Diclofenac diethylamine gel plaster composition, gel plaster and preparation methods therefor

Abstract

A diclofenac diethylamine gel plaster composition, a gel plaster and preparation methods therefor. The diclofenac diethylamine gel plaster composition comprises the following components in parts by weight: 1-3 parts of diclofenac diethylamine, 5-30 parts of a gel skeleton component, 0.1-0.6 parts of a cross-linking agent, 0.01-0.4 parts of an acidic pH regulator, 0.5-6 parts of an alkaline pH regulator, and 60-85 parts of a solvent, wherein the pH value of the gel plaster composition is 6.5-8.2. The preparation methods for the diclofenac diethylamine gel plaster composition and the diclofenac diethylamine gel plaster provided in the present invention are simpler and have better stability; the provided diclofenac diethylamine gel plaster composition has better stability; and the provided diclofenac diethylamine gel plaster has better formability and a better appearance.

Description

Diclofenac diethylamine gel patch composition, gel patch and preparation method thereof Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a diclofenac diethylamine gel patch composition, a diclofenac diethylamine gel patch and a preparation method thereof. Background Art

[0002] Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties. Commonly used clinically are diclofenac sodium, diclofenac potassium, and diclofenac diethylamine. Their active ingredients can penetrate the skin and reach inflamed areas, alleviating acute and chronic inflammatory reactions, reducing swelling and alleviating pain.

[0003] Currently, the transdermal formulations of diclofenac diethylamine available in China primarily include latexes and gels, with reports also circulating regarding patches. Compared to latexes, gels, and patches, gel patches (also known as papus) are a method of uniformly mixing the drug with a suitable hydrophilic matrix and then applying it to the surface of a backing material. These patches offer improved compatibility, permeability, sweat resistance, and reusability. They are also non-sensitizing and non-irritating to the skin, offer excellent application comfort, and promote the penetration and absorption of the drug.

[0004] Patent CN113940924A discloses a stable diclofenac diethylamine gel patch and a preparation method thereof. The gel patch comprises a non-woven fabric layer, a patch matrix layer, and a protective layer. The patch matrix layer comprises diclofenac diethylamine, an aqueous gel matrix, and a crystal inhibitor. It is believed that by preparing the drug into an O / W emulsion, crystal precipitation of diclofenac diethylamine can be significantly inhibited. The addition of a crystal inhibitor can more effectively inhibit crystallization of diclofenac diethylamine, effectively improving the stability of the gel patch and enhancing its bioavailability. However, compared with conventional preparation methods, preparing the drug into an O / W emulsion requires the preparation of an additional aqueous phase and an oil phase, resulting in a cumbersome process. Furthermore, the diclofenac diethylamine is first prepared into an emulsion, which is prone to bubble generation. Furthermore, because the emulsion is unstable and delaminates after a period of time, it must be used immediately after preparation, resulting in poor process stability.

[0005] Therefore, it is a technical problem to be solved to provide a diclofenac diethylamine gel patch with a simple preparation process and good stability.

[0006] Summary of the Invention

[0007] The present invention aims to provide a diclofenac diethylamine gel patch composition with a simple preparation process and good stability, as well as a diclofenac diethylamine gel patch with good formability and appearance. The present invention suppresses crystallization by adjusting the pH of the diclofenac diethylamine gel patch composition and using a non-emulsifying process to increase the solubility of diclofenac diethylamine. Furthermore, the formability and appearance of the diclofenac diethylamine gel patch are improved by adjusting the type and amount of a tackifier.

[0008] The present invention improves the solubility of diclofenac diethylamine by adjusting the pH value of the diclofenac diethylamine gel patch composition to 6.5-8.2, thereby achieving the effect of inhibiting crystallization. However, the diclofenac diethylamine gel patch prepared under this pH value condition has poor formability. For example, obvious bubbles appear on the surface of the freshly prepared gel patch, and the patch has poor adhesion and does not adhere to the protective layer. It takes a long time for the bubbles to disappear.

[0009] The technology of the present invention provides the following technical solutions:

[0010] In one aspect, the present invention provides a diclofenac diethylamine gel patch composition, comprising the following components, by weight: 1 to 3 parts of diclofenac diethylamine, 5 to 30 parts of a gel skeleton component, 0.1 to 0.6 parts of a cross-linking agent, 0.01 to 0.4 parts of an acidic pH regulator, 0.5 to 6 parts of an alkaline pH regulator, and 60 to 85 parts of a solvent. The pH value of the gel patch composition is 6.5-8.2.

[0011] In some embodiments, the gel skeleton component includes any one or a combination of at least two of sodium polyacrylate, polyvinyl alcohol, carbomer, gelatin, and gum arabic.

[0012] Preferably, the gel skeleton component includes sodium polyacrylate.

[0013] In some embodiments, the acidic pH adjuster includes any one of citric acid, tartaric acid, lactic acid, oleic acid, phosphoric acid, fumaric acid, malic acid, and ethylenediaminetetraacetic acid, or a combination of at least two thereof.

[0014] Preferably, the acidic pH adjuster comprises tartaric acid.

[0015] In some embodiments, the cross-linking agent includes any one of aluminum glyoxylate, aluminum chloride, and aluminum hydroxide, or a combination of at least two thereof.

[0016] Preferably, the cross-linking agent comprises aluminum glycol hydroxide.

[0017] In some embodiments, the alkaline pH adjuster includes any one of triethanolamine, sodium tartrate, diethylamine, and sodium bicarbonate, or a combination of at least two thereof.

[0018] Preferably, the alkaline pH adjuster comprises triethanolamine and / or diethylamine.

[0019] In some embodiments, the solvent is any one of glycerol, purified water, propylene glycol, ethylene glycol, polyethylene glycol, butylene glycol, and sorbitol, or a combination of at least two thereof.

[0020] Preferably, the solvent comprises glycerol, purified water, or propylene glycol.

[0021] In some embodiments, the gel patch composition further comprises 0 to 8 parts of a viscosity enhancer, and the viscosity enhancer comprises sodium carboxymethyl cellulose and polyvinyl alcohol.

[0022] Preferably, the weight ratio of the sodium carboxymethyl cellulose and polyvinyl alcohol is 1 to 2:1.

[0023] In some embodiments, the gel patch composition further comprises 0 to 3 parts of a transdermal penetration enhancer;

[0024] Preferably, the transdermal penetration enhancer includes any one of laurocapram, isopropyl myristate, menthol, and dimethylaminopropane, or a combination of at least two thereof.

[0025] Preferably, the gel patch composition further comprises 0 to 0.3 parts of a cross-linking regulator.

[0026] Preferably, the cross-linking regulator includes any one of disodium ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid, ethylenediaminediacetic acid, and ethylene glycol ditetraacetic acid, or a combination of at least two thereof.

[0027] In some embodiments, the gel patch composition comprises the following components in parts by weight: 1 to 3 parts of diclofenac diethylamine, 5 to 30 parts of a gel skeleton component, 0.1 to 0.6 parts of a cross-linking agent, 0.01 to 0.4 parts of an acidic pH regulator, 0.5 to 6 parts of an alkaline pH regulator, 60 to 85 parts of a solvent, 0 to 8 parts of a viscosity enhancer, 0 to 3 parts of a transdermal penetration enhancer, and 0 to 0.3 parts of a cross-linking regulator.

[0028] In a second aspect, the present invention provides a method for preparing a diclofenac diethylamine gel patch composition, characterized in that the preparation method comprises:

[0029] Step 1: mixing an acidic pH regulator and a solvent to obtain a first mixture;

[0030] Step 2: performing a second mixing of the cross-linking agent, the gel skeleton component and the solvent to obtain a second mixture;

[0031] Step 3: mixing diclofenac diethylamine and the solvent for a third time to obtain a third mixture;

[0032] Step 4: mixing the first mixture and the second mixture to obtain a gel matrix; mixing the alkaline pH regulator with the gel matrix to obtain a fourth mixture; and then uniformly mixing the third mixture and the fourth mixture to obtain a diclofenac diethylamine gel patch composition.

[0033] In some embodiments, the first mixed material further comprises a viscosity enhancer, the second mixed material further comprises any one or a combination of at least two of a transdermal penetration enhancer, a cross-linking regulator and a viscosity enhancer, and the third mixed material further comprises a transdermal penetration enhancer.

[0034] In a third aspect, the present invention provides a diclofenac diethylamine gel patch, comprising a backing layer, a patch matrix layer, and a protective layer arranged in sequence, and the raw materials for preparing the patch matrix layer include the diclofenac diethylamine gel patch composition.

[0035] In some embodiments, the preparation method includes: coating the diclofenac diethylamine gel patch composition on a backing layer to form a patch matrix layer with a backing layer; and compounding a protective layer on the patch matrix layer with a backing layer to obtain the diclofenac diethylamine gel patch.

[0036] Preferably, the protective layer is selected from release paper, plastic film or release film (polyethylene composite film, polypropylene film, etc.), and the backing layer is selected from cotton cloth or non-woven fabric.

[0037] The present invention has the following beneficial effects:

[0038] 1. Provide a simple and more stable diclofenac diethylamine gel patch composition and a preparation method of diclofenac diethylamine gel patch;

[0039] 2. Provide a diclofenac diethylamine gel patch composition with good stability, and a diclofenac diethylamine gel patch with good formability and appearance. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] FIG1 is a graph showing the in vivo drug-dose curve of the diclofenac diethylamine gel patch according to the method described in Example 22. DETAILED DESCRIPTION

[0041] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0042] As used herein, the terms "comprises," "including," "having," "containing" or any other variations thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a listed element is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

[0043] "Optionally" or "either" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event occurs and instances where it does not.

[0044] The indefinite articles "a" and "an" before the elements or components of the present invention do not limit the quantity requirement (i.e. the number of times they appear). Therefore, "a" or "an" should be interpreted as including one or at least one, and elements or components in the singular also include plural forms, unless the quantity clearly refers to only the singular form.

[0045] In the present invention, features defined as "first" or "second" may explicitly or implicitly include one or more of the features, and are used to distinguish and describe features, without regard to order or importance. In the description of the present invention, unless otherwise specified, "plurality" means two or more.

[0046] Example 1-4 Preparation of Diclofenac Diethylamine Gel Patch (Changing the Type of Alkaline pH Regulator)

[0047] Table 1 Prescription table of Examples 1-4

[0048] Preparation method:

[0049] Step 1: dissolving tartaric acid in purified water to obtain an aqueous phase;

[0050] Step 2: Disperse sodium polyacrylate and aluminum glycolate in glycerol and stir evenly to prepare an oil phase;

[0051] Step 3: dissolving diclofenac diethylamine in propylene glycol to prepare a diclofenac diethylamine solution;

[0052] Step 4: mixing the aqueous phase and the oil phase and stirring uniformly to obtain a gel matrix; adding triethanolamine / diethylamine / sodium hydroxide to the uniformly mixed gel matrix and stirring uniformly; then quickly adding the diclofenac diethylamine solution and stirring and mixing uniformly to obtain a diclofenac diethylamine gel patch composition, i.e., a drug-containing patch matrix layer; the pH values ​​of the diclofenac diethylamine gel patch compositions in Examples 1-4 were measured to be 7.7, 7.8, 8.0, and 5.8, respectively;

[0053] Step 5: evenly apply the diclofenac diethylamine gel patch composition onto a non-woven fabric, let it stand to form, laminate it with a polypropylene embossed film, and cut it into a desired size to obtain the diclofenac diethylamine gel patch.

[0054] The pH value of the diclofenac diethylamine gel patch composition in each example was determined by adding 30 mL of freshly boiled and cooled purified water to 1 g of the diclofenac diethylamine gel patch composition, homogenizing the mixture, and measuring the pH with a pH meter. The pH value was averaged after three replicate measurements.

[0055] Example 5-9 Preparation of Diclofenac Diethylamine Gel Patch (Changing the Content of Alkaline pH Regulator)

[0056] Table 2 Prescriptions for Examples 5-9

[0057] Preparation method:

[0058] Step 1: dissolving tartaric acid in purified water to obtain an aqueous phase;

[0059] Step 2: Disperse sodium polyacrylate and aluminum glycolate in glycerol and stir evenly to prepare an oil phase;

[0060] Step 3: dissolving diclofenac diethylamine in propylene glycol to prepare a diclofenac diethylamine solution;

[0061] Step 4: mixing the aqueous phase and the oil phase, stirring evenly to obtain a gel matrix; adding triethanolamine to the uniformly mixed gel matrix, stirring evenly, and then quickly adding the diclofenac diethylamine solution, stirring and mixing evenly to obtain a diclofenac diethylamine gel patch composition, i.e., a drug-containing patch matrix layer. The pH values ​​of the diclofenac diethylamine gel patch compositions in Examples 5-9 were measured to be 7.4, 7.7, 8.2, 6.3, and 8.5, respectively;

[0062] Step 5: evenly apply the diclofenac diethylamine gel patch composition onto a non-woven fabric, let it stand to form, laminate it with a polypropylene embossed film, and cut it into a desired size to obtain the diclofenac diethylamine gel patch.

[0063] Example 10-12 Preparation of Diclofenac Diethylamine Gel Patch (Varying the Type of Tackifier)

[0064] Table 3 Prescription table of Examples 10-12

[0065] Preparation method:

[0066] Step 1: dissolve tartaric acid in purified water, then add povidone or polyvinyl alcohol (if any) and heat to dissolve to obtain an aqueous phase;

[0067] Step 2: Disperse sodium polyacrylate, aluminum glycolate, and sodium carboxymethyl cellulose (if any) in glycerol and stir evenly to prepare an oil phase;

[0068] Step 3: dissolving diclofenac diethylamine in propylene glycol to prepare a diclofenac diethylamine solution;

[0069] Step 4: mixing the aqueous phase and the oil phase and stirring uniformly to obtain a gel matrix; adding triethanolamine to the uniformly mixed gel matrix and stirring uniformly; then quickly adding the diclofenac diethylamine solution and stirring and mixing uniformly to obtain a diclofenac diethylamine gel patch composition, i.e., a drug-containing patch matrix layer; the pH values ​​of the diclofenac diethylamine gel patch compositions in Examples 10-12 were measured to be 7.7, 7.8, and 7.6, respectively;

[0070] Step 5: evenly apply the diclofenac diethylamine gel patch composition onto a non-woven fabric, let it stand to form, laminate it with a polypropylene embossed film, and cut it into a desired size to obtain the diclofenac diethylamine gel patch.

[0071] Example 13-17 Preparation of Diclofenac Diethylamine Gel Patch (Varying the Amount of Tackifier)

[0072] Table 4 Prescription table of Examples 13-17

[0073] Preparation method:

[0074] Step 1: dissolve tartaric acid in purified water, then add polyvinyl alcohol and heat to dissolve to obtain an aqueous phase;

[0075] Step 2: Disperse sodium polyacrylate, aluminum glycolate, and sodium carboxymethyl cellulose in glycerol and stir evenly to prepare an oil phase;

[0076] Step 3: dissolving diclofenac diethylamine in propylene glycol to prepare a diclofenac diethylamine solution;

[0077] Step 4: mixing the aqueous phase and the oil phase and stirring uniformly to obtain a gel matrix; adding triethanolamine to the uniformly mixed gel matrix and stirring uniformly; then quickly adding the diclofenac diethylamine solution and stirring and mixing uniformly to obtain a diclofenac diethylamine gel patch composition, i.e., a drug-containing patch matrix layer; the pH values ​​of the diclofenac diethylamine gel patch compositions in Examples 13-17 were measured to be 7.8, 7.8, 7.7, 7.6, and 7.7, respectively;

[0078] Step 5: evenly apply the diclofenac diethylamine gel patch composition onto a non-woven fabric, let it stand to form, laminate it with a polypropylene embossed film, and cut it into a desired size to obtain the diclofenac diethylamine gel patch.

[0079] Example 18 Preparation of Diclofenac Diethylamine Gel Patch

[0080] Table 5 Prescription of Example 18

[0081] Preparation method:

[0082] Step 1: dissolve tartaric acid in purified water, then add polyvinyl alcohol and heat to dissolve to obtain an aqueous phase;

[0083] Step 2: Disperse sodium polyacrylate, disodium edetate, aluminum glycolate, isopropyl myristate, and sodium carboxymethyl cellulose in glycerol and stir evenly to prepare an oil phase;

[0084] Step 3: dissolving diclofenac diethylamine in propylene glycol, and then adding menthol and stirring to dissolve, to prepare a diclofenac diethylamine solution;

[0085] Step 4: mixing the aqueous phase and the oil phase and stirring evenly to obtain a gel matrix; adding triethanolamine to the mixed gel matrix and stirring evenly, then quickly adding the diclofenac diethylamine solution and stirring and mixing evenly to obtain a diclofenac diethylamine gel patch composition, i.e., a drug-containing patch matrix layer; the pH value of the diclofenac diethylamine gel patch composition is measured to be 7.7;

[0086] Step 5: evenly apply the diclofenac diethylamine gel patch composition onto a non-woven fabric, let it stand to form, laminate it with a polypropylene embossed film, and cut it into a desired size to obtain the diclofenac diethylamine gel patch.

[0087] Example 19 Crystallinity Investigation

[0088] Inspection method: Take a part of the paste on a glass slide and observe whether there is crystallization under a polarizing microscope. The inspection results are shown in the following table:

[0089] Table 6 Crystallinity investigation results of Examples 1-9

[0090] After using a non-emulsification process to prepare diclofenac diethylamine gel patch, it was found that the patch would have the problem of crystallization. In order to improve this problem, the present invention tried to change the solvent for dissolving diclofenac diethylamine, such as using crotamiton, diethylene glycol monoethyl ether, oleic acid, coconut oil alcohol-caprylate / caprate, etc.; or adding some cosolvents, such as urea, isooctyl alcohol, citric acid, etc., but none of them could inhibit the crystallization of the patch. Until it was found that adding alkaline pH regulators, such as triethanolamine and diethylamine, could inhibit the crystallization of the patch; and the pH value of the patch needed to be adjusted to above 6.5 to prevent the precipitation of diclofenac diethylamine. However, too strong alkalinity would cause the cross-linking time of the patch to be too long. Therefore, when using triethanolamine, the dosage should be controlled at 2 to 6 parts. Because diethylamine has a stronger alkalinity, the dosage should be controlled at 0.5 to 3.5 parts when using diethylamine.

[0091] Example 20 Coating Investigation

[0092] Inspection method: Observe the appearance of the patch with the naked eye. The inspection results are shown in the following table:

[0093] Table 7 Coating inspection results of Examples 5-17

[0094] The addition of an alkaline pH regulator resolved the crystallization problem, but the resulting diclofenac diethylamine gel patch had fine pores on its surface. The applicants attempted to reduce the amount of crosslinker to slow down crosslinking and adjust the crosslinking state, or to change the composition of the gel matrix to make the paste thicker; none of these efforts could improve the pores on the patch's surface. The authors discovered that adding a viscosity enhancer to the formulation could improve the pores on the patch's surface. Furthermore, the combined use of sodium carboxymethylcellulose and polyvinyl alcohol significantly improved the patch's appearance, resulting in virtually no pores on the applied patch surface and enhanced adhesion to the backing layer. The ratio of sodium carboxymethylcellulose to polyvinyl alcohol also affected the patch's appearance. Excessive sodium carboxymethylcellulose made the patch hard and difficult to apply, while too little sodium carboxymethylcellulose did not significantly improve the patch's appearance. A sodium carboxymethylcellulose:polyvinyl alcohol weight ratio of 1 to 2:1 achieved the best appearance-improving effect.

[0095] Example 20 Skin irritation test

[0096] Twelve rabbits (half male and half female) were divided into two groups and subjected to a skin irritation test on the diclofenac diethylamine gel patch prepared in Example 18. Using a full-body left-right side self-comparison method, the gel patch prepared in Example 18 was administered to the left side, while a control substance (blank sample) was administered to the right side. During the administration period and within 3 days after the last administration, no erythema or edema developed on either side, and no abnormal reactions were observed. This indicates that the diclofenac diethylamine gel patch prepared in Example 18 is non-irritating to the skin.

[0097] Example 21 Skin allergy test

[0098] According to the "Technical Guidance for Research on Irritation, Allergy, and Hemolysis of Chemical Drugs" issued by the State Food and Drug Administration, a skin allergy test was conducted on the diclofenac diethylamine gel patch prepared in Example 18. Forty SPF-grade guinea pigs (half male and half female) were randomly divided into groups: Example 18 group (20), a blank control group (10), and a positive control group (10 for each of the sensitizers: 2,4-dinitrochlorobenzene). On the first, eighth, and 15th days of the experiment, topical administration of the drug was performed on the hairless area on the right side for sensitization. On the 29th day of the experiment, topical administration of the drug was performed on the hairless area on the left side for provocation. Skin allergic reactions were observed 6, 24, and 48 hours after provocation. The results showed that the mean provocation response of the Example 18 group and the blank control group was 0, indicating no allergic reaction, while the mean provocation response of the positive control group was 10, indicating a sensitization rate of 100%, indicating extremely high lethality. This indicates that the diclofenac diethylamine gel patch prepared in Example 18 is non-allergenic to the skin.

[0099] Example 22 Pharmacokinetic Experiment

[0100] Get Japanese big-eared white rabbit, weighing 2.0 ± 0.2kg, be randomly evenly divided into a, b totally 2 groups, every group 8 (male and female half and half), give respectively the diclofenac diethylamine gel plaster that embodiment 18 prepares, commercially available latex (Voltaren, 1%). The hair of rabbit back spine both sides is taken off one day before administration, and 12h fasting does not can't help water before administration. Each group is administered at a dosage of 150mg / kg, and gel plaster is affixed to both sides of back part, and latex smear is administered. 15min, 30min, 1, 2, 3, 4, 6, 8, 12, 24, 48h after administration, take respectively 2ml of rabbit ear margin venous blood, detect blood drug concentration (μ g / ml). With time as horizontal coordinate, blood drug concentration is vertical coordinate and makes drug-time curve. The result is as shown in Figure 1, and from drug-time curve, the bioavailability of diclofenac diethylamine gel plaster obviously improves.

Claims

1. A diclofenac diethylamine gel patch composition, characterized in that, The composition comprises the following components by weight: 1 to 3 parts of diclofenac diethylamine, 5 to 30 parts of gel skeleton components, 0.1 to 0.6 parts of cross-linking agent, 0.01 to 0.4 parts of acidic pH regulator, 0.5 to 6 parts of alkaline pH regulator and 60 to 85 parts of solvent, wherein the pH value of the gel patch composition is 6.5-8.

2.

2. The diclofenac diethylamine gel patch composition according to claim 1, characterized in that The gel skeleton component includes any one of sodium polyacrylate, polyvinyl alcohol, carbomer, gelatin, and gum arabic, or a combination of at least two of them; the acidic pH regulator includes any one of citric acid, tartaric acid, lactic acid, oleic acid, phosphoric acid, fumaric acid, malic acid, and ethylenediaminetetraacetic acid, or a combination of at least two of them; the cross-linking agent includes any one of aluminum glycolate, aluminum chloride, and aluminum hydroxide, or a combination of at least two of them; and the solvent is any one of glycerol, purified water, propylene glycol, ethylene glycol, polyethylene glycol, butylene glycol, and sorbitol, or a combination of at least two of them.

3. The diclofenac diethylamine gel patch composition according to claim 1, characterized in that: The alkaline pH regulator includes any one of triethanolamine, sodium tartrate, diethylamine, and sodium bicarbonate, or a combination of at least two of them.

4. The diclofenac diethylamine gel patch composition according to claim 1, characterized in that: The gel patch composition further comprises 0 to 8 parts of a viscosity enhancer, and the viscosity enhancer comprises sodium carboxymethyl cellulose and polyvinyl alcohol.

5. The diclofenac diethylamine gel patch composition according to claim 4, characterized in that: The weight ratio of the sodium carboxymethyl cellulose to the polyvinyl alcohol is 1-2:

1.

6. The diclofenac diethylamine gel patch composition according to claim 1, characterized in that: The gel patch composition also includes 0 to 3 parts of a transdermal penetration enhancer, which includes any one of laurocapram, isopropyl myristate, menthol, and dimethylaminopropane or a combination of at least two of them; the gel patch composition also includes 0 to 0.3 parts of a cross-linking regulator, which includes any one of disodium ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid, ethylenediaminediacetic acid, and ethylene glycol ditetraacetic acid or a combination of at least two of them.

7. The diclofenac diethylamine gel patch composition according to any one of claims 1 to 6, characterized in that: The gel patch composition comprises the following components in parts by weight: 1 to 3 parts of diclofenac diethylamine, 5 to 30 parts of gel skeleton components, 0.1 to 0.6 parts of cross-linking agent, 0.01 to 0.4 parts of acidic pH regulator, 0.5 to 6 parts of alkaline pH regulator, 60 to 85 parts of solvent, 0 to 8 parts of viscosity enhancer, 0 to 3 parts of transdermal penetration enhancer, and 0 to 0.3 parts of cross-linking regulator.

8. A method for preparing the diclofenac diethylamine gel patch composition according to any one of claims 1 to 7, characterized in that: The preparation method comprises: Step 1: first mixing an acidic pH regulator and a solvent to obtain a first mixture; Step 2: performing a second mixing of the cross-linking agent, the gel skeleton component and the solvent to obtain a second mixture; Step 3: mixing diclofenac diethylamine and the solvent for a third time to obtain a third mixture; Step 4: mixing the first mixture and the second mixture to obtain a gel matrix; mixing the alkaline pH regulator with the gel matrix to obtain a fourth mixture, and then mixing the third mixture and the fourth mixture evenly to obtain a diclofenac diethylamine gel patch composition.

9. The method for preparing the diclofenac diethylamine gel patch composition according to claim 8, characterized in that: The first mixed material further includes a viscosity enhancer; the second mixed material further includes any one or a combination of at least two of a transdermal penetration enhancer, a cross-linking regulator and a viscosity enhancer; and the third mixed material further includes a transdermal penetration enhancer.

10. A diclofenac diethylamine gel patch, characterized in that: The diclofenac diethylamine gel patch comprises a backing layer, a patch matrix layer and a protective layer arranged in sequence, and the raw materials for preparing the patch matrix layer comprise the diclofenac diethylamine gel patch composition according to any one of claims 1 to 7.

11. A method for preparing the diclofenac diethylamine gel patch as claimed in claim 10, characterized in that: The preparation method comprises: coating a diclofenac diethylamine gel patch composition on a backing layer to form a patch matrix layer with a backing layer; and compounding a protective layer on the patch matrix layer with a backing layer to obtain the diclofenac diethylamine gel patch.

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