Amorphous calcium phosphate gel and its preparation method and application

Abstract

The embodiment of the present invention discloses an amorphous calcium phosphate gel and a preparation method and application thereof. The method comprises: adding aminomethyl propanol to a propylene glycol solution containing a calcium source to obtain a mixed solution; slowly adding a phosphoric acid solution to the mixed solution to obtain an amorphous calcium phosphate gel. The amorphous calcium phosphate gel provided by the present invention has excellent stability, and no obvious phase change occurs after being placed at room temperature for 12 months; no toxic or harmful reagents are used in the preparation process, the production process is safe and environmentally friendly, and the safety of the product is also guaranteed; the method and process are simple, and the large-scale production of the product can be realized, providing a basis for the wide application of amorphous calcium phosphate gel in oral care.

Description

Technical Field

[0001] The embodiments of the present invention relate to the field of oral care technology, and specifically to an amorphous calcium phosphate gel and a preparation method and application thereof. Background Art

[0002] Tooth tissues include three calcified hard tissues, namely enamel, dentin and cementum, and one soft tissue, dental pulp. Enamel is the hardest component of tooth tissues, covering the entire outer layer of the crown, and is the first line of defense for the entire tooth tissue against external damage. Inorganic matter accounts for 96-97% of the total weight of enamel, organic matter accounts for 0.4-0.9%, and water accounts for 3.6-2.1%. Inorganic matter mainly exists in the form of hydroxyapatite crystals.

[0003] Tooth tissue is exposed to the oral cavity for a long time, and is subjected to long-term immersion in saliva and plaque, as well as long-term consumption of acidic foods and drinks, which will cause the enamel on the surface of the teeth to be eroded and demineralized. Enamel erosion is mainly due to the fact that the hydroxyapatite crystals, the main component of enamel, are in a dynamic equilibrium of dissolution and redeposition when immersed in saliva or beverages, where the dissolution rate depends on the pH value of the contact liquid and the concentration of calcium and phosphate ions in the contact liquid. When the pH value of the contact liquid is lower than 5.5 and does not contain sufficient calcium and phosphate ions, the hydroxyapatite in the enamel will tend to dissolve, which can easily lead to enamel demineralization. When the contact liquid is rich in high concentrations of calcium and phosphate ions, and the pH is > 5.5, the reaction equilibrium will proceed in the direction of calcium phosphate deposition, thereby allowing demineralized teeth to be remineralized. Continuous enamel erosion and demineralization are one of the main causes of tooth sensitivity and caries.

[0004] Amorphous calcium phosphate is rich in calcium ions and phosphate ions. When added to oral care products, it can strengthen tooth enamel, prevent tooth decay, and resist tooth sensitivity. Currently, amorphous calcium phosphate prepared by the sol-gel method has the problem of poor stability, which limits its application in oral care products. Summary of the invention

[0005] To this end, the embodiments of the present invention provide an amorphous calcium phosphate gel and a preparation method and application thereof.

[0006] In order to achieve the above purpose, the embodiment of the present invention provides the following technical solutions:

[0007] According to a first aspect of an embodiment of the present invention, the present invention provides a method for preparing an amorphous calcium phosphate gel, the method comprising: adding aminomethyl propanol to a propylene glycol solution containing a calcium source to obtain a mixed solution; and slowly adding a phosphoric acid solution to the mixed solution to obtain the amorphous calcium phosphate gel.

[0008] The present invention adopts an anhydrous system to prepare amorphous calcium phosphate gel. The applicant has found through extensive research that adding a phase stabilizer aminomethyl propanol (C4H 11 NO, CAS No.: 124-68-5), the prepared amorphous calcium phosphate gel can not undergo phase change for a longer period of time and has excellent stability. At the same time, the reagents used in the method are safe and avoid harm to the human body to the greatest extent.

[0009] Furthermore, the mass ratio of the aminomethyl propanol to the propylene glycol solution containing a calcium source is 1:20 to 1:2. Studies have found that the amount of the phase stabilizer aminomethyl propanol significantly affects the stability of the product. When the amount of aminomethyl propanol is low, the prepared amorphous calcium phosphate gel is easily transformed into a crystalline calcium phosphate. When the amount of aminomethyl propanol is high, the pH value of the prepared amorphous calcium phosphate gel increases, which is not conducive to its wide application in oral care products. Under the above-mentioned mass ratio, aminomethyl propanol and the propylene glycol solution containing a calcium source can improve the stability of the amorphous calcium phosphate gel while also helping to expand its scope of application in oral care products.

[0010] Furthermore, the molar concentration of phosphoric acid in the phosphoric acid solution is 0.03 mol / L to 2 mol / L, and the mass ratio of the phosphoric acid solution to the mixed solution is 1:5 to 4:5. Studies have found that when the molar concentration of phosphoric acid is too low or too high, the prepared amorphous calcium phosphate is easy to transform into a crystalline state. Under the above conditions, it is more conducive to improving the stability of the amorphous calcium phosphate gel.

[0011] Furthermore, the phosphoric acid solution is a mixed solution of phosphoric acid and an organic solvent, and the organic solvent is propylene glycol and / or glycerol, preferably propylene glycol.

[0012] Further, the molar concentration of calcium ions in the propylene glycol solution containing the calcium source is 0.02 mol / L to 1 mol / L, and the calcium source is calcium citrate, calcium acetate, calcium gluconate, calcium hydride, calcium fluoride, calcium chloride or calcium chloride hydrate. Among them, the calcium chloride hydrate is calcium chloride dihydrate, calcium chloride tetrahydrate or calcium chloride hexahydrate. Calcium chloride and its hydrate are easier to obtain and have better solubility in propylene glycol. Therefore, the calcium source is preferably calcium chloride or calcium chloride hydrate.

[0013] Furthermore, the addition rate of the phosphoric acid solution is 20 ml / min to 500 ml / min. Studies have found that the addition rate affects the crystal form of calcium phosphate. When the addition rate is too slow, the generated amorphous calcium phosphate is not easy to disperse, resulting in excessively high local concentrations for phase transition. When the addition rate is too fast, amorphous calcium phosphate gel cannot be obtained.

[0014] Furthermore, the preparation method of the propylene glycol solution containing the calcium source is: the calcium source and propylene glycol are stirred at a temperature of 60° C. to 90° C. until dissolved, and then cooled to room temperature to obtain a clear liquid.

[0015] According to a second aspect of an embodiment of the present invention, the present invention provides an amorphous calcium phosphate gel, which is prepared by the method described in any one of the above items.

[0016] According to a third aspect of an embodiment of the present invention, the present invention provides the use of the amorphous calcium phosphate gel as described above in an oral care product, wherein the oral care product is an anhydrous oral care product, and the anhydrous oral care product is preferably a gel or a toothpaste.

[0017] Furthermore, the mass percentage of the amorphous calcium phosphate gel in the oral care product is 10% to 50%.

[0018] It is understandable that the anhydrous oral care product also includes commonly used adjuvants in oral care, such as thickeners, solvents, sweeteners, abrasives, surfactants and flavors, etc. Among them, the thickener can be carbomer or xanthan gum, etc.; the solvent can be polyethylene glycol, glycerol or propylene glycol, etc.; the sweetener can be xylitol, sucralose or saccharin sodium, etc.; the abrasive can be hydrated silica, calcium hydrogen phosphate or calcium carbonate, etc.; the surfactant can be sodium methyl taurate, sodium lauryl sulfate or cocoyl propyl betaine, etc.; the flavor can be several or even dozens of spices, blended in a certain proportion to have a certain aroma or fragrance, and a blended fragrance for a certain purpose.

[0019] The preparation method of the anhydrous oral care product can be carried out according to conventional methods in the art. As an example, when the anhydrous oral care product is a gel, its preparation method is as follows:

[0020] (1) placing a solvent in an emulsifying stirring pot, adding a thickener, and homogenizing and stirring the mixture. Then, the mixture is heated to 50 to 80° C. and kept at this temperature for 10 to 30 minutes under stirring conditions to allow the colloid to fully swell, and then cooled to below 30° C. to obtain a first mixture;

[0021] (2) adding a sweetener to the first mixture and stirring at a low speed to mix uniformly to obtain a second mixture;

[0022] (3) adding amorphous calcium phosphate gel to the second mixture, stirring at a low speed to mix evenly, to obtain a third mixture;

[0023] (4) adding essence to the third mixture, stirring at a low speed to mix evenly, and degassing to obtain the gel.

[0024] When the anhydrous oral care product is toothpaste, the preparation method thereof is as follows:

[0025] (1) placing a solvent in an emulsifying stirring pot, adding a thickener, homogenizing and stirring, and then heating to 50 to 80° C. and keeping the temperature for 10 to 30 minutes under stirring to allow the colloid to fully swell, and then cooling to below 30° C. to obtain a first mixture;

[0026] (2) adding a sweetener to the first mixture and stirring at a low speed to mix uniformly to obtain a second mixture;

[0027] (3) adding amorphous calcium phosphate gel to the second mixture, stirring at a low speed to mix evenly, to obtain a third mixture;

[0028] (4) adding a friction agent to the third mixture, stirring and mixing at a low speed to obtain a fourth mixture;

[0029] (5) adding essence and / or surfactant to the fourth mixture, stirring at a low speed to mix evenly, and degassing to obtain the toothpaste.

[0030] The embodiments of the present invention have the following advantages:

[0031] The amorphous calcium phosphate gel provided by the present invention has excellent stability, and no obvious phase change occurs when placed at room temperature for 12 months; no toxic or harmful reagents are used in the preparation process, the production process is safe and environmentally friendly, and the safety of the product is also guaranteed; the method and process are simple, and large-scale production of the product can be achieved, providing a basis for the wide application of amorphous calcium phosphate gel in oral care. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the implementation methods of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for the implementation methods or the description of the prior art. Obviously, the drawings in the following description are only exemplary, and for ordinary technicians in this field, other implementation drawings can be derived from the provided drawings without creative work.

[0033] Figure 1 This is a transmission electron micrograph of the amorphous calcium phosphate gel of Example 1 of the present invention after being placed at room temperature for one week;

[0034] Figure 2 This is a transmission electron microscopic image of the amorphous calcium phosphate gel of Example 1 of the present invention after being placed at room temperature for three months;

[0035] Figure 3 This is a transmission electron microscopic image of the amorphous calcium phosphate gel of Example 1 of the present invention after being placed at room temperature for twelve months;

[0036] Figure 4 is the X-ray diffraction pattern of the amorphous calcium phosphate gel of Example 1 of the present invention;

[0037] Figure 5 The following are scanning electron microscope images of the dental module before and after being treated with the oral care product of Example 4 of the present invention, (a) before treatment, (b) after treatment. DETAILED DESCRIPTION

[0038] The following is a description of the implementation of the present invention by specific embodiments. People familiar with the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0039] Example 1

[0040] This embodiment provides a method for preparing an amorphous calcium phosphate gel:

[0041] (1) 3000 g of propylene glycol is placed in an emulsifying pot, 300 g of calcium chloride dihydrate is added, stirring is started, and heating is started to 85° C. to completely dissolve the calcium chloride dihydrate in the propylene glycol, and the mixture is cooled to room temperature. 700 g of aminomethyl propanol is added to the obtained clear liquid, and the mixture is stirred evenly to obtain a mixed liquid;

[0042] (2) dissolving 180 g of phosphoric acid (85%) in 1500 g of propylene glycol and mixing well to obtain a phosphoric acid solution;

[0043] (3) Under stirring conditions at a rotation speed of 20 rpm / min, the phosphoric acid solution of step (2) is added to the mixed solution of step (1) at a speed of 30 ml / min. After the addition is completed, an amorphous calcium phosphate gel is obtained.

[0044] Example 2

[0045] This embodiment provides a method for preparing an amorphous calcium phosphate gel:

[0046] (1) 3000 g of propylene glycol was placed in an emulsifying pot, 28 g of calcium chloride was added, stirring was started, and heating was started to 60° C. to completely dissolve the calcium chloride in the propylene glycol, and the mixture was cooled to room temperature. 160 g of aminomethyl propanol was added to the obtained clear liquid, and the mixture was stirred evenly to obtain a mixed liquid;

[0047] (2) dissolving 20 g of phosphoric acid (85%) in 1700 g of propylene glycol and stirring to obtain a phosphoric acid solution;

[0048] (3) Under stirring conditions at a rotation speed of 25 rpm / min, the phosphoric acid solution of step (2) is added to the mixed solution of step (1) at a speed of 100 ml / min. After the addition is completed, an amorphous calcium phosphate gel is obtained.

[0049] Example 3

[0050] This embodiment provides a method for preparing an amorphous calcium phosphate gel:

[0051] (1) 100 g of calcium chloride, 250 g of calcium chloride dihydrate and 3000 g of propylene glycol are placed in an emulsifying pot, stirred, and heated to 60° C. to completely dissolve the calcium chloride and calcium chloride dihydrate in the propylene glycol, cooled to room temperature, and 1200 g of aminomethyl propanol is added to the obtained clear liquid, stirred evenly, to obtain a mixed liquid;

[0052] (2) dissolving 180 g of phosphoric acid (85%) in 900 g of propylene glycol and stirring to obtain a phosphoric acid solution;

[0053] (3) Under stirring conditions at a rotation speed of 15 rpm / min, the phosphoric acid solution of step (2) is added to the mixed solution of step (1) at a rate of 50 ml / min. After the addition is completed, an amorphous calcium phosphate gel is obtained.

[0054] Example 4

[0055] This embodiment provides an oral care product (gel), the raw materials of which are, by weight: 45.5 parts of the amorphous calcium phosphate gel of Example 1, 20 parts of polyethylene glycol, 30 parts of glycerol, 1.5 parts of carbomer, 2 parts of xylitol, and 1 part of flavor.

[0056] The preparation method of the above-mentioned oral care product comprises:

[0057] (1) placing polyethylene glycol in an emulsifying stirring pot, adding carbomer, and homogenizing and stirring evenly; adding glycerol, and then heating to 60° C. and keeping the temperature for 15 minutes under stirring to allow the colloid to fully swell, and then cooling to below 30° C. to obtain a first mixture;

[0058] (2) adding xylitol to the first mixture to obtain a second mixture;

[0059] (3) adding amorphous calcium phosphate gel to the second mixture, stirring at a low speed to mix evenly, to obtain a third mixture;

[0060] (4) Add essence to the third mixture, stir at a low speed to mix evenly, and degas to obtain a gel.

[0061] Example 5

[0062] The present embodiment provides an oral care product (toothpaste), the raw materials of which are, by weight: 30 parts of the amorphous calcium phosphate gel of Example 3, 30 parts of polyethylene glycol, 1.5 parts of carbomer, 2 parts of xylitol, 20 parts of hydrated silica, 13.5 parts of calcium hydrogen phosphate, 1 part of flavor, and 2 parts of sodium methyl taurate.

[0063] The preparation method of the above-mentioned oral care product comprises:

[0064] (1) placing polyethylene glycol in an emulsifying stirring pot, adding carbomer, and homogenizing and stirring; then heating to 60° C. and keeping the temperature for 15 minutes under stirring to allow the colloid to fully swell, and then cooling to below 30° C. to obtain a first mixture;

[0065] (2) adding xylitol to the first mixture to obtain a second mixture;

[0066] (3) adding amorphous calcium phosphate gel to the second mixture, stirring at a low speed to mix evenly, to obtain a third mixture;

[0067] (4) adding hydrated silica and calcium hydrogen phosphate to the third mixture, stirring at a low speed to mix evenly, to obtain a fourth mixture;

[0068] (5) Add flavor and sodium methyl taurate to the fourth mixture, stir at a low speed to mix evenly, and degas to obtain toothpaste.

[0069] Comparative Example 1

[0070] This comparative example provides a method for preparing an amorphous calcium phosphate gel, which differs from Example 1 only in that aminomethyl propanol is not used.

[0071] Test Case

[0072] 1. Transmission electron microscopy

[0073] The amorphous calcium phosphate gel sample prepared in Example 1 was placed at room temperature (25±1° C.) for one week and observed using a transmission electron microscope. Figure 1 The above samples were placed under the same conditions for three months and twelve months, and the transmission electron microscope ( Figure 2-3 ) showed that the micelles were still clearly clustered, and no obvious aggregation, growth, or crystallization occurred. The transmission electron microscopic observation results of the amorphous calcium phosphate gel samples prepared in Examples 2-3 placed at room temperature for one week, three months, and twelve months were not significantly different from those in Example 1.

[0074] The amorphous calcium phosphate sample prepared in Comparative Example 1 could not form a stable gel state and transformed into a crystalline state after being placed at room temperature for 20 minutes.

[0075] The above results show that the amorphous calcium phosphate gel provided by the present invention has excellent stability.

[0076] 2. X-ray diffraction

[0077] The amorphous calcium phosphate gel prepared in Example 1 was analyzed by X-ray diffraction. Figure 4The X-ray diffraction patterns of the amorphous calcium phosphate gel samples prepared in Example 2-3 are not significantly different from those in Example 1.

[0078] The above results show that the amorphous calcium phosphate gel provided by the present invention does not contain a crystalline phase and is a pure amorphous phase.

[0079] 3. Blocking of dentin pores

[0080] 1 gram of the oral care product of Example 4 was applied to the dental module with exposed dentin pores after phosphoric acid etching, and kept for 1 minute. The sample remaining on the surface of the dental module was washed off, and after drying, it was observed under a scanning electron microscope. Figure 5 After treatment, the pores in the dentin can be effectively filled.

[0081] The above results indicate that the oral care product provided by the present invention can effectively block the dentin pores, thereby alleviating tooth sensitivity caused by the exposure of the dentin pores.

[0082] Although the present invention has been described in detail above by general description and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A method for preparing an amorphous calcium phosphate gel, characterized in that: The method comprises: adding aminomethyl propanol to the propylene glycol solution containing a calcium source to obtain a mixed solution; Slowly adding phosphoric acid solution into the mixed solution to obtain the amorphous calcium phosphate gel.

2. The method for preparing amorphous calcium phosphate gel according to claim 1, wherein The mass ratio of the aminomethyl propanol to the propylene glycol solution containing a calcium source is 1:20 to 1:

2.

3. The preparation method of amorphous calcium phosphate gel according to claim 1, characterized in that, The molar concentration of phosphoric acid in the phosphoric acid solution is 0.03 mol / L to 2 mol / L, and the mass ratio of the phosphoric acid solution to the mixed solution is 1:5 to 4:

5.

4. The preparation method of amorphous calcium phosphate gel according to claim 1, characterized in that, The phosphoric acid solution is a mixed solution of phosphoric acid and an organic solvent, and the organic solvent is propylene glycol and / or glycerol.

5. The preparation method of amorphous calcium phosphate gel according to claim 1, characterized in that, The molar concentration of calcium ions in the propylene glycol solution containing the calcium source is 0.02 mol / L to 1 mol / L, and the calcium source is calcium citrate, calcium acetate, calcium gluconate, calcium hydride, calcium fluoride, calcium chloride or calcium chloride hydrate.

6. The method for preparing amorphous calcium phosphate gel according to claim 1, wherein The adding speed of the phosphoric acid solution is 20 ml / min to 500 ml / min.

7. The method for preparing amorphous calcium phosphate gel according to claim 1, wherein The preparation method of the propylene glycol solution containing the calcium source is as follows: the calcium source and propylene glycol are stirred at a temperature of 60° C. to 90° C. until dissolved, and then cooled to room temperature to obtain a clear liquid.

8. An amorphous calcium phosphate gel, characterized in that: It is prepared by the method according to any one of claims 1 to 7.

9. Use of the amorphous calcium phosphate gel according to claim 8 in oral care products, characterized in that: The oral care product is an anhydrous oral care product.

10. The use according to claim 9, characterized in that: The mass percentage of the amorphous calcium phosphate gel in the oral care product is 10% to 50%.

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