Compound capsicum flurbiprofen gel ointment as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pharmaceutical compound patches, and particularly relates to a compound capsicum flurbiprofen gel ointment as well as a preparation method and application thereof. The gel ointment comprises an anti-sticking layer, an ointment body layer and a lining layer, the paste layer is composed of a matrix and a main drug; the flurbiprofen eye drops are prepared from the following components in percentage by weight: 7.4 percent to 9.3 percent of a framework material, 22.6 percent to 28.4 percent of a humectant, 0.12 percent to 0.36 percent of a cross-linking agent, 0.16 percent to 0.40 percent of a cross-linking regulator, 0.68 percent to 1.53 percent of a filling agent, 0.90 percent to 2.75 percent of an adhesive, 0.25 percent of a pepper extract, 0.20 percent of flurbiprofen, 0.22 percent to 4.45 percent of a penetration enhancer, 0.82 percent to 1.75 percent of an anti-irritation component and the balance of distilled water. The paste body layer of the gel paste is obtained. The invention also provides application of the gel ointment in treating arthritis and muscular pain.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical compound patches, in particular to a compound capsicum flurbiprofen gel paste and a preparation method and application thereof. Background Art

[0002] Rheumatoid arthritis (RA) is a common, multi-communicating, and difficult-to-treat inflammatory disease that can lead to destructive joint disease, severe disability, and increased mortality. Joint and muscle pain is one of the main symptoms of many diseases such as rheumatism and arthritis. In addition, soft tissue injuries, joint sprains, lumbar muscle strains, and other traumas in daily life can also cause varying degrees of joint and muscle pain, causing mobility problems that seriously affect patients' lives.

[0003] At present, non-steroidal anti-inflammatory drugs are usually used to control the level of inflammatory factors in the body to achieve temporary relief for these diseases, as well as invasive treatments such as intra-articular injection of glucocorticoids, surgical treatment, and artificial joint replacement for rheumatism, arthritis, etc. In addition, the most widely used method is transdermal administration. At present, transdermal drug delivery preparations have become the most commonly used treatment for RA. The drug penetrates through the skin to produce a therapeutic effect, which greatly reduces the toxic and side effects. In addition, the patch, cream, gel, etc. can be removed at any time, and the drug delivery can be interrupted, which greatly improves the safety of medication. Elderly and young patients can also be conveniently administered, which improves compliance. The development and application of transdermal drug delivery will be more far-reaching and in-depth.

[0004] Transdermal drug delivery preparations generally include ointments, rubber plasters, gel plasters, patches, etc. Traditional patches have a small drug loading, and certain defects in viscosity and air permeability make compliance poor. Compared with traditional patches, the water-soluble polymer material of the gel plaster can be cross-linked with a high-valent metal ion cross-linking agent to form a three-dimensional network structure to encapsulate a large amount of drugs, and its thickness is more than ten times that of traditional patches, which greatly increases the content of drugs in the patch. While increasing the drug loading, it can maintain the effective dose of the drug for a long time and constantly. In addition, the gel plaster has good air permeability, suitable adhesion, will not produce a strong tearing pain and can be repeatedly pasted, and the hydrophilic material can absorb the exudate of tissue fluid at the administration site. So far, my country has a variety of gel plasters such as flurbiprofen gel patch, lidocaine gel patch, ketoprofen gel patch, loxoprofen sodium gel patch, indomethacin gel patch, etc. on the market. Due to the great development difficulty and high technical barriers of gel patches in terms of matrix and transdermal absorption, the domestic market is not yet fully developed.

[0005] Transdermal drug delivery system (TDDS), also known as transdermal therapeutic depot preparations, refers to a type of controlled-release preparation in which drugs are absorbed through the skin through capillaries at a certain rate into the human circulation and exert systemic or local therapeutic effects, exerting their effects through diffusion. TDDS is not limited by the oral first-pass effect and can directly act on the target site to exert its efficacy, avoiding the first-pass effect of the liver and the interference of gastrointestinal factors, reducing the toxic and side effects of drugs, reducing the number of dosing times and alleviating the burden of various drugs on various organs in the human body. Transdermal drug delivery preparations generally include ointments, gel pastes, patches, etc. The rapid development of polymer materials in the medical field has made new transdermal drug delivery preparations such as gels and hydrophilic gel pastes widely concerned.

[0006] However, there are still many problems in the current research on gel ointments, such as unreasonable matrix ratio, unsatisfactory transdermal absorption, unstable product quality, easy ointment removal, ointment leakage and poor skin adherence, etc., which require further improvement to meet market demand. Summary of the invention

[0007] The invention aims to provide a compound capsicum flurbiprofen gel ointment and a preparation method and application thereof.

[0008] To achieve the above purpose, the present invention adopts the following technical solution:

[0009] A compound capsicum flurbiprofen gel paste comprises an anti-adhesive layer, a paste layer and a lining layer; the paste layer is composed of a matrix and a main drug; by weight percentage, the following components comprise 7.4% to 9.3% of a skeleton material, 22.6% to 28.4% of a moisturizer, 0.12% to 0.36% of a cross-linking agent, 0.16% to 0.40% of a cross-linking regulator, 0.68% to 1.53% of a filler, 0.90% to 2.75% of an adhesive, 0.25% of a capsicum extract, 0.20% of flurbiprofen, 0.22% to 4.45% of a penetration enhancer, 0.82% to 1.75% of an anti-irritant component, and the remaining components are distilled water.

[0010] The paste layer is located between the release film and the backing film.

[0011] The moisturizing agent is propylene glycol and / or glycerol;

[0012] The cross-linking agent is one or more of aluminum chloride, aluminum hydroxide, and aluminum glycolate;

[0013] The cross-linking regulator is one or more of tartaric acid, citric acid, malic acid, and EDTA;

[0014] The filler is one or two of kaolin, titanium dioxide and zinc chloride;

[0015] The adhesive is one or both of gelatin and / or PVPK-90;

[0016] The penetration enhancer is propylene glycol and / or menthol;

[0017] The anti-irritation component is one or more of peppermint oil, camphor and vitamin E.

[0018] When the penetration enhancers are propylene glycol and menthol, the mass ratio of propylene glycol to menthol in the system is 1:1.

[0019] The pepper extract is

[0020] (1) crushing and sieving dried red pepper to obtain pepper powder;

[0021] (2) After the pepper powder is dried, it is soaked with ethanol, extracted repeatedly, and the solid-liquid separation is performed to remove the ethanol in the filtrate to obtain a pepper extract concentrate, and the pepper extract concentrate is dried to obtain a pepper extract.

[0022] In the step (2), the mass volume ratio of chili powder to ethanol is 1g:(5-20)mL according to the solid-liquid ratio; and the infiltration time is 15-120min.

[0023] The concentration of the ethanol solution used is 60% to 100%; the number of extractions is 1 to 5 times, and the time for each extraction is 15 to 90 minutes; and the solid-liquid separation is preferably performed by suction filtration.

[0024] The extraction method is selected from one of ultrasonic extraction, ultrasonic combined with reduced pressure internal boiling, heating reflux extraction, Soxhlet extraction and microwave extraction.

[0025] The method for removing ethanol from the filtrate is preferably to use a rotary evaporator to remove ethanol from the filtered extract at a temperature range of 40 to 80°C.

[0026] A method for preparing the compound capsicum flurbiprofen gel ointment,

[0027] Step 1: Weigh the API according to the ratio of the API of the compound gel ointment;

[0028] Step 2: Heat to melt the moisturizer, uniformly disperse the pepper extract and flurbiprofen in the moisturizer in sequence, add the skeleton material and filler after mixing, add the penetration enhancer, anti-irritation component, and cross-linking regulator after mixing, and obtain phase A;

[0029] Step 3: The crosslinking agent is dissolved in water, and the adhesive is fully heated and swelled to obtain phase B;

[0030] Step 4: Disperse phase B evenly in phase A, stir evenly, quickly apply it on non-woven fabric, and cure it at room temperature for 48 hours.

[0031] In the steps 2, 3 and 4, the heating, melting, swelling and coating temperatures may be the same or different and may be selected from 30 to 65°C.

[0032] Furthermore, in the steps 2 and 3, the heating melting, swelling and coating temperatures can be the same or different and can be selected from 30 to 65° C., more preferably 35 to 50° C. The same temperature is selected for the hot melting in the two steps, the same temperature is selected for the swelling in the two steps, and the same temperature is selected for the coating in the two steps.

[0033] An application of the compound capsicum flurbiprofen gel paste, and an application of the compound capsicum flurbiprofen gel paste as a medicine for treating arthritis or muscle pain.

[0034] By selecting the appropriate cross-linking agent and penetration enhancer type and dosage, a high drug loading gel ointment is selected as a transdermal dosage form. The analgesic and anti-inflammatory mechanism of Cap and Flu is combined to develop a compound warm analgesic gel ointment, increase the efficacy of single Cap and Flu preparations, avoid the toxic and side effects of large doses of a single drug, increase transdermal absorption, and play a better role in treating RA. At the same time, the preparation process of the present invention is easy to stir, the various phases are mutually integrated, the obtained paste is uniform in color, has no obvious particles, is easy to apply, has no broken strips and overflow, has suitable adhesion, and has excellent product quality.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] The matrix of the compound capsicum flurbiprofen gel paste of the present invention is the most suitable prescription ratio, so that the patch product has a good appearance and shape, is smooth and delicate, has no residue after peeling, has suitable adhesion, is easy to apply, and is convenient for production. At the same time, the present invention has stable process, reasonable and feasible, controllable quality, easy stirring in the preparation process, each phase is mutually integrated, the obtained paste has uniform color, no obvious particles, is easy to apply, has no phenomenon such as broken strips and leaking paste, and has good product quality.

[0037] The gel ointment of the present invention has uniform components in the matrix layer, and the main drugs (capsicum extract and flurbiprofen) and other auxiliary materials can be fully and evenly dispersed in the matrix without obvious drug precipitation phenomenon, and has good adhesion and cohesion, good elasticity and flexibility, and is easy to apply and remove without residue. In addition, the compound warming analgesic gel ointment developed by the analgesic and anti-inflammatory action mechanism of the compound gel ointment is obtained, the therapeutic effect of a single Cap and Flu preparation is increased, the toxic and side effects of a large dose of a single drug are avoided, and a better effect of treating arthritis is played. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Comparison of capsaicin content in extracts extracted with different ethanol concentrations.

[0039] Figure 2In vitro release of three batches of samples from Example 4 DETAILED DESCRIPTION

[0040] The present invention is further described in detail below in conjunction with specific embodiments. Unless otherwise specified, the experimental methods used below are all conventional methods in the art, and the ingredients or materials used are all ingredients or materials available through commercial channels unless otherwise specified. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments.

[0041] The invention obtains a pepper extract by a specific extraction method, the content of capsaicin in the extract is relatively high, the method is simple and feasible, the extraction efficiency is high, the solvent toxicity and pollution are relatively small, and the pepper extract is compounded with flurbiprofen to exert an analgesic effect of the pepper extract via TRPV1; the effect of inhibiting COX-2 and promoting the production of anti-inflammatory factors such as IL-10 is combined with the effect of flurbiprofen inhibiting COX, reducing PG and blocking pain delivery, thereby producing better anti-inflammatory and analgesic effects, and avoiding the toxic and side effects of large-dose administration of a single drug, so that the paste is easy to stir when preparing the ointment, and each phase is mutually integrated, and the prepared paste has uniform color, no obvious particles, is easy to apply, has no broken strips and overflow phenomena, has suitable adhesion, and has excellent product quality.

[0042] Examples 1-3

[0043] The compound gel ointment comprises an anti-adhesive layer, a paste layer and a lining layer; wherein the paste layer is composed of a matrix and a main drug; after the components are mixed and cross-linked into a three-dimensional structure, a drug-containing gel ointment is obtained; the specific ingredients of the paste layer are shown in Table 1 below in terms of mass percentage, and the remainder is water.

[0044] Table 1

[0045]

[0046] The preparation method of the pepper extract used in this embodiment is:

[0047] The dried and sieved pepper powder is added with anhydrous ethanol as an extraction solvent at a solid-liquid ratio of 1:10 (w / w), soaked in the solvent for 30 minutes at a temperature of 60°C, ultrasonically extracted for 15 minutes at a power of 500W and a frequency of 50kHz, filtered and collected, and most of the ethanol in the filtered extract is spun out using a rotary evaporator within a temperature range of 40°C to obtain a concentrated solution, which is dried to obtain a pepper extract. The preparation method of the compound gel paste is as follows:

[0048] (1) Weighing the API according to the proportion of the API of the compound gel ointment;

[0049] (2) Heat molten glycerol at 35°C, uniformly disperse the capsicum extract and flurbiprofen in the glycerol in sequence, mix well, add partially neutralized sodium polyacrylate and kaolin, mix well, add any one of the penetrants listed in the above table, camphor, vitamin E, and finally add aluminum glycolate and EDTA and mix well to obtain phase A.

[0050] (3) Tartaric acid is dissolved in water and gelatin is fully heated to swell to obtain phase B.

[0051] (4) Phase B is evenly dispersed in phase A, stirred evenly, and quickly coated on the non-woven fabric at a coating temperature of 35°C;

[0052] (5) Attach the anti-sticking layer to the applied paste; and cure it at room temperature for more than 48 hours.

[0053] Embodiment 4-5

[0054] The compound gel ointment comprises an anti-adhesive layer, a paste layer and a lining layer; wherein the paste layer is composed of a matrix and a main drug; after the components are mixed and cross-linked into a three-dimensional structure, a drug-containing gel ointment is obtained; the specific paste layer ingredients are shown in Table 2 in terms of mass percentage, and the remainder is water.

[0055] Table 2

[0056]

[0057] The preparation method of the pepper extract used in this embodiment is:

[0058] The dried and sieved pepper powder is added with anhydrous ethanol as an extraction solvent at a solid-liquid ratio of 1:15 (w / w), soaked in the solvent for 45 minutes at a temperature of 70°C, ultrasonically extracted for 30 minutes at a power of 500W and a frequency of 50kHz, filtered and collected, and most of the ethanol in the filtered extract is spun out using a rotary evaporator within a temperature range of 40°C to obtain a concentrated solution, which is dried to obtain a pepper extract. The preparation method of the compound gel paste is as follows:

[0059] (1) Weighing the API according to the proportion of the API of the compound gel ointment;

[0060] (2) Heat molten glycerol at 50°C, uniformly disperse the capsicum extract and flurbiprofen therein in sequence, add partially neutralized sodium polyacrylate and kaolin after mixing, add menthol, camphor, vitamin E after mixing, and finally add aluminum glycolate and EDTA and mix well to obtain phase A.

[0061] (3) Tartaric acid is dissolved in water, and gelatin or PVPK-30 or PVPK-90 is fully heated and swollen to obtain phase B.

[0062] (4) Phase B is evenly dispersed in phase A, stirred evenly, and quickly coated on the non-woven fabric at a coating temperature of 50°C;

[0063] (5) Attach the anti-sticking layer to the applied paste; and cure it at room temperature for more than 48 hours.

[0064] According to the following self-determined inspection standard (0-10 points) for the gel ointment matrix, 1) the matrix uniformity of each embodiment and comparative example is

[0065] 0: The gel paste has particles, clumps, and uneven thickness.

[0066] 10: The matrix is ​​uniform, the color is uniform, and there are no insoluble particles.

[0067] 2) Spreadability

[0068] 0: Difficult to coat. During coating, the matrix is ​​broken or cross-linked too strongly, making it impossible to spread the coating.

[0069] 10: The ointment is easy to spread, the matrix can be continuous during application, and the ointment is easy to push.

[0070] 3) Film residue

[0071] 0: Residual matrix on the skin or the surface of the ointment is destroyed.

[0072] 10: No residue on the skin and the matrix is ​​intact.

[0073] 4) Repeated adhesion

[0074] 0: Unable to stick repeatedly, poor substrate adhesion.

[0075] 10: After repeated peeling and sticking, the ointment has excellent viscosity and no residue.

[0076] 5) Skin followability

[0077] 0: Cannot stick to the skin and will fall off with a light shake.

[0078] 10: Shake several times, the ointment adheres well and does not fall off.

[0079] Table 3

[0080]

[0081] After cross-linking, the matrix itself has a certain degree of viscosity, but this adhesion is generally insufficient, so adding additional adhesives to increase the matrix adhesion is a good choice. The choice of adhesive is a major factor affecting the adhesion of gel ointments. Gelatin takes a long time to swell during the preparation process, and when gelatin is used as an adhesive, it is easy to not swell completely, and undissolved gelatin particles appear on the surface of the ointment; when the polyvinyl pyrrolidone series is used as an adhesive, PVPK-90 has a shorter swelling time and performs well in terms of uniformity, spreadability, and adhesion; while PVPK-30 exhibits relatively weak adhesion and does not play a significant role in increasing viscosity.

[0082] Comparative Example 5

[0083] According to the matrix formula and corresponding preparation described in Example 4 above, the only difference is that the active pharmaceutical ingredients are pepper extract and ethylene glycol salicylate. The amount of each substance added is shown in the table below.

[0084]

[0085] The preparation method of the pepper extract used in this comparative example is:

[0086] The dried and sieved pepper powder is added with anhydrous ethanol as an extraction solvent at a solid-liquid ratio of 1:15 (w / w), soaked in the solvent for 45 minutes at a temperature of 70°C, ultrasonically extracted for 30 minutes at a power of 500W and a frequency of 50kHz, filtered and collected, and most of the ethanol in the filtered extract is spun out using a rotary evaporator within a temperature range of 40°C to obtain a concentrated solution, which is dried to obtain a pepper extract. The preparation method of the compound gel paste is as follows:

[0087] (1) Weighing the API according to the proportion of the API of the compound gel ointment;

[0088] (2) Heat molten propylene glycol at 50°C, uniformly disperse the capsicum extract and ethylene glycol salicylate therein, mix well, add partially neutralized sodium polyacrylate and kaolin, mix well, add menthol, camphor, vitamin E, and finally add aluminum glycolate and EDTA and mix well to obtain phase A.

[0089] (3) Tartaric acid is dissolved in water, and PVPK-90 is fully heated to swell, thereby obtaining phase B.

[0090] (4) Phase B is evenly dispersed in phase A, stirred evenly, and quickly coated on the non-woven fabric at a coating temperature of 50°C;

[0091] (5) Attach the anti-sticking layer to the applied paste; and cure it at room temperature for more than 48 hours.

[0092] The penetration effects of the ointments obtained in the above-mentioned embodiments and comparative examples were measured by an in vitro transdermal test, and the specific method was as follows:

[0093] The horizontal double chamber diffusion cell method (area of ​​about 1.5 cm2) was used to investigate the in vitro permeability of Cap and Flu in the compound gel ointment. The rotor speed in the transdermal experiment was set to 600 rpm and the temperature was 32 ± 0.5 °C. The pre-treated low-temperature frozen ex vivo mouse skin was taken out and placed in a room temperature environment. It was thawed after about 30 minutes and rinsed with physiological saline. The filter paper absorbed excess moisture. The mouse skin that could cover the area of ​​the diffusion cell was cut, the homemade gel ointment was cut into a suitable size, the anti-adhesive layer was peeled off, and it was carefully attached to one side of the skin stratum corneum. The bubbles between the gel ointment and the mouse skin were removed. The skin and the gel ointment were fixed between the two chambers of the diffusion cell with a clip. It was placed in a multifunctional transdermal diffusion instrument, and 4.0 mL of PBS solution with pH 7.4 of 20% ethanol was used as the receiving medium. 2.0 mL was sampled from the receiving cell at 2, 4, 6, 8, 10, 12, and 24 hours, and 2.0 mL of isothermal blank medium was added after sampling to ensure that it was in a constant leak tank condition. The sample solutions were filtered through a 0.45 μm filter membrane and analyzed by HPLC.

[0094]

[0095] Menthol and propylene glycol have good penetration-enhancing effects on Cap and Flu, respectively. Menthol:propylene glycol in a ratio of 1:1 was further screened as a composite penetration-enhancing system, which had the best effect of promoting transdermal absorption.

[0096] Then, the ointment obtained in Example 5 was further subjected to in vitro release assay. This experiment conducted in vitro release of three batches of samples, specifically:

[0097] The release rate determination method is as follows: 20% ethanol pH 7.4 PBS solution is used as the release medium, 900 mL is measured and placed in a dissolution cup, the self-made gel paste is torn off the anti-sticking layer and fixed between two layers of discs, the temperature is 32℃±0.5℃, the rotation speed is 50rpm, and the release experiment is carried out. 5 mL of samples are taken at 1, 2, 4, 6, 8, 10, 12, and 24 hours, and 5 mL of isothermal blank release medium is added after sampling. The sample is filtered through a 0.45μm filter membrane, and the filtrate is analyzed by HPLC to record the Cap and Flu peak areas (see Figure 2 ).

[0098] Depend on Figure 2 It can be seen that in Example 5, Cap releases about 50% in 8 to 10 hours, Flu releases about 50% in 8 hours, and after 24 hours, Cap and Flu release a cumulative amount of about 70% to 80%, indicating good release.

[0099] At the same time, the ointment obtained in Example 5 was subjected to a classic analgesic animal experiment: the mouse writhing method, to evaluate the effectiveness of analgesics, the ambient temperature was selected to be 22°C, and 1.0% acetic acid solution (v / v) was intraperitoneally injected to cause mice to produce a writhing reaction. Although both Comparative Example 5 and Example 5 had obvious analgesic effects, and the writhing reaction latency of Example 4 was longer, the pain inhibition rate % was greater than that of Comparative Example 5.

[0100]

Claims

1. A compound capsicum flurbiprofen gel paste, comprising an anti-adhesive layer, a paste layer, and a lining layer; characterized in that: The paste layer is composed of a matrix and a main drug; by weight percentage, 7.4% to 9.3% of skeleton material, 22.6% to 28.4% of moisturizer, 0.12% to 0.36% of cross-linking agent, 0.16% to 0.40% of cross-linking regulator, 0.68% to 1.53% of filler, 0.90% to 2.75% of adhesive, 0.25% of pepper extract, 0.20% of flurbiprofen, 0.22% to 4.45% of penetration enhancer, 0.82% to 1.75% of anti-irritation component, and the remaining components are distilled water.

2. The compound capsicum flurbiprofen gel paste according to claim 1, characterized in that: The paste layer is located between the release film and the backing film.

3. The compound capsicum flurbiprofen gel paste according to claim 1, characterized in that: The moisturizing agent is propylene glycol and / or glycerol; The cross-linking agent is one or more of aluminum chloride, aluminum hydroxide, and aluminum glycolate; The cross-linking regulator is one or more of tartaric acid, citric acid, malic acid, and EDTA; The filler is one or two of kaolin, titanium dioxide and zinc chloride; The adhesive is one or both of gelatin and / or PVPK-90; The penetration enhancer is propylene glycol and / or menthol; The anti-irritation component is one or more of peppermint oil, camphor and vitamin E.

4. The compound capsicum flurbiprofen gel paste according to claim 3, characterized in that: When the penetration enhancers are propylene glycol and menthol, the mass ratio of propylene glycol to menthol in the system is 1:

1.

5. The compound capsicum flurbiprofen gel paste according to claim 1, characterized in that: The pepper extract is (1) crushing and sieving dried red pepper to obtain pepper powder; (2) After the pepper powder is dried, it is soaked with ethanol, extracted repeatedly, and the solid-liquid separation is performed to remove the ethanol in the filtrate to obtain a pepper extract concentrate, and the pepper extract concentrate is dried to obtain a pepper extract.

6. The compound capsicum flurbiprofen gel paste according to claim 5, characterized in that: In the step (2), the mass volume ratio of chili powder to ethanol is 1g:(5-20)mL according to the solid-liquid ratio; and the infiltration time is 15-120min.

7. A method for preparing the compound capsicum flurbiprofen gel paste according to claim 1, characterized in that: Step 1: Weigh the API according to the ratio of the API of the compound gel ointment; Step 2: Heat to melt the moisturizer, uniformly disperse the pepper extract and flurbiprofen in the moisturizer in sequence, add the skeleton material and filler after mixing, add the penetration enhancer, anti-irritation component, and cross-linking regulator after mixing, and obtain phase A; Step 3: The crosslinking agent is dissolved in water, and the adhesive is fully heated and swelled to obtain phase B; Step 4: Disperse phase B evenly in phase A, stir evenly, quickly apply it on non-woven fabric, and cure it at room temperature for 48 hours.

8. The method for preparing the compound capsicum flurbiprofen gel paste according to claim 7, wherein: In the steps 2, 3 and 4, the heating, melting, swelling and coating temperatures may be the same or different and may be selected from 30 to 65°C.

9. An application of the compound capsicum flurbiprofen gel paste according to claim 1, characterized in that: The compound capsicum flurbiprofen gel ointment is used as a medicine for treating arthritis or muscle pain.

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