CN115607464B - Antibacterial stain-removing toothpaste and preparation method thereof - Google Patents

Abstract

The invention provides antibacterial stain-removing toothpaste and a preparation method thereof, and belongs to the technical field of toothpaste. After pretreatment of nano montmorillonite, the surface is modified by polydopamine, dipotassium glycyrrhizinate, sodium azulene sulfonate and paeonol are fixed, porous silicon dioxide is coated on the surface, lysozyme and glucanase are fixed, a modified friction agent is obtained, and then the modified friction agent is uniformly mixed with sodium alginate microspheres, a humectant, a sweetener, a foaming agent, a thickening agent, essence and water which are embedded with probiotics and prebiotics, and the antibacterial stain-removing toothpaste is prepared by vacuum degassing. The toothpaste provided by the invention can effectively inhibit the adhesion and aggregation of oral bacteria, and remove the stain dirt on the surface of teeth, and each functional component can synergistically and fundamentally remove the stains to inhibit the formation of dental plaque, and also has the effects of astringing and soothing and repairing dental ulcers, so that the effects of nursing the oral cavity and removing the stains in the oral cavity are achieved, and oral diseases such as periodontitis, gingivitis, dental calculus, dental caries and halitosis can be prevented, so that the toothpaste has a wide application prospect.

Description

Antibacterial stain-removing toothpaste and preparation method thereof

Technical Field

The invention relates to the technical field of toothpaste, in particular to antibacterial stain-removing toothpaste and a preparation method thereof.

Background

With the enhancement of people's awareness of health and improvement of quality of life, there is a great enhancement to the attention of oral care. Most diseases of people are caused by oral cavity, and maintaining oral hygiene is an important link for preventing diseases, and the key of maintaining oral hygiene is to maintain tooth hygiene. If the teeth are not hygienic, a large number of microorganisms are propagated therein to erode the teeth, causing bad breath, gum swelling, etc., and more serious dental diseases may also cause other serious systemic diseases. Plaque is a bacterial ecological environment present in the tooth surface or periodontal pocket where bacteria grow, develop and decay and undergo complex metabolic activities of matter under defined conditions, bacteria and their products will destroy the teeth and periodontal tissue. Plaque is a soft, unmineralized colony of bacteria that adheres to tooth surfaces and is not readily noticeable in small amounts. However, with the increase of time, bacterial plaque is not removed in time, which causes stubborn spots and stains which cannot be removed by daily oral care, and the surfaces of teeth lose luster and turn yellow and dark.

The tooth whitening toothpaste disclosed in Chinese patent CN101889960B is prepared from an adhesive, a foaming agent, a humectant, a sweetener, a friction agent, a spice, deionized water, a covering agent, a preservative and a stain removing agent according to a conventional method, wherein the friction agent adopted by the tooth whitening and stain removing toothpaste is precipitated silica, and the stain removing agent is sodium phytate. Although precipitated silica is the first choice of a toothpaste abrasive at present, has a better abrasive stain removal effect, the addition of precipitated silica can make the obtained toothpaste unstable and has higher requirements on other components in the toothpaste formula, and experiments prove that not all precipitated silica is suitable for preparing the stain removal type toothpaste, and different silica can cause great differences in stain removal effect and toothpaste performance as abrasive. In the white tooth extract toothpaste, the stain remover is sodium phytate, the sodium phytate is a natural extract, has extremely strong chelation effect with metal ions, is a safe and efficient ion complexing agent, is safe and reliable as the stain remover in the toothpaste, and can inhibit the formation of dental calculus. However, in practical applications, it has been found that the type of precipitated silica has a great influence on the performance of sodium phytate in removing stains.

Meanwhile, at present, consumers have strong demands on whitening teeth, are enthusiastic for whitening teeth, and a part of people whiten teeth by means of tooth washing and the like, but have high cost and certain risks. Most people are on the body of various toothpaste with whitening effect, the existing whitening toothpaste mostly adopts special granular friction agent or peroxide to be added into the toothpaste to achieve the whitening effect, but the granular friction agent can damage tooth enamel and damage tooth surfaces, so that tooth stains are easier to deposit on the tooth surfaces. Bleaching teeth with peroxide is quick, but has a definite irritation to the oral cavity and a definite risk.

Therefore, the toothpaste is developed, can effectively remove dental plaque, prevent the expansion of dental plaque, treat the occurrence of related oral diseases, has a definite whitening and stain removing effect, and has a wide application prospect.

Disclosure of Invention

The invention aims to provide antibacterial stain-removing toothpaste and a preparation method thereof, which are mild and non-irritating, can effectively inhibit the adhesion and aggregation of oral bacteria, remove color stain stains on the surfaces of teeth, can synergistically and fundamentally remove the stains to inhibit the formation of dental plaque, have the effects of astringing and comfort and repairing dental ulcer, achieve the effects of nursing the oral cavity and removing the stains in the oral cavity, can also prevent periodontitis, gingivitis, dental calculus, dental caries, halitosis and other oral diseases, and have wide application prospects.

The technical scheme of the invention is realized as follows:

the invention provides a preparation method of antibacterial stain-removing toothpaste, which comprises the steps of pretreating nano montmorillonite, modifying the surface by polydopamine, fixing dipotassium glycyrrhizinate, sodium azulene sulfonate and paeonol, coating porous silicon dioxide on the surface, fixing lysozyme and glucanase to obtain a modified friction agent, uniformly mixing the modified friction agent with sodium alginate microspheres embedded with probiotics and prebiotics, a humectant, a sweetener, a foaming agent, a thickening agent, essence and water, and carrying out vacuum degassing to obtain paste.

As a further improvement of the invention, the method comprises the following steps:

s1, surface treatment of nano montmorillonite: soaking nano montmorillonite in alkali liquor, centrifuging, washing and drying to obtain pretreated nano montmorillonite;

s2, polydopamine modification treatment: uniformly dispersing the pretreated nano montmorillonite prepared in the step S1 in water, adding dopamine hydrochloride and a catalyst, heating for reaction, centrifuging, washing and drying to obtain polydopamine modified montmorillonite;

s3, fixing a composite preparation: uniformly mixing dipotassium glycyrrhizinate, sodium azulene sulfonate and paeonol, dissolving in an ethanol water solution, adding the polydopamine modified montmorillonite prepared in the step S2, uniformly dispersing by ultrasonic, heating for reaction, centrifuging, washing and drying to obtain modified montmorillonite;

S4, coating silicon dioxide: dissolving alkyl orthosilicate in ethanol water solution, adding the modified montmorillonite prepared in the step S3, uniformly dispersing by ultrasonic, adjusting the pH value of the solution to be alkaline, adding a pore-forming agent and an emulsifying agent, emulsifying, stirring for reaction, centrifuging, washing and drying to obtain the modified montmorillonite coated with porous silicon dioxide;

s5, immobilization of complex enzyme: dissolving lysozyme and glucanase in water to obtain an antibacterial enzyme mixed solution, adding the modified montmorillonite coated with the porous silica prepared in the step S4, stirring and fixing, and volatilizing at normal temperature to obtain a modified friction agent;

s6, preparing microspheres embedded with probiotics and prebiotics: mixing the composite probiotics and the composite prebiotics in water, adding sodium alginate for dissolution, adding the mixture into silicone oil, quickly emulsifying the mixture by a film, dripping a calcium chloride solution, and curing the mixture at normal temperature to obtain microspheres embedded with the probiotics and the prebiotics;

s7, preparing antibacterial stain-removing toothpaste: uniformly mixing the modified friction agent prepared in the step S5, the microspheres embedded with probiotics and prebiotics prepared in the step S6, a humectant, a sweetener, a foaming agent, a thickening agent, essence and water, stirring and mixing at a high speed, and vacuum degassing to obtain paste, thus obtaining the antibacterial stain-removing toothpaste.

As a further improvement of the invention, the grain diameter of the nano montmorillonite in the step S1 is smaller than 100nm, the alkali liquor is 1-3mol/L NaOH or KOH solution, and the soaking time is 30-50min; the mass ratio of the pretreated nano montmorillonite, the dopamine hydrochloride and the catalyst in the step S2 is 15:17-22:1-3, and the catalyst containsWith 3-5wt% of CoCl ₂ The temperature of the heating reaction is 50-70 ℃ and the time is 2-3h.

As a further improvement of the invention, in the step S3, the mass ratio of dipotassium glycyrrhizinate, sodium azulene sulfonate, paeonol and polydopamine modified montmorillonite is 3-5:2-4:1-3:30, the concentration of ethanol in the ethanol water solution is 40-60wt% and the balance is water, the temperature of the heating reaction is 40-50 ℃ and the time is 1-2h; the alkyl orthosilicate in the step S4 is ethyl orthosilicate or methyl orthosilicate, the mass ratio of the alkyl orthosilicate to the modified montmorillonite to the pore-forming agent to the emulsifier is 5-10:12-17:1-3:0.5-1, the ethanol content in the ethanol water solution is 50-70wt%, the balance is water, the pH value of the solution is adjusted to 8-9, the condition of emulsification is 12000-15000r/min for 3-5min, the pore-forming agent is at least one of polyoxyethylene sorbitan fatty acid ester, polyethylene glycol octyl phenyl ether, cetyl trimethyl ammonium bromide, ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and PEO106-PPO70-PEO10, and the emulsifier is at least one of Tween-20, tween-40, tween-60 and Tween-80.

As a further improvement of the present invention, the mass ratio of lysozyme, glucanase and porous silica coated modified montmorillonite in step S5 is 2-4:1-3:15-20; in the step S6, the compound probiotics are selected from at least two of lactobacillus acidophilus, lactobacillus paracasei and lactobacillus salivarius, the compound probiotics are selected from fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, isomaltooligosaccharide, soybean oligosaccharide and inulin, the mass ratio of the compound probiotics to sodium alginate is 5-10:2-4:17-25, the concentration of the calcium chloride solution is 3-5wt%, the pore diameter of the membrane in the rapid membrane emulsification is 1000-3000nm, and the normal temperature solidification time is 30-50min.

As a further improvement of the invention, the compound probiotics are a mixture of lactobacillus paracasei and lactobacillus salivarius, and the mass ratio is 3-5:7; the compound prebiotics are a mixture of fructo-oligosaccharide and xylo-oligosaccharide, and the mass ratio is 3-5:1.

As a further improvement of the present invention, the mass ratio of the modified friction agent, the microsphere embedding the probiotics and the prebiotics, the humectant, the sweetener, the foaming agent, the thickener, the essence and the water in the step S7 is 20-40:4-7, 20-35, 0.1-0.2, 1-3, 0.5-1.5, 1-1.5, 30-50; the rotating speed of the high-speed stirring and mixing is 1000-1200r/min, and the mixing time is 15-30min.

As a further improvement of the present invention, the humectant is at least one selected from glycerin, sorbitol and polyethylene glycol 400; the sweetener is at least one selected from sucralose, aspartame, acesulfame potassium, sodium cyclamate, saccharin and xylitol; the foaming agent is betaine; the thickener is at least one selected from xanthan gum, carrageenan and sodium carboxymethyl cellulose.

As a further improvement of the invention, the method specifically comprises the following steps:

s1, surface treatment of nano montmorillonite: soaking nano montmorillonite with particle size smaller than 100nm in 1-3mol/L NaOH or KOH solution for 30-50min, centrifuging, washing, and drying to obtain pretreated nano montmorillonite;

s2, polydopamine modification treatment: uniformly dispersing 15 parts by weight of the pretreated nano montmorillonite prepared in the step S1 in water, adding 17-22 parts by weight of dopamine hydrochloride and 1-3 parts by weight of catalyst, heating to 50-70 ℃ for reacting for 2-3 hours, centrifuging, washing and drying to obtain polydopamine modified montmorillonite;

the catalyst contains 3-5wt% of CoCl ₂ Tris-HCl solution with pH value of 5-6;

s3, fixing a composite preparation: uniformly mixing 3-5 parts by weight of dipotassium glycyrrhizinate, 2-4 parts by weight of sodium azulene sulfonate and 1-3 parts by weight of paeonol, dissolving in 100 parts by weight of 40-60wt% ethanol water solution, adding 30 parts by weight of polydopamine modified montmorillonite prepared in the step S2, uniformly dispersing by ultrasonic, heating to 40-50 ℃ for reacting for 1-2 hours, centrifuging, washing and drying to obtain modified montmorillonite;

S4, coating silicon dioxide: dissolving 5-10 parts by weight of tetraethoxysilane or tetramethylsilicate in 100 parts by weight of 50-70wt% ethanol water solution, adding 12-17 parts by weight of the modified montmorillonite prepared in the step S3, uniformly dispersing by ultrasonic, adjusting the pH value of the solution to 8-9, adding 1-3 parts by weight of pore-forming agent and 0.5-1 part by weight of emulsifying agent, emulsifying for 3-5min at 12000-15000r/min, stirring for reaction, centrifuging, washing and drying to obtain the modified montmorillonite coated with porous silica;

s5, immobilization of complex enzyme: dissolving 2-4 parts by weight of lysozyme and 1-3 parts by weight of dextranase in 20 parts by weight of water to obtain an antibacterial enzyme mixed solution, adding 15-20 parts by weight of the modified montmorillonite coated with the porous silica prepared in the step S4, stirring and fixing, and volatilizing at normal temperature to obtain a modified friction agent;

s6, preparing microspheres embedded with probiotics and prebiotics: mixing 5-10 parts by weight of composite probiotics and 2-4 parts by weight of composite prebiotics into 50 parts by weight of water, adding 17-25 parts by weight of sodium alginate solution and 2-3 parts by weight of emulsifier solution, adding 100 parts by weight of silicone oil, adding a rapid membrane with the aperture of 1000-3000nm for emulsification, dropwise adding 10-15 parts by weight of 3-5wt% of calcium chloride solution, and curing at normal temperature for 30-50min to obtain microspheres embedded with probiotics and prebiotics;

The compound probiotics are a mixture of lactobacillus paracasei and lactobacillus salivarius, and the mass ratio is 3-5:7;

the compound prebiotics are a mixture of fructo-oligosaccharide and xylo-oligosaccharide, and the mass ratio is 3-5:1;

s7, preparing antibacterial stain-removing toothpaste: uniformly mixing 20-40 parts by weight of the modified friction agent prepared in the step S5, 4-7 parts by weight of the microspheres embedded with probiotics and prebiotics prepared in the step S6, 20-35 parts by weight of humectant, 0.1-0.2 part by weight of sweetener, 1-3 parts by weight of foaming agent, 0.5-1.5 parts by weight of thickener, 1-1.5 parts by weight of essence and 30-50 parts by weight of water, stirring and mixing for 15-30min at 1000-1200r/min, and vacuum degassing to obtain the antibacterial stain-removing toothpaste.

The invention further protects the antibacterial stain-removing toothpaste prepared by the preparation method.

The invention has the following beneficial effects:

actinobacillus actinomycetemcomitans is a gram-negative oral pathogenic bacterium with high pathogenic potential, and is easy to colonise in the oral cavity to form dental plaque biomembrane with complex structure, so as to cause periodontal disease. Meanwhile, actinobacillus actinomyces with actinobacillus can secrete and synthesize various high virulence factors to cause occurrence and development of periodontitis, thereby causing symptoms such as gingival bleeding, tooth loosening, halitosis and the like. Porphyromonas gingivalis is a typical pathogenic bacterium for gingivitis, which is a gram-negative obligate anaerobic bacterium, a dominant pathogenic bacterium for periodontal subgingival plaque. Streptococcus mutans is a causative agent of caries, and can form water-insoluble polysaccharides on tooth surface, and firmly adhere to tooth surface; under the same pH condition, the streptococcus mutans can dissolve more calcium than streptococcus sanguinis, lactobacillus and the like; streptococcus mutans can convert sucrose into glucan and convert glucose into lactic acid almost entirely.

Dipotassium glycyrrhizinate can inhibit and kill actinobacillus and streptococcus mutans, thereby completely inhibiting dental plaque formation. Paeonol is colorless or white or yellowish glossy needle crystal, has strong antibacterial effect on Staphylococcus aureus, streptococcus faecalis, escherichia coli, etc., and has tranquilizing, antiinflammatory, antipyretic, antiallergic, etc. Sodium azulene sulfonate is an active ingredient of chamomile, has strong pepsin resistance, anti-inflammation, antibacterial, antiallergic and mucosa metabolism promoting effects, and inhibits inflammatory cells from releasing histamine through local direct action; increase synthesis of prostaglandin E2 in mucosa, promote granulation and epithelial cell regeneration, and has good effect of repairing epithelial cells with high safety. The three components are compounded and enter the oral cavity, so that the surface of harmful bacteria becomes uneven, partial bacteria are broken, intracellular substances flow out, the integrity of bacterial cells is destroyed, and the prepared toothpaste has good effects of inhibiting bacteria, resisting bacteria, diminishing inflammation, relieving fever, repairing epithelial cells and promoting mucosa metabolism, and can effectively inhibit the formation of dental plaque, inhibit gingival bleeding, loosening teeth, halitosis and repairing dental ulcer.

According to the invention, polydopamine is modified on the surface of nano montmorillonite, and groups such as rich hydroxyl, amino and carboxyl groups of polydopamine can form hydrogen bond fixation with dipotassium glycyrrhizinate, paeonol and sodium azulenesulfonate, so that the composite preparation can be stably fixed on polydopamine modified montmorillonite, and further through sol-gel reaction, a layer of porous silica (under the action of a pore-forming agent) is coated on the surface, the strength of particles can be further enhanced by coating the porous silica, and meanwhile, a larger specific surface area is provided, so that abundant site fixation is provided for lysozyme and glucanase, and the prepared modified friction agent not only can play the function of the friction agent, but also can play the effects of an antibacterial agent, an anti-inflammatory agent and the like.

Streptococcus mutans has been widely recognized as a major causative agent of dental caries in oral bacteria. The mechanism responsible for caries formation is that Glucosyltransferases (GTFs) in streptococcus mutans break down sucrose and synthesize extracellular polysaccharides that can attach to the tooth surface, and on the other hand, acids produced by streptococcus mutans promote tooth demineralization, which is exacerbated by the presence of oral sugars, which are critical to protect the teeth, prevent glucan synthesis and acid production. Streptococcus mutans can synthesize alpha-1, 6 glycosidic chain-enriched glucans, alpha-1, 3 glycosidic chain-enriched glucans, and water-soluble glucans by the resulting glucosyltransferase.

Glucanase is capable of efficiently decomposing glucan produced by Streptococcus mutans, thereby preventing caries and plaque formation.

Lysozyme is a nonspecific substance component, can inhibit microbial growth, and can not generate drug resistance after long-term use. The lysozyme can effectively hydrolyze peptidoglycan of bacterial cell walls, and has different content of peptidoglycan in cell walls of gram-positive bacteria (G+), such as staphylococcus aureus, bacillus subtilis, micrococcus muralis and the like, and gram-negative bacteria (G-), such as escherichia coli, clostridium nucleatum, porphyromonas gingivalis, pneumobacillus and the like, and the cell walls of G+ bacteria almost completely consist of peptidoglycan, and only the inner wall layers of G-bacteria are peptidoglycan, so that the lysozyme has good inhibition and killing effects on G+ bacteria and also has a certain inhibition effect on G-bacteria. Lysozyme can selectively lyse the cell wall of the target microorganism to inactivate it, and the mammal has no cell wall, so that lysozyme has no damage to oral tissues, but plays a role in protection.

The probiotics can compete with oral pathogenic bacteria for binding sites to block the colonization of pathogenic bacteria, so that pathogenic bacteria are discharged from the oral cavity, and the oral health is improved. The metabolites produced by probiotics, such as organic acids, bacteriocins, etc., can effectively inhibit the growth of pathogenic bacteria and the formation of biological films.

Lactobacillus paracasei is the most common lactobacillus in oral microbiota, and the inactivated bacteria powder can generate coagulation and precipitation with oral pathogenic bacteria. The lactobacillus salivarius can inhibit the growth of caries pathogenic bacteria, thereby preventing and treating caries, and has a certain adsorption effect, and can well colonize and grow on the surface of intestinal tract to play a role in immunity. The surface of the probiotics and the pathogenic bacteria simultaneously have-CH ₂ -and-CH ₃ The low surface energy functional group can cause co-agglomeration of probiotics and pathogenic bacteria with similar low surface energy groups, the surface roughness of the probiotics is ra=19.5 nm, and the surface roughness of the probiotics is coarser than that of the pathogenic bacteria, so that the probiotics have stronger adhesion effect, and can compete with the pathogenic bacteria for adhesion sites in the oral cavity so as to reduce the number of the pathogenic bacteria. Through the compounding with the prebiotics, the sodium alginate shell is embedded with the probiotics and the prebiotics, so that the survival rate of the probiotics can be remarkably improved, the microsphere shell is broken in the repeated friction process of the friction agent in the toothpaste, and the probiotics and the prebiotics are dissolved out, so that the effects of bacteriostasis, antibiosis and oral health protection are achieved.

Xylo-oligosaccharide and fructo-oligosaccharide are prebiotics, and the fructo-oligosaccharide can selectively proliferate bifidobacteria, so that the microecological balance of intestinal tracts is regulated, and the health of the intestinal tracts is maintained. The xylo-oligosaccharide is also called xylo-oligosaccharide, is a functional polymeric sugar formed by combining 2-7 xylose molecules with beta-1, 4 glycosidic bonds, is difficult to decompose by human digestive enzymes, has good acid and thermal stability, has extremely strong bifidobacterium proliferation function, inhibits the growth of harmful bacteria, and enables probiotics to proliferate in a large amount in intestinal tracts. The fructo-oligosaccharide is used as water-soluble dietary fiber, can stimulate intestinal peristalsis after being taken, change osmotic pressure of intestinal contents, increase fecal moisture, play roles in relaxing bowel and relieving constipation, and can also effectively reduce the contents of free fatty acid, triglyceride and serum cholesterol in human body, thereby having an effect of improving cardiovascular diseases such as arteriosclerosis, hypertension and the like. The xylo-oligosaccharide and fructo-oligosaccharide can also be fermented by intestinal bacteria to generate short-chain fatty acids such as acetic acid, propionic acid, butyric acid and the like, lactic acid and the like, reduce the pH value of the intestinal environment, inhibit the growth and reproduction of harmful bacteria and pathogenic bacteria, and reduce the generation and accumulation of endotoxin and putrefying substances in the field.

The modified friction agent and the compound probiotics have antibacterial effect, and the compound probiotics comprise fructo-oligosaccharides which can proliferate beneficial bacteria, so that on one hand, lysozyme and glucanase in the modified friction agent show antibacterial effect, on the other hand, xylo-oligosaccharides and fructo-oligosaccharides form a competitive relationship with pathogenic bacteria through the proliferation of beneficial bacteria, and on the other hand, oral pathogenic bacteria are indirectly inhibited. Under multiple effects, the prepared toothpaste has good antibacterial, plaque removing and stain removing effects.

The invention provides antibacterial stain-removing toothpaste, which is mild and non-irritating, can effectively inhibit the adhesion and aggregation of oral bacteria, simultaneously remove color stain stains on the surfaces of teeth, and can be used for fundamentally removing stains in a synergistic way to inhibit the formation of dental plaque, has the effects of astringing and soothing the nerves and repairing dental ulcers, achieves the effects of nursing the oral cavity and removing the oral stains, can also prevent periodontitis, gingivitis, dental calculus, dental caries, halitosis and other oral diseases, and has wide application prospect.

Detailed Description

The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Nanometer montmorillonite, less than 100nm, content greater than 99%, is purchased from mineral product processing plant in Gangshou county; dipotassium glycyrrhizinate with content of more than 98%, and Gansu general planting biotechnology Co., ltd; sodium azulene sulfonate, content greater than 95%, commercially available from Huzhou Pu Rui biomedical technologies Co., ltd; paeonol content is greater than 98%, and is purchased from Shanghai Yuan Ye Biotechnology Co. Lysozyme, a pale yellow or white solid powder, and glucanase was beta-glucanase, all purchased from the company of biosciences, limited biosciences, henghua, nanning. Lactobacillus paracasei, 200 hundred million cfu/g, purchased from Sesamum indicum Biotechnology Co., ltd; lactobacillus salivarius, which is lactobacillus salivarius JYLS-372, 100 hundred million cfu/g, purchased from Jia Yi bioengineering Co., ltd; fructo-oligosaccharides and xylo-oligosaccharides were purchased from Nanjing pine crown biotechnology limited.

Example 1

The embodiment provides a preparation method of antibacterial stain-removing toothpaste, which specifically comprises the following steps:

s1, surface treatment of nano montmorillonite: soaking nano montmorillonite with particle size smaller than 100nm in 1mol/L NaOH solution for 30min, centrifuging for 15min at 5000r/min, washing with clear water, and drying at 70deg.C for 2h to obtain pretreated nano montmorillonite;

S2, polydopamine modification treatment: adding 15 parts by weight of the pretreated nano montmorillonite prepared in the step S1 into water, performing 1000W ultrasonic dispersion for 20min, adding 17 parts by weight of dopamine hydrochloride and 1 part by weight of catalyst, heating to 50 ℃ for reaction for 2h, centrifuging for 15min 5000r/min, washing with clear water, and drying at 70 ℃ for 2h to obtain polydopamine modified montmorillonite;

the catalyst was a catalyst containing 3wt% of CoCl ₂ Tris-HCl solution with pH 5;

s3, fixing a composite preparation: uniformly mixing 3 parts by weight of dipotassium glycyrrhizinate, 2 parts by weight of sodium azulene sulfonate and 1 part by weight of paeonol, dissolving in 100 parts by weight of 40wt% ethanol water solution, adding 30 parts by weight of polydopamine modified montmorillonite prepared in the step S2, performing 1500W ultrasonic dispersion for 20min, heating to 40 ℃ to react for 1h, performing 5000r/min centrifugation for 15min, washing with clear water, and drying at 70 ℃ for 2h to obtain modified montmorillonite;

s4, coating silicon dioxide: dissolving 5 parts by weight of ethyl orthosilicate in 100 parts by weight of 50wt% ethanol water solution, adding 12 parts by weight of the modified montmorillonite prepared in the step S3, performing 1500W ultrasonic dispersion for 20min, adjusting the pH value of the solution to 8, adding 1 part by weight of cetyl trimethyl ammonium bromide and 0.5 part by weight of tween-40, performing emulsification for 3min, stirring for 3h, performing centrifugation for 15min 5000r/min, washing with clear water, and drying at 70 ℃ for 2h to obtain the modified montmorillonite coated with porous silica;

S5, immobilization of complex enzyme: dissolving 2 parts by weight of lysozyme and 1 part by weight of dextranase in 20 parts by weight of water to obtain an antibacterial enzyme mixed solution, adding 15 parts by weight of the modified montmorillonite coated with the porous silica prepared in the step S4, stirring and fixing for 30min at a rotating speed of 500/min, and volatilizing at normal temperature to obtain a modified friction agent;

s6, preparing microspheres embedded with probiotics and prebiotics: mixing 5 parts by weight of composite probiotics and 2 parts by weight of composite prebiotics into 50 parts by weight of water, adding 17 parts by weight of sodium alginate solution and 2 parts by weight of tween-80 solution into 100 parts by weight of silicone oil, emulsifying by a rapid membrane with the aperture of 1000nm, dripping 10 parts by weight of 3wt% calcium chloride solution, and curing for 30 minutes at normal temperature to obtain microspheres embedded with the probiotics and the prebiotics;

the compound probiotics are a mixture of lactobacillus paracasei and lactobacillus salivarius, and the mass ratio is 3:7;

the compound prebiotics are a mixture of fructo-oligosaccharide and xylo-oligosaccharide, and the mass ratio is 3:1;

s7, preparing antibacterial stain-removing toothpaste: uniformly mixing 20 parts by weight of the modified friction agent prepared in the step S5, 4 parts by weight of the microspheres embedded with the probiotics and the prebiotics prepared in the step S6, 20 parts by weight of polyethylene glycol 400, 0.1 part by weight of saccharin, 1 part by weight of betaine, 0.5 part by weight of xanthan gum, 1 part by weight of lemon essence and 30 parts by weight of water, stirring and mixing for 15min at 1000r/min, and vacuum degassing to form paste, thereby preparing the antibacterial stain-removing toothpaste.

Example 2

The embodiment provides a preparation method of antibacterial stain-removing toothpaste, which specifically comprises the following steps:

s1, surface treatment of nano montmorillonite: soaking nano montmorillonite with particle size smaller than 100nm in 3mol/L KOH solution for 50min, centrifuging for 15min at 5000r/min, washing with clear water, and drying at 70deg.C for 2h to obtain pretreated nano montmorillonite;

s2, polydopamine modification treatment: adding 15 parts by weight of the pretreated nano montmorillonite prepared in the step S1 into water, performing 1000W ultrasonic dispersion for 20min, adding 22 parts by weight of dopamine hydrochloride and 3 parts by weight of catalyst, heating to 70 ℃ for reaction for 3h, centrifuging for 15min 5000r/min, washing with clear water, and drying at 70 ℃ for 2h to obtain polydopamine modified montmorillonite;

the catalyst was a catalyst containing 5wt% of CoCl ₂ Tris-HCl solution with pH 6;

s3, fixing a composite preparation: uniformly mixing 5 parts by weight of dipotassium glycyrrhizinate, 4 parts by weight of sodium azulene sulfonate and 3 parts by weight of paeonol, dissolving in 100 parts by weight of 60wt% ethanol water solution, adding 30 parts by weight of polydopamine modified montmorillonite prepared in the step S2, performing 1500W ultrasonic dispersion for 20min, heating to 50 ℃ to react for 2h, performing 5000r/min centrifugation for 15min, washing with clear water, and drying at 70 ℃ for 2h to obtain modified montmorillonite;

S4, coating silicon dioxide: dissolving 10 parts by weight of methyl orthosilicate in 100 parts by weight of 70wt% ethanol water solution, adding 17 parts by weight of the modified montmorillonite prepared in the step S3, performing 1500W ultrasonic dispersion for 20min, adjusting the pH value of the solution to 9, adding 3 parts by weight of ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and 1 part by weight of tween-60, emulsifying for 5min at 15000r/min, stirring for reacting for 5h, centrifuging for 15min at 5000r/min, washing with clear water, and drying at 70 ℃ for 2h to obtain the modified montmorillonite coated with porous silica;

s5, immobilization of complex enzyme: dissolving 4 parts by weight of lysozyme and 3 parts by weight of glucanase in 20 parts by weight of water to obtain an antibacterial enzyme mixed solution, adding 20 parts by weight of the modified montmorillonite coated with the porous silica prepared in the step S4, stirring and fixing for 50min at a rotating speed of 500/min, and volatilizing at normal temperature to obtain a modified friction agent;

s6, preparing microspheres embedded with probiotics and prebiotics: mixing 10 parts by weight of composite probiotics and 4 parts by weight of composite prebiotics into 50 parts by weight of water, adding 25 parts by weight of sodium alginate and 3 parts by weight of tween-80 for dissolution, adding 100 parts by weight of silicone oil, adding 15 parts by weight of 5wt% calcium chloride solution after emulsification of a rapid membrane with the pore diameter of 3000nm, and curing at normal temperature for 50 minutes to obtain microspheres embedded with the probiotics and the prebiotics;

The compound probiotics are a mixture of lactobacillus paracasei and lactobacillus salivarius, and the mass ratio is 5:7;

the compound prebiotics are a mixture of fructo-oligosaccharide and xylo-oligosaccharide, and the mass ratio is 5:1;

s7, preparing antibacterial stain-removing toothpaste: uniformly mixing 40 parts by weight of the modified friction agent prepared in the step S5, 7 parts by weight of the microspheres embedded with the probiotics and the prebiotics prepared in the step S6, 35 parts by weight of glycerin, 0.2 part by weight of xylitol, 3 parts by weight of betaine, 1.5 parts by weight of sodium carboxymethyl cellulose, 1.5 parts by weight of lemon essence and 50 parts by weight of water, stirring and mixing for 30min at 1200r/min, and vacuum degassing to form paste, thus obtaining the antibacterial stain-removing toothpaste.

Example 3

The embodiment provides a preparation method of antibacterial stain-removing toothpaste, which specifically comprises the following steps:

s1, surface treatment of nano montmorillonite: soaking nano montmorillonite with particle size smaller than 100nm in 2mol/L NaOH solution for 40min, centrifuging for 15min at 5000r/min, washing with clear water, and drying at 70deg.C for 2h to obtain pretreated nano montmorillonite;

s2, polydopamine modification treatment: adding 15 parts by weight of the pretreated nano montmorillonite prepared in the step S1 into water, performing 1000W ultrasonic dispersion for 20min, adding 20 parts by weight of dopamine hydrochloride and 2 parts by weight of catalyst, heating to 60 ℃ to react for 2.5h, centrifuging for 15min at 5000r/min, washing with clear water, and drying at 70 ℃ for 2h to obtain polydopamine modified montmorillonite;

The catalyst was a catalyst containing 4wt% CoCl ₂ Tris-HCl solution with pH 5.5;

s3, fixing a composite preparation: uniformly mixing 4 parts by weight of dipotassium glycyrrhizinate, 3 parts by weight of sodium azulene sulfonate and 2 parts by weight of paeonol, dissolving in 100 parts by weight of 50wt% ethanol water solution, adding 30 parts by weight of polydopamine modified montmorillonite prepared in the step S2, performing 1500W ultrasonic dispersion for 20min, heating to 45 ℃ to react for 1.5h, centrifuging for 15min 5000r/min, washing with clear water, and drying at 70 ℃ for 2h to obtain modified montmorillonite;

s4, coating silicon dioxide: dissolving 7 parts by weight of tetraethoxysilane in 100 parts by weight of 60wt% ethanol water solution, adding 15 parts by weight of the modified montmorillonite prepared in the step S3, performing 1500W ultrasonic dispersion for 20min, adjusting the pH value of the solution to 8.5, adding 2 parts by weight of polyoxyethylene sorbitan fatty acid ester and 0.7 part by weight of tween-80, emulsifying for 4min at 13500r/min, stirring for reacting for 4h, centrifuging for 15min at 5000r/min, washing with clear water, and drying at 70 ℃ for 2h to obtain the modified montmorillonite coated with porous silica;

s5, immobilization of complex enzyme: dissolving 3 parts by weight of lysozyme and 2 parts by weight of glucanase in 20 parts by weight of water to obtain an antibacterial enzyme mixed solution, adding 17 parts by weight of the modified montmorillonite coated with the porous silica prepared in the step S4, stirring and fixing for 40min at a rotating speed of 500/min, and volatilizing at normal temperature to obtain a modified friction agent;

S6, preparing microspheres embedded with probiotics and prebiotics: mixing 7 parts by weight of composite probiotics and 3 parts by weight of composite prebiotics in 50 parts by weight of water, adding 22 parts by weight of sodium alginate and 2.5 parts by weight of tween-80 for dissolution, adding 100 parts by weight of silicone oil, emulsifying by a rapid membrane with the aperture of 2000nm, dripping 12 parts by weight of 4wt% calcium chloride solution, and curing at normal temperature for 40min to obtain microspheres embedded with the probiotics and the prebiotics;

the compound probiotics are a mixture of lactobacillus paracasei and lactobacillus salivarius, and the mass ratio is 4:7;

the compound prebiotics are a mixture of fructo-oligosaccharide and xylo-oligosaccharide, and the mass ratio is 4:1;

s7, preparing antibacterial stain-removing toothpaste: uniformly mixing 30 parts by weight of the modified friction agent prepared in the step S5, 5 parts by weight of the microspheres embedded with the probiotics and the prebiotics prepared in the step S6, 27 parts by weight of polyethylene glycol 400, 0.15 part by weight of sucralose, 2 parts by weight of betaine, 1 part by weight of carrageenan, 1.2 parts by weight of lemon essence and 40 parts by weight of water, stirring and mixing for 20min at 1100r/min, and vacuum degassing to obtain paste, thereby preparing the antibacterial stain-removing toothpaste.

Example 4

The difference compared to example 3 is that the complex probiotics are single lactobacillus paracasei.

Example 5

The difference compared to example 3 is that the complex probiotics are single lactobacillus salivarius.

Example 6

The difference compared to example 3 is that the complex prebiotic is a single fructooligosaccharide.

Example 7

The difference compared to example 3 is that the complex prebiotic is a single xylo-oligosaccharide.

Comparative example 1

In comparison with example 3, the difference is that step S2 is not performed.

Comparative example 2

The difference from example 3 is that dipotassium glycyrrhizinate was not added in step S3.

Comparative example 3

The difference compared with example 3 is that sodium azulene sulfonate was not added in step S3.

Comparative example 4

The difference compared to example 3 is that paeonol is not added in step S3.

Comparative example 5

In comparison with example 3, the difference is that step S3 is not performed.

Comparative example 6

In comparison with example 3, the difference is that step S4 is not performed.

Comparative example 7

The difference compared to example 3 is that no lysozyme was added in step S5.

Comparative example 8

The difference compared to example 3 is that no glucanase is added in step S5.

Comparative example 9

In comparison with example 3, the difference is that step S5 is not performed.

Comparative example 10

The difference compared to example 3 is that no complex probiotics are added in step S6.

Comparative example 11

The difference compared to example 3 is that no complex prebiotics are added in step S6.

Comparative example 12

The difference compared to example 3 is that the complex probiotics and complex prebiotics are simply mixed in step S6, without sodium alginate entrapment.

Comparative example 13

The difference compared to example 3 is that the modified abrasive is replaced by an equal amount of silica in step S7.

Comparative example 14

The difference compared to example 3 is that no microspheres embedding probiotics and prebiotics are added in step S7.

Comparative example 15

The difference compared to example 3 is that no microspheres embedding probiotics and prebiotics are added in step S7, the modified abrasive is replaced by an equal amount of silica.

Test example 1 inhibition of Actinobacillus actinomycetemcomitans ATCC 29523

Strain sources: actinobacillus concomitatus ATCC 29523 is provided by the national academy of sciences of Guangdong province. Streptococcus mutans CGMCC 12499, fusobacterium nucleatum ATCC25586, provided by university of Jiangsu food institute.

Preparing bacterial liquid:

1. actinomycetes companion bacterial liquid: culturing actinobacillus actinomyces ATCC 29523 with blood plate culture medium (TSA+5% defibrinated sheep blood) at 37deg.C and 5% CO ₂ Culturing for 48 hr under environment, and adjusting thallus concentration to 1×10 with PBS phosphate buffer solution (pH=7.2) ⁹ CFU/mL。

2. Streptococcus mutans CGMCC 12499 bacterial liquid: inoculating Streptococcus mutans CGMCC 12499 bacteria on blood plate, and placing into a culture medium containing 80% N ₂ 、10％ H ₂ 、10％ CO ₂ Culturing in anaerobic bag at 37deg.C for 48 hr, and regulating thallus concentration to 1×10 ⁹ CFU/mL。

3. Fusobacterium nucleatum ATCC25586: inoculating Fusobacterium nucleatum ATCC25586 on blood plate, placing into the culture medium containing 80% N ₂ 、10％ H ₂ 、10％ CO ₂ Culturing in anaerobic bag at 37deg.C for 48 hr, and regulating thallus concentration to 1×10 ⁹ CFU/mL。

Repeatedly rubbing 1mL of the antibacterial stain-removing toothpaste prepared in examples 1-7 and comparative examples 1-15 with a toothbrush for 5min, adding into 50mL of water, and mixing uniformly to obtain toothpaste liquid;

(1) 100 mu L of prepared toothpaste is sucked into oxford cup holes by using actinobacillus actinomyces, streptococcus mutans and clostridium nucleatum suspension respectively through a oxford cup double-layer plate method, and the diameter of a bacteriostasis ring is measured after a culture dish is cultured for 48 hours at 37 ℃, and the results are shown in table 1.

TABLE 1

(2) Mixing with prepared actinobacillus concomitans, streptococcus mutans and clostridium nucleatum bacterial suspension according to the volume of 1:1, standing for 1h, gently sucking 100 mu L of supernatant, diluting by a ten-fold dilution method, sucking 100 mu L of dilution liquid with different proportions, culturing at 37 ℃ for 48h, counting, comparing the reduction amount of actinobacillus concomitans, and obtaining the result shown in Table 2.

TABLE 2

As shown in the table above, the antibacterial stain-removing toothpaste prepared in the examples 1-3 of the invention has good effects of inhibiting actinobacillus actinomycetemcomitans, streptococcus mutans and fusobacterium nucleatum after use.

Test example 2 stability test

The antibacterial stain-removing toothpaste prepared in examples 1-7 and comparative examples 1-15 was subjected to an accelerated test, placed in an electrothermal constant temperature oven at 45 ℃ for 3 months, taken out and compared with a sample stored at normal temperature, and the appearance, fragrance and pH value of the high temperature sample were observed to infer the stability of the toothpaste within 3 years of shelf life.

The results are shown in Table 3

TABLE 3 Table 3

As is clear from the above table, in the acceleration test of the antibacterial stain-removing toothpaste prepared in examples 1 to 3 of the present invention, the appearance, fragrance and pH value were not greatly changed after the toothpaste was left at 45℃for 3 months.

Test example 3 Effect of paraxylene on mouse auricle swelling

240 NIH male mice (SPF grade) were divided into 24 groups, distilled water was used as a negative control group, fluocinolone acetonide ointment was used as a positive control group, and antibacterial stain-removing toothpastes prepared in examples 1 to 7 and comparative examples 1 to 15 were used as test groups 1 to 7 and comparative groups 1 to 15.

The animals in each group are respectively given corresponding test substances at the right ear except the negative control group after 30min of xylene inflammation, the dosage is 0.1 g/animal, and the animals are uniformly smeared on the inner and outer surfaces of the right auricle when being given. The right auricle of the negative control group animals was given distilled water at a dose of 0.1 mL/animal. After the test object is given for 1h, the cervical vertebra of the animal is dislocation and sacrificed, auricles on two sides are cut off, the test object on the right auricle is cleaned by normal saline, and the water cost is wiped. Overlapping auricles on two sides, punching down left and right lugs by using a puncher with the diameter of 8mm, weighing the lugs respectively, and calculating a swelling value, wherein the smaller the swelling value is, the better the anti-inflammatory effect is.

Swelling value = m _{Right ear tab} -m _{Left ear tab}

The results are shown in Table 4.

TABLE 4 Table 4

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Note that: p < 0.01 and P < 0.05 compared to the negative control group.

As shown in the table above, the antibacterial stain-removing toothpaste prepared in the examples 1-3 of the invention has good anti-inflammatory effect.

Test example 4

The antibacterial stain-removing toothpastes prepared in examples 1 to 7 and comparative examples 1 to 15, and the friction value Ra of the commercially available toothpastes of the same kind were tested by the toothpaste friction value test method (GB/T35832-2018), and the results are shown in Table 5.

TABLE 5

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As can be seen from the above table, the antibacterial stain-removing toothpaste prepared in examples 1 to 3 of the present invention has a relatively low friction value. When the toothpaste with a large friction value is used for a long time, the toothpaste can clean teeth well, but also abrade teeth, so that enamel is lost. The higher the abrasion value is, the higher the abrasion degree of teeth is, the whitening toothpaste has the effect of removing facial stains, and the abrasive cleaning and stain removing effects are higher than those of other types of toothpastes, so that the friction value is also improved to a certain extent. The toothpaste is selected from products with high cleaning rate and relatively small friction value. The dental plaque can be well removed by inhibiting the growth of harmful bacteria in the oral cavity, and the teeth can be better cleaned and whitened by the interaction between different abrasive materials and the moderate friction with the teeth.

Examples 4 and 5 are different from example 3 in that the composite probiotics are single Lactobacillus paracasei or Lactobacillus salivarius, and the inhibition effect on actinobacillus, streptococcus mutans, and Fusobacterium nucleatum is reduced. Comparative example 10 differs from example 3 in that no complex probiotics were added in step S6The bacteria have obviously reduced inhibition effect on actinobacillus actinomycetemcomitans, streptococcus mutans and fusobacterium nucleatum. Lactobacillus paracasei is the most common lactobacillus in oral microbiota, and the inactivated bacteria powder can generate coagulation and precipitation with oral pathogenic bacteria. The lactobacillus salivarius can inhibit the growth of caries pathogenic bacteria, thereby preventing and treating caries, and has a certain adsorption effect, and can well colonize and grow on the surface of intestinal tract to play a role in immunity. The surface of the probiotics and the pathogenic bacteria simultaneously have-CH ₂ -and-CH ₃ The low surface energy functional group can cause co-agglomeration of probiotics and pathogenic bacteria with similar low surface energy groups, the surface roughness of the probiotics is ra=19.5 nm, and the surface roughness of the probiotics is coarser than that of the pathogenic bacteria, so that the probiotics have stronger adhesion effect, and can compete with the pathogenic bacteria for adhesion sites in the oral cavity so as to reduce the number of the pathogenic bacteria. The probiotics can compete with oral pathogenic bacteria for binding sites to block the colonization of pathogenic bacteria, so that pathogenic bacteria are discharged from the oral cavity, and the oral health is improved. The metabolites produced by probiotics, such as organic acids, bacteriocins, etc., can effectively inhibit the growth of pathogenic bacteria and the formation of biological films.

Examples 6 and 7 are different from example 3 in that the complex prebiotics are single fructo-oligosaccharides or xylo-oligosaccharides, and the inhibition effect on actinobacillus actinomycetes, streptococcus mutans and fusobacterium nucleatum is slightly reduced. Comparative example 11 is different from example 3 in that the inhibition effect on actinobacillus actinomycetemcomitans, streptococcus mutans, and fusobacterium nucleatum is reduced in step S6 without adding the complex prebiotics. Xylo-oligosaccharide and fructo-oligosaccharide are prebiotics, and the fructo-oligosaccharide can selectively proliferate bifidobacteria, so that the microecological balance of intestinal tracts is regulated, and the health of the intestinal tracts is maintained. The xylo-oligosaccharide is also called xylo-oligosaccharide, is a functional polymeric sugar formed by combining 2-7 xylose molecules with beta-1, 4 glycosidic bonds, is difficult to decompose by human digestive enzymes, has good acid and thermal stability, has extremely strong bifidobacterium proliferation function, inhibits the growth of harmful bacteria, and enables probiotics to proliferate in a large amount in intestinal tracts. The fructo-oligosaccharide is used as water-soluble dietary fiber, can stimulate intestinal peristalsis after being taken, change osmotic pressure of intestinal contents, increase fecal moisture, play roles in relaxing bowel and relieving constipation, and can also effectively reduce the contents of free fatty acid, triglyceride and serum cholesterol in human body, thereby having an effect of improving cardiovascular diseases such as arteriosclerosis, hypertension and the like. The xylo-oligosaccharide and fructo-oligosaccharide can also be fermented by intestinal bacteria to generate short-chain fatty acids such as acetic acid, propionic acid, butyric acid and the like, lactic acid and the like, reduce the pH value of the intestinal environment, inhibit the growth and reproduction of harmful bacteria and pathogenic bacteria, and reduce the generation and accumulation of endotoxin and putrefying substances in the field.

Comparative example 1 is different from example 3 in that step S2 was not performed, the inhibition effect on actinobacillus actinomycetemcomitans, streptococcus mutans and Fusobacterium nucleatum was reduced, the swelling value was increased, and the appearance of the paste was slightly changed after 3 months at 45 ℃. Comparative example 6 is different from example 3 in that step S4 was not performed, the inhibition effect on actinobacillus actinomycetemcomitans, streptococcus mutans and Fusobacterium nucleatum was decreased, and the friction value Ra was decreased. According to the invention, polydopamine is modified on the surface of nano montmorillonite, and groups such as rich hydroxyl, amino and carboxyl groups of polydopamine can form hydrogen bond fixation with dipotassium glycyrrhizinate, paeonol and sodium azulenesulfonate, so that the composite preparation can be stably fixed on polydopamine modified montmorillonite, and further through sol-gel reaction, a layer of porous silica (under the action of a pore-forming agent) is coated on the surface, the strength of particles can be further enhanced by coating the porous silica, and meanwhile, a larger specific surface area is provided, so that abundant site fixation is provided for lysozyme and glucanase, and the prepared modified friction agent not only can play the function of the friction agent, but also can play the effects of an antibacterial agent, an anti-inflammatory agent and the like.

Comparative examples 2, 3 and 4 are different from example 3 in that dipotassium glycyrrhizinate, sodium azulenesulfonate or paeonol is not added in step S3, the inhibition effect on actinobacillus, streptococcus mutans and fusobacterium nucleatum is reduced, and the swelling value is improved. Comparative example 5 is different from example 3 in that step S3 was not performed, the inhibition effect on actinobacillus actinomycetemcomitans, streptococcus mutans and Fusobacterium nucleatum was significantly reduced, and the swelling value was significantly increased. Dipotassium glycyrrhizinate can inhibit and kill actinobacillus and streptococcus mutans, thereby completely inhibiting dental plaque formation. Paeonol is colorless or white or yellowish glossy needle crystal, has strong antibacterial effect on Staphylococcus aureus, streptococcus faecalis, escherichia coli, etc., and has tranquilizing, antiinflammatory, antipyretic, antiallergic, etc. Sodium azulene sulfonate is an active ingredient of chamomile, has strong pepsin resistance, anti-inflammation, antibacterial, antiallergic and mucosa metabolism promoting effects, and inhibits inflammatory cells from releasing histamine through local direct action; increase synthesis of prostaglandin E2 in mucosa, promote granulation and epithelial cell regeneration, and has good effect of repairing epithelial cells with high safety. The three components are compounded and enter the oral cavity, so that the surface of harmful bacteria becomes uneven, partial bacteria are broken, intracellular substances flow out, the integrity of bacterial cells is destroyed, and the prepared toothpaste has good effects of inhibiting bacteria, resisting bacteria, diminishing inflammation, relieving fever, repairing epithelial cells and promoting mucosa metabolism, and can effectively inhibit the formation of dental plaque, inhibit gingival bleeding, loosening teeth, halitosis and repairing dental ulcer.

Comparative examples 7 and 8 are different from example 3 in that no lysozyme or glucanase was added in step S5, the inhibition effect on actinobacillus, streptococcus mutans and fusobacterium nucleatum was significantly reduced, and the swelling value was increased. Comparative example 9 is different from example 3 in that step S5 was not performed, the inhibition effect on actinobacillus actinomycetemcomitans, streptococcus mutans and Fusobacterium nucleatum was significantly reduced, and the swelling value was significantly increased. Streptococcus mutans has been widely recognized as a major causative agent of dental caries in oral bacteria. The mechanism responsible for caries formation is that Glucosyltransferases (GTFs) in streptococcus mutans break down sucrose and synthesize extracellular polysaccharides that can attach to the tooth surface, and on the other hand, acids produced by streptococcus mutans promote tooth demineralization, which is exacerbated by the presence of oral sugars, which are critical to protect the teeth, prevent glucan synthesis and acid production. Streptococcus mutans can synthesize alpha-1, 6 glycosidic chain-enriched glucans, alpha-1, 3 glycosidic chain-enriched glucans, and water-soluble glucans by the resulting glucosyltransferase. Glucanase is capable of efficiently decomposing glucan produced by Streptococcus mutans, thereby preventing caries and plaque formation. Lysozyme is a nonspecific substance component, can inhibit microbial growth, and can not generate drug resistance after long-term use. The lysozyme can effectively hydrolyze peptidoglycan of bacterial cell walls, and has different content of peptidoglycan in cell walls of gram-positive bacteria (G+), such as staphylococcus aureus, bacillus subtilis, micrococcus muralis and the like, and gram-negative bacteria (G-), such as escherichia coli, clostridium nucleatum, porphyromonas gingivalis, pneumobacillus and the like, and the cell walls of G+ bacteria almost completely consist of peptidoglycan, and only the inner wall layers of G-bacteria are peptidoglycan, so that the lysozyme has good inhibition and killing effects on G+ bacteria and also has a certain inhibition effect on G-bacteria. Lysozyme can selectively lyse the cell wall of the target microorganism to inactivate it, and the mammal has no cell wall, so that lysozyme has no damage to oral tissues, but plays a role in protection.

Comparative example 12 is different from example 3 in that the complex probiotics and complex prebiotics in step S6 are simply mixed, sodium alginate embedding is not performed, inhibition effect on actinobacillus actinomycetes, streptococcus mutans and fusobacterium nucleatum is obviously reduced, and swelling value is improved. Through the compounding with the prebiotics, the sodium alginate shell is embedded with the probiotics and the prebiotics, so that the survival rate of the probiotics can be remarkably improved, the microsphere shell is broken in the repeated friction process of the friction agent in the toothpaste, and the probiotics and the prebiotics are dissolved out, so that the effects of bacteriostasis, antibiosis and oral health protection are achieved.

Comparative example 13 is different from example 3 in that the modified abrasive is replaced with an equivalent amount of silica in step S7, the inhibition effect on actinobacillus actinomycetes, streptococcus mutans, fusobacterium nucleatum is significantly reduced, the swelling value is significantly improved, and the friction value Ra is improved. Comparative example 14 is different from example 3 in that the inhibition effect on actinobacillus actinomycetemcomitans, streptococcus mutans, and fusobacterium nucleatum is significantly reduced in step S7 without adding the microspheres embedding probiotics and prebiotics. Comparative example 15 is different from example 3 in that the microspheres embedded with probiotics and prebiotics are not added in step S7, the modified abrasive is replaced by equal amount of silica, the inhibition effect on actinobacillus actinomycetes, streptococcus mutans and fusobacterium nucleatum is obviously reduced, the swelling value is obviously improved, and the friction value Ra is improved. The modified friction agent and the compound probiotics have antibacterial effect, and the compound probiotics comprise fructo-oligosaccharides which can proliferate beneficial bacteria, so that on one hand, lysozyme and glucanase in the modified friction agent show antibacterial effect, on the other hand, xylo-oligosaccharides and fructo-oligosaccharides form a competitive relationship with pathogenic bacteria through the proliferation of beneficial bacteria, and on the other hand, oral pathogenic bacteria are indirectly inhibited. Under multiple effects, the prepared toothpaste has good antibacterial, plaque removing and stain removing effects.

The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.

Claims (9)

1. The preparation method of the antibacterial stain-removing toothpaste is characterized by comprising the following steps of:

s1, surface treatment of nano montmorillonite: soaking nano montmorillonite in alkali liquor, centrifuging, washing and drying to obtain pretreated nano montmorillonite;

s2, polydopamine modification treatment: uniformly dispersing the pretreated nano montmorillonite prepared in the step S1 in water, adding dopamine hydrochloride and a catalyst, heating for reaction, centrifuging, washing and drying to obtain polydopamine modified montmorillonite; the mass ratio of the pretreated nano montmorillonite to the dopamine hydrochloride to the catalyst is 15:17-22:1-3;

s3, fixing a composite preparation: uniformly mixing dipotassium glycyrrhizinate, sodium azulene sulfonate and paeonol, dissolving in an ethanol water solution, adding the polydopamine modified montmorillonite prepared in the step S2, uniformly dispersing by ultrasonic, heating for reaction, centrifuging, washing and drying to obtain modified montmorillonite; the mass ratio of the dipotassium glycyrrhizinate to the sodium azulene sulfonate to the paeonol to the polydopamine modified montmorillonite is 3-5:2-4:1-3:30;

S4, coating silicon dioxide: dissolving alkyl orthosilicate in ethanol water solution, adding the modified montmorillonite prepared in the step S3, uniformly dispersing by ultrasonic, adjusting the pH value of the solution to be alkaline, adding a pore-forming agent and an emulsifying agent, emulsifying, stirring for reaction, centrifuging, washing and drying to obtain the modified montmorillonite coated with porous silicon dioxide; the mass ratio of the alkyl orthosilicate to the modified montmorillonite to the pore-forming agent to the emulsifier is 5-10:12-17:1-3:0.5-1;

s5, immobilization of complex enzyme: dissolving lysozyme and glucanase in water to obtain an antibacterial enzyme mixed solution, adding the modified montmorillonite coated with the porous silica prepared in the step S4, stirring and fixing, and volatilizing at normal temperature to obtain a modified friction agent; the mass ratio of the lysozyme to the glucanase to the modified montmorillonite coated with the porous silicon dioxide is 2-4:1-3:15-20;

s6, preparing microspheres embedded with probiotics and prebiotics: mixing the composite probiotics and the composite prebiotics in water, adding sodium alginate for dissolution, adding the mixture into silicone oil, quickly emulsifying the mixture by a film, dripping a calcium chloride solution, and curing the mixture at normal temperature to obtain microspheres embedded with the probiotics and the prebiotics; the mass ratio of the composite probiotics to the composite prebiotics to the sodium alginate is 5-10:2-4:17-25;

S7, preparing antibacterial stain-removing toothpaste: uniformly mixing the modified friction agent prepared in the step S5, the microspheres embedded with probiotics and prebiotics prepared in the step S6, a humectant, a sweetener, a foaming agent, a thickening agent, essence and water, stirring and mixing at a high speed, and vacuum degassing to obtain paste, thus obtaining the antibacterial stain-removing toothpaste; the mass ratio of the modified friction agent to the microspheres embedded with probiotics to the prebiotics to the humectant to the sweetener to the foaming agent to the thickener to the essence to the water is 20-40:4-7, 20-35, 0.1-0.2, 1-3, 0.5-1.5, 1-1.5 and 30-50.

2. The preparation method according to claim 1, wherein the nano montmorillonite in the step S1 has a particle size smaller than 100nm, the alkali solution is 1-3mol/L NaOH or KOH solution, and the soaking time is 30-50min; the catalyst in step S2 is a catalyst containing 3-5wt% of CoCl ₂ The temperature of the heating reaction is 50-70 ℃ and the time is 2-3h.

3. The preparation method according to claim 1, wherein the concentration of ethanol in the aqueous ethanol solution in step S3 is 40-60wt% and the balance is water, and the heating reaction is performed at a temperature of 40-50 ℃ for a time of 1-2 hours; the alkyl orthosilicate in the step S4 is ethyl orthosilicate or methyl orthosilicate, the ethanol content in the ethanol aqueous solution is 50-70wt%, the balance is water, the pH value of the solution is adjusted to 8-9, the condition of emulsification is 12000-15000r/min, the emulsification is carried out for 3-5min, the pore-forming agent is at least one selected from polyoxyethylene sorbitan fatty acid ester, polyethylene glycol octyl phenyl ether, cetyl trimethyl ammonium bromide, ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and PEO106-PPO70-PEO10, and the emulsifying agent is at least one selected from Tween-20, tween-40, tween-60 and Tween-80.

4. The preparation method according to claim 1, wherein the compound probiotics in the step S6 are at least two selected from lactobacillus acidophilus, lactobacillus paracasei and lactobacillus salivarius, the compound probiotics are selected from fructo-oligosaccharides, galacto-oligosaccharides, xylo-oligosaccharides, isomaltooligosaccharides, soy oligosaccharides and inulin, the concentration of the calcium chloride solution is 3-5wt%, the pore diameter of the membrane in the rapid membrane emulsification is 1000-3000nm, and the normal temperature solidification time is 30-50min.

5. The preparation method according to claim 4, wherein the compound probiotics are a mixture of lactobacillus paracasei and lactobacillus salivarius, and the mass ratio is 3-5:7; the compound prebiotics are a mixture of fructo-oligosaccharide and xylo-oligosaccharide, and the mass ratio is 3-5:1.

6. The method according to claim 1, wherein the high-speed stirring and mixing in step S7 is performed at a rotational speed of 1000-1200r/min for 15-30min.

7. The method of claim 1, wherein the humectant is at least one member selected from the group consisting of glycerin, sorbitol, and polyethylene glycol 400; the sweetener is at least one selected from sucralose, aspartame, acesulfame potassium, sodium cyclamate, saccharin and xylitol; the foaming agent is betaine; the thickener is at least one selected from xanthan gum, carrageenan and sodium carboxymethyl cellulose.

8. The preparation method according to claim 1, characterized by comprising the following steps:

s1, surface treatment of nano montmorillonite: soaking nano montmorillonite with particle size smaller than 100nm in 1-3mol/L NaOH or KOH solution for 30-50min, centrifuging, washing, and drying to obtain pretreated nano montmorillonite;

s2, polydopamine modification treatment: uniformly dispersing 15 parts by weight of the pretreated nano montmorillonite prepared in the step S1 in water, adding 17-22 parts by weight of dopamine hydrochloride and 1-3 parts by weight of catalyst, heating to 50-70 ℃ for reacting for 2-3 hours, centrifuging, washing and drying to obtain polydopamine modified montmorillonite;

the catalyst contains 3-5wt% of CoCl ₂ Tris-HCl solution with pH value of 5-6;

s3, fixing a composite preparation: uniformly mixing 3-5 parts by weight of dipotassium glycyrrhizinate, 2-4 parts by weight of sodium azulene sulfonate and 1-3 parts by weight of paeonol, dissolving in 100 parts by weight of 40-60wt% ethanol water solution, adding 30 parts by weight of polydopamine modified montmorillonite prepared in the step S2, uniformly dispersing by ultrasonic, heating to 40-50 ℃ for reacting for 1-2 hours, centrifuging, washing and drying to obtain modified montmorillonite;

s4, coating silicon dioxide: dissolving 5-10 parts by weight of tetraethoxysilane or tetramethylsilicate in 100 parts by weight of 50-70wt% ethanol water solution, adding 12-17 parts by weight of the modified montmorillonite prepared in the step S3, uniformly dispersing by ultrasonic, adjusting the pH value of the solution to 8-9, adding 1-3 parts by weight of pore-forming agent and 0.5-1 part by weight of emulsifying agent, emulsifying for 3-5min at 12000-15000r/min, stirring for reaction, centrifuging, washing and drying to obtain the modified montmorillonite coated with porous silica;

S5, immobilization of complex enzyme: dissolving 2-4 parts by weight of lysozyme and 1-3 parts by weight of dextranase in 20 parts by weight of water to obtain an antibacterial enzyme mixed solution, adding 15-20 parts by weight of the modified montmorillonite coated with the porous silica prepared in the step S4, stirring and fixing, and volatilizing at normal temperature to obtain a modified friction agent;

s6, preparing microspheres embedded with probiotics and prebiotics: mixing 5-10 parts by weight of composite probiotics and 2-4 parts by weight of composite prebiotics in 50 parts by weight of water, adding 17-25 parts by weight of sodium alginate and 2-3 parts by weight of emulsifying agent for dissolution, adding 100 parts by weight of silicone oil, adding a rapid membrane with the aperture of 1000-3000nm for emulsification, dropwise adding 10-15 parts by weight of 3-5wt% of calcium chloride solution, and curing at normal temperature for 30-50min to obtain microspheres embedded with the probiotics and the prebiotics;

the compound probiotics are a mixture of lactobacillus paracasei and lactobacillus salivarius, and the mass ratio is 3-5:7;

the compound prebiotics are a mixture of fructo-oligosaccharide and xylo-oligosaccharide, and the mass ratio is 3-5:1;

s7, preparing antibacterial stain-removing toothpaste: uniformly mixing 20-40 parts by weight of the modified friction agent prepared in the step S5, 4-7 parts by weight of the microspheres embedded with probiotics and prebiotics prepared in the step S6, 20-35 parts by weight of humectant, 0.1-0.2 part by weight of sweetener, 1-3 parts by weight of foaming agent, 0.5-1.5 parts by weight of thickener, 1-1.5 parts by weight of essence and 30-50 parts by weight of water, stirring and mixing for 15-30min at 1000-1200r/min, and vacuum degassing to obtain the antibacterial stain-removing toothpaste.

9. A bacteriostatic stain-removing toothpaste prepared by the preparation method as claimed in any one of claims 1 to 8.