A carbamide peroxide tooth whitening gel and a method of making the same

Abstract

The present application provides a kind of urea peroxide tooth whitening gel and its preparation method, comprising: sodium fluoride solution is mixed with gum arabic solution uniformly, under the condition of stirring and heating, gelatin solution is added, and microsphere suspension is obtained;Pentanedial is added to the microsphere suspension and stirred, and intermediate microspheres are obtained;The intermediate microspheres are added to sodium alginate solution, the suspension is dropped into calcium chloride solution for gelation, and the composite microspheres are taken out and soaked in chitosan solution for oscillation, to obtain double-layer sustained-release microspheres;Carbomer is dispersed in deionized water, and after standing and swelling, a dispersion is obtained, glycerol, xylitol, double-layer sustained-release microspheres, urea peroxide and stabilizer are added to the dispersion, and after mixing uniformly, triethanolamine is added, to obtain urea peroxide tooth whitening gel.The gel product obtained by the present application has the advantages of efficient whitening, long-term anticaries, low irritation and high stability, etc., effectively solving the problems of easy decomposition and easy sensitivity of active ingredients in traditional products.

Description

Technical Field

[0001] This invention belongs to the field of teeth whitening technology, and relates to a urea peroxide teeth whitening gel and its preparation method. Background Technology

[0002] Currently, with the increasing demand for oral aesthetics, teeth whitening has become a widely popular cosmetic procedure. Tooth staining is mainly divided into extrinsic and intrinsic staining. Extrinsic staining is mostly caused by pigments from food (such as coffee, tea, and tobacco) adhering to the enamel surface or penetrating into its interior. Intrinsic staining may originate from factors such as excessive intake of tetracycline drugs or fluoride during tooth development. To improve tooth appearance, chemical bleaching is widely used because it can effectively decompose pigment molecules. Peroxide compounds, such as hydrogen peroxide and urea peroxide, are core ingredients in teeth whitening products because they release reactive oxygen species that oxidize and decompose pigment groups in teeth.

[0003] Among existing teeth whitening technologies, urea peroxide is often used in both at-home and professional teeth whitening products because it slowly decomposes and releases hydrogen peroxide in the oral environment, resulting in a relatively gentle effect. However, these peroxide-based whitening gels still face several challenges in practical application and storage. On the one hand, peroxides, especially in their aqueous solution state, have poor chemical stability and are easily decomposed under light or certain temperature conditions, causing the active ingredients to degrade prematurely during storage and transportation, affecting the final whitening effect. On the other hand, some users experience tooth sensitivity during or after the whitening process. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide a urea peroxide teeth whitening gel and its preparation method. By forming a gelatin-gum arabic composite cohesive layer and a sodium alginate-chitosan polyelectrolyte coating layer on the surface of a sodium fluoride core material, a long-lasting and stable sustained-release effect of sodium fluoride is achieved, effectively alleviating the sensitivity problem to teeth caused during the urea peroxide whitening process. The resulting gel product has advantages such as high-efficiency whitening, long-term caries prevention, low irritation, and high stability, effectively solving the problems of easy decomposition of active ingredients and easy sensitivity caused by traditional products.

[0005] To achieve this objective, the present invention adopts the following technical solution:

[0006] In a first aspect, the present invention provides a method for preparing urea peroxide teeth whitening gel, the method comprising:

[0007] Step 1: Mix sodium fluoride solution and gum arabic solution evenly, add gelatin solution under stirring and heating conditions, and then adjust the pH value to obtain microsphere suspension; under ice water bath conditions, add glutaraldehyde to the microsphere suspension and mix and stir, and finally obtain intermediate microspheres after filtration and washing.

[0008] Step II: Add the intermediate microspheres to sodium alginate solution to obtain a suspension, and then drop the suspension into calcium chloride solution to gel the microspheres and form composite microspheres. After removing the composite microspheres, soak them in chitosan solution and shake them. Finally, after filtration, washing and drying, double-layered sustained-release microspheres are obtained.

[0009] Step III: Disperse carbomer in deionized water, allow it to stand and swell to obtain a dispersion, add glycerol, xylitol, the bilayer sustained-release microspheres, urea peroxide and stabilizer to the dispersion, mix well and then add triethanolamine, continue mixing and stirring to initiate gelation, and obtain the urea peroxide teeth whitening gel.

[0010] This invention forms a gelatin-gum arabic composite cohesive layer and a sodium alginate-chitosan polyelectrolyte coating layer on the surface of a sodium fluoride core material. The inner layer acts as an initial buffer barrier to control the diffusion of sodium fluoride, while the outer layer provides mechanical protection through a denser polyelectrolyte coating layer and achieves a long-lasting and stable sustained-release effect of sodium fluoride through ion exchange. This invention also combines urea peroxide with bilayer sustained-release microspheres containing sodium fluoride. During the urea peroxide bleaching process, the bilayer sustained-release microspheres continuously release fluoride ions, effectively alleviating the sensitivity issues caused by urea peroxide whitening. The resulting gel product has advantages such as high-efficiency whitening, long-term caries prevention, low irritation, and high stability, effectively solving the problems of easy decomposition of active ingredients and sensitivity in traditional products.

[0011] This invention first mixes sodium fluoride solution and gum arabic solution, then adds gelatin solution under stirring and heating conditions. The pH is then adjusted to obtain a microsphere suspension. Glutaraldehyde is then added in an ice-water bath for cross-linking. Gum arabic is an anionic polysaccharide, while gelatin is positively charged under acidic conditions. When the two are mixed, adjusting the pH to near their isoelectric point causes phase separation, forming a complex that encapsulates sodium fluoride, thus forming primary microspheres. Glutaraldehyde is then added, and a cross-linking reaction is carried out in a low-temperature ice-water bath. Glutaraldehyde acts as a cross-linking agent, reacting with the amino groups of gelatin in a Schiff base reaction to solidify the microsphere structure. Through the coagulation reaction between gelatin and gum arabic, and the chemical cross-linking between gelatin and glutaraldehyde, a relatively loose hydrophilic network is formed, effectively encapsulating the sodium fluoride core material within the gelatin-gum arabic composite coagulation layer, forming intermediate microspheres. The gelatin-gum arabic composite coagulating layer not only protects sodium fluoride from external environmental influences and improves its stability, but also controls the slow release of sodium fluoride in the early stages of use, preventing premature or excessive release of fluoride ions, reducing direct irritation to tooth enamel, and ensuring long-term caries prevention.

[0012] Subsequently, the intermediate microspheres were added to a sodium alginate solution to form a suspension, which was then dropped into a calcium chloride solution for gelation, forming composite microspheres. Sodium alginate is an anionic polysaccharide. When the suspension is dropped into the calcium chloride solution, calcium ions crosslink with the carboxyl groups of sodium alginate, forming a calcium alginate gel network that encapsulates the intermediate microspheres. The composite microspheres were then dispersed in a chitosan solution and shaken. Chitosan, as a cationic polysaccharide, interacts with the negative charge of sodium alginate via electrostatic attraction to form a polyelectrolyte complex. Based on the electrostatic interaction between sodium alginate and chitosan, two polyelectrolytes with opposite charges, a denser and more stable sodium alginate-chitosan polyelectrolyte coating layer is formed on the surface of the composite microspheres. This polyelectrolyte coating layer has better mechanical strength and water resistance, effectively protecting the inner structure and preventing premature disintegration during storage or initial use, as well as preventing rupture within the gel matrix, thus ensuring the persistence and stability of fluoride ion release. The fluoride ions released by the double-layered slow-release microspheres can react with the hydroxyapatite on the tooth surface to form more stable fluorapatite. Fluorapatite can reduce the permeability of tooth enamel to a certain extent, seal the dentinal tubules, and thus enhance the tooth's resistance to external stimuli.

[0013] Finally, in this invention, carbomer is dispersed in deionized water and allowed to swell to obtain a dispersion. Then, glycerin, xylitol, bilayer sustained-release microspheres, urea peroxide, and a stabilizer are added and mixed thoroughly. Triethanolamine is then added to initiate gelation, ultimately yielding a teeth whitening gel. Carbomer is a polyacrylic acid polymer that swells in water to form a colloidal dispersion. Upon addition of triethanolamine, the carboxyl groups of carbomer are neutralized, resulting in molecular chain extension and cross-linking, forming a three-dimensional network structure, thus achieving gelation. Glycerin, as a humectant, improves the lubricity and durability of the gel product. Xylitol not only provides sweetness and improves taste but also has anti-caries properties. The stabilizer uses a metal chelating agent to inhibit the catalytic decomposition of urea peroxide by chelating metal ions, enhancing chemical stability. Urea peroxide, as a whitening ingredient, slowly decomposes in the oral environment, releasing hydrogen peroxide to oxidize and decompose pigments. The bilayer sustained-release microspheres continuously release fluoride ions, enhancing the acid resistance of tooth enamel and reducing tooth sensitivity that may occur during the whitening process. The gel matrix provides suitable viscosity and adhesion, ensuring that the gel product can evenly cover the tooth surface and is less likely to run into the gum area, thereby reducing irritation to the gums.

[0014] As a preferred technical solution of the present invention, in step I, the mass fraction of the sodium fluoride solution is 10~20wt%, for example, it can be 10wt%, 11wt%, 12wt%, 13wt%, 14wt%, 15wt%, 16wt%, 17wt%, 18wt%, 19wt%, or 20wt%, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0015] In some alternative examples, the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is 1:1.5 to 1:2, for example, it can be 1:1.5, 1:1.55, 1:1.6, 1:1.65, 1:1.7, 1:1.75, 1:1.8, 1:1.85, 1:1.9, 1:1.95 or 1:2, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0016] This invention specifically limits the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution to 1:1.5 to 1:2. When the amount of gum arabic is within the range specified in this invention, its molecular chains can form a suitable network structure with gelatin, achieving tight coating through hydrogen bonding and electrostatic attraction. Under stirring and heating conditions, this promotes the uniform formation of microspheres, making the microsphere size distribution more concentrated, improving the coating efficiency of the sodium fluoride core material, and ensuring that the sodium fluoride core material is effectively isolated. At the same time, the appropriate addition ratio avoids the aggregation or breakage of microspheres caused by excessive or insufficient gum arabic, thus enhancing the mechanical strength of the microspheres.

[0017] When the amount of gum arabic is below the lower limit defined in this invention, its negative charge is insufficient to form a stable electrostatic complex with the positive charge of gelatin. This results in insufficient coating thickness and uneven distribution, preventing the sodium fluoride core material from being completely encapsulated and exposing it partially to the external environment. Consequently, sodium fluoride becomes susceptible to decomposition due to environmental influences. Furthermore, an excessively thin coating layer leads to an excessively rapid release rate of sodium fluoride, failing to achieve a sustained-release effect. In addition, during the subsequent glutaraldehyde crosslinking process, a thin coating layer can also lead to incomplete crosslinking, reduced mechanical strength of the microspheres, and increased susceptibility to microsphere rupture in subsequent steps, resulting in premature release of sodium fluoride.

[0018] When the amount of gum arabic exceeds the upper limit defined in this invention, the excessive negative charge masks the positive charge of the gelatin, resulting in a loose and thick coating layer. This not only has poor mechanical strength and makes it prone to breakage during subsequent processing, but also leads to premature leakage of sodium fluoride. Furthermore, the excessively thick coating layer also affects the diffusion of sodium fluoride, resulting in a slow release rate and reduced anti-allergic effect. In addition, excessive gum arabic molecular chains will entangle themselves during stirring, increasing the solution viscosity and hindering the uniform formation of microspheres, ultimately leading to excessively large microsphere sizes or aggregation.

[0019] In some optional instances, the gum arabic solution contains 5 to 8 wt% gum arabic, for example, 5.0 wt%, 5.5 wt%, 6.0 wt%, 6.5 wt%, 7.0 wt%, 7.5 wt%, or 8.0 wt%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0020] In some optional examples, in step I, the gelatin solution is added to the mixed solution of the sodium fluoride solution and the gum arabic solution at a stirring speed of 300-500 rpm and a heating temperature of 40-50°C. The stirring speed can be 300 rpm, 320 rpm, 340 rpm, 360 rpm, 380 rpm, 400 rpm, 420 rpm, 440 rpm, 460 rpm, 480 rpm, or 500 rpm, and the heating temperature can be 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C, or 50°C, limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0021] In some alternative examples, gelatin is dissolved in hot water at 50-60°C and mixed thoroughly to obtain the gelatin solution. For example, the temperature may be 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, 56°C, 57°C, 58°C, 59°C, or 60°C, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0022] In some optional instances, the mass fraction of gelatin in the gelatin solution is 5 to 8 wt%, for example, it may be 5.0 wt%, 5.5 wt%, 6.0 wt%, 6.5 wt%, 7.0 wt%, 7.5 wt%, or 8.0 wt%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0023] In some alternative instances, after adding the gelatin solution, acid is added dropwise to adjust the pH of the mixed solution to 4.5-5, for example, 4.5, 4.55, 4.6, 4.65, 4.7, 4.75, 4.8, 4.85, 4.9, 4.95, or 5. Then, mixing and stirring are continued for 30-40 minutes to complete the coagulation reaction and obtain a microsphere suspension, for example, for 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, or 40 minutes, but not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0024] In some optional instances, the temperature of the ice-water bath in step I is 0~5℃, for example, it can be 0℃, 0.5℃, 1℃, 1.5℃, 2℃, 2.5℃, 3℃, 3.5℃, 4℃, 4.5℃ or 5℃, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0025] In some alternative instances, the mass ratio of glutaraldehyde to gelatin in the gelatin solution is 0.05:1 to 0.1:1, for example, it can be 0.05:1, 0.055:1, 0.06:1, 0.065:1, 0.07:1, 0.075:1, 0.08:1, 0.085:1, 0.09:1, 0.095:1 or 0.1:1, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0026] This invention specifically limits the mass ratio of glutaraldehyde to gelatin in the gelatin solution to 0.05:1 to 0.1:1. Within this range, moderate cross-linking can be achieved, allowing glutaraldehyde molecules to undergo a sufficient Schiff base reaction with the amino groups on the gelatin chains, forming a uniformly distributed covalent network. This network structure significantly enhances the mechanical strength of the microspheres, enabling them to withstand the external forces during subsequent processing and preventing structural damage. Simultaneously, the appropriate degree of cross-linking ensures the mechanical strength of the microspheres without resulting in an overly dense structure, providing an ideal diffusion channel for the continuous, slow, and stable release of sodium fluoride.

[0027] When the amount of glutaraldehyde is lower than the lower limit of the range defined in this invention, the cross-linking reaction will be insufficient, and the gelatin molecular chains will not form enough covalent bonds. The resulting microsphere structure will have poor mechanical strength and will be prone to deformation or breakage during subsequent processing, causing the coated sodium fluoride to leak out prematurely and failing to achieve an effective sustained-release function.

[0028] When the amount of glutaraldehyde exceeds the upper limit of the range defined in this invention, it will lead to excessive cross-linking, making the microsphere structure too hard and dense, and significantly reducing the porosity of the coating layer. This will not only excessively delay or even hinder the release of sodium fluoride, affecting its normal anti-allergic effect, but also increase the brittleness of the microspheres, making them easy to break due to external force in the gel matrix.

[0029] In some optional instances, after adding the glutaraldehyde, mixing and stirring are continued for 1 to 2 hours, for example, 1.0 h, 1.1 h, 1.2 h, 1.3 h, 1.4 h, 1.5 h, 1.6 h, 1.7 h, 1.8 h, 1.9 h, or 2.0 h, but not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0030] The microspheres formed by the complex coagulation reaction between gelatin and gum arabic are mainly bound together by electrostatic and hydrogen bonding, which are relatively weak and easily broken by external environmental influences. This invention incorporates glutaraldehyde as a crosslinking agent, which reacts with the amino groups on the gelatin molecules via a Schiff base reaction to form a covalent network. This chemical crosslinking of glutaraldehyde and gelatin solidifies the microsphere structure, increasing its mechanical strength and enabling it to withstand subsequent filtration, washing, and other treatments, while also preventing premature release of sodium fluoride during storage or use.

[0031] The cross-linking process is carried out in a low-temperature ice-water bath primarily to control the reaction rate and avoid side reactions. At high temperatures, the cross-linking reaction between glutaraldehyde and gelatin is too rapid, leading to uneven or excessive cross-linking, causing the microspheres to become brittle or aggregate. Low temperatures slow down the reaction rate, resulting in a more uniform cross-linking process and ensuring each microsphere achieves an appropriate degree of cross-linking. Simultaneously, the low temperature helps maintain the molecular structure of gelatin, as gelatin is prone to denaturation and hydrolysis at high temperatures, affecting its coating function. Furthermore, the ice-water bath inhibits the volatilization and decomposition of glutaraldehyde, maintaining the stability of the reaction system and thus improving the coating quality of the microspheres.

[0032] In some optional instances, in step II, the sodium alginate solution contains 2 to 3 wt% sodium alginate, for example, 2.0 wt%, 2.1 wt%, 2.2 wt%, 2.3 wt%, 2.4 wt%, 2.5 wt%, 2.6 wt%, 2.7 wt%, 2.8 wt%, 2.9 wt%, or 3.0 wt%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0033] In some alternative examples, the mass ratio of the intermediate microspheres to the sodium alginate in the sodium alginate solution is 1:0.5 to 1:1, for example, it can be 1:0.5, 1:0.55, 1:0.6, 1:0.65, 1:0.7, 1:0.75, 1:0.8, 1:0.85, 1:0.9, 1:0.95 or 1:1, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0034] The present invention specifically limits the mass ratio of the intermediate microspheres to sodium alginate in the sodium alginate solution to 1:0.5 to 1:1. Within this mass ratio range, it can ensure that a coating layer of uniform and moderate thickness is formed on the surface of the intermediate microspheres. This ensures that the coating layer is neither too thin, which would result in insufficient protection of the sodium fluoride core material, nor too thick, which would affect the normal release of sodium fluoride.

[0035] When the amount of sodium alginate is below the lower limit defined in this invention, the sodium alginate cannot completely cover the surface of the intermediate microspheres, resulting in an incomplete coating layer. Parts of the intermediate microspheres are directly exposed to the external environment, and sodium fluoride is easily decomposed by changes in external humidity or pH. Simultaneously, the incomplete coating layer reduces the mechanical strength of the microspheres, making them prone to breakage during subsequent processing, leading to premature leakage of sodium fluoride and affecting the sustained-release effect. Furthermore, due to the incomplete sodium alginate coating on the surface of the composite microspheres, chitosan cannot form a uniform outer coating through electrostatic interaction, weakening the overall performance of the bilayer sustained-release microspheres.

[0036] When the amount of sodium alginate exceeds the upper limit specified in this invention, it results in an excessively thick coating layer and an overly dense structure, hindering the diffusion of sodium fluoride and reducing its slow-release rate. Furthermore, excessive sodium alginate increases the viscosity of the suspension, making it difficult to extrude smoothly through the syringe. This leads to uneven droplet size distribution, and for larger droplets, calcium ions cannot diffuse sufficiently into the droplet interior, causing cross-linking to occur only on the droplet surface, forming a hard shell. Insufficient internal cross-linking further affects the sodium fluoride release rate.

[0037] In some optional instances, while the calcium chloride solution is being stirred, the suspension is squeezed out and dripped into the calcium chloride solution using a syringe. The suspension droplets are allowed to stand in the calcium chloride solution for 20 to 30 minutes to achieve gel solidification, for example, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, or 30 minutes, but are not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0038] In some optional instances, the calcium chloride solution contains 3 to 5 wt% calcium chloride, for example, 3.0 wt%, 3.2 wt%, 3.4 wt%, 3.6 wt%, 3.8 wt%, 4.0 wt%, 4.2 wt%, 4.4 wt%, 4.6 wt%, 4.8 wt%, or 5.0 wt%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0039] This invention limits the mass fraction of the calcium chloride solution to 3-5 wt%. When the mass fraction of the calcium chloride solution is less than 3 wt%, the calcium ion concentration is insufficient, the cross-linking reaction rate is slow and incomplete, and the resulting gel microspheres have low strength and are easily deformed. When the mass fraction of the calcium chloride solution is greater than 5 wt%, the high concentration of calcium ions causes instantaneous cross-linking on the droplet surface, forming an overly dense outer shell, which severely hinders the continued diffusion of calcium ions into the interior of the microspheres, ultimately resulting in a heterogeneous microsphere structure with a hardened outer shell but a liquefied interior.

[0040] In some optional instances, in step II, the chitosan solution consists of chitosan and an acetic acid solution.

[0041] In some optional examples, the chitosan solution contains 0.5 to 1 wt% chitosan by mass, for example, 0.5 wt%, 0.55 wt%, 0.6 wt%, 0.65 wt%, 0.7 wt%, 0.75 wt%, 0.8 wt%, 0.85 wt%, 0.9 wt%, 0.95 wt%, or 1 wt%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0042] Chitosan, as a cationic polysaccharide, has positively charged amino groups on its molecular chains under acidic conditions, while the sodium alginate coating layer carries a negative charge. When the composite microspheres are immersed in a chitosan solution, the two interact electrostatically to form a stable polyelectrolyte complex, resulting in a sodium alginate-chitosan polyelectrolyte coating layer on the surface of the microspheres. This invention specifically limits the mass fraction of chitosan in the chitosan solution to 0.5~1wt%. Within this range, the chitosan molecular chains can uniformly cover the surface of the sodium alginate coating layer, forming a continuous and moderately thick polyelectrolyte coating layer. This avoids incomplete coating due to excessively low chitosan concentration or excessive accumulation due to excessively high chitosan concentration.

[0043] When the mass fraction of chitosan in the chitosan solution is less than 0.5 wt%, the positively charged chitosan molecules are unable to form a continuous and complete coating on the negatively charged surface of the microspheres. The polyelectrolyte composite reaction is insufficient, and the final coating layer is very thin, resulting in poor mechanical strength of the microspheres. They are easily damaged during subsequent processing and cannot effectively protect the inner structure of the microspheres. At the same time, due to the incomplete coating, fluoride ions can be rapidly released through the uncoated areas, and the sustained-release effect cannot be achieved.

[0044] When the chitosan mass fraction in the chitosan solution exceeds 1 wt%, it leads to excessive stacking of chitosan molecular chains, forming an excessively thick polyelectrolyte coating layer on the microsphere surface. This hinders the diffusion and swelling of fluoride ions, thus impeding the release of sodium fluoride. Simultaneously, it results in excessively large particle sizes of the final bilayer sustained-release microspheres, affecting their uniform dispersion in the gel matrix, causing microsphere aggregation, and ultimately leading to high product viscosity and poor flowability.

[0045] In some optional examples, the oscillation time of the composite microspheres in the chitosan solution is 20 to 30 minutes, for example, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes or 30 minutes, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0046] In some optional instances, the composite microspheres are oscillated in the chitosan solution at a speed of 50 to 100 rpm, for example, 50 rpm, 55 rpm, 60 rpm, 65 rpm, 70 rpm, 75 rpm, 80 rpm, 85 rpm, 90 rpm, 95 rpm or 100 rpm, but not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0047] In some optional instances, the drying temperature is 40 to 50°C, for example, 40°C, 41°C, 42°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0048] In some optional instances, the drying time is 8 to 10 hours, for example, 8.0 hours, 8.2 hours, 8.4 hours, 8.6 hours, 8.8 hours, 9.0 hours, 9.2 hours, 9.4 hours, 9.6 hours, 9.8 hours, or 10.0 hours, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0049] This invention forms a gelatin-gum arabic composite coagulation layer and a sodium alginate-chitosan polyelectrolyte coating layer on the surface of a sodium fluoride core material. The two coating layers have a synergistic effect. Through the coagulation reaction between gelatin and gum arabic and the chemical cross-linking reaction between glutaraldehyde and gelatin, a relatively loose and highly hydrophilic gel network structure is formed. When the bilayer sustained-release microspheres are in the oral saliva environment, water gradually penetrates into the inner layer, causing the gel network to swell. After the sodium fluoride encapsulated in it dissolves, it diffuses out through the tortuous gel network channels driven by the concentration difference. The gelatin-gum arabic composite coagulation layer constitutes the first sustained-release barrier, which can effectively prevent the sudden release of sodium fluoride.

[0050] However, due to the relatively loose structure and low mechanical strength of the gelatin-gum arabic composite coagulation layer, sodium fluoride is more susceptible to decomposition by the external environment without the outer sodium alginate-chitosan polyelectrolyte coating layer. At the same time, the single inner microsphere is also easily deformed or even ruptured by external forces, causing premature leakage of sodium fluoride. This results in an excessively fast release rate of fluoride ions in the early stages of use, followed by a rapid decrease in the release rate in the later stages, making it impossible to achieve a sustained and stable slow release.

[0051] Therefore, this invention can strengthen and protect the structure by forming a sodium alginate-chitosan polyelectrolyte coating layer on the surface of the gelatin-gum arabic composite coagulation layer. The sodium alginate, after being cross-linked with calcium ions, forms an ion gel network, which is more compact than the gelatin-gum arabic composite coagulation layer. The polyelectrolyte complex formed by the combination of chitosan and sodium alginate through electrostatic interaction further enhances the compactness and stability of the polyelectrolyte coating layer. Sodium and potassium ions in saliva will undergo ion exchange with calcium ions in the polyelectrolyte coating layer, thereby slowly loosening the outer gel structure, regulating the permeation rate of fluoride ions, and achieving long-term stable release of fluoride ions.

[0052] Without the inner gelatin-gum arabic composite coagulating layer, directly placing the sodium fluoride core material within the sodium alginate-chitosan polyelectrolyte coating layer presents several problems. First, the compatibility between the sodium fluoride core material and the sodium alginate-chitosan polyelectrolyte coating layer is poor. Sodium fluoride is a highly water-soluble inorganic salt crystal, and its surface properties make it difficult to form a tight and strong interfacial bond with the polyelectrolyte coating layer, resulting in a loose microsphere structure. Second, without the inner hydrophilic gel network as a buffer, sodium fluoride will directly contact the polyelectrolyte coating layer. Once the microspheres are placed in the oral environment, the moisture in the mouth will rapidly permeate through the polyelectrolyte coating layer, directly dissolving the sodium fluoride inside. Due to the extremely rapid dissolution of sodium fluoride, a high concentration will instantly form inside the microsphere, generating a huge concentration gradient. Under the influence of this concentration gradient, fluoride ions will break through the polyelectrolyte coating layer and be released rapidly, failing to achieve a stable and sustained-release effect.

[0053] In some optional instances, the static swelling time in step III is 8 to 12 hours, for example, 8.0 hours, 8.5 hours, 9.0 hours, 9.5 hours, 10.0 hours, 10.5 hours, 11.0 hours, 11.5 hours, or 12.0 hours, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0054] In some optional examples, the mixing and stirring speed of the dispersion, the glycerol, the xylitol, the bilayer sustained-release microspheres, the urea peroxide, and the stabilizer is 300 to 500 rpm, for example, 300 rpm, 320 rpm, 340 rpm, 360 rpm, 380 rpm, 400 rpm, 420 rpm, 440 rpm, 460 rpm, 480 rpm, or 500 rpm, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0055] In some optional examples, the mixing and stirring time of the dispersion, the glycerol, the xylitol, the bilayer sustained-release microspheres, the urea peroxide, and the stabilizer is 40 to 50 minutes, for example, 40 minutes, 41 minutes, 42 minutes, 43 minutes, 44 minutes, 45 minutes, 46 minutes, 47 minutes, 48 ​​minutes, 49 minutes, or 50 minutes, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0056] In some alternative instances, in step III, triethanolamine is added to the resulting mixed solution to adjust its pH to 6.5-7, for example, 6.5, 6.55, 6.6, 6.65, 6.7, 6.75, 6.8, 6.85, 6.9, 6.95 or 7, but not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0057] In some optional instances, the mixing speed after adding triethanolamine is adjusted to 30-50 rpm, for example, 30 rpm, 32 rpm, 34 rpm, 36 rpm, 38 rpm, 40 rpm, 42 rpm, 44 rpm, 46 rpm, 48 rpm or 50 rpm, but not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0058] In some optional instances, after adding triethanolamine, mixing and stirring are continued for 1 to 2 hours, for example, 1.0 h, 1.1 h, 1.2 h, 1.3 h, 1.4 h, 1.5 h, 1.6 h, 1.7 h, 1.8 h, 1.9 h, or 2.0 h, but not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0059] Carbomer is a polyacrylic acid polymer containing a large number of carboxyl groups in its molecular chain. In this invention, carbomer is dispersed in deionized water and allowed to swell for 8-12 hours. This allows sufficient time for the carbomer powder to fully hydrate and for its molecular chains to fully expand. If the swelling time is too short, the carbomer powder will exist as incompletely hydrated, fish-eye-like gel clumps, preventing the formation of a uniform, smooth gel matrix and resulting in a grainy texture in the product.

[0060] Subsequently, glycerol, xylitol, bilayer sustained-release microspheres, urea peroxide, and a stabilizer were added to the dispersion. Glycerol serves as a humectant and plasticizer, xylitol as a sweetener and anti-caries component, urea peroxide as a whitening active ingredient, and the stabilizer prevents urea peroxide, as the whitening active ingredient, from prematurely decomposing and becoming ineffective during storage.

[0061] Urea peroxide is chemically unstable and easily decomposes. Trace amounts of metal ions in the gel can act as catalysts for its decomposition, accelerating its breakdown into hydrogen peroxide, which further decomposes into water and oxygen, causing the product to lose its whitening effect. This invention adds a stabilizer to the gel product. The stabilizer is a highly efficient metal ion chelating agent that can chelate with metal ions to form a very stable, water-soluble complex. Once the metal ions are chelated and encapsulated by the stabilizer, they can no longer contact the urea peroxide molecules, thus blocking the decomposition of urea peroxide and ensuring the stability of its whitening activity.

[0062] Finally, triethanolamine is added to initiate the gelation reaction. As an organic base, triethanolamine can neutralize the carboxyl groups on the carbomer molecular chain, causing them to ionize into carboxylate anions. The negative charge generated on the molecular chain causes the carbomer molecular chain to fully extend due to electrostatic repulsion and to intertwine and crosslink with each other, transforming from a liquid state with good fluidity into a viscoelastic gel state.

[0063] In a second aspect, the present invention provides a urea peroxide teeth whitening gel prepared by the preparation method described in the first aspect, wherein the urea peroxide teeth whitening gel comprises carbomer, triethanolamine, glycerin, xylitol, bilayer sustained-release microspheres, urea peroxide, stabilizer and deionized water.

[0064] The bilayer sustained-release microspheres comprise a sodium fluoride core and a gelatin-gum arabic composite coagulation layer and a sodium alginate-chitosan polyelectrolyte coating layer sequentially coated on the surface.

[0065] In some optional examples, based on 100 parts by weight of the said urea peroxide teeth whitening gel, it comprises the following components in parts by weight:

[0066] Carbomer 0.5 to 1 part;

[0067] Triethanolamine 0.5-1 part;

[0068] 10-15 parts glycerin;

[0069] 2-4 parts xylitol;

[0070] 3-5 parts of bilayer sustained-release microspheres;

[0071] 8-10 parts of urea peroxide;

[0072] Stabilizer 0.5~1 part;

[0073] The rest is deionized water.

[0074] The carbomer can be present in the following proportions by weight: 0.5 parts, 0.55 parts, 0.6 parts, 0.65 parts, 0.7 parts, 0.75 parts, 0.8 parts, 0.85 parts, 0.9 parts, 0.95 parts, or 1 part; the triethanolamine can be present in the following proportions by weight: 0.5 parts, 0.55 parts, 0.6 parts, 0.65 parts, 0.7 parts, 0.75 parts, 0.8 parts, 0.85 parts, 0.9 parts, 0.95 parts, or 1 part; the glycerol can be present in the following proportions by weight: 10 parts, 10.5 parts, 11 parts, 11.5 parts, 12 parts, 12.5 parts, 13 parts, 13.5 parts, 14 parts, 14.5 parts, or 15 parts; and the xylitol can be present in the following proportions by weight: 2.0 parts, 2.2 parts, 2.4 parts, 2.6 parts, 2.8 parts, 3.0 parts, 3.2 parts, or 3.4 parts. The weight parts of bilayer sustained-release microspheres can be 3.0, 3.2, 3.4, 3.6, 3.8, 4.0, 4.2, 4.4, 4.6, 4.8, or 5.0 parts; the weight parts of urea peroxide can be 8.0, 8.2, 8.4, 8.6, 8.8, 9.0, 9.2, 9.4, 9.6, 9.8, or 10.0 parts; the weight parts of stabilizer can be 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, or 1 part, but are not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0075] Carbomer, as the main component of the gel matrix, is present in a range of 0.5 to 1 part by weight. This ensures that the final gel product has suitable viscoelasticity, can evenly cover the tooth surface, and is not easily lost to the gum area. When its addition amount is less than 0.5 parts, the gel product will have high fluidity, affecting its durability and coverage on the tooth surface; when its addition amount is more than 1 part, the gel product will be too viscous, hindering the release of active ingredients.

[0076] The triethanolamine is added in amounts ranging from 0.5 to 1 part by weight. Its function is to neutralize carbomer to initiate gelation. Adding an appropriate amount of triethanolamine can also adjust the pH of the gel product to a suitable range. When the amount added is less than 0.5 parts, the neutralization reaction with carbomer is incomplete, leading to difficulty in gel formation and structural instability. When the amount added is greater than 1 part, it results in an excessively alkaline product, accelerating the decomposition of urea peroxide and reducing the whitening effect of the gel product.

[0077] The weight range of glycerin is 10-15 parts. As a humectant and plasticizer, glycerin helps retain moisture in the gel through its hygroscopic properties, preventing it from drying out too quickly and improving the user experience. When the amount added is less than 10 parts, the moisturizing effect is poor, and the gel is prone to cracking after application, affecting the user experience. When the amount added is more than 15 parts, it will lead to excessively high viscosity of the gel product, which will affect the uniform dispersion of the components in the gel product.

[0078] The weight range of xylitol is 2-4 parts. Xylitol is a pentose sugar alcohol whose molecular structure can interfere with the metabolic process of bacteria in dental plaque, reducing acid production and thus lowering the risk of tooth decay. At the same time, xylitol can also provide sweetness, masking the unpleasant taste of other components. When its addition amount is less than 2 parts, the anti-caries function and taste improvement effect are not obvious; when its addition amount is more than 4 parts, it will increase the viscosity of the product, thereby affecting the uniformity of dispersion of various components in the gel product.

[0079] The bilayer sustained-release microspheres, with a weight range of 3-5 parts, comprise a sodium fluoride core and a surface-coated gelatin-gum arabic composite layer and a sodium alginate-chitosan polyelectrolyte coating layer. These microspheres control the release of sodium fluoride through diffusion and swelling, enhancing the enamel's acid resistance and reducing tooth sensitivity during whitening. When the addition amount is less than 3 parts, the release of sodium fluoride is insufficient, resulting in a poor sensitivity-relieving effect; when the addition amount is greater than 5 parts, aggregation is likely to occur, affecting the product's texture uniformity.

[0080] The weight range of urea peroxide is 8-10 parts. As a whitening ingredient, urea peroxide decomposes in the oral environment to produce hydrogen peroxide, which breaks down pigment molecules on the tooth surface through an oxidation reaction. When its addition amount is less than 8 parts, the release of reactive oxygen species is insufficient, and the whitening effect of the gel product is not obvious; when its addition amount is more than 10 parts, it will increase tooth sensitivity and irritation to the gums.

[0081] The stabilizer is added in amounts ranging from 0.5 to 1 part by weight. Its function is to inhibit the catalytic decomposition of urea peroxide by chelating metal ions, thus ensuring the whitening effect of the product. When the amount added is less than 0.5 parts, the chelating effect is insufficient, and it cannot effectively protect urea peroxide, which is easily decomposed, resulting in a poorer whitening effect.

[0082] In some optional instances, the stabilizer includes pentasodium diethylenetriaminepentaacetate.

[0083] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0084] This invention forms a gelatin-gum arabic composite cohesive layer and a sodium alginate-chitosan polyelectrolyte coating layer on the surface of a sodium fluoride core material. The inner layer acts as an initial buffer barrier to control the diffusion of sodium fluoride, while the outer layer provides mechanical protection through a denser polyelectrolyte coating layer and achieves a long-lasting and stable sustained-release effect of sodium fluoride through ion exchange. This invention also combines urea peroxide with bilayer sustained-release microspheres containing sodium fluoride. During the urea peroxide bleaching process, the bilayer sustained-release microspheres continuously release fluoride ions, effectively alleviating the sensitivity issues caused by urea peroxide whitening. The resulting gel product has advantages such as high-efficiency whitening, long-term caries prevention, low irritation, and high stability, effectively solving the problems of easy decomposition of active ingredients and sensitivity in traditional products. Attached Figure Description

[0085] Figure 1 The process flow diagrams are for preparing the teeth whitening gels provided in Examples 1-13 of this invention.

[0086] Figure 2 The infrared spectrum of the bilayer sustained-release microspheres prepared in Example 1 of this invention;

[0087] Figure 3 Real-life photos showing the whitening effect of the whitening gel provided to the experimental and control groups on extracted human teeth. Detailed Implementation

[0088] The technical solutions of the present invention will be described in detail below with reference to specific embodiments and accompanying drawings. The embodiments described herein are specific implementations of the present invention, used to illustrate the concept of the present invention; these descriptions are explanatory and exemplary, and should not be construed as limiting the implementation methods or the scope of protection of the present invention. In addition to the embodiments described herein, those skilled in the art can employ other obvious technical solutions based on the content disclosed in the claims and specification of this application. These technical solutions include those that make any obvious substitutions and modifications to the embodiments described herein.

[0089] Example 1

[0090] This embodiment provides a method for preparing urea peroxide teeth whitening gel, such as... Figure 1 As shown, the preparation method specifically includes the following steps:

[0091] (1) Mix a sodium fluoride solution with a mass fraction of 10 wt% and a gum arabic solution with a mass fraction of 5 wt%, wherein the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is 1:1.5, and stir evenly to obtain a mixed solution;

[0092] Gelatin was dissolved in hot water at 50°C and mixed evenly to obtain a gelatin solution with a mass fraction of 5 wt%. At a stirring speed of 300 rpm and a heating temperature of 40°C, the above gelatin solution with an equal volume to the gum arabic solution was added to the mixed solution composed of sodium fluoride solution and gum arabic solution. Then, 5% (v / v) acetic acid solution was added dropwise to adjust the pH value of the mixed solution to 4.5. The mixture was stirred for 40 min to complete the coagulation reaction and obtain a microsphere suspension.

[0093] Glutaraldehyde was added to the microsphere suspension under ice-water bath conditions at 0℃. The mass ratio of glutaraldehyde to gelatin in the gelatin solution was 0.05:1. After mixing and stirring for 1 hour, the mixture was filtered and washed to obtain intermediate microspheres.

[0094] (2) Add the intermediate microspheres to a sodium alginate solution with a mass fraction of 2 wt% to obtain a suspension. The mass ratio of the intermediate microspheres to the sodium alginate in the sodium alginate solution is 1:0.5.

[0095] A calcium chloride solution with a mass fraction of 3 wt% was prepared. While stirring the calcium chloride solution, the suspension prepared above was squeezed out and dripped into the calcium chloride solution using a syringe. The suspension droplets were allowed to stand in the calcium chloride solution for 30 minutes to achieve gel solidification and form composite microspheres.

[0096] Chitosan and 1 wt% acetic acid solution were mixed evenly to obtain a chitosan solution with a mass fraction of 0.5 wt%. The composite microspheres were taken out and dispersed in the chitosan solution prepared above. The mixture was shaken at 50 rpm for 30 min, then filtered. The residue was washed with deionized water until neutral. After washing, it was dried at 40℃ for 10 h to obtain bilayer sustained-release microspheres.

[0097] (3) Disperse 0.5 parts of carbomer in 69 parts of deionized water, let it stand and swell for 8 hours to obtain a dispersion, add 10 parts of glycerol, 4 parts of xylitol, 5 parts of bilayer sustained-release microspheres, 10 parts of urea peroxide and 1 part of diethylenetriaminepentaacetic acid pentasodium to the dispersion, mix and stir at 300 rpm for 50 min, then add 0.5 parts of triethanolamine to adjust the pH of the mixed solution to 6.5, adjust the stirring speed to 30 rpm, and continue mixing and stirring for 2 hours to complete gelation, and obtain the urea peroxide teeth whitening gel.

[0098] Figure 2 The image shows the infrared spectrum of the bilayer sustained-release microspheres prepared in this embodiment. As can be seen from the image, at 3350 cm⁻¹... -1 The broad absorption peak at 3000 cm⁻¹ is attributed to the stretching vibrations of OH and NH bonds, originating from the hydroxyl and amino groups in gelatin, chitosan, gum arabic, and sodium alginate molecules; -1The nearby absorption peaks are attributed to the stretching vibrations of the CH bonds, which originate from the methylene and methyl groups in the framework of all organic components; 1630 cm⁻¹ -1 The strong absorption peak at 1430 cm⁻¹ is attributed to the C=O stretching vibration of the amide I band and the asymmetric stretching vibration of the carboxylate ion, mainly originating from the amide groups of gelatin and the carboxyl groups of gum arabic and sodium alginate; -1 The absorption peak at 1040 cm⁻¹ is attributed to the bending vibration of the CH bond and the symmetric stretching vibration of -COO⁻, originating from the organic framework and acidic polysaccharides; -1 The absorption peak at 930 cm⁻¹ is attributed to the stretching vibrations of the COC and CO bonds, which originate from the ether bonds and hydroxyl groups of the sugar rings in each polysaccharide component; -1 The absorption peak at 885 cm⁻¹ is attributed to the COC bonds in the sugar rings of the chitosan molecular chain; -1 The characteristic absorption peak at this location is attributed to the characteristic vibrations of the sodium alginate glycoring structure. The presence of these characteristic functional groups indicates that this embodiment prepared bilayer sustained-release microspheres composed of a gelatin-gum arabic composite coagulation layer and a sodium alginate-chitosan polyelectrolyte coating layer.

[0099] Example 2

[0100] This embodiment provides a method for preparing urea peroxide teeth whitening gel, such as... Figure 1 As shown, the preparation method specifically includes the following steps:

[0101] (1) A sodium fluoride solution with a mass fraction of 12 wt% and a gum arabic solution with a mass fraction of 6 wt% are mixed, wherein the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is 1:1.6. After stirring evenly, a mixed solution is obtained.

[0102] Gelatin was dissolved in hot water at 52°C and mixed evenly to obtain a gelatin solution with a mass fraction of 6 wt%. At a stirring speed of 350 rpm and a heating temperature of 42°C, the above gelatin solution with an equal volume to the gum arabic solution was added to the mixed solution composed of sodium fluoride solution and gum arabic solution. Then, 5% (v / v) acetic acid solution was added dropwise to adjust the pH value of the mixed solution to 4.6. The mixture was stirred for 38 min to complete the coagulation reaction and obtain a microsphere suspension.

[0103] Glutaraldehyde was added to the microsphere suspension under ice-water bath conditions at 1℃. The mass ratio of glutaraldehyde to gelatin in the gelatin solution was 0.06:1. After mixing and stirring for 1.2 h, the mixture was filtered and washed to obtain intermediate microspheres.

[0104] (2) The intermediate microspheres were added to a sodium alginate solution with a mass fraction of 2.2 wt% to obtain a suspension. The mass ratio of the intermediate microspheres to the sodium alginate in the sodium alginate solution was 1:0.6.

[0105] A calcium chloride solution with a mass fraction of 3.5 wt% was prepared. While stirring the calcium chloride solution, the suspension prepared above was squeezed out and dripped into the calcium chloride solution using a syringe. The suspension droplets were allowed to stand in the calcium chloride solution for 28 minutes to achieve gel solidification and form composite microspheres.

[0106] Chitosan and 1 wt% acetic acid solution were mixed evenly to obtain a chitosan solution with a mass fraction of 0.6 wt%. The composite microspheres were taken out and dispersed in the chitosan solution prepared above. The mixture was shaken at 60 rpm for 28 min, then filtered. The residue was washed with deionized water until neutral. After washing, it was dried at 42℃ for 9.5 h to obtain bilayer sustained-release microspheres.

[0107] (3) Disperse 0.6 parts of carbomer in 69.3 parts of deionized water and let it stand for 9 hours to swell to obtain a dispersion. Add 12 parts of glycerol, 4 parts of xylitol, 4 parts of bilayer sustained-release microspheres, 8.5 parts of urea peroxide and 1 part of diethylenetriaminepentaacetic acid pentasodium to the dispersion. Mix and stir at 350 rpm for 48 minutes. Then add 0.6 parts of triethanolamine to adjust the pH of the mixed solution to 6.6. Adjust the stirring speed to 35 rpm and continue mixing and stirring for 1.8 hours to complete gelation and obtain the urea peroxide teeth whitening gel.

[0108] Example 3

[0109] This embodiment provides a method for preparing urea peroxide teeth whitening gel, such as... Figure 1 As shown, the preparation method specifically includes the following steps:

[0110] (1) A sodium fluoride solution with a mass fraction of 15 wt% and a gum arabic solution with a mass fraction of 6 wt% are mixed, wherein the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is 1:1.7. After stirring evenly, a mixed solution is obtained.

[0111] Gelatin was dissolved in hot water at 55°C and mixed evenly to obtain a gelatin solution with a mass fraction of 6 wt%. At a stirring speed of 400 rpm and a heating temperature of 45°C, the above gelatin solution with an equal volume to the gum arabic solution was added to the mixed solution composed of sodium fluoride solution and gum arabic solution. Then, 5% (v / v) acetic acid solution was added dropwise to adjust the pH value of the mixed solution to 4.7. The mixture was stirred for 35 min to complete the coagulation reaction and obtain a microsphere suspension.

[0112] Glutaraldehyde was added to the microsphere suspension under ice-water bath conditions at 2℃. The mass ratio of glutaraldehyde to gelatin in the gelatin solution was 0.07:1. After mixing and stirring for 1.5h, the mixture was filtered and washed to obtain intermediate microspheres.

[0113] (2) Add the intermediate microspheres to a sodium alginate solution with a mass fraction of 2.5 wt% to obtain a suspension. The mass ratio of the intermediate microspheres to the sodium alginate in the sodium alginate solution is 1:0.7.

[0114] A calcium chloride solution with a mass fraction of 4 wt% was prepared. While stirring the calcium chloride solution, the suspension prepared above was squeezed out and dripped into the calcium chloride solution using a syringe. The suspension droplets were allowed to stand in the calcium chloride solution for 25 minutes to achieve gel solidification and form composite microspheres.

[0115] Chitosan and 1 wt% acetic acid solution were mixed evenly to obtain a chitosan solution with a mass fraction of 0.7 wt%. The composite microspheres were taken out and dispersed in the chitosan solution prepared above. The mixture was shaken at 70 rpm for 25 min, then filtered. The retentate was washed with deionized water until neutral. After washing, it was dried at 45℃ for 9 h to obtain bilayer sustained-release microspheres.

[0116] (3) Disperse 0.7 parts of carbomer in 69.1 parts of deionized water and let it stand for 10 hours to swell to obtain a dispersion. Add 13 parts of glycerol, 3 parts of xylitol, 4 parts of bilayer sustained-release microspheres, 9 parts of urea peroxide and 0.5 parts of diethylenetriaminepentaacetic acid pentasodium to the dispersion. Mix and stir at 400 rpm for 45 minutes. Then add 0.7 parts of triethanolamine to adjust the pH of the mixed solution to 6.7. Adjust the stirring speed to 40 rpm and continue mixing and stirring for 1.5 hours to complete gelation and obtain the urea peroxide teeth whitening gel.

[0117] Example 4

[0118] This embodiment provides a method for preparing urea peroxide teeth whitening gel, such as... Figure 1 As shown, the preparation method specifically includes the following steps:

[0119] (1) A sodium fluoride solution with a mass fraction of 18 wt% and a gum arabic solution with a mass fraction of 7 wt% are mixed, wherein the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is 1:1.8. After stirring evenly, a mixed solution is obtained.

[0120] Gelatin was dissolved in hot water at 58°C and mixed evenly to obtain a gelatin solution with a mass fraction of 7 wt%. At a stirring speed of 450 rpm and a heating temperature of 48°C, the above gelatin solution with an equal volume to the gum arabic solution was added to the mixed solution composed of sodium fluoride solution and gum arabic solution. Then, 5% (v / v) acetic acid solution was added dropwise to adjust the pH value of the mixed solution to 4.8. The mixture was stirred for 32 min to complete the coagulation reaction and obtain a microsphere suspension.

[0121] Glutaraldehyde was added to the microsphere suspension under ice-water bath conditions at 3°C. The mass ratio of glutaraldehyde to gelatin in the gelatin solution was 0.08:1. After mixing and stirring for 1.8 h, the mixture was filtered and washed to obtain intermediate microspheres.

[0122] (2) The intermediate microspheres were added to a sodium alginate solution with a mass fraction of 2.8 wt% to obtain a suspension. The mass ratio of the intermediate microspheres to the sodium alginate in the sodium alginate solution was 1:0.8.

[0123] A calcium chloride solution with a mass fraction of 4.5 wt% was prepared. While stirring the calcium chloride solution, the suspension prepared above was squeezed out and dripped into the calcium chloride solution using a syringe. The suspension droplets were allowed to stand in the calcium chloride solution for 22 minutes to achieve gel solidification and form composite microspheres.

[0124] Chitosan and 1 wt% acetic acid solution were mixed evenly to obtain a chitosan solution with a mass fraction of 0.8 wt%. The composite microspheres were taken out and dispersed in the chitosan solution prepared above. The mixture was shaken at 80 rpm for 22 min, then filtered. The retentate was washed with deionized water until neutral. After washing, it was dried at 48℃ for 8.5 h to obtain bilayer sustained-release microspheres.

[0125] (3) Disperse 0.8 parts of carbomer in 68.8 parts of deionized water and let it stand for 11 hours to swell to obtain a dispersion. Add 14 parts of glycerol, 2 parts of xylitol, 5 parts of bilayer sustained-release microspheres, 8 parts of urea peroxide and 0.6 parts of diethylenetriaminepentaacetic acid pentasodium to the dispersion. Mix and stir at 450 rpm for 42 minutes. Then add 0.8 parts of triethanolamine to adjust the pH of the mixed solution to 6.8. Adjust the stirring speed to 45 rpm and continue mixing and stirring for 1.2 hours to complete gelation and obtain the urea peroxide teeth whitening gel.

[0126] Example 5

[0127] This embodiment provides a method for preparing urea peroxide teeth whitening gel, such as... Figure 1 As shown, the preparation method specifically includes the following steps:

[0128] (1) Mix a sodium fluoride solution with a mass fraction of 20 wt% and a gum arabic solution with a mass fraction of 8 wt%, wherein the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is 1:2, and stir evenly to obtain a mixed solution.

[0129] Gelatin was dissolved in hot water at 60°C and mixed evenly to obtain a gelatin solution with a mass fraction of 8 wt%. At a stirring speed of 500 rpm and a heating temperature of 50°C, the above gelatin solution with an equal volume to the gum arabic solution was added to the mixed solution composed of sodium fluoride solution and gum arabic solution. Then, 5% (v / v) acetic acid solution was added dropwise to adjust the pH value of the mixed solution to 5. The mixture was stirred for 30 min to complete the coagulation reaction and obtain a microsphere suspension.

[0130] Glutaraldehyde was added to the microsphere suspension under ice-water bath conditions at 5℃. The mass ratio of glutaraldehyde to gelatin in the gelatin solution was 0.1:1. After mixing and stirring for 2 hours, the mixture was filtered and washed to obtain intermediate microspheres.

[0131] (2) Add the intermediate microspheres to a sodium alginate solution with a mass fraction of 3 wt% to obtain a suspension. The mass ratio of the intermediate microspheres to the sodium alginate in the sodium alginate solution is 1:1.

[0132] A calcium chloride solution with a mass fraction of 5 wt% was prepared. While stirring the calcium chloride solution, the suspension prepared above was squeezed out and dripped into the calcium chloride solution using a syringe. The suspension droplets were allowed to stand in the calcium chloride solution for 20 minutes to achieve gel solidification and form composite microspheres.

[0133] Chitosan and 1 wt% acetic acid solution were mixed evenly to obtain a chitosan solution with a mass fraction of 1 wt%. The composite microspheres were taken out and dispersed in the chitosan solution prepared above. The mixture was shaken at 100 rpm for 20 min, then filtered. The retentate was washed with deionized water until neutral. After washing, it was dried at 50℃ for 8 h to obtain bilayer sustained-release microspheres.

[0134] (3) Disperse 1 part of carbomer in 68.3 parts of deionized water, let it stand and swell for 12 hours to obtain a dispersion, add 15 parts of glycerol, 2.5 parts of xylitol, 3 parts of bilayer sustained-release microspheres, 8.5 parts of urea peroxide and 0.7 parts of diethylenetriaminepentaacetic acid pentasodium to the dispersion, mix and stir at 500 rpm for 40 minutes, then add 1 part of triethanolamine to adjust the pH of the mixed solution to 7, adjust the stirring speed to 50 rpm, and continue mixing and stirring for 1 hour to complete gelation, and obtain the urea peroxide teeth whitening gel.

[0135] Example 6

[0136] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Embodiment 1 is that in step (1), the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is adjusted to 1:1. Other operating steps and process parameters are exactly the same as in Embodiment 1.

[0137] Example 7

[0138] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Embodiment 1 is that in step (1), the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is adjusted to 1:3. Other operating steps and process parameters are exactly the same as in Embodiment 1.

[0139] Example 8

[0140] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Example 1 is that in step (1), the mass ratio of glutaraldehyde to gelatin in the gelatin solution is adjusted to 0.01:1. Other operation steps and process parameters are exactly the same as in Example 1.

[0141] Example 9

[0142] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Example 1 is that in step (1), the mass ratio of glutaraldehyde to gelatin in the gelatin solution is adjusted to 0.2:1. Other operation steps and process parameters are exactly the same as in Example 1.

[0143] Example 10

[0144] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Embodiment 1 is that in step (2), the mass ratio of the intermediate microspheres to sodium alginate in the sodium alginate solution is adjusted to 1:0.1. Other operation steps and process parameters are exactly the same as in Embodiment 1.

[0145] Example 11

[0146] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Embodiment 1 is that in step (2), the mass ratio of the intermediate microspheres to sodium alginate in the sodium alginate solution is adjusted to 1:1.5. Other operation steps and process parameters are exactly the same as in Embodiment 1.

[0147] Example 12

[0148] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Embodiment 1 is that in step (2), the mass fraction of chitosan in the chitosan solution is adjusted to 0.1 wt%, while the other operation steps and process parameters are exactly the same as in Embodiment 1.

[0149] Example 13

[0150] This embodiment provides a method for preparing urea peroxide teeth whitening gel. The difference from Embodiment 1 is that in step (2), the mass fraction of chitosan in the chitosan solution is adjusted to 1.5 wt%, while the other operation steps and process parameters are exactly the same as in Embodiment 1.

[0151] The efficacy of the urea peroxide teeth whitening gels prepared in Examples 1-13 was evaluated, and the specific evaluation process is as follows:

[0152] (1) Whiteness difference △L*

[0153] Extracted human teeth were selected, cleaned, and soaked in coffee solution for 24 hours. Teeth were randomly divided into an experimental group (applied with the urea peroxide teeth whitening gel prepared in Examples 1-13) and a control group (applied with blank gel without urea peroxide and double-layered sustained-release microspheres). The gel was evenly applied to the tooth surface and left in a simulated oral environment (temperature 37℃, humidity 95%) for 30 minutes, then rinsed clean. This treatment was performed once daily for 14 consecutive days. Using a calibrated colorimeter, the L values ​​of the central region of the teeth were measured before treatment, after day 7, and after day 14, and recorded as L0, L1, and L2, respectively. The whiteness difference ΔL* was calculated using the following formula:

[0154] △L after treatment on day 7 * =L1-L0;

[0155] △L after treatment on day 14 * =L2-L0.

[0156] Figure 3The images show the whitening effects of the whitening gels provided to the experimental group (the urea peroxide teeth whitening gel provided in Example 1) and the control group (a gel without urea peroxide and double-layered sustained-release microspheres, with other components and proportions exactly the same as in Example 1) on extracted human teeth. As can be seen from the images, after 14 days of treatment, the teeth samples in the control group did not show significant improvement in color, brightness, or cleanliness. The appearance of the teeth on day 0 and day 14 was almost identical, and the initial yellowish-brown stains (especially in the cervical region) were still clearly visible. The overall color tone of the teeth did not lighten significantly, and the improvement in brightness and whiteness was negligible. This indicates that the gel matrix without urea peroxide and double-layered sustained-release microspheres does not have an effective whitening and stain removal function. In comparison, after the same 14-day treatment cycle, the experimental group's tooth samples showed a significant whitening effect. A large amount of yellowish-brown stains on the tooth surface were removed, and the overall color became significantly lighter and whiter, changing from the initial yellowish-brown tone to a natural milky white. Pigment deposits in the neck area of ​​the teeth, which are usually difficult to clean, were also effectively removed, with particularly outstanding improvement effects. The teeth looked cleaner and brighter, achieving the ideal whitening effect.

[0157] (2) Cumulative release rate of fluoride ions

[0158] Precisely prepare a fluoride ion standard stock solution (1000 ppm). Dilute the stock solution with deionized water and total ionic strength adjustment buffer (TISAB) at a 1:1 volume ratio to prepare standard solutions with five different concentration gradients (0.1 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, and 5.0 ppm).

[0159] The fluoride ion electrode and the reference electrode were immersed in the standard solution. Under magnetic stirring, the potential values ​​(mV) were measured sequentially from low concentration to high concentration. A standard curve was plotted with the potential value (mV) as the ordinate and the negative logarithm of the fluoride ion concentration (-log[F⁻]) as the abscissa, and the linear regression equation was obtained.

[0160] Prepare 6 groups of gel samples prepared in Examples 1-13, 1.0 g of each gel sample. Place each gel sample in a clean conical flask, add 50.0 mL of release medium (0.1 M, pH=4.0 sodium lactate buffer) at 37°C, mix well, seal the conical flask, and place it in a constant temperature shaking water bath at 37°C with a shaking speed of 100 rpm.

[0161] Five minutes later, aspirate 1.0 mL of release medium from the conical flask, and simultaneously add 1.0 mL of fresh, 37°C release medium to the flask to maintain a constant total volume. Mix the 1.0 mL sample solution with an equal volume of TISAB solution, ready for analysis. Take samples at 15 minutes and 30 minutes following the same procedure.

[0162] The test solution mixed with TISAB was placed in a small beaker, a fluoride ion electrode was inserted, and the potential value after stabilization was measured under magnetic stirring. The potential value was substituted into the linear regression equation to calculate the fluoride ion concentration in the test solution. The cumulative release of fluoride ions (mg) at different times was calculated using the following formula:

[0163] Q t (mg) = C t (mg / L)×V(L).

[0164] The theoretical total amount of fluoride ions (W) in the gel sample was determined using the acid hydrolysis method. 总 The cumulative fluoride ion release rate (%) at each time point is calculated using the following formula:

[0165] Cumulative release rate (%) = (Q t / W 总 ) × 100%.

[0166] The test results are shown in Table 1.

[0167] Table 1. Evaluation data on the efficacy of urea peroxide teeth whitening gels prepared in Examples 1-13

[0168]

[0169] The test data from Examples 1, 6, and 7 show that in Example 6, the amount of gum arabic was too small, resulting in a less dense microsphere structure and poorer encapsulation. Fluoride ions were released too quickly in the initial stage, affecting the duration of their effect. In Example 7, the amount of gum arabic was too large. Although it delayed the release of fluoride ions, the gel structure was too viscous and dense, which significantly delayed the release of fluoride ions. After use, a large amount of fluoride ions still failed to exert their anti-caries and anti-allergy effects.

[0170] The test data from Examples 1, 8, and 9 show that in Example 8, the amount of glutaraldehyde added was too low, resulting in insufficient cross-linking of the gelatin and weak mechanical strength of the microspheres. This made it impossible to effectively control the release rate of fluoride ions, thus failing to maintain the anti-allergy effect. In Example 9, the amount of glutaraldehyde added was too high, causing excessive cross-linking and forming an overly dense network structure. This significantly delayed the release of fluoride ions, and a large number of fluoride ions remained unexerted in preventing tooth decay and allergies after use.

[0171] The test data from Examples 1, 10, and 11 show that in Example 10, the amount of sodium alginate added was too low, resulting in a thin polyelectrolyte coating layer formed with chitosan, which could not effectively achieve a sustained-release effect. Fluoride ions were released rapidly within 5 minutes, resulting in a lack of sustained anti-allergy effect in the later stages. In Example 11, the amount of sodium alginate added was too high, resulting in a polyelectrolyte coating layer that was too thick and too dense, which significantly delayed the release of fluoride ions. After use, a large number of fluoride ions still failed to exert their anti-caries and anti-allergy effects.

[0172] The test data from Examples 1, 12, and 13 show that the chitosan solution in Example 12 had a low mass fraction, resulting in poor film-forming properties and difficulty in forming a complete and robust polyelectrolyte coating with sodium alginate. This resulted in poor protection and controlled release of sodium fluoride, affecting the sustained and stable performance of its anti-caries and anti-allergy effects. In Example 13, the chitosan solution had a high mass fraction, leading to excessively high gel viscosity, strong intermolecular forces, and an overly dense network structure. This significantly delayed the release of fluoride ions, and a large number of fluoride ions remained unexerted in their anti-caries and anti-allergy effects after use.

[0173] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A method for preparing a urea peroxide teeth whitening gel, characterized in that, The preparation method includes: Step 1: Mix sodium fluoride solution and gum arabic solution evenly, wherein the mass ratio of sodium fluoride in the sodium fluoride solution to gum arabic in the gum arabic solution is 1:1.5 to 1:2; add gelatin solution under stirring and heating conditions, and then adjust the pH value to obtain a microsphere suspension; add glutaraldehyde to the microsphere suspension under ice-water bath conditions and mix and stir, wherein the mass ratio of glutaraldehyde to gelatin in the gelatin solution is 0.05:1 to 0.1:1; finally, after filtration and washing, obtain intermediate microspheres. Step II: The intermediate microspheres are added to a sodium alginate solution to obtain a suspension, wherein the mass ratio of the intermediate microspheres to sodium alginate in the sodium alginate solution is 1:0.5 to 1:1; the suspension is then added dropwise to a calcium chloride solution for gelation to form composite microspheres, wherein the mass fraction of calcium chloride in the calcium chloride solution is 3 to 5 wt%; the composite microspheres are then removed and immersed in a chitosan solution for shaking, wherein the chitosan solution is composed of chitosan and acetic acid solution, and the mass fraction of chitosan in the chitosan solution is 0.5 to 1 wt%; finally, after filtration, washing, and drying, bilayer sustained-release microspheres are obtained. Step III: Disperse carbomer in deionized water, allow it to stand and swell to obtain a dispersion, add glycerol, xylitol, the bilayer sustained-release microspheres, urea peroxide and stabilizer to the dispersion, mix evenly and then add triethanolamine, continue mixing and stirring to initiate gelation, and obtain the urea peroxide teeth whitening gel. Based on 100 parts by weight of the aforementioned urea peroxide teeth whitening gel, it comprises the following components in parts by weight: Carbomer 0.5 to 1 part; Triethanolamine 0.5-1 part; 10-15 parts glycerin; 2-4 parts xylitol; 3-5 parts of bilayer sustained-release microspheres; 8-10 parts of urea peroxide; Stabilizer 0.5~1 part; The rest is deionized water.

2. The preparation method according to claim 1, characterized in that, In step I, the sodium fluoride solution has a mass fraction of 10-20 wt%. The gum arabic solution contains 5-8 wt% gum arabic.

3. The preparation method according to claim 1, characterized in that, In step I, the gelatin solution is added to the mixed solution composed of the sodium fluoride solution and the gum arabic solution at a stirring speed of 300-500 rpm and a heating temperature of 40-50°C. Gelatin is dissolved in hot water at 50-60°C and mixed evenly to obtain the gelatin solution. The gelatin solution contains 5-8 wt% gelatin. After adding the gelatin solution, acid is added dropwise to adjust the pH of the mixed solution to 4.5-5. Then, mixing and stirring are continued for 30-40 minutes to complete the coagulation reaction and obtain a microsphere suspension.

4. The preparation method according to claim 1, characterized in that, In step I, the temperature of the ice-water bath is 0~5℃; After adding the glutaraldehyde, continue mixing and stirring for 1-2 hours.

5. The preparation method according to claim 1, characterized in that, In step II, the sodium alginate solution contains 2-3 wt% sodium alginate. While stirring the calcium chloride solution, the suspension is squeezed out and dripped into the calcium chloride solution using a syringe. The suspension droplets are left to stand in the calcium chloride solution for 20-30 minutes to achieve gel solidification.

6. The preparation method according to claim 1, characterized in that, In step II, the composite microspheres are shaken in the chitosan solution for 20-30 minutes; The composite microspheres were oscillated at a speed of 50-100 rpm in the chitosan solution.

7. The preparation method according to claim 1, characterized in that, In step III, the static swelling time is 8-12 hours; The mixing and stirring speed of the dispersion, the glycerol, the xylitol, the bilayer sustained-release microspheres, the urea peroxide and the stabilizer is 300~500 rpm; The dispersion, glycerol, xylitol, bilayer sustained-release microspheres, urea peroxide, and stabilizer are mixed and stirred for 40-50 minutes.

8. The preparation method according to claim 1, characterized in that, In step III, triethanolamine is added to the obtained mixed solution to adjust its pH to 6.5-7; After adding triethanolamine, adjust the mixing speed to 30-50 rpm; After adding triethanolamine, continue mixing and stirring for 1-2 hours.

9. A urea peroxide teeth whitening gel prepared by the preparation method according to any one of claims 1 to 8, characterized in that, The urea peroxide teeth whitening gel comprises carbomer, triethanolamine, glycerin, xylitol, bilayer sustained-release microspheres, urea peroxide, stabilizer, and deionized water; The bilayer sustained-release microspheres comprise a sodium fluoride core and a gelatin-gum arabic composite coagulation layer and a sodium alginate-chitosan polyelectrolyte coating layer sequentially coated on the surface.

10. The urea peroxide teeth whitening gel according to claim 9, characterized in that, The stabilizer includes diethylenetriaminepentaacetic acid pentasodium.

Images