Auxiliary diagnosis detection strip and detection method for xerostomia

Abstract

The invention discloses a saliva flow rate detection strip for auxiliary diagnosis of xerostomia and a detection method thereof. The detection strip comprises strip-shaped filter paper pretreated by fluorescein sodium, the filter paper is packaged in a food-grade plastic shell, one end of the filter paper extends out of the shell to form a 0.5 cm sampling part, and scale marks are arranged on the filter paper. During detection, the sampling part is placed under the tongue for 3 minutes, saliva infiltrates along the filter paper under the capillary action and dissolves the fluorescein sodium for color development, and the flow rate of the unstimulated saliva can be obtained through conversion by reading the infiltration length. The detection strip can effectively distinguish a control person from a sicca syndrome patient, a xerostomia patient and the like. The problems that a traditional method is long in consumed time, poor in experience and inconvenient to operate are solved, and a detection tool which is rapid, objective and standardized and is in seamless butt joint with an existing diagnostic standard is provided.

Description

Technical Field

[0001] This invention relates to the field of chemical test strips and chemical detection technology, specifically to an auxiliary diagnostic test strip and detection method for xerostomia. Background Technology

[0002] Sjögren's syndrome is a common autoimmune disease in rheumatology, with a global prevalence of 0.1%–0.6%, and a primary case prevalence of 0.29%–0.77% in China. This large patient population has created an urgent need for diagnosis and treatment and significant market potential. In 2016, the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria included "unstimulated total salivary flow rate ≤ 0.1 mL / min" as an independent scoring item, clearly defining its status as a key indicator for disease diagnosis. Salivary flow rate directly reflects the functional status of salivary glands, and its objective assessment is a core element of diagnosis, especially for the approximately 30% of patients who are anti-SSA / SSB antibody negative. However, the current mainstream clinical method for static salivary flow rate testing requires subjects to fast, abstain from water and smoking for at least 1 hour, avoid oral care interventions, and actively spit saliva into a container for 10 minutes in a seated, forward-leaning position. The flow rate is calculated by converting the total amount (≥0.1 ml / min for normal adults, and ≤0.05 ml / min for patients with Sjögren's syndrome). This method has drawbacks such as being time-consuming, having a poor patient experience, and being easily affected by subjective factors, which limits its clinical acceptability and diagnostic efficiency.

[0003] Existing technologies have disclosed relevant detection methods. For example, Japanese patent application JP2002005930A discloses a saliva flow test strip. This test strip is made of absorbent strip paper (such as Whatman filter paper), one end of which is printed with a water-soluble dye or a reagent that changes color in response to saliva, and the paper has graduations. In use, the dye-printed end is placed in the oral vestibule (between the lower lip and lower alveolar bone) for a certain period of time, and the saliva flow rate is estimated by measuring the distance the dye travels with saliva or the length of the colored portion of the test strip. However, in actual testing, the lips must be closed after inserting the test strip, and since the filter paper is exposed on the lip surface, the values ​​are directly interfered with by saliva on the lip surface, affecting the accuracy of the data; furthermore, due to the digestive effect of saliva, the filter paper cannot be dissolved, making the test impossible; in addition, during open-mouth testing, the saliva flow rate cannot be detected even in normal individuals due to air evaporation between the lower lip and lower alveolar bone. Therefore, the Japanese patent is impractical and requires further optimization. Clinical practice still needs a more accurate, convenient saliva flow rate testing tool and method that can be aligned with current authoritative diagnostic standards in actual clinical work. Summary of the Invention

[0004] The purpose of this invention is to provide a scientifically designed and structurally simple medical saliva flow rate detection tool and method. Based on the capillary adsorption principle of standard filter paper, the saliva secretion flow rate is converted into the wetting length of sodium fluorescein test paper, thereby achieving quantitative and accurate detection of saliva flow rate.

[0005] This invention provides a scientifically designed and structurally simple medical saliva flow rate detection tool and method. Based on the capillary adsorption principle of standard filter paper, it converts the saliva secretion flow rate into the wetting length of sodium fluorescein test paper, thereby achieving quantitative and accurate detection of saliva flow rate. Attached Figure Description

[0006] To more clearly illustrate the technical solutions in the specific embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0007] Figure 1 This is a schematic diagram of the detection strip of the present invention. Figure 1 ; Figure 2 This is a schematic diagram of the detection strip of the present invention. Figure 2 ; Figure 3 This is a schematic diagram of the detection process of the detection strip of the present invention. Figure 1 ; Figure 4 This is a schematic diagram of the detection process of the detection strip of the present invention. Figure 2 ; Figure 5 This is a schematic diagram comparing the salivary flow rate of the control group and the disease group implementing the method of the present invention; Figure 6 This is a schematic diagram illustrating the detection specificity and sensitivity of saliva flow rate in implementing the present invention; Figure 7 This is a schematic diagram illustrating the correlation between the saliva flow rate detected by the method of this invention and the traditional saliva flow rate detection in the control group; Figure 8 This is a schematic diagram illustrating the correlation between the salivary flow rate detected by the method of this invention and the traditional salivary flow rate detection in the disease group; Figure description: 1-Test paper; 2-Upper plastic shell; 3-Lower plastic shell; 4-Transparent plastic shell. Detailed Implementation

[0008] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, it should not be construed that the scope of the subject matter of the present invention is limited to the following embodiments. All modifications, substitutions and alterations made based on ordinary technical knowledge and conventional means in the art without departing from the above-described technical concept of the present invention are included within the scope of the present invention.

[0009] Example 1: A salivary flow rate test strip is provided for assisting in the diagnosis of xerostomia. For example... Figure 1 and Figure 2 As shown, the detection strip mainly consists of the following parts: Core testing component: Strip test paper 1 made of Whatman 41# filter paper soaked and dried with sodium fluorescein solution. This pretreatment process ensures that the sodium fluorescein component is evenly distributed in all the pores of the filter paper, forming a colorimetric layer. This material is consistent with the standardized Schirmer tear test paper, possessing accurate and stable capillary absorbency, ensuring the comparability and repeatability of test results.

[0010] Secure Packaging Structure: The strip-shaped filter paper is encapsulated within a food-grade safe plastic shell. One end of the shell has an opening, allowing one end of the filter paper to extend approximately 0.5 cm beyond the shell, forming a sampling section for contact with saliva. The shell body adopts a split design, with the upper plastic shell 2 and the lower plastic shell 3 forming a hollow protective frame. For easy observation, the upper plastic shell 2 integrates a transparent plastic cap 4. The opening end of the shell body is angled to ensure the test strip 1 fully contacts saliva in the mouth. The shell body completely encloses the rest of the test strip, effectively preventing direct contact between the user's hands or mouth and the test strip, thus improving safety and hygiene. A removable protective layer is also separately provided outside the sampling section. This protective layer is either release paper or has a tear-off section, which is used to peel it off to expose the sampling section during use.

[0011] Quantitative interpretation design: Clear millimeter-scale lines are printed along the length of the strip filter paper. The zero point (starting point) of the scale line precisely corresponds to the boundary between the sampling section and the plastic outer casing. This design allows the operator to intuitively and accurately read the capillary wetting distance of saliva along the test paper within a set time.

[0012] This test strip addresses the issues of poor patient experience and low acceptance. Its plastic casing and contact-only sampling completely eliminate the embarrassment and discomfort of prolonged spitting required by traditional methods, significantly improving the patient experience. It also solves the problems of cumbersome operation and low efficiency. Its integrated structure allows for immediate use without the need for collection containers, drastically reducing testing time from the traditional 10-15 minutes to 3 minutes, simplifying medical procedures and improving outpatient screening efficiency. Furthermore, it addresses the issues of subjective results and large errors. Utilizing the stable capillary effect of standardized filter paper, it objectively converts saliva flow rate into a visually measurable infiltration length, eliminating subjective and accidental errors caused by spitting force and environmental evaporation in traditional methods, achieving quantitative and standardized testing. The structure is simple, low-cost, requires no complex equipment, and has a unified standard for result interpretation.

[0013] Example 2: This example provides a method for measuring unstimulated whole saliva flow rate using the test strip described in Example 1, and its efficacy is verified through rigorous clinical trials.

[0014] Detection principle and operation: refer to Figure 3 and Figure 4 This method is based on the principle of capillary adsorption. Standardized preparation before testing is required: all subjects must fast and abstain from water for 1 hour, and are prohibited from smoking and chewing; their mouths must be cleaned to remove food residue. The testing environment is controlled at room temperature of 22-25℃ and relative humidity of 50%-60% to minimize environmental interference. During testing, the protective layer of the sampling section is removed. The subject sits with their head slightly tilted forward, placing the sampling section of the test strip under the tongue, keeping the strip roughly horizontal. Saliva is drawn into the test strip by capillary action, dissolving the sodium fluorescein and forming a distinct yellow-green infiltration front. After 3 minutes, the test strip is removed, and the scale value reached by the infiltration front is immediately read, yielding the 3-minute infiltration length (mm). Using a pre-established conversion formula, this length value can be converted into the unstimulated total saliva flow rate (mL / min) required for clinical diagnostic standards.

[0015] Comparative validation trials: To verify the accuracy and reliability of this method, the following clinical controlled studies were designed and executed: Study Subjects: The study included patients with Sjögren's syndrome meeting the 2016 ACR / EULAR criteria (male-to-female ratio 1:9) and 40 age- and sex-matched patients with osteoarthritis or fibromyalgia without dry mouth symptoms as controls. The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Zunyi Medical University, and all participants signed informed consent forms. All participants were fully informed and signed written informed consent forms, demonstrated good compliance, had no serious life or psychological obstacles affecting the execution of the experiment, and committed to cooperating with follow-up and related examinations. Exclusion criteria for study subjects were as follows: those with other autoimmune diseases; those with active oral lesions such as oral ulcers; those with severe cardiovascular or cerebrovascular diseases, respiratory diseases, or malignant tumors; and those who had recently taken medications affecting saliva secretion (specific medication categories needed).

[0016] Control method: A traditional static salivary flow rate measurement method was used as a control. This involved collecting all naturally secreted saliva from the subject within 15 minutes using sterile graduated centrifuge tubes, measuring the total volume, and calculating the flow rate (mL / min). Each subject underwent parallel measurements using both the traditional method (15-minute collection) and the method of this invention (3-minute detection) to ensure data comparability. Strict control was maintained over the testing environment (room temperature 22-25℃, humidity 50%-60%) and the subject's condition. The test results obtained using this invention are referenced... Figure 5 .

[0017] This embodiment uses SPSS 26.0 software for data analysis. First, normality tests (Shapiro-Wilk test) and homogeneity of variance tests (Levene test) are performed. If the flow rates between the two groups conform to a normal distribution and have homogeneity of variance, an independent samples t-test is used; otherwise, a Mann-Whitney U test is used. A p-value < 0.05 is considered statistically significant. A receiver operating characteristic (ROC) curve is constructed, with disease status (patient / control) as the dependent variable and the flow rate detected in this invention as the independent variable. The area under the curve (AUC) is calculated using the trapezoidal method to assess diagnostic efficacy (AUC 0.5–0.7 indicates low diagnostic value, 0.7–0.9 indicates moderate value, and > 0.9 indicates high value). Spearman correlation analysis is used to assess the correlation between the results of the two methods (|r| ≤ 0.3 indicates weak correlation, 0.3 < |r| ≤ 0.7 indicates moderate correlation, and |r| > 0.7 indicates strong correlation; p < 0.05 indicates statistically significant correlation).

[0018] Specifically as follows: Differentiating effectiveness: Reference Figure 5 The average infiltration length at 3 minutes was 12.9 mm in the patient group and 25.9 mm in the control group, with a highly statistically significant difference between the two groups (P<0.001). This indicates that the present invention can effectively distinguish between patients and control groups.

[0019] Diagnostic efficacy: Reference Figure 6 Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the flow rate detection method of this invention for diagnosis was 0.92 (>0.9), demonstrating its high diagnostic value and good sensitivity and specificity.

[0020] Equivalence (Relevance): Reference Figure 7 and Figure 8 Spearman correlation analysis showed that, in both the patient and control groups, the flow rate detected by this invention was significantly and strongly correlated with the results of traditional methods (control group r=0.91, P<0.001; patient group r=0.95, P<0.001). In conclusion, the clinical validation results of the saliva flow rate detection strip of this invention demonstrate its excellent detection efficacy and high consistency with traditional methods, making it a suitable standardized tool for saliva flow rate detection in clinical practice.

[0021] This embodiment verifies that the method achieves the following technical effects: It achieves rapid and accurate standardized detection: simplifying the complex saliva flow rate measurement into a standardized 3-minute procedure and obtaining quantitative results that are highly consistent with the 15-minute gold standard method.

[0022] Seamlessly aligned with international diagnostic standards: Test results can be directly converted and applied to the "Unstimulated Whole Saliva Flow Rate" scoring item in the 2016 ACR / EULAR classification criteria, resulting in low clinical adaptation costs.

[0023] It provides a reliable tool for clinical use: Empirical data show that the test strip has excellent diagnostic discrimination ability, sensitivity and specificity, and is especially suitable for functional assessment of suspected patients with negative antibodies. It can be used as a reliable tool for auxiliary diagnosis and disease monitoring.

[0024] In summary, Sjögren's syndrome has a clearly defined patient population, and its diagnosis heavily relies on objective assessment of salivary gland function. However, existing assessment methods each have significant shortcomings. Traditional salivary flow rate testing suffers from poor user experience and low accuracy. The invention of the "saliva flow rate test strip" directly addresses the pain points of current clinical practice. By providing a more accurate, convenient, and user-friendly standardized measurement tool, it is expected to improve the diagnostic level of Sjögren's syndrome, particularly in early screening and primary healthcare. Therefore, it has significant clinical necessity and market potential.

[0025] The above provides a detailed description of the auxiliary diagnostic strip and detection method for xerostomia provided by this invention. Specific examples have been used to illustrate the structure and working principle of this invention. The descriptions of the embodiments above are merely for the purpose of helping to understand the method and core ideas of this invention. It should be noted that those skilled in the art can make various improvements and modifications to this invention without departing from its principles, and these improvements and modifications also fall within the scope of protection of the claims of this invention.

Claims

1. An auxiliary diagnostic test strip for xerostomia, characterized in that: The device includes a strip of filter paper that adsorbs saliva through capillary action. A plastic shell is fitted and fixed to the outside of the strip of filter paper. One end of the plastic shell has an opening for the strip of filter paper to extend out. The extended part constitutes a sampling part for direct contact with saliva under the tongue. The sampling part is 0.5 cm long. The strip filter paper has a scale line printed along its length to quantify the saliva wetting length. The zero point of the scale line corresponds to the baseline where the sampling part meets the plastic shell packaging boundary, so as to directly read the wetting distance of saliva within a set time.

2. The auxiliary diagnostic test strip for xerostomia according to claim 1, characterized in that: A fluorescein coating is formed on the surface and in the internal pores of the strip filter paper through pretreatment with fluorescein sodium. This coating is used to produce a color reaction when in contact with saliva.

3. The auxiliary diagnostic test strip for xerostomia according to claim 1, characterized in that: The plastic casing is made of food-grade safe plastic.

4. The auxiliary diagnostic test strip for xerostomia according to claim 1, characterized in that: The strip filter paper has a length of 70 mm, a width of 10 mm, and a thickness of 0.11 mm.

5. The auxiliary diagnostic test strip for xerostomia according to claim 1, characterized in that: The sampling section is wrapped with a waterproof protective layer, which is a food-grade plastic shell, and is used to isolate and protect the sampling section during use.

6. A method for detection using the auxiliary diagnostic test strip according to any one of claims 1-5, characterized in that: First, remove the protective layer of the sampling section to expose it. Place the exposed sampling section under the subject's tongue for 3 minutes. Second, remove the test strip and read the final scale value reached by the saliva's wetting front on the strip filter paper. Finally, if the wetting length within 3 minutes is less than 20 mm, it indicates that the subject's unstimulated saliva flow rate is below the normal reference threshold.

7. The method for detection using auxiliary diagnostic test strips according to claim 6, characterized in that: The test was conducted in a state where the subject's oral cavity was not subjected to any physical or chemical stimulation, and the saliva collected by the test strip was unstimulated saliva that had naturally accumulated in the sublingual region.

8. The method for detection using auxiliary diagnostic test strips according to claim 6, characterized in that: During the testing process, ensure that the sampling area is in full contact with the surface of the sublingual gland tissue.

9. The method for detection using auxiliary diagnostic test strips according to claim 8, characterized in that: During the insertion and removal of the test strip, it is kept in a nearly horizontal position to avoid the saliva being affected by gravity due to siphon effect caused by tilting, thereby ensuring the accuracy of the interpretation results.

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