Transdermal patch containing flurbiprofen and preparation method thereof

Abstract

According to the flurbiprofen-containing transdermal patch and the preparation method thereof, the problems that an existing transdermal patch is low in medicine permeability, large in skin irritation or poor in adhesion and the like are solved, and the obtained transdermal patch is moderate in adhesion performance, free of colloid residues during stripping, small in skin irritation, good in medicine permeability, convenient to take and rapid in effect; the patient compliance is improved; compared with a conventional preparation method of a solvent type patch, the preparation method provided by the invention does not need to use an organic solvent and drying equipment, and the whole preparation method is simple and suitable for industrial large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a transdermal patch containing flurbiprofen and its preparation method. Background Technology

[0002] Flurbiprofen is a nonsteroidal anti-inflammatory drug (NSAID) widely used in the field of antipyretic and analgesic applications. Its indications include anti-inflammatory and analgesic effects on the following conditions and symptoms: osteoarthritis, frozen shoulder, tendinitis and tenosynovitis, peritendinitis, lateral epicondylitis (tennis elbow), muscle pain, and swelling and pain caused by trauma. Currently, flurbiprofen tablets, granules, and gel patches are available on the market both domestically and internationally.

[0003] Existing formulations suffer from gastrointestinal irritation and a significant first-pass effect. Long-term oral flurbiprofen may cause side effects such as gastrointestinal discomfort and liver or kidney damage. To avoid these side effects, topical administration is an ideal method. Topical administration, by directly targeting the lesion site, not only increases local drug concentration and enhances efficacy but also reduces systemic absorption, thereby minimizing systemic side effects. However, existing transdermal patches suffer from drawbacks such as low drug penetration, high skin irritation, and poor adhesion. Summary of the Invention

[0004] The purpose of this invention is to provide a transdermal patch containing flurbiprofen, based on existing technology, which overcomes the problems of low drug penetration, high skin irritation, or poor adhesion that are common in existing transdermal patches. The resulting transdermal patch has moderate adhesion properties, leaves no colloid residue upon peeling, causes little skin irritation, has good drug penetration, is convenient to administer, has a rapid onset of action, and improves patient compliance.

[0005] The second objective of this invention is to provide a method for preparing the above-mentioned transdermal patch containing flurbiprofen, which, compared with conventional solvent-based patch preparation methods, does not require the use of organic solvents and drying equipment, and the entire preparation method is simple and suitable for large-scale industrial production.

[0006] The technical solution of the present invention is as follows:

[0007] A transdermal patch containing flurbiprofen includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of a mixture of flurbiprofen, L-menthol, terpene polymers and white mineral oil, white mineral oil, styrene-isoprene-styrene block copolymer, polybutene, butylated hydroxytoluene and 2-mercaptobenzimidazole.

[0008] In this invention, the active ingredient is flurbiprofen, the penetration enhancer is L-menthol, the base agent is a styrene-isoprene-styrene block copolymer and polybutene, the tackifier is a mixture of terpene polymer and white mineral oil, the plasticizer is white mineral oil, and the stabilizer is butylated hydroxytoluene and 2-mercaptobenzimidazole. Specifically, the tackifier, a mixture of terpene polymer and white mineral oil, is sourced from YASUHARA CHEMICAL CO.,LTD; the plasticizer, white mineral oil, is sourced from Sonorbonne Ltd.; and the base agent, a mixture of styrene-isoprene-styrene block copolymer and polybutene, is sourced from ENEOS Corporation.

[0009] The transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the thickness of the ointment layer is 50-100 μm.

[0010] In this invention, white mineral oil is used as the plasticizer, and the prepared transdermal patch has a smooth surface, good adhesion, moderate adhesion performance, low skin irritation, no skin residue when peeled off, and fits well. However, if other similar plasticizers are used, such as diethyl phthalate, the prepared transdermal patch has poor adhesion and leaves residue.

[0011] In this invention, the tackifier is a mixture of terpene polymer and white mineral oil. The resulting transdermal patch has a smooth surface, good adhesion, moderate adhesion performance, low skin irritation, no skin residue upon peeling, and fits well. In contrast, using other similar plasticizers, such as hydrogenated rosin resin, results in transdermal patches with good adhesion but slight residue. Using alicyclic saturated hydrocarbon resin as a plasticizer results in transdermal patches with poor cohesion and some residue on the skin.

[0012] In one embodiment, the transdermal patch containing flurbiprofen mentioned in this invention comprises a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 1-3 parts flurbiprofen, 1-3 parts L-menthol, 8-30 parts a mixture of terpene polymer and white mineral oil, 35-50 parts white mineral oil, 20-35 parts styrene-isoprene-styrene block copolymer, 5-20 parts polybutene, 0.2-0.8 parts dibutylhydroxytoluene, and 0.2-0.8 parts 2-mercaptobenzimidazole.

[0013] In a preferred embodiment, the transdermal patch containing flurbiprofen mentioned in this invention comprises a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2-2.5 parts flurbiprofen, 1.5-2.5 parts L-menthol, 10-28 parts a mixture of terpene polymer and white mineral oil, 36-48 parts white mineral oil, 27-29 parts styrene-isoprene-styrene block copolymer, 6-18 parts polybutene, 0.4-0.6 parts butylated hydroxytoluene, and 0.4-0.6 parts 2-mercaptobenzimidazole.

[0014] In a more preferred embodiment, the transdermal patch containing flurbiprofen mentioned in this invention comprises a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 12-25 parts a mixture of terpene polymer and white mineral oil, 38.75-46.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 8-15 parts polybutene, 0.5 parts butylated hydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0015] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 12 parts a mixture of terpene polymer and white mineral oil, 42.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 12 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0016] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 16 parts a mixture of terpene polymer and white mineral oil, 42.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 12 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0017] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 25 parts a mixture of terpene polymer and white mineral oil, 42.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 12 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0018] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 16 parts a mixture of terpene polymer and white mineral oil, 38.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 12 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0019] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 16 parts a mixture of terpene polymer and white mineral oil, 40.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 12 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0020] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 16 parts a mixture of terpene polymer and white mineral oil, 46.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 12 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0021] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 25 parts a mixture of terpene polymer and white mineral oil, 42.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 8 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0022] For example, the transdermal patch containing flurbiprofen mentioned in this invention includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 25 parts a mixture of terpene polymer and white mineral oil, 42.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 15 parts polybutene, 0.5 parts dibutylhydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

[0023] The present invention also provides a method for preparing the above-mentioned transdermal patch containing flurbiprofen, comprising the following steps:

[0024] (1) Mix a mixture of styrene-isoprene-styrene block copolymer, polybutene, terpene polymer and white mineral oil, white mineral oil, butylated hydroxytoluene and 2-mercaptobenzimidazole, heat the mixture to 140-160℃ and stir until completely dissolved to obtain a uniformly mixed molten mixture.

[0025] (2) Under vacuum conditions, add flurbiprofen and L-menthol to the molten mixture obtained in step (1), stir evenly to form an ointment, coat the obtained ointment evenly on the anti-adhesive layer to form an ointment layer, cover the surface of the ointment layer with a backing layer, and cut to obtain a transdermal patch containing flurbiprofen.

[0026] In this invention, in step (1), the mixture of terpene polymer and white mineral oil is sourced from YASUHARACHEMICAL CO.,LTD; the white mineral oil is sourced from Sonorbonne LLC.

[0027] In this invention, in step (1), the resulting mixture is heated to 140-160°C, preferably 145-155°C, and more preferably 150°C.

[0028] In this invention, in step (2), the vacuum degree is controlled to be ≥-0.09MPa under vacuum conditions. The thickness of the paste layer is 50-100μm.

[0029] Compared with conventional solvent-based patches, the preparation method provided by this invention does not require the use of organic solvents and drying equipment, and the entire preparation method is simple and suitable for large-scale industrial production.

[0030] The advantages of using the technical solution of this invention are as follows:

[0031] This invention provides a transdermal patch containing flurbiprofen, overcoming the problems of low drug penetration, high skin irritation, or poor adhesion that are common in existing transdermal patches. The resulting transdermal patch has moderate adhesion properties, leaves no colloid residue upon peeling, causes minimal skin irritation, has good drug penetration, is convenient to administer, has a rapid onset of action, and improves patient compliance. Compared with conventional solvent-based patch preparation methods, the preparation method provided by this invention does not require the use of organic solvents and drying equipment, and the entire preparation method is simple and suitable for large-scale industrial production. Detailed Implementation

[0032] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0033] Examples 1-8

[0034] A transdermal patch containing flurbiprofen includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the composition and weight of the ointment layer are shown in Table 1.

[0035] Table 1. Components and Dosage

[0036]

[0037] The preparation method of the transdermal patch in Example 1 includes the following steps:

[0038] (1) Mix the base agent (styrene-isoprene-styrene block copolymer and polybutene), the tackifier (a mixture of terpene polymer and white mineral oil), the plasticizer (white mineral oil) and the stabilizer (butylated hydroxytoluene and 2-mercaptobenzimidazole), heat the mixture to 150°C and stir until completely dissolved to obtain a uniformly mixed molten mixture;

[0039] (2) Under vacuum conditions, when the vacuum degree is controlled to be ≥-0.09MPa, add the active ingredient (flurbiprofen) and the penetration enhancer (L-menthol) to the molten mixture obtained in step (1), stir evenly to make a paste, and evenly coat the obtained paste on the anti-adhesive layer to form a paste layer with a thickness of 50-100μm. Cover the surface of the paste layer with a backing layer, and after cutting, a transdermal patch containing flurbiprofen is obtained.

[0040] In the preparation process, compared with Example 1, the difference between Examples 2-8 lies in the different amounts of some components.

[0041] Comparative Examples 1-8

[0042] A transdermal patch containing flurbiprofen includes a backing layer and an ointment layer coated on the surface of the backing layer, wherein the composition and weight of the ointment layer are shown in Table 2.

[0043] Table 2 Components and Dosage

[0044]

[0045] In the preparation process, compared with Example 1, the difference in Comparative Example 1 is that white mineral oil is replaced with diethyl phthalate; the difference in Comparative Example 2 is that the mixture of terpene polymer and white mineral oil is replaced with hydrogenated rosin resin; the difference in Comparative Example 3 is that the mixture of terpene polymer and white mineral oil is replaced with alicyclic saturated hydrocarbon resin; the difference in Comparative Example 4 is that polybutene is replaced with polyisobutylene; and the difference in Comparative Examples 5-8 is that the amount of some components is different.

[0046] The effects of the type and amount of base agent, thickener, and plasticizer in the ointment layer on the adhesive properties and overall physical properties of transdermal patches were investigated. Transdermal patches containing flurbiprofen were prepared using different materials and amounts, and their adhesive properties and cumulative penetration rate were evaluated. The results are shown in Tables 3-6.

[0047] Table 3 Adhesion performance in the examples

[0048]

[0049] Table 4 Adhesion properties in comparative examples

[0050]

[0051]

[0052] As shown in Table 3, the transdermal patches prepared in Examples 1-8 of this invention have a smooth surface, good adhesion, moderate adhesion performance, low skin irritation, no skin residue when peeled off, and fit well during use.

[0053] Table 4 shows that in Comparative Example 1, replacing the plasticizer white mineral oil with diethyl phthalate resulted in a transdermal patch with poor adhesion and residue. In Comparative Example 2, replacing the mixture of tackifier terpene polymer and white mineral oil with hydrogenated rosin resin resulted in a transdermal patch with good adhesion and slight residue. In Comparative Example 3, replacing the mixture of tackifier terpene polymer and white mineral oil with alicyclic saturated hydrocarbon resin resulted in a transdermal patch with poor cohesion and residue on the skin. In Comparative Example 4, replacing polybutene with polyisobutylene in the base resulted in a transdermal patch with no residue on the skin, but it was relatively hard. The adhesion was poor. In Comparative Example 5, the amount of plasticizer white mineral oil was too high, resulting in a soft transdermal patch with poor adhesion, which easily peeled off the skin. In Comparative Example 6, the amount of the mixture of tackifier terpene polymer and white mineral oil was too high, resulting in an overly sticky transdermal patch with significant skin residue and high peel strength, which may cause skin irritation during use. In Comparative Example 7, the amount of polybutene in the base agent was too high, resulting in a smooth surface and good adhesion of the transdermal patch. In Comparative Example 8, the amount of styrene-isoprene-styrene block copolymer in the base agent was too high, resulting in a smooth surface and good adhesion of the transdermal patch. In summary, the cumulative penetration rate of Comparative Examples 2, 7, and 8, which showed better adhesion performance, was evaluated.

[0054] Table 5 shows the cumulative permeation rate in the examples.

[0055]

[0056]

[0057] Table 6 shows the cumulative permeability in the comparative examples.

[0058]

[0059]

[0060] As shown in Table 5, the transdermal patches prepared in Examples 1-8 of this invention have a faster penetration rate, enabling the drug to exert a sustained analgesic effect through the human epidermis.

[0061] As shown in Table 6, the transdermal patch prepared in Comparative Example 2 using hydrogenated rosin resin as a tackifier had good adhesion and slight residue, but its overall release level was slightly worse than that of the mixture of terpene polymer and white mineral oil used in this invention. In Comparative Examples 7 and 8, increasing the amount of polybutene and styrene-isoprene-styrene block copolymer in the base agents had little effect on the adhesive properties of the prepared transdermal patches, but the overall release rate was too slow to achieve a rapid onset of action.

[0062] Quality evaluation method for flurbiprofen transdermal patches:

[0063] Drug penetration rate: using the Franz diffusion cell method (2.0 cm) 2 To determine the in vitro drug permeation, pH 7.4 phosphate buffer was used as the receiving medium, and the skin of Bama miniature pigs was used as the permeation barrier. Samples were taken at 1h, 2h, 4h, 6h, 12h, and 24h at a rotation speed of 600rpm and a temperature of 32℃±0.5℃ to calculate the cumulative release of flurbiprofen from the patch.

[0064] Adhesion: The following test was conducted according to the Adhesion Determination Method 0952 of the 2020 edition of the Chinese Pharmacopoeia. Before the test, the patch should be placed at 18-25℃ and relative humidity of 40%-70% for more than 2 hours:

[0065] (1) Initial adhesion: Adjust the angle of the inclined plate to 30°, fix the backing of the adhesive to the inclined plate with double-sided tape, place the specified steel ball on the horizontal line, and let it fall freely from the inclined plane. Record the steel ball with the largest adhesive number.

[0066] (2) Adhesion holding force: The adhesive side of the patch is attached to the surface of the test plate and placed vertically. A weight of a specified mass (1 kg) is suspended along the length of the patch, and the time it takes for the patch to fall off the adhesive plate is recorded.

[0067] (3) Peel strength: Roll the adhesive back and forth 2-3 times under the action of its own weight to ensure full contact with the test plate, and let it stand for 20 minutes. Fold the adhesive in half to make the peel angle 180°, and conduct the test to determine the peel strength.

[0068] (4) Adhesion: Cut the patch into 50mm×70mm pieces, with the adhesive side facing up, place it on the sample loading module, align it with the appropriate scale line, tear off a small portion of the release film on both sides, press down the exposed adhesive sides with the pressure strip, carefully remove the release film, and place it naturally in the center on the fixture base plate, so that the sample adheres flatly to the base plate. Press the pressure plate horizontally down, and fix the base plate and pressure plate with the bolts on both sides, so that the adhesive side of the sample on the rectangular strip is evenly stretched, place it on the instrument, and conduct the test to determine the adhesion.

[0069] Comprehensive evaluation: Based on the test results of initial tack, holding tack, peel strength, and adhesion, each formulation is comprehensively rated and divided into four levels: excellent, good, average, and poor.

[0070] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications may still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions may be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A transdermal patch containing flurbiprofen, characterized in that, It includes a backing layer and a paste layer coated on the surface of the backing layer, the paste layer being made of a mixture of flurbiprofen, L-menthol, terpene polymer and white mineral oil, white mineral oil, styrene-isoprene-styrene block copolymer, polybutene, dibutylhydroxytoluene and 2-mercaptobenzimidazole.

2. The transdermal patch containing flurbiprofen according to claim 1, characterized in that, The mixture of the terpene polymer and the white mineral oil was sourced from YASUHARA CHEMICAL CO.,LTD; the white mineral oil was sourced from Sonorbonne LLC.

3. The transdermal patch containing flurbiprofen according to claim 2, characterized in that, The ointment layer is made of the following components in parts by weight: 1-3 parts flurbiprofen, 1-3 parts L-menthol, 8-30 parts a mixture of terpene polymer and white mineral oil, 35-50 parts white mineral oil, 20-35 parts styrene-isoprene-styrene block copolymer, 5-20 parts polybutene, 0.2-0.8 parts dibutylhydroxytoluene, and 0.2-0.8 parts 2-mercaptobenzimidazole.

4. The transdermal patch containing flurbiprofen according to claim 3, characterized in that, The ointment layer is made of the following components in parts by weight: 2-2.5 parts flurbiprofen, 1.5-2.5 parts L-menthol, 10-28 parts a mixture of terpene polymer and white mineral oil, 36-48 parts white mineral oil, 27-29 parts styrene-isoprene-styrene block copolymer, 6-18 parts polybutene, 0.4-0.6 parts butylated hydroxytoluene and 0.4-0.6 parts 2-mercaptobenzimidazole.

5. The transdermal patch containing flurbiprofen according to claim 4, characterized in that, The ointment layer is made of the following components in parts by weight: 2.25 parts flurbiprofen, 2 parts L-menthol, 12-25 parts a mixture of terpene polymer and white mineral oil, 38.75-46.75 parts white mineral oil, 28 parts styrene-isoprene-styrene block copolymer, 8-15 parts polybutene, 0.5 parts butylated hydroxytoluene, and 0.5 parts 2-mercaptobenzimidazole.

6. The transdermal patch containing flurbiprofen according to claim 5, characterized in that, The ointment layer is made of the following components in parts by weight: Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 12 parts, white mineral oil 42.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 12 parts, butylated hydroxytoluene 0.5 parts and 2-mercaptobenzimidazole 0.5 parts; Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 16 parts, white mineral oil 42.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 12 parts, butylated hydroxytoluene 0.5 parts and 2-mercaptobenzimidazole 0.5 parts; Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 25 parts, white mineral oil 42.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 12 parts, butylated hydroxytoluene 0.5 parts and 2-mercaptobenzimidazole 0.5 parts; Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 16 parts, white mineral oil 38.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 12 parts, butylated hydroxytoluene 0.5 parts and 2-mercaptobenzimidazole 0.5 parts; Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 16 parts, white mineral oil 40.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 12 parts, butylated hydroxytoluene 0.5 parts and 2-mercaptobenzimidazole 0.5 parts; Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 16 parts, white mineral oil 46.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 12 parts, butylated hydroxytoluene 0.5 parts and 2-mercaptobenzimidazole 0.5 parts; Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 25 parts, white mineral oil 42.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 8 parts, butylated hydroxytoluene 0.5 parts, and 2-mercaptobenzimidazole 0.5 parts; Flurbiprofen 2.25 parts, L-menthol 2 parts, a mixture of terpene polymer and white mineral oil 25 parts, white mineral oil 42.75 parts, styrene-isoprene-styrene block copolymer 28 parts, polybutene 15 parts, butylated hydroxytoluene 0.5 parts and 2-mercaptobenzimidazole 0.5 parts.

7. The transdermal patch containing flurbiprofen according to any one of claims 1-6, characterized in that, The thickness of the ointment layer is 50-100 μm.

8. The method for preparing the transdermal patch containing flurbiprofen according to claim 1, characterized in that, Includes the following steps: (1) Mix a mixture of styrene-isoprene-styrene block copolymer, polybutene, terpene polymer and white mineral oil, white mineral oil, butylated hydroxytoluene and 2-mercaptobenzimidazole, heat the mixture to 140-160℃ and stir until completely dissolved to obtain a uniformly mixed molten mixture. (2) Under vacuum conditions, add flurbiprofen and L-menthol to the molten mixture obtained in step (1), stir evenly to form an ointment, coat the obtained ointment evenly on the anti-adhesive layer to form an ointment layer, cover the surface of the ointment layer with a backing layer, and cut to obtain a transdermal patch containing flurbiprofen.

9. The method for preparing the transdermal patch containing flurbiprofen according to claim 8, characterized in that, In step (1), the mixture of the terpene polymer and the white mineral oil is derived from YASUHARA CHEMICAL CO., LTD; the white mineral oil is derived from Sonorbonne LLC; and the resulting mixture is heated to 145-155°C, preferably 150°C.

10. The method for preparing the transdermal patch containing flurbiprofen according to claim 8, characterized in that, In step (2), under vacuum conditions, the vacuum degree is controlled to be ≥-0.09MPa; the thickness of the paste layer is 50-100μm.

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