Gel with excellent ion resistance and preparation method thereof

Abstract

The invention relates to the technical field of oral care products, in particular to gel with excellent ion resistance and a preparation method thereof. The gel with excellent ion resistance is characterized by being prepared from the following raw materials in parts by weight: 1-10 parts of a biological gelling agent, 0.1-8 parts of an ion component, 0.01-5 parts of an auxiliary gelling agent, 1-30 parts of a humectant and 0.1-5 parts of a pH (Potential of Hydrogen) regulator, the biological gelling agent comprises at least one of carbomer and poloxamer; the Carbomer comprises at least one of a Carbomer 974 NF, a Carbomer 980 NF, a Carbomer ETD2020 NF, and a Carbomer Ultratrez10 NF, and the number of the Carbomer is at least one. According to the technical scheme, the technical problem that in the prior art, an oral desensitization gel which is ideal in biocompatibility, ion-resistant stability, rheological property, rapid desensitization and tooth demineralization inhibition effect and simple and feasible in preparation process is lacked is solved, and the oral desensitization gel has ideal popularization and application prospects.

Description

Technical Field

[0001] This invention relates to the field of oral care products technology, specifically to a gel with excellent ion resistance and its preparation method. Background Technology

[0002] Tooth sensitivity is a common symptom shared by various dental diseases such as tooth decay, wear, trauma, gingival recession, and exposed tooth necks, significantly disrupting patients' eating and daily lives. While existing solutions offer some relief, several shortcomings remain. In daily oral care, traditional desensitizing products like toothpaste and mouthwash require repeated daily use to alleviate tooth sensitivity. Their desensitizing ingredients are often potassium salts, strontium salts, and fluoride, typically requiring high concentrations to achieve optimal results. This not only increases the risk of cytotoxicity and mucosal irritation, leading to poor biocompatibility, but also results in insufficient product stability, causing quality issues such as significant viscosity reduction, layering, or crystal precipitation. In the medical field, while medical laser desensitization offers rapid results, high cure rates, and low recurrence rates, its high cost limits its widespread adoption in my country, failing to meet the needs of a large number of patients.

[0003] Against this backdrop, developing a novel oral desensitizing gel has become a promising solution. This gel should rapidly form a stable, dense, and highly adhesive protective film in sensitive areas of teeth, effectively sealing open dentinal tubules and blocking the transmission of external stimuli at the source. Simultaneously, it should provide a high concentration of active ingredients such as potassium and fluoride to sensitive areas for an extended period. However, most gel matrices (e.g., carbomer) are highly sensitive to their gel environment, especially in the presence of ions, which significantly reduces their thickening efficiency. This characteristic has become a major bottleneck in their application. The active ingredients required for oral desensitization are mostly ionic, severely limiting the development of oral care gels based on carbomer and similar matrices.

[0004] Chinese patent CN116492474A discloses a stable ion-resistant gel matrix composition, which combines carbomer with cationic Bletilla striata polysaccharide (CBSP) to prepare a gel matrix with good ion resistance and rheological properties. However, this technical solution has obvious shortcomings: Bletilla striata polysaccharide needs to be prepared through a multi-step cationic modification process including alkalization, etherification, dialysis, and freeze-drying, which is complex, time-consuming, and significantly increases the production cycle and cost.

[0005] Chinese patent CN117530956A discloses a desensitizing gel that can inhibit tooth demineralization. It utilizes a combination of carbomer 940 with potassium salts, fluoride, and glycyrrhizin, which forms a three-dimensional network structure through a cross-linking reaction. This, combined with thermal cross-linking technology, achieves both desensitization and anti-demineralization effects. However, this method still has drawbacks: the gel's adhesion depends on the network structure formed by cross-linking, and the cross-linking reaction is highly dependent on preparation conditions such as temperature and time, increasing the complexity of the production process and the risk of quality fluctuations.

[0006] In summary, existing technologies cannot simultaneously meet the comprehensive requirements of oral desensitizing gels for biocompatibility, rheological properties, ion stability, rapid desensitization effect, and production feasibility. Developing a well-balanced, safe, and efficient oral desensitizing gel has significant practical significance and application value. Summary of the Invention

[0007] The present invention aims to provide a gel with excellent ion resistance to solve the technical problems of existing technologies that lack oral desensitizing gels with ideal biocompatibility, ion resistance stability, rheological properties, rapid desensitization and inhibition of tooth demineralization effects, and simple and easy preparation process.

[0008] To achieve the above objectives, the present invention adopts the following technical solution: A gel with excellent ion resistance, comprising, by weight, 1-10 parts of biogelatinizing agent, 0.1-8 parts of ionic component, 0.01-5 parts of auxiliary gelatinizing agent, 1-30 parts of humectant, and 0.1-5 parts of pH adjuster; The biogelling agent includes at least one of carbomer and poloxamer; the carbomer includes at least one of carbomer 974NF, carbomer 980NF, carbomer ETD2020NF, and carbomer Ultrez10NF.

[0009] Furthermore, the carbomer includes at least a combination of carbomer 980NF and carbomer ETD2020NF.

[0010] Furthermore, the mass ratio of Carbomer 980NF to Carbomer ETD2020NF is (1-5):(0.5-3).

[0011] Furthermore, the auxiliary gelling agent includes at least one of disodium ethylenediaminetetraacetate, carboxymethyl chitosan, sodium hyaluronate, sodium phytate, sodium citrate, and tetrasodium diacetate of glutamate.

[0012] Furthermore, the moisturizer includes at least one of propylene glycol, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1500, glycerin, sorbitol, Tween 40, and Tween 60.

[0013] Furthermore, the ionic component includes at least one of sodium fluoride, sodium monofluorophosphate, stannous fluoride, oraflu, potassium nitrate, potassium citrate, potassium chloride, strontium chloride, and strontium carbonate.

[0014] Furthermore, the pH adjuster includes at least one of sodium hydroxide, triethanolamine, sodium bicarbonate, potassium hydroxide, and potassium carbonate.

[0015] Furthermore, its raw materials also include 0.01-3 parts sweetener and 0.01-1 part preservative.

[0016] This technical solution also provides a method for preparing a gel with excellent ion resistance, comprising the following steps performed sequentially: S1: Pre-disperse the bio-gelling agent and auxiliary gelling agent with a humectant to obtain liquid phase A; S2: Liquid phase A and water are mixed at a mass ratio of (2-30):(60-90), and dispersed under vacuum conditions by stirring at a speed of ≥4000 rpm for 10-15 min, and then allowed to stand for 1-3 h to obtain liquid phase B; S3: Add pH adjuster to liquid phase B, and stir at 2000-3000 rpm for 5-10 min under vacuum to obtain gel C; S4: Under vacuum and stirring at 2000-3000 rpm, add the ionic component to gel C in portions. The first addition is 0.01-2 parts, followed by 0.01-2 parts each time, with an interval of 3-5 minutes. Then, under vacuum, stir at 2000-3000 rpm for 10-15 minutes to obtain gel D. S5: Add other excipients to gel D, stir evenly, and stir at 1000-1500 rpm for 5-10 minutes under vacuum conditions to complete the preparation.

[0017] Furthermore, in step S2, the temperature is controlled at 30-35℃, and in steps S3-S5, the temperature is controlled at below 30℃.

[0018] The technical principle of this technical solution is as follows: In this technical solution, based on the compounding and multi-component synergistic mechanism of bio-gelling agents, a stable three-dimensional network structure is constructed to solve the technical bottleneck of poor ion resistance of traditional gel matrices, while achieving the efficient action of desensitizing active ingredients.

[0019] In terms of gelling system construction, this invention preferably uses carbomer 980NF and carbomer ETD2020NF to form a composite biogelling agent core. When these two are blended in a certain mass ratio, they provide good initial viscosity and structural stability for the gel. Simultaneously, auxiliary gelling agents such as carboxymethyl chitosan are introduced to construct a multi-layered ion buffer network, avoiding the decrease in gel stability caused by the addition of ionic components. Regarding the mechanism of action of the active ingredients, the ionic components in the formulation (such as potassium nitrate and sodium fluoride) continuously act on the sensitive areas of the teeth through the sustained-release effect of the gel network: potassium ions in potassium nitrate can quickly penetrate into the dentinal tubules, inhibiting nerve ending excitation and achieving rapid desensitization; fluoride ions can combine with hydroxyapatite on the tooth surface to form fluorapatite, enhancing the enamel's resistance to demineralization. The gel system can form a dense protective film on the tooth surface, sealing open dentinal tubules, blocking the transmission of external stimuli such as cold, heat, acid, and sweetness, while prolonging the action time of the active ingredients.

[0020] This invention ensures the uniformity and stability of the gel network structure through specific preparation process parameters, further enhancing the synergistic effect of the formulation. The core of process control is reflected in the following three aspects: The first is a swelling mechanism combining pre-dispersion and vacuum dispersion: the bio-gelling agent and auxiliary gelling agent are pre-dispersed with a humectant, and then dispersed under vacuum stirring conditions of 30-35℃ and ≥4000rpm. This not only breaks the initial aggregation between gelling agent molecules through high-speed shearing, but also uses the vacuum environment to remove air bubbles introduced during stirring. At the same time, the temperature is controlled to accelerate the expansion and swelling of the gelling agent molecular chains, laying the foundation for the formation of a uniform network.

[0021] Secondly, the ionic components are added in stages: the ionic components are added in small doses at multiple intervals, accompanied by vacuum stirring at 2000-3000 rpm. This design ensures that the ionic components are evenly distributed in the gel network, avoiding damage to the network structure caused by excessively high local ion concentrations, and gradually building a stable "gelling agent-ion" composite system, rather than a simple physical mixing.

[0022] Thirdly, precise control of temperature and pH: Step S2 controls the temperature to 30-35℃ to promote swelling, while steps S3-S5 control the temperature below 30℃ to avoid degradation of the gelling agent molecular chains due to high temperatures. The addition of a pH adjuster maintains the final pH of the gel within the physiological range of 6.5-7.5, ensuring that the carbomer carboxyl groups are fully dissociated to form a stable network, avoiding irritation to the oral mucosa from excessively acidic or alkaline environments, and simultaneously ensuring the chemical stability of the ionic components.

[0023] Compared with existing technologies, the gel and its preparation method of the present invention achieve breakthroughs in multiple dimensions such as performance, safety, and production feasibility. The specific beneficial effects are as follows: (1) Significantly improved ion resistance stability Through the synergistic complexation of composite gelling agents and auxiliary gelling agents, the multi-layered ion buffer network constructed by the gel effectively resists the erosion of ionic components. Verified by a 45℃ accelerated aging test, the gel showed no significant changes in properties or appearance during a 6-month storage period, maintaining stable consistency and viscosity, without exhibiting common problems in traditional gels such as layering, crystal precipitation, or significant viscosity decrease. This technical solution ensures the uniformity and stability of the gel, achieving improved ion resistance and rheological properties. This effect overcomes the bottleneck of reduced thickening efficiency of existing carbomer-based gels in ionic environments, solves the long-term storage quality risk of oral desensitizing gels due to the addition of ionic active ingredients, and extends the product's shelf life. Compared to the cationic modification system of Chinese patent CN116492474A, this invention eliminates the need for complex polysaccharide modification processes, significantly simplifying the production process while achieving equivalent ion resistance.

[0024] (2) Excellent biocompatibility The carbomer 980NF, carbomer ETD2020NF, and carboxymethyl chitosan selected in this invention are all biocompatible raw materials. Experiments have verified that the gel prepared by this method has no irritating reaction, and the pH value is maintained within the physiological range of 6.5-7.5, which is highly compatible with the oral cavity environment. Compared with the cytotoxic risks brought about by the high proportion of potassium salts and strontium salts in traditional desensitizing products, this invention, through the sustained-release effect of the gel network, ensures the effective concentration of active ingredients while reducing the irritation caused by excessively high local component concentrations. It can meet the needs of long-term daily use and solves the safety hazards of poor biocompatibility of existing desensitizing products.

[0025] (3) The desensitization and anti-demineralization effects are synergistic and highly efficient. The gel's composite network structure combines high adhesion with sustained-release properties: on one hand, the dense gel film adheres tightly to the tooth surface, sealing open dentinal tubules and blocking external stimuli at the source; on the other hand, the potassium ions (or other desensitizing ions) encapsulated in the network can quickly penetrate into the dentinal tubules, inhibiting nerve excitation and achieving immediate desensitization, while fluoride ions are slowly released and combine with tooth enamel to form an anti-demineralization protective layer, achieving long-lasting protection. This synergistic effect solves the problem of traditional toothpaste requiring long-term use to be effective, balancing the need for rapid onset of action and long-term protection, providing an efficient and convenient solution for patients with sensitive teeth.

[0026] (4) The preparation process is simple and controllable. The preparation process of this invention does not require complex modification reactions or high-temperature crosslinking treatments. The uniform and stable preparation of gels can be achieved through conventional operations such as pre-dispersion, vacuum stirring, and fractional sample addition. The process parameters are well-defined (such as stirring speed, temperature range, and time interval), and the requirements for production equipment are low. This effectively avoids the risk of quality fluctuations caused by the strong dependence of the crosslinking reaction on temperature and time in existing technologies (such as CN117530956A).

[0027] (5) Excellent overall performance This invention is the first to achieve simultaneous optimization of "ion resistance stability, biocompatibility, rapid desensitization effect, and production feasibility" in oral desensitizing gels. Compared to existing technologies that often focus on improving a single performance aspect, this invention, through the synergistic design of formulation and process, enables the product to achieve a balanced advantage in storage stability, safety of use, therapeutic effectiveness, and production economy. It fills the gap in existing technologies for well-balanced oral desensitizing gels and has significant practical significance and market application value. Attached Figure Description

[0028] Figure 1 Typical photographs of gel transparency of some samples in Experiment Example 1 (A: Test 6; B: Test 7; C: Test 16; D: Test 19; E: Test 23). Detailed Implementation

[0029] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto. Unless otherwise specified, the technical means used in the following embodiments and experimental examples are conventional means well known to those skilled in the art, and the materials and reagents used can all be obtained commercially.

[0030] Example 1: Formulation and preparation method of a gel with excellent ion resistance (1) Formula composition The gel with excellent ion resistance comprises, by weight, the following raw materials: 1-10 parts of biogelatinizer (preferably 3-7 parts, more preferably 3-4 parts), 0.1-8 parts of ionic component (preferably 1.25-5.25 parts, more preferably 3.25 parts), 0.01-5 parts of auxiliary gelatinizer, 1-30 parts of humectant, 0.1-5 parts of pH adjuster, and the balance being water.

[0031] Preferably, based on the above, 0.01-3 parts of sweetener and 0.01-1 part of preservative are added, with the remainder being water.

[0032] The biogelling agent includes at least one of carbomer and poloxamer. Poloxamer 407 is preferred. The carbomer includes at least one of carbomer 974NF, carbomer 980NF, carbomer ETD2020NF, and carbomer Ultraz10NF. Preferably, the carbomer includes at least a combination of carbomer 980NF and carbomer ETD2020NF, and the remaining biogelling agent may be added to poloxamer or other types of carbomer to fill the total mass fraction of the biogelling agent. Preferably, carbomer Ultraz10NF is not used. The mass ratio of carbomer 980NF to carbomer ETD2020NF is (1-5):(0.5-3) (i.e., a mass ratio of 0.33-10), a more preferred mass ratio is 1-5, and even more preferably a mass ratio of 2.

[0033] The specific descriptions of each carbomer are as follows: Carbomer 974NF (supplier: Lubrizol) is a pharmaceutical-grade type B acrylic homopolymer, produced by crosslinking acrylic acid and allyl sucrose ether using a non-benzene solvent process. Carbomer 980NF (supplier: Lubrizol) is a polymeric excipient, a crosslinked copolymer of acrylic acid and allyl sucrose or pentaerythritol allyl ether produced by non-benzene solvent polymerization, belonging to type C carbomer homopolymers. Carbomer ETD2020NF (supplier: Lubrizol) is an acrylate / C10-30 alkyl acrylate crosslinked copolymer. Carbomer Ultraz 10NF (supplier: Lubrizol) is a type A carbomer copolymer, polymerized using a co-solvent mixture of ethyl acetate and cyclohexane.

[0034] The auxiliary gelling agent includes at least one of disodium ethylenediaminetetraacetate, carboxymethyl chitosan, sodium hyaluronate, sodium phytate, sodium citrate, and tetrasodium diacetate of glutamate.

[0035] The moisturizers include at least one of propylene glycol, PEG300, PEG400, PEG1500, glycerin, sorbitol, Tween 40, and Tween 60.

[0036] pH adjusters include at least one of sodium hydroxide, triethanolamine, sodium bicarbonate, potassium hydroxide, and potassium carbonate.

[0037] The ionic components include at least one of sodium fluoride, sodium monofluorophosphate, stannous fluoride, olafonium, potassium nitrate, potassium citrate, potassium chloride, strontium chloride, and strontium carbonate. These ionic components are the active ingredients in the gel of this formulation and are the desensitizing agents for teeth.

[0038] The sweeteners and preservatives may be any sweeteners and preservatives available in the prior art that can be used in oral care products.

[0039] (2) Preparation method The preparation process includes the following steps: S1: Pre-disperse the bio-gelling agent and auxiliary gelling agent with a humectant to obtain liquid phase A.

[0040] S2: Liquid phase A and water are mixed at a mass ratio of (2-30):(60-90), and stirred and dispersed at high speed (4000-5000 rpm) for 10-15 minutes under vacuum (not lower than -680 mmHg; the upper limit of vacuum is absolute vacuum, that is, -760 mmHg gauge pressure is the theoretical limit; it is difficult to achieve with general equipment, so the vacuum is maintained at a level not lower than -680 mmHg, that is, within the range of -760 mmHg to -680 mmHg). After standing for 1-3 hours, the bio-gelling agent is fully swollen and dissolved to obtain liquid phase B.

[0041] S3: Add pH adjuster to liquid phase B, and stir at medium speed (2000-3000 rpm) for 5-10 minutes under vacuum (not lower than -680 mmHg) to obtain gel C.

[0042] S4: Add the ionic component to gel C in portions, stirring at medium speed (2000-3000 rpm) during the addition process. The initial addition is 0.01-2 parts, followed by an additional 0.01-2 parts each time, with intervals of 3-5 minutes, for a total addition of 0.1-8 parts. After the addition is complete, continue stirring at medium speed (2000-3000 rpm) under vacuum (not lower than -680 mmHg) for 10-15 minutes to obtain gel D.

[0043] S5: Add other excipients (e.g., sweeteners, preservatives, etc.) to gel D, stir evenly, and stir at low speed (1000-1500 rpm) for 5-10 minutes under vacuum (not lower than -680 mmHg) to complete the preparation.

[0044] Step S1 is performed at room temperature, step S2 controls the temperature at 30-35℃, and steps S3-5 control the temperature below 30℃ (preferably 20-30℃, excluding the 30℃ endpoint).

[0045] (3) Product characteristics The gel with excellent ion resistance obtained by the above method has the following characteristics: Storage stability of the gel: After storage at 45°C for 6 months, there were no significant changes in its properties, appearance, and performance.

[0046] Gel consistency: It can maintain a certain consistency without significant changes when stored at 45°C for 6 months.

[0047] Gel viscosity: It can maintain a certain viscosity without significant changes when stored at 45℃ for 6 months.

[0048] The pH value of the gel is 6.5-7.5.

[0049] Biocompatibility of the gel: No oral mucosal irritation, no skin sensitization, and no thermal reaction.

[0050] The ion-resistant gel in this formulation has the following uses: it can quickly relieve tooth sensitivity symptoms, forming a stable network structure that effectively adheres to the tooth surface; it has excellent ion resistance stability, and its gel performance remains stable after passing high-temperature accelerated aging tests; it has good biocompatibility, with no oral mucosal irritation, no skin sensitization, and no thermal reaction, making it mild and safe to use; and it has a synergistic effect, effectively and quickly relieving tooth sensitivity symptoms and inhibiting tooth demineralization.

[0051] (4) Specific formula and preparation process (Test 1-27) Test 1 was prepared using the following formula: The gel, exhibiting excellent ion resistance, comprises, by weight, the following raw materials: 3 parts bio-gelling agent, 1.25 parts ionic component, 1 part auxiliary gelling agent, 5 parts humectant (polyethylene glycol 400), 1.5 parts pH adjuster (sodium hydroxide), 0.3 parts sweetener (sucralose), 0.5 parts preservative (phenoxyethanol), with the remainder being water to bring the total to 100 parts. The auxiliary gelling agent is carboxymethyl chitosan, supplied by Shaanxi Langde Biotechnology Co., Ltd. The ionic component is potassium nitrate and sodium fluoride in a mass ratio of 1:0.25. The bio-gelling agent is carbomer 980NF. Detailed formulation composition is shown in Table 1.

[0052] The gel for this test 1 was prepared using the following method: S1: Under normal temperature conditions (around 25℃), the bio-gelling agent and auxiliary gelling agent are pre-dispersed with a humectant to obtain liquid phase A.

[0053] S2: Liquid phase A and water are mixed at a mass ratio of 20:70 and stirred and dispersed at high speed (approximately 4000 rpm) under vacuum (not lower than -680 mmHg) for 12 minutes. After standing for 2 hours, the bio-gelling agent is fully swollen and dissolved to obtain liquid phase B.

[0054] S3: Add pH adjuster and the remaining water (the water left over after step S2 in the formula) to liquid phase B, and stir at medium speed (about 3000 rpm) for 8 minutes under vacuum (not lower than -680 mmHg) to obtain gel C.

[0055] S4: Add the ionic components to gel C in portions. The first addition is one-quarter of the total mass of the ionic components. Then, add one-quarter of the total mass of the ionic components each time, with an interval of 5 minutes between each addition, until all the ionic components have been added. Stir at a medium speed (about 3000 rpm) for 15 minutes under vacuum (not lower than -680 mmHg) to obtain gel D.

[0056] S5: Add sweetener and preservative to gel D, stir evenly, and stir at low speed (about 2000 rpm) for 10 minutes under vacuum (not lower than -680 mmHg) to complete the preparation.

[0057] Step S2 controls the temperature at 30℃, and steps S3-5 control the temperature at 25℃.

[0058] For the formulations of the experimental groups for other tests, please refer to Tables 1, 2 and 3. Unless otherwise specified, the preparation method shall be the same as that for Test 1 (including Test 1-18, Test 26 and Test 27).

[0059] Table 1: Formulation composition of tests 1-10 (parts, total 100 parts)

[0060] Table 2: Formulation composition of tests 11-18 (parts, total 100 parts)

[0061] Table 3: Formulation composition of test 19-27 (parts, total 100 parts)

[0062] The preparation methods for Tests 19-25 are as follows: Test 19 The formulation for this comparative example is the same as that for Test 6, except for the preparation process. The preparation process for Test 1 and the formulation for Test 6 are followed, except that steps S1 and S2 are combined. The specific operation is as follows: At a temperature of 30°C, the bio-gelling agent, auxiliary gelling agent, humectant and water (in the same proportion as in Test 1) were mixed and dispersed by high-speed stirring in the manner of Test 1. After standing, the bio-gelling agent was allowed to fully swell and dissolve to obtain liquid phase B.

[0063] Subsequent steps were performed exactly as in Test 1 to obtain the oral gel of this comparative example.

[0064] Test 20 The formulation for this comparative example is the same as that for Test 6, except for the preparation process. The preparation process for Test 1 and the formulation for Test 6 are followed, except that step S3 is adjusted by changing the stirring speed from medium speed (approximately 3000 rpm) to high speed (approximately 4000 rpm).

[0065] Test 21 The formulation for this comparative example is the same as that for Test 6, except for the preparation process. The preparation process for Test 1 and the formulation for Test 6 are followed, except that step S2 is adjusted by changing the stirring speed from high speed (approximately 4000 rpm) to medium speed (approximately 3000 rpm).

[0066] Test 22 The formulation for this comparative example is the same as that for Test 6, except for the preparation process. The preparation process was carried out according to the method used in Test 1 and the formulation used in Test 6, with the entire process conducted at 30°C.

[0067] Test 23 The formulation for this comparative example is the same as that for Test 6, except for the preparation process. The preparation process was carried out according to the method used in Test 1 and the formulation used in Test 6, with the entire process conducted at 25°C.

[0068] Test 24 The formulation for this comparative example is the same as that for Test 6, except for the preparation process. The preparation process was carried out according to the method used in Test 1 and the formulation used in Test 6, with the entire process conducted at 40°C.

[0069] Test 25 The formulation of this comparative example is the same as that of test 6, except for the preparation process: The bio-gelling agent and auxiliary gelling agent were pre-dispersed with a humectant to obtain liquid phase A. The ionic components, sweetener, preservatives, and other excipients were pre-dissolved in water to obtain liquid phase B. Liquid phase A was mixed with water and dispersed under vacuum at high speed (≥4000 rpm) for 15 min, then allowed to stand for 2 h to allow the bio-gelling agent to fully swell and dissolve, resulting in liquid phase C (temperature controlled at 35℃). A pH adjuster was added to liquid phase C, and the mixture was stirred under vacuum at medium speed (3000 rpm) for 10 min to obtain gel D (temperature controlled at 25℃). Liquid phase B was added to gel D, and the mixture was stirred under vacuum at medium speed for a total time of 30 min to complete the preparation (temperature controlled at 25℃).

[0070] Experimental Example 1: Gel Formation State and Stability Viscosity test method: The gel viscosity was determined using a Borelfeld rotational viscometer at room temperature of 25°C, with a TE (95) rotor, a rotation speed of 10 rpm, and a test time of 1 min.

[0071] Consistency test method: A toothpaste consistency frame is used, with the distance between the two steel wires being 3mm, 6mm, 9mm, 12mm, and so on. A standard cap with a central hole diameter of 3mm is screwed onto the sample to be tested, and the gel is squeezed out. Starting from the first steel wire on the consistency frame, the gel strip is squeezed across the remaining steel wires in sequence, so that the gel is laid horizontally across the steel wires. Three strips are squeezed out for each sample. After squeezing, the sample is allowed to stand for 1 minute. The maximum distance of the gel strip that spans the steel wires without breaking is taken as the measurement result.

[0072] The experimental results are detailed in Table 4. Typical photographs of the gel transparency of some samples are also available. Figure 1 .

[0073] Table 4: Formation state and stability of gels after preparation in tests 1-27

[0074] The experimental results are analyzed as follows: (1) Implementation of this solution The gels obtained from tests 3, 4, 6, 7, 15, and 18 all exhibited suitable immediate colloidal viscosity and consistency (tested immediately after preparation). The immediate colloidal viscosity ranged from 70 to 115 mPa·s, and the immediate colloidal consistency ranged from 12 to 24. Furthermore, in the accelerated aging experiment, the colloidal viscosity and consistency did not change significantly, indicating good stability. Therefore, a biogelatinizer of 3-7 parts is preferred, and the active ingredient for tooth desensitization is preferred at 1.25-5.25 parts. The biogelatinizer should contain at least a combination of Carbomer 980NF and Carbomer ETD2020NF. Adding Poloxamer 407 and Carbomer 974NF to this combination will not affect the immediate colloidal viscosity, consistency, or the stability of these two parameters. A combination of Carbomer 980NF and Carbomer ETD2020NF of 3-6 parts is preferred. The optimal mass ratio of carbomer 980NF to carbomer ETD2020NF is 1-5. It should be further noted that no fluoride ions were added in test 18, resulting in the disappearance of the corresponding therapeutic effect.

[0075] Tests 6, 7, and 15 represent the optimal methods, showing the following gel characteristics: suitable immediate colloidal viscosity and consistency, transparency, and no significant changes after accelerated aging. Therefore, as a further preferred method, 3-5 parts of the bio-gelling agent and 3.5 parts of the tooth desensitizing active ingredient are used. Furthermore, the bio-gelling agent must contain at least a combination of Carbomer 980NF and Carbomer ETD2020NF. Adding 1 part of Poloxamer 407 or 2 parts of Carbomer 974NF to this combination will not affect the immediate colloidal viscosity, consistency, or the stability of these two parameters. The combination of Carbomer 980NF and Carbomer ETD2020NF is used in a ratio of 3 parts, with a mass ratio of 2:1.

[0076] (2) Effect of carbomer type on gel properties Tests 1 and 2 only added either Carbomer 980NF or Carbomer ETD2020NF, and the results showed that the gel had low immediate viscosity and was thin. Comparing Tests 1, 2, and 6, the total amount of bio-gelling agent in the three experimental groups was the same (3 parts each), and all other components except the bio-gelling agent were identical in the three experimental groups. The only difference was the composition of the bio-gelling agent in the three experimental groups: Test 6 contained 2 parts Carbomer 980NF and 1 part Carbomer ETD2020NF; Test 1 contained 3 parts Carbomer 980NF; and Test 2 contained 3 parts Carbomer ETD2020NF. Theoretically, the immediate viscosity and consistency of the gel in Test 6 should be between those of the gels in Tests 1 and 2. However, the experimental results showed that the immediate viscosity and consistency of the gel in Test 6 were significantly improved compared to Tests 1 and 2, achieving an unexpected technical effect. This demonstrates that there is a synergistic effect between the Carbomer 980NF and the Carbomer ETD2020NF, and their combination is indispensable in this solution.

[0077] In addition, the inventors also experimented with other types of carbomer. Test 5 used a combination of carbomer ETD2020NF and poloxamer 407; Test 11 used a combination of carbomer 980NF and carbomer Ultraz 10NF; Test 12 used a combination of carbomer 980NF and carbomer 974NF; Test 13 used a combination of carbomer Ultraz 10NF and carbomer ETD2020NF; and Test 14 used a combination of carbomer 974NF and carbomer ETD2020NF. All of these results showed excessively low instantaneous viscosity and consistency, and severe aging. Particularly in the experimental group with added carbomer Ultraz 10NF, a significant decrease in gel transparency was observed. Therefore, the combination of carbomer 980NF and carbomer ETD2020NF plays a crucial role in maintaining the performance of the gel in this formulation. Although tests 16 and 17 used the combination of Carbomer 980NF and Carbomer ETD2020NF from this scheme, the addition of Carbomer Ultraz 10NF to this combination resulted in unsatisfactory gel transparency. While adding a certain amount of Carbomer Ultraz 10NF to the combination of Carbomer 980NF and Carbomer ETD2020NF does not affect gel properties (viscosity, consistency, and anti-aging properties), to ensure a good appearance, it is preferable not to add Carbomer Ultraz 10NF to the gel in this scheme.

[0078] (3) Effect of the ratio of Carbomer 980NF to Carbomer ETD2020NF on gel properties In Test 26, the ratio of Carbomer 980NF to Carbomer ETD2020NF was too low, resulting in unsatisfactory anti-aging performance of the gel. In Test 27, the ratio of Carbomer 980NF to Carbomer ETD2020NF was too high, also resulting in unsatisfactory anti-aging performance of the gel.

[0079] Based on the preferred implementation of this scheme, the ratio of Carbomer 980NF to Carbomer ETD2020NF is preferably maintained between 1 and 5.

[0080] (4) Effect of the amount of biogelling agent on gel properties The total amount of biogelant used in Test 8 was as high as 10 parts, resulting in high immediate colloid viscosity and consistency, and a significant decrease in viscosity after accelerated aging. Therefore, excessively high biogelant content is not conducive to maintaining product performance.

[0081] (5) Effect of ion concentration (active ingredient for tooth desensitization) on gel properties In Test 10, the amount of tooth-desensitizing active ingredient added was too high, resulting in a low immediate gel viscosity. Based on the preferred implementation method of this solution, the amount of tooth-desensitizing active ingredient added should be between 1.25 and 5.25 parts.

[0082] In addition, the ion concentration of test 9 was very low, which had little impact on the gel performance, but the product also lost its corresponding functions of relieving tooth sensitivity and promoting mineralization.

[0083] (6) Effect of preparation process on gel properties Tests 19-25 explored different preparation processes and revealed that the process significantly impacted gel performance: parameters such as the order and method of adding materials, stirring speed, and temperature greatly affected the gel's formation and stability. The optimal process was as follows: pre-dispersion of the bio-gelling agent and auxiliary gelling agent with a humectant; phased addition of ionic components; high stirring speed during bio-gelling agent dispersion and swelling (step S2); medium stirring speed during gel formation and ionic component addition (steps S3 and S4); and low stirring speed during auxiliary material addition (step S5); temperature controlled at 30-35℃ during bio-gelling agent dispersion and swelling (step S2); and temperature controlled below 30℃ during gel formation and ionic component / auxiliary material addition (steps S3, S4, and S5).

[0084] Test 19 combined steps S1 and S2, directly mixing the biogelatinizer, auxiliary gelatinizer, and total water. The results showed that the instant gel had problems with clumping, small particles, low viscosity, and consistency.

[0085] Test 25 did not employ a strategy of gradually adding ionic components, resulting in an excessively low immediate viscosity of the gel, causing it to thin out, which was inconsistent with expectations.

[0086] The performance difference between Test 20 (stirring speed increased from medium speed 3000 rpm to high speed 4000 rpm in step S3) and Test 21 (stirring speed decreased from high speed 4000 rpm to medium speed 3000 rpm in step S2) directly reflects the impact of stirring speed on different stages of the process. In Test 20, step S3 is the mixing stage of liquid phase B and pH adjuster. Although high-speed stirring (4000 rpm) can improve dispersion efficiency, excessive shear force causes local damage to the gelling agent network structure, resulting in a lower immediate colloidal viscosity. After accelerated aging, the viscosity decreases significantly, and the colloidal substance becomes thinner. In Test 21, step S2 is the swelling stage after pre-dispersion of the gelling agent. Medium-speed stirring (3000 rpm) is insufficient to break up the gelling agent agglomerates. There are clumps and particles in the immediate gel, and there is no significant change in clumps and particles after accelerated aging. Based on the baseline process of Test 6 (S2 high-speed 4000rpm pre-dispersion, S3 medium-speed 3000rpm mixing), it can be seen that the pre-dispersion stage of the gelling agent requires high-speed stirring to ensure uniform dispersion, while the subsequent mixing stage requires medium-speed stirring to protect the formed network structure and avoid excessive shearing that leads to performance degradation.

[0087] Temperature variable experiments in Test 22 (30℃ throughout), Test 23 (25℃ throughout), and Test 24 (40℃ throughout) revealed the regulatory effect of temperature on the swelling, cross-linking, and system stability of the gelling agent. The immediate gel in Test 22 (30℃) contained a few agglomerates and small particles. The immediate gel in Test 23 (25℃) had low viscosity and poor transparency; the immediate gel in Test 24 (40℃) also contained agglomerates and small particles. Therefore, the temperature control method used in this scheme is essential for maintaining gel performance.

[0088] Experimental Example 2: Biocompatibility (Cytotoxicity) Experimental methods: The cytotoxicity of each test group was studied using the membrane diffusion method according to GB / T 16886.5.

[0089] Negative control group: φ5mm filter paper soaked in PBS (1×) solution.

[0090] Positive control group: φ5mm filter paper soaked in 6.3% phenol solution.

[0091] Sample preparation: After the prepared gel sample is saturated with φ5mm filter paper, it is placed directly for testing.

[0092] The grading criteria are detailed in Table 5, and the experimental results are detailed in Table 6.

[0093] Table 5: Reaction gradation of agar diffusion test

[0094] Table 6: Cytotoxicity test results of different gel samples

[0095] In tests 3, 6, 8, and 17, the use of a combination of carbomer 980NF and carbomer ETD2020NF as biogelling agents significantly reduced the in vitro cytotoxicity of oral care gels. Tests 19 and 25 showed cytotoxicity levels of 3 and 4, respectively, indicating that the preparation process also has a significant impact on the in vitro cytotoxicity of oral care gels. Tests 1, 2, 5, and 11-14, which did not use the combination of carbomer 980NF and carbomer ETD2020NF, exhibited a certain degree of cytotoxicity.

[0096] Experiment Example 3: Relieving Tooth Sensitivity and Inhibiting Tooth Demineralization Clinical trials were conducted using samples from tests 1, 5, 6, and 18 of this invention.

[0097] Number of participants: 120 in total (divided into 4 groups of 30 each).

[0098] Subject selection criteria: middle-aged (age: 30-50), with no fewer than 20 remaining teeth in the mouth, no dental caries, no history of dental treatment, and subjects experiencing significant pain from temperature and sweet / sour stimuli, as well as significant pain from probe stimulation.

[0099] Instructions for use: Apply 2g of the test gel to the dental tray. Each group of subjects should wear the dental tray for 30 minutes and then rinse their mouths with water. Use once a day for 7 consecutive days.

[0100] Follow-up appointment times: 1 day, 3 days, 7 days, 14 days.

[0101] Tooth sensitivity rating scale: 0 (no pain), 1-3 (mild pain), 4-6 (moderate pain), 7-10 (severe pain).

[0102] Demineralization inhibition effect score: The Vickers value of the tooth surface microhardness at which the subject’s sensitivity and pain are most obvious is measured, and the average value is taken as the score. The effect is reflected by the tooth surface microhardness.

[0103] The experimental results are detailed in Table 6.

[0104] Table 6: Results of Clinical Trials on Relieving Tooth Sensitivity and Inhibiting Tooth Demineralization

[0105] The experiments showed that the gel in Test 6 had the most significant therapeutic effect, reducing tooth sensitivity and pain in the subjects to mild pain, with no significant recurrence observed in subsequent observations. The improvement in tooth surface microhardness was also significant, and no adverse events occurred. Test 18, lacking the active ingredient sodium fluoride, achieved a significantly less effective therapeutic effect than Test 6. Tests 1 and 5 did not use Carbomer 980NF and Carbomer ETD2020NF in combination, resulting in poor therapeutic effects.

[0106] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A gel with excellent ion resistance, characterized in that: By weight, its raw materials include 1-10 parts of bio-gelling agent, 0.1-8 parts of ionic component, 0.01-5 parts of auxiliary gelling agent, 1-30 parts of humectant, and 0.1-5 parts of pH adjuster; The biogelling agent includes at least one of carbomer and poloxamer; the carbomer includes at least one of carbomer 974NF, carbomer 980NF, carbomer ETD2020NF, and carbomer Ultrez10NF.

2. The gel with excellent ion resistance according to claim 1, characterized in that: The carbomer includes at least a combination of carbomer 980NF and carbomer ETD2020NF.

3. The gel with excellent ion resistance according to claim 2, characterized in that: The mass ratio of Carbomer 980NF to Carbomer ETD2020NF is (1-5):(0.5-3).

4. The gel with excellent ion resistance according to claim 1, characterized in that: The auxiliary gelling agent includes at least one of disodium ethylenediaminetetraacetate, carboxymethyl chitosan, sodium hyaluronate, sodium phytate, sodium citrate, and tetrasodium diacetate of glutamate.

5. A gel with excellent ion resistance according to claim 1, characterized in that: The humectant includes at least one of propylene glycol, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1500, glycerin, sorbitol, Tween 40, and Tween 60.

6. The gel with excellent ion resistance according to claim 1, characterized in that: The ionic components include at least one of sodium fluoride, sodium monofluorophosphate, stannous fluoride, oraflu, potassium nitrate, potassium citrate, potassium chloride, strontium chloride, and strontium carbonate.

7. The gel with excellent ion resistance according to claim 1, characterized in that: The pH adjuster includes at least one of sodium hydroxide, triethanolamine, sodium bicarbonate, potassium hydroxide, and potassium carbonate.

8. A gel with excellent ion resistance according to any one of claims 1-7, characterized in that: Its ingredients also include 0.01-3 parts sweetener and 0.01-1 part preservative.

9. The method for preparing a gel with excellent ion resistance according to claim 7, characterized in that: The following steps are performed sequentially: S1: Pre-disperse the bio-gelling agent and auxiliary gelling agent with a humectant to obtain liquid phase A; S2: Liquid phase A and water are mixed at a mass ratio of (2-30):(60-90), and dispersed under vacuum conditions by stirring at a speed of ≥4000 rpm for 10-15 min, and then allowed to stand for 1-3 h to obtain liquid phase B; S3: Add pH adjuster to liquid phase B, and stir at 2000-3000 rpm for 5-10 min under vacuum to obtain gel C; S4: Under vacuum and stirring at 2000-3000 rpm, add the ionic component to gel C in portions. The first addition is 0.01-2 parts, followed by 0.01-2 parts each time, with an interval of 3-5 minutes. Then, under vacuum, stir at 2000-3000 rpm for 10-15 minutes to obtain gel D. S5: Add other excipients to gel D, stir evenly, and stir at 1000-1500 rpm for 5-10 minutes under vacuum conditions to complete the preparation.

10. The method for preparing a gel with excellent ion resistance according to claim 1, characterized in that: Step S2 controls the temperature to 30-35℃, and steps S3-S5 control the temperature to be below 30℃.

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