A self-sampling mouthwash emulsion composition, a self-sampling mouthwash emulsion and its application
By combining sodium hexadecyl sulfonate, guanidine derivatives, and amino derivatives in the self-sampling gargle wash composition, the discomfort problem of traditional respiratory virus diagnostic methods is solved, achieving efficient elution and DNA dissolution of respiratory viruses and bacteria, thus improving the patient experience.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- CHINA PRELIMINARY (BEIJING) SCI & TECH RES INST
- Filing Date
- 2023-07-06
- Publication Date
- 2026-06-30
AI Technical Summary
Traditional respiratory virus diagnostic methods, such as deep swab tests of the oropharynx or nasopharynx, are uncomfortable for patients and pose a risk of bleeding in some wards. There is a need to develop a patient-friendly self-sampling method to improve the elution capacity of respiratory viruses, bacteria and other pathogens.
The self-sampling gargle wash composition contains sodium hexadecyl sulfonate, guanidine derivatives and amino derivatives, which enhance the rinsing ability through compounding, and edible silicone oil and ethanol are added to improve the taste and reduce foaming.
It significantly improved the elution capacity of self-sampling gargle wash against respiratory viruses and bacteria, increased the DNA dissolution rate, and improved the taste and reduced foaming.
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Abstract
Description
Technical Field
[0001] This application relates to the field of pharmaceutical technology, specifically to a self-sampling mouthwash emulsion composition, a self-sampling mouthwash emulsion, and its application. Background Technology
[0002] Traditionally, the diagnosis of respiratory viruses relies on deep swabs taken from the oropharynx or nasopharynx by healthcare workers, and the process can be uncomfortable for patients. Furthermore, in some wards, such as hematology and oncology departments, swabbing may be discouraged to avoid bleeding complications in patients with severe thrombocytopenia.
[0003] Self-collection has the potential to serve as a strategy for molecular diagnostics of respiratory viruses, reducing patient discomfort during deep swab testing of the oropharynx or nasopharynx. Self-collection primarily involves self-swabs and self-sampling rinse solutions. Studies have shown that both self-swabs and self-sampling rinse solutions can be used to diagnose common respiratory viruses, such as influenza virus, rhinovirus, adenovirus, SARS-CoV-2, and endemic human coronaviruses. Among these, self-sampling rinse solutions are patient-friendly and effectively sample the upper respiratory tract for viral infection.
[0004] Therefore, there is a need to develop a self-sampling gargle wash that can elute oral mucosal cells and oral fluids, and the cells and fluids eluted by this self-sampling gargle wash should be mainly used for the diagnosis of common respiratory viruses, bacteria and other pathogenic microorganisms in the population. Summary of the Invention
[0005] In order to improve the ability to wash away respiratory viruses, bacteria and other pathogenic microorganisms in the oral cavity during self-sampling, this application provides a self-sampling mouthwash eluent composition, a self-sampling mouthwash eluent and its application.
[0006] In the first aspect, this application provides a self-sampling mouthwash composition, which adopts the following technical solution:
[0007] A self-sampling mouthwash composition, based on the self-sampling mouthwash composition, comprising 0.1-2.5 wt% sodium hexadecyl sulfonate (SDS, CAS No. 15015-81-3), 0.05-1.0 wt% guanidine derivative acid, and 0.05-1.0 wt% amino derivative.
[0008] In some embodiments of this application, the guanidine derivative is selected from guanidine phosphate, guanidine aminosulfonate, aminoguanidine mordant, guanidine stearate, metformin, arginine, and high-arginine.
[0009] In some embodiments of this application, the amount of the guanidine derivative is 0.05 to 0.5 wt%, for example: 0.1 wt%, 0.2 wt%, 0.25 wt%, etc.
[0010] In some embodiments of this application, the amino derivative is selected from m-aminophenylaminourea, aminobenzene, methyl carbamate, ornithine, and lysine.
[0011] In some embodiments of this application, the amount of the amino derivative is 0.05 to 0.5 wt%, for example: 0.1 wt%, 0.2 wt%, 0.25 wt%, etc.
[0012] In some embodiments of this application, the weight ratio of the guanidine derivative to the amino derivative is (0.8–1.2):(0.8–1.2). Further, the weight ratio of the guanidine derivative to the amino derivative is (0.9–1.1):(0.9–1.1). Even further, the weight ratio of the guanidine derivative to the amino derivative is 1:1.
[0013] In some embodiments of this application, the amount of sodium hexadecyl sulfonate used is 0.12–1.25 wt%, for example: 0.12 wt%, 0.25 wt%, 0.5 wt%, 0.75 wt%, 1 wt%, 1.25 wt%, etc. Further, the amount of sodium hexadecyl sulfonate used is 0.12–0.25 wt%.
[0014] In some embodiments of this application, the weight ratio of the total amount of the guanidine derivative and the amino derivative to the amount of sodium hexadecyl sulfonate is 1:(1 to 1.5). Further, the weight ratio of the total amount of the guanidine derivative and the amino derivative to the amount of sodium hexadecyl sulfonate is 1:(1.2 to 1.25).
[0015] In some embodiments of this application, the self-sampling gargling wash composition further includes 0.01–0.5 wt% edible silicone oil, for example: 0.01 wt%, 0.02 wt%, 0.03 wt%, 0.04 wt%, 0.05 wt%, 0.06 wt%, 0.07 wt%, 0.08 wt%, 0.09 wt%, 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, etc. Further, the amount of edible silicone oil used is 0.05 wt%.
[0016] In some embodiments of this application, the self-sampling gargling wash composition further includes 0.05-1 wt% ethanol, for example: 0.05 wt%, 0.06 wt%, 0.07 wt%, 0.08 wt%, 0.09 wt%, 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.7 wt%, 0.8 wt%, 0.9 wt%, etc.
[0017] In some embodiments of this application, the self-sampling gargle wash composition further includes water.
[0018] Secondly, the self-sampling mouthwash provided in this application adopts the following technical solution:
[0019] A self-sampling mouthwash wash, the raw materials of which include the self-sampling mouthwash wash composition provided in the first aspect of this application.
[0020] Thirdly, this application provides a method for preparing a self-sampling mouthwash wash, which adopts the following technical solution:
[0021] A method for preparing a self-sampling mouthwash wash, the method comprising the following steps:
[0022] The raw materials of the self-sampling mouthwash are mixed to obtain the self-sampling mouthwash.
[0023] In some embodiments of this application, the raw materials of the self-sampling gargle wash are mixed and then filtered.
[0024] In some embodiments of this application, the mesh size of the sieve used for filtration is 100 to 200 mesh, for example: 110 mesh, 120 mesh, 130 mesh, 140 mesh, 145 mesh, 150 mesh, 155 mesh, 160 mesh, 170 mesh, 180 mesh.
[0025] Fourthly, this application provides the application of a self-sampling gargle wash solution in the oral collection of respiratory viruses.
[0026] In some embodiments of this application, the respiratory viruses include, but are not limited to, influenza viruses, rhinoviruses, adenoviruses, and coronaviruses.
[0027] In some embodiments of this application, the coronaviruses include, but are not limited to, 2019 novel coronavirus (2019-nCoV), human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1), SARS coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV).
[0028] In summary, this application has the following beneficial effects:
[0029] First, this application improves the elution capacity of the self-sampling mouthwash solution against respiratory viruses, bacteria, and other pathogenic microorganisms in the oral cavity during self-sampling by simultaneously combining sodium hexadecyl sulfonate with guanidine derivatives and amino derivatives.
[0030] Secondly, by combining guanidine derivatives and amino derivatives, this application can not only improve the taste of the self-sampling mouthwash rinse solution, but also reduce the foaming of the self-sampling mouthwash rinse solution.
[0031] Third, by combining sodium hexadecyl sulfonate with both guanidine derivatives and amino derivatives, this application significantly improves the DNA dissolution rate of its self-sampling gargle eluent. Detailed Implementation
[0032] In this application, the guanidine derivative can be understood as a compound containing a guanidine group, and the amino derivative can be understood as a compound containing an amino group.
[0033] The present application will be further described in detail below with reference to the embodiments.
[0034] The raw materials used in this application can be obtained by purchase. Where the molecular structure of the raw material is chiral, unless otherwise specified, the raw material is a racemic mixture.
[0035] Preparation of self-sampling mouthwash rinse solution
[0036] Examples 1-5 and Comparative Examples 1-10
[0037] Table 1. Ingredients (by weight) of self-sampled mouthwash and rinse solutions from Examples 1-5 and Comparative Examples 1-10
[0038]
[0039]
[0040] The preparation method of the self-sampling mouthwash and eluent in Examples 1-5 and Comparative Examples 1-10 is as follows: the raw materials of the self-sampling mouthwash and eluent are mixed and filtered sequentially to obtain the self-sampling mouthwash and eluent. The sieve used for filtration has a mesh size of 150.
[0041] Performance testing of self-sampling mouthwash extract
[0042] Assay for cell elution capacity :
[0043] The method for detecting cell elution capacity specifically includes the following steps:
[0044] (1) HL7702 cells were seeded into a 6-well cell culture plate at a density of 5 × 10⁶ cells / well. 4 cells / mL;
[0045] (2) After incubation for 24 hours, remove the culture medium and add 1 mL of self-sampling rinsing solution to 3 wells of the 6-well cell seeding plate.
[0046] (3) After shaking on the shaker for 10 minutes, the solution from the three wells was aspirated and placed in an EP tube for cell counting;
[0047] (4) Take photos of the 6-well cell seeding plate before and after shaking, and compare the residual cells on the surface of the 6-well cell seeding plate before and after shaking.
[0048] The cell counting results of self-sampled mouthwash washes from Examples 1-5 and Comparative Examples 1-10 are shown in Table 1.
[0049] Table 2. Cell count results of self-sampled rinse washes from Examples 1-5 and Comparative Examples 1-10.
[0050]
[0051]
[0052] As can be seen from Table 2, the self-sampling gargle wash of this application has excellent cell elution ability.
[0053] Comparing Example 2 and Comparative Examples 6-7, it can be seen that the total weight of arginine and lysine used in Example 2 and Comparative Examples 6-7 is the same. However, in Example 2, sodium hexadecyl sulfonate is compounded with both arginine and lysine, while in Comparative Examples 6, sodium hexadecyl sulfonate is compounded with only arginine and only lysine. Compared to Comparative Example 6, the cell count result of Example 2 is improved by 39.29%; compared to Comparative Example 7, the cell count result of Example 2 is improved by 56%. Therefore, it is evident that the simultaneous compounding of sodium hexadecyl sulfonate with arginine and lysine significantly enhances the cell elution capacity of the self-sampling gargle wash of this application.
[0054] Similarly, comparing Example 3 and Comparative Examples 8-9 reveals that while the total weight of arginine and lysine used in Examples 3 and 8-9 was the same, in Example 3, sodium hexadecyl sulfonate was compounded with both arginine and lysine, in Comparative Example 8, sodium hexadecyl sulfonate was compounded with only arginine, and in Comparative Example 9, sodium hexadecyl sulfonate was compounded with only lysine. Compared to Comparative Example 8, the cell count result in Example 3 increased by 288.89%; compared to Comparative Example 9, the cell count result in Example 3 increased by 337.5%. Therefore, the simultaneous compounding of sodium hexadecyl sulfonate with arginine and lysine significantly enhances the cell elution capacity of the self-sampling gargle wash of this application.
[0055] Comparing Examples 3 and 4, it can be seen that, compared to Example 3, Example 4 used edible silicone oil; and compared to Example 3, the cell counting result of Example 4 was improved by 8.57%. Therefore, the use of edible silicone oil slightly improves the cell elution ability of the self-sampling mouthwash wash solution of this application.
[0056] Comparing Examples 3 and 5, Example 5 incorporated the use of ethanol compared to Example 3; and the cell counting results of Example 5 were 2.86% higher than those of Example 3. This demonstrates that the use of edible silicone oil slightly improved the cell elution capacity of the self-sampling mouthwash solution of this application.
[0057] Sensory test :
[0058] We are recruiting 15 test subjects aged 25 to 30.
[0059] The method for taste testing is as follows: Each tester rinses their mouth with 10-15 mL of self-sampled mouthwash for 15 seconds and then evaluates the taste to determine whether the self-sampled mouthwash is acidic, bitter, or comfortable and not tight after use.
[0060] The criteria for evaluating taste are as follows: if at least 8 out of the aforementioned 15 testers obtain consistent taste evaluation results, then the taste evaluation results can be used; otherwise, the taste test will be repeated.
[0061] The evaluation method for appearance is as follows: each test subject rinses their mouth with 10-15 mL of self-sampled rinse eluent for 15-30 seconds and observes the foam in the self-sampled rinse eluent during the rinsing process.
[0062] The criteria for assessing foam conditions are as follows:
[0063] (1) If the foam in the self-sampled mouthwash disappears within 5 seconds, it is judged to be basically foam-free;
[0064] (2) If the foam in the self-sampled mouthwash disappears within 5 to 30 seconds, it is considered to have less foam.
[0065] (3) If the foam in the self-sampled mouthwash disappears within 30 to 45 seconds, it is judged as foam+;
[0066] (4) If the foam in the self-sampled mouthwash disappears within 45 to 60 seconds, it is judged as foam++.
[0067] (5) If the foam in the self-sampled mouthwash disappears within 60 to 80 seconds, it is judged as foam+++;
[0068] (6) If there is a large amount of foam in the self-sampled mouthwash and the foam does not disappear in large quantities after 80 seconds, it is judged as foam++++.
[0069] If at least 8 out of the aforementioned 15 testers obtain consistent foam conditions, the appearance judgment result can be used; otherwise, the appearance test will be repeated.
[0070] The sensory test results of the self-sampled gargling washes from Examples 1-5 and Comparative Examples 1-10 are shown in Table 3.
[0071] Table 3. Sensory test results of self-sampled mouthwash washes from Examples 1-5 and Comparative Examples 1-10
[0072]
[0073]
[0074] As can be seen from Table 3, by comparing Comparative Examples 5 and 8-9, it can be seen that the use of arginine alone and the use of lysine alone can improve the taste of the self-sampling mouthwash rinse solution of this application, without affecting the foaming properties of the self-sampling mouthwash rinse solution of this application.
[0075] By comparing Example 3 and Comparative Example 5, it can be seen that the combined use of arginine and lysine can not only improve the taste of the self-sampling mouthwash rinse solution of this application, but also reduce the foaming of the self-sampling mouthwash rinse solution of this application.
[0076] Comparative examples 3-5 show that both edible silicone oil and ethanol can improve the appearance of the self-sampling rinse solution of this application. However, edible silicone oil has no significant effect on the taste of the self-sampling rinse solution of this application, while ethanol makes the self-sampling rinse solution of this application have an irritating taste.
[0077] Tests to detect DNA solubility
[0078] The test method for DNA solubility specifically includes the following steps:
[0079] (1) Mix 5 mg of calf DNA (calf DNA) and 10 mL of self-sampling rinse eluent and stir on a magnetic stirrer. After stirring for a certain time (1 min, 2 min, and 5 min), take 400 μL of the self-sampling rinse eluent containing calf DNA and dilute it with water to 4 mL. Use ultraviolet-visible absorption spectroscopy (UV method) to detect the absorbance of the diluted self-sampling rinse eluent containing calf DNA in the wavelength range of 200–400 nm. Plot the absorption curve with wavelength as the abscissa and absorbance as the ordinate, and obtain the maximum absorbance A from the absorption curve. max-1 ;
[0080] (2) Mix 5 mg of calf DNA (calf DNA) and 10 mL of self-sampling rinse eluent and stir on a magnetic stirrer until the calf DNA is completely dissolved. Take 400 μL of the completely dissolved calf DNA self-sampling rinse eluent and dilute it with water to 4 mL. Use ultraviolet-visible absorption spectroscopy (UV method) to detect the absorbance of the diluted solution of the completely dissolved calf DNA self-sampling rinse eluent in the wavelength range of 200-400 nm. Plot the absorption curve with wavelength as the abscissa and absorbance as the ordinate, and obtain the maximum absorbance A from the absorption curve. max-2 ;
[0081] (3) Calculate the percentage of DNA dissolved in the self-sampling rinse wash solution at different stirring times.
[0082] The calculation formula is:
[0083] Self-sampling rinse eluates from Examples 3-4 and Comparative Examples 5, 8-9 were selected, and the percentage of DNA dissolved in the self-sampling rinse eluates was measured. PBS buffer was used as a control group, and the percentage of DNA dissolved in PBS buffer was measured. The results of the DNA dissolution percentage measurements are shown in Table 4.
[0084] Table 4 Results of DNA dissolution percentage detection
[0085]
[0086] As can be seen from Table 4, the self-sampling rinsing solution of this application significantly increased the DNA dissolution rate, and could dissolve more than 40% of the DNA within one minute.
[0087] Comparative examples 5 and 8-9 show that the combination of sodium hexadecyl sulfonate and arginine or sodium hexadecyl sulfonate and lysine slightly improves the dissolution rate of DNA in the self-sampling rinsing solution of this application.
[0088] By comparing Example 3 and Comparative Example 5, it can be seen that sodium hexadecyl sulfonate, when combined with both arginine and lysine, significantly improves the DNA dissolution rate of the self-sampling gargle eluent of this application.
[0089] Comparative examples 3-4 show that the use of edible silicone oil not only does not negatively affect the DNA dissolution rate of the self-sampling rinse eluent of this application, but can also slightly increase the DNA dissolution rate of the self-sampling rinse eluent of this application.
[0090] It is understood that the above embodiments are merely exemplary implementations used to illustrate the principles of this application, and this application is not limited thereto. For those skilled in the art, various modifications and improvements can be made without departing from the spirit and substance of this application, and these modifications and improvements are also considered to be within the scope of protection of this application.
Claims
1. A self-sampling mouthwash composition, characterized in that, Based on the self-sampling mouthwash composition, the self-sampling mouthwash composition comprises: Sodium hexadecyl sulfonate 0.1–2.5 wt%, guanidine derivative 0.05–1.0 wt%, amino derivative 0.05–1.0 wt%; The weight ratio of the guanidinium derivative to the amino derivative is (0.8–1.2):(0.8–1.2).
2. The self-sampling mouthwash composition according to claim 1, characterized in that, The guanidine derivatives are selected from guanidine phosphate, guanidine aminosulfonate, aminoguanidine mordant, guanidine stearate, metformin, arginine, and high arginine; The amount of the guanidine derivative used is 0.05 to 0.5 wt%.
3. The self-sampling mouthwash composition according to claim 1, characterized in that, The amino derivative is selected from m-aminophenylaminourea, aminophenyl, methyl carbamate, ornithine, and lysine; The amount of the amino derivative used is 0.05 to 0.5 wt%.
4. The self-sampling mouthwash composition according to claim 1, characterized in that, The sodium hexadecyl sulfonate is 0.12–1.25 wt%; The amount of sodium hexadecyl sulfonate used is 0.12 to 0.25 wt%.
5. The self-sampling mouthwash composition according to claim 1, characterized in that, The weight ratio of the total amount of the guanidine derivative and the amino derivative to the amount of sodium hexadecyl sulfonate is 1:(1-1.5). The weight ratio of the total amount of the guanidine derivative and the amino derivative to the amount of sodium hexadecyl sulfonate is 1:(1.2 to 1.25).
6. The self-sampling mouthwash composition according to claim 1, characterized in that, The self-sampling gargling wash composition also includes 0.01–0.5 wt% edible silicone oil; The amount of the edible silicone oil used is 0.05 wt%.
7. The self-sampling gargling wash composition according to claim 1, characterized in that, The self-sampling gargle wash composition also includes 0.05–1 wt% ethanol.
8. A self-sampling mouthwash wash, characterized in that, The raw materials of the self-sampling gargle wash include the self-sampling gargle wash composition as described in any one of claims 1 to 7.
9. The application of the self-sampling gargle wash solution as described in claim 8 in oral self-collection of respiratory viruses; The respiratory viruses include influenza virus, rhinovirus, adenovirus, and coronavirus.