Traditional Chinese medicine oral ulcer pasting film with local anesthesia effect as well as preparation method and application of traditional Chinese medicine oral ulcer pasting film

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a traditional Chinese medicine oral ulcer patch with a local anesthesia effect and a preparation method and application thereof. The invention discloses a traditional Chinese medicine oral ulcer pasting film with a local anesthesia effect. The traditional Chinese medicine oral ulcer pasting film is prepared from the following components in parts by mass: 16-22 parts of indigo naturalis, 1.6-2.2 parts of borneol, 0.7-1.1 parts of propolis, 120-142.5 parts of asarum, 1-5 parts of glycerol, 45-75 parts of polyvinyl alcohol, 1.5-4.5 parts of hydroxy propyl cellulose and 0.5-1 part of carbomer. The traditional Chinese medicine oral ulcer patch is prepared from pure traditional Chinese medicine components, has a remarkable local anesthesia effect and a good treatment effect, and is simple in preparation method, low in cost and easy to popularize and apply.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a traditional Chinese medicine oral ulcer patch with local anesthetic effect, and a preparation method and application thereof. Background Art

[0002] In the field of oral care and treatment, oral ulcer is a common disease that causes great inconvenience to patients' daily lives. The treatment of oral ulcer has always been one of the focuses of medical research.

[0003] Traditional treatments for oral ulcers include ointments, mouthwashes, and sprays. While these methods can temporarily relieve symptoms, they often have limitations. For example, ointments and sprays require frequent application, have a short residence time in the mouth, and are easily diluted by saliva, affecting their effectiveness. Furthermore, these treatments may require patients to possess certain procedural skills to ensure the medication is precisely targeted to the ulcer site.

[0004] In recent years, oral patches (PAOFs) have gained increasing attention as a novel drug delivery system, offering more sustained and stable drug release. These patches adhere closely to the oral lining, reducing swallowing and saliva dilution, thereby increasing local drug concentration and efficacy. However, existing oral patches are mostly based on Western medicine ingredients, such as those containing antibiotics and hormones, and long-term use can lead to drug resistance and side effects.

[0005] Although oral patches provide an effective way to administer medication, existing products still have some shortcomings. First, patches containing Western medicine ingredients may cause allergic reactions or other side effects, limiting their scope of application. Second, although Western anesthetics can provide rapid analgesic effects, they may be accompanied by addiction and safety issues. In addition, the cost of Western medicine ingredients is relatively high, which increases the financial burden on patients. Finally, there is a lack of patches containing Chinese medicine ingredients with effective local anesthetic ingredients on the market, which fails to fully utilize the unique advantages of Chinese medicine in the treatment of oral ulcers, such as lower side effects and cost-effectiveness.

[0006] During the research and practice of this method, the inventors discovered that existing technologies have limitations in treating oral ulcers, particularly in providing safe, effective, and economical treatment options. Therefore, the development of a novel oral ulcer patch based on traditional Chinese medicine has important clinical and social value. This present invention addresses the shortcomings of the existing technology by providing a traditional Chinese medicine oral ulcer patch with local anesthetic properties and a method for its preparation, aiming to provide a safer, more effective, and economical oral ulcer treatment option. Summary of the Invention

[0007] The present invention relates to a traditional Chinese medicine oral ulcer patch with local anesthetic properties and its preparation method. The patch provides long-lasting analgesia, reduces the side effects and dependency of Western anesthetics, and leverages the natural advantages of traditional Chinese medicine ingredients to enhance the safety and affordability of treatment. Specifically, the patch, made from a specific ratio of traditional Chinese medicine ingredients and film-forming materials, is designed to rapidly relieve pain and promote healing of oral ulcers, significantly improving patient comfort and treatment compliance.

[0008] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0009] The invention provides a traditional Chinese medicine oral ulcer patch with a local anesthetic effect. The traditional Chinese medicine oral ulcer patch is prepared from the following components in parts by mass: 16-22 parts of indigo naturalis (which has a significant heat-clearing and detoxifying effect and can effectively reduce the inflammatory response of the oral ulcer site), 1.6-2.2 parts of borneol (which has a cooling and analgesic effect and can relieve the pain caused by the oral ulcer), 0.7-1.1 parts of propolis (which has antibacterial and anti-inflammatory effects and promotes tissue regeneration, and is helpful for the healing of the ulcer surface), 120-142.5 parts of asarum (which has a local anesthetic effect and can relieve the pain caused by the oral ulcer), 1-5 parts of glycerin (as a moisturizer and can increase the flexibility and fit of the patch), 45-75 parts of polyvinyl alcohol (a film-forming material with good film-forming property and stability), 1.5-4.5 parts of hydroxypropyl cellulose (an auxiliary film-forming material and can enhance the strength and toughness of the patch), and 0.5-1 part of carbomer (a thickener and stabilizer and can improve the texture and stability of the patch).

[0010] Preferably, the type of carbomer is 934P.

[0011] Preferably, the indigo naturalis is indigo naturalis powder with a particle size of 100 to 300 meshes (ensuring its particle size is uniform, which is conducive to the release and absorption of the drug);

[0012] Preferably, the asarum is asarum powder or asarum extract with a particle size of 100 to 300 meshes;

[0013] Preferably, the preparation method of the asarum extract is: mixing asarum and ethanol at a material ratio of 1g:30-50mL, soaking at 55-65℃ for 2-5h, then ultrasonically extracting for 30-60min, filtering to obtain a filtrate and a residue; repeating the above operation on the residue and extracting it again, combining the two filtrates, rotary distilling off the ethanol, and fixing the volume to a volume of 100-200mL of asarum extract for every 50g of asarum.

[0014] The present invention also provides a method for preparing the traditional Chinese medicine oral ulcer patch with local anesthetic effect, comprising the following steps:

[0015] (1) Indigo naturalis, borneol, and propolis are sequentially added to asarum to mix to obtain material 1;

[0016] (2) polyvinyl alcohol, hydroxypropyl cellulose, and carbomer are mixed with water to swell, and glycerin is added and mixed to obtain material 2;

[0017] (3) Mix the material 1 and the material 2, spread the mixture on a silica gel plate by a homogenous slurry casting method, bake, peel off the film and cut to obtain.

[0018] Preferably, the baking temperature is 35-65° C. and the baking time is 12-16 h (this step is the key to film forming. By controlling the drying temperature and time, it can be ensured that the film has appropriate hardness and stability while ensuring that the active ingredients of the drug are not destroyed).

[0019] Preferably, the swelling time is 21 to 25 hours.

[0020] The present invention also provides the use of the traditional Chinese medicine oral ulcer patch with local anesthetic effect in preparing oral ulcer treatment drugs.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The Chinese medicine oral ulcer patch of the present invention is made of pure Chinese medicinal ingredients, has a significant local anesthetic effect and good therapeutic effect, and is simple to prepare, low in cost, and easy to promote and apply. The patch is made of a proportion of active ingredients and a matrix component. The active ingredients mainly include Indigo Naturalis, Borneol, Propolis, and Asarum Extract. Indigo Naturalis, a commonly used heat-clearing and detoxifying drug in Chinese medicine, has the effects of clearing heat and detoxifying, cooling blood and relieving pain, and has a significant therapeutic effect on oral ulcers. Borneol has the effects of clearing heat and relieving pain, and refreshing the mind, and can quickly relieve the pain caused by oral ulcers. Propolis contains rich nutrients and bioactive substances, has antibacterial and anti-inflammatory effects, promotes tissue repair, and helps the healing of ulcer surfaces. Asarum Extract, one of the important active ingredients, has a significant local anesthetic effect and can further alleviate the patient's pain. The components work synergistically, directly adhering to the ulcer surface to form a closed and moist treatment environment, slowly releasing the drug, and accelerating wound healing.

[0023] The matrix components include glycerin, polyvinyl alcohol, hydroxypropyl cellulose, carbomer 934P, and distilled water, which together form the basic structure of the patch, effectively isolating the complex oral environment and creating favorable conditions for wound recovery. This traditional Chinese medicine oral ulcer patch achieves safe drug delivery while avoiding external irritation. Its pure traditional Chinese medicine formula is mild and non-irritating, safe and reliable, and demonstrates excellent healing effects and long-lasting effects. Furthermore, the preparation process is simple and cost-effective, indicating that this invention has broad clinical application prospects and market potential.

[0024] This invention utilizes traditional Chinese medicine ingredients with excellent local anesthetic properties to achieve rapid and long-lasting analgesia. Advanced film preparation techniques ensure uniform dispersion of the active ingredients within the film, and sustained-release technology controls the drug release rate to maintain a lasting therapeutic effect. The carefully designed film structure and adhesive properties ensure a stable adherence to the oral mucosa, preventing it from falling off, enhancing patient comfort.

[0025] The oral ulcer patch of the present invention can quickly relieve pain, and the patch can quickly release local anesthetic components, effectively reducing the pain patients feel when eating and talking; it promotes healing, and the Chinese medicinal ingredients in the patch not only relieve pain, but also promote ulcer healing, speeding up the recovery process; it is long-lasting and effective, and the application of sustained-release technology allows the drug to continuously act on the ulcer surface, improving the treatment effect; it is easy to use, and the design of the patch is easy for patients to apply by themselves without the need for complicated operations, thereby improving the convenience of treatment; it is highly safe, reduces the use of Western medicine ingredients, reduces the risk of side effects, and makes the patch more suitable for long-term and frequent use. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The present invention is a flow chart of the preparation method of the Chinese medicine oral ulcer patch with local anesthetic effect;

[0027] Figure 2 This is a physical picture of the Chinese medicine oral ulcer patch with local anesthetic effect of the present invention;

[0028] Figure 3 This is a diagram showing the treatment process of oral ulcers in rats in the oral ulcer model of the present invention, 24 hours after modeling (DAY0), 24 hours after the 1st to 6th day of drug administration (DAY1 to DAY6), the model group, the positive drug group, the blank film group, the asarum-containing film group, and the asarum-free film group. The oral mucosa of normal rats (complete blank control group) was used as a control.

[0029] Figure 4 This is a statistical graph of the oral ulcer area of rats in the oral ulcer model of the present invention, 24 hours after modeling (dosage day 0), 24 hours after the first to sixth days of drug administration (dosage day 1 to 6 days), the model group, the positive drug group, the blank film group, the asarum-containing film group, and the non-asarum-containing film group.

[0030] Figure 5 This is a statistical chart of the time when rats start eating on the first and second days after administration in the oral ulcer model of the present invention.

[0031] Figure 6 Figure 2 shows pathological sections of oral mucosal tissue in rats with oral ulcers, 24 hours after administration on day 2 of the oral ulcer model. A: blank control group; B: model group; C: positive drug group; D: blank film group; E: asarum-containing film group; F: non-asarum-containing film group.

[0032] Figure 7 Figure 2 shows pathological sections of oral mucosal tissue in rats with oral ulcers, 24 hours after administration on the fourth day of the oral ulcer model. A: blank control group; B: model group; C: positive drug group; D: blank film group; E: asarum-containing film group; F: non-asarum-containing film group.

[0033] Figure 8 Figure 2 shows pathological sections of oral mucosal tissue in rats with oral ulcers, 24 hours after administration on day 6 of the oral ulcer model. A: blank control group; B: model group; C: positive drug group; D: blank film group; E: asarum-containing film group; F: non-asarum-containing film group. DETAILED DESCRIPTION

[0034] The following will be combined with the accompanying drawings to clearly and completely describe the technical solutions in the experimental examples of the present invention. Obviously, the experimental examples described are only part of the experimental examples of the present invention, not all of the experimental examples. Based on the experimental examples of the present invention, all other experimental examples obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0035] In the present invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0036] The present invention provides a traditional Chinese medicine oral ulcer patch with local anesthetic effect, the patch comprising a medicinal component and a matrix component;

[0037] Accurately calculate the amount of medicinal ingredients prescribed per square meter:

[0038] The medicinal ingredients include 16-22g of Indigo Naturalis, 1.6-2.2g of Borneol, 0.7-1.1g of Propolis, and 120-142.5mL of Asarum extract;

[0039] The matrix components include 1-5 mL of glycerol, 45-75 g of polyvinyl alcohol (PVA17-88), 1.5-4.5 g of hydroxypropyl cellulose (HPC), and 0.5-1 g of carbomer 934P.

[0040] According to the precise calculation of the prescription amount of the medicinal ingredient per square meter, the medicinal ingredient provided by the present invention includes 16 to 22 g of Indigo Naturalis, preferably 17 to 21 g, and more preferably 18 to 20 g;

[0041] In the present invention, the particle size of the Indigo Naturalis is preferably 100-300 mesh, more preferably 100-250 mesh, and most preferably 100-200 mesh;

[0042] According to the precise calculation of the prescription amount of the medicinal ingredient per square meter, the medicinal ingredient provided by the present invention includes 1.6 to 2.2 g of borneol, preferably 1.7 to 2.1 g, and more preferably 1.8 to 2.0 g;

[0043] According to the precise calculation of the prescription amount of the medicinal ingredient per square meter, the medicinal ingredient provided by the present invention includes 0.7 to 1.1 g of propolis, preferably 0.8 to 1.0 g, and more preferably 0.7 to 0.9 g;

[0044] According to the precise calculation of the prescription amount of the medicinal ingredient per square meter, the medicinal ingredient provided by the present invention includes 120 to 142.5 mL of asarum extract, preferably 122.5 to 140 mL, and more preferably 125 to 137.5 mL.

[0045] Based on the volume of the asarum extract, the medicinal ingredients provided by the present invention include 40 to 60 g of asarum powder; the asarum powder is preferably 40 to 60 g, and more preferably 45 to 55 g.

[0046] In the present invention, the asarum extract is preferably prepared by extracting asarum with ethanol; the asarum extract is preferably prepared by using asarum powder; the asarum to ethanol material ratio is 1g:30-50mL, more preferably 1g:32.5-47.5mL, most preferably 1g:35-45mL; the soaking time is 2-5h, more preferably 2.5-3.5h, most preferably 2.75-3.25h; the temperature for extracting asarum with ethanol is preferably 52.5- 67.5℃, more preferably 55-65℃, most preferably 57.5-62.5℃; time is preferably 25-45min, more preferably 30-45min, most preferably 35-45min; solid-liquid mass ratio is preferably 3-4:10-13, more preferably 3-4:10-11, most preferably 4:10-11; rotary evaporation temperature is 37.5-52.5℃, more preferably 40-50℃, most preferably 42.5-47.5℃.

[0047] According to the precise calculation of the prescribed amount of the matrix component per square meter, the matrix component provided by the present invention includes 1 to 5 mL of glycerol, preferably 1.5 to 4.5 mL, and more preferably 2 to 4 mL.

[0048] According to the precise calculation of the prescription amount of the matrix component per square meter, the matrix component provided by the present invention includes 45 to 75 g of polyvinyl alcohol (PVA17-88), preferably 50 to 70 g, and more preferably 55 to 65 g.

[0049] According to the precise calculation of the prescription amount of the matrix component per square meter, the matrix component provided by the present invention includes 1.5 to 4.5 g of hydroxypropyl cellulose (HPC), preferably 2 to 4 g, and more preferably 2.5 to 3.5 g.

[0050] According to the precise calculation of the prescription amount of the matrix component per square meter, the matrix component provided by the present invention includes 0.5 to 1 g of Carbomer 934P, preferably 0.6 to 0.9 g, and more preferably 0.7 to 0.8 g.

[0051] The present invention also provides a method for preparing the Chinese medicine oral ulcer patch described in the above technical solution, comprising the following steps:

[0052] Mixing the indigo naturalis, borneol, propolis and asarum extract to obtain a first mixture;

[0053] Swelling glycerin, polyvinyl alcohol (PVA17-88), hydroxypropyl cellulose (HPC), and carbomer 934P in distilled water to obtain a second mixture;

[0054] The first mixture and the second mixture are fully mixed at a mixing temperature of 35-65° C., preferably 40-60° C., more preferably 45-55° C. The final mixture is obtained and dried to obtain the traditional Chinese medicine oral ulcer patch with local anesthetic effect.

[0055] The invention swells the matrix components in distilled water and then mixes the matrix components with indigo naturalis, borneol, propolis and asarum extract to obtain a final mixture.

[0056] In the present invention, the volume ratio of the mass of the polyvinyl alcohol (PVA17-88) to water is preferably 0.18 to 0.25 g / mL, more preferably 0.19 to 0.24 g / mL, and most preferably 0.20 to 0.23 g / mL; the swelling time is preferably 21 to 25 h, more preferably 22 to 25 h, and most preferably 23 to 25 h.

[0057] The present invention does not have any special limitation on the mixing process, and the final mixture can be mixed uniformly using a method well known to those skilled in the art.

[0058] After obtaining the final mixture, the present invention dries the final mixture on the anti-sticking layer to obtain the traditional Chinese medicine oral ulcer patch with local anesthetic effect.

[0059] In the present invention, the anti-sticking layer is preferably a silica gel plate; the drying film-laying process is preferably a slurry casting method; the drying temperature is preferably 35 to 65°C, more preferably 40 to 60°C, and most preferably 45 to 55°C; the drying time is preferably 10.5 to 13.5h, more preferably 11 to 13h, and most preferably 11.5 to 12.5h; the drying is preferably carried out in a drying oven.

[0060] The technical solutions provided by the present invention are described in detail below with reference to experimental examples, but they should not be construed as limiting the scope of protection of the present invention.

[0061] Example 1

[0062] A method for preparing a traditional Chinese medicine oral ulcer patch with local anesthetic effect, comprising the following steps:

[0063] The first step is to prepare the Asarum extract

[0064] 50g of Asarum was extracted using ethanol. The extraction method involved mixing Asarum with ethanol at a ratio of 1g:40mL. Two portions were soaked at 60°C for 3 hours, followed by ultrasonic extraction at 300W for 40 minutes, and the filtrate was filtered to obtain a filtrate. The filter residue was then subjected to the same process again with another portion of ethanol. The two filtrates were combined and then rotary evaporated at 45°C to remove the ethanol. Finally, the ethanol was diluted to 137.5mL per 50g of Asarum to ensure the effective ingredient content of the extract. After cooling to room temperature, 137.5mL of Asarum extract was obtained, which was sealed and refrigerated at 4°C for storage.

[0065] Step 2: Preparation of Chinese medicinal materials

[0066] Use a balance to weigh 19 g of Indigo Naturalis (200 mesh), 1.9 g of Borneol, and 0.9 g of Propolis.

[0067] Step 3: Film preparation

[0068] (1) Preparation of active ingredients:

[0069] Add Indigo Naturalis, Borneol and Propolis into 137.5 mL of Asarum extract in sequence. Mix and dissolve the above ingredients thoroughly.

[0070] (2) Matrix preparation:

[0071] Dissolve 60 g of polyvinyl alcohol (PVA17-88), 3 g of hydroxypropyl cellulose (HPC), and 0.75 g of carbomer 934P in 280 mL of distilled water. Add 3 mL of glycerol and mix thoroughly.

[0072] (3) Mixed drying

[0073] The active ingredients and the matrix are thoroughly mixed in a water bath, the mixture is spread on a silica gel plate by a homogenous casting method, placed in an oven at 60°C for 12 hours, the film is peeled off, cut, sterilized, and packaged to obtain the traditional Chinese medicine oral ulcer patch with local anesthetic effect.

[0074] Based on the medicinal ingredients in the traditional Chinese medicine oral ulcer patch with local anesthetic effect, the optimal formulation of the matrix component of the present invention was screened. The following test example was performed by using L9(3 4) The orthogonal table was used to investigate the three factors of matrix components, namely the three levels of factor A polyvinyl alcohol (PVA17-88), factor B hydroxypropyl cellulose (HPC), and factor C carbomer 934P, to obtain the optimal prescription of traditional Chinese medicine oral ulcer patch with local anesthetic effect.

[0075] (1) Preparation of 100 mL of artificial saliva

[0076] Weigh 0.500 g of sodium carboxymethyl cellulose, 1.500 g of sorbitol, 0.042 g of sodium chloride, 0.060 g of potassium chloride, 0.007 g of calcium chloride dehydrate, 0.003 g of chlorhexidine acetate, and 0.017 g of dipotassium hydrogen phosphate respectively, dissolve them in an appropriate amount of deionized water to a volume of 100 mL, and mix well.

[0077] (2) Adhesion test:

[0078] Three randomly selected 3cm × 2.5cm film samples were used to measure adhesion force (F) using the rubber method. The upper platform was attached to the bottom of the balance tray, and the lower platform was fixed to the laboratory table. Two 3cm × 5cm pieces of porcine large intestine lining (the mucosa was removed after the contents were removed from the porcine large intestine and soaked in a pH 7.4 phosphate buffer at 32 degrees Celsius for 30 minutes) were cut and fixed to the two platforms with the mucosal surface facing outward. The moistened sample was placed between the two mucosal surfaces and gently pressed for 2 minutes. A beaker was placed on another tray and water was continuously added. The mass at equilibrium was recorded as W1. Water was continued to be added until the two platforms separated, and the mass was recorded as W2. MF was calculated according to the formula MF = (W2 - W1) × g, where g is the acceleration due to gravity, which is 9.8 kg·N. -1 .

[0079] (3) Adhesion time test:

[0080] Adhesion time: Randomly select three 2cm×2cm film samples for testing. Fix the cleaned porcine large intestine outer membrane to the inner wall of a beaker. Moisten the film with 50μL of artificial saliva and adhere it to the porcine large intestine inner membrane. Press gently for 20s. Stir uniformly in 100mL of artificial saliva at 37°C. Observe the adhesion time and record the data (T1).

[0081] (4) Solubility test:

[0082] Randomly select three 1cm×1cm film samples and place them in a beaker containing 100mL of artificial saliva. Stir at 37°C and 100 rpm. Observe the time it takes for the film to break or dissolve, and record the data. Alternatively, place 100mL of artificial saliva in a beaker on an electromagnetic stirrer in a 37°C water bath at 30 rpm. Place the test film (1cm×1cm) in the water bath. Start timing and record the film dissolution time (T2).

[0083] Experimental Example 1

[0084] Based on the precise calculation of the prescribed dosage of the matrix components per square meter, the factor levels for Sample 1 in the orthogonal experiment were 20g of polyvinyl alcohol (PVA17-88), 1.5g of hydroxypropyl cellulose (HPC), and 0.75g of carbomer 934P (based on the method of Example 1, the same below). The measured parameters for the sample were adhesion time (T1) of 24 minutes, dissolution time (T2) of 11.6 minutes, and adhesion force of 0.42N.

[0085] Experimental Example 2

[0086] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 20g of polyvinyl alcohol (PVA17-88), 3g of hydroxypropyl cellulose (HPC), and 1.5g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 29 minutes, dissolution time (T2) of 9.7 minutes, and adhesion force of 1.14N.

[0087] Experimental Example 3

[0088] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 20g of polyvinyl alcohol (PVA17-88), 4.5g of hydroxypropyl cellulose (HPC), and 2.25g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 23 minutes, dissolution time (T2) of 17.0 minutes, and adhesion force of 0.74N.

[0089] Experimental Example 4

[0090] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 40g of polyvinyl alcohol (PVA17-88), 1.5g of hydroxypropyl cellulose (HPC), and 1.5g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 7 minutes, dissolution time (T2) of 21.6 minutes, and adhesion force of 0.51N.

[0091] Experimental Example 5

[0092] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 40g of polyvinyl alcohol (PVA17-88), 3g of hydroxypropyl cellulose (HPC), and 2.25g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 45 minutes, dissolution time (T2) of 40.3 minutes, and adhesion force of 0.98N.

[0093] Experimental Example 6

[0094] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 40g of polyvinyl alcohol (PVA17-88), 4.5g of hydroxypropyl cellulose (HPC), and 0.75g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 37 minutes, dissolution time (T2) of 41.3 minutes, and adhesion force of 1.84N.

[0095] Experimental Example 7

[0096] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 60g of polyvinyl alcohol (PVA17-88), 1.5g of hydroxypropyl cellulose (HPC), and 2.25g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 49 minutes, dissolution time (T2) of 26.3 minutes, and adhesion force of 0.60N.

[0097] Experimental Example 8

[0098] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 60g of polyvinyl alcohol (PVA17-88), 3g of hydroxypropyl cellulose (HPC), and 0.75g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 111 minutes, dissolution time (T2) of 76.6 minutes, and adhesion force of 1.31N.

[0099] Experimental Example 9

[0100] Based on the precise calculation of the prescribed dosage of matrix components per square meter, the factor levels for sample No. 1 in the orthogonal experiment were 60g of polyvinyl alcohol (PVA17-88), 4.5g of hydroxypropyl cellulose (HPC), and 1.5g of carbomer 934P. The measured parameters for the sample were adhesion time (T1) of 60 minutes, dissolution time (T2) of 75.0 minutes, and adhesion force of 0.37N.

[0101] Experimental Example 10

[0102] Screening of the optimal prescription of the Chinese medicine oral ulcer patch with local anesthetic effect of the present invention

[0103] Through experimental data measurement, the present invention statistically analyzed three indicators of nine samples after orthogonal table design, namely adhesion, adhesion time, and dissolution. The average level of the three basic indicators of each factor was calculated, and the measured indicators of the prepared film samples were weighted and scored. The evaluation indicators were adhesion time (T1, 40 points), dissolution time (T2, 30 points) and adhesion (G, 30 points), with a total score of 100 points. The calculation formula is:

[0104] Score = [(0.4×T1 / T1max×100)+(0.3×T2 / T2max×100)+(0.3×G / Gmax×100)].

[0105] As shown in Table 1, it was finally concluded that the optimal level of factor A was level 3, the optimal level of factor B was level 2, and the optimal level of factor C was level 1. That is, the optimal prescription was 60 g of polyvinyl alcohol (PVA17-88), 3 g of hydroxypropyl cellulose (HPC), and 0.75 g of carbomer 934P per square meter of film.

[0106] Table 1 Data for optimal prescription screening

[0107]

[0108] Experimental Example 11 Preparation of oral film

[0109] (1) Preparation of active ingredients:

[0110] Add 19g of Indigo Naturalis (200 mesh), 1.9g of Borneol, and 0.8g of Propolis to 137.5mL of Asarum extract in sequence. The above ingredients must be fully mixed and dissolved.

[0111] Preparation of Asarum Extract

[0112] 50g of Asarum was extracted using ethanol. The extraction method involved mixing Asarum with ethanol at a ratio of 1g:40mL. Two portions were soaked at 60°C for 3 hours, followed by ultrasonic extraction at 300W for 40 minutes, and the filtrate was filtered to obtain a filtrate. The filter residue was then subjected to the same process again with another portion of ethanol. The two filtrates were combined and then rotary evaporated at 45°C to remove the ethanol. Finally, the ethanol was diluted to 137.5mL per 50g of Asarum to ensure the effective ingredient content of the extract. After cooling to room temperature, 137.5mL of Asarum extract was obtained, which was sealed and refrigerated at 4°C for storage.

[0113] (2) Matrix preparation:

[0114] Dissolve 60 g of polyvinyl alcohol (PVA17-88), 3 g of hydroxypropyl cellulose (HPC), and 0.75 g of carbomer 934P in 275 mL of distilled water for 24 h. Add 3 mL of glycerol and mix thoroughly.

[0115] (3) Mixed drying

[0116] The active ingredients and the matrix were thoroughly mixed in a water bath at 50°C. The mixture was spread on a silica gel plate by a homogenous casting method, placed in a drying oven at 50°C for 12 hours, removed the film, cut, sterilized, and packaged to obtain the traditional Chinese medicine oral ulcer patch with local anesthetic effect.

[0117] Experimental Example 12 Preparation of Oral Film

[0118] (1) Preparation of active ingredients:

[0119] Add 16g of Indigo Naturalis (200 mesh), 1.6g of Borneol, and 0.7g of Propolis to 120mL of Asarum extract in sequence. The above ingredients must be fully mixed and dissolved.

[0120] Preparation of Asarum Extract

[0121] 50g of Asarum was extracted using ethanol. The extraction method involved mixing Asarum with ethanol at a ratio of 1g:40mL. Two portions were soaked at 60°C for 3 hours, followed by ultrasonic extraction at 300W for 40 minutes, and the filtrate was filtered to obtain a filtrate. The filter residue was then subjected to the same process again with another portion of ethanol. The two filtrates were combined and then rotary evaporated at 45°C to remove the ethanol. Finally, the ethanol was diluted to 137.5mL per 50g of Asarum to ensure the effective ingredient content of the extract. After cooling to room temperature, 137.5mL of Asarum extract was obtained, which was sealed and refrigerated at 4°C for storage.

[0122] (2) Matrix preparation:

[0123] Dissolve 45 g of polyvinyl alcohol (PVA17-88), 1.5 g of hydroxypropyl cellulose (HPC), and 0.5 g of carbomer 934P in 260 mL of distilled water for 21 h. Add 1 mL of glycerol and mix thoroughly.

[0124] (3) Mixed drying

[0125] The active ingredients and the matrix were thoroughly mixed in a water bath at 35°C. The mixture was spread on a silica gel plate by a homogenous casting method, placed in a drying oven at a temperature of 35°C for 10.5 hours, removed from the film, sheared, sterilized, and packaged to obtain the traditional Chinese medicine oral ulcer patch with local anesthetic effect.

[0126] Experimental Example 13

[0127] Oral film preparation

[0128] (1) Preparation of active ingredients:

[0129] Add 22g of Indigo Naturalis (200 mesh), 2.2g of Borneol, and 1.1g of Propolis to 142.5mL of Asarum extract in sequence. Mix the above ingredients thoroughly and dissolve them.

[0130] (2) Matrix preparation:

[0131] Dissolve 75 g of polyvinyl alcohol (PVA17-88), 4.5 g of hydroxypropyl cellulose (HPC), and 1 g of carbomer 934P in 290 mL of distilled water for 25 h. Add 5 mL of glycerol and mix thoroughly.

[0132] Preparation of Asarum Extract

[0133] 50g of Asarum was extracted using ethanol. The extraction method involved mixing Asarum with ethanol at a ratio of 1g:40mL. Two portions were soaked at 60°C for 3 hours, followed by ultrasonic extraction at 300W for 40 minutes, and the filtrate was filtered to obtain a filtrate. The filter residue was then subjected to the same process again with another portion of ethanol. The two filtrates were combined and then rotary evaporated at 45°C to remove the ethanol. Finally, the ethanol was diluted to 137.5mL per 50g of Asarum to ensure the effective ingredient content of the extract. After cooling to room temperature, 137.5mL of Asarum extract was obtained, which was sealed and refrigerated at 4°C for storage.

[0134] (3) Mixed drying

[0135] The active ingredients and the matrix were thoroughly mixed in a water bath at 65°C. The mixture was spread on a silica gel plate by a homogenous casting method, placed in a drying oven at 65°C for 13.5 hours, removed from the film, sheared, sterilized, and packaged to obtain the traditional Chinese medicine oral ulcer patch with local anesthetic effect.

[0136] The optimal prescription obtained by orthogonal table screening and the traditional Chinese medicine oral ulcer patch with local anesthetic effect showed good measurement conditions, as shown in Table 2.

[0137] Table 2 Data of the optimal prescription samples

[0138]

[0139] Experimental Example 14 Evaluation of the Effect of Patching in Treating Oral Ulcers

[0140] 1. Animal model preparation: 36 healthy SD male rats were taken and anesthetized with 25% urethane 4mL / kg intraperitoneal injection. The labial mucosa of the lower incisor of the SD rats was dried with sterile cotton balls. A 3mm×3mm cotton ball was placed in 50% glacial acetic acid for 5 seconds and then removed. It was immediately placed on the dried labial mucosa for 60 seconds. The treated area was wiped with a sterile cotton ball containing physiological saline to remove residual acetic acid. In this way, a rat oral ulcer model was established. 24 hours after modeling, the condition of the local mucosa of the modeling area of the rat was observed. If an ulcer of about 0.5cm in diameter was formed, the rat's lips were moist, drooling, and there was congestion, redness, swelling, and pseudomembrane around it, indicating that the ulcer model was successful (see Figure 3 , 24 h after modeling, DAY0).

[0141] 2. Animal grouping and drug administration

[0142] The rats with successful modeling were randomly divided into 5 groups, namely model group, positive drug group, blank film group, asarum-containing film group, and asarum-free film group, with 6 rats in each group. In addition, 6 healthy SD male rats were taken as normal control group (complete blank control group).

[0143] Apply the drug to the rats requiring treatment: Cut the patch into 5mm x 5mm pieces, moisten it in advance, and apply it to the affected area of the rat's oral ulcer. Press gently to ensure a firm bond. Administer the drug once daily for 6 consecutive days. Take photos of the ulcer surface 24 hours after each dose, and record the time the rat begins eating after dosing.

[0144] 3. Determination of oral ulcer area in rats

[0145] After taking photos of the rats' oral ulcers, the oral ulcer areas of the rats in each group were measured using ImageJ software before administration and 24 h after administration on days 1, 2, 3, 4, 5, and 6.

[0146] 4. Observation of pathological changes in oral ulcer mucosa of rats

[0147] Two rats were killed 24 hours after administration on the 2nd, 4th and 6th days respectively. The mucosal tissues of oral ulcers in each group were fixed with 4% paraformaldehyde, embedded in paraffin, fixed and dehydrated, and then stained with HE for light microscopy.

[0148] 5. Effect on ulcer area in oral ulcer model rats ( Figure 3 , Figure 4 )

[0149] Twenty-four hours after modeling, the oral mucosal surface of rats in the normal control group was smooth, with no inflammatory edema. The modeled area of rats in the other groups showed a sunken defect, with redness and swelling surrounding the depression and a yellow-white pseudomembrane covering the surface. Over seven consecutive days of observation, the lower lip of rats in the model group was swollen, and the pseudomembrane thickened over the ulcer surface, but the ulcer area did not change significantly. Twenty-four hours after dosing on day one, there was no significant difference in ulcer area among the modeling groups (including those receiving and not receiving the drug). Twenty-four hours after dosing on day two, the ulcer area in the positive drug group and the asarum-containing film group was significantly reduced (*, P < 0.05; **, P < 0.01). There was no significant difference in ulcer area between the blank film group, the non-asarum-containing film group, and the model group. Twenty-four hours after dosing on days three, four, five, and six, the ulcer area in the positive drug group, the asarum-containing film group, and the non-asarum-containing film group was significantly reduced (*, P < 0.05; **, P < 0.01). This shows that the therapeutic effect of the group containing asarum film is equivalent to that of the positive drug group, and the group without asarum film also has a good therapeutic effect.

[0150] 6. Time to start eating after medication ( Figure 5 )

[0151] After the first dose, the positive drug group started eating significantly earlier than the model group and was comparable to the blank control group (**, P < 0.01). After the second dose, the asarum-containing film group started eating significantly earlier than the model group (*, P < 0.05). This suggests that the asarum-containing film group has a better local anesthetic effect.

[0152] 7. Effects on pathological changes of oral mucosal tissue in rats with oral ulcer model

[0153] Figure 6 、 Figure 7 and Figure 8 The following are pathological sections of oral mucosa tissues of rats with oral ulcer model 24 hours after the second day, 24 hours after the fourth day, and 24 hours after the sixth day of administration. Figure 6 、 Figure 7 and Figure 8 Figure A represents the blank control group: The rat oral mucosal epithelium is intact, with loose connective tissue underneath and orderly arranged cells. There are no pathological changes such as vascular hemorrhage and inflammatory cell infiltration. Compared with the blank control group, the model group showed severe damage to the oral mucosa, with loss of squamous epithelium, necrotic tissue covering the surface, and extensive inflammatory cell infiltration and vascular hemorrhage.

[0154] After 2 days of drug treatment, each group received Figure 6 Compared with the model group, the positive drug group and the asarum drug module restored relatively complete keratinized layer and squamous epithelium in the rat oral mucosa, with a small amount of inflammatory cell infiltration and no vascular bleeding. The blank module and the module without asarum drug showed severe damage to the oral mucosa and severe mucosal thickening.

[0155] After 4 days of drug treatment, each group received Figure 7 Compared with the model group, both the positive drug group and the asarum-containing drug module restored relatively complete keratinized and squamous epithelium in the rat oral mucosa, with minimal inflammatory cell infiltration and no vascular bleeding. The blank module and the module without asarum drug showed severe damage to the oral mucosa and thickening. The oral mucosa of the module without asarum drug began to repair, and the thickening was reduced.

[0156] After 6 days of drug treatment, each group received Figure 8 Compared with the model group, the positive drug group, the asarum-containing drug module, and the asarum-free drug module all restored relatively complete keratinized layers and squamous epithelium in the rat oral mucosa, with a small amount of inflammatory cell infiltration and no vascular bleeding. The blank module group had severe oral mucosal damage and thickening.

[0157] Compared with the model group, the positive drug group, the drug module containing asarum and the drug module without asarum all had a better effect on promoting the healing of oral ulcers induced by glacial acetic acid in rats. Among them, the positive drug group and the drug module containing asarum had the fastest healing effect, followed by the drug module without asarum.

[0158] As can be seen from the above experimental examples, the Chinese medicine oral ulcer patch of the present invention, by virtue of its unique Chinese medicine formula and advanced preparation process, achieves rapid analgesia and effective healing of oral ulcers. Among them, components such as borneol and asarum extract have significant local anesthetic effects, which can quickly alleviate the patient's pain. At the same time, ingredients such as indigo naturalis and propolis in the patch can also promote the healing of the ulcer surface and accelerate the recovery process. In addition, the patch is made of film-forming materials such as polyvinyl alcohol, can fit closely on the oral mucosa, is not easy to fall off, and ensures the sustained release and therapeutic effect of the drug. The Chinese medicine oral ulcer patch of the present invention not only has a significant therapeutic effect, but also has a simple preparation process, low cost, and is easy to promote and apply. It integrates the essence of traditional Chinese medicine and modern formulation technology, provides a safe, effective and economical treatment plan for patients with oral ulcers, and has broad market prospects and social value.

[0159] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A Chinese medicine oral ulcer patch with local anesthetic effect, characterized in that: The invention is prepared from the following components in parts by weight: 16-22 parts of indigo naturalis, 1.6-2.2 parts of borneol, 0.7-1.1 parts of propolis, 120-142.5 parts of asarum, 1-5 parts of glycerin, 45-75 parts of polyvinyl alcohol, 1.5-4.5 parts of hydroxypropyl cellulose and 0.5-1 part of carbomer.

2. The Chinese medicine oral ulcer patch with local anesthetic effect according to claim 1, characterized in that: The carbomer is of type 934P.

3. The Chinese medicine oral ulcer patch with local anesthetic effect according to claim 1, characterized in that: The indigo naturalis is indigo naturalis powder with a particle size of 100 to 300 meshes.

4. The Chinese medicine oral ulcer patch with local anesthetic effect according to claim 1, characterized in that The asarum is asarum powder or asarum extract with a particle size of 100 to 300 meshes.

5. The Chinese medicine oral ulcer patch with local anesthetic effect according to claim 4, characterized in that: The preparation method of the asarum extract comprises the following steps: mixing asarum with ethanol at a material ratio of 1 g:30-50 mL, soaking at 55-65° C. for 2-5 hours, ultrasonically extracting for 30-60 minutes, and filtering to obtain a filtrate and a filter residue; repeating the above operation on the filter residue for extraction again, combining the two filtrates, rotary distilling off the ethanol, and fixing the volume to a volume of 100-200 mL of asarum extract per 50 g of asarum.

6. The method for preparing the Chinese medicine oral ulcer patch with local anesthetic effect according to any one of claims 1 to 5, characterized in that: The steps include: (1) Indigo naturalis, borneol, and propolis are sequentially added to asarum to mix to obtain material 1; (2) polyvinyl alcohol, hydroxypropyl cellulose, and carbomer are mixed with water to swell, and glycerin is added and mixed to obtain material 2; (3) Mix the material 1 and the material 2, spread the mixture on a silica gel plate by a homogenous slurry casting method, bake, peel off the film and cut to obtain.

7. The method for preparing the Chinese medicine oral ulcer patch with local anesthetic effect according to claim 5, characterized in that: The baking temperature is 35-65° C. and the baking time is 12-16 hours.

8. The method for preparing the Chinese medicine oral ulcer patch with local anesthetic effect according to claim 5, characterized in that: The swelling time is 21 to 25 hours.

9. Use of the traditional Chinese medicine oral ulcer patch with local anesthetic effect according to any one of claims 1 to 5 in the preparation of a drug for treating oral ulcers.

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