Blueberry tea flavone oral patch and application thereof

Abstract

The invention relates to a raspberry tea flavone oral patch and application thereof. The raspberry tea flavone oral patch is composed of a medicated adhesion layer and a hydrophobic protection layer, the medicine-containing adhesion layer is prepared from 10 to 50 mg of a raspberry tea flavonoid extract and pharmaceutically acceptable auxiliary materials; the mass ratio of flavonoid compounds in the raspberry tea flavonoid extract is larger than or equal to 65 wt%, and particularly the ratio of dihydromyricetin in the raspberry tea flavonoid extract is larger than or equal to 35 wt%. The raspberry tea flavone oral patch provided by the invention has a good treatment effect on oral ulcer, and can be used for treating the oral ulcer, especially non-infectious oral ulcer.

Description

Technical Field

[0001] The present invention relates to the technical field of flavonoid biological agents of moyeam tea, and particularly relates to an oral patch of moyeam tea flavonoids and its application. Background Art

[0002] Oral ulcer is a common oral mucosal lesion. The conventional treatment methods are to blow Bingpeng powder on the wound surface or frequently wash the oral cavity with mouthwash. However, the retention time of Bingpeng powder is short, and it is difficult for the drug to continuously exert its effect. Moreover, frequent stimulation by mouthwash causes pain and discomfort, making it difficult for patients to persevere. Oral patches are a new dosage form developed in recent years - double-layer patches. The drug is in the adhesive layer that contacts the mucosal surface, while the inert layer faces the oral cavity, and the drug is unidirectionally released onto the ulcer surface, thereby prolonging the action time of the drug and improving the bioavailability. For example, in Chinese Patent CN109125281B, the adhesive layer of dexamethasone acetate oral patch uses dexamethasone acetate as the active ingredient. Dexamethasone acetate is a hormonal drug. Although it can promote the healing of oral ulcers, some patients may experience side effects such as skin allergic reactions after use. Long-term use may also inhibit the immune system function, increase the risk of infection, and even affect the endocrine system and cause other adverse symptoms.

[0003] Moyeam tea refers to a tea product processed from the tender stems and leaves growing on the plants of Ampelopsis rossedenttata of the genus Ampelopsis in the family Vitaceae. Its chemical components mainly include flavonoids, polysaccharides, steroids and other chemical components, and have biological activities such as anti-inflammatory, antibacterial, antioxidant, antiviral, etc. The total flavonoid content is about 44%, and the main component in the total flavonoids is dihydromyricetin. Among them, dihydromyricetin has a variety of biological activities and pharmacological effects, and is one of the research hotspots of the efficacy of moyeam tea extracts at present. For example, in Patent CN 100389766 C, dihydromyricetin extracted from the dried tender stems and leaves of Ampelopsis grossedentata has the effects of preventing immune oral mucosal ulcers and promoting the healing of Staphylococcus epidermidis-infected oral ulcers, but its effective dose reaches 250 mg / kg. In addition, in Patent CN 102058532 B, an oral spray is prepared with a water extract of dihydromyricetin (the concentration of dihydromyricetin is 50 mg / ml) as the raw material for the treatment of oral ulcers. However, the preparation process of the water extract of dihydromyricetin is complex and the cost is high. Moreover, the oral spray will cause certain irritation and pain and discomfort, making it difficult for patients to persevere in using it. And in moyeam tea, in addition to dihydromyricetin, the total flavonoids also contain a variety of flavonoid substances that have not been effectively utilized. Therefore, it is of great significance to study more safe and effective oral preparations based on moyeam tea for the treatment of oral ulcers. Summary of the Invention

[0004] In view of the above deficiencies or improvement requirements of the prior art, the present invention provides a bud tea flavonoid oral patch and its application. The purpose is to find that the oral patch prepared with the bud tea flavonoid extract (flavonoid compound content ≥ 65 wt%) as the active ingredient has a treatment effect equivalent to that of the existing dexamethasone acetate oral patch for non-infectious oral ulcers, and the bud tea flavonoids have good safety and no side effects, thereby solving the technical problem of side effects existing in the treatment of oral ulcers with the existing dexamethasone acetate oral patch.

[0005] To achieve the above object, according to one aspect of the present invention, a bud tea flavonoid oral patch is provided, which is composed of a medicated adhesive layer and a hydrophobic protective layer; the medicated adhesive layer includes 10 - 50 mg of bud tea flavonoid extract and pharmaceutically acceptable excipients; the mass ratio of flavonoid compounds in the bud tea flavonoid extract ≥ 65 wt%.

[0006] Preferably, in the bud tea flavonoid oral patch, the proportion of dihydromyricetin in the bud tea flavonoid extract ≥ 35 wt%.

[0007] Preferably, as an oral patch for treating non-infectious oral ulcers, the content of the bud tea flavonoid extract in the bud tea flavonoid oral patch is 10 - 30 mg / patch.

[0008] Preferably, in the bud tea flavonoid oral patch, the proportion of dihydromyricetin in the bud tea flavonoid extract is 45 - 65 wt%.

[0009] Preferably, for the bud tea flavonoid oral patch, the bud tea flavonoid extract is prepared according to the following method:

[0010] (1) Prepare the bud tea extract: Crush the old leaves and branches of the bud tea, extract with a solvent containing 10 - 60 wt% organic alcohol, filter and collect the filtrate; add water to the filter residue and extract by gentle boiling, filter and collect the filtrate; combine the filtrates to obtain the bud tea extract.

[0011] (2) Prepare the bud tea flavonoid extract: Recover the organic solvent in the bud tea extract under reduced pressure, concentrate to 1 / 2 - 1 / 3 of the original volume, and separate to obtain filter residue A and filtrate B; dissolve filter residue A repeatedly with acetone, filter, combine the filtrates, recover acetone, and dry to obtain the extracted dihydromyricetin.

[0012] Dissolve the precipitate insoluble in acetone with hot water, mix it with filtrate B, concentrate the mixture to a specific gravity of 1.05 - 1.20, add an organic solvent for extraction, separate to obtain the organic solvent extract, and recover the organic solvent under reduced pressure and dry the solid matter to obtain the extracted bud tea flavonoids.

[0013] Mix the extracted dihydromyricetin and bud tea flavonoids to obtain the bud tea flavonoid extract.

[0014] Preferably, for the flavonoid oral patch of Ampelopsis grossedentata, the solvent containing 10-60 wt% of organic alcohol in step (1) is heated to slightly boiling for extraction 1-2 times; in step (2), extraction is carried out at a volume ratio of organic solvent to mixed solution of 1-3:1 for 1-3 times.

[0015] Preferably, for the flavonoid oral patch of Ampelopsis grossedentata, vitamin B is further included in the drug-containing adhesive layer. 2 The pharmaceutically acceptable excipients include one or more of bioadhesives, fillers, binders, and lubricants.

[0016] Preferably, for the flavonoid oral patch of Ampelopsis grossedentata, the hydrophobic protective layer includes a hydrophobic material and a lubricant, and the hydrophobic material is one or more of triethyl citrate, polyacrylic resin II, hydroxypropyl methylcellulose phthalate, hypromellose acetate succinate, and methyl methacrylate-methyl acrylate copolymer.

[0017] According to another aspect of the present invention, there is also provided the use of the flavonoid oral patch of Ampelopsis grossedentata as described in the present invention as a drug for treating oral ulcers.

[0018] Preferably, for the use, the flavonoid oral patch of Ampelopsis grossedentata is used as a drug for treating non-infectious oral ulcers.

[0019] Generally speaking, compared with the prior art by the above technical solution conceived by the present invention, since it is found that the therapeutic effect of the flavonoid oral patch of Ampelopsis grossedentata on oral ulcers is equivalent to that of the existing dexamethasone acetate oral patch, the following beneficial effects can be achieved:

[0020] The flavonoid oral patch of Ampelopsis grossedentata provided by the present invention is composed of a drug-containing adhesive layer and a hydrophobic protective layer; the drug-containing adhesive layer includes 10-50 mg of flavonoid extract of Ampelopsis grossedentata and pharmaceutically acceptable excipients; the mass ratio of flavonoid compounds in the flavonoid extract of Ampelopsis grossedentata is ≥ 65 wt%. The experimental results show that the oral patch containing a low dose of flavonoid extract of Ampelopsis grossedentata has a significant effect on promoting the healing of oral ulcers, and its therapeutic effect on oral ulcers is equivalent to that of the existing dexamethasone acetate oral patch, and it can be used to treat oral ulcers, especially for treating non-infectious oral ulcers. Detailed Embodiments

[0021] To further elaborate on the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the following will describe in detail the specific embodiments, structures, features, and effects according to the present invention in combination with preferred embodiments.

[0022] In Chinese Patent CN101450087B, it is mentioned that the effective ingredient of Adonis amurensis Regel et Radde in promoting the healing of oral ulcer surface is the total flavonoid component. An Adonis amurensis Regel et Radde total flavonoid oral patch is prepared with the Adonis amurensis Regel et Radde total flavonoid extract as the effective ingredient. However, the experimental results show that applying 20 - 30 mg of Adonis amurensis Regel et Radde total flavonoid per day has no effect on treating oral ulcers, and applying at least 40 mg of Adonis amurensis Regel et Radde total flavonoid per day has a certain effect on promoting the healing of mechanically damaged oral ulcers.

[0023] The present invention discovers that an oral patch containing low-dose flavonoids from Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang has a significant effect on promoting the healing of oral ulcers, and its therapeutic effect on oral ulcers is equivalent to that of the existing dexamethasone acetate oral patch, and it can be used to treat oral ulcers, especially non-infectious oral ulcers.

[0024] Based on this, the present invention provides an Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid oral patch, which is a double-layer tablet, including an adhesive layer containing medicine and a hydrophobic protective layer; the adhesive layer containing medicine includes 10 - 50 mg of Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid extract and pharmaceutically acceptable excipients, and the mass ratio of flavonoid compounds in the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid extract is ≥ 65 wt%.

[0025] In some embodiments, it is preferred that the proportion of dihydromyricetin in the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid extract is ≥ 35 wt%.

[0026] In the oral patch for treating non-infectious oral ulcers, the content of the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid extract is 10 - 30 mg per tablet; it is preferred that the proportion of dihydromyricetin in the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid extract is 45 - 65 wt%. In some embodiments, the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid extract is prepared according to the following method:

[0027] (1) Prepare an Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang extract

[0028] Crush the old leaves and branches of Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang, extract with a solvent containing 10 - 60 wt% organic alcohol for 1 - 2 times, filter and collect the filtrate; add water to the filter residue and extract at a gentle boil for 1 - 2 times, filter and collect the filtrate; combine the filtrates to obtain the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang extract.

[0029] (2) Prepare the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang flavonoid extract

[0030] Under reduced pressure, recover the organic solvent in the Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang extract and concentrate it to 1 / 2 - 1 / 3 of the original volume, let it stand and separate to obtain filter residue A and filtrate B. Filter residue A is repeatedly dissolved and filtered with acetone, the filtrates are combined, acetone is recovered, and dried to obtain the extracted dihydromyricetin.

[0031] The acetone-insoluble precipitate is dissolved in hot water and mixed with filtrate B. The mixture is concentrated to a specific gravity of 1.05 - 1.20, and an organic solvent is added for extraction. The organic solvent extract is separated, the organic solvent is recovered by vacuum concentration, and the solid matter is dried to obtain the extracted ampelopsis grossedentata flavonoids.

[0032] Mix the extracted dihydromyricetin and ampelopsis grossedentata flavonoids to obtain the ampelopsis grossedentata flavonoid extract. The content of dihydromyricetin in the ampelopsis grossedentata flavonoid extract is 45 - 65 wt%.

[0033] In some embodiments, the solvent of 10 - 60 wt% organic alcohol in step (1) is a mixed solvent of methanol or ethanol and water, the content of methanol or ethanol in the mixed solvent is 10 - 60 wt%, and the preferred organic alcohol is ethanol; and the solvent containing 10 - 60 wt% organic alcohol is heated to slightly boiling for extraction 1 - 2 times.

[0034] In some embodiments, the conditions for recovering the organic solvent by vacuum concentration are a vacuum degree of 0.01 - 0.1 Mpa and a temperature of 40 - 80 °C.

[0035] In some embodiments, in step (2), extraction is carried out according to a volume ratio of organic solvent to the mixture of 1 - 3:1, and extraction is carried out 1 - 3 times. The extraction solvent is one of n-butanol, ethyl acetate, n-pentanol or chloroform. The extraction method can be stirring extraction, standing and separating at room temperature or at a low temperature of 4 - 10 °C, or extraction is carried out using an organic solvent continuous flow extraction separator.

[0036] Furthermore, the drug-containing adhesive layer further contains vitamin B 2 , and the pharmaceutically acceptable excipients include one or more of bioadhesives, fillers, binders, and lubricants.

[0037] The hydrophobic protective layer includes a hydrophobic material and a lubricant. Among them, the hydrophobic material includes one or more of triethyl citrate, polyacrylic resin II, hydroxypropyl methylcellulose phthalate, hypromellose acetate succinate, and methyl methacrylate-methyl acrylate copolymer; preferably, the hydrophobic material is triethyl citrate.

[0038] The lubricant includes magnesium stearate.

[0039] In addition, the present invention also provides a preparation method of the ampelopsis grossedentata flavonoid oral patch as described in the present invention, which includes the following steps:

[0040] (1) Mix the ampelopsis grossedentata flavonoid extract with other excipients except magnesium stearate, granulate, and then mix with magnesium stearate to form drug-loaded granules.

[0041] (2) Granulate the hydrophobic material, and then mix with magnesium stearate to form hydrophobic protective granules.

[0042] (3) Compress the obtained drug-loaded particles and hydrophobic protective particles into a bilayer tablet.

[0043] In some embodiments, the obtained drug-loaded particles and hydrophobic protective particles are compressed into a bilayer tablet at one time.

[0044] In some embodiments, the drug-loaded particles are first compressed into a tablet as the bottom layer, and then the hydrophobic protective layer particles are pressed onto the bottom layer to be compressed into a bilayer tablet for the second time.

[0045] In addition, the present invention also provides the use of the ampelopsis grossedentata flavonoid oral patch as described in the present invention as a drug for treating oral ulcers; especially as a drug for treating non-infectious oral ulcers, such as for treating traumatic oral ulcers.

[0046] The following are examples

[0047] In the experimental methods in the following examples, unless otherwise specified, they are all conventional methods. The raw materials, reagent materials, etc. used in the following examples, unless otherwise specified, are all commercially available products. Some of the raw materials are obtained by self-extraction.

[0048] Dextrin, carbomer, magnesium stearate, polyacrylic resin II resin, triethyl citrate, hydroxypropyl methylcellulose all comply with the provisions of the Chinese Pharmacopoeia 2015 edition.

[0049] Double-layer tablet press:

[0050] Ampelopsis grossedentata flavonoids are obtained by the following method:

[0051] (1) Prepare an ampelopsis grossedentata extract: Crush the old leaves and branches of ampelopsis grossedentata, extract with an organic solvent containing 10-60 wt% methanol or ethanol 1-2 times, filter and collect the filtrate for extracting dihydromyricetin and hydrophobic ampelopsis grossedentata flavonoids; add water to the filter residue and extract by boiling gently 1-2 times, filter and collect the filtrate for extracting water-soluble ampelopsis grossedentata flavonoids; combine the filtrates to obtain the ampelopsis grossedentata extract;

[0052] (2) Prepare an ampelopsis grossedentata flavonoid extract: Recover the organic solvent in the ampelopsis grossedentata extract under reduced pressure and concentrate it to 1 / 2-1 / 3 of the original volume, let it stand and separate to obtain filter residue A and filtrate B; repeatedly dissolve and filter filter residue A with acetone, combine the filtrates, recover acetone, and dry to obtain the extracted dihydromyricetin;

[0053] Dissolve the precipitate insoluble in acetone with hot water and mix it with filtrate B, concentrate the mixture to a specific gravity of 1.05-1.20, add an organic solvent for extraction, separate to obtain the organic solvent extract, recover the organic solvent by reduced pressure concentration, and dry the solid matter to obtain the extracted ampelopsis grossedentata flavonoids (crude product), which includes hydrophobic ampelopsis grossedentata flavonoids and water-soluble ampelopsis grossedentata flavonoids;

[0054] Mix the extracted dihydromyricetin and ampelopsis grossedentata flavonoids to obtain the ampelopsis grossedentata flavonoid extract (the flavonoid compound content ≥ 65 wt%, and the mass proportion of dihydromyricetin in the ampelopsis grossedentata flavonoid extract ≥ 35 wt%). Among them, the conditions for vacuum concentration recovery are a vacuum degree of 0.01 - 0.1 Mpa and a temperature of 40 - 80 °C.

[0055] Example 1 Ampelopsis Grossedentata Flavonoid Oral Patch (1000 pieces) and Its Preparation Method

[0056] The prescription for 1000 ampelopsis grossedentata flavonoid oral patches (specification: diameter 8 mm, ampelopsis grossedentata flavonoid dose 30 mg / piece) is as follows:

[0057] ① Prescription for the drug-containing adhesive layer

[0058] Ampelopsis grossedentata flavonoid extract (powder, total flavonoid content 65 wt%, mass proportion of dihydromyricetin in the ampelopsis grossedentata flavonoid extract 45 wt%): 30 g, vitamin B 2 : 5 g, carbomer 971P: 25 g, dextrin: 20 g, magnesium stearate: 1.5 g.

[0059] ② Prescription for the hydrophobic protective layer

[0060] Triethyl citrate: 20 g, magnesium stearate: 0.5 g.

[0061] The preparation method is as follows:

[0062] (1) Prepare the drug-loaded granules: Mix the prescribed amount of ampelopsis grossedentata flavonoid extract powder, carbomer, and dextrin, use 95% (v / v) ethanol solution as the wetting agent, granulate, dry, and screen; then mix with the prescribed amount of magnesium stearate to prepare the drug-loaded granules.

[0063] (2) Prepare the granules for the hydrophobic protective layer: Use anhydrous ethanol as the wetting agent for the prescribed amount of triethyl citrate, granulate, dry, and screen, and then mix with the prescribed amount of magnesium stearate to prepare the granules for the hydrophobic protective layer.

[0064] (3) Tableting: Use the double-tableting method to press the above two kinds of granules into a double-layer tablet.

[0065] Example 2 Ampelopsis Grossedentata Flavonoid Oral Patch (1000 pieces) and Its Preparation Method

[0066] The prescription for 1000 ampelopsis grossedentata flavonoid oral patches (specification: diameter 8 mm, ampelopsis grossedentata flavonoid extract dose 50 mg / piece) is as follows:

[0067] ① Prescription for the drug-containing adhesive layer

[0068] Flavonoid extract of Ampelopsis grossedentata (powder, total flavonoid content is 65 wt%, mass proportion of dihydromyricetin in the flavonoid extract of Ampelopsis grossedentata is 35 wt%): 50 g, vitamin B 2 : 5 g, carbomer 934P: 15 g, hypromellose: 17.5 g, starch: 15 g, magnesium stearate: 1.75 g.

[0069] ② Prescription of the hydrophobic protective layer

[0070] Triethyl citrate: 15 g, magnesium stearate: 1.5 g.

[0071] Prepared by the following method:

[0072] (1) Prepare drug-loaded granules: Mix the prescribed amount of flavonoid extract powder of Ampelopsis grossedentata, vitamin B 2 , carbomer, hypromellose, and starch, make granules by dry method and then mix with magnesium stearate to prepare drug-loaded granules.

[0073] (2) Tabletting: Press the above drug-loaded granules into tablets with a diameter of 8 mm and a tablet weight of about 80 mg.

[0074] (3) Prepare granules of the hydrophobic protective layer: Use anhydrous ethanol as a wetting agent for the prescribed amount of triethyl citrate, granulate, dry, screen, and then mix with the prescribed amount of magnesium stearate to prepare granules of the hydrophobic protective layer.

[0075] (4) Using the drug-containing tablet as the base, press the granules of the hydrophobic protective layer on the drug-containing base to form tablets with two colors on the upper and lower parts, and each tablet weighs about 100 mg.

[0076] Example 3 Ampelopsis grossedentata flavonoid oral patch (1000 tablets) and its preparation method

[0077] The prescription of 1000 Ampelopsis grossedentata flavonoid oral patches (specification: diameter 8 mm, Ampelopsis grossedentata flavonoid extract dose is 10 mg / tablet) is as follows:

[0078] ① Prescription of the drug-containing adhesive layer

[0079] Flavonoid extract of Ampelopsis grossedentata (powder, total flavonoid content is 65 wt%, mass proportion of dihydromyricetin in the flavonoid extract of Ampelopsis grossedentata is 45 wt%): 10 g, vitamin B 2 : 1.5 g, carbomer 971P: 25 g, dextrin: 20 g, magnesium stearate: 1.5 g.

[0080] ② Prescription of the hydrophobic protective layer

[0081] Triethyl citrate: 20 g, magnesium stearate: 0.5 g.

[0082] The preparation method is the same as that of Example 1.

[0083] Determination of the Safety and Stability of the Oral Patch of Flavonoids from Ampelopsis grossedentata in Example 4

[0084] The results of the stability test showed that: the products prepared according to the present invention were subjected to an accelerated test in a constant temperature and humidity chamber at 40±2°C and 75%±5%. Samples were taken at 0, 1, 2, and 3 months after placement, and their properties, identification, weight difference, dissolution, content determination, and hygienic examination were detected; the products prepared according to the present invention were also subjected to a long-term stability test at room temperature. The results showed that the oral patch of flavonoids from Ampelopsis grossedentata provided by the present invention had good stability.

[0085] In addition, the results of the irritation experiment showed that: the oral patch of flavonoids from Ampelopsis grossedentata had no obvious irritating effect on the oral mucosa of rats after single and multiple administrations.

[0086] The results of the acute toxicity test showed that the LD50 of the flavonoid extract from Ampelopsis grossedentata by intragastric administration was >10 g / kg.

[0087] Therapeutic Effect of the Oral Patch of Flavonoids from Ampelopsis grossedentata in Example 5

[0088] The active ingredient of Yike Tie (Dexamethasone Acetate Adhesive Tablets) is dexamethasone acetate, which can be used for the treatment of non-infectious oral ulcers (such as traumatic oral ulcers). In this example, Yike Tie oral patch was used as a positive control, and a pharmacodynamic study of the oral patch of flavonoids from Ampelopsis grossedentata was carried out by establishing a rat traumatic oral ulcer model through chemical drug burning method, as follows:

[0089] Experimental animals: Male SD rats, SPF (Specific Pathogen Free) grade, weighing 200-120 g, provided by Hubei Experimental Animal Center, animal certificate number: SCXK(E)2022-0002.

[0090] Method for constructing a traumatic oral ulcer model: After the rats were purchased, they were adaptively fed for one week and then the modeling began. Specifically: 20% urethane solution was intraperitoneally injected at a dose of 5 mL / kg to anesthetize the rats. A double-ended open plastic tube with a length of 5 cm and an inner diameter of 0.4 cm was taken, and a small cotton ball was placed at one end of the tube to the opening. The cotton ball end was vertically and flatly attached to the inner mucosa of the lower lip of the rat, and 50% glacial acetic acid solution was slowly dropped from the other end. The cotton was infiltrated with glacial acetic acid without flowing out, and the mucosa was burned for 90 seconds. Then the excess glacial acetic acid solution was wiped off with a cotton swab. 24 hours after modeling, the lips of the rats were moist, and obvious ulcers appeared in the experimental area, with a yellowish-white surface, and some had ulceration and exudation, indicating that the modeling was successful.

[0091] Grouping and administration of rats: After the model was established, the ulcer surface of the rats was observed. The ulcer surfaces of rats in each group were covered with yellowish-white pseudomembranes, with obvious exudation, obvious hyperemia, severe inflammatory reactions, and sunken wound surfaces, indicating that the oral ulcer model was successfully constructed. After the model was established, the rats were randomly divided into an oral ulcer model group, a blank tablet group (containing excipients), a Dexamethasone Acetate Adhesive Tablets control group, and a Ampelopsis grossedentata flavonoid oral patch group (each tablet contained 10 mg of Ampelopsis grossedentata flavonoid extract), with 8 rats in each group. After 24 hours, the ulcer area was measured and the rats were administered. Before each administration, a 20% urethane solution was intraperitoneally injected at a dose of 3 mL / kg to slightly anesthetize the rats for easy administration. Before administration, the oral surface of the rats was gently wiped with a cotton swab dipped in physiological saline, and then the rats were administered. The patch was kept on the wound surface for 30 minutes, administered once a day, one tablet each time, and continuously administered for 4 days.

[0092] After 4 days of administration, it was observed that there was still exudation in the model group and the blank tablet group, the ulcer surface shrank but the injury was still severe, and the inflammatory reaction was heavy. While the ulcer surfaces of the Ampelopsis grossedentata flavonoid oral patch group and the Dexamethasone Acetate Adhesive Tablets group were smooth, the wound surfaces healed well, the inflammatory reaction was mild, and the wound surfaces were basically healed.

[0093] The ulcer area is the main index for the healing degree of oral ulcers and the evaluation of the efficacy of drugs. In this example, a vernier caliper was used to regularly measure the maximum transverse diameter (d1) and the maximum longitudinal diameter (d2) of the ulcer every day, and the ulcer area was calculated (ulcer area = π × d1 × d2 × 1 / 4). The SPSS 22.0 statistical software was used for data processing, and the results are shown in the following table.

[0094] Table 1 Oral ulcer area of animals in each group (mm 2 , ±SD, n = 8)

[0095]

[0096] In the table, the adhesive layer of the oral patch in the blank tablet group did not contain Ampelopsis grossedentata flavonoids; the adhesive layer of the oral patch in the Ampelopsis grossedentata flavonoid group contained 10 mg of Ampelopsis grossedentata flavonoid extract; the active ingredient of the oral patch in the Dexamethasone Acetate Adhesive Tablets group was dexamethasone acetate; among them, the data of each group were expressed as mean ± standard deviation, and P < 0.05 was considered statistically significant.

[0097] It can be seen from the statistical results in Table 1 that there was no statistical difference in the ulcer area of rats in each group before administration. Subsequently, there was no statistical difference between the blank tablet group and the model group in the measurement data every day (P > 0.05), indicating that the excipients in the Ampelopsis grossedentata flavonoid oral patch itself did not have the effect of treating oral ulcers.

[0098] On the 1st, 2nd, 3rd, and 4th days of drug administration, there were significant differences between the Ampelopsis grossedentata flavonoid oral patch group and the Yike Tie group and the model group (P < 0.01), and there was no obvious difference between the Ampelopsis grossedentata flavonoid oral patch group and the Yike Tie group. Both could significantly promote the healing of traumatic oral ulcers in rats, indicating that the Ampelopsis grossedentata flavonoid oral patch has the effect of treating non-infectious oral ulcers, and its therapeutic effect is equivalent to that of the existing Yike Tie oral patch. It can be used as a substitute for the Yike Tie oral patch to promote the healing of oral ulcers and is used to treat oral ulcers.

[0099] As described above, it is only a preferred embodiment of the present invention, and there is no limitation to the present invention in any form. Although the present invention has been disclosed as above with the preferred embodiment, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to equivalent embodiments by using the disclosed technical content without departing from the technical solution of the present invention. However, any brief modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the technical solution content of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A berry tea flavonoid oral patch, characterized in that: It consists of a drug-containing adhesion layer and a hydrophobic protective layer; the drug-containing adhesion layer includes 10-50 mg of berry tea flavonoid extract and pharmaceutically acceptable excipients; the mass proportion of flavonoid compounds in the berry tea flavonoid extract is ≥65wt%.

2. The berry tea flavonoid oral patch according to claim 1, characterized in that: The proportion of dihydromyricetin in the berry tea flavonoids extract is ≥35wt%.

3. The berry tea flavonoid oral patch according to claim 2, characterized in that: As an oral patch for treating non-infectious oral ulcers, the content of the berry tea flavonoids extract is 10-30 mg / piece.

4. The berry tea flavonoid oral patch according to claim 3, characterized in that: The proportion of dihydromyricetin in the berry tea flavonoids extract is 45-65 wt %.

5. The berry tea flavonoid oral patch according to claim 1, characterized in that: The berry tea flavonoid extract is prepared according to the following method: (1) preparing berry tea extract: crushing old leaves and branches of berry tea, extracting with a solvent containing 10-60 wt% of organic alcohol, filtering and collecting the filtrate; adding water to the residue for extraction at a slight boiling point, filtering and collecting the filtrate; combining the filtrates to obtain the berry tea extract; (2) Preparation of berry tea flavonoid extract: recovering the organic solvent in the berry tea extract under reduced pressure, concentrating it to 1 / 2 to 1 / 3 of the original volume, and separating to obtain a filter residue A and a filtrate B; wherein the filter residue A is repeatedly dissolved and filtered with acetone, the filtrate is combined, the acetone is recovered, and the extracted dihydromyricetin is obtained by drying; The precipitate insoluble in acetone is dissolved in hot water and then mixed with filtrate B, the mixed solution is concentrated to a specific gravity of 1.05 to 1.20, an organic solvent is added for extraction, and an organic solvent extract is obtained by separation, the organic solvent is recovered by decompression, and the solid is dried to obtain the extracted berry tea flavonoids; The extracted dihydromyricetin and berry tea flavonoids are mixed to obtain a berry tea flavonoid extract.

6. The berry tea flavonoid oral patch according to claim 5, characterized in that: The solvent containing 10-60 wt% of organic alcohol in step (1) is heated to a slight boiling point and extracted 1-2 times; in step (2), extraction is performed according to a volume ratio of organic solvent to mixed liquid of 1-3:1, and the extraction is performed 1-3 times.

7. The berry tea flavonoid oral patch according to any one of claims 1 to 6, characterized in that: The drug-containing adhesive layer also includes vitamin B2, and the pharmaceutically acceptable excipients include one or more of bioadhesives, fillers, adhesives, and lubricants.

8. The berry tea flavonoid oral patch according to claim 7, characterized in that: The hydrophobic protective layer comprises a hydrophobic material and a lubricant, wherein the hydrophobic material is one or more of triethyl citrate, polyacrylic acid resin II, hydroxypropyl methylcellulose acylate, hydroxypropyl methylcellulose acetate succinate, and methacrylic acid-methyl acrylate copolymer.

9. Use of the berry tea flavonoid oral patch according to any one of claims 1 to 6 as a drug for treating oral ulcers.

10. The use according to claim 9, characterized in that The berry tea flavonoid oral patch is used as a medicine for treating non-infectious oral ulcers.

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