometer analysis.
Preferably, said insoluble carbonate is a metal carbonate.Preferably, said insoluble carbonate preparation comprise in calcium carbonate, magnesium carbonate and the zinc carbonate one of at least.Can use carbonate mixture.
Insoluble carbonate for example calcium carbonate is the nonabsorbable chemical compound of neutralizing acid example hydrochloric acid.Hydrochloric acid exists under one's belt naturally.For example hydrochloric acid and calcium carbonate reaction generate calcium chloride, water and carbon dioxide.When calcium carbonate added hydrochloric acid, neutralization reaction took place quickly and effectively, and the amount of the carbon dioxide of release equals to be neutralized the amount of acid.Same reaction all takes place in any carbonate.Therefore other insoluble carbonate also can obtain identical result, and the acceptable carbonate of any physiology all can be used in the method for the present invention.
Preferably, said water-insoluble carbonate contains at least about 1 atom %, more preferably at least about 5 atom %, particularly at least about the selected isotope of 10 atom %.
The natural isotopic abundance of carbon isotope is about 98.93 atom %'s
12C and 1.07 atom %'s
13C.Therefore, with respect to
12C contains
13The insoluble carbonate that the amount of C surpasses 1.07 atom % is enrichment
13C.When measuring isotope, with the isotopic amount of selecting to comprise in the insoluble carbonate to obtain suitable strong signal.High isotopic content possibly cause expensive and be difficult to the accurately shortcoming of measurement.Therefore usually with in the preferred carbonate
13C content is no more than about 20 atom %, more preferably no more than about 10 atom %.
In addition, the present invention considers to use in the method for the invention
14C replaces
13The probability of C.Therefore, above-mentioned with
13In the various aspects of the present invention and embodiment that C is relevant,
13C all can quilt
14C replaces, and it has same effectiveness.With about
13The unique respective change of the described method of C is to be adopted be used for measuring in the carbon dioxide excretory
14C and background
14The character of the analytical method of the ratio of C.In this case, work as use
14C replaces
13During C, need to adopt scintillation counter or acceleration mass spectrograph that the specimen of breath of breathing out is analyzed.In addition, also the carbonate enrichment is worked as in prediction
14During C, the isotopic content that is tending towards above-mentioned low scope will be suitable.
In one embodiment, said preparation is preferably selected from tablet, capsule and lozenge.Said preparation can be the form of powder or suspensoid.
Preferably, said preparation is a dosage unit.More preferably, it is 250mg at least, particularly at least about the dosage unit of 500mg.
Preferably, the total amount that gives patient's insoluble carbonate is at least about 5g, more preferably at least about 7.5g, particularly at least about 10g, for example at least about 12g.Some patients possibly give the insoluble carbonate of higher total amount, for example at least about 15g, or at least about 20g.Preferably, said insoluble carbonate is with at least about 3g.h
-1, more preferably at least about 5g.h
-1Speed give the patient.The amount of these carbonate is all measured by absolute value, therefore in the said preparation other composition for example the weight of binding agent and capsule encapsulation material etc. do not included.The amount of said carbonate usually will be for making the carbonate facics that exists under one's belt excessive for gastric acid.
13C is a kind of naturally occurring cold (on-radiation) isotope, and it exists in body on a small quantity.Behind the chemical compound of picked-up enrichment, it was got rid of in 12 hours basically, and level is back to normally.
Reaction between the acid in insoluble carbonate and the stomach makes acid be neutralized.Acid in the stomach is neutralized stimulates gastric mucosa to produce the gastrin gastrin, and gastrin is a kind of further excretory hormone of hydrochloric acid of inducing.In the presence of excess calcium carbonate, this further excretory hydrochloric acid also will be neutralized, thereby induce further secretion.The amount that test period produces carbon dioxide is identical with the amount of same endocrine acid of time.
The carbon dioxide that produces under one's belt as aforesaid neutral result is absorbed into blood flow.It participates in the lung exchange process then, drains through exhaling with the carbon dioxide that body endogenous cause of ill metabolic activity produces.The present invention overcome compare with the carbon dioxide that metabolism produces how to confirm to give behind the insoluble carbonate because of in the gastric acid with the problem of the carbon dioxide that produces.
Isotopic content reaches the stable time and depends on the reactant in the stomach in the carbon dioxide of breathing out, and particularly to the gastrin reaction that produces and the speed of secretion acid, and the carbon dioxide that produces in the stomach reaches the time of Css in blood.Usually will need 60 minutes or the above carbon dioxide that makes exhalation in isotopic content stable, sometimes at least about 120 minutes.Therefore; Material or preparation initial of can preferred steps (i) containing water-insoluble carbonate give and (ii) in making the carbon dioxide of exhalation, obtain to breathe out behind selected or every kind of selected isotopic stable content interval between other sample; It is at least about 60 minutes; Preferably, for example be at least about 150 minutes at least about 120 minutes.
Method of the present invention can preferably include further step (e), and said step (e) comprises repeating step (c) and (d) with selected in the carbon dioxide of estimate breathing out or whether every kind of selected isotopic content is stable.
Method of the present invention can preferably include at least two steps that contain water-insoluble carbonate material or preparation to mammal.Preferably, the interval that gives continuously between the step is at least about 5 minutes, more preferably at least about 10 minutes, repeat to give to guarantee the excessive under one's belt existence of carbonate.The amount of the water-insoluble carbonate that preferably, gives to mammal is known.This can help to guarantee the excessive under one's belt existence of the carbonate that is given.
Method of the present invention comprises the insoluble carbonate (with one or more isotopic labelings) that gives oral dose.Individuality is periodically gone into collection container through the suction pipe breath, and measures selected isotopic content in the breath.
When carrying out gastric acid secretion mensuration, preferably fasting of individuality.Reason to this is different with feed state servant's gastrointestinal physiology in fasting.Other mammal is like this too.
Difference under fasting and the feed state is significant, and refers to not only in the stomach whether deprivation of food.The EMG activity of stomach is very different with the mobility under fasting and the feed state.Except fasted/fed differences, for the dosage form of solution, food and different sizes, the gastric emptying time is different.Generally speaking, the gastric emptying under the feed state is lower than the gastric emptying under the fasting state.Generally speaking, big not digestion object (with slow distintegrant type) for example granularity (diameter) is 7mm or bigger, its emptying than little object for example granularity be the slower of 4mm, and above-mentioned both emptyings of flowing fluid ratio are faster.
For example, under fasting state, migrating myoelectric complexes (MMC) the III phase of big not digestion object (comprising undecomposed dosage form) undigested material in indication emptying stomach, just from stomach, discharge when being also referred to as house keeper's phase or house keeper's ripple and occurring.Under fasting state, solution and small-particle suspension are discharged from stomach basically continuously, and need not wait until in the human body approximately whenever the appearance at a distance from house keeper's ripple of 60 to 90 minutes.
When pickuping food, the multiple MMC cycle stops, the motion feature significant change of stomach.After the dining, stomach grinds the food of picked-up under the help of gastric acid and digestive enzyme, makes it slowly to become granule.The food of granule and solution state (or medicine) gets into duodenum through pyloric valve.The foodstuff (particularly fatty acid and aminoacid) that begins in the metaduodenum of taking food causes this " feed stomach state ", it is characterized by the slower and shortage MMC of gastric emptying.Bigger object (not digest food fragment, non-decomposition dosage form) up to whole canteen thing all be degraded to can be through pylorus granule and gastrointestinal system perceive the material that stays under one's belt and just from stomach, discharge when indigestible.
Except effect discussed above, the pH value of stomach rises to about pH5 when having meal, and in about 2 hours, reduces to about pH2 then.In addition, food can cushion the acid of stomachial secretion, and therefore the acid of a part can not be neutralized by carbonate.
In the present invention, patient's not feed at least 4 hours is represented in fasting.Preferably not feed at least 8 hours before said method begins is at least one (promptly at least about 12 hours) whole night during the fasting before the test more preferably.Yet although picked-up a bit and a sup or water not satisfactory, if stomach mobility or pH are not had appreciable impact, still can allow.
Method of the present invention is carried out among the patient on the feed to measure because the sour excretory variation that the food of picked-up measured quantity causes, condition be at in-vitro evaluation the buffers active of test meal.
The interval that interval promptly gives between the carbonate dosage continuously, can be identical or different.Similarly, collecting the interval (being interval) of continuous exhalation sample can be identical or different.
Preferably, give step or determination step or both all repeat 2 times at least, more preferably at least 3 times, further preferably at least 5 times.If necessary, can carry out 10 times or more times repetition.
Interval time between the collection of interval time between the successive doses and the sample of breathing out continuously can be mutually the same or they can be different.
Preferably, the interval between the successive doses is 1 to 30 minute, more preferably at least 5 minutes, and more preferably at least 10 minutes.
Preferably, the interval between the collection of the sample of breathing out continuously is 1 to 600 minute, more preferably from about 15 minutes.
Preferably, said method comprises monitors selected or every kind of selected isotopic content step over time in the carbon dioxide of breathing out, and said monitoring is for example carried out through drawing variation diagram.
Be described below, the result who measures to time diagram is relevant with actual gastric acid secretion amount.The scale that uses among the figure is represented the variation of isotope with respect to baseline values.When selected isotope does
14During C, baseline values can be with respect to background
14The C level is measured.When selected isotope does
13During C, baseline values can give before the enriched with carbon hydrochlorate through mensuration
13C content is confirmed.In case about the stomach reactant be absorbed into blood samples of patients and reached stable state, then isotopic content will be tending towards over time reflecting in time because of in the gastric acid with the amount of the carbon dioxide that is produced.
For confirming the actual amount of gastric acid secretion, at first must change, to obtain the amount of carbon dioxide of actual generation to these figure.This can comprise with sack collects the gas of breathing out, Analysis for CO then
2Content.CO
2Analyzing also to adopt running system or other technologies to carry out.
The carbon dioxide that produces in maybe not every body is drained by exhaling, and sub-fraction maybe be elsewhere, for example in urine or in diffusing into slow balance volume.This will depend on individual patient, possibly be the target of further studying, but the recovery of carbon dioxide can be assumed to 80% in this test.
When selected isotope does
13During C, can draw expression formula: give in the carbonate expiration before about following variable
13C/
12C ratio (baseline ratio) gives in the carbonate expiration afterwards
13C/
12The C ratio, and in the carbonate
13C/
12The C ratio.In giving to exhale behind the carbonate
13The rising of C is owing to from the neutral enriched with carbon hydrochlorate of gastric acid
13The existence of C.
The total amount of carbon dioxide can be measured through being collected in the Douglas bag in the expiration.Its carbon dioxide that is produced by homergy adds in the gastric acid to be formed with the carbon dioxide of the carbonate generation of taking in.Employing is about the expression formula of said different proportion, and we can calculate in the bag mole from the carbon dioxide of neutral carbonate then.
For making this result of calculation relevant, need carry out some hypothesis with actual gastric acid secretion.
At first, should suppose in giving carbonate expiration before
13C/
12C ratio (baseline ratio) is time to time change not.In this test, this variation can be treated to ignore reliably.The second, although the amount of the carbon dioxide that produces owing to homergy in exhaling possibly change significantly, if Douglas bag is used for before and after being collected in this collection at once
13C/
12C ratio measuring then this variation will obtain proofreading and correct, from
13C/
12The C ratio is calculated sour secretory volume.The 3rd, must supposition also drain without exhaling by the part of the carbon dioxide of acid neutralization generation.
Follow-up calculating comprises based on the reaction in the stomach:
2HCl+CaCO
3→CO
2+H
2O+CaCl
2，
The molal quantity of the carbon dioxide of therefore breathing out and the molal quantity ratio of reaction acid are 2, carry out the correction without the excretory carbon dioxide of exhaling.
Embodiment 1
In 4 hours, whenever people volunteer is given the usefulness 10 atom %'s of oral dose at a distance from 15 minutes
13The calcium carbonate of C labelling.Oral dose contains the 250mg calcium carbonate.The sample of (expiration) gas of will breathing out is every to be gone in suitable collection container such as the test tube to obtain from the experimenter through exhalation at a distance from 10 minutes.The gas of breathing out is carried out mass spectral analysis, to measure in the carbon dioxide of breathing out
13C with
12The ratio of C.The result provides in Fig. 1.
The ratio of drawing among Fig. 1 shows to be used
13The result of two tests that the calcium carbonate of C labelling carries out shows
13C raises, and it began to reach plateau in the time of about 120 minutes.The time that reaches plateau possibly change because of the patient is different.
Notice that during about first 120 minutes, having carbon dioxide to drain increases, and plateau after this occurs.Observed plateau possibly be the needs owing to carbon dioxide balance in carbon dioxide and the lung in carbon dioxide and equilibrated needs of blood and the blood in the reactant in the stomach, the stomach.Research is in the past thought possibly also exist a carbon dioxide exchange pond in the body.
Therefore, think when approximate the acid that is neutralized in the stomach amount pass through the expiration excretory
13CO
2Be lower than through homaluria or then occur plateau when detaining the amount in the chamber of non-exchange or slowly exchange.For obtaining result accurately, selected isotopic content is important in the breath when measuring during selected isotopic stable content in the breath, and said mensuration is for example carried out through the continuous sample of replication breath.
In second test, give experimenter 20mg omeprazole every day, gave for two weeks, and twice of repeated trials under the identical in other respects condition.Fig. 2 demonstration is compared in this case with initial test
13The amount of the carbon dioxide of C labelling significantly reduces.
Give that the experimenter has carried out other twice test again under the condition of omeprazole that dosage is 40mg identical in other respects then just comprising every day.Fig. 3 has shown similar result.
It is consistent that this result produces the observation that such medicine maximal acid is suppressed with oral 20mg omeprazole in most of individualities, therefore uses 40mg not give benefit to this experimenter.
Embodiment 2
People volunteer is given the usefulness 10 atom %'s of initial oral dose 2g
13The calcium carbonate of C labelling, every said calcium carbonate that gave other 500mg dosage at a distance from 5 minutes in 3 hours then.The sample of (expiration) gas of will breathing out is every to be gone in suitable collection container such as the test tube to obtain from the experimenter through exhalation at a distance from 15 minutes.The gas of breathing out is carried out mass spectral analysis, to measure in the carbon dioxide of breathing out
13C with
12The ratio of C.The result provides in Fig. 4.
The ratio of drawing among Fig. 4 shows to be used
13The result of two tests that the calcium carbonate of C labelling carries out shows
13C raises, and it began to reach plateau in the time of about 120 minutes.The time that reaches plateau possibly change because of the patient is different.
In second test, give experimenter 20mg omeprazole every day, give a week, repeated trials under the identical in other respects condition.Fig. 2 demonstration is compared in this case with initial test
13The amount of the carbon dioxide of C labelling significantly reduces.
More than illustrative method of the present invention can further improve.
Above data are only based on an experimenter, and further improvement will comprise research widely.These figure not have consideration contingent variation in the generation of carbon dioxide in the general metabolism of experimenter.Possible different patients is drained and is detained variant.
Past was not also carried out the acid secretion research that alkali stimulates, but use test meal or injection sercretogogue.Use will make the relation of the mole form between the amount that can estimate excretory carbon dioxide and excretory acid in the expiration more than a patient's further experiment work.
Possibly establish the sour excretory common scope of alkali stimulation and the effect that the checking pharmacology presses down acid through the Different Individual that compares sufficient amount.
An impossible in the past potential advantageous application will comprise having no under one's belt in the sour excretory pernicious anemia individuality and make an experiment.This will indicate whether to have any " spilling "
13During C exhales through gastrointestinal mucosa and entering.
Above embodiment and relevant Fig. 1-5 are illustrated in the test result of the gastric acid output of reacting the experimenter has remarkable and essential difference.This has confirmed that this technology can detect sour excretory difference when use presses down the acid treatment.
Table 1 comprises the data set that produces each figure.The calcium carbonate of each test is described in text and in the legend of each figure with the dosage that presses down sour medicine (if taking).
Except
13C/
12Beyond the C ratio, also possibly measure the total CO 2 excretion.Expection provides more consistent result.Similarly, possibly measure the blood plasma gastrin to confirm degree through the stimulation that picked-up was provided of calcium carbonate.
This test can be used in the epidemiological study, in the Physiologic Studies of gastric acid secretion and be used in the pharmaceuticals industry identifying and upgrade and the general use of the research of more effective acid inhibitor.This test is in Clinical Processing, and is particularly valuable especially to pressing down in the sour responseless individuality at those.It can be used for differentiating the individuality that acid inhibitor is not had reaction and needs extraordinary dosage.In addition, it also can be used to detect and obtains to press down acid and further Drug therapy can not those useful individualities.Have a spot of individuality Drug therapy is had no effect at all, this method makes can differentiate these individualities.
Claims (15)
1. method of measuring stomachial secretion amount in the mammal said method comprising the steps of:
A. give the preparation that said mammal contains excessive water-insoluble carbonate, with stomach in acid reaction, at least a being selected from of wherein said insoluble carbonate enrichment
13C,
14C,
17O with
18The isotope of the known quantity of O, and wherein said preparation do not comprise except that said water-insoluble carbonate with stomach in any composition of acid reaction,
B. make selected isotopic stable content in the carbon dioxide of exhalation,
C. obtain to contain carbon dioxide the breath sample and
D. measure selected isotopic content in the carbon dioxide of breathing out.
2. the process of claim 1 wherein that the step of measuring isotopic content comprises mensuration
13C with
12The ratio of C.
3. the method for claim 2, the step of wherein measuring isotopic content comprises the use mass spectrograph.
4. the process of claim 1 wherein that the step of measuring isotopic content comprises in the carbon dioxide of measuring exhalation
14C and background
14The ratio of C.
5. the method for claim 4, the step of wherein measuring isotopic content comprise to be used scintillation counter or quickens mass spectrograph.
6. the method for claim 1, before giving the step of said carbonate, it comprises the step that obtains to contain the breath sample of carbon dioxide and measure selected isotopic content in the carbon dioxide of breathing out.
7. the method for claim 1, it comprises further step (e), whether said step (e) comprises repeating step (c) and (d), stable to estimate in the carbon dioxide of breathing out selected isotopic content.
8. the method for claim 1, it comprises at least two steps that contain the preparation of said water-insoluble carbonate to said mammal.
9. the method for claim 8, the interval that wherein gives continuously between the step is at least 5 minutes.
10. the process of claim 1 wherein and give and (ii) make the interval that obtains between the breath sample behind the selected isotopic stable content in the carbon dioxide of exhalation be at least 60 minutes in preparation initial that step (i) contains said water-insoluble carbonate.
11. the process of claim 1 wherein that the amount that gives said mammiferous said water-insoluble carbonate is known.
12. the process of claim 1 wherein said insoluble carbonate comprise in calcium carbonate, magnesium carbonate and the zinc carbonate one of at least.
13. the process of claim 1 wherein that said mammal is the people.
14. the method for claim 1, it comprises the step of the time being mapped with selected isotopic content in the carbon dioxide of breathing out.
15. the process of claim 1 wherein that said water-insoluble carbonate contains the selected isotope of at least 1 atom %.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0514194.0 | 2005-07-12 | ||
| GB0514194A GB0514194D0 (en) | 2005-07-12 | 2005-07-12 | Measurement of gastric acid secretion |
| GB0601079.7 | 2006-01-19 | ||
| GB0601079A GB0601079D0 (en) | 2006-01-19 | 2006-01-19 | Measurement of gastric acid secretion |
| PCT/GB2006/002580 WO2007007100A2 (en) | 2005-07-12 | 2006-07-12 | Measurement of gastric acid secretion |
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| Publication Number | Publication Date |
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| CN101262891A CN101262891A (en) | 2008-09-10 |
| CN101262891B true CN101262891B (en) | 2012-09-05 |
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| CN200680033499XA Expired - Fee Related CN101262891B (en) | 2005-07-12 | 2006-07-12 | Measurement of gastric acid secretion |
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| GB (1) | GB0514194D0 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2618145B1 (en) * | 2010-08-19 | 2016-11-23 | Otsuka Pharmaceutical Co., Ltd. | Method for quantitative measurement of gastric acidity using 13c carbonate salt |
| ITUD20130021A1 (en) * | 2013-02-20 | 2014-08-21 | Alifax Holding S P A | PROCEDURE FOR THE IDENTIFICATION OF BACTERIAL CLASSES THROUGH GAS CHROMATOGRAPHY / MASS SPECTROMETRY IN BIOLOGICAL SAMPLES |
-
2005
- 2005-07-12 GB GB0514194A patent/GB0514194D0/en not_active Ceased
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2006
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Non-Patent Citations (3)
| Title |
|---|
| C. P. LLOYD-JONES.Determination of carbon-14 in biological material by flaskcombustion and suspension scintillation counting of carbon-14 labelled calcium carbonate.Analyst95.1970,95366-369. * |
| I. Ya. Vasilenko et al..Kinetics of metabolism of organic and inorganic 14Ccompounds.Journal of Hygiene, Epidemiology, Microbiology and Immunology26 1.1982,26(1),21-30. |
| I. Ya. Vasilenko et al..Kinetics of metabolism of organic and inorganic 14Ccompounds.Journal of Hygiene, Epidemiology, Microbiology and Immunology26 1.1982,26(1),21-30. * |
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| CN101262891A (en) | 2008-09-10 |
| GB0514194D0 (en) | 2005-08-17 |
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