Triptolide acupoint application for rheumatoid arthritis

Abstract

The application discloses a triptolide acupoint sticking plaster suitable for rheumatoid arthritis, which comprises a backing layer, a pressure-sensitive adhesive layer, a medicine layer and a release layer, one side of the pressure-sensitive adhesive layer is pasted with one side of the backing layer, one side of the medicine layer is pasted with the other side of the pressure-sensitive adhesive layer, and one side of the release layer is pasted with the other side of the medicine layer, and the medicine layer takes triptolide as a medicine active substance. Compared with the prior art, the triptolide acupoint sticking plaster has the advantages of convenient use, low safety and toxicity, slow release, high bioavailability and the like, and is more suitable for skin in appearance, and has a good treatment effect on rheumatoid arthritis.

Description

Technical Field

[0001] This invention relates to the field of acupoint application technology, and in particular to a triptolide acupoint application suitable for rheumatoid arthritis. Background Technology

[0002] Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, the etiology of which is not fully understood. In my country, there are as many as 4.8 million RA patients, and the prevalence is increasing year by year. RA is characterized by chronic, progressive inflammation of the synovial membrane of the joints, causing joint pain and swelling. If the condition is not well controlled and treated, it can lead to joint deformities, disability, and multiple organ failure, causing immense suffering to patients. Therefore, the treatment of RA remains a focus of attention in my country's medical community and a challenge that medical researchers have been striving to overcome.

[0003] Tripterygium wilfordii Hook. f., a woody vine belonging to the genus Tripterygium in the family Celastraceae, is a traditional Chinese medicine with the effects of dispelling wind and dampness, relaxing muscles and promoting blood circulation, reducing swelling and relieving pain. It is one of the most widely used and effective traditional Chinese medicines for treating rheumatoid arthritis (RA). Tripterygium wilfordii (TP), also known as triptolide, is an epoxidized diterpene lactone compound isolated from Tripterygium wilfordii. TP has strong biological activity and a clear efficacy, and is the most important active ingredient in Tripterygium wilfordii for treating RA. On the one hand, TP can inhibit the expression of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2), reducing the inflammatory response in RA. On the other hand, TP can promote osteoclast apoptosis, reduce bone loss in RA patients, and thus alleviate the symptoms of RA. However, due to its poor water solubility in vivo, TP is poorly absorbed in the gastrointestinal tract and is easily metabolized, resulting in low bioavailability and limited drug concentrations reaching inflamed joints, which greatly restricts its clinical efficacy. Furthermore, TP has significant adverse reactions such as gastrointestinal ulceration, hepatotoxicity, and nephrotoxicity. Its non-specific distribution in the body (abundant in normal tissues, but limited concentrations at inflamed joints) leads to a "high toxicity, low efficacy" phenomenon, further reducing its clinical efficacy and safety. Therefore, developing a suitable administration route to directly target TP to the inflamed sites of rheumatoid arthritis (RA) is of great significance for improving the efficacy of TP in treating RA.

[0004] Acupoint application is a promising method of drug delivery, avoiding adverse reactions such as gastrointestinal, hepatic, and renal damage caused by oral administration and low drug utilization leading to "high toxicity and low efficacy." Acupoint application, a traditional Chinese medicine treatment, involves applying medication to specific acupoints on the body surface. The medication stimulates these acupoints, regulating meridians and blood circulation to treat diseases. Currently, acupoint application is widely used in the clinical treatment of rheumatoid arthritis (RA). However, traditional methods often involve mixing various Chinese herbal powders with ginger juice, rice wine, etc., by hand until the mixture reaches the appropriate consistency, then shaping it into herbal cakes, which are then applied to the corresponding acupoints. To enhance the stimulation of the acupoints and improve efficacy, the herbs used to make the cakes are often bubbly, resulting in a pungent odor and potential side effects. For individuals with sensitive skin, acupoint application can easily cause skin allergies, even leading to skin damage, fever, and other inflammatory symptoms. In the preparation of acupoint patch medicated cakes, due to the manual preparation process, the dosage of drugs and adjusting solvents often contains certain errors, affecting the efficacy of the patch. Currently, acupoint patches are mainly used to treat respiratory diseases, and there are few reports on acupoint patches suitable for RA. The reported acupoint patch drug components are all empirical formulas from various medical institutions, and their formulations and the adhesion of the patch medicated cakes are not entirely consistent, resulting in poor stability during use. At the same time, because the dressing material is often hard, it restricts the patient's joint movement during use, resulting in low comfort. Therefore, constructing suitable drug carriers and dressing materials is crucial for improving the efficacy of acupoint patch treatment for RA.

[0005] Inspired by acupoint application therapy, modern medicine employs transdermal drug delivery to treat rheumatoid arthritis (RA), which can reduce the toxicity of oral triptolide (TP) administration, suggesting that TP may be a potential drug carrier for acupoint applications. However, because TP does not easily penetrate the stratum corneum, direct transdermal administration through acupoints is also poorly absorbed. Direct transdermal TP administration also causes skin irritation and reduces patient compliance. Cubic liquid crystals, with structures and chemical properties similar to cell membranes, can penetrate the stratum corneum and offer advantages such as simple preparation processes, high drug loading capacity, high adhesion, and avoidance of drug degradation, making them a preferred choice for transdermal administration. Compared to other TP formulations, triptolide cubic liquid crystals exhibit excellent transdermal penetration and sustained-release effects, while significantly reducing the skin irritation of triptolide, making them the optimal formulation for transdermal TP administration. Furthermore, traditional acupoint applications stimulate acupoints through medication but lack physical stimulation, thus failing to fully utilize the therapeutic effects of acupoints. Therefore, how to modify the dosage form of TP and the structure of acupoint patches to better fit the skin and achieve the technical effects of improving the skin's absorption of drugs and enhancing drug stability is a technical problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0006] In view of some problems existing in the prior art, the technical problem to be solved by the present invention is to provide a triptolide acupoint patch suitable for rheumatoid arthritis (RA). The biggest drawback of traditional acupoint patches is that the patch medication is not standardized, resulting in unstable efficacy. This patent improves traditional acupoint patch products by using a standardized process to prepare triptolide cubic liquid crystal as the drug carrier for the acupoint patch. At the same time, through the syndrome differentiation and treatment system of traditional Chinese medicine, individualized acupoint prescriptions suitable for the patient's constitution are selected. Through acupoint patch therapy technology, triptolide can directly stimulate specific acupoints of RA patients, targeting the lesion for drug delivery, thereby improving the clinical efficacy of traditional Chinese medicine triptolide in treating RA. The improved triptolide cubic liquid crystal acupoint patch not only exerts the efficacy of traditional patches but also improves the bioavailability of TP and reduces the toxic side effects of TP, achieving a "low-toxicity and high-efficiency" effect.

[0007] Furthermore, we have improved the appearance of the acupoint patch. The raised structure of the pressure-sensitive layer directly stimulates acupoints, providing physical stimulation to activate receptors in the acupoint area, opening the stratum corneum of the skin, promoting drug absorption, and improving efficacy. The drug layer incorporates a hydrogel formulation, which better adheres to the skin, reduces skin allergic reactions, improves the quality stability of the acupoint patch, and enhances the skin's absorption of triptolide on the patch, thereby improving the therapeutic effect on rheumatoid arthritis.

[0008] To achieve the above objectives, the present invention provides a triptolide acupoint patch suitable for rheumatoid arthritis, the triptolide acupoint patch comprising: a backing layer; a pressure-sensitive adhesive layer, one side of which is adhered to one side of the backing layer, and one side of which is provided with nipple-shaped protrusions; a drug layer, one side of which is adhered to the other side of the pressure-sensitive adhesive layer; and an anti-adhesion layer, one side of which is adhered to the other side of the adhesive layer.

[0009] In the first aspect, the drug layer is prepared by the following method: water, methacrylic acid hydrogel and leucine aminopeptidase are mixed and stirred at 300-500 rpm for 10-30 minutes to obtain a gel precursor. The obtained gel precursor is then added to triptolide cubic liquid crystal and stirred at 400-600 rpm for 20-50 minutes. The mixture is then poured into a mold of the drug layer and irradiated with light for 2-3 minutes to obtain the drug layer.

[0010] In the first aspect, the mass ratio of water, methacrylated hydrogel, and leucine aminopeptidase is 50~80:3~5:0.05~0.15; the mass ratio of methacrylated hydrogel to triptolide cubic liquid crystal is 3~5:20~30.

[0011] In the first aspect, the triptolide cubic liquid crystal is prepared by the following method: triptolide is added to polyethylene glycol 400 and stirred at 300-500 rpm until the triptolide dissolves to obtain a drug solution; then phytanetriol is added to the drug solution and stirred at 400-600 rpm for 30-60 minutes in a 60°C water bath; then water is added and stirring is continued at 400-600 rpm for 3 minutes to obtain the triptolide cubic liquid crystal.

[0012] In the first aspect, the mass ratio of triptolide to polyethylene glycol 400 is (8.6~12) mg:(3~10) g; the mass ratio of polyethylene glycol 400, phytanetriol, and water is 3~10:48~60:35~50. In the first aspect, the backing layer is made of waterproof fibers.

[0013] In the first aspect, the pressure-sensitive adhesive layer is made of polyacrylate pressure-sensitive adhesive.

[0014] In the first aspect, the anti-stick layer is made of an anti-stick material.

[0015] In the first aspect, the dimensions of the other side of the drug layer, the pressure-sensitive adhesive layer, and the anti-stick layer are the same.

[0016] In the first aspect, the diameter of the nipple-shaped protrusions provided on one side of the pressure-sensitive adhesive layer is 0.1~100 μm.

[0017] Beneficial effects: Due to the adoption of the above technical solutions, compared with the existing technology, the present invention has the following advantages: 1. Compared with transdermal drug delivery, which only delivers medication to the skin and lacks site precision, acupoint patches can precisely act on acupoints, allowing the drug to exert a dual effect of both the drug and the acupoint through stimulation, and directly reach the lesion; 2. Compared with oral drug delivery, acupoint patches have lower toxicity, higher bioavailability, are convenient, and are easily accepted by patients; 3. Compared with traditional acupoint patches and triptolide acupoint patches, traditional acupoint patches have no specificity for RA treatment, while triptolide acupoint patches have screened out the most effective active pharmaceutical ingredient of Tripterygium wilfordii, triptolide, improving the efficacy of acupoint patches; 4. Advantages of triptolide cubic liquid crystal: It can penetrate the stratum corneum of the skin, has high bioavailability, good sustained release, and low skin irritation; 5. Improved appearance of acupoint patches: The raised areas of the pressure-sensitive adhesive have the effect of acupoint pressing, while promoting drug absorption. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of this specification or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 This is a schematic diagram of the structure of the Tripterygium wilfordii extract acupoint patch for rheumatoid arthritis according to the present invention; Figure 2 This is a graph showing the relationship between arthritis scores and time in mice; Figure 3 This is a bar chart showing the arthritis scores of rats. Attached image description: 1. Backing layer; 2. Pressure-sensitive adhesive layer; 3. Papillary protrusions; 4. Drug layer; 5. Anti-stick layer. Detailed Implementation

[0021] The technical solutions in the embodiments of this specification will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this specification, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments in this specification are within the scope of protection of this invention.

[0022] Example 1 This embodiment provides a triptolide acupoint patch suitable for rheumatoid arthritis. The triptolide acupoint patch includes: a backing layer 1; a pressure-sensitive adhesive layer 2, one side of which is adhered to one side of the backing layer 1, and one side of the pressure-sensitive adhesive layer 2 is provided with nipple-shaped protrusions 3; a drug layer 4, one side of which is adhered to the other side of the pressure-sensitive adhesive layer 2; and an anti-adhesion layer 5, one side of which is adhered to the other side of the drug layer 4.

[0023] The Tripterygium wilfordii acupoint patch of this invention uses Tripterygium wilfordii as the main active ingredient in the drug layer. By applying the patch to specific acupoints corresponding to the affected joints in rheumatoid arthritis, it achieves the technical effect of relieving or treating arthritis. This invention is an acupoint drug delivery method, precisely applying the patch to the acupoint skin. Transdermal drug delivery, on the other hand, only delivers the drug to the skin and lacks site precision. The acupoint patch can precisely act on the acupoint skin, allowing the drug to exert a dual effect of drug and acupoint stimulation, achieving a combination of acupoint and drug, enhancing efficacy and reducing toxicity. Furthermore, in the acupoint patch of this invention, one side of the drug layer is adhered to the anti-adhesive layer, making it easy to peel off the anti-adhesive layer and apply the drug layer to the joint acupoint during use. The other side of the drug layer is adhered to the pressure-sensitive adhesive layer, which serves to adhere the drug layer and the backing layer, ensuring adhesion between the drug layer and the backing layer. The lining layer is waterproof and breathable, preventing the drug layer from becoming less effective due to exposure to sunlight or contamination from dust, water, or other stains on the skin and acupoints. This also prevents the exposed drug layer from becoming unsightly, easily detaching from the skin, or experiencing reduced efficacy. Simultaneously, the side of the pressure-sensitive adhesive layer that adheres to the backing layer has nipple-shaped protrusions. When the patch is applied to acupoints corresponding to arthritis, pressing these protrusions stimulates the acupoint, increasing the temperature and enhancing the transdermal permeability of the active substances in the drug layer. Furthermore, this stimulation allows the triptolide to precisely target the acupoint, exerting a dual effect of both the drug and the acupoint, directly reaching the lesion and improving the therapeutic effect of the patch on arthritis. In addition, compared with oral administration, the acupoint patch of the present invention has the advantages of low toxicity, high bioavailability, convenience, and easy acceptance by patients. Compared with traditional acupoint patches, the triptolide acupoint patch has screened out the most effective active pharmaceutical ingredient of Tripterygium wilfordii - triptolide, which improves the efficacy of the acupoint patch. Furthermore, the drug layer of the present invention is the main active substance, and the skin irritation of triptolide is reduced by preparing triptolide cubic liquid crystal. The triptolide cubic liquid crystal is a nanostructure that can penetrate the stratum corneum of the skin, has high bioavailability, and good sustained-release effect.

[0024] In some possible implementations, the drug layer 4 is prepared by the following method: water, methacrylic acid hydrogel, and leucine aminopeptidase are mixed and stirred at 300-500 rpm for 10-30 minutes to obtain a gel precursor. The obtained gel precursor is then added to triptolide cubic liquid crystal and stirred at 400-600 rpm for 20-50 minutes. The mixture is then poured into a mold of the drug layer 4 and irradiated with light for 2-3 minutes to obtain the drug layer. The mass ratio of water, methacrylic acid hydrogel, and leucine aminopeptidase is 50-80:3-5:0.05-0.15; the mass ratio of methacrylic acid hydrogel to triptolide cubic liquid crystal is 3-5:20-30.

[0025] Specifically, the triptolide cubic liquid crystal can penetrate the stratum corneum of the skin, exhibiting high bioavailability, good sustained-release properties, and low skin irritation. Simultaneously, the methacrylated hydrogel and leucine aminopeptidase also possess high bioavailability and are non-irritating to the skin. The prepared hydrogel serves as the framework for the triptolide cubic liquid crystal, allowing it to adhere to the skin in a hydrogel form as a drug layer. This increases the skin affinity of the triptolide cubic liquid crystal while avoiding the skin irritation caused by the hydrogel directly encapsulating triptolide.

[0026] In some possible implementations, the triptolide cubic liquid crystal is prepared by the following method: triptolide is added to polyethylene glycol 400 and stirred at 300-500 rpm until the triptolide dissolves to obtain a drug solution; then phytanetriol is added to the drug solution and stirred at 400-600 rpm for 30-60 minutes in a 60°C water bath; then water is added and stirring is continued at 400-600 rpm for 3 minutes to obtain the triptolide cubic liquid crystal; the mass ratio of triptolide to polyethylene glycol 400 is (8.6-12) mg:(3-10) g; the mass ratio of polyethylene glycol 400, phytanetriol and water is 3-10:48-60:35-50.

[0027] Specifically, using low-molecular-weight polyol polyethylene glycol 400 as a stabilizer, phytanetriol as an amphiphilic lipid molecule, and triptolide as a coating active substance, a triptolide cubic liquid crystal was prepared. This reduced the skin irritation of triptolide. At the same time, during transdermal acupoint administration, the triptolide cubic liquid crystal could slowly release triptolide through the stratum corneum of the skin, allowing triptolide to reach the lesion site of arthritis and improving the therapeutic effect of the patch on rheumatoid arthritis.

[0028] In some possible implementations, the backing layer 1 is made of waterproof fiber; the pressure-sensitive adhesive layer 2 is made of polyacrylate pressure-sensitive adhesive; and the anti-stick layer 5 is made of anti-stick material.

[0029] Specifically, the backing layer made of waterproof fiber has a waterproof and breathable effect, which can prevent the drug layer from getting dirty and affecting the efficacy and adhesion; the pressure-sensitive adhesive layer made of polyacrylate pressure-sensitive adhesive has nipple-shaped protrusions, which will not damage the skin when pressing the nipple-shaped protrusions; the anti-adhesive layer made of anti-adhesive material adheres to the drug layer, making it easy to peel off the drug layer and apply to the skin, without affecting the adhesion between the drug layer and the skin.

[0030] In some possible implementations, the dimensions of the other side of the drug layer 4, the pressure-sensitive adhesive layer 2, and the anti-adhesive layer 5 are the same; the diameter of the nipple-shaped protrusions on one side of the pressure-sensitive adhesive layer is 0.1~100 μm.

[0031] Specifically, the anti-adhesive layer completely covers the drug layer, and the pressure-sensitive adhesive layer and the drug layer are completely covered on one side to prevent the drug layer from being exposed to strong light. The side of the pressure-sensitive adhesive layer that is bonded to the backing layer has nipple-shaped protrusions, which can stimulate acupoints by pressing the nipple-shaped protrusions, thereby stimulating the acupoints with the drug and improving the skin's absorption of the drug.

[0032] To further illustrate the technical solution of this application and support the technical problem to be solved by this application, the preparation method of [the substance] is illustrated with specific examples below, such as Example 1.

[0033] Example 1 A triptolide acupoint patch for rheumatoid arthritis, comprising: a backing layer 1; a pressure-sensitive adhesive layer 2, one side of which is adhered to one side of the backing layer 1, and one side of the pressure-sensitive adhesive layer 2 having nipple-like protrusions 3 with a diameter of 2 μm; a drug layer 4, one side of which is adhered to the other side of the pressure-sensitive adhesive layer 2; and an anti-adhesion layer 5, one side of which is adhered to the other side of the drug layer 4. The preparation method of the drug layer 4 specifically includes: mixing 60 g of water, 4 g of methacrylic acid hydrogel and 0.1 g of leucine aminopeptidase, stirring at 400 rpm for 20 minutes to obtain a gel precursor, then adding the obtained gel precursor to 25 g of triptolide cubic liquid crystal, stirring at 500 rpm for 30 minutes, pouring into the mold of the drug layer, and then irradiating under an LED light for 3 minutes to obtain the drug layer; The preparation method of the triptolide cubic liquid crystal specifically includes: adding 10 mg of triptolide to 6 g of polyethylene glycol 400 and stirring at 400 rpm until the triptolide dissolves to obtain a drug solution; then adding 50 g of phytanetriol to the drug solution and stirring at 500 rpm for 40 minutes in a 60°C water bath; then adding 45 g of water and continuing to stir at 500 rpm for 3 minutes to obtain the triptolide cubic liquid crystal.

[0034] The performance of the acupoint patch described in Example 1 is as follows: Arthritis test of drug effect on rheumatoid arthritis: The arthritis scoring test of the drug used rats as the test subjects. The specific steps are as follows: 1. Modeling and grouping: 10 6-week-old SPF-grade female SD rats weighing 180-200 g were randomly selected as the normal control group. Then, 60 6-week-old SPF-grade female SD rats weighing 180-200 g were randomly selected to construct a collagen-induced arthritis (CIA) rat model. The rats in the normal control group and the rats used to construct the CIA rat model were fed the same. For the rats used to construct the CIA rat model, after 7 days of adaptive feeding, 2 mg / mL bovine type II collagen solution and complete Freund's adjuvant were emulsified thoroughly to obtain an emulsion. 200 μL of the emulsion was injected intradermally at the base of the tail and 100 μL was injected intradermally on the back of the rat for the first immunization, and this was counted as day 0. On day 7, 200 μL of the emulsion was injected intradermally at the base of the tail again. 100 μL of emulsifier was injected intradermally into the back of rats for secondary immunization. The injection sites were then observed daily for any discharge or ulceration. Erythema, red spots, and swelling were also observed in the knee and ankle joints. On day 14, successfully constructed CIA rat models were selected according to the clinical arthritis scoring criteria (Modern Immunology, 2018, 38(03):210-216). A clinical arthritis score greater than or equal to 6 points was considered a successful model. The maximum clinical arthritis score for each rat was 16 points. Rats were randomly selected from the successfully constructed CIA rat models. Thirty rats were selected and randomly divided into three groups of 10 each: a model control group, an acupoint application example group, and an oral administration control group. The arthritis score of each group was calculated as the average of the group values. 2. Drug efficacy test: During the drug test, the normal control group and the model control group received no treatment other than normal feeding. In the acupoint application example group, in addition to normal feeding, the hair around the joints of the rats was shaved, and the acupoint application patch of this invention was applied to the joints. In the rat experiment, the triptolide content in one acupoint application patch of this invention was 2.78%. μg, the patch fully targets the acupoints corresponding to the rat joints. The acupoints targeted by the patch are formulated according to international TCM clinical practice guidelines and the key affected areas of rheumatoid arthritis. The acupoints are as follows: 1) Shoulder joint: Tianzong, Jianliao, Jianzhen, and Jiannei Ashi points; 2) Elbow joint: Quchi and Chize; 3) Wrist joint: Yangchi, Waiguan, Yangxi, and Wangu; 4) Finger joint: Baxie; 5) Knee joint: Yanglingquan, Dubi, Xiyangguan, and Liangqiu. Each patch is applied for 12 hours, and the nipple-like protrusions of the pressure-sensitive adhesive layer are pressed during the application to stimulate the acupoints. The patch is applied once a day, with 26 days as one course of treatment. In addition to normal feeding, the oral control group was treated with Tripterygium wilfordii glycosides by gavage once a day at a dose of 9g.31 μg / (kg·d), with 26 days constituting one course of treatment; arthritis scores were assessed every 3 days in the four groups of rats, and the average score for each group was used. The scoring criteria were as follows: 0 points: normal; 1 point: red spots, mild redness and swelling of the ankle and wrist joints; 2 points: moderate swelling of the ankle or wrist joints; 3 points: severe redness and swelling, even affecting the fingertips; 4 points: inflammation in all four limbs, even unable to bear weight. Results regarding arthritis in rats from the normal control group, model control group, acupoint application example group, and oral administration control group are shown below. Figure 2 and Figure 3 Among them, compared with the normal control group, #p<0.05, ##p<0.01, and compared with the model control group, p < 0.05 p < 0.01.

[0035] Figure 2 The graph showing the relationship between arthritis scores and time in mice is provided by... Figure 2 It can be seen that days 1-7 constitute the initial immunization phase for modeling, and days 7-14 constitute the secondary immunization phase. After the secondary immunization, the arthritis scores of the model rats were all above 10. From day 14 onwards, both the acupoint application example group and the oral control group began receiving medication. From day 14 to day 40, the arthritis score of the normal control group remained at 0, indicating that rats without CIA modeling did not have arthritis. The arthritis score of the model control group remained high, indicating that the arthritis condition of the rats did not improve after the modeling was stopped. Arthritis is a lifelong disease before drug treatment. In the acupoint application group, the arthritis score of rats decreased after drug administration and application. On day 40 after initial immunization, i.e., day 26 after drug administration, the arthritis score dropped below 9, and the arthritis score was lower than that of the oral control group. The oral control group showed a faster onset of therapeutic effect on arthritis after drug administration than the acupoint application group. However, on day 26 after drug administration, the arthritis score of rats in the acupoint application group was lower than that in the oral control group, indicating a better therapeutic effect on arthritis. In conclusion, on day 26 after drug administration, the acupoint application group showed a better therapeutic effect on rheumatoid arthritis than the oral control group.

[0036] Figure 3 A bar chart of arthritis scores in rats, by Figure 3 It was found that on the 40th day from the initial immunization to the end of the administration, i.e. the 26th day after administration, the arthritis scores of both the acupoint application example group and the oral control group were lower than those of the model control group. The arthritis score of the acupoint application example group was lower than that of the oral control group, indicating that both the acupoint application example group and the oral control group had a therapeutic effect on rheumatoid arthritis, but the acupoint application had a better therapeutic effect on rheumatoid arthritis than the oral medication.

Claims

1. A triptolide acupoint patch for rheumatoid arthritis, characterized in that, The Tripterygium wilfordii A-formin acupoint application includes: Backing layer (1); Pressure-sensitive adhesive layer (2), one side of the pressure-sensitive adhesive layer (2) is bonded to one side of the backing layer (1), and one side of the pressure-sensitive adhesive layer (2) is provided with nipple-shaped protrusions (3). Drug layer (4), one side of the drug layer (4) is adhered to the other side of the pressure-sensitive adhesive layer (2); An anti-adhesion layer (5) is attached to one side of the drug layer (4); the drug layer (4) is prepared by the following method: water, methacrylic acid hydrogel and leucine aminopeptidase are mixed and stirred at 300-500 rpm for 10-30 minutes to obtain a gel precursor. The obtained gel precursor is then added to triptolide cubic liquid crystal and stirred at 400-600 rpm for 20-50 minutes. The mixture is then poured into the mold of the drug layer and irradiated with light for 2-3 minutes to obtain the drug layer. The triptolide-formin cubic liquid crystal was prepared by the following method: Tripterygium wilfordii was added to polyethylene glycol 400 and stirred at 300-500 rpm until dissolved to obtain a drug solution. Phytanetriol was then added to the drug solution and stirred at 400-600 rpm for 30-60 minutes in a 60°C water bath. Water was then added and the mixture was stirred at 400-600 rpm for 3 minutes to obtain a triptolide cubic liquid crystal.

2. The triptolide acupoint patch for rheumatoid arthritis as described in claim 1, characterized in that: The mass ratio of water, methacrylated hydrogel, and leucine aminopeptidase is 50~80:3~5:0.05~0.15; the mass ratio of methacrylated hydrogel to triptolide cubic liquid crystal is 3~5:20~30.

3. The triptolide acupoint patch for rheumatoid arthritis as described in claim 2, characterized in that: The mass ratio of triptolide to polyethylene glycol 400 is (8.6~12) mg: (3~10) g; the mass ratio of polyethylene glycol 400, phytanetriol and water is 3~10:48~60:35~50.

4. The triptolide acupoint patch for rheumatoid arthritis as described in claim 3, characterized in that: The backing layer (1) is made of waterproof fibers.

5. The triptolide acupoint patch for rheumatoid arthritis as described in claim 4, characterized in that: The pressure-sensitive adhesive layer (2) is made of polyacrylate pressure-sensitive adhesive.

6. The triptolide acupoint patch for rheumatoid arthritis as described in claim 5, characterized in that: The anti-stick layer (5) is made of an anti-stick material.

7. The triptolide acupoint patch for rheumatoid arthritis as described in claim 6, characterized in that: The dimensions of the other side of the drug layer (4), the pressure-sensitive adhesive layer (2), and the anti-stick layer (5) are the same.

8. The triptolide acupoint patch for rheumatoid arthritis as described in claim 7, characterized in that: The diameter of the nipple-shaped protrusions on one side of the pressure-sensitive adhesive layer is 0.1~100 μm.

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