Triamcinolone acetonide lidocaine oral gel spray and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations and preparation thereof, and particularly relates to triamcinolone acetonide lidocaine oral gel spray and a preparation method thereof. The triamcinolone acetonide and lidocaine oral gel spray is prepared from the following components: lidocaine hydrochloride, triamcinolone acetonide, phospholipid, natural fatty glyceride, a non-aqueous solvent, a solubilizer and a flavoring agent. The preparation method of the triamcinolone acetonide and lidocaine oral gel spray comprises the following steps: mixing the non-aqueous solvent and the solubilizer, adding triamcinolone acetonide and lidocaine hydrochloride for dissolving, adding the phospholipid and the natural fatty glyceride, uniformly mixing, and adding the flavoring agent to obtain a mixed liquid medicine; sterilizing and filtering; and filling the liquid medicine. The triamcinolone acetonide lidocaine oral gel spray provided by the invention is good in film-forming property, adhesion, drug dispersibility and drug sustained release performance, and the invention also provides a preparation method of the triamcinolone acetonide lidocaine oral gel spray.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations and preparations thereof, and particularly relates to triamcinolone acetonide lidocaine oral gel spray and a preparation method thereof. Background Art

[0002] Oral ulcer is a common oral disease in which the oral mucosa is damaged, resulting in depressions ranging in size from rice grains to soybeans, with surrounding congestion and obvious local burning pain. 95% of the ulcers in the mouth are recurrent oral ulcers (commonly known as mouth sores), which are one of the most common oral mucosal diseases. Recurrent oral ulcers are also known as recurrent aphthous ulcers (RAU) and recurrent aphthous stomatitis. The incidence rate is high and it is easy to relapse. The incidence rate in the general population is 25%, and the recurrence rate in 3 months is 50%. The disease is mainly manifested by the repeated appearance of round or oval ulcers in the non-keratinized oral mucosa such as lips, tongue, cheeks and soft palate, accompanied by local redness, swelling and burning pain, and has the characteristics of periodicity, recurrence and self-limitation. The ulcer healing period is generally 7 to 14 days, and the course of the disease can be up to 3 months in severe cases. There is no specific method to cure oral ulcers at home and abroad. The treatment is mainly symptomatic, and the treatment goals are to relieve pain, promote ulcer healing, and prolong the interval between recurrences.

[0003] At present, the drugs for treating oral ulcers include local analgesics (such as lidocaine gel, spray, benzydamine mouthwash, etc.), local corticosteroids (such as adhesive patches containing dexamethasone and hydrocortisone, etc.), local antibacterial and disinfectant drugs (such as chlorhexidine mouthwash, etc.), and local anti-inflammatory preparations (prostaglandin gel, etc.). Most of the therapeutic drugs used are combined, with short maintenance time, limited treatment effect, and patients need to take drugs frequently, which leads to poor compliance.

[0004] Triamcinolone acetonide, as an adrenal cortex hormone, is recommended for the treatment of oral ulcers. It has similar effects to dexamethasone, with strong anti-inflammatory and anti-allergic effects, 20-40 times stronger than hydrocortisone. Currently, triamcinolone acetonide oral ointment is available for the treatment of oral ulcers. It is applied and easily licked by saliva during use, resulting in poor drug efficacy and failure to relieve the patient's pain.

[0005] Lidocaine, as a local anesthetic, is a derivative of cocaine, but it is not hallucinogenic or addictive. It is clinically used to relieve pain in oral ulcers. It takes effect immediately after application and the effect lasts for 1-3 hours. Currently on the market is compound chamomile lidocaine gel, which can quickly relieve the pain caused by oral ulcers, but has no anti-inflammatory effect, and the duration of the drug effect is short, which affects the patient's eating.

[0006] Currently, there is no product on the market for treating oral ulcers that can achieve the combined effects of long-term and high effectiveness. Summary of the invention

[0007] The technical problem to be solved by the present invention is to overcome the above-mentioned defects of the prior art and provide triamcinolone acetonide lidocaine oral gel spray, which has good film adhesion, drug dispersibility and drug sustained release performance. The present invention also provides a preparation method thereof.

[0008] Each 1 mL of triamcinolone acetonide lidocaine oral gel spray of the present invention comprises the following ingredients: Lidocaine hydrochloride 5-45 mg; Triamcinolone acetonide 0.5-10mg; Phospholipids 200-500 mg; Natural fatty acid glycerides 300-650mg; Non-aqueous solvent 100-300 mg; Solubilizer 1-20 mg; Flavoring agent 0-5mg.

[0009] The phospholipid is one of soybean lecithin and egg yolk lecithin, wherein the content of phosphatidylcholine is 50%-99%, preferably soybean lecithin.

[0010] The natural fatty acid glyceride is one of monoolein, diolein, triolein and linolein, preferably diolein.

[0011] The non-aqueous solvent is one or more of anhydrous ethanol, propylene glycol, glycerol, benzyl alcohol, dimethyl sulfoxide, and N-methyl-2-pyrrolidone (NMP), preferably anhydrous ethanol, propylene glycol, and glycerol.

[0012] The solubilizing agent is one of Tween 80, Tween 20, polyethylene glycol 300, polyethylene glycol 400, castor oil, hydrogenated castor oil, sesame oil, corn oil, soybean oil, olive oil, peppermint oil, sunflower oil, medium chain triglycerides, ethyl oleate, triacetin, ethyl lactate, benzyl benzoate, ethyl benzoate, and triethyl citrate. Tween 80, polyethylene glycol 400, Tween 20, and medium chain triglycerides are preferred.

[0013] The flavoring agent is peppermint oil, lemon flavor, strawberry flavor, mango flavor, blueberry flavor, grape flavor, passion fruit flavor, lychee flavor, orange flavor, raisin flavor, jasmine powder flavor, rose flavor, gardenia flavor, cherry flavor, tea flavor, preferably peppermint oil, lemon flavor, and orange flavor.

[0014] The preparation method of the triamcinolone acetonide lidocaine oral gel spray comprises the following steps: 1) Preparation of intermediates: firstly, the non-aqueous solvent and the solubilizer are mixed, then triamcinolone acetonide and lidocaine hydrochloride are added to dissolve, then phospholipids and natural fatty acid glycerides are added to mix, and finally, the flavoring agent is added to obtain a mixed liquid; 2) Sterilization filtration: The mixed liquid is sterilized and filtered through a three-stage filtration system; the filter material is polytetrafluoroethylene (PTFE) or polyvinylidene fluoride (PVDF); 3) Filling of liquid medicine: Fill the filtered and sterilized liquid medicine to obtain triamcinolone acetonide lidocaine oral gel spray. It can be directly sealed with a liquid spray pump head or sealed with a high-density polyethylene cap. When using it, the patient can install the matching spray pump head by himself.

[0015] In the three-stage sterilization filtration described in step 2), the first stage is filtered using a 0.45μm-0.8μm filter, and the second and third stages are filtered using a 0.1μm-0.22μm filter, and the filtration temperature is 20-40°C.

[0016] The liquid medicine is filled into medium borosilicate glass tube bottles, polyethylene bottles or polyester bottles in a Class A clean environment.

[0017] The obtained triamcinolone acetonide lidocaine oral gel spray is administered by topical administration.

[0018] The present invention combines triamcinolone acetonide and lidocaine for the first time to prepare a compound in-situ gel preparation for the treatment of oral ulcers, which has a long-term synergistic effect of analgesia and anti-inflammatory. When used, the product is sprayed onto the oral lesion, and grease accumulates on the surface of saliva, spontaneously forming a sphere, which is interconnected and quickly arranged into a thin gel skeleton to form a physical barrier. The physical barrier has strong bioadhesion and provides protection for up to 8-12 hours. Lidocaine significantly relieves pain. Triamcinolone acetonide is anti-inflammatory and promotes repair. At the same time, the barrier effect of the in-situ gel allows patients to eat without worries. For patients with oral ulcers classified as III and IV, their nutritional status can be significantly improved. For patients with oral ulcers undergoing radiotherapy and chemotherapy, it can help them successfully complete the entire radiotherapy and chemotherapy cycle. The treatment scheme of the novel drug delivery preparation provided by the present invention has broad application prospects in the field of oral ulcer treatment.

[0019] The invention uses lidocaine hydrochloride and triamcinolone acetonide as therapeutic drugs, uses phospholipids and glycerides as matrix materials, uses a non-aqueous solvent to dissolve the drugs into the matrix, adds a solubilizer to promote drug dissolution, and adds a flavoring agent to improve the taste of the drugs, thereby providing patients with a more effective and longer-lasting pain relief and oral ulcer treatment solution. The in-situ gel drug loading is used to extend the drug action time, reduce the number of drug administrations, reduce drug side effects, and improve patient medication compliance.

[0020] Compared with the prior art, the present invention has the following beneficial effects: (1) The triamcinolone acetonide lidocaine oral gel spray of the present invention is used for local administration by spraying onto oral ulcers, and has a "double-layer protection" function. While forming a protective film to protect the wound surface, the drug is slowly released to continuously exert the analgesic and healing-promoting effects. Compared with other dosage forms, the spray of the present invention is easy to use, forms a drug reservoir for long-term release of drugs, achieves a synergistic therapeutic effect of combined medication, and improves the patient's medication compliance.

[0021] (2) The triamcinolone acetonide lidocaine oral gel spray of the present invention is a kind of in situ gel. It is liquid at room temperature before use in the oral cavity. Industrial production is easy to achieve and the cost is controllable. The materials used are all from natural sources, have no immunogenicity and irritation, and will not cause inflammatory response in the body.

[0022] (3) The preparation method of the triamcinolone acetonide-lidocaine oral gel spray of the present invention increases the biocompatibility of triamcinolone acetonide and lidocaine, prolongs the duration of medication, reduces the number of medications, and improves patient compliance. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Schematic diagram of the evaluation of the adhesion performance of the triamcinolone acetonide lidocaine oral gel spray preparations prepared in Examples 1-6 and Comparative Examples 1-3.

[0024] Figure 2 The in vitro cumulative release curves of lidocaine hydrochloride of the triamcinolone acetonide lidocaine oral gel spray preparations prepared in Examples 1-6 and Comparative Examples 1-3 at different times.

[0025] Figure 3 The in vitro cumulative release curves of triamcinolone acetonide at different times for the triamcinolone acetonide lidocaine oral gel spray preparations prepared in Examples 1-6 and Comparative Examples 1-3. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with specific embodiments.

[0027] The raw materials used in the following examples and comparative examples are all commercially available products.

[0028] Lidocaine hydrochloride: Commercially available from Shandong Chenghui Shuangda Pharmaceutical Co., Ltd., white or nearly white crystalline powder, highly soluble in water and easily soluble in ethanol.

[0029] Triamcinolone acetonide: Commercially available from Tianjin Pacific Chemical Pharmaceutical Co., Ltd., it is an adrenal cortical hormone drug, white to off-white crystalline powder, slightly soluble in methanol or ethanol, and very slightly soluble in water.

[0030] Example 1 Each 1 mL of triamcinolone acetonide lidocaine oral gel spray contains the following ingredients: Lidocaine hydrochloride 5 mg; Triamcinolone acetonide 0.5 mg; Soy lecithin 200mg; Glyceryl dioleate 650mg; Anhydrous ethanol 86.5 mg; Propylene glycol 56 mg; Tween 80 1mg; Peppermint oil 1mg; The preparation method of the triamcinolone acetonide lidocaine oral gel spray comprises the following steps: 1) Preparation of intermediates: In a stainless steel liquid preparation system, first add anhydrous ethanol, propylene glycol and Tween 80, then weigh triamcinolone acetonide and lidocaine hydrochloride and dissolve them. After 10 minutes, when all the drugs are dissolved, add soybean lecithin and dioleyl glycerol and stir at 300 r / min to mix well, and finally add peppermint oil; 2) Sterilization filtration: The prepared liquid medicine is sterilized and filtered through a three-stage filtration system, including a first-stage 0.45μm filter and a second-stage 0.1μm filter. The filtration temperature is 20°C and the filter material is polytetrafluoroethylene (PTFE). 3) Liquid filling: Fill the sterilized liquid into medium borosilicate glass tube bottles in a Class A clean environment and seal them directly with a liquid spray pump head.

[0031] Example 2 Each 1 mL of triamcinolone acetonide lidocaine oral gel spray contains the following ingredients: Lidocaine hydrochloride 25 mg; Triamcinolone acetonide 3mg; Soy lecithin 500mg; Glyceryl dioleate 318 mg; Anhydrous ethanol 149 mg; Macrogol 400 3mg; Orange flavor 2mg; The preparation method of the triamcinolone acetonide lidocaine oral gel spray comprises the following steps: 1) Preparation of intermediates: In a stainless steel liquid preparation system, first add anhydrous ethanol and polyethylene glycol 400, then weigh triamcinolone acetonide and lidocaine hydrochloride to dissolve them. After all the drugs are dissolved, weigh soybean lecithin and dioleyl glycerol and stir at 150r / min to mix well, and finally add orange flavor; 2) Sterilization filtration: The prepared drug solution is sterilized and filtered through a three-stage filtration system, with the first stage being a 0.45 μm filter and the second and third stages being 0.22 μm filters. The filtration temperature is 28°C and the filter material is polyvinylidene fluoride (PVDF); 3) Liquid filling: Fill the sterilized liquid into medium borosilicate glass tube bottles in a Class A clean environment and seal them directly with a liquid spray pump head.

[0032] Example 3 Each 1 mL of triamcinolone acetonide lidocaine oral gel spray contains the following ingredients: Lidocaine hydrochloride 45 mg; Triamcinolone acetonide 10mg; Soy lecithin 283mg; Linoleic acid glyceride 341mg; Propylene glycol 300 mg; Tween 20 20mg; Lemon essence 1mg; The preparation method of the triamcinolone acetonide lidocaine oral gel spray comprises the following steps: 1) Preparation of intermediates: In a stainless steel liquid preparation system, first add propylene glycol and Tween 20, then weigh triamcinolone acetonide and lidocaine hydrochloride to dissolve them, after all the drugs are dissolved, weigh soybean lecithin and linoleic acid glyceride and stir to mix, and finally add lemon essence; 2) Sterilization filtration: The prepared liquid medicine is sterilized and filtered through a three-stage filtration system, including a first-stage 0.8μm filter and a second-stage 0.1μm filter. The filtration temperature is 40°C and the filter material is polytetrafluoroethylene (PTFE). 3) Liquid filling: The sterilized liquid medicine is filled into polyethylene bottles in a Class A clean environment and the liquid spray pump head is directly sealed.

[0033] Example 4 Each 1 mL of triamcinolone acetonide lidocaine oral gel spray contains the following ingredients: Lidocaine hydrochloride 15 mg; Triamcinolone acetonide 4mg; Egg yolk lecithin 471mg; Glyceryl dioleate 300mg; NMP 100mg; Anhydrous ethanol 100 mg; Tween 80 8mg; Strawberry flavor 2mg; The preparation method of the triamcinolone acetonide lidocaine oral gel spray comprises the following steps: 1) Preparation of intermediates: In a stainless steel liquid preparation system, first add NMP, anhydrous ethanol and Tween 80, then weigh triamcinolone acetonide and lidocaine hydrochloride to dissolve them, after all the drugs are dissolved, weigh egg yolk lecithin and dioleylglycerol, stir and mix, and finally add strawberry flavor; 2) Sterilization filtration: The prepared drug solution is sterilized and filtered through a three-stage filtration system, including a first-stage 0.8μm filter and a second-stage 0.22μm filter. The filtration temperature is 35°C and the filter material is polyvinylidene fluoride (PVDF). 3) Filling of liquid medicine: The sterilized liquid medicine is filled into a polyester bottle in a Class A clean environment. It is sealed with a high-density polyethylene cap, and the patient installs the matching spray pump head by himself when using it.

[0034] Example 5 Each 1 mL of triamcinolone acetonide lidocaine oral gel spray contains the following ingredients: Lidocaine hydrochloride 15 mg; Triamcinolone acetonide 1mg; Soy lecithin 394mg; Glyceryl monooleate 475mg; Benzyl alcohol 100 mg; Tween 80 10mg; Jasmine powder flavor 5mg; The preparation method of the triamcinolone acetonide lidocaine oral gel spray comprises the following steps: 1) Preparation of intermediates: In a stainless steel liquid preparation system, first add benzyl alcohol and Tween 80, then weigh triamcinolone acetonide and lidocaine hydrochloride to dissolve them, after all the drugs are dissolved, weigh soybean lecithin and monooleylglycerol, stir and mix, and finally add jasmine powder flavor; 2) Sterilization filtration: The prepared liquid medicine is sterilized and filtered through a three-stage filtration system, including a first-stage 0.45μm filter and a second-stage and third-stage 0.22μm filter. The filtration temperature is 30°C and the filter material is polytetrafluoroethylene (PTFE). 3) Liquid filling: The sterilized liquid is filled into medium borosilicate glass tube bottles in a Class A clean environment. The liquid spray pump head is directly sealed.

[0035] Example 6 Each 1 mL of triamcinolone acetonide lidocaine oral gel spray contains the following ingredients: Lidocaine hydrochloride 15 mg; Triamcinolone acetonide 1mg; Soy lecithin 500mg; Triolein 319mg; Glycerol 158mg; Medium chain triglycerides 7mg; The preparation method of the triamcinolone acetonide lidocaine oral gel spray comprises the following steps: 1) Preparation of intermediates: In a stainless steel liquid preparation system, first add glycerol and medium-chain triglycerides, then weigh triamcinolone acetonide and lidocaine hydrochloride to dissolve them, and after all the drugs are dissolved, weigh soybean lecithin and triolein and stir to mix; 2) Sterilization filtration: The prepared drug solution is sterilized and filtered through a three-stage filtration system, including a 0.8μm filter for the first stage and a 0.22μm filter for the second and third stages. The filtration temperature is 20°C and the filter material is polyvinylidene fluoride (PVDF); 3) Filling of drug solution: The sterilized drug solution is filled into a polyethylene bottle in a Class A clean environment and sealed with a high-density polyethylene cap. When in use, the patient installs the matching spray pump head by himself.

[0036] Comparative Example 1 The ingredients and preparation methods of the pharmaceutical preparations in this comparative example are the same as those in Example 1, except that 200 mg of soybean lecithin is removed from the ingredients. The rest is exactly the same as in Example 1.

[0037] Comparative Example 2 The ingredients and preparation methods of the pharmaceutical preparations in this comparative example are the same as those in Example 1, except that 650 mg of diolein is removed from the ingredients. The rest is exactly the same as in Example 1.

[0038] Comparative Example 3 This comparative example uses water as a solvent, and each 1 mL of the oral gel spray contains the following ingredients: Lidocaine hydrochloride 5 mg; Triamcinolone acetonide 0.5 mg; Sodium carboxymethylcellulose 20 mg; Carrageenan 7mg; Diglycerol 600mg; Water 360mg; Sodium citrate 2mg; Potassium sorbate 0.5 mg; Strawberry flavor 5mg; The preparation method of the composition comprises the following steps: 1) Dispersing lidocaine hydrochloride, triamcinolone acetonide and sodium carboxymethyl cellulose in diglycerol; 2) Dissolve the remaining components in water; 3) Pour the solution in 1) into the solution in 2) and stir evenly.

[0039] Evaluation test (1) Film-forming performance evaluation The triamcinolone acetonide lidocaine oral gel spray prepared in Examples 1-6 and Comparative Examples 1-3 were respectively taken, and the film-forming property was evaluated according to the following method: a culture dish with an inner diameter of 10 cm was taken, 0.28 g of physiological saline was evenly sprayed in the culture dish, and then 0.16 g of triamcinolone acetonide lidocaine oral gel was evenly sprayed on the inner surface of the culture dish, and placed in a 37° C. incubator for 5 minutes to observe whether a thin film was formed. If a film could be formed, it was yes, and if a film could not be formed, it was no. The film-forming property results are shown in Table 1.

[0040] Table 1 Film forming results

[0041] From the data in Table 1, it can be seen that the oral ulcer gels involved in the present invention all have good film-forming properties, while the film-forming properties of Comparative Examples 1-2 are poor. The finished product of Comparative Example 3 is a hydrogel, which is completely different from the gel matrix involved in the present invention and has no film-forming property.

[0042] (2) Adhesion performance evaluation Take the triamcinolone acetonide lidocaine oral gel spray prepared in Examples 1-6 and Comparative Examples 1-3 respectively, and evaluate the adhesion performance according to the following method: install the gel probe on the texture analyzer, set the probe running speed to 2mm / s, the trigger force to 5g, the interval between two compressions to 5s, and the compression degree to 50%. Then weigh 1g of the prepared triamcinolone acetonide lidocaine oral gel spray and place it in a 5mL vial, add an equal amount of physiological saline, let it stand for 30min, wait for the gel to solidify, take it out with a small spoon, and place the gel on the texture analyzer test bench for adhesion strength test. Repeat three times for each gel. Adhesion performance evaluation is as follows: Figure 1 As shown (the adhesion strength is taken as the average value).

[0043] Depend on Figure 1 It can be seen that the oral ulcer gel of the present invention has good adhesion, and the adhesion strength is above 10 kPa, while the adhesion of Comparative Examples 1-2 is poor, and Comparative Example 3 has no adhesion at all.

[0044] (3) Investigation of in vitro release The triamcinolone acetonide lidocaine oral gels prepared in the above Examples 1-6 and Comparative Examples 1-3 were subjected to an in vitro release test.

[0045] Take 1 mL of triamcinolone acetonide lidocaine oral gel (equivalent to 20 mg of lidocaine and 1 mg of triamcinolone acetonide) in the basket of the dissolution instrument. Immerse the basket in pH=7.4 PBS buffer. After the oral gel solidifies, install the basket on the rotating rod of the dissolution instrument, add 500 mL of pH=7.4 PBS buffer medium, place it in the dissolution instrument at 37℃±0.5℃, rotate at 100r / min, and take 2.0 mL samples at 0h, 1h, 2h, 4h, 6h, 8h, 12h, 16h, 20h, and 24h without rehydration.

[0046] The sample was filtered through a 0.45μm filter membrane as the test sample solution; the content of lidocaine hydrochloride was determined according to high performance liquid chromatography (General Rules 0512 of the Fourth Part of the 2020 Edition of the Chinese Pharmacopoeia), using a Shim-Pack-GIST C18 column with specifications of 4.6×250mm, 5µm, and a phosphate solution and acetonitrile in a volume ratio of 50:50 as the mobile phase. Phosphate buffer is 1.3mL of 1mol / L sodium dihydrogen phosphate solution and 32.5mL of 0.5mol / L disodium hydrogen phosphate solution mixed, diluted with water to 1000mL, and adjusted to pH 8 with phosphoric acid. The flow rate is 1.0mL / min, the column temperature is 35℃, the detection wavelength is 254nm, and the injection volume is 20µL.

[0047] The content of triamcinolone acetonide was determined according to the high performance liquid chromatography method (General Rules 0512 of Part IV of the 2020 edition of the Chinese Pharmacopoeia), using a Shim-Pack-GIST C18 chromatographic column with specifications of 4.6×250mm, 5µm, methanol and water 525:475 as the mobile phase, a flow rate of 1.0mL / min, a column temperature of 35°C, a detection wavelength of 240nm, and an injection volume of 20µL.

[0048] Accurately weigh an appropriate amount of lidocaine hydrochloride reference substance, dissolve it in phosphate solution and dilute it to make a solution containing about 0.1 mg of lidocaine hydrochloride per 1 mL as a control solution. Weigh an appropriate amount of triamcinolone acetonide reference substance, dissolve it in mobile phase and dilute it to make a solution containing 0.1 mg of triamcinolone acetonide per 1 mL as a control solution. Add them to the test sample solution to be tested respectively, calculate the cumulative release at different times by peak area using the external standard method, and draw a cumulative release curve. The measurement results of the cumulative release of lidocaine hydrochloride are shown in Table 2, and the cumulative release curve is shown in Figure 2 The results of the cumulative release of triamcinolone acetonide are shown in Table 3, and the cumulative release curve is shown in Table 3. Figure 3 shown.

[0049] Table 2 Determination results of the cumulative release of lidocaine hydrochloride

[0050] Table 3 The results of the determination of the cumulative release of triamcinolone acetonide

[0051] From Table 2-3 and Figure 2-3 It can be seen that the triamcinolone acetonide lidocaine oral gel spray prepared by Examples 1-6 has a sustained release effect of greater than or equal to 12h, which slowly releases the drug in the preparation and prolongs the action time, thereby reducing the number of administrations and greatly improving patient compliance. Comparative Examples 1 and 2 do not have a sustained release effect, and the release degree reaches more than 90% in 1h. The sustained release result of Comparative Example 3 is poor. Examples 1 and 3 show that the oral gel drug with the addition of solubilizer Tween 20 has a faster release rate of the drug. Examples 1, 5 and 6 show that the type of solvent has little effect on the release of the drug in the oral gel.

Claims

1. A triamcinolone acetonide lidocaine oral gel spray, characterized in that: Each 1 mL of the oral gel spray contains the following ingredients: Lidocaine hydrochloride 5-45 mg; Triamcinolone acetonide 0.5-10mg; Phospholipids 200-500 mg; Natural fatty acid glycerides 300-650mg; Non-aqueous solvent 100-300 mg; Solubilizer 1-20 mg; Flavoring agent 0-5mg.

2. The triamcinolone acetonide lidocaine oral gel spray according to claim 1, characterized in that: The phospholipid is one of soybean lecithin and egg yolk lecithin, wherein the content of phosphatidylcholine is 50%-99%.

3. The triamcinolone acetonide lidocaine oral gel spray according to claim 1, characterized in that: The natural fatty acid glyceride is one of monoolein, diolein, triolein and linolein.

4. The triamcinolone acetonide lidocaine oral gel spray according to claim 1, characterized in that: The non-aqueous solvent is one or more of anhydrous ethanol, propylene glycol, glycerol, benzyl alcohol, dimethyl sulfoxide, and N-methyl-2-pyrrolidone.

5. The triamcinolone acetonide lidocaine oral gel spray according to claim 1, characterized in that: The solubilizing agent is one of Tween 80, Tween 20, polyethylene glycol 300, polyethylene glycol 400, castor oil, hydrogenated castor oil, sesame oil, corn oil, soybean oil, olive oil, peppermint oil, sunflower seed oil, medium chain triglycerides, ethyl oleate, triacetin, ethyl lactate, benzyl benzoate, ethyl benzoate, and triethyl citrate.

6. The triamcinolone acetonide lidocaine oral gel spray according to claim 1, characterized in that: The flavor corrector is peppermint oil, lemon flavor, strawberry flavor, mango flavor, blueberry flavor, grape flavor, passion fruit flavor, lychee flavor, orange flavor, raisin flavor, jasmine powder flavor, rose flavor, gardenia flavor, cherry flavor, and tea flavor.

7. A method for preparing the triamcinolone acetonide lidocaine oral gel spray according to any one of claims 1 to 6, characterized in that: The following steps are involved: 1) Preparation of intermediates: firstly, the non-aqueous solvent and the solubilizer are mixed, then triamcinolone acetonide and lidocaine hydrochloride are added to dissolve, then phospholipids and natural fatty acid glycerides are added to mix, and finally, the flavoring agent is added to obtain a mixed liquid; 2) Sterilization filtration: The mixed liquid is sterilized and filtered through a three-stage filtration system; 3) Filling the drug solution: filling the filtered and sterilized drug solution to obtain the triamcinolone acetonide lidocaine oral gel spray.

8. The method for preparing the triamcinolone acetonide lidocaine oral gel spray according to claim 7, characterized in that: In the three-stage sterilization filtration described in step 2), the first stage is filtered using a 0.45μm-0.8μm filter, and the second and third stages are filtered using a 0.1μm-0.22μm filter, and the filtration temperature is 20-40°C.

9. The method for preparing the triamcinolone acetonide lidocaine oral gel spray according to claim 7, characterized in that: The liquid medicine is filled into medium borosilicate glass tube bottles, polyethylene bottles or polyester bottles in a Class A clean environment.

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