Detection reagent for lung bacterial infection detection and application thereof

Abstract

The invention provides a detection reagent for lung bacterial infection detection and application thereof, and relates to the technical field of medical diagnostic preparations. The detection reagent is an atomized solution capable of being inhaled by the nose, and the atomized solution capable of being inhaled by the nose is mainly prepared from C13 urea freeze-dried powder. The detection reagent is used as a nasal inhalation atomized solution and can directly target lung pathogens in an aerosol inhalation manner, so that efficient and non-invasive bacterial pneumonia diagnosis is realized, and the problems of sampling limitation and operation risk caused by dependence of existing traditional lung inflammation diagnosis on sputum culture or invasive bronchoalveolar lavage are effectively relieved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical diagnostic preparations, and particularly relates to a detection reagent for detecting pulmonary bacterial infections and its application. Background Art

[0002] Bacterial lung diseases, such as bacterial pneumonia, pulmonary tuberculosis, lung abscess, bacterial bronchitis, cystic fibrosis-related infections, and atypical pneumonia, not only affect respiratory function but may also spread throughout the body, posing a greater threat to patients with low immunity or chronic lung diseases.

[0003] Traditional diagnosis relies on sputum culture or invasive bronchoalveolar lavage, which has sampling limitations and operational risks, and is particularly unsuitable for children or patients who are unable to expectorate sputum.

[0004] Therefore, it has become extremely necessary and urgent to research and develop a detection reagent for bacterial lung infections that can be applied to nasal atomization inhalation for detection.

[0005] In view of this, the present invention is specifically proposed. Summary of the Invention

[0006] The purpose of the present invention is to provide a detection reagent for detecting pulmonary bacterial infections, which can achieve efficient and non-invasive diagnosis of bacterial pneumonia, effectively alleviating the problems of existing traditional pulmonary inflammation diagnosis relying on sputum culture or invasive bronchoalveolar lavage, with sampling limitations and operational risks.

[0007] To achieve the above object of the present invention, the following technical solutions are specifically adopted:

[0008] A detection reagent for detecting pulmonary bacterial infections provided by the present invention is a nasal inhalation atomization solution;

[0009] The nasal inhalation atomization solution is mainly prepared from freeze-dried carbon-13 urea powder.

[0010] Further, the pulmonary bacterial infection refers to pulmonary urease-producing bacterial infection.

[0011] Further, the nasal inhalation atomization solution is an isotonic aqueous solution, and the osmotic pressure range of the isotonic aqueous solution is 290 - 310 mOsm.

[0012] Further, the preparation method of the nasal inhalation atomization solution includes:

[0013] Preparing freeze-dried powder from carbon-13 urea and NaCl according to the osmotic pressure range, and dissolving it with water during use to obtain a nasal inhalation atomization solution.

[0014] Further, when dissolving, the ratio of the freeze-dried powder to water is 20 mg / 3 mL.

[0015] The application of the detection reagent provided by the present invention for detecting pulmonary bacterial infection in the preparation of screening products for bacterial pulmonary diseases.

[0016] Furthermore, the screening product for bacterial pulmonary diseases is a product for detecting the infection of urease-producing bacteria in the lungs.

[0017] Furthermore, the administration method of the application is to inhale a unit dose of the detection reagent by nasal atomization, and then judge whether there is an infection of urease-producing bacteria based on the isotope detection result of the exhaled gas sample.

[0018] Even further, the unit dose of the detection reagent is 3 mL, and the amount of freeze-dried carbon-13 urea in 3 mL is 20 mg.

[0019] Even further, the isotope detection result is the 13CO / 12CO isotope ratio of the exhaled gas sample, denoted as the DOB value;

[0020] When the DOB value of the exhaled gas sample ≥ 2.2% after 5 minutes of inhalation administration of the nasal inhalable aerosol solution, it is judged that there is an infection of urease-producing bacteria in the lungs.

[0021] Compared with the prior art, the beneficial effects of the present invention are:

[0022] A detection reagent provided by the present invention for detecting pulmonary bacterial infection, the detection reagent is a nasal inhalable aerosol solution; the nasal inhalable aerosol solution is mainly prepared from freeze-dried carbon-13 urea. The detection reagent is a nasal inhalable aerosol solution, which can directly target pulmonary pathogens through the way of aerosol inhalation, realize the diagnosis of bacterial pneumonia with high efficiency and non-invasiveness, and further effectively alleviate the problems of sampling limitations and operation risks existing in the existing traditional diagnosis of pulmonary inflammation relying on sputum culture or invasive bronchoalveolar lavage. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required to be used in the description of the specific embodiments or the prior art. Obviously, the following drawings are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0024] Figure 1 It is the detection flow chart of the nasal atomization inhalation detection reagent for detecting pulmonary bacterial infection of the present invention provided by Experimental Example 1 of the present invention;

[0025] Figure 2Flow chart for isotope detection and judgment of the nasal atomization inhalation detection reagent for detecting pulmonary bacterial infection provided in Experimental Example 1 of the present invention. Detailed implementation manners

[0026] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0027] According to one aspect of the present invention, a detection reagent for detecting pulmonary bacterial infection, the detection reagent is a nasal inhalation atomized solution;

[0028] The nasal inhalation atomized solution is mainly prepared from carbon-13 urea lyophilized powder.

[0029] It should be noted that in the prior art, although the carbon-13 urea breath test (13C-UBT) has been used for detecting Helicobacter pylori, there are still great difficulties in detecting pulmonary bacterial infection by the carbon-13 urea breath test, which is mainly determined by its oral administration method. On the one hand, oral administration is interfered by systemic metabolism. Oral urea needs to be absorbed through the digestive tract and then enter the blood circulation, and background metabolism may affect the detection accuracy. On the other hand, the local concentration in the lungs is low. Urea needs to reach the lungs through the blood circulation and it is difficult to directly target pulmonary pathogens.

[0030] In view of this, the present invention provides a detection reagent for detecting pulmonary bacterial infection. The detection reagent is a nasal inhalation atomized solution, which can directly target pulmonary pathogens by atomization inhalation, realizing efficient and non-invasive diagnosis of bacterial pneumonia, and effectively alleviating the problems of sampling limitations and operation risks in the existing traditional diagnosis of pulmonary inflammation relying on sputum culture or invasive bronchoalveolar lavage.

[0031] In a preferred implementation manner of the present invention, the pulmonary bacterial infection refers to pulmonary urease-producing bacterial infection.

[0032] In a preferred implementation manner of the present invention, the nasal inhalation atomized solution is an isotonic aqueous solution, and the osmotic pressure range of the isotonic aqueous solution is 290-310 mOsm.

[0033] As a preferred implementation manner, within the above osmotic pressure range, the nasal inhalation atomized solution has a better urea concentration and NaCl concentration. In the nasal inhalation atomized solution, the urea concentration is 109 mmol / L, and the concentration of the NaCl solution is 0.5%-0.9%.

[0034] For example: Dissolve 20 mg of carbon-13 urea in 3 mL of water, and add 15.84 mg of NaCl to adjust to an isosmotic pressure (290 mOsm / L). The concentration of urea is 109 mmol / L, and the concentration of the NaCl solution is 15.84 mg / 3 mL ≈ 5.28 mg / mL = 0.528% (W / V) (within the range of 0.5% to 0.9%, safe and effective).

[0035] If the urea concentration is too low, it may cause inaccurate DOB detection, resulting in misjudgment of the bacterial infection result. If the urea concentration is too high, such as higher than the concentration of 50 mg of carbon-13 urea dissolved in 3 mL of water, when adjusted to an isosmotic pressure, less NaCl needs to be added, and its concentration is lower than the 0.5% requirement, which will affect the safety of the atomized solution.

[0036] In a preferred embodiment of the present invention, the preparation method of the nasal inhalable atomized solution includes: preparing carbon-13 urea and NaCl into a lyophilized powder according to the osmotic pressure range, and dissolving it with water during use to obtain a nasal inhalable atomized solution.

[0037] In a preferred embodiment of the present invention, when dissolving, the ratio of the lyophilized powder to water is 20 mg / 3 mL.

[0038] Preferably, the preparation method of the nasal inhalable atomized solution is: making 20 mg of carbon-13 urea and 16 mg of NaCl (total osmotic pressure 291.7 mOsm / L) into a lyophilized powder, dissolving it in 3 mL of sterile water during use, and introducing the solution into an atomizer for atomized inhalation.

[0039] According to one aspect of the present invention, the application of a detection reagent for detecting pulmonary bacterial infection in the preparation of a screening product for bacterial lung diseases.

[0040] Specifically, the screening product for bacterial lung diseases is a product for detecting the infection of urease-producing bacteria in the lungs.

[0041] In a preferred embodiment of the present invention, the administration method of the application is nasal atomized inhalation of a unit dose of the detection reagent, and then judging whether there is an infection of urease-producing bacteria according to the isotope detection result of the exhaled gas sample.

[0042] In the above preferred embodiment, the unit dose of the detection reagent is 3 mL, and the amount of carbon-13 urea lyophilized powder in 3 mL is 20 mg.

[0043] In the above preferred embodiment, the isotope detection result is the 13CO / 12CO isotope ratio of the exhaled gas sample, denoted as the DOB value;

[0044] When the DOB value of the exhaled gas sample is ≥ 2.2% after 5 minutes of inhalation administration of the nasal inhalation atomization solution, it is determined that there are urease-producing bacteria in the pulmonary infection.

[0045] Preferably, the detection method for using the detection reagent for detecting pulmonary bacterial infection includes the following steps:

[0046] (1), Atomization administration: Atomize 13C-urea solution (dose 20 mg) through a medical nebulizer and inhale it into the lungs.

[0047] (2), Exhaled gas collection: Collect the exhaled gas of the patient at 0 minute before inhalation, and then collect the exhaled gas of the patient at 5, 10, and 15 minutes within 5 - 15 minutes after inhalation.

[0048] (3), Isotope detection: Use an infrared spectrometer to measure the δ value of 13CO / 12CO in the exhaled gas and calculate the increment (DOB) relative to the baseline.

[0049] (4), Result determination: If the DOB value is DOB ≥ 2.2% at 5 minutes, it indicates the presence of urease-producing bacterial infection.

[0050] It should be noted that since some patients have a slow reaction after atomization and the effective peak value may be after 5 minutes, to avoid misdiagnosis, the DOB value is also detected at 10 minutes and 15 minutes in this application.

[0051] In summary, the advantages of the detection reagent for detecting pulmonary bacterial infection of the present invention applied to the screening of bacterial pulmonary diseases can be summarized as:

[0052] 1. The detection method of the present invention is non-invasive, avoiding the radiation risk of traditional detection methods and the discomfort caused by invasive operations.

[0053] 2. The present invention is based on the metabolic differences of pulmonary microorganisms in carbon 13 urea for detection, with high specificity and accuracy, and can effectively distinguish different types of pneumonia.

[0054] 3. The detection process of the present invention is fast and convenient. The patient only needs to inhale the atomization solution and exhale the gas, without complex preparation work and long waiting time, and is suitable for large-scale clinical screening and diagnosis.

[0055] Next, the technical solution of the present invention will be further described in conjunction with the embodiments.

[0056] Example 1

[0057] A detection reagent for detecting pulmonary bacterial infection, the preparation method of the detection reagent includes:

[0058] 20 mg of carbon-13 urea and 16 mg of NaCl (total isosmotic pressure 291.7 mOsm / L) are made into a lyophilized powder, which is dissolved in 3 mL of sterile water during use to obtain a detection reagent.

[0059] The concentration of urea in the reagent is 109 mmol / L, and the concentration of the NaCl solution is 0.533%.

[0060] Example 2

[0061] 20 mg of carbon-13 urea and 17 mg of NaCl (total isosmotic pressure 303.2 mOsm / L) are made into a lyophilized powder, which is dissolved in 3 mL of sterile water during use to obtain a detection reagent.

[0062] The concentration of urea in the reagent is 109 mmol / L, and the concentration of the NaCl solution is 0.567%.

[0063] Comparative Example 1

[0064] 50 mg of carbon-13 urea and 3.2 mg of NaCl (total osmotic pressure 309.5 mOsm / L) are made into a lyophilized powder, which is dissolved in 3 mL of sterile water during use to obtain a detection reagent.

[0065] The concentration of urea in the reagent is 273 mmol / L, and the concentration of NaCl is 0.107%.

[0066] The concentration of NaCl in this example is not within the safe range of 0.5% - 0.9%.

[0067] Experimental Example 1

[0068] This experimental example verifies the detection effect of the nasal aerosol inhalation detection reagent of the present invention for detecting pulmonary bacterial infection.

[0069] Figure 1 It is the detection flow chart of the nasal aerosol inhalation detection reagent of the present invention for detecting pulmonary bacterial infection.

[0070] Figure 2 It is the isotope detection and judgment flow chart of the nasal aerosol inhalation detection reagent of the present invention for detecting pulmonary bacterial infection.

[0071] The specific method for detecting inflammation is as follows:

[0072] (1). Volunteer grouping: 3 patients with cystic fibrosis are used as the experimental group, and 3 normal patients without pulmonary inflammation are used as the negative control group.

[0073] (2) The volunteers in the above experimental group and negative control group used the detection reagent prepared in Example 1 to collect exhaled gas at 0 minutes, and then performed nasal inhalation aerosol administration through a medical nebulizer for 10 minutes.

[0074] (3) After the administration in step (2) was completed, exhaled gas was collected three times at 5, 10, and 15 minutes after aerosol inhalation administration into a special collection bag.

[0075] (4) Use an infrared spectrometer to analyze the 13CO / 12CO ratio of the exhaled gas sample in the collection bag in step (3), and record the DOB value;

[0076] When the DOB value of the exhaled gas sample ≥ 2.2% after 5 minutes of nasal inhalation aerosol solution inhalation administration, it is determined that there are urease-producing bacteria in the lung infection, and the test results are shown in Table 1.

[0077] Table 1:

[0078]

[0079]

[0080] As can be seen from Table 1 above, the detection reagent for lung bacterial infection detection in Example 1 of this application has better detection accuracy.

[0081] In Comparative Example 1, due to the too low concentration of NaCl, for safety reasons, no subsequent verification experiments were carried out in this application.

[0082] Note: The nasal aerosol inhalation detection reagent of this application has requirements for the concentration of NaCl. When NaCl is lower than 0.45% (hypotonic): water infiltrates into cells, which may cause mucosal edema and cell rupture; while when NaCl is higher than 0.9% (hypertonic): cells dehydrate, causing mucosal dryness, inflammation and even bronchospasm. Therefore, for safety reasons, samples that do not meet the standards did not undergo subsequent experiments.

[0083] Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A detection reagent for detecting pulmonary bacterial infections, characterized in that, The detection reagent is a nasal inhalation aerosol solution; The nasal inhalation aerosol solution is mainly prepared from freeze-dried carbon-13 urea powder.

2. The detection reagent for detecting pulmonary bacterial infection according to claim 1, wherein The pulmonary bacterial infection refers to the infection of urease-producing bacteria in the lungs.

3. The detection reagent for detecting pulmonary bacterial infection according to claim 1, characterized in that, The nasal inhalation aerosol solution is an isotonic aqueous solution, and the osmotic pressure range of the isotonic aqueous solution is 290-310 mOsm.

4. The detection reagent for detecting pulmonary bacterial infection according to claim 1, characterized in that, The preparation method of the nasal inhalation aerosol solution includes: According to the osmotic pressure range, carbon-13 urea and NaCl are prepared into freeze-dried powder, and dissolved in water during use to obtain a nasal inhalation aerosol solution.

5. The detection reagent for detecting pulmonary bacterial infection according to claim 3, characterized in that, During dissolution, the ratio of the freeze-dried powder to water is 20 mg / 3 mL.

6. Use of the detection reagent for detecting pulmonary bacterial infection according to any one of claims 1-5 in the preparation of a screening product for bacterial pulmonary diseases.

7. The application according to claim 6, characterized in that, The screening product for bacterial pulmonary diseases is a product for detecting the infection of urease-producing bacteria in the lungs.

8. The application according to claim 6, wherein The administration method of the use is to inhale a unit dose of the detection reagent by nasal atomization, and then judge whether there is an infection of urease-producing bacteria according to the isotope detection result of the exhaled gas sample.

9. The application according to claim 8, characterized in that, The unit dose of the detection reagent is 3 mL, and the amount of carbon-13 urea freeze-dried powder in 3 mL is 20 mg.

10. The application according to claim 8, characterized in that, The isotope detection result is the 13CO / 12CO isotope ratio of the exhaled gas sample, denoted as the DOB value; If the DOB value of the exhaled gas sample is ≥ 2.2% 5 minutes after the nasal inhalation of the aerosol solution, it is judged that there is an infection of urease-producing bacteria in the lungs.

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