Oral care composition containing oxilafluorine and condensed phosphate and application of oral care composition

Abstract

The invention discloses an oral care composition containing oxilafluorine and condensed phosphate and application of the oral care composition, and belongs to the technical field of oral care, the oral care composition comprises the oxilafluorine and the condensed phosphate, and the mass ratio of the oxilafluorine to the condensed phosphate is (0.1-1.9): (0.5-8.0); the condensed phosphate is water-soluble condensed phosphate; the condensed phosphate comprises one or more of hexametaphosphate, tripolyphosphate and trimetaphosphate. According to the invention, it is found for the first time that compounding of the oxilafluorine and the specific condensed phosphate generates a significant synergistic effect, effective repair of a demineralization area on a secondary surface layer of enamel is realized, and the purpose of deep mineralization is achieved; the oxilafluorine can obviously relieve the stimulation effect of condensed phosphate on oral mucosa, the effect is particularly important for oral ulcer patients, and the use comfort of the oral care product can be obviously improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of oral care, and in particular relates to an oral care composition comprising olaflurane and a condensed phosphate and an application thereof. Background Art

[0002] As people's attention to oral health grows, the variety and efficacy of oral care products are constantly innovating and developing. Fluoride, a key ingredient in preventing dental caries, has been 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 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 possesses significant surface activity, forming a stable surface film that enhances the retention of fluoride ions on the tooth surface while helping to inhibit the growth of oral bacteria. Although Olafur has greater affinity for tooth surfaces than ordinary fluorides, fluorides used alone, including Olafur, have limited effects on deep enamel remineralization. This is because fluoride ions primarily act on the surface of the enamel and have difficulty penetrating the subsurface and deeper demineralized areas, preventing comprehensive remineralization. Furthermore, excessively high fluoride concentrations can cause adverse reactions such as dental fluorosis, limiting their application dosage.

[0004] Condensed phosphates are complex substances composed of multiple phosphate groups linked by shared oxygen atoms. They primarily fall into two categories: cyclic phosphates and polyphosphates. Cyclic phosphates (such as sodium trimetaphosphate and sodium octametaphosphate) have a cyclic structure, characterized by high stability and the ability to form complexes under specific conditions. Polyphosphates (such as sodium tripolyphosphate and sodium hexapolyphosphate) have a linear structure and possess excellent chelating ability and dispersibility. However, condensed phosphates have a significant drawback: they can be irritating to the oral mucosa, particularly for patients with oral ulcers, potentially causing discomfort and pain.

[0005] The structural formula of olafluanid involved in the present invention is:

[0006] Condensed phosphate structure: . Summary of the Invention

[0007] The purpose of this section is to summarize some aspects of embodiments of the present invention and to briefly introduce some preferred embodiments.

[0008] As one aspect of the present invention, the present invention provides an oral care composition comprising olafluan and a condensed phosphate, wherein the mass ratio of olafluan to the condensed phosphate is 0.65-0.66:1-5, calculated as a percentage by mass; and the mass concentration of the condensed phosphate is 1-5%. The condensed phosphate is a water-soluble condensed phosphate; The condensed phosphate is hexametaphosphate, tripolyphosphate or trimetaphosphate.

[0009] As a preferred embodiment of the oral care composition comprising olafluan and a condensed phosphate according to the present invention, the condensed phosphate is sodium hexametaphosphate, sodium tripolyphosphate or sodium trimetaphosphate.

[0010] A preferred embodiment of the oral care composition comprising olafluan and condensed phosphate according to the present invention comprises dissolving the olafluan and condensed phosphate in water to obtain the oral care composition.

[0011] As a preferred embodiment of the oral care composition comprising olafluan and condensed phosphate according to the present invention, the molecular structural formula of olafluan is: .

[0012] The present invention also provides use of the composition in preparing oral care products.

[0013] Preferably, in the composition, the mass concentration of the condensed phosphate in the oral care product is 1-5%.

[0014] Preferably, the oral care products include toothpaste, mouthwash, gel, oral spray, oral patch, and tooth patch.

[0015] The present invention has the following beneficial effects: By controlling the ratio of olafluan to condensed phosphates, the present invention has discovered for the first time that the combination of olafluan and specific condensed phosphates produces a significant synergistic effect, effectively repairing subsurface demineralized areas 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 olafluan and condensed phosphates significantly enhances the acid resistance and physical strength of tooth enamel. The present invention unexpectedly discovered that olafluan can significantly reduce the irritation of condensed phosphates on the oral mucosa. This effect is particularly important for patients with oral ulcers and can significantly improve the comfort of oral care products. Irritation testing showed that the composition of the present invention reduced mucosal irritation by approximately 50% compared to the same concentration of condensed phosphate alone. It is speculated that this phenomenon may be related to the formation of a complex between olafluan and the condensed phosphate, thereby reducing the irritation of the condensed phosphate. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments, wherein: Figure 1 The thickness of the mineralized layer of some test groups under polarized light microscope.

[0017] Figure 2 The thermal analysis spectrum of the product was obtained by differential scanning calorimetry (DSC). DETAILED DESCRIPTION

[0018] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with specific embodiments.

[0019] The English abbreviations and glossaries involved in the present invention are as follows: DMSO: dimethyl sulfoxide; HTP: sodium hexametaphosphate (powder, soluble in water); IL-6: interleukin-6; MFP: sodium monofluorophosphate; MTT: Thiazolyl blue; NaF: sodium fluoride; OLF:Olaflu 27 H 60 F2N2O3); OMP: sodium octametaphosphate (powder, soluble in water); ppm: parts per million ppmF: parts per million fluorine content STPP: sodium tripolyphosphate (powder, easily soluble in water); TMP: sodium trimetaphosphate (powder, soluble in water); TSPP: Sodium pyrophosphate (powder, easily soluble in water).

[0020] Example: Preparation of sample solution and test solution: Artificial saliva (1 L): Dissolve 166.5 mg of calcium chloride, 156.8 mg of potassium dihydrogen phosphate, 15 mg of sodium fluoride, 4766.0 mg of 4-hydroxyethylpiperazineethanesulfonic acid, and 9691.6 mg of potassium chloride in 800 ml of deionized water. Once completely dissolved, adjust the pH to 7.0 with NaOH solution and bring the volume to 1 L.

[0021] Demineralization solution (1 L): 2.2 mmol / L calcium chloride dihydrate, 2.2 mmol / L potassium dihydrogen phosphate, 50 mmol / L acetic acid, adjust the pH to 4.5 with 1 mol / L sodium hydroxide solution, and add deionized water to make up to 1 L.

[0022] Silver nitrate solution (300g / L): Dissolve 300.0g of silver nitrate in 1L of deionized water.

[0023] MTT solution (0.5 mg / mL): Dissolve 5 mg of thiazolyl blue powder in 10 mL of phosphate buffer solution.

[0024] 0.5% TMP solution: Weigh 0.5 g of sodium trimetaphosphate and dissolve it in 99.5 mL of deionized water.

[0025] 1% TMP solution: Weigh 1.0 g of sodium trimetaphosphate and dissolve it in 99 mL of deionized water.

[0026] 3% TMP solution: Weigh 3.0 g of sodium trimetaphosphate and dissolve it in 97 mL of deionized water.

[0027] 5% TMP solution: Weigh 5.0 g of sodium trimetaphosphate and dissolve it in 95 mL of deionized water.

[0028] 1% HTP solution: Weigh 1.0 g of sodium hexametaphosphate and dissolve it in 99 mL of deionized water.

[0029] 3% HTP solution: Weigh 3.0 g of sodium hexametaphosphate and dissolve it in 97 mL of deionized water.

[0030] 5% HTP solution: Weigh 5.0 g of sodium hexametaphosphate and dissolve it in 95 mL of deionized water.

[0031] 1% STPP solution: Weigh 1.0 g of sodium tripolyphosphate and dissolve it in 99 mL of deionized water.

[0032] 3% STPP solution: Weigh 3.0 g of sodium tripolyphosphate and dissolve it in 97 mL of deionized water.

[0033] 5% STPP solution: Weigh 5.0 g of sodium tripolyphosphate and dissolve it in 95 mL of deionized water.

[0034] 3% OMP solution: Weigh 3.0 g of sodium octametaphosphate and dissolve it in 97 mL of deionized water.

[0035] 3% TSPP solution: Weigh 3.0 g of sodium pyrophosphate and dissolve it in 97 mL of deionized water.

[0036] 500ppmF (OLF) solution: Weigh 656.3mg of Olaflu and dissolve it in 100mL of deionized water to obtain an Olaflu solution containing 500ppm fluorine.

[0037] 1000ppmF (OLF) solution: Weigh 1312.6mg of Olaflu and dissolve it in 100mL of deionized water to obtain an Olaflu solution containing 1000ppm fluorine.

[0038] 500ppmF (NaF) solution: Weigh 110.5mg of sodium fluoride and dissolve it in 100mL of deionized water to obtain a sodium fluoride solution containing 500ppm fluorine.

[0039] 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.

[0040] 0.5% TMP + 500ppm F (OLF) solution: Weigh 0.5g sodium trimetaphosphate and 0.656g olafluor and dissolve them in 98.8g deionized water to obtain a solution containing 0.5% sodium trimetaphosphate and 500ppm fluorine.

[0041] 0.5% TMP + 1000ppm F (OLF) solution: Weigh 0.5g sodium trimetaphosphate and 1.31g olafluan and dissolve them in 98.2g deionized water to obtain a solution containing 0.5% sodium trimetaphosphate and 1000ppm fluorine.

[0042] 1% TMP + 500ppm F (OLF) solution: Weigh 1.0g of sodium trimetaphosphate and 0.656g of olafluan and dissolve them in 98.3g of deionized water to obtain a solution containing 1% sodium trimetaphosphate and 500ppm fluorine.

[0043] 3% TMP + 500ppm F (OLF) solution: Weigh 3.0g of sodium trimetaphosphate and 0.656g of olafluan and dissolve them in 96.3g of deionized water to obtain a solution containing 3% sodium trimetaphosphate and 500ppm fluorine.

[0044] 5% TMP + 500ppm F (OLF) solution: Weigh 5.0g of sodium trimetaphosphate and 0.656g of olafluan and dissolve them in 94.3g of deionized water to obtain a solution containing 5% sodium trimetaphosphate and 500ppm fluorine.

[0045] 1% HTP + 500ppm F (OLF) solution: Weigh 1.0g of sodium hexametaphosphate and 0.656g of olafluan and dissolve them in 98.3g of deionized water to obtain a solution containing 1% sodium hexametaphosphate and 500ppm fluorine.

[0046] 3% HTP + 500ppm F (OLF) solution: Weigh 3.0g of sodium hexametaphosphate and 0.656g of olafluan and dissolve them in 96.3g of deionized water to obtain a solution containing 3% sodium hexametaphosphate and 500ppm fluorine.

[0047] 5% HTP + 500ppm F (OLF) solution: Weigh 5.0g of sodium hexametaphosphate and 0.656g of olafluor and dissolve them in 94.3g of deionized water to obtain a solution containing 5% sodium hexametaphosphate and 500ppm fluorine.

[0048] 1% STPP + 500ppm F (OLF) solution: Weigh 1.0g of sodium tripolyphosphate and 0.656g of olafluanid and dissolve them in 98.3g of deionized water to obtain a solution containing 1% sodium tripolyphosphate and 500ppm fluorine.

[0049] 3% STPP + 500ppm F (OLF) solution: Weigh 3.0g of sodium tripolyphosphate and 0.656g of olafluanid and dissolve them in 96.3g of deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluorine.

[0050] 5% STPP + 500ppm F (OLF) solution: Weigh 5.0g of sodium tripolyphosphate and 0.656g of olafluanid and dissolve them in 94.3g of deionized water to obtain a solution containing 5% sodium tripolyphosphate and 500ppm fluorine.

[0051] 1% TMP + 500ppm F (NaF) solution: Weigh 1.0g of sodium trimetaphosphate and 0.111g of sodium fluoride and dissolve them in 98.9g of deionized water to obtain a solution containing 1% sodium trimetaphosphate and 500ppm fluoride.

[0052] 3% TMP + 500ppm F (NaF) solution: Weigh 3.0g of sodium trimetaphosphate and 0.111g of sodium fluoride and dissolve them in 96.9g of deionized water to obtain a solution containing 3% sodium trimetaphosphate and 500ppm fluoride.

[0053] 5% TMP + 500ppm F (NaF) solution: Weigh 5.0g sodium trimetaphosphate and 0.111g sodium fluoride and dissolve them in 94.9g deionized water to obtain a solution containing 5% sodium trimetaphosphate and 500ppm fluoride.

[0054] 1% STPP + 500ppm F (NaF) solution: Weigh 1.0g of sodium tripolyphosphate and 0.111g of sodium fluoride and dissolve them in 98.9g of deionized water to obtain a solution containing 1% sodium tripolyphosphate and 500ppm fluoride.

[0055] 3% STPP + 500ppm F (NaF) solution: Weigh 3.0g of sodium tripolyphosphate and 0.111g of sodium fluoride and dissolve them in 96.9g of deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluoride.

[0056] 5% STPP + 500ppm F (NaF) solution: Weigh 5.0g of sodium tripolyphosphate and 0.111g of sodium fluoride and dissolve them in 94.9g of deionized water to obtain a solution containing 5% sodium tripolyphosphate and 500ppm fluoride.

[0057] 1% TMP + 500ppm F (MFP) solution: Weigh 1.0g of sodium trimetaphosphate and 0.379g of sodium monofluorophosphate and dissolve them in 98.6g of deionized water to obtain a solution containing 1% sodium trimetaphosphate and 500ppm fluorine.

[0058] 3% TMP + 500ppm F (MFP) solution: Weigh 3.0g of sodium trimetaphosphate and 0.379g of sodium monofluorophosphate and dissolve them in 96.6g of deionized water to obtain a solution containing 3% sodium trimetaphosphate and 500ppm fluorine.

[0059] 5% TMP + 500ppm F (MFP) solution: Weigh 5.0g of sodium trimetaphosphate and 0.379g of sodium monofluorophosphate and dissolve them in 94.6g of deionized water to obtain a solution containing 5% sodium trimetaphosphate and 500ppm fluorine.

[0060] 1% STPP + 500ppm F (MFP) solution: Weigh 1.0g of sodium tripolyphosphate and 0.379g of sodium monofluorophosphate and dissolve them in 98.6g of deionized water to obtain a solution containing 1% sodium tripolyphosphate and 500ppm fluorine.

[0061] 3% STPP + 500ppm F (MFP) solution: Weigh 3.0g of sodium tripolyphosphate and 0.379g of sodium monofluorophosphate and dissolve them in 96.6g of deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluorine.

[0062] 5% STPP + 500ppm F (MFP) solution: Weigh 5.0g of sodium tripolyphosphate and 0.379g of sodium monofluorophosphate and dissolve them in 94.6g of deionized water to obtain a solution containing 3% sodium tripolyphosphate and 500ppm fluorine.

[0063] Comparative Example 1: 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 and is prepared into an aqueous solution of the required concentration for subsequent efficacy evaluation.

[0064] Comparative Example 2: Referring to Example 2 of patent DE2523363, tris-[N,N,N'-tris(2-hydroxyethyl)-N'-octadecyl-1,3-diaminopropane-monohydrofluoride]-trimetaphosphate was prepared. This substance is a viscous amorphous substance and is prepared into an aqueous solution of the required concentration for subsequent efficacy evaluation.

[0065] Comparative Example 3: 3% OMP + 500ppm F (OLF) solution: Weigh 3.0g of sodium octametaphosphate and 0.656g of olafluan and dissolve them in 96.3g of deionized water to obtain a solution containing 3% sodium octametaphosphate and 500ppm fluorine.

[0066] Comparative Example 4: 3% TSPP + 500ppm F (OLF) solution: Weigh 3.0g sodium pyrophosphate and 0.656g olafluanid and dissolve them in 96.3g deionized water to obtain a solution containing 3% sodium pyrophosphate and 500ppm fluorine.

[0067] Test Example 1: Enamel Remineralization Test: Five enamel blocks of the same specifications were selected for each group for this test. The enamel block samples were placed in a demineralizing solution for 3 hours, rinsed with deionized water, and blown dry. The hardness value HV1 after acid etching was tested. The tooth blocks were then immersed in each test sample solution, rinsed with deionized water after 5 minutes, added with artificial saliva, and treated at 37°C for 12 hours. The treatment cycle was repeated twice a day. The hardness value HV2 was tested after 15 days. The hardness improvement value ΔHV = HV2-HV1, and the hardness improvement rate = ΔHV / HV1 were calculated. The results are shown in Table 1.

[0068] The Bliss independence model calculation formula is used to determine whether it is an additive effect or a synergistic effect: Bliss independence model calculation formula (Bliss synergy value): ΔE=Eab-(Ea+Eb-Ea*Eb); in: Eab: hardness improvement rate of compound group; Ea&Eb: Hardness improvement rate of single-addition group; Judging criteria: ΔE>0: synergistic effect; ΔE=0: additive effect; ΔE<0: antagonistic effect; The remineralized enamel blocks of the control group, 500ppmF (OLF) group, 3%TMP group, 3%TMP+500ppmF (OLF) group, and 3%STPP+500ppmF (OLF) group were cut and polished, and the differences in the thickness of the mineralized layer of each group were observed using a polarized light microscope. The black vertical line in the picture represents the thickness of the mineralized layer. The results are shown in the attached figure. Figure 1 .

[0069] Table 1

[0070]

[0071]

[0072] In terms of remineralization, the effects of the three phosphates combined with fluoride were independent of phosphate concentration, with the optimal combination ratio being 3% phosphate and 500ppmF fluoride. The synergistic value ΔE for the combination of 0.5% TMP and 500ppmF (OLF) was approximately 0, indicating no synergistic effect between the two. However, starting from a 1% concentration of TMP, the combination with 500ppmF (OLF) exhibited a synergistic effect.

[0073] Compared to using 3% TMP, HTP, or STPP alone, the enamel hardness improvement values ​​were significantly increased when the three were combined with 500ppmF(OLF). Based on the Bliss independence model, the synergistic values ​​ΔE of the three combined with 500ppmF(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 500ppmF(OLF) can synergistically promote the remineralization of tooth enamel.

[0074] The remineralization effect of the 3% TMP + 500ppm F (OLF) group was significantly better than that of the 3% TMP + 500ppm F (NaF) group or the 3% TMP + 500ppm F (MFP) group. The remineralization effect of the 3% STPP + 500ppm F (OLF) group was significantly better than that of the 3% STPP + 500ppm F (NaF) or 3% STPP + 500ppm F (MFP) groups. This suggests that the combination of olaflurane and phosphates promotes enamel remineralization and is significantly more effective than the combination of sodium fluoride or sodium monofluorophosphate with condensed phosphates.

[0075] The remineralization effect of fluoride combined with condensed phosphate was superior to that of a salt compound formed in proportion with an amine base, hydrofluoric acid, and condensed phosphoric acid. Control Example 1, a salt formed by the amine base portion of 1.5 molecules of olafluanid with 1 molecule of cyclic phosphoric acid, showed a slight improvement in efficacy at the same phosphorus concentration as 3% TMP (0.911%), but was significantly inferior to that of either the fluoride alone or the combined group. Control Example 2, a salt formed by 1 molecule of amine base, 1 molecule of hydrofluoric acid, and 1 / 3 molecule of cyclic phosphoric acid. At a concentration of 500ppmF, the percentage of phosphorus in Control Example 2 was 0.0816%, equivalent to 0.269% TMP. The efficacy of Control Example 2 at this concentration was inferior to that of the 0.5%TMP+500ppmF (OLF) compound group; at a concentration of 1000ppmF, the percentage of phosphorus in Control Example 2 was 0.0816%, equivalent to 0.538%TMP. The efficacy of Control Example 2 at this concentration was significantly inferior to that of the 0.5%TMP+1000ppmF (OLF) compound group, and slightly stronger than that of the 0.5%TMP+500ppmF (OLF) compound group.

[0076] Polarized light microscope observation test results showed that the mineralized layer thickness in the 500ppmF(OLF)+3%TMP and 500ppmF(OLF)+3%STPP groups was the highest, and was much higher than that in the 500ppmF(OLF) group.

[0077] Compared with HTP, the remineralization effect of 3% OMP and 500ppm F (OLF), both of which are cyclic phosphates, was significantly weaker than that of 3% HTP and 500ppm F (OLF) (P < 0.001), and the synergistic value ΔE of their combination was 0, indicating that there was no synergistic effect between the two.

[0078] Compared with STPP, the remineralization effect of 3% TSPP and 500ppm F (OLF), both of which are linear phosphates, was significantly weaker than that of 3% STPP and 500ppm F (OLF) (P < 0.001), and the synergistic value ΔE of their combination was 0, indicating that there was no synergistic effect between the two.

[0079] The above results indicate that the combination of larger ring cyclic phosphates or shorter chain linear phosphates (sodium pyrophosphate) with olafluanid has no synergistic effect in promoting remineralization.

[0080] Test Example 2: In-depth caries prevention test: Five enamel blocks were selected from each group for this test. The blocks were placed in a demineralization solution for 3 hours, rinsed with deionized water, and air-dried. The blocks were then immersed in the solution containing the test sample. Control blocks were immersed in deionized water. After 5 minutes, each block was rinsed with deionized water, incubated with artificial saliva, and incubated at 37°C for 12 hours. This treatment cycle was repeated twice daily. After 15 days, the depth of demineralization in each group of samples was measured using MicroCT. The results are shown in Table 2.

[0081] Table 2

[0082] Each sample group had a certain effect on inhibiting the demineralization of tooth enamel. When TMP, HTP, or STPP were combined with 500ppmF (OLF), the demineralization depth was significantly reduced compared to the use of condensed phosphates or 500ppmF (OLF) alone. This shows that the combination of olafluan and phosphate significantly increased the mineralization depth of tooth enamel. In addition, the deep caries prevention effect of olafluan combined with two condensed phosphates was significantly better than the combination of sodium fluoride, sodium monofluorophosphate and two condensed phosphates.

[0083] Test Example 3: Oral cell viability test: Human gingival fibroblasts (HGF-1) were plated at 30,000 per well in 96-well plates. After the cells adhered, they were treated with different samples for 24 hours, and the supernatants were collected for IL-6 analysis. Simultaneously, 200 μL of 0.5 mg / mL MTT solution was added to the cells. After incubation at 37°C for 4 hours, the supernatant was removed, and 100 μL of DMSO was added to each well to dissolve the crystals. The OD value at 570 nm was measured with 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 to 1. The normalized IL-6 content of each sample group is shown in Table 4.

[0084] The survival rate is calculated as follows: Survival rate (%) = (OD value of experimental group - OD value of blank group) / (OD value of control group - OD value of blank group) Table 3

[0085] Conclusion: 3% TMP, HTP, and STPP all exhibited strong cytotoxicity. Combining 500 ppm fluoride (OLF) with TMP and STPP, respectively, significantly reduced cytotoxicity. This suggests that olafluanid can reduce the cytotoxicity of phosphates on oral epithelial cells, whereas sodium fluoride and sodium monofluorophosphate, with the same fluoride content, had no such effect. The cytotoxicity of Control Example 1 was comparable to that of 3% TMP.

[0086] Table 4

[0087] Test results showed that 3% TMP, HTP, and STPP significantly increased the expression of the inflammatory factor IL-6 in oral epithelial cells. Combining 500 ppm F (OLF) with TMP and STPP, respectively, significantly reduced IL-6 levels. This suggests that olafluanid can reduce phosphate-induced inflammation, while sodium fluoride and sodium monofluorophosphate with the same fluoride content have no such effect.

[0088] Test Example 5: Oral mucosal irritation test: According to the biological evaluation standard YY / T0127.13-2018 for oral medical devices, an oral mucosal irritation test was conducted, and a cotton ball with a diameter of about 10 mm was placed in the test solution to soak it. Five healthy, newly adult golden hamsters were selected for each group for the test. The test samples of different groups were placed in the cheek pouch of each experimental animal, and the other side was not treated as a control. The animals were killed after 2 weeks, and the cheek pouch mucosa was observed for irritation, damage, congestion, swelling, erosion, and ulcers. The cheek pouch on the test side and the cheek pouch on the control side of the same animal were compared, and the status of each measured cheek pouch was recorded. The clinical manifestations of the oral mucosa were scored according to Table 5. The observation scores of each animal in each period were added and then divided by the total number of observed animals to obtain the average score of each animal. The experimental results are shown in Table 6.

[0089] Oral mucosal reaction scoring system: Table 5

[0090] Table 6

[0091] TMP, HTP, and STPP at a concentration of 3% are highly irritating to the oral mucosa. However, when combined with 500ppm of fluorine (OLF), their oral mucosal irritation was significantly reduced, indicating that the addition of olafluanid can help reduce the oral mucosal irritation of condensed phosphates.

[0092] Test Example 6: Oral mucosal irritation test under oral ulcer conditions: Five healthy big-eared white rabbits were selected for each group for the test. The inside and outside of the animal's mouth were disinfected with 2 mol / L Sanisol, and a 300 g / L silver nitrate solution was applied to the buccal mucosa near the vestibule groove in the buccal pouch of the animal three times with a cotton ball. The animal was rinsed with normal saline. An ulcer was formed about one day later, and the size of the ulcer of each animal was recorded. The model of each animal was made in the same position as much as possible, and the size and depth were consistent. After that, the ulcer on the right buccal mucosa of each animal was smeared with each test solution once a day, and the ulcer on the left buccal mucosa was not given any treatment as a blank control. After 4 days, the size of the ulcer on the right side was measured with tracing paper, and the ulcer area (mm) was calculated. 2 ). The experimental results are shown in Table 7.

[0093] Table 7

[0094] Conclusion: TMP, HTP, and STPP at a concentration of 3% all increased the ulcer area of ​​oral ulcers. When combined with 500ppmF (OLF), oral mucosal irritation was significantly reduced. However, when 3% TMP was combined with 500ppmF of sodium fluoride or sodium monofluorophosphate, oral mucosal irritation was not significantly different from that before combination. This suggests that the addition of olafluan helps reduce the oral mucosal irritation of condensed phosphates, while sodium fluoride and sodium monofluorophosphate do not have this effect.

[0095] Test Example 7: Characterization of the mixture of olafluanid and sodium trimetaphosphate: 3.0g of sodium trimetaphosphate was dissolved in 97g of an aqueous solution of olafluan containing 500ppm fluorine. The liquid component was removed under reduced pressure to obtain a white solid. A small amount of the solid, olafluan and sodium trimetaphosphate were sampled and thermally analyzed using a differential scanning calorimeter (DSC). The spectrum is shown in the attached figure. Figure 2 ,like Figure 2 As shown, after being dissolved and mixed, olafluanid and sodium trimetaphosphate retained their respective maximum thermal transition temperatures during the thermal analysis test, indicating that no chemical reaction occurred between the components of the two substances after mixing, and no single-component salt described in patent DE2523363 was formed.

[0096] 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 the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. An oral care composition comprising olaflurane and a condensed phosphate, characterized in that: The invention comprises olafluanid and condensed phosphate, wherein the mass ratio of olafluanid to condensed phosphate is 0.65-0.66:1-5, and the mass concentration of the condensed phosphate is 1-5%. The condensed phosphate is a water-soluble condensed phosphate; The condensed phosphate is hexametaphosphate, tripolyphosphate or trimetaphosphate.

2. The oral care composition comprising olaflurane and a condensed phosphate according to claim 1, wherein: The condensed phosphate is sodium hexametaphosphate, sodium tripolyphosphate or sodium trimetaphosphate.

3. The oral care composition comprising olafluanid and condensed phosphate according to claim 1 or 2, characterized in that: The method comprises dissolving the olafluan and condensed phosphate in water to obtain the oral care composition.

4. The oral care composition comprising olaflurane and a condensed phosphate according to claim 1 or 2, characterized in that: The molecular structural formula of the olafluanid is: 。 5. Use of the composition according to claim 1 in preparing oral care products.

6. The use according to claim 5, characterized in that: In the composition, the mass concentration of the condensed phosphate in the oral care product is 1-5%.

7. The use according to claim 6, characterized in that: The oral care products include toothpaste, mouthwash, gel, oral spray, oral patch, and tooth patch.

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