An oral care composition comprising olaflur and condensed phosphate salt and uses thereof

Abstract

The application discloses an oral care composition containing olaflur and condensed phosphate and application thereof, and belongs to the technical field of oral care, and comprises olaflur and condensed phosphate, wherein the mass ratio of olaflur to condensed phosphate is 0.1-1.9:0.5-8.0 in terms of mass percentage; the condensed phosphate is water-soluble condensed phosphate; and the condensed phosphate comprises one or more of hexametaphosphate, tripolyphosphate and trimetaphosphate. It is found for the first time that the compounding of olaflur and specific condensed phosphate produces a significant synergistic effect, realizes effective repair of the demineralized area of the sub-surface layer of dental enamel, and achieves the purpose of deep mineralization; olaflur can significantly reduce the stimulation of condensed phosphate on oral mucosa, and this effect is particularly important for patients with oral ulcer, and can significantly improve the use comfort of oral care products.

Description

Technical Field

[0001] This invention belongs to the field of oral care technology, specifically relating to an oral care composition containing olaflu and condensed phosphate and its application. Background Technology

[0002] As people pay more attention to oral health, the types and efficacy of oral care products are constantly being innovated and developed. Among them, fluoride, as a key ingredient in preventing tooth decay, is widely used in oral care products such as toothpaste and mouthwash. Condensed phosphates, due to their unique chemical properties, show great potential in oral health care and treatment.

[0003] Olafur is an organic fluoride that provides fluoride ions that promote enamel remineralization and enhance teeth's resistance to acid. Furthermore, compared to traditional inorganic fluorides (such as sodium fluoride, stannous fluoride, and sodium monofluorophosphate), Olafur exhibits significant surface activity, forming a stable surface film that enhances the retention of fluoride ions on the tooth surface and helps inhibit the growth of oral bacteria. Although Olafur has better tooth surface affinity than ordinary fluorides, the deep enamel remineralization effect is limited when using fluorides alone, including Olafur. This is because fluoride ions primarily act on the enamel surface and cannot penetrate into the subsurface and deeper demineralized areas, thus failing to achieve a comprehensive remineralization effect. In addition, excessively high concentrations of fluoride may cause adverse reactions such as dental fluorosis, limiting its application dosage.

[0004] Condensed phosphates are complex substances composed of multiple phosphate groups linked by shared oxygen atoms, mainly including cyclic phosphates and polyphosphates. Cyclic phosphates (such as sodium trimetaphosphate and sodium octamethphosphate) have a cyclic structure and are characterized by high stability, capable of forming complexes under specific conditions. Polyphosphates (such as sodium tripolyphosphate and sodium hexadecimalate) have a linear structure and possess good chelating ability and dispersibility. However, condensed phosphates have a significant drawback: they can irritate the oral mucosa, especially causing discomfort and pain for patients with oral ulcers.

[0005] The structural formula of the olafol involved in this invention is:

[0006]

[0007] Condensed phosphate structure:

[0008] . Summary of the Invention

[0009] The purpose of this section is to outline some aspects of the embodiments of the present invention and to briefly describe some preferred embodiments.

[0010] As one aspect of the present invention, the present invention provides an oral care composition comprising olaflu and condensed phosphate, wherein the mass ratio of olaflu to condensed phosphate is 0.65~0.66:1~5 by mass percentage; and the mass concentration of the condensed phosphate is 1~5%.

[0011] The condensed phosphate is a water-soluble condensed phosphate;

[0012] The condensed phosphate is hexametaphosphate, tripolyphosphate, or trimetaphosphate.

[0013] As a preferred embodiment of the oral care composition comprising olaflu and condensed phosphate according to the present invention, the condensed phosphate is sodium hexametaphosphate, sodium tripolyphosphate, or sodium trimetaphosphate.

[0014] As a preferred embodiment of the oral care composition comprising olaflu and condensed phosphate according to the present invention, the oral care composition is obtained by dissolving the olaflu and condensed phosphate in water.

[0015] As a preferred embodiment of the oral care composition comprising olaflu and condensed phosphate according to the present invention, the molecular structural formula of olaflu is:

[0016] .

[0017] The present invention also provides the use of the composition in the preparation of oral care products.

[0018] Preferably, the condensed phosphate in the composition has a mass concentration of 1-5% in the oral care product.

[0019] Preferably, the oral care products include toothpaste, mouthwash, gel, oral spray, oral veneers, and dental veneers.

[0020] The beneficial effects of this invention are as follows: By controlling the ratio of olafron to condensed phosphate, this invention is the first to discover that the combination of olafron and a specific condensed phosphate produces a significant synergistic effect, achieving effective repair of demineralized areas in the subsurface layer of tooth enamel and achieving deep mineralization. Experimental data show that, compared to other fluorides (such as sodium fluoride and sodium monofluorophosphate), the combination of olafron and condensed phosphate significantly enhances the acid resistance and physical strength of tooth enamel. This invention unexpectedly discovered that olafron can significantly reduce the irritation of condensed phosphate to the oral mucosa. This effect is particularly important for patients with oral ulcers, significantly improving the comfort of oral care products. Irritation tests show that, compared to using the same concentration of condensed phosphate alone, the composition of this invention reduces mucosal irritation by approximately 50%. It is speculated that this phenomenon may be related to the formation of a complex between olafron and condensed phosphate, thereby reducing the irritation of condensed phosphate. Attached Figure Description

[0021] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below, wherein:

[0022] Figure 1 The thickness of the mineralized layer in some test groups is shown under a polarized light microscope.

[0023] Figure 2 This is a thermal analysis spectrum obtained from differential scanning calorimetry (DSC). Detailed Implementation

[0024] To make the above-mentioned objectives, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to specific examples.

[0025] The English abbreviations and definitions involved in this invention are as follows:

[0026] DMSO: Dimethyl sulfoxide;

[0027] HTP: Sodium hexametaphosphate (powder, easily soluble in water);

[0028] IL-6: Interleukin-6;

[0029] MFP: Sodium monofluorophosphate;

[0030] MTT: Thiazole Blue;

[0031] NaF: Sodium fluoride;

[0032] OLF: Oraflu (C 27 H 60 F2N2O3);

[0033] OMP: Sodium octamethasone (powder, easily soluble in water);

[0034] ppm: parts per million

[0035] ppmF: Parts per million of fluorine content

[0036] STPP: Sodium tripolyphosphate (powder, easily soluble in water);

[0037] TMP: Sodium tripolyphosphate (powder, soluble in water);

[0038] TSPP: Sodium pyrophosphate (powder, easily soluble in water).

[0039] Example:

[0040] Preparation of sample solutions and test solutions:

[0041] Artificial saliva (1L): Dissolve 166.5mg calcium chloride, 156.8mg dipotassium hydrogen phosphate, 15mg sodium fluoride, 4766.0mg 4-hydroxyethylpiperazine ethanesulfonic acid and 9691.6mg potassium chloride in 800ml deionized water. After complete dissolution, adjust the pH to 7.0 with NaOH solution and bring the volume to 1L.

[0042] Demineralization solution (1L): 2.2 mmol / L calcium chloride dihydrate, 2.2 mmol / L potassium dihydrogen phosphate, 50 mmol / L acetic acid, pH adjusted to 4.5 with 1 mol / L sodium hydroxide solution, and deionized water added to bring the volume to 1L.

[0043] Silver nitrate solution (300g / L): Dissolve 300.0g of silver nitrate in 1L of deionized water.

[0044] MTT solution (0.5 mg / mL): Dissolve 5 mg of thiazolyl blue powder in 10 mL of phosphate buffer solution.

[0045] 0.5% TMP solution: Weigh 0.5g of sodium trimetaphosphate and dissolve it in 99.5mL of deionized water.

[0046] 1% TMP solution: Weigh 1.0g of sodium trimetaphosphate and dissolve it in 99mL of deionized water.

[0047] 3% TMP solution: Weigh 3.0g of sodium trimetaphosphate and dissolve it in 97mL of deionized water.

[0048] 5% TMP solution: Weigh 5.0g of sodium trimetaphosphate and dissolve it in 95mL of deionized water.

[0049] 1% HTP solution: Weigh 1.0g of sodium hexametaphosphate and dissolve it in 99mL of deionized water.

[0050] 3% HTP solution: Weigh 3.0g of sodium hexametaphosphate and dissolve it in 97mL of deionized water.

[0051] 5% HTP solution: Weigh 5.0g of sodium hexametaphosphate and dissolve it in 95mL of deionized water.

[0052] 1% STPP solution: Weigh 1.0g of sodium tripolyphosphate and dissolve it in 99mL of deionized water.

[0053] 3% STPP solution: Weigh 3.0g of sodium tripolyphosphate and dissolve it in 97mL of deionized water.

[0054] 5% STPP solution: Weigh 5.0g of sodium tripolyphosphate and dissolve it in 95mL of deionized water.

[0055] 3% OMP solution: Weigh 3.0g of sodium octamethasone and dissolve it in 97mL of deionized water.

[0056] 3% TSPP solution: Weigh 3.0g of sodium pyrophosphate and dissolve it in 97mL of deionized water.

[0057] 500ppm F (OLF) solution: Weigh 656.3mg of olaflu and dissolve it in 100mL of deionized water to obtain an olaflu solution containing 500ppm fluorine.

[0058] 1000ppm F (OLF) solution: Weigh 1312.6mg of olaflu and dissolve it in 100mL of deionized water to obtain an olaflu solution containing 1000ppm fluorine.

[0059] 500ppm F (NaF) solution: Weigh 110.5mg of sodium fluoride and dissolve it in 100mL of deionized water to obtain a sodium fluoride solution containing 500ppm fluoride.

[0060] 500ppmF (MFP) solution: Weigh 378.8mg of sodium monofluorophosphate and dissolve it in 100mL of deionized water to obtain a sodium monofluorophosphate solution containing 500ppm fluorine.

[0061] 0.5% TMP + 500ppm F (OLF) solution: Weigh 0.5g sodium trimetaphosphate and 0.656g olafluridine, dissolve them in 98.8g deionized water to obtain a solution containing 0.5% sodium trimetaphosphate and 500ppm fluorine.

[0062] 0.5% TMP + 1000ppm F (OLF) solution: Weigh 0.5g sodium trimetaphosphate and 1.31g olafluridine, dissolve them in 98.2g deionized water to obtain a solution containing 0.5% sodium trimetaphosphate and 1000ppm fluorine.

[0063] 1% TMP + 500ppm F (OLF) solution: Weigh 1.0g sodium trimetaphosphate and 0.656g olafluridine, dissolve them in 98.3g deionized water to obtain a solution containing 1% sodium trimetaphosphate and 500ppm fluorine.

[0064] 3% TMP + 500ppm F (OLF) solution: Weigh 3.0g sodium trimetaphosphate and 0.656g olafluridine, dissolve them in 96.3g deionized water to obtain a solution containing 3% sodium trimetaphosphate and 500ppm fluorine.

[0065] 5% TMP + 500ppm F (OLF) solution: Weigh 5.0g sodium trimetaphosphate and 0.656g olafluridine, dissolve them in 94.3g deionized water to obtain a solution containing 5% sodium trimetaphosphate and 500ppm fluorine.

[0066] 1% HTP + 500ppm F (OLF) solution: Weigh 1.0g sodium hexametaphosphate and 0.656g olafluridine, dissolve them in 98.3g deionized water to obtain a solution containing 1% sodium hexametaphosphate and 500ppm fluorine.

[0067] 3% HTP + 500ppm F (OLF) solution: Weigh 3.0g sodium hexametaphosphate and 0.656g olafluridine, dissolve them in 96.3g deionized water to obtain a solution containing 3% sodium hexametaphosphate and 500ppm fluorine.

[0068] 5% HTP + 500ppm F (OLF) solution: Weigh 5.0g sodium hexametaphosphate and 0.656g olafluridine, dissolve them in 94.3g deionized water to obtain a solution containing 5% sodium hexametaphosphate and 500ppm fluorine.

[0069] 1% STPP + 500ppm F (OLF) solution: Weigh 1.0g sodium tripolyphosphate and 0.656g olaf, dissolve them in 98.3g deionized water to obtain a solution containing 1% sodium tripolyphosphate and 500ppm fluorine.

[0070] 3% STPP + 500ppm F (OLF) solution: Weigh 3.0g sodium tripolyphosphate and 0.656g olaf, dissolve them in 96.3g deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluorine.

[0071] 5% STPP + 500ppm F (OLF) solution: Weigh 5.0g sodium tripolyphosphate and 0.656g olaf, dissolve them in 94.3g deionized water to obtain a solution containing 5% sodium tripolyphosphate and 500ppm fluorine.

[0072] 1% TMP + 500ppm F (NaF) solution: Weigh 1.0g sodium trimetaphosphate and 0.111g sodium fluoride, dissolve them in 98.9g deionized water to obtain a solution containing 1% sodium trimetaphosphate and 500ppm fluoride.

[0073] 3% TMP + 500ppm F (NaF) solution: Weigh 3.0g sodium trimetaphosphate and 0.111g sodium fluoride, dissolve them in 96.9g deionized water to obtain a solution containing 3% sodium trimetaphosphate and 500ppm fluorine.

[0074] 5% TMP + 500ppm F (NaF) solution: Weigh 5.0g sodium trimetaphosphate and 0.111g sodium fluoride, dissolve them in 94.9g deionized water to obtain a solution containing 5% sodium trimetaphosphate and 500ppm fluoride.

[0075] 1% STPP + 500ppm F (NaF) solution: Weigh 1.0g sodium tripolyphosphate and 0.111g sodium fluoride, dissolve them in 98.9g deionized water to obtain a solution containing 1% sodium tripolyphosphate and 500ppm fluorine.

[0076] 3% STPP + 500ppm F (NaF) solution: Weigh 3.0g sodium tripolyphosphate and 0.111g sodium fluoride, dissolve them in 96.9g deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluorine.

[0077] 5% STPP + 500ppm F (NaF) solution: Weigh 5.0g sodium tripolyphosphate and 0.111g sodium fluoride, dissolve them in 94.9g deionized water to obtain a solution containing 5% sodium tripolyphosphate and 500ppm fluorine.

[0078] 1% TMP + 500ppmF (MFP) solution: Weigh 1.0g sodium trimetaphosphate and 0.379g sodium monofluorophosphate, dissolve them in 98.6g deionized water to obtain a solution containing 1% sodium trimetaphosphate and 500ppm fluorine.

[0079] 3% TMP + 500ppmF (MFP) solution: Weigh 3.0g sodium trimetaphosphate and 0.379g sodium monofluorophosphate, dissolve them in 96.6g deionized water to obtain a solution containing 3% sodium trimetaphosphate and 500ppm fluorine.

[0080] 5% TMP + 500ppmF (MFP) solution: Weigh 5.0g sodium trimetaphosphate and 0.379g sodium monofluorophosphate, dissolve them in 94.6g deionized water to obtain a solution containing 5% sodium trimetaphosphate and 500ppm fluorine.

[0081] 1% STPP + 500ppmF (MFP) solution: Weigh 1.0g sodium tripolyphosphate and 0.379g sodium monofluorophosphate, dissolve them in 98.6g deionized water to obtain a solution containing 1% sodium tripolyphosphate and 500ppm fluorine.

[0082] 3% STPP + 500ppmF (MFP) solution: Weigh 3.0g sodium tripolyphosphate and 0.379g sodium monofluorophosphate, dissolve them in 96.6g deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluorine.

[0083] 5% STPP + 500ppmF (MFP) solution: Weigh 5.0g sodium tripolyphosphate and 0.379g sodium monofluorophosphate, dissolve them in 94.6g deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluorine.

[0084] Compare with Example 1:

[0085] Referring to Example 1 of patent DE2523363, N,N,N'-tris(2-hydroxyethyl)-N'-octadecyl-1,3-diaminopropane trimetaphosphate was prepared. This substance is a viscous amorphous substance, which was prepared as an aqueous solution of the required concentration for subsequent efficacy evaluation.

[0086]

[0087] Compare with Example 2:

[0088] Referring to Example 2 of patent DE2523363, tris-[N,N,N'-tris(2-hydroxyethyl)-N'-octadecyl-1,3-diaminopropane-monohydrofluoride]-trimethophosphate was prepared. This substance is a viscous amorphous substance, which was prepared as an aqueous solution of the required concentration for subsequent efficacy evaluation.

[0089]

[0090] Compare with Example 3:

[0091] 3% OMP + 500ppmF (OLF) solution: Weigh 3.0g sodium octamethasone and 0.656g olafluridine, dissolve them in 96.3g deionized water to obtain a solution containing both 3% sodium octamethasone and 500ppm fluorine.

[0092] Compare with Example 4:

[0093] 3% TSPP + 500ppm F (OLF) solution: Weigh 3.0g sodium pyrophosphate and 0.656g olafluridine, dissolve them in 96.3g deionized water to obtain a solution containing 3% sodium pyrophosphate and 500ppm fluorine.

[0094] Test Example 1:

[0095] Enamel remineralization test:

[0096] Five identical enamel blocks were selected for each group for this test. The enamel block samples were immersed in demineralization solution for 3 hours, rinsed with deionized water, and dried. The hardness value HV1 after acid etching was measured. The blocks were then immersed in the test solution for 5 minutes, rinsed with deionized water, and treated with artificial saliva at 37°C for 12 hours. This treatment cycle was repeated twice daily. The hardness value HV2 was measured after 15 days. The hardness improvement value ΔHV = HV2 - HV1 was calculated, and the hardness improvement rate = ΔHV / HV1. The results are shown in Table 1.

[0097] Determine whether it is an additive or synergistic effect using the formula of the Bliss independent model:

[0098] The formula for calculating the Bliss independent model (Bliss co-value) is: ΔE = Eab - (Ea + Eb - Ea * Eb);

[0099] in:

[0100] Eab: Hardness enhancement rate of the compound group;

[0101] Ea & Eb: Hardness improvement rate of the single addition group;

[0102] Judgment criteria:

[0103] ΔE>0: synergistic effect; ΔE=0: additive effect; ΔE<0: antagonistic effect;

[0104] Separately, remineralized enamel blocks were taken from the control group, the 500ppmF (OLF) group, the 3%TMP group, the 3%TMP+500ppmF (OLF) group, and the 3%STPP+500ppmF (OLF) group. After cutting and polishing, the differences in mineralization layer thickness among the groups were observed using a polarized light microscope. The black vertical lines in the images represent the mineralization layer thickness. The results are shown in the appendix. Figure 1 .

[0105] Table 1

[0106]

[0107]

[0108]

[0109] In terms of remineralization, the combination effect of the three phosphates and fluorides was not concentration-dependent, with 3% phosphate and 500 ppmF fluoride being the optimal combination ratio. The synergistic value ΔE of 0.5% TMP combined with 500 ppmF (OLF) was approximately 0, indicating no synergistic effect. However, starting from 1% TMP, the combination with 500 ppmF (OLF) showed a synergistic effect.

[0110] Compared to using 3% TMP, HTP, or STPP alone, the enamel hardness enhancement values ​​of all three significantly increased when combined with 500ppm F(OLF). According to the Bliss independent model, the synergistic values ​​ΔE of the three combined with 500ppm F(OLF) were 0.39, 0.29, and 0.41, respectively, all greater than 0, indicating that the combination of 3% TMP, 3% HTP, and 3% STPP with 500ppm F(OLF) can synergistically promote enamel remineralization.

[0111] The remineralization effect of the 3% TMP + 500ppmF (OLF) group was significantly better than that of the 3% TMP + 500ppmF (NaF) group or the 3% TMP + 500ppmF (MFP) group. Similarly, the remineralization effect of the 3% STPP + 500ppmF (OLF) group was significantly better than that of the 3% STPP + 500ppmF (NaF) or 3% STPP + 500ppmF (MFP) groups. This indicates that the combination of olaflumethrin and phosphate helps promote enamel remineralization, and its effect is significantly better than that of sodium fluoride or sodium monofluorophosphate combined with condensed phosphate.

[0112] The remineralization effect of the compound of fluoride and condensed phosphate is better than that of the salt compound formed by amine base, hydrofluoric acid and condensed phosphoric acid in a certain proportion; Control Example 1 is a salt formed by 1.5 molecules of olaflurane amine base and 1 molecule of cyclic phosphoric acid. Although the efficacy is slightly improved at the same phosphorus concentration (0.911%) as 3% TMP, it is significantly worse than the fluoride alone group or the compound group. Control Example 2 is a salt formed by 1 molecule of amine base + 1 molecule of hydrofluoric acid + 1 / 3 molecule of cyclic phosphoric acid. At a concentration of 500 ppmF, the phosphorus percentage of Control Example 2 was 0.0816%, equivalent to 0.269% TMP. At this concentration, Control Example 2 was less effective than the 0.5% TMP + 500 ppmF (OLF) combination group. At a concentration of 1000 ppmF, the phosphorus percentage of Control Example 2 was 0.0816%, equivalent to 0.538% TMP. At this concentration, Control Example 2 was significantly less effective than the 0.5% TMP + 1000 ppmF (OLF) combination group, but slightly more effective than the 0.5% TMP + 500 ppmF (OLF) combination group.

[0113] Polarized light microscopy observation results showed that the mineralized layer thickness of the 500ppmF(OLF)+3%TMP and 500ppmF(OLF)+3%STPP groups was the highest, and much higher than that of the 500ppmF(OLF) group.

[0114] Compared with HTP, the remineralization effect of 3% OMP and 500ppmF (OLF), which belong to the same cyclic phosphate group, was significantly weaker than that of 3% HTP and 500ppmF (OLF) (P<0.001), and the synergistic value of the combination was ΔE≈0, indicating that there was no synergistic effect between the two.

[0115] Compared with STPP, the remineralization effect of 3% TSPP and 500ppmF(OLF), which are both linear phosphates, was significantly weaker than that of 3% STPP and 500ppmF(OLF) (P<0.001), and the synergistic value of the combination was ΔE≈0, indicating that there was no synergistic effect between the two.

[0116] The above demonstrates that the combined use of larger cyclic phosphates or shorter-chain linear phosphates (sodium pyrophosphate) with olaflu does not have a synergistic effect on promoting remineralization.

[0117] Test Example 2:

[0118] Deep caries prevention test:

[0119] Five enamel blocks were selected for each group for this test. The enamel block samples were immersed in demineralization solution for 3 hours, rinsed with deionized water, and dried. Then, the blocks were immersed in the respective test sample solutions, with the control group blocks immersed in deionized water. After 5 minutes, each block was rinsed with deionized water, artificial saliva was added, and the samples were treated at 37°C for 12 hours. This treatment cycle was repeated twice daily. After 15 days, the demineralization depth of each group's samples was detected using MicroCT, and the results are shown in Table 2.

[0120] Table 2

[0121]

[0122] All sample groups showed some effect in inhibiting enamel demineralization. However, when TMP, HTP, or STPP were combined with 500 ppm F (OLF), the demineralization depth was significantly reduced compared to using condensed phosphates or 500 ppm F (OLF) alone. This indicates that olafrad, when combined with phosphates, significantly improved the mineralization depth of enamel. Furthermore, the depth-preventing caries effect of olafrad combined with the two condensed phosphates was significantly better than that of sodium fluoride and sodium monofluorophosphate combined with the two condensed phosphates.

[0123] Test Example 3:

[0124] Oral cell viability test:

[0125] Human gingival fibroblasts (HGF-1) were seeded at a rate of 30,000 cells / well in 96-well plates. After cell adhesion, different samples were added for 24 hours, and the supernatant was collected to detect the IL-6 content. Simultaneously, 200 μL of 0.5 mg / mL MTT solution was added to the cells, and the cells were incubated at 37°C for 4 hours. After incubation, the supernatant was removed, and 100 μL of DMSO was added to each well to dissolve and crystallize the cells. The OD value at 570 nm was measured using a microplate reader, and the cell viability (%) of each group was calculated. The results are shown in Table 3. The IL-6 content in the supernatant of each group was also measured. The IL-6 content of the control group was set as 1. The normalized IL-6 content of each sample group is shown in Table 4.

[0126] The survival rate calculation formula is as follows:

[0127] Survival rate (%) = (OD value of experimental group - OD value of blank group) / (OD value of control group - OD value of blank group)

[0128] Table 3

[0129]

[0130] Conclusion: 3% TMP, HTP, and STPP all exhibited strong cytotoxicity. However, the cytotoxicity was significantly reduced when 500 ppm OLF was used in combination with TMP and STPP. This indicates that olaflurane can reduce the cytotoxicity of phosphate to oral epithelial cells, while sodium fluoride and sodium monofluorophosphate with the same fluorine content did not have this effect. Control Example 1 showed comparable cytotoxicity to 3% TMP.

[0131] Table 4

[0132]

[0133] Test results showed that 3% TMP, HTP, and STPP all significantly increased the expression level of the inflammatory factor IL-6 in oral epithelial cells. When 500 ppm F (OLF) was used in combination with TMP and STPP, the IL-6 content significantly decreased. This indicates that olaflurane can reduce phosphate-induced inflammation, while sodium fluoride and sodium monofluorophosphate with the same fluoride content did not have this effect.

[0134] Test Example 5:

[0135] Oral mucosal irritation test:

[0136] Oral mucosal irritation was tested according to the biological evaluation standard for oral medical devices YY / T0127.13-2018. Cotton balls approximately 10 mm in diameter were soaked in the test solution. Five healthy, juvenile golden hamsters were selected for each group. Test samples from different groups were placed in the cheek pouches of each animal, with the other cheek left untreated as a control. Animals were sacrificed after two weeks, and the cheek pouch mucosa was observed for irritation, damage, congestion, swelling, erosion, and ulceration. The condition of the cheek pouches on the test and control sides of the same animal was compared, and the status of the cheek pouches was recorded for each measurement. Clinical manifestations of the oral mucosa were scored according to Table 5. The scores of each animal at each period were summed and then divided by the total number of animals observed to obtain the average score per animal. The experimental results are shown in Table 6.

[0137] Oral mucosal response scoring system:

[0138] Table 5

[0139]

[0140] Table 6

[0141]

[0142] At a concentration of 3%, TMP, HTP, and STPP are highly irritating to the oral mucosa. However, when these three are combined with 500 ppm F (OLF), their oral mucosal irritation is significantly reduced, indicating that the addition of olaflu helps to alleviate the oral mucosal irritation caused by condensed phosphate.

[0143] Test Example 6:

[0144] Oral mucosal irritation test under oral ulcer conditions:

[0145] Five healthy white rabbits were selected for each group for the test. The oral cavity and surrounding area of ​​the animals were disinfected with 2 mol / L benzalkonium chloride solution. Cotton balls soaked in 300 g / L silver nitrate solution were applied three times to the buccal mucosa near the vestibular sulcus on both sides of the animal's cheek pouches. The area was then rinsed with physiological saline. Ulcers formed approximately one day later. The size of the ulcers for each animal was recorded, and the models were created in the same location, size, and depth as much as possible. Subsequently, the test solution was applied to the ulcers on the right buccal mucosa of each animal once daily. Ulcers on the left buccal mucosa were left untreated as a blank control. Four days later, the size of the right ulcer was plotted on tracing paper, and the ulcer area (mm²) was calculated. 2 The experimental results are shown in Table 7.

[0146] Table 7

[0147]

[0148] Conclusion: 3% concentrations of TMP, HTP, and STPP all increased the ulcer area of ​​oral ulcers. When combined with 500 ppm F (OLF), the oral mucosal irritation of all three significantly decreased. However, when 3% TMP was combined with 500 ppm F of sodium fluoride or sodium monofluorophosphate, there was no significant difference in oral mucosal irritation compared to before the combination. This indicates that the addition of olaflurane helps reduce the oral mucosal irritation caused by condensed phosphates, while sodium fluoride and sodium monofluorophosphate do not have this effect.

[0149] Test Example 7:

[0150] Characterization of the mixture of olafluridine and sodium trimetaphosphate:

[0151] 3.0 g of sodium trimetaphosphate was dissolved in 97 g of an aqueous solution of olafron containing 500 ppm fluorine. The liquid components were removed under reduced pressure to obtain a white solid. Small amounts of this solid, olafron, and sodium trimetaphosphate were taken and subjected to differential scanning calorimetry (DSC) for thermal analysis. The resulting spectra are shown in the attached figure. Figure 2 ,like Figure 2 As shown, after being dissolved and mixed, olaflumethrin and sodium trimetaphosphate retained their respective maximum thermal transition temperatures during the thermal analysis process, indicating that no chemical reaction occurred between the components after the two substances were mixed, and no single-component salt was formed as described in patent DE2523363.

[0152] 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 it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. An oral care composition comprising olaflur and a condensed phosphate salt, characterized in that: The oral care composition consists of olaflur and condensed phosphate, the mass ratio of olaflur to condensed phosphate is 0.65-0.66:1-5 in mass percentage; the condensed phosphate has a mass concentration of 1-5%; the olaflur has a concentration of 500 ppm in terms of fluorine; The condensed phosphate is sodium hexametaphosphate, sodium tripolyphosphate or sodium trimetaphosphate.

2. The oral care composition comprising olaflur and condensed phosphate salt according to claim 1 characterized in that: The method comprises dissolving the olaflur and condensed phosphate in water to obtain the oral care composition.

3. The oral care composition comprising olaflur and condensed phosphate salt according to either claim 1 or 2, characterized in that: The molecular structural formula of the olaflur is: 。 4. Use of the composition according to claim 1 in the preparation of an oral care product.

5. Use according to claim 4, characterized in that: In the composition, the condensed phosphate has a mass concentration of 1-5% in the oral care product.

6. Use according to claim 5, characterized in that: The oral care product comprises toothpaste, mouthwash, gel, oral spray, oral patch, dental patch.

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