A tooth desensitizer capable of radically curing tooth sensitivity, its preparation method and application

Abstract

The present invention relates to a tooth desensitizer capable of radically curing tooth sensitivity, its preparation method and application. The tooth desensitizer is nanoparticles. By weight, its raw materials include 2-4 parts of collagen, 4-6 parts of glutaraldehyde, 1-3 parts of lidocaine, 5-15 parts of calcium chloride, and 5-15 parts of sodium phosphate. The weight ratio of calcium chloride to sodium phosphate is 1:1. When in use, an aqueous solution can be prepared and applied to the tooth sensitive part. In the aqueous solution, the nanoparticles can easily enter the dentinal tubules through Brownian motion and the capillary siphon effect of the dentinal tubules, so as to release lidocaine and directly act on the dental nerve for immediate desensitization, and block the dentinal tubules through in-situ biomineralization of collagen and calcium phosphate salts, realizing the radical cure of tooth sensitivity.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomaterials, and particularly relates to a tooth desensitizer capable of radically curing tooth sensitivity, a preparation method thereof, and an application thereof. Background Art

[0002] The common cause of tooth sensitivity is the defect (incompleteness) of enamel. External stimuli can directly contact dentin. There are many dentinal tubules in dentin, and there are nerves in the dentinal tubules. External stimuli stimulate the pulp nerves along the dentinal tubules, resulting in sensitivity. Therefore, the treatment of tooth sensitivity usually reduces the sensitivity of dental nerves, but to achieve a complete cure, it is necessary to block the dentinal tubules to avoid the exposure of dentinal tubules.

[0003] The dentinal tubules are radially arranged from the pulp surface to the dentino-enamel junction, relatively straight at the cusp and apical parts, and S-shaped curved at the cervical part. The end of the tubule near the pulp is thicker, with a diameter of 3 μm to 4 μm, and the end near the surface is thinner, being 1 μm. The dentinal tubules are thin and long in structure.

[0004] In current common tooth desensitizers, desensitizing components such as lidocaine are mainly contained in gels or resins. When in use, the gel or resin needs to be applied to the tooth sensitive area. If it is a light-curing resin, light also needs to be given to cure the resin and fix it in the sensitive area. Since gels and resins are semi-solids and have a relatively strong binding force on desensitizing components, it is difficult for desensitizing components to act on the inside of dentinal tubules, greatly weakening the desensitizing ability and blocking ability of the product.

[0005] In the prior art, there are also methods to form an active coating that can promote remineralization on dentin, especially inside dental micropores, so as to achieve the purpose of deeply sealing dental micropores. These coatings include polydopamine coatings, tannic acid / iron ion complex coatings, etc. However, these methods have many defects that limit their application in actual treatment, including long-time coating preparation, the dark color of the coating affecting aesthetics, poor stability under acid-base conditions, etc. In addition, during the remineralization process, proteins in saliva will form an acquired film on dentin, and the formation of the acquired film will provide sites for bacterial adhesion, promoting the formation of biofilms, thus causing symptoms such as pulpitis. Summary of the Invention

[0006] Aiming at the above current technical deficiencies, through specific formula component combinations, a desensitizer is provided that can penetrate into dentinal tubules, accumulate in dentinal tubules, block dentinal tubules through mineralization, and achieve a complete cure for tooth sensitivity.

[0007] In the first aspect of the present invention, a tooth desensitizer capable of radically curing tooth sensitivity is provided. The tooth desensitizer is nanoparticles, and by weight, its raw materials include 2-4 parts of collagen, 4-6 parts of glutaraldehyde, 1-3 parts of lidocaine, 5-15 parts of calcium chloride, and 5-15 parts of sodium phosphate, and the weight ratio of calcium chloride to sodium phosphate is 1:1.

[0008] In this system, glutaraldehyde can crosslink with collagen to form a dense nano-network structure, encapsulating lidocaine, calcium chloride, and sodium phosphate therein to form nanoparticles. Among them, lidocaine, as a nerve anesthetic, can directly act on the dental nerve to play a desensitizing role. Collagen and calcium phosphate salts can accumulate in the dentinal tubules and form a dense inorganic calcium salt structure through biomineralization.

[0009] Further, by weight, it includes 3-4 parts of collagen, 4-6 parts of glutaraldehyde, 2-3 parts of lidocaine, 8-15 parts of calcium chloride, and 8-15 parts of sodium phosphate.

[0010] Further, the collagen: glutaraldehyde = 1:1.3-2.5, and the size of the nanoparticles formed after crosslinking is more suitable for filling the dental tubules.

[0011] Further, the diameter of the nanoparticles is 50nm-200nm, which is beneficial for entering the dentinal tubules. If the size is too large or too small, the desensitizing effect of the nano-drug will be unsatisfactory. When the nano-size is less than 50nm, it is not conducive to the retention of nanoparticles in the dentinal tubules, and when it is too large, it is not conducive to entering the dentinal tubules.

[0012] On the other hand, the present invention also provides a preparation method of the tooth desensitizer, including the steps:

[0013] First, add collagen, lidocaine, calcium chloride, and sodium phosphate to purified water and disperse and dissolve them to obtain a homogeneous solution; then add glutaraldehyde to the above homogeneous solution and disperse it evenly to obtain a mixed solution; then add the mixed solution to dichloromethane, homogenize and disperse it, and finally remove dichloromethane and freeze-dry to obtain the tooth desensitizer.

[0014] Further, in the mixed solution, by weight percentage, the collagen content is 2%-4%, the glutaraldehyde content is 4%-6%, the lidocaine content is 1%-3%, the calcium chloride content is 5%-15%, the sodium phosphate content is 5%-15%, and the balance is purified water; the weight ratio of calcium chloride to sodium phosphate is 1:1.

[0015] Further, the collagen: glutaraldehyde = 1:1.3-2.5.

[0016] Further, the mass ratio of dichloromethane to the mixed solution is 1:1.

[0017] Further, the homogenization rate is 10,000 r / min to 13,000 r / min, and the homogenization time is ≥1 h, so as to obtain nanoparticles with appropriate sizes and uniform dispersion.

[0018] Another aspect of the present invention also provides an application of the tooth desensitizer described above in tooth desensitizing products.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The tooth desensitizer of the present invention is in the form of nanoparticles. When in use, an aqueous solution can be prepared and then applied to the tooth sensitive area. In the aqueous solution, the nanoparticles can easily enter the dentinal tubules through Brownian motion and the capillary siphon effect of the dentinal tubules, thereby releasing lidocaine to directly act on the dental nerve for immediate desensitization, and in-situ biomineralization of collagen and calcium phosphate salts is carried out to block the dentinal tubules, achieving a complete cure for tooth sensitivity. By optimizing the preparation method and component content, the obtained nanoparticles have appropriate sizes, can effectively enter the dentinal tubules, improve the desensitization effect, and can achieve a complete cure for tooth sensitivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a picture of the tooth desensitizer of the embodiment of the present invention;

[0022] Figure 2 It is a scanning electron microscope image of the tooth desensitizer of the embodiment of the present invention before and after blocking the dentinal tubules. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0023] The following specific embodiments are used to further illustrate the present invention, but the embodiments do not limit the present invention in any form. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the technical field.

[0024] Unless otherwise specified, the reagents and materials used in the following embodiments are all commercially available.

[0025] Example 1

[0026] This example provides a tooth desensitizer that can cure tooth sensitivity, and the specific preparation method is as follows:

[0027] Prepare 3 g of collagen, 5 g of glutaraldehyde, 2 g of lidocaine, 10 g of calcium chloride, 10 g of sodium phosphate, and 70 g of purified water;

[0028] First, add collagen, lidocaine, calcium chloride, and sodium phosphate to purified water and disperse and dissolve them to obtain a homogeneous solution; then add glutaraldehyde to the above homogeneous solution and disperse it evenly to obtain a mixed solution; then add the mixed solution to 100 g of dichloromethane, and use a homogenizer to homogenize and stir it hermetically at a homogenization rate of 12000 r / min for 2 h. Remove dichloromethane through a vacuum rotary evaporator to obtain cross-linked nanoparticles, and finally freeze-dry the cross-linked nanoparticles to obtain a tooth desensitizer sample.

[0029] Example 2

[0030] This example provides a tooth desensitizer that can cure tooth sensitivity. The specific preparation method is as follows:

[0031] Prepare 2 g of collagen, 4 g of glutaraldehyde, 1 g of lidocaine, 5 g of calcium chloride, 5 g of sodium phosphate, and 83 g of purified water;

[0032] First, add collagen, lidocaine, calcium chloride, and sodium phosphate to purified water and disperse and dissolve them to obtain a homogeneous solution; then add glutaraldehyde to the above homogeneous solution and disperse it evenly to obtain a mixed solution; then add the mixed solution to 100 g of dichloromethane, and use a homogenizer to homogenize and stir it hermetically at a homogenization rate of 10000 r / min for 1 h. Remove dichloromethane through a vacuum rotary evaporator to obtain cross-linked nanoparticles, and finally freeze-dry the cross-linked nanoparticles to obtain a tooth desensitizer sample.

[0033] Example 3

[0034] This example provides a tooth desensitizer that can cure tooth sensitivity. The specific preparation method is as follows:

[0035] Prepare 4 g of collagen, 6 g of glutaraldehyde, 3 g of lidocaine, 15 g of calcium chloride, 15 g of sodium phosphate, and 57 g of purified water;

[0036] First, add collagen, lidocaine, calcium chloride, and sodium phosphate to purified water and disperse and dissolve them to obtain a homogeneous solution; then add glutaraldehyde to the above homogeneous solution and disperse it evenly to obtain a mixed solution; then add the mixed solution to 100 g of dichloromethane, and use a homogenizer to homogenize and stir it hermetically at a homogenization rate of 13000 r / min for 3 h. Remove dichloromethane through a vacuum rotary evaporator to obtain cross-linked nanoparticles, and finally freeze-dry the cross-linked nanoparticles to obtain a tooth desensitizer sample.

[0037] Example 4

[0038] This example provides a tooth desensitizer that can cure tooth sensitivity. The specific preparation method is as follows:

[0039] Prepare 3 g of collagen, 4 g of glutaraldehyde, 3 g of lidocaine, 8 g of calcium chloride, 8 g of sodium phosphate, and 74 g of purified water;

[0040] First, add collagen, lidocaine, calcium chloride, and sodium phosphate to purified water and disperse and dissolve them to obtain a homogeneous solution; then add glutaraldehyde to the above homogeneous solution and disperse it evenly to obtain a mixed solution; next, add the mixed solution to 100 g of dichloromethane and homogenize and stir it in a closed state at a homogenization rate of 11000 r / min for 4 h. Remove dichloromethane through a vacuum rotary evaporator to obtain cross-linked nanoparticles. Finally, freeze-dry the cross-linked nanoparticles to obtain a tooth desensitizer sample.

[0041] Comparative Example 1 is the same as Example 1, except that the amount of collagen used is 1.5 g and the amount of glutaraldehyde used is 3.5 g, and the other components and preparation methods are the same as those in Example 1.

[0042] Comparative Example 2 is the same as Example 1, except that the amount of collagen used is 4.5 g and the amount of glutaraldehyde used is 6.5 g, and the other components and preparation methods are the same as those in Example 1.

[0043] Comparative Example 3 is the same as Example 1, except that the amount of lidocaine used is 0.5 g and the amount of purified water used is 71.5 g, and the other components and preparation methods are the same as those in Example 1.

[0044] Comparative Example 4 is the same as Example 1, except that the amount of lidocaine used is 3.5 g and the amount of purified water used is 68.5 g, and the other components and preparation methods are the same as those in Example 1.

[0045] Comparative Example 5 is the same as Example 1, except that the amount of calcium chloride used is 4.5 g, the amount of sodium phosphate used is 4.5 g, and the amount of purified water used is 81 g, and the other components and preparation methods are the same as those in Example 1.

[0046] Comparative Example 6 is the same as Example 1, except that the amount of calcium chloride used is 16 g, the amount of sodium phosphate used is 16 g, and the amount of purified water used is 58 g, and the other components and preparation methods are the same as those in Example 1.

[0047] Comparative Example 7 is the same as Example 1, except that the homogenization rate is 9000 r / min, and the other components and preparation methods are the same as those in Example 1.

[0048] Comparative Example 8 is the same as Example 1, except that the homogenization rate is 14000 r / min, and the other components and preparation methods are the same as those in Example 1.

[0049] Comparative Example 9 is the same as Example 1, except that the homogenization time is 50 min, and the other components and preparation methods are the same as those in Example 1.

[0050] The materials used in each example and comparative example are shown in Table 1.

[0051] Table 1 Materials Used in Each Example and Comparative Example

[0052]

[0053]

[0054] Samples of Examples 1 - 4 and Comparative Examples 1 - 9 were selected to evaluate the size of the nanoparticle samples, drug release ability, dentinal tubule occlusion rate, and desensitization efficiency in subjects.

[0055] The specific evaluation methods and criteria are as follows:

[0056] Nanodrug size: The size of the nanodrug was detected by a Malvern laser scattering particle size analyzer (DLS). The normal distribution mean of the nanodrug size should be between 50 nm and 200 nm.

[0057] Drug release ability: The nanodrug was formulated into a 5% concentration with artificial saliva and placed in an environment at 37°C. At the 12 - h node, the release ratio of lidocaine was detected and analyzed by an ultraviolet spectrophotometer, and it should be not less than 70%.

[0058] Dentinal tubule occlusion rate: Human dentin slice test samples were prepared in advance according to the standard "YY / T 1829 - 2022 Dentistry - In Vitro Evaluation Method for the Occlusion Effect of Dentinal Tubules". Then, the samples of Examples 1 - 4 and Comparative Examples 1 - 9 were mixed with purified water to a 5% concentration. The human dentin slice test samples were immersed in the mixed solution. After 5 minutes, the human dentin slices were taken out, the surface of the human dentin slices was rinsed clean with purified water, and then immersed in artificial saliva for storage. The above operations were repeated 2 times a day for a total of 14 days. After 14 days, the occlusion situation of the dentinal tubules in the human dentin slice samples was observed by a scanning electron microscope, and the occlusion rate was calculated. The purpose of this test was to simulate the product use process and observe the occlusion effect of the product on dentinal tubules. Dentinal tubule occlusion rate = (n0 - n1) / n0 × 100%. n0 is the number of open dentinal tubules in the control group; n1 is the number of unoccluded dentinal tubules in the experimental group.

[0059] The dentinal tubule occlusion rate should be not less than 80%.

[0060] Desensitization efficiency in subjects:

[0061] 65 volunteers with tooth sensitivity symptoms were recruited to try the samples of Examples 1 - 4 and Comparative Examples 1 - 9. The volunteers were randomly divided into 13 groups, with 5 people in each group. The samples prepared from Examples 1 - 4 and Comparative Examples 1 - 9 were used as the test products and applied to the 13 groups of subjects respectively.

[0062] Usage: Before the volunteers try the product, they need to clean their oral cavity and dental hygiene. Before using the product, prepare an aqueous solution with a concentration of 5% (mass fraction) of the dental desensitizing nanoparticles with purified water. After mixing evenly, apply it to the sensitive parts of the teeth. After 5 minutes, you can gargle to remove the product. Use it once in the morning and once in the evening every day for 15 consecutive days. Professional personnel will score the trial effect to evaluate the immediate desensitization effect of the product, the dental desensitization effect on the 15th day, and the recurrence situation one month after stopping the treatment.

[0063] Define the curative effect indicators as follows:

[0064] Effective: Immediate desensitization is effective (7 - 10 points), dental desensitization on the 15th day is effective (7 - 10 points), and there is no recurrence one month after stopping the treatment (7 - 10 points).

[0065] Invalid: Other situations are regarded as invalid.

[0066] Effective rate = number of effective people / 5 × 100%

[0067] The overall test results are shown in Table 2, and Table 3 is a detailed comparison list of the trial effects of the examples and comparative examples.

[0068] Table 2: Performance test results of the implementation cases and comparative examples

[0069]

[0070]

[0071] Table 3: Detailed comparison list of the trial effects of the examples and comparative examples

[0072]

[0073]

[0074]

[0075] Figure 1 This is a picture of the dental desensitizing agent nanoparticles synthesized in the embodiment of the present invention. After freeze-drying, the particles are white powder. When used, an aqueous solution is prepared and then applied to the sensitive parts. The nanoparticles in the aqueous solution enter the dentinal tubules through Brownian motion and the capillary siphon effect of the dentinal tubules. As the nanoparticles continue to swell, lidocaine is released and directly acts on the dental nerve for immediate desensitization. The collagen and calcium phosphate salts in it undergo in-situ biomineralization to block the dentinal tubules, achieving a complete cure for tooth sensitivity. Figure 2 These are scanning electron microscope pictures of the dentinal tubules before and after use.

[0076] Both too large and too small nanoparticle sizes affect the desensitization effect. A size greater than 200 nm is not conducive to the entry of nanoparticles into dentinal tubules, and a nanoparticle size less than 50 nm is not conducive to the retention of nanoparticles in dentinal tubules.

[0077] From the results of the above examples and comparative examples, it can be seen that the dosage and ratio of collagen and glutaraldehyde will affect the size of the finally synthesized nanoparticles. Only when the collagen concentration in the mixed solution is 2-4%, glutaraldehyde is 4-6%, and collagen: glutaraldehyde = 1:1.3-2.5 can nanoparticles with appropriate sizes be cross-linked. The content of lidocaine will directly affect the immediate desensitization effect. If the dosage is too small, the drug release is small, and if it is too much, it will also have a certain impact on the particle size. When the concentration in the mixed solution is 1-3 wt%, the nanoparticles obtained have a better desensitization effect and appropriate size. The addition amounts of calcium chloride and sodium phosphate will affect the dentinal tubule occlusion rate and nanoparticle size. During preparation, the average rate and homogenization time will affect the finally synthesized nanoparticle size, thereby affecting the final desensitization effect.

[0078] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.

[0079] The above-described embodiments only represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention patent should be subject to the appended claims.

Claims

1. A tooth desensitizer that can cure tooth sensitivity, characterized in that, The tooth desensitizer is nanoparticles. By weight, its raw materials include 3 - 4 parts of collagen, 4 - 6 parts of glutaraldehyde, 2 - 3 parts of lidocaine, 8 - 15 parts of calcium chloride, and 8 - 15 parts of sodium phosphate. The weight ratio of calcium chloride to sodium phosphate is 1:

1. The preparation method of the tooth desensitizer includes the steps: First, add collagen, lidocaine, calcium chloride, and sodium phosphate into purified water to disperse and dissolve to obtain a homogeneous solution. Then add glutaraldehyde to the above homogeneous solution and disperse evenly to obtain a mixed solution. Next, add the mixed solution into dichloromethane, homogenize and disperse, and finally remove dichloromethane and freeze-dry to obtain the tooth desensitizer. The homogenization rate is 10,000 r / min - 13,000 r / min, and the homogenization time is ≥1 h.

2. The tooth desensitizer according to claim 1, wherein, By mass ratio, the collagen: glutaraldehyde = 1:1.3 - 2.

5.

3. The tooth desensitizer according to claim 1, wherein the diameter of the nanoparticles is 50 nm - 200 nm.

4. The tooth desensitizer according to claim 1, wherein In the mixed solution, by weight percentage, the collagen content is 3% - 4%, the glutaraldehyde content is 4% - 6%, the lidocaine content is 2% - 3%, the calcium chloride content is 8% - 15%, the sodium phosphate content is 8% - 15%, and the balance is purified water. The weight ratio of calcium chloride to sodium phosphate is 1:

1.

5. The tooth desensitizer according to claim 1, wherein The mass ratio of dichloromethane to the mixed solution is 1:

1.

6. Use of the tooth desensitizer according to any one of claims 1 - 5 in the preparation of a tooth desensitizing product.

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