Gel emplastrum for treating arthralgia and preparation method thereof

Abstract

The invention relates to the technical field of external use of medicines, and discloses a gel emplastrum for treating arthralgia and a preparation method thereof.The gel emplastrum is prepared by doping lipid nanoparticles containing diclofenac diethylamine and wrapped by a bimolecular layer into a gel matrix, the sustained and controlled drug release effect is achieved, meanwhile, a penetrating agent is doped into the gel matrix, and the effect of treating arthralgia is achieved. The transdermal absorption effect of the medicine is enhanced, the dosage of the medicine is reduced, meanwhile, the surface modifier is used for modifying the paper nanoparticles, the stability of the product is enhanced, and production and storage are facilitated.

Description

Technical Field

[0001] The invention relates to the technical field of external medicines, and in particular to a gel plaster for treating joint pain and a preparation method thereof. Background Art

[0002] Rheumatoid arthritis and chronic lumbar muscle strain are common clinical diseases with pain, swelling and limited activity as the main symptoms. Among the drugs for clinical treatment of such pain, Chinese medicine external application patches are the most accepted by patients because they can be directly applied to the affected part, and the drug is absorbed through the skin and reaches the lesion directly. In the prior art, for example, a Chinese medicine analgesic plaster for treating joint pain, lumbago and the like disclosed in Chinese patent number CN1903295A and its preparation method, the effective ingredients in each medicine are extracted by crushing, ethanol extraction, water extraction, ethanol precipitation, steam distillation and other methods to extract volatile oil, which has low bioavailability and short shelf life, and is not conducive to storage.

[0003] In recent years, lipid nanoparticles (LNPs) have received extensive attention in drug delivery systems due to their good biocompatibility and targeting properties. However, when lipid nanoparticles are used in gel patch preparations, their transdermal absorption effect is still low, which directly affects the bioavailability of gel patch preparations. At the same time, if lipid nanoparticles are placed for a long time, the particle size will grow and the drug will degrade, which is not conducive to industrial production. Summary of the invention

[0004] In order to solve the technical problems of low bioavailability and slow onset of action of traditional Chinese medicine external patches proposed in the above background technology, decreased stability of lipid nanoparticles after long-term storage leading to particle size growth and drug degradation, the present invention provides a gel patch for treating joint pain and a preparation method thereof, which enhances the drug onset and reduces the drug dosage by adding laurocapram (azone) to the gel matrix, and at the same time, improves the preparation method of lipid nanoparticles, enhances the stability of lipid nanoparticles and prolongs the storage time.

[0005] The specific technical scheme of the present invention is: a method for preparing a gel patch for treating joint pain, comprising the following steps: 1) slowly adding carbomer into water with continuous stirring, heating to 60-65° C., adding 0.05-0.1 wt % sodium hyaluronate, 0.8-1 wt % azone and 0.2-0.4 wt % phenoxyethanol, and mixing well to obtain a pretreated gel matrix; 2) adding a lipid nanoparticle suspension for treating joint pain to the pretreated gel matrix, stirring continuously until the mixture is uniform, and cooling and standing to obtain a gel layer; 3) The gel layer is evenly spread on the backing material to obtain a gel layer, and an anti-adhesive layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0006] The invention combines lipid nanoparticle technology with gel patch preparation technology, and incorporates lipid nanoparticles for treating joint pain into a gel matrix to control the drug release rate, thereby ensuring that the drug release rate remains relatively constant during the drug administration process; at the same time, the drug is wrapped in a closed space to increase the stability of the drug, and azone is added to the gel matrix as a permeation agent to increase the bioavailability of the drug while reducing the dosage of the drug and avoiding drug abuse. At the same time, the preparation method of the lipid nanoparticles is improved to enhance the stability of the lipid nanoparticles, reduce biodegradation and particle size increase caused by long storage time, and reduce the activity of the drug.

[0007] Preferably, in step 1), deionized water is used.

[0008] Preferably, in step 1), the stirring time is 30 to 45 minutes.

[0009] Preferably, in step 2), the standing time is 30 to 60 minutes.

[0010] Furthermore, the method for preparing the lipid nanoparticle suspension for treating joint pain in step 2) comprises the following steps: S1. 100-110 mg of phosphatidylcholine, 50-55 mg of cholesterol, 5-6 mg of antioxidant and 5-6 mg of surface modifier are added to 10-20 ml of chloroform, and after being fully dissolved, a lipid film is prepared by rotary evaporation; S2. Add 2 to 3 ml of phosphate buffer containing 20 to 25 mg of diclofenac diethylamine to the lipid film, and shake until the lipid film is hydrated to obtain a primary emulsion; S3. After circulatory homogenization and centrifugation of the colostrum, a stabilizer #stabilizer addition amount is added to obtain a lipid nanoparticle suspension for treating joint pain.

[0011] Furthermore, the antioxidant in S1) is one or more of vitamin E, ascorbyl palmitate and tea polyphenols.

[0012] Furthermore, in S1), the surface modifier is one or more of polyethylene glycol disuccinate, cholesterol sulfate, and cholesterol succinate.

[0013] Furthermore, in S2), the pH value of the phosphate buffer is 7-8.

[0014] Preferably, the pH value of the phosphate buffer is 7.4.

[0015] Furthermore, in S3), the number of cycles of homogenization is ≥5.

[0016] Furthermore, in S3), the temperature of circulating homogenization and centrifugation is 0-4°C.

[0017] Furthermore, the phosphatidylcholine is one of DPPC and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine.

[0018] Furthermore, the particle size of the lipid nanoparticles in the lipid nanoparticle suspension is 100-200 nm.

[0019] Furthermore, a gel patch for treating joint pain.

[0020] Compared with the prior art, the beneficial effects of the present invention are: 1) Lipid nanoparticles for treating joint pain are incorporated into the gel matrix to achieve sustained and controlled release of the drug.

[0021] 2) Adding azone to the gel matrix increases the bioavailability of the drug and reduces the dosage of the drug.

[0022] 3) Improve the preparation method of lipid nanoparticles to enhance the stability of lipid nanoparticles and reduce biodegradation and particle size increase caused by long storage time, thereby reducing the activity of drugs. DETAILED DESCRIPTION

[0023] The present invention will be further described below in conjunction with the embodiments.

[0024] Specific examples and comparative examples.

[0025] Example 1 1) Preparation of lipid nanoparticles 100 mg of phosphatidylcholine, 50 mg of cholesterol, 5 mg of vitamin E and 5 mg of cholesterol sulfate were dissolved in 10 ml of chloroform. After complete dissolution, the chloroform was completely removed using a nitrogen blow-drying device to form a uniform lipid film at the bottom of the container; 2 ml of phosphate buffer solution with a pH of 7.4 containing 20 mg of diclofenac diethylamine was shaken until the lipid film was fully hydrated to obtain a primary emulsion; The primary emulsion was circulated for 5 times at 4°C using a high-pressure homogenizer, and then centrifuged at 10,000 rpm for 10 minutes to obtain a lipid nanoparticle suspension for treating joint pain. The lipid nanoparticle suspension for treating joint pain was stored at 4°C.

[0026] 2) Preparation of gel layer 2 g of carbomer was slowly added to 100 ml of deionized water and stirred for 20 min. After the carbomer was fully expanded, it was heated in a 60° C. water bath, 100 mg of sodium hyaluronate, 160 mg of azone and 40 mg of phenoxyethanol were added, and stirred for 10 min. 2 ml of the lipid nanoparticle suspension for treating joint pain prepared in step 1) was added, and stirred for 5 min. The mixture was cooled to 25° C. and allowed to stand for 30 min.

[0027] 3) Packaging material: The gel layer prepared in step 2) is evenly spread on the backing material, and an anti-sticking layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0028] 4) Performance testing The particle size of lipid nanoparticles in the gel patch for treating joint pain was tested after being placed for 1 day, 7 days, 30 days, and 90 days.

[0029] The washed pig skin was fixed to the release port of the Franz diffusion cell, and pH 7.4 phosphate buffer was added to the receiving chamber as the release medium to keep the endothelial layer in close contact with the solution. The gel patch with the cover lining removed was applied to the skin, and the water bath was adjusted to keep the temperature of the outer layer constant at (32±0.5)℃, the stirring speed was 600rpm, and 4ml of the release medium was absorbed at 0, 1h, 2h, 4h, 6h, 8h, 12h, and 24h, respectively, and an equal amount of PBS solution was added at the same time to calculate the cumulative absorption percentage (i.e., the percentage of the cumulative diclofenac diethylamine permeated to the total amount of diclofenac diethylamine in the drug reservoir).

[0030] Comparative Example 1 The difference between this comparative example and Example 1 is that, in step 1) of this comparative example, cholesterol sulfate is not added, and the rest of the process is the same as that of Example 1, and the specific steps are as follows: 1) Preparation of lipid nanoparticles Dissolve 100 mg of phosphatidylcholine, 50 mg of cholesterol, and 5 mg of vitamin E in 10 ml of chloroform. After they are completely dissolved, use a nitrogen drying device to remove all the chloroform to form a uniform lipid film at the bottom of the container. 2 ml of phosphate buffer at pH 7.4 containing 20 mg of diclofenac diethylamine was shaken until the lipid film was fully hydrated to obtain a primary emulsion; The primary emulsion was circulated for 5 times at 4°C using a high-pressure homogenizer, and then centrifuged at 10,000 rpm for 10 minutes to obtain a lipid nanoparticle suspension for treating joint pain. The lipid nanoparticle suspension for treating joint pain was stored at 4°C.

[0031] 2) Preparation of gel layer 2 g of carbomer was slowly added to 100 ml of deionized water and stirred for 20 min. After the carbomer was fully expanded, it was heated in a 60° C. water bath, 100 mg of sodium hyaluronate, 160 mg of azone and 40 mg of phenoxyethanol were added, and stirred for 10 min. 2 ml of the lipid nanoparticle suspension for treating joint pain prepared in step 1) was added, and stirred for 5 min. The mixture was cooled to 25° C. and allowed to stand for 30 min.

[0032] 3) Packaging material: The gel layer prepared in step 2) is evenly spread on the backing material, and an anti-sticking layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0033] 4) Performance testing The particle size of lipid nanoparticles in the gel patch for treating joint pain was tested after being placed for 1 day, 7 days, 30 days, and 90 days.

[0034] The washed pig skin was fixed to the release port of the Franz diffusion cell, and pH 7.4 phosphate buffer was added to the receiving chamber as the release medium to keep the endothelial layer in close contact with the solution. The gel patch with the cover lining removed was applied to the skin, and the water bath was adjusted to keep the temperature of the outer layer constant at (32±0.5)℃, the stirring speed was 600rpm, and 4ml of the release medium was absorbed at 0, 1h, 2h, 4h, 6h, 8h, 12h, and 24h, respectively, and an equal amount of PBS solution was added at the same time to calculate the cumulative absorption percentage (i.e., the percentage of the cumulative diclofenac diethylamine permeated to the total amount of diclofenac diethylamine in the drug reservoir).

[0035] Comparative Example 2 The difference between this comparative example and Example 1 is that in step 1) of this comparative example, the amount of cholesterol sulfate added is 15 mg, and the rest of the process is the same as that of Example 1, and the specific steps are as follows: 1) Preparation of lipid nanoparticles 100 mg of phosphatidylcholine, 50 mg of cholesterol, 5 mg of vitamin E and 15 mg of cholesterol sulfate were dissolved in 10 ml of chloroform. After complete dissolution, the chloroform was completely removed using a nitrogen blow-drying device to form a uniform lipid film at the bottom of the container; 2 ml of phosphate buffer solution with a pH of 7.4 containing 20 mg of diclofenac diethylamine was shaken until the lipid film was fully hydrated to obtain a primary emulsion; The primary emulsion was circulated for 5 times at 4°C using a high-pressure homogenizer, and then centrifuged at 10,000 rpm for 10 minutes to obtain a lipid nanoparticle suspension for treating joint pain. The lipid nanoparticle suspension for treating joint pain was stored at 4°C.

[0036] 2) Preparation of gel layer 2 g of carbomer was slowly added to 100 ml of deionized water and stirred for 20 min. After the carbomer was fully expanded, it was heated in a 60° C. water bath, 100 mg of sodium hyaluronate, 160 mg of azone and 40 mg of phenoxyethanol were added, and stirred for 10 min. 2 ml of the lipid nanoparticle suspension for treating joint pain prepared in step 1) was added, and stirred for 5 min. The mixture was cooled to 25° C. and allowed to stand for 30 min.

[0037] 3) Packaging material: The gel layer prepared in step 2) is evenly spread on the backing material, and an anti-sticking layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0038] 4) Performance testing The particle size of lipid nanoparticles in the gel patch for treating joint pain was tested after being placed for 1 day, 7 days, 30 days, and 90 days.

[0039] The washed pig skin was fixed to the release port of the Franz diffusion cell, and pH 7.4 phosphate buffer was added to the receiving chamber as the release medium to keep the endothelial layer in close contact with the solution. The gel patch with the cover lining removed was applied to the skin, and the water bath was adjusted to keep the temperature of the outer layer constant at (32±0.5)℃, the stirring speed was 600rpm, and 4ml of the release medium was absorbed at 0, 1h, 2h, 4h, 6h, 8h, 12h, and 24h, respectively, and an equal amount of PBS solution was added at the same time to calculate the cumulative absorption percentage (i.e., the percentage of the cumulative diclofenac diethylamine permeated to the total amount of diclofenac diethylamine in the drug reservoir).

[0040] Table 1 Effects of surface modifiers on the stability of lipid nanoparticles According to the data in Table 1, when no surface modifier is added, the lipid nanoparticles finally formed are easy to aggregate, reducing the uniformity and dispersibility of the preparation; when too much surface modifier is added, the particle size of the lipid nanoparticles will increase, affecting the transdermal absorption efficiency, and also causing the particles to aggregate. The reasons are speculated to be: too much surface modifier will lead to enhanced interaction between particles and the formation of larger aggregates; when too little surface modifier is added, the interaction force between particles is not enough to overcome the van der Waals force and other attractive forces, resulting in particle aggregation.

[0041] Comparative Example 3 The difference between this comparative example and Example 1 is that, in this comparative example, azone is not added in step 2), and the remaining processes are the same as in Example 1, and the specific steps are: 1) Preparation of lipid nanoparticles 100 mg of phosphatidylcholine, 50 mg of cholesterol, 5 mg of vitamin E and 5 mg of cholesterol sulfate were dissolved in 10 ml of chloroform. After complete dissolution, the chloroform was completely removed using a nitrogen blow-drying device to form a uniform lipid film at the bottom of the container; 2 ml of phosphate buffer solution with a pH of 7.4 containing 20 mg of diclofenac diethylamine was shaken until the lipid film was fully hydrated to obtain a primary emulsion; The primary emulsion was circulated for 5 times at 4°C using a high-pressure homogenizer, and then centrifuged at 10,000 rpm for 10 minutes to obtain a lipid nanoparticle suspension for treating joint pain. The lipid nanoparticle suspension for treating joint pain was stored at 4°C.

[0042] 2) Preparation of gel layer Slowly add 2 g of carbomer to 100 ml of deionized water and stir for 20 min. After the carbomer is fully expanded, heat it in a 60° C. water bath, add 100 mg of sodium hyaluronate and 40 mg of phenoxyethanol, stir for 10 min, add 2 ml of the lipid nanoparticle suspension for treating joint pain prepared in step 1), stir for 5 min, cool to 25° C., and let stand for 30 min.

[0043] 3) Packaging materials The gel layer prepared in step 2) is evenly spread on the backing material, and an anti-sticking layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0044] 4) Performance testing The particle size of lipid nanoparticles in the gel patch for treating joint pain was tested after being placed for 1 day, 7 days, 30 days, and 90 days.

[0045] The washed pig skin was fixed to the release port of the Franz diffusion cell, and pH 7.4 phosphate buffer was added to the receiving chamber as the release medium to keep the endothelial layer in close contact with the solution. The gel patch with the cover lining removed was applied to the skin, and the water bath was adjusted to keep the temperature of the outer layer constant at (32±0.5)℃, the stirring speed was 600rpm, and 4ml of the release medium was absorbed at 0, 1h, 2h, 4h, 6h, 8h, 12h, and 24h, respectively, and an equal amount of PBS solution was added at the same time to calculate the cumulative absorption percentage (i.e., the percentage of the cumulative diclofenac diethylamine permeated to the total amount of diclofenac diethylamine in the drug reservoir).

[0046] Comparative Example 4 The difference between this comparative example and Example 1 is that, in this comparative example, the addition amount of azone is 200 mg, and the rest of the process is the same as that of Example 1, and the specific steps are: 1) Preparation of lipid nanoparticles 100 mg of phosphatidylcholine, 50 mg of cholesterol, 5 mg of vitamin E and 5 mg of cholesterol sulfate were dissolved in 10 ml of chloroform. After complete dissolution, the chloroform was completely removed using a nitrogen blow-drying device to form a uniform lipid film at the bottom of the container; 2 ml of phosphate buffer solution with a pH of 7.4 containing 20 mg of diclofenac diethylamine was shaken until the lipid film was fully hydrated to obtain a primary emulsion; The primary emulsion was circulated for 5 times at 4°C using a high-pressure homogenizer, and then centrifuged at 10,000 rpm for 10 minutes to obtain a lipid nanoparticle suspension for treating joint pain. The lipid nanoparticle suspension for treating joint pain was stored at 4°C.

[0047] 2) Preparation of gel layer 2 g of carbomer was slowly added to 100 ml of deionized water and stirred for 20 min. After the carbomer was fully expanded, it was heated in a 60° C. water bath, 100 mg of sodium hyaluronate, 200 mg of azone and 40 mg of phenoxyethanol were added, and stirred for 10 min. 2 ml of the lipid nanoparticle suspension for treating joint pain prepared in step 1) was added, and stirred for 5 min. The mixture was cooled to 25° C. and allowed to stand for 30 min.

[0048] 3) Packaging material: The gel layer prepared in step 2) is evenly spread on the backing material, and an anti-sticking layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0049] 4) Performance testing The particle size of lipid nanoparticles in the gel patch for treating joint pain was tested after being placed for 1 day, 7 days, 30 days, and 90 days.

[0050] The washed pig skin was fixed to the release port of the Franz diffusion cell, and pH 7.4 phosphate buffer was added to the receiving chamber as the release medium to keep the endothelial layer in close contact with the solution. The gel patch with the cover lining removed was applied to the skin, and the water bath was adjusted to keep the temperature of the outer layer constant at (32±0.5)℃, the stirring speed was 600rpm, and 4ml of the release medium was absorbed at 0, 1h, 2h, 4h, 6h, 8h, 12h, and 24h, respectively, and an equal amount of PBS solution was added at the same time to calculate the cumulative absorption percentage (i.e., the percentage of the cumulative diclofenac diethylamine permeated to the total amount of diclofenac diethylamine in the drug reservoir).

[0051] Table 2 Effect of penetrant on diffusion rate of gel patch From the data in Table 2, when no permeabilizing agent (azone) is added to the gel matrix, the ability of the drug to penetrate the skin is significantly reduced, and the drug takes effect more slowly; when an excessive amount of permeabilizing agent is added, a large amount of the drug will penetrate the skin into the body circulation in a short period of time, and a good sustained-controlled release effect cannot be achieved. The reasons are speculated to be: no permeabilizing agent is added or the amount of permeabilizing agent added is too low, which cannot effectively improve the transdermal absorption of the drug, resulting in insufficient local concentration, affecting the timeliness and effectiveness of treatment; if the amount of permeabilizing agent added is too high, the sustained-controlled release effect will be invalid, and the effect of uniform treatment cannot be achieved. At the same time, high concentrations of permeabilizing agents can cause skin irritation, redness, swelling and even allergic reactions, which is not conducive to large-scale promotion and reduces corporate benefits.

[0052] Example 2 1) Preparation of lipid nanoparticles 100 mg of phosphatidylcholine, 50 mg of cholesterol, 5 mg of tea polyphenols and 5 mg of cholesterol succinate were dissolved in 10 ml of chloroform. After complete dissolution, the chloroform was completely removed using a nitrogen blow-drying device to form a uniform lipid film at the bottom of the container; 2 ml of phosphate buffer solution with a pH of 7.4 containing 20 mg of diclofenac diethylamine was shaken until the lipid film was fully hydrated to obtain a primary emulsion; The primary emulsion was circulated for 5 times at 4°C using a high-pressure homogenizer, and then centrifuged at 10,000 rpm for 10 minutes to obtain a lipid nanoparticle suspension for treating joint pain. The lipid nanoparticle suspension for treating joint pain was stored at 4°C.

[0053] 2) Preparation of gel layer 2 g of carbomer was slowly added to 100 ml of deionized water and stirred for 20 min. After the carbomer was fully expanded, it was heated in a 60° C. water bath, 100 mg of sodium hyaluronate, 160 mg of azone and 40 mg of phenoxyethanol were added, and stirred for 10 min. 2 ml of the lipid nanoparticle suspension for treating joint pain prepared in step 1) was added, and stirred for 5 min. The mixture was cooled to 25° C. and allowed to stand for 30 min.

[0054] 3) Packaging material: The gel layer prepared in step 2) is evenly spread on the backing material, and an anti-sticking layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0055] 4) Performance testing The particle size of lipid nanoparticles in the gel patch for treating joint pain was tested after being placed for 1 day, 7 days, 30 days, and 90 days.

[0056] The washed pig skin was fixed to the release port of the Franz diffusion cell, and pH 7.4 phosphate buffer was added to the receiving chamber as the release medium to keep the endothelial layer in close contact with the solution. The gel patch with the cover lining removed was applied to the skin, and the water bath was adjusted to keep the temperature of the outer layer constant at (32±0.5)℃, the stirring speed was 600rpm, and 4ml of the release medium was absorbed at 0, 1h, 2h, 4h, 6h, 8h, 12h, and 24h, respectively, and an equal amount of PBS solution was added at the same time to calculate the cumulative absorption percentage (i.e., the percentage of the cumulative diclofenac diethylamine permeated to the total amount of diclofenac diethylamine in the drug reservoir).

[0057] Example 3 1) Preparation of lipid nanoparticles Dissolve 100 mg of phosphatidylcholine, 50 mg of cholesterol, 5 mg of ascorbyl palmitate and 5 mg of polyethylene glycol dimyristoylglycerol in 10 ml of chloroform. After complete dissolution, use a nitrogen blow-drying device to remove all chloroform to form a uniform lipid film at the bottom of the container. 3 ml of phosphate buffer at pH 7.4 containing 22 mg of diclofenac diethylamine was shaken until the lipid film was fully hydrated to obtain a primary emulsion; The primary emulsion was circulated for 5 times at 4°C using a high-pressure homogenizer, and then centrifuged at 10,000 rpm for 10 minutes to obtain a lipid nanoparticle suspension for treating joint pain. The lipid nanoparticle suspension for treating joint pain was stored at 4°C.

[0058] 2) Preparation of gel layer 2 g of carbomer was slowly added to 100 ml of deionized water and stirred for 20 min. After the carbomer was fully expanded, it was heated in a water bath at 65° C., 100 mg of sodium hyaluronate, 160 mg of azone and 40 mg of phenoxyethanol were added, and stirred for 10 min. 2 ml of the lipid nanoparticle suspension for treating joint pain prepared in step 1) was added, and stirred for 5 min. The mixture was cooled to 25° C. and allowed to stand for 30 min.

[0059] 3) Packaging material: The gel layer prepared in step 2) is evenly spread on the backing material, and an anti-sticking layer is spread on the gel layer to obtain a gel plaster for treating joint pain.

[0060] 4) Performance testing The particle size of lipid nanoparticles in the gel patch for treating joint pain was tested after being placed for 1 day, 7 days, 30 days, and 90 days.

[0061] The washed pig skin was fixed to the release port of the Franz diffusion cell, and pH 7.4 phosphate buffer was added to the receiving chamber as the release medium to keep the endothelial layer in close contact with the solution. The gel patch with the cover lining removed was applied to the skin, and the water bath was adjusted to keep the temperature of the outer layer constant at (32±0.5)℃, the stirring speed was 600rpm, and 4ml of the release medium was absorbed at 0, 1h, 2h, 4h, 6h, 8h, 12h, and 24h, respectively, and an equal amount of PBS solution was added at the same time to calculate the cumulative absorption percentage (i.e., the percentage of the cumulative diclofenac diethylamine permeated to the total amount of diclofenac diethylamine in the drug reservoir).

[0062] The raw materials and equipment used in the present invention, unless otherwise specified, are all commonly used raw materials and equipment in the art; the methods used in the present invention, unless otherwise specified, are all conventional methods in the art.

[0063] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent transformation made to the above embodiment based on the technical essence of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A method for preparing a gel patch for treating joint pain, characterized in that: The following steps are involved: 1) Slowly add carbomer into water and continue stirring, heat to 60-65°C, add 0.05-0.1wt% sodium hyaluronate, 0.8-1wt% azone and 0.2-0.4wt% phenoxyethanol, mix well to obtain a pretreated gel matrix; 2) Adding the lipid nanoparticle suspension for treating joint pain to the pretreated gel matrix, stirring continuously until the mixture is uniformly mixed, cooling to 25-27°C, and standing to obtain a gel layer; 3) The gel layer is evenly spread on the backing material to obtain a gel layer, and an anti-adhesive layer is spread on the gel layer to obtain a gel patch for treating joint pain.

2. The method for preparing a gel patch for treating joint pain according to claim 1, characterized in that: The method for preparing the lipid nanoparticle suspension for treating joint pain in step 2) comprises the following steps: S1.100~110mg phosphatidylcholine, 50~55mg cholesterol, 5~6mg antioxidant and 5~6mg surface modifier are added into 10~20ml chloroform, and after fully dissolved, a lipid film is prepared by rotary evaporation; S2. Add 2-3 ml of phosphate buffer containing 20-25 mg of diclofenac diethylamine to the lipid film, and shake until the lipid film is hydrated to obtain a primary emulsion; S3. After circulatory homogenization and centrifugation of the colostrum, a stabilizer #stabilizer addition amount is added to obtain a lipid nanoparticle suspension for treating joint pain.

3. The method for preparing a gel patch for treating joint pain according to claim 2, characterized in that: The antioxidant in S1) is one or more of vitamin E, ascorbyl palmitate and tea polyphenols.

4. A method for preparing a gel patch for treating joint pain according to claim 2 or 3, characterized in that: S1), the surface modifier is one or more of polyethylene glycol disuccinate, cholesterol sulfate, and cholesterol succinate.

5. The method for preparing a gel patch for treating joint pain according to claim 2, characterized in that: In S2), the pH value of the phosphate buffer is 7-8.

6. The method for preparing a gel patch for treating joint pain according to claim 2, characterized in that: In S3), the number of homogenization cycles is ≥ 5.

7. The method for preparing a gel patch for treating joint pain according to claim 2, characterized in that: In S3), the temperature of circulating homogenization and centrifugation is 0~4℃.

8. The method for preparing a gel patch for treating joint pain according to claim 2, characterized in that: Phosphatidylcholine is one of DPPC and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine.

9. The method for preparing a gel patch for treating joint pain according to claim 1, characterized in that: The particle size of the lipid nanoparticles in the lipid nanoparticle suspension is 100-200 nm.

10. A gel patch prepared by the method for preparing a gel patch for treating joint pain according to any one of claims 1 to 9.

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