Oral care composition for enhancing antibacterial efficiency and application thereof in oral care

Abstract

According to the oral care composition capable of enhancing the antibacterial efficiency, provided by the invention, on the basis of keeping an effective component domiphen, glyceryl stearate is adopted as solid lipid nanoparticles to load domiphen, so that the antibacterial characteristic of domiphen can be effectively exerted, and meanwhile, the stability and durability of domiphen in an oral environment are improved; and potential stimulation to oral mucosa is reduced.

Description

Technical Field

[0001] The invention relates to the field of oral care, and in particular to an oral care composition with enhanced antibacterial efficacy and application thereof in oral care. Background Art

[0002] Mouthwash is an auxiliary product for oral hygiene care. Its role is not limited to covering up bad breath, but also includes cleaning the mouth, removing food debris, reducing the number of bacteria, and preventing oral diseases. The active ingredients contained in these products can quickly take effect on the oral environment, reaching hard-to-clean areas including the gaps between teeth, and assist in maintaining oral hygiene. As people pay more attention to personal hygiene and appearance, mouthwash has become a part of many people's daily hygiene habits.

[0003] Among various antibacterial ingredients, domiphene is recognized for its antibacterial effect and safety. As a cationic surfactant, domiphene can bind to the bacterial cell wall, destroy the cell structure, and effectively reduce the pathogens in the oral cavity. It has a broad-spectrum antibacterial property and has an inhibitory effect on many common oral pathogens, such as Streptococcus mutans and Porphyromonas gingivalis.

[0004] However, current mouthwash products containing domiphene encounter some difficulties in practical application. First, the antibacterial effect of domiphene in the mouth may lack persistence, which is mainly due to the variability of the oral environment, including factors such as pH, temperature, saliva composition and fluidity, all of which may affect the effect of antibacterial agents. In particular, when the oral environment is acidic, the activity of domiphene may be reduced.

[0005] Secondly, the flow of saliva in the mouth and the pH changes caused by eating habits may quickly reduce the concentration of antibacterial components in mouthwash, affecting the duration of its antibacterial effect. Long-term reliance on a single antibacterial mechanism may disrupt the normal balance of oral flora and affect the natural defense capabilities of the mouth.

[0006] In addition, as a cationic surfactant, domiphene may interact with the oral mucosa. If used improperly, it may cause mucosal irritation or discomfort, affecting the user's experience.

[0007] Therefore, the development of new mouthwash products, aimed at effectively exerting the antibacterial properties of domiphene, while improving its stability and persistence in the oral environment and reducing potential irritation to the oral mucosa, is the key to the development of oral care products. This involves improving the existing formula of domiphene, exploring more efficient carrier systems and auxiliary ingredients, and in-depth research on factors affecting the oral environment. Summary of the invention

[0008] The present invention aims to provide an oral care composition with enhanced antibacterial efficacy. On the basis of maintaining the active ingredient domiphene, stearyl glyceryl is used as solid lipid nanoparticles to load domiphene, which can effectively exert the antibacterial properties of domiphene, while improving its stability and durability in the oral environment, and reducing potential irritation to the oral mucosa. In addition, the present invention also provides a preparation method of the oral care composition and its application in oral care. The details are as follows:

[0009] The present invention provides an oral care liquid composition with enhanced antibacterial efficacy, which comprises the following components based on 100 wt% of the total amount of the oral care liquid composition:

[0010] Solid lipid nanoparticles loaded with domiphene (SLN-domiphene) 0.2-5.0wt%, preferably 0.5-3.0wt%;

[0011] Fluoride 0.01-0.05wt%, preferably 0.02-0.04wt%;

[0012] pH regulator 0.2-1wt%, preferably 0.5-0.8wt%;

[0013] Preservative 0.05%-0.3wt%, preferably 0.1-0.2wt%;

[0014] and the balance is pure water;

[0015] Wherein the solid lipid nanoparticles loaded with domiphene are prepared by the following method:

[0016] (1) Melting and mixing: mixing glyceryl stearate and domiphene in a weight ratio of 95:5 to 99:1, and heating to 75-80° C. to ensure that the domiphene is evenly dispersed to form a liquid mixture;

[0017] (2) Cooling and emulsification: The molten mixture is rapidly cooled to 0-5°C and added to an aqueous phase containing an emulsifier (such as lecithin or Tween 80) under continuous stirring to form an oil-water emulsion;

[0018] (3) High-pressure homogenization: The emulsion is homogenized using a high-pressure homogenizer. The shear force generated by the high pressure refines the emulsion droplets to a particle size of 50-200 nm to form a dispersed system of solid lipid nanoparticles (SLNs);

[0019] (4) Solidification and washing: The homogenized emulsion is solidified at a low temperature of 0-5°C to form solid lipid nanoparticles, and the unencapsulated drugs and emulsifiers are removed by centrifugation to collect the solid lipid nanoparticles.

[0020] In one embodiment, the high-pressure homogenizer in step (3) homogenizes the emulsion by setting the homogenization pressure to 100-200 MPa and performing 5-10 homogenization cycles until the emulsion droplets are refined to a particle size of 50-200 nm and the polydispersity index of the solid lipid nanoparticles is less than 0.3;

[0021] In one embodiment, the centrifugation condition in step (4) is 10000-15000 rad / min for 10-20 minutes;

[0022] In one embodiment, the emulsifier is selected from one or more of lecithin, Tween 20, Tween 80, Span 80, and polysorbate 80; preferably lecithin or Tween 80; based on the total weight (solid content) of SLNs, the amount of the emulsifier added is 2-10wt%;

[0023] In one embodiment, the fluoride is selected from one or more of sodium fluoride, ammonium fluoride, stannous fluoride, and sodium monofluorophosphate, preferably sodium fluoride or sodium monofluorophosphate;

[0024] In one embodiment, the pH regulator is selected from one or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate and sodium carbonate, preferably sodium bicarbonate or disodium hydrogen phosphate;

[0025] In one embodiment, the preservative is selected from one or more of phenoxyethanol, parabens, santolin, and ε-polyphenol, preferably phenoxyethanol or parabens.

[0026] In one embodiment, the oral care liquid composition further includes the following auxiliary components:

[0027] Moisturizer: 0.5%-2.0%

[0028] Natural antibacterial ingredients; 0.1%-1.0%

[0029] Antioxidant: 0.01%-0.1%

[0030] Prebiotics: 0.5%-1.5%

[0031] Fragrance: 0.01%-0.2%

[0032] Sweetener: 0.1%-0.5%

[0033] In one embodiment, the moisturizing agent is selected from one or more of glycerol, sorbitol, propylene glycol, and sodium hyaluronate, preferably glycerol or sodium hyaluronate;

[0034] In one embodiment, the natural antibacterial ingredient is selected from one or more of green tea extract, tea tree oil, calendula extract, and garlic extract, preferably green tea extract or tea tree oil;

[0035] In one embodiment, the antioxidant is selected from one or more of vitamin E, vitamin C, selenium, and coenzyme Q10, preferably vitamin E or vitamin C;

[0036] In one embodiment, the prebiotic is selected from one or more of fructan, oligofructose, inulin, and β-glucan, preferably fructan or oligofructose;

[0037] In one embodiment, the fragrance is selected from one or more of peppermint oil, spearmint essential oil, limonene, and eucalyptus oil, preferably peppermint oil or spearmint essential oil;

[0038] In one embodiment, the sweetener is selected from one or more of xylitol, stevioside, erythritol, and aspartame, preferably xylitol or stevioside;

[0039] The present invention also provides a method for preparing the oral care liquid composition, comprising the following steps:

[0040] 1) Solid lipid nanoparticle loading of domiphene: Stearyl glyceryl and domiphene were mixed and melted at 75-80° C. according to the above method to form a uniform liquid mixture, and then solid lipid nanoparticles were prepared through high pressure homogenization and solidification washing steps;

[0041] 2) Raw material preparation: accurately weighing domiphene, fluoride, preservatives and auxiliary ingredients loaded on solid lipid nanoparticles according to the formula ratio, including but not limited to moisturizers, natural antibacterial ingredients, antioxidants, prebiotics, flavors and sweeteners;

[0042] 3) Solution preparation: dissolving fluoride, preservative and auxiliary components in water according to the formula ratio to form a mixed solution;

[0043] 4) Emulsification and mixing: adding the solid lipid nanoparticles loaded with domiphene obtained in step 2) to the mixed solution of step 5) to form a uniform emulsion under continuous stirring;

[0044] 5) pH adjustment: The pH value of the oral care solution is adjusted to 6.5 to 7.5 by a pH adjuster.

[0045] The invention also provides an application of the oral care liquid composition in oral care.

[0046] Compared with the prior art, the present invention has the following beneficial effects:

[0047] By loading domiphene into solid lipid nanoparticles, especially using glyceryl stearate as the solid lipid nanoparticles with pH responsiveness, domiphene can be preferentially degraded and released in the low pH and inflammatory areas of the oral cavity, thereby achieving precise antibacterial effect, and the drug loading amount of domiphene can be appropriately reduced compared with the existing technology;

[0048] Moreover, unlike the traditional polylactic acid-glycolic acid copolymer (PLGA) carrier, the degradation products of stearyl glycerol are oily stearic acid and glycerol, which will not further lower the pH value of the oral environment, thus avoiding the reduction of the antibacterial efficacy of domiphene.

[0049] At the same time, these degradation products form a protective layer at the site of inflammation, helping to relieve pain and protect the damaged oral mucosa.

[0050] The combined action of domiphene with fluoride, pH buffer and preservative can help domiphene to better exert its antibacterial effect and ensure the activity and stability of domiphene in the oral care composition. DETAILED DESCRIPTION

[0051] Although the present invention has been described to a certain extent, it is obvious that appropriate changes in various conditions can be made without departing from the spirit and scope of the present invention. It is understood that the present invention is not limited to the embodiments described, but belongs to the scope of the claims, which includes equivalent replacements of each factor described.

[0052] The core invention of the present invention is to load domiphene with specific solid lipid nanoparticles in an oral care liquid composition containing the antibacterial agent domiphene. The specific loading method is:

[0053] (1) Melting and mixing: mixing glyceryl stearate and domiphene in a weight ratio of 95:5 to 99:1, and heating to 75-80° C. to ensure that the domiphene is evenly dispersed to form a liquid mixture;

[0054] (2) Cooling and emulsification: the molten mixture is rapidly cooled to 0-5°C and added to an aqueous phase containing an emulsifier under continuous stirring to form an oil-water emulsion; the emulsifier is selected from one or more of lecithin, Tween 20, Tween 80, Span 80, and polysorbate 80; preferably lecithin or Tween 80; based on the total weight (solid content) of SLNs, the amount of the emulsifier added is 2-10 wt%;

[0055] (3) High-pressure homogenization: The emulsion is homogenized using a high-pressure homogenizer. The shear force generated by the high pressure refines the emulsion droplets to a particle size of 50-200 nm to form a dispersed system of solid lipid nanoparticles (SLNs);

[0056] Specifically, the high-pressure homogenizer homogenizes the emulsion as follows: the homogenization pressure is set to 100-200 MPa, and 5-10 homogenization cycles are performed; until the emulsion droplets are refined to a particle size of 50-200 nm and the polydispersity index of SLNs is less than 0.3;

[0057] (4) Solidification and washing: The homogenized emulsion is solidified at a low temperature of 0-5°C to form solid lipid nanoparticles, and the unencapsulated drugs and emulsifiers are removed by centrifugation to collect the solid lipid nanoparticles. The centrifugation conditions are 10000-15000 rad / min for 10-20 minutes.

[0058] Through the above steps, domiphene is encapsulated in stearic acid glyceryl solid lipid nanoparticles.

[0059] After obtaining solid lipid nanoparticle-loaded domiphene (abbreviated as "SLN-domiphene"), an oral care liquid composition is formed, which comprises the following components based on 100 wt% of the total amount of the oral care liquid composition:

[0060] Solid lipid nanoparticles loaded with domiphene (SLN-domiphene) 0.2-5.0wt%, preferably 0.5-3.0wt%;

[0061] Fluoride 0.01-0.05wt%, preferably 0.02-0.04wt%;

[0062] pH regulator 0.2-1wt%, preferably 0.5-0.8wt%;

[0063] Preservative 0.05%-0.3wt%, preferably 0.1-0.2wt%;

[0064] and the balance is pure water;

[0065] The fluoride is selected from one or more of sodium fluoride, ammonium fluoride, stannous fluoride and sodium monofluorophosphate, preferably sodium fluoride or sodium monofluorophosphate; the oral care composition contains fluoride to enhance the acid resistance of teeth, prevent tooth decay, and provide fluoride ions required for tooth remineralization.

[0066] The pH regulator is selected from one or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate and sodium carbonate, preferably sodium bicarbonate or disodium hydrogen phosphate; by adding the pH regulator, the appropriate pH value of the oral care product can be maintained, which is mild to the oral mucosa and helps maintain the natural pH balance in the oral cavity.

[0067] The preservative is selected from one or more of phenoxyethanol, parabens, santoline, and ε-polyphenol, preferably phenoxyethanol or parabens. Adding a preservative can extend the shelf life of the product, prevent the growth of microorganisms, and ensure the safety and stability of the product.

[0068] Furthermore, the oral care liquid composition also includes the following auxiliary components:

[0069] Moisturizer; 0.5%-2.0%, used to keep the oral cavity moist and avoid dryness. Sodium hyaluronate has excellent moisturizing properties and helps to keep the oral cavity comfortable. The moisturizer is selected from one or more of glycerol, sorbitol, propylene glycol, and sodium hyaluronate, preferably glycerol or sodium hyaluronate;

[0070] Natural antibacterial ingredients; 0.1%-1.0%, having antibacterial and anti-inflammatory effects, helping to reduce oral bacteria and maintain oral health, the natural antibacterial ingredients are selected from one or more of green tea extract, tea tree oil, calendula extract, garlic extract, preferably green tea extract or tea tree oil;

[0071] Antioxidant; 0.01%-0.1%, which can neutralize free radicals and protect oral cells from damage; the antioxidant is selected from one or more of vitamin E, vitamin C, selenium, and coenzyme Q10, preferably vitamin E or vitamin C;

[0072] Prebiotics; 0.5%-1.5%, which can promote the growth of beneficial bacteria and improve oral microecology; the prebiotics are selected from one or more of fructan, oligofructose, inulin, and β-glucan, preferably fructan or oligofructose;

[0073] Flavor; 0.01%-0.2%; provides a fresh taste, improves breath, and enhances the user experience; the flavor is selected from one or more of peppermint oil, spearmint essential oil, limonene, and eucalyptus oil, preferably peppermint oil or spearmint essential oil;

[0074] Sweetener; 0.1%-0.5%; increase the sweetness of the product while being friendly to teeth; the sweetener is selected from one or more of xylitol, stevioside, erythritol, and aspartame, preferably xylitol or stevioside;

[0075] The above ingredients work together to enhance the overall effect of oral care solution, including cleaning, anti-caries, antibacterial, moisturizing, anti-oxidation and improving taste.

[0076] The present invention also provides a method for preparing the oral care liquid composition, comprising the following steps:

[0077] 1) Solid lipid nanoparticle loading of domiphene: Stearyl glyceryl and domiphene were mixed and melted at 75-80° C. according to the above method to form a uniform liquid mixture, and then solid lipid nanoparticles were prepared through high pressure homogenization and solidification washing steps;

[0078] 2) Raw material preparation: accurately weighing domiphene, fluoride, preservatives and auxiliary ingredients loaded on solid lipid nanoparticles according to the formula ratio, including but not limited to moisturizers, natural antibacterial ingredients, antioxidants, prebiotics, flavors and sweeteners;

[0079] 3) Solution preparation: dissolving fluoride, preservative and auxiliary components in water according to the formula ratio to form a mixed solution;

[0080] 4) Emulsification and mixing: adding the solid lipid nanoparticles loaded with domiphene obtained in step 2) to the mixed solution of step 5) to form a uniform emulsion under continuous stirring;

[0081] 5) pH adjustment: The pH value of the oral care solution is adjusted to 6.5 to 7.5 by a pH adjuster.

[0082] The invention also provides an application of the oral care liquid composition in oral care.

[0083] The oral care liquid composition and the preparation method thereof provided by the present invention are described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention. In addition, if no specific conditions are specified in the examples of the present invention, the conventional conditions or the conditions recommended by the manufacturer are used; if the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially.

[0084] 1. Preparation of oral care liquid composition in Examples and Comparative Examples

[0085] Example 1

[0086] 97 g of stearic acid glyceryl and 3 g of domiphene were mixed and heated to 78°C to form a liquid mixture, which was then rapidly cooled to 0°C and added to 1000 ml of deionized water containing 5 g of lecithin at a stirring rate of 100 rad / min to form an oil-water emulsion; the homogenization pressure of the high-pressure homogenizer (model PSI-30) was set to 150 MPa, and 6 homogenization cycles were performed. The average particle size of the emulsion droplets was 97.2 nm, and the polydispersity index of SLNs was 0.23; the homogenized emulsion was then solidified at 0°C for 30 min, centrifuged at a speed of 12000 rad / min for 15 min, and the solid lipid nanoparticles after centrifugation were collected.

[0087] 0.03 g of sodium fluoride, 0.2 g of phenoxyethanol, 1 g of glycerol, 0.5 g of fructan, 0.05 g of vitamin E, 0.5 g of green tea extract, 0.1 g of peppermint oil, and 0.3 g of xylitol were dissolved in water, and then 3 g of domiphene loaded with solid lipid nanoparticles was added, and the mixture was stirred continuously until a uniform emulsion was formed. Then, disodium hydrogen phosphate was added as a pH regulator to adjust the pH value to 6.8, and then the remaining water was added until the total amount of the oral care composition was 100 g.

[0088] Example 2

[0089] Compared with Example 1, 1 g of glycerol, 1 g of fructan, 0.05 g of vitamin E, 0.5 g of green tea extract, 0.1 g of peppermint oil, and 0.3 g of xylitol as auxiliary ingredients are not added. When the other ingredients and process conditions remain unchanged, disodium hydrogen phosphate is used as a pH regulator to adjust the pH value to 6.8, and then the remaining water is added to a total amount of 100 g of the oral care composition.

[0090] Example 3

[0091] 95 g of stearic acid glyceryl and 5 g of domiphene were mixed and heated to 75°C to form a liquid mixture, which was then rapidly cooled to 0°C and added to 1000 ml of deionized water containing 10 g of lecithin at a stirring rate of 100 rad / min to form an oil-water emulsion; the homogenization pressure of the high-pressure homogenizer (model PSI-30) was set to 200 MPa, and 10 homogenization cycles were performed. The average particle size of the emulsion droplets was 53.1 nm, and the polydispersity index of SLNs was 0.19; the homogenized emulsion was then solidified at 0°C for 30 min, centrifuged at 12000 rad / min for 15 min, and the solid lipid nanoparticles after centrifugation were collected.

[0092] 0.05 g of sodium monofluorophosphate, 0.3 g of paraben, 2 g of glycerol, 1 g of fructan, 0.1 g of vitamin E, 1 g of green tea extract, 0.2 g of peppermint oil, and 0.5 g of xylitol were dissolved in water, and then 5 g of domiphene loaded on solid lipid nanoparticles was added, and the mixture was stirred continuously until a uniform emulsion was formed. Then, disodium hydrogen phosphate was added as a pH regulator to adjust the pH value to 7.2, and then the remaining water was added to a total amount of 100 g of the oral care composition.

[0093] Example 4

[0094] 99 g of stearic acid glyceryl was mixed with 1 g of domiphene and heated to 80°C to form a liquid mixture, which was then rapidly cooled to 5°C and added to 1000 ml of deionized water containing 2 g of lecithin at a stirring rate of 100 rad / min to form an oil-water emulsion; the homogenization pressure of the high-pressure homogenizer (model PSI-30) was set to 100 MPa, and 5 homogenization cycles were performed. The average particle size of the emulsion droplets was 194.7 nm, and the polydispersity index of SLNs was 0.28; the homogenized emulsion was then solidified at 5°C for 30 min, centrifuged at a speed of 12000 rad / min for 15 min, and the solid lipid nanoparticles after centrifugation were collected.

[0095] 0.01 g of sodium fluoride, 0.05 g of santolin, 0.5 g of glycerol, 0.5 g of fructan, 0.01 g of vitamin E, 0.1 g of green tea extract, 0.01 g of peppermint oil, and 0.1 g of xylitol were dissolved in water, and then 0.2 g of domiphene loaded on solid lipid nanoparticles was added, and the mixture was stirred continuously until a uniform emulsion was formed. Then, disodium hydrogen phosphate was added as a pH regulator to adjust the pH value to 7.0, and then the remaining water was added to a total amount of 100 g of the oral care composition.

[0096] Comparative Example 1

[0097] 0.03 g of sodium fluoride, 0.2 g of phenoxyethanol, 1 g of glycerin, 0.5 g of fructan, 0.05 g of vitamin E, 0.5 g of green tea extract, 0.1 g of peppermint oil, and 0.3 g of xylitol were dissolved in water, and then 0.1 g of domiphene was added, and then disodium hydrogen phosphate was added as a pH adjuster to adjust the pH value to 6.8, and then the remaining water was added to make the total amount of the oral care composition 100 g.

[0098] Comparative Example 2

[0099] Compared with Example 1, the difference is that the carrier material is replaced by polylactic acid-glycolic acid copolymer by stearic acid glyceryl ester, the homogenization pressure of the high-pressure homogenizer (model PSI-30) is set to 150MPa, and 6 homogenization cycles are performed. The average particle size of the emulsion droplets is 92.5nm, and the polydispersity index of SLNs is 0.21; then the homogenized emulsion is solidified at 0°C for 30min, and the centrifuge is continued for 15min at a speed of 12000rad / min, and the solid lipid nanoparticles after centrifugation are collected. Under the same conditions as the other ingredients and process conditions, disodium hydrogen phosphate is used as a pH regulator to adjust the pH value to 6.8, and then the remaining water is added to the total amount of the oral care composition to 100g.

[0100] Comparative Example 3

[0101] Compared with Example 1, the difference is that 90g of stearic acid glyceryl is mixed with 10g of domiphene, the homogenization pressure of the high-pressure homogenizer (model PSI-30) is set to 150MPa, and 6 homogenization cycles are performed, the average particle size of the emulsion droplets is 103.0nm, and the polydispersity index of SLNs is 0.27; then the homogenized emulsion is solidified at 0°C for 30min, and the centrifuge is continued for 15min at a speed of 12000rad / min, and the solid lipid nanoparticles after centrifugation are collected. Under the same conditions of the other ingredients and process conditions, disodium hydrogen phosphate is used as a pH regulator to adjust the pH value to 6.8, and the remaining water is added to the total amount of the oral care composition to 100g.

[0102] Comparative Example 4

[0103] Compared with Example 1, the difference is that 10 g of solid lipid nanoparticle-loaded domiphene is added, and the other ingredients and process conditions remain unchanged. Sodium hydrogen phosphate is used as a pH regulator to adjust the pH value to 6.8, and then the remaining water is added to a total amount of 100 g of the oral care composition.

[0104] Comparative Example 5

[0105] Compared with Example 1, the difference is that disodium hydrogen phosphate is not added as a pH regulator, the pH value is not adjusted, and the remaining water is added to a total amount of 100 g of the oral care composition, and the pH value of the oral care composition is 6.3.

[0106] Comparative Example 6

[0107] Compared with Example 1, the difference is that phenoxyethanol is not added, and the other ingredients and process conditions remain unchanged. Disodium hydrogen phosphate is used as a pH regulator to adjust the pH value to 6.8, and then the remaining water is added to a total amount of 100 g of the oral care composition.

[0108] 2. In vitro antibacterial effect verification test

[0109] The Streptococcus mutans liquid was adjusted to 0.5 McFarland standard and evenly coated on the culture medium. A sterile punch was used to punch holes on the culture medium with a hole diameter of 10 mm and a hole depth of 10 mm. The oral care solutions of Examples 1-4 and Comparative Examples 1-6 were added to the culture medium, respectively. Sterile water was selected as the control group. After being placed at room temperature for 30 minutes, the mixture was placed in a constant temperature incubator at 37° C. and cultured for 24 hours. The diameter of the inhibition zone (defined as the shortest distance from the edge of the hole in the culture medium to the edge of the area where bacteria cannot grow) was observed and measured.

[0110] Table 1 is the in vitro antibacterial effect verification results of Examples 1-4, Comparative Examples 1-6 and the control group:

[0111]

[0112]

[0113] In the antibacterial effect verification test, when the oral care solution has antibacterial activity, it will form a clear area on the bacterial culture medium, wherein bacteria cannot grow, and this area is the inhibition zone. The larger the diameter of the inhibition zone, the stronger the antibacterial effect of the care solution in this area. The oral care solution of embodiment 1-4 and comparative example 1-6 is injected into the culture medium, and the domiphene with solid lipid nanoparticle load of embodiment 1-4 can reach the position where the mutans streptococcus liquid is concentrated more concentratedly, and therefore has a larger inhibition zone. Comparative example 1 does not use SLNs technology, and domiphene can not concentrate on the mutans streptococcus position well, comparative example 2 uses PLGA as a load carrier, and it is proved that the domiphene after its load can not be concentrated at the position where the mutans streptococcus liquid is concentrated, and comparative example 3 is the situation that the domiphene load is large, and it is possible that the load is too large at this time, and the stability of SLNs is affected, and then the antibacterial effect is affected, comparative example 5 does not carry out pH adjustment, and pH has an impact on the antibacterial activity of domiphene, and comparative example 6 does not add preservatives, and also has an impact on the overall antibacterial effect. Comparative Example 4 proves that under the action of high dose of domiphene, its antibacterial effect is not further improved.

[0114] 3. Sensory Evaluation Test

[0115] The oral care solutions of Examples 1-4 and Comparative Examples 1-5 were subjected to sensory tests consisting of 8 test subjects in the test group. Each test subject was an individual with oral ulcers but otherwise healthy, arranged on an objective basis according to specified requirements. Sensory analysis was performed according to ISO4121-2003 under test conditions in accordance with ISO 8589, and 8 test subjects were counted to evaluate different samples.

[0116] Good - Pain at the site of inflammation was significantly reduced during and after gargling

[0117] General - slight relief of pain in the inflamed area during and after rinsing

[0118] No effect - no relief of pain at the site of inflammation during or after gargling

[0119] Table 2 shows the sensory test results of Examples 1-6 and Comparative Examples 1-9

[0120]

[0121]

[0122] The results in Table 2 show that after excluding individual differences, the overall sensory experience of Examples 1-4 is good, while for Comparative Examples 1-6, which are not in the form of loading or use PLGA as a SLNs carrier, and do not add preservatives or perform pH adjustment, the pain caused by inflammation still exists, and the signs of relief are not obvious.

[0123] The above is only a preferred embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. An oral care liquid composition with enhanced antibacterial efficacy, characterized in that: Based on the total amount of the oral care liquid composition being 100 wt%, the composition comprises the following components: Solid lipid nanoparticles loaded with domiphene: 0.2-5.0wt%; Fluoride: 0.01-0.05wt%; pH regulator: 0.2-1wt%; Preservative 0.05%-0.3wt%; and the balance is pure water; The solid lipid nanoparticle-loaded domiphene is prepared by the following method: (1) Melting and mixing: Glyceryl stearate and domiphene are mixed in a weight ratio of 95:5 to 99:1, and heated to 75-80° C. to ensure that the domiphene is evenly dispersed to form a liquid mixture; (2) Cooling and emulsification: The molten mixture is rapidly cooled to 0-5°C and added to the aqueous phase containing the emulsifier under continuous stirring to form an oil-water emulsion; (3) High-pressure homogenization: The emulsion is homogenized by a high-pressure homogenizer, and the shear force generated by the high pressure is used to refine the emulsion droplets to a particle size of 50-200 nm, forming a dispersed system of solid lipid nanoparticles; (4) Solidification and washing: The homogenized solid lipid nanoparticle dispersion system is solidified at a low temperature of 0-5°C to form solid lipid nanoparticles, and the unencapsulated drugs and emulsifiers are removed by centrifugation to collect the solid lipid nanoparticles.

2. The oral care liquid composition according to claim 1, characterized in that In step (3), the high-pressure homogenizer homogenizes the emulsion by setting the homogenization pressure to 100-200 MPa and performing 5-10 homogenization cycles until the emulsion droplets are refined to a particle size of 50-200 nm and the polydispersity index of the solid lipid nanoparticles is less than 0.

3.

3. The oral care liquid composition according to claim 1, characterized in that The centrifugation condition in step (4) is 10000-15000 rad / min for 10-20 minutes.

4. The oral care liquid composition according to claim 1, characterized in that The emulsifier is selected from one or more of lecithin, Tween 20, Tween 80, Span 80, and polysorbate 80. Based on the total weight (solid content) of SLNs, the amount of the emulsifier added is 2-10 wt %.

5. The oral care liquid composition according to claim 1, characterized in that: The fluoride is selected from one or more of sodium fluoride, ammonium fluoride, stannous fluoride, sodium monofluorophosphate; and / or The pH regulator is selected from one or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate and sodium carbonate; and / or The preservative is selected from one or more of phenoxyethanol, parabens, santolin, and ε-polyphenol.

6. The oral care liquid composition according to claim 1, characterized in that: The oral care liquid composition also includes the following auxiliary components: Moisturizer: 0.5%-2.0%; Natural antibacterial ingredients: 0.1%-1.0%; Antioxidant: 0.01%-0.1%; Prebiotics: 0.5%-1.5%; Fragrance: 0.01%-0.2%; Sweetener: 0.1%-0.5%; Wherein, the moisturizing agent is selected from one or more of glycerin, sorbitol, propylene glycol, and sodium hyaluronate; The natural antibacterial ingredient is selected from one or more of green tea extract, tea tree oil, calendula extract, and garlic extract; The antioxidant is selected from one or more of vitamin E, vitamin C, selenium, and coenzyme Q10; The prebiotics are selected from one or more of fructan, oligofructose, inulin, and β-glucan; The fragrance is selected from one or more of peppermint oil, spearmint essential oil, limonene, and eucalyptus oil; The sweetener is selected from one or more of xylitol, stevioside, erythritol and aspartame.

7. A method for preparing the oral care liquid composition according to claim 1, characterized in that: The steps include: (1) Solid lipid nanoparticle loading of domiphene: stearyl glyceryl and domiphene are mixed according to a formula ratio and melted at 75-80° C. to form a uniform liquid mixture, and then solid lipid nanoparticles are prepared through high-pressure homogenization and solidification washing steps; (2) Raw material preparation: accurately weighing domiphene, fluoride, preservatives, and auxiliary ingredients loaded on solid lipid nanoparticles according to the formula ratio, including but not limited to moisturizers, natural antibacterial ingredients, antioxidants, prebiotics, flavors, and sweeteners; (3) Solution preparation: dissolving fluoride, preservative and auxiliary ingredients in water according to the formula ratio to form a mixed solution; (4) Emulsification and mixing: adding the solid lipid nanoparticles loaded with domiphene obtained in step 2) to the mixed solution of step 5) to form a uniform emulsion under continuous stirring; (5) pH adjustment: The pH value of the oral care solution is adjusted to 6.5 to 7.5 using a pH adjuster.

8. Use of the oral care liquid composition according to claim 1 in oral care.

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