Composition for oral care and application thereof

Abstract

The invention discloses a composition for oral care and application thereof. The mouthwash is prepared from a solvent, a humectant, a preservative, a solubilizer and functional substances, wherein the functional substances are prepared from beta-glucan, dipotassium glycyrrhizinate and copper blue peptide. The composition for oral care disclosed by the invention is prepared from glucan, glycyrrhizinate and copper blue peptide. According to the oral care composition disclosed by the invention, the glucan, the glycyrrhizinate and the argireline are organically combined and can stably exist in the oral care composition disclosed by the invention, so that the stability of the composition of the argireline for oral care is improved; the oral care composition has the effects of repairing oral mucosa, relieving oral ulcer stimulation and resisting inflammation, and can be prepared into various oral care products.

Description

Technical Field

[0001] The present application relates to the technical field of oral care, and in particular to a composition for oral care and application thereof. Background Art

[0002] As people pay more and more attention to oral health, the oral care product market is also growing. However, although there are many kinds of mouthwash products on the market, they are not ideal in repairing oral mucosal damage and relieving the irritation caused by oral ulcers.

[0003] Oral ulcer is a common oral problem, which not only brings pain and discomfort to people, but also affects eating and speaking. When suffering from oral ulcer, many people are eager to find a product that can quickly relieve symptoms and promote the repair of oral mucosa.

[0004] In this context, it is of great significance to carry out research and development of mouthwash that can effectively repair oral mucosa. It can not only meet people's needs for oral health, but also bring new opportunities to the oral care market.

[0005] Blue copper peptide, also known as blue copper peptide, copper peptide, tripeptide or glycyl-L-histidyl-L-lysine, is a polypeptide. Since the compatibility of blue copper peptide itself is relatively complicated, it is easy to cause the uncontrollable and unstable formulation; therefore, there has been no research and report on the use of blue copper peptide in toothpaste and mouthwash. Summary of the invention

[0006] The object of the present application is to provide an improved composition for oral care and its application.

[0007] In order to achieve the above objectives, this application adopts the following technical solutions:

[0008] The first aspect of the present application discloses a composition for oral care, comprising dextran, glycyrrhizic acid salt and blue copper peptide.

[0009] The embodiment of the present application uses a combination of glucan, glycyrrhizic acid salt and blue copper peptide as the main functional component of the oral care composition. On the one hand, the combination of blue copper peptide and glucan, especially β-glucan, and glycyrrhizic acid salt, such as dipotassium glycyrrhizinate, can be stably present in the oral care composition of the present application, making the oral care composition of the present application stable and controllable, which has important value and significance for mouthwash, toothpaste, oral spray and oral repair gel. On the other hand, the organic combination of glucan, glycyrrhizic acid salt and blue copper peptide makes the oral care composition of the embodiment of the present application have a good oral mucosal repair effect, as well as relieve oral ulcer irritation and anti-inflammatory effect; therefore, the composition of the embodiment of the present application has a wide range of application and can be made into various oral care products, including but not limited to mouthwash, gargle, oral spray and oral repair gel, etc. These oral care products have good anti-inflammatory and repair effects.

[0010] It can be understood that the key to this application is the organic combination of glucan, glycyrrhizic acid salt and blue copper peptide. The other components in the oral care composition can be determined according to the specific product. For example, when used to prepare mouthwash, the oral care composition of this application can also include solvents, moisturizers, preservatives, solubilizers, etc. according to needs. The specific selection of these ingredients can refer to the prior art. However, in order to ensure that the three functional substances of glucan, glycyrrhizic acid salt and blue copper peptide can play a better role, the further improved technical solution of this application specifically limits the solvents, moisturizers, preservatives and solubilizers.

[0011] It should also be noted that the functional substances of the present application mainly include glucan, glycyrrhizic acid salt and blue copper peptide, which can be composed of only these three functional substances, or other existing functional substances can be added according to needs or product requirements. In principle, as long as the added functional substances do not have incompatibility with the glucan, glycyrrhizic acid salt and blue copper peptide of the present application; that is, the added functional substances will not affect the glucan, glycyrrhizic acid salt and blue copper peptide of the present application to perform their functions, nor will they affect the stability of the three.

[0012] In one implementation of the present application, the glucan includes α-glucan and β-glucan.

[0013] In one implementation of the present application, the glucan is preferably β-glucan.

[0014] In one implementation of the present application, the glycyrrhizic acid salt is dipotassium glycyrrhizinate.

[0015] In one implementation of the present application, the oral care composition of the present application further comprises a solvent for dispersing or dissolving glucan, glycyrrhizic acid salt and blue copper peptide.

[0016] In one implementation of the present application, the solvent is preferably water.

[0017] In one implementation of the present application, the amount of dextran is 0.005-10% of the total weight of the composition, the amount of glycyrrhizic acid salt is 0.005-10% of the total weight of the composition, and the amount of blue copper peptide is 0.005-10% of the total weight of the composition.

[0018] In one implementation of the present application, the oral care composition of the present application further includes a moisturizer.

[0019] In one implementation of the present application, the humectant includes at least one of glycerin, propylene glycol, sorbitol and 1,2-hexanediol.

[0020] In one implementation of the present application, the moisturizer is preferably composed of glycerin, propylene glycol, sorbitol and 1,2-hexanediol.

[0021] In one implementation of the present application, the amount of glycerol used is 1-50% of the total weight of the composition, the amount of propylene glycol used is 1-50% of the total weight of the composition, the amount of sorbitol used is 1-50% of the total weight of the composition, and the amount of 1,2-hexanediol used is 0.05-10% of the total weight of the composition.

[0022] In one implementation of the present application, the oral care composition of the present application further comprises a preservative.

[0023] In one implementation of the present application, the preservatives include methylparaben and ethylhexylglycerin.

[0024] In one implementation of the present application, the amount of methylparaben used is 0.05-5% of the total weight of the composition, and the amount of ethylhexylglycerin used is 0.005-10% of the total weight of the composition.

[0025] In one implementation of the present application, the oral care composition of the present application further includes a solubilizer.

[0026] In one implementation of the present application, the solubilizer is poloxamer 407.

[0027] In one implementation of the present application, the amount of Poloxamer 407 is 0.01-10% of the total weight of the composition.

[0028] In one implementation of the present application, the oral care composition of the present application further comprises a sweetener.

[0029] In one implementation of the present application, the sweetener is xylitol.

[0030] In one implementation of the present application, the amount of xylitol used is 1-30% of the total weight of the composition.

[0031] The second aspect of the present application discloses the use of the oral care composition of the present application in preparing a mouthwash, an oral spray or an oral repair gel.

[0032] The third aspect of the present application discloses a mouthwash prepared using the oral care composition of the present application.

[0033] The mouthwash of the present application, due to the use of the oral care composition of the present application, has the advantages of good stability and strong controllability. In addition, the organic combination of glucan, glycyrrhizic acid salt and blue copper peptide makes the mouthwash of the present application have a good oral mucosal repair effect, as well as relieve oral ulcer irritation and anti-inflammatory effect. It can be understood that the mouthwash of the present application adopts the oral care composition of the present application, and the other components of the mouthwash can refer to the prior art, as long as they do not affect the stability and performance of glucan, glycyrrhizic acid salt and blue copper peptide.

[0034] The fourth aspect of the present application discloses an oral spray prepared using the oral care composition of the present application.

[0035] It should be noted that the oral spray of the present application is actually the oral care composition or mouthwash of the present application directly atomized. The oral spray and mouthwash of the present application are only different in the way of use, and the other components and dosages are the same or similar.

[0036] The fifth aspect of the present application discloses an oral care gel prepared using the oral care composition of the present application.

[0037] In one implementation of the present application, the oral care gel of the present application includes the oral care composition of the present application and a thickener.

[0038] In one implementation of the present application, the thickener is xanthan gum.

[0039] In one implementation of the present application, the amount of xanthan gum used is 0.05-10% of the total weight of the oral care gel.

[0040] It should be noted that the oral care gel of the present application is the oral care composition or mouthwash of the present application made into a gel to meet different usage requirements. The specific method of forming the oral care gel can refer to the prior art, for example, adding a thickener such as xanthan gum to the mouthwash. It can be understood that xanthan gum is only a proven thickener in one implementation of the present application that can ensure the stability of the efficacy of the present application, and it is not excluded that other thickeners or gel-forming agents that can produce similar functions can also be used.

[0041] Due to the adoption of the above technical solution, the beneficial effects of this application are:

[0042] The oral care composition of the present application comprises dextran, glycyrrhizic acid salt and blue copper peptide, which are organically combined and can be stably present in the oral care composition of the present application, thereby improving the stability of the composition of blue copper peptide for oral care. The oral care composition of the present application has the effects of repairing oral mucosa, relieving irritation of oral ulcers and anti-inflammatory, and can be made into various oral care products. DETAILED DESCRIPTION

[0043] Blue copper peptides have excellent anti-inflammatory and antioxidant effects, and can promote the synthesis of collagen and elastin, stimulate the production of glycosaminoglycans, and facilitate mucosal repair; however, due to the incompatibility issues of blue copper peptides, there have been no related studies or reports on the use of blue copper peptides in toothpaste or mouthwash.

[0044] Through in-depth research on the physiological characteristics of oral mucosa and the occurrence mechanism of oral ulcers, combined with advanced technologies and formulas, this application has developed an oral care composition that can effectively repair oral mucosa and relieve oral ulcer irritation. When used as a mouthwash, it can provide better protection for oral health.

[0045] The oral care composition of the present application comprises: dextran, glycyrrhizic acid salt and blue copper peptide.

[0046] Glucans, such as β-glucan, have anti-inflammatory, tissue regeneration and wound repair effects. High-purity β-glucan, due to its large molecular weight, can easily form a barrier on the oral surface to supplement the oral barrier function. Secondly, due to the presence of specific binding sites for β-glucan on human cells (Langerhans cells), β-glucan can bind to intracellular receptors (Dectin-1) to increase the activity of T cells and B cells and maintain the balance of the oral immune system.

[0047] Glycyrrhizic acid salts can be naturally extracted, such as dipotassium glycyrrhizinate, which has mineralocorticoid and glucocorticoid effects, can regulate the excitability of cholinergic nerves, leading to reduced permeability of capillary walls and cell membranes, reduced inflammatory exudation, and inhibiting the formation and release of histamine and other toxic substances, thereby playing a good anti-inflammatory effect. When dipotassium glycyrrhizinate acts on LPS-stimulated RAW264.7 cells, it can inhibit the secretion of inflammatory mediators NO and inflammatory cytokines IL-6 to varying degrees.

[0048] Blue copper peptides can promote the synthesis of collagen and elastin, stimulate the production of glycosaminoglycans, and have antioxidant effects against free radicals. After oral mucosal tissue damage, it triggers SPARC specific hydrolysis to produce GHK to transport Cu 2+, generating GHK-Cu, which acts on relevant sites, thereby reducing the release of inflammatory response factors such as iron oxide, TNF-α, IL-6, IL-1β, etc. by fibroblasts, inhibiting inflammatory response, and promoting fibroblast growth, collagen and elastin synthesis.

[0049] In short, blue copper peptide has a powerful ability to promote the production of collagen and elastin and repair damaged skin; glucan can enhance the immunity of oral mucosa and provide a good protective barrier for the skin; dipotassium glycyrrhizinate has anti-inflammatory and soothing effects, reducing the discomfort of oral mucosal damage; the synergistic use of the three has better oral mucosal repair effects, as well as relieving oral ulcer irritation and anti-inflammatory effects; and, more importantly, this application study found that the combination of the three has good stability in products such as mouthwash, mouth spray, and oral repair gel, which solves the instability problem of blue copper peptide caused by incompatibility taboos.

[0050] The present application is further described in detail below through specific examples. The following examples are only used to further illustrate the present application and should not be construed as limiting the present application.

[0051] Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.

[0052] Embodiment 1

[0053] The oral care composition of this example includes glucan, glycyrrhizic acid salt and blue copper peptide; wherein the glucan is β-glucan and the glycyrrhizic acid salt is dipotassium glycyrrhizinate. In this example, the oral care composition is made into a mouthwash and its stability and oral mucosal repair performance are tested. Specifically including:

[0054] 1. Preparation of mouthwash

[0055] In this example, each component is weighed according to the percentage of total weight: water 60.25%, glycerol 10%, methylparaben 0.15%, ethylhexylglycerol 0.2%, propylene glycol 6%, β-glucan 0.2%, blue copper peptide 0.2%, dipotassium glycyrrhizinate 1%, xylitol 1%, poloxamer 407 3%, sorbitol 16%, 1,2-hexanediol 2%; each component is dispersed in solvent water to obtain the mouthwash of this example.

[0056] 2. Mouthwash stability test

[0057] The mouthwash prepared in this example was placed under room temperature 25°C, heat resistance 45°C, heat resistance 50°C, normal temperature light (light box), cold resistance 5°C, and cold resistance -18°C for twelve weeks. The pH value, appearance and odor of the mouthwash were observed every week to judge the stability of the mouthwash. The results are shown in Table 1.

[0058] Table 1 Mouthwash stability test results

[0059]

[0060]

[0061]

[0062] The results in Table 1 show that the mouthwash prepared in this example has good stability at both 50°C and -18°C, and has good long-term stability. This example tested the stability of the mouthwash at high and low temperatures for 3 months, and therefore, it can be inferred that it should be able to be stored at room temperature for a longer time and maintain stability.

[0063] 3. Test of mouthwash on people with oral ulcers

[0064] In this case, 15 patients with obvious oral ulcers were randomly selected for testing. The specific test method is: use 15mL of the mouthwash in this case each time, 3-5 times a day, and do not drink water or eat for half an hour after rinsing your mouth. Scoring mechanism: 10-point system: 0 points (very bad) → 10 points (very good). The test results are shown in Table 2.

[0065] Table 2 Test results of mouthwash on oral ulcers

[0066]

[0067] The results in Table 2 show that 98% of the testers believed that there was significant immediate relief and improvement; 80% of the testers believed that there was relief of inflammation and pain after one day of use; and 90% of the testers believed that there was significant relief of inflammation and pain after 3 and 7 days of use.

[0068] 4. Oral mucosal repair efficacy evaluation test

[0069] 1. Materials and Methods

[0070] The mouthwash prepared in this example was used to test rats.

[0071] Experimental animals and feeding environment SPF grade SD rats, 20, male, 6-8 weeks old, provided by Zhuhai Baishitong Biotechnology Co., Ltd., production license number: SCXK (Guangdong) 2020-0051, laboratory animal quality certificate number: No. 44822700040609. Feed was provided by Jiangsu Medison Biomedicine Co., Ltd., production license number: Su Feed Certificate (2023) 10030, quality certificate number: NO. 12024051303. Rats were raised in the barrier laboratory of this unit, and the experimental animal use license number was SYXK (Guangdong) 2023-0137. The laboratory temperature was 20℃~26℃, and the relative humidity was 40%~70%. Feeding conditions: 5 rats / cage. 10h:14h day and night lighting was used.

[0072] Dose selection and experimental grouping: In this experiment, the prepared mouthwash stock solution was used as the test sample, and a model control group and a test sample group were set up, with 10 SD rats in each group.

[0073] Main instruments and reagents: Shuangjie brand JJ3000 electronic balance; FA301181 electronic digital caliper; glacial acetic acid.

[0074] Test method:

[0075] (1) Preparation of oral ulcer model: An oral ulcer model was established with reference to GQT / ZY-YB-97.

[0076] (2) Ulcer intervention test: rats with successful modeling were randomly divided into a model control group and a test sample group according to the size of the ulcer area, with 10 rats in each group. The test sample group was given the corresponding test substance, and 100 μL of the test sample was evenly applied to the oral ulcer surface with a pipette, 3 times a day for 5 consecutive days.

[0077] (3) Index detection

[0078] Before sampling (before sampling on the first day) and on the 1st, 2nd, 3rd, 4th and 5th days after sampling, measure the maximum longitudinal diameter (d1) and maximum transverse diameter (d2) of oral ulcers. Use a compass to cut the maximum longitudinal diameter and maximum transverse diameter of the ulcer and carve them on the measuring paper, and then use a digital micrometer to measure the diameter.

[0079] (4) Detection indicators and calculation methods

[0080] ①Ulcer area S = d1 × d2 × π / 4 (π is 3.14);

[0081] ②Ulcer area reduction value Dn = ulcer area S0 - ulcer area Sn

[0082] Wherein, S0=0, ulcer area before sampling; n=1, 2, 3, 4, 5, ulcer area on the 1st, 2nd, 3rd, 4th, 5th day after sampling;

[0083] ③ Final ulcer area reduction rate (%) = (ulcer area S0-ulcer area S5) / ulcer area S0×100%;

[0084] ④Ulcer healing and healing rate;

[0085] ⑤Weight.

[0086] Statistical analysis of test data

[0087] The experimental data were expressed as mean ± standard deviation (X ± S) and were analyzed using SPSS statistical software. The T test was used to compare the test sample group with the model control group, and P < 0.05 was considered statistically significant.

[0088] Result evaluation: If any of the following conditions are met, it may indicate that the test substance has a certain effect on oral mucosal repair:

[0089] ①Compared with the model control group, the final ulcer area reduction rate of the test sample group increased, and the difference was statistically significant (P<0.05);

[0090] ②The healing rate of the test sample group was higher than that of the model control group.

[0091] 2. Test results

[0092] (1) Effects of the test samples on rat body weight

[0093] The test results of the effects of the test samples on the body weight of rats are shown in Table 3.

[0094] Table 3 Body weight changes of rats (X±S, n=10)

[0095] Group Initial body weight (g) Final body weight (g) Weight gain (g) Model control group 191.6±9.1 227.5±9.7 35.9±4.4 Test sample group 196.6±5.2 229.3±7.1 32.7±4.9

[0096] The results in Table 3 show that during the experiment, no obvious abnormalities were observed in the rats in the model control group and the test sample group. Compared with the model control group, there were no statistically significant differences in the initial body weight, final body weight and body weight gain of the rats in the test sample group (P>0.05), indicating that the test sample had no effect on the body weight of the rats.

[0097] (2) Effects of the test samples on the area of ​​oral ulcers in rats

[0098] The test results of the effects of the test samples on the oral ulcer area of ​​rats are shown in Table 4.

[0099] Table 4 Oral ulcer area of ​​rats (X±S, n=10)

[0100]

[0101]

[0102] In Table 4, “*” indicates P < 0.05 compared with the model control group.

[0103] The results in Table 4 show that before the administration of the sample, there was no statistically significant difference in the ulcer area between the model control group and the test sample group (P>0.05). After the administration of the sample, compared with the model control group, the ulcer area of ​​the test sample group on the 1st, 2nd, 3rd, 4th and 5th day was reduced, and the differences were statistically significant (P<0.05).

[0104] (3) Effects of the test samples on the healing of oral ulcers in rats

[0105] The test results of the effects of the test samples on the healing of oral ulcers in rats are shown in Table 5.

[0106] Table 5 Decrease in area and healing of oral ulcers in rats (X±S, n=10)

[0107] Group Model control group Test sample group <![CDATA[The ulcer area reduction value on the first day (mm 2 )]]> -2.54±3.10 -0.09±1.63* <![CDATA[Area reduction value of ulcer on the second day (mm 2 )]]> -1.98±4.34 2.96±2.90* <![CDATA[The ulcer area reduction value on the 3rd day (mm 2 )]]> 2.77±2.12 6.65±2.83* <![CDATA[The ulcer area reduction value on the 4th day (mm 2 )]]> 5.10±2.53 7.96±2.54* <![CDATA[The ulcer area reduction value on the 5th day (mm 2 )]]> 7.62±1.81 12.00±6.08* Ulcer area reduction rate on the 3rd day (%) 11.93±8.86 29.46±10.26* Final ulcer area reduction rate (%) 33.96±5.23 53.802±5.16* Final healing rate (%) 0 20

[0108] In Table 5, “*” indicates that P < 0.05 compared with the model control group; “-” indicates an increase in ulcer area. For example, “model control group”, “decline in ulcer area on day 1”, “-2.54” means that the ulcer area in this group increased by 2.54 mm 2 .

[0109] The results in Table 5 show that after sample administration, the decrease in ulcer area on days 1, 2, 3, 4, and 5 in the test sample group was statistically significant compared with the model control group (P < 0.05). During the test period, the final healing rate of the model control group was 0%, and the final healing rate of the test sample group was 20%. Compared with the model control group, the final ulcer area decrease rate of the test sample group increased, and the difference was statistically significant (P < 0.05).

[0110] 3. Conclusion

[0111] Under the conditions of this experiment, the final ulcer area decrease rate of rats in the test sample group was higher than that in the model control group, and the difference was statistically significant (P < 0.05). The final healing rate of the test sample group was higher than that in the model control group, indicating that the test sample had a repairing effect on the oral mucosa.

[0112] 5. Oral mucosal irritation test

[0113] 1. Materials and Methods

[0114] The mouthwash prepared in this example was used to test rats.

[0115] Animals and feeding environment Three SPF-grade golden hamsters, aged 42 to 70 days, were provided by Beijing Weitonglihua Experimental Animal Technology Co., Ltd., with the production license number of experimental animals: SCXK (Beijing) 2021-0011, and the quality certificate number: No. 110011241104423028. Feed was provided by Keao Xieli (Tianjin) Feed Co., Ltd. After the animals were purchased, they were used after passing the quarantine in the animal room of our hospital. The experimental animal use license number is SYXK (Guangdong) 2023-0137, and the temperature of the animal room is 20℃~26℃, and the relative humidity is 40%~70%.

[0116] Test method (multiple exposure method)

[0117] (1) Take three male golden hamsters that have passed the quarantine. Anesthetize the animals and clean and disinfect the tissues inside and outside the animals' mouths with iodine.

[0118] (2) Soak the test substance with a cotton ball with a diameter of 10 mm, record the volume of the test substance used, and place it in one cheek pouch of the hamster. Place a cotton ball soaked in saline in the other cheek pouch as a negative control. The contact time is 5 minutes, and it is repeated once every hour for a total of 4 times. Check the cheek pouch after each contact and before repeated placement. Observe the cheek pouch with the naked eye 24 hours after the last contact.

[0119] (3) 24 hours after the last contact, the animals were painlessly sacrificed, and the mucosa and surrounding tissues at the contact site of the sample were obtained, fixed with 10% formalin, embedded in conventional paraffin, and semi-continuously sectioned, with 5 sections taken at intervals, and stained with HE.

[0120] Result determination: The results were determined according to 10.1.2 Table 1 Oral Mucosal Reaction Scoring System, 10.2.2 Table 2 Oral Mucosal Tissue Reaction Scoring System and 11.2 Table 3 Oral Mucosal Tissue Reaction Grading in YY / T 0127.13-2018 “Biological Evaluation of Oral Medical Devices Part 13: Oral Mucosal Irritation Test”.

[0121] 2. Results

[0122] The test results are shown in Tables 6 and 7.

[0123] Table 6 Score table for naked eye observation of oral mucosa reaction of golden hamsters after the last exposure to the test substances

[0124] Animal No. Sample 24h scoring Compare 24h scoring 1 0 0 2 0 0 3 0 0 Average score per animal 0 0

[0125] Table 7 Response scores of the test substances to the oral mucosal tissue of golden hamsters

[0126]

[0127] The test results show that after the sample is given, the average score of the 24-hour reaction of the mucosa at the sample placement position observed by naked eyes is 0. The observation results of the oral mucosal reaction of the golden hamster are shown in Table 6, and the observation results of the oral mucosal tissue reaction are shown in Table 7. It can be seen that under the conditions of this test, the test result is no irritation.

[0128] 6. Consumer Evaluation Report Questionnaire

[0129] The mouthwash prepared in this example was entrusted to the Guangzhou Quality Supervision and Inspection Institute for a consumer questionnaire evaluation, i.e., a consumer evaluation test after the mouthwash was used, which specifically included:

[0130] (I) Test method

[0131] 1. Experimental Design

[0132] A randomized, single-blind research design was used. Subjects were recruited to use the test substance according to the test requirements and then fill out a consumer questionnaire. The mean, proportion and statistical significance of each option in the survey question were statistically analyzed.

[0133] 2. Sample Description

[0134] Directions for use: Put 15mL of mouthwash in your mouth, leave it on the teeth, oral mucosa, tongue tip, palate, and throat for 30 seconds, rinse once and spit it out.

[0135] 3. Test time and location

[0136] Test time: 2024.06.21

[0137] Test location: Room 308, Quality Inspection Building, No. 1-2, Zhujiang Road, Chaotian Industrial Zone, Shilou Town, Panyu District, Guangzhou

[0138] 4. Test process

[0139] The trial process includes: visiting the laboratory; explaining the trial situation, signing the informed consent; inclusion / exclusion; using mouthwash and filling out questionnaires as required; and the end of the trial. All processes were carried out on the same day.

[0140] 5. Subject Screening

[0141] Inclusion criteria:

[0142] (1) Healthy adults (18-40 years old);

[0143] (2) Have the habit of using mouthwash in daily life;

[0144] (3) Mild oral ulcer symptoms (round or oval ulcers on the mucous membranes of the lips, cheeks, soft palate or gums of the mouth, with a white or yellow center, redness and swelling around the periphery, and pain);

[0145] (4) Willing to sign the informed consent form.

[0146] Exclusion criteria:

[0147] (1) Subjects suffer from severe oral diseases or chronic diseases; any severe periodontal diseases;

[0148] (2) open dental caries or mucosal lesions in the oral cavity;

[0149] (3) History of allergy to the test product;

[0150] (4) Women are pregnant, breastfeeding, or planning to become pregnant;

[0151] (5) The presence of any disease or condition that the trial investigator believes may affect the examination procedures and the safe completion of the trial by the subjects.

[0152] 6.Indicator Description

[0153] (1) The subjective evaluation scoring criteria are shown in Table 8.

[0154] Table 8 Subjective evaluation scoring criteria

[0155]

[0156]

[0157] Note: When the subjects make subjective evaluations, the scoring results are rounded to integers.

[0158] (2) Effectiveness: The questionnaire had a choice of “obvious improvement”, “completely non-irritating”, “very convenient / acceptable”, etc. The effective rate was the percentage of the total number of subjects to the total number of valid subjects.

[0159] 7. Statistical methods

[0160] SPSS27 software was used to perform descriptive statistics on the questionnaire data. The significance test of the efficiency was conducted through the binomial test. The null hypothesis was that the efficiency of each question was not significantly different from 50%, and the test level was α = 0.05.

[0161] (II) Project completion status

[0162] 1. Completion status of subjects

[0163] 32 qualified subjects were selected. All 32 subjects completed the trial test as required, including 8 males and 24 females, with the youngest age of 20 years old and the oldest age of 40 years old, and the average age of 33±5 years old.

[0164] 2. Questionnaire evaluation results

[0165] The questionnaire evaluation results are shown in Tables 9 and 10.

[0166] Table 9 Questionnaire scoring results

[0167]

[0168]

[0169] In the table, the score decrease degree (%) = (T0-T n )÷T0×100%, where T0 is the mean score of the question item at time T0, T n It is the average score of similar question items when n is equal to 1 and 2. “ / ” means that the indicator is not evaluated.

[0170] Table 10 Questionnaire scoring results

[0171]

[0172]

[0173] In the table, 1. A represents "obvious improvement", "obvious stimulation", "very convenient / accepted", B represents "improvement", "stimulation", "convenient / accepted", "effective", C represents "uncertain", "no tendency", D represents "no improvement", "no stimulation", "inconvenient / accepted", and E represents "no improvement at all", "no stimulation at all", "very inconvenient / accepted". 2. Effectiveness: "*" indicates that the effective rate is greater than 50% and is statistically significant (P < 0.05). Effectiveness (%) = (n A +n B )÷n×100%, where n A is the number of people who choose option A, n B is the number of people in option B, and n is the effective number of subjects. Only question 6 in stage T1 uses the following formula: Effectiveness (%) = (n D +n E )÷n×100%, where n D is the number of people who choose option D, n E is the number of people who choose option E, and n is the effective number of subjects.

[0174] In summary, under the conditions of this experiment, 32 healthy adult subjects aged 18-40 years old were asked to evaluate the efficacy of the test substance after using it under normal circumstances. The results are as follows:

[0175] (1) Before using mouthwash, the subjects' subjective evaluation of the discomfort of oral mucosal ulcer symptoms had an average score of 7.1 (significant discomfort). After gargling with mouthwash for 30 seconds for the first time, the average score was 4.4 (mild discomfort), which was a 37.5% decrease compared with before using mouthwash. After gargling with the test substance for 30 seconds for the second time, the average score was 3.5 (mild discomfort), which was a 51.1% decrease compared with before using mouthwash.

[0176] (2) Before using mouthwash, the subjects' average subjective pain score for oral mucosal ulcer symptoms was 6.8 (a little painful). After gargling with mouthwash for 30 seconds for the first time, the average score was 4.3 (mild pain), which was a 36.6% decrease in the subjective score compared with before using mouthwash. After gargling with the test substance for 30 seconds for the second time, the average score was 3.5 (mild pain), which was a 49.0% decrease in the subjective score compared with before using mouthwash.

[0177] (3) Before using mouthwash, the subjects' average subjective evaluation score of oral mucosal ulcer swelling was 6.7 (a little swollen). After gargling with mouthwash for 30 seconds for the first time, the average score was 4.5 (slightly swollen). Compared with before using mouthwash, the subjective score decreased by 32.4%. After gargling with the test substance for 30 seconds for the second time, the average score was 3.5 (slightly swollen). Compared with before using mouthwash, the subjective score decreased by 47.3%.

[0178] (4) Before using the mouthwash, the subjects' subjective evaluation of gingival redness and swelling had an average score of 6.6 (a little red and swollen). After gargling with the mouthwash for 30 seconds for the first time, the average score was 4.3 (slightly red and swollen). Compared with before using the mouthwash, the subjective score decreased by 34.2%. After gargling with the test substance for 30 seconds for the second time, the average score was 3.5 (slightly red and swollen). Compared with before using the mouthwash, the subjective score decreased by 47.0%.

[0179] (5) After gargling with mouthwash for 30 seconds for the first time, 68.8% of the subjects felt that the symptoms of oral mucosal ulcers had improved; and 90.6% of the subjects felt that it was gentle, comfortable and non-irritating (P < 0.05).

[0180] (6) 96.9% of the subjects believed that this mouthwash was more convenient than other mouthwash products used to treat oral ulcer symptoms (P < 0.05).

[0181] (7) After gargling with mouthwash for 30 seconds for the second time, 81.3% of the subjects felt that the symptoms of oral mucosal ulcers had improved (P < 0.05).

[0182] (8) After using the mouthwash for 30 minutes, 96.9% of the subjects agreed that the pain of oral ulcers was relieved continuously within 30 minutes (P < 0.05); 96.9% of the subjects agreed that the discomfort in the oral cavity was relieved continuously within 30 minutes (P < 0.05).

[0183] (9) After using the mouthwash for 60 minutes, 96.9% of the subjects agreed that the pain of oral ulcers was relieved continuously within 60 minutes (P < 0.05); 100.0% of the subjects agreed that the discomfort in the oral cavity was relieved continuously within 60 minutes (P < 0.05).

[0184] Embodiment 2

[0185] In this example, based on Example 1, the dosage of each component is optimized and improved, as shown in Table 11.

[0186] Table 11 Mouthwash formula

[0187] Raw material name Test 1 Test 2 Test 3 Test 4 Test 5 Test 6 Comparison 1 Comparison 2 Contrast 3 Contrast 4 Contrast 5 Contrast 6 glycerin 50％ 1％ 10％ 5％ 15％ 3％ 10％ 10％ 10％ 10％ 10％ 10％ Methylparaben 0.05％ 1％ 1.2％ 1.5％ 0.5％ 0.1％ 0.15％ 0.15％ 0.15％ 0.15％ 0.15％ 0.15％ Ethylhexylglycerin 0.005％ 1％ 1.2％ 1.5％ 1.8％ 2％ 0.2％ 0.2％ 0.2％ 0.2％ 0.2％ 0.2％ Propylene glycol 1％ 20％ 5％ 10％ 15％ 3％ 6％ 6％ 6％ 6％ 6％ 6％ β-Glucan 0.005％ 8％ 5％ 10％ 2％ 1％ / 0.2％ 0.2％ / 0.2 / Blue Copper Peptide 0.005％ 8％ 5％ 10％ 2％ 1％ 0.2％ / 0.2％ 0.2％ / / Dipotassium glycyrrhizinate 0.005％ 8％ 5％ 10％ 2％ 1％ 0.2％ 0.2％ / / / 0.2 Xylitol 1％ 10％ 5％ 15％ 8％ 2％ 1％ 1％ 1％ 1％ 1％ 1％ Poloxamer 407 0.01％ 7％ 5％ 10％ 1％ 1％ 3％ 3％ 3％ 3％ 3％ 3％ Sorbitol 1％ 2％ 20％ 5％ 10％ 50％ 16％ 16％ 16％ 16％ 16％ 16％ 1,2-Hexanediol 0.05％ 0.5％ 1％ 1.2％ 1.5％ 0.1％ 2％ 2％ 2％ 2％ 2％ 2％

[0188] In the formulations of Table 11, the solvent for all tests and comparisons is water, and the balance is water.

[0189] According to the formula in Table 11, twelve kinds of mouthwashes were prepared in this example, wherein the dosage of each component was adjusted in Test 1 to Test 6, and only one or two functional substances were used in Comparison 1 to Comparison 6, respectively.

[0190] The twelve mouthwashes in Table 11 were subjected to “II. Mouthwash stability test” in the manner of Example 1. The stability results after three months of storage are shown in Table 12.

[0191] Table 12 Stability test results of different formula mouthwashes placed for three months

[0192]

[0193]

[0194]

[0195]

[0196] The results of Table 12 show that the mouthwash of Test 1 has good stability. From Test 2 to Test 6, as the content of the three major functional ingredients increases, the stability weakens. As for Comparison 1 to Comparison 6, although the stability is good, the efficacy is insufficient, that is, there is no combination of the three major functional ingredients, so it will affect the oral repair effect. In short, the amount of β-glucan is 0.005-10% of the total weight, the amount of dipotassium glycyrrhizinate is 0.005-10% of the total weight, and the amount of blue copper peptide is 0.005-10% of the total weight. Such a ratio and combination can meet both relatively good stability and good oral repair effects.

[0197] The twelve mouthwashes in Table 11 were tested in the manner of Example 1 in "III. Test of mouthwash on oral ulcer patients". In this example, 15 patients with obvious oral ulcers were randomly selected for testing. The specific testing method was: 15 mL of the mouthwash in this example was used each time, 3-5 times a day, and no water or food was consumed half an hour after rinsing the mouth. Scoring mechanism: 10-point system: 0 points (very bad) → 10 points (very good). The test results are shown in Table 13.

[0198] Table 13 Test results of mouthwash on oral ulcers (all total test results of 15 people)

[0199]

[0200] The results in Table 13 show that the combination of the three major effects produces a synergistic effect, and the inflammation relief and pain relief effects are more obvious; and when the added amount is low, the effect is obviously better than that of a single functional substance.

[0201] Embodiment 3

[0202] The oral care composition of this example includes glucan, glycyrrhizic acid salt and blue copper peptide; wherein the glucan is β-glucan and the glycyrrhizic acid salt is dipotassium glycyrrhizinate. In this example, the oral care composition is made into an oral spray and its stability and oral mucosal repair performance are tested. Specifically, it includes:

[0203] In this example, oral spray was prepared according to the formula and dosage ratio of Table 14.

[0204] Table 14 Oral spray formulation

[0205] Raw material name Formula % effect water 50.85 Solvents glycerin 10 Moisturizer Methylparaben 0.15 preservative Ethylhexylglycerin 0.2 preservative Propylene glycol 6 Moisturizer β-Glucan 0.4 Functional substances Blue Copper Peptide 0.4 Functional substances Dipotassium glycyrrhizinate 2 Functional substances Xylitol 4 Sweeteners Poloxamer 407 4 Solubilizer Sorbitol 20 Moisturizer 1,2-Hexanediol 2 Moisturizer

[0206] Repair mouth spray stability test

[0207] The mouth spray prepared in this example was placed under room temperature 25°C, heat resistance 45°C, heat resistance 50°C, normal temperature light (light box), cold resistance 5°C, and cold resistance -18°C for twelve weeks, and the pH value, appearance and odor of the mouth spray were observed to judge the stability of the mouth spray. The results are shown in Table 15.

[0208] Table 15 Mouth spray stability test results

[0209]

[0210] The results in Table 15 show that the mouth spray prepared in this example has good stability at both 50°C and -18°C, and has good long-term stability. This example tested the stability of the mouth spray at high and low temperatures for 3 months, and therefore, it can be inferred that it can be placed at room temperature for a longer time and maintain stability.

[0211] Test of oral spray on people with oral ulcers

[0212] In this case, 15 patients with obvious oral ulcers were randomly selected for testing. The specific testing method is: use the oral spray of this case 1-2mL each time, 2-3 times a day, and do not drink water or eat for half an hour after oral spraying. Scoring mechanism: 10-point system: 0 points (very bad) → 10 points (very good). The test results are shown in Table 16.

[0213] Table 16 Test results of mouth spray on oral ulcers

[0214]

[0215]

[0216] The results in Table 16 show that 99% of the testers believed that there was significant immediate relief and improvement; 90% of the testers believed that there was relief of inflammation and pain after one day of use; and 90% of the testers believed that there was significant relief of inflammation and pain after 3 and 7 days of use.

[0217] Based on the above experiments, this example further optimized and improved the dosage of each component, as shown in Table 17.

[0218] Table 17 Mouth spray formula

[0219] Raw material name Test 7 Test 8 Test 9 Test 10 Test 11 Test 12 Contrast 7 Contrast 8 Contrast 9 Contrast 10 Contrast 11 Contrast 12 glycerin 50％ 10％ 15％ 5％ 15％ 3％ 10％ 10％ 10％ 10％ 10％ 10％ Methylparaben 0.05％ 1％ 1.2％ 1.5％ 0.5％ 0.1％ 0.15％ 0.15％ 0.15％ 0.15％ 0.15％ 0.15％ Ethylhexylglycerin 0.005％ 1％ 1.2％ 1.5％ 1.8％ 2％ 0.2％ 0.2％ 0.2％ 0.2％ 0.2％ 0.2％ Propylene glycol 1％ 20％ 5％ 10％ 15％ 3％ 6％ 6％ 6％ 6％ 6％ 6％ β-Glucan 0.005％ 8％ 5％ 10％ 2％ 1％ / 0.4％ 0.4％ / 0.4％ / Blue Copper Peptide 0.005％ 8％ 5％ 10％ 2％ 1％ 0.4％ / 0.4％ 0.4％ / / Dipotassium glycyrrhizinate 0.005％ 8％ 5％ 10％ 2％ 1％ 0.4％ 0.4％ / / / 0.4％ Xylitol 1％ 10％ 5％ 15％ 8％ 2％ 4％ 4％ 4％ 4％ 4％ 4％ Poloxamer 407 0.01％ 7％ 5％ 10％ 1％ 1％ 6％ 6％ 6％ 6％ 6％ 6％ Sorbitol 1％ 2％ 20％ 5％ 10％ 50％ 20％ 20％ 20％ 20％ 20％ 20％ 1,2-Hexanediol 0.05％ 0.5％ 1％ 1.2％ 1.5％ 0.1％ 2％ 2％ 2％ 2％ 2％ 2％

[0220] In the formulations of Table 17, the solvent for all tests and comparisons is water, and the balance is water.

[0221] According to the formula in Table 17, twelve mouth sprays were prepared in this example, wherein the dosage of each component was adjusted in Test 7 to Test 12, and only one or two functional substances were used in Comparison 7 to Comparison 12, respectively.

[0222] The mouth spray in Table 17 was subjected to stability test in the same manner, and the stability results after three months are shown in Table 18.

[0223] Table 18 Stability test results of different mouth sprays

[0224]

[0225]

[0226]

[0227]

[0228] The stability results of the oral spray in this example are similar to those of the mouthwash in Example 2, that is, the higher the content of the three functional ingredients, the more unstable it is. In addition, the amount of β-glucan is 0.005-10% of the total weight, the amount of dipotassium glycyrrhizinate is 0.005-10% of the total weight, and the amount of blue copper peptide is 0.005-10% of the total weight. Such a ratio and combination can meet both relatively good stability and good oral repair effects.

[0229] In this case, 15 patients with obvious oral ulcers were randomly selected for testing. The specific testing method is: use the oral spray of this case 1-2mL each time, 2-3 times a day, and do not drink water or eat for half an hour after oral spraying. Scoring mechanism: 10-point system: 0 points (very bad) → 10 points (very good). The test results are shown in Table 19.

[0230] Table 19 Test results of oral spray on oral ulcers (all are the total test results of 15 people, spray 2-3 times a day)

[0231]

[0232]

[0233] The results in Table 19 show that the technical effect produced by the combination of the three major effects is significantly better than that of a single functional substance. Therefore, the three major functional substances can produce a synergistic effect to enhance the effects of inflammation relief and pain relief.

[0234] Embodiment 4

[0235] The oral care composition of this example includes glucan, glycyrrhizic acid salt and blue copper peptide; wherein the glucan is β-glucan and the glycyrrhizic acid salt is dipotassium glycyrrhizinate. In this example, the oral care composition is made into an oral repair gel, and its stability and oral mucosal repair performance are tested. Specifically including:

[0236] In this example, an oral care gel was prepared according to the formula and dosage ratio in Table 20.

[0237] Table 20 Oral Care Gel Formula

[0238] Raw material name Example: Formula % effect water 58.1 Solvents glycerin 10 Moisturizer Methylparaben 0.15 preservative Ethylhexylglycerin 0.2 preservative Propylene glycol 6 Moisturizer Xanthan gum 0.15 Thickener β-Glucan 0.2 Functional substances Blue Copper Peptide 0.2 Functional substances Dipotassium glycyrrhizinate 1 Functional substances Xylitol 2 Sweeteners Poloxamer 407 8 Solubilizer Sorbitol 12 Moisturizer 1,2-Hexanediol 2 Moisturizer

[0239] Repair gel stability test

[0240] The gel prepared in this example was placed under room temperature 25°C, heat resistance 45°C, heat resistance 50°C, normal temperature light (light box), cold resistance 5°C, and cold resistance -18°C for twelve weeks. The pH value, appearance and odor of the gel were observed to judge the stability of the gel. The results are shown in Table 21.

[0241] Table 21 Gel stability test results

[0242]

[0243]

[0244] The results in Table 21 show that the gel prepared in this example has good stability at both 50°C and -18°C, and has good long-term stability. In this example, the gel was tested for good stability at both high and low temperatures for 3 months, so it can be inferred that it can be stored at room temperature for a longer time and maintain stability.

[0245] Testing of the gel on people with mouth ulcers

[0246] In this case, 15 patients with obvious oral ulcers were randomly selected for testing. The specific testing method was: 1 mL of the oral gel of this case was used 2-3 times a day, and no water or food was consumed half an hour after use. Scoring mechanism: 10-point system: 0 (very bad) → 10 (very good). The test results are shown in Table 22.

[0247] Table 22 Test results of oral gel on oral ulcers

[0248]

[0249] The results in Table 22 show that 99% of the testers believed that there was significant immediate relief and improvement; 90% of the testers believed that there was relief of inflammation and pain after one day of use; and 98% of the testers believed that there was significant relief of inflammation and pain after 3 and 7 days of use.

[0250] Based on the above experiments, this example further optimized and improved the dosage of each component, as shown in Table 23.

[0251] Table 23 Gel formula

[0252]

[0253]

[0254] In the formulations of Table 23, the solvent for all tests and comparisons is water, and the balance is water.

[0255] According to the formula in Table 23, twelve kinds of oral gels were prepared in this example, wherein the dosage of each component was adjusted in Test 13 to Test 18, and only one or two functional substances were used in Comparative 13 to Comparative 18.

[0256] The stability test of the oral gel in Table 23 was carried out in the same manner. The stability results after three months are shown in Table 24.

[0257] Table 24 Stability test results of different oral gels

[0258]

[0259]

[0260]

[0261] The stability results of the oral gel in this example are similar to those of the mouthwash in Example 2, that is, the higher the content of the three functional ingredients, the more unstable it is. In addition, the amount of β-glucan is 0.005-10% of the total weight, the amount of dipotassium glycyrrhizinate is 0.005-10% of the total weight, and the amount of blue copper peptide is 0.005-10% of the total weight. Such a ratio and combination can meet both relatively good stability and good oral repair effects.

[0262] In this case, 15 patients with obvious oral ulcers were randomly selected for testing. The specific testing method is: use 1-2 mL of the gel in this case each time, 2-3 times a day, and do not drink water or eat for half an hour after use. Scoring mechanism: 10-point system: 0 points (very bad) → 10 points (very good). The test results are shown in Table 25.

[0263] Table 25 Test results of gel on oral ulcers (all are the total test results of 15 people, applied 1-2 times a day)

[0264]

[0265] The results of Table 25 show that the technical effects of experiments 13 to 18 of the three major functional combinations are significantly better than those of single functional substances, such as comparisons 13 to 18; this shows that the combination of the three major functional substances can produce a synergistic effect and enhance the effects of relieving inflammation and pain.

[0266] The above contents are further detailed descriptions of the present application in combination with specific implementation methods, and it cannot be determined that the specific implementation of the present application is limited to these descriptions. For ordinary technicians in the technical field to which the present application belongs, several simple deductions or substitutions can be made without departing from the concept of the present application.

Claims

1. A composition for oral care, characterized in that: Includes dextran, glycyrrhizinate and blue copper peptides.

2. The composition according to claim 1, characterized in that: The glucan includes α-glucan and / or β-glucan.

3. The composition according to claim 1, characterized in that: The glycyrrhizic acid salt is dipotassium glycyrrhizinate.

4. The composition according to any one of claims 1 to 3, characterized in that: Also included is a solvent for dispersing or dissolving dextran, glycyrrhizinate and blue copper peptide.

5. The composition according to claim 4, characterized in that: The solvent is water.

6. The composition according to claim 4, characterized in that: The amount of the dextran is 0.005-10% of the total weight of the composition, the amount of the glycyrrhizic acid salt is 0.005-10% of the total weight of the composition, and the amount of the blue copper peptide is 0.005-10% of the total weight of the composition.

7. The composition according to claim 4, characterized in that: Also includes moisturizer.

8. The composition according to claim 7, characterized in that: The humectant includes at least one of glycerin, propylene glycol, sorbitol and 1,2-hexanediol.

9. The composition according to claim 8, characterized in that: The moisturizing agent consists of glycerin, propylene glycol, sorbitol and 1,2-hexanediol.

10. The composition according to claim 9, characterized in that: The amount of glycerol used is 1-50% of the total weight of the composition, the amount of propylene glycol used is 1-50% of the total weight of the composition, the amount of sorbitol used is 1-50% of the total weight of the composition, and the amount of 1,2-hexanediol used is 0.05-10% of the total weight of the composition.

11. The composition according to claim 4, characterized in that: Also includes preservatives.

12. The composition according to claim 11, characterized in that: Such preservatives include methylparaben and ethylhexylglycerin.

13. The composition according to claim 12, characterized in that: The amount of the methylparaben used is 0.05-5% of the total weight of the composition, and the amount of the ethylhexylglycerin used is 0.005-10% of the total weight of the composition.

14. The composition according to claim 4, characterized in that: Also included are solubilizing agents.

15. The composition according to claim 14, characterized in that: The solubilizing agent is poloxamer 407.

16. The composition according to claim 15, characterized in that: The amount of Poloxamer 407 used is 0.01-10% of the total weight of the composition.

17. The composition according to claim 4, characterized in that: Sweeteners are also included.

18. The composition according to claim 17, characterized in that: The sweetener is xylitol.

19. The composition according to claim 18, characterized in that: The amount of xylitol used is 1-30% of the total weight of the composition.

20. Use of the composition according to any one of claims 1 to 19 in preparing a mouthwash, an oral spray or an oral care gel.

21. A mouthwash prepared using the composition according to any one of claims 1 to 19.

22. An oral spray prepared using the composition of any one of claims 1 to 19.

23. An oral care gel prepared using the composition according to any one of claims 1 to 19.

24. The oral care gel according to claim 23, characterized in that: The invention comprises the composition according to any one of claims 1 to 19 and a thickener.

25. The oral care gel according to claim 24, characterized in that: The thickener is xanthan gum.

26. The oral care gel according to claim 25, characterized in that: The amount of xanthan gum used is 0.05-10% of the total weight of the oral care gel.

Images