A pulp capping agent with the functions of inflammation control and promotion of odontogenic differentiation and its preparation method

Abstract

The present invention belongs to the technical field of biomedical materials, and provides a pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation and a preparation method thereof. The pulp capping agent provided by the present invention comprises a powder and a liquid. The powder mainly comprises a magnesium-containing compound and a calcium phosphate mineral in a specific ratio, and the liquid is a citric acid aqueous solution with a specific concentration. The pulp capping agent provided by the present invention can release magnesium ions, promote the odontogenic differentiation of dental pulp stem cells, and is beneficial to the formation of reparative dentin; it can undergo a curing reaction to form a magnesium citrate chelate, enabling the paste to cure rapidly, with a short curing time, curing in 9-12 minutes, and can also increase the pH value near the dental pulp tissue to about 8 and maintain it for at least 18 days to control inflammation; the strength of the pulp capping agent after curing is increased, and the pulp capping agent can be used in a direct pulp capping agent, shortening the operation time and reducing the cost.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and more specifically, to a pulp capping agent with functions of inflammation control and promotion of odontogenic differentiation and a preparation method thereof. Background Art

[0002] The dental pulp is located in the center of the tooth and is composed of blood vessels, nerves and connective tissues, which plays an important role in maintaining the function of the tooth. First, the blood vessels in the dental pulp can provide moisture and nutrients for the tooth to prevent it from becoming brittle; second, the nerve tissue in the dental pulp enables the tooth to sense external pressure, temperature and pain; more importantly, the dental pulp can also respond to minor traumas and form reparative dentin to protect the dental pulp. However, when pulp exposure is caused by major traumas, deep caries or cavity preparation, etc., it is difficult for the dental pulp to spontaneously form reparative dentin, and it will also develop into pulpitis, resulting in the destruction of the dental pulp tissue.

[0003] Direct pulp capping is an effective method to maintain the vitality of the dental pulp after pulp exposure. Its principle is to directly place the pulp capping agent on the exposed pulp site to control inflammation and promote the formation of reparative dentin. Calcium hydroxide has always been considered the "gold standard" of pulp capping agents. After being used for pulp capping, it causes the pH value at the pulp exposure site to increase (generally controlled at about 12), resulting in superficial pulp necrosis, and then reparative dentin gradually forms under the necrotic tissue. However, due to the slow dissolution of calcium hydroxide, oral bacteria are likely to invade the dental pulp tissue along the dissolution pores, causing pulpitis or pulp necrosis. In recent years, some new pulp capping agents have emerged, such as Mineral Trioxide Aggregate (MTA) and bio-ceramic materials (I Root repair materials Bioaggregate Putty, iRootBP), both of which have excellent therapeutic effects and have replaced calcium hydroxide in clinical applications. It is reported that the mechanism of iRootBP promoting the formation of reparative dentin is similar to that of calcium hydroxide. The clinical efficacy of iRootBP is better than that of MTA, and the operation is more convenient. It is a more ideal pulp capping agent in clinical practice (Zhou Jin, Wang Ding. Study on the clinical effects and influencing factors of direct pulp capping with iRootBP Plus and MTA [J]. Journal of Clinical Stomatology, 2020(3):3; Huang Weiman, Zhang Dongjie, Hu Xuchu, et al. Clinical efficacy observation of iRootBP Plus and MTA for direct pulp capping of young permanent teeth [J]. Chinese Journal of Stomatological Research: Electronic Edition, 2017, 11(6):5.). However, iRootBP is slightly soluble in water, and it is inevitable that external bacteria will invade due to dissolution. Moreover, the setting time of iRootBP is relatively long (about 350 min), resulting in too long operation time. The high price of iRootBP increases the economic burden on patients and limits its wide application.

[0004] To shorten the setting time of pulp capping agents, existing patents have reported achieving the goal of shortening the setting time by using photo-curing. For example, bioactive glass / photo-curing resin composite pulp capping agents can be photo-cured within 60 s (Chinese Patent CN110859755A); notoginsenoside / methyl methacrylate gelatin composite pulp capping agents can be photo-cured within 5 min (Chinese Patent CN112569122A). However, the incompletely cured components or photo-curing agents in the above pulp capping agents have cytotoxicity. If leakage occurs, it will cause pulp inflammation (Arakawa, M., et al. Direct pulp capping with an auto-cured sealant resin and a self-etching primer. American journal of dentistry, 2003, 16: 61-65). Magnesium phosphate cement (MPC) composed of magnesium oxide and ammonium dihydrogen phosphate solution has the characteristics of rapid setting and provides a relatively high alkaline environment, which is beneficial to inflammation control. However, the setting time of MPC is too fast (about 3 min), and it is easy to set before being coated on the pulp to be repaired, resulting in inability to fill, which is not conducive to clinical application (Yu, S., et al. Magnesium phosphate based cement with improved setting, strength and cytocompatibility properties by adding Ca(H 2 PO 4 ) 2 ·H 2 O and citric acid. Journal of the Mechanical Behavior of Biomedical Materials, 2019, 91: 229-236).

[0005] Therefore, in view of the above problems in existing pulp treatments, it is necessary to develop a new type of pulp capping agent that can be used in direct pulp capping, which can not only provide an alkaline environment with an appropriate alkalinity (pH value 8-10), control inflammation and promote the formation of reparative dentin, avoid the invasion of external bacteria into the pulp tissue due to dissolution, but also cure within a suitable time (10 ± 2 minutes), shorten the operation time and reduce the cost. Summary of the Invention

[0006] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. For this purpose, the present invention provides a pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation and a preparation method thereof. The pulp capping agent provided by the present invention can make the pH value of the surrounding environment reach about 8 within no more than 6 hours after use and maintain it for at least 18 days. It can increase the alkalinity in the pulp surrounding tissue in a short time and play an anti-inflammatory role. It can promote the odontogenic differentiation of dental pulp stem cells by increasing the pH value and releasing magnesium ions. It can be used in direct pulp capping. The setting time is short, and it can be set within 9 - 12 minutes. The strength after setting is increased, which can avoid the invasion of external bacteria into the pulp tissue due to dissolution.

[0007] The first aspect of the present invention provides a pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation.

[0008] Specifically, a pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation includes a powder and a liquid;

[0009] The powder includes a magnesium-containing compound and a calcium phosphate mineral;

[0010] The liquid includes an aqueous citric acid solution;

[0011] The mass of the magnesium-containing compound accounts for 20 - 50% of the total mass of the powder;

[0012] The mass of the calcium phosphate mineral accounts for 50 - 80% of the total mass of the powder;

[0013] The concentration of the aqueous citric acid solution is 1 - 3 mol / L;

[0014] The solid-liquid ratio of the pulp capping agent is 0.5 - 10 g / mL.

[0015] The pulp capping agent provided by the present invention comprises a powder and a liquid. The powder mainly selects magnesium-containing compounds and calcium phosphate minerals with specific mass ratios, and the liquid mainly selects a citric acid aqueous solution with a specific concentration. The magnesium-containing compound can undergo a chelation reaction with the citric acid aqueous solution for curing, shortening the curing time, and can be cured within 9 - 12 minutes; the magnesium-containing compound can release magnesium ions, promoting the odontogenic differentiation of dental pulp stem cells and forming reparative dentin; the magnesium-containing compound is greatly in excess relative to citric acid, and the excess magnesium-containing compound can continue to react with hydrogen ions in the solution to generate magnesium ions and hydroxide ions. Since there are no additional hydrogen ions for the hydroxide ions to neutralize at this time, the solution will be alkaline. A part of the hydroxide ions combines with magnesium ions to form strongly alkaline magnesium hydroxide, which can increase the pH value around the exposed dental pulp and control inflammation. Moreover, the calcium phosphate mineral can gradually solidify to form hydroxyapatite in an alkaline environment, and the formation of a new phase will increase the density of the system, thereby contributing to improving the strength of the pulp capping agent after curing. The present invention uses a citric acid aqueous solution with a specific concentration to generate magnesium citrate chelate through a chelation reaction with metal cations in the magnesium-containing compound, promoting the curing of the pulp capping agent and controlling the curing time within a suitable range, so that it will not harden before the pulp capping agent is placed on the pulp to be repaired and cannot be filled, nor will it affect the surgical process due to too slow curing. The pulp capping agent of the present invention has good clinical application potential.

[0016] Preferably, the mass of the magnesium-containing compound accounts for 20 - 40% of the total mass of the powder.

[0017] More preferably, the mass of the magnesium-containing compound accounts for 21 - 40% of the total mass of the powder.

[0018] Preferably, the mass of the calcium phosphate mineral accounts for 60 - 80% of the total mass of the powder.

[0019] More preferably, the mass of the calcium phosphate mineral accounts for 60 - 79% of the total mass of the powder.

[0020] Preferably, the concentration of the citric acid aqueous solution is 1.5 - 3 mol / L.

[0021] More preferably, the concentration of the citric acid aqueous solution is 1.5 - 2.5 mol / L.

[0022] Further preferably, the concentration of the citric acid aqueous solution is 1.5 - 2 mol / L.

[0023] Preferably, the magnesium-containing compound is one or more of magnesium oxide, magnesium hydroxide, and magnesium salts.

[0024] More preferably, the magnesium-containing compound is magnesium oxide.

[0025] Preferably, the magnesium oxide is magnesium oxide particles and / or magnesium oxide powder.

[0026] More preferably, the magnesium oxide is magnesium oxide particles or powder obtained by sintering a magnesium oxide precursor.

[0027] Preferably, the magnesium oxide precursor is basic magnesium carbonate.

[0028] Preferably, the magnesium oxide is light magnesium oxide and / or heavy magnesium oxide.

[0029] Preferably, the magnesium hydroxide is magnesium hydroxide particles and / or magnesium hydroxide powder.

[0030] Preferably, the magnesium salt is one or more of magnesium carbonate, magnesium chloride, and magnesium nitrate.

[0031] Preferably, the calcium phosphate mineral is hydroxyapatite and / or calcium phosphate salt.

[0032] Preferably, the calcium phosphate mineral is calcium phosphate salt.

[0033] Preferably, the calcium phosphate salt is one or more of tricalcium phosphate, tetracalcium phosphate, and calcium hydrogen phosphate.

[0034] Preferably, the tricalcium phosphate is α-tricalcium phosphate and / or β-tricalcium phosphate.

[0035] Preferably, the calcium hydrogen phosphate is anhydrous calcium hydrogen phosphate and / or dicalcium phosphate dihydrate. Calcium hydrogen phosphate is slightly soluble in water and difficult to directly react with citric acid. The main function of calcium hydrogen phosphate is to generate hydroxyapatite in an alkaline environment.

[0036] Preferably, the solid-liquid ratio of the pulp capping agent is 0.5 - 7.5 g / mL.

[0037] Preferably, the pH value of the pulp capping agent is 8 - 10.

[0038] More preferably, the pH value of the pulp capping agent is 8.6 - 9.8.

[0039] Preferably, the pulp capping agent is in a paste form. The preparation in paste form is more convenient for clinical use.

[0040] The second aspect of the present invention provides a method for preparing a pulp capping agent having the functions of inflammation control and promoting odontogenic differentiation.

[0041] A method for preparing a pulp capping agent having the functions of inflammation control and promoting odontogenic differentiation, comprising the following steps:

[0042] Mix the powder and the liquid into a slurry to obtain the pulp capping agent.

[0043] Preferably, before use, the magnesium-containing compound further includes being pre-screened through a sieve with a pore size of 90 - 110 μm.

[0044] Preferably, before use, the calcium phosphate mineral further includes being pre-screened through a sieve with a pore size of 90 - 110 μm.

[0045] The third aspect of the present invention provides an application of a pulp capping agent having the functions of inflammation control and promoting odontogenic differentiation.

[0046] An application of a pulp capping agent having the functions of inflammation control and promoting odontogenic differentiation in the preparation of biomedical materials.

[0047] Preferably, the biomedical material is a dental biomedical material.

[0048] Preferably, the dental biomedical material is a dental biomedical material for direct pulp capping.

[0049] Preferably, the direct pulp capping is to place the pulp capping agent on the pulp to be treated, compact it, and cure it.

[0050] Preferably, the curing time is 9 - 12 min.

[0051] Preferably, after curing, the pulp to be treated is sequentially filled with an acid etchant and a light-curing resin. The acid etchant and the light-curing resin help to protect the pulp capping agent from external erosion.

[0052] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0053] (1) The pulp capping agent provided by the present invention includes a powder and a liquid. The powder mainly includes a magnesium-containing compound and a calcium phosphate mineral in a specific ratio, and the liquid includes a citric acid aqueous solution. The curing time of the pulp capping agent provided by the present invention is short, and curing can be completed in 9 - 12 min. Compared with the commonly used iRootBP in clinical practice, the curing time is greatly shortened. It can increase the pH value near the pulp tissue and maintain it at about 8 for at least 18 days, effectively controlling inflammation. The calcium phosphate mineral in the pulp capping agent gradually cures to form hydroxyapatite in an alkaline environment, which helps to improve the strength of the cured pulp capping agent;

[0054] (2) The preparation method of the pulp capping agent provided by the present invention is simple and easy to operate, the raw materials are easily available, and the preparation cost is low, which helps to reduce the economic burden on patients. Moreover, the prepared pulp capping agent is in a paste form, which is more convenient for clinical use;

[0055] (3) The prepared pulp capping agent of the present invention can be used in the preparation of biomedical materials, can be used in direct pulp capping for the treatment of the pulp, forms reparative dentin at the exposed part of the pulp, has the functions of inflammation control and promoting odontogenic differentiation, and can also shorten the operation time. Brief Description of the Drawings

[0056] Figure 1Appearance diagram of the pulp capping agent of Example 1 and Comparative Example 5 of the present invention;

[0057] Figure 2 Comparison diagram of the setting times of the pulp capping agents of Example 1 and Comparative Example 5 of the present invention;

[0058] Figure 3 Trend diagram of the pH value change after the pulp capping agents of Example 1 and Comparative Example 5 of the present invention are placed in high - glucose complete medium (DMEM);

[0059] Figure 4 Flow chart of the pulp capping agents of Example 1 and Comparative Example 5 of the present invention for direct pulp capping in rats;

[0060] Figure 5 Masson staining photographs 4 weeks after the pulp capping agents of Example 1 and Comparative Example 5 of the present invention are used for direct pulp capping in rats. Detailed implementation manners

[0061] In order to make those skilled in the art more clearly understand the technical solutions described in the present invention, the following examples are listed for illustration. It should be noted that the following examples do not limit the scope of protection required by the present invention.

[0062] Unless otherwise specified, the raw materials, reagents or devices used in the following examples can be obtained from conventional commercial channels or can be obtained by existing known methods.

[0063] Example 1

[0064] A pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation, comprising a powder and a liquid;

[0065] The powder, by mass percentage, comprises 21% magnesium oxide and 79% calcium hydrogen phosphate dihydrate;

[0066] The liquid is a 1.5 mol / L aqueous citric acid solution.

[0067] The preparation method of the above - mentioned pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation comprises the following steps:

[0068] (1) Take magnesium oxide and calcium hydrogen phosphate dihydrate according to the ratio, mix them evenly to obtain a powder, and set it aside;

[0069] (2) Prepare a 1.5 mol / L aqueous citric acid solution and set it aside;

[0070] (3) Weigh 0.1 g of magnesium oxide / calcium hydrogen phosphate dihydrate composite powder, then add 200 μL of aqueous citric acid solution (solid - liquid ratio is 0.5 g / mL), mix evenly to form a white paste, which is the pulp capping agent (or called the novel pulp capping agent). As Figure 1As shown, the new pulp capping agent is a paste, similar to iRoot BP, with a pH value of about 8.6. Among them, Figure 1 In this, "paste" means a paste.

[0071] Example 2

[0072] A pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation, comprising a powder and a liquid;

[0073] The powder, calculated by mass percentage, includes 25% magnesium oxide, 10% magnesium hydroxide, 5% magnesium nitrate, 50% dicalcium hydrogen phosphate dihydrate, and 10% hydroxyapatite;

[0074] The liquid is a 2mol / L aqueous citric acid solution.

[0075] The preparation method of the above-mentioned pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation includes the following steps:

[0076] (1) Take magnesium oxide, magnesium hydroxide, magnesium nitrate, dicalcium hydrogen phosphate dihydrate, and hydroxyapatite according to the ratio, mix them evenly to obtain a powder, and set aside after mixing evenly;

[0077] (2) Prepare a 2mol / L aqueous citric acid solution for later use;

[0078] (3) Weigh 0.1g of the powder, then add 40μL of the aqueous citric acid solution (the solid-liquid ratio is 2.5g / mL), and mix evenly to form a white paste with a pH value of 8.9.

[0079] Example 3

[0080] A pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation, comprising a powder and a liquid;

[0081] The powder, calculated by mass percentage, includes 30% magnesium oxide, 5% magnesium hydroxide, 5% magnesium carbonate, 50% dicalcium hydrogen phosphate dihydrate, and 10% α-tricalcium phosphate;

[0082] The liquid is a 2.5mol / L aqueous citric acid solution.

[0083] The preparation method of the above-mentioned pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation includes the following steps:

[0084] (1) Take magnesium oxide, magnesium hydroxide, magnesium carbonate, dicalcium hydrogen phosphate dihydrate, and α-tricalcium phosphate according to the ratio, mix them evenly to obtain a powder, and set aside;

[0085] (2) Prepare a 2.5mol / L aqueous citric acid solution for later use;

[0086] (3) Weigh 0.1 g of the powder, then add 20 μL of citric acid aqueous solution (solid-liquid ratio is 5 g / mL), mix evenly to form a white paste with a pH value of 9.3.

[0087] Example 4

[0088] A pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation, comprising a powder and a liquid;

[0089] By mass percentage, the powder includes 45% magnesium oxide, 5% magnesium chloride, 40% calcium hydrogen phosphate dihydrate, and 10% tetracalcium phosphate;

[0090] The liquid is a 3 mol / L citric acid aqueous solution.

[0091] The preparation method of the above pulp capping agent with the functions of inflammation control and promoting odontogenic differentiation includes the following steps:

[0092] (1) Take magnesium oxide, magnesium chloride, calcium hydrogen phosphate dihydrate, and tetracalcium phosphate according to the ratio and place them in a 5 mL centrifuge tube, mix evenly to obtain the powder;

[0093] (2) Weigh 0.57 g of citric acid and place it in a 5 mL centrifuge tube, then add 1 mL of deionized water, dissolve it fully to obtain a 3 mol / L citric acid aqueous solution for standby;

[0094] (3) Weigh 0.1 g of the powder, then add 10 μL of citric acid aqueous solution (solid-liquid ratio is 10 g / mL), mix evenly to form a white paste with a pH value of 9.8.

[0095] Comparative Example 1

[0096] A pulp capping agent includes a powder and a liquid. The powder is a composite powder of magnesium oxide, calcium hydrogen phosphate dihydrate, and hydroxyapatite, and the liquid is a 0.5 mol / L citric acid aqueous solution.

[0097] The preparation method of the above pulp capping agent includes the following steps:

[0098] (1) Prepare a composite powder of magnesium oxide / calcium hydrogen phosphate dihydrate / hydroxyapatite (the mass ratio of magnesium oxide is 30%, the mass ratio of calcium hydrogen phosphate dihydrate is 50%, and the mass ratio of hydroxyapatite is 20%), mix evenly for standby;

[0099] (2) Prepare a 0.5 mol / L citric acid aqueous solution for standby;

[0100] (3) Weigh 0.1 g of the powder, then add 40 μL of citric acid aqueous solution (solid-liquid ratio is 2.5 g / mL), mix evenly.

[0101] Comparative Example 2

[0102] A pulp capping agent comprises a powder and a liquid. The powder is a composite powder of magnesium oxide, calcium hydrogen phosphate dihydrate, and hydroxyapatite, and the liquid is a 4 mol / L aqueous citric acid solution.

[0103] The preparation method of the above pulp capping agent comprises the following steps:

[0104] (1) Prepare a composite powder of magnesium oxide / calcium hydrogen phosphate dihydrate / hydroxyapatite (the mass percentage of magnesium oxide is 30%, and the mass percentage of calcium hydrogen phosphate dihydrate is 70%), mix evenly and set aside;

[0105] (2) Prepare a 4 mol / L aqueous citric acid solution and set aside;

[0106] (3) Weigh 0.1 g of the powder, then add 40 μL of the aqueous citric acid solution (the solid-liquid ratio is 2.5 g / mL), and mix evenly.

[0107] Comparative Example 3

[0108] A pulp capping agent comprises a powder and a liquid. The powder is a composite powder of magnesium oxide, calcium hydrogen phosphate dihydrate, and hydroxyapatite, and the liquid is a 1.5 mol / L aqueous citric acid solution.

[0109] The preparation method of the above pulp capping agent comprises the following steps:

[0110] (1) Prepare a composite powder of magnesium oxide / calcium hydrogen phosphate dihydrate / hydroxyapatite (the mass proportion of magnesium oxide is 15%, the mass proportion of calcium hydrogen phosphate dihydrate is 55%, and the mass proportion of hydroxyapatite is 30%), mix evenly and set aside;

[0111] (2) Prepare a 1.5 mol / L aqueous citric acid solution and set aside;

[0112] (3) Weigh 0.1 g of the powder, then add 40 μL of the aqueous citric acid solution (the solid-liquid ratio is 2.5 g / mL), and mix evenly. After testing, the pH of the pulp capping agent paste is 6.5.

[0113] Comparative Example 4

[0114] A pulp capping agent comprises a powder and a liquid. The powder is a composite powder of magnesium oxide, calcium hydrogen phosphate dihydrate, and hydroxyapatite, and the liquid is a 1.5 mol / L aqueous citric acid solution.

[0115] The preparation method of the above pulp capping agent comprises the following steps:

[0116] (1) Prepare a composite powder of magnesium oxide / calcium hydrogen phosphate dihydrate / hydroxyapatite (the mass proportion of magnesium oxide is 55%, the mass proportion of calcium hydrogen phosphate dihydrate is 35%, and the mass proportion of hydroxyapatite is 10%), mix evenly and set aside;

[0117] (2) Prepare a citric acid aqueous solution with a concentration of 1.5 mol / L for later use;

[0118] (3) Weigh 0.1 g of the powder, then add 40 μL of the citric acid aqueous solution (the solid-liquid ratio is 2.5 g / mL), and mix evenly.

[0119] Comparative Example 5

[0120] Commercially available pulp capping agent iRootBP.

[0121] Application Example

[0122] Respectively use the above-prepared pulp capping agents for direct pulp capping of rats. The operation steps are as follows:

[0123] 1. Material implantation: Use a bur to prepare the first molar of the rat, and expose the dental pulp using a K-file; Set up a blank group, an iRootBP group, and a novel pulp capping agent group. Among them, no treatment is given to the blank group, the iRootBP group is filled with iRootBP of Comparative Example 5, and the novel pulp capping agent group is filled with the pulp capping agents prepared in Examples 1-4 respectively, and compacted with a filling instrument;

[0124] 2. Acid etching: Use an acid etchant to treat the crown and dentin around the pulp exposure site;

[0125] 3. Acid etchant removal: Remove the acid etchant;

[0126] 4. Resin sealing: Fill with light-curing resin, and after 30 s under ultraviolet light, the resin is cured.

[0127] The above operation process is as Figure 4 shown, and successively includes the steps of pulp capping agent material implantation - acid etching - acid etchant removal - resin sealing.

[0128] Product effect test

[0129] 1. Curing time and pH value of the pulp capping agent

[0130] The process for measuring the curing time: After the pulp capping agent slurry is mixed evenly, insert a needle of a certain weight vertically into the slurry every 5 min. If the distance that the needle enters the slurry is less than 1 mm, it is determined that the slurry has been cured at this time, and the time used at this moment is the curing time of the slurry.

[0131] Fill the white slurry formed in Example 1 into a circular mold and measure the curing time. The results are as Figure 2 shown. Among them, Figure 2 the Setting time is the curing time. From Figure 2It can be seen that the setting time of the pulp capping agents prepared in Examples 1-4 of the present invention is 9-12 minutes, which is much shorter than the setting time (350 min) of the iRootBP pulp capping agent in Comparative Example 5. The setting times and pH values of the pulp capping agents prepared in the above examples and comparative examples are summarized in Table 1.

[0132] Table 1 Setting times and pH values of the pulp capping agents prepared in each example and comparative example

[0133]

[0134]

[0135] From the results of the above table, it can be seen that the setting time of Examples 1-4 of the present invention is controlled at about 10 min. By adding calcium hydrogen phosphate dihydrate, the present invention controls the setting time within a suitable range. Moreover, the shortening of the setting time can also reflect, indirectly, the improvement of the strength of the pulp capping agent (mainly referring to the ability of the pulp capping agent to resist external pressure deformation), that is, the denseness of the pulp capping agent is improved. However, the pulp capping agents prepared in Comparative Example 1 and Comparative Example 4 set too quickly, which is not conducive to clinical operation. In addition, the pH value of the pulp capping agent of the present application is alkaline, which can provide an alkaline environment and promote the formation of reparative dentin.

[0136] 2. The pulp capping agent provides an alkaline environment

[0137] To verify whether the pulp capping agent can increase the pH value of the environment, the same volume of the novel pulp capping agent (i.e., the pulp capping agent prepared in Example 1) and iRootBP were placed in 10 mL of DMEM medium with a pH value of 7.4 and incubated in an environment at 37 °C. The pH value of the solution was measured at different times, and the results are as Figure 3 shown, where Figure 3The pH Value is the pH value, Time is the time, and day is the number of days. As can be seen from the figure, the pH values of the pulp capping agent prepared in Example 1 and the iRootBP solution both reached about 8.3 after 6 h. However, subsequently, the pH value of the iRootBP solution gradually increased and reached the highest at the 17th day, about 12. Although the inflammation can be controlled in this alkaline environment, it also causes the immediate death of inflammatory cells and fails to exert the functions of angiogenesis and tissue reconstruction of inflammatory cells (moderate inflammation is beneficial to angiogenesis and tissue reconstruction). The pH value in the solution of the novel pulp capping agent group reached the highest at 24 h, about 8.6, and basically remained at about 8 within the subsequent 17 days. This indicates that compared with the iRootBP pulp capping agent in Comparative Example 1, the pulp capping agent provided by the present invention provides a moderate alkaline environment, in which this alkaline environment will not immediately cause the death of inflammatory cells, but while moderately controlling inflammation, utilizes the tissue reconstruction function of inflammatory cells to repair the pulp tissue and is also beneficial to the formation of reparative dentin. Moreover, the pulp capping agent of the present invention maintains the pH value at about 8 for a longer time, at least 18 days.

[0138] 3. To evaluate the formation of reparative dentin after using different pulp capping agents, the operation steps are as follows:

[0139] (1) Anesthetize the rats by intraperitoneal injection of a 4% chloral hydrate solution, and then use a high-speed dental handpiece equipped with a 1 / 2 round bur to grind off the enamel and dentin in the middle of the first maxillary molar of the rats to expose the pulp.

[0140] (2) Fill the prepared pulp capping agent at the pulp exposure site; wait for it to solidify, apply the acid etchant around the first molar; after 30 s, wipe off the acid etchant with a cotton ball, then evenly apply the adhesive, and irradiate with an ultraviolet lamp for 20 s; finally, apply the light-curing resin on the surface of the adhesive and irradiate with an ultraviolet lamp for 30 s.

[0141] (3) After 4 weeks, sacrifice the rats and collect the first molars of the rats.

[0142] (4) Perform rapid decalcification treatment on the first molars.

[0143] (5) Dehydrate the decalcified molars step by step (successively using ethanol aqueous solutions with ethanol volume percentages of 15%, 30%, 50%, 70%, 80%, 95%, and 100%), make them transparent, infiltrate with paraffin, and then perform paraffin embedding.

[0144] (6) Perform paraffin sectioning and Masson staining, and take pictures. The results are as Figure 5 shown, where the black arrow indicates the position of the pulp opening; the black square indicates the formation of reparative dentin near the pulp opening; the light square indicates the calcification of the pulp part.

[0145] It can be seen from Figure 5 the results that the sizes of the pulp chamber openings in the three experimental groups are close. As shown by the black arrows, obvious dentin-like tissues appear near the pulp chamber openings in the new pulp capping agent group (i.e., the pulp capping agent prepared in Example 1), while the dentin-like tissues in the iRootBP group are not fully formed (as shown by the black square), indicating that the new pulp capping agent has a better effect on promoting the formation of reparative dentin. In addition, obvious pulp tissue calcification appears in the blank group (as shown by the light-colored square), while the pulp tissues in the new pulp capping agent group and the iRootBP group are normal, which indicates that both the new pulp capping agent group and the iRootBP group effectively control the inflammatory reaction and inhibit the pulp calcification caused by pulp inflammation. Among them Figure 5 Blank is the blank group.

[0146] The pulp capping agents prepared in Examples 2-4 of the present invention have a treatment inflammatory effect equivalent to that of the pulp capping agent in Example 1, as well as a function of promoting odontogenic differentiation.

[0147] The acidic solution used in the present invention is an aqueous citric acid solution. The chelation of citric acid with metal cations is mainly utilized. Citric acid reacts with magnesium-containing compounds such as magnesium oxide to form magnesium citrate chelate, which accelerates the curing of the pulp capping agent. However, in Comparative Examples 1 and 2, aqueous citric acid solutions with too low and too high concentrations were used respectively, resulting in too fast or too slow curing of the pulp capping agent.

[0148] Magnesium oxide, one of the powder components of the pulp capping agent of the present invention, is used in a much larger amount relative to citric acid to ensure that in addition to reacting with citric acid, magnesium hydroxide can also be generated to provide an alkaline environment to control inflammation. It can be seen from the results of Comparative Example 3 and Comparative Example 4 that too little or too much amount of magnesium oxide cannot provide a suitable alkaline environment or curing time.

[0149] Moreover, the pulp capping agent of the present invention forms hydroxyapatite that is insoluble in water after curing. Hydroxyapatite is similar to the inorganic components of dentin, so it can be tightly combined and will not dissolve slowly, avoiding the invasion of external bacteria into the pulp tissue.

Claims

1. A pulp capping agent, characterized in that, it is composed of a powder and a liquid; the powder is composed of a magnesium-containing compound and a calcium phosphate mineral; the liquid is an aqueous citric acid solution; the mass of the magnesium-containing compound accounts for 20-50% of the total mass of the powder; the mass of the calcium phosphate mineral accounts for 50-80% of the total mass of the powder; the concentration of the aqueous citric acid solution is 1.5-3 mol / L; the solid-liquid ratio of the pulp capping agent is 0.5-10 g / mL.

2. The pulp capping agent according to claim 1, characterized in that, the magnesium-containing compound is one or more of magnesium oxide, magnesium hydroxide, and magnesium salts.

3. The pulp capping agent according to claim 1, characterized in that, the calcium phosphate mineral is hydroxyapatite and / or calcium phosphate salt, and the calcium phosphate salt is one or more of tricalcium phosphate, tetracalcium phosphate, and calcium hydrogen phosphate.

4. The pulp capping agent according to claim 1, characterized in that, the mass of the magnesium-containing compound accounts for 20-40% of the total mass of the powder.

5. The pulp capping agent according to claim 1, characterized in that, the mass of the calcium phosphate mineral accounts for 60-80% of the total mass of the powder.

6. The pulp capping agent according to claim 1, characterized in that, the solid-liquid ratio of the pulp capping agent is 0.5-7.5 g / mL.

7. The pulp capping agent according to claim 1, characterized in that, the pH value of the pulp capping agent is 8-10.

8. A preparation method of the pulp capping agent according to any one of claims 1-7, characterized in that, it includes the following steps: Mix the powder and the liquid into a slurry to obtain the pulp capping agent.

9. Use of the pulp capping agent according to any one of claims 1-7 in the preparation of biomedical materials.

Images