Oral pH adjusting gel spray and preparation method thereof

Abstract

The invention discloses an oral pH adjusting gel spray, which comprises high polymer material chitosan, beta-glycerophosphate, vanillin, acetic acid water, ethanol and distilled water, and is characterized in that the hydrophobic interaction and electrostatic interaction between the high polymer material chitosan and beta-sodium glycerophosphate are utilized to form temperature sensitivity of sol-gel transition at physiological temperature; the preparation method comprises the following steps: carrying out a Schiff base reaction between a high polymer material chitosan and vanillin to generate an imine bond so as to form pH sensitivity, and thus obtaining the oral pH adjusting gel spray with temperature-sensitive and pH-sensitive double intelligent responses. The hydrophobic interaction and electrostatic interaction between CS and beta-GP are utilized to form temperature sensitivity of sol-gel transition at the physiological temperature; and the oral mucosa and tooth health of gastroesophageal reflux patients can be protected.

Description

Technical Field

[0001] The invention relates to the technical field of oral care, health care and medical treatment, and in particular to a method for preparing an oral pH regulating gel spray. Background Art

[0002] According to statistics, about 13-19% of people worldwide suffer from gastroesophageal reflux disease (GERD) to varying degrees, and the probability of disease increases with age. As my country gradually progresses into an aging society, the number of patients with gastroesophageal reflux in my country is gradually increasing. GERD not only causes non-cardiac chest pain, esophagitis, persistent cough, asthma and other diseases, but most importantly, it causes harm to oral health. Patients often have symptoms such as sour mouth, bad breath, bitter taste, ulcers and tooth corrosion. Although there are some drugs for GERD, such as H2 receptor blockers (cimetidine, ranitidine, famotidine and nizatidine, etc.), proton pump inhibitors (omeprazole, esomeprazole, rabeprazole, lansoprazole and pantoprazole, etc.), and gastric motility and neutralization of gastric acid (aluminum hydroxide gel, etc.), the treatment effect is still not ideal. The reason is that the strong acidity of gastric juice corrodes the oral cavity. When the pH of the oral cavity is less than 5, it will corrode the teeth, and the pH of refluxed gastric juice is often less than 2, which is extremely corrosive to the teeth. Even among children, more than 37% of GERD patients have varying degrees of corrosion on their deciduous teeth and constant pressure. Currently, there are many products on the market for maintaining oral health, such as breath fresheners, xylitol, and antibacterial mouthwashes, but few products with pH adjustment function.

[0003] The present invention is designed and developed specifically for the clinical problem that during sleep at night, continuous gastric reflux in GERD patients will cause the oral pH to decrease, thereby seriously corroding the oral mucosa and teeth. First of all, the spray is used because the spray is an important dosage form and is the most widely used because of its convenience. However, the action time of conventional gargles and sprays in the mouth is too short to achieve the ideal effect, and it is necessary to design a spray that has both sprayability and good adhesion. Moreover, the current oral medications cannot solve the following two demands at the same time: 1. Temperature sensitivity, that is, it is a sol liquid with good fluidity at room temperature to ensure sprayability, and it is transformed into a gel at a human body temperature of 37 degrees to ensure long-term protection of adhesion; 2. pH sensitivity, that is, when the gastric reflux causes the oral pH to drop, the protective film degrades to produce alkaline substances to neutralize the gastric acid to regulate the pH. The more gastric juice refluxes, the faster the protective film degrades to produce a protective effect. Therefore, there is a need for a gel spray that can regulate the pH of the oral cavity. Summary of the invention

[0004] In order to solve one or some technical problems existing in the prior art, one of the purposes of the present application is to provide an oral pH regulating gel spray, which utilizes the hydrophobic interaction and electrostatic interaction between CS and β-GP to form temperature sensitivity of sol-gel transition at physiological temperature; utilizes the Schiff base reaction between CS and vanillin to produce imine bond to form pH sensitivity, and has both temperature-sensitive and pH-sensitive dual intelligent responses, which is particularly suitable for protecting the oral mucosa and dental health of patients with gastroesophageal reflux.

[0005] The second purpose of the present application is to provide a method for preparing an oral pH regulating gel spray, which has a simple preparation method and is easy to operate.

[0006] In order to solve the above existing technical problems, one of the purposes of this application is achieved by adopting the following technical solution:

[0007] An oral pH regulating gel spray comprises a polymer material chitosan, β-glycerophosphate, vanillin, acetic acid water, ethanol and distilled water, and utilizes the hydrophobic interaction and electrostatic interaction between the polymer material chitosan and sodium β-glycerophosphate to form temperature sensitivity for sol-gel transition at physiological temperature; utilizes the Schiff base reaction between the polymer material chitosan and vanillin to produce an imine bond to form pH sensitivity, thereby obtaining an oral pH regulating gel spray with dual intelligent responses of temperature sensitivity and pH sensitivity.

[0008] The second purpose of this application is achieved by the following technical solution:

[0009] A method for preparing an oral pH regulating gel spray, the preparation method comprising the steps of:

[0010] S1, preparing a chitosan solution with an acetic acid aqueous solution having a concentration of 0.5-5 (v / v)% and a polymer material chitosan, wherein the concentration of the chitosan solution is 0.1-5 (w / v)%;

[0011] S2, preparing a sodium β-glycerophosphate aqueous solution with β-glycerophosphate and distilled water, wherein the concentration of β-glycerophosphate in the sodium β-glycerophosphate aqueous solution is 20-50 (w / v) %;

[0012] S3, preparing a vanillin ethanol solution with vanillin and ethanol, wherein the concentration of vanillin in the vanillin ethanol solution is 10-60 (w / v) %;

[0013] S4, stirring the three solutions prepared in steps S1-S3 respectively and placing them at 0-25°C for a certain period of time;

[0014] S5, taking 10-50 ml of the chitosan solution treated in step S4, slowly dripping 0.5-5 ml of sodium β-glycerophosphate aqueous solution and 0.5-5 ml of vanillin solution in sequence, and stirring at 0-25° C. in the dark for 5-24 h;

[0015] S6, taking out the product treated in step S5, placing it in a dialysis container, washing it three times with excess distilled water, and then freeze-drying it for 12-72 hours to obtain a dry hydrogel powder;

[0016] S7. Take the hydrogel powder obtained in step S6, sterilize it with 15-25 kGy radiation, and then prepare it with distilled water at room temperature 0-25° C. into a 0.3-20 (w / v) % aqueous solution, and put it into a hydraulic steel or a manual pump spray bottle to prepare a final gel spray.

[0017] Preferably, the chitosan solution has a deacetylation degree of ≥95% and a viscosity of 100-200 mPa.s.

[0018] Preferably, the chitosan solution, the sodium β-glycerophosphate aqueous solution and the vanillin ethanol solution are allowed to stand for 6 to 12 hours.

[0019] Preferably, the soaking time for each washing in step S6 is 60 to 75 minutes.

[0020] Preferably, the concentration of the acetic acid aqueous solution in step S1 is 0.9-1.2 (v / v)%, the concentration of the chitosan solution is 0.8 (w / v)%; the concentration of β-glycerophosphate in the sodium β-glycerophosphate aqueous solution is 45-50 (w / v)%; and the concentration of vanillin in the vanillin ethanol solution is 30-35 (w / v)%.

[0021] Preferably, the ambient temperature of the standing state in step S4 is 4-7° C., and the standing state is overnight.

[0022] Preferably, in step S5, the molar ratio of the chitosan solution to the sodium β-glycerophosphate aqueous solution and the vanillin solution is 10:0.5-1:0.5-1, the molar ratio of the sodium β-glycerophosphate aqueous solution and the vanillin solution is 1:1, and the mixture is stirred in the dark at a temperature of 4-7°C for 12 hours.

[0023] Preferably, the washing and soaking time of the product in step S6 is not less than 1 hour each time.

[0024] Preferably, the hydrogel powder is sterilized by 15 kGy radiation and is prepared with distilled water at a room temperature of 4 to 7° C. to form an aqueous solution with a concentration of 1 to 1.5 (w / v) %.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The natural polymer materials chitosan (CS), sodium β-glycerophosphate (β-GP) and vanillin are used as raw materials, and cross-linked to form a semi-interpenetrating network hydrogel. The Schiff base reaction between the polymer material chitosan CS and vanillin produces an imine bond to form pH sensitivity, and obtains an oral pH regulating gel spray with both temperature sensitivity and pH sensitivity. The hydrophobic interaction and electrostatic interaction between CS and β-GP form the temperature sensitivity of the sol-gel transition at physiological temperature; the Schiff base reaction between CS and vanillin produces an imine bond to form pH sensitivity. The gel can be firmly attached to the oral mucosa and teeth, thereby avoiding the phenomenon of falling off due to saliva or swallowing and other routine actions. The neutralization effect is achieved by adding sodium β-glycerophosphate to react with acid, thereby achieving the effect of regulating the pH of the oral cavity. The gel spray is a sol liquid with good fluidity at room temperature, ensuring sprayability, and can be transformed into a gel at physiological temperature to ensure long-term adhesion protection. This oral pH regulating gel spray, which has both temperature sensitivity and pH sensitivity as dual intelligent responses, is particularly suitable for protecting the oral mucosa and dental health of patients with gastroesophageal reflux. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It is a schematic diagram of determining the cumulative release amount of vanillin in a solution by ultraviolet spectrophotometry in the present invention. DETAILED DESCRIPTION

[0028] Below, the present application is further described in conjunction with the accompanying drawings and specific implementation methods. It should be noted that, under the premise of no conflict, the various embodiments or technical features described below can be arbitrarily combined to form a new embodiment.

[0029] In the description of the present application, it should be understood that the terms "up", "down", "left", "right", etc., indicating directions or positional relationships are based on the directions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as a limitation on the present application.

[0030] The terms "first", "second", etc. in this application are used to distinguish similar objects, and are not used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present application can be implemented in an order other than those illustrated or described here, and the objects distinguished by "first", "second", etc. are generally of one type, and the number of objects is not limited. For example, the first object can be one or more. In addition, "and / or" in the specification and claims represents at least one of the connected objects, and the character " / " generally indicates that the objects associated with each other are in an "or" relationship.

[0031] An oral pH regulating gel spray comprises a polymer material chitosan, β-glycerophosphate, vanillin, acetic acid water, ethanol and distilled water, and utilizes the hydrophobic interaction and electrostatic interaction between the polymer material chitosan and sodium β-glycerophosphate to form temperature sensitivity for sol-gel transition at physiological temperature; utilizes the Schiff base reaction between the polymer material chitosan and vanillin to produce an imine bond to form pH sensitivity, thereby obtaining an oral pH regulating gel spray with dual intelligent responses of temperature sensitivity and pH sensitivity.

[0032] The natural polymer materials chitosan (CS), sodium β-glycerophosphate (β-GP) and vanillin are used as raw materials, and cross-linked to form a semi-interpenetrating network hydrogel. The Schiff base reaction between the polymer material chitosan CS and vanillin produces an imine bond to form pH sensitivity, and obtains an oral pH regulating gel spray with both temperature sensitivity and pH sensitivity. The hydrophobic interaction and electrostatic interaction between CS and β-GP form the temperature sensitivity of the sol-gel transition at physiological temperature; the Schiff base reaction between CS and vanillin produces an imine bond to form pH sensitivity. The gel can be firmly attached to the oral mucosa and teeth, thereby avoiding the phenomenon of falling off due to saliva or swallowing and other routine actions. The neutralization effect is achieved by adding sodium β-glycerophosphate to react with acid, thereby achieving the effect of regulating the pH of the oral cavity. The gel spray is a sol liquid with good fluidity at room temperature, ensuring sprayability, and can be transformed into a gel at physiological temperature to ensure long-term adhesion protection. This oral pH regulating gel spray, which has both temperature sensitivity and pH sensitivity as dual intelligent responses, is particularly suitable for protecting the oral mucosa and dental health of patients with gastroesophageal reflux.

[0033] When the above-mentioned oral pH regulating gel spray is prepared by adding water, the preparation method adopted is as follows:

[0034] A method for preparing an oral pH regulating gel spray, the preparation method comprising the steps of:

[0035] S1, preparing a chitosan solution with an acetic acid aqueous solution having a concentration of 0.5-5 (v / v)% and a polymer material chitosan, wherein the concentration of the chitosan solution is 0.1-5 (w / v)%;

[0036] S2, preparing a sodium β-glycerophosphate aqueous solution with β-glycerophosphate and distilled water, wherein the concentration of β-glycerophosphate in the sodium β-glycerophosphate aqueous solution is 20-50 (w / v) %;

[0037] S3, preparing a vanillin ethanol solution with vanillin and ethanol, wherein the concentration of vanillin in the vanillin ethanol solution is 10-60 (w / v) %;

[0038] S4, stirring the three solutions prepared in steps S1-S3 respectively and placing them at 0-25°C for a certain period of time;

[0039] S5, taking 10-50 ml of the chitosan solution treated in step S4, slowly dripping 0.5-5 ml of sodium β-glycerophosphate aqueous solution and 0.5-5 ml of vanillin solution in sequence, and stirring at 0-25° C. in the dark for 5-24 h;

[0040] S6, taking out the product treated in step S5, placing it in a dialysis container, washing it three times with excess distilled water, and then freeze-drying it for 12-72 hours to obtain a dry hydrogel powder;

[0041] S7. Take the hydrogel powder obtained in step S6, sterilize it with 15-25 kGy radiation, and then prepare it with distilled water at room temperature 0-25° C. into a 0.3-20 (w / v) % aqueous solution, and put it into a hydraulic steel or a manual pump spray bottle to prepare a final gel spray.

[0042] Since conventional gargles and sprays have too short an oral action time and cannot achieve the desired effect, the gel spray prepared by the above method is a sol liquid with good fluidity at room temperature to ensure sprayability, and can be transformed into a gel at physiological temperature to ensure long-term adhesion protection; when the environmental pH is neutral, the degradation is less, and when the pH drops, the gel film degrades to produce alkaline substances to neutralize the acidity, producing a protective effect, which can effectively solve the problem that conventional gargles and sprays have too short an oral action time and cannot achieve the desired effect. The gel can make it firmly adhere to the oral mucosa and teeth, thereby avoiding the phenomenon of falling off due to saliva or swallowing and other conventional actions. Among them, when the oral pH is less than 5, it will corrode the teeth, and the pH of the refluxed gastric juice is often less than 2, which is extremely corrosive to the teeth. Therefore, in order to solve this problem, β-sodium glycerophosphate is added to the oral pH regulating gel spray. Because it is a weak alkaline property, it can be diluted when the gel is explained, and β-sodium glycerophosphate can react with the acid to achieve a neutralization effect, thereby achieving the effect of regulating the oral pH. The whole formula uses natural polymer materials chitosan, sodium β-glycerophosphate (β-GP) and vanillin as raw materials, and cross-links to form a semi-interpenetrating network hydrogel. The hydrophobic interaction and electrostatic interaction between the polymer material chitosan CS and sodium β-glycerophosphate (β-GP) form the temperature sensitivity of the sol-gel transition at physiological temperature; the Schiff base reaction between the polymer material chitosan CS and vanillin produces an imine bond to form pH sensitivity, and obtains an oral pH regulating gel spray with both temperature sensitivity and pH sensitivity. When the environmental pH is neutral, the degradation is less, and when the pH drops, for example, due to gastric reflux, the oral pH will drop. At this time, the gel attached to the oral cavity will be degraded, and the gel film will be degraded to produce alkaline substances to neutralize the acidity. The sodium glycerophosphate in the degradation product is alkaline and can play a neutralizing role, thereby producing a protective effect on the oral cavity, which is particularly suitable for the oral mucosa and dental health protection of patients with gastroesophageal reflux. And the gel spray is a sol liquid with good fluidity at room temperature, which ensures sprayability, and can be transformed into a gel at physiological temperature to ensure long-term adhesion protection.

[0043] A further improvement is that the deacetylation degree of the chitosan solution is ≥95% and the viscosity is 100-200 mPa.s.

[0044] Since chitosan is obtained from chitin through a deacetylation process, the properties of raw materials with different deacetylation degrees and viscosities vary greatly. Therefore, in order to ensure that the oral pH regulating gel spray has good viscosity and coagulation efficiency during subsequent use, the deacetylation degree of the chitosan solution should be ≥95%, and the viscosity should be 100-200mPa.s. Under this condition, the temperature and concentration conditions for the subsequent sol-gel transition can better meet the needs of the human oral cavity and internal organs.

[0045] A further improvement is that the chitosan solution, the sodium β-glycerophosphate aqueous solution and the vanillin ethanol solution are allowed to stand for 6 to 12 hours.

[0046] It enables each solution to reach the reaction temperature as a whole, and the product after the reaction is more uniform.

[0047] A further improvement is that the soaking time for each washing in step S6 is 60 to 75 minutes.

[0048] By washing for more than one hour, unreacted acid and other components can be effectively cleaned to avoid affecting the gel effect.

[0049] The actual effects of the oral pH regulating gel spray prepared by the above preparation method are as follows:

[0050] Embodiment 1

[0051] A chitosan solution (deacetylation degree ≥ 95%, viscosity 100-200 mPa.s) was prepared with a 0.5 (v / v)% acetic acid aqueous solution to a concentration of 0.1 (w / v)%; a β-sodium glycerophosphate aqueous solution was prepared to a concentration of 20 (w / v)%; a vanillin ethanol solution was prepared to a concentration of 10 (w / v)%; the above three solutions were stirred evenly and placed at 0°C overnight; 10 ml of the prepared chitosan solution was taken, and 0.5 ml of β-sodium glycerophosphate aqueous solution and 0.5 ml of vanillin solution were slowly dripped in sequence, and the temperature was maintained at 0°C and stirred for 5 hours in the dark; after the reaction was completed, the product was taken out, washed three times with excess distilled water (immersed for 1 hour each time), and then freeze-dried for 12 hours to obtain a dry hydrogel powder; the dry hydrogel powder was sterilized by 15 kGy radiation, and a 0.3 (w / v)% aqueous solution was prepared at 0°C, and added to a hydraulic steel bottle or a manual pump spray bottle to obtain the final gel spray. The sol-gel transition time of the sol was 300 s when measured by the inversion method at 37°C.

[0052] Embodiment 2

[0053] A chitosan solution (deacetylation degree ≥ 95%, viscosity 100-200 mPa.s) was prepared with an acetic acid aqueous solution of 0.9 (v / v)% to a concentration of 0.8 (w / v)%; a β-sodium glycerophosphate aqueous solution was prepared to a concentration of 50 (w / v)%; a vanillin ethanol solution was prepared to a concentration of 30 (w / v)%; the above three solutions were stirred evenly and placed at 4°C overnight; 10 ml of the prepared chitosan solution was taken, and 0.5 ml of the β-sodium glycerophosphate aqueous solution and 0.5 ml of the vanillin solution were slowly dripped in sequence, and the temperature was maintained at 4°C and stirred for 12 hours in the dark; after the reaction was completed, the product was taken out, washed three times with excess distilled water (immersed for 1 hour each time), and then freeze-dried for 72 hours to obtain a dry hydrogel powder; the dry hydrogel powder was sterilized by 15 kGy radiation, and a 1 (w / v)% aqueous solution was prepared at 4°C, and added to a hydraulic steel bottle or a manual pump spray bottle to obtain the final gel spray. The sol-gel transition time of the sol at 37°C was 120s as determined by the inversion method; the sol exhibited pH-sensitive swelling and degradation behavior under different pH aqueous solution conditions (the cumulative release of vanillin in the solution was determined by UV spectrophotometry), see Figure 1 .

[0054] Embodiment 3

[0055] A chitosan solution (deacetylation degree ≥ 95%, viscosity 100-200 mPa.s) was prepared with a 5 (w / v)% acetic acid aqueous solution; a β-sodium glycerophosphate aqueous solution was prepared with a concentration of 50 (w / v)%; a vanillin ethanol solution was prepared with a concentration of 60 (w / v)%; the above three solutions were stirred evenly and placed at 25°C overnight; 10 ml of the prepared chitosan solution was taken, and 5 ml of the β-sodium glycerophosphate aqueous solution and 5 ml of the vanillin solution were slowly dripped in sequence, and the temperature was maintained at 25°C and stirred for 24 hours in the dark; after the reaction was completed, the product was taken out, washed three times with excess distilled water (immersed for 1 hour each time), and then freeze-dried for 72 hours to obtain a dry hydrogel powder; the dry hydrogel powder was sterilized by 25 kGy radiation, and a 20 (w / v)% aqueous solution was prepared at 25°C, and added to a hydraulic steel bottle or a manual pump spray bottle to obtain the final gel spray. The sol-gel transition time of the sol was 630 s when measured by the inversion method at 37°C.

[0056] It can be seen from Examples 1-3 that when the concentration of the acetic acid aqueous solution in step S1 is 0.9-1.2 (v / v)%, the concentration of the chitosan solution is 0.8 (w / v)%; the concentration of β-glycerophosphate in the sodium β-glycerophosphate aqueous solution is 45-50 (w / v)%; the concentration of vanillin in the vanillin ethanol solution is 30-35 (w / v)%; the ambient temperature in step S4 is 4-7° C. and the solution is allowed to stand overnight; the molar ratio of the chitosan solution to the sodium β-glycerophosphate aqueous solution and the vanillin solution in step S5 is 10: 0.5~1:0.5~1, the molar ratio of the sodium β-glycerophosphate aqueous solution and the vanillin solution is 1:1, and they are stirred for 12 hours in a dark place at a temperature of 4~7°C; the product in step S6 is washed and soaked for no less than 1 hour each time; the hydrogel powder is sterilized by 15kGy radiation, and is configured with distilled water at a room temperature of 4~7°C to form an oral pH regulating gel spray with a concentration of 1~1.5 (w / v)% aqueous solution, which has the shortest sol-gel transition time and the fastest coagulation efficiency when measured by the inversion method at a temperature of 37°C. Among them, because gastric juice will intermittently reflux during sleep at night, long-term retention must be ensured, and the pH adjustment function is best to produce intelligent regulation under the stimulation of gastric juice reflux, because gastric juice reflux may be intermittent, and it will not work if alkaline substances are held in the mouth for a long time waiting for neutralization when gastric juice refluxes. Considering that the pH value of the alkaline environment is above 7.2 for a long time, it is more conducive to the growth of Gram-negative bacteria. Therefore, the oral pH adjusting gel spray can form good adhesion and can provide long-term (at least 8 hours) oral retention. While producing effective protection effects, it can also automatically adapt and adjust pH-sensitive swelling and degradation behaviors under different pH aqueous solution conditions.

[0057] The above-mentioned implementation modes are only preferred implementation modes of the present application and cannot be used to limit the scope of protection of the present application. Any non-substantial changes and substitutions made by technicians in this field on the basis of the present application shall fall within the scope of protection required by the present application.

Claims

1. An oral pH regulating gel spray, characterized in that: The invention comprises polymer materials chitosan, β-glycerophosphate, vanillin, acetic acid water, ethanol and distilled water, and utilizes the hydrophobic interaction and electrostatic interaction between the polymer material chitosan and sodium β-glycerophosphate to form temperature sensitivity of sol-gel transition at physiological temperature; utilizes the Schiff base reaction between the polymer material chitosan and vanillin to produce imine bond to form pH sensitivity, thereby obtaining an oral pH regulating gel spray with dual intelligent responses of temperature sensitivity and pH sensitivity.

2. A method for preparing the oral pH regulating gel spray according to claim 1, characterized in that: The steps of the preparation method include: S1, preparing a chitosan solution with an acetic acid aqueous solution having a concentration of 0.5-5 (v / v)% and a polymer material chitosan, wherein the concentration of the chitosan solution is 0.1-5 (w / v)%; S2, preparing a sodium β-glycerophosphate aqueous solution with β-glycerophosphate and distilled water, wherein the concentration of β-glycerophosphate in the sodium β-glycerophosphate aqueous solution is 20-50 (w / v) %; S3, preparing a vanillin ethanol solution with vanillin and ethanol, wherein the concentration of vanillin in the vanillin ethanol solution is 10-60 (w / v) %; S4, stirring the three solutions prepared in steps S1-S3 respectively and placing them at 0-25°C for a certain period of time; S5, taking 10-50 ml of the chitosan solution treated in step S4, slowly dripping 0.5-5 ml of sodium β-glycerophosphate aqueous solution and 0.5-5 ml of vanillin solution in sequence, and stirring at 0-25° C. in the dark for 5-24 h; S6, taking out the product treated in step S5, placing it in a dialysis container, washing it three times with excess distilled water, and then freeze-drying it for 12-72 hours to obtain a dry hydrogel powder; S7. Take the hydrogel powder obtained in step S6, sterilize it with 15-25 kGy radiation, and then prepare it with distilled water at room temperature 0-25° C. into a 0.3-20 (w / v) % aqueous solution, and put it into a hydraulic steel or a manual pump spray bottle to prepare a final gel spray.

3. The method for preparing an oral pH regulating gel spray according to claim 1, characterized in that: The deacetylation degree of the chitosan solution is ≥95%, and the viscosity is 100-200 mPa.s.

4. The method for preparing an oral pH regulating gel spray according to claim 1, characterized in that: The chitosan solution, the sodium beta-glycerophosphate aqueous solution and the vanillin ethanol solution are allowed to stand for 6 to 12 hours.

5. The method for preparing an oral pH regulating gel spray according to claim 1, characterized in that: In step S6, the soaking time for each washing is 60 to 75 minutes.

6. The method for preparing an oral pH regulating gel spray according to claim 1, characterized in that: The concentration of the acetic acid aqueous solution in step S1 is 0.9-1.2 (v / v)%, the concentration of the chitosan solution is 0.8 (w / v)%, the concentration of β-glycerophosphate in the sodium β-glycerophosphate aqueous solution is 45-50 (w / v)%, and the concentration of vanillin in the vanillin ethanol solution is 30-35 (w / v)%.

7. The method for preparing an oral pH regulating gel spray according to claim 6, characterized in that: The ambient temperature of the standing still in step S4 is 4-7° C., and the standing still is overnight.

8. The method for preparing an oral pH regulating gel spray according to claim 7, characterized in that: In step S5, the molar ratio of the chitosan solution to the sodium β-glycerophosphate aqueous solution and the vanillin solution is 10:0.5-1:0.5-1, and the molar ratio of the sodium β-glycerophosphate aqueous solution and the vanillin solution is 1:

1. The mixture is stirred at 4-7°C in the dark for 12 hours.

9. The method for preparing an oral pH regulating gel spray according to claim 8, characterized in that: The product in step S6 is washed and soaked for no less than 1 hour each time.

10. The method for preparing an oral pH regulating gel spray according to claim 9, characterized in that: The hydrogel powder is sterilized by 15 kGy radiation and is prepared with distilled water at a room temperature of 4 to 7° C. to form an aqueous solution with a concentration of 1 to 1.5 (w / v) %.

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