Sustained-release gel for treating oral diseases as well as preparation method and application of sustained-release gel

Abstract

The invention discloses sustained-release gel for treating oral diseases as well as a preparation method and application of the sustained-release gel. The slow-release gel provided by the invention is prepared from the following components in parts by weight: 0.3 to 1.5 parts of yeast beta-glucan, 2 to 4 parts of maltooligosaccharide and 0.5 to 2 parts of carbomer. The yeast beta-glucan comprises ultra-low molecular weight yeast beta-glucan, low molecular weight yeast beta-glucan, medium molecular weight yeast beta-glucan and high molecular weight yeast beta-glucan. The components are reasonably matched, so that the stability of the product is improved. The carbomer and the high molecular weight yeast beta-glucan form a protective layer on oral mucosa, ulcer surface and periodontal tissue surface, so that the active ingredients are continuously released in the oral cavity, the local effective concentration is maintained, the active ingredients directly act on the oral diseased region, the treatment effect is improved, the action time is prolonged, and the bioavailability is improved. Meanwhile, the sustained-release gel disclosed by the invention is clear in components, high in safety and wide in application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of biotechnology, and particularly relates to a sustained-release gel for treating oral diseases, a preparation method thereof, and an application thereof. Background Art

[0002] The oral cavity is prone to various pathological phenomena under the damage of external physical and chemical factors, the invasion of pathogens, abnormal dentofacial development, and systemic diseases. For example, dental caries, gingival bleeding, oral ulcers, gingivitis or periodontitis, gingival atrophy, etc., are usually accompanied by bad breath, toothache, etc., which are unbearable. Although oral diseases occur in the oral cavity, they actually produce many viruses. Through blood circulation, they can spread to other parts of the body, infect cardiovascular tissues, cause cardiovascular diseases, cause diabetes, and even the brain will be deeply affected. Therefore, oral health should be taken seriously by people.

[0003] Most of the compositions for treating oral problems in the related art only aim at relieving bad breath or treating oral ulcers, and cannot achieve good effects in improving oral hygiene, preventing and treating oral diseases. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. For this purpose, the present invention provides a sustained-release gel for treating oral diseases.

[0005] The present invention also provides a preparation method of the above-mentioned sustained-release gel.

[0006] The present invention also provides an application of the above-mentioned sustained-release gel.

[0007] The present invention also provides a drug.

[0008] According to a first aspect of the present invention, there is provided a sustained-release gel for treating oral diseases, which comprises 0.3-1.5 parts of yeast β-glucan, 2-4 parts of maltodextrin, and 0.5-2 parts of carbomer by weight.

[0009] The yeast β-glucan includes ultra-low molecular weight yeast β-glucan, low molecular weight yeast β-glucan, medium molecular weight yeast β-glucan, and high molecular weight yeast β-glucan.

[0010] The mass ratio of the ultra-low molecular weight yeast β-glucan, the low molecular weight yeast β-glucan, the medium molecular weight yeast β-glucan to the high molecular weight yeast β-glucan is (1-3):(1-5):(2-4):(1-4).

[0011] According to some embodiments of the present invention, the treatment of oral diseases includes inhibiting the proliferation of oral bacteria, treating periodontitis, treating oral ulcers, and treating bacterial gastric ulcers.

[0012] According to some embodiments of the invention, the oral bacteria include Helicobacter pylori and Porphyromonas gingivalis.

[0013] The present invention rationally matches and co-encapsulates four yeast β-glucans of different molecular weights (ultra-low molecular weight yeast β-glucan, low molecular weight yeast β-glucan, medium molecular weight yeast β-glucan and high molecular weight yeast β-glucan), and has an outstanding comprehensive effect. The ultra-low molecular weight yeast β-glucan is easily absorbed by the oral mucosa and can regulate local immune response; the low molecular weight yeast β-glucan activates immune cells in the oral cavity, enhances the ability to clear bacteria, and inhibits Helicobacter pylori; the medium molecular weight yeast β-glucan can inhibit the attachment and growth of periodontal pathogens; carbomer and high molecular weight β-glucan form a protective layer on the oral mucosa, ulcer surface and periodontal tissue surface, reduce the invasion of bacteria and inflammatory factors, and can also prolong the action time of active ingredients; oligosaccharides regulate the oral microecology, inhibit the excessive growth of pathogens, and reduce the risk of secondary infection of ulcers.

[0014] According to some embodiments of the present invention, the molecular weight of the ultra-low molecular weight yeast β-glucan is less than 1 WDa.

[0015] According to some preferred embodiments of the present invention, the molecular weight of the ultra-low molecular weight yeast β-glucan is less than 5000 Da.

[0016] According to some embodiments of the present invention, the molecular weight of the low molecular weight yeast β-glucan is 1 WDa to 50 WDa.

[0017] According to some preferred embodiments of the present invention, the molecular weight of the low molecular weight yeast β-glucan is 5WDa to 20WDa.

[0018] According to some embodiments of the present invention, the molecular weight of the medium molecular weight yeast β-glucan is 50 WDa to 200 WDa.

[0019] According to some preferred embodiments of the present invention, the molecular weight of the medium molecular weight yeast β-glucan is 50 WDa to 150 WDa.

[0020] According to some embodiments of the invention, the molecular weight of the high molecular weight yeast β-glucan is >200 WDa.

[0021] According to some preferred embodiments of the present invention, the molecular weight of the high molecular weight yeast β-glucan is >300 WDa.

[0022] According to some embodiments of the present invention, the molecular weight of the mannan is >50 WDa.

[0023] According to some embodiments of the present invention, the yeast β-glucan has a β-1,3-linkage as the main chain, and contains 1-2 glucose side chains linked by β-1,6 on average every 3-7 main-chain glucose residues.

[0024] According to some embodiments of the present invention, the composition further comprises 0.01-0.1 parts of peppermint oil.

[0025] According to some embodiments of the present invention, the composition further comprises 0.01-0.05 parts of peppermint oil.

[0026] According to some embodiments of the present invention, the composition further comprises water.

[0027] According to some embodiments of the present invention, the composition further comprises 0.01-30 parts of auxiliary materials, preferably 0.05-10 parts.

[0028] Further, the auxiliary materials include at least one of a sweetening agent, a preservative, and a pH regulator.

[0029] According to some embodiments of the present invention, the sweetening agent includes at least one of sodium saccharin, cyclamate, sucralose, aspartame, alitame, neotame, stevioside, and xylitol.

[0030] According to some embodiments of the present invention, the preservative includes at least one of sodium methylparaben, benzoic acid, sodium benzoate, phenoxyethanol, sorbic acid, or sodium sorbate; preferably sodium methylparaben.

[0031] According to some embodiments of the present invention, the pH regulator includes citric acid.

[0032] According to the second aspect of the present invention, there is provided a preparation method of the above composition, comprising the following step: mixing each component to obtain the composition.

[0033] According to the third aspect of the present invention, there is provided an application of the above composition in any one of the following:

[0034] (1) Preparing a product for inhibiting oral bacteria;

[0035] (2) Preparing a product for treating periodontitis;

[0036] (3) Preparing a product for treating oral ulcers;

[0037] (4) Preparing a product for treating bacterial gastric ulcers.

[0038] According to some embodiments of the present invention, the oral bacteria include Helicobacter pylori and Porphyromonas gingivalis.

[0039] According to a fourth aspect of the present invention, there is provided an article comprising the above-mentioned sustained-release gel, and the article is a product for inhibiting oral bacteria, treating periodontitis, treating oral ulcers, and / or treating bacterial gastric ulcers.

[0040] According to some embodiments of the present invention, the article comprises a drug and a medical device.

[0041] According to some embodiments of the present invention, the drug further comprises a pharmaceutically acceptable excipient;

[0042] Furthermore, the excipient includes at least one of a diluent, a filler, a binder, an absorption enhancer, a surfactant, an adsorption carrier, a lubricant, and a flavoring agent.

[0043] The diluent can be commonly used in the art and includes at least one of calcium sulfate, calcium bicarbonate, and calcium carbonate; the filler can be commonly used in the art and includes at least one of starch, sucrose, and lactose; the binder can be commonly used in the art and includes at least one of cellulose derivatives, alginates, gelatin, and polyvinylpyrrolidone; the absorption enhancer can be a quaternary ammonium compound commonly used in the art; the surfactant can be cetyl alcohol commonly used in the art; the adsorption carrier can be commonly used in the art and includes at least one of kaolin or saponite clay; the lubricant can be commonly used in the art and includes at least one of talc, calcium stearate, magnesium stearate, and polyethylene glycol; the flavoring agent can be commonly used in the art and includes at least one of rose oil, rose essence, lemon oil, lemon essence, vanilla essence, vanillin, banana essence, pineapple essence, peppermint oil, orange peel oil, and apple essence.

[0044] According to some embodiments of the present invention, the dosage form of the drug is a gel, a cream, a solution, a spray, a patch, a powder, an ointment, a drop, a suppository, a lozenge, a granule, a patch, a capsule, a tablet, or a pill.

[0045] According to some embodiments of the present invention, the medical device is a gel.

[0046] According to some embodiments of the present invention, it has at least the following beneficial effects:

[0047] In the present invention, by reasonably matching ultra-low molecular weight yeast β-glucan, low molecular weight yeast β-glucan, medium molecular weight yeast β-glucan, high molecular weight yeast β-glucan, carbomer, and isomaltooligosaccharide, the product stability is improved. Among them, carbomer and high molecular weight yeast β-glucan form a protective layer on the oral mucosa, ulcer surface, and periodontal tissue surface, enabling the active ingredients to be continuously released in the oral cavity, maintaining the local effective concentration, directly acting on the oral lesion site, improving the treatment effect, prolonging the action time, and increasing the bioavailability. At the same time, the components in the gel of the present invention are clear and have high safety, and have broad application prospects.

[0048] Other features and advantages of the present invention will be set forth in the following description, and in part will be obvious from the description, or may be learned by practice of the present invention. Detailed implementation mode

[0049] The concept of the present invention and the technical effects produced will be clearly and completely described below in conjunction with embodiments to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative efforts shall fall within the scope of protection of the present invention.

[0050] Unless otherwise specified, the test methods used in the embodiments are all conventional methods; the materials, reagents, etc. used, unless otherwise specified, are all reagents and materials that can be obtained from commercial channels.

[0051] The terms "preferably", "more preferably", etc. in the present invention refer to embodiments of the present invention that can provide certain beneficial effects in certain cases. However, in the same case or other cases, other embodiments may also be preferred. In addition, the description of one or more preferred embodiments does not imply that other embodiments are not available, nor is it intended to exclude other embodiments from the scope of the present invention.

[0052] When a numerical range is disclosed herein, the above range is considered continuous and includes the minimum and maximum values of the range, as well as each value therebetween. Further, when the range refers to integers, it includes each integer between the minimum and maximum values of the range. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all sub-ranges subsumed therein.

[0053] "Prepared from" is synonymous with "comprising". As used herein, the terms "comprising", "including", "having", "containing" or any other variation thereof are intended to cover non-exclusive inclusion. For example, a composition, step, method, article or device comprising the listed elements is not necessarily limited to those elements, but may include other elements not expressly listed or elements inherent to such composition, step, method, article or device.

[0054] "Parts by mass" refers to the basic measurement unit representing the mass ratio relationship of multiple components. 1 part can represent any unit mass, such as 1 g or 2.689 g, etc. If the mass of component A is a parts by mass and the mass of component B is b parts by mass, it represents the mass ratio of component A to component B as a:b. Or, it means the mass of component A is aK and the mass of component B is bK (K is an arbitrary number representing the multiplication factor). It should not be misunderstood that, different from the number of mass parts, the sum of the mass parts of all components is not limited to 100 parts.

[0055] Unless otherwise specified, "about" in the present invention means that the allowable error is within ±10%.

[0056] The yeast β-glucan used in the present invention is a yeast β-glucan with a β-1,3-linkage as the main chain, and on average, 1-2 glucose side chains with β-1,6-linkage are contained on every 3-7 main-chain glucose residues.

[0057] Preparation of Yeast β-Glucans with Different Molecular Weights in Example 1

[0058] In this example, yeast β-glucans with different molecular weights were prepared. The specific process is as follows:

[0059] Take an appropriate amount of commercially available yeast β-glucan, dissolve it in purified water, shake well to obtain a yeast β-glucan solution of about 40 mg / mL, and filter it through a 0.22 μm filter membrane.

[0060] Pack the swollen chromatography packing into a column, use purified water to press the column until the column uniformity meets the requirements; after packing the column, use 3-5 times the column volume of pure water to balance the chromatography column. After the chromatography column is balanced, load the sample with a loading concentration of 40 mg / mL. Use pure water for elution, discard the first 50 mL of the eluate collected, then collect the eluate in fractions, and then use high-performance gel permeation chromatography to measure its molecular weight distribution. Combine the eluates with consistent polysaccharide molecular weight distributions, concentrate them, and then freeze-dry. Ultra-low molecular weight yeast β-glucan with a molecular weight <10 kDa, low molecular weight yeast β-glucan with a molecular weight of 10 kDa - 50 kDa, medium molecular weight yeast β-glucan with a molecular weight of 50 kDa - 200 kDa, and high molecular weight yeast β-glucan with a molecular weight >200 kDa are respectively prepared.

[0061] Example 2

[0062] This example provides a sustained-release gel for treating oral diseases, containing the following components in parts by mass:

[0063] Carbomer 1.2%;

[0064] Ultra-low molecular weight yeast β-glucan prepared in Example 1 0.2%;

[0065] 0.4% of the low-molecular-weight yeast β-glucan prepared in Example 1;

[0066] 0.3% of the medium-molecular-weight yeast β-glucan prepared in Example 1;

[0067] 0.1% of the high-molecular-weight yeast β-glucan prepared in Example 1;

[0068] 2% of isomaltooligosaccharide;

[0069] 0.03% of aspartame;

[0070] 0.03% of sodium methylparaben;

[0071] An appropriate amount of citric acid (the pH can be adjusted to 5.5 - 6.0, and in this example, it is 5.5);

[0072] 0.03% of peppermint oil;

[0073] The balance is deionized water.

[0074] Taking the total amount as 100 g as the system, the preparation method of the sustained-release gel for treating oral diseases with the above ratios is as follows:

[0075] (1) Disperse 1.2 g of carbomer in 80 mL of deionized water and let it stand for swelling.

[0076] (2) Dissolve 1.0 g of β-glucan and 2.0 g of isomaltooligosaccharide in 10 mL of deionized water, add the carbomer matrix, and homogenize and stir.

[0077] (3) Add 0.03 g of aspartame and 0.03 g of sodium methylparaben and stir to dissolve.

[0078] (4) Adjust the pH to 5.8 with citric acid, add 0.03 g of peppermint oil, and mix evenly.

[0079] (5) Make up the deionized water to 100 g, perform vacuum degassing, and then fill and sterilize.

[0080] Example 3

[0081] This example provides a sustained-release gel for treating oral diseases, containing the following components in parts by mass:

[0082] 1.0% of carbomer;

[0083] 0.2% of the ultra-low-molecular-weight yeast β-glucan prepared in Example 1;

[0084] 0.4% of the low-molecular-weight yeast β-glucan prepared in Example 1;

[0085] 0.3% of medium molecular weight yeast β-glucan prepared in Example 1;

[0086] 0.3% of high molecular weight yeast β-glucan prepared in Example 1;

[0087] 2% of isomaltooligosaccharide;

[0088] 0.03% of aspartame;

[0089] 0.03% of sodium methylparaben;

[0090] Appropriate amount of citric acid (the pH can be adjusted to 5.5 - 6.0, and in this example it is 5.5);

[0091] 0.03% of peppermint oil;

[0092] The balance is deionized water.

[0093] The preparation method is the same as that of Example 2.

[0094] Example 4

[0095] This example provides a sustained-release gel for treating oral diseases, containing the following components in parts by mass:

[0096] 1.2% of carbomer;

[0097] 0.2% of ultra-low molecular weight yeast β-glucan prepared in Example 1;

[0098] 0.2% of low molecular weight yeast β-glucan prepared in Example 1;

[0099] 0.3% of medium molecular weight yeast β-glucan prepared in Example 1;

[0100] 0.2% of high molecular weight yeast β-glucan prepared in Example 1;

[0101] 3% of isomaltooligosaccharide;

[0102] 0.03% of aspartame;

[0103] 0.03% of sodium methylparaben;

[0104] Appropriate amount of citric acid (the pH can be adjusted to 5.5 - 6.0, and in this example it is 5.5);

[0105] 0.03% of peppermint oil;

[0106] The balance is deionized water.

[0107] The preparation method is the same as that of Example 2.

[0108] Comparative Example 1

[0109] This comparative example provides a sustained-release gel for treating oral diseases. Referring to the formulation and preparation method of Example 2, the difference lies in that it does not contain ultra-low molecular weight yeast β-glucan.

[0110] Comparative Example 2

[0111] This comparative example provides a sustained-release gel for treating oral diseases. Referring to the formulation and preparation method of Example 2, the difference lies in that it does not contain low molecular weight yeast β-glucan.

[0112] Comparative Example 3

[0113] This comparative example provides a sustained-release gel for treating oral diseases. Referring to the formulation and preparation method of Example 2, the difference lies in that it does not contain medium molecular weight yeast β-glucan.

[0114] Comparative Example 4

[0115] This comparative example provides a sustained-release gel for treating oral diseases. Referring to the formulation and preparation method of Example 2, the difference lies in that it does not contain high molecular weight yeast β-glucan.

[0116] Comparative Example 5

[0117] This comparative example provides a sustained-release gel for treating oral diseases. Referring to the formulation and preparation method of Example 2, the difference lies in that 0.2% of ultra-low molecular weight yeast β-glucan, 0.4% of low molecular weight yeast β-glucan, 0.3% of medium molecular weight yeast β-glucan, and 0.1% of high molecular weight yeast β-glucan are replaced with 0.5% of ultra-low molecular weight yeast β-glucan and 0.5% of medium molecular weight yeast β-glucan.

[0118] Comparative Example 6

[0119] This comparative example provides a sustained-release gel for treating oral diseases. Referring to the formulation and preparation method of Example 2, the difference lies in that 0.2% of ultra-low molecular weight yeast β-glucan, 0.4% of low molecular weight yeast β-glucan, 0.3% of medium molecular weight yeast β-glucan, and 0.1% of high molecular weight yeast β-glucan are replaced with 0.6% of low molecular weight yeast β-glucan and 0.4% of medium molecular weight yeast β-glucan.

[0120] Comparative Example 7

[0121] This comparative example provides a sustained-release gel for treating oral diseases. Referring to the formulation and preparation method of Example 1, the difference lies in that ultra-low molecular weight yeast β-glucan, low molecular weight yeast β-glucan, medium molecular weight yeast β-glucan, and high molecular weight yeast β-glucan are replaced with 1.0 part of oat β-glucan.

[0122] Test Example

[0123] This test example tested the performance of the sustained-release gels prepared in the examples and comparative examples for treating oral diseases.

[0124] 1. Adhesion Performance Test

[0125] Method: A porcine oral mucosa model was used to simulate saliva flushing (flow rate 1.2 mL / min), and the complete detachment time of the gel was recorded.

[0126] Experimental Materials and Methods:

[0127] 1) Preparation of Mucosa Model

[0128] Materials: Fresh porcine oral mucosa (purchased from a slaughterhouse, stored in 4°C saline, and used within 24 hours).

[0129] Treatment: Cut the mucosa into 3 cm × 3 cm segments with a thickness of about 2 mm; rinse with saline to remove surface mucus and blot dry with filter paper.

[0130] 2) Preparation of Simulated Saliva

[0131] Prepare artificial saliva according to the ISO / TR 10271 standard: 0.4 g / L NaCl, 0.4 g / L KCl, CaCl 2 ·2H₂O 0.795 g / L, Na₂HPO 4 ₄ 0.78 g / L, urea 1.0 g / L, pH 6.8 ± 0.1.

[0132] 3) Adhesion Test Device

[0133] Self-made flushing device:

[0134] Constant flow pump (flow rate 1.2 mL / min, accuracy ±0.1 mL).

[0135] 37°C constant temperature water bath (simulating oral temperature).

[0136] Mucosa fixing platform (tilt angle 15°, simulating tongue movement).

[0137] 4) Experimental Procedure:

[0138] A Sample Preparation:

[0139] Experimental Group: The sustained-release gel prepared in Example 2 of the present invention.

[0140] Control Group: Commercially available 1.0% carbomer gel (without isomaltooligosaccharide).

[0141] B Operation Process:

[0142] Take 0.5 g of the gel (the experimental group's sustained-release gel and the control group's commercially available 1.0% carbomer gel respectively), and evenly coat it on the mucosal surface (with a thickness of about 1 mm).

[0143] Fix the mucosa on the flushing platform and start the constant flow pump for continuous flushing.

[0144] Record the complete shedding time of the gel (verified by visual inspection + gravimetric method: weigh the mucosa every 30 minutes until the weight change < 5%).

[0145] Repeatability: Each experiment in each group was repeated 6 times, and the mean ± standard deviation was taken.

[0146] Table 1

[0147] Group Adhesion time (hours) Gel prepared in Example 2 6.5±0.3 Commercially available carbomer gel 3.2±0.4

[0148] The results are shown in Table 1. It can be seen from the table that the adhesion time of the gel of the present invention is increased by 103% compared with the commercially available product.

[0149] 2. Bacteriostatic test

[0150] Strain culture: Take 3 mL of the Helicobacter pylori culture solution cultured to the logarithmic phase, centrifuge at 5000 g for 5 min, resuspend the bacterial cells with liquid brain heart medium, and adjust the bacterial liquid concentration to 1.5×10 6 CFU / mL.

[0151] Experimental method: Respectively take 0.1 g of the sustained-release gels prepared in Examples 2-4 and Comparative Examples 1-7 in the test group, dilute and filter them with 1 ml of sterile water, and add them to the corresponding culture media respectively; the blank control group adds an equal amount of sterile water; inoculate 0.1 mL of the corresponding bacterial liquid in the experimental group and the control group respectively. After culturing at 30 °C for one day, measure OD600 by ultraviolet spectrophotometer. The experiment was repeated 3 times, and the results were averaged.

[0152] Calculate the bacteriostatic rate (bacteriostatic rate = (OD600 of the blank control group - OD600 of the test group) / OD600 of the blank control group * 100%).

[0153] Table 2

[0154] Group Bacteriostatic rate Example 2 87％ Example 3 83％ Example 4 82％ Control Example 1 41％ Control Example 2 49％ Control Example 3 45％ Control Example 4 58％ Control Example 5 65％ Control Example 6 52％ Control Example 7 14％

[0155] The results are shown in Table 2. It can be seen from Table 2 that compared with the control group, the growth of bacterial cells was significantly inhibited after adding the sustained-release gel prepared in the example to the culture medium, and the bacteriostatic rate was greater than 80%.

[0156] 3. Recurrence rate of bacterial gastric ulcer

[0157] Randomly select 40 volunteers (20 males and 20 females) who have suffered from bacterial gastric ulcers caused by Helicobacter pylori infection, but the gastric ulcers still recur periodically, and Helicobacter pylori is detected in the oral cavity. All of them are informed consenters and are randomly divided into a control group and an experimental group, with 10 males and 10 females in each group.

[0158] The volunteers in the experimental group used about 2 mL of the gel provided in Example 2 to apply to the oral cavity every morning and evening for 30 consecutive days; while the control group did not receive any treatment. On the 30th day, saliva was collected from the oral cavities of the 40 volunteers to detect Helicobacter pylori in the oral cavity using a Helicobacter pylori detection kit, and at the same time, the number of volunteers with recurrent bacterial gastric ulcers within 30 days was counted.

[0159] Table 3

[0160]

[0161]

[0162] As shown in Table 3, it can be seen from the table that only 2 volunteers in the experimental group were detected with Helicobacter pylori in the oral cavity, and none of the volunteers had a recurrence of gastric ulcers during this period. While Helicobacter pylori was detected in the oral cavities of all volunteers in the control group, and 3 volunteers had symptoms of recurrent gastric ulcers. The results show that the sustained-release gel of the present invention can effectively inhibit Helicobacter pylori and reduce the recurrence rate of bacterial gastric ulcers.

[0163] 4. Periodontitis treatment experiment

[0164] Take 30 male SPF-grade Wistar rats at about 5 weeks of age and raise them in an environment with constant temperature and humidity under a 12-hour light and 12-hour dark cycle. All rats were allowed to adapt to the environment and diet for the first week, and then were randomly divided into 3 groups of 10 rats each according to the principle of consistent average body weight, namely a blank control group (blank group), a periodontitis model group (model group), and a sustained-release gel intervention group prepared in Example 2 (experimental group). The experimental period was maintained for 5 weeks. The blank control group was fed with normal feed and drinking water during the experiment. Except for the blank group, the model group and the probiotic group were both subjected to periodontitis modeling for one week. During the modeling period, 200 μL of a Porphyromonas gingivalis suspension (suspension concentration 10 9 CFU / mL) was wiped on the gums every day. After wiping, feeding and drinking water were stopped for 1 h to determine its successful colonization in the rat oral cavity, that is, the modeling was successful.

[0165] After successful model establishment, the experimental group wiped the sustained-release gel twice a day (once in the morning and once in the evening) on the molars of the rats. That is, a cotton swab saturated with the bacterial solution was applied to each quarter of the rat's oral teeth for a uniform action time of 15 s until the end of the 5th week of the experiment; the model group and the blank group wiped an equal amount of clear water. During the experiment, both the periodontitis model group and the experimental group were fed with feed Keyes 2000 and drinking water supplemented with 10% sucrose. The composition of Keyes 2000 feed (w / w): wheat flour 6%, milk powder 28%, sucrose 56%, yeast 4%, alfalfa powder 3%, liver powder 1%, salt 2%.

[0166] At the 2nd week and the 5th week after the end of model establishment, samples were taken from the rat's oral teeth respectively. The obtained samples were diluted and spread on the corresponding solid plates for viable bacteria counting as a test for pathogenic bacteria colonization. The solid plates used for colony counting were: BHI solid medium supplemented with 12 μg / mL ampicillin and 5% (v / v) defibrinated sheep blood, and the Porphyromonas gingivalis in the rat's oral cavity was counted in combination with the colony morphological characteristics.

[0167] Table 4

[0168] Group The 2nd week The 5th week Model group <![CDATA[4.7×10 5 CFU / mL]]> <![CDATA[2.4×10 6 CFU / mL <!-- 8 -->]]> Experimental group <![CDATA[1.6×10 5 CFU / mL]]> <![CDATA[3.2×10 3 CFU / mL]]>

[0169] As shown in Table 4, it can be seen from the table that compared with the model group, the sustained-release gel prepared by the method of the present invention can effectively reduce the number of Porphyromonas gingivalis in the rat's oral cavity and can be used for the treatment of periodontitis.

[0170] 5. Treatment experiment for recurrent oral ulcers

[0171] Randomly select 60 patients with recurrent oral ulcers, all of whom are informed consent patients, and evenly divide them into an experimental group (the sustained-release gel prepared in Example 2 of the present invention) and a control group (commercially available carboxymethyl chitosan gel). The volunteers in the experimental group and the control group apply an equal amount of gel to the oral ulcers every morning and evening, and the healing time and the pain relief rate within 24 hours are statistically counted.

[0172] Table 5

[0173] Evaluation index Test group (n = 30) Control group (n = 30) Average healing time (days) 4.2±0.8 5.8±1.2 24-hour pain relief rate 93％(28 / 30) 73％(22 / 30) Adverse reaction rate 0％(0 / 30) 6.7％(2 / 30)

[0174] As shown in Table 5, it can be seen from the table that the sustained-release gel prepared by the present invention significantly shortens the ulcer healing time, the pain relief rate is better than that of the control group, and there are no adverse reactions and the safety is good.

[0175] The above has described the embodiments of the present invention in detail. However, the present invention is not limited to the above embodiments, and various changes can be made without departing from the gist of the present invention within the scope of knowledge possessed by those of ordinary skill in the art. In addition, the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

Claims

1. A sustained-release gel for treating oral diseases, characterized in that: The invention comprises, by weight, 0.3 to 1.5 parts of yeast beta-glucan, 2 to 4 parts of maltooligosaccharide and 0.5 to 2 parts of carbomer; The yeast β-glucan includes ultra-low molecular weight yeast β-glucan, low molecular weight yeast β-glucan, medium molecular weight yeast β-glucan and high molecular weight yeast β-glucan; The mass ratio of the ultra-low molecular weight yeast β-glucan, the low molecular weight yeast β-glucan, the medium molecular weight yeast β-glucan and the high molecular weight yeast β-glucan is (1-3): (1-5): (2-4): (1-4).

2. The sustained-release gel according to claim 1, characterized in that The molecular weight of the ultra-low molecular weight yeast β-glucan is less than 1 WDa; and / or, the molecular weight of the low molecular weight yeast β-glucan is 1WDa to 50WDa; and / or, the molecular weight of the medium molecular weight yeast β-glucan is 50 WDa to 200 WDa; And / or, the molecular weight of the high molecular weight yeast β-glucan is >200 WDa.

3. The sustained-release gel according to claim 1, characterized in that The composition further comprises 0.01 to 0.1 parts of peppermint oil.

4. The sustained-release gel according to claim 1, characterized in that The composition further comprises 0.01 to 30 parts of auxiliary materials.

5. The sustained-release gel according to claim 4, characterized in that The auxiliary material includes at least one of a sweetener, a preservative, and a pH adjuster.

6. The sustained-release gel according to claim 5, characterized in that The sweetener includes at least one of saccharin sodium, sodium cyclamate, sucralose, aspartame, alitame, neotame, stevioside and xylitol; and / or, the preservative comprises at least one of sodium methylparaben, benzoic acid, sodium benzoate, phenoxyethanol, sorbic acid or sodium sorbate; And / or, the pH adjuster comprises citric acid.

7. A method for preparing the sustained-release gel according to any one of claims 1 to 6, characterized in that: The following steps are involved: Mix all the components.

8. Use of the sustained-release gel according to any one of claims 1 to 6 in any one of the following: (1) Preparing products for inhibiting oral bacteria; (2) preparing products for treating periodontitis; (3) Preparation of products for treating oral ulcers; (4) Prepare products for treating bacterial gastric ulcers.

9. The use according to claim 8, characterized in that: The oral bacteria include Helicobacter pylori and Porphyromonas gingivalis.

10. A product, characterized in that The invention comprises the sustained-release gel as described in any one of claims 1 to 6.

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