Caulis sinomenii gel plaster as well as preparation method and application thereof

Abstract

The invention discloses a caulis sinomenii gel plaster as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparations. The caulis sinomenii gel plaster comprises a backing layer, a medicine storage layer and a release layer, and the medicine storage layer is prepared from the following components in parts by weight: 3-12 parts of caulis sinomenii and 5-15 parts of a gel matrix. The caulis sinomenii gel plaster disclosed by the invention has a remarkable curative effect by improving the prescription of the active ingredients and the gel matrix. The preparation method comprises the following steps: extracting caulis sinomenii with an ethanol water solution, concentrating and drying to obtain an extract, preparing the caulis sinomenii extract into the gel plaster, and the pharmacodynamic test result shows that the gel plaster has a remarkable curative effect, is dose-dependent, and has the characteristics of high initial adhesion and good application comfort.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, and relates to a Qingfengteng gel plaster, its preparation method and its application. Background Technology

[0002] *Sinomenium acutum* contains abundant alkaloids, among which sinomenine (SIN), an isoquinoline morphine-type alkaloid, is the main alkaloid in *Sinomenium acutum*. Since the 1950s, Japanese scholars have isolated 10 alkaloids from *Sinomenium acutum*, including SIN, disinomenine, sinactine, acutumine, tuduranine, magnoflorine, isosinomenine, acutumidine, michelalbine, and stepharine. Chinese scholars have also successively isolated sinoacutine, 8,14-dihydrosalutaridine, stepharanine, bianfugenine, and sinomendine from the domestic Chinese sinoacutine plant. Subsequently, scholars isolated syringin, syringaresinol-4',4'-Obis-β-D-glucoside, 6-O-demethylmenisporphine, acutuminine, tetrahydropalmatine, palmatine, epiberberine, cheilanthifoline, telitoxine, and dehydrocheilanthifoline from *Sinomenium acutum*. In addition, DL-syringaresinol, cetylpalmitate, β-sitosterol, and stigmasterol were also isolated from *Sinomenium acutum*.

[0003] The CAS number for sinomenine is 115-53-7, its molecular weight is 329.39, its chemical name is (9a,13a,14a)-7,8-disehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one, and its molecular formula is C2. 19 H23 NO4, needle-like crystals (crystallized from benzene), has a melting point of 161℃, which rises to 182℃ after melting. It is readily soluble in ethanol, acetone, chloroform, and dilute alkalis, and slightly soluble in water, ether, and benzene.

[0004] Sinomenine, the most abundant active ingredient in *Sinomenium acutum*, has attracted widespread attention due to its diverse pharmacological activities, including anti-inflammatory and analgesic effects. It has shown significant efficacy in improving osteoarthritis, frozen shoulder, and muscle pain. Currently, sinomenine hydrochloride tablets, sustained-release tablets, enteric-coated tablets, and capsules are available, all for oral administration. Their main functions are: dispelling wind and dampness, promoting blood circulation and relieving pain, and reducing swelling. They are used for wind-cold-dampness syndrome, characterized by muscle soreness, joint swelling and pain, difficulty in flexion and extension, numbness and stiffness, and symptoms of rheumatoid arthritis. Existing marketed preparations use sinomenine monomer as the active ingredient and are administered in the form of hydrochloride (i.e., sinomenine hydrochloride). For example, patent application CN102399187A from Hunan Zhengqing Pharmaceutical Group Co., Ltd. (hereinafter referred to as "Zhengqing") discloses a method for preparing sinomenine hydrochloride, including the preparation of crude sinomenine hydrochloride and a refining process. The preparation method is as follows: Take coarse *Sinomenium acutum* powder, moisten with hydrochloric acid, and percolate. The percolate is extracted and crystallized to obtain crude *Sinomenium acutum* hydrochloride. Take the crude *Sinomenium acutum* hydrochloride, add ethanol or purified water, heat under reflux until dissolved, add activated carbon, filter, cool, crystallize, filter again, and wash the filter cake with ethanol until the filtrate is colorless to obtain *Sinomenium acutum* hydrochloride. Zhengqing's patent application CN102397267A further discloses a method for preparing *Sinomenium acutum* hydrochloride poultices, employing a percolation method, using *Sinomenium acutum* hydrochloride as the raw material, and adding excipients to prepare the poultice. Zhengqing's patent application CN102600113A discloses a method for preparing *Sinomenium acutum* hydrochloride poultices without organic solvents, also using *Sinomenium acutum* hydrochloride as the active ingredient.

[0005] Currently, there are no studies or reports on the preparation of gel patches using Sinomenium acutum extract as the main ingredient. Summary of the Invention

[0006] This invention relates to a Sinomenium acutum gel patch, which includes a backing layer, a drug reservoir layer and a release layer, wherein the drug reservoir layer is composed of the following components in parts by weight: 3-12 parts of Sinomenium acutum and 5-15 parts of gel matrix.

[0007] In some embodiments, the *Sinomenium acutum* is extracted, concentrated, and dried using an aqueous ethanol solution to obtain a *Sinomenium acutum* extract.

[0008] In some embodiments, no acid or alkali is added during the extraction of Sinomenium acutum, and the alkaloids in Sinomenium acutum do not form salts.

[0009] In some embodiments, the gel matrix of the gel patch includes: a polymeric framework material, a humectant, a thickener, a crosslinking agent, a crosslinking regulator, a penetration enhancer, a pH adjuster, a filler, and water.

[0010] In some embodiments, the polymeric framework material comprises one or more of sodium polyacrylate, partially neutralized sodium polyacrylate, carbomer, and polyvinyl alcohol. The polymeric framework material is used in an amount of 6–12% by weight relative to the total weight of the gel matrix. A combination of partially neutralized sodium polyacrylate and polyvinyl alcohol is preferred, with the amounts of each being 4–7% and 2–3%, respectively.

[0011] In some embodiments, the humectant includes one or more of glycerin, propylene glycol, 1,3-butanediol, urea, sorbitol, and polyethylene glycol. The humectant is used in an amount of 20-30% by weight relative to the total weight of the gel matrix.

[0012] In some embodiments, the thickener comprises one or more of gelatin, sodium carboxymethyl cellulose, polyacrylic acid solution, methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, acrylic acid grafted starch, povidone solution, and polyvinylpyrrolidone. The amount used, by weight percentage, is 10-25% relative to the total weight of the gel matrix. Preferably, the thickener is one or more of gelatin, sodium carboxymethyl cellulose, polyacrylic acid solution, and methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion.

[0013] In some embodiments, the crosslinking agent includes one or more of aluminum hydroxide, aluminum hydroxide, aluminum oxide, aluminum hydroxide gel, and aluminum trichloride. The amount used, by weight percentage, is between 0.1% and 1% relative to the total weight of the gel matrix. Preferably, aluminum hydroxide or aluminum hydroxide is used.

[0014] In some embodiments, the crosslinking regulator includes one or both of disodium edetate and tetrasodium edetate. The amount used, by weight percentage, is between 0.1% and 2% relative to the total weight of the gel matrix. Disodium edetate is preferred.

[0015] In some embodiments, the pH adjuster is one or more of tartaric acid, lactic acid, malic acid, L-tartaric acid, citric acid, and phosphoric acid. The amount used, by weight percentage, is 0.1% to 2% relative to the total weight of the gel matrix, with tartaric acid being preferred.

[0016] In some embodiments, the filler includes one or more of kaolin, talc, titanium dioxide, micronized silica, silicon dioxide, and diatomaceous earth. The amount used, by weight percentage, is 1-10% relative to the total weight of the gel matrix. Kaolin is preferred.

[0017] In some embodiments, the release layer of the gel patch includes a release film or release paper.

[0018] In some embodiments, the *Sinomenium acutum* gel patch, relative to the total weight of the gel matrix, comprises, by weight percentage: Polymer framework materials 6-12%, Moisturizer 20-30%, Tackifier 10-25%, Crosslinking agent 0.1-1%, Crosslinking regulator 0.1-2%, pH adjuster 0.1-2%, Filler 1-10%, Water content: 15-55%.

[0019] In some embodiments, the *Sinomenium acutum* gel patch, relative to the total weight of the gel matrix, comprises, by weight percentage:

[0020] According to another aspect of the present invention, a method for preparing the above-mentioned Sinomenium acutum gel patch is also provided, comprising the following steps: (1) Preparation of Sinomenium acutum extract: Sinomenium acutum was pulverized, extracted with ethanol aqueous solution, concentrated and dried to obtain Sinomenium acutum extract; (2) Preparation of aqueous mixture: Add crosslinking regulator, humectant and thickener to water, then add Sinomenium acutum extract, mix well to obtain aqueous mixture; (3) Preparation of oil phase mixture: Add the skeleton material, thickener, crosslinking agent and filler to glycerol, mix well to obtain oil phase mixture; (4) Prepare pH adjustment solution: Dissolve the pH adjustment agent in water; (5) Mixing and preparing paste: Mix the oil phase mixture and the water phase mixture evenly, then add the pH adjuster solution and thickener, mix evenly to obtain the total paste; (6) Coating and cutting: The total mixture is evenly coated and cut to obtain the gel patch.

[0021] In some embodiments, the concentration of the ethanol aqueous solution in step (1) is 20-70%.

[0022] In some embodiments, the tackifier in step (5) is a polyacrylic acid solution.

[0023] The present invention also relates to the use of the gel patch in the preparation of remedies for osteoarthritis, frozen shoulder and muscle pain.

[0024] By adopting the above technical solution, the beneficial effects of the present invention are as follows: The inventors discovered that directly preparing a gel patch from sinomenine hydrochloride or sinomenine showed no significant therapeutic effect in pharmacodynamic tests. However, sinomenine extract was obtained by extracting, concentrating, and drying sinomenine in an ethanol-water solution without adding acid or alkali; the alkaloids in sinomenine do not form salts; and when this extract was further prepared into a gel patch, pharmacodynamic tests showed significant therapeutic effects.

[0025] Through matrix formulation improvements, the drug release capability is excellent. Based on a 12-month long-term stability study and in vitro release experiments, the in vitro release of the Sinomenium acutum extract gel patch of this invention is stable, the quality is stable, and it meets pharmaceutical standards.

[0026] The Sinomenium acutum gel patch of the present invention provides localized drug administration and has significant therapeutic effects. It acts directly on the local painful area, which can increase the local drug concentration, enhance the therapeutic effect, and reduce gastrointestinal and systemic side effects.

[0027] Terminology Definition In this invention, the "release film" or "release paper" mainly serves to isolate the adhesive drug reservoir layer. After the "release film" or "release paper" comes into contact with the drug reservoir layer, it exhibits an extremely light and stable release force.

[0028] In this invention, the term "Qingfengteng extract" refers to the extract obtained by pulverizing the dried stems of *Qingfengteng* or *Qingfengteng* (both belonging to the Menispermaceae family), extracting them with an ethanol-water solution (including but not limited to one or more of reflux extraction, soaking extraction, or percolation extraction), concentrating the extract, and drying it. Attached Figure Description

[0029] Figure 1 This is the cumulative release curve of the Qingfengteng gel patch. Detailed Implementation

[0030] The present application will be further described in detail below through specific embodiments. The following embodiments are only for further illustration of the present application and should not be construed as limiting the present application.

[0031] In the following examples, sinomenine hydrochloride was purchased from Shaanxi Datian Biotechnology Co., Ltd.

[0032] In the following examples, sinomenine was prepared by the following method: sinomenine hydrochloride was added to a mixture of dichloromethane and water, and sodium carbonate aqueous solution was added dropwise while stirring. After complete dissolution, the mixture was allowed to stand and separate into layers. The dichloromethane layer was washed with water until neutral, and then concentrated to dryness to obtain a white solid, which is sinomenine.

[0033] Unless otherwise specified, all reagents and raw materials used in this invention are commercially available.

[0034] Examples 1-4 The specifications of Examples 1 to 4 are equivalent to 3g, 6g, 9g and 12g of Sinomenium acutum, respectively, and contain 5g of gel matrix. The gel matrix formulations in Examples 1 to 4 are shown in Table 1 as a percentage of the total weight of the gel matrix.

[0035] Table 1

[0036] Manufacturing method (1) Preparation of Sinomenium acutum extract S1 Extraction: Crush *Sinomenium acutum*, moisten with 40% ethanol for 2 hours, then add an appropriate amount of 40% ethanol and soak for 24 hours. Percolate to obtain the percolate for later use.

[0037] S2 Concentration: The percolate is concentrated under reduced pressure to 1.0–1.3 g / cm³. 3 .

[0038] S3 Drying: The concentrate is dried under reduced pressure until the moisture content is below 10% to obtain the extract of *Sinomenium acutum*.

[0039] (2) Preparation of aqueous phase: Add gelatin, polyvinyl alcohol, disodium edetate and Sinomenium acutum extract to water and stir evenly.

[0040] (3) Preparation of oil phase: Sodium carboxymethyl cellulose, aluminum hydroxyl, kaolin, and partially neutralized sodium polyacrylate are added to glycerol and stirred evenly.

[0041] (4) Prepare tartaric acid solution: Dissolve tartaric acid in water.

[0042] (5) Mixing and preparing the paste: Mix the oil phase and the water phase evenly, then add tartaric acid solution and polyacrylic acid solution, and mix evenly to obtain the total paste.

[0043] (6) Coating and cutting: Coat and cut the total mixture evenly.

[0044] Examples 5-8 The specifications of Examples 5-8 are equivalent to 3g, 6g, 9g and 12g of Sinomenium acutum, respectively, and contain 15g of gel matrix. The gel matrix formulations of Examples 5-8 are shown in Table 2 as a percentage of the total weight of the gel matrix.

[0045] Table 2

[0046] Manufacturing method (1) Preparation of Sinomenium acutum extract S1 Extraction: Crush the *Sinomenium acutum* and heat it under reflux for 2 hours with 10 times the amount of ethanol solution. Extract three times and combine the extracts.

[0047] S2 Concentration: The extract is concentrated under reduced pressure to 1.0–1.3 g / cm³. 3 .

[0048] S3 Drying: The concentrate is dried under reduced pressure until the moisture content is below 10% to obtain the extract of *Sinomenium acutum*.

[0049] (2) Preparation of aqueous phase: Add disodium edetate, glycerin, gelatin, carbomer and Sinomenium acutum extract to water and stir well.

[0050] (3) Preparation of oil phase: Add part of the neutralized sodium polyacrylate, sodium carboxymethyl cellulose, aluminum hydroxide, kaolin and / or silica to glycerol and stir until homogeneous.

[0051] (4) Prepare citric acid solution: Dissolve citric acid in water.

[0052] (5) Mixing and preparing the paste: Mix the oil phase and the water phase evenly, then add citric acid solution, polyacrylic acid solution and methyl acrylate-2-ethylhexyl acrylic acid copolymer resin emulsion, and stir evenly to obtain the total paste.

[0053] (6) Coating and cutting: Coat and cut the total mixture evenly.

[0054] Comparative Examples 1-6 Preparation of sinomenine gel plaster Blank plaster (Comparative Example 1), sinomenine hydrochloride gel plaster (Comparative Example 2), and sinomenine gel plaster (Comparative Examples 3-6) were prepared according to the formulations in the table below. The specification of Comparative Example 2 was 100 mg of sinomenine hydrochloride per plaster (calculated as sinomenine). The specifications of Comparative Examples 3-6 were 25, 50, 75, and 150 mg of sinomenine per plaster, respectively. The preparation contained 5 g of gel matrix. The gel matrix formulations of Comparative Examples 1-6 are shown in Table 3 as a percentage of the total weight of the gel matrix.

[0055] Table 3

[0056] Manufacturing method (1) Preparation of aqueous phase: Add gelatin, polyvinyl alcohol, disodium edetate, sinomenine or sinomenine hydrochloride to water and stir evenly.

[0057] (2) Preparation of oil phase: Sodium carboxymethyl cellulose, aluminum hydroxyl, kaolin, and partially neutralized sodium polyacrylate are added to glycerol and stirred evenly.

[0058] (3) Preparation of tartaric acid solution: Dissolve tartaric acid in water.

[0059] (4) Mixing and preparing the paste: Mix the oil phase and the water phase evenly, then add tartaric acid solution and polyacrylic acid solution to obtain the total paste.

[0060] (5) Coating and cutting: Coat and cut the total mixture evenly.

[0061] Example 9 The content of sinomenine in the gel patches of Comparative Examples 1-6 and Examples 1-8 was determined by high performance liquid chromatography, and the results are shown in Table 4 below.

[0062] Table 4

[0063] Table 4 shows the detection results of sinomenine content in the preparation. The results show that Comparative Example 1 was a blank plaster with a sinomenine content of 0; the sinomenine content in Comparative Examples 3, Example 1, and Example 5 were 24.2 mg / patch, 21.5 mg / patch, and 20.1 mg / patch, respectively, indicating that the sinomenine content was at the same level; similarly, at the same dosage, the sinomenine content in Comparative Examples 4, Example 2, and Example 6; Comparative Examples 5, Example 3, and Example 7 (each plaster equivalent to 9g of Sinomenium acutum); and Comparative Examples 2, 6, 4, and 8 was at the same level.

[0064] Application examples

[0065] Referring to Method 1 (Determination of Initial Tack) of General Chapter 0952, Part IV of the Chinese Pharmacopoeia (2020 Edition), the initial tack was determined using the rolling ball ramp stop method. Three test samples were taken, the protective layer removed, and placed in the center of an inclined plate with a 30° angle, paste side up. The upper 10cm and lower 15cm of the ramp were covered with a 0.025mm thick polyester film, leaving a 5cm paste surface exposed in the middle. Steel balls of different diameters were rolled freely down the ramp. The initial tack was evaluated based on the number of the largest steel ball that the adhesive surface could adhere to. The results showed that the *Sinomenium acutum* gel patches in Examples 1-8 adhered to steel balls numbered 23, 24, 26, 21, 18, 23, 24, and 20, respectively, indicating good initial tack performance.

[0066] Determination of the content of Qingfengteng gel plaster Take one patch of each of the Qingfengteng gel plasters prepared in Examples 1 to 8, remove the cover, weigh accurately, place in a beaker, add an appropriate amount of water, heat to boiling until the backing separates from the plaster, remove the backing, wash with water until there is no plaster residue on the backing, air dry, dry at 105°C for 30 minutes, transfer to a desiccator, cool for 30 minutes, weigh accurately, the weight loss is the weight of the plaster, the result should be calculated according to the following formula, and should be 90 to 110% of the labeled amount.

[0067]

[0068] The results showed that the contents of the Sinomenium acutum gel plasters prepared in Examples 1-8 were 97%, 99%, 98%, 99%, 99%, 98%, 97%, and 99%, respectively, which met the requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0069] Excipient properties test of Qingfengteng gel patch Take one patch of each of the Qingfengteng gel plasters prepared in Examples 1 to 8, place them in a constant temperature and humidity chamber at 37°C and 64% relative humidity for 30 minutes, take them out, and fix the test sample on a flat steel plate with a clamp. The angle between the steel plate and the horizontal plane is 60°. After 24 hours, there should be no dripping on the plaster surface.

[0070] Ten pieces of each batch of Sinomenium acutum gel plaster prepared in Examples 1-8 were tested. The results showed that none of the samples flowed, which met the excipient test requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0071] Stability study of Qingfengteng gel patch According to the stability protocol, the stability of the self-made samples (selected from Examples 1 to 4) that were retained for observation was investigated for 12 months. The statistical results of the sample quality stability are shown in Table 5.

[0072] Table 5

[0073] The above experimental results show that the Qingfengteng gel plaster of the present invention has excellent long-term stability, maintains stable quality after 12 months of storage, has a long shelf life, and meets pharmaceutical standards.

[0074] In vitro release study of Qingfengteng gel patch The above-mentioned Qingfengteng gel patches from Examples 1 to 8 were subjected to in vitro release experiments. The experimental instrument was a TK-24BL transdermal ...

[0075] Experimental Procedure: Using a polyethersulfone membrane (0.45 μm pore size) as the separator and pH 7.4 PBS at 32 ± 0.5 °C as the receiving medium, the in vitro release characteristics of each sample through a vertical diffusion cell were determined. All receiving liquid was collected at 1, 2, 4, 6, 8, and 12 hours, with an equal volume of receiving liquid added simultaneously. The collected receiving liquid was filtered through a 0.45 μm filter membrane, and the filtrate was used as the test solution. The content of the main component in the solution was determined, and the result was calculated.

[0076] Figure 1 This is a schematic diagram illustrating the in vitro release results of the Sinomenium acutum gel patch. Figure 1 It can be seen that the cumulative release rate of the Sinomenium acutum gel patch in vitro after 12 hours can reach more than 90%, indicating that the Sinomenium acutum gel patch of the present invention can stably and effectively release Sinomenine.

[0077] Effects of Qingfengteng gel plaster on experimental rabbit model of periarthritis of the shoulder Sixty-eight qualified New Zealand rabbits of ordinary grade were selected and divided into a normal control group (n=8) and a model group (n=60). Hair was removed from the outer right shoulder of each rabbit in each group, with an area of ​​10cm × 10cm. The model group animals were fixed in a prone position, with their right forelimb connected and fixed to a horizontal rocking cradle. After rocking for 6 hours, ice packs were applied for 4 hours daily for 3 days. Successful model establishment was considered achieved when the soft tissue of the shoulder area was swollen, with local congestion or ecchymosis. The day after the last model establishment, the circumference of the shoulder joint swelling was measured in each group. Fifty-six model animals were selected and divided into a stratified grouping method based on the shoulder joint swelling circumference: a model control group, two control groups, six control groups, and groups 1-4 of the examples, with eight animals in each group. Before daily administration, the following plasters were cut to an area of ​​7.0cm × 10.0cm: sinomenine hydrochloride gel plaster, sinomenine gel plaster, sinomenium acutum gel plaster, and blank plaster. The right shoulder joint area of ​​each group was prepared periodically. The experimental rabbits in each group were directly treated with the corresponding concentration of the test substance or control substance applied to the right shoulder joint area. Medical breathable adhesive tape was used to fix the plaster to prevent it from falling off. The medication was administered twice daily, with the second dose removed before the next day's administration, with a 12-hour interval between the two doses. The normal control group and the model control group received blank plasters of equal area using the same administration method.

[0078] The pain threshold of the shoulder joint of each group of experimental rabbits was measured using a pain pressure meter before administration, on day 4 after administration, and the day after the last administration.

[0079] The circumference of shoulder joint swelling in each group of experimental rabbits was measured using the suture method and vernier calipers before drug administration, on day 4 after drug administration, and the day after the last drug administration.

[0080] After the last drug withdrawal, the experimental rabbits in each group were anesthetized by intravenous injection of propofol at 15 mg / kg, and then euthanized by femoral artery pleophoresis. The skin of the model site of the experimental rabbits was cut open, and the right biceps femoris muscle tissue was dissected and harvested. The tissue homogenate was prepared with 0.9% sodium chloride injection at a ratio of 1:9. The contents of TNF-α, IL-6, PGE-2 and TGF-β1 in the biceps femoris muscle tissue were determined by ELISA.

[0081] Experimental results (1) Effect on the swelling circumference of the shoulder joint in experimental rabbits Compared with the normal control group, the shoulder joint swelling circumference of the experimental rabbits in the model control group was significantly increased before drug administration, on day 4 after drug administration, and on the day after the last drug administration (P≤0.01).

[0082] Compared with the model control group, the shoulder joint swelling circumference of rabbits in Comparative Example 2 and Comparative Example 6 was slightly reduced on day 4 after administration and the day after the last administration (P≤0.05 or P≤0.01), while the shoulder joint swelling circumference of rabbits in Examples 2-4 was significantly reduced on day 4 after administration and the day after the last administration (P≤0.05 or P≤0.01). The experimental results are shown in Table 6 below.

[0083] Table 6

[0084] Note: Compared with the normal control group, ++P≤0.01; compared with the model control group, *P≤0.05, **P≤0.01.

[0085] (2) Effect on shoulder pain threshold in experimental rabbits Compared with the normal control group, the shoulder pain threshold of the experimental rabbits in the model control group was significantly reduced before drug administration, on day 4 after drug administration, and on the day after the last drug administration (P≤0.01).

[0086] Compared with the model control group, the shoulder pain threshold of rabbits in Comparative Example 2 and Comparative Example 6 was slightly increased the day after the last administration (P≤0.05), while the shoulder pain threshold of rabbits in Examples 2-4 was significantly increased the day after the last administration (P≤0.01). The experimental results are shown in Table 7 below.

[0087] Table 7

[0088] Note: Compared with the normal control group, ++P≤0.01; compared with the model control group, *P≤0.05, **P≤0.01.

[0089] (3) Effects on cytokines in the biceps femoris muscle tissue of the shoulder joint Compared with the normal control group, the levels of TNF-α, IL-6, PGE-2, and TGF-β1 in the biceps femoris muscle tissue of the experimental rabbits in the model control group were significantly increased (P≤0.01).

[0090] Compared with the model control group, the TNF-α content in the biceps femoris muscle tissue of rabbits in Example 1 group was significantly reduced (P≤0.05), and the contents of TNF-α, IL-6, and TGF-β1 in the biceps femoris muscle tissue of rabbits in Example 4 group were significantly reduced (P≤0.05). The experimental results are shown in Table 8 below.

[0091] Table 8

[0092] Note: Compared with the normal control group, +P≤0.05, ++P≤0.01; compared with the model control group, *P≤0.05, **P≤0.01.

[0093] This study induced a rabbit model of periarthritis of the shoulder using continuous mechanical strain combined with ice application to evaluate and compare the pharmacological effects of sinomenine hydrochloride gel patch, sinomenine gel patch, and sinomenium acutum extract gel patch on osteoarthritis.

[0094] The observation results are as follows (1) Effect of shoulder joint swelling circumference: The shoulder joint swelling circumference of rabbits in groups 2-4 of Example 1 was significantly reduced on day 4 after administration and the day after the last administration. The shoulder joint swelling circumference of rabbits in groups 2 and 6 of Comparative Example 2 was slightly reduced on day 4 after administration and the day after the last administration (P≤0.05 or P≤0.01).

[0095] (2) Effect of shoulder pain threshold: The shoulder pain threshold of rabbits in groups 2 to 4 of Examples was significantly increased on the day after the last administration (P≤0.01), while the shoulder pain threshold of rabbits in groups 2 and 6 of Comparative Examples was slightly increased on the day after the last administration (P≤0.05).

[0096] (3) Effects on cytokines in the biceps femoris tissue of the shoulder joint: The TNF-α content in the biceps femoris tissue of the experimental rabbits in Example 1 was significantly reduced (P≤0.05), and the contents of TNF-α, IL-6 and TGF-β1 in the biceps femoris tissue of the experimental rabbits in Example 4 were significantly reduced (P≤0.05).

[0097] Under the experimental conditions, Example 1 can slightly increase the shoulder pain threshold of experimental rabbits and reduce the TNF-α level in the biceps femoris tissue of model experimental rabbits; Examples 2-4 can reduce the swelling circumference of the shoulder joint, increase the shoulder pain threshold of experimental rabbits, and reduce the TNF-α content in the biceps femoris tissue of experimental rabbits. In addition, Example 4 can significantly reduce the levels of TNF-α, IL-6, and TGF-β1 in the biceps femoris tissue of model experimental rabbits.

[0098] The results showed that sinomenine hydrochloride gel patch and sinomenine gel patch did not have a significant effect on improving the experimental rabbit frozen shoulder model, while sinomenine gel patch had a significant effect on improving the experimental rabbit frozen shoulder model.

[0099] The above description, in conjunction with specific embodiments, provides a further detailed explanation of this application and should not be construed as limiting the specific implementation of this application to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of this application, and all such modifications or substitutions should be considered within the scope of protection of this application.

Claims

1. A type of Qingfengteng gel patch, characterized in that, The gel patch comprises: a backing layer, a drug reservoir layer, and a release layer; wherein, the drug reservoir layer, by weight, comprises the following components: 3-12 parts of Sinomenium acutum and 5-15 parts of gel matrix. The gel matrix comprises, by weight percentage, the following components relative to the total weight of the gel matrix: Polymer framework materials 6-12%, Moisturizer 20-30%, Tackifier 10-25%, Crosslinking agent 0.1-1%, Crosslinking regulator 0.1-2%, pH adjuster 0.1-2%, Filler 1-10%, Water content: 15-55%.

2. The Sinomenium acutum gel patch according to claim 1, characterized in that, The *Sinomenium acutum* was extracted, concentrated, and dried using an ethanol-water solution to obtain *Sinomenium acutum* extract.

3. The Sinomenium acutum gel patch according to claim 1 or 2, characterized in that, The polymeric framework material includes one or more of sodium polyacrylate, partially neutralized sodium polyacrylate, carbomer, and polyvinyl alcohol.

4. The Sinomenium acutum gel patch according to claim 1 or 2, characterized in that, The humectant includes one or more of glycerin, propylene glycol, 1,3-butanediol, urea, sorbitol, and polyethylene glycol; and / or the thickener includes one or more of gelatin, sodium carboxymethyl cellulose, polyacrylic acid solution, methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, acrylic acid grafted starch, povidone solution, and polyvinylpyrrolidone.

5. The Sinomenium acutum gel patch according to claim 1 or 2, characterized in that, The crosslinking agent includes one or more of aluminum hydroxyl, aluminum hydroxide, aluminum oxide, aluminum hydroxide gel, and aluminum trichloride; and / or the crosslinking regulator includes one or two of disodium edetate and tetrasodium edetate.

6. The Sinomenium acutum gel patch according to claim 1 or 2, characterized in that, The pH adjuster is selected from one or more of tartaric acid, lactic acid, malic acid, L-tartaric acid, citric acid, and phosphoric acid; and / or the filler is selected from one or more of kaolin, talc, titanium dioxide, micronized silica, silica, and diatomaceous earth.

7. The method for preparing the Sinomenium acutum gel plaster according to any one of claims 1 to 6, characterized in that, Includes the following steps: (1) Preparation of Sinomenium acutum extract: Sinomenium acutum was pulverized, extracted with ethanol aqueous solution, concentrated and dried to obtain Sinomenium acutum extract; (2) Preparation of aqueous mixture: Add crosslinking regulator, humectant and thickener to water, then add Sinomenium acutum extract, mix well to obtain aqueous mixture; (3) Preparation of oil phase mixture: Add polymer backbone material, crosslinking agent, filler and thickener to glycerol, mix well to obtain oil phase mixture; (4) Prepare pH adjustment solution: Dissolve the pH adjustment agent in water; (5) Mixing and preparing paste: Mix the oil phase mixture and the water phase mixture evenly, then add the pH adjuster solution and thickener, mix evenly to obtain the total paste; (6) Coating and cutting: The total mixture is evenly coated and cut to obtain the gel patch.

8. The use of the Sinomenium acutum gel plaster according to any one of claims 1 to 6 or the Sinomenium acutum gel plaster prepared by the preparation method according to claim 7 in the preparation of drugs for treating osteoarthritis, frozen shoulder and muscle pain.

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