A sustained release system for oral care products and methods of making and using the same

Abstract

This invention belongs to the field of compositions of polymeric compounds for oral care products, specifically relating to a sustained-release system for oral care products, its preparation method, and its application. This invention discloses that when a cationic polymeric compound, sodium alginate, and ectoine are used in combination, a unique OraReliX™ sustained-release system can be formed on the tooth surface. The core working principle of this system is as follows: the cationic substance adheres to the negatively charged tooth surface through electrostatic adsorption, forming a cationic network; sodium alginate regulates the network density through polyelectrolyte complexation with this cationic network, while reversibly binding calcium ions; ectoine stabilizes the oral microenvironment and protects the sustained-release network structure. The synergistic effect of these three components significantly slows down the release rate of calcium ions, prolonging their effective retention time in the oral cavity.

Description

Technical Field

[0001] This invention belongs to the field of compositions of polymeric compounds for oral care products, and specifically relates to a sustained-release system for oral care products, its preparation method and application. Background Technology

[0002] Tooth decay and dentin hypersensitivity are common oral health problems. Enamel demineralization is an early stage of tooth decay formation, while exposure of dentinal tubules is the main cause of dentin hypersensitivity. Sodium calcium phosphosilicate (also known as NovaMin or bioactive glass) is a bioactive material composed of elements such as calcium, phosphorus, silicon, and sodium, with a structure consistent with the mineral composition of healthy teeth and bones. When sodium calcium phosphosilicate comes into contact with saliva, it releases calcium and phosphate ions, forming a hydroxyapatite layer that covers the dentin surface, sealing the dentinal tubules to relieve sensitivity and promote remineralization. However, existing sodium calcium phosphosilicate toothpastes have the following shortcomings: First, there is the problem of uncontrolled ion release rate. Sodium calcium phosphosilicate rapidly releases calcium and phosphate ions upon contact with water or saliva. The release process lacks a regulatory mechanism, resulting in a large release of active ingredients at the beginning of brushing. This not only wastes the active ingredients but also, the high concentration of calcium ions may combine with non-target ions to form precipitates, reducing remineralization efficiency. Studies have shown that the rapid formation of calcium fluoride reduces the concentration of calcium ions in the oral cavity. Therefore, a slow-release strategy is best for active ions. Second, there is the problem of insufficient targeting. The release of calcium ions in existing sodium calcium phosphosilicate toothpastes lacks selectivity and cannot achieve precise delivery to target tooth surfaces (such as sensitive areas). A large number of calcium ions are expelled with rinsing, affecting the utilization efficiency of active ingredients. Third, existing slow-release technologies are complex and costly. Some studies have attempted to encapsulate sodium calcium phosphosilicate using microencapsulation technology to achieve slow release, such as using monoglycerides as wall materials to prepare sodium calcium phosphosilicate microcapsules. However, the microcapsule preparation process is complex and costly, and the wall material rupture conditions are difficult to control precisely. Currently, there is no known technical solution that utilizes the electrostatic adsorption between cationic substances and the negative charge on the tooth surface (especially enamel) to construct a sustained-release system, thereby achieving targeted sustained release of effective ingredients such as calcium ions in anhydrous toothpaste. Therefore, developing a simple, efficient, and compatible sustained-release technology with existing anhydrous toothpaste systems has significant practical value.

[0003] The inventors of this invention unexpectedly discovered that combining a cationic polymer, sodium alginate, and ectoine creates a unique "slow-release system" (OraReliX™) on the tooth surface. The core principle of this system is as follows: the cationic polymer adheres to the negatively charged tooth surface via electrostatic adsorption, forming a cationic network; sodium alginate interacts with this cationic network through polyelectrolyte complexation to regulate network density and reversibly bind calcium ions; ectoine stabilizes the oral microenvironment and protects the slow-release network structure. The synergistic effect of these three components significantly slows the release rate of calcium ions, extending their effective retention time in the oral cavity. Summary of the Invention

[0004] This invention provides an oral care composition containing a polymeric compound (hereinafter referred to as a sustained-release system), characterized in that the sustained-release system comprises a cationic polymeric compound, sodium alginate, and ectoine; the cationic polymeric compound is selected from one or more of cationic hyaluronic acid, chitosan and its derivatives, cationic cellulose, cationic guar gum, and polyquaternary ammonium salts; the mass ratio of the cationic polymeric compound, sodium alginate, and ectoine is 1-10:1-10:1-5, preferably 5:3:2, 10:1:5, 1:1:1, or 1:10:1.

[0005] Another embodiment of the present invention provides the application of the above-described sustained-release system in the preparation of oral care products. These oral care products are used to prevent and treat tooth decay, dentin hypersensitivity, repair tooth enamel, remineralize tooth surfaces, or alleviate gum problems.

[0006] Another embodiment of the present invention provides an oral care composition, characterized in that the composition contains the above-mentioned sustained-release system and sodium calcium phosphosilicate, wherein the mass ratio of the sustained-release system to sodium calcium phosphosilicate is 1:5-10. This composition enables the effective concentration of calcium ions in saliva to be maintained for at least 30 minutes, preferably 60 minutes, after brushing.

[0007] Another embodiment of the present invention provides the above-described oral care composition, characterized in that the composition further comprises excipients acceptable for oral care.

[0008] Another embodiment of the present invention provides an oral care composition comprising the above-described sustained-release system, characterized in that, by weight percentage, it comprises: the above-described sustained-release system, sodium calcium phosphosilicate 5%-18%, humectant 52.74%-75.2%, abrasive 12%-35%, thickener 0.1%-2%, surfactant 0.3%-1%, sweetener 0.1%-1%, flavoring 0.5%-2%, with the remainder optionally being other excipients acceptable in oral care, wherein the weight of the sustained-release system is 10%-20% of the sodium calcium phosphosilicate, and the mass ratio of the cationic polymer, sodium alginate, and ectoine in the sustained-release system is 1-10:1-10:1-5, preferably 5:3:2, 10:1:5, 1:1:1, or 1:10:1. Other acceptable excipients in oral care are ingredients not included in the formulation, including one or more of the following: whitening agents (preferably titanium dioxide), stabilizers (preferably lithium magnesium silicate), pigments (natural or artificial pigments), antioxidants, pH adjusters, and water.

[0009] Another embodiment of the present invention provides a method for preparing the above-described oral care composition, characterized by comprising the following steps:

[0010] (1) Mix an appropriate amount of moisturizer, cationic polymer, sodium alginate and ectoine, and stir evenly at room temperature to 50°C to form the first mixture;

[0011] (2) Mix and disperse sodium calcium phosphosilicate, abrasive, and thickener evenly to form a second mixture;

[0012] (3) Dissolve surfactants, sweeteners, flavorings, and other oral care excipients (if any) in the remaining humectant to form a third mixture;

[0013] (4) The second mixture and the third mixture are added to the first mixture under stirring conditions, vacuum degassing and homogenization treatment are performed to obtain the oral care composition.

[0014] In step (1), the amount of moisturizer used is selected from 70%-90% (preferably 80%) of the total mass of the moisturizer, and the mixing temperature is preferably 30-45℃. Note: If there are two or more types of moisturizers, the corresponding mass percentage of each moisturizer should be mixed separately.

[0015] Another embodiment of the present invention provides the use of the above-described oral care composition in the preparation of oral care products for the prevention and / or treatment of dental caries, dentin hypersensitivity, enamel repair, remineralization of tooth surfaces, or relief of gingival problems.

[0016] The oral care products described in this invention are selected from toothpaste, tooth powder, oral gel, mouthwash, chewing gum, oral spray, teeth whitening strips, denture care products, or anti-caries medical devices, and can be anhydrous or aqueous.

[0017] The oral care excipients described in this invention are selected from one or more commonly used humectants, abrasives, thickeners, surfactants, sweeteners, flavorings, whitening agents (such as titanium dioxide), stabilizers, pigments (natural or artificial), antioxidants, pH adjusters, and water. The preferred humectants are glycerin, sorbitol, polyethylene glycol, and propylene glycol; the preferred abrasives are silica, hydrated silica, calcium carbonate, dicalcium phosphate, aluminum hydroxide, calcium pyrophosphate, and hydroxyapatite; the preferred thickeners are carbomer, xanthan gum, hydroxyethyl cellulose, hydroxypropyl methylcellulose, guar gum, and sodium carboxymethyl cellulose; and the preferred surfactants are sodium lauryl sulfate, sodium lauroyl sarcosinate, sodium lauryl sulfate, cocamidopropyl betaine, and poloxamer. The ingredients include one or more of the following: sweeteners preferably include trichlorogalactose, sodium saccharin, xylitol, steviol glycosides, aspartame, etc.; flavorings preferably include lemon flavoring, peppermint flavoring, spearmint flavoring, etc.; acid-base regulators preferably include sodium pyrophosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium carbonate, sodium bicarbonate, etc.; stabilizers preferably include sodium phytate, lithium magnesium silicate, ethylenediaminetetraacetic acid or its salts, etc.; and antioxidants preferably include vitamin C, vitamin E, etc.

[0018] Compared with the prior art, the advantages of the present invention are as follows: (1) The core inventive concept of the present invention is to utilize positively charged cationic polymer compounds to form a uniform and dense cationic sustained-release network on the tooth surface through electrostatic adsorption with the inherent negative ion sites (negatively charged collagen fibers, phosphate residues, etc.) on the tooth and oral mucosa surfaces. This cationic sustained-release network, on the one hand, delays the diffusion rate of calcium ions released by sodium phosphosilicate calcium through steric hindrance and electrostatic action, and on the other hand, utilizes the active functional groups in the cationic polymer compounds to form complexation with calcium ions, thereby realizing the "capture-retention-sustaining release" process of calcium ions. Finally, after brushing and rinsing, calcium ions can be continuously released to the target tooth surface at a controlled rate, achieving targeted, long-lasting, and efficient remineralization repair. (2) In the sustained-release system of this invention, the cationic polymer and sodium alginate attract each other in solution through electrostatic attraction, forming a physically cross-linked network structure. The cationic polymer (such as cationic hyaluronic acid) in the sustained-release system can achieve tooth surface anchoring, electrostatically attract sodium alginate, construct a network, competitively bind Ca²⁺, and delay release. Simultaneously, sodium alginate and cationic hyaluronic acid form a polyelectrolyte network, regulating density and reversibly binding Ca²⁺, providing secondary sustained release. Ectoin plays a role in stabilizing the oral microenvironment, ensuring biocompatibility during the long-term release process. This invention overcomes the shortcomings of the prior art and provides an oral care sustained-release system (OraReliX™) composed of cationic polymers, sodium alginate, and ectoin. This system can significantly prolong the residence time of calcium ions released from sodium phosphosilicate calcium in the oral cavity, achieving stable and sustained release. This buffer system has a clear composition, significant effect, and is easy to industrialize, showing broad application prospects in oral care products. Detailed Implementation

[0019] To facilitate a further understanding of the present invention, the following embodiments are provided for more detailed description. However, these embodiments are only for a better understanding of the invention and are not intended to limit the scope or implementation principles of the invention. The implementation of the present invention is not limited to the following. The ingredients used in the formulations of the following embodiments are all commercially available, and the cationic cellulose used is polyquaternium-10 (PQ-10).

[0020] Example 1

[0021] Formula 1: 0.5% cationic hyaluronic acid, 0.3% sodium alginate, 0.2% ectoine, 5% sodium calcium phosphosilicate, 50% glycerin, 25% polyethylene glycol, 12% silicon dioxide, 2% carbomer, 0.3% sodium dodecyl sulfate, 1% sodium saccharin, 2% lemon flavor, and 1.7% lithium magnesium silicate.

[0022] Formula 2: 0.5% cationic cellulose, 0.3% sodium alginate, 0.2% ectoine, 5% sodium calcium phosphosilicate, 50% glycerin, 25% polyethylene glycol, 12% silicon dioxide, 2% carbomer, 0.3% sodium dodecyl sulfate, 1% sodium saccharin, 2% lemon flavoring, and 1.7% lithium magnesium silicate.

[0023] Formula 3: Cationic guar gum 0.5%, sodium alginate 0.3%, ectoine 0.2%, sodium calcium phosphosilicate 5%, glycerin 50%, polyethylene glycol 25%, silicon dioxide 12%, carbomer 2%, sodium dodecyl sulfate 0.3%, sodium saccharin 1%, lemon flavor 2%, lithium magnesium silicate 1.7%.

[0024] Formula 4: Hyaluronic acid 0.5%, sodium alginate 0.3%, ectoine 0.2%, sodium calcium phosphosilicate 5%, glycerin 50%, polyethylene glycol 25%, silicon dioxide 12%, carbomer 2%, sodium dodecyl sulfate 0.3%, sodium saccharin 1%, lemon flavor 2%, lithium magnesium silicate 1.7%.

[0025] Formula 5: 0.5% cationic hyaluronic acid, 0.3% sodium alginate, 5% sodium calcium phosphosilicate, 0.2% glycerin, 25% polyethylene glycol, 12% silicon dioxide, 2% carbomer, 0.3% sodium dodecyl sulfate, 1% sodium saccharin, 2% lemon flavor, and 1.7% lithium magnesium silicate.

[0026] Formula 6: Cationic hyaluronic acid 0.6%, sodium alginate 0.06%, ectoine 0.3%, sodium calcium phosphosilicate 9.6%, glycerin 52.74%, silicon dioxide 35%, carbomer 0.1%, sodium lauryl sulfate 1%, sodium saccharin 0.1%, lemon flavor 0.5%.

[0027] Formula 7: Cationic hyaluronic acid 0.3%, sodium alginate 0.3%, ectoine 0.3%, sodium calcium phosphosilicate 5%, glycerin 62.5%, silicon dioxide 30%, carbomer 0.5%, sodium lauryl sulfate 0.3%, sodium saccharin 0.3%, lemon flavor 0.5%.

[0028] Formula 8: Cationic hyaluronic acid 0.3%, sodium alginate 3%, ectoine 0.3%, sodium calcium phosphosilicate 18%, glycerin 58.8%, silicon dioxide 18%, carbomer 0.5%, sodium lauryl sulfate 0.3%, sodium saccharin 0.3%, lemon flavor 0.5%.

[0029] The general preparation method of the oral care composition of the present invention is as follows: according to the formula amount, by mass percentage.

[0030] (1) Mix an appropriate amount of humectant (preferably 80% of the total mass), cationic polymer, sodium alginate and ectoine, and stir evenly at 30-45°C (preferably 40°C) to form a first mixture;

[0031] (2) Mix and disperse sodium calcium phosphosilicate, abrasive, and thickener evenly to form a second mixture;

[0032] (3) Mix the surfactant, sweetener, flavoring, other ingredients (if any) with the remaining humectant to form a third mixture;

[0033] (4) The second mixture and the third mixture are added to the first mixture under stirring conditions, vacuum degassing and homogenization treatment are performed to obtain the oral care composition.

[0034] Optionally, step (5) involves filling and sealing the oral care composition prepared in step (4) using an ozone-sterilized aluminum-plastic composite tube.

[0035] In this embodiment, the humectant is glycerin and polyethylene glycol; the abrasive is silica; the thickener is carbomer; the surfactant is sodium dodecyl sulfate; the sweetener is sodium saccharin; the flavor is lemon flavor; and the other component is lithium magnesium silicate (as a stabilizer).

[0036] Example 2: Calcium Ion Sustained-Release Effect Test

[0037] (1) Subject selection

[0038] Ten healthy volunteers (half male and half female, aged 20-40 years) without oral diseases were selected. All participants signed informed consent forms.

[0039] (2) Test method

[0040] Each subject used oral care compositions (toothpaste) of formulations one through eight from Example 1, with each test (one formulation) spaced 3 days apart. The procedure for each test was as follows:

[0041] Do not brush your teeth or consume calcium-containing foods or beverages for 12 hours prior to the test. Upon waking in the morning (7:00-8:00 AM), collect a 2 mL resting saliva sample (baseline before brushing). Use 1.0 g toothpaste (approximately a pea-sized amount) and brush your teeth for 2 minutes using the standard Bass brushing technique. Rinse your mouth three times with water (approximately 20 mL each time, 3 seconds each time). Collect 2 mL saliva samples at 5 min (network capture and delayed release phase), 20 min (stable release and network saturation phase), 30 min (network structure maintenance and sustained release phase), and 60 min (sustained sustained release and long-lasting effect phase) after brushing. Centrifuge all saliva samples (3000 rpm, 10 min), collect the supernatant, and determine the calcium ion concentration using a calcium ion selective electrode (Orion), expressed as μmol / L. Calculate the net calcium ion concentration (net increase = measured value - baseline value before brushing) at each time point (5 min, 20 min, 30 min, 60 min), and observe the peak concentration C of the net increase. max And calculate the sustained-release index (%) = C 60min / C max ×100%.

[0042] (3) The test results are shown in the table below (mean ± standard deviation of 10 subjects)

[0043] Formula 1 242.5±12.1 328.6±15.2 282.3±13.4 196.7±11.2 59.9% Formula 2 221.3±11.7 305.3±12.5 258.4±12.1 172.5±10.6 56.5% Formula 3 230.6±12.0 339.2±17.3 290.5±13.7 189.8±11.0 56.0% Formula 4 418.3±18.6 103.5±9.1 50.2±5.1 20.1±3.3 4.8% Formula 5 286.5±13.8 271.3±12.1 185.2±10.0 83.4±6.1 29.1% Formula Six 305.2±14.3 379.5±15.8 280.2±13.9 192.7±10.8 50.8% Formula Seven 268.3±12.6 296.2±13.3 265.1±12.2 152.4±10.1 51.5% Formula 8 360.4±15.3 392.5±16.0 305.3±14.2 207.3±11.5 52.8%

[0044] The test results above show that the oral care composition (toothpaste) containing the complete sustained-release system of the present invention can still reach more than 50% of the peak calcium ion concentration in saliva 60 minutes after brushing. The sustained-release system of the present invention avoids the "burst release" phenomenon of calcium ions, which is conducive to the continuous deposition of calcium ions on the tooth surface and improves remineralization efficiency.

Claims

1. A sustained-release system containing a polymer compound, characterized in that... The sustained-release system comprises a cationic polymer, sodium alginate, and ectoine; the cationic polymer is selected from one or more of cationic hyaluronic acid, chitosan and its derivatives, cationic cellulose, cationic guar gum, and polyquaternary ammonium salts; the mass ratio of the cationic polymer, sodium alginate, and ectoine is 1-10:1-10:1-5.

2. The use of the sustained-release system according to claim 1 in the preparation of oral care products.

3. An oral care composition, characterized in that... The composition contains the sustained-release system as described in claim 1 and sodium calcium phosphosilicate, wherein the mass ratio of the sustained-release system to sodium calcium phosphosilicate is 1:5-10.

4. The oral care composition according to claim 3, characterized in that... The composition also contains excipients acceptable for oral care.

5. An oral care composition comprising the sustained-release system of claim 1, characterized in that, The product comprises, by weight percentage: the sustained-release system of claim 1, 5%-18% sodium calcium phosphosilicate, 52.74%-75.2% humectant, 12%-35% abrasive, 0.1%-2% thickener, 0.3%-1% surfactant, 0.1%-1% sweetener, 0.5%-2% flavoring, with the balance being other excipients acceptable in oral care, wherein the weight of the sustained-release system is 10%-20% of the sodium calcium phosphosilicate.

6. The oral care composition according to claim 5, characterized in that... Other acceptable excipients in oral care include whitening agents, stabilizers, pigments, antioxidants, pH adjusters, and one or more of the following in water:

7. A method for preparing the oral care composition according to any one of claims 5-6, characterized in that... Includes the following steps: (1) Mix an appropriate amount of moisturizer, cationic polymer, sodium alginate and ectoine, and stir evenly at room temperature to 50°C to form the first mixture; (2) Mix and disperse sodium calcium phosphosilicate, abrasive, and thickener evenly to form a second mixture; (3) Dissolve surfactants, sweeteners, flavorings, and other oral care excipients (optionally acceptable) in the remaining humectant to form a third mixture; (4) The second mixture and the third mixture are added to the first mixture under stirring conditions, vacuum degassing and homogenization treatment are performed to obtain the oral care composition.

8. The preparation method according to claim 7, characterized in that... In step (1), the amount of moisturizer used is selected from 70%-90% of the total mass of the moisturizer.

9. The use of the oral care composition according to any one of claims 3-6 in the preparation of oral care products for the prevention and / or treatment of dental caries, dentin hypersensitivity, enamel repair, remineralization of tooth surfaces, or relief of gingival problems.

10. The application as described in claim 2 or 9, characterized in that... The oral care products are selected from toothpaste, tooth powder, oral gel, mouthwash, chewing gum, oral spray, teeth whitening strips, denture care products, or anti-caries medical devices.