A child oral care composition and method of making the same

Abstract

The present application belongs to the technical field of oral care products, and particularly relates to a children's oral care composition and a preparation method thereof. The present application discloses a children's oral care composition, which comprises the following components: human recombinant enamel matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract and ginger root extract. The composition has excellent inhibitory effect on cariogenic bacteria (such as Streptococcus mutans and Streptococcus sobrinus). The ginger root extract is prepared by an ultrasonic alcohol extraction + fermentation process. The children's oral care composition prepared by the present application is applied to the preparation of children's toothpaste. The children's toothpaste has excellent plaque removal, bacteriostatic and remineralization effects and high safety, and has wide market application value in the field of children's caries prevention oral care products.

Description

Technical Field

[0001] This invention belongs to the field of oral care products technology, specifically relating to a children's oral care composition and its preparation method. Background Technology

[0002] Dental caries is an infectious oral disease caused by the erosion of tooth enamel, which can lead to some systemic complications. It is one of the most common oral diseases in children. The main factor directly causing dental caries is dental plaque, which adheres to the tooth surface. Plaque is a dense, thin film composed of bacteria, their extracellular polysaccharides, and salivary glycoproteins, among other matrix components. Due to its long-term accumulation and constant adhesion to the enamel surface, plaque affects the synthesis of tooth organic matter.

[0003] Streptococcus mutans and Streptococcus distantly are important components of the oral microbiome, playing a crucial role in the occurrence and development of dental caries. Streptococcus mutans is one of the most common cariogenic bacteria in the oral cavity, exhibiting strong cariogenicity. It also produces extracellular polysaccharides such as glucan, which facilitate plaque formation and adhesion to the tooth surface, enhancing plaque's resistance to rinsing. Streptococcus distantlyly also poses a threat to oral health, especially in children and adolescents, and is closely related to the occurrence of early dental caries.

[0004] Primary teeth are less mineralized than adult teeth, and children often eat various snacks and their brushing is often incomplete, making them more susceptible to cavities. Therefore, cavity prevention is crucial. Currently, most children's anti-cavity toothpastes on the market contain fluoride. While a small amount of fluoride can prevent cavities, children are prone to swallowing toothpaste, posing a risk of excessive fluoride intake. In conclusion, developing a fluoride-free, highly safe children's oral care product that inhibits Streptococcus mutans and distant streptococci is a current research trend in children's oral care products. Summary of the Invention

[0005] In view of the above-mentioned defects or improvement needs of the prior art, the present invention provides a children's oral care composition and its preparation method. The children's oral care composition of the present invention can effectively inhibit cariogenic bacteria and has high safety.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a pediatric oral care composition comprising the following components: human recombinant ameliorative matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract, and ginger root extract; wherein the mass ratio of the human recombinant ameliorative matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract, and ginger root extract is (0.001-0.1):(0.05-0.5):(0.01-0.5):(0.001-0.1):(0.001-0.05). The preparation method of the ginger root extract includes the following steps: W1. Weigh ginger powder, add 60%-75% ethanol aqueous solution, extract with ultrasonic assistance, centrifuge and retain the supernatant to obtain ginger root extract; W2. Weigh each component of the fermentation medium according to the formula, mix them evenly, sterilize at 121℃ for 20-25 min, and cool to 28-35℃ to obtain the fermentation medium; wherein, the fermentation medium contains the following components by weight: 15-25 parts of ginger root extract prepared in step W1, 18-25 parts of glucose, 2-6 parts of tryptone, 2-4 parts of yeast powder, 1-3 parts of triamine citrate, 4-6 parts of sodium acetate, 0.3-0.6 parts of magnesium sulfate, 0.04-0.08 parts of manganese sulfate, 1.5-3 parts of dipotassium hydrogen phosphate, 0.8-1.2 parts of Tween 80, and 1000 parts of deionized water; W3. First, inoculate *Kluyveromyces martensii* into the fermentation medium prepared in step W2 for aerobic fermentation, then inoculate *Lactobacillus curvatureis* for anaerobic fermentation. After fermentation, centrifuge, collect the supernatant, filter and sterilize to obtain the ginger root extract; wherein, the preservation number of *Kluyveromyces martensii* is CCTCC NO: M 2022014, and the preservation number of *Lactobacillus curvatureis* is CGMCC No. 21575.

[0007] In this invention, enamel matrix protein is a matrix protein secreted by ameloblasts that regulates tooth mineralization. Enamel matrix protein contains protein components such as amelogenin, ameloblastin, and ameloprotein. After ameloblasts secrete amelogenin, enamel rapidly undergoes biomineralization under the induction of dentin. Amelogenin plays a crucial role in many factors, including the initiation of enamel mineralization, the formation and arrangement of crystal nuclei. Amelogenin provides the necessary scaffold for enamel biomineralization and can also control the rate of crystal growth, maintain crystal growth, and promote enamel biomineralization. This can reduce the adhesion of cariogenic bacteria and acid production that damages enamel, thereby preventing or improving dental caries.

[0008] Casein phosphopeptides can form unstable bonds with calcium ions, ensuring that calcium ions remain in a free state while preventing them from being bound by the metabolites of harmful bacteria in the mouth to form calculi. They have high absorption rates, enhance immunity, promote calcium deposition and calcification in bones and teeth, and repair damaged teeth, thus playing a role in preventing tooth decay.

[0009] Peach fruit extract possesses a variety of biological activities, including antibacterial activity, moisturizing, anti-inflammatory, antioxidant, anti-aging, and soothing effects. Among these, flavonoids and phenolic acids are the main antioxidant components. Flavonoids also have effects such as lowering blood sugar and cholesterol. Steroids and terpenes have anti-tumor, anti-inflammatory, and antibacterial activities. Peach fruit extract protects the periodontal environment and prevents or improves dental caries by inhibiting cariogenic bacteria, suppressing inflammatory pathways, and reducing oxidative damage.

[0010] Ginger root extract has a strong inhibitory effect on Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis, and also has anti-inflammatory and analgesic effects. It can effectively prevent or improve dental caries, relieve gingival bleeding, and relieve oral problems such as gingival redness and inflammation.

[0011] Preferably, the mass ratio of the human recombinant enamel matrix protein, casein phosphopeptide, calcium lactate, peach extract and ginger root extract is 0.05:0.12:0.05:0.08:0.02.

[0012] Preferably, in step W1, the ratio of ginger powder to ethanol aqueous solution is 1g: 22-28mL.

[0013] Preferably, in step W1, the ultrasonic-assisted extraction time is 15-20 min, the temperature is 50-60℃, and the power is 280-320W.

[0014] Preferably, in step W1, the centrifugation speed is 5000-6000 rpm and the time is 12-18 min.

[0015] Preferably, in step W3, the total inoculation amount of Kluyveromyces martensii and Lactobacillus curvature is 3-6% v / v of the fermentation medium.

[0016] Preferably, in step W3, the inoculation ratio of Kluyveromyces martensii to Lactobacillus curvature is 0.7-1.5:1.7-2.3.

[0017] More preferably, the inoculation ratio of Kluyveromyces martensii to Lactobacillus curvature is 1.1:1.9.

[0018] Preferably, in step W3, the viable counts of both *Kluyveromyces martensii* and *Lactobacillus curvatureus* are 1.0 × 10⁻⁶. 8 CFU / mL.

[0019] Preferably, the aerobic fermentation in step W3 is carried out at 33-38°C by introducing sterile air with an aeration ratio of 0.3-0.6 vvm for 24-36 hours.

[0020] Preferably, the anaerobic fermentation in step W3 is carried out at 33-38℃ for 12-24 hours.

[0021] Preferably, in step W3, the centrifugation speed is 2500-3500 rpm and the time is 20-30 min.

[0022] Preferably, in step W3, the filtration sterilization is performed using a sterile filter membrane with a pore size of 0.22 μm.

[0023] Secondly, the present invention provides the use of the children's oral care composition described in the first aspect in the preparation of children's oral care products for the prevention or improvement of dental caries.

[0024] Preferably, the children's oral care product includes any one of toothpaste, mouthwash, and oral spray.

[0025] Thirdly, the present invention provides a children's toothpaste comprising the following raw materials in weight percentages: 0.1%-8% of the children's oral care composition described in the first aspect, 10%-25% of abrasive, 0.1%-1% of buffer, 35%-60% of humectant, 0.5%-2.5% of surfactant, 0.1%-1.5% of thickener, 0.01%-1% of taste modifier, 0.001%-0.5% of enzyme, 0.1%-1% of preservative, 0.5%-1.5% of fragrance, and the balance being deionized water.

[0026] Preferably, the friction agent includes at least one of silicon dioxide, calcium carbonate, and calcium hydrogen phosphate.

[0027] Preferably, the buffer comprises pyrophosphate.

[0028] More preferably, the pyrophosphate includes at least one of potassium pyrophosphate, potassium hydrogen pyrophosphate, sodium pyrophosphate, and sodium hydrogen pyrophosphate.

[0029] Preferably, the moisturizer includes at least one of sorbitol, polyethylene glycol, glycerin, and propylene glycol.

[0030] More preferably, the polyethylene glycol includes at least one of polyethylene glycol-8 and polyethylene glycol-12.

[0031] Preferably, the surfactant includes at least one of anionic surfactants, nonionic surfactants, amphoteric surfactants, and biosurfactants.

[0032] More preferably, the anionic surfactant includes at least one of sodium lauryl sulfate and sodium lauryl ether sulfate.

[0033] More preferably, the nonionic surfactant comprises an alkyl glycoside.

[0034] More preferably, the amphoteric surfactant includes at least one of cocamidopropyl betaine, sodium lauroyl sarcosinate, sodium lauroyl glutamate, and sodium cocoyl glutamate.

[0035] More preferably, the biosurfactant includes at least one of rhamnolipid and sophorolipid.

[0036] Preferably, the thickener includes at least one of xanthan gum, cellulose gum, cassia gum, carrageenan, and guar gum.

[0037] Preferably, the taste modifier includes at least one of sucralose, sodium saccharin, steviol glycosides, xylitol, and erythritol.

[0038] Preferably, the bioenzyme is selected from at least one of glucanase, lysozyme, protease, glucosyloxidase, amylase, papain, and bromelain.

[0039] Preferably, the preservative includes at least one selected from plant antibacterial agents, sodium benzoate, benzyl alcohol, ethylhexylglycerin, octyl glycol, pentylene glycol, and p-hydroxyacetophenone.

[0040] Fourthly, the present invention provides a method for preparing the children's toothpaste described in the first aspect, comprising the following steps: S1. Add the children's oral care composition, buffer, and taste modifier to deionized water, stir well, and obtain the first solution; S2. Add humectant and preservative to the first solution, stir well, then add biological enzyme, stir well to obtain the second solution; S3. Mix the friction agent and thickener to obtain the first mixture; S4. Mix the first mixture with the second solution, then add the surfactant and fragrance, stir evenly and degas to obtain the children's toothpaste.

[0041] The beneficial effects of this invention are: The pediatric oral care composition of this invention is prepared by compounding human recombinant enamel matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract, and ginger root extract. The composition has excellent inhibitory effects on cariogenic bacteria Streptococcus mutans and Streptococcus distantly related. Among them, ginger root extract is prepared by ultrasonic alcohol extraction + fermentation process. Different fermentation methods, strains, and inoculum ratios will affect the fermentation effect, thereby affecting the effect of the composition.

[0042] The oral care composition for children prepared according to the present invention is applied to the preparation of children's toothpaste. The children's toothpaste has excellent plaque removal ability and high safety, and has broad market application value in the field of children's anti-caries oral care products. Detailed Implementation

[0043] To further illustrate the technical means and effects of the present invention in achieving the intended purpose, the following detailed description of the specific embodiments, structure, features and effects of the present invention, in conjunction with the composition, is provided below.

[0044] For the following compositions, unless otherwise specified, experimental methods are generally performed under standard conditions or as recommended by the manufacturer. Unless otherwise specified, all materials and reagents used are commercially available.

[0045] Some of the raw materials and their sources are as follows: Human recombinant enamel matrix protein was purchased from Bestway Biotechnology Co., Ltd. Casein phosphopeptide was purchased from Guangzhou Green Extract Biotechnology Co., Ltd. Calcium lactate was purchased from Purac Biochem bv (PU) in the Netherlands; Peach fruit extract was purchased from Guangzhou Ximu Biotechnology Co., Ltd. The ginger powder was purchased from Lanzhou Waterles Biotechnology Co., Ltd.

[0046] Ginger root extract① Its preparation method includes the following steps: W1. Weigh ginger powder, add 60% ethanol aqueous solution, extract with ultrasonic assistance, centrifuge and retain the supernatant to obtain ginger root extract. W2. Weigh each component of the fermentation medium according to the formula, mix them evenly, sterilize at 121℃ for 20 min, and cool to 28℃ to obtain the fermentation medium. W3. First, inoculate *Kluyveromyces martensii* into the fermentation medium prepared in step W2 for aerobic fermentation, then inoculate *Lactobacillus curvularis* for anaerobic fermentation. After fermentation, centrifuge, take the supernatant, filter and sterilize to obtain the ginger root extract. In step W1, the ratio of ginger powder to ethanol aqueous solution is 1g:22mL, the ultrasonic-assisted extraction time is 20min, the temperature is 50℃, and the power is 320W, and the centrifugation speed is 5000rpm and the time is 18min. The fermentation medium in step W2 contains the following components by weight: 15 parts of ginger root extract prepared in step W1, 25 parts of glucose, 2 parts of tryptone, 2 parts of yeast powder, 1 part of triamine citrate, 4 parts of sodium acetate, 0.6 parts of magnesium sulfate, 0.08 parts of manganese sulfate, 3 parts of dipotassium hydrogen phosphate, 1.2 parts of Tween 80, and 1000 parts of deionized water; In step W3, the preservation number of *Kluyveromyces martensii* is CCTCC NO: M 2022014, and the preservation number of *Lactobacillus curvatureii* is CGMCC No. 21575; the total inoculum size of *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 3% v / v of the fermentation medium; the inoculum ratio of *Kluyveromyces martensii* to *Lactobacillus curvatureii* is 1.5:2.3; and the viable count of both *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 1.0 × 10⁻⁶. 8CFU / mL; the aerobic fermentation is carried out at 33°C with sterile air at an aeration ratio of 0.6 vvm for 36 h; the anaerobic fermentation is carried out at 33°C for 24 h; the centrifugation speed is 3500 rpm and the time is 20 min; the filtration sterilization is carried out using a sterile filter membrane with a pore size of 0.22 μm.

[0047] Ginger root extract ② Its preparation method includes the following steps: W1. Weigh ginger powder, add 70% ethanol aqueous solution, extract with ultrasonic assistance, centrifuge and retain the supernatant to obtain ginger root extract. W2. Weigh each component of the fermentation medium according to the formula, mix them evenly, sterilize at 121℃ for 23 min, and cool to 32℃ to obtain the fermentation medium. W3. First, inoculate *Kluyveromyces martensii* into the fermentation medium prepared in step W2 for aerobic fermentation, then inoculate *Lactobacillus curvularis* for anaerobic fermentation. After fermentation, centrifuge, take the supernatant, filter and sterilize to obtain the ginger root extract. In step W1, the ratio of ginger powder to ethanol aqueous solution is 1g:25mL, the ultrasonic-assisted extraction time is 17min, the temperature is 55℃, and the power is 300W, and the centrifugation speed is 5500 rpm for 15min. The fermentation medium in step W2 contains the following components by weight: 20 parts of ginger root extract prepared in step W1, 22 parts of glucose, 4 parts of tryptone, 3 parts of yeast powder, 2 parts of triamine citrate, 5 parts of sodium acetate, 0.5 parts of magnesium sulfate, 0.05 parts of manganese sulfate, 2.2 parts of dipotassium hydrogen phosphate, 1.0 part of Tween 80, and 1000 parts of deionized water; In step W3, the preservation number of *Kluyveromyces martensii* is CCTCC NO: M 2022014, and the preservation number of *Lactobacillus curvatureii* is CGMCC No. 21575; the total inoculum size of *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 5% v / v of the fermentation medium; the inoculum ratio of *Kluyveromyces martensii* to *Lactobacillus curvatureii* is 1.1:1.9; and the viable count of both *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 1.0 × 10⁻⁶. 8 CFU / mL; the aerobic fermentation is carried out at 35°C with sterile air at an aeration ratio of 0.5 vvm for 30 h; the anaerobic fermentation is carried out at 35°C for 18 h; the centrifugation speed is 3000 rpm and the time is 25 min; the filtration sterilization is carried out using a sterile filter membrane with a pore size of 0.22 μm.

[0048] Ginger root extract ③ Its preparation method includes the following steps: W1. Weigh ginger powder, add 75% ethanol aqueous solution, extract with ultrasonic assistance, centrifuge and retain the supernatant to obtain ginger root extract. W2. Weigh each component of the fermentation medium according to the formula, mix them evenly, sterilize at 121℃ for 25 min, and cool to 35℃ to obtain the fermentation medium. W3. First, inoculate *Kluyveromyces martensii* into the fermentation medium prepared in step W2 for aerobic fermentation, then inoculate *Lactobacillus curvularis* for anaerobic fermentation. After fermentation, centrifuge, take the supernatant, filter and sterilize to obtain the ginger root extract. In step W1, the ratio of ginger powder to ethanol aqueous solution is 1g:28mL, the ultrasonic-assisted extraction time is 15min, the temperature is 60℃, and the power is 280W, and the centrifugation speed is 6000 rpm for 12min. The fermentation medium in step W2 contains the following components by weight: 25 parts of ginger root extract prepared in step W1, 18 parts of glucose, 6 parts of tryptone, 4 parts of yeast powder, 3 parts of triamine citrate, 6 parts of sodium acetate, 0.3 parts of magnesium sulfate, 0.04 parts of manganese sulfate, 1.5 parts of dipotassium hydrogen phosphate, 0.8 parts of Tween 80, and 1000 parts of deionized water; In step W3, the preservation number of *Kluyveromyces martensii* is CCTCC NO: M 2022014, and the preservation number of *Lactobacillus curvatureii* is CGMCC No. 21575; the total inoculum size of *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 6% v / v of the fermentation medium; the inoculum ratio of *Kluyveromyces martensii* to *Lactobacillus curvatureii* is 0.7:1.7; and the viable count of both *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 1.0 × 10⁻⁶. 8 CFU / mL; the aerobic fermentation is carried out at 38℃ with sterile air at an aeration ratio of 0.3vvm for 24 hours; the anaerobic fermentation is carried out at 38℃ for 12 hours; the centrifugation speed is 2500 rpm and the time is 30 min; the filtration sterilization is carried out using a sterile filter membrane with a pore size of 0.22μm.

[0049] Ginger root extract ④ Compared to ginger root extract ②, the difference lies in the preparation method of ginger root extract ④, where step W3 involves inoculating only *Kluyveromyces martensii* for aerobic fermentation; the total inoculation amount of *Kluyveromyces martensii* is 5% v / v of the fermentation medium; and the viable count of *Kluyveromyces martensii* is 1.0 × 10⁻⁶. 8CFU / mL; The aerobic fermentation was carried out at 35°C with sterile air at an aeration ratio of 0.5vvm for 48 hours. Other steps and parameters were the same as those of ginger root extract ②.

[0050] Ginger root extract⑤ Compared to ginger root extract ②, the difference lies in the preparation method of ginger root extract ⑤, where step W3 involves inoculating only *Lactobacillus curvaturei* for anaerobic fermentation; the total inoculation amount of *Lactobacillus curvaturei* is 5% v / v of the fermentation medium; and the viable count of *Lactobacillus curvaturei* is 1.0 × 10⁻⁶. 8 CFU / mL; the anaerobic fermentation was carried out at 35℃ for 48h, and other steps and parameters were the same as those of ginger root extract ②.

[0051] Ginger root extract ⑥ Compared with ginger root extract ②, the difference lies in the preparation method of ginger root extract ⑥. In step W3, Lactobacillus curvatureis is first inoculated for anaerobic fermentation, and then Kluyveromyces martensii is inoculated for aerobic fermentation. All other steps and parameters are the same as those of ginger root extract ②.

[0052] Ginger root extract⑦ Compared with ginger root extract ②, the difference is that in ginger root extract ⑦, Saccharomyces cerevisiae with preservation number CGMCC No.14964 is used instead of Kluyveromyces martensii with preservation number CCTCC NO: M 2022014. All other steps and parameters are the same as those of ginger root extract ②.

[0053] Ginger root extract⑧ Compared with ginger root extract ②, the difference is that in ginger root extract ⑧, Lactobacillus fermentum with preservation number CGMCC No. 4648 is used instead of Lactobacillus curvaturei with preservation number CGMCC No. 21575. All other steps and parameters are the same as those of ginger root extract ②.

[0054] Ginger root extract ⑨ Compared with ginger root extract ②, the difference is that in ginger root extract ⑨, the strain of *Kluyveromyces martensii* with accession number CGMCC NO.13499 is used instead of *Kluyveromyces martensii* with accession number CCTCC NO: M 2022014. All other steps and parameters are the same as those of ginger root extract ②.

[0055] Ginger root extract⑩ Compared with ginger root extract ②, the difference is that in ginger root extract ⑩, Lactobacillus curvaturei with preservation number CCTCC NO: M2016540 is used instead of Lactobacillus curvaturei with preservation number CGMCC No. 21575. All other steps and parameters are the same as those of ginger root extract ②.

[0056] ginger root extract

[0057] Compared with ginger root extract ②, the difference lies in the inoculation ratio of Kluyveromyces marxifolia and Lactobacillus curvature in ginger root extract ⑪ being 1.9:1.1, while the other steps and parameters are the same as those of ginger root extract ②.

[0058] The component composition (parts by weight) of compositions 1-5 in this invention is shown in Table 1 below. Each component is weighed according to the formula amount, mixed and homogenized to obtain each composition.

[0059] Table 1. Components and weight parts of compositions 1-5 Composition 1 0.05 0.12 0.05 0.08 0.02 ① Composition 2 0.05 0.12 0.05 0.08 0.02 ② Composition 3 0.05 0.12 0.05 0.08 0.02 ③ Composition 4 0.001 0.05 0.01 0.001 0.001 ② Composition 5 0.1 0.5 0.5 0.1 0.05 ② Composition ① Compared with composition 2, the difference is that peach fruit extract is not added to composition ①, and the missing amount is made up with ginger root extract ②. All other steps and parameters are the same as those of composition 2.

[0060] Composition ② Compared with composition 2, the difference is that ginger root extract ② is not added to composition ②, and the missing amount is made up with peach fruit extract. All other steps and parameters are the same as those of composition 2.

[0061] Composition ③ Compared with composition 2, the difference is that ginger root extract ④ is used in composition ⑤ to replace ginger root extract ② in an equal amount, while the other steps and parameters are the same as those of composition 2.

[0062] Composition ④ Compared with composition 2, the difference is that ginger root extract ⑤ is used in composition ⑥ to replace ginger root extract ② in an equal amount, while the other steps and parameters are the same as those of composition 2.

[0063] Composition ⑤ Compared with composition 2, the difference is that ginger root extract ⑥ is used in composition ⑤ to replace ginger root extract ② in an equal amount, while other steps and parameters are the same as those of composition 2.

[0064] Composition ⑥ Compared with composition 2, the difference is that ginger root extract ⑦ is used in composition ⑥ to replace ginger root extract ② in an equal amount, while other steps and parameters are the same as those of composition 2.

[0065] Composition ⑦ Compared with composition 2, the difference is that ginger root extract ⑧ is used in composition ⑦ to replace ginger root extract ② in an equal amount, while other steps and parameters are the same as those of composition 2.

[0066] Composition ⑧ Compared with composition 2, the difference is that ginger root extract ⑨ is used in composition ⑧ to replace ginger root extract ② in an equal amount, while other steps and parameters are the same as those of composition 2.

[0067] Composition 9 Compared with composition 2, the difference is that ginger root extract ⑨ is used in composition ⑩ in an equal amount to replace ginger root extract ②, while the other steps and parameters are the same as those of composition 2.

[0068] Composition ⑩ The difference between composition 10 and composition 2 is that composition 10 uses ginger root extract. Replace ginger root extract ② with an equal amount, and keep all other steps and parameters the same as those for composition 2.

[0069] Test Example 1: Antibacterial Performance Test of the Composition Streptococcus mutans is one of the most common cariogenic bacteria in the oral cavity, exhibiting strong cariogenicity. It also produces extracellular polysaccharides such as glucan, which contribute to plaque formation and adhesion to the tooth surface, enhancing plaque's resistance to rinsing. Distal Streptococcus also poses a threat to oral health, especially in children and adolescents, and is closely related to the occurrence of early tooth decay.

[0070] This test example evaluates the caries prevention performance of the compositions by testing the antibacterial properties of compositions 1-5 and compositions ①-⑩ against Streptococcus mutans and Streptococcus pyogenes.

[0071] The specific testing steps are as follows: Sample preparation: Dilute compositions 1-5 and compositions ①-⑨ with sterile physiological saline to a concentration of 1.0 mg / mL for the test solution; Streptococcus mutans and Streptococcus distantly revived for 48 h were inoculated into BHI liquid medium and cultured anaerobically at 37 °C for 24 h. The bacteria were then collected by centrifugation at 3500 r / min for 15 min. After washing the bacteria twice with sterile physiological saline, sterile physiological saline was added to prepare a bacterial suspension and the absorbance (OD) at 540 nm was set to 1.0. The suspension was then stored at 4 °C for later use. Take neutral qualitative filter paper and punch it into 6mm diameter circular filter paper discs. Place them in a clean, dry glass petri dish for dry heat sterilization. Under aseptic conditions, add the filter paper discs of the sample group to 1mL of the test solution. Add the filter paper discs of the positive control group to 1mL of chlorhexidine (compound chlorhexidine mouthwash stock solution) at a concentration of 1.2mg / mL. Add the filter paper discs of the blank control group to 1mL of sterile physiological saline. Soak the filter paper discs of each group in a refrigerator overnight, then dry them in a desiccator and store them in a sealed container at 4℃. Prepare for use; Use sterile cotton swabs to evenly spread the cultured Streptococcus mutans and distant Streptococcus onto sterilized broth agar plates. Using sterile tweezers, place filter paper discs on the surface of the broth agar plates according to the sample group and positive control group, respectively. Gently press the filter paper discs with the tweezers to ensure proper contact with the agar, with equal spacing between each disc. After incubation in a 37℃ anaerobic incubator for 24 hours, measure the diameter of each inhibition zone (inhibition diameter = inhibition zone diameter - disc diameter) using calipers. The data are presented as average values, and the experimental results are shown in Table 2.

[0072] Table 2 Performance test data of the composition Blank control group 0.00 0.00 Positive control group 7.96 8.73 Composition 1 7.05 7.64 Composition 2 8.13 8.59 Composition 3 7.22 7.57 Composition 4 7.69 8.36 Composition 5 7.74 8.25 Composition ① 4.76 4.80 Composition ② 4.57 5.09 Composition ③ 5.30 5.72 Composition ④ 5.14 5.51 Composition ⑤ 6.02 6.54 Composition ⑥ 5.58 6.05 Composition ⑦ 5.75 6.23 Composition ⑧ 6.47 6.76 Composition 9 6.61 6.94 Composition ⑩ 7.13 7.48 Compared with composition 2, compositions ①-② do not contain either peach fruit extract or ginger root extract; compositions ③-⑤ involve the preparation process of ginger root extract in which only *Kluyveromyces martensii* is inoculated for aerobic fermentation, or only *Lactobacillus curvilinearis* is inoculated for anaerobic fermentation, or *Lactobacillus curvilinearis* is inoculated for anaerobic fermentation first, and then *Kluyveromyces martensii* is inoculated for aerobic fermentation; compositions ⑥-⑦ involve the preparation process of ginger root extract in which other yeasts (i.e., *Saccharomyces cerevisiae*) are used instead of *Kluyveromyces martensii*, or other lactobacilli (i.e., *Lactobacillus fermentum*) are used instead of *Lactobacillus curvilinearis*; compositions ⑧-⑨ involve the preparation process of ginger root extract in which *Kluyveromyces martensii* and *Lactobacillus curvilinearis* with different preservation numbers are used for fermentation; and composition ⑩ involves the preparation process in which the inoculation ratio of *Kluyveromyces martensii* and *Lactobacillus curvilinearis* is not within the scope of this application.

[0073] From the data on the inhibition diameters of Streptococcus mutans and Streptococcus pyogenes in compositions 1-5 in Table 2, it can be seen that the composition has a better antibacterial effect when the mass ratio of human recombinant amber matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract, and ginger root extract is (0.001-0.1):(0.05-0.5):(0.01-0.5):(0.001-0.1):(0.001-0.05). Combining the data of composition 2 and compositions 4-5 in Table 2, it can be seen that the composition has the best effect when the mass ratio of human recombinant amber matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract, and ginger root extract is 0.05:0.12:0.05:0.08:0.02.

[0074] As can be seen from the data of composition 2 and compositions ①-② in Table 2, peach fruit extract and ginger root extract can synergistically enhance the antibacterial ability of the composition against Streptococcus mutans and Streptococcus pyogenes.

[0075] As can be seen from the data of composition 2 and compositions ③-⑩ in Table 2, different fermentation methods, different fermentation strains, and different inoculation ratios will all affect the fermentation effect, thereby affecting the antibacterial effect of the composition. Composition 2 of the present invention has excellent antibacterial and anti-caries effects.

[0076] Application example: A children's toothpaste with oral care benefits for children. Compositions 1-5 and compositions ①-⑩ were added to children's toothpaste to obtain children's toothpastes of application examples 1-5 and comparative application examples 1-10.

[0077] The children's toothpaste with oral care effects comprises the following ingredients by weight percentage: 0.5% of the children's oral care composition, 20% silica, 0.5% sodium pyrophosphate, 45% sorbitol, 10% glycerin, 1% cocamidopropyl betaine, 0.5% sodium lauryl ether sulfate, 0.6% xanthan gum, 0.3% xylitol, 0.01% dextranase, 0.35% caprylyl glycol, 0.14% ethylhexylglycerin, 1% fragrance, and the balance being deionized water.

[0078] The preparation method of the children's toothpaste with oral care effects specifically includes the following steps: S1. Add the children's oral care composition, sodium pyrophosphate, and xylitol to deionized water, stir well, and obtain the first solution; S2. Add sorbitol, glycerol, caprylyl glycol and ethylhexylglycerol to the first solution, stir well, then add dextranase and stir well to obtain the second solution; S3. Mix silica and xanthan gum to obtain the first mixture; S4. Mix the first mixture with the second solution, then add cocamidopropyl betaine, sodium lauryl ether sulfate, and fragrance. Stir well and degas to obtain the children's toothpaste.

[0079] Comparative Application Example 11 Compared with Application Example 1, the difference is that the children's toothpaste in Comparative Application Example 11 does not contain a children's oral care composition, and uses an equal amount of deionized water instead of the composition. The preparation method is the same as that in Application Example 1.

[0080] Test Example 2: Toothpaste Performance Test 1) Dental plaque removal ability: 160 subjects were randomly divided into 16 groups of 10 subjects each. Subjects used the toothpaste prepared in Application Examples 1-5 and Control Examples 1-11, respectively, brushing their teeth twice a day, morning and evening, using 2g of toothpaste each time, for 3 months, using the horizontal scrubbing method. After 3 months, the subjects aspirated bacteria from the other side of the back of their tongues, and then incubated the collected samples on blood agar medium under anaerobic conditions at 37°C. After 72 hours, the average bacterial colony forming units were calculated, and the colony forming unit reduction rate (CFU reduction rate) was calculated according to the following formula. The data are presented as average values. The experimental results are shown in Table 3. ; In the formula: CFU 使用前 These are the colony-forming units of each group before use; CFU 使用3个月后 These are the colony-forming units for each group after 3 months of use.

[0081] 2) Antibacterial performance test: The toothpastes prepared according to the antibacterial performance test method in Test Example 1 were tested in the corresponding test examples 1-5 and comparative application examples 1-11; Sample preparation: The toothpastes prepared in application examples 1-5 and comparative application examples 1-11 were diluted with sterile physiological saline to a test solution with a concentration of 1.0 mg / mL; The data are presented as average values, and the test results are shown in Table 3.

[0082] 3) Remineralization performance test: 1. Preparation of enamel specimens: Freshly extracted bovine teeth were selected, cut into pieces approximately 5mm × 5mm in size, and inlaid in polymethyl methacrylate resin. Under water cooling conditions, the enamel surface of the tooth grinding block was polished on a polishing machine using a P180 grinding wheel until it was completely exposed and the surface of the tooth grinding block was level. Then, P600 and 2500 silicon carbide sandpaper were used to polish it smooth in sequence. Finally, a soft cloth with 1µm diamond polishing paste was used to polish it to a mirror finish. The prepared tooth grinding blocks were stored in deionized water for later use. 2. Preparation of artificial saliva: Weigh 0.246g calcium nitrate, 0.1225g potassium dihydrogen phosphate, 9.685g potassium chloride, and 4.184g bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane into a 1L beaker, add 800mL deionized water, stir thoroughly to dissolve, and adjust the pH to 7.0±0.05 with 1mol / L HCl; transfer this solution to a 1L volumetric flask and dilute to the mark with deionized water. 3. Preparation of demineralization solution: Weigh 5g of citric acid into a 500mL volumetric flask, add deionized water to make up to 500mL, and adjust the pH to 3.80 using 1mol / L NaOH solution; 4. Screening of Enamel Specimens: The hardness of enamel specimens was measured using a Vickers hardness tester (100g pressure, 5s loading time). Four points were measured on each specimen, with each point at least 0.5mm from the edge of the tooth block. The four points were evenly distributed, with a minimum distance of 1mm between each point. The hardness of the enamel specimen was the average of the four measurements, recorded as HV0 (the baseline value for enamel hardness). A hardness value of (300-350) kg / mm² was selected. 2 Specimens from between were included in this study; 5. Preparation of toothpaste slurry for test samples: Weigh a certain amount of the toothpaste to be tested and deionized water according to the ratio of 1g:1.3mL (toothpaste:water), stir and mix well while avoiding foaming; add 5mL of toothpaste slurry to each tooth enamel specimen; the preparation method of toothpaste slurry for each group is the same; 6. Demineralization treatment: Immerse the enamel specimen in 1% citric acid for 30 minutes at a temperature controlled at 37℃±2℃, stirring with a propeller at low speed (60 r / min), keeping the propeller 5 cm above the enamel specimen. Then, thoroughly rinse the specimen with deionized water and dry it. Use a Vickers hardness tester (100g pressure, 5s loading time) to measure the hardness of the demineralized enamel specimen. Measure four points on each specimen, ensuring the measurement points are at least 0.5 mm from the edge of the tooth block, and distribute the four points evenly. Measurement points should be spaced at least 1 mm apart. The hardness of the enamel specimen is the average of four measurements, denoted as HV1 (hardness value of enamel after demineralization). Demineralized enamel samples are screened, and then randomly divided into 16 experimental groups: application examples 1-5, control examples 1-10, and a blank control group, with 8 samples in each group. After grouping, an independent samples t-test is used to test the Vickers surface hardness values ​​of the two groups, requiring no significant difference between the two groups (P>0.05). 7. Experimental Cycle: In the experimental group, the toothpaste slurry was used to soak the specimen for 15 minutes under constant temperature and humidity conditions (37℃±2℃, 100 rpm / min). The specimen was then thoroughly rinsed with deionized water, and subsequently soaked in artificial saliva under constant temperature and humidity conditions (6 hours, same temperature and 100 rpm / min). The toothpaste slurry was then used to soak the specimen for 15 minutes under constant temperature and humidity conditions (same temperature and 100 rpm / min), and the specimen was thoroughly rinsed with deionized water. Finally, the specimen was soaked overnight in artificial saliva under constant temperature and humidity conditions (37℃±2℃, 100 rpm / min). This process was repeated for 7 days. The blank control group was treated with the same amount of deionized water instead of toothpaste slurry, with all other treatments the same as the experimental group. 8. Hardness test: After the cycle ends on day 7, the hardness of the enamel specimen is measured using a Vickers hardness tester (pressure 100g, loading time 5s). Four points are measured for each specimen. The distance between the measurement point and the edge of the tooth block should not be less than 0.5mm. The four measurement points should be evenly distributed, and the distance between each measurement point should not be less than 1mm. The hardness of the enamel specimen is the average of the four measurements, which is recorded as HV2 (hardness value of enamel after remineralization). 9. Experimental data are expressed as mean ± standard deviation (Mean ± SD); the experimental results are shown in Table 4.

[0083] Table 3 Toothpaste performance test data Blank control group / 0.00 0.00 Positive control group / 8.01 8.51 Application Example 1 67.45 6.93 7.47 Application Example 2 71.96 7.85 8.30 Application Example 3 68.13 6.86 7.39 Application Example 4 69.82 7.48 7.92 Application Example 5 70.01 7.34 8.08 Comparative Application Example 1 48.23 4.57 4.75 Comparative Application Example 2 47.28 4.30 4.91 Comparative Application Example 3 51.39 5.02 5.53 Comparative Application Example 4 50.42 4.84 5.46 Comparative Application Example 5 58.25 5.83 6.32 Comparative Application Example 6 53.92 5.35 5.87 Comparative Application Example 7 55.46 5.48 6.09 Comparative Application Example 8 61.24 6.11 6.63 Comparative Application Example 9 60.57 6.26 6.78 Comparative Application Example 10 64.18 6.80 7.26 Comparative Application Example 11 5.89 0.62 0.71 Table 4 Remineralization test data Blank control group 335.32±10.42 142.56±4.38 147.47±5.07 Application Example 1 333.25±9.28 141.35±5.40 <![CDATA[180.43±6.95 * ]]> Application Example 2 339.13±8.57 144.52±5.37 <![CDATA[189.35±7.81 * ]]> Application Example 3 331.48±9.66 142.69±6.15 <![CDATA[182.57±8.73 * ]]> Application Example 4 336.46±8.95 144.37±5.96 <![CDATA[186.46±7.34 * ]]> Application Example 5 335.52±10.14 145.28±5.39 <![CDATA[188.34±7.12 * ]]> Comparative Application Example 1 330.46±7.89 146.87±6.42 <![CDATA[171.62±6.30 * ]]> Comparative Application Example 2 332.19±7.97 143.65±5.63 <![CDATA[167.78±5.29 * ]]> Comparative Application Example 3 336.24±8.83 140.79±5.74 <![CDATA[168.54±6.13 * ]]> Comparative Application Example 4 333.45±9.02 141.86±6.85 <![CDATA[168.34±7.02 * ]]> Comparative Application Example 5 337.53±8.28 144.91±7.17 <![CDATA[176.89±6.87 * ]]> Comparative Application Example 6 335.18±8.95 146.65±4.26 <![CDATA[176.58±6.58 * <!-- 11 -->]]> Comparative Application Example 7 338.04±8.73 149.34±5.99 <![CDATA[180.64±5.91 * ]]> Comparative Application Example 8 334.57±7.81 145.20±5.48 <![CDATA[179.35±7.89 * ]]> Comparative Application Example 9 332.46±7.14 142.78±4.93 <![CDATA[177.52±6.94 * ]]> Comparative Application Example 10 340.25±8.19 147.86±6.04 <![CDATA[184.46±7.35 * ]]> Note:" * "" indicates that the remineralization values ​​of Application Examples 1-5 and Comparative Application Examples 1-10 are compared with the blank control group, P < 0.05.

[0084] Compared with Application Example 2, the compositions in Comparative Application Examples 1-2 do not contain either peach fruit extract or ginger root extract. In Comparative Application Examples 3-5, the preparation process of ginger root extract involves inoculating only *Kluyveromyces martensii* for aerobic fermentation, or only inoculating only *Lactobacillus curvilinearis* for anaerobic fermentation, or first inoculating *Lactobacillus curvilinearis* for anaerobic fermentation and then inoculating *Kluyveromyces martensii* for aerobic fermentation. In Comparative Application Examples 6-7, the preparation process of ginger root extract involves replacing *Kluyveromyces martensii* with other yeasts (i.e., *Saccharomyces cerevisiae*) or replacing *Lactobacillus curvilinearis* with other lactobacilli (i.e., *Lactobacillus fermentum*). In Comparative Application Examples 8-9, the preparation process of ginger root extract involves fermentation using *Kluyveromyces martensii* and *Lactobacillus curvilinearis* with different preservation numbers. In Comparative Application Example 10, the inoculation ratio of *Kluyveromyces martensii* and *Lactobacillus curvilinearis* in the preparation process is not within the scope of this application.

[0085] From the data on colony-forming unit reduction rate, inhibition diameter of Streptococcus mutans and Streptococcus pyogenes, and remineralization test in Application Examples 1-5 in Tables 3-4, it can be seen that when the mass ratio of human recombinant enamel matrix protein, casein phosphopeptide, calcium lactate, peach extract, and ginger root extract is (0.001-0.1):(0.05-0.5):(0.01-0.5):(0.001-0.1):(0.001-0.05), the toothpaste has a better effect on plaque removal, antibacterial activity, and remineralization. Combining the data from Application Examples 2 and 4-5 in Tables 3-4, it can be seen that when the mass ratio of human recombinant enamel matrix protein, casein phosphopeptide, calcium lactate, peach extract, and ginger root extract is 0.05:0.12:0.05:0.08:0.02, the toothpaste has the best effect.

[0086] As can be seen from the data in Tables 3-4 of Application Example 2 and Comparative Application Examples 1-2, peach fruit extract and ginger root extract can synergistically improve the plaque removal, antibacterial and remineralization capabilities of toothpaste.

[0087] As can be seen from the data in Application Example 2 and Comparative Application Example 3-10 in Tables 3-4, different fermentation methods, different fermentation strains, and different inoculum ratios all affect the fermentation effect, thereby affecting the plaque removal effect of toothpaste and thus improving the toothpaste's effect in preventing or improving tooth decay.

[0088] Test Example 3: Acute Oral Toxicity Test Acute oral toxicity tests were conducted on the children's toothpaste prepared according to the acute oral toxicity test method in the 2007 edition of the "Cosmetic Hygiene Standard". The tests corresponded to cases 1-5.

[0089] Sixty healthy KM mice weighing 24-28g were selected for the experiment, with 10 mice in each group, half male and half female. The experimental group was given toothpaste prepared in Examples 1-5 by gavage. The toothpaste was diluted with physiological saline to a mass concentration of 2% before gavage. 1 mL / 100g of mice was gavage once a day. The control group was given the same amount of physiological saline by gavage once a day. The gavage was carried out for 14 consecutive days. The condition of the mice was observed after each gavage, and the number of dead mice was counted.

[0090] The results showed that no abnormal symptoms were observed in the KM mice in each group within 14 days, the mortality rate was 0, and the children's toothpaste prepared in Examples 1-5 all met the LD50 standard. 50 The requirement of >5000mg / kg indicates that the oral toxicity rating of the children's toothpaste provided by this invention is practically non-toxic, demonstrating its high safety.

[0091] The above description is merely a preferred composition of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with preferred compositions, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent compositions without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above compositions based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A children's oral care composition, characterized in that, The composition comprises the following components: human recombinant amber matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract, and ginger root extract; wherein the mass ratio of the human recombinant amber matrix protein, casein phosphopeptide, calcium lactate, peach fruit extract, and ginger root extract is (0.001-0.1):(0.05-0.5):(0.01-0.5):(0.001-0.1):(0.001-0.05). The preparation method of the ginger root extract includes the following steps: W1. Weigh ginger powder, add 60%-75% ethanol aqueous solution, extract with ultrasonic assistance, centrifuge and retain the supernatant to obtain ginger root extract; W2. Weigh each component of the fermentation medium according to the formula, mix them evenly, sterilize at 121℃ for 20-25 min, and cool to 28-35℃ to obtain the fermentation medium; wherein, the fermentation medium contains the following components by weight: 15-25 parts of ginger root extract prepared in step W1, 18-25 parts of glucose, 2-6 parts of tryptone, 2-4 parts of yeast powder, 1-3 parts of triamine citrate, 4-6 parts of sodium acetate, 0.3-0.6 parts of magnesium sulfate, 0.04-0.08 parts of manganese sulfate, 1.5-3 parts of dipotassium hydrogen phosphate, 0.8-1.2 parts of Tween 80, and 1000 parts of deionized water; W3. First, inoculate *Kluyveromyces martensii* into the fermentation medium prepared in step W2 for aerobic fermentation, then inoculate *Lactobacillus curvatureis* for anaerobic fermentation. After fermentation, centrifuge, collect the supernatant, filter and sterilize to obtain the ginger root extract; wherein, the preservation number of *Kluyveromyces martensii* is CCTCC NO: M 2022014, and the preservation number of *Lactobacillus curvatureis* is CGMCC No. 21575.

2. The pediatric oral care composition as described in claim 1, characterized in that, The mass ratio of the human recombinant enamel matrix protein, casein phosphopeptide, calcium lactate, peach extract, and ginger root extract is 0.05:0.12:0.05:0.08:0.

02.

3. The pediatric oral care composition as described in claim 1, characterized in that, In step W1, the ratio of ginger powder to ethanol aqueous solution is 1g:22-28mL. The ultrasonic-assisted extraction time is 15-20min, the temperature is 50-60℃, and the power is 280-320W. The centrifugation speed is 5000-6000 rpm and the time is 12-18min.

4. The pediatric oral care composition as described in claim 1, characterized in that, In step W3, the total inoculum size of *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 3-6% v / v of the fermentation medium; the inoculum ratio of *Kluyveromyces martensii* to *Lactobacillus curvatureii* is 0.7-1.5:1.7-2.3; and the viable count of both *Kluyveromyces martensii* and *Lactobacillus curvatureii* is 1.0 × 10⁻⁶. 8 CFU / mL.

5. The pediatric oral care composition as described in claim 4, characterized in that, The inoculation ratio of Kluyveromyces martensii to Lactobacillus curvature was 1.1:1.

9.

6. The pediatric oral care composition as claimed in claim 1, characterized in that, In step W3, the aerobic fermentation is carried out at 33-38℃ with sterile air at an aeration ratio of 0.3-0.6 vvm for 24-36 hours; the anaerobic fermentation is carried out at 33-38℃ for 12-24 hours.

7. The use of the child oral care composition according to any one of claims 1-6 in the preparation of a child oral care product for the prevention or improvement of dental caries.

8. The application as described in claim 7, characterized in that, The children's oral care products include any one of toothpaste, mouthwash, and oral spray.

9. A children's toothpaste, characterized in that, The product comprises the following ingredients by weight percentage: 0.1%-8% of the children's oral care composition according to any one of claims 1-6, 10%-25% of abrasive, 0.1%-1% of buffer, 35%-60% of humectant, 0.5%-2.5% of surfactant, 0.1%-1.5% of thickener, 0.01%-1% of taste modifier, 0.001%-0.5% of enzyme, 0.1%-1% of preservative, 0.5%-1.5% of flavoring, and the balance being deionized water; The friction agent includes at least one of silica, calcium carbonate, and calcium hydrogen phosphate; The buffer includes pyrophosphate; The moisturizer includes at least one of sorbitol, polyethylene glycol, glycerin, and propylene glycol; The surfactant includes at least one of anionic surfactants, nonionic surfactants, amphoteric surfactants, and biosurfactants; The thickener includes at least one of xanthan gum, cellulose gum, cassia gum, carrageenan, and guar gum; The taste modifier includes at least one of sucralose, sodium saccharin, steviol glycosides, xylitol, and erythritol; The bioenzyme is selected from at least one of glucanase, lysozyme, protease, glucosyloxidase, amylase, papain, and bromelain; The preservative includes at least one of the following: plant antibacterial agent, sodium benzoate, benzyl alcohol, ethylhexylglycerin, octyl glycol, pentylene glycol, and p-hydroxyacetophenone.

10. A method for preparing children's toothpaste as described in claim 9, characterized in that, Includes the following steps: S1. Add the children's oral care composition, buffer, and taste modifier to deionized water, stir well, and obtain the first solution; S2. Add humectant and preservative to the first solution, stir well, then add biological enzyme, stir well to obtain the second solution; S3. Mix the friction agent and thickener to obtain the first mixture; S4. Mix the first mixture with the second solution, then add the surfactant and fragrance, stir evenly and degas to obtain the children's toothpaste.