Biomimetic photosensitizer-modified nitrogen-doped titanium dioxide-based photodynamic bleaching agent, method of preparation and use thereof

Abstract

The application provides a kind of biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent, its preparation method and purposes, belong to the technical field of tooth bleaching.The preparation method of the application includes: step one, preparation of nitrogen-doped titanium dioxide material;Step two, preparation of surface amino-functionalized nitrogen-doped titanium dioxide material: chitosan, acetic acid aqueous solution and nitrogen-doped titanium dioxide are mixed, and epoxy chloropropane crosslinking agent is added to continue the reaction;Step three, preparation of Ce6 photosensitizer modified nitrogen-doped titanium dioxide material: Ce6, DMSO, EDC, NHS are mixed, the carboxyl group of Ce6 is activated, then 25mL surface amino-functionalized nitrogen-doped titanium dioxide material dispersion liquid is added dropwise into the activated Ce6 solution, and reacts for 24h;Step four, the product of step three is used to prepare biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent.

Description

Technical Field

[0001] This invention belongs to the field of teeth bleaching technology, and relates to a biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent, its preparation method, and its application in teeth photodynamic bleaching. Background Technology

[0002] Tooth discoloration is mainly caused by pigment deposition, medications, and fluoride poisoning. With the improvement of modern living standards, teeth whitening and restoration have received increasing attention. Currently, dental bleaching typically involves exposing teeth to a 25% to 35% hydrogen peroxide bleaching agent, combined with laser irradiation to activate the hydrogen peroxide. To achieve a certain whitening and restoration effect, a high concentration of hydrogen peroxide bleaching agent is required. While it can bring significant whitening results, high concentrations of hydrogen peroxide have certain side effects, such as damaging tooth enamel, increasing tooth or gum sensitivity, irritating oral soft tissues, and causing oral tissue cytotoxicity. Therefore, it is essential to develop a low-irritation teeth whitening and restoration material that ensures the whitening and restoration effect while improving the biocompatibility of teeth and oral soft tissues.

[0003] Photodynamic therapy (PDT), a novel technology utilizing the photodynamic effect for disease diagnosis and treatment, involves a photosensitizer transferring energy to oxygen molecules under the radiation of light of a specific wavelength, generating highly reactive singlet oxygen. Dihydroporphyrin E6 (Ce6), serving as the backbone of chlorophyll a, b, and heme d, is a biomimetic photosensitizer. Due to its high singlet oxygen production efficiency and biocompatibility, it has already been applied to photodynamic therapy for tumors. Therefore, it holds promise for future applications in teeth whitening and restoration. Summary of the Invention

[0004] This invention is made to solve the above-mentioned problems, and aims to provide a biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent, its preparation method and its application in photodynamic bleaching of teeth.

[0005] This invention provides a method for preparing a biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent, characterized by the following steps: Step 1, preparing nitrogen-doped titanium dioxide material: Under stirring conditions, isopropoxy titanium is added dropwise to water to obtain a uniform colloidal solution. Then, concentrated nitric acid is slowly added to the sol to obtain a translucent solution. Vigorous stirring continues until the translucent solution becomes completely transparent, obtaining a transparent solution. Ammonia is then added dropwise to the transparent solution until the pH value reaches 9, resulting in a dark yellow precipitate. Finally, the precipitate is filtered, washed, and dried to obtain the nitrogen-doped titanium dioxide material. Step 2, preparing surface-amino-functionalized nitrogen-doped titanium dioxide material: Chitosan, an aqueous acetic acid solution, and nitrogen-doped titanium dioxide are mixed and ultrasonically treated to form a uniform dispersion. Then, epoxy resin is added... The chloropropane crosslinking agent continued to react, and finally, after centrifugation and washing, surface amino-functionalized nitrogen-doped titanium dioxide material was obtained; Step 3, Ce6 photosensitizer-modified nitrogen-doped titanium dioxide material was prepared: dihydroporphyrin e6 was mixed with dimethyl sulfoxide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to activate the carboxyl group of dihydroporphyrin e6, and an activated Ce6 solution was obtained. Then, 25 mL of the dispersion of surface amino-functionalized nitrogen-doped titanium dioxide material was added dropwise to the activated Ce6 solution, and the reaction was carried out for 24 h to obtain biomimetic photosensitizer-modified nitrogen-doped titanium dioxide material; Step 4, biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent was prepared: biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent was prepared using the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide material.

[0006] The preparation method of the biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent provided by the present invention may also have the following characteristics: wherein, in step one, the mass-volume ratio of isopropoxy titanium to water is (5.5g-6.5g):30mL, the volume ratio of concentrated nitric acid to water is (7.5mL-8.5mL):30mL, and the ammonia content in the ammonia water is 25-28%.

[0007] The preparation method of the biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent provided by the present invention may also have the following characteristics: in step two, the volume ratio of acetic acid aqueous solution to epichlorohydrin crosslinking agent is 25 mL: 100 μL, and the reaction time after adding epichlorohydrin crosslinking agent is 4 h.

[0008] The preparation method of the biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent provided by the present invention may also have the following characteristics: wherein, in step three, the ratio of dihydroporphyrin E6, dimethyl sulfoxide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide is 30mg:25mL:200mg:400mg, and the dispersion of the surface amino-functionalized nitrogen-doped titanium dioxide material is a 10mg / mL solution prepared by dissolving the surface amino-functionalized nitrogen-doped titanium dioxide material in distilled water.

[0009] The preparation method of the biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent provided by the present invention may also have the following features: in step four, the biomimetic photosensitizer modified nitrogen-doped titanium dioxide material is prepared into a water-soluble dispersion, excipients are added, and a gel-like preparation is made to obtain the tooth photodynamic bleaching agent.

[0010] The present invention also provides a biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent, characterized in that it is prepared by the above-mentioned preparation method of biomimetic photosensitizer modified nitrogen-doped titanium dioxide material.

[0011] This invention also provides an application of a biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent in the photodynamic bleaching of teeth.

[0012] In the application of the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent provided by this invention in the photodynamic bleaching of teeth, it can also have the following characteristics: the application includes: uniformly applying the photodynamic bleaching agent to the tooth surface, and simultaneously irradiating it with visible blue light from a dental curing lamp with a wavelength range of 400-500nm to promote the generation of hydroxyl radicals and singlet oxygen. The generated hydroxyl radicals and singlet oxygen can further achieve the teeth whitening and repair effect by destroying the pigments on the tooth surface.

[0013] The role and effect of invention

[0014] This invention relates to a biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent, its preparation method, and its application in photodynamic bleaching of teeth. By combining Ce6 photosensitizer with nitrogen-doped titanium dioxide, a material with excellent visible light photocatalytic properties, a biomimetic photosensitizer-modified nitrogen-doped titanium dioxide material is prepared. This material is uniformly coated onto the tooth surface, and simultaneously irradiated with visible blue light from a dental curing lamp with a wavelength range of 400-500 nm. This promotes the generation of hydroxyl radicals and singlet oxygen. The generated hydroxyl radicals and singlet oxygen can further destroy pigments on the tooth surface, achieving a better teeth whitening and repair effect. As a novel photodynamic bleaching agent, the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide material avoids the damage to teeth caused by traditional hydrogen peroxide bleaching agents, thus ensuring biocompatibility while improving whitening and repair effects. Attached Figure Description

[0015] Figure 1 These are photographs of teeth after treatment with Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent in Application Example 1 of the present invention and 30% hydrogen peroxide bleaching agent in Comparative Example 1.

[0016] Figure 2 These are scanning electron microscope images of teeth treated with Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent in Application Example 1 of the present invention and with 30% hydrogen peroxide bleaching agent in Comparative Example 1. Detailed Implementation

[0017] To make the technical means, creative features, objectives and effects of the present invention easy to understand, the following embodiments, in conjunction with the accompanying drawings, specifically illustrate the present invention's biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent, its preparation method, and its application in photodynamic bleaching of teeth.

[0018] <Example 1>

[0019] Example 1 provides a biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent and its preparation method.

[0020] The preparation method of the Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent in Example 1 includes the following steps:

[0021] Step 1: Preparation of nitrogen-doped titanium dioxide material: 6.0 g of titanium isopropoxy (IV) was added dropwise to 30.0 mL of water under magnetic stirring to obtain a homogeneous colloidal solution. Then, 8.0 mL of concentrated nitric acid was slowly added to the sol to obtain a translucent solution. Vigorous stirring was continued for half an hour until the translucent solution became completely transparent. Then, ammonia solution with an ammonia content of 25-28% was added dropwise to the transparent solution until the pH value of the solution reached 9, resulting in a dark yellow precipitate. Finally, the dark yellow precipitate was filtered, washed with water, and dried in air at room temperature to obtain nitrogen-doped titanium dioxide material, which was then stored for later use.

[0022] Step 2, preparation of surface amino-functionalized nitrogen-doped titanium dioxide material: 500 mg chitosan, 25 mL acetic acid aqueous solution (2.5%, v / v) and 250 mg of the above nitrogen-doped titanium dioxide were mixed and ultrasonically treated until a uniform dispersion was formed. Then 100 μL epichlorohydrin crosslinking agent was added and the reaction was continued for 4 h. Finally, the mixture was centrifuged and washed to obtain surface amino-functionalized nitrogen-doped titanium dioxide material.

[0023] Step 3: Preparation of Ce6 photosensitizer-modified nitrogen-doped titanium dioxide material: 30 mg Ce6 was mixed with 25 mL dimethyl sulfoxide (DMSO), 200 mg 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC), and 400 mg N-hydroxysuccinimide (NHS) to activate the carboxyl groups of Ce6 for 4 h, obtaining an activated Ce6 solution. Then, 25 mL of the above-mentioned surface-amino-functionalized nitrogen-doped titanium dioxide material dispersion (10 mg / mL) was added dropwise to the activated Ce6 solution, and the reaction was allowed to proceed for 24 h to obtain the Ce6 photosensitizer-modified nitrogen-doped titanium dioxide material.

[0024] Step 4: Preparation of Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent: Dissolve 100 mg of Ce6 photosensitizer-modified nitrogen-doped titanium dioxide material in distilled water to prepare a 10 mg / mL solution, add 500 mg of hyaluronic acid, and stir evenly into a paste to obtain Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent.

[0025] <Example 2>

[0026] Example 2 provides a Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent and its preparation method. The only difference between this preparation method and Example 1 is that step four is different; the remaining steps are exactly the same.

[0027] Step four in Example 2, preparation of Ce6 photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent: 100 mg of Ce6 photosensitizer modified nitrogen-doped titanium dioxide material was dissolved in distilled water to prepare a 20 mg / mL solution, 40 mg of menthol and 400 mg of sodium alginate were added, and the mixture was stirred evenly into a paste.

[0028] <Application Example 1>

[0029] The Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent prepared in Example 1 was uniformly applied to the labial enamel surface of the teeth (approximately 2 mm thick). Simultaneously, visible blue light from a dental curing lamp with a wavelength range of 400-500 nm was used for irradiation. During irradiation, the distance between the dental curing lamp and the labial surface of the teeth was maintained at 20 cm. The visible blue light from the dental curing lamp irradiated the surface of the photodynamic bleaching agent, thereby promoting the generation of hydroxyl radicals and singlet oxygen. The irradiation time was 30 minutes, after which the photodynamic bleaching agent was removed from the tooth surface and the teeth were rinsed clean.

[0030] <Comparative Example 1>

[0031] The nitrogen-doped titanium dioxide photodynamic bleaching agent was modified with 30% H2O2 instead of the Ce6 photosensitizer prepared in Example 2. A dental curing lamp with visible blue light in the wavelength range of 400-500 nm was still used for irradiation, maintaining a distance of 20 cm between the lamp and the labial surface of the tooth. The irradiation time was 30 minutes, after which the H2O2 was removed and the tooth was rinsed clean.

[0032] The teeth of Application Example 1 and Comparative Example 1 were photographed and compared by scanning electron microscopy to compare the bleaching (whitening) effect of the Ce6 photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent of the present invention with that of the traditional H2O2 bleaching agent.

[0033] Figure 1 These are photographs of teeth after treatment with Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent in Application Example 1 of the present invention and 30% hydrogen peroxide bleaching agent in Comparative Example 1. Figure 2 These are scanning electron microscope images of teeth treated with Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent in Application Example 1 of the present invention and with 30% hydrogen peroxide bleaching agent in Comparative Example 1.

[0034] like Figure 1-2 As shown in Application Example 1 of the present invention, the Ce6 photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent is a novel photodynamic bleaching agent that can avoid the damage to teeth caused by traditional hydrogen peroxide bleaching agents, thereby improving the whitening and repair effect while ensuring biocompatibility.

Claims

1. A method for preparing a biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent, characterized in that, Includes the following steps: Step 1, Preparation of nitrogen-doped titanium dioxide material: Under stirring conditions, titanium isopropoxy is added dropwise to water to obtain a uniform colloidal solution. Then, concentrated nitric acid is slowly added to the sol to obtain a translucent solution. Vigorous stirring is continued until the translucent solution becomes completely transparent to obtain a transparent solution. Then, ammonia is added dropwise to the transparent solution until the pH value of the solution is 9, resulting in a dark yellow precipitate. Finally, the dark yellow precipitate is filtered, washed, and dried to obtain the nitrogen-doped titanium dioxide material. Step 2, preparation of surface amino-functionalized nitrogen-doped titanium dioxide material: chitosan, acetic acid aqueous solution and the nitrogen-doped titanium dioxide are mixed and ultrasonically treated to form a uniform dispersion. Then epichlorohydrin crosslinking agent is added to continue the reaction. Finally, centrifugation and washing are performed to obtain the surface amino-functionalized nitrogen-doped titanium dioxide material. Step 3: Preparation of Ce6 photosensitizer-modified nitrogen-doped titanium dioxide material: Dihydroporphyrin e6 was mixed with dimethyl sulfoxide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to activate the carboxyl group of dihydroporphyrin e6, resulting in an activated Ce6 solution. Then, 25 mL of the dispersion of surface amino-functionalized nitrogen-doped titanium dioxide material was added dropwise to the activated Ce6 solution, and the reaction was carried out for 24 h to obtain the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide material. Step 4: Preparation of biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent: The biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent is prepared using the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide material.

2. The preparation method of the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent according to claim 1, characterized in that: in, In step one, the mass-to-volume ratio of the isopropoxy titanium to the water is (5.5g-6.5g):30mL, the volume ratio of the concentrated nitric acid to the water is (7.5mL-8.5mL):30mL, and the ammonia content in the ammonia water is 25-28%.

3. The preparation method of the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent according to claim 1, characterized in that: in, In step two, the volume ratio of the acetic acid aqueous solution to the epichlorohydrin crosslinking agent is 25 mL: 100 μL, and the reaction continues for 4 hours after the epichlorohydrin crosslinking agent is added.

4. The preparation method of the biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent according to claim 1, characterized in that: in, In step three, the ratio of dihydroporphyrin E6, dimethyl sulfoxide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide is 30 mg: 25 mL: 200 mg: 400 mg. The dispersion of the surface amino-functionalized nitrogen-doped titanium dioxide material is a 10 mg / mL solution prepared by dissolving the surface amino-functionalized nitrogen-doped titanium dioxide material in distilled water.

5. The preparation method of the biomimetic photosensitizer modified nitrogen-doped titanium dioxide photodynamic bleaching agent according to claim 1, characterized in that: in, In step four, the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide material is formulated into a water-soluble dispersion, and excipients are added to form a gel-like preparation, thereby obtaining the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent.

6. A biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent, characterized in that: It is prepared by the preparation method of nitrogen-doped titanium dioxide photodynamic bleaching agent modified with biomimetic photosensitizer as described in any one of claims 1-5.

7. The application of the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent as described in claim 6 in the preparation of dental photodynamic bleaching products.

8. The application of the biomimetic photosensitizer-modified nitrogen-doped titanium dioxide photodynamic bleaching agent according to claim 6 or 7 in the preparation of dental photodynamic bleaching products, characterized in that: in, The application includes: uniformly applying the photodynamic tooth whitening product to the tooth surface, and simultaneously irradiating it with visible blue light from a dental curing lamp with a wavelength range of 400-500 nm to promote the generation of hydroxyl radicals and singlet oxygen. The generated hydroxyl radicals and singlet oxygen can further destroy the pigments on the tooth surface to achieve a tooth whitening and repair effect.

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