A bioactive glass oral desensitizing ointment and its preparation method

Abstract

This invention discloses a bioactive glass oral desensitizing ointment and its preparation method, belonging to the technical field of oral desensitizing ointments. The oral desensitizing ointment comprises the following raw materials in parts by weight: 5-15 parts bioactive glass, 2-4 parts silica, 0.5-2 parts antibacterial and anti-inflammatory agent, 10-25 parts glycerin, 20-30 parts humectant, 2-4 parts surfactant, 0.5-1.5 parts fragrance, 0.5-2 parts gelling agent, and 30-50 parts purified water. The oral desensitizing ointment prepared by this invention exhibits good antibacterial properties and dentinal tubule sealing rate.

Description

Technical Field

[0001] This invention relates to the field of oral desensitizing ointment technology, specifically to a bioactive glass oral desensitizing ointment and its preparation method. Background Technology

[0002] Dentin hypersensitivity is a common and prevalent oral disease, primarily characterized by brief but intense sharp pain in teeth when exposed to external stimuli such as cold, heat, acid, sweetness, or mechanical stimulation (e.g., brushing). When tooth enamel wears away or gum recession exposes the dentin, the densely packed dentinal tubules within it directly communicate with the oral environment. External stimuli cause abnormal fluid flow within these tubules, which in turn irritates the dental pulp nerves deep within the dentin, triggering pain. Current desensitizing oral care products on the market mainly suffer from the following problems: First, desensitizing agents, such as potassium nitrate, only temporarily numb the nerves and cannot fundamentally seal the tubules, thus only treating the symptoms, not the root cause. Second, physical blocking agents, such as calcium carbonate, while able to block the tubules, often form a weak and unstable sealing layer that easily falls off under the acidic environment of the mouth and mechanical friction. This fails to provide continuous protection during brushing breaks, allowing cariogenic bacteria and periodontal pathogens to re-aggregate and produce acid, corroding the newly formed remineralized layer and resulting in unsatisfactory desensitization effects.

[0003] Chinese invention patent CN120549781A discloses an oral care desensitizing paste and its preparation method. The oral care desensitizing paste includes the following components: bioactive glass, strontium chloride, sodium chloride, silicon dioxide, sodium carboxymethyl cellulose, polyethylene glycol 400, xanthan gum solution, sodium lauryl sulfate, sodium lauroyl sarcosinate, titanium dioxide, β-glucan, sodium saccharin, sorbitol, methylparaben, propylparaben, edible flavoring, and water. This oral care desensitizing paste can be used to treat tooth sensitivity and inhibit and reduce dental plaque, but its dentinal tubule sealing rate needs to be improved. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the purpose of this invention is to provide a bioactive glass oral desensitizing ointment and its preparation method.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A bioactive glass oral desensitizing cream, comprising the following raw materials in parts by weight:

[0007] 5-15 parts bioactive glass, 2-4 parts silica, 0.5-2 parts antibacterial and anti-inflammatory agent, 10-25 parts glycerin, 20-30 parts moisturizer, 2-4 parts surfactant, 0.5-1.5 parts fragrance, 0.5-2 parts gelling agent, and 30-50 parts purified water;

[0008] The antibacterial and anti-inflammatory agent is prepared by the following method:

[0009] S1: 3,5-Dimethoxy-4'-hydroxystilbene reacts with 11-chloroundecanoic acid to form an ether compound.

[0010] S2: The ether-based compound reacts with 8-dimethylamino-1-octanol to form an ester-based tertiary amine compound.

[0011] S3: 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol reacts with epichlorohydrin to form a triepoxide compound.

[0012] S4: Ester-based tertiary amine compounds react with triepoxide compounds to generate antibacterial and anti-inflammatory agents.

[0013] In step S1, the molar ratio of 3,5-dimethoxy-4'-hydroxystilbene to 11-chloroundecanoic acid is 1:(1.1-1.2).

[0014] In step S2, the molar ratio of the ether compound to 8-dimethylamino-1-octanol is 1:(1.1-1.2).

[0015] In step S3, the molar ratio of 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol to epichlorohydrin is 1:(3.05-3.1).

[0016] In step S4, the molar ratio of the ester-based tertiary amine compound to the tricyclic oxide compound is (3.1-3.2):1.

[0017] The surfactant is one of cocamidopropyl betaine and sodium dodecyl sulfate.

[0018] The humectant is polyethylene glycol.

[0019] The spice is peppermint oil.

[0020] The gelling agent is xanthan gum.

[0021] A method for preparing a bioactive glass oral desensitizing paste includes the following steps:

[0022] (1) Weigh out the following by weight: 5-15 parts of bioactive glass, 2-4 parts of silica, 0.5-2 parts of antibacterial and anti-inflammatory agent, 10-25 parts of glycerin, 20-30 parts of moisturizer, 2-4 parts of surfactant, 0.5-1.5 parts of fragrance, 0.5-2 parts of gelling agent, and 30-50 parts of purified water;

[0023] (2) Heat purified water to 60℃-70℃, add gelling agent, stir until completely dissolved to obtain aqueous phase; mix glycerin, moisturizer, surfactant and fragrance, heat to 50℃-60℃, stir and mix well to obtain oil phase; slowly add oil phase to aqueous phase, then add bioactive glass, silica and antibacterial and anti-inflammatory agent, emulsify and defoam under vacuum to obtain oral desensitizing ointment.

[0024] Due to the adoption of the above technical solutions, the beneficial effects of the present invention include:

[0025] The oral desensitizing ointment prepared by this invention has good antibacterial properties and dentinal tubule sealing rate. Attached Figure Description

[0026] Figure 1 The 1H NMR spectrum of 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol prepared in Example 1;

[0027] Figure 2 The high-resolution mass spectrum of 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol prepared in Example 1;

[0028] Figure 3 The 1H NMR spectrum of the ether-based compound prepared in step S1 of Example 2;

[0029] Figure 4 This is a high-resolution mass spectrum of the ether-based compound prepared in step S1 of Example 2;

[0030] Figure 5 The 1H NMR spectrum of the ester-based tertiary amine compound prepared in step S2 of Example 2;

[0031] Figure 6 This is a high-resolution mass spectrum of the ester-based tertiary amine compound prepared in step S2 of Example 2;

[0032] Figure 7 The 1H NMR spectrum of the triepoxide compound prepared in step S3 of Example 2;

[0033] Figure 8 This is a high-resolution mass spectrum of the tricyclic oxide compound prepared in step S3 of Example 2;

[0034] Figure 9 The 1H NMR spectrum of the antibacterial and anti-inflammatory agent prepared in step S4 of Example 2;

[0035] Figure 10 The image shows a high-resolution mass spectrum of the antibacterial and anti-inflammatory agent prepared in step S4 of Example 2. Detailed Implementation

[0036] The following description, in conjunction with specific embodiments, provides further details, but the present invention is not limited to these embodiments.

[0037] Example 1: Preparation of 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol:

[0038] Under nitrogen protection, 150 ml of chloroform and 0.1 mol of p-hydroxybenzonitrile were added to the reactor and stirred until homogeneous. Then, 2 ml of trifluoromethanesulfonic acid was added, and the reaction was carried out at room temperature for 13 h. Next, 20 ml of saturated NH4Cl solution was slowly added while stirring continuously for 20 min. After standing and separation, the organic phase was washed twice with saturated brine (50 ml each time) and slowly added to 200 ml of n-hexane. The mixture was stirred, and a precipitate was formed. The precipitate was filtered and dried under vacuum at 60 °C for 10 h to obtain 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol. The reaction equation is shown below.

[0039]

[0040] Its proton nuclear magnetic resonance spectrum is as follows Figure 1 As shown, its 1H NMR spectrum data are as follows: 1 H NMR (400 MHz, Chloroform- d δ 8.91 (s, 3H), 8.10 – 7.80 (m, 6H), 7.74 – 7.54 (m, 6H); its carbon NMR data are as follows: 13 C NMR (100 MHz, Chloroform- d δ 171.53, 160.16, 131.40, 126.12, 115.47; its high-resolution mass spectrum is shown below. Figure 2 As shown, HRMS (m / z): 358.1116 [M+H] + .

[0041] Example 2: Preparation of antibacterial and anti-inflammatory agents:

[0042] S1: Add 200 ml of anhydrous acetone, 0.1 mol of 3,5-dimethoxy-4'-hydroxystilbene, and 0.11 mol of 11-chloroundecanoic acid to the reactor, stir and mix well, then add 30 g of potassium carbonate, heat to reflux, react for 24 h, cool to room temperature, and perform column chromatography on the reaction solution using a silica gel column (eluent composed of ethyl acetate and petroleum ether in a volume ratio of 1:5). Distill under reduced pressure at 45 °C for 2 h, and dry under vacuum at 50 °C for 12 h to obtain the ether compound; the reaction equation is shown below:

[0043]

[0044] Its proton nuclear magnetic resonance spectrum is as follows Figure 3 As shown, its 1H NMR spectrum data are as follows: 1 H NMR (400 MHz, Chloroform- d δ 10.33 (s, 1H), 7.44 – 7.37 (m, 2H), 7.06 – 6.96 (m, 2H), 6.93– 6.41 (m, 5H), 4.00 (t, J = 6.3 Hz, 2H), 3.80 (s, 6H), 2.28 (t, J = 8.9 Hz, 2H), 1.82 – 1.23 (m, 16H); its carbon NMR data are as follows: 13 C NMR (100 MHz, Chloroform- d δ 178.97, 160.96, 159.34, 138.92, 129.40, 128.40, 128.35, 128.24, 114.40, 104.87, 99.19, 68.35, 55.36, 34.27, 29.55, 29.49, 29.29, 29.28, 29.25, 28.94, 25.97, 25.12; its high-resolution mass spectrum is shown below. Figure 4 As shown, HRMS (m / z): 441.2568 [M+H] + .

[0045] S2: Add 300 mL of toluene, 0.1 mol of the ether compound, 0.11 mol of DCC (N,N'-dicyclohexylcarbodiimide), and 0.01 mol of DMAP (4-dimethylaminopyridine) to the reactor, stir for 10 min, then add 0.11 mol of 8-dimethylamino-1-octanol, and react at room temperature for 12 h; filter, wash the filtrate successively with 100 mL of 2 wt% dilute hydrochloric acid, 100 mL of saturated sodium bicarbonate solution, and 100 mL of saturated brine, dry with 10 g of anhydrous sodium sulfate for 30 min, filter, rotary evaporate at 45 °C for 3 h, purify by silica gel column chromatography (eluent: ethyl acetate / petroleum ether (V / V=1:1), distill under reduced pressure at 50 °C for 2 h, and dry under vacuum at 50 °C for 12 h to obtain the ester-based tertiary amine compound; the reaction equation is shown below:

[0046]

[0047] Its proton nuclear magnetic resonance spectrum is as follows Figure 5 As shown, its 1H NMR spectrum data are as follows: 1 H NMR (400 MHz, Chloroform-d δ 7.53 – 7.37 (m, 2H), 7.07 – 6.96 (m, 2H), 6.93 – 6.34 (m, 5H), 4.06 (dt, J = 6.2 Hz, 4H), 3.80 (s, 6H), 2.54 (t, J = 6.0 Hz, 2H), 2.34 (s, 6H), 2.30 (d, J = 8.5 Hz, 2H), 1.80 – 1.22 (m, 28H); its carbon NMR data are as follows: 13 C NMR (100 MHz, Chloroform- d δ 173.91, 160.96, 159.34, 138.92, 129.40, 128.40, 128.35, 128.24, 114.40, 104.87, 99.19, 68.35, 64.58, 60.29, 55.36, 45.29, 34.33, 29.55, 29.50, 29.49, 29.41, 29.36, 29.28, 29.14, 29.04, 28.94, 28.67, 25.97, 25.92, 25.15; its high-resolution mass spectrum is as follows: Figure 6 As shown, HRMS (m / z): 596.4241 [M+H] + .

[0048] S3: Add 300 ml of DMF (N,N-dimethylformamide), 0.1 mol of 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol, 0.305 mol of epichlorohydrin, and 0.005 mol of tetrabutylammonium bromide to the reactor, stir and mix well, raise the temperature to 80°C, react for 5 h, lower the temperature to 70°C, and slowly add 165 ml of DMF. 2M sodium hydroxide solution was added dropwise over 20 minutes, and the reaction was allowed to proceed for 2 hours. The mixture was then cooled to room temperature and slowly added to 1000 ml of ice water. The mixture was transferred to a separatory funnel and extracted three times with 400 ml of ethyl acetate each time. The organic phase was washed twice with 200 ml of deionized water each time, followed by one wash with 200 ml of saturated sodium chloride solution. The mixture was dried over 20 g of anhydrous sodium sulfate for 1 hour, filtered, and the filtrate was distilled under reduced pressure at 70°C for 3 hours to obtain the crude product. The crude product was slowly poured into 300 ml of n-hexane, stirred, and a solid precipitated. The solid was filtered, washed twice with 100 ml of cold n-hexane each time, and dried under vacuum at 50°C for 10 hours to obtain the triepoxide compound. The reaction equation is shown below.

[0049]

[0050] Its proton nuclear magnetic resonance spectrum is as follows Figure 7 As shown, its 1H NMR spectrum data are as follows: 1 H NMR (400 MHz, DMSO- d 6 δ 8.27 – 7.99 (m, 6H), 7.40 – 7.17 (m, 6H), 4.19 (dd, J = 11.8, 3.3 Hz, 3H), 3.94 (dd, J = 11.8, 3.2 Hz, 3H), 3.59 – 3.41 (m, 3H), 3.29 (dd, J = 7.6, 2.9 Hz, 3H), 3.04 (dd, J = 7.7, 2.9 Hz, 3H); its carbon NMR data are as follows: 13 C NMR (100MHz, Chloroform- d δ 171.37, 159.85, 130.77, 127.21, 114.83, 69.65, 50.41, 45.11; its high-resolution mass spectrum is shown below. Figure 8 As shown, HRMS (m / z): 526.1903 [M+H] + .

[0051] S4: Add 1000 ml anhydrous ethanol, 0.31 mol of ester-based tertiary amine compound, 30 ml of 36 wt% hydrochloric acid, and 0.1 mol of triepoxide compound to the reactor. Stir and mix well, reflux for 12 h, and then distill under reduced pressure at 50 °C for 2 h to obtain the crude product. Dissolve the crude product in 800 ml of 60 °C methanol, and slowly add 60 °C hot acetone dropwise until the solution becomes turbid. Cool to room temperature, crystals precipitate, collect the crystals by vacuum filtration, wash the crystals with 300 ml of cold acetone, and dry under vacuum at 60 °C for 8 h to obtain the antibacterial and anti-inflammatory agent. The reaction equation is shown below:

[0052]

[0053] Its proton nuclear magnetic resonance spectrum is as follows Figure 9 As shown, its 1H NMR spectrum data are as follows: 1 H NMR (400 MHz, Chloroform- d) δ 8.25 – 8.13 (m, 6H), 7.43 – 7.37 (m, 6H), 7.33 – 7.24 (m,6H), 7.06 – 6.84 (m, 12H), 6.63 (d, J = 2.2 Hz, 6H), 6.44 (t, J = 2.2 Hz,3H), 6.08 – 5.99 (m, 3H), 4.34 – 3.94 (m, 21H), 3.80 (s, 18H), 3.73 – 3.38(m, 12H), 3.25 (s, 18H), 2.31 (t, J = 8.5 Hz, 6H), 1.83 – 1.20 (m, 84H); The carbon NMR data are as follows: 13 C NMR (100 MHz, Chloroform- d ) δ 173.91, 171.37, 160.96,160.79, 159.34, 138.92, 130.61, 129.40, 128.40, 128.35, 128.24, 127.21,114.85, 114.40, 104.87, 99.19, 69.88, 68.35, 66.36, 64.62, 64.58, 55.36,53.23, 34.33, 29.55, 29.49, 29.41, 29.36, 29.28, 29.24, 28.94, 28.82, 28.67, 25.97, 25.92, 25.15, 24.65, 23.44; its high-resolution mass spectrum is as follows: Figure 10 As shown, HRMS (m / z): 771.8291 [M-3Cl] 3+ .

[0054] Example 3: Preparation of antibacterial and anti-inflammatory agents:

[0055] S1: Add 200 ml of anhydrous acetone, 0.1 mol of 3,5-dimethoxy-4'-hydroxystilbene, and 0.115 mol of 11-chloroundecanoic acid to the reactor, stir and mix well, then add 30 g of potassium carbonate, heat to reflux, react for 24 h, cool to room temperature, and perform column chromatography on the reaction solution using a silica gel column (the eluent consists of ethyl acetate and petroleum ether in a volume ratio of 1:5). Distill under reduced pressure at 45 °C for 2 h, and dry under vacuum at 50 °C for 12 h to obtain the ether-based compound;

[0056] S2: Add 300 mL toluene, 0.1 mol of ether compound, 0.11 mol of DCC and 0.01 mol of DMAP to the reactor and stir for 10 min; then add 0.115 mol of 8-dimethylamino-1-octanol and react at room temperature for 10 h; filter, and wash the filtrate successively with 100 mL of 2 wt% dilute hydrochloric acid, 100 mL of saturated sodium bicarbonate solution and 100 mL of saturated brine, dry with 10 g of anhydrous sodium sulfate for 30 min, filter, rotary evaporate at 45 °C for 3 h, purify by silica gel column chromatography (eluent is ethyl acetate / petroleum ether (V / V=1:1), distill under reduced pressure at 50 °C for 2 h, and dry under vacuum at 50 °C for 12 h to obtain ester-based tertiary amine compound;

[0057] S3: Add 300 ml DMF, 0.1 mol 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol, 0.308 mol epichlorohydrin, and 0.005 mol tetrabutylammonium bromide to the reactor, stir to mix, heat to 85°C, react for 4.5 h, cool to 70°C, and slowly add 165 ml of DMF dropwise. Add 2M sodium hydroxide solution dropwise for 20 min, react for 2 h; cool to room temperature, slowly add 1000 ml of ice water, transfer to a separatory funnel, then extract three times with ethyl acetate (400 ml each time), wash the organic phase twice with deionized water (200 ml each time), wash once with 200 ml of saturated sodium chloride solution, dry with 20 g of anhydrous sodium sulfate for 1 h, filter, and distill the filtrate under reduced pressure at 70 °C for 3 h to obtain the crude product. Slowly pour the crude product into 300 ml of n-hexane, stir, precipitate the solid, filter, wash twice with cold n-hexane (100 ml each time), and dry under vacuum at 50 °C for 10 h to obtain the tricyclic oxide compound;

[0058] S4: Add 1000 ml anhydrous ethanol, 0.315 mol of ester-based tertiary amine compound, 30 ml of 36 wt% hydrochloric acid, and 0.1 mol of triepoxide compound to the reactor, stir and mix well, and reflux for 11 h; distill under reduced pressure at 50 °C for 2 h to obtain crude product; dissolve the crude product in 800 ml of 60 °C methanol, slowly add 60 °C hot acetone dropwise until the solution becomes turbid, cool to room temperature, precipitate crystals, collect the crystals by vacuum filtration, wash the crystals with 300 ml of cold acetone, and dry under vacuum at 60 °C for 8 h to obtain antibacterial and anti-inflammatory agent.

[0059] Example 4: Preparation of antibacterial and anti-inflammatory agents:

[0060] S1: Add 200 ml of anhydrous acetone, 0.1 mol of 3,5-dimethoxy-4'-hydroxystilbene, and 0.12 mol of 11-chloroundecanoic acid to the reactor, stir and mix well, then add 30 g of potassium carbonate, heat to reflux, and react for 24 h; cool to room temperature, and perform column chromatography on the reaction solution using a silica gel column (the eluent consists of ethyl acetate and petroleum ether in a volume ratio of 1:5), distill under reduced pressure at 45 °C for 2 h, and dry under vacuum at 50 °C for 12 h to obtain the ether-based compound;

[0061] S2: Add 300 mL toluene, 0.1 mol of ether compound, 0.11 mol of DCC and 0.01 mol of DMAP to the reactor, heat to 60 °C and stir for 10 min; then add 0.12 mol of 8-dimethylamino-1-octanol and react at room temperature for 8 h; filter, wash the filtrate successively with 100 mL of 2 wt% dilute hydrochloric acid, 100 mL of saturated sodium bicarbonate solution and 100 mL of saturated brine, dry with 10 g of anhydrous sodium sulfate for 30 min, filter, rotary evaporate at 45 °C for 3 h, purify by silica gel column chromatography (eluent is ethyl acetate / petroleum ether (V / V=1:1), distill under reduced pressure at 50 °C for 2 h, and dry under vacuum at 50 °C for 12 h to obtain ester-based tertiary amine compound;

[0062] S3: Add 300 ml DMF, 0.1 mol 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol, 0.31 mol epichlorohydrin, and 0.005 mol tetrabutylammonium bromide to the reactor, stir and mix well, raise the temperature to 90°C, react for 4 h, lower the temperature to 70°C, and slowly add 165 ml of DMF dropwise. Add 2M sodium hydroxide solution dropwise for 20 min, react for 2 h; cool to room temperature, slowly add 1000 ml of ice water, transfer to a separatory funnel, then extract three times with ethyl acetate (400 ml each time), wash the organic phase twice with deionized water (200 ml each time), wash once with 200 ml of saturated sodium chloride solution, dry with 20 g of anhydrous sodium sulfate for 1 h, filter, and distill the filtrate under reduced pressure at 70 °C for 3 h to obtain the crude product. Slowly pour the crude product into 300 ml of n-hexane, stir, precipitate the solid, filter, wash twice with cold n-hexane (100 ml each time), and dry under vacuum at 50 °C for 10 h to obtain the tricyclic oxide compound;

[0063] S4: Add 1000 ml anhydrous ethanol, 0.32 mol of ester-based tertiary amine compound, 30 ml of 36 wt% hydrochloric acid, and 0.1 mol of triepoxide compound to the reactor, stir and mix well, reflux for 10 h, and then distill under reduced pressure at 50 °C for 2 h to obtain crude product; dissolve the crude product in 800 ml of 60 °C methanol, slowly add 60 °C hot acetone dropwise until the solution becomes turbid, cool to room temperature, precipitate crystals, collect the crystals by vacuum filtration, wash the crystals with 300 ml of cold acetone, and dry under vacuum at 60 °C for 8 h to obtain antibacterial and anti-inflammatory agent.

[0064] Example 5: Preparation of oral desensitizing ointment:

[0065] (1) 50g of bioactive glass, 20g of silica, 5g of antibacterial and anti-inflammatory agent (prepared in Example 1), 100g of glycerin, 200g of moisturizer (polyethylene glycol (PEG800)), 20g of surfactant (cocamidopropyl betaine), 5g of fragrance (peppermint oil), 5g of gelling agent (xanthan gum), and 300g of purified water;

[0066] (2) Heat purified water to 60°C, add gelling agent, stir at 600 r / min until completely dissolved to obtain aqueous phase; mix glycerin, moisturizer, surfactant and fragrance, heat to 50°C, stir at 400 r / min for 10 min to obtain oil phase; slowly add oil phase to aqueous phase, then add bioactive glass, silica and antibacterial and anti-inflammatory agent, stir at 800 r / min for 25 min to emulsify, and then degas under vacuum to obtain oral desensitizing ointment.

[0067] Example 6: Preparation of oral desensitizing ointment:

[0068] (1) 100g of bioactive glass, 30g of silica, 10g of antibacterial and anti-inflammatory agent (prepared in Example 2), 150g of glycerin, 250g of moisturizer (polyethylene glycol (PEG800)), 30g of surfactant (sodium dodecyl sulfate), 10g of fragrance (peppermint oil), 10g of gelling agent (xanthan gum), and 400g of purified water;

[0069] (2) Heat purified water to 65°C, add gelling agent, stir at 600 r / min until completely dissolved to obtain aqueous phase; mix glycerin, moisturizer, surfactant and fragrance, heat to 55°C, stir at 400 r / min for 10 min to obtain oil phase; slowly add oil phase to aqueous phase, then add bioactive glass, silica and antibacterial and anti-inflammatory agent, stir at 800 r / min for 25 min and then vacuum degas to obtain oral desensitizing ointment.

[0070] Example 7 Preparation of oral desensitizing ointment:

[0071] (1) 150g of bioactive glass, 40g of silica, 20g of antibacterial and anti-inflammatory agent (prepared in Example 3), 250g of glycerin, 300g of moisturizer (polyethylene glycol (PEG800)), 40g of surfactant (cocamidopropyl betaine), 15g of fragrance (peppermint oil), 20g of gelling agent (xanthan gum), and 500g of purified water;

[0072] (2) Heat purified water to 70°C, add gelling agent, stir at 600 r / min until completely dissolved to obtain aqueous phase; mix glycerin, moisturizer, surfactant and fragrance, heat to 60°C, stir at 400 r / min for 10 min to obtain oil phase; slowly add oil phase to aqueous phase, then add bioactive glass, silica and antibacterial and anti-inflammatory agent, stir at 800 r / min for 25 min and then vacuum degas to obtain oral desensitizing ointment.

[0073] Comparative Example 1

[0074] The raw material composition and preparation method of the bioactive glass oral desensitizing ointment are basically the same as those in Example 6, except that the antibacterial and anti-inflammatory agent is replaced with an equal weight of an antibacterial and anti-inflammatory agent prepared by the following method:

[0075] The preparation method of the antibacterial and anti-inflammatory agent is basically the same as that in Example 3, except that 11-chloroundecanoic acid in step S1 is replaced with an equimolar amount of 6-chlorohexanoic acid.

[0076] Comparative Example 2

[0077] The raw material composition and preparation method of the bioactive glass oral desensitizing ointment are basically the same as those in Example 6, except that the antibacterial and anti-inflammatory agent is replaced with an equal weight of an antibacterial and anti-inflammatory agent prepared by the following method:

[0078] The preparation method of the antibacterial and anti-inflammatory agent is basically the same as that in Example 3, except that the 3,5-dimethoxy-4'-hydroxystilbene in step S1 is replaced with an equimolar amount of 3-hydroxy-5-methoxystilbene.

[0079] Comparative Example 3

[0080] The raw material composition and preparation method of the bioactive glass oral desensitizing ointment are basically the same as those in Example 6, except that the antibacterial and anti-inflammatory agent is replaced with an equal weight of an antibacterial and anti-inflammatory agent prepared by the following method:

[0081] The preparation method of the antibacterial and anti-inflammatory agent is basically the same as that in Example 3, except that 8-dimethylamino-1-octanol in step S2 is replaced with an equimolar amount of 4-dimethylamino-1-butanol.

[0082] Comparative Example 4

[0083] The raw material composition and preparation method of the bioactive glass oral desensitizing ointment are basically the same as those in Example 6, except that the antibacterial and anti-inflammatory agent is replaced with an equal weight of an antibacterial and anti-inflammatory agent prepared by the following method:

[0084] The preparation method of the antibacterial and anti-inflammatory agent is basically the same as that in Example 3, except that 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol in step S3 is replaced with an equimolar amount of 4,4',4''-methylenetriphenol.

[0085] Comparative Example 5

[0086] The raw material composition and preparation method of the bioactive glass oral desensitizing ointment are basically the same as those in Example 6, except that the antibacterial and anti-inflammatory agent is replaced with an equal weight of an antibacterial and anti-inflammatory agent prepared by the following method:

[0087] The preparation method of the antibacterial and anti-inflammatory agent is basically the same as that in Example 3, except that the amount of ester-based tertiary amine compound added in step S4 is 0.215 mol.

[0088] Comparative Example 6

[0089] The raw material composition and preparation method of the bioactive glass oral desensitizing ointment are basically the same as those in Example 6, except that the antibacterial and anti-inflammatory agent is replaced with an equal weight of an antibacterial and anti-inflammatory agent prepared by the following method:

[0090] S1: Add 300 ml DMF, 0.1 mol 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol, 0.308 mol epichlorohydrin, and 0.005 mol tetrabutylammonium bromide to the reactor, stir and mix well, raise the temperature to 85°C, react for 4.5 h, lower the temperature to 70°C, and slowly add 165 ml of DMF dropwise. Add 2M sodium hydroxide solution dropwise for 20 min, react for 2 h; cool to room temperature, slowly add 1000 ml of ice water, transfer to a separatory funnel, then extract three times with ethyl acetate (400 ml each time), wash the organic phase twice with deionized water (200 ml each time), wash once with 200 ml of saturated sodium chloride solution, dry with 20 g of anhydrous sodium sulfate for 1 h, filter, and distill the filtrate under reduced pressure at 70 °C for 3 h to obtain the crude product. Slowly pour the crude product into 300 ml of n-hexane, stir, precipitate the solid, filter, wash twice with cold n-hexane (100 ml each time), and dry under vacuum at 50 °C for 10 h to obtain the tricyclic oxide compound;

[0091] S2: Add 1000 ml anhydrous ethanol, 0.315 mol 8-dimethylamino-1-octanol, 30 ml 36 wt% hydrochloric acid, and 0.1 mol triepoxide to the reactor. Stir and mix well, reflux for 11 h, and then distill under reduced pressure at 50 °C for 2 h to obtain the crude product. Dissolve the crude product in 800 ml 60 °C methanol, and slowly add 60 °C hot acetone dropwise until the solution becomes turbid. Cool to room temperature, precipitate crystals, collect the crystals by vacuum filtration, wash the crystals with 300 ml cold acetone, and dry under vacuum at 60 °C for 8 h to obtain the antibacterial and anti-inflammatory agent.

[0092] The bioactive glass used in the embodiments and comparative examples of this application is medical grade HQ-BG45s-D1, produced by Kunshan Overseas Chinese Science and Technology New Materials Co., Ltd.; the average particle size of the silica is 15nm, purchased from Shanghai Sipu Chemical Co., Ltd.; and the xanthan gum is Keltrol CG-T.

[0093] The oral desensitizing ointments prepared according to the embodiments and comparative examples of this application were subjected to antibacterial and dentinal tubule sealing rate experiments. The test results are shown in Table 1.

[0094] Antibacterial test:

[0095] 1. Use a sterile cotton swab to apply a solution with a concentration of 5×10⁻⁶. 5 A CFU / ml suspension of the test bacteria (Streptococcus mutans (ATCC 25175)) was evenly spread three times on the surface of a nutrient agar plate. After each spread, the plate should be rotated 60°. Finally, a cotton swab was used to swab around the edge of the plate, and the plate was covered.

[0096] 2. Apply oral desensitizing ointment to the center of the culture medium plate, forming a 5mm diameter and 2mm thick disc. After application, gently press the disc with sterile forceps to ensure it adheres tightly to the plate surface. Cover the plate and incubate at 37℃ for 24 hours. Observe the results. Measure the diameter of the inhibition zone using calipers.

[0097] Evaluation criteria for antibacterial test: When the diameter of the inhibition zone is greater than 10 mm, it is judged to have antibacterial effect; when the diameter of the inhibition zone is less than or equal to 10 mm, it is judged to have no antibacterial effect.

[0098] Dentin tubule sealing rate test:

[0099] 1. Take 45 healthy and intact premolars from cattle, divide them into 9 groups of 5 teeth each, grind away the enamel on the occlusal surface with a diamond needle to expose the dentin, cut off the root, and place them in an ultrasonic cleaner to remove debris from the dentinal tubules.

[0100] 2. Apply the oral desensitizing ointment prepared in the examples and comparative examples evenly to moist bovine teeth with exposed dentinal tubules, simulating brushing. The application dosage is 2 g / cm³. 2After standing for 5 minutes, rinse with distilled water until no residue remains. Repeat this process every 2 hours or more, for a total of 15 times. Then rinse with high-pressure water.

[0101] 3. The sealing effect of dentinal tubules was examined using an electron microscope at 500x magnification.

[0102] The formula for calculating the dentinal tubule sealing rate is as follows:

[0103] Dentin tubule closure rate (%) = (1 - N1 / N2) × 100%

[0104] Where: N1: The number of dentinal tubules that remain open in the image after treatment with desensitizing cream and rinsing; N2: The total number of all dentinal tubules in the same area before treatment.

[0105] Table 1 Performance Indicators of Oral Desensitizing Cream

[0106]

[0107] As can be seen from Table 1, the oral desensitizing ointments prepared in Examples 5, 6, and 7 have good antibacterial properties and dentinal tubule sealing rates.

[0108] The antibacterial and anti-inflammatory agent added to the oral desensitizing ointment prepared in this application has a three-arm structure with a triazine ring as the core. A long-chain alkyl group connects a quaternary ammonium salt group to a dimethoxystilbene group, enhancing the antibacterial properties and dentinal tubule sealing ability of the oral desensitizing ointment. The quaternary ammonium salt group of the antibacterial and anti-inflammatory agent adsorbs onto the negatively charged bacterial cell membrane through a positively charged nitrogen atom, disrupting membrane integrity and leading to bacterial death, thus providing broad-spectrum antibacterial activity. The dimethoxystilbene group has anti-inflammatory and antioxidant activity, which can relieve pulp sensitivity and inhibit the growth of sensitizing bacteria. In terms of dentinal tubule sealing, long-chain alkyl groups, as hydrophobic and flexible molecular chains, interact with van der Waals forces present on the dentin surface. This interaction drives the rapid spread of antibacterial and anti-inflammatory agents on the dentin surface, expanding the contact area and forming a uniform adsorption layer. The rigid planar structures of the triazine and benzene rings, through intermolecular forces (such as π-π stacking), form transverse and tight cross-links with neighboring molecules, enhancing the structural stability of the composite sealing layer. Furthermore, the three-arm structure can effectively extend to the exposed openings of the dentinal tubules and their interiors, achieving filling and blocking of the tubules through physical spatial barrier effects. In summary, the synergistic effect of long-chain alkyl groups with the triazine and benzene rings forms a high-coverage, high-stability composite sealing layer that effectively resists the erosion and dissolution of saliva, thus achieving a durable and stable seal for the dentinal tubules.

[0109] The antibacterial and anti-inflammatory agent used in Comparative Example 1 had shorter hydrophobic segments, which reduced its ability to penetrate and destroy bacterial cell membranes, resulting in reduced antibacterial efficiency. It also made it difficult to form a dense and stable hydrophobic barrier on the dentin surface, resulting in a poorer physical sealing effect on dentinal tubules and making them more susceptible to being washed away by saliva.

[0110] The reason for the decreased performance of the antibacterial and anti-inflammatory agent used in Comparative Example 4 is the absence of the triazine ring in the central rigid planar structure, which results in a looser and more flexible molecular conformation, making it difficult to form a dense and orderly physical barrier, thereby weakening the persistence of the seal and reducing its efficiency in interacting with the bacterial membrane.

[0111] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. However, any modifications, alterations, and variations made by those skilled in the art without departing from the scope of the present invention based on the disclosed technical content are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, and variations made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the present invention.

Claims

1. A bioactive glass oral desensitizing paste, characterized in that, The ingredients include the following parts by weight: 5-15 parts bioactive glass, 2-4 parts silica, 0.5-2 parts antibacterial and anti-inflammatory agent, 10-25 parts glycerin, 20-30 parts moisturizer, 2-4 parts surfactant, 0.5-1.5 parts fragrance, 0.5-2 parts gelling agent, and 30-50 parts purified water; The chemical structural formula of the antibacterial and anti-inflammatory agent is as follows: ； The antibacterial and anti-inflammatory agent is prepared by the following method: S1: 3,5-Dimethoxy-4'-hydroxystilbene reacts with 11-chloroundecanoic acid to form an ether compound. S2: The ether-based compound reacts with 8-dimethylamino-1-octanol to form an ester-based tertiary amine compound. S3: 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol reacts with epichlorohydrin to form a triepoxide compound. S4: Ester-based tertiary amine compounds react with triepoxide compounds to generate antibacterial and anti-inflammatory agents.

2. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, In step S1, the molar ratio of 3,5-dimethoxy-4'-hydroxystilbene to 11-chloroundecanoic acid is 1:(1.1-1.2).

3. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, In step S2, the molar ratio of the ether compound to 8-dimethylamino-1-octanol is 1:(1.1-1.2).

4. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, In step S3, the molar ratio of 4,4',4''-(1,3,5-triazine-2,4,6-triyl)triphenol to epichlorohydrin is 1:(3.05-3.1).

5. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, In step S4, the molar ratio of the ester-based tertiary amine compound to the tricyclic oxide compound is (3.1-3.2):

1.

6. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, The surfactant is one of cocamidopropyl betaine and sodium dodecyl sulfate.

7. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, The humectant is polyethylene glycol.

8. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, The spice is peppermint oil.

9. The bioactive glass oral desensitizing ointment according to claim 1, characterized in that, The gelling agent is xanthan gum.

10. A method for preparing a bioactive glass oral desensitizing ointment according to any one of claims 1-9, characterized in that, Includes the following steps: (1) Weigh out the following by weight: 5-15 parts of bioactive glass, 2-4 parts of silica, 0.5-2 parts of antibacterial and anti-inflammatory agent, 10-25 parts of glycerin, 20-30 parts of moisturizer, 2-4 parts of surfactant, 0.5-1.5 parts of fragrance, 0.5-2 parts of gelling agent, and 30-50 parts of purified water; (2) Heat purified water to 60℃-70℃, add gelling agent, stir until completely dissolved to obtain aqueous phase; mix glycerin, moisturizer, surfactant and fragrance, heat to 50℃-60℃, stir and mix well to obtain oil phase; slowly add oil phase to aqueous phase, then add bioactive glass, silica and antibacterial and anti-inflammatory agent, emulsify and defoam under vacuum to obtain oral desensitizing ointment.

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