Tooth desensitizer capable of radically treating tooth sensitivity as well as preparation method and application of tooth desensitizer

Abstract

The invention relates to a tooth desensitizer capable of radically treating tooth sensitivity and a preparation method and application thereof.The tooth desensitizer is nanoparticles and comprises, by weight, 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 the calcium chloride to the sodium phosphate is 1: 1. When in use, an aqueous solution can be prepared and applied to sensitive parts of teeth, and the nanoparticles in the aqueous solution easily enter dentinal tubules through Brownian movement and capillary siphonic effect of the dentinal tubules, so that lidocaine is released to directly act on dental nerves for immediate desensitization; and dentinal tubules are blocked through collagen and calcium phosphate in-situ biomineralization, so that the tooth sensitivity is thoroughly and radically treated.

Description

Technical Field

[0001] The invention belongs to the technical field of biomaterials, and in particular relates to a tooth desensitizing agent capable of radically curing tooth sensitivity, and a preparation method and application thereof. Background Art

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

[0003] The dentinal tubules are arranged radially from the pulp surface to the enamel-dentin junction. They are straight at the apex and root apex, and are "S"-shaped at the neck. The end of the tubule near the pulp is thicker, with a diameter of 3μm to 4μm, and the end near the surface is thinner, with a diameter of 1μm. The dentinal tubules are thin and long in structure.

[0004] The current common tooth desensitizers, desensitizing ingredients such as Licardoine, are mainly contained in gel or resin. When using, the gel or resin needs to be applied to the sensitive parts of the teeth. If it is a light-cured resin, it is also necessary to apply light to cure the resin to the sensitive part. Because gel and resin are semi-solid, they have a strong binding force on the desensitizing ingredients, making it difficult for the desensitizing ingredients to act on the inside of the dentinal tubules, greatly weakening the desensitization and blocking abilities of the product.

[0005] In the prior art, there are also methods that achieve the purpose of deeply sealing the dentinal pores by forming an active coating that promotes remineralization on the dentin, especially inside the dentinal pores. 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 coating preparation time, dark coatings that affect appearance, poor stability under acid-base conditions, etc. In addition, during the remineralization process, proteins in saliva will form acquired films on the dentin, and the formation of acquired films will provide sites for bacterial adhesion, promote the formation of biofilms, and thus cause symptoms such as pulpitis. Summary of the invention

[0006] In view of the above-mentioned current technical deficiencies, a desensitizing agent is provided through a combination of specific formula ingredients, which can penetrate deeply into the dentinal tubules, accumulate in the dentinal tubules, block the dentinal tubules through mineralization, and achieve a complete cure for tooth sensitivity.

[0007] The first aspect of the present invention provides a tooth desensitizing agent that can cure tooth sensitivity. The tooth desensitizing agent is a nanoparticle. In terms of weight, its raw materials include 2 to 4 parts of collagen, 4 to 6 parts of glutaraldehyde, 1 to 3 parts of lidocaine, 5 to 15 parts of calcium chloride, and 5 to 15 parts of sodium phosphate. The weight ratio of calcium chloride to sodium phosphate is 1:1.

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

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

[0010] Furthermore, the ratio of collagen to glutaraldehyde is 1:1.3-2.5, and the size of the nanoparticles formed after cross-linking is suitable for tooth canal filling.

[0011] Furthermore, the nanoparticles have a diameter of 50nm to 200nm, which is conducive to entering the dentinal tubules. Too large or too small a size will lead to unsatisfactory desensitization effects of the nanomedicine. A nanoparticle size less than 50nm is not conducive to the retention of the nanoparticles in the dentinal tubules, and too large a size is not conducive to entering the dentinal tubules.

[0012] Another aspect of the present invention also provides a method for preparing the tooth desensitizing agent, comprising the steps of:

[0013] First, collagen, lidocaine, calcium chloride and sodium phosphate are added to purified water for dispersion and dissolution to obtain a uniform solution; then glutaraldehyde is added to the uniform solution for uniform dispersion to obtain a mixed solution; then the mixed solution is added to dichloromethane for uniform dispersion, and finally the dichloromethane is removed and freeze-dried to obtain the tooth desensitizing agent.

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

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

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

[0017] Furthermore, the homogenization rate is 10000 r / min to 13000 r / min, and the homogenization time is ≥ 1 h, so as to obtain nanoparticles with appropriate size and uniform dispersion.

[0018] Another aspect of the present invention also provides the use of the tooth desensitizing agent in tooth desensitizing products.

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

[0020] The tooth desensitizing agent of the present invention is a nanoparticle that can be used by preparing an aqueous solution and then applied to the sensitive part of the tooth. In the aqueous solution, the nanoparticles 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 nerves for immediate desensitization, and block the dentinal tubules through in-situ biomineralization of collagen and calcium phosphate salts, thereby achieving a complete cure for tooth sensitivity. Combined with the preparation method and the optimization of the component content, the obtained nanoparticles are of appropriate size, 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 This is a picture of a tooth desensitizing agent according to an embodiment of the present invention;

[0022] Figure 2 This is a scanning electron microscope image of the tooth desensitizer before and after blocking the dentinal tubules according to an embodiment of the present invention. DETAILED DESCRIPTION

[0023] The present invention is further described below with reference to specific examples, but the examples 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 art.

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

[0025] Example 1

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

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

[0028] First, collagen, lidocaine, calcium chloride, and sodium phosphate are added to purified water to disperse and dissolve to obtain a uniform solution; then glutaraldehyde is added to the above uniform solution and dispersed evenly to obtain a mixed solution; then the mixed solution is added to 100g of dichloromethane, and a homogenizer is used to homogenize and stir for 2 hours at a homogenization rate of 12000r / min. The dichloromethane is removed by a vacuum rotary evaporator to obtain cross-linked nanoparticles, and finally the cross-linked nanoparticles are freeze-dried to obtain a tooth desensitizer sample.

[0029] Example 2

[0030] This embodiment provides a tooth desensitizing agent that can cure tooth sensitivity, and the specific preparation method is as follows:

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

[0032] First, collagen, lidocaine, calcium chloride, and sodium phosphate are added to purified water to disperse and dissolve to obtain a uniform solution; then glutaraldehyde is added to the above uniform solution and dispersed evenly to obtain a mixed solution; then the mixed solution is added to 100g of dichloromethane, and a homogenizer is used to homogenize and stir for 1 hour at a homogenization rate of 10000r / min. The dichloromethane is removed by a vacuum rotary evaporator to obtain cross-linked nanoparticles, and finally the cross-linked nanoparticles are freeze-dried to obtain a tooth desensitizer sample.

[0033] Example 3

[0034] This embodiment provides a tooth desensitizing agent that can cure tooth sensitivity, and the specific preparation method is as follows:

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

[0036] First, collagen, lidocaine, calcium chloride, and sodium phosphate are added to purified water to disperse and dissolve to obtain a uniform solution; then glutaraldehyde is added to the above uniform solution and dispersed evenly to obtain a mixed solution; then the mixed solution is added to 100g of dichloromethane, and a homogenizer is used to homogenize and stir for 3 hours at a homogenization rate of 13000r / min. The dichloromethane is removed by a vacuum rotary evaporator to obtain cross-linked nanoparticles, and finally the cross-linked nanoparticles are freeze-dried to obtain a tooth desensitizer sample.

[0037] Example 4

[0038] This embodiment provides a tooth desensitizing agent that can cure tooth sensitivity, and the specific preparation method is as follows:

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

[0040] First, collagen, lidocaine, calcium chloride, and sodium phosphate are added to purified water to disperse and dissolve to obtain a uniform solution; then glutaraldehyde is added to the above uniform solution and dispersed evenly to obtain a mixed solution; then the mixed solution is added to 100g of dichloromethane, and a homogenizer is used to homogenize and stir for 4 hours at a homogenization rate of 11000r / min. The dichloromethane is removed by a vacuum rotary evaporator to obtain cross-linked nanoparticles, and finally the cross-linked nanoparticles are freeze-dried 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, the amount of glutaraldehyde used is 3.5 g, and the other components and preparation method are the same as Example 1.

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

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

[0044] Comparative Example 4 is the same as Example 1, except that the amount of lidocaine used is 3.5 g, the amount of purified water used is 68.5 g, and the other components and preparation method are the same as 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, the amount of purified water used is 81 g, and the remaining components and preparation method are the same as 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, the amount of purified water used is 58 g, and the remaining components and preparation method are the same as 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 method are the same as 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 method are the same as 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 method are the same as Example 1.

[0050] The materials used in the embodiments and comparative examples are shown in Table 1.

[0051] Table 1 Materials used in each embodiment and comparative example

[0052]

[0053]

[0054] The samples of Examples 1-4 and Comparative Examples 1-9 were selected to evaluate the nanoparticle sample size, drug release capacity, dentin tubule blocking rate, and desensitization effectiveness of the subjects.

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

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

[0057] Drug release capacity: The nano drug is prepared into a concentration of 5% with artificial saliva and placed in an environment of 37°C. The release ratio of lidocaine is detected and analyzed by ultraviolet spectrophotometer at the 12th hour node, which should be no less than 70%.

[0058] Dentin tubule blocking rate: According to the standard "YY / T 1829-2022 Dentistry Dentin Tubule Blocking Effect In Vitro Evaluation Method", prepare the human dentin slice test sample in advance, and then mix the samples of Examples 1-4 and Comparative Examples 1-9 with purified water to a concentration of 5%. Immerse the human dentin slice test sample in the mixed solution, take out the human dentin slice after 5 minutes, rinse the surface of the human dentin slice with purified water, and immerse it in artificial saliva for preservation; repeat the above operation twice a day for a total of 14 days. After 14 days, observe the dentinal tubule blocking of the human dentin slice sample by scanning electron microscopy, and calculate the blocking rate. The purpose of this test is to simulate the product use process and observe the blocking effect of the product on the dentinal tubules. Dental tubule blocking rate = (n0-n1) / n0×100%. n0 is the number of open dental tubules in the control group; n1 is the number of unblocked dental tubules in the experimental group.

[0059] The occlusion rate of dentinal tubules should be no less than 80%.

[0060] Desensitization effectiveness of subjects:

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

[0062] Usage: Volunteers need to clean their mouths and teeth before trying the product. Before using the product, prepare the tooth desensitizing nanoparticles with purified water into a 5% concentration (mass fraction) aqueous solution, mix well and apply to sensitive parts of the teeth. After keeping it for 5 minutes, rinse your mouth and remove the product. Use it once in the morning and evening every day for 15 consecutive days. Professionals will score the trial effect to evaluate the immediate desensitization effect of the product, the tooth desensitization effect on the 15th day, and the recurrence after stopping treatment for 1 month.

[0063] The efficacy indicators are defined as follows:

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

[0065] Invalid: Other cases are considered invalid.

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

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

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

[0069]

[0070]

[0071] Table 3: Comparison of the results of the examples and the comparative examples

[0072]

[0073]

[0074]

[0075] Figure 1 This is a picture of the tooth desensitizer nanoparticles synthesized in an embodiment of the present invention. After freeze-drying, the particles are in the form of white powder. When used, they are prepared with an aqueous solution and then applied to 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 to directly act on the dental nerves for immediate desensitization. The collagen and calcium phosphate in the solution are biomineralized in situ to block the dentinal tubules, achieving a complete cure for tooth sensitivity. Figure 2 Scanning electron microscope images of dentinal tubule occlusion before and after use.

[0076] Nanoparticles that are too large or too small will affect the desensitization effect. Nanoparticles larger than 200 nm are not conducive to the entry of nanoparticles into the dentinal tubules, and nanoparticles smaller than 50 nm are not conducive to the retention of nanoparticles in the dentinal tubules.

[0077] It can be seen from the above-mentioned embodiments and comparative examples that the dosage and ratio of collagen and glutaraldehyde will affect the size of the nanoparticles synthesized at last. Only when the concentration of collagen in the mixed solution is 2-4%, glutaraldehyde is 4-6%, and collagen: glutaraldehyde=1:1.3-2.5, can the nanoparticles of suitable size be cross-linked. The content of lidocaine will directly affect the immediate desensitization effect. If the dosage is too little, the drug release is small, and too much also has a certain effect on the particle size. The nanoparticles obtained when the concentration is 1-3wt% in the mixed solution have a better desensitization effect and are of suitable size. The addition of calcium chloride and sodium phosphate will affect the dentinal tubule blocking rate and the size of nanoparticles. During preparation, the mean rate and homogenization time will have an impact on the nanometer size synthesized at the most, thereby affecting the final desensitization effect.

[0078] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0079] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A tooth desensitizer capable of curing tooth sensitivity, characterized in that: The tooth desensitizing agent is nanoparticles, and its raw materials include 2 to 4 parts of collagen, 4 to 6 parts of glutaraldehyde, 1 to 3 parts of lidocaine, 5 to 15 parts of calcium chloride, and 5 to 15 parts of sodium phosphate, and the weight ratio of calcium chloride to sodium phosphate is 1:

1.

2. The tooth desensitizing agent according to claim 1, characterized in that, in parts by weight, it comprises 3 to 4 parts of collagen, 4 to 6 parts of glutaraldehyde, 2 to 3 parts of lidocaine, 8 to 15 parts of calcium chloride, and 8 to 15 parts of sodium phosphate.

3. The tooth desensitizing agent according to claim 1, characterized in that According to the mass ratio, the collagen: glutaraldehyde = 1: 1.3-2.

5. The tooth desensitizing agent according to claim 1 , wherein the diameter of the nanoparticles is 50 nm to 200 nm.

5. The method for preparing the tooth desensitizing agent according to any one of claims 1 to 4, characterized in that: Includes steps: First, collagen, lidocaine, calcium chloride and sodium phosphate are added to purified water for dispersion and dissolution to obtain a uniform solution; then glutaraldehyde is added to the uniform solution for uniform dispersion to obtain a mixed solution; then the mixed solution is added to dichloromethane for uniform dispersion, and finally the dichloromethane is removed and freeze-dried to obtain the tooth desensitizing agent.

6. The preparation method according to claim 5, characterized in that: In the mixed solution, according to weight percentage, the collagen content is 2% to 4%, the glutaraldehyde content is 4% to 6%, the lidocaine content is 1% to 3%, the calcium chloride content is 5% to 15%, the sodium phosphate content is 5% to 15%, and the balance is purified water; the weight ratio of the calcium chloride to the sodium phosphate is 1:

1.

7. The preparation method according to claim 5, characterized in that: According to the mass ratio, the collagen: glutaraldehyde = 1: 1.3-2.

5.

8. The preparation method according to claim 5, characterized in that: The mass ratio of the dichloromethane to the mixed solution is 1:

1.

9. The preparation method according to claim 5, characterized in that: The homogenization rate is 10000r / min to 13000r / min, and the homogenization time is ≥1h.

10. Use of the tooth desensitizing agent according to any one of claims 1 to 4 or the tooth desensitizing agent prepared by the preparation method according to any one of claims 5 to 9 in tooth desensitizing products.

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