NMN-containing gingival atrophy preventing and tooth whitening composition and preparation method thereof

Abstract

The invention relates to the technical field of medical supplies, and particularly discloses an NMN-containing gingival atrophy preventing and tooth whitening composition, which is prepared from the following raw materials in percentage by weight: 3 to 8 percent of bioactive glass, 10 to 20 percent of polyethylene glycol 6000, 60 to 70 percent of glycerol, 10 to 20 percent of silicon dioxide, 0.1 to 0.5 percent of beta-nicotinamide mononucleotide (NMN), 0.1 to 0.5 percent of sodium hyaluronate, 0.1 to 0.5 percent of sodium hyaluronate, and the balance of water. The NMN component can act together with the bioactive glass to generate better effects of preventing and treating gingival atrophy and whitening teeth.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical supplies, in particular to a gingival atrophy prevention and tooth whitening composition containing NMN and a preparation method thereof. BACKGROUND

[0002] Gingival atrophy and tooth whitening have always been important issues in the field of oral care. With the improvement of people's awareness of oral health, the market demand for products that effectively prevent and treat gingival atrophy and whiten teeth is increasing. Gingival atrophy not only causes tooth sensitivity and pain, but also can cause more serious periodontal diseases. The appearance of white teeth is also increasingly concerned by consumers. However, the existing tooth care products on the market are mainly single-function, which cannot meet the demand of preventing gingival atrophy and whitening teeth at the same time. In addition, some whitening products containing strong oxidizing agents such as hydrogen peroxide have a certain whitening effect, but long-term use may cause damage to tooth enamel or irritation to the gums.

[0003] In recent years, beta-nicotinamide mononucleotide (NMN) has been gradually applied to various health products as an important anti-aging and cell repair ingredient. NMN has the functions of antioxidant, anti-inflammatory and promoting cell metabolism, and has potential positive effects on gum health and tooth whitening. However, the research and application of effectively combining NMN into oral care products, especially combining with other compositions and whitening agents to achieve multiple effects, are still relatively few. Therefore, the development of a gingival atrophy prevention and tooth whitening composition containing NMN not only meets the multiple needs of consumers, but also provides a new direction for the innovation of oral care products. SUMMARY

[0004] The present application aims to provide a gingival atrophy prevention and tooth whitening composition containing NMN and a preparation method thereof to solve the problems raised in the background.

[0005] The bioactive mineral has the effects of repairing, replacing and regenerating the body tissues, and forming a bond between the tissues and the materials.

[0006] To achieve the above-mentioned purpose, the present application provides the following technical solutions: A gingival atrophy prevention and tooth whitening composition containing NMN, which is prepared from the following raw materials in the following weight percentages: bioactive mineral 3-8%, high molecular weight polyethylene glycol 10-20%, glycerol 60-70%, silicon dioxide 10-20%, and beta-nicotinamide mononucleotide (NMN) 0.1-0.5%.

[0007] Preferably, the bioactive mineral is bioactive glass, and the high molecular weight polyethylene glycol is polyethylene glycol 6000.

[0008] Preferably, the composition is prepared from the following raw materials by weight percentage: bioactive glass 3%, polyethylene glycol 6000 20%, glycerol 66.5%, silicon dioxide 10%, beta-nicotinamide mononucleotide (NMN) 0.5%.

[0009] Preferably, the composition is prepared from the following raw materials by weight percentage: bioactive glass 5%, polyethylene glycol 6000 15%, glycerol 65%, silicon dioxide 14.9%, beta-nicotinamide mononucleotide (NMN) 0.1%.

[0010] Preferably, the composition is prepared from the following raw materials by weight percentage: bioactive glass 8%, polyethylene glycol 6000 12%, glycerol 59.8%, silicon dioxide 20%, beta-nicotinamide mononucleotide (NMN) 0.2%.

[0011] A method for preparing a gingival atrophy-preventing and tooth-whitening composition containing NMN as described in any of the preceding items, comprising the following steps: Weigh a certain amount of materials for standby; Add high-molecular polyethylene glycol to a container containing glycerol, stir and heat to 40-50℃ until completely dissolved to obtain a base solution; Add bioactive minerals and beta-nicotinamide mononucleotide (NMN) to the base solution in sequence, and continue stirring for 60 minutes to ensure uniform mixing; Let stand, and measure the pH value of the solution using a pH meter; Add silicon dioxide to adjust the viscosity of the solution; Package the composition to obtain the finished product.

[0012] Technical effects and advantages of the present application: The present application first uses bioactive glass and NMN simultaneously in a dental composition. Bioactive glass has a gingival repair and anti-atrophy effect. Bioactive glass releases calcium, phosphorus and other ions after contacting saliva, stimulates alveolar bone regeneration and forms a hydroxyapatite protective layer, can repair exposed tooth roots and gum recession, and improves gum atrophy symptoms. Clinical cases show that it can effectively inhibit gum bleeding and promote ulcer healing. At the same time, it can repair enamel microdamage through remineralization, reduce dentin exposure, and relieve tooth sensitivity; its alkaline properties can neutralize the acidic environment of the oral cavity, inhibit pigment deposition, and long-term use can improve black spots and yellowing of teeth.

[0013] NMN (nicotinamide mononucleotide) can activate NAD+ metabolism, enhance the energy metabolism of gingival and periodontal tissue cells, and possibly delay gingival cell aging and promote regeneration. The NMN component can effectively promote cell regeneration and repair, enhance the antioxidant capacity of gingival tissue, and slow down the process of gingival atrophy. In addition, NMN can promote the health of cells on the surface of teeth, maintain the luster and whiteness of enamel, and make teeth more beautiful.

[0014] The present application accidentally discovered in research that bioactive glass and NMN can produce a synergistic effect, and compared with the use of one component alone, the combination use has a significant effect on gingival atrophy and tooth whitening, and produces an unexpected technical effect.

[0015] In addition, the silica in the composition of the present application has a mild friction effect, which can gently remove pigments and dirt on the surface of teeth, and can further improve the whitening effect.

[0016] The composition uses a safe and mild ingredient ratio, does not contain harmful strong oxidizing agents, reduces the potential damage to teeth and gums caused by long-term use, and the synergistic effect of NMN and other ingredients makes the product not only effectively realize tooth care during use, but also provide a good use experience.

[0017] The present application ensures the stability and sustained effectiveness of the ingredients in the oral environment by reasonable formulation of the composition.

[0018] Active ingredient selection experiment: The proliferation of gingival fibroblasts is a conventional experimental method for determining whether active ingredients can prevent and treat gingival atrophy. The present application evaluates the proliferation activity of active ingredients on HGFs by the effect of active ingredients on the proliferation of human gingival fibroblasts (HGFs), and verifies the effect of active ingredients on preventing and treating gingival atrophy. The effects of bioactive glass and NMN (β-nicotinamide mononucleotide) alone and in combination on the proliferation of human gingival fibroblasts (HGFs) are compared.

[0019] 1. Sample preparation method: a suitable amount of bioactive glass was dissolved in DMEM culture medium (without serum), ultrasonically treated (40 kHz, 30 min), centrifuged (3000 rpm, 10 min), and the supernatant was filtered and sterilized (0.22 μm filter membrane). The final concentration was adjusted to 5% w / v), NMN, LPS, and EGF were dissolved in sterile PBS, and DMEM without active ingredients was used as a blank control.

[0020] 2. Cell culture and treatment Cell line: primary human gingival fibroblasts (HGFs); culture condition: DMEM + 10% FBS + 1% penicillin, 37℃, 5% CO2; plating: proliferation experiment, 96-well plate, 3000 cells / well (100 μL culture medium); cell synchronization: change to serum-free medium for 12 h after plating for 24 h.

[0021] 3. Experimental grouping and treatment Blank control group: normal DMEM medium; LPS injury group: DMEM + LPS (1 μg / mL, to induce inflammation); Bioactive glass group: LPS + bioactive glass extract (5% w / v, simulated remineralization concentration); NMN group: LPS + NMN (100 μM, conventional concentration of antioxidant and anti-aging); Bioactive glass + NMN combination group: LPS + bioactive glass extract 5% + NMN 100 μM; Positive control group: LPS + EGF (10 ng / mL, known proliferation-promoting factor); Treatment time: 48 h (proliferation experiment).

[0022] 4. CCK-8 detection of cell proliferation Steps: 1) Add 10 μL CCK-8 reagent to each well; 2) incubate at 37℃ for 2 h; 3) measure the absorbance at 450 nm (OD value) using a microplate reader.

[0023] Calculate the cell proliferation rate according to the OD, and the results are shown in Table 1.

[0024] Table 1. Results of cell proliferation experiment

[0025] * Compared with the blank control group, p<0.05; # Compared with the LPS injury group, p<0.05.

[0026] From the experimental results, it can be seen that LPS significantly inhibits HGFs proliferation (reduces to 65%), and the bioactive glass and NMN single group can improve the cell proliferation inhibition caused by LPS, that is, the cell proliferation rate is increased, but from the data, the improvement is not significant, while the bioactive glass+NMN combined group significantly improves the effect of cell proliferation, and the proliferation is restored to nearly 96%, close to the effect of using the proliferation factor EGF, which is significantly better than single treatment (p<0.05). The present application significantly improves the proliferation effect of the composition on cells by adding a small amount of NMN to the bioactive glass, indicating that the composition has a more excellent effect of preventing gum atrophy. Based on the above experimental research, the present application selects to combine bioactive glass and NMN together to prepare a tooth efficacy composition. DETAILED DESCRIPTION

[0027] The technical solutions in the embodiments of the present application will be described below in a clear and complete manner. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application. The component contents of the embodiments of the present application are determined by experimental screening, and the active ingredient is determined based on the screening experiment. Embodiment 1

[0028] A gum atrophy-preventing and tooth whitening composition containing NMN, the composition is prepared from the following raw materials in weight percentage: bioactive glass 3%, polyethylene glycol 6000 20%, glycerol 66.5%, silicon dioxide 10%, and beta-nicotinamide mononucleotide (NMN) 0.5%.

[0029] The preparation method of the composition comprises the following steps: Weigh a certain amount of materials for standby; Add the high-molecular polyethylene glycol into the container containing glycerol, stir and heat to 40-50℃ until completely dissolved to obtain a base solution; Add the bioactive mineral and beta-nicotinamide mononucleotide (NMN) into the base solution in sequence, continuously stir for 60 minutes to ensure uniform mixing; Rest, measure the pH value of the solution with a pH meter; Add silicon dioxide to adjust the viscosity of the solution; Package the composition to obtain the finished product. Embodiment 2

[0030] A gingival recession-preventing and tooth whitening composition containing NMN, which is prepared from the following raw materials in weight percentage: bioactive glass 5%, polyethylene glycol 6000 15%, glycerol 65%, silicon dioxide 14.9%, beta-nicotinamide mononucleotide (NMN) 0.1%.

[0031] The preparation method of the composition is the same as Example 1. Example 3

[0032] A gingival recession-preventing and tooth whitening composition containing NMN, which is prepared from the following raw materials in weight percentage: bioactive glass 8%, polyethylene glycol 6000 12%, glycerol 59.8%, silicon dioxide 20%, beta-nicotinamide mononucleotide (NMN) 0.2%.

[0033] The preparation method of the composition is the same as Example 1.

[0034] In the above three groups of examples, polyethylene glycol 6000 is a surfactant and a humectant, glycerol is a humectant, and both of them play a role as a matrix, beta-nicotinamide mononucleotide (NMN) and bioactive glass are active ingredients, and silicon dioxide is an abrasive and can also adjust the viscosity.

[0035] Comparative Example 1 A gingival recession-preventing and tooth whitening composition containing NMN, which is prepared from the following raw materials in weight percentage: bioactive glass 15.1%, polyethylene glycol 6000 10%, glycerol 60%, silicon dioxide 14.9%.

[0036] The preparation method is referred to Example 1.

[0037] Comparative Example 2 A gingival recession-preventing and tooth whitening composition containing NMN, which is prepared from the following raw materials in weight percentage: nicotinamide mononucleotide (NMN) 2%, polyethylene glycol 6000 16%, glycerol 67%, silicon dioxide 15%.

[0038] The preparation method is referred to Example 1.

[0039] Tooth whitening experiment: Further evaluation of the tooth whitening effect of a gel composition prepared by combining bioactive glass and NMN (beta-nicotinamide mononucleotide): 1. Experimental grouping Negative control group: artificial saliva soaking Positive control group: 10% urea peroxide gel Bioactive glass group: Comparative Example 1 gel NMN group: Comparative Example 2 gel Experimental group of the present application: gel composition of examples 1-3 2. Sample preparation Ex vivo teeth: non-carious ex vivo bovine teeth (n=70) were collected, ultrasonically cleaned and then immersed in coffee / tea solution (37°C, 72 h) to establish an exogenous staining model.

[0040] Sample allocation: 10 teeth per group, randomly allocated, baseline color step (ΔΕ value) measured before treatment.

[0041] 3. Experimental method 1) Whitening treatment Treatment period: corresponding agent was applied daily (20 min / time, 2 times / day) for 14 days.

[0042] Treatment mode: gel group: uniform coverage of the tooth surface (thickness 0.5 mm), solution group: immersion in 2 mL solution.

[0043] Rinse: after each treatment, the teeth were rinsed with artificial saliva for 30 s.

[0044] 2) Color measurement (evaluation of whitening effect) Instrument: spectrophotometer, time points: baseline (0 days), day 14; parameters: ΔE value (color difference change): ΔE = √[(ΔL*)² + (Δa*)² + (Δb*)²], ΔE > 2 is a visible difference to the naked eye. L* represents lightness, a* represents red-green, and b* represents yellow-blue. Results are shown in Table 2. Table 2 Whitening effect

[0045] * p<0.05 compared with negative control ** p<0.01; # p<0.05 compared with single component group.

[0046] The experimental results show that the composition prepared by the combination of the two active ingredients has a whitening effect close to that of the urea peroxide group, but the peroxide can cause damage to the tooth surface, especially the enamel, and long-term use has an adverse effect on the teeth. The composition containing only the bioactive glass with an increased content has a certain effect on tooth whitening, and the NMN alone has no significant effect on tooth whitening. However, the combination of the two significantly improves the tooth whitening effect of the composition, which is of significant meaning. The mechanism is that the bioactive glass reduces enamel demineralization, restores tooth transparency, and reduces tooth discoloration caused by bacterial metabolites. NMN can further promote the synthesis of gum collagen and improve gum color. However, NMN alone cannot directly act on the pigment deposition on the tooth surface and the structural coloring of the enamel due to the lack of functional groups that directly interact with pigments. The physical adsorption of bioactive glass and the metabolic support of NMN are the reasons for the significant improvement in the whitening effect when the two are combined.

[0047] Conclusion: From the above active selection and specific comparison experiments of the product, it can be seen that the composition prepared by the combination of bioactive glass and NMN has significant advantages in the prevention and treatment of gum atrophy and tooth whitening.

Claims

1. A gingival recession-preventing, tooth-whitening composition containing NMN, characterized by: The composition is prepared from the following raw materials in the following weight percentages: bioactive mineral 3-8%, high molecular polyethylene glycol 10-20%, glycerol 60-70%, silicon dioxide 10-20%, and β-nicotinamide mononucleotide (NMN) 0.1-0.5%.

2. The gingival recession-preventing and tooth-whitening composition containing NMN according to claim 1, characterized by: The bioactive mineral is bioactive glass, and the high molecular polyethylene glycol is polyethylene glycol 6000.

3. The gingival recession-preventing and tooth-whitening composition containing NMN according to claim 2, characterized by: The composition is prepared from the following raw materials in the following weight percentages: bioactive glass 3%, polyethylene glycol 6000 20%, glycerol 66.5%, silicon dioxide 10%, and β-nicotinamide mononucleotide (NMN) 0.5%.

4. The gingival recession-preventing and tooth-whitening composition containing NMN according to claim 2, characterized by: The composition is prepared from the following raw materials in the following weight percentages: bioactive glass 5%, polyethylene glycol 6000 15%, glycerol 65%, silicon dioxide 14.9%, and β-nicotinamide mononucleotide (NMN) 0.1%.

5. The gingival recession-preventing and tooth-whitening composition containing NMN according to claim 2, characterized by: The composition is prepared from the following raw materials in the following weight percentages: bioactive glass 8%, polyethylene glycol 6000 12%, glycerol 59.8%, silicon dioxide 20%, and β-nicotinamide mononucleotide (NMN) 0.2%.

6. A method for preparing the anti-gingivitis, tooth whitening composition containing NMN according to any one of claims 1 to 5, characterized by, The method comprises the following steps: Weighing a certain amount of materials for standby; Adding the high molecular polyethylene glycol into a container containing glycerol, stirring and heating to 40-50℃ until completely dissolved to obtain a base solution; Adding the bioactive mineral and β-nicotinamide mononucleotide (NMN) into the base solution in sequence, continuously stirring for 60 minutes to ensure uniform mixing; Measuring the pH value of the solution using a pH meter; Adding silicon dioxide to adjust the viscosity of the solution; Packaging the composition to obtain the finished product.

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