KR100490378B1 - System for diagnosing helicobacter pylori with c-14 urea breath test - Google Patents

Abstract

The present invention relates to a Helicobacter pylori detection system used for diagnosing Helicobacter pylori using the C-14 urea breath test method, wherein the detection system is composed of an aspirator and a radiation detection device, the aspirator is in aerobic The upper absorbent pads are respectively inserted into upper and lower portions of the carbon dioxide absorbent to insert carbon dioxide absorbents for absorbing carbon dioxide into the crystal form and to prevent external leakage of the carbon dioxide absorbents and absorb water generated by the reaction of the carbon dioxide and carbon dioxide absorbents. And a lower absorption pad is disposed, and a backflow preventing sponge is disposed on an upper end of the upper absorption pad, and a tube-type collection filter including a β-radiation-permeable membrane including an upper cap and a lower cap for sealing the inlet and outlet of the exhalation unit. Consists of the radioactivity The traveling value includes an outer box, an inner lead, a counting gas inlet and a counting gas outlet, and grooves are formed to fix the collection filter therein, and the counting gas is injected through the counting gas inlet, and then the counting gas outlet. It is discharged through the interior of the radioactive detector is maintained at atmospheric pressure, the collection filter is characterized in that the amount of radiation emitted from the radioactive isotope C-14 in the state inserted into the detector. The detection system can not only capture the breath in a short time, but also increase the radioactivity detection efficiency.

Description

Helicobacter pylori detection system used to diagnose Helicobacter pylori using the C-14 urea breath test {SYSTEM FOR DIAGNOSING HELICOBACTER PYLORI WITH C-14 UREA BREATH TEST}

The present invention relates to a Helicobacter pylori detection system for diagnosing Helicobacter pylori using the urea breath test method, and more particularly to a Helicobacter pylori detection system using a C-14 urea breath test method that is a radioisotope.

Helicobacter pylori is a bacterium in the gastric mucosa that was first discovered in 1983 by Australian doctor Dr. Warren and Dr. Marshall. The H. pylori is a Gram-negative bacterium having a spiral torso and 4 to 8 flagella, which causes infections of the stomach, diseases such as gastritis, gastric ulcer and stomach cancer, and duodenum and pancreas. Known as a carrier for

The diagnosis of Helicobacter pylori infection is largely classified into biopsy, serological and urea breath test. Among these, the biopsy is the most basic and representative test, which has the advantage of not only the presence of Helicobacter pylori, but also the state of inflammation, malignancy and benignness of ulcers, but it is accompanied by pain and excessive time and cost. I have a problem. The serological and urea breath tests have the advantage of relatively accurate diagnosis of the presence of Helicobacter pylori without endoscopy, and among them, the diagnosis by the urea breath test, which can test the Helicobacter, is highlighted.

Enzymatic exhalation test (UBT) is based on the principle that urease secreted by Helicobacter pylori decomposes urea. Specifically, urease secreted by urease secreted in the presence of Helicobacter pylori after ingestion of a diagnostic reagent, urea Is decomposed into carbon dioxide and ammonia, and it is collected and analyzed by analyzing the carbon dioxide discharged from the expiratory air. It is a test method to determine whether helicobacter pylori is infected. Divided. C-14 UBT is a test method using C-14 labeled urea, a radioactive isotope, as a diagnostic reagent. The effect of a commercially available diagnostic reagent on a single dose is one day for the general person during the day. It has been approved for use by the US FDA for the degree of exposure to radiation in life. However, as interest in health increases, efforts are being made to reduce the amount of C-14 included in the diagnostic reagents.

Conventional techniques for the Helicobacter pylori detection system using the C-14 UBT method include a device and a method for carbon dioxide capture and analysis (Registration No .: 10-0314565), which is patented by North System Avesa, Sweden. This patent is ¹⁴ C-labeled compound, in particular ¹⁴ C in for collecting and analyzing apparatus of the present in the exhalation of the administration of the labeled urea (urea) From ¹⁴ CO _2, generally formed in a flat rectangular first and second duct Elements, wherein the first and second duct forming elements are joined to each other at each edge except one of their short edges to form a duct, the first duct forming element comprising a matrix element for CO ₂ absorption; and An apparatus for capturing and analyzing ¹⁴ CO ₂ comprising an indicator for detecting CO ₂ absorption and a film element having a low β-radiation absorbance which can be inserted or inserted between the β-radiation measuring instrument and the matrix element. The core technology of the patent is a breath card ( ^TM ) that captures ¹⁴ CO ₂ discharged into exhalation and has a flat rectangular shape, which includes a carbon dioxide absorption matrix and a carbon dioxide absorption detection indicator. The carbon dioxide absorption matrix consists of a matrix and lithium hydroxide, sodium hydroxide, calcium hydroxide and mixtures thereof, which are easily absorbed by carbon dioxide, and the indicator for detecting carbon dioxide absorption changes the pH indicator, especially pH change over pH 10 as color change. It is an indicator.

The method of use is to blow the ¹⁴ CO ₂ gas through the exhalation to the entrance of the exhalation card until the color of the carbon dioxide absorption detector changes color and measure it as a β-radiation measuring instrument. Exhalation cards currently on the market typically run for a period of 2 to 3 minutes to ensure sufficient ¹⁴ CO ₂ gas. The ¹⁴ CO ₂ gas that enters the aerobic guard is absorbed into the carbon dioxide absorption matrix, and the absorption principle is, for example, lithium carbonate is trapped in the matrix by a chemical reaction of 2LiOH + ¹⁴ CO ₂ → Li ₂ CO ₃ + H ₂ O. The presence of H. pylori carriers is determined by measuring the amount of C-14 radiation in lithium carbonate collected on the exhalation card using a Geiger-Muller Counter (hereinafter referred to as GM Counter).

The conventional technology has a merit of simplifying the measurement procedure compared to the liquid scintillation coefficient UBT test method according to the conventional PY test (patent registration US4830010), but it does not interfere with the determination of carriers by using a GM counter with low detection efficiency. Very low reproducibility of the test has a disadvantage of low reliability. In addition, since lithium hydroxide, a strong base material used as an absorbent of the carbon dioxide absorbing matrix, is changed to lithium carbonate by chemical reaction with carbon dioxide, the subject has a long inconvenience of having to blow an exhalation card for about 2 minutes or more. In addition, the indicator for detecting carbon dioxide absorption adjusts the amount of ¹⁴ CO ₂ flow in color due to the pH change, so that accurate quantification is impossible, which causes problems in quantitative analysis of radioactivity.

The first object of the present invention is to solve the radiation exposure problem, which is the biggest problem of the C-14 UBT method, to shorten the collection time and quantitative analysis of C-14, and to improve the detection efficiency. -14 To ensure that the labeled compound's radioactivity remains below the exemption level (half of the exemption). More specifically, the present invention provides a detection system that effectively collects C-14 and measures the collected gas with high efficiency, so that the amount of radioactivity of the C-14 labeled compound included in the diagnostic reagent is less than or equal to the regulatory exemption amount. 2 levels).

The present invention is a Helicobacter detection system for diagnosing the presence of Helicobacter pylori by the urea breath test method, wherein the Helicobacter pylori detection system is composed of an aerobic capture device and a radiation detection device, the aerobic capture device absorbs carbon dioxide in aerobic The upper absorbent pad is inserted into the crystalline form to prevent external leakage of the carbon dioxide absorbent and absorb H ₂ O generated by the reaction of the carbon dioxide and the carbon dioxide absorbent, respectively, The lower absorbent pad is disposed, the backflow prevention sponge is positioned on the upper side of the upper absorbent pad, and is composed of a tube-type collecting filter composed of a β-radial permeable membrane including an upper cap and a lower cap to block the inlet and outlet of the exhalation. The radiation detection device is a cathode A gas filled radiation detector including an outer box, an inner anode wire, an insulator, a gas inlet for counting and a gas outlet for counting, and having a groove formed therein for fixing the collecting filter therein, wherein the collecting filter is formed inside the detector. The present invention relates to a Helicobacter pylori detection system for diagnosing the presence or absence of Helicobacter pylori by the urea breath test method characterized by measuring the amount of radioactivity of ¹⁴ CO ₂ inserted and absorbed in the collection filter.

The Helicobacter pylori detection system according to the present invention includes a trapping filter in the form of a tube specially designed to effectively collect ¹⁴ CO ₂ discharged to the expiration. For the sake of understanding, the process before being discharged to the expiration is described as follows. First, oral administration of a diagnostic reagent containing an element labeled with C-14, a radioisotope. If C-14 Oral administration of the labeled component is Helicobacter pylori is to which the C-14 by the urease secreted cover elements in the above hydrolysis and generating a ¹⁴ CO _2, the resulting ¹⁴ CO ₂ is discharged through the exhalation On the other hand, in the case of non-Hycobacter pylori carriers, urease is not secreted, most of the orally administered urea is absorbed by the digestive organs and then excreted so that ¹⁴ CO ₂ is not generated during exhalation. Therefore, ¹⁴ CO ₂ discharged to the expiratory air is collected by using an appropriate expiration device and analyzed by the radioactivity detector to determine whether the carrier of Helicobacter pylori.

Figure 1 shows an aerobic trap device used in the detection system of the present invention. As shown in FIG. 1, the exhalation trap is a tube-shaped trapping filter 100 composed of a β-radiation-permeable membrane 5, and the inside of the trapping filter 100 absorbs carbon dioxide in aerobic air. The carbon dioxide absorbent 3 is inserted into the crystal form, and upper and lower absorbent pads 2 and lower absorbent pads 4 are respectively disposed on upper and lower portions of the carbon dioxide absorbent 3. The upper absorbent pad 2 and the lower absorbent pad 4 prevent external leakage of the carbon dioxide absorbent 3 and absorb H ₂ O generated by the reaction of the carbon dioxide and the carbon dioxide absorbent 3. In addition, a backflow preventing sponge 1 is disposed at an upper end of the upper absorbent pad 2 to prevent backflow of the carbon dioxide absorbent 3. The inlet 6 and the outlet 7 into which the exhalation is injected into the collection filter 100 are sealed by the upper cap 8 and the lower cap 9 so that the inside of the collecting filter 100 is contaminated before and after the collection of the exhalation. Prevent it.

Hereinafter, the capture filter 100 will be described in more detail. ¹⁴ CO ₂ in the exhaled air injected into the inlet 6 of the collecting filter of FIG. 1 is collected by the carbon dioxide absorbent 3 mounted inside the collecting filter 100. The prior art collecting device, namely the collecting device by North System Avesa, has a flat rectangular shape in the form of a card, and the absorption matrix contained therein is a thin film, so that the amount of carbon dioxide absorbent applied to the matrix is saturated. Although it takes about 2 to 3 minutes to the state, the collection filter device of the present invention can fill a large amount of absorbent in the crystalline state in the form of a tube, so that carbon dioxide is brought into contact with the crystal surface of a large area in a short time, thereby further improving the collection capacity. It is possible to reduce the collection time. According to an embodiment of the present invention, the time required for capturing carbon dioxide in the exhalation using the capture filter 100 of the present invention is only about 40 to 60 seconds, using a conventional North System Abessa exhalation card. When compared to the time required (about 2-3 minutes) it was confirmed that a lot of time can be shortened. Examples of the carbon dioxide absorbent 3 inserted into the collection filter in a crystalline state include lithium hydroxide, sodium hydroxide, calcium hydroxide and potassium hydroxide. More preferably, potassium hydroxide. The reaction for capturing carbon dioxide in aerobic air using potassium hydroxide is shown in Scheme 1.

2KOH + ¹⁴ CO ₂ → K ₂ ¹⁴ CO ₃ + H ₂ O

As can be seen in Scheme 1, ¹⁴ CO ₂ is transformed into potassium carbonate (K ₂ ¹⁴ CO ₃ ) by reacting with potassium hydroxide, the radioisotope C-14 in the potassium carbonate emits β-radiation, The released β-radiation is analyzed using the following detection apparatus to quantify the amount of ¹⁴ CO ₂ in the exhalation.

On the other hand, since an error may occur due to the difference in the amount of exhalation, it is necessary to constantly quantify the amount of exhalation collected in the collecting device for accurate analysis. The exhalation card of the above-described North Systems Avessa card is capable of qualitative analysis but not quantitative analysis. In the present invention, when collecting the exhalation using the collecting filter 100 shown in Figure 1, by attaching a gas flow gauge to the bottom of the collecting filter 1 to quantify the amount of gas flowing through the collecting filter 100 It is a 2nd characteristic. 2 is a view showing a state in which the collecting filter 100 is connected to the gas flow gauge 200 when collecting the exhalation. The collecting filter 100 is connected to the gas flow gauge 200 by the connecting member 300 at the outlet of the collecting filter (8 in FIG. 1). When exhalation is injected into the collection filter 100, gas excluding carbon dioxide in the exhalation passes through the collection filter 100 and then moves to the gas flow gauge 200, where the gas flow gauge 200 is located. The flow rate is measured by the flow rate sensor 21 disposed inside the. The flow rate sensor 21 may generate a specific signal to stop the inflow of the exhalation to the collection filter 100 when the amount of gas passing through the gas flow gauge exceeds a predetermined value. The gas flow gauge 200 may be detachably attached to the connection member 300 so that the gas flow gauge 200 may be used semi-permanently, unlike the collection filter, and the gas passing through the gas flow gauge 200 is collected by a filter (not shown). Can be.

The collection filter 100 collecting the C-14 by the above procedure is mounted on the detection site of the specially designed radiation detection device to count the amount of radioactivity to diagnose the presence or absence of carriers of Helicobacter pylori. The radiation detection device used in the present invention is to complement the problem of low detection efficiency of the short-wind GM counter used in the prior art. Specifically, in the case of the conventional detection device, unlike the collecting device outside the detection device, the detection device used in the detection system according to the present invention is a method of fixing the collecting device inside. In addition, the conventional detection device is used to seal the counting gas, the radiation detection device used in the present invention is a method of flowing the counting gas through the inlet and outlet. Figure 3 shows a radiation detection apparatus used in the Helicobacter pylori detection system of the present invention. As shown in FIG. 3, the radiation detection apparatus 400 includes an outer box 41, an inner conductive wire 42, a counting gas inlet 43, and a counting gas outlet 44, and the collection filter 100. ) Is provided with a groove 45 for fixing therein. The counting gas flows through the counting gas inlet 43 and the counting gas outlet 44, and thus, unlike the sealed type, the counting gas has an advantage that the inside of the detection device 400 is maintained at normal pressure. This maintenance at normal pressure can reduce the thickness of the β-permeable membrane 5 of the collection filter 100 and thus increase the amount of β-radiation emitted from C-14. P-10 gas (Ar 90% + CH ₄ 10%), which is commonly employed in the art, was used as a counting gas for measuring the radioactivity detector.

The β-radiation emitted by the ¹⁴ CO ₂ absorbed by the collection filter 100 generates a pulse due to ionization by interaction with the counting gas, which is pulse measuring means (not shown) through the conductive wire 42. The electrical signal is measured. Reference numeral 46 denotes an insulator to electrically insulate the conductors.

Detailed operation procedures of the present invention are as follows.

First, as shown in FIG. 2, the tube-type collection filter 100 and the gas flow gauge 200 are connected to each other by the connection member 300. The inlet 6 of the collecting filter 100 in the mouth and exhaled blows a certain amount of ¹⁴ CO ₂ gas, and stops when an alarm sounds from the flow rate sensor 21 in which the flow rate is preset for quantification. 100 is separated from the gas flow gauge 200. In this process, the ¹⁴ CO ₂ gas is absorbed by the carbon dioxide absorbent 3 inserted into the collection filter. The separated collection filter 100 is mounted inside the radioactivity detection device 400 to count the amount of radioactivity emitted from C-14 which is a radioisotope. The radiation detection device 400 connected to the high voltage counter operates for a predetermined time (about 1 to 2 minutes) to measure the amount of C-14 radiation in the collection filter 100, and during operation, the counting gas enters the inlet 43. It is discharged to the outlet 44.

Hereinafter, an Example is given and this invention is demonstrated more concretely.

Example 1 Preparation of Collection Filter

The polyethylene scintillation vial (Scintillation Vial) manufactured by SIMPORT Co., Ltd. was fabricated in the form of a tube shown in FIG. 1, and after the lower absorbent pad 4 was inserted, the carbon dioxide absorbent 3 was filled inside the tube, and then After the absorption pad 2 was inserted, the backflow prevention sponge 1 was inserted again. The filling amount of the carbon dioxide absorbent (3) was 10 g, and nonwoven fabric was used as the upper and lower absorbent pads 2 and 4, and polyethylene foam was used as the backflow prevention sponge (1).

Example 2 Carbon Dioxide Absorbent Performance Evaluation

In order to evaluate the performance of the carbon dioxide absorbent, lithium hydroxide, sodium hydroxide and potassium hydroxide (produced by Japan Junsei Co., Ltd.) were put in 10 g of collection filters, and the carbon dioxide was blown with an expiration for about 2 minutes. For analysis, XRD (X-ray diffractometer) was used to confirm that lithium carbonate, sodium carbonate, and potassium carbonate were changed. In order to compare the absorbing ability of these absorbents, each absorbent 1.6 mg of each absorbent was measured in an elemental analyzer (EA1110-FISONS). The amount of carbon in each material was quantitatively analyzed, and the results showed that potassium carbonate was distributed 2-5% more than lithium carbonate and sodium carbonate.

Example 3: Manufacture of Radioactivity Detection Device

In the manufacture of the radiation detection apparatus, a detection box was manufactured in the form of FIG. 3 using 10 mm thick aluminum.

The inner wire 42 was formed by arranging the wire in the form of FIG. 3, and the inlet 43 and the outlet 44 of the counting gas made holes in the detection box, sandwiched couplings, and connected by using a tie gun hose. Installed in the flow timer and gas cylinder.

The counting gas filled in the gas cylinder was P-10 gas (Ar 90% + CH ₄ 10%), and the gas flow timer used LUDLUM's model T-1031. In addition, the high voltage power supply counter used LUDLUM's Model 2000 scaler.

Example 4 Performance of Radioactivity Detection Device

To evaluate the performance of the radiation detection apparatus, the performance was evaluated using a C-14 Vial Standard Source (Beckman Activity: 104 dpm), which is similar to the collection filter tube of the present invention. The detection efficiency was about 10-14%.

Example 5 Comparison of the Detection Effects of Helicobacter Pylori Carriers

Select 6 test subjects and orally administer C-14 urea capsules (North System Avesa) with 200ml of water, wait 10 minutes for reaction in the stomach, and then collect the breath card (Breath Card). Exhaled ^TM ) (from North System Avesa) stopped when the label showing collection concentration changed from orange to yellow (it took 2 to 4 minutes) and was analyzed by Heliprobe Analyzer (product of North System Avesa) Got.

As a result of the analysis, 5 patients were identified as carriers of Helicobacter pylori, and two of them, namely, A and B groups, were divided into groups A and B after 10 days, orally administered with C-14 urea capsules in the same manner, and waited about 10 minutes. In the collection filter of the present invention, group A was exhaled for 1 minute and group B for 3 minutes. Each collection filter tube was measured for 3 minutes by a specially manufactured radiation detector of the present invention, and the results are shown in Table 1 below.

division A1 A2 B1 B2 Prior art inspection 193 cpm 230 cpm 162 cpm 316 cpm Invention test 288 cpm 264 cpm 1277 cpm 1732 cpm

As can be seen from Table 1, the detection system according to the present invention can capture the breath in a short time, it can be seen that the detection efficiency is quite high.

The Helicobacter pylori detection system according to the present invention can easily diagnose the infection of Helicobacter pylori, etc., and can significantly reduce the amount of radioisotope labeled on the compound such as urea as the detection efficiency is remarkably improved. Can be reduced. In addition, improved detection efficiency enables more accurate and accurate inspections.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a cross-sectional view showing tube cross-sectional views of a collection filter used in the Helicobacter pylori detection system of the present invention before and after CO ₂ injection.

2 is a perspective view of a collection filter used in the Helicobacter pylori detection system of the present invention, including a gas flow gauge.

3 is a diagram showing a cross-sectional view of a radiation detection apparatus used in the Helicobacter pylori detection system of the present invention with the collection filter described above.

Claims (3)

In the Helicobacter detection system for diagnosing the presence of Helicobacter pylori by the urea breath test method, the Helicobacter pylori detection system is composed of an aerobic trap and a radioactivity detector, the aerobic trap is a carbon dioxide for absorbing carbon dioxide in the aerobic The upper absorbent pad and the lower absorbent pad are respectively provided on the upper and lower portions of the carbon dioxide absorbent to insert the absorbent into the crystal form and to prevent external leakage of the carbon dioxide absorbent and to absorb H ₂ O generated by the reaction of the carbon dioxide and the carbon dioxide absorbent. It is disposed, and the top of the upper absorption pad is a sponge for preventing the backflow, consisting of a tube-type capture filter consisting of a β-radiation-permeable membrane including an upper cap and a lower cap for sealing the inlet and outlet of the exhalation, the The radiation detector is external And an inner lead, a counting gas inlet and a counting gas outlet, and a groove for fixing the collection filter therein is formed, and the counting gas is injected through the counting gas inlet and then discharged through the counting gas outlet. The interior of the detection apparatus is maintained at atmospheric pressure, and the collection filter uses the C-14 urea breath test method, wherein the amount of radioactivity emitted from the radioisotope C-14 is measured while being inserted into the interior of the detection apparatus. Helicobacter pylori detection system used to diagnose Helicobacter pylori. According to claim 1, Helicobacter pylori is characterized in that when collecting the exhalation using the collecting filter, the exhalation is collected in a state in which the gas flow gauge is connected to the lower portion of the collecting filter to quantify the amount of gas flowing through the collecting filter. Detection system. The Helicobacter pylori detection system according to claim 1, wherein the carbon dioxide absorbent is potassium hydroxide.