Preparation method of trollflower oral gel for preventing and treating oral diseases

Abstract

The invention relates to the technical field of oral care, in particular to a preparation method of trollius chinensis oral gel for preventing and treating oral diseases, which comprises the following steps: swelling carbomer and sodium hyaluronate in purified water under preset swelling conditions to obtain a phase I; determining whether the swelling processes of the carbomer, the sodium hyaluronate and the purified water are qualified or not based on the swelling equilibrium characterization parameters, and determining and adjusting the swelling time according to a difference value; determining whether the swelling uniformity of the carbomer, the sodium hyaluronate and the purified water reaches the standard or not based on the dispersion uniformity characteristic value, and determining and adjusting the stirring rate according to the relative difference; determining whether the I-phase stability is qualified or not based on the response stability index, and determining and adjusting the swelling temperature according to the ratio; mixing the trollius chinensis bunge extract with an ethanol solution to obtain a phase II; fusing glycerol, menthol and absolute ethyl alcohol to obtain a phase III; and mixing the phase II and the phase III, and adding triethanolamine to obtain the trollflower oral gel. The preparation stability of the trollflower oral gel is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of oral care, in particular to a preparation method of a Trollius chinensis oral gel for preventing and treating oral diseases. BACKGROUND

[0002] Caries is a progressive lesion of dental hard tissue caused by the combined action of multiple factors in the oral cavity, which is characterized by the demineralization of inorganic matter and the decomposition of organic matter. Streptococcus mutans is considered to be the main pathogenic bacteria in the progression of caries, and Candida albicans is also a pathogenic bacterium that causes caries. In addition to participating in the formation of biofilm, Candida albicans can also cause caries due to its strong acid-producing ability and acid tolerance. Its acid-producing ability is stronger than that of Streptococcus mutans, and it can decompose various sugars. Aphthous ulcer, also known as acute pseudomembranous candidal stomatitis or snow mouth disease, is an acute pseudomembranous injury of the oral mucosa caused by the overgrowth of superficial Candida albicans. Candida albicans can invade host cells by mediating endocytosis, that is, the host cell membrane wraps Candida albicans and transports it into the cell. Candida albicans secretes toxic metabolites such as proteases, phospholipases, and hydrolases, causing damage to host tissues and causing acute toxic reactions. Oral ulcers are the result of the combined action of multiple factors. Among microbial infections, common bacteria such as Streptococcus and Staphylococcus may invade when the oral mucosa is damaged, leading to the formation of ulcers.

[0003] Chinese Patent Application Publication No. CN104523689A discloses an oral gel and a preparation method thereof. The gel uses water or ethanol-containing water as a solvent, and the contents of the components in the gel are as follows: zolpidem tartrate 0.5 g / 100 ml, solubilizer 0.3-10 g / 100 ml, gel base 1-20 g / 100 ml, pH adjuster 0.5-5 g / 100 ml, flavoring agent 0.01-2 g / 100 ml, and preservative 0.01-0.5 g / 100 ml. The pH of the oral gel is 7.4-8.0. In the ethanol-containing water, the volume fraction of ethanol is 0.1-5%.

[0004] However, the existing technology has the following problems: insufficient swelling can cause the molecular chains of carbomer to not fully stretch, the porosity of the gel network is uneven, and thus the preparation stability of the Trollius chinensis oral gel is low. SUMMARY

[0005] Therefore, the present application provides a preparation method of a Trollius chinensis oral gel for preventing and treating oral diseases, which overcomes the problem in the prior art that insufficient swelling can cause the molecular chains of carbomer to not fully stretch, the porosity of the gel network is uneven, and thus the preparation stability of the Trollius chinensis oral gel is low.

[0006] To achieve the above-mentioned purpose, the present application provides a preparation method of a Trollius chinensis oral gel for preventing and treating oral diseases, which comprises the following steps:

[0007] swelling the carbomer and sodium hyaluronate in purified water under preset swelling conditions to obtain a phase I;

[0008] acquiring viscosity data during the swelling process, determining a swelling equilibrium characteristic parameter based on the viscosity data to determine whether the swelling process of the carbomer, sodium hyaluronate and purified water is qualified, and determining to adjust the swelling time of the swelling process according to the difference between the swelling equilibrium characteristic parameter and a preset swelling equilibrium characteristic parameter;

[0009] acquiring transmittance and turbidity data of the phase I, determining a dispersion uniformity characteristic value based on the transmittance and turbidity data to determine whether the swelling uniformity of the carbomer, sodium hyaluronate and purified water is qualified, and determining to adjust the stirring rate of the swelling process according to the relative difference between the dispersion uniformity characteristic value and a preset dispersion uniformity characteristic value;

[0010] acquiring pH value and particle size distribution of the phase I, determining a response stability index based on the pH value and particle size distribution to determine whether the stability of the phase I is qualified, and determining to adjust the swelling temperature of the swelling process according to the ratio of the preset response stability index to the response stability index;

[0011] mixing the trollius chinensis extract and the ethanol solution under preset mixing conditions to obtain a phase II;

[0012] dissolving and mixing glycerol, menthol and anhydrous ethanol under preset dissolving and mixing conditions to obtain a phase III;

[0013] mixing the phase II and the phase III and adding triethanolamine under preset neutralization conditions to obtain the trollius chinensis oral gel.

[0014] Further, the unqualified swelling process of the carbomer, sodium hyaluronate and purified water is determined based on the comparison result that the swelling equilibrium characteristic parameter is greater than the preset swelling equilibrium characteristic parameter, wherein,

[0015] The swelling equilibrium characteristic parameter is determined according to the equilibrium viscosity and the maximum viscosity increase value.

[0016] Further, the determination process of adjusting the swelling time includes:

[0017] calculating the difference between the swelling equilibrium characteristic parameter under the unqualified swelling process of the carbomer, sodium hyaluronate and purified water and the preset swelling equilibrium characteristic parameter;

[0018] determining to increase the swelling time by a first preset swelling time adjustment coefficient based on the comparison result that the difference is less than or equal to a preset difference;

[0019] determining to increase the swelling time by a second preset swelling time adjustment coefficient based on the comparison result that the difference is greater than the preset difference.

[0020] Further, the swelling uniformity of the carbomer, sodium hyaluronate and purified water is determined to be substandard based on a comparison result that the dispersion uniformity characteristic value is greater than a preset dispersion uniformity characteristic value, wherein,

[0021] The dispersion uniformity characteristic value is determined according to the transmittance, the transmittance average value, the turbidity value and the turbidity average value.

[0022] Further, the process of adjusting the stirring rate comprises:

[0023] The relative difference between the dispersion uniformity characteristic value under the condition that the uniformity of the carbomer, sodium hyaluronate and purified water is substandard and the preset dispersion uniformity characteristic value is calculated;

[0024] Based on the comparison result that the relative difference is less than or equal to a preset relative difference, the stirring rate is increased by a first preset stirring rate adjustment coefficient;

[0025] Based on the comparison result that the relative difference is greater than the preset relative difference, the stirring rate is increased by a second preset stirring rate adjustment coefficient.

[0026] Further, the stability of the I phase is determined to be substandard based on a comparison result that the response stability index is greater than a preset response stability index, wherein,

[0027] The response stability index is determined according to the maximum pH value, the minimum pH value, the average pH value, the maximum particle size, the minimum particle size and the average particle size.

[0028] Further, the process of adjusting the swelling temperature comprises:

[0029] The ratio of the preset response stability index to the response stability index under the condition that the stability of the I phase is substandard is calculated;

[0030] Based on the comparison result that the ratio is less than or equal to a preset ratio, the stirring rate is increased by a first preset swelling temperature adjustment coefficient;

[0031] Based on the comparison result that the ratio is greater than the preset ratio, the stirring rate is increased by a second preset swelling temperature adjustment coefficient.

[0032] Further, the preset mixing condition is that the mixing temperature is 28-32℃ and the mixing time is 15-25min.

[0033] Further, the preset dissolution condition is that the dissolution temperature is 38-42℃, the mixing time is 13-17min and the mixing stirring speed is 250-350rpm.

[0034] Further, the preset neutralization condition is that the neutralization temperature is 25-30 DEG C, and the pH of the Gypsophila oldhamiana oral gel after neutralization is 6.2-6.8.

[0035] Compared with the prior art, the present application has the beneficial effects that, by swelling the carbomer and sodium hyaluronate in purified water under preset conditions to form a phase I, the swelling equilibrium characteristic parameters are calculated by real-time monitoring of viscosity data, the swelling time is adjusted to ensure full balance of the system, the stirring rate is adjusted according to the dispersion uniformity characteristic value of the phase I to eliminate local concentration gradient, the uniform dispersion of the polymer network is ensured, the swelling temperature is regulated according to the response stability index to inhibit side reactions, the stability of the Gypsophila oldhamiana oral gel is improved, the degree of deviation from equilibrium of the swelling process is quantified, the balance achievement rate of the carbomer-sodium hyaluronate swelling system is improved by closed-loop regulation of the stirring rate and temperature, the standard deviation of the polymer network distribution is reduced, the uneven gel strength caused by local agglomeration is reduced, the retention rate of the active ingredients of the Gypsophila oldhamiana extract is improved, and thus the stability of the preparation of the Gypsophila oldhamiana oral gel is improved.

[0036] Further, by monitoring the viscosity change of the carbomer and sodium hyaluronate swelling system, whether the swelling process is qualified is determined according to the swelling equilibrium characteristic parameters, and when unqualified, the swelling time is adjusted to ensure the balance of the system, the determination accuracy of the end point of the swelling process is improved, the production consistency is improved, the gel network defects caused by insufficient swelling are inhibited, and the stability of the Gypsophila oldhamiana oral gel is improved.

[0037] Further, by monitoring the optical properties of the swelling system, the swelling uniformity is determined according to the dispersion uniformity characteristic value, and when uneven, the stirring rate is adjusted to eliminate local concentration gradient, the microstructure standard deviation of the carbomer-sodium hyaluronate swelling system is reduced, and the gel strength difference caused by local agglomeration is avoided. When DIS is greater than 0.75, the stirring rate compensation is triggered, the uniformity of the polymer chain distribution is improved, and thus the porosity unevenness is reduced, the early warning of bubble interference or raw material agglomeration is improved, and thus the stability of the preparation of the Gypsophila oldhamiana oral gel is improved.

[0038] Further, by monitoring the pH fluctuation and particle size change of the swelling system, the stability of the phase I is determined according to the response stability index, and when unstable, the swelling temperature is adjusted to ensure the stability in the preparation of the polymer gel, and thus the abnormal crosslinking of the molecular chain caused by local pH deviation is reduced, the retention rate of the active ingredients of the Gypsophila oldhamiana extract is improved, and thus the stability of the preparation of the Gypsophila oldhamiana oral gel is improved. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 The flow chart of the preparation method of the Gypsophila oldhamiana oral gel for preventing and treating oral diseases according to the embodiment of the present application;

[0040] Figure 2Flow chart for determining whether the swelling process is qualified for the embodiment of the present application;

[0041] Figure 3 Flow chart for determining whether the swelling uniformity meets the standard for the embodiment of the present application;

[0042] Figure 4 Flow chart for determining whether the I phase stability is qualified for the embodiment of the present application. DETAILED DESCRIPTION

[0043] In order to make the objects and advantages of the present application clearer, the present application will be further described below in conjunction with embodiments; it should be understood that the specific embodiments described herein are only used to explain the present application and not used to limit the present application.

[0044] The preferred embodiments of the present application will be described below with reference to the accompanying drawings. It should be understood by those skilled in the art that these embodiments are only used to explain the technical principles of the present application and not used to limit the protection scope of the present application.

[0045] It should be pointed out that the data in the present embodiment are obtained by comprehensive analysis and evaluation of historical detection data and corresponding historical detection results in the three months before the present detection by the present application. Those skilled in the art can understand that the determination mode of the present application for a single parameter can be to select the value with the highest proportion as the preset standard parameter according to the data distribution, to use weighted summation to obtain the value as the preset standard parameter, to substitute each historical data into a specific formula and to obtain the value by the formula as the preset standard parameter or other selection modes, as long as the present application can clearly define different specific situations in the single determination process by the obtained value.

[0046] Please refer to Figure 1 As shown in the figure, it is a flow chart of the preparation method of the Trollius oral gel for preventing and treating oral diseases according to the embodiment of the present application.

[0047] The preparation method of the Trollius oral gel for preventing and treating oral diseases according to the embodiment of the present application comprises:

[0048] Step S1, swelling carboxymethyl cellulose and sodium hyaluronate in purified water under preset swelling conditions to obtain a phase I;

[0049] Step S2, obtaining viscosity data in the swelling process, determining a swelling equilibrium characteristic parameter based on the viscosity data to determine whether the swelling process of carboxymethyl cellulose, sodium hyaluronate and purified water is qualified, and determining the swelling time of the swelling process according to the difference between the swelling equilibrium characteristic parameter and a preset swelling equilibrium characteristic parameter;

[0050] Step S3, obtaining the transmittance and turbidity data of the I phase, determining the dispersion uniformity characteristic value based on the transmittance and turbidity data, to determine whether the swelling uniformity of the carbomer, sodium hyaluronate and purified water meets the standard, and determining the stirring rate of the swelling process according to the relative difference between the dispersion uniformity characteristic value and the preset dispersion uniformity characteristic value;

[0051] Step S4, obtaining the pH value and particle size distribution of the I phase, determining the response stability index based on the pH value and particle size distribution, to determine whether the stability of the I phase is qualified, and determining the swelling temperature of the swelling process according to the ratio of the preset response stability index to the response stability index;

[0052] Step S5, mixing the extract of the Trollius chinensis Bunge and the ethanol solution under the preset mixing condition to obtain a II phase;

[0053] Step S6, solvating glycerol, menthol and anhydrous ethanol under the preset solvating condition to obtain a III phase;

[0054] Step S7, mixing the II phase and the III phase and adding triethanolamine under the preset neutralization condition to obtain the Trollius chinensis Bunge oral gel.

[0055] Specifically, the present application forms the I phase by swelling the carbomer and the sodium hyaluronate in the purified water under the preset condition, calculates the swelling equilibrium characteristic parameter by real-time monitoring of the viscosity data, adjusts the swelling time to ensure that the system is fully balanced, adjusts the stirring rate according to the dispersion uniformity characteristic value of the I phase to eliminate the local concentration gradient, ensures the uniform dispersion of the polymer network, adjusts the swelling temperature according to the response stability index to inhibit the side reaction, improves the stability of the Trollius chinensis Bunge oral gel, quantifies the degree of deviation from the equilibrium of the swelling process, and combines the closed-loop regulation of the stirring rate and the temperature, thereby improving the equilibrium achievement rate of the carbomer-sodium hyaluronate swelling system, reducing the standard deviation of the polymer network distribution, reducing the uneven gel strength caused by local agglomeration, improving the retention rate of the active ingredients of the Trollius chinensis Bunge extract, and thereby improving the stability of the Trollius chinensis Bunge oral gel preparation.

[0056] Specifically, in the step S1, the purified water accounts for 70-95% of the total weight of the Trollius chinensis Bunge oral gel, preferably 84%, the carbomer accounts for 0.8-2.2% of the total weight of the Trollius chinensis Bunge oral gel, preferably 1.5%, the sodium hyaluronate accounts for 0.1-2% of the total weight of the Trollius chinensis Bunge oral gel, preferably 1.0%, and the preset swelling condition is that the swelling temperature is 23-27℃, preferably 25℃, the swelling time is 3.5-4.5h, preferably 4h, and the stirring rate is 50-100rpm, preferably 70rpm.

[0057] Please refer to Figure 2 shown, which is the flow chart for determining whether the swelling process is qualified according to the embodiment of the present application.

[0058] Specifically, in the embodiment of the present application, the swelling process of carbomer, sodium hyaluronate and purified water is determined according to the comparison result of the swelling equilibrium characterization parameter determined according to the viscosity data and the preset swelling equilibrium characterization parameter under the condition that the carbomer and the sodium hyaluronate are swelled in the purified water.

[0059] When the swelling equilibrium characterization parameter is less than or equal to the preset swelling equilibrium characterization parameter, it is determined that the swelling process is qualified.

[0060] When the swelling equilibrium characterization parameter is greater than the preset swelling equilibrium characterization parameter, it is determined that the swelling process is unqualified.

[0061] In the embodiment of the present application, the preset swelling equilibrium characterization parameter has a value range of [0.1, 0.2], and is preferably 0.15, but the above value is not limited thereto, and the skilled person in the art can also adjust the value according to actual needs.

[0062] In the embodiment of the present application, the process of obtaining the swelling equilibrium characterization parameter is as follows: during the swelling process of carbomer and sodium hyaluronate in purified water, the viscosity data of the mixed system is measured at a preset time interval, wherein the preset time interval is 2 min; the viscosity value obtained each time and the corresponding measurement time are recorded; the viscosity measurement is continuously performed until the difference between the viscosity values measured adjacent to each other is less than or equal to a preset difference value, and the average value of the viscosity values measured adjacent to each other at this time is taken as the equilibrium viscosity, wherein the preset difference value is 0.05; the difference between the maximum viscosity value occurring during the swelling process and the equilibrium viscosity is denoted as the maximum viscosity increase value; and the ratio of the maximum viscosity increase value to the equilibrium viscosity is the swelling equilibrium characterization parameter.

[0063] Specifically, in the embodiment of the present application, the swelling time is adjusted according to the comparison result of the difference between the swelling equilibrium characterization parameter and the preset swelling equilibrium characterization parameter and a preset difference value under the condition that the swelling process of carbomer, sodium hyaluronate and purified water is unqualified.

[0064] When the difference is less than or equal to the preset difference value, it is determined that the swelling time is increased to a corresponding value by a first preset swelling time adjustment coefficient 1.5.

[0065] When the difference is greater than the preset difference value, it is determined that the swelling time is increased to a corresponding value by a second preset swelling time adjustment coefficient 1.7.

[0066] Wherein, the difference is the difference between the swelling equilibrium characterization parameter and the preset swelling equilibrium characterization parameter.

[0067] In the embodiment of the present application, the preset difference value is in the range of [0.05, 0.09], preferably 0.07, but the above-mentioned value is not limited thereto, and the person skilled in the art can also adjust the value according to the actual needs.

[0068] In the embodiment of the present application, the increased swelling time is the product of the swelling time and the preset swelling time adjustment coefficient, the preset swelling time adjustment coefficient includes the first preset swelling time adjustment coefficient, the value of which is 1.5, and the second preset swelling time adjustment coefficient, the value of which is 1.7. In order to ensure that the adjusted swelling time meets the actual needs, the adjustment range should not be too large, so the adjustment coefficient is set to control the adjustment range.

[0069] Specifically, the present application determines whether the swelling process is qualified according to the swelling equilibrium characteristic parameter by monitoring the viscosity change of the carbomer and sodium hyaluronate swelling system, and adjusts the swelling time when it is unqualified to ensure system balance, improves the accuracy of the swelling process endpoint determination, improves the production consistency, suppresses the gel network defects caused by insufficient swelling, and improves the stability of the marshmallow oral gel.

[0070] Please refer to Figure 3 As shown in the figure, it is the flow chart for determining whether the swelling uniformity meets the standard in the embodiment of the present application.

[0071] Specifically, under the condition of determining that the swelling obtains I phase, the present application determines whether the swelling uniformity of carbomer, sodium hyaluronate and purified water meets the standard according to the comparison result of the dispersion uniformity characteristic value determined according to the light transmittance and turbidity data of the I phase and the preset dispersion uniformity characteristic value;

[0072] When the dispersion uniformity characteristic value is less than or equal to the preset dispersion uniformity characteristic value, it is determined that the swelling uniformity meets the standard;

[0073] When the dispersion uniformity characteristic value is greater than the preset dispersion uniformity characteristic value, it is determined that the swelling uniformity does not meet the standard.

[0074] In the embodiment of the present application, the preset dispersion uniformity characteristic value is in the range of [0.7, 0.8], preferably 0.75, but the above-mentioned value is not limited thereto, and the person skilled in the art can also adjust the value according to the actual needs.

[0075] In the embodiment of the present application, the process of obtaining the dispersion uniformity characteristic value is as follows: a plurality of different sampling points are selected in phase I; samples are taken from each sampling point, and the light transmittance of each sample is measured by a light transmittance meter and the turbidity value is measured by a turbidimeter; the average value of the light transmittance and the average value of the turbidity of all sampling points are calculated respectively; the absolute difference value of the light transmittance of each sampling point and the average value of the light transmittance is calculated, and the maximum absolute difference value and the average value of the light transmittance are recorded as the light transmittance uniformity index; the absolute difference value of the turbidity value of each sampling point and the average value of the turbidity is calculated; the maximum absolute difference value and the average value of the turbidity are recorded as the turbidity uniformity index; and the arithmetic mean of the light transmittance uniformity index and the turbidity uniformity index is the dispersion uniformity characteristic value.

[0076] Specifically, under the condition that the swelling uniformity of carbomer, sodium hyaluronate and purified water does not meet the standard, the relative difference between the dispersion uniformity characteristic value and the preset dispersion uniformity characteristic value is determined according to the comparison result of the preset relative difference, and the stirring speed is adjusted.

[0077] When the relative difference is less than or equal to the preset relative difference, the stirring speed is increased to a corresponding value by a first preset stirring speed adjustment coefficient 1.10.

[0078] When the relative difference is greater than the preset relative difference, the stirring speed 1.20 is increased to a corresponding value by a second preset stirring speed adjustment coefficient.

[0079] The relative difference is the relative difference between the dispersion uniformity characteristic value and the preset dispersion uniformity characteristic value.

[0080] In the embodiment of the present application, the preset relative difference is in the range of [0.2, 0.3], preferably 0.25, but the above value is not limited thereto, and the skilled person in the art can also adjust the value according to actual needs.

[0081] In the embodiment of the present application, the increased stirring speed is the product of the stirring speed and the preset stirring speed adjustment coefficient, the preset stirring speed adjustment coefficient includes the first preset stirring speed adjustment coefficient, the value of which is 1.10, and the second preset stirring speed adjustment coefficient, the value of which is 1.20, in order to ensure that the adjusted adjustment coefficient meets the actual needs, the adjustment range should not be too large, so the adjustment coefficient is set to control the adjustment range.

[0082] Specifically, the present application determines the swelling uniformity according to the dispersion uniformity characteristic value by monitoring the optical properties of the swelling system, adjusts the stirring rate when the uniformity is uneven to eliminate local concentration gradient, reduces the microstructure standard deviation of the carbomer-sodium hyaluronate swelling system, and avoids the difference in gel strength caused by local aggregation. When DIS>0.75, the stirring rate compensation is triggered, the uniformity of the polymer chain distribution is improved, the porosity unevenness is reduced, the early warning of bubble interference or raw material aggregation is improved, and thus the stability of the gypsophila oral gel preparation is improved.

[0083] Please refer to Figure 4 The present application is shown in the flow chart of determining whether the I phase stability is qualified or not.

[0084] Specifically, the present application determines whether the I phase stability is qualified or not according to the comparison result of the response stability index determined according to the pH value and particle size distribution of the I phase and the preset response stability index;

[0085] When the response stability index is less than or equal to the preset response stability index, it is determined that the I phase stability is qualified;

[0086] When the response stability index is greater than the preset response stability index, it is determined that the I phase stability is unqualified.

[0087] In the embodiment of the present application, the preset response stability index has a value range of [0.02, 0.12], preferably 0.06, but the above value is not limited thereto, and the skilled person in the art can also adjust the value according to the actual needs.

[0088] In the embodiment of the present application, the process of obtaining the response stability index is as follows: the I phase is divided into several parallel samples, which are placed in the same constant temperature environment, and detected at several time points within a preset test period, wherein the preset test period is 7 days; the pH value of each sample is measured at each time point, and the particle size distribution is measured by a laser particle size analyzer; the average pH value of the several parallel samples at each time point is calculated to obtain an average pH sequence at several time points, and the difference between the maximum value and the minimum value in the average pH sequence is calculated, which is denoted as the pH fluctuation amplitude; the ratio of the pH fluctuation amplitude to the average pH value at the initial time point is denoted as the pH stability coefficient; the average particle size of the several parallel samples at each time point is calculated to obtain an average particle size sequence at several time points, and the difference between the maximum value and the minimum value in the average particle size sequence is calculated, which is denoted as the particle size fluctuation amplitude; the ratio of the particle size fluctuation amplitude to the average particle size at the initial time point is denoted as the particle size stability coefficient; the arithmetic average of the pH stability coefficient and the particle size stability coefficient is the response stability index.

[0089] Specifically, under the condition that the I-phase stability is determined to be unqualified, the swelling temperature is adjusted according to a comparison result of a ratio of a preset response stability index and the response stability index and a preset ratio.

[0090] When the ratio is less than or equal to the preset ratio, it is determined to increase the stirring rate 1.17 to a corresponding value by a first preset swelling temperature adjustment coefficient;

[0091] When the ratio is greater than the preset ratio, it is determined to increase the stirring rate 1.27 to a corresponding value by a second preset swelling temperature adjustment coefficient;

[0092] The ratio is a ratio of a preset response stability index and the response stability index.

[0093] In the embodiment of the application, the preset ratio is in the range of [0.6, 0.7], and preferably 0.65, but the above value is not limited thereto, and a person skilled in the art can adjust the value according to actual needs.

[0094] In the embodiment of the application, the increased swelling temperature is a product of the swelling temperature and a preset swelling temperature adjustment coefficient, the preset swelling temperature adjustment coefficient includes a first preset swelling temperature adjustment coefficient with a value of 1.5 and a second preset swelling temperature adjustment coefficient with a value of 1.7, so as to ensure that the adjusted swelling time meets the actual needs, and the adjustment range is not too large, so the adjustment coefficient is set to control the adjustment range.

[0095] Specifically, the application determines the I-phase stability according to the response stability index by monitoring the pH fluctuation and particle size change of the swelling system, and adjusts the swelling temperature when the stability is unstable, so as to ensure the stability in the preparation of the polymer gel, thereby reducing the abnormal crosslinking of molecular chains caused by local pH deviation, improving the retention rate of active ingredients of the Trollius chinensis extract, and improving the stability of the Trollius chinensis oral gel preparation.

[0096] Specifically, in the step S2, the Trollius chinensis extract accounts for 0.5-1.5% of the total weight of the Trollius chinensis oral gel, preferably 1%, the ethanol solution accounts for 0.2-1.2% of the total weight of the Trollius chinensis oral gel, preferably 0.5%, and the preset mixing condition is that the mixing temperature is 28-32 DEG C, preferably 30 DEG C, and the mixing time is 15-25 min, preferably 20 min.

[0097] Specifically, in the step S3, the glycerin accounts for 5-15% of the total weight of the gypsophila oral gel, preferably 10%, the menthol accounts for 0.1-0.9% of the total weight of the gypsophila oral gel, preferably 0.5%, the anhydrous ethanol accounts for 0.5-1.5% of the total weight of the gypsophila oral gel, preferably 1.0%, and the preset dissolving condition is that the dissolving temperature is 38-42℃, preferably 40℃, the mixing time is 13-17 min, preferably 15 min, and the mixing stirring speed is 250-350 rpm, preferably 300 rpm.

[0098] Specifically, in the step S4, the triethanolamine accounts for 0.3-0.7% of the total weight of the gypsophila oral gel, preferably 0.5%, and the preset neutralization condition is that the neutralization temperature is 25-30℃, preferably 27℃, and the pH of the gypsophila oral gel after neutralization is 6.2-6.8, preferably 6.5.

[0099] Specifically, after obtaining the gypsophila oral gel, the gypsophila oral gel is subjected to heat resistance, cold resistance and bacteriostatic circle experiments.

[0100] In the embodiment of the present application, the heat resistance experiment process is that the gypsophila oral gel is placed in a 55℃ constant temperature oven for 6h and then taken out to restore to room temperature.

[0101] In the embodiment of the present application, the cold resistance experiment process is that the gypsophila oral gel is placed in a-20℃ refrigerator for 24h and then taken out to restore to room temperature.

[0102] In the embodiment of the present application, the bacteriostatic circle experiment process is that 1×10 6 CFU / mL of streptococcus mutans bacterial suspension is 0.2ml on BHI solid culture medium, 1×10 6 CFU / mL of candida albicans bacterial suspension is 100ul on LB solid culture medium, 1×10 6 CFU / mL of staphylococcus aureus bacterial suspension is 100ul on LB solid culture medium, and after uniform coating, 2 holes with a diameter of 6mm are punched on the solid culture medium with a puncher, 40ul of gypsophila oral gel is added into the holes, and then the holes are moved into a 37℃, 5% CO 2 incubator for 24h, and then taken out, and the diameter of the bacteriostatic circle is measured using a vernier caliper.

[0103] Example 1:

[0104] The embodiment adopts all the preferred parameters in the specification, phase I, purified water 840g, carbomer 15g, sodium hyaluronate 10g, phase II, glory extract 10g, 50% ethanol solution 5g, phase III, glycerol 100g, menthol 5g, anhydrous ethanol 10g, neutralizing agent, triethanolamine 5g.

[0105] The swelling equilibrium characterization parameter in the embodiment is 0.14, the dispersion uniformity characteristic value is 0.73, the response stability index is 0.055, the heat resistance experiment passes, the cold resistance experiment passes, the bacteriostatic ring diameter of streptococcus mutans is 12.8mm, the bacteriostatic ring diameter of Candida albicans is 10.5mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 15.2mm.

[0106] Example 2:

[0107] The embodiment adopts the minimum dosage in the specification, phase I, purified water 950g, carbomer 8g, sodium hyaluronate 1g, phase II, glory extract 5g, 50% ethanol solution 2g, phase III, glycerol 50g, menthol 1g, anhydrous ethanol 5g, neutralizing agent, triethanolamine 3g.

[0108] The swelling equilibrium characterization parameter in the embodiment is 0.19, the dispersion uniformity characteristic value is 0.79, the response stability index is 0.115, the heat resistance experiment slightly separates water, the cold resistance experiment slightly separates water, the bacteriostatic ring diameter of streptococcus mutans is 8.2mm, the bacteriostatic ring diameter of Candida albicans is 6.0mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 9.0mm.

[0109] Example 3:

[0110] The embodiment adopts the maximum dosage in the specification, phase I, purified water 700g, carbomer 22g, sodium hyaluronate 20g, phase II, glory extract 15g, 50% ethanol solution 12g, phase III, glycerol 150g, menthol 9g, anhydrous ethanol 15g, neutralizing agent, triethanolamine 7g.

[0111] The swelling equilibrium characterization parameter in the embodiment is 0.18, the dispersion uniformity characteristic value is 0.78, the response stability index is 0.105, the heat resistance experiment passes, the cold resistance experiment passes, the bacteriostatic ring diameter of streptococcus mutans is 15.1mm, the bacteriostatic ring diameter of Candida albicans is 12.5mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 16.5mm.

[0112] Example 4:

[0113] Except for the reaction condition, the rest is the same as example 1, the swelling time of the embodiment is 2h.

[0114] The swelling equilibrium characterization parameter in this embodiment is 0.25, and after the swelling time is prolonged, the swelling equilibrium characterization parameter is 0.15, the dispersion uniformity characteristic value is 0.78, the response stability index is 0.105, the heat resistance experiment passes, the cold resistance experiment passes, the bacteriostatic ring diameter of Streptococcus mutans is 13.3 mm, the bacteriostatic ring diameter of Candida albicans is 10.8 mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 14.5 mm.

[0115] Example 5:

[0116] Except that it does not contain sodium hyaluronate, the rest is the same as example 1.

[0117] The swelling equilibrium characterization parameter in this embodiment is 0.25, the dispersion uniformity characteristic value is 0.78, the response stability index is 0.105, the heat resistance experiment passes, the cold resistance experiment passes, the bacteriostatic ring diameter of Streptococcus mutans is 13.0 mm, the bacteriostatic ring diameter of Candida albicans is 10.5 mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 14.2 mm.

[0118] Comparative example 1:

[0119] In this embodiment, the swelling time is not adjusted according to the instructions, and the rest is the same as example 4.

[0120] The heat resistance experiment in this embodiment is obviously water separation, the cold resistance experiment is serious water separation, the bacteriostatic ring diameter of Streptococcus mutans is 10.5 mm, the bacteriostatic ring diameter of Candida albicans is 8.0 mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 11.8 mm.

[0121] Comparative example 2:

[0122] In this embodiment, except that the swelling temperature is 40℃, the rest is the same as example 1.

[0123] The heat resistance experiment in this embodiment does not pass, the cold resistance experiment does not pass, the bacteriostatic ring diameter of Streptococcus mutans is 7.0 mm, the bacteriostatic ring diameter of Candida albicans is 5.5 mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 8.0 mm.

[0124] Comparative example 3:

[0125] Except that the Trollius extract is replaced by chlorhexidine, the rest is the same as example 1.

[0126] The heat resistance experiment in this embodiment passes, the cold resistance experiment passes, the bacteriostatic ring diameter of Streptococcus mutans is 12.0 mm, the bacteriostatic ring diameter of Candida albicans is 7.5 mm, and the bacteriostatic ring diameter of Staphylococcus aureus is 10.0 mm.

[0127] Table 1 Performance test results of examples and comparative examples

[0128]

[0129]

[0130] The data in the analysis table shows that the bacteriostatic effect of Example 5 is slightly lower than that of Example 1, which indicates that the addition of sodium hyaluronate helps to disperse and stabilize the active ingredient, the extract of Potentilla Faba, and improves the product's effect in the bacteriostatic circle experiment and the heat and cold resistance experiment. Comparative Example 3, as a positive control, has a smaller bacteriostatic circle than the groups containing Potentilla Faba, which proves the strong bactericidal effect of the Potentilla Faba oral gel chemical bactericide of the present application. Comparative Example 1 uses a fixed short-time swelling mechanism without adjustment, which results in the stability and bacteriostatic effect of the Potentilla Faba oral gel being worse than those of Example 1, which is intelligently optimized. Comparative Example 2 has a too high swelling temperature, which leads to the destruction of the gel matrix and the failure of the product's stability and bacteriostatic effect.

[0131] So far, the technical solutions of the present application have been described in combination with the preferred embodiments shown in the drawings, but those skilled in the art can easily understand that the protection scope of the present application is obviously not limited to these specific embodiments. Those skilled in the art can make equivalent changes or replacements to the related technical features without deviating from the principles of the present application, and the technical solutions after these changes or replacements will all fall within the protection scope of the present application.

Claims

1. A method for preparing a pot marigold oral gel for preventing and treating oral diseases, characterized by, The method comprises the following steps: swelling the carbomer and sodium hyaluronate in purified water under preset swelling conditions to obtain a phase I; acquiring viscosity data during the swelling process, determining a swelling equilibrium characteristic parameter based on the viscosity data, determining whether the swelling process of the carbomer, sodium hyaluronate and purified water is qualified, and determining an adjustment swelling time of the swelling process according to a difference between the swelling equilibrium characteristic parameter and a preset swelling equilibrium characteristic parameter; acquiring transmittance and turbidity data of the phase I, determining a dispersion uniformity characteristic value based on the transmittance and turbidity data, determining whether the swelling uniformity of the carbomer, sodium hyaluronate and purified water is qualified, and determining an adjustment stirring rate of the swelling process according to a relative difference between the dispersion uniformity characteristic value and a preset dispersion uniformity characteristic value; acquiring pH value and particle size distribution of the phase I, determining a response stability index based on the pH value and particle size distribution, determining whether the stability of the phase I is qualified, and determining an adjustment swelling temperature of the swelling process according to a ratio between a preset response stability index and the response stability index; mixing the trollius chinensis extract and the ethanol solution under preset mixing conditions to obtain a phase II; dissolving and fusing glycerol, menthol and anhydrous ethanol under preset dissolving and fusing conditions to obtain a phase III; mixing the phase II and the phase III and adding triethanolamine under preset neutralization conditions to obtain the trollius chinensis oral gel.

2. The method of preparing the viola odorata mouth gel for the prevention and treatment of oral diseases according to claim 1, characterized in that, The unqualified swelling process of the carbomer, sodium hyaluronate and purified water is determined based on a comparison result that the swelling equilibrium characteristic parameter is greater than the preset swelling equilibrium characteristic parameter, wherein The swelling equilibrium characteristic parameter is determined according to an equilibrium viscosity and a maximum viscosity increase value.

3. The method of preparing the viola odorata mouth gel for the treatment of oral diseases according to claim 1, characterized in that, The determination process of the adjustment swelling time comprises: calculating a difference between the swelling equilibrium characteristic parameter under the unqualified swelling process of the carbomer, sodium hyaluronate and purified water and the preset swelling equilibrium characteristic parameter; determining to increase the swelling time by a first preset swelling time adjustment coefficient based on a comparison result that the difference is less than or equal to a preset difference; determining to increase the swelling time by a second preset swelling time adjustment coefficient based on a comparison result that the difference is greater than the preset difference.

4. The method of preparing the viola odorata oral gel for the prevention and treatment of oral diseases according to claim 1, characterized in that, The unqualified swelling uniformity of the carbomer, sodium hyaluronate and purified water is determined based on a comparison result that the dispersion uniformity characteristic value is greater than the preset dispersion uniformity characteristic value, wherein The dispersion uniformity characteristic value is determined according to a transmittance, a transmittance average value, a turbidity value and a turbidity average value.

5. The method of preparing the viola odorata mouth gel for the treatment of oral diseases according to claim 1, characterized in that, The process of adjusting the stirring rate comprises: calculating a relative difference between the dispersion uniformity characteristic value under the unqualified uniformity of the carbomer, sodium hyaluronate and purified water and the preset dispersion uniformity characteristic value; determining to increase the stirring rate by a first preset stirring rate adjustment coefficient based on a comparison result that the relative difference is less than or equal to a preset relative difference; determining to increase the stirring rate by a second preset stirring rate adjustment coefficient based on a comparison result that the relative difference is greater than the preset relative difference.

6. The method of preparing the viola odorata mouth gel for the treatment of oral diseases according to claim 1, characterized in that, The unqualified stability of the phase I is determined based on a comparison result that the response stability index is greater than a preset response stability index, wherein The response stability index is determined according to a pH maximum value, a pH minimum value, a pH average value, a particle size maximum value, a particle size minimum value and a particle size average value.

7. The method of preparing the viola odorata mouth gel for the treatment of oral diseases according to claim 1, characterized in that, The process of adjusting the swelling temperature comprises: The ratio of the preset response stability index to the response stability index under the stability unqualified condition of phase I; Based on the comparison result that the ratio is less than or equal to the preset ratio, it is determined to increase the stirring rate by the first preset swelling temperature adjustment coefficient; Based on the comparison result that the ratio is greater than the preset ratio, it is determined to increase the stirring rate by the second preset swelling temperature adjustment coefficient.

8. The method of preparing the viola odorata mouth gel for the treatment of oral diseases according to claim 1, characterized in that, The preset mixing condition is that the mixing temperature is 28-32℃, and the mixing time is 15-25min.

9. The method of preparing the viola odorata oral gel for the treatment of oral diseases according to claim 1, characterized in that, The preset dissolving condition is that the dissolving temperature is 38-42℃, the mixing time is 13-17min, and the mixing stirring speed is 250-350rpm.

10. The method of preparing the viola odorata oral gel for the treatment of oral diseases according to claim 1, characterized in that, The preset neutralization condition is that the neutralization temperature is 25-30℃, and the pH of the Gypsophila oldhamiana oral gel after neutralization is 6.2-6.8.

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