Bioactive gel for treating oral ulcer and preparation method thereof
By preparing a multilayer structure of nanoemulsion and gel matrix, the adhesion and persistence problems of existing oral ulcer treatment products are solved, achieving multiple functions such as anti-inflammatory, analgesic and tissue regeneration promotion, promoting ulcer healing, and significantly improving treatment effect and patient experience.
Patent Information
- Application Number
- CN202511900157.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-16
- Publication Date
- 2026-01-23
AI Technical Summary
Existing oral ulcer treatment products are inadequate in terms of adhesion, persistence, and therapeutic effect, failing to effectively promote the repair and healing of ulcer surfaces, and may cause side effects.
Bioactive gels are prepared using nanotechnology. By mixing the active drug components as nanoemulsions with the gel matrix to form a multilayer structure, the drug is ensured to adhere to the ulcer surface for a long time and be released slowly. Combined with anti-inflammatory, analgesic and healing-promoting components, a sustained therapeutic effect is achieved.
It increases the concentration of the drug at the ulcer site, reduces systemic side effects, prolongs the duration of drug action, enables continuous treatment, promotes ulcer healing, and significantly improves treatment efficacy and patient experience.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of medical gel preparation, in particular to a bioactive gel for treating oral ulcer and a preparation method thereof. BACKGROUND
[0002] Oral ulcer, also known as "apthous ulcer", is a common oral mucosa disease, which often occurs in the tongue, lips, cheeks, vestibular sulcus, soft palate and other parts, and has periodicity. Patients often feel unbearable pain, especially when eating sour, salty, cold, hot and other foods, which seriously affects the patient's life and work. The incidence of oral ulcer in the general population is not less than 10%, and the prevalence rate in specific population can be more than 60%. Hospitalized patients are more likely to have oral ulcers due to their special health conditions, such as long-term use of drugs (such as antibiotics, immunosuppressants), physical weakness after surgery, malnutrition, etc. In addition, cancer patients receiving radiotherapy and chemotherapy, patients with systemic lupus erythematosus and other autoimmune diseases, and patients with impaired immune systems are all high-risk groups for oral ulcers. Although it is not a life-threatening disease, the occurrence of oral ulcers often means more complex health challenges for patients, especially hospitalized patients, and can significantly affect the patient's diet, speech and quality of life. Therefore, in recent years, research on oral ulcers in patients has gradually attracted attention, aiming to find effective prevention and treatment methods to alleviate the patient's pain and improve overall care.
[0003] At present, for the treatment of oral ulcer, the products used in clinical practice are powders, ointments, films, mouthwashes, etc., the main purpose of which is to relieve inflammation and pain. Although these products have certain curative effects on oral ulcers, they do not have the ability to induce the growth of tissue cells, and lack sufficient promoting effect on the repair and healing of the ulcer surface. In addition, the existing products have the disadvantages of poor local adhesion, easy loss with saliva, and inconvenient use, etc. The therapeutic effect of these products is affected to a certain extent by the movement of the masticatory muscle when the patient speaks and eats, etc. For example, the oral ulcer product in powder form is quickly lost with saliva after being applied to the affected area. The film has a strong foreign body sensation when used, and the shape of the film is different from that of the ulcer surface, resulting in imperfect adhesion. The mouthwash can only stay in the oral cavity for 3-5 minutes, and cannot adhere to the ulcer mucosa. The effect time is short, and repeated gargling is required. The use of chlorhexidine mouthwash, an antibacterial mouthwash, for a long time may cause oral staining, taste changes or dry mouth, etc. SUMMARY
[0004] In view of the deficiencies of the prior art, the present application provides a bioactive gel for treating oral ulcer and a preparation method thereof, aiming to provide a bioactive gel that can adhere to the ulcer surface for a long time, relieve pain, eliminate inflammation and promote tissue repair.
[0005] To solve the above technical problems, the technical solutions provided by the present application are as follows.
[0006] Firstly, the present application provides a preparation method of a bioactive gel for treating oral ulcer, which comprises the following steps: Step 1, preparing a gel matrix: mixing a gel material with deionized water to obtain the gel matrix, wherein the gel material is selected from at least one of hyaluronic acid, gelatin, polyvinyl alcohol and carbomer 940; Step 2, preparing a nanoemulsion containing an active pharmaceutical ingredient: dissolving the active pharmaceutical ingredient in a solvent to obtain an active pharmaceutical solution, mixing a surfactant with the active pharmaceutical solution, and then performing nanoization treatment to obtain a nanoemulsion with a droplet particle size of 20-100 nm; the surfactant is a complex of a non-ionic surfactant and a co-surfactant, and the weight ratio of the complex of the non-ionic surfactant and the co-surfactant is (2-4) : 1; Step 3, preparing a gel precursor solution: mixing the nanoemulsion prepared in step 2 and the gel matrix prepared in step 1 at a temperature of 25°C to obtain the gel precursor solution; Step 4, adjusting the pH value of the gel precursor solution prepared in step 3 to 6.5-7.5 using a pH adjuster, and then performing cross-linking solidification and sterilization treatment to obtain the bioactive gel for treating oral ulcer.
[0007] Further, in the gel matrix of step 1, the mass-volume concentration of hyaluronic acid is 0.1-2%, the mass-volume concentration of gelatin is 0.2-4%, the mass-volume concentration of polyvinyl alcohol is 0.5-4%, and the mass-volume concentration of carbomer 940 is 1-1.5%; the molecular weight of the hyaluronic acid is 120-180 MD. By controlling the concentration of the gel material in the gel matrix, the hydrophilicity of the gel matrix can be accurately regulated, the degradation time of the gel in the oral environment can be controlled, and the drug release can be ensured to match the healing period of the ulcer.
[0008] Further, the gel matrix in step 1 further comprises a lubricant. The addition of the lubricant can adjust the viscosity of the gel matrix and promote the dispersion of the drug nanoemulsion in the gel matrix. In some embodiments of the present application, glycerol is selected as the lubricant. In a low-temperature environment, glycerol can inhibit water crystallization and improve the low-temperature stability of the gel.
[0009] Further, the active pharmaceutical ingredients in step 2 are selected from at least one of anti-inflammatory agents, analgesics, healing promoters, and antibacterial agents. Anti-inflammatory agents can effectively reduce the swelling and pain around the ulcer; analgesics can relieve the pain of the ulcer part; healing promoters can accelerate the healing process of the ulcer and promote the repair of oral mucosa; antibacterial agents can reduce bacterial infection in the oral cavity and prevent the ulcer from further deterioration. The present application can accelerate the healing process of the ulcer and shorten the treatment time through the synergistic effect of various functional components such as anti-inflammatory, analgesic, healing promotion, and antibacterial.
[0010] In some embodiments of the present application, the anti-inflammatory agent is selected from at least one of dexamethasone sodium phosphate, aloe extract, honeysuckle extract; the analgesic is selected from at least one of lidocaine, benzocaine, menthol; the healing promoter is selected from at least one of carboxymethyl chitosan, glycyrrhizic acid, vitamin E, epidermal growth factor, fibroblast growth factor; and the antibacterial agent is selected from at least one of tea tree oil, propolis extract.
[0011] Further, the nanofication treatment in step 2 includes high-pressure homogenization and ultrasonic emulsification. By controlling the operating parameters of high-pressure homogenization or ultrasonic emulsification, the control of the droplet size of the nanoemulsion can be achieved. The present application controls the droplet size of the nanoemulsion within the range of 20-100 nm, which can increase the stability of the drug package and reduce the possibility of rapid drug release.
[0012] Further, the active pharmaceutical ingredients in step 2 include lipid-soluble components and water-soluble components. The lipid-soluble components are dissolved using an organic solvent, and the water-soluble components are dissolved using deionized water, which can ensure the effective dissolution of the active pharmaceutical ingredients in the solution, increase the drug loading capacity of the drug, and avoid drug precipitation.
[0013] Further, the non-ionic surfactant in step 2 is selected from at least one of Tween surfactants and polyoxyethylene hydrogenated castor oil, and the co-surfactant is selected from at least one of ethanol, n-propanol, and isopropanol. The combination of non-ionic surfactants and co-surfactants ensures the uniform dispersion and stability of the nanoemulsion in the gel matrix.
[0014] Further, the gel matrix in step 3 is divided into two parts, and the nanoemulsion is mixed with one part of the gel matrix at a temperature of 25°C to form a pre-gel, and the pre-gel is mixed with the other part of the gel matrix at a temperature of 25°C to obtain a gel precursor liquid. The present application is designed with a multi-layer structure. In the preparation process, the nanoemulsion is first mixed with part of the gel matrix to form a pre-gel, and then mixed with the remaining gel matrix to form a multi-layer structure. The outer layer of the gel has a higher cross-linking density, which acts as a barrier to slow down the drug release; the inner layer is embedded with nanoemulsion, which provides sustained drug supply.
[0015] Further, the pH regulator in step 4 is selected from any one of lactic acid, citric acid, sodium hydroxide, and triethanolamine. The present application uses lactic acid or citric acid as an acidic regulator, and uses sodium hydroxide or triethanolamine as an alkaline regulator. The pH value of the gel is adjusted to the range of 6.5-7.5 by the pH regulator, so that it is suitable for use in the oral environment and will not cause irritation or discomfort.
[0016] In the second aspect, it can be understood that the bioactive gel for treating oral ulcers prepared by any one of the above preparation methods also belongs to the protection scope of the present application.
[0017] The present application solves the problem of uneven dispersion of fat-soluble substances in aqueous gels by dissolving the drug for treating oral ulcers in a solvent to prepare a solution, and then preparing the solution into a nanoemulsion. The dispersion of the drug components in the nanoemulsion can be further improved by using a combination of surfactants. By loading the drug into the nanoemulsion and then mixing the nanoemulsion with the gel matrix at low temperature (<25℃), the highly uniform distribution of the nanoemulsion in the gel matrix is ensured, avoiding drug sedimentation or agglomeration, thereby ensuring the uniform dispersion of the drug in the gel matrix. The encapsulation of the drug by the nanoemulsion droplets and the network structure of the gel matrix give the gel good drug release effect. By precisely controlling the particle size of the nanoemulsion droplets, the drug release effect is further improved.
[0018] The present application prepares a gel matrix by selecting a biocompatible polymer material as the gel material. The gel matrix not only can adhere to the surface of the oral mucosa and form a protective barrier on the ulcer surface, effectively isolating the irritation and erosion of external objects (food, beverages, saliva), but also can provide sustained drug release to the ulcer surface, prolong the residence time of the drug on the ulcer surface, continuously exert the therapeutic effect, and enhance the therapeutic effect.
[0019] The innovation of the present application lies in the use of nanotechnology to precisely target the ulcer site with nanoparticles carrying antibacterial drugs, anti-inflammatory drugs, or growth factors. This unique approach significantly increases the concentration of drugs in the lesion area, while significantly reducing systemic side effects. Moreover, the nanoparticles can slowly release the drug, greatly prolonging the residence time of the drug on the ulcer surface, continuously exerting the multiple effects of anti-inflammatory, analgesic, and promoting tissue regeneration, accelerating the ulcer healing process, and effectively reducing scar formation.
[0020] Compared with traditional oral ulcer treatment preparations, the present application has the following outstanding advantages: (1) the nano drug delivery system can significantly increase the local concentration of drugs at the ulcer site, reduce the side effects caused by systemic absorption; (2) the drug action time is prolonged by intelligent sustained-release technology, and the sustained treatment effect is realized; (3) the three functions of anti-inflammatory, analgesic and tissue regeneration are innovatively integrated, which can effectively relieve pain, inhibit inflammatory reaction and promote wound repair; (4) the unique bioadhesion performance ensures the long-term retention of the gel in the oral environment, and improves the treatment efficiency.
[0021] In summary, the present application has the following beneficial technical effects: The preparation method provided by the present application solves the problem of uneven dispersion of fat-soluble drugs in aqueous gel, improves the sustained-release effect of drugs in oral ulcer gel, and enhances the treatment effect of oral ulcer gel. The bioactive gel for treating oral ulcer provided by the present application has high biocompatibility and strong adhesion, not only has good drug sustained-release effect, but also can realize the simultaneous action of multiple functions such as anti-inflammatory, analgesic, promoting tissue regeneration, etc., promote the healing of ulcer, shorten the treatment time, and significantly improve the treatment experience of patients. The preparation process of the present application is simple and convenient to use, which provides a safer, more efficient and comfortable solution for the treatment of oral ulcer. DETAILED DESCRIPTION
[0022] In order to enable those skilled in the art to better understand the technical solutions of the present application, the present application will be further described in detail below in combination with specific embodiments. Unless otherwise specified, the materials and reagents used in the following examples can be obtained through conventional commercial channels.
[0023] Example 1: The present embodiment provides a kind of bioactive gel for treating oral ulcer, and its preparation raw material includes: carbomer 940, glycerol, vitamin E, propolis extract, tea tree oil, menthol, dexamethasone sodium phosphate, carboxymethyl chitosan, polyoxyethylene hydrogenated castor oil (RH40), ethanol.
[0024] Its preparation method is as follows: (1) dissolve carbomer 940 (1 % w / v) in deionized water, add appropriate amount of glycerol (5wt%) and stir at 45 DEG C to form a uniform viscous liquid, i.e. gel matrix is obtained; (2) Vitamin E (0.1 wt %), propolis extract (0.01 wt %), tea tree oil (0.3 wt %) and menthol (0.02 wt %) are added into ethanol, stirred and dissolved to obtain a first active drug solution; dexamethasone sodium phosphate (0.05 wt %) is added into medium-chain triglyceride, stirred and dissolved to obtain a second active drug solution; carboxymethyl chitosan (0.1 wt %) is added into deionized water, stirred and dissolved to obtain a third active drug solution; the first, second and third active drug solutions are mixed in equal volume, stirred at 90 rpm for 1 h to obtain a uniformly dispersed mixture, the mixture is added into a container containing a surfactant (mass ratio: mixture: surfactant = 0.1: 100), stirred at 90 rpm for 1 h, and then transferred into a high-pressure homogenizer to prepare a nanoemulsion with a droplet size of 20-50 nm; the surfactant is a complex of RH40 and ethanol, and the mass ratio of RH40: ethanol is 4: 1; (3) The nanoemulsion is mixed with a gel matrix (mass ratio: nanoemulsion: gel matrix = 1: 10), stirred at 25°C at 120 rpm for 1 h, lactic acid is added to adjust the pH value to 6.8, and then cross-linked and cured by ultraviolet light to obtain a gel. The prepared gel is filled into a sterile tube and subjected to irradiation sterilization treatment, and finally a bioactive gel for treating oral ulcer is obtained.
[0025] Example 2: The present embodiment provides a bioactive gel for treating oral ulcer, and the preparation raw materials thereof include: hyaluronic acid (molecular weight 120-180 MD), gelatin, benzocaine, glycyrrhizic acid, tea tree oil, aloe extract, Tween 80 and ethanol.
[0026] The preparation method is as follows: (1) Hyaluronic acid (1% w / v) and gelatin (2% w / v) are dissolved in deionized water, stirred at 45°C until a uniform viscous liquid is formed, and a gel matrix is obtained. (2) Benzocaine (0.1 wt %), tea tree oil (0.3 wt %) and aloe extract (3 wt %) are added to ethanol, stirred and dissolved to obtain a first active drug solution; glycyrrhizic acid (0.05 wt %) is added to deionized water, heated to 60°C, stirred and dissolved to obtain a second active drug solution; the first active drug solution and the second active drug solution are mixed in equal amounts, stirred at 90 rpm for 1 h to obtain a uniformly dispersed mixture, the mixture is added to a container containing a surfactant (mass ratio: mixture: surfactant = 0.2: 100), stirred at 90 rpm for 1 h, and then transferred to a high-pressure homogenizer to prepare a nanoemulsion with droplet particle size of 40-60 nm; the surfactant is a complex of Tween 80 and ethanol, and the mass ratio of Tween 80: ethanol is 3: 1; (3) The nanoemulsion is mixed with the gel matrix (mass ratio: nanoemulsion: gel matrix = 1: 10), stirred at 25°C at 120 rpm for 1 h, lactic acid is added to adjust the pH value to 7.0, then cross-linked and cured by ultraviolet light to obtain a gel, the prepared gel is filled into sterile tubes and subjected to irradiation sterilization treatment, and finally a bioactive gel for treating oral ulcers is obtained.
[0027] Example 3: The present embodiment provides a bioactive gel for treating oral ulcers, and the preparation raw materials thereof include: hyaluronic acid (molecular weight 120-180 MD), polyvinyl alcohol, glycerol, vitamin E, propolis extract, tea tree oil, menthol, dexamethasone sodium phosphate, carboxymethyl chitosan, polyoxyethylene hydrogenated castor oil (RH40), and ethanol.
[0028] The preparation method is as follows: (1) Hyaluronic acid (1 % w / v) and polyvinyl alcohol (2% w / v) are dissolved in deionized water, and an appropriate amount of glycerol (5 wt %) is added and stirred at 45°C to form a uniform viscous liquid, which is the gel matrix; (2) Vitamin E (0.1 wt %), propolis extract (0.01 wt %), tea tree oil (0.3 wt %) and menthol (0.02 wt %) are added into ethanol, stirred and dissolved to obtain a first active drug solution; dexamethasone sodium phosphate (0.05 wt %) is added into medium-chain triglyceride, stirred and dissolved to obtain a second active drug solution; carboxymethyl chitosan (0.1 wt %) is added into deionized water, stirred and dissolved to obtain a third active drug solution; the first, second and third active drug solutions are mixed in equal volume, stirred at 90 rpm for 1 h to obtain a uniformly dispersed mixed solution, which is added into a container containing a surfactant (mass ratio: mixed solution: surfactant = 0.3: 100), stirred at 90 rpm for 1 h, and then transferred into a high-pressure homogenizer to prepare a nanoemulsion with droplet size of 50-100 nm; the surfactant is a complex of RH40 and ethanol, and the mass ratio of RH40: ethanol is 2: 1; (3) The nanoemulsion is mixed with the gel matrix (mass ratio: nanoemulsion: gel matrix = 1: 10), the gel matrix is divided into two equal parts, the nanoemulsion is mixed with one part of the gel matrix at 25°C and 120 rpm for 30 min to form a pre-gel, and then the pre-gel is mixed with the other part of the gel matrix at 25°C and 120 rpm for 30 min, triethanolamine is added to adjust the pH value to 7.5, and then the gel is cured by ultraviolet light crosslinking to obtain a gel. The prepared gel is filled into a sterile tube and subjected to irradiation sterilization treatment, and finally a bioactive gel for treating oral ulcer is obtained.
[0029] Example 4: The present embodiment provides a bioactive gel for treating oral ulcer, and the preparation raw materials thereof include: carbomer 940, dexamethasone sodium phosphate, Tween 80 and ethanol.
[0030] The preparation method is as follows: (1) Carbomer 940 (1.5 % w / v) is dissolved in deionized water, stirred at 45°C until a uniform viscous liquid is formed, i.e. a gel matrix is obtained; (2) Dexamethasone sodium phosphate (0.1 wt %) is added into medium-chain triglyceride, stirred and dissolved to obtain an active drug solution; the active drug solution is added into a container containing a surfactant (mass ratio: active drug solution: surfactant = 0.1: 100), stirred at 90 rpm for 1 h, and then transferred into a high-pressure homogenizer to prepare a nanoemulsion with droplet size of 20-50 nm; the surfactant is a complex of Tween 80 and ethanol, and the mass ratio of Tween 80: ethanol is 2.5: 1; (3) The nanoemulsion is mixed with the gel matrix (mass ratio: nanoemulsion: gel matrix = 1:10), stirred at 120 rpm for 1 h at 25°C, and then triethanolamine is added to adjust the pH value to 7. The gel is obtained by ultraviolet light cross-linking and curing. The prepared gel is filled into sterile tubes and treated by irradiation sterilization to obtain a bioactive gel for treating oral ulcers.
[0031] Comparative Example 1: This comparative example provides a bioactive gel for treating oral ulcers, which is prepared from the same raw materials as Example 1 (without a surfactant).
[0032] The preparation method is as follows: (1) Carbopol 940 (1% w / v) is dissolved in deionized water, and an appropriate amount of glycerol (5 wt%) is added to form a uniform viscous liquid at 45°C to obtain a gel matrix; (2) Vitamin E (0.1 wt%), propolis extract (0.01 wt%), tea tree oil (0.3 wt%), menthol (0.02 wt%), dexamethasone sodium phosphate (0.05 wt%), and carboxymethyl chitosan (0.1 wt%) are added to the gel matrix. After stirring at 500 rpm for 2 h, lactic acid is added to adjust the pH value to 6.8. The gel is obtained by ultraviolet light cross-linking and curing. The prepared gel is filled into sterile tubes and treated by irradiation sterilization to obtain a bioactive gel for treating oral ulcers.
[0033] Comparative Example 2: This comparative example provides a bioactive gel for treating oral ulcers, which is prepared from the same raw materials as Example 4 (without a surfactant).
[0034] The preparation method is as follows: (1) Carbopol 940 (1.5% w / v) is dissolved in deionized water to form a uniform viscous liquid at 45°C to obtain a gel matrix; (2) Dexamethasone sodium phosphate (0.1 wt%) is added to medium-chain triglyceride to obtain an active drug solution by stirring and dissolving. The active drug solution is then added to the gel matrix, stirred at 500 rpm for 2 h, and then triethanolamine is added to adjust the pH value to 7. The gel is obtained by ultraviolet light cross-linking and curing. The prepared gel is filled into sterile tubes and treated by irradiation sterilization to obtain a bioactive gel for treating oral ulcers.
[0035] Experimental analysis: I. Animal safety and effectiveness experiment Experimental subjects: 70 guinea pigs were selected, after anesthesia, a cotton ball soaked with phenol solution was used to burn the mouse sublingual for 60s to prepare an ulcer surface with a diameter of 5mm, and randomly divided into experimental groups 1-4, control groups 1-3, 10 mice in each group.
[0036] Dosing method: The experimental groups 1-4 were applied with the oral ulcer gel prepared in examples 1-4 every morning and evening, twice a day, 1mg each time, for 5 consecutive days; the control group 1 was applied with the oral ulcer gel prepared in comparative example 1 every morning and evening, the control group 2 was applied with the oral ulcer gel prepared in comparative example 2 every morning and evening, the control group 3 was applied with salt water every day, twice a day, 1mg each time, for 5 consecutive days; Effect evaluation: 0 degree: no ulcer under the tongue; I degree: ulcer exists, no obvious pseudomembrane at the ulcer site; II degree: a thin yellow-white pseudomembrane on the surface of the ulcer; III degree: a thicker pseudomembrane on the surface of the ulcer, with inflammatory edema around the ulcer; IV degree: thick pseudomembrane on the surface of the ulcer, with severe inflammatory edema around the ulcer.
[0037] Experimental results analysis: The effect evaluation statistics were carried out after 7 days of experiment, and the statistical results are shown in Table 1.
[0038] Table 1. Ulcer surface healing table
[0039] As can be seen from Table 1, the bioactive gel provided by examples 1-3 has a good repairing effect on the ulcer surface, and the bioactive gel provided by example 1 has a better repairing effect on the ulcer surface than comparative example 1 and example 4 than comparative example 2.
[0040] II. Release performance experiment of gel Franz transdermal diffusion apparatus was used, glass paper was placed between the supply pool and the receiving pool, and the supply pool and the receiving pool were clamped and fixed with clips. Artificial saliva ((Na2HPO42.38g, KH2PO40.19g, NaCl 0.8g dissolved in 1000mL water) was injected into the receiving pool, so that the inner surface of the dialysis bag was completely immersed therein, and there was no air bubble between them. The temperature was controlled at oral temperature, i.e. 37℃, and the rotation speed was 500r / min. 0.3g of gel was added to each supply pool. Sampling (receiving pool) was taken at set time points, and an equal amount of receiving liquid was supplemented. HPLC was used for determination (C18 column, 4.6mm x 250mm, stationary phase matrix 5um, mobile phase acetonitrile: 0.02% formic acid = 30:70, flow rate 1ml / min, detection wavelength 230nm, column temperature 35℃, injection volume 20uL). The release of gel in the receiving liquid of examples 1, 4, comparative examples 1 and 2 at different time points was calculated as a percentage, and the results are shown in Table 2 below.
[0041] Table 2. Results of sustained-release performance test of the bioactive gel
[0042] As can be seen from Table 2, Example 1 has better sustained-release performance than Comparative Example 1, and Example 4 has better sustained-release performance than Comparative Example 2.
[0043] In summary, the bioactive gel for treating oral ulcer provided by the present application has high biocompatibility and strong adhesion, not only has good drug sustained-release effect, but also can realize the simultaneous action of multiple functions such as anti-inflammatory, analgesic, and promoting tissue regeneration, promotes the healing of ulcer, shortens the treatment time, and significantly improves the treatment experience of patients.
[0044] The above is only the preferred embodiment of the present application, and it should be pointed out that the above preferred embodiment should not be regarded as a limitation of the present application, and the protection scope of the present application should be limited by the scope defined by the claims. For ordinary skilled persons in the art, several improvements and refinements can be made without departing from the spirit and scope of the present application, and these improvements and refinements should also be regarded as the protection scope of the present application.
Claims
1. A method for preparing a bioactive gel for the treatment of oral ulcers, characterized by: The method comprises the following steps: Step 1, preparing a gel matrix: mixing a gel material with deionized water to obtain the gel matrix, wherein the gel material is at least one selected from hyaluronic acid, gelatin, polyvinyl alcohol and carbomer 940; Step 2, preparing a nanoemulsion containing an active pharmaceutical ingredient: dissolving the active pharmaceutical ingredient in a solvent to obtain an active pharmaceutical solution, mixing a surfactant with the active pharmaceutical solution, and then performing nanoization treatment to obtain a nanoemulsion with a droplet particle size of 20-100 nm; the surfactant is a complex of a non-ionic surfactant and a co-surfactant, and the weight ratio of the complex of the non-ionic surfactant and the co-surfactant is (2-4) : 1; Step 3, preparing a gel precursor liquid: mixing the nanoemulsion prepared in step 2 with the gel matrix prepared in step 1 at a temperature of 25°C to obtain the gel precursor liquid; Step 4, adjusting the pH value of the gel precursor liquid prepared in step 3 to 6.5-7.5 using a pH adjuster, and then performing cross-linking solidification and sterilization treatment to obtain a bioactive gel for treating oral ulcers.
2. The method of claim 1, wherein: In the gel matrix of step 1, the mass-volume concentration of hyaluronic acid is 0.1-2%, the mass-volume concentration of gelatin is 0.2-4%, the mass-volume concentration of polyvinyl alcohol is 0.5-4%, and the mass-volume concentration of carbomer 940 is 1-1.5%; the molecular weight of the hyaluronic acid is 120-180 MD.
3. The method of claim 1, wherein: The gel matrix in step 1 further comprises a lubricant.
4. The method of claim 1, wherein: The active pharmaceutical ingredient in step 2 is at least one selected from anti-inflammatory agents, analgesics, healing promoters and antibacterial agents.
5. The method of claim 1, wherein: The nanoization treatment in step 2 comprises high-pressure homogenization and ultrasonic emulsification.
6. The method of claim 1, wherein: The active pharmaceutical ingredient in step 2 comprises fat-soluble components and water-soluble components, the solvent for dissolving the fat-soluble components is an organic solvent, and the solvent for dissolving the water-soluble components is deionized water.
7. The method of claim 1, wherein: The non-ionic surfactant in step 2 is at least one selected from Tween surfactants and polyoxyethylene hydrogenated castor oil, and the co-surfactant is at least one selected from ethanol, n-propanol and isopropanol.
8. The method of claim 1, wherein: In step 3, the gel matrix is divided into two portions, the nanoemulsion is mixed with one portion of the gel matrix at a temperature of 25°C to form a pre-gel, and the pre-gel is then mixed with the other portion of the gel matrix at a temperature of 25°C to obtain the gel precursor liquid.
9. The method of claim 1, wherein: The pH adjuster in step 4 is any one selected from lactic acid, citric acid, sodium hydroxide and triethanolamine.
10. A bioactive gel for the treatment of oral ulcers, characterized in that: The bioactive gel is prepared by the preparation method of any one of claims 1-9.