Buccal product and preparation method thereof

Abstract

The invention discloses a buccal product and a preparation method thereof, the buccal product comprises a composition, the composition comprises an active mixture, a lysozyme mixture and a first filler which are uniformly mixed together, the active mixture comprises an active agent and a second filler, and at least part of the active agent coats the surface layer of the second filler; the lysozyme mixture comprises lysozyme and a carrier, and the carrier is used for reducing the inactivation risk of the lysozyme; the preparation method comprises the following steps: obtaining a lysozyme mixture; preparing a coating solution containing an active agent, and carrying out coating and granulation treatment on the second filling agent to obtain a granular active mixture; and mixing the first filler, the active mixture and the lysozyme mixture, and packaging to obtain the buccal product. The buccal product can effectively dissolve tooth stains, inhibit growth of oral pathogenic bacteria, reduce inflammatory response and protect oral mucosa, so that the dual effects of preventing oral problems and whitening teeth are achieved.

Description

Technical Field

[0001] The present application relates to the technical field of oral products, and in particular to an oral product and a preparation method thereof. Background Art

[0002] At present, the following technical problems are common in the research and development of oral products and other related products: conventional oral products mostly contain nicotine and flavorings, etc. Long-term use may lead to pigment deposition on the tooth surface (such as smoke stains), mucosal inflammation or bacterial infection, and some ingredients may corrode tooth enamel and damage dental health; because oral products contain nicotine active substances, long-term use of oral products may cause dryness or burning sensation of the oral mucosa, which is especially unfriendly to sensitive people; in addition, traditional oral products usually do not contain whitening ingredients or protect the oral mucosa. Therefore, their whitening effect is limited and cannot significantly improve tooth color.

[0003] Therefore, there is an urgent need to develop an oral product that can prevent oral problems. Summary of the Invention

[0004] The technical problem to be solved by the present application is to provide an oral product and a preparation method thereof.

[0005] The technical solution adopted by the present application to solve its technical problems is: an oral product, which includes a composition, the composition includes an active mixture, a lysozyme mixture and a first filler that are uniformly mixed together, wherein: the active mixture includes an active agent and a second filler, and at least part of the active agent is coated on the surface of the second filler; the lysozyme mixture includes lysozyme and a carrier, and the carrier is used to reduce the risk of lysozyme inactivation.

[0006] In some embodiments, the lysozyme mixture comprises, by weight, 2 to 8 parts of a binder, 40 to 50 parts of a carrier, 1 to 4 parts of a pH adjuster A, 2 to 8 parts of a pH adjuster B, 2 to 20 parts of lysozyme, and 1 to 7 parts of a cross-linking agent.

[0007] In some embodiments, the binder includes at least one of aloe vera gel, chitosan gel, recombinant human epidermal growth factor gel and Centella asiatica extract gel; and / or, the carrier includes at least one of chitosan, polyacrylic acid, polylactic acid-glycolic acid copolymer, 724 resin, N-isopolyacrylamide copolymer and hyaluronic acid; and / or, the pH adjuster A is weakly acidic, and the pH adjuster A includes at least one of carbonic acid, acetic acid, malic acid and citric acid; and / or, the pH adjuster B is weakly alkaline, and the pH adjuster B includes at least one of sodium citrate, sodium phosphate and acetate; and / or, the cross-linking agent includes at least one of sodium tripolyphosphate, genipin, cross-linked starch, calcium alginate or cross-linked polyvidone.

[0008] In some embodiments, the first filler includes at least one of mannitol, erythritol, isomalt, anhydrous lactitol, sorbitol, and maltitol; and / or, the second filler includes at least one of microcrystalline cellulose, erythritol, wood cellulose, and porous starch; and / or, the active agent includes at least one of nicotine and nicotine derivatives.

[0009] In some embodiments, the active mixture further includes at least one of a sweetening agent, a binder, pH regulator C, and a flavoring agent.

[0010] In some embodiments, the oral product further includes a permeable bag, and the composition is encapsulated within the permeable bag.

[0011] In some embodiments, the content of lysozyme in the oral product does not exceed 2%.

[0012] The present application also provides a method for preparing an oral product for preparing the oral product according to any one of the foregoing, the preparation method including: obtaining a lysozyme mixture including lysozyme and a carrier coated outside the lysozyme; preparing a coating solution containing an active agent, coating and granulating the second filler to obtain a granular active mixture; mixing the first filler, the active mixture, and the lysozyme mixture to prepare a composition of the oral product, and encapsulating the composition to obtain the oral product.

[0013] In some embodiments, obtaining the lysozyme mixture includes: obtaining solid particles of a carrier-coated lysozyme by an ion gel method; after freeze-drying the solid particles, adding a binder and stirring, adding pH regulator B to adjust the pH to 6-7, and then performing freeze-drying to obtain the lysozyme mixture.

[0014] In some embodiments, preparing a coating solution containing an active agent, coating and granulating the second filler to obtain a granular active mixture includes: preparing a coating solution using an active agent, pH regulator C, and a binder; coating the second filler with the coating solution to obtain coated particles, where the active agent is located on the outer layer of the second filler in the coated particles; preparing a flavor solution using a flavoring agent and a sweetening agent, and granulating the coated particles to obtain a granular active mixture.

[0015] Advantages of the present application:

[0016] The present application adds a lysozyme mixture to the oral product. The lysozyme mixture includes lysozyme and a carrier. The lysozyme is used to clean teeth and the oral cavity, and the carrier is used to reduce the risk of inactivation of lysozyme, enabling the oral product to effectively dissolve dental stains, inhibit the growth of oral pathogenic bacteria, reduce inflammatory reactions, and protect the oral mucosa, thereby achieving the dual effects of preventing oral problems and whitening teeth.

[0017] In this application, a lysozyme mixture is first prepared, and through coating and granulation treatments, a granular active mixture is obtained. Then, the lysozyme mixture, the active mixture, and a first filler are mixed to prepare an orally dissolving product, which improves the preparation process flow of the orally dissolving product, has good process stability, and reduces production costs. The obtained orally dissolving product has good stability and has good tooth whitening and antibacterial effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present application will be further described below in conjunction with the drawings and embodiments. In the drawings:

[0019] Figure 1 is the single measurement result diagram of Examples 1-4 of the present application and Comparative Examples 1 and 2;

[0020] Figure 2 is the nicotine content detection result diagram of Examples 1-4 of the present application and Comparative Examples 1 and 2;

[0021] Figure 3 is the nicotine dissolution ratio detection result diagram of Examples 1-4 of the present application and Comparative Examples 1 and 2;

[0022] Figure 4 is the tooth whitening effect test result diagram of Examples 1-4 of the present application, Comparative Examples 1 and 2, and the control group;

[0023] Figure 5 is the antibacterial test result diagram of Examples 1-4 of the present application, Comparative Examples 1 and 2, and the control group;

[0024] Figure 6 is the moisture content detection result diagram of Examples 1-4 of the present application and Comparative Examples 1 and 2;

[0025] Figure 7 is the pH value detection result diagram of Examples 1-4 of the present application and Comparative Examples 1 and 2. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0026] For a clearer understanding of the technical features, objectives, and effects of the present application, the present application will be further described in detail below in conjunction with the embodiments. These embodiments are only used to explain the present application and do not constitute a limitation on the protection scope of the present application. Similarly, the following embodiments are only some embodiments of the present application rather than all embodiments. All other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the protection scope of the present application.

[0027] The present application provides an oral product, which comprises a composition. The composition includes an active mixture, a lysozyme mixture, and a first filler uniformly mixed together, wherein: the active mixture includes an active agent and a second filler, and at least part of the active agent is coated on the surface layer of the second filler; the lysozyme mixture includes lysozyme and a carrier, and the carrier is used to reduce the risk of lysozyme inactivation. In some embodiments, by mass parts, the composition includes 31.2 - 123 parts of the active mixture, 1 - 10 parts of the lysozyme mixture, and 10 - 40 parts of the first filler. It can be understood that the mass parts of each component in the composition can be selected according to actual taste and texture requirements.

[0028] By mass parts, each part of the lysozyme mixture includes: 2 - 8 parts of a binder, 40 - 50 parts of a carrier, 1 - 4 parts of a pH regulator A, 2 - 8 parts of a pH regulator B, 2 - 20 parts of lysozyme, and 1 - 7 parts of a crosslinking agent, wherein the lysozyme is used for cleaning teeth and oral cavity. Specifically, the binder includes at least one of aloe vera gel, chitosan gel, recombinant human epidermal growth factor gel, and centella asiatica extract gel. The carrier includes at least one of polyacrylic acid (PAA), poly (lactic - co - glycolic acid) (PLGA), 724 resin, N - isopropylacrylamide copolymer, chitosan, and hyaluronic acid, and the carrier can also be other natural polysaccharides except chitosan and hyaluronic acid. The pH regulator A is weakly acidic and includes at least one of carbonic acid, acetic acid, malic acid, and citric acid. The pH regulator B is weakly basic and includes at least one of sodium citrate, sodium phosphate, and acetate, wherein sodium citrate has excellent buffering performance and high safety, and can effectively chelate metal ions such as Ca 2 +, Mg2 +, etc., reduce the interference of metal ions on the activity of lysozyme, and improve the stability of lysozyme. The crosslinking agent includes at least one of sodium tripolyphosphate (TPP), genipin, crosslinked starch, calcium alginate, or crosslinked polyvinylpyrrolidone. In some embodiments, by mass parts, each part of the lysozyme mixture further includes 20 - 50 parts of a solvent A, and the solvent A can be deionized water.

[0029] Since excessive intake of lysozyme is not advisable, in some embodiments, the percentage content of lysozyme in the oral product does not exceed 2%, such as 0.5%, 1%, 1.5%, 2%, etc., and no specific limitation is made here.

[0030] In the active mixture, the second filler includes at least one of microcrystalline cellulose, erythritol, wood cellulose, and porous starch. The active agent includes at least one of nicotine and nicotine derivatives. Nicotine includes, but is not limited to, natural nicotine and synthetic nicotine. Nicotine derivatives include, but are not limited to, nicotine salts, nicotine in a matrix such as a sugar matrix or an organometallic complex, nicotine-resin combinations, nicotine inclusion complexes, and non-covalently bound nicotine. Among them, non-covalently bound nicotine includes, but is not limited to, nicotine lactate, nicotine malate, nicotine salicylate, nicotine cyclodextrin inclusion complex, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride, nicotine benzoate, etc. Nicotine derivatives also include nicotine with substituents, such as hexamethyl nicotine, hexamethyl nicotine lactate, hexamethyl nicotine malate, hexamethyl nicotine salicylate, hexamethyl nicotine cyclodextrin inclusion complex, hexamethyl nicotine hydrochloride, hexamethyl nicotine dihydrochloride, hexamethyl nicotine tartrate, hexamethyl nicotine tartrate dihydrate, hexamethyl nicotine sulfate, hexamethyl nicotine zinc chloride, hexamethyl nicotine benzoate, and one or more mixtures thereof.

[0031] In some embodiments, the active agent may further include other substances with specific active properties, such as caffeine, tea polyphenols, etc., to meet the different needs of users.

[0032] In some embodiments, the active mixture further includes at least one of a sweetener, a binder, a pH regulator C, and a flavor. Among them, the sweetener includes at least one of acesulfame potassium, sucralose, steviol glycoside, aspartame, and sodium saccharin. The binder includes at least one of gum arabic, hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, gelatin, sodium alginate, polyvinylpyrrolidone, and polyethylene glycol. The pH regulator C is alkaline, and the pH regulator C includes at least one of sodium bicarbonate, sodium carbonate, sodium hydroxide, and sodium hexametaphosphate. The flavor includes at least one of mint flavor, mango flavor, lemon flavor, blueberry flavor, and coffee flavor. The flavor may also be other edible flavors of different tastes, which will not be elaborated one by one in this application.

[0033] In some embodiments, measured by mass parts, the active mixture includes 15 to 70 parts of the second filler, 10 to 20 parts of the active agent, 0.2 to 2 parts of the sweetener, 0.5 to 6 parts of the binder, 0.5 to 5 parts of the pH regulator C, 5 to 20 parts of the flavor. The active mixture further includes 8 to 20 parts of solvent B, and the solvent B can be deionized water.

[0034] The first filler includes at least one of mannitol, erythritol, isomaltitol, anhydrous lactitol, sorbitol, and maltitol, and the first filler may further include other sugar alcohols.

[0035] In some embodiments, the buccal product further includes a permeation bag, and the composition is encapsulated in the permeation bag. When a user takes the buccal product, saliva can permeate through the permeation bag to dissolve at least part of the substances in the composition.

[0036] This application aims to solve the problems of irritation and damage to teeth and oral mucosa caused by active substances in traditional buccal products during long-term use. By adding a lysozyme mixture to the buccal product, dental plaque can be effectively dissolved, and the growth of harmful oral bacteria can be inhibited, thereby helping consumers achieve the dual effects of preventing oral problems and whitening teeth. The components such as lysozyme, binder, and carrier in the lysozyme mixture interact with each other to inhibit the growth of oral bacteria, and at the same time repair the oral mucosa, playing a role in protecting the oral mucosa. In addition, the anti-inflammatory and antibacterial properties of lysozyme can help prevent oral ulcers. As a natural antibacterial substance, lysozyme may enhance local oral immunity and help resist pathogens.

[0037] This application also provides a preparation method of a buccal product for preparing the aforementioned buccal product, and the preparation method includes the following steps:

[0038] S1. Obtain a lysozyme mixture, which includes lysozyme and a carrier coated on the outer side of the lysozyme.

[0039] Obtaining the lysozyme mixture includes: obtaining solid particles with the carrier coating the lysozyme by the ion gel method; after freeze-drying the solid particles, adding a binder and stirring, adding pH regulator B to adjust the pH to 6-7, and then performing freeze-drying to obtain the lysozyme mixture.

[0040] Specifically, step S1 includes the following sub-steps:

[0041] S1.1. Prepare solutions: Weigh 40-50 parts of the carrier to prepare a carrier solution with a mass fraction of 0.8%-1.2%, and add 1-4 parts of pH regulator A to adjust the pH to 4- 6. The solvent of the carrier solution can be acetic acid. Weigh 2-20 parts of lysozyme to prepare a lysozyme aqueous solution with a mass fraction of 0.3%-0.7%, and add 2-8 parts of pH regulator B to adjust the pH to 5-7. Weigh 1-7 parts of the crosslinking agent and add it to 20-50 parts of solvent A. The volume ratio of the crosslinking agent to solvent A is 1:(8-12) to obtain a crosslinking agent solution with a mass fraction of 0.08%-0.12%. Specifically, the mass fraction of the carrier solution can be 1%, add pH regulator A to adjust the pH to 5, the mass fraction of the lysozyme aqueous solution can be 0.5%, add pH regulator B to adjust the pH to 6, the volume ratio of the crosslinking agent to solvent A can be 1:10, and the mass fraction of the crosslinking agent solution can be 0.1%.

[0042] S1.2. Hybrid Crosslinking: Mix and stir the carrier solution and the lysozyme aqueous solution at a volume ratio of (2 - 4):1, then add the crosslinking agent solution dropwise for crosslinking stirring and centrifugation, and then collect the solid particles. Among them, the mixing and stirring can be carried out by magnetic stirring, with a rotation speed of 400 rpm - 800 rpm and a time of 20 min - 40 min; the crosslinking stirring time is 10 min - 30 min; the rotation speed for centrifugation is 8000 rpm - 12000 rpm and the time is 10 min - 30 min. Specifically, the volume ratio of the carrier solution to the lysozyme aqueous solution can be 3:1, the rotation speed for mixing and stirring can be 600 rpm, and the time can be 30 min; the crosslinking stirring time can be 20 min; the rotation speed for centrifugation is 10000 rpm and the time is 20 min. It should be noted that the specific process parameters of hybrid crosslinking can be dynamically adjusted according to specific production conditions, and will not be limited one by one in this application.

[0043] S1.3. Freeze-drying: Freeze-dry the solid particles to obtain the carrier-lysozyme composite powder.

[0044] S1.4. Mixing the Finished Product: Add the carrier-lysozyme composite powder to 2 - 8 parts of the binder solution for low-speed stirring. The mass ratio of the carrier-lysozyme composite powder to the binder is 1:(4 - 6). Then add pH regulator B to adjust the pH to 6 - 7, and then dry to obtain the lysozyme mixture. In one embodiment, the binder solution is an aloe vera gel solution with a pre-prepared concentration range of 5% - 20%. Among them, the rotation speed for low-speed stirring is 100 rpm - 300 rpm and the time is 20 min - 40 min. Specifically, the rotation speed for low-speed stirring can be 200 rpm and the time can be 30 min; the mass ratio of the carrier-lysozyme composite powder to the binder can be 1:5, and pH regulator B is added to adjust the pH to 6.5. It should be noted that the specific process parameters of mixing the finished product can be dynamically adjusted according to specific production conditions, and will not be limited one by one in this application.

[0045] Among them, the freeze-drying in step S1.3 and the drying in step S1.4 can be carried out using a freeze dryer.

[0046] S2. Prepare the coating solution containing the active agent, coat and granulate the second filler to obtain the granular active mixture.

[0047] Preparing the coating solution containing the active agent, coating and granulating the second filler to obtain the granular active mixture includes: preparing the coating solution using the active agent, pH regulator C, and binder; coating the second filler with the coating solution to obtain the coated particles, with the active agent located on the outer layer of the second filler in the coated particles; preparing the flavor solution using the essence and sweetener, and granulating the coated particles to obtain the granular active mixture.

[0048] Specifically, step S2 includes the following sub-steps:

[0049] S2.1. Prepare the coating solution: Weigh 10 - 20 parts of the active agent and dissolve it in 8 - 20 parts of solvent B, add 0.5 - 5 parts of pH regulator C to adjust the pH to 6 - 7, then add 0.5 - 6 parts of binder and stir to obtain the coating solution containing the active agent. Among them, the stirring time is 0.5 - 1.5 hours. Specifically, add pH regulator C to adjust the pH to 6.5, and the stirring time can be 1 hour. It should be noted that the specific process parameters for preparing the coating solution can be dynamically adjusted according to specific production conditions, and will not be limited one by one in this application.

[0050] S2.2. Prepare the flavor solution: Weigh 5 - 20 parts of essence, add 0.2 - 2 parts of sweetener and stir to obtain the flavor solution. Among them, stirring can be carried out using a stirrer, and the stirring time is 0.3 - 0.7 hours. Specifically, the stirring time can be 0.5 hours. It should be noted that the specific process parameters for stirring can be dynamically adjusted according to specific production conditions, and will not be limited one by one in this application.

[0051] S2.3. Coating: Use the coating solution to coat 15 - 70 parts of the second filler to obtain coated particles. Among them, the coating solution is sprayed through an atomizing nozzle using a fluidized bed and a peristaltic pump. The specific process parameters are as follows: the inlet air temperature is 60°C - 70°C, the material temperature is 40°C - 45°C, the liquid spraying rate is 8 mL / min - 12 mL / min, the fan speed is 800 rpm - 1600 rpm, and the moisture content of the material is less than 5%. Specifically, the inlet air temperature can be 65°C, the material temperature can be 43°C, the liquid spraying rate can be 10 mL / min, the fan speed can be 1200 rpm, and the moisture content of the material is less than 5% is sufficient. If the second filler includes at least two components, in order to accelerate the release of nicotine in the active agent, the at least two components can be pre-mixed and then coated. Among them, the mixing process can be mixing for 0.5 hours using a three-dimensional mixer. It should be noted that the specific process parameters for coating can be dynamically adjusted according to specific production conditions, and will not be limited one by one in this application.

[0052] S2.4 Granulation: The coated particles are granulated with a flavor solution to obtain granular active mixture. Among them, when the flavor solution coats the coated particles, spray granulation can be used. The flavor solution is sprayed through an atomizing nozzle by a fluidized bed and a peristaltic pump. The specific process parameters are as follows: the inlet air temperature is 60°C - 70°C, the material temperature is 35°C - 40°C, the liquid spraying rate is 6 mL / min - 10 mL / min, the fan speed is 800 rpm - 1600 rpm, and the moisture content of the material is less than 5%. Specifically, the inlet air temperature can be 65°C, the material temperature can be 37°C, the liquid spraying rate can be 8 mL / min, the fan speed can be 1200 rpm, and the moisture content of the material is less than 5% is sufficient. It should be noted that the specific process parameters of granulation can be dynamically adjusted according to specific production conditions, and are not limited one by one in this application.

[0053] S3 Mixing: The first filler, the active mixture and the lysozyme mixture are mixed to obtain the composition of the buccal product, and the composition is encapsulated to obtain the buccal product. Among them, mixing can be carried out by a three-dimensional mixer, and the mixing time is 0.5 - 1.5 hours, such as 1 hour. It should be noted that the specific process parameters of mixing can be dynamically adjusted according to specific production conditions, and no specific limitations are made in this application. Encapsulation can be carried out by a buccal product encapsulating machine, and the composition is encapsulated with non-woven fabric, boxed and heat-sealed. When the first filler contains components with strong moisture absorption, such as mannitol, if it is mixed earlier, such as mixing the second filler and the first filler before step S2.3, the components of the first filler will dissolve during the granulation process. Therefore, it is preferred to add the first filler in the final mixing step.

[0054] It can be understood that in the above preparation method of the buccal product, the process parameters of each step can be selected according to actual process conditions, and no specific limitations are made here.

[0055] The buccal product containing lysozyme prepared in this application has the following effects:

[0056] 1. Tooth whitening: The buccal product can effectively dissolve dental stains and inhibit the growth of harmful bacteria in the oral cavity, thereby helping consumers achieve the dual effects of preventing oral problems and whitening teeth.

[0057] 2. Protecting oral mucosa: The buccal product can effectively inhibit the growth of oral pathogenic bacteria and reduce inflammatory reactions, thereby protecting the oral mucosa. The lysozyme buccal product can effectively decompose the cell walls of bacteria and inhibit the growth of bacteria, thereby reducing harmful bacteria in the oral cavity and preventing oral diseases such as gingivitis and periodontitis.

[0058] 3. Reducing bad breath: The lysozyme in the buccal product helps reduce bad breath and improve the breath by inhibiting bacteria that produce odor gases such as hydrogen sulfide.

[0059] 4. Maintain oral health: Reduce the formation of dental plaque and tartar, prevent dental caries, and keep the oral cavity clean.

[0060] 5. Improve immunity: Lysozyme in the buccal products, as a natural antibacterial substance, may enhance local oral immunity and help resist pathogens.

[0061] 6. Optimize the formulation process: The buccal products containing lysozyme of the present application can optimize the formulation of traditional buccal products, improve the preparation method of buccal products, and reduce production costs.

[0062] The buccal products of the present application and their preparation methods can effectively solve the key problems of traditional buccal products in terms of tooth staining, oral mucosa irritation, and bacterial infection during use, can enhance oral health, and achieve the dual effects of preventing oral problems and whitening teeth.

[0063] The following is illustrated by specific examples:

[0064] The buccal products of Examples 1 to 4 and Comparative Examples 1 and 2 are prepared by using the preparation method of the above-mentioned buccal products of the present application. Among them, no lysozyme mixture is added to the buccal products of Comparative Examples 1 and 2. The components and their mass fractions of the composition in the buccal products of Examples 1 to 4 and Comparative Examples 1 and 2 are shown in Table 1, and the components and their mass fractions of the lysozyme mixture in the composition of Examples 1 to 4 are shown in Table 2.

[0065] Table 1 Components of the composition in the buccal products of Examples 1 to 4 and Comparative Examples 1 and 2

[0066]

[0067] Table 2 Components of the lysozyme mixture in the composition of Examples 1 to 4

[0068]

[0069]

[0070] It can be understood that in the above Examples 1 to 4 and their alternative schemes, the components of the first filler can be replaced by at least one of mannitol, erythritol, isomalt, anhydrous lactitol, sorbitol, and maltitol; in the active mixture, the components of the second filler, sweetener, binder, solvent B, pH regulator C, flavor, and active agent can be replaced by other components of the corresponding components in the aforementioned buccal products, which will not be elaborated here; in the lysozyme mixture, the components of the binder, carrier, pH regulator A, pH regulator B, solvent A, and crosslinking agent can be replaced by other components of the corresponding components in the aforementioned buccal products, which will not be elaborated here.

[0071] Performance test:

[0072] The single-weight tests, nicotine content detections, nicotine dissolution ratio detections, tooth whitening effect tests, antibacterial tests, moisture detections, and pH value detections were respectively carried out on the buccal products of Examples 1 to 4 and Comparative Examples 1 and 2. The specific test results are as follows:

[0073] I. Single-weight test

[0074] When encapsulating the composition of the buccal product, a single-weight stability test was carried out. The weight of each buccal product was designed to be 0.5 g. The single-weight stability verification was carried out using an electronic balance with ten-thousandth precision. Each test was repeated five times, and the average value was taken. The test results are shown in Table 3 and Figure 1 as follows.

[0075] Table 3 Single-weight test results

[0076]

[0077]

[0078] According to the single-weight average values in Table 3 and Figure 1 it can be seen that the stability of the composition in each buccal product is good, and the single weight basically fluctuates within 0.5 ± 10%, which is suitable for automated encapsulation production.

[0079] II. Nicotine content detection

[0080] The nicotine content was detected based on a high-performance liquid chromatography-gas chromatography instrument (HPLC-AgLient GC 8890). The reagents used included: isopropanol (chromatographic grade), ethanol (chromatographic grade) standard, nicotine standard solution in isopropanol, and n-heptadecane (internal standard). The test results are as Figure 2 follows.

[0081] Test method: Cut a small opening in the packaging bag of the buccal product, accurately weigh the middle powder sample (accurate to 0.0001 g) and place it in a 10 mL volumetric flask. After diluting to volume with ethanol standard, first mix it with a vortex mixer, and then ultrasonically extract it with an ultrasonic cleaner for 30 min. After standing, filter the supernatant through a 0.22 μm filter membrane, and transfer 100 μL of the test solution, add 800 μL of isopropanol and 100 μL of n-heptadecane standard stock solution, and fill it into a 1 mL injection vial and mix well for testing.

[0082] According to the content of the active agent in the composition of the oral product and the content of pure nicotine in the active agent, the set nicotine content of the oral product can be calculated to be 30 mg / g. The test results show that the actual nicotine contents in the oral products of Examples 1 to 4 and Comparative Examples 1 and 2 are 29.01 mg / g, 29.23 mg / g, 29.10 mg / g, 29.45 mg / g, 29.09 mg / g, and 29.31 mg / g respectively, and the nicotine loss amounts are all within ±10%, indicating that the preparation method of the present application has good stability.

[0083] III. Detection of nicotine dissolution ratio

[0084] Based on the test with an Agilent 708-DS dissolution tester, the method: paddle method dissolution; rotation speed: 50 rpm; dissolution medium: 0.8 g / L potassium chloride solution, and the pH value is adjusted to 6.8 with sodium bicarbonate; dissolution volume: 500 mL; filter membrane: 0.2 μm; sampling volume: 1.5 mL, without replenishing the solution. The sampling points are: 1 min, 3 min, 5 min, 10 min, 20 min, 30 min, 45 min, 60 min. Samples are taken at different sampling points and the nicotine content (mg / g) is detected. The test results are shown in Table 4 and Figure 3 as follows.

[0085] Table 4 Detection results of nicotine dissolution ratio

[0086]

[0087] According to Table 4 and Figure 3 it can be seen that the dissolution processes of nicotine in the oral products of Examples 1 to 4 and Comparative Examples 1 and 2 all conform to the first-order kinetic equation. Therefore, the first-order kinetic equation is used to fit the nicotine dissolution curve. Since the designed nicotine contents of each oral product are the same, the dissolution curve is basically positively correlated with the amount of the binder. Therefore, from the nicotine content data in the first 10 minutes, it can be seen that the nicotine dissolution of Example 1 and Comparative Example 1 is slower than that of other oral products because the amounts of the binder in these two oral products are the largest, indicating that the thickness of the coating layer is the thickest, so the nicotine dissolution rate is slower than that of other oral products. Most of the nicotine in Examples 1 to 4 and Comparative Examples 1 and 2 is dissolved within 10 minutes, indicating that the nicotine dissolution efficiencies of these oral products are similar.

[0088] IV. Tooth whitening effect test

[0089] Based on a programmable thermostatic and humidistatic chamber, long-term verification was carried out to simulate the oral environment. The test conditions were designed as follows: temperature 37°C, humidity 90%. The artificial dentures were immersed in artificial saliva based on the DIN V53160-1 standard for testing. A 3nh T7020 spectrophotometric colorimeter was used to examine the discoloration degree of the artificial dentures. The chromaticity (L*) of the teeth after using the oral products was detected, and a white color card was used as the chromaticity standard for the standard sample.

[0090] Test method: Place one artificial denture in each centrifuge tube, and at the same time add one oral product, keeping the amounts of nicotine and artificial saliva unchanged (if there is no loss of nicotine content, it can be not added, and the amount of artificial saliva needs to be supplemented to cover the artificial denture); at the same time, set up a blank control group, with only artificial dentures and artificial saliva in the centrifuge tube without adding oral products, to simulate the discoloration of teeth during long-term use of oral products by the human body. The test results are shown in Table 5 and Figure 4 as follows.

[0091] Table 5 Test Results of Tooth Whitening Effect

[0092]

[0093] According to the test results, it can be seen that in Examples 1-4 with the addition of lysozyme mixture, the discoloration degree of teeth after long-term use of oral products is better than that of Comparative Examples 1 and 2 without the addition of lysozyme mixture. In addition, compared with the control group, after long-term use of oral products, even if lysozyme is added to protect the teeth, the discoloration degree of the teeth will still be deeper than that of the teeth without using oral products. Therefore, it can be concluded that after adding lysozyme to oral products, long-term use of oral products can play a role in slowing down tooth discoloration, but the color will still be deeper compared with the teeth without using oral products. Therefore, although lysozyme is added to oral products, tooth whitening can be achieved, and long-term use of oral products has a slowing effect on tooth discoloration, but using oral products will still cause tooth discoloration.

[0094] V. Bacteriostatic Test

[0095] Test method: R1. Use experimental strains Streptococcus mutans, Streptococcus sanguinis, Actinomyces viscosus, and Staphylococcus aureus. After resuscitating each strain for 48 h, inoculate them into BHI (brain heart infusion) liquid medium respectively, and anaerobically culture them for 24 h under 80% N2 + 20% CO2. Use a CrystaL SpecTM turbidimeter to measure the concentration of each bacterial suspension, and then adjust the concentration of the bacterial suspension to 3×10 8 CFU / mL.

[0096] R2. Determination of minimum concentration: Using the liquid two-fold dilution method, prepare lysozyme media (pH 7.2) with concentrations of 0.2 mg / mL, 0.5 mg / mL, 1 mg / mL, 3 mg / mL, and 5 mg / mL in BHI liquid medium. Take 50 μL of the diluted bacterial solution and inoculate it into 1 mL of each lysozyme medium. Incubate anaerobically at 95% N2 + 5% CO2 and 37°C for 24 h. Against a black background, visually observe the lowest drug concentration at which no turbidity appears as the minimum inhibitory concentration (MIC) value. The results show that the MIC values of lysozyme against Streptococcus mutans, Streptococcus sanguinis, Actinomyces viscosus, and Staphylococcus aureus are 0.2 mg / mL, 0.2 mg / mL, 0.5 mg / mL, and 0.2 mg / mL, respectively. From this, the amount of lysozyme can be determined, and lysozyme can produce an antibacterial effect at a concentration of 0.2 mg / mL.

[0097] R3. Place one oral product from Examples 1 - 4 and Comparative Examples 1 and 2 into 25 mL of artificial saliva. At the same time, set up a control group without an oral product. Use a blender and a homogenizer to stir for 2 h to completely dissolve the oral products into the artificial saliva, obtaining the liquid medicines of Examples 1 - 4, Comparative Examples 1 and 2, and the control group. Subsequently, use a neutral qualitative filter paper with a diameter of 6 mm, take 1 mL of the liquid medicine, and dry the drug-containing paper in a freeze-drying vacuum dryer, and store it sealed at 4°C.

[0098] R4. Inoculate Streptococcus mutans, Streptococcus sanguinis, Actinomyces viscosus, and Staphylococcus aureus into 5 mL of BHI solution respectively, and incubate anaerobically at 95% N2 + 5% CO2 and 37°C for 18 h. Using the McFarland turbidity standard, adjust the bacterial solution concentration to 10 8 CFU / mL. Take 50 μL of the bacterial solution and inoculate it into a 100 mm agar medium petri dish. Clamp the drug-containing paper from the previous step and place it on the agar surface, gently press the paper to make it in proper contact with the agar. After incubating at 95% N2 + 5% CO2 and 37°C for 48 h, use a vernier caliper to measure the size of the inhibition zone of each drug-containing paper. The results are shown in Table 6 and Figure 5 as follows.

[0099] Table 6 Antibacterial test results

[0100]

[0101] According to the test results, it can be seen that the buccal products of Examples 1 to 4 added with lysozyme have inhibitory effects on Streptococcus mutans, Streptococcus sanguinis, Actinomyces viscosus and Staphylococcus aureus in the oral cavity; the buccal products of Comparative Examples 1 and 2 do not have inhibitory effects on most bacteria because they do not contain lysozyme; the control group does not contain lysozyme and thus does not have an inhibitory effect on bacteria. The test results also show that nicotine does not have an inhibitory effect on bacteria either. It can also be considered that under the condition of not adding lysozyme, the buccal products have a promoting effect on the growth of bacteria. Long-term use of the buccal products will promote the increase of oral bacteria, causing inflammation of the oral mucosa, etc. The oral mucosa will be damaged under the stimulation of nicotine, and then trigger inflammation. Therefore, adding a lysozyme mixture to the buccal products of the present application can inhibit the growth of oral bacteria, and thus play a role in protecting the oral mucosa.

[0102] VI. Product stability test:

[0103] Based on a programmable constant temperature and humidity test chamber, an environmental accelerated experiment was carried out to simulate the environmental conditions of air transportation, sea transportation and the country where it is located. The environmental test conditions were set as follows: temperature 50°C, humidity 90%, and placement time 5d. The samples were sealed and stored in the box.

[0104] 1. Moisture content detection: Based on the Japanese KEM 710S-ADP611 equipment, the moisture content of the buccal products before and after the environmental test was measured. The moisture content was required to be within 5%. The test results are shown in Table 7 and Figure 6 as follows.

[0105] Table 7 Moisture content detection results

[0106]

[0107]

[0108] According to the test data, the moisture content of each buccal product after the environmental test is slightly higher than that before the environmental test, but the moisture content is lower than 5%. It can be considered that the buccal products have good stability during long-term storage and have reached the product use stability requirements.

[0109] 2. pH value test: The pH value was measured using a Thermo Fisher Orion Pro Star pH211 desktop pH meter. The test results are shown in Table 8 and Figure 7 as follows.

[0110] Table 8 pH value detection results

[0111]

[0112] According to the design, the pH value of each buccal product is between 6 and 7. It can be seen from the test data that the pH value changes little before and after the cycle test and is basically between 6 and 7. Therefore, it can be considered that the stability of the buccal product is good. At the same time, since lysozyme has good stability in the pH range of 4.0 - 7.0, the lysozyme still has activity after the cycle test of the product.

[0113] In this application, by adding lysozyme as a functional component of the buccal product, it can effectively dissolve dental plaque, inhibit the growth of harmful oral bacteria, reduce inflammatory reactions, and thus protect the oral mucosa, achieving the dual effects of preventing oral problems and whitening teeth. The components such as lysozyme, binder, and carrier in the lysozyme mixture interact with each other to inhibit the growth of oral bacteria and repair the oral mucosa, playing a role in protecting the oral mucosa. According to the antibacterial test results, the addition of 0.2 mg / mL of lysozyme can inhibit the growth of bacteria. Therefore, reasonably adjusting the content ratio of lysozyme can well control the antibacterial and oral mucosa protection effects of the buccal product.

[0114] It should be noted that, without conflict, the embodiments in this application and the features in the embodiments can be combined with each other.

[0115] It can be understood that the above embodiments only represent the preferred implementation modes of this application, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the patent scope of this application. It should be pointed out that for those of ordinary skill in the art, without departing from the concept of this application, the above technical features can be freely combined, and several deformations and improvements can also be made, all of which belong to the protection scope of this application. Therefore, all equivalent transformations and modifications made to the scope of the claims of this application should fall within the scope covered by the claims of this application.

Claims

1. An oral product, characterized in that, Comprising a composition, the composition comprising an active mixture, a lysozyme mixture and a first filler uniformly mixed together, wherein: The active mixture comprises an active agent and a second filler, and at least part of the active agent is coated on the surface layer of the second filler; The lysozyme mixture comprises lysozyme and a carrier, and the carrier is used to reduce the risk of inactivation of the lysozyme.

2. The oral product according to claim 1, wherein By mass parts, the lysozyme mixture comprises: 2-8 parts of a binder, 40-50 parts of a carrier, 1-4 parts of a pH regulator A, 2-8 parts of a pH regulator B, 2-20 parts of lysozyme and 1-7 parts of a crosslinking agent.

3. The oral product according to claim 2, wherein The binder comprises at least one of aloe vera gel, chitosan gel, recombinant human epidermal growth factor gel and centella asiatica extract gel; and / or, The carrier comprises at least one of chitosan, polyacrylic acid, poly(lactic-co-glycolic acid), 724 resin, N-isopropylacrylamide copolymer and hyaluronic acid; and / or, The pH regulator A is weakly acidic, and the pH regulator A comprises at least one of carbonic acid, acetic acid, malic acid and citric acid; and / or, The pH regulator B is weakly basic, and the pH regulator B comprises at least one of sodium citrate, sodium phosphate and acetate; and / or, The crosslinking agent comprises at least one of sodium tripolyphosphate, genipin, crosslinked starch, calcium alginate or crosslinked povidone.

4. The oral product according to claim 1, characterized in that, The first filler comprises at least one of mannitol, erythritol, isomaltitol, anhydrous lactitol, sorbitol and maltitol; and / or, The second filler comprises at least one of microcrystalline cellulose, erythritol, wood cellulose and porous starch; and / or, The active agent comprises at least one of nicotine and nicotine derivatives.

5. The oral product according to claim 1, characterized in that, The active mixture further comprises at least one of a sweetener, a binder, a pH regulator C and a flavoring.

6. The oral product according to claim 1, characterized in that, The buccal product further comprises a permeation bag, and the composition is encapsulated in the permeation bag.

7. The oral product according to any one of claims 1 to 6, characterized in that, The content of lysozyme in the buccal product does not exceed 2%.

8. A method for preparing an oral product, characterized in that, For preparing the buccal product according to any one of claims 1 to 7, comprising: Obtaining a lysozyme mixture, the lysozyme mixture comprising lysozyme and a carrier coated outside the lysozyme; Preparing a coating solution containing an active agent, and performing coating and granulation treatment on a second filler to obtain a granular active mixture; Mixing the first filler, the active mixture and the lysozyme mixture to prepare the composition of the buccal product, and encapsulating the composition to obtain the buccal product.

9. The preparation method of the oral product according to claim 8, wherein The obtaining of the lysozyme mixture comprises: Obtaining solid particles of carrier-coated lysozyme by an ion gel method; After freeze-drying the solid particles, adding a binder and stirring, adding a pH regulator B to adjust the pH to 6-7, and then performing freeze-drying to obtain the lysozyme mixture.

10. The preparation method of the oral product according to claim 8, characterized in that, The preparing of the coating solution containing an active agent, and performing coating and granulation treatment on a second filler to obtain a granular active mixture, comprises: Preparing the coating solution with an active agent, a pH regulator C and a binder; The second filler is coated with the coating solution to obtain coated granules, and in the coated granules, the active agent is located on the outer layer of the second filler; A flavor solution is prepared using flavoring and sweeteners, and the coated granules are granulated to obtain the granular active mixture.

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